2nd International Congress of Plastic Dermatology

Transcript

Vol. 4, n. 1, January-April 2008
Physical and microbiological properties of a new nail protective medical device
Adele Sparavigna, Michele Setaro, Linda Frisenda
The use of antisense oligonucleotides in skin lightening products
Melizza Bautista, Falen Lockett, Jaimie Mecca, Wanphimon Sawatdeekhachornphat,
Angelica Castro, Sujani Yarlagadda, Salvador Gonzalez, Neena Philips
Coating on micronized titanium dioxide increases safety and maintains efficacy as sunscreen filter
Jayson Goodner, Uma Patil, Yousun Lim, Sujani Yarlagadda,
Angelica Castro, Salvador Gonzalez, Neena Philips
Study on the effectiveness of a silicone gel in treating surgical wounds
Vincenzo De Giorgi, Serena Sestini, Barbara Alfaioli,
Marta Grazzini, Agata Janowska, Andrea Saggini, Torello Lotti
New way to protect the skin against sunlight damages
Riccarda Serri
Dark skin dermocosmetology
Stefano Veraldi
Cosmetic use of poly-L-lactic acid for skin rejuvenation: New indications
Alessio Redaelli
The reflectance confocal microscopy in the study of hair follicle pigmentary unit
Fabio Rinaldi, Giammaria Giuliani
Kaposi’s sarcoma: Story of a 30-year clinical experience
Lucia Brambilla, Vinicio Boneschi
Anti-aging principles into cosmetic products. The challenges
Piera Fileccia
2nd International Congress of Plastic Dermatology
Milan, March 6-8, 2008 A B S T R A C T S
Indexed in: EMBASE, EMNursing, Compendex, GEOBASE
Cari Colleghi,
circa un anno fa è partita la grande macchina organizzativa del 2° Congresso Internazionale di Dermatologia Plastica 2008.
I mesi sono apparentemente volati ma sono stati pieni di idee che hanno dato vita ad un evento importante per la
nostra storia.
Il 2° Congresso ISPLAD sarà ricordato per l’alto valore scientifico delle comunicazioni, per gli oltre duecento relatori, per la partecipazione di numerosi e validi colleghi stranieri, per gli oltre cinquanta giornalisti accreditati, per i
numerosi work-shop, per i corsi formativi, per l’entusiasmo e la professionalità di chi ha coordinato e organizzato gli
eventi, per i numerosissimi dermatologi partecipanti.
Non sarà dimenticata la stima e la fiducia dei numerosi sponsor che ci hanno permesso di realizzare tutto questo.
Resterà nelle nostre
mani un ricordo concreto di questi
momenti vissuti: sarà questa nostra riviDear Colleagues,
Just over a year ago, the grand organizational plans for the 2nd International Congress of
sta, il vostro JPD che state per leggere.
Plastic Dermatology were formed.
Un JPD speciale, non solo per la bella
The months seem to have flown by and they were full of creative ideas that gave life to this
copertina color oro, ma per la presenza,
extremely important event in our history. The 2nd ISPLAD Congress will be remembered for the
oltre ad importanti articoli, degli abstract
quality and scientific value of the presentations, the impressive number of over 200 speakers,
dei lavori congressuali, che potranno così
the participation of both locally-based dermatologists and respected colleagues from all over
essere letti e conosciuti da tutta la Comuthe world, as well as its workshops and training courses. I am quite sure that the enthusiasm
nità Scientifica Internazionale.
and professionalism of the event’s coordinators and the more-than-50 accredited journalists
Un grande impegno editoriale che dimowon’t be forgotten for a long time to come either. We remain incredibly thankful for the trust
stra il coraggio e la lungimiranza del noand faith of our sponsors who aided us in accomplishing our goals. With our journal, we hold
stro editore.
in our hands a concrete memory of all these shared moments: your JPD awaits you.
Un particolare ringraziamento va ad AnThis will be a special edition, not only because of its magnificent gold cover, but also for the
tonio Di Maio, Managing Editor e anima
presence of abstracts from the congressional research papers, in addition to other important
pulsante del JPD. Ci sorprende sempre la
articles. By these means, the fruits of labour of our congress will be read and made known to
sua passione nel raggiungere gli obiettivi,
the international scientific community. This has been an intense editorial undertaking and
la sua disponibilità ad ogni iniziativa e il
clearly demonstrates the courage and foresight of our editor. I take this chance to extend spesuo gran cuore.
cial thanks to Antonio Di Maio, managing editor and lively soul behind the JPD. He never fails
Ma tornando all’ISPLAD permettetemi di
to surprise us with his passion in achieving objectives, his helpfulness in every initiative, and
r i c o rd a re l’importante riconoscimento
his big heart.
che abbiamo ricevuto nell’essere stati acTurning once more to ISPLAD, we are all very proud of the recognition we have received
colti ufficialmente dalla Lega Internaziothrough our official acceptance to the International League of Dermatological Societies. This
nale delle Società Scientifiche Dermatonew status will allow us to participate in important decisions regarding the future of internalogiche (ILDS), fatto che ci permetterà di
tional dermatology.
partecipare attivamente alle decisioni che
I hope you enjoy the congress and readings.
r i g u a rderanno il futuro della Dermatologia Internazionale.
Antonino Di Pietro
Buon Congresso e buona lettura.
Journal of Plastic Dermatology 2008; 4, 1
1
Sommario
Journal of Plastic Dermatology
pag. 5
Adele Sparavigna, Michele Setaro, Linda Frisenda
Editor
Antonino Di Pietro (Italy)
pag. 17
Melizza Bautista, Falen Lockett, Jaimie Mecca, Wanphimon Sawatdeekhachornphat,
Angelica Castro, Sujani Yarlagadda, Salvador Gonzalez, Neena Philips
Editor in Chief
Francesco Bruno (Italy)
Co-Editors
Salvador Gonzalez (USA)
Pedro Jaen (Spain)
pag. 21
Coating on micronized titanium dioxide increases safety
and maintains efficacy as sunscreen filter
Jayson Goodner, Uma Patil, Yousun Lim, Sujani Yarlagadda,
Angelica Castro, Salvador Gonzalez, Neena Philips
Associate Editors
Francesco Antonaccio (Italy)
Mariuccia Bucci (Italy)
Franco Buttafarro (Italy)
Ornella De Pità (Italy)
Giulio Ferranti (Italy)
Andrea Giacomelli (Italy)
Alda Malasoma (Italy)
Steven Nisticò (Italy)
Elisabetta Perosino (Italy)
Andrea Romani (Italy)
Nerys Roberts (UK)
pag. 25
Studio prospettico sull’evoluzione delle ferite chirurgiche
trattate con gel al silicone
Vincenzo De Giorgi, Serena Sestini, Barbara Alfaioli, Marta Grazzini,
Agata Janowska, Andrea Saggini, Torello Lotti
Incrementare la protezione cutanea da fotoinvecchiamento e danno solare
pag. 33
Editorial Board
Lucio Andreassi (Italy)
Kenneth Arndt (USA)
Bernd Rüdiger Balda (Austria)
H.S. Black (USA)
Lucia Brambilla (Italy)
Günter Burg (Switzerland)
Michele Carruba (Italy)
Vincenzo De Sanctis (Italy)
Aldo Di Carlo (Italy)
Robin Eady AJ (UK)
Paolo Fabbri (Italy)
Ferdinando Ippolito (Italy)
Giuseppe Micali (Italy)
Martin Charles Jr Mihm (USA)
Joe Pace (Malta)
Lucio Pastore (Italy)
Gerd Plewig (Germany)
Riccarda Serri (Italy)
Adele Sparavigna (Italy)
Abel Torres (USA)
Stefano Veraldi (Italy)
Umberto Veronesi (Italy)
Riccarda Serri
pag. 37
pag. 41
Dermocosmetologia della pelle scura
Stefano Veraldi
Uso cosmetico dell’acido L-polilattico per il ringiovanimento cutaneo:
nuove indicazioni
Alessio Redaelli
pag. 49
The reflectance confocal microscopy in the study of hair follicle pigmentary unit
pag. 55
Fabio Rinaldi, Giammaria Giuliani
Ambulatorio sarcoma di Kaposi: racconto dell’incontro con una patologia
e di una esperienza medica durata 30 anni
Lucia Brambilla, Vinicio Boneschi
pag. 63
I principi attivi antiaging nei prodotti cosmetici. Le sfide
(Seconda di due parti)
Piera Fileccia
pag. 73 2nd International Congress of Plastic Dermatology
Milan, March 6-8, 2008 A B S T R A C T S
Managing Editor
Antonio Di Maio
English editing
Rewadee Anujapad
Direttore Responsabile
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3
Physical and microbiological properties
of a new nail protective medical device
Adele Sparavigna1
Michele Setaro2
Linda Frisenda3
SU M M A R Y
Physical and microbiological
properties of a new nail protective
medical device
The study evaluated the physical and microbiological properties of a hydro-alcoholic,
film-forming solution containing hydroxypropyl-chitosan (HPCH) at different concentrations, and that forms the basis of a new medical device, including also piroctone olamine as a preservative, with protective activity for both toenails and fingernails. The following physical properties of 1% hydroxypropyl-chitosan solution were
investigated either in vitro by using bovine hoof slices (as a well recognized model
of human nails) or in vivo on healthy human nails: the film-forming capability, the
adhesion of the product on the nail surface, the protective properties against abrasion (mechanical aggression) and temperature (physical aggression).
The application of HPCH solution on a bovine nail slice, after evaporation of the solvent, forms a thin film that is very evident when examining the surface of the slice
with a microscope scanner. The surface covered by HPCH film appears smoother
compared to the irregular, rough surface of the control nail plate.
Hydroxypropyl chitosan film adheres well to the nail surface during the stripping
test, while the same film does not adhere so well to glass.
The test therefore confirms the existence of the film-forming capacity of hydro x ypropylchitosan selective to nail tissue, unlike that observed with common cosmetic nail varnish or glue.
The presence of the HPCH film is also demonstrated by the thermography test performed in vivo on the nails of a healthy volunteer, which found a reduction in the
temperature of the nail surface as a result of the presence of the film.
Lastly, the film protects the surface of the nail from mechanical damage caused by
abrasion, as demonstrated by the abrasion test performed in vivo on a healthy volunteer, which found significantly less abrasion on the nail surface protected by the
HPCH film. The paper also investigated the microbiological properties and protection against nail fungal colonization provided by hydroxypropyl-chitosan solutions,
with or without the preservative agent.
When some drops of the HPCH solutions were put on a Petri dish inoculated with T.
mentagrophytes, the growth of the nail pathogen on the HPCH film was prevented
by a physical mechanism. In a further in vitro experiment, the application of 10-20
µL of the device (0.5% HPCH and 0.5% piroctone olamine) on a bovine nail slice put
on a Petri dish inoculated with T. rubrum, prevented the growth of the pathogen
within and around the nail, by forming dose-dependent inhibition rings. Finally, the
device prevented the in vitro nail experimental infection by T. rubrum either when
applied before or after the bovine nail slices contamination. No growth of the nail
pathogen was observed after transplant of the nail fragments, treated with the
device, in a new plate not inoculated with the fungus, while on the contrary a regular growth was recorded for control nail plates.
In conclusion, our data show that the new medical device, when applied on the nails,
is capable to form a film, that adheres and penetrates into the nail structure, by supporting it and forming a protective film against physical and microbiological agents.
In particular, the device prevents the nail infections by common pathogens such as T.
mentagrophytes and T. rubrum in experimental infection models.
KEY WORDS: Hydroxy-propyl chitosan (HPCH), Nail film-forming, Physical protection,
Microbiological protection
DermIng s.r.l., Monza, Milano (Italy)
2
Tecnolab del Lago Maggiore s.r.l.,
Verbania Fondotoce (Italy)
3
Polichem SA, Lugano (Switzerland)
1
5
A. Sparavigna, M. Setaro, L. Frisenda
I
ntroduction
The strength and physical character of
the nail is attributable to both its constituents
and design. The nail tensile, flexure and tearing
strength changes with age, sex and the digit
from which the nail derived. The nail is 1000
times more permeable to water than the skin,
and consequently the nail structure reacts to
prolonged or repeated contact with water.
Immersion of the nail in water for an hour
increases its weight by over 20%, moreover it
renders the nail more flexible.1
The aspect of the nails may be affected by: longitudinal grooves, that may represent physiological
long-lasting conditions as shallow and delicate
furrows, and that become more prominent with
age and in certain pathological conditions; longitudinal ridges, i.e. small rectilinear projections
that usually extend from the proximal nail fold
until the free edge of the nail; oblique lines, more
common in children than in adults; transverse
lines in form of sulci, that reflect a temporary
reduction in nail matrix activity and are considered as retrospective indicators of a trauma or
other pathological conditions.1
Lamellar splitting (onychoschizia) is a condition found in 27-35% of normal adult women.
The distal portion of the nail splits horizontally
in this condition. It is common in people who
carry out a great deal of housework, whose nails
are repeatedly soaked in water and then dried.
Changes in the fingernails of old people are
mostly related to diminished tissue repair and
inflammatory or degenerative changes of the
distal interphalangeal joint. These influences
are associated with reduced rate of longitudinal
nail growth, thinning of the nail plate and
accentuation of longitudinal ridges.1
Variations in thickness and consistency of the
toenails occur in the elderly and are mostly attributable to changes in peripheral circulation.
Repetitive and prolonged wetting and drying of
f i n g e rnails is the single most common cause of
splitting and ridges of the nails. Splitting of the
nails is rarely caused by internal disease or vitamin deficiency, nail polish remover causes onychoschizia (lamellar splitting), finally trauma to
the fingers contributes to onychoschizia.
Healthy looking nails should be smooth, curved,
void of any spotting, and should not have any hollows or ridges. Nail polishes are used since centuries with the aim to beautify, colour or hidden
defects of the nails. Basic ingredients of the nail
6
polishes are film forming agents, resins and plasticizers, solvents, and colouring agents. In addition
to the traditional products, other products with
selective ingredients become available with the
aim to reinforce and protect the nails. The use of a
nail varnish, normally a water insoluble polyvinyl
resin film, has the disadvantage that the removal
of the nail varnish by an organic solvent or by nail
filing can further damage the nail structure, by
increasing brittleness and splitting, and rendering
the nail keratin less resistant to the fungal infections. Among the cosmetic damages of the nails,
the following can be included: breaking, splitting,
fracturing, brittleness, white spots or ridges, poor
nail growth, color or shape changes. Nails in bad
conditions can be very harmful for the personal
image, if neglected can cause chronic infections,
associated to long-lasting embarrassment and
pain. Noteworthy, they may be considered a social
problem and/or a professional illness.
Medicated nail lacquers are also available, which
contain monoester resins as film forming agents,
and antifungal agents as active ingredients, intended to manage nail diseases such as onychomycosis, but less effective than expected on the basis
of their in vitro antifungal activity. In fact, the
commercially available medicated nail lacquers
have some limitations due to the characteristics of
the film-forming agents, which have no affinity to
keratin and act as occlusive medications. Those
entrap the active ingredient and reduce its diffusion from subsequent applications, as a result of
the formation of thick lacquer layers that tend to
split easily. The insoluble films need solvents and
nail-file to be removed weekly or even more frequently, procedures that damage the nail structure and render it more prone to reinfection.2
To overcome the a.m. problems of the nail lacquers, an innovative proprietary technology of
hydrolacquer has been developed by the Swiss
company Polichem, by employing chitin derived hydrosoluble amino-polysaccharides. The
new technology is based on hydroalcoholic
solutions of hydroxypropyl-chitosan (HPCH), a
water soluble semi-synthetic derivative of chitosan, which acts as a film forming agent. HPCH
dissolves in high percentage in water, has affinity to air, is a highly plastic substance and
forms a highly elastic film, it increases the
dispersion of other ingredients, and its safety
profile is excellent. Hydroxypropyl-chitosan is
endowed with adhesive properties towards different biological tissues due to their positive
charge. Moreover, the free hydroxypropyl grou-
ps of HPCH interact with keratin, by hydrogen
binding and other weak interactions that contribute to the improved drug transport and
release.3 The nail application of hydrolacquers
prepared according to the ONY-TEC® technology, even for chronic treatments like in onychomycosis, is easy and accepted by the
patients due to the simple (rinsing) removal
procedure and no need of nail filing.
The ONY-TEC® technology proved capable to increase nail permeation of actives,4 to support the
nail structure and to protect it against external
agents. When used as the basis of compositions
with antimycotic agents, the ONY-TEC® technology strengthened the efficacy of antimycotic agents.5
A new medical device (Myfungar®, Polichem SA)
has recently been developed, based on the above
innovative technology, for nail protection against
e x t e rnal agents. The composition of the device
includes hydroxypropyl-chitosan as a film forming agent, water and ethanol for a prompt evaporation after application on the toenails or fing e rnails, and piroctone olamine, a well known6
preservative agent with a broad antimicrobial
spectrum. Aim of this study was to investigate the
protective activity of the device and of its main
ingredient against physical and microbiological
agents by in-vitro and in-vivo functionality tests.
properties and protection
Physical
against physical agents
The investigations were performed by
using a hydro-alcoholic solution containing 1%
hydroxypropyl-chitosan (HPCH).
1) Film forming effect
Method
The assessment of the film forming effect was
done in 2 in vitro studies by applying the product on the surface of bovine hoof slices (cut by
criotomy) to check the film thickness and the
covering property.
Two investigations were performed:
a) In the first investigation, we took a silicon cast
of an untreated bovine hoof slice. HPCH
solution was then applied to this layer and
the silicon cast was taken again. The casts
were observed by the stereo microscope, and
images were obtained for the optical profilometry assessment. The casts were then
subjected to gold metallisation for scanning
electronic microscope (SEM) observation.
b) In the second investigation, HPCH solution
was applied to hoof slices, which were
observed directly by means of a reflected
light stereo microscope, then prepared by
means of the gold metallisation process and
observed with an electronic microscope.
For the most effective observation of the
thickness of the product applied, transverse
sections were examined at the level of the
central portion of the layers.
Results
The analysis of the images shows that the
HPCH film is relatively thin, with a polished
appearance which reproduces the underlying
weft and reduces the surface roughness, by filling the holes and the uneven surface of the nail
slices (Figures 1 and 2). The profile measurement analysis carried out on the casts confirms
an evident decrease of superficial roughness
Figure 1.
Scan electron microscopy
of a nail slice surface
untreated (left)
or covered by
the hydroxypropyl-chitosan
film (right).
7
index (RA), calculated as the absolute mean of
all the deviations from the mean.
Figure 2.
Scan electron microscopy
of a nail slice covered by
the hydroxypropyl-chitosan film
(section – magnification 1.5K x).
2) Adhesion
Method
In order to observe the adhesive capacity of the
product, we adopted the methods set out in the
EN ISO 2409: 1994 standard. This standard
describes a test method for the in vitro assessment of the resistance of a coating against detachment from a support. To do this, a square
mesh section is cut into the coating until the
support is reached. The supports used were
bovine hoof slices and a microscope slide. As
they were not completely applicable, given the
nature of the support and product, the terms of
the standard were used as general guidelines.
a) Application to the bovine hoof slices
The product was first pigmented with a few
drops of methylene blue, then observed
with a stereo microscope to ensure that the
colouring agent was evenly distributed over
the sample surface. The product was
applied by a brush. Once the product had
dried on the surface, a square mesh section
was cut into it using a scalpel. On completion of this operation, an adhesive tape in
accordance with the specifications set out in
the standard was applied to the cut section.
The tape was then removed as described in
the standard and applied to a slide to observe it under a transmitted light microscope
in two different types of lighting, in order to
analyse the material removed by the tape.
b) Application to the microscope slide
We followed the same procedure, with the
exception of the pigmentation of the product, and used a single type of lighting.
Results
The analysis of the images shows that the product in the test a) has good cohesion and re s istance to detachment from the nail surface
(Figure 3); this is confirmed by the absence of
any HPCH particles on the stripped tape. In the
test b) there is a detachment of particles of HPCH
film evident on the stripped tape (Figure 4).
3) Anti-abrasion effectiveness
Method
The anti-abrasion effectiveness test involved
provoking a series of incisions on the surface of
the test object. With a view to producing the
same type of incision in the different test conditions, we used a Dermal Torque Meter (D i a
Stron UK), which is fitted with a special probe
which terminates in a rotating disc. With this
Figure 3.
Test of adhesiveness
of the hydroxypropyl-chitosan film
on nail slice surface.
Figure 4.
Test of adhesiveness
of hydroxypropyl-chitosan film
on glass slide surface.
8
Figure 5.
Protection of nail abrasion by
hydroxypropyl-chitosan film
on in vivo human nails.
instrument and its software, it is possible to
programme the torsion torque applicable to the
rotating disc, to which a circular section of type
150 abrasive paper is attached. The probe is
then placed on the surface to be subjected to
abrasion. To check the protective properties of
HPCH film, we proceeded in two stages:
a) In vivo study: the product was applied by
means of a brush on fingernails of 3 healthy
volunteers. Abrasion was then applied to the
treated and untreated nails. Silicon casts of
treated and untreated nails were taken after
abrasion and analyzed by computerized profile measurement. Silicon casts were taken on
treated and abraded nails after washing. The
casts were then prepared using the gold
metallisation process for the scanning electronic microscope (SEM) procedure.
b) In vitro study: The product was applied by
means of a brush to a bovine hoof layer, which
was then subjected to abrasion along with
another, untreated layer. With this method, it
was possible to directly observe the surface
under examination. The layers were observed
with the stereo microscope, then prepared by
means of the gold metallisation process and
o b s e rved by SEM. The product was then
applied to another layer, which was subjected
to abrasion, then washed with water. The
samples were observed by means of a reflected
light stereo microscope.
Results
a) In vivo study: the analysis of the images
shows that the untreated surface of human
nails has very deep incisions with jagged
edges and a significant quantity of material
removed, while the treated surface has shallower incisions with regular edges and a
minimum quantity of material removed. The
analysis of the images of the layer which was
washed following abrasion also confirms the
previous observations (Figure 5).
b) In vitro study: the optical profilometry of the
casts confirms these results, showing a more
regular and less deep profile, and the analysis of the casts under the electronic microscope also shows a more regular surface.
4) Thermographic activity
Method
The product was applied by a brush to the
thumb nail of a volunteer. The product was left
to dry, and the thumb was then placed in front of
a thermal video camera properly configured and
calibrated to highlight the nail surface.
In vivo images of the treated and the untreated
thumb nails were then obtained.
Results
The analysis of the images shows that, when the
thumb nail is covered by HPCH film, the area
with a higher temperature is smaller than in the
untreated thumb nail (Figure 6).
Figure 6.
Effect of hydroxypropyl-chitosan film
on in vivo thermography
of human thumb nails.
9
properties
and protection against fungal
Microbiological
colonization
The investigations were performed by
using solutions containing different concentrations of HPCH and eventually a preservative
agent as specified.
5) Protective film against the growth
of T. mentagrophytes
Method
Sabouraud Dextrose Agar (SDA) square plates
were prepared by inoculating 0.5-1.0 x 103 T.
mentagrophytes (DSMZ) CFU/mL of agar, according to standard pro c e d u res. Two hydro alcoholic solutions containing 0.3% and 1.0%
hydroxypropyl-chitosan respectively, were put
on the surface of the inoculated plates. The
growth of the pathogenic agent was observed
after 5 days of incubation.
Results
There was a full growth of T. mentagrophytes in
the whole plate, with the exception of the place
where HPCH formed a protective film on agar
surface. In fact, the hydroxypropyl-chitosan
film prevented the fungus hyphae from penetrating the film and growing on the same
(Figure 7). The study concluded that the device
does form a physical protection against the
microbiological agent.
6) Prevention of in vitro growth
of T. rubrum on bovine nail slices
Method
SDA square plates were prepared by inoculating
0.5-1.0 x 103 T. rubrum (DSMZ) CFU/mL of
agar, according to standard procedures. The
device (Myfungar®, Polichem SA, containing
0.5% HPCH and 0.5% of piroctone olamine as
a preservative) was added on the surface of the
agar plate either by adsorbing 10 µL of the solution on a 10 mm neutral disk or by placing 10
and 20 µL of the solution on 10 x 20 mm 75
µm thickness nail slices obtained from bovine
hooves. A 0.5% HPCH (10 µL) solution on a
disk was used as a control. The plates were then
incubated at 32 ± 1 °C for 5 days.
Results
The HPCH control area showed an abundant
growth of T. rubrum. The areas inoculated with
the Myfungar® device, placed on nail slices,
showed dose-dependent inhibition rings at the
2 doses tested. The results are summarized in
10
Figure 8. Inhibition rings of T. rubrum growth
were visually evaluated as a consequence of
protective activity of the device against pathogen growing onto the nail plates.
7) Prevention of in vitro nail experimental
infection by T. rubrum
Figure 7.
Growth of T. mentagrophytes
after application of 0.3 (left)
or 1% (right)
hydro alcoholic HPCH solution.
No growth is observed
over the HPCH film.
Method
a) Application of test products before nail contamination: SDA square plates were prepared by inoculating 0.5-1.0 x 103 T. rubrum
(DSMZ) CFU/mL of agar, according to standard procedures. Three and four bovine
nail slices with a 50-90 µm thickness were
inserted vertically and at an equal distances
into the agar until they touched the base of
the plate, in a way that each nail protruded
from the agar by 4-5 mm. All the nail fragments had previously been immersed in the
test preparations of the device (Myfungar®)
and left to dry. The tests were done in duplicate. The plate with 4 nail fragments was
used to assess the fungal growth and the
presence of inhibition rings after 7, 14 and
21 days of incubation. The plate, containing
3 fragments, was used for the withdrawal of
Figure 8.
Inhibition rings of T. rubrum growth
by application of 10 or 20 µL
octopirox (Myfungar®) device solution
on bovine nail slices
or on disk.
Control: 10 µL HPCH solution.
an entire nail fragment after one, two, three
weeks respectively. Each withdrawn nail
fragment was inserted singularly in a sterile
SDA plate (not infected), then incubated
and examined after three weeks to check,
through the presence or absence of fungal
growth, whether the preventive treatment
had brought about a definitive inhibition of
the fungus. An identical experimental procedure to that above described was carried
out with untreated nails (control) and nails
treated with HPCH solution.
b) Application of test product after nail contamination: SDA square plates were prepared
by inoculating 0.5-1.0 x 103 T. rubrum
(DSMZ) CFU/mL of agar, according to stand a rd pro c e d u res. Numerous plates of untreated bovine nail slices with a thickness of 100150 µm were then placed on each plate, as
described above. Thicker fragments were
used in this experiment, in order to assess
the activity with the mycelium embedded
m o re deeply in the nail. The plates were then
incubated at 26 °C.
After one week, the entire surface of the plates and the nails inserted in them were
evenly covered by the mycelium. Seven, 14
and 21 days after the sowing of the dermatophytes, a nail fragment completely covered
in the mycelium was withdrawn and brushed with the device (Myfungar®), HPCH
solution, or without treatment (control).
After drying the nail was inserted in the agar
layer of new plates in which the dermatophytes had not been sown. The plate was
then incubated and examined once a week
for 21 days to assess the fungal growth.
Results
a) The fungal growth inhibition rings produced by spreading the device in the agar is
summarized in Table 1. The control nails
(no treatment) and those treated with
HPCH solution showed no inhibition rings
and the small fungal colonies present when
the nail was inserted in the agar rapidly
invaded the entire surface of the dish. The
nails treated with the device produced small
inhibition rings. The table also contains the
results obtained with the transplant of the
treated or control nails, withdrawn after 7,
14 and 21 days of insertion in the agar
already containing the fungal colonies, into
new dishes containing nutritional medium
only. The growth of T. rubrum was inhibited
by the device at all time points.
b) Data on fungal growth produced by nail
fragments deeply contaminated by the
mycelium of T. rubrum and subsequently
treated with the device are reported in the
Table 2. T. rubrum strain was eradicated,
with absence of growth after 3 weeks.
HPCH solution was devoid of any effect in
this experiment, as the growth of T. rubrum
was similar to that of untreated controls.
Test product
MEAN RING* (mm) AFTER DAYS
3
6 9 12 15 18 21
Myfungar®
2
2
2
2
0
0
Control
0
0
0
0
0
HPCH solution
0
0
0
0
0
Growth after transplant on day
7**
14** 21**
0
–
–
–
0
0
+
+
+
0
0
+
+
+
* = mean of 4 values
+ = growth; – = no growth
** the presence or absence of fungal growth was assessed 3 weeks after transplant
Table 1. Prevention of in vitro nail experimental infection by T. rubrum.
Test a) – application of test products before nail contamination.
Weeks after contamination
Growth* after transplant days
®
Myfungar
Control
HPCH solution
1
2
3
7
14
21
7
14
21
7
14
21
–
+
+
–
+
+
–
+
+
–
+
+
–
+
+
–
+
+
–
+
+
–
+
+
–
+
+
*fungal growth in the transplanted Petri dish
Table 2. Prevention of in vitro nail experimental infection by T. rubrum.
Test b) – application of test products 1, 2 or 3 weeks after nail contamination.
11
D
iscussion
Common cosmetic or medicated nail
varnishes based on water insoluble polyvinyl or
monoester resin films have the disadvantage
that the removal of the nail varnish by an organic solvent or by nail filing further damages the
nail structure and renders the nail keratin less
resistant to the fungal infections. This may be
one of the reasons for a lower than expected
efficacy rate of traditional antifungal nail varnishes in the management of onychomycosis.
The new hydrolacquer technology developed
by Polichem overcomes the problem evidenced
by the polyvinyl resin film, by employing an
innovative film forming agent, hydroxypropylchitosan (HPCH), which has the characteristic
of being an hydrosoluble amino-polysaccharide. Applied as an hydroalcoholic solution in a
series of in vitro and in vivo investigational studies, the solution quickly evaporates, by forming a thin film that demonstrates unique properties of affinity and selective adhesiveness to
the keratin structure of the nail. The film
appears to penetrate into the keratin holes and
to smoothen the uneven keratin surface, by
physically supporting the nail and by protecting
it against mechanical and other physical agents.
The physical support and the protective activity
of HPCH stays in place and it is not vanished by
the removal procedures. In fact, contrary to the
traditional nail laquers, the HPCH film can be
removed just by water and care should be used
to leave it on the nails long enough to allow its
action (for example, by applying it in the evening before bedding or after shower on dry nails
and avoiding washing for 6 hours).
Moreover, in our experience, the film formed
after the evaporation of the medical device was
able to prevent the growth of the most common
nail pathogens within and around the nail in
experimental infection models. According to literature data,7 the selective affinity for keratin
results in an intimate contact of HPCH with the
nail surface that allows a better passive diffusion
of ingredients to the nail compared to common
medicated nail lacquers. Our data on the microbiological properties of the new medical device
are in full agreement with the a.m. report.
In conclusion, our data show that the new medical device, when applied on the nails, is capable
to form a film, that adheres and penetrates into
the nail structure, by supporting it and forming a
protective film against physical and microbiologi-
12
cal agents. In particular, the device may prevent
the nail infections by common pathogens such as
T. mentagrophytes and T. rubrum. Furthermore, it
is easy to apply and does not require specific
removal, characteristic that may improve the
patient’s compliance to treatment.
References
1. Dawber RPR, de Berker DAR, Baran R.
Science of the nail apparatus. In: Baran and Dawber’s
Disease of the nails and their management, 3rd Ed.
Blackwell Sciencie 2001
2. Tosti A, Baran R., et al. Onychomycosis and its treatment. In: Baran, R. et al., editors. A text atlas of nail disorders. Techniques in investigation and diagnosis, 3rd Edn.
London: Martin Dunitz 2003, p. 143
3. Legora M, Mailland F, Mechanism of adherence to the
nail surface of a film formed by water soluble chitosan.
Proc. 16th Congress EADV, Vienna, 16-20 May 2007
4. Monti D, Saccomani L, Chetoni P, Burgalassi S, Saettone
MF, Mailland F. In vitro transungual permeation of
ciclopirox from a hydroxypropyl-chitosan-based, water-soluble nail lacquer. Drug development and Industrial
Pharmacy 2005; 31:11
5. Baran R, Mailland F. Transungual delivery of drugs: new
perspectives. Proc. 34th Annual ESDR Meeting, Vienna,
September 9-11th 2004, in J Invest Dermatol 2004;
123:A74
6. INCI - International Nomenclature Cosmetic Ingredient.
Monograph of Octopirox, 2008
7. Monti D, Saccomani L, Chetoni P, Burgalassi S, Mailland
F. HPCH-based nail lacquers: “ex vivo” study on permeation of three antimycotics through bovine hoof membranes
Proc. 5th World Meeting on Pharmaceutics and Pharmaceutical Technology, Geneva (Switzerland), 27-30 March
2006
Acknowledgements
We gratefully acknowledge the cooperation of the following Scientists:
Dr. Daniela Monti, Dr. Luigi Saccomani - Dept.
Biorganic Chemistry, Univ. Pisa (Italy) - for
kindly providing the bovine nail slices;
Prof. Francesco Dubini and D r. Maria Grazia
Bellotti - Institute of Microbiology - Univ. Milan
(Italy) - for the investigations on experimental
onychomycosis;
Dr. Alessandra Frangi - Microbiological Lab.
IPAS Ligornetto (Switzerland) - for the other
microbiological investigations.
The use of antisense oligonucleotides
in skin lightening products
Melizza Bautista1
Falen Lockett1
Jaimie Mecca1
Wanphimon Sawatdeekhachornphat1
Angelica Castro1
Sujani Yarlagadda1
Salvador Gonzalez2
Neena Philips1
SU M M A R Y
The use of antisense oligonucleotides
in skin lightening products
Developments in gene sequencing, safety, specificity and simplicity of the concept
have resulted in the investigation and development of antisense oligonucleotides as
therapeutic agents. Most current skin lighteners work to inhibit tyrosinase to deactivate melanin synthesis, leading to lighter and brighter skin. Antisense oligonucleotides work by interfering with the gene expression of tyrosinase, and the production of melanin ceases as a result. Topical application of antisense oligonucleotides is effective on pigmented spots and non-pigmented skin. Antisense technology is in its early stages and additional trials with proper controls should be conducted to ensure efficacy, proper specificity, and safety.
KEY WORDS: Melanogenesis, Anti-sense oligonucleotides, Brightening, Cosmetics
Background
Many women who seek affordable
and “safer” cosmetic remedies for skin lightening look to topical skin lightening creams and
soaps as alternates to invasive laser and chemical peel treatments. These products have become increasingly popular amongst women of
color, particularly in Asian countries, where
those with lighter skin are perceived as more
youthful, successful and attractive. Many relate
this shared cultural ideology to historical times
when darker skin was associated with being a
laborer, who worked outdoors in fields or
farms, and lighter skin to upper classmen who
enjoyed their privileges indoors. 1
Women not only look to skin lighteners for a
brighter, youthful appearance, but also to correct the uneven appearance of dark spots or
blotches that occur on the skin.
Hyperpigmentation can be triggered by an array
of factors that include genetic predisposition (as
in freckles), environmental stress (as in solar
lentigines, age spots caused by UV exposure),
and hormonal fluctuations as melasma. 5 Skin
lighteners help to even skin appearance and
improve self-perception.
Skin color is primarily due to the pigment,
melanin, in the skin. Yet, the determinant of
skin color also considers factors such as the
thickness of the skin and the presence of pigments such as carotene which, in excess, contributes an orange-yellow tint. The density and
dilation of blood vessels as well as the oxygen
content in the blood also play a role in how
pink or red the skin appears in contrast to a
bluish hint when oxygen levels are deficient.
Ultimately, it is the active degree of melanogenesis that determines how dark or light skin
becomes. Melanin exists as two main types in
the skin, eumelanin, which is responsible for
the black or brown pigmentation, and pheomelanin, which gives yellow or red hues seen as
red heads. Dark skinned people produce more
melanin than do light skinned people. 5
Synthesis of melanin occurs within melanocytes
in the stratum basale of the epidermis.
Melanocytes are stimulated to produce melanin
in response to UV radiation. Melanin is stored
within melanosomes that are transferred to
other cells (keratinocytes) via microtubules and
actin filaments to protect the nucleus of other
cells from UV damage. 3
Melanogenesis is regulated by the enzyme tyro s inase, tyrosinase-related protein TRP1 and TRP-2.
Tyrosinase regulates the hydrolysis of tyrosine to
form L-dihydroxyphenylalanine (L-DOPA) and
further dehydroxylation to dopaquinione.
1School of Natural Sciences, University College,
Fairleigh Dickinson University, Teaneck, NJ, USA
2Dermatology Service, Memorial Sloan
Kettering Cancer Center, New York, NY, USA
17
M. Bautista, F. Lockett, J. Mecca, W. Sawatdeekhachornphat, A.Castro, S. Yarlagadda, S. Gonzalez, N. Philips
Dopaquinone combines with cysteine to produce pheomelanins or is converted to dopachrome, which, through TRP-1 and TRP-2, produce
eumelanins that leads to tanning. 2,4
Current methods of skin whitening, via tyrosinase inhibition, include the use of hydroquinone (HQ), natural extracts such as arbutin, exfoliants such as AHA’s, and intense pulse light
(IPL). 6,7 HQ is found in common foods such as
wheat, berries, coffee and tea. HQ inhibits tyrosinase, by interfering with copper binding and
other possible mechanisms include selective
cytotoxicity of melanocytes with melanosome
degradation, inhibition of melanin synthesis.
Information is available on the reproductive,
development or carcinogenic effects of HQ in
humans. EPA however has not classified HQ for
carcinogenicity. Common side effects are redness, mild burning, and itching.
Arbutin is an extract from cranberries, blueberries, and bearberry plant. Arbutin competitively
and reversibly inhibits tyrosinase without affecting RNA melanin synthesis. Also, Arbutin inhibits melanosome maturation and is less cytotoxic to melanocytes in comparison to HQ. It is
a very safe skin agent for external use without
unpleasant odor or side effects.
AHA preparations are commonly found with
glycolic acid (GA) 5%- 20% and lactic acid
(LA) 8%-12%. Both are effective and safe peeling agents in epidermal melasma 6. AHAs have
been used for centuries to treat dry skin, acne,
actinic damage, and improve skin texture ,
color, and wrinkles. AHA suppresses melanin
activity by directly inhibiting tyrosinase without
affecting mRNA and protein expression.
IPL photo facial is a new way to improve skin.
Unlike a laser which emits one specific wavelength of light, IPL emits a broad spectrum of
light with each pulse. The broad spectrum of
light in each pulse allows it to treat a variety of
skin imperfections simultaneously. IPL penetrates skin and attacks the root of skin blemishes
and imperfections. The treatment side effects
are mild swelling after treatment. 7
of current topical
depigmenting agents
Drawbacks
Antisense oligonucleotides are small and welldefined synthetic single-stranded nucleic acid
fragments which are synthesized to bind to the
messenger RNA (mRNA) of a targeted gene.
18
When the antisense sequence binds to the
mRNA sequence, it prevents synthesis of a protein. 4 This synthesized nucleic acid is termed
an “anti-sense” oligonucleotide because its base
sequence is complementary to the gene’s messenger RNA (mRNA), which is called the “sense”
sequence. They are different from conventional
drugs in the respect that they are designed to
act upstream by preventing the translation of
mRNA into proteins instead of interacting with
protein molecules after they are produced. 8
The use of antisense oligonucleotides as therapy
was first introduced by Zamecnik andStephenson
in 1978 who synthesized a 13-nucleotide oligonucleotide complement to the terminal sequences of Rous sarcoma virus 35S RNA, which
interfered with viral production. 4 As a result of
the specificity to a targeted gene that can be
c reated antisense therapy has presented itself to
being applicable in various fields including the
cosmetic products and specifically skin lightening where effective actives are few. 9
Most skin-lightening or depigmenting agents
such as kojic acid, arbutin, ferulic acid, hydroquinone, guaiacol, and resorcinol reduce or
block melanin production by inhibiting tyrosinase, which catalyzes the production of melanin by oxidation. Antisense oligonucleotides
inactivate the gene information by binding to
the messenger RNA so that translation cannot
occur, halting the production of tyrosinase formation. 10 Also many of the skin lightening
agents are unstable, moderately irritating to the
skin, and potentially toxic because a high concentration must be used for perceptible effectiveness. Antisense oligonucleotides offer unprecedented specificity, biological stability, efficient
uptake and accumulation in cells by liposome
encapsulation, for skin lightening cosmetic prod u c ts4.
The FDA has approved the sale and distribution
of the first antisense oligonucleotides to treat
cytomegalovirus retinitis, Vitravene. 9
The approval of Vitravene, no doubt, provides
encouragement to extend the antisense technology to cosmetic products such as skin lightening products. LVMH Recherche of Christian
Dior Parfums has conducted in vitro and in vivo
clinical studies of a cosmetic product to evaluate the effect of antisense oligonucleotides on
human melanogenesis. LVMH claims this report
to be the first with a positive result in a cosmetic product based on antisense therapy. 4
The synergistic combination of TRP-1 and
PKC-[beta]I antisense oligonucleotides led to
increased inhibition of the tyrosinase enzyme’s
activity on human melanocytes and an observed in vivo skin lightening effect in both pigmented spots and nonpigmented areas. 4,11 This
result is encouraging for the expanded use of
antisense technology in cosmetics. 4
directions
of antisense technology
Discussion/future
The challenge to antisense technology
is that it is still in the early stages and additional trials are needed to ensure safety, efficacy
and specificity. The clinical data obtained is
References
1. Wadyka S. Trouble Spots Got You Down.
Lighten Up. The New York Times. 2005; (www.nytimes.com.
Accessed on 2007 Dec 12)
2. Behrooz K. Melanin Biosynthesis Pathway and the
Depigmenting Effect of Retinoids. Jahrom Univ of Med
Sciences. 2005; W8.4:1(www.eadv2005.com accessed on
2007 Dec 12)
promising. The use of phosphorothioates and
the therapeutic effects they are thought to induce should be examined critically because their
backbone can cause sequence-independent
effects. New chemical modifications of oligonucleotides are being developed that address the
issue of degradation by nucleases and would
prevent the formation of degradation products
with cytotoxic potential.9
Acknowledgement
The paper composes Biochemistry/
Microtoxicity course in the Cosmetic science
program.
meceuticals for women of color. J. of Drugs in Derm. 2007;
6:1-32
7. Purcell E, Condon C. Intense pulsed light therapy in the
management of hereditary benign telangiectasia. Br J Plast
Surg. 2004; 57:453-5
8. Weiss B. Antisense Oligodeoxynucleotides and Antisense
RNA: Novel Pharma and Thera Agents, CRC Press 1997
3. Mitsunori F. Elucidation of Melanin Transport
Mechanism, A Fresh Turn in Membrane Trafficking
Research. 2005; 292. (http://www.riken.jp. accessed on
2007 Dec 12)
9. Dias N, Stein CA. Antisense Oligonucleotides: Basic
Concepts and Mechanisms. Mole Cancer Thera. 2002;
1:347-355
4. Lazou K, Sadick NS, Kurfurst R, Bonnet-Duquennoy M.,
Neveu M., Nizard C, Heusele C, Schnebert S, Perrier E.
The use of antisense strategy to modulate human melanogenesis, J of Drugs in Derm. 2007; 1-6. (http://findarticles.com. accessed on 2007 Dec 12)
10. Uwe S, Max H, Hearing VJ. Cosmetic or dermatological
preparations comprising oligopeptides for lightening the skin
of age marks and/or for preventing tanning of the skin, in
particular tanning of the skin caused by UV radiation. 2001;
(http://www.patentstorm.us. accessed on 2007 Dec 12)
5. Shai A, Maibach H, Baran R. Handbook of Cosmetic
Skin Care. 1. Ed1: Martin Dunitz Ltd. 2002
11. Kurfurst R, Duquennoy MB, Lazou K, Decup L,
Nizard.C, Schnebert S. Role and modulation of tyrosinase/tyrosinase related protein-1 complex and PKC beta-I
in melanogenesis. Intern J of Cosmetics, 2005; 27:59-62
6. Bansal SB, Draelos ZD. Insight into skin lightening cos-
19
Coating on micronized titanium
dioxide increases safety and maintains
efficacy as sunscreen filter
Jayson Goodner1
Uma Patil1
Yousun Lim1
Sujani Yarlagadda1
Angelica Castro1
Salvador Gonzalez2
Neena Philips1
SU M M A R Y
Coating on micronized titanium
dioxide increases safety and
maintains efficacy as sunscreen filter
Micronized titanium dioxide (TiO2) is a widely used sunscreen ultraviolet (UV) radiation filter. The penetration of micronized TiO2 into the dermis, and its photocatalytic activity leading to generation of reactive oxygen species is a widespread concern .
The coating of TiO2 with antioxidants and polymers reduces or eliminates photocatalytic activity. Further, chemical grafting of anti-oxidant molecules with an additional hydrophobic polymer coating directly onto TiO2 particle surfaces eliminates photocatalytic degradation while maintaining effective screen against UV radiation.
KEY WORDS: Micronized titanium dioxide, Sunscreen filter, UV radiation
nanotechnology
for UV radiation protection
Titanium
Consumers that use sunscreens
without titanium dioxide (TiO2) are exposed to
more UV radiation than consumers relying on
titanium products for sun protection.
Consumers using sunscreens without titanium
are exposed to an average of 20% more UVA
radiation and increased risks for UVA radiationinduced skin damage, premature aging, wrinkling, and immune system damage.
Despite the benefits of using titanium based
sunscreens, there is concern regarding the possible absorption of micronized titanium particles into the dermal layer of the skin. The technology for micronzing titanium is a recent development and the health risks associated with
them have not been fully researched. The benefit from TiO2 for UV radiation protection needs
to be balanced against concerns that nanoparticles may be unusually toxic to body systems.
The risks of Ti O2 a re based on its sunscre e n
p roperties: the high surface reactivity of tiny
particles and their ability to penetrate body
tissues.
The potential risks raise two key questions:
(1) Does micronized titanium dioxide penetrate
the dermis;
(2) does it damage cells due to its photocatalytic activity.
Prior to the 1990, larger titanium particles were
used that left white tints/residues and did not
adhere to skin. The development of nano-sized
TiO2 was primarily based on consumer feedback on the whitening effect that conventional
titanium particles produced. Curre n t l y, the
typical size range for titanium in sunscreens is
10-100 nm. At these sizes titanium leaves a lesser whitish tint and forms a smoother barrier on
skin. 1
Nanoparticles are currently widely used in sunscreens but they are rarely noted on product
labels. There is evidence that the smaller particle titanium offers improved UV protection
compared to conventional-sized counterparts
as well2. An estimated 1,000 tons of nanoparticles were used in sunscreen worldwide during
2003-04. 3 Alternate UVA radiation sunscreen
chemicals are zinc oxide, avobenzone and
Mexoryl SX. Of all current sunscreen chemicals,
1School of Natural Sciences, University College,
Fairleigh Dickinson University, Teaneck, NJ, USA
2Dermatology Service, Memorial Sloan Kettering
Cancer Center, New York, NY, USA
21
J. Goodner, U. Patil, Y. Lim, S. Yarlagadda, A. Castro, S. Gonzalez, N. Philips
titanium dioxide offers the best UVA radiation
protection.
2. Popov AP, Priezzhev AV, Lademann J, et al. TiO2
nanoparticles as an effective UV-B radiation skin-protective
compound in sunscreens. Journal of Physics D: Applied
Physics 2005; 38:2564
T
3. Borm PJ, Robbins D, Haubold S, et al. The potential risks
of nanomaterials: a review carried out for ECETOC. Part
Fibre Toxicol 2006; 3:11
itanium toxicity
and skin penetration
The primary toxicity concern of nanotitanium particles is free radical generation leading to oxidative stress and inflammation; that
damages proteins, lipids and DNA. 4,5 Titanium
has also been shown to induce oxidative stress in
tissues, especially when catalyzed by UV light. In
addition, nano-titanium particles, extracted from
sunscreens, on skin are activated by UV light to
generate reactive oxygen species damaging skin
DNA and cell structure s.6 Titanium hydroxyl
radicals produced by UV radiation facilitate DNA
and cell damage. 7-10 Diverse coatings, such as
magnesium and various polymers, greatly reduce
UV radiation reactivity of nano titanium 11, with
more recent technology showing that chemical
grafting of anti-oxidant molecules and polymers
directly onto titanium particles eliminates its’
photocatalytic degradation. 12 T h e re are no
reports on the absorption of small-scale titanium
sunscreen ingredients through healthy/intact skin
or damaged skin. 13-16 In contrast, traditional sunscreens like oxybenzone and octinoxate absorb
into healthy skin, and by acting like estrogens
raise risks for breast cancer, and hormone-driven
uterine damage. 17
Conclusion
The current weight of evidence suggests that nano titanium does not penetrate the
skin. The advancements and additions to nanotechnology makes titanium-based formulations
among the safest, most effective sunscreens on
the market.
Acknowledgement
The paper composes Biochemistry/Microtoxicity course in the Cosmetic Science program.
References
1. Nohynek GJ, Lademann J, Ribaud C, et al.
Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol 2007; 37:251
22
4. Nel A, Xia T, Madler L, et al. Toxic potential of materials at the nanolevel. Science 2006; 311:622
5. Oberdorster G, Maynard A, Donaldson K, et al.
Principles for characterizing the potential human health
effects from exposure to nanomaterials: elements of a
screening strategy. Part Fibre Toxicol 2005; 2:8
6. Hidaka H, Kobayashi H, Koike T, et al. DNA Damage
Photoinduced by Cosmetic Pigments and Sunscreen Agents
under Solar Exposure and Artifical UV Illumination. J Oleo
Sci 2006; 55:249
7. Dunford R, Salinaro A, Cai L, et al. Chemical oxidation
and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett 1997; 418:87
8. Uchino T, Tokunaga H, Ando M, et al. Quantitative
determination of OH radical generation and its cytotoxicity induced by TiO(2)-UVA treatment. Toxicol In Vitro 2002;
16:629
9. Sayes CM, Wahi R, Kurian PA, et al. Correlating
nanoscale titaniam structure with toxicity: a cytotoxicity
and inflammatory response study with human dermal
fibroblasts and human lung epithelial cells. Toxicol Sci.
2006; 92:174-85
10. Wang JJ, Sanderson BJ, Wang H. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells. Mutat Res 2007; 628:99
11. Wakefield G, Lipscomb S, Holland E, et al. The effects
of manganese doping on UVA absorption and free radical
generation of micronised titanium dioxide and its consequences for the photostability of UVA absorbing organic
sunscreen components. Photochem Photobiol Sci 2004;
3:648
12. Lee WA, Pernodet N, Li B, et al. Multicomponent polymer coating to block photocatalytic activity of Ti O 2
nanoparticles. Chem Commun 2007; 4815
13. Baroli B, Ennas MG, Loffredo F, et al. Penetration of
Metallic Nanoparticles in Human Full-Thickness Skin. J
Invest Dermatol 2007; 127:1701
14. Cross SE, Innes B, Roberts MS, et al. Human Skin
Penetration of Sunscreen Nanoparticles: In-vitro
Assessment of a Novel Micronized Zinc Oxide Formulation.
Skin Pharmacol Physiol 2007; 20:148
15. Gamer AO, Leibold E, Van-Ravenzwaay B. The in vitro
absorption of microfine zinc oxide and titanium dioxide
through porcine skin. Toxicol In Vitro 2006; 20:301
16. Lademann J, Weigmann H, Rickmeyer C, et al.
Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular
orifice. Skin Pharmacology and Applied Skin Physiology
1999; 12:247
17. Schlumpf M, Cotton B, Conscience M, et al. In vitro and
in vivo estrogenicity of UV screens. Environ Health Perspect
2001; 109:239
Studio prospettico sull’evoluzione
delle ferite chirurgiche trattate con gel
al silicone
Vincenzo De Giorgi
Serena Sestini
Barbara Alfaioli
Marta Grazzini
Agata Janowska
Andrea Saggini
Torello Lotti
SU M M A R Y
Study on the effectiveness
of a silicone gel in treating
surgical wounds
The management of scars originating either from surgery or trauma is of notable significance in preventing the formation of evident scarring. What matters nowadays is
not only addressing the functional alterations caused by these scars, but also the minor
esthetic alterations that can cause serious psychological problems for patients. The
surgeon is thus becoming more and more involved, beyond the surgical operation itself,
in managing esthetic results and can deploy a range of therapeutic procedures to minimize the formation of prominent scars. This is also true in view of the increasing
demand for purely aesthetic surgery ranging from the removal of common seborrheic
keratoses, to blepharoplasty or major breast reconstruction.
The aim of our study was thus the evaluation of the effectiveness of a silicone gel
(Zeraderm ultra silicone gel™) in treating surgical wounds compared with a control
group of the same phenotype and same scar site for which no product was advised.
We evaluated the minimum aesthetic “d a m a g e” following surgery, in particular.
Therefore, not only we considered the formation or absence of the classic keloid or
hypertrophic scar, but above all whether the early application of the product on the
wound led to, compared to the control group, the formation of more acceptable and
minimum “a e s t h e t i c” damage even within the parameters of so-called “physiologic a l” scars.
KEY WORDS: Silicone gel, Surgical wounds
Introduzione
La gestione di ferite, sia chirurgiche,
sia traumatiche, assume un’importanza notevole al fine di evitare la formazione di cicatrici
particolarmente evidenti.
Al giorno d’oggi infatti sono diventate estremamente importanti, non soltanto le alterazioni
funzionali che tali cicatrici possono provocare,
ma anche piccole alterazioni estetiche, che portano in alcuni pazienti gravi problematiche psicologiche. È sempre più compito e dovere del
chirurgo occuparsi, al di là del vero e proprio
intervento, anche dei risultati estetici di tale
intervento e mettere in atto tutte le procedure
terapeutiche al fine di minimizzare la formazione di cicatrici evidenti. Tutto ciò anche vista la
continua e crescente richiesta di interventi a fini
puramente estetici, dall’asportazione di una
banale cheratosi seborroica, ad una blefaroplastica e ad una importante ricostruzione mammaria.
Da un’analisi della letteratura ci accorgiamo
che, mentre è unanimemente descritta e riconosciuta la cicatrice cheloidea (… cicatrice che si
estende oltre il tessuto danneggiato e ricopre i tessuti normali …), non vi è consenso su quando la
cicatrice sia da considerarsi “normale” e “fisiologica” e quando invece debba essere considerata
“ipertrofica”. Questa confusione genera spesso
negli stessi chirurghi una gestione inappropriata delle ferite, che per la maggior parte dei casi
Dipartimento di Scienze Dermatologiche ,
Università di Firenze
25
V. De Giorgi, S. Sestini, B.Alfaioli, M. Grazzini, A. Janowska, A. Saggini, T. Lotti
si estrinseca in un “non trattamento” della ferita,
una volta avvenuta la rimozione dei punti. È
infatti esperienza comune sentire il detto “l a
cicatrice la fa il paziente”. Tale enunciato, che ha
in parte anche delle giuste basi scientifiche,
poteva essere appropriato qualche decennio fa,
ma attualmente non ha più giustificazione.
Infatti il trattamento e la prevenzione delle cicatrici si caratterizza oggigiorno per l’ampia varietà
di terapie e tecniche utilizzate. Molti di questi
trattamenti si sono affermati a seguito di una
ampia diffusione nel corso degli ultimi anni,
mentre solo una minoranza risulta effettivamente supportata da studi prospettici che abbiano
incluso dei gruppi di controllo adeguati.
Le valutazioni sull’efficacia sono state ulteriormente limitate dalla difficoltà di quantificare le
modificazioni obiettive delle lesioni cicatriziali e
dal fatto che le cicatrici tendono naturalmente a
migliorare nel tempo. 1
L’utilizzo del silicone in varie forme ha rappresentato un’opzione per il trattamento delle cicatrici a partire dall’inizio degli anni ’80. Esistono
in letteratura più di dieci studi randomizzati e
controllati, che dimostrano come l’utilizzo del
silicone costituisca una scelta terapeutica sicura
ed efficace per le cicatrici cheloidee. 1-8
Inizialmente erano utilizzate piastre al silicone,
che potevano risultare scomode per i pazienti,
anche a seconda delle sedi della ferita, e quindi
mal tollerate. 4 L’impiego, invece, di prodotti in
gel a base di silicone risulta estremamente
comodo, raggiungendo una buona compliance
da parte del paziente. 9
Lo scopo dello studio è stato la valutazione dell’efficacia di un gel al silicone (Zeraderm ultra
gel™) nel trattamento delle ferite chirurgiche
rispetto ad un gruppo di controllo con stesso
fenotipo e stessa sede cicatriziale, a cui non è
stato consigliato alcun prodotto.
In particolare è stato valutato il minimo “danno”
estetico residuato all’intervento chirurgico. Non
Gruppo di studio
Gruppo di controllo
e metodi
Materiali
Sono stati inclusi nello studio 110
pazienti (55 di sesso maschile, 55 di sesso femminile) (Tabella 1), sottoposti ad interventi di
d e r m o c h i r u rgia ambulatoriale presso il
Dipartimento di Scienze Dermatologiche dell’Università di Firenze, nel periodo maggio-luglio
2005.
I suddetti pazienti sono stati divisi in due gruppi: un gruppo di studio ed un gruppo di controllo.
Tutti i pazienti sono stati sottoposti ad interventi di escissione chirurgica di lesioni cutanee
melanocitarie (nevi melanocitici, melanomi),
lesioni cutanee neoplastiche non melanocitarie
(carcinoma basocellulare, carcinoma spinocellulare, angiocheratoma, tumori annessiali),
lesioni cutanee benigne (cheratosi seborroiche,
lipomi). Sono stati esclusi dallo studio i pazienti con escissioni chirurgiche di dermatofibromi,
di cisti sebacee e di lesioni cutanee in flogosi.
I pazienti arruolati presentavano il seguente
fototipo secondo Fitzpatrick: 5% tipo I, 21%
tipo II, 47% tipo III, 27% tipo IV.
Tutti i casi sono stati operati dallo stesso chirurgo mediante lama fredda (VDG) e sono stati utilizzati gli stessi materiali per la sutura e per la
N°
pazienti
Età
media
Mediana
Range
età
Lesioni
Arti sup.
(%)
Lesioni
Arti inf.
(%)
Lesioni
Tronco
(%)
Lesioni
Volto
(%)
65
(33 m, 32 f)
45
(22 m, 23 f)
52
49
26-81
25%
20%
38%
17%
48
45
23-76
30%
24%
34%
12%
Tabella 1. Caratteristiche dei pazienti.
26
è stato quindi giudicato soltanto la formazione
o non del classico cheloide o della cicatrice
ipertrofica, ma soprattutto se l’applicazione precoce del prodotto sulla ferita si estrinsechi,
rispetto al gruppo di controllo, con la formazione di un migliore e minimo “danno” estetico
anche nell’ambito della cicatrice cosiddetta
“fisiologica”.
Inoltre è stata valutata la compliance del paziente rispetto allo stesso prodotto, valutando la
presenza di dolore, prurito, senso di presenza
della ferita in corso di cicatrizzazione.
Studio prospettico sull’evoluzione delle ferite chirurgiche trattate con gel al silicone
a
b
c
Figura 1.
medicazione. A tutti i pazienti è stato detto di
sospendere l’attività sportiva per un periodo di
4 settimane.
Al gruppo di studio (65 pazienti) è stato prescritto l’uso di gel al silicone da applicare sulla
ferita due volte al giorno per 60 giorni dopo la
rimozione dei punti di sutura. Invece al gruppo
di controllo (45 pazienti) non è stata prescritta
alcuna terapia preventiva.
Tutti i pazienti, sia del gruppo di studio, sia del
gruppo di controllo, sono stati visitati a cadenza mensile per i primi tre mesi dall’intervento e
successivamente ogni 2 mesi per un follow-up
complessivo di 8 mesi dalla data dell’interven-
to, sempre dagli stessi dermatologi (VDG, SS) al
fine di mantenere una valutazione riproducibile
nei vari pazienti. Durante ogni visita di controllo è stata effettuata una documentazione iconografica ed è stata valutata l’evoluzione della
cicatrice nel tempo. In particolare è stato utilizzato, un videocapillaroscopio digitale per verificare la precoce comparsa sulla cicatrice di
vascolarizzazione, testimoniata dalla presenza
di teleangectasie.
Inoltre è stata valutata la presenza di allodinia e/o
di “p rurito evocato” mediante l’utilizzo di un fine
pennello, sfruttando un test già utilizzato in neurologia per la valutazione delle pare s t e s i e .
L’induzione del dolore e/o prurito è stata scatenata attraverso il delicato movimento del pennello
sulla cute, partendo a circa 5 cm dalla cicatrice
(cute pericicatriziale) e venendo poi a spostarsi
lentamente in direzione centripeta, verso il centro della cicatrice. Per ogni paziente il test è stato
effettuato almeno 3 volte e la presenza di aree
nelle quali il paziente sentiva dolore e/o prurito
sono state marcate con una penna dermografica.
Il paziente è stato istruito di informare l’investigatore alla prima sensazione di dolore o di prurito provata. Le aree alle quali il pennello elicitava
una risposta sono state marcate con una penna
verde quando il paziente riferiva prurito e con
una penna rossa quando provava dolore.
A tutti i pazienti, ad ogni controllo, è stato chiesto di quantificare su una scala tarata da 0 a 10,
il peggiore dolore e/o prurito provato nell’ulti-
27
mo mese a livello cicatriziale/pericicatriziale. La
severità della sensazione variava da nessun
dolore/prurito alla fine della scala (severità = 0),
al massimo dolore/prurito all’altro estremo della
scala (severità = 10).
Ai pazienti è stato anche chiesto di riferire eventuali altre sensazioni o sintomi associati alla
cicatrice ed eventuali altri trattamenti effettuati
durante il periodo di osservazione, così da
escludere dallo studio i pazienti che abbiano
iniziato terapie influenzanti la cicatrizzazione
(ad es. terapia cortico-steroidea), come anche i
pazienti che non abbiano rispettato il protocollo di studio (2 applicazioni di prodotto al giorno per 60 giorni).
Risultati
Gruppo di Studio
Tutti i 65 pazienti (33 maschi e 32
femmine) con un’età media di 52 anni (range
26-81) che sono stati arruolati, hanno portato a
termine lo studio.
In 16 pazienti le lesioni sono localizzate a livello degli arti superiori (braccio, avambraccio e
mano), in 13 pazienti a livello dell’arto inferiore (coscia, gamba e piede), in 11 pazienti al
volto (Figura 1) e nei rimanenti le lesioni sono
localizzate a livello del tronco.
In 18 pazienti (27%) abbiamo avuto la formazione di una cicatrice non fisiologica (Tabella
2). In particolare, in 10 pazienti (15%) abbiamo
avuto una cicatrice diastasica, in 6 pazienti
(9%) una cicatrice ipertrofica e in 2 pazienti
(3%) una cicatrice atrofica. Non abbiamo invece registrato cicatrici cheloidee.
I casi in cui abbiamo avuto una cicatrice diastasica erano localizzati agli arti inferiori in 6 casi
e a livello del tronco nei rimanenti 4. Le cicatrici localizzate agli arti inferiori interessavano in 4
casi pazienti con un’età superiore ai 65 anni,
che all’esame obiettivo presentavano i segni clinici di una lieve-moderata insufficienza venosa.
Gruppo di studio
Gruppo di controllo
Gruppo di controllo
Nei 45 pazienti (22 maschi e 23 femmine) del gruppo di controllo abbiamo rilevato
una cicatrice alterata in 25 pazienti (55%)
(Tabella 2). In particolare abbiamo registrato la
formazione di cicatrici cheloidee in 5 pazienti
(11%), cicatrici ipertrofiche in 10 pazienti
(22%), cicatrici diastasiche in 8 pazienti (18%)
e cicatrici atrofiche in 2 pazienti (4%).
Le cicatrici cheloidee erano localizzate in 1 caso
a livello di un arto superiore, in 2 casi a livello
toracico e in 2 casi a livello deltoideo.
Alterazioni
cicatrice
Cicatrici
cheloidee
Cicatrici
ipertrofiche
Cicatrici
diastatiche
Cicatrici
atrofiche
27%
55%
0%
11%
9%
22%
15%
18%
3%
4%
Tabella 2. Caratteristiche cicatrici.
28
Invece, le cicatrici ipertrofiche hanno interessato in 4 casi pazienti di età inferiore ai 48 anni,
ed erano localizzate in 3 casi a livello sternale,
in 2 casi in regione deltoidea e in 1 caso a livello addominale.
Un paziente con cicatrice atrofica era diabetico.
L’aspetto clinico delle cicatrici mostrava in 10
pazienti (15%) un’eritema perilesione ed in 8
pazienti (12%) la presenza di teleangectasie,
monitorizzate mediante videocapillaroscopio
digitale.
Tredici pazienti (20%) hanno riferito la presenza di dolore durante la fase di cicatrizzazione, la
severità di tale sensazione era lieve-moderata,
alla scala tarata variava da 3 a 5, alcuni pazienti parlavano di “sensazione di fastidio”, più che di
un vero dolore.
Invece, sei pazienti (9%) hanno riferito la presenza di prurito, di severità variabile da 3 a 6
alla scala tarata.
Al test di stimolazione con un fine pennello, 12
pazienti (18%) hanno riferito la presenza di
parestesie, in particolare prurito e dolore, il
primo più frequentemente in sede pericicatriziale, mentre il secondo era prevalente al centro
della cicatrice (Tabella 3).
Da sottolineare che il lieve dolore era sempre
riferito dai pazienti con cicatrice ipertrofica.
Nessun paziente ha mostrato effetti collaterali
all’applicazione del gel al silicone.
Il 30% dei pazienti si è lamentato del costo del
prodotto.
Dolore riferito
Gruppo di studio
Gruppo di controllo
20%
47%
Eritema Teleangectasie
15%
30%
12%
47%
Parestesie
spontanee
Parestesie
provocate
9%
35%
18%
58%
Tabella 3. Sintomatologia ed aspetto clinico cicatrici.
Nessuna terapia
44%
Automedicazione
13%
Farmacista
27%
Familiare
13%
Erboristeria
3%
Tabella 4. Gestione cicatrici nel gruppo di controllo (45 pazienti).
Le cicatrici ipertrofiche e diastasiche non hanno
mostrato preferenza di sede.
In 35 pazienti la cicatrice era particolarmente
visibile per la presenza di teleangectasie (47%)
ed eritema perilesionale (30%).
Ventuno pazienti (47%) hanno riferito dolore o
fastidio durante la fase di cicatrizzazione, la cui
severità alla scala tarata variava da 4 a 7. Invece
16 pazienti (35%) hanno riferito prurito in sede
cicatriziale.
Al test di stimolazione, 26 pazienti (58%)
hanno presentato alterazioni della sensibilità,
prurito presente in sede pericicatriziale e cicatriziale, mentre il dolore presente su tutta la
superficie cicatriziale (Tabella 3).
Il 44% dei pazienti riferiva di non aver effettuato alcuna terapia per la cicatrice ed il restante
gruppo di pazienti riferiva applicazioni non continuative di prodotti di vario genere (creme idratanti, antibiotiche, in automedicazione o su consiglio di familiari, farmacisti, o erboristi (Tabella
4). Nessun paziente, nonostante il dolore riferito, si è rivolto al proprio medico curante.
Discussione
La cicatrizzazione rimane ancora un
grande problema per il chirurgo, nonostante l’esplosione scientifica degli ultimi anni. La maggiore difficoltà deriva probabilmente dal fatto
che la riparazione di una ferita è un processo
biologico complesso, che coinvolge un insieme
di fattori correlati e interdipendenti. La numerosità delle cellule e dei mediatori biologici
coinvolti determina l’influenzabilità del meccanismo di riparazione da parte di più fattori
(sistemici, locali, legati all’ambiente e legati alla
medicazione). Proprio la moltitudine dei fattori
coinvolti costituisce la base per una difficile
spiegazione dell’influenza di un singolo elemento nella formazione di una cicatrice.
In questo studio abbiamo cercato di minimizzare i fattori di disturbo, quali il sesso, l’età, il
fototipo, la sede della cicatrice, venendo a confrontare le lesioni per lo più simili per tali variabili, così da considerare solo il ruolo svolto dal
gel al silicone.
Abbiamo così dimostrato come l’utilizzazione
precoce di tale gel possa influenzare il processo
di cicatrizzazione. Infatti abbiamo riscontrato la
formazione di cicatrici patologiche solo nel
27% dei pazienti del gruppo di studio, contro il
55% dei pazienti del gruppo di controllo. In
particolare nel gruppo di studio abbiamo osservato una ridotta formazione di cicatrici cheloidee e ipertrofiche, infatti non abbiamo avuto la
formazione di cheloidi, mentre tali cicatrici si
sono formate nell’11% dei pazienti del gruppo
di controllo; così come le cicatrici ipertrofiche si
sono formate nel 9% dei pazienti del gruppo di
studio, contro il 22% di quelli di controllo.
Dalla letteratura si evince come la capacità dei
gel al silicone di influenzare la cicatrizzazione
sia essenzialmente imputabile ad un meccanismo di azione simile a quello delle lamine di
silicone. Infatti l’equi-attività del gel è dovuta al
suo non assorbimento e alla formazione di una
membrana impermeabile all’acqua e parzialmente impermeabile ai gas, che agisce come un
ulteriore strato corneo a protezione ed idratazione della cicatrice. L’azione occlusiva che si
viene a esercitare aumenta così la tensione di
idratazione locale e a sua volta l’idratazione inibisce la proliferazione dei fibroblasti e la loro
capacità di produrre collageno. 5
Altri meccanismi che sembrano coinvolti nell’azione del silicone in gel sulla riduzione della
29
produzione di sostanza extracellulare e di collageno sono: la riduzione della pressione di O ,
l’induzione di differenze di temperatura di 1°C
e l’induzione di campi elettrostatici in grado di
contrastare l’eccessiva crescita cicatriziale favorita dai mastociti. 7 Inoltre un recente studio sui
fibroblasti in coltura ha dimostrato che tali gel
sono in grado di influenzare l’espressione di fattori di crescita, in particolare del fattore di crescita dei fibroblasti, citochina chiave nel processo di cicatrizzazione. 6
Quindi i gel al silicone agirebbero in molteplici
modi, influenzando il processo di cicatrizzazione sia attraverso l’induzione di modificazioni
fisiche, sia attraverso la modificazione dei livelli citochinici, avendo sempre come target finale
il fibroblasto.
Tra le cicatrici patologiche, un discorso diverso
meritano invece le cicatrici diastasiche e le atrofiche. La loro percentuale di formazione è
sostanzialmente sovrapponibile nei due gruppi
di pazienti. È ipotizzabile che in questi casi la
cicatrizzazione sia alterata a livello “basale” e
quindi minimamente influenzabile dalla medicazione. Infatti la loro formazione è probabilmente da attribuire all’alterazione di due processi biologici di base: la vascolarizzazione periferica e il metabolismo dei glucocorticoidi.
Infatti, la formazione delle cicatrici diastasiche è
risultata più frequente a livello degli arti inferiori e a livello del dorso, aree cutanee normalmente sottoposte a continue sollecitazioni meccaniche (movimento e tensione, rispettivamente). Inoltre per le cicatrici diastasiche degli arti
inferiori, la maggioranza dei pazienti mostrava i
segni di una lieve-moderata affezione vascolare
venosa periferica, quindi con possibilità di
compromissione della cicatrizzazione, per un’anomalia degli scambi gassosi, tanto importanti
in un tessuto dinamico in formazione, quale è la
cicatrice.
Per quanto riguarda le cicatrici atrofiche, in un
caso su quattro il paziente era diabetico, in questo caso è ipotizzabile una riduzione nella sintesi di collageno, con conseguente influenza di
tutta la crescita cellulare della fase riparativa.
Dal nostro studio emerge anche un’efficacia del
gel nella riduzione dell’eritema e delle teleangectasie, infatti l’eritema è stato osservato nel
15% dei pazienti del gruppo di studio, contro il
30% di quelli di controllo; invece le teleangectasie nel 12% versus il 47%.
La diminuzione del “rossore” associato alla cicatrice si è dimostrato molto importante nell’ac2
30
cettabilità della cicatrice stessa da parte del
paziente.
L’azione del gel al silicone sulla neovascolarizzazione è da imputare alla capacità di diminuire i
livelli del fattore di crescita dei fibroblasti, citochina responsabile di scatenare una cascata di
mediatori attivi sulla neoangiogenesi. 6,10
Per quanto riguarda il prurito e il dolore, il gruppo di studio ha evidenziato una ridotta incidenza (9% versus 35% e 20% versus 47%, rispettivamente), una limitata estensione di tali sintomi,
venendo il dolore ad essere presente solo al centro della cicatrice e non esteso per la sua intera
superficie, e anche una ridotta severità.
La riduzione delle parestesie è mantenuta anche
dopo stimolazione con il pennello, infatti solo il
18% dei pazienti del gruppo di studio ha dato
esito positivo, contro il 58% del gruppo di controllo.
Una possibile spiegazione della riduzione delle
parestesie è da collegare alla capacità del gel di
ridurre la sintesi di collageno, venendo quindi a
diminuire la pressione fisica esercitata dalle
fibre sui nervi periferici e di conseguenza riducendo anche lo stimolo alla rigenerazione nervosa che è spesso osservata a livello della periferia delle cicatrici patologiche. 11 La riduzione
delle parestesie, in particolare il prurito, è anche
da imputare alla capacità dei gel al silicone di
ridurre il numero dei mastociti in sede cicatriziale/pericicatriziale e la loro attività di degranulazione. 12 Infatti, tra i mediatori liberati dai
mastociti, quelli che elicitano una sensazione
pruriginosa sono l’istamina e il fattore di crescita per i nervi, i quali creano un circolo vizioso,
inducendo uno la liberazione dell’altro, e
venendo così a stimolare cronicamente i nocicettori. La riduzione dei livelli di tali molecole a
livello cicatriziale è quindi responsabile di una
diminuzione delle parestesie. 11
Nel gruppo di studio abbiamo inoltre evidenziato come i pazienti con cicatrici in aree fotoesposte (volto, scollo, avambraccio e mano) non
abbiano sviluppato un’alterazione della pigmentazione, rispetto ai pazienti con cicatrici in
aree non fotoesposte. Questo aspetto è degno di
nota anche in considerazione del periodo del
nostro studio, infatti sono stati arruolati pazienti in maggio-luglio, quando l’esposizione solare
è massima e spesso inevitabile (volto). La mancata insorgenza di iperpigmentazioni nelle cicatrici in formazione è da imputare alla protezione dello schermo solare presente nel gel da noi
testato. Quest’azione è molto importante, in
quanto la presenza di alterazioni della pigmentazione cicatriziale influenza il risultato estetico
e aumenta la percezione della “presenza” della
cicatrice da parte del paziente, soprattutto
essendo interessate aree fotoesposte e quindi
difficilmente mascherabili.
I pazienti del gruppo di studio non hanno
mostrato effetti collaterali dopo l’applicazione
del gel e hanno dimostrato una buona compliance. In particolare le pazienti di sesso femminile, con cicatrici al volto, hanno particolarmente gradito la possibilità di potersi truccare
regolarmente dopo l’applicazione.
Bibliografia
1. Mustoe TA, Cooter RD, Gold MH, et al.
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2. Lyle WG. Silicone gel sheeting. Plast Rec Surg 2001;
107:272-5
3. Shigeki S, Nobuoka N, Murakami T, et al. Release and
skin distribution of silicone-related compouns from silicone
gel sheet in vitro. Skin Pharmacol Appl Skin Physiol 1999;
12:284-8
4. Paul Kelly A. Medical and surgical therapies for keloids.
Dermatologic Therapy 2004; 17:212-18
5. Chang CC, Kuo YF, Chiu HC, et al. Hydration, not silicone, modulates the effects of keratinocytes on fibroblasts. J
Surg Res 1995; 59:705-11
6. Hanasono MM, Lum J, Carroll LA, et al. The effect of silicone gel on basic fibroblast growth factor levels in fibroblast cell culture. Arch Facial plast Surg 2004; 6:88-93
7. Eishi K, Bae SJ, Ogawa F, et al. Silicone gel sheets relieve
pain and pruritus with clinical improvement of keloid: pos-
In conclusione, il nostro studio mostra la capacità del gel di silicone di ridurre la formazione
delle cicatrici cheloidee e ipertrofiche e i segni/
sintomi associati ad una cicatrice in formazione
(parestesie, senso di tensione e alterazioni cromatiche). Infatti, anche se le ipotesi patogenetiche sono molteplici e probabilmente da verificare ulteriormente, l’obiettività clinica dimostra che
il gel di silicone favorisce la riduzione dello spessore del tessuto cicatriziale e quindi l’ammorbidirsi, il levigarsi e l’appiattirsi della cicatrice,
riducendo al minimo l’esito cicatriziale e venendo così a migliorare il risultando estetico.
sible target of mast cells. J Dermatolog Treat 2003;
14:248-52
8. Gold MH, Foster TD, Adair MA, et al. Prevention of
hypertrophic scars and keloids by prophylactic use of topical silicone gel sheets following a surgical procedure in a
office setting. Dermatol Surg 2001; 27:641-4
9. Chan KY, Lau CL, Adeeb SM, et al. A randomized,
placebo-controlled, double-blind, prospective clinical trial
of silicone gel in prevention of hypertrophic scar development in median sternotomy wound. Plast Reconstr Surg
2005; 116:1013-20
10. Singer JA, Clark RAF. Cutaneous wound healing. New
Engl J Med 1999; 341:738-46
11. Lee SS, Yosipovitch G, Chan YH, et al. Pruritus, pain,
and small nerve fiber function in keloids: a controlled study.
J Am Acad Dermatol 2004; 51:1002-6
12. Lee YS; Vijayasingam S. Mast cell and myofobroblasts
in keloid: a light microscopic, immunohistochemical and
ultrastructural study. Ann Acad Med Singapore 1995;
24:902-5
31
Incrementare la protezione cutanea
da fotoinvecchiamento e danno solare
Riccarda Serri
SU M M A R Y
New way to protect the skin against
sunlight damages
UV-induced oxidative stress causes the production of a large amount of reactive oxygen
species (ROS) that can damage DNA, proteins and lipids. In the skin the more important consequences of ROS are photoaging and cancer. Topical antioxidants (L-ascorbic
acid and alpha-tocopherol and ferulic acid) attenuate the damaging effects of ROS and
can impair many of the events that contribute to epidermal toxicity and disease.
KEY WORDS: Oxidative stress, Skin, ROS, Topical antioxidants
tress ossidativo
Introduzione
S
Luce solare più vita in una atmosfera
I ROS (Reactive Oxygen Species, o radiricca di ossigeno causano una serie di stress alla
cute umana. L’apice del fotodanneggiamento è
r a p p resentato dai tumori della pelle, mentre
segni più o meno marcati e frequenti sono
invecchiamento precoce, disturbi della pigmentazione, secchezza, etc.
P e rché avvenga la reazione fotochimica, i raggi
ultravioletti (UV) provenienti dal sole devono
e s s e re assorbiti da un cro m o f o ro: da queste re azioni fotochimiche possono derivare modificazioni al DNA, incluse ossidazione degli acidi
nucleici cellulari, e modificazioni a proteine e
lipidi epidermici. L’accumulo di queste re a z i oni si traduce in fotodanneggiamento e fotoinvecchiamento.
L’organismo umano è bene organizzato per
affro n t a re lo stress ossidativo, ricorrendo a
antiossidanti enzimatici e non enzimatici: tuttavia, la luce solare e altri generatori di radicali
liberi (come l’inquinamento atmosferico, il
fumo di sigaretta) possono re n d e re inadeguate
le capacita di controllo naturali, e scatenare
quindi danni ossidativi.
Tra i cromofori (sostanze in grado di assorbire
i RUV), uno dei più importanti dal punto di
vista biologico è il DNA. Un secondo cro m o f oro per le reazioni fotochimiche nella cute è l’acido urocanico, prodotto dal metabolismo
della filaggrina.
cali liberi dell’ossigeno) sono composti chimici
caratterizzati dalla presenza di elettroni spaiati
che posseggono una elevata reattività, e che sono,
pertanto, in grado di interagire con i sistemi biologici, provocando profonde alterazioni.
In circostanze normali la formazione di radicali
liberi nell’organismo è tenuta sotto controllo da
un sistema adeguato di difesa che comprende,
come detto, meccanismi enzimatici e non enzimatici di neutralizzazione.
Tuttavia la produzione abnorme di radicali liberi
può, in alcune circostanze, saturare i normali
meccanismi di difesa, particolare in aree localizzate come la pelle, dando origine allo stress ossidativo che comporta rilevanti alterazioni del
metabolismo, attraverso la per ossidazione dei
lipidi della membrana cellulare, e danni a livello
delle proteine, degli zuccheri e degli acidi nucleici. Nelle membrane cellulari, la presenza di fosfolipidi ricchi in acidi grassi polinsaturi è fondamentale per conferire alle membrane stesse un
buon grado di compattezza e permeabilità, e per
permettere il corretto funzionamento della cellula. Tuttavia questi acidi, per il loro grado di insaturazione, risultano essere il substrato ideale per
gli attacchi dei radicali liberi, venendo ossidati in
corrispondenza dei doppi legami (lipo-perossidazione), con conseguente alterazione del potenziale di membrana. Anche le proteine – sia struttu-
Specialista in Dermatologia
33
R. Serri
rali che enzimatiche – subiscono , da parte dei
radicali liberi, profonde modificazioni per effetto
della alterazione dei singoli amminoacidi. Una
delle conseguenze più evidenti di tali alterazioni,
nella cute, è la diminuzione della flessibilità delle
fibre collagene, all’interno delle quali si formano
dei veri centri di propagazione radicalica.
Lo stress ossidativo, in definitiva, rappresenta il
fattore più importante dei percorsi biochimici che
portano al fotoinvecchiamento e ai carcinomi
cutanei.
topici
Antiossidanti
Sebbene la pelle sia ben dotata di sistemi antiossidanti endogeni molto efficienti, l’ulteriore aggiunta di antiossidanti topici si è dimostrata essere estremamente utile nella prevenzione
del photoaging e di altri tipi di danni cutanei legati a radiazione solare acuta o cronica.
Ovviamente gli antiossidanti topici – per essere
utili e per poter “lavorare”, in modo da implementare i “reservoir” antiossidanti cutanei – debbono essere formulati in maniera tale che l’assorbimento per cutaneo sia ottimizzato. Uno degli
antiossidanti più utili – e più studiati – in questo
senso, è l’acido L-ascorbico, che deve essere in
forma non ionizzata per penetrare nella cute.
L’acido L-acorbico protegge la cute dai danni
indotti sia dagli UVA, sia dagli UVB.
I lavori dell’americano Sheldon Pinnell – le cui
prime pubblicazioni sulla fotoprotezione indotta
dall’acido L-ascorbico risalgono al 1988- hanno
dimostrato che un composto al 15% di acido Lascorbico e 1% di alfa-tocoferolo, formulato a un
pH più basso di 3,5 per consentire l’assorbimento per cutaneo, provvede ad un incremento della
fotoprotezione quando applicato topicamente
sulla cute. Tale combinazione limita l’eritema
fotoindotto, il danno cellulare (misurato attraverso le sunburn cells) e la formazione dei dimeri
della timina. Per migliorare la stabilità e per incrementare il potere antiossidante, è stato aggiunto
un ulteriore coantiossidante a tale composto, l’acido ferulico, una molecola antiossidante ubiquitaria nelle piante (due molecole di ferulico
appaiate assomigliano a una molecola di curcuma
longa, o turmeric acid).
L’acido ferulico è un antiossidante sia lipo, sia
idrosolubile, dalle notevoli proprietà di scavenger
dei radicali liberi. In pratica, l’acido ferulico presente nel composto di acido L-ascorbico e di allfa
tocoferolo provvede sia a una maggiore stabilità
34
del composto stesso, sia implementa l’azione
antiossidante delle altre sostanze.
indotti dai raggi
avioletti
Radicaliultrliberi
I filtri solari applicati sulla cute non
sono in grado, da soli, di bloccare la formazione
di radicali liberi da irradiazione UVA: l’aggiunta di
composti antiossidanti topici a base di acido Lascorbico, alfa tocoferolo e acido ferulico incrementa notevolmente la protezione dall stress ossidativo, l’infiammazione indotta da UVA, e, in
definitiva, limita e previene il fotodanneggiamento. L’acido ferulico, in particolare, migliora la stabilità dell’acido ascorbico nelle formulazioni
acquose, ed incrementa marcatamente la fotoprotezione contro le radiazioni solari. Entrambi questi effetti sono probabilmente correlati con le proprietà antiossidanti dell’acido ferulico (acido presente in quasi tutte le piante).
Il ferulico è scavenger (spazzino) dei radicali
idrossilici, dell’ossido nitrico, e del superossido.
L’acido ferulico possiete la dimostrata capacità di
penetrare nella cute quando applicato topicamente, e di proteggere dall’eritema indotto da UVB.
ConcluSiasiolenipiante, sia gli animali (inclusi gli
animali “umani”) utilizzano un network di antiossidanti, che lavorano assieme armonicamente, per
proteggersi dai raggi solari.
L’applicazione di antiossidanti topici – che devono essere efficaci e in grado di penetrare – aggiunge al reservoir antiossidante cutaneo una ulteriore protezione contro tutti i danni fotoindotti.
letture consigliate
Lin FH, Lin JY, Gupta RD, To u rnas JA, Burch JA,
Selim MA, Monteiro-Riviere NA, Grichnik JM, Zielinski J,
Pinnell SR. Ferulic acid stabilizes a solution of vitamins C and
E and doubles its photoprotection of skin. J Invest Dermatol.
2005 Oct; 125(4):826-32.
Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM,
Monteiro-Riviere NA, Pinnell SR. UV photoprotection by
combination topical antioxidants vitamin C and vitamin E. J
Am Acad Dermatol. 2003 Jun; 48(6):866-74.
D a rr D, Dunston S, Faust H, Pinnell S. Effectiveness of
antioxidants (vitamin C and E) with and without sunscreens
as topical photoprotectants. Acta Derm Venereol. 1996 Jul;
76(4):264-8.
Dermocosmetologia della pelle scura
Stefano Veraldi
SU M M A R Y
Dark skin dermocosmetology
The main differences between dark and white skin are: more and larger singly distributed melanosomes in the keratinocytes and corneocytes and more sweat and sebaceous
glands in dark skin. Cutaneous diseases which afflict white skin also occur in dark skin,
however some of these diseases may occur more commonly in dark skin people or present in a different manner. Due to immigration in the last years dark people are incre a sing in number in Italy, and dermatologists should be aware of these variations in presentation to properly diagnose and manage these diseases.
KEY WORDS: Dark skin, Dermocosmetology
anatomiche
tra pelle scura e chiara
Differenze
Qualche anno fa è stato aperto, presso
il nostro Istituto, un ambulatorio per la diagnosi e la terapia delle malattie infettive, parassitarie e tropicali della cute. Questa iniziativa ci ha
permesso, tra le tante opportunità, di visitare
numerosi pazienti con pelle scura.
La pelle chiara e quella scura presentano una
diversa anatomia. Nell’epidermide della pelle
scura si riscontrano un film idro-lipidico di
superficie più ricco in acidi grassi, uno strato corneo più compatto e spesso e melanosomi pre s e nti anche nei cheratinociti dello strato corneo; i
melanosomi, inoltre, sono dispersi e di maggiori
dimensioni. Al contrario, non esistono differenze
tra pelle chiara e pelle scura per quanto riguarda
il numero, la distribuzione e la morfologia dei
melanociti. Il derma e il sottocute non presentano diff e renze significative rispetto alla pelle chiara. Le ghiandole sebacee e sudoripare sono, nella
pelle scura, più diffuse, più numerose, di maggiori dimensioni e ipersecernenti. I peli sono
meno diffusi e presentano un fusto incurvato e
spiraliforme, con una sezione di taglio appiattita
ed ellittica. Le unghie non presentano differenze
rispetto alla pelle chiara. Considerata nel complesso, la pelle scura si differenzia da quella chiara fondamentalmente per il colore, dovuto alla
particolare anatomia dei melanosomi.
del dermatologo
RuoloQuesta
diversa anatomia presuppone
una diversa fisiologia, che condiziona una
diversa incidenza e/o presentazione clinica delle
malattie con espressività cutanea. Si pensi, nel
primo caso, alla rosacea (meno frequente su
Istituto di Scienze Dermatologiche,
Università di Milano,
Fondazione I.R.C.C.S., Ospedale Maggiore Policlinico,
Mangiagalli e Regina Elena
37
S.Veraldi
pelle scura) e alla vitiligine (più frequente su
pelle scura); nel secondo, all’eritema: tutti i dermatologi sanno che su pelle chiara l’eritema
appare come un arrossamento, di colore variabile dal rosa al rosso acceso, che scompare alla
digitopressione, ma non tutti i dermatologi
sanno che su pelle scura l’eritema appare di
colore grigiastro.
La diversa presentazione clinica delle malattie
su pelle scura necessita di una sorta di revisione critica, da parte del dermatologo, della metodologia di lettura delle malattie cutanee. Il dermatologo si trova nuovamente a dover affrontare il problema della morfologia delle lesioni
sulla pelle che già da tempo era abituato a considerare come acquisite e definite. Si avrà quindi un ritorno alla clinica pura, intesa come
osservazione e classificazione di quadri dermatologici noti, ma con presentazioni cliniche
nuove o atipiche: a questo fenomeno è stato
dato il nome di sindrome di Salgari 2. Inoltre, è
da ricordare che le malattie che si osservano su
pelle scura si osservano anche su pelle chiara:
non esistono quindi malattie cutanee specifiche
della pelle scura.
Un altro aspetto interessante emerso negli ultimi anni è quello legato, per usare un termine
impegnativo, all’integrazione. Molto semplicemente, individui con pelle scura che nel recente passato si recavano dal dermatologo per una
malattia, oggi lo consultano spesso per problematiche cosmetologiche. Il passaggio da una
domanda “medica” a una domanda “cosmetologica” non è altro che una spia dell’integrazione di
una cultura in un’altra.
Nella nostra esperienza, le più frequenti richieste da parte di soggetti con pelle scura riguardano la diagnosi e la terapia dell’acne, delle follicoliti, delle alterazioni della pigmentazione
(dalla vitiligine al melasma), delle alterazioni
della cicatrizzazione (cicatrici ipertrofiche e
cheloidi) e delle alopecie (spesso causate da
traumatismi chimici, termici e meccanici).
Il dermatologo italiano si deve quindi adeguare,
in tempi brevi, con una nuova cultura a una
nuova realtà sociale.
Letture consigliate
Veraldi S, Leigheb G, Morrone A. Atlas of dermatological diseases on dark skin
Basset A, Liautaud B, Ndiaye B. Dermatology of black skin.
Oxford Unìversity Press, Oxford, 1986
38
Du Vivier A. Atlas of infections of the skín. Gower Medical
Pub., London, 1991
Canìzares O, Harman RRM. Clinical tropical dermatology,
Blackwell Scientifìc Publications, 1992
Mahmotud AAF Tropical and geographical medicine.
McGraw-HIII Inc., New York, 1993
Gioannini P, Caramello P. Patologia infettiva dell'immigrato. Edizioni Minerva Medica, Torino, 1994
Schaller KF. Color atlas of tropical dermatology and venereology. Speinger-Verlag, Berlin, 1994
Morrone A. Salute e società multiculturale. Medicina transculturale e immigratì extracomunitari nell’Italia del 2000.
Raffaello Cortina Editore, Milano, 1995
Parish LC, Witkowski JA, Vassileva S. Color atlas of cutaneous infections. Blackwell Science Inc., Boston, 1995
Rosen T. Clinical dermatology in black patients. Pigreco,
Bari, 1995
Harahap M. Dìagnosis and treatrnent of skin ìnfections.
Blackwell Science, Oxford, 1997
Veraldi S, Rizzitelli G, Caputo R. Dermatologia dì importazione. Poletto, Milano, 1997
Johnson BL Jr, Moy RL, White GM. Ethnic skìn. Medical
and surgical. Mosby, Saint Louis, 1998
Morrone A. L’altra faccia di Gaia. Salute, migrazione e
ambiente tra Nord e Sud del Pianeta. Armando Editore,
Roma, 1999
Morrone A. Dermatologia internazionale per immagini.
Edizioni Grafiche Mazzucchelli, Settimo Milanese
(Milano), 1999
Steffen R, DuPont HL. Manual of travel medicine and
health. B.C. Decker Inc., Hamilton, 1999
Lesher JL Jr. An atlas of microbiology of the skin. The
Parthenon Publ. Group, New York, 2000
Morrone A, Mazzali M. Le stelle e la rana. La salute dei
migranti: diritti e ingiustizie. Franco Angeli, Milano, 2000
Morrone A, Mazzali M, Tumiati MC. La babele ambulante
Parole íntorno ai mondi che migrano. Sensibili alle Foglie,
Dogliani (Cuneo), 2000
Veraldi S, Caputo R. Dermatologia di importazione.
Poletto, Milano, 2000
Albanese G, De Marchi R, Leigheb G, Morrone A, Petrini
N. Pietrantonio V, Veraldi S. Atlante di dermatologia esotica e su pelle nera. Edizìoni Medico Scientifiche, Pavia.
2001
Bianchini C, Marangi M, Morrone A, Meledandri G.
Medicina internazionale. Societá Editrice Universo, Roma,
2001
Pollard AJ, Murdoch DR. Travel medicine. Health Press,
Oxford, 2001
Donofrio P, Del Sorbo A, Donofrio P, La Forza MT, Papa A.
Atlante di dermatologia in bianco e nero. Edizioni Dermo,
Napoli, 2006
Uso cosmetico dell’acido L-polilattico
per il ringiovanimento cutaneo:
nuove indicazioni
Alessio Redaelli
SU M M A R Y
Cosmetic use of poly-L-lactic acid
for skin rejuvenation: New indications
Background: Bio-reconstructive materials have enjoyed a notable increase over the
recent years, thanks to their effectiveness and lack of side effects.
Objective: To provide updated information on injectable Poly-L-lactic acid to doctors
who wish to use it, highlighting the varied indications and describing the correct techniques for use.
Materials and methods: Poly-L-lactic acid has been diluted and prepared according to
the current models. It has been diluted with quantities from 4 ml to 8 ml of water per
injectable dose, including 0.5 cc of 3% mepivacain without adrenaline, depending on
indications. In addition to the traditional indications in the lower third of the face, it has
been used for the rejuvenation of the neck, décolleté, and hands as well as for the revitalization of the arms and the medial part of the thighs. Prior tests for allergies are not
necessary.
Results: Excellent results are confirmed in the lower third of the face, the jawline and
the mid-jawline. The preliminary results for the other, more difficult to treat areas other
than the face are positive but need to be confirmed with further studies conducted over
time. For the most part, the results were extremely well-received by the patients. The
immediate side effects were edemas, hematomas and redness - all of which disappeared
in a matter of days. Instances of nodules and hypercorrections were extremely rare.
Conclusions: The possibility of modifying the dilution both in terms of timing, amount
of injectable material employed, as well as quantity of water used, renders Poly-L-lactic acid an extremely versatile substance, which lends itself to new indications that will
be discussed in the article. Poly-L-lactic acid allows for a natural-looking and long-lasting correction that may last for years.
KEY WORDS: Poly-L-lactic acid, Fibro-connective reconstruction, Volumes
Introduzione
Nella storia della medicina estetica, si
sono susseguite dagli anni ‘70 ad oggi numerose tecniche, alcune delle quali sparite nel giro di
pochi anni per la sostanziale inutilità, altre divenute pilastri irrinunciabili. All’era del collagene,
negli anni ‘70, è seguito l’arrivo dell’acido ialuronico che ha rivoluzionato il trattamento estetico fino ai giorni nostri: si tratta di un materiale molto sicuro, senza finalmente il bisogno di
prove allergiche, di immediato risultato. È il
materiale più usato da allora sino ad oggi.
I materiali non riassorbibili nel frattempo
hanno visto assottigliare il loro uso fondamentalmente per la loro intrinseca pericolosità nel
tempo.
Poi è venuta l’era della tossina botulinica che è
andata a trattare una parte fondamentale della
medicina estetica: quella dovuta al movimento.
Ormai tutti i medici estetici sanno che ridurre la
mimica eccessiva rappresenta un passo fondamentale nella lotta all’invecchiamento. Anche
gli altri colleghi medici e perfino i media hanno
abbandonato quella ostilità preconcetta che ne
ha caratterizzato la nascita.
Centro medico Agorà, Milano
41
A. Redaelli
Nel frattempo la cura dell’epidermide ha visto
la nascita di innumerevoli peeling, laser ed altre
tecniche non invasive.
Ma sin dagli anni ‘90 soprattutto in Francia si
era visto che i volumi del sottocute se si assottigliano, danno un aspetto nettamente più vecchio, se non addirittura malato! Basti pensare ai
pazienti HIV positivi, in cura con farmaci antiretrovirali, che sviluppano quella classica lipodistrofia della zona malare.
Per questi pazienti è nato l’acido L-polilattico
(PLLA), che il CNR francese ha messo a punto
all’inizio degli anni ‘90. I risultati sin dall’inizio
sono stati molto interessanti, ma gravati dalla
p resenza di alcuni effetti collaterali, in particolare i noduli di collagene, che ne hanno offuscato
per qualche anno la grande carica innovativa.
Il passaggio al trattamento semplicemente
cosmetico, nelle pazienti che necessitavano di
una ristrutturazione sottocutanea importante fu
brevissimo.
Col tempo si capì che la diluizione era troppo
ridotta, che andava iniettato profondamente e
non nel derma, che non andava iniettato in
quantità eccessive per ciascuna iniezione, e che
andava massaggiato con cura per permetterne
una diffusione omogenea.
Inoltre la ditta distributrice, dal 2004 ha deciso
per la formazione obbligatoria dei medici utilizzatori.
Questa è stata probabilmente la chiave di volta
nell’azzerare gli effetti collaterali, in particolare i
noduli sottocutanei: Infatti la stragrande maggioranza di questi problemi si sono rivelati essere errori di tecnica.
Per la restituzione dei volumi non abbiamo
molte tecniche a disposizione:
Lipofilling classico, che resta un trattamento
chirurgico, spesso con risultati non duraturi.
Lipofilling sec. Coleman, con risultati buoni,
ma tuttavia invasivo: non tutti i pazienti, se
non una piccola minoranza, decidono di
affrontare il problema chirurgicamente.
Fillers riassorbibili: sicuri ma non duraturi.
Fillers non riassorbibili: intrinsecamente più
pericolosi, e ormai in decadenza e poco usati.
Il PLLA è l’unico materiale che permette di
ricostruire i giusti volumi sottocutanei di un
viso invecchiato senza riempirlo ma tramite
una ristrutturazione fibroconnettivale dei tessuti molli sottocutanei.
Questo articolo scientifico pone le basi della
tecnica usata dall’Autore sia nelle indicazioni
classiche, sia nelle indicazioni emergenti.
42
Materiali
L’Acido L-polilattico
Il PLLA è un biomateriale sintetico
che il CNR francese ha studiato negli anni ‘60
per impianti, vettori e sostituti del plasma. La
formula di struttura è visibile in Figura 1.
È un materiale riassorbibile, biocompatibile e
completamente biodegradabile.
È stato usato estensivamente per suture riassorbirli, per impianti intraossei ed impianti nei tessuti molli. Ultimamente viene usato anche nei
fili di sospensione per il lifting miniinvasivo del
viso (silhouette suture).
È un poliestere alifatico: un polimero dell’acido
lattico. È di sintesi chimica ed ha un peso molecolare di 170.000 Daltons.
Tutti i poliesteri alifatici ed in particolare l’acido
lattico sono biocompatibili, completamente
riassorbibili e immunologicamente inerti.
Il PLLA iniettabile per uso cosmetico (Sculptra®)
è costituito da microparticelle del diametro di
circa 40 micron sospese in un gel di sodio-carbossi-metil cellulosa, materiale assai ben conosciuto e con un profilo di sicurezza molto alto.
In Italia sono in commercio confezioni da 150 mg.
Il PLLA non è di origine animale ma è un prodotto sintetico e quindi non è necessario un test
allergico preventivo. Non è richiesto dalla legge,
non dalla ditta, e l’Autore non ne sente il bisogno non avendo mai avuto casi di allergia sicura al prodotto. Il PLLA ha un profilo di sicurezza molto elevato sia nel trattamento dei soggetti HIV positivi sia in tutti gli altri pazienti.
Il PLLA è approvato dalla FDA americana per la
correzione della lipoatrofia in pazienti HIV
positivi.
Meccanismo di azione
Il meccanismo di azione non è completamente chiarito, anche se Gogolewski et al.
hanno dato un grande aiuto nella intrinseca
comprensione del meccanismo.
Il suo riassorbimento avviene per idratazione,
rottura dei legami covalenti, perdita di peso
H O
CH3
O C C O C C
CH3
H O
Figura 1. Formula dell’acido L-polilattico.
n
Uso cosmetico dell’acido L-polilattico per il ringiovanimento cutaneo: nuove indicazioni
molecolare, solubilizzazione, degradazione ed
infine eliminazione come CO2. Alla fine quindi
il PLLA è completamente riassorbibile.
I volumi sono aumentati per una blanda reazione al PLLA con formazione di collagene di tipo
fibrotico.
Tale reazione è di norma fredda.
Il meccanismo di azione ed il rationale d’uso
consigliano quindi un approccio al paziente
sempre prudenziale e graduale.
Metodi
Tecnica personale
La diluizione del principio attivo (150
mg) è tra i particolari di tecnica maggiormente
importanti e più utili per adattare l’impianto
alle varie indicazioni. Infatti il PLLA è un materiale particolarmente versatile, utilizzabile in
numerosi distretti corporei.
La risposta del distretto trattato è direttamente
proporzionale a tre particolari di tecnica:
La maggiore o minore diluizione
Nella confezione di Sculptra® troviamo 150 mg
di PLLA. Questi possono essere diluiti con maggiore o minore quantitativo di acqua.
Normalmente l’Autore usa 5,5 ml di acqua per
p reparazioni iniettabili e 0,5 ml di mepivacaina
cloridrato al 3% senza adrenalina. Non usa invece lidocaina per la sua intrinseca maggiore pericolosità e per la sua lentezza nell’insorgenza dell’effetto anestetico.
Se si diluisce con un minore quantitativo di
acqua, la risposta del sottocute infiltrato sarà
più importante, se la diluizione sarà maggiore, il
quantitativo di principio attivo iniettato sarà
minore e minore la risposta del tessuto ricevente.
Area trattata
Sochi naso-genieni
Guance
Mento e bordo
mandibolare
Zigomi
Collo e décolleté
Distr. Intermandib.
Mani
Rivitalizzazioni
Tabella 1. Diluizioni ed aghi.
Diluizione base Diluizione definitiva Ago usato
5-5 cc
5-6 cc
5-6 cc
1:1
1:1
1:1
26 G
26 G
26 G
4-6 cc
6-7 cc
5-6 cc
6 cc
6 cc
1:1
1:1
1:1
1:1
1:4
26 G
26 G
26 G
26 G
27 G
Il maggiore o minore tempo di diluizione
Se la dispersione (ricordiamo sempre che si tratta di una dispersione e non di una soluzione) è
preparata poco tempo prima, da 3 sino a 5 ore
prima, la risposta del tessuto sarà maggiore.
Quanto maggiore invece sarà il tempo interc o rso tra la preparazione della sospensione e l’infiltrazione, tanto maggiore sarà l’idratazione dell’idrogel e minore la risposta del tessuto ricevente.
Il quantitativo di principio attivo iniettato
con ogni iniezione
È fondamentale non iniettare troppo quantitativo di principio attivo diluito per ogni iniezione
perché questo potrebbe portare in seguito alla
formazione di un accumulo di collagene in quel
determinato punto. È stato calcolato dall’Autore
che il quantitativo più giusto è 0,1 ml nel terzo
inferiore del volto e 0,05 ml nelle zone difficili
(collo, décolleté).
Medici con maggiore esperienza possono arrivare ad iniettare 0,2 ml per iniezione. Ma
l’Autore pensa che comunque sia meglio fare 2
iniezioni da 0,1 che una sola da 0,2: più prudente soprattutto quando ancora non si conosce perfettamente il paziente e la sua risposta.
Quindi, di norma, il PLLA viene diluito 24 ore
prima della seduta iniettiva.
Dopo la diluizione, il materiale va tenuto a temperatura ambiente.
È assai importante miscelare accuratamente il
p reparato prima di iniettare, mediante un
miscelatore elettrico o mediante scuotimento
manuale (come ultimamente preferito da alcuni
degli utilizzatori).
È altrettanto importante scuotere la siringa
durante l’uso per mantenere una soluzione
omogenea. Questo per non rischiare di iniettare una soluzione poco concentrata in un punto
ed iperconcentrata in un altro.
La diluizione dipende dalle zone da trattare e
dalla sessione di trattamento (Tabella 1).
Il PLLA trova indicazione nelle rughe, in particolare quelle della guancia, o del mento o per le
cicatrici depresse, ma la sua principale ed innovativa indicazione è sui volumi: zigomi, guance,
collo. L’Autore associa quasi nel 100% dei casi il
trattamento del bordo mandibolare e di tutto il
distretto intermandibolare.
I risultati dell’infiltrazione con PLLA vanno
spiegati bene al paziente prima di iniziare il
trattamento: si ha un riempimento iniziale,
transitorio ed evanescente in 2-3 gg dovuto al
volume di acqua iniettato.
43
A. Redaelli
Non si tratta del risultato voluto. Solo in seguito
si manifesta il riempimento tard i v o, che appare
durante le successive sedute con risultato definitivo almeno 3-4 mesi dopo l’ultima seduta, frutto della stimolazione della neocollagenesi.
La maggioranza dei grandi utilizzatori ed anche
l’Autore, prevedono sedute successive: generalmente le prime sedute sono a distanza di 30-40
giorni, ma in alcune pazienti anche solo una
seduta può essere sufficiente.
Viene sempre completamente discusso e firmato un consenso informato scritto.
I pazienti vengono fotografati, studiati in modo
approfondito e disegnati prima del trattamento
per decidere accuratamente dove eseguire l’impianto e in che quantitativo. Quindi anche in
questo caso la prudenza e la gradualità sono da
raccomandare.
Le iniezioni devono essere sempre profonde,
ma la reale profondità è determinata dalla zona
da trattare: più si correggono grossi volumi più
si inietta profondamente e poco diluiti.
Sicuramente il derma superficiale e medio non
vanno mai iniettati, ma anche nel derma
profondo è meglio iniettare dopo una discreta
esperienza.
Normalmente l’Autore raccomanda di non iniett a re più di 0,1 ml per ogni iniezione preferendo
fare il maggior numero di iniezioni possibili per
raggiungere l’effetto riempitivo desiderato.
Nelle zone difficili e quanto più il medico è alle
prime esperienze, tanto più è meglio iniettare
quantitativi ancora inferiori, 0,05 ml.
Un lungo massaggio al termine della seduta, di
almeno 5-7 minuti resta assolutamente irrinunciabile. Non va demandato a personale non
opportunamente addestrato.
Anche i pazienti, nei giorni seguenti, sono
istruiti per fare nelle zone trattate un massaggio
di 5 minuti due volte al giorno.
Nuove indicazioni
Distretto del bordo mandibolare
e zona intermandibolare
Attenuare la caduta dell’area della guancia che
crea a livello del bordo mandibolare quella classica ptosi, resta un ottima indicazione del PLLA.
Ma l’Autore sempre più di frequente allarga l’area trattata anche al distretto intermandibolare.
Infatti questo tende col tempo alla ptosi ed inoltre in moltissimi casi crea quel difetto chiamato
doppio mento non per problemi di adipe ma
per problemi di cedimento. In questi casi il
PLLA trova sicuramente indicazione.
44
Figura 2.
La diluizione di base è 6 ml e le iniezioni prevedono un quantitativo di 0,1 ml ciascuna.
La tecnica iniettiva è sempre lineare retrograda
e va eseguita secondo il vettore principale di
trazione che poi darà quell’effetto lifting caratteristico (Figura 2).
Collo e décolleté
Il collo non va trattato se il sottocutaneo è poco
rappresentato, se la cute è sottile e se la mimica
eccessiva.
Al contrario trovano ottima indicazione i
pazienti con cute spessa e sottocute ben rappresentato e con profonde collane di venere. Non
trovano indicazione le bande platismatiche
ipertrofiche.
Sul collo si seguono sempre i vettori anche se
qualche iniezione è meglio sia intersecata.
Inoltre va trattato, come di norma, tutto il
distretto e mai le singole rughe.
Il décolleté viene trattato con iniezioni sempre
nel sottocute e sempre quando questo è di
discreto spessore.
Bisogna evitare iniezioni solo nelle rughe verticali ma trattare tutto il distretto a tappeto.
La diluizione usata resta quella standard di 6 ml.
A volte, se la cute non è molto spessa, è possibile usare una diluizione maggiore anche ad 8 ml.
Il quantitativo di liquido da iniettare per ogni
iniezione invece deve essere prudenziale e non
superare gli 0,05 ml. Di regola inoltre la diluizione viene fatta almeno 24 ore prima per permettere una migliore idratazione del principio attivo.
Mani
Anche le mani trovano, a parere dell’Autore,
un’ottima indicazione: sino ad oggi, infatti, le tecniche a disposizione per questo problema, erano
pochissime:
1. il lipofilling di Coleman, tecnica molto efficace,
ma sicuramente chirurgica e non all’altezza
della maggior parte dei medici estetici;
2. i filler riassorbibili a maggiore reticolazione,
ma di durata limitata. Inoltre se iniettati in strato spesso possono trasparire attraverso la cute
e dare un colorito bluastro (ghiaccio) assai inestetico;
3. il PLLA, che è probabilmente l’unica alternativa, con risultati di lunga durata e grande naturalezza.
La diluizione di base resta sempre 6 ml e le iniezioni devono prevedere un quantitativo massimo
di liquido di 0,05 ml.
La tecnica utilizzata dall’Autore è sempre lineare
retrograda, ma anche una tecnica a micro depositi molto ravvicinati, seguita dal solito lungo massaggio è fattibile.
Rivitalizzazione
Questo termine normalmente non è indicato per
il PLLA che per definizione provoca una bioristrutturazione e non una biorivitalizzazione.
Ma in alcune ampie zone che tendono col tempo
a cedere e divenire ptosiche come l’interno delle
braccia e delle cosce, è stata messa a punto questa
nuova tecnica con risultati soddisfacenti.
La diluizione è particolare: infatti ad un ml della
normale diluizione (fatta con 6 ml) si aggiungono
3 ml di acqua per preparazioni iniettabili. Alla
fine quindi abbiamo 4 ml totali col quantitativo di
principio attivo di 1 ml.
Questa sospensione meno concentrata viene utilizzata per eseguire gli impianti a livello delle aree
da rivitalizzare. Si utilizza una tecnica a rete con
maglie di circa 1 cm con tecnica lineare retrograda prima in un senso ed infine in quello ortogonale.
Questa tecnica si è rivelata soprattutto utile nella
prevenzione della ptosi per l’azione del collagene
fibrotico che si forma e fornisce un sostegno assai
utile, soprattutto nel tempo.
Cicatrici profonde ed esiti ascessuali
Molte pazienti hanno richiesto la regolarizzazione
di cicatrici. Normalmente, anche sul volto, questa
resta un’ottima indicazione. Ma rispondono bene
anche esiti ascessuali introflessi del gluteo.
La diluizione usata è quella classica con 6 ml e i
quantitativi di principio attivo da iniettare sono
elevati. Per gli esiti ascessuali, l’Autore usa quasi
sempre tutti i 150 mg.
Al termine della seduta è molto importante fare
un lungo massaggio per uniformare l’impianto.
Sempre, comunque, ai pazienti è richiesto di fare
un massaggio di 5 minuti due volte al giorno per
una decina di giorn i .
Inoltre si consiglia di evitare l’esposizione al sole
per almeno 15 giorni.
e discussione
RisultatiBisogna
dire, dopo un’esperienza ormai
decennale nell’uso del PLLA, che il gradimento
dei pazienti è sempre molto alto: sia per gli ottimi
risultati che si ottengono nel tempo, sia perché i
pazienti sono stati accuratamente selezionati, evitando di trattare quei pazienti che preferiscono
risultati immediati.
Inoltre è da sottolineare che il risultato del PLLA
migliora nettamente nei mesi e non è infrequente
rivedere un paziente dopo molti mesi dall’ultima
seduta e trovarlo ulteriormente e nettamente
migliorato. Infatti anche il derma tende col tempo
a compattarsi e la cute sovrastante a distendersi.
I risultati migliori si confermano nel terzo inferiore del volto: zigomi, guance e solchi della marionetta hanno sempre risultati ottimi.
Per quanto attiene alla correzione degli zigomi e
della regione malare, non sono assolutamente
comparabili i risultati ottenibili con altri materiali come l’acido ialuronico a macroparticelle, o
anche i materiali non riassorbibili che non pre v edono una fine integrazione con il tessuto ospite.
Restano impianti visibili e non naturali soprattutto durante i movimenti: pensiamo allo zigomo
durante il sorriso.
L’impianto di PLLA invece è sempre assolutamente naturale ed intimamente integrato coi tessuti
circostanti.
Questo lo rende un materiale molto ben accettato
anche dagli uomini che normalmente non accettano correzioni se non estremamente naturali.
Anche i solchi naso genieni, spesso, danno risultati insperati (Figure 3 e 4).
Un’ottima indicazione resta la paziente giovane,
molto magra, che vorrebbe apparire appena più
grassa soprattutto nel viso, ma non vi riesce assolutamente. I risultati, anche in questo caso, sono
molto naturali (Figure 5 e 6) ed ottenibili con un
numero di sedute molto limitato.
Restano invece zone pericolose tutte quelle mimi-
45
A. Redaelli
che e con scarsa rappresentazione del tessuto sottocutaneo come fronte, zona del canto laterale e
temporale, anche se questa indicazione è proposta da alcuni grandi utilizzatori. La loro esperienza non è da paragonare a quella della media dei
colleghi. Meglio evitare rischi. In queste zone con
sottocute poco rappresentato e cute sottile un
minimo iperdosaggio potrebbe essere molto visibile. Molto buono è il risultato sul bordo mandibolare se soprattutto integrato dal distretto intermandibolare.
Si osserva sempre una netta regolarizzazione del
bordo con una apparente risalita (vedi Figura 4).
Resta fondamentale eseguire delle fotografie accurate ma soprattutto standardizzate dei pazienti.
L’Autore esegue di regola 5 foto: la prima in antero-posteriore, indi a 45° destra e sinistra e di profilo destro e sinistro. Inoltre, nelle foto laterali
viene sempre rispettato il piano di Frankfort, che
permette di mantenere le medesime inclinazioni e
rendere le foto comparabili nel tempo (Figura 7).
Senza fotografie ben fatte sarà molto difficile valu-
tare i risultati nel tempo e discuterli con il paziente. Per quanto riguarda le nuove indicazioni, sicuramente sono necessari ulteriori esperienze e
studi scientifici e statistici più accurati per poter
valutare risultati ed effetti collaterali.
Ad oggi, secondo l’esperienza dell’Autore non si
sono riscontrati effetti collaterali maggiori e pericolosi. In particolare i noduli non sono mai stati
riscontrati negli ultimi anni.
Questo dato è sicuramente in relazione anche con
la decisione della ditta distributrice di non vendere il prodotto se non a medici che hanno frequentato un corso di apprendimento dedicato.
Questo ha permesso di ridurre la frequenza degli
errori di tecnica a limiti prossimi allo zero.
ni
ConcluLasioriduzione
dei volumi e la perdita di
tonicità e compattezza del derma sono divenuti
negli ultimi anni aspetti della correzione estetica
DOPO
PRIMA
46
Figura 3.
Figura 4.
Figura 5.
Figura 6.
Figura 7. Piano di Frankfort.
di grandissima importanza. Inoltre, ad un periodo in cui alcuni colleghi ed alcuni media privilegiavano correzioni a volte un poco esagerate e
non naturali, ne è seguito un altro ove la correzione naturale ed assolutamente non visibile ha
p reso il sopravvento. Sicuramente i migliori
risultati si ottengono dalla integrazione delle
Letture consigliate
t e cniche, ed in questo senso la fibroristrutturazione mediante PLLA non può non essere conosciuta da ogni medico estetico che desideri essere completo.
Il PLLA, a parere dell’Autore, è un materiale
molto versatile, che presenta caratteristiche che
lo rendono unico: in particolare la possibilità di
diversificarne la preparazione a seconda delle
indicazioni resta un aspetto molto interessante.
I risultati nel terzo inferiore del volto si confermano ottimi e molto naturali.
I risultati nelle indicazioni emergenti dovranno
essere confermati con studi scientifici, ma i
risultati preliminari sono sicuramente incoraggianti.
Anche la drastica riduzione degli effetti collaterali maggiori, i noduli, sicuramente dovuti ad
errori tecnici soprattutto nei primi anni di utilizzo del PLLA, conferma che la strada intrapresa è
quella giusta. Il training divenuto obbligatorio
per i medici utilizzatori in tutto il mondo deciso
dalla ditta distributrice è stata la scelta giusta per
un materiale di grande impatto estetico.
1. Apikian M. Adverse reactions to polylactic
acid injections in the periorbital area. J Cosmet Dermatol
2007; 6:95
13. Morgan AM. Localized reactions to injected therapeutic materials. Part 2. Surgical agents. J Cutan Pathol 1995;
22:289
2. BETA. New fill to treat facial wasting. Spring 2002;
15:10
14. Redaelli A. Cosmetic use of polylactic acid for hand
rejuvenation: report on 27 patients. J Cosmet Dermatol
2006; 5:233
3. Berry J. New-Fill for an old face. Posit Aware 2002; 13:34
4. Berger DS. New facial filling treatment for lipodystrophy.
Posit Aware 2001; 12:17
5. Boix V. Polylactic acid implants. A new smile for lipoatrophic faces? AIDS 2003; 21; 17:2471
6. Clarke DP. Dermal implants: safety of products injected
for soft tissue augmentation. J Am Acad Dermatol 1989;
21:992
7. Kronenthal R.L. Biodegradabile Polymers in medicine
and surgery. Polym Sci Tecnol 1975; 8:120
8. Kulkarni RK. Polylactic acid for surgical implants. Arch
Surg 1966; 93:839
9. Laglenne S. Le new fill. Objectif peau 2000; 8:58
10. Laglenne S. Un noveau produit de comblement des
rides, entirerment resorbable. Dermatologie 2000; 54:30
11. Lombardi T. Orofacial granulomas after injection of
cosmetic fillers. Histopathologic and clinical study of 11
cases. J Oral Pathol Med 2004; 33:115
12. Moran JM, Pazzano D, Bonassar LJ. Characterization
of polylactic Acid-polyglycolic Acid composites for cartilage
tissue engineering. Tissue Eng 2003; 9:63
15. Redaelli A. Uso cosmetico dell’acido polilattico per il
ringiovanimento cutaneo: revisione della nostra casistica su
398 pazienti. La Medicina Estetica, 29, 3, luglio/sett 2005
439
16. Robert P. Biocompatibility and resorbability of a polylactic acid membrane for periodontal guided tissue regeneration. Biomaterials 1993; 14:353
17. Rudolph CM. Foreign body granulomas due to
injectable aesthetic microimplants. Am J Surg Pathol 1999;
23:113
18. Surma J. Il ringiovanimento del viso con le tecniche
combinate: peeling TCA, Botox e iniezioni di New Fill.
Congresso Nazionale di Medicina Estetica. Milano 11-13
Ottobre 2002
19. Valantin MA, et al. Polylactic acid implants (New-Fill)
to correct facial lipoatrophy in HIV-infected patients:
results of the open-label study VEGA. AIDS 2003; 17:2533
20. Vleggaar D. Facial enhancement and the European
experience with Sculptra. J Drug Derm 2004; 542
21. Vleggaar D. Facial Volumetric Correction with
Injectable Poly-l-Lactic Acid Dermatologic Surgery 2005;
31 (s4), 1511
47
Fifth International Congress of Hair Research, Vancouver
The reflectance confocal microscopy
in the study of hair follicle pigmentary unit
Fabio Rinaldi
Giammaria Giuliani
SU M M A R Y
The reflectance confocal microscopy in
the study of hair follicle pigmentary unit
In this study we evaluated the imaging of hair follicle pigmentary unit using a
Reflectance Confocal Microscopy (RCM) in pigmented and white hair in early canities.
We used this imaging technique to test the effects of five active principles on anagen prolongation and melanocyte function.
KEY WORDS: Reflectance confocal microscopy, Hair follicle, Canities
Introduction
Hair graying is an evident
sign of human aging, and little is
known about its causes. The activity
of melanocyte in the hair matrix is
under hair follicle cyclical control,
where anagen and melanogenesys are
tightly coupled, in the so-called pigmentary unit.
Melanocytes in the hair bulb are terminally diff e rentiated and die in early
catagen via apoptosis.
In canities it is possible to show the
alteration in keratinocyte differe n t i ation and proliferation and pigment
loss. It is not infrequent to see spontaneous repigmentation in hair shaft
in early canities, or in hair shaft
during a pharmacological treatment
in androgenic alopecia.
In this study we evaluated the imaging of hair follicle pigmentary unit
using a Reflectance Confocal
M i c roscopy (RCM) in pigmented and
white hair in early canities. We used
this imaging technique to test the
e ffects of five active principles on
anagen prolongation and melanocyte
function.
Confocal
Reflectance
Microscopy (RCM)
The principle of RCM involves the use of a point source of light
(near-infrared laser, 800 – 1064 nm)
International Hair Research Fo u n d a t i o n
Milan, Italy
49
that illuminates a small spot within
tissue.
The reflected light (Reflectance) is
then imaged onto a detector after passing through a small pinhole, and
only the region of the specimen that is
on focus (Confocal) is detected, in a
very thin horizontal tissue plane
(Microscopy).
Near-infrared wavelengths produce
strong back-scattering from melanoso-
mes, despite melanin absorption,
because they have a high refractive
index. This means that cells containing melanin, such as melanocytes,
image brightly.
RMC offers a very important contribution to medical research in vivo and
clinical care for scalp physiology and
diseases.
RMC is a valid imaging technique to
study hair follicle pigmentary unit.
pigmentary unit in
RMC aofpigmented
hair follicle
In hair bulb, melanin provides strong contrast:
1) its refractive index of approximately 1.7 near 600 nm significantly
exceeds that of the surrounding
cytoplasm;
2) within keratinocytes, melanin granules are packaged in melanoso-
Anagen phase
ORS melanocytes
Matrix melanocyte
Keratinocytes
Dermal papilla melanocyte
Pigmented hair
Anagen phase
Pigmented hair
Catagen phase
Melanocytes are usually round
or oval
but
Fusiform
or dendritic shapes
are recognized
50
Melanocytes decreased, size reduced
F. Rinaldi, G. Giuliani
Pigmented hair
Telogen phase
White hair
Anagen phase
Melanocytes disappeared
Few melanocytes, less brightly
Androgenic alopecia
Vitiligo
Anagen phase
Dystrophic anagen
Keratinocytes
Melanocytes decreased
Lack of melanocytes
mes, whose size of approximately
0.6-1.3 µm is nearly equal to wavelength.
trial, randomize,
Clinicaldouble
blind test
60 men suffered from androgenic alopecia and early canities,
voluntaries, were divided in 5 groups
of 12 subjects each.In every group, 6
subjects received a topic liposomial
mask with active ingredients, 6
subjects a placebo mask. Each subject
had to put 2 grams of the mask on
the scalp, rinsing out after 15 minutes, every three days for 1 month
before hair transplant, and 2 months
after. We studied the modification of
white hair by digital images, dermoscopic evaluation, RCM in a defined
area (tattoo) of the parietal scalp, at
basal line and after 2 (t1) and 4 (t2)
months.
The tested active principles, in liposomes, were
1) Kelline
2%
2) SOD
4%
3) Fenilalanine
2%
4) Parrotine
1%
5) Emblica Officinalis
5%
Reduction of graying hair
250
Placebo
200
Emblica o.
150
Parrotine
100
Fenialan
SOD
50
Kelline
0
White hair treated
New melanocytes in ORS
Melanocytes increased in DP
t0
t1
t2
51
Results65% (average) of the
subjects treated with kelline, fenilalanina and parrotine had a significative
increase in pigmented hair (from
basal line to T2) respect all placebo
groups (p< 0.01), as graphic shows.
Conclusion
In our opinion, RMC is a
valid and easy imaging technique to
study scalp physiology and diseases in
vivo, and also the hair follicle pigmentary unit. Images of hair growth
cycle can be well highlighted, and
melanin pigment has been found to
provide a natural contrast for confocal
scanning.
RMC can show any modification of
hair follicle pigmentary unit in normal, aging, and pathological hair, and
it sets a new paradigm of instant quasihistologic examination of hair, better
than the light microscopy.
We used RMC to evaluate the efficacy
of 5 active principles to treat early
canities, comparing this data with traditional techniques (digital images,
dermoscopic evaluation) used in clinical trials. The evidence of melanocytes
in hair matrix, dermal papilla and
ORS can help to better objective the
real efficacy of a topical treatment.
Lectures
Rinaldi F, Sorbellini E. Tricocosmetology 2005: Poletto Editore
Rinaldi F, Sorbellini E, et al. Reflectance
Confocal Microscopy: New diagnostic technique
52
in the efficacy evaluation of hair cosmetics.
Cosmetic Technology 2005; 5:9
Tobin DJ, Paus R. Graying: gerontobiology of the
hair follicle pigmentary unit. Exp Gero n t o l
2001; 36:29
Sharov A et al. Changes in different melanocyte
population during hair follicle involution (catagen). J Invest Dermatol 2005; 125: 1259
Rajadhyaksha M et al. In vivo confocal scanning
laser microscopy of human skin: melanin provides strong contrast. J Invest Dermatol 1995;
104: 946
Ambulatorio sarcoma di Kaposi: racconto
dell’incontro con una patologia e di una
esperienza medica durata 30 anni
Lucia Brambilla
Vinicio Boneschi
SU M M A R Y
Kaposi’s sarcoma: Story of a 30-year
clinical experience
Kaposi’s sarcoma is a rare angioproliferative tumour derived from endothelial cells.
For almost 30 years, two dermatologists have been dedicating their professional life
to the study of this disorder, and more precisely to its viral, immunological and therapeutic aspects. Their experience, based on the evaluation and treatment of 710
patients with classic or iatrogenic Kaposi’s sarcoma in a dedicated outpatient service,
led them to the proposal of a clinical classification and a variety of effective appro a c hes for treating this disease. Much of this large experience has been gained by collaborating with other clinicians and researchers, and the hope is that the results of these
precious interactions will be even more brilliant in the future.
KEY WORDS: Kaposi’s sarcoma
Introduzione
Il sarcoma di Kaposi (SK) è un tumore vascolare maligno che colpisce prevalentemente la cute sotto forma di noduli o placche
violacee intensamente vascolarizzate, ma anche
raramente le mucose e gli organi interni, ed è
caratterizzato da una proliferazione tumorale di
cellule endoteliali. Il virus HHV8 è presente nel
100% delle lesioni sarcomatose delle quattro
varianti conosciute del SK: variante classica,
africana, iatrogena e HIV-correlata. Nel presente scritto si tratta delle varianti classica e iatrogena raccolte nella casistica più numerosa
attualmente descritta, e si racconta l’esperienza
trentennale dell’ambulatorio dedicato al SK.
Storia Anno 1979: nel salone a sedici letti
della Seconda Clinica Dermatologica del Policlinico
di Milano, diretta dal Prof. Piero Caccialanza prima
e dal Prof. Aldo Finzi poi, un paziente ricoverato
aveva attirato il nostro interesse sia per la presentazione clinica che per il nome della malattia di
cui soffriva da alcuni anni: morbo di Kaposi.
Malattia misteriosa e strana, da alcuni chiamata
anche sarcoma, di presentazione rara ma non
tanto, che a dispetto del suo nome veniva descritta a decorso lento e indolente, a volte spontaneamente regressivo, e che proprio per questo, anche
in considerazione della mancanza di valide terapie, i vecchi dermatologi lasciavano al suo decorso naturale: neppure le creme, gli unguenti e le
paste di vari colori che erano in bella vista sul carrello delle medicazioni riuscivano a modificarn e
quanto meno l’aspetto dando l’illusione di un’azione terapeutica. Il SK, con il suo decorso lento
e indolente e la localizzazione alle mani e piedi,
aveva però tolto al signor Alfredo, settantenne in
buona salute generale, la gioia di vivere che traeva dalla cura dell’orto: non riusciva più a impugnare con vigoria vanga e zappa né a stare a lungo
in piedi. In verità qualche terapia medica si attuava in tali pazienti, con estratti di avocado e soia
per os o penicillina endovena, spesso con risultati nulli o a volte con concomitante miglioramento spontaneo; la plesioroentgenterapia, unico
valido strumento per far regredire le manifestazioni di aspetto più aggressivo, non era scevra da
complicanze precoci o tardive, anche peggiori
Istituto di Scienze Dermatologiche,
Fondazione IRCCS Ospedale Maggiore Policlinico,
Mangiagalli e Regina Elena
Milano
55
L. Brambilla, V. Boneschi
della malattia stessa se impiegata da operatori con
non vasta esperienza per mancanza di casistica.
Eppure per i sarcomi veri l’approccio era ed è chirurgico e/o oncologico; esclusa la chirurgia, che
non poteva certo togliere le placche infiltrative
alle palme e piante, non poteva essere d’utilità
una chemioterapia per il signor Alfredo? “Ma alla
sua età come può affrontare cicli di chemioterapia
sicuramente tossici e dall’esito incerto, più perniciosi
della malattia stessa?”
La domanda che veniva posta dai colleghi più
anziani aveva di certo un suo fondamento, era
quindi necessario consultare un oncologo esperto. In quegli anni al Policlinico era consulente
oncologo il Prof. Gino Luporini e con lui e il suo
staff che operava all’Ospedale San Carlo (Gianni
Beretta, Maurizia Clerici, Roberto Labianca) furono
presi accordi per affrontare il problema. La scelta
del chemioterapico cadde sugli alcaloidi della
vinca 1, 2 per la loro maneggevolezza, basso costo
ed esperienza d’uso. La vincristina per via sistemica venne scartata per effetti negativi in particolare neuropatici mentre si confermò eccellente nel
suo impiego intralesionale in noduli esofitici 3,4
(Figure 1a e b).
Con la vinblastina endovena 1,5 si ottennero i
primi buoni risultati con effetti collaterali accettabili: il signor Alfredo tornò a lavorare nel suo
orto e questo gli diede lo slancio per continuare a frequentare per altri vent’anni in buon compenso psico-fisico il nostro ambulatorio dedicato al “morbo” (Figure 2a e b).
Morbo che non finiva di stupire e interessare in
quanto i colleghi nefrologi e chirurghi, e di riflesso i dermatologi, dal 1969 si andavano sempre
più imbattendo in una complicanza terribile che
metteva in pericolo la vita dei trapiantati renali in
terapia immunosoppressiva, in particolare se
effettuata con ciclosporina: una variante a volte
particolarmente aggressiva e disseminata del SK,
accompagnata da interessamento viscerale, scarsamente o nulla responsiva alle chemioterapie che
venivano tentate se non si riusciva a ridurre la
s o p p ressione immunitaria. Inoltre erano del
marzo 1981 le prime segnalazioni negli Stati
Uniti della sconcertante associazione tra gravi
infezioni opportuniste e SK nei gruppi di pazienti omosessuali.
La nostra conoscenza del morbo nella sua variante mediterranea stava avvenendo quindi in anni
che avrebbero imposto all’attenzione di specialisti
di molte branche una malattia cutanea che pareva, per la sua relativa rarità e circoscrizione a
pochi gruppi etnici (popolazioni del bacino del
56
Figura 1a.
Nodulo
di Sarcoma di Kaposi
all’indice sinistro.
Figura 1b.
Dopo infiltrazione
con vincristina solfato.
Figura 2a.
La mano
del signor Alfredo
con placche infiltrative
di sarcoma di Kaposi.
Figura 2b.
Dopo chemioterapia
sistemica con vinblastina.
Ambulatorio sarcoma di Kaposi: racconto dell’incontro con una patologia e di una esperienza medica durata 30 anni
Mediterraneo, Africani della fascia sub-sahariana
affetti da una forma endemica del bambino e dell’adulto), destinata a re s t a re quasi una curiosità di
nicchia.
Per molti anni le somministrazioni di chemioterapici sono state da noi effettuate senza ausilio
infermieristico in una piccola stanza messa a
disposizione dal Prof. Finzi: tale terapia era fuori
dagli schemi curativi della tradizione dermatologica e molte furono le resistenze, sia da parte
degli infermieri che di alcuni colleghi e scuole
dermatologiche. In alcuni casi le critiche ci
hanno spronato non solo a cerc a re farmaci singoli o in associazione di più rapida efficacia e
migliore tollerabilità e compliance, ma anche di
formulare criteri oggettivi in base ai quali poter
decidere quando e come iniziare la terapia sistemica; abbiamo quindi proposto una stadiazione
per la malattia di Kaposi classica che riteniamo di
valido aiuto per impostare la terapia 6 (Tabella 1).
In tale lavoro di messa a punto siamo stati
affiancati per molti anni da altri colleghi dermatologi preziosi per il loro entusiasmo e spirito di collaborazione, tra cui Silvia Fossati e Silvia
F e rrucci, entrambe ora assistenti di ruolo,
rispettivamente all’Ospedale di Gallarate e al
Policlinico di Milano, nonché da laureandi, borsisti e specializzandi che hanno svolto le loro
tesi su vari aspetti del SK.
Nel frattempo da altri centri e regioni cominciavano ad affluire pazienti e arrivavano richieste di collaborazione. Di pari passo quindi con
l’aumento del numero dei pazienti seguiti e, se
necessario, trattati, si sono andate moltiplicando le pubblicazioni sull’argomento, sia in
campo nazionale che internazionale. 7-14
Sull’onda del rinnovato interesse per la malattia
inoltre sono degli anni ottanta e novanta gli
studi immunologici ed istologici anche correlati all’influenza della chemioterapia nonché
quelli genetici, in particolare nei rari casi di
familiarità, ed epidemiologici condotti con varie
scuole di immunologi e infettivologi. 15-25
Un successivo forte stimolo allo studio della
nostra popolazione di pazienti, che nel frattempo aveva superato le duecento unità a metà
degli anni novanta, arrivò nel 1994 con la scoperta del virus erpetico correlato al SK, HHV8,
da parte di Chang e Moore.
Con il contributo fondamentale del Prof. Emilio
Berti, e in collaborazione con Carlo Parravicini e
Mario Corbellino, rispettivamente patologo e
infettivologo dell’Ospedale Sacco di Milano,
furono messe a punto le prime indagini anticorpali sui nostri pazienti con la variante classica e su quelli trapiantati di rene e in attesa di
trapianto seguiti dai colleghi nefrologi e chirurghi. Tali indagini hanno permesso la pubblicazione su riviste internazionali tra gli anni
novanta e duemila di studi epidemiologici e
patogenetici riguardanti l’HHV8. 26-30
Ha fatto seguito nel 2002 la collaborazione con
l ’Istituto Superiore di Sanità per un protocollo terapeutico che ha previsto l’uso della terapia antiretrovirale; tale collaborazione ci ha permesso di
diventare uno dei Centri di riferimento nazionale per la malattia: molti oncologi e dermatologi ci
affidano ora i loro pazienti, così che siamo ora ad
una casistica di 710 pazienti, la più numerosa
mai raccolta e seguita nel mondo.
Un altro lavoro partirà tra poco, sempre con
l ’Istituto Superiore di Sanità per l’uso dell’associazione di uno dei nostri protocolli di chemioterapia 31 con la terapia antiretrovirale.
Dagli Stati Uniti è stata richiesta dal Pro f .
Goedert, tramite la Lega Italiana per la Lotta contro i Tumori di Ragusa (dott.ssa Lina Lauria), la
nostra collaborazione per verificare l’efficacia di
una terapia transdermica che potesse servire
come terapia domiciliare per le forme nodulari
o in placca meno impegnative. 32
La constatazione che l’HHV8 sia necessario ma
Aspetto clinico
Lesioni prevalenti
Comportamento
Evoluzione
Complicanze
1. Nodulare
Noduli e/o macule
Non aggressivo
Linfedema
2. Infiltrativo
(± v)
3. Florido
(± v)
4. Generalizzato
(± v)
Placche infiltrative
Localmente aggressivo
Noduli placche angiomatose
e/o vegetanti
Noduli placche angiomatose
e/o vegetanti
Localmente aggressivo
Lenta (a)
Veloce (b)
Lenta (a)
Veloce (b)
Lenta (a)
Veloce (b)
Lenta (a)
Veloce (b)
Disseminato aggressivo
Linforragia, Emorragia
Dolore, Ulcerazioni
Impotenza funzionale
Tabella 1. Stadiazione del sarcoma di Kaposi classico.
57
Terapia
Somministrazione
N° pazienti
trattati
(tot= 294)
Pazienti
con remissione
completa o parziale
Interferone
3 milioni IU 3 v/sett
21
75%
Vinblastina
Induzione: 4, 6, 8 mg e.v. sett.
Mantenimento: 10 mg e.v. ogni 3 sett.
83
60%
Vinblastina +
Bleomicina
Vinblastina (schema precedente)
Bleomicina 15 mg i.m.
ogni 3 sett. dal termine dell’induzione
56
99%
Induzione: 17,5 mg/m2 ogni 2 sett.
per 5 somministrazioni
Mantenimento: 29 mg/m2 ogni 3 sett.
16
66%
Vinorelbina
150 mg/die per 3 gg ogni 3 sett. e.v.
23
55%
Etoposide
100 mg /m2 die per 3-5 giorni
ogni 3 sett. per os.
36
65%
Epirubicina
20 mg e.v. sett
10
50%
Paclitaxel
100 mg/sett.
22
91%
2
Gemcitabina
1200 mg/m e.v./sett. per 2 sett.
seguiti da una di intervallo
21
100%
Doxorubicina
liposomiale
20 mg/m2 ogni 3 sett.
6
100%
Tabella 2. Esperienza su 294 pazienti affetti da sarcoma di Kaposi classico e trattati con chemioterapia sistemica.
non sufficiente per l’insorgenza della malattia
ha stimolato molti studi in campo immunologico, virologico e genetico. È proprio in questi
ambiti che si sono sviluppate le nostre collaborazioni con l’IRCCS Fondazione Don Gnocchi di
Milano (Roberta Mancuso e Mario Clerici) e il
Laboratorio di Immunologia del Dipartimento di
Scienze e Tecnologie Biomediche dell’Università di
Milano (Mario Clerici, Maria L. Villa, Silvia Della
Bella) che hanno portato ad ulteriori pubblicazioni. 33-35
L’ultimo studio pubblicato dimostra che le cellule progenitrici endoteliali, presenti nel sangue
periferico di pazienti con SK, sono stabilmente
infettate con l’HHV8; sono quindi un potenziale reservoir del virus in grado di determinare,
localizzandosi in sedi permissive, l’insorgenza
simultanea o in tempi diversi delle lesioni di SK
in vari distretti corporei.36
Questa evidenza apre nuove prospettive in campo
diagnostico e forse a più lungo termine in campo
terapeutico.
Il nostro impegno con le scienze biomediche non
ci ha mai fatto comunque perdere di vista il rapporto diretto con i pazienti ed in particolare l’aspetto terapeutico; confluiti dal 2003 nell’Istituto
di Scienze Dermatologiche, la nostra attività è pro-
58
seguita sotto la guida del Prof. Ruggero Caputo e
prosegue ora sotto quella del Prof. Carlo Crosti di
cui abbiamo già apprezzato il vivo interessamento. Ultimamente poi abbiamo alcune giovani
forze collaborative nel nostro gruppo: dottorandi
di ricerca (Monica Bellinvia) e borsisti (Athanasia
Tourlaki e Bianca Maria Scoppio). Né si è mai interrotta la collaborazione con il gruppo oncologico
di Lucilla Tedeschi, Antonella Romanelli e Aurora
Miedico dell’Ospedale San Carlo di Milano che ci ha
permesso di elaborare algoritmi terapeutici basati
su schemi di chemioterapia che tengano conto
della fragilità dei nostri pazienti, spesso anziani e
afflitti da patologie sistemiche 31, 37 (Tabella 2).
Sempre in ambito terapeutico il nostro interesse è stato attirato dalla possibilità di effettuare
l’elastocompressione di segmenti di arti resi linfedematosi dalla malattia mediante calze e
guanti confezionati su misura e periodicamente
riadattati in base al variare delle dimensioni
degli arti stessi; l’alleggerimento della stasi linfatica così ottenuto non solo ha beneficio sul
t rofismo cutaneo in generale, ma permette
anche di stabilizzare o migliorare la malattia
senza necessità di ricorrere a terapie sistemiche,
con influenza positiva anche dal punto di vista
psicologico. 38
Ambulatorio sarcoma di Kaposi: racconto dell’incontro con una patologia e di una esperienza medica durata 30 anni
Quest’ultimo approccio al malato di Kaposi classico ribadisce la nostra convinzione, che in parte
si ricollega al comportamento dei dermatologi di
vecchia scuola, che spesso ci si può astenere da
terapie aggressive e limitarsi a ridurre l’eventuale
linfedema, ad effettuare piccole infiltrazioni intralesionali di vincristina, a eliminare i fattori favorenti (steroidi, immunosoppressori) o a condurre
un semplice follow-up; le terapie sistemiche a
nostro avviso vanno iniziate con l’intento non
solo se possibile di ottenere la remissione della
malattia, ma soprattutto di migliorare la qualità di
vita di pazienti anziani.
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L. Immunologic and immunogenetic features of primary
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16. Brambilla L, Boneschi V, Melotti E, Marinig C. Significance of genetic factors in familial Kaposi’s sarcoma. Report
of two cases. Ann It Derm Clin Sper 1985; 39:193-201
17. Brambilla L, Boneschi V, Melotti E, Hepeisen SM.
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1986; 6:25-28
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Gen Rev Derm 1986; 23:34
19. Brambilla L, Boneschi V, Pigatto P, Finzi AF, Marinig C,
Renoldi P, Fiorini GF. Histological and immunological features
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20. Brambilla L, Fiorini GF, Chianese R, Boneschi V, Parini
F, Fossati S. Immunological modifications in primari
Kaposi’s sarcoma before and after chemotherapy It Gen Rev
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21. Brambilla L, Boneschi V, De Blasio A, Chiappino G,
Mellotti E, Hepeisen S: Sarcoma di Kaposi mediterraneo,
Patologie associate in una casistica di 100 pazienti Giorn It
Derm Ven 1988; 123:477-480
22. Brambilla L, Chianese R, Bernasconi P, Parini F,
Gagliano MG, Fiorini GF: Alterations of In-Vi t ro
Lymphocyte Proliferation and Immunoglobulin Production
in Primary Kaposi’s Sarcoma Ann It Derm Clin Sper 1988;
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23. Brambilla L, Vanoli M, Chiappino G, Della Bella S,
Coppola C, Boneschi V, Finzi AF: Mediterranean Kaposi’s
Sarcoma: interleukin production and HLA antigens. J
Investigative Derm 1989; 93:543
24. V. Toschi, L. Brambilla, A. Motta, R .Remoldi, P.A.
Giarola, C. Castelli, A. Gibelli: Livelli plasmatici di fattore
VIII antigene e fibronectina in pazienti con sarcoma di
Kaposi primitivo Acta Gerontol 1989; 39:93-97
25. Fossati S, Boneschi V, Ferrucci S, Brambilla L: Human
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27. Corbellino M, Bestetti G, Poirel L, Aubin J-T, Brambilla
L, Pizzutto M, Capra M, Berti E, Galli M, Parravicini C. Is
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S, Presicce P, Boneschi V, Berti E, Villa ML. Quantitative
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34. Guerini F, Agliardi C, Mancuso R, Brambilla L, Biffi R,
F e rrucci S, Zanetta L, Zanzottera M, Brambati M,
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Parravicini C, Fossati S. Human Herpesvirus 8 DNA in the
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ML, Della Bella S. Circulating endothelial progenitor cells
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www.isplad.org
61
I principi attivi antiaging nei prodotti
cosmetici. Le sfide
(Seconda di due parti)
Piera Fileccia
SU M M A R Y
Anti-aging principles into
cosmetic products. The challenges
New anti-aging cosmetic proposals are linked with our updates on wound healing.
New antioxidants strongly reduce ROS generation in epidermis and dermis, so blocking dermis degradation. Growth factors actively stimulate dermal remodeling phase
(the key to reverse the visible signs of aging) and peptides carry enzymatic cofactors,
usually copper, and reduce subconscious muscle movement over time.
KEY WORDS: Aging, Antioxidants, Peptides, Growth factors
Introduzione
L’inizio del terzo millennio si contraddistingue, per quanto concerne il mondo cosmetico, con una conferma dell’enorme interesse per
le molecole attive sull’invecchiamento. 1
La richiesta di questi prodotti è in costante
incremento, stimolata, tra l’altro, da un bombardamento di informazioni senza precedenti.
Attraverso il web tutti possono accedere a “pseudo” informazioni su prodotti di tutti i tipi, che
cavalcano l’idea di origini esotiche o, al contrario, ipertecnologiche, che possono essere acquistati liberamente e recapitati in poche ore, per i
quali non esiste alcuna interfaccia nel caso di
eventi avversi.
E spesso si tratta di nostri pazienti, che a noi
hanno chiesto un buon prodotto “da notte” o un
siero per “il contorno degli occhi” e che magari
non ci siamo sforzati di ascoltare, visto che dei
cosmetici “uno vale l’altro” e può andare bene
anche l’ultimo che ci hanno presentato…
Riannodare i fili di questo collegamento è la
sfida che si apre per noi, specialisti dei trattamenti sulla pelle “cosiddetta sana”.
Necessariamente la nostra competenza passa
anche attraverso la conoscenza dei cosmeceutici, quei dermocosmetici d’elite in cui è giusto
ricercare “in primis” la tutela delle esigenze del
nostro paziente e della nostra professionalità,
facendoli diventare elemento indispensabile
della nostra prescrizione, magari proposta anticipatamente alla richiesta, per riprenderci la
titolarità della gestione corretta dell’invecchiamento cutaneo.
antiaging: le sfide
Molecole
Qual è oggi l’obiettivo di un cosmeceutico?
Prevenire il danno da UV
Ridurre la formazione di radicali liberi
Migliorare la barriera lipidica
Migliorare il tono della pelle
Levigare la superficie
Ridurre le rughe sottili e le pieghe 2
Nel cosmeceutico il claim principale viene
sostenuto dai cosiddetti “principi attivi” ma ben
sappiamo quanto una formula razionale, ispirata alla tutela delle caratteristiche superficiali
della pelle diventi un elemento indispensabile
nell’attuazione dell’attività.
Le molecole che andremo a descrivere appartengono alla famiglia degli antiossidanti (idebenone), stimolanti della sintesi del collagene
(peptidi, fattori di crescita), addensanti (ProXylane™).
Specialista in Dermatologia, Roma
63
P. Fileccia
1. Gli antiossidanti
Il danno prodotto dai radicali liberi
coinvolge irreversibilmente le strutture vitali
della cellula, in particolare il DNA. Inoltre,
interferendo direttamente con i fattori di regolazione tessutale, sovra esprimono activator protein 1 (AP-1) e nuclear transcription factor-kappa
B (NF-kB): AP-1 è responsabile della produzione di metalloproteinasi che degradano il collagene, contribuendo alla comparsa delle rughe.
NF-kB sovra regola la trascrizione di mediatori
proinfiammatori come interleuchina 1, 6, 8 e
tumor necrosis factor-!. 3
Attraverso recettori superficiali, questi mediatori proinfiammatori eliminano ulteriormente AP1 e NF-kB, amplificando il danno.
L’aggiunta di antiossidanti nei prodotti cosmetici viene utilizzata da tempo per contrastare il
danno fotoindotto ma, com’è noto, si tratta di
molecole molto instabili, che necessitano di formulazioni adatte per mantenerle in forma attiva. Solo il superamento della sfida formulativa
trasforma in attività i presupposti teorici della
loro attività.
1.a Idebenone
Si tratta di un analogo sintetico del coenzima
Q10. Le sue minori dimensioni molecolari presuppongono un assorbimento facilitato. 4
Nel primo studio sull’idebenone, la sua capacità
antiossidante è stata paragonata al tocoferolo, al
coenzima Q10, all’acido ascorbico, all’acido
lipoico e alla chinetina, cimentando le molecole in 5 test di ossidazione biologica, per ognuno
dei quali veniva dato uno score massimo di 20.
Il punteggio totale per i 5 test è evidenziato in
Tabella 1. In questo lavoro è stato sottolineato il
valore di EPF (Environmental Protection Factor)
che misura la capacità protettiva rispetto allo
stress ambientale. 5
Test
Gli studi clinici sono stati condotti con concentrazioni 0,5 e 1% in lozione, applicati sulle zone
di rugosità e macchie del viso due volte al dì per
6 settimane: si è avuto un miglioramento globale rispettivamente di 30 e 33%. In conclusione
entrambe le formulazioni sono risultate valide. 6
In vendita in USA come Prevage®, l’idebenone
viene applicato la mattina prima del fotoprotettore per fornire alla pelle un’ulteriore protezione contro il fotodanneggiamento.
2. Gli stimolatori della sintesi del collagene
L’esposizione cumulativa agli UV
causa alterazioni dermiche che interessano il
collagene, l’elastina e i glicosaminoglicani.
Istologicamente il danno attinico cutaneo può
esser considerato come una ferita cronica, per
cui molte sostanze che stimolano la cicatrizzazione possono essere utili.
Una delle categorie più interessanti è quella dei
peptidi.
2.a I peptidi
Già dagli anni ’30, gli estratti di lievito venivano utilizzati nelle medicazioni delle ferite.
L’attività è da attribuire a peptidi di basso peso
molecolare, che sovra regolano i fattori di crescita cellulare, determinando una stimolazione
dell’angiogenesi nel tessuto di granulazione e
della sintesi di collagene. 7
Ad oggi esistono almeno 500 proteine assortite
derivate dal Saccharomyces cerevisiae.
Quando vengono addizionati ad un’estremità
lipofila (es. acido palmitico) o ad un veicolo
liposomiale penetrano attraverso l’epidermide e
raggiungono il derma, dove possono svolgere 3
funzioni:
proteine di segnale, per aumentare la sintesi
del collagene;
carrier di rame;
Idebenone
Tocoferolo
Kinetin
Ubichinone
Vit. C
Ac. lipoico
20
20
16
19
20
95
16
20
10
17
17
80
11
10
20
10
17
68
6
15
5
12
17
55
0
20
3
12
17
52
5
5
4
20
7
41
Sun burn cell assay
Foto chemiluminescenza
Prodotti ossidativi primari
Prodotti ossidativi secondari
Cheratinociti irradiati con UVB
Punteggio totale (EPF score)
(da Mac Daniel D, Neudeker B, Dinardo J, modificato)
Tabella 1. Stress ossidativo: punteggio della capacità protettiva totale (EPF).
64
Fattori di crescita
HB-EGF
FGF 1,2,4
PDGF
IGF-1
TGF-"1 e "2
TGF-"3
IL-1! e -"
TNF-!
Target cellulari e attività
Mitogeno di cheratinociti e fibroblasti
Angiogenico e mitogeno dei fibroblasti
Chemiotattico per fibroblasti, macrofagi;
attivatore macrofagi; mitogeno fibroblasti
e produzione della matrice
Mitogeno fibroblasti e cellule endoteliali
Migrazione cheratinociti, chemiotattico
per macrofagi e fibroblasti
Anti cicatrizzante
Espressione dei fattori di crescita
nei macrofagi, cheratinociti e fibroblasti
Simile alle IL-1
(da Metha RC e Fitzpatrick RE, modificato) (11)
Tabella 2. I fattori di crescita nella cicatrizzazione tessutale.
neurotrasmettitori in grado di destabilizzare il
sistema SNARE.
2.a.1 Delle proteine di segnale la più studiata è
la sequenza lisina-treonina-treonina-lisina-serina (KTTKS), trovata sul procollagene di tipo I. È
stato dimostrato che questo pentapeptide stimola la regolazione a feed-back di nuova sintesi di
collagene e la produzione di matrice proteica
extracellulare (collagene I e II, fibronectina).8
2.a.2 I peptidi carrier trasportano elementi- traccia essenziali per il funzionamento enzimatico. I
carrier più noti sono i trasportatori di rame.
Il rame è un elemento essenziale per la riparazione delle ferite, i processi enzimatici e l’angiogenesi. È un cofattore essenziale per la sintesi di
collagene ed elastina, inibisce le metalloproteinasi e riduce l’attività della collagenasi; è cofatt o re della lisil ossidasi, tappa importante nella
sintesi di collagene ed elastina. Il complesso tripeptidico glicil-istidil-lisina si complessa spontaneamente con il rame e ne facilita l’uptake
intracellulare. Usato come cosmeceutico, questo
peptide migliora la consistenza e la texture della
pelle, le rughe sottili e l’iperpigmentazione. 9
2.a.3 I peptidi che interferiscono con la neurotrasmissione vengono usati per mimare l’attività
della tossina botulinica.
Inseriti nelle formulazioni cosmetiche, sono
teoricamente in condizione di innalzare la soglia minima per l’avvio della contrazione muscolare, riducendo progressivamente la contrazione involontaria dei muscoli mimici.
Semplicemente per inquadrare l’attività dei
peptidi più noti, ricordiamo che la propagazione del potenziale d’azione a livello della fibra
nervosa pre-sinaptica determina l’apertura dei
canali del calcio e la conseguente aggregazione
del complesso SNARE (Synaptosomal Associated
Protein Receptor), composto da tre proteine:
Synaptosomal Associated Pro t e i n (SNAP 25),
Synaptobrevina o Vesicle Associated Membrane
Protein (VAMP) e Sintaxina. 10
I peptidi agiscono impedendo l’aggregazione e
la complessazione delle proteine SNARE.
Acetil esapeptide-3 (Argirelina®) inibisce la
complessazione di SNARE, pentapeptide-3
(Vialox®) è invece un antagonista competitivo
del recettore della membrana postsinaptica dell’aceticolina e Leuphasyl®, pentapeptide a sequenza brevettata, modula i canali del calcio,
riducendone l’ingresso all’arrivo del potenziale
presinaptico.
Nonostante le perplessità sulla reale possibilità
che meccanismi d’azione così sofisticati possano portare a un miglioramento della mimica del
volto, le aziende hanno fornito studi in vitro e in
vivo, placebo-controllo, sulla riduzione della
profondità delle rughe attraverso la valutazione
delle repliche siliconiche.
2.b I fattori di crescita
Alcuni degli effetti biochimici dell’invecchiamento cutaneo intrinseco ed estrinseco sono
simili a quelli che si realizzano nel corso delle
ferite e della cicatrizzazione.
Sia una ferita e che il danno UV inducono
infiammazione, con formazione di ROS ed enzimi proteolitici che degradano la matrice extracellulare.
Per l’avvio della cicatrizzazione è necessaria la
rapida risoluzione del fatto infiammatorio da
parte di fattori di crescita e citochine, la cui attività è sintetizzata in Tabella 2.
Lo stadio finale del “wound healing” è il rimodellamento del derma. Il collagene III e l’elastina
prodotti dalla matrice extracellulare durante la
fase di granulazione vengono sostituiti da strutt u re fibrose più resistenti ed è in questo
momento del rimodellamento, che può durare
anche diversi mesi, la chiave per interferire con
i segni visibili dell’invecchiamento.
Sono disponibili cosmeceutici che forniscono
fattori di crescita tessutali e citochine alla strategia per l’invecchiamento cutaneo. La loro
applicazione topica si è dimostrata utile nel
ridurre i segni dell’aging. 12
65
P. Fileccia
Poiché si tratta di molecole di grandi dimensioni (> 15000 Da) è impensabile che possano
penetrare attraverso l’epidermide intatta ma,
evidentemente,qualcosa viene assorbito, visti i
risultati clinici ottenuti con l’applicazione su
cute integra. 13
Si deve postulare la penetrazione transfollicolare e ghiandolare, seguita da interazioni con i
cheratinociti basali e dalla liberazione di citochine, che inviano segnali ai fibroblasti dermici,
inducendo la rigenerazione e il rimodellamento
della matrice extracellulare dermica. 14
3. Gli addensanti
Si tratta di molecole in grado di stimolare la sintesi dei glicosaminoglicani (GAG),
alla cui capacità di trattenere acqua è dovuta la
viscosità della pelle.
3.a Pro-Xylane™
Brevetto L’Oreal, è un derivato dello xylosio, che
promuove e sostiene la sintesi dei GAG.
La sintesi di questa molecola rientra nei principi
della cosiddetta chimica “verde”, per cui si utilizzano fonti vegetali (in questo caso il faggio) e procedimenti “eco-friendly”, in cui si utilizza come
solvente solo l’acqua, senza spreco energetico. La
molecola ottenuta risulta essere biodegradabile,
non accumulabile, biocompatibile. 15
Studi in vitro hanno evidenziato che Pro-Xylane™
stimola la sintesi di GAG nel derma;
aumenta l’espressione dei recettori che fissano
l’ac. ialuronico (CD 44);
stimola la sintesi di collagene VI, fondamentale per la giunzione dermo-epidermica.
Studi in vivo su donne in menopausa dopo 3
mesi di trattamento evidenziano nel derma
superficiale (zona di Grenz) un riarrangiamento
delle fibre elastiche ed aumento della fibrillina 1
e del condroitin-6-solfato, entrambi carenti
nelle rughe. 16
Conclusioni
Questo e x c u r s u s,per forza di cose non
esaustivo, sulle ultime proposte antiaging
mostra quanto la dermocosmesi si adegui rapidamente alle finissime interazioni esistenti tra
cute ed ambiente e tra le sue diverse strutture .
Viene spontaneo chiedersi come possano molecole complesse e di grandi dimensioni superare
la barriera epidermica integra e raggiungere il
loro target.
66
Una spiegazione potrebbe essere legata al fatto
che la cute senile è più sottile, più suscettibile
alle variazioni esterne, che impiega molto
tempo per riparare eventuali alterazioni della
barriera 17, per cui la presenza di “enhancers”
lipofili nella formula può agevolare la penetrazione intraepidermica e da questa poi interagire
con il derma e il microcircolo. 18
Un altro punto delicato è la labilità degli ingredienti attivi proposti: basti pensare agli antiossidanti o ai fattori di crescita, ad esempio, notoriamente instabili quando non sono nel loro
ambiente fisiologico e facilmente degradati da
emulsionanti o solventi.
Ma la sfida è troppo interessante: sempre più
frequentemente studi controllati ci mostrano i
vantaggi inequivocabili dell’utilizzo degli
antiossidanti e dei fattori di crescita in associazione ai retinoidi per la ristrutturazione della
matrice dermica, del microcircolo e della barriera epidermica nella “terapia cosmetica” dell’invecchiamento.
È chiaro che il cosmetico del futuro stravolgerà
i criteri formulativi noti e necessiterà di tecnologie sofisticate per garantire alla nostra competenza e alla richiesta del consumatore l’attività
vantata.
Bibliografia
1. Kreyden OP. Antiaging- a specific topic or
just a social trend?. J Cosmet Dermatol 2005; 4:228
2. Baldwin H. Cosmeceuticals in dermatology. Skin &
Aging Suppl May 2006; 10
3. Meyer M, PahlHL, Baeuerle PA. Regulation of the transcription factors NF-kappa B and AP-1 by redox changes.
Chem Biol Interact 1994; 91:91
4. Farris P. Idebenone, green tea, and coffeeberry extract:
new and innovative antioxidants. Derm Ther 2007; 20:322
5. Mc Daniel D, Neudecker B, Dinardo J, et al. Idebenone:
a new antioxidant-Part I: relative assessment of oxidative
stress protection capacity compared to commonly known
antioxidants. J Cosmet Dermatol 2005; 4:10
6. Mc Daniel D, Neudecker B, Dinardo J, et al. Clinical efficacy assessment in photodamaged skin of 0,5% e 1,0%
idebenone. J Cosmet Dermatol 2005; 4:167
7. Canapp SO, Farese JP, Schultz GS, et al. The effect of
topical tripeptide-copper on healing of ischemic open
wounds. Vet Surg 2003; 32:515
8. Katayama K, Armendariz-Borunda J, Raghow R, et al.
A pentapeptide from type I procollagen promotes extracellular matrix production. J Biol Chem 1993; 268:9941
9. Simeon A, Emonard H, Hornebeck W. The tripeptide
copper-complex glycil-L-histidyl-L-lysine-Cu2+ stimulates
matrix metalloproteinase-2-expression by fibroblast cultures. Life Sci 2000; 67:2257
10. Bali J, Thakur R. Poison as a cure: a clinical review of
botulinum toxin as an invaluable drug. J Venom Anim
Toxins 2005; 11:412
11. Metha RC, Fitzpatrick RE. Endogenous growth factors
as cosmeceuticals. Derm Ther 2007; 20:350
12. Ricciarelli R., Fitzpatrick RE, Rostan EF. Reversal of
photodamage with topical growth factors: a pilot study. J
Cosmet Laser Ther 2003; 5:25
13. Gold MH, Goldman MP, Biron J. Efficacy of novel skin
cream containing mixture of human growth factors and
cytokines for skin rejeuvenation. J Drug Dermatol 2007;
6:197
14. Werner S, Krieg T, Smola H. Keratinocyte- fibroblast
interaction in wound healing. J Invest Dermatol 2007;
127:998
15. Di Maio A, Cazzola P. Pro-Xylane™: un prodotto della
chimica verde per contrastare l’invecchiamento cutaneo. J
Plast Dermatol 2006; 2(2):71
16. De Lacharriere O. Skin aging, from clinical signs to biological targets: Pro-xylane™. XI st World Congress of
Dermatology, Buenos Aires 2007
17. Ghadially R, Brown BE, Sequeira-Martin SM, et al. The
aged epidermal permeability barrier. Structural, functional,
and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995; 95:2281
18. Transdermal and topical delivery of therapeutic peptides and proteins. In: Banga AK. Therapeutic peptides and
proteins: formulation, processing, and delivery system. 2nd
ed. Boca Raton, FL: CRC Press; 2005
ISPLAD - ADOI
2008
Corsi di Aggiornamento in Dermatologia Plastica
Caro Collega,
anche quest’anno l’ISPLAD (International-Italian Society of Plastic-Aesthetic and Oncologic Dermatology), come nei precedenti anni, organizza degli Incontri di aggiornamento in Dermatologia Plastica per i suoi circa 2.000 Soci e per tutti i
medici cultori della materia. Gli argomenti trattati saranno come sempre di grande attualità e interesse per i partecipanti.
Quest’anno l’organizzazione scientifica dei corsi vedrà la collaborazione dell’ISPLAD con l’ADOI (Associazione
Dermatologi Ospedalieri Italiani).
Le tematiche che verranno affrontate riguarderanno i problemi delle mucose e della cute circostante. Si parlerà di fisiopatologia, di farmacologia, dermocosmesi, filler, peeling, tossina botulinica, terapie strumentali, prevenzione etc.
Qui di seguito riportiamo il relativo programma scientifico.
Visitate: www.isplad.org
Programma “Mucose e Perimucose”:
Prima giornata:
Sessione occhio e distretto perioculare
Ore 14.00 Registrazione dei Partecipanti
ore 9.00
Ore 15.00 Inizio dei lavori e saluto dei Presidenti
Presidente ADOI: Dr. Patrizio Mulas
Presidente ISPLAD: Prof. Antonino Di Pietro
Presidente del Corso: Dr. Federico Ricciuti
Sessione mucose genitali
ore 15.15
ore 15.30
ore 15.45
ore 16.00
ore 16.15
ore 16.30
ore 16.45
ore 17.00
ore 17.15
ore 17.30
ore 17.45
ore 18.30
Il reperto istologico correlazioni
anatomo-cliniche
La clinica delle patologie infiammatorie
e neoplastiche vulvari
Le manifestazioni cliniche
del distretto perianale
HPV e patologia vulvare: il ruolo del vaccino
DAC dei genitali femminili
Linee guida nella paziente in menopausa
Menopausa, cute e integrazione
Terapia fotodinamica nel distretto genitale
Terapie Dermoplastiche vulvari
Uso non estetico della tossina botulinica
vaginismo e ragadi: il parere del neurologo
Discussione
Termine dei lavori
Seconda giornata:
Ore 8.00
Ore 8.45
Registrazione dei Partecipanti
Inizio dei lavori
ore 9.15
ore 9.45
ore 10.00
ore 10.15
ore 11.00
Clinica delle patologia del distretto
perioculare
Correzione degli inestetismi cutanei
del distretto perioculare
Chirurgia dermatologica del distretto
perioculare
Laser, laser frazionato e la luce pulsata
nel distretto perioculare
Discussione
Coffee Break
Sessione mucosa orale
e distretto peribuccale
ore 11.30
ore 11.50
ore 12.05
ore 12.20
ore 12.35
ore 12.50
ore 13.05
ore 13.20
ore 13.35
ore 13.50
ore 14.30
ore 15.00
Lettura magistrale: La psoriasi delle mucose
Clinica delle patologie infiammatorie
e neoplastiche del distretto periorale
Correzione degli inestetismi cutanei
del distretto periorale
Filler nel distretto periorale
Tossina botulinica nel distretto periorale
Terapia fotodinamica nel distretto periorale
Spettroscopia Raman e laser terapia
nelle lesione mucose del cavo orale
Alta tecnologia nel distretto periorale
Chirurgia delle lesioni nel distretto periorale
Discussione
Consegna questionario ECM
Termine dei lavori
I programmi definitivi con i relatori saranno pubblicati sulle pagine del sito www.isplad.org.
Tutti gli incontri verranno sottoposti alla Commissione ECM del Ministero della Salute per l’assegnazione di crediti
formativi validi per l’aggiornamento continuo del medico; per tutti i corsi sono previsti un numero massimo di 200
partecipanti.
69
Scheda Iscrizione:
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continuo del medico; per tutti i corsi sono previsti un numero massimo di 200 partecipanti.
Per qualsiasi chiarimento è a disposizione la Segreteria Organizzativa ISPLAD, ai seguenti numeri: tel. 02 20404227, fax 02 29526964 o al seguente
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line, inviando via fax la copia dell’avvenuto pagamento.
Corso/i a cui intendo partecipare:
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70
ISPLAD
2nd International Congress
of Plastic Dermatology
Milan, March 6-8, 2008
ABSTRACTS
ISPLAD 2nd International Congress of Plastic Dermatology, Milan, March 6-8, 2008
THE ROLE OF DERMOSCOPY DURING
PREGNANCY: CASE HISTORIES
A. Agolzer
During pregnancy, many physiological and pathological alterations may appear to the disadvantage of various organs and
systems. Also the skin and skin annexes may be involved by
these alterations due to hormonal, metabolic and immunological factors. Skin neoformations (of melanocytic and nonmelanocytic origin) can change during this period. We therefore present some case histories of nevi that underwent dermatoscopic alterations during pregnancy and in the post-partum. In literature, cases of onset of melanomas have been
described during pregnancy. Recent publication state that the
prognosis of skin melanomas with onset during pregnancy is
not worse than those that appear in non-pregnant women.
ANTIBIOTIC RESISTEANCE IN ACNE
G. Alessandrini
Antibiotic resistance in acne is creating major concerns
throughout the world. The open questions are related to the
possible causes of this phenomenon and the corrections that
can be made. The adoption of ad-hoc guidelines for acne at
the international level and the use of subantimicrobial doses
of tetracyclines can be useful in the attempt to reduce this
phenomenon. The dermatologist and the patient will treat
acne with greater attention to this parameter. The advent of
new topical therapies with antiinflammatory action can be
the key to solving this emerging need. Finally it is crucial to
see how, in the next few years, antibiotic resistance is going
to be investigated.
BOTULINUM TOXIN: ANALYSIS, INDICATIONS
AND INJECTION TECHNIQUES
F. Antonaccio
The botulinum toxin is a drug: therefore, using it to smooth
wrinkles is a medical treatment which calls for the Specialist to
abide by specific rules of conduct and caution.
The patient must be provided with correct information on suitable indications, contraindications, optional treatments and
side effects.
The pharmacology of botulinum, the face anatomy and previous treatments (namely fillers) must be well known in advance.
Conceptually and practically, the injection technique differs
from the traditional filler technique since botulinum is a protein that must be accurately injected in the muscle in very low
dosages through a very thin face needle. The protein temporarily inhibits the release of acetylcholine i.e. the chemical mediator liberated at nerve ending as neurotransmitter. As a result,
there is a muscle relaxation and a considerable reduction of
continuous muscle contraction, often spontaneous and involu n t a ry, on the upper facial tissues that give the typical frowned
and “a n g r y” expression. The improvement on the skin and
wrinkles is well visible 3-7 days after treatment and lasts 4
months on average. Injections must be periodically repeated
not only to maintain the results but also to prevent new expre ssion lines from appearing on the face.
Face rejuvenation techniques can combine other dermoplastic
treatments such as chemical peelings, biorevitalization, re a bsorbable intradermal fillers, and laser resurfacing to obtain
excellent results as reported and confirmed by international scientific literature.
PEELING INDICATIONS AND LIMITS
F. Antonaccio
E v e ry day, the skin suffers the harmful action of sun radiation.
Fibroblasts play a key role in maintaining the homeostasis of
the derma, in the presence of dermal alterations that occur with
photoageing. Many cytokines regulate the growth and the functionality of fibroblasts and influence the formation and re m o delling of dermal tissue. These cells start synthesizing abnormal
amounts of elastin and collagen for the activation of the corresponding gene on behalf of a series of cytokines discharged
into the cell environment in response to sun radiation. In
addition, photoageing implies an increased activity of extracellular matrix metalloproteinasis (MMPs) that degrade type
I collagen (main extracellular component of the skin) and
elastin.
Photoageing classifications (according to Mark Rubin) correlate visible skin alterations with the corresponding histological picture.
Histological studies on skin treated with peeling for antiageing purposes has evidenced, as well as the normalization of
the skin, the possibility to stimulate a reaction of dermal
remodelling and repair with consequential formation of neocollagen and an increase of the thickness in the Grenz zone,
a band of papillary derma of normal aspect. The Grenz zone
represents a defence reaction and compensation by the
fibroblasts that are still integral.
This is at the basis of the improvement of the manifestations
of photoageing, especially of the fine actinic wrinkles that the
plastic dermatologist achieves with chemical peeling.
PEELING WITH TRI-CHLORINE ACID
F. Antonaccio
This chemical peel consists of the application of one or more
substances in order to cause a controlled destruction of the
cutaneous layers and hence the acceleration and regeneration of the epidermis and by varying degrees the repair of the
dermis with the formation of neo collagen.
75
It is an outpatient treatment and is effective in photo-ageing,
various forms of acne, epidermal and dermal melasma, and
acne scars. It is counter indicated on patients with fibroblastic diathesis, atopic dermatitis, acute eczema or urticaria or
during pregnancy. It is also unsuitable for patients with unrealistic expectations. TCA is one of the most frequently used
peels and used in various concentrations, usually between
10% - 50%. Many variables influence the depth of the peel,
concentration, application technique, skin and photo type,
and the density of the annexed area. The understanding of
skin disease and the correlation between the clinical and histological picture are necessary to choose the most appropriate peeling: very superficial, superficial or medium-deep.
In order to optimise the therapeutic outcome and complication free, the choice of patient is fundamental and the information and care instructions about post peeling must be
accurate.
Lectures
Ayres S. III. Superficial chemosurgery in treating aging skin. Arch.
Dermatol. 1962; 85: 125-133.
Collins PS. The chemical peel. Clin. Dermatol. 1987; 5:57-74.
Van Scott EJ, Yu RJ. Alpha hydroxy acids: procedures for use in clinical
practice. Cutis 1989; 43: 222-228.
Van Scott EJ, Yu RJ. Hyperkeratinization, corneocyte cohesion and alpha
hydroxy acids. J. Am. Acad. Dermatol. 1984; 11: 867-879.
Mishima Y. Histopathology of functional pigmentary disorders. Cutis 1978;
21: 225-230.
Stegman SJ. A comparative histologic study of the effects of three peeling agents
and dermabrasion on normal and sundamaged skin. An. Aesth. Plast. Surg.
1982; 6: 123-135.
Resnik SS, Lewis LA. The cosmetic uses of trichloroacetic acid peeling in
dermatology. South Med. J 1973; 66: 225-227.
Resnik SS, Lewis LA, Cohen BH. Trichloroacetic acid peeling. Cutis 1976;
17: 127-129.
Spira M, Gerow FJ, Hardy SB. Complications of chemical face peeling. Plast.
Reconstr. Surg. 1974; 54: 397-403.
BIMED 3: A NEW THERAPEUTIC PROTOCOL
FOR CELLULITIS
P.A. Bacci
In 1998 we proposed a protocol called BIMED (Biorheological Integrated Methodology with Dynamic therapy) to
treat lymphoadenema and the various forms of cellulitis.
This strategy always started from a precise diagnosis and
evolved after the introduction of an advanced classification
of cellulitis. (Code TCD) which led to new endocrinological
and metabolic criteria. The BIMED protocol is a combination
of different highly experimented methods to investigate these
defects that are generally caused by an interstitial swelling
and is designed to treat the different forms of cellulitis. In
particular, it is used on the six areas mostly affected by this
disorder: arteriolar microcirculation, venolymphatic micro-
76
circulation, the supporting connective tissue the local and
systemic fatty tissue, the local nervous system and the interstitial matrix.
Recent studies on the physiopathology of different forms of
cellulitis have paved the way to new more sophisticated
strategies that hail a new era in the medical, physical and surgical treatment of cellulitis with the use of the four BIMED 3
integrated methods.
This protocol envisages the use of a basic physical therapy
based on the revolutionary concept of “compressive microvibration”, of a physical strategy that leads to a controlled
i n c rease in the tissue temperature capable of reducing
swelling and degenerative processes, of an integrated
approach to deliver several drugs and of an intratissue laser
strategy for the non surgical reduction of the fatty tissue and
the regeneration of the connective tissue.
This integrated methodology is applied according to the
individual clinical diagnosis. It is a protocol based on two
years of observations and clinical studies which has proved
to be effective in the different forms of cellulitis and which is
presented in a scientific setting for the first time.
LYMPHODRAINAGE WITH LYMPHOISOPHORESIS AND LED COMBINED TECHNIQUE
P.A. Bacci
Lymphodrainage is one of the basic methods for the treatment of the lympho venous stasis, both in the curative and
in the preventive phase. The reduction of lymphatic toxins
brings an improvement in the metabolic functions of the
extracellular matrix and of the cellular activities.
Among the various proposals, thanks to the good results
achieved in the cosmetic and phlebologic sectors, it is possible to present a combined technique.
It is a sequence of methods starting with a lymphatic depuration of tissues through electric waves that create a difference of potential in the axis lower limbs – upper emisoma
thus promoting the physiological drainage; this method is
also called “simulated deambulation” because it is similar to
a step. After this first depurative phase, some instruments are
used for the transdermic introduction of suitable substances
chosen by the doctor, exploiting the capabilities of an ultrasonic cavitation of 25,000 mHz and a sequence of electric
different waves, called isophoresis and allowing the distribution of these substances in the depurated tissues, energetically activated through vibration and electricity, like a
mesotheraphy without needles.
The session, which lasts about an hour, ends with a 35 seconds exposure to a yellow-red sequence of laser energy produced by low energy diodes (LED – Light Emitting Diodes)
which activate cells without producing thermic energy.
This sequence of methods is a complete treatment cycle with
draining, curative and energetic activities, which is particu-
larly useful in those cases of painful edematous cellulite
hypodermosis, following fractures, lymphoedemas and
evolving and chronic lipolymphoedemas.
EXPERIENCE ON THE THIRD INFERIOR
AND SPECIFIC CHARACTERISTICS
M. Basso
The Italian Ministry of Health has authorized the use of botulinic toxin for aesthetic use. Botulinic toxin is a drug, so
using it for correcting wrinkles is a pharmacological treatment, and therefore, as always, precise rules of ethical conduct must be followed by the physician.
It is opportune to correctly inform the patient on the
approved indications, contraindications, possible alternative
treatments and the possible side-effects. It is fundamental to
have a thorough knowledge of the pharmacology of botulinic toxin, of the anatomy of the face, the previous experiences
of wrinkle treatment, especially with fillers. The injection
technique where this drug is injected with great precision
into the muscle by using a very thin needle, produces a temporary reduction in the liberation of acetylcholine, the chemical mediator that determines the transmission of the nervous impulse at the level of the neuromuscular joint. Thus
the relaxation of the muscle involved is obtained with a consequential significant reduction of the continued traction,
often involuntary and unconsciously, on the overlying skin
tissues that produces the typical angry and corrugated look:
the effect of this relaxation on the skin and the wrinkles
becomes visible after 3-7 days from the injection and in average lasts for 4 months. It is therefore necessary to periodically repeat these injections, not just to maintain the results
obtained, but also to carry out an important preventive
action on the formation of expression marks: this concept is
fundamental for younger people who tend to prematurely
develop these wrinkles due to the excessive activity of their
mimic muscles that reflect emotions such as sadness, anger
and surprise. It is fundamental to locate with precision the
injection sites and the dosage by carefully observing the
design, the position and the deepness of the wrinkles on the
patient’s face in relaxed position, if there are asymmetries and
the contraction of the mimic muscles of the area needing
treatment. The authors present their experience with botulinic toxin in the areas of gabella, the forehead, around the
eyes, the lips, the neck and décolleté.
BOTULINUM TOXIN: FROM THEORY
TO PRACTICE - A PERSONAL EXPERIENCE
M. Basso
The Italian Ministry of Public Health has authorised botulinum for esthetic usage. The botulinum toxin is a drug:
therefore, using it to smooth wrinkles is a medical treatment
which calls for the Specialist to abide by specific rules of conduct and caution. The patient must be provided with correct
information on suitable indications, contraindications,
optional treatments and side effects.
The pharmacology of botulinum, the face anatomy and previous treatments (namely fillers) must be well known in
advance. Conceptually and practically, the injection technique differs from the traditional filler technique since botulinum is a protein that must be accurately injected in the
muscle in very low dosages through a very thin face needle.
The protein temporarily inhibits the release of acetylcholine
i.e. the chemical mediator liberated at nerve ending as neurotransmitter.
As a result, there is a muscle relaxation and a considerable
reduction of continuous muscle contraction, often spontaneous and involuntary, on the upper facial tissues that give
the typical frowned and “angry” expression. The improvement on the skin and wrinkles is well visible 3-7 days after
treatment and lasts 4 months on average.
Injections must be periodically repeated not only to maintain
the results but also to prevent new expression lines from
appearing on the face: this is needed in young women who
can early see wrinkles appear on the face due to an overactivity of mimic muscles expressing emotions such as sadness, anger or surprise.
It is fundamentally needed to accurately define the injection
sites and the dosages by observing the shape, location and
depth of the wrinkles at rest on the patient’s face, asymmetries, if any, and the contraction of the mimic muscles of the
area to be treated. The authors present their experience with
botulinum on eyebrow, forehead, periocular and lip areas.
KAPOSI’S SARCOMA: WHERE ARE WE AT?
M. Bellinvia, L. Brambilla, A. Taddeo, S. Della Bella
The classic Kaposi’s Sarcoma (cSK) is a rare angioproliferative
disease triggered by the herpes virus HHV-8. Such infective
agent is required but not sufficient by itself to the development of the disease: other factors, such as the immune system status, affect its onset and its clinical appearance.
Since the discovery of the role played by HHV-8, researches
have focused on factors favoring the development of cSK not
correlated to immune deficiency, such as environmental variables, those related to viral genotype and to host genetic
characteristics. Such studies have been conducted by us also
in rare but not isolated family cases. On the other hand we
tried to understand how the virus interacts with the host
immune system in the affected individual by dosing the viral
load in lesions, in peripheral blood and in the saliva, studying the micro-environment, the cytochemical pattern and
virus reservoir cells, with special attention to the role of dendritic and endothelial cells.
77
We will briefly present the researches currently under way
and the first results obtained in terms of lab evaluation of the
chemical framework and the possible prognostic factors.
FACIAL REJUVENATION: THE AMERICAN
EXPERIENCE WITH BOTULINUM TYPE A,
50 UNITS AND LATEST GENERATION FILLERS
A. Benedetto
Injections of botulinum toxin and fillers have become the
dermatologist’s preferred techniques for non-invasive facial
rejuvenation for today’s no nonsense, no downtime, upwardly mobile cosmetic patient. Injectable hyaluronic acid is the
most versatile soft tissue filler that can be used virtually anywhere on the face. Juvéderm™ Ultra and Juvéderm™ Ultra
Plus are currently the longest lasting, FDA approved
hyaluronic acid fillers used in the United States to replenish
area of soft tissue loss resulting from photo-damage and
chronological ageing.
Injections of Botulinum toxin type A (Botox®) weaken facial
mimetic muscles which are responsible for the dynamic
wrinkles which depict negative moods of an aging face.
Juvéderm™ Ultra and Juvéderm™ Ultra Plus injected into
strategic places around the face can recreate natural contours
and rejuvenate the face. When followed by injections of
Botox® into adjacent mimetic facial muscles one can elegantly diminish facial wrinkling while augmenting and prolonging the facial enhancement provided by Juvéderm™ Ultra and
Juvéderm™ Ultra Plus.
The success of Botox® injections is predicated upon the precise identification of the muscle to be treated and the accurate injection technique to produce the proper results of
muscle relaxation.
The success of Juvéderm™ Ultra and Juvéderm™ Ultra Plus
injections is predicated upon the correct assessment of various facial contouring defects and soft tissue loss and applying proper injection techniques when treating different parts
of the face.
Patient selection and treatment techniques will be demonstrated with pre- and post-treatment photographs.
CARBOSSITHERAPY
F.M. Bianchi
Carbossitherapy appeared in France in 1932, in the SPA of
Royat (Clermont-Ferrand), for the treatment of vascular diseases. The treatment was made by dry or water carbon-gas
baths. Since then, thousands of patients with vascular problems have been treated.
In Italy, carbossitherapy is available at the SPA of Rabbi (TN)
which has the same characteristics of the French Spas.
Today, gas can be administered subcutaneously thanks to a
device that can release carbon dioxide under control with
pre-set dosages and release time; this technique has permitted out-patient carbossitherapy for the treatment of many
pathologies such as cellulitis, local adiposities, microcirculatory pathologies.
This therapy has recently been applied in Plastic
Dermatology too to treat skin aging and enhance tissue elasticity before liposuctions or liftings.
RADIOFREQUENCY IN THE TREATMENT
FOR ACNE
MEDICAL LIABILITY IN PLASTIC DERMATOLOGY:
THE VALUE OF INFORMED CONSENT
F. Bini, P. Cappugi, C. Comacchi
A. Bernardini de Pace
RF has recently opened up new perspectives in the treatment
of skin relaxation. Its effect can be seen mainly on the dermal
structures, while respecting of the skin. In the derma there
are the sebaceous glands that play a role in the acne inflammatory process.
The authors propose to evaluate the effects of RF on acneic
skin and therefore the possible efficacy in the treatment of
this pathology, both in the healed forms and in the different
stages of activity and levels of seriousness.
• The doctor’s obligation to inform: the doctor has the duty to
inform the patient on his/her health status, the therapy,
laser or surgery proposed in advance as well as on the
risks/benefits of the medical treatment. This is true for
plastic surgery and dermatology too.
• Features and purposes of preventive information: information
must be truthful, exhaustive and understandable for the
78
patient who receives it. The patient must be enabled to offset risks and benefits and, consequently, freely and consciously decide whether he/she accepts the treatment. This
is all the more important in the sector of esthetics, unless
the treatment is aimed at helping the patient recover from
a pathological condition.
• The legal value of patient’s informed consent: once the patient
has received the doctor’s preventive information, he/she
must necessarily give his/her consent to the medical-surgical treatment in order for this treatment to be legal. In particular, the informed consent must be individual and clear,
it must refer to a specific treatment and be the result of a
doctor-patient interaction.
• Doctor’s liability: failure to provide information or the provision of non-exhaustive information as well as the execution of a treatment, therapy or surgery without the patient’s
consent, entails the liability of the doctor who may be sued
for damages by the unsatisfied patient.
REMODELLING THE BODY
BY USING RADIO FREQUENCY
THE DIFFICULT MELANOMA
R. Bono
F. Bini, C. Comacchi, E. Damiani
Radio Frequency (RF) is a non-surgical method indicated for
the treatment of skin relaxation. Initially used to rejuvenate
the face and the neck, it has steadily been used to treat also
other skin regions.
This study intends to evaluate the effects of RF on the relaxation of the glutei. Patients with average to serious relaxations are enrolled and treated with RF weekly.
The protocol does not include the use of particular substances in association with RF.
KAPOSI’S SARCOMA: COMMON
AND UNCOMMON CLINICAL ASPECTS
V. Boneschi
The peculiar clinical aspects of Kaposi’s Sarcoma (KS) are
lesion polycentricity, multishape aspect and evolutive
nature. Usually, immature and mature vascular proliferation
characterizing the disease generates primitive angiomatous
nodular aspects and the evolution of maculas of infiltrating
plaques. The pre f e r red onset locations with acral circulation
are in particular feet and legs, where the limphatic vascular
component is abundant, leading to organized and irreversible lymphatic edema, which over time can favor the
onset of papillary stasis.
Uncommon appearance of KS is re p resented by small isolated angiomatous nodules limited to the head (eye lids,
auricles, front) and to genitals, simulating a pyogenic granuloma.
The speed of evolution of each lesion and of the disease
overall, affect secondary clinical aspects: hyperkeratosis
covering plaques and nodules; nodule ulceration and superinfection; formation of pseudobulla on nodular lesions or
plaques (due to the re g ression of the cell-fused proliferative
component replaced by wide lymphatic vascular deficiencies); lymphorrhagia in areas of lymphatic edema and
pseudobulla; deep eccymotic plaques that act as base of fast
evolving nodular lesions; single nodule necrosis with small
base (until they detach spontaneously).
In rare cases, that are particularly aggressive, we witnessed
the development of big largely ulcerated and necrotic neoplastic masses which, from an histological point of view,
look angiosarcomatose. In such cases, bone structures may
be involved with absorption and destruction; we observed
cases of deep node development with incorporation of
lower limbs neurovascular trunks.
In aggressive skin forms we often see lesions in the gastroenteric tract and in rare cases we also witnessed simultaneous skin and lymph node onset, despite any obvious
immune system deficiency.
Despite goals achieved in primary prevention and early diagnosis of melanoma, also with the support of dermatoscopy, the
incidence of melanoma continues to rise and mortality remains
stable. One of the reasons for such failure is the diagnostic difficulties encountered with the identification of “d i fficult
melanomas” such as the ones similar to nevuses, the featureless
ones, the acromyc ones and the nodular melanoma (NM).
Nodular melanoma accounts for about 15% of melanomas and
besides providing very few diagnostic elements, it grows very
rapidly. It can appear on a pre-existing superficial spreading
melanoma or appearing ex novo. From a clinical point of view,
the NM does not show atypical melanocyte lesions, but it may
be symmetric, with regular edges, variable color, which is not
always homogeneous, rapidly changing in size and elevation.
From a dermoscopic point of view, the lesion can appear perfectly symmetric and dominated by spread pigmentation, color
ranging from black to brown, to blue, to purple, marking the
presence of melanin in all skin layers and in the surface skin.
Differential diagnosis of nodular melanoma can be extremely
challenging. In fact, proliferation since the onset towards the
deeper layers of the skin and the lack of a radial growth phase,
does not often provide us with the typical SSM dermoscopic
signs. In assessing a clinically detected lesion, showing little
clinical and dermoscopic signs, it is very useful to pay attention
to the lesion peripheral area. In fact, there we can identify some
elements telling us that we are dealing with a “melanocyte”
lesion. Inside nodular lesions with little or no pigmentation at
all, we can observe vascular structures which characterize the
“atypical vascular pattern” consisting of “milk-red” globules, dotlike and linear irregular vessels. If a nodule or a plaque is present, without any other general dermoscopic sign, either local
or specific (nets, dots and globules, blotches, black or bluish
color,…) the vascular pattern by itself, especially if atypical,
could lead us to a correct diagnosis. The “nevus like” melanoma
can really be regarded as a “false negative”. In fact, if we stick to
the definition, it refers to a nevus-like melanoma as a lesion
presenting clinical and dermoscopic features similar to those of
the melanocytic nevus. Thanks to the spreading of diagnostic
instruments, such as digital dermatoscopy, we have been able
to describe such melanomas; in fact their surgical removal and
subsequent diagnosis is quite accidental!
They are usually removed for the following reasons: 1) subjective irritation such as itching, pain, …; 2) aesthetic reasons; 3)
subjective evaluations such as color (black or dark brown),
modifications or simply because they are different from the
other nevuses the patient has (ugly duckling); 4) as a pre v e ntive measure in high risk patients.
Unfortunately it is often not diagnosed because it does not
show any sign of malignancy (it looks like a nevus!) and difficulties increases when the patient has a lot of nevuses on
his/her body. Despite such difficulties we need to place spe-
81
cial attention on those lesions presenting the following characteristics: short sections of thickened reticule, low pigmentation in the center, hyper or hypo outlying pigmentation,
hyper or hypo multifocal pigmentation.
THE FOLLOW-UP OF PATIENTS
WITH MELANOMAS
U. Bottoni
The follow-up of cancer patients entails continued medical
control in order to evaluate the characteristics and the efficacy
of the therapeutic strategies applied to control the neoplastic
disease. Follow-up provides clinical and instrumental data on
the possible residual disease, on the relapses, metastasis or
onset of other malignant neoplasias (secondary). Patient follow-up contemporaneously provides information on the health
conditions of a specific population with regard to a specific cancer. The follow-up of a cancer patient is therefore fundamental
for the creation of a Register of the local and national tumours.
An accurate staging of patients affected by melanomas according to the latest directives of the American Joint Committee for
Cancer (AJCC 2001-2) is of fundamental importance to proceed with a correct follow-up of patients with melanoma. The
aim of the follow-up of patients affected by melanoma is the
diagnosis of the relapses and of the symptomatic and non
symptomatic (instrumental investigation) metastases, the diagnosis of a second primitive melanoma (multiple melanomas),
the diagnosis of any other pathologies (surrenal adenomas,
liver carcinomas, non-Hodgkin lymphomas). In literature there
are many papers that discuss and propose guidelines for a correct follow-up of patients with melanomas. They are essentially retrospective non-controlled studies. Thus, the utility of a
prolonged follow-up of patients with melanomas is still an
issue. Protocols including guidelines, such as the one proposed
jointly by the GIDO (Gruppo Italiano di Dermatologia
Oncologica) and the GIPMs (Gruppo Italiano Polidisciplinare
sul Melanoma) are in the meanwhile very useful for a rational
management of such patients. In fact, individuals with a thin
melanoma scarcely tend to relapse and therefore do not need to
go through complex instrumental investigations; vice versa,
Stage 3 patients affected by loco regional lymph- glandular
metastases, have to undergo rigorous clinical and instrumental
controls because the risk for metastases within 5 years is high
(>50%).
KAPOSIS’S SARCOMA:
LOCAL AND SYSTEMIC THERAPIES,
REVIEW AND LATEST TRENDS
L. Brambilla
In 29 years of experience we observed 655 patients affected
by Kaposi’s Sarcoma, mainly of classic type, but also of iatro-
82
genic type. Many of them were treated with local and/or systemic chemotherapy. Based on such a broad number of cases,
we developed a staging system in order to be able to better
decide the best therapeutic strategy and useful approach,
especially for compromised and elderly patients.
In the initial stages, (I and II with slow progression) we opt
for clinical observation, intra-lesion chemotherapy
(Vincristine) for isolated nodules, radiotherapy in selected
cases and compressive therapy with elastic stockings. In
stages II with fast progression, III and IV, single or polychemotherapy is the basic approach we followed, with the
use of elastic stockings as useful aid. As first line treatment,
we use: a) Vinblastine: induction 4, 6, 8 mg e.v./week, maintenance 10 mg e.v. every 3 weeks or b) Vinblastine (as above)
+ Bleomicyne 15 mg i.m. every 2 weeks after induction with
Vinblastine. As secondary line therapy: a) Vinorelbine:
induction: 17.5 mg/m2 every 2 week for 5 cycles; maintenance 29 mg/ m2 every 3 weeks, or Etoposide 150 mg/day
e.v. for 3 consecutive days every 3 weeks, or Gemcitabine
1200 mg/ m2 e.v. /week for 2 weeks, with a three week interval, or Epirubicine 20 mg e.v. /week. All these chemotherapy treatments should be continued until the best clinical
result is achieved, followed by three consolidation cycles.
Among the most recent therapies, we would like to recall:
Paclitaxel 100 mg e.v./week; Liposomal Doxorubicin 20 mg/
m2 every 3 weeks for 6 cycles; protease inhibitors.
We will present and discuss the therapy guidelines, as well as
our personal experience.
COSMETOLOGY IN ONCOLOGY
L. Brambilla, B. Scoppio
…“Every happy or painful event in our life leave indelible signs
on our skin”.
Cosmetology sets to be a new tool to relieve the psychological burden caused by skin alterations subsequent to antitumor treatments in oncologic patients.
The skin defect, perceived as a “brand” identifying and differenciating us from the rest of the world, generate psychological discomfort which affects self-acceptance and relationships. Due to the close link existing between physical aspect
and social/psychological parameters, dermocosmetology
could be helpful because, by mitigating skin imperfections,
the patient aesthetic appearance improves, as well as the
quality of his/her daily life. This is the approach that was followed by the “Cosmetic, Toiletries and Fragrance Association”
through the “Look good feel better” campaign which from the
90s provides suitable tools to patients who had undergone
chemotherapy and radiotherapy, in order to allow them to
better cope with therapy side effects. Scars, alopecia, pigmentation changes and nail dystrophy are often related to
chemotherapic substance toxicity or they are secondary to
other oncologic treatments. In cases where medicine can
only partially treat the disease, it is useful to adopt an
approach that sees the patient as a person, which keeps
his/her disease into account, without disregarding his/her
inner world, which can certainly affect and be affected by
organic symptoms. Our presentation describes a project
related to the reorganization of the oncology, dermatology,
and cosmetology service established within a broader program of humanization, already implemented in the
Oncology Ward of the San Carlo Hospital in Milan.
Lectures
Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr
Opin Oncol 2002; 14:212.
Graham JA, Kligman AM. The Psychology of cosmetics treatments. New York:
Praeger Publishers; 1985.
Bassi R. Introduzione alla dermatologia psicosomatica. Bollati Boringhieri; 2006.
and surgical treatments is preferable to associate the use of
topical cosmetics and supplements. Anticellulitis supplements are made of substances of vegetable origin, that can
carry out draining, lipolytic and anti-inflammatory actions,
and improve microcirculation.
Usually, they contain fibres, vegetable extracts and amino
acids. There come in various forms: tablets, drops or packets. They act in different ways: some slow down the absorption of fat and sugar, others accelerate metabolism or reduce
appetite, then there are others that improve microcirculation
or carry out a toning action.
The author illustrates the most frequently used active principles to counter cellulitis.
LECI-LYSIS
M. Bucci
ACNE FROM THE GYNAECOLOGICAL POINT
OF VIEW
V. Bruni
Acne appearance, above all during the post-menarchal period, can represent a cutaneous indication of hyperandrogenism, which can be linked to the polycistic ovary syndrome and more rarely to the andronegenital late-onset syndrome. A preventive diagnosis is of great importance and,
concerning the polycistic ovary syndrome, it should make
reference to the international defining criteria of the various
phenotypic expressivities. The gynaecological advice for acne
appearance can be an important occasion to set up a prevention activity, built on lifestyle and on the possible treatment
of the associated glucidic metabolism, together with a personalized treatment.
As results of a pylosebaceous unity hyperactivity, acne can be
t reated thanks to an endocrine treatment with estro progestogen, which should be balanced with effective oestrogenic dosage in low quantities, choosing progestogen preparations of antiandrogenic activity or increasing the associated
androgens treatment. It should be noted that presently the
use of these drugs is not provided by the Italian National
Health Service (INHS) with this indication and that the prescription should be made by taking into consideration
dosages, the possible side effects and the relationship
between risks and benefits.
Phosphatidylcholine (PC) is a phospholipid found in great
quantities in our organism, especially in cell membranes,
plasma, liver and nervous tissue. In the nervous tissue it is
found in the cell membranes of neurons and has a role in
forming acetylcholine, indispensable for the transmission of
nervous impulses. PC is used per OS or parentally for its
hypolipemizing activity. In fact, it can lower the level of cholesterol, LDL and triglycerides.
In 1989, Bobkova et al. showed that PC increases the receptor properties of the cell membrane of adipocytes, by increasing their sensitivity to insulin and therefore causing the
acceleration of lipolysis.
In 2001, on Dermatology Surgery, the Brazilian dermatologist Patricia Rittes published the first article on the lipolytic
effects of phosphatidylcholine injected directly into the subeyelid adipose deposits. This article had already been presented as a scientific communication at the 54th Brazilian
Congress of Dermatology in 1999.
In 2003, the same author, on Aesthetic Plastic Surgery and
on the Aesthetic Surgery Journal published some articles on
the lipolytic action of phosphatidylcholine on the adipose
deposits of the limbs and other body regions.
Dr. Rittes declared that between 1995 and 2003, she had
treated over 8,500 patients, on whom she had performed
24,000 treatment, of which 2,000 on baggy eyelids.
Currently, phosphatidylcholine is employed in the treatment
of adipose deposits of the limbs, under the eyelids and under
the chin.
SUPPLEMENTS FOR CELLULITIS
M. Bucci
THE SURGICAL APPROACH
TO AUTOLOGOUS HAIR TRANSPLANT
Cellulitis is a degenerative disorder of the adipose tissue
characterised by a pathological condition ranging from
minor to more serious forms. The therapeutic strategy
should be multi-factorial and as well as the various medical
F. Buttafarro
Male-pattern baldness or common baldness is a very frequent scalp condition. It causes a change in the aesthetic
83
profile of the subject and it induces psychological and relational problems, thus affecting quality of life. In case of
female baldness, it is necessary to carefully evaluate treatment
options such as autologous transplant but with real and re a listic expectations. Women experience hair thinning and baldness as a severe physical impairment which leads to a significant decrease in their self-esteem and creates enormous re l ational, social and work difficulties. The treatment of baldness
is diff e rent in males and females. Male-pattern baldness can
be treated in three diff e rent ways with: 1) Minoxidil (a 2%5% lotion) 2) Finasteride (1 mg / die) 3) Surg e ry. Instead
female baldness requires a diff e rent approach in that finasteride is not indicated and minoxidil seems to be less eff e ctive. There f o re in females, surgery is the only valid option
unless there are hormonal alterations. There are several surgical techniques that can be used to treat this condition and
they can be used separately or can be combined to obtain the
best result. The most widely used procedure is autologous
transplant with mini and micro grafts. Under local anesthesia, a certain number of viable cell roots are transferred from
the areas that are not predisposed to hair loss (lateral regions
and the nape) to areas with hair thinning or without hair
roots. In a megasession, it is possible to harvest about 35004000 roots that are then transplanted onto the bald areas.
This procedure provides a very satisfactory cosmetic and natural result. This technique appears to be simple, but actually
re q u i res an experienced and esthetically-oriented surgical
team. If it is correctly performed by experienced hands, it is
possible to obtain life-long and completely natural results
even on very large bald areas. Planning and designing the
frontal line re q u i res great experience because it is the surgeon’s signature of the procedure.
LASER THERAPY IN CUTANEOUS
HYPERPIGMENTATION
F. Buttafarro
The interaction between Laser light and skin vary considerably according to the Laser used, the energy released from
the tissue, the optical decoy with which it interferes. The latter have a great importance to determine the choice and the
use of different Lasers because they can absorb different
wavelengths. Optical decoys are re p resented by chromophores present in the tissue that are essentially tissue
water, melanin, haemoglobin, carotenoids. The lasers we
have can be divided, according to the specific interactions
with their biological targets, into three major categories: 1)
organ systems that can be identified with surgical interventions and that have water as main chromophore; 2) tissue
systems that can be identified with vascular intervention and
that have oxyhemoglobin as main chromophore; 3) systems
with sub-cellular action that can be identified with Qswitched systems and have as chromophore some exogenous
84
and endogenous pigmented elements. Today, the quantity of
laser equipments that we can use for different dermosurgical
pathologies is increasing and with very high costs, often
unsustainable from the professionists of this field.
In the treatment of cutaneous hyperpigmentation, that are
very different between each other, we can use all three of
these systems mentioned above but the operator must correctly handle different systems and at the same time make an
exact diagnosis of the lesion to be treated. The author presents a roundup of different uses of Lasers for the treatment
of cutaneous hyperpigmentation.
PHOTODYNAMIC THERAPY:
GENERAL PRINCIPLES
P. Calzavara Pinton, M.Venturini
The photodynamic therapy (PDT) is a bimodal therapy in
which the local or systemic administration of a photosensitizing agent is followed by the application of a light source
on the target area.
In medicine, the following photosensitizing agents are mainly used: tetrapyrrolic agents such as porphyrines, chlorines
and cyanines.
Following irradiation, the photosensitizing agent is capable
of exciting the molecules and realising energy to the molecules’ free or complex oxygen in lipid/protein structures. In
the first case, there is generation of reactive oxygen species
(ROS) with strong oxydating action and cytotoxic effect. All
currently used photosensitizing agents are very selective, i.e.
they can penetrate and store in cancer cells or the endothelium of newly formed vessels of tumor parenchyma and help
save a relative area of adjacent healthy tissue.
The photobiological effects in the clinical application of
aminolevulinic acid (ALA) and its derivative methyl-ester
(MAL) have been thoroughly studied in the last 15 years.
Unlike ALA, MAL is a lipophilic derivative that can ensure a
better intra-cell penetration and exploits a higher number of
uptake mechanisms through the plasma membrane.
PHOTODYNAMIC THERAPY FOR SKIN
CONDITIONS AND PHOTOREJUVENATION
P. Calzavara Pinton, M. Venturini
Some degree of improvement of clinical signs of photoaging
was reported as unexpected and positive side effect on
peripheral areas surrounding actinic keratosis lesions treated
by photodynamic therapy with aminolevulinic acid (ALA).
The goal of the study was to assess the level of efficacy and
tolerability of photodynamic therapy with methyl aminolevulinate (MAL) in the treatment of face photoaging in
patients affected by actinic keratosis.
Twenty patients affected by multiple actinic keratosis
(n=137) and showing severe signs of photodamaging were
treated on their entire face with two monthly treatments with
MAL-PDT. Metvix® (Galderma, France) was applied by
occlusive medications for 3 hours before exposure to 37
J/cm2 of red light (Aklilite® CL 128, Photocure, Norway). The
percentage of clinical remission of actinic keratosis lesions
was 88.3%, and the global score (that we used to assess photoaging) showed a marked improvement. In particular,
major improvements were noticed on focal hyperpigmented
areas, thin lines, wrinkles and yellowish color of the skin,
while the treatment succeeded in modifying deep wrinkles,
teleangiectasy, facial erythema and sebaceous gland hypertrophy. High resolution ultrasonography showed that treated
skin underwent an overall increase in thickness, an increased
pixel and area count and a reduction in the subepidermal
low-echogenic band (SLEB).
MINI-INVASIVE LIPOASPIRATION
G. Campiglio
this sort of product is that of formulating a product that is
not available in the normal distribution cycle.
The choice of the drug-cosmetic surely accounts for an
important occasion for the doctor’s therapy.
Drug-cosmetics are products that make use of pharmacologically active molecules, not found in cosmetics, administered
along with targeted and particular excipients.
The creation of a base made up of excipients with particular
chemical-physical characteristics to which the active principles of various nature and concentration are added, allow to
come up with a specific product tailored on the patient’s
needs and characteristics (type of skin, phototype, and individual allergies) and his/her pathology.
In this way, it is possible to employ diff e rent concentrations of
active principles and combine one or more active principles.
EVALUATION OF THE OXIDATIVE STRESS
IN SPORTSMEN INTEGRATED WITH SOD
EXTRACTED FROM CUCUMIS MELO
M. Cavallini, E. Fasola, E.L. Iorio
In this presentation, a mini-invasive approach to lipoaspiration of different body areas is described. According to this
technique, multiple surgery sessions in local anesthesia allow
to obtain long-lasting results with a low percentage of risks
for the patient and a quick restarting of social life.
CUTANEOUS PHOTODYNAMIC THERAPY:
FUTURE PERSPECTIVES
P. Cappugi, A. Corsi, F. Bini, GIRTEF (Gruppo Italiano
Radiofrequenze e Terapia Fotodinamica)
In 1998 I started to treat some clinical cases of actinic keratosis and cutaneous non-melanoma tumors with excellent
results. Two years ago I started to treat ulcers of the lower
extremity with very good results. We can also foresee, on the
basis of clinical and experimental studies, that new photosenzitising will be included in the official therapy to treat
cutaneous tumors or many inflammatory cutaneous pathologies, to consider the photodynamic therapy more safe, efficacious and feasible.
GALENICALS AND DRUG COSMETICS
Free radicals in the oxygen, called ROS, are produced daily
during the common processes to defend the body against
pathologic and /or environmental events.
In many cases the hyper-production of ROS cannot be
drained: surplus of these free radicals induce the so-called
oxidative stress.
This condition occurs in silence during the time and extends
to all the body and it is strongly connected to the ageing
processes.
The risks inducing oxidative stress are different: acute or
chronic pathologies, poisonous habits like tabagism, confused lifestyles with a non-balanced diet, psychophysical or
pre-agonistic stress are generally considered as positive.
ROS’ dangerous activity is physiologically opposed by an
enzymatic complex of antioxidants which includes: the
superoxidedismutasis, catalase, glutathione peroxidise, as
well as a group of other substances with a low molecular
weight like carotenoids, flavonoids and ascorbate.
The authors, after these considerations, have evaluated the
level of the oxidative stress throughout a photometry of capillary blood in two different categories of sportsmen, men
and women and in different sports, before and after taking
SOD extracted by Cucumis Melo per os.
M. Castiglioni
Nowadays, the preparation of more targeted and personalised products is becoming an increasingly important need
for physicians.
Providing your patient with a specific and unique product, as
well as fidelising your client to your own office, may be of
great help for your therapy.
The rationale that ought to induce a physician to prescribe
THE PRINCIPLES OF REMODELLING
L. Celleno
Many cosmetic functional principles are employed nowadays
in the attempt to counter the effects of skin ageing with different aims. The concept of “remodelling” has recently been
introduced in publicity communication to describe an action
85
that is so effective that you obtain a tangible effect on tissue
relaxation induced by senescence.
The functional principles adopted for this aim have different
action mechanisms and are often used in synergy to counter
the various pathogenic processes of ageing.
Botox-like substances act upon muscle-mimic wrinkles,
obtaining considerable effects if used every day, without
manifesting to date any relevant collateral effects.
Substances of vegetable origin are widely used nowadays by
women, that have the ability to act in the same way as estrogenic hormones but without inducing systemic effects.
Other substances generally derived from molecules that
compose the human derma, carry out more than one function being agents that produce a film on the surface, but also
able to penetrate into the skin thanks to their molecular
weight. These substances promote the synthesis of new molecules that are part of the fundamental substance of the
derma and are often linked to other functional molecules,
such as derivates of vitamin A to promote other specific cellular functions.
As well as specific substances that are now well defined,
there are many “vegetable extracts” whose complex contents
show different and effective actions.
Although achieving a “remodelling” of the face by using only
cosmetic products seems utopia, it is also concretely plausible to contrast the phenomena of skin ageing by improving
the aspect and the health of the skin.
MULTILAYER PEELING IN THE TREATMENT
OF PHOTO AGEING AND MELANINIC
HYPERPIGEMENTATION
L. Celleno, F. Tamburi
Chemical peeling utilizes the so called Keratolitic substances
which cause cell elimination by reducing the intercorneal
and interkeratinic adhesion. According to how deep the
solution penetrates, the peeling is superficial, medium or
deep. The principal chemical agents used as an outpatient
therapy are (glycolic acid, salicylic acid, Pyruvic acid,
trichloroacetic acid) and nearly always a single component.
Occasionally a topical therapy is prescribed for home application to enhance the outcome of the outpatient treatment
(for example retinoic acid hydroquinone) and to reduce or
avoid possible negative side effects (topical cortisone, antiinflammatory medication).
The substances used in the outpatient peeling are rarely prescribed for patient use since there is a risk of synergic
empowerment.
We have recently devised an outpatient peeling mixture,
which we call a “Multilevel” peeling. It is a collection of several therapeutic agents where each reacts at a different level
and with a specific goal, retinoic acid, salicylic acid, Pyruvic
acid, Hydroquinone. In this mixture, these are the two prin-
86
ciple keratolytic substances which facilitate the deeper penetration of the other components, retinoic acid and
Hydroquinone. Since this mixture could be defined as a
medium-superficial peeling, it has high tolerability and can
in fact be applied more than once in the same sitting.
We have used this peeling for a year now, during which time
it has proven to be an efficient treatment in active phase
acne, fotoageing and melanin hyper-pigmentation.
COMMUNICATION WITH THE PATIENT
AND INFORMED CONSENT
V. Cirfera
Informed consent is given by an adequately informed patient
who can make a free, and voluntary decision to accept the
therapeutic and diagnostic approach proposed by his medical doctor in order to treat or improve one or more health
problems.
Therefore the doctor is given the confidence and the legitimacy to treat the patient, in addition to the medical authorization provided under the law. Indeed this is not a purely
bureaucratic and formal deed, but it is the necessary condition to transform an act that is paradoxically “against the law”,
such as the violation of the psycho-physical integrity in surgical and invasive procedures into a “legal” act” whose aim is
the very essence of bio-medical science (1).
Many health-care professionals still neglect to ask for this
consent, with the risk of civil and criminal liabilities whenever a medical or surgical procedure results into an unfair
damage to the individual.
The informed consent is also required on the basis of recent
ordinary case law (2). This process envisages a series of steps:
first the patient is informed, secondly the patient shows to
have correctly understood the doctor’s information, so as to
be able to accept it or not; thirdly the patient gives his/her
consent, preferably in writing that can be used as proof of the
free agreement between the patient and the doctor and as an
instrument to protect health care professionals in case of litigation (3).
There are very particular contractual and extracontractual
liability clauses in the informed consent in Dermatology procedures that entail some risk for the patient. In the field of
esthetic medicine, the right to be informed is even more specific, given the very nature of the requirements of patientsclients, that is the result of the health procedure, which, in
this context, is evaluated according to the information provided (4).
Peeling is a method or better it is a series of outpatient esthetic or clinical and esthetic procedures (5), often considered
trivial and without adverse effects. In order to achieve an
ideal agreement between the parties, to deliver highly professional procedures and to obtain a result without criticisms
and protests, it is necessary to find the right time to look at
their indications, contraindications and adequately inform
the patient with a simple and essential language as to the
nature of the peeling substances to be applied, the interaction between these substances and the skin, the technical
and operational modalities, the planning of the sessions, the
risk-benefit analysis of treatment, the alternatives and especially the limitations in terms of results, so as not to create
false expectations, disappointment and regret, that are frequent causes of litigation (6).
reversibility of the obtained effect following the implant,
technical and operational modalities, duration of the filling
effect, the risk/benefit ratio, especially in the case of permanent implants, alternatives with respect to the primary proposed procedure and, finally, any probable or possible results
that can be achieved by the proposed method (6). It is advisable (7) that the consensus form contains, besides general
pre-printed information, many blank spaces to allow suitable
integrations concerning specific cases, otherwise the contract
will not be valid due to insufficient information.
References
1. Milan Court: V sect.. civ. Sent. n° 3520/2005.
2. Civil Court of cassation, Section III, 19/10/2006, n. 22390
3. Civil cassation, Section III, 24-10-2007, n. 22327
4. Civil Cassation Section III, n. 9617/99
5. Labrini G., Guerriero G., Landi F. L., Teofoli P., Cirfera V. Peeling chimico:
linee guida. D.A. Organo Ufficiale AIDA Associazione Italiana Dermatologia
Ambulatoriale, Anno XIV – Aprile-Giugno 2006, (2): 7-16.
6. Cirfera V., Labrini G., Toma G., Vinci P. Il consenso informato in
Dermatologia: obbligo o discrezione? Atti del XVI Congresso Nazionale AIDA,
Bari 20-23 Giugno 2007.
COMMUNICATION WITH THE PATIENT
AND INFORMED CONSENSUS
V. Cirfera
Informed consensus is a medical act which has an important
legal value in clinical practice, and which is unavoidable in
plastic interventions (1), as it represents the true essence of
the contract subscribed by the doctor and his patient, who
by resorting to “filler procedures” wants to correct or improve
a clinical alteration or a purely aesthetic defect (2). For this
reason, information represents a validating moment for consensus, because it is aimed at making the patient-customer
fully understand the procedure proposed by the doctor in
order to achieve the desired result (3).
The increased number of performed filler procedures causes
a relevant increase of professional risks due to the events in
which final results sometimes do not meet expectations or
promises; sometimes, negative events occur with regard to
the adopted procedure and they should not always be associated to malpractice, but very often they are due to the lack
of understanding between doctor and patient on the real
goals of fillers and because of insufficient communication
and information.
In line with the Court of Cassation rulings on informed consensus (4, 5), keeping into account the recommendations
issued by scientific societies of this sector, but also its and
other experiences, the content of a correct informed consensus form concerning filler should be simple and clear, tuned
according to the level of understanding of the patient, presenting indications and contraindications of the procedure,
the nature of the substance or the administered material,
References
1. Cirfera V. Informed Consensus for fillers. ECM Updating Course
in aesthetic and corrective dermatology with legal and medical aspects,
Turin 19/05/2007-Rome 26/05/2007.
http://www.dermatologialegale.it/news.php?id_news=07052007
2. Cirfera V. Medical-legal aspects of peeling in Journal of Plastic Dermatology
2007, 3(1): 41-49. ISPLAD.
3.XVI AIDA National Congress, Bari 20-23/06/07. Cirfera V. Informed
Consensus in Dermatology: mandatory or discretionary tool?
http://www.dermatologialegale.it/news.php?id_news=13082007.
4. Civil Court of Cassation no. 364/1997.
5. Civil Court of Cassation no. 10014/1994.
6. Cirfera V. Legal and medial aspects and informed consensus: ECM
Advanced updating course in aesthetic and corrective dermatology, SIDEC,
Rome, October 20th 2007.
7. Lorè C., Cirfera V. Vinci. P. in Professional updating course on dermatology
and Law, Copertino (Le), 30/09/2007: Ethics, Aesthetics and Liabilities,
promoted by the Ateneo research group on legal-medical sciences, Prof. Cosimo
Lorè, University of Siena. http://www.scienzemedicolegali.it/didattica.html.
Questionnaire
1. All the following statements are false but one. Which one?
a. Informed consensus is a bureaucratic procedure that only
applies to invasive surgery.
b. Informed consensus is mandatory by law in dermatology
and aesthetic procedures.
c. Informed consensus in medicine and surgery, both for
clinical and aesthetic purposes, is a medical act with legal
value and it is an obligation for the doctor in compliance
with constitutional and bioethical principles, specific deontological, civil and criminal norms, as witnessed by numerous legal cases on the subject.
d. Informed consensus in aesthetic dermatology should
always be obtained on written forms, otherwise the patientcustomer and health care operator contract will not be valid
e. Informed consensus for filler only concerns permanent
ones as they are invasive, risky and dangerous.
2. Informed consensus is:
a. A single medical-legal act.
b. A medical-legal act to be fully performed before a procedure is carried out.
c. A multiple medical-legal act involving the relatives of a
conscious patient aged 18 or older.
d. A medical-legal act simply included in the medical record.
87
e. A multiple medical-legal act assuming the full understanding of the patient of received information, concerning
the suggested diagnostic-therapeutic approach aimed at the
resolution or improvement of a given aesthetic and/or physical-psychological health status.
3. In informed consensus concerning fillers, it is advisable, for
validity purposes, to inform the patient-customer on:
a. Nature of the substance or material that will be administered and its reversibility.
b. Technical-operational modalities and duration of the filling effect.
c. Risk/benefit ratio, especially for permanent implants.
d. Alternatives with respect to the primary suggested procedure and the possible final results achievable by that method.
e. All previous statements are true.
STRATEGIES TO PREVENT PROFESSIONAL
RISKS
V. Cirfera
Knowing clinical risk and to analysing how to reveal possible professional errors in the surgical medical practise is an
absolutely necessary reflexive moment to make any possible
strategy to prevent risk-associated personal damages.
Recently “Risk management” is considered as the main priority in the activity of Ministry of Health, regarding quality and
safety of the health services (1) and is an unquestionable and
ethical duty of each physician, according to art. 14 of the
2006 code.
The specified “ratio” is the intent to guarantee safety in
healthcare. Without it the professional can be questioned
considering it of bad quality. On the contrary, the contentious for a presumptive malpractice is unjust, as for most
of the suits against physicians (2) in which he has given all
his care in the health service but in which unforeseen complications occurred and/or their results were different from
what the patient expected. So, it is indisputable that medicine is a high risk profession: in Italy a physician with 20
years of experience could have 80% probably to be convened
for damages related to his intervention on a patient (3). In
the last years, this reality did not spare medical or surgical
disciplines such as dermatology, historically exempt from
contentious or just in part involved in it compared to other
professional branches like orthopaedics, gynaecology, obstetrics and invasive surgery (4, 5).
Surely the reason of the contentious increment in dermatology can find a support in the recent escalation of aesthetic
outpatient interventions, unfortunately not without problems if dealt by unskilled professionals. Furthermore, we
cannot disregard contentious due to the omission of early
diagnosis, because on the one hand the high quality of technical and technological skills have without doubt increased
the chances of an early diagnosis and cure but there is on the
88
other hand the certain less excusable risk of human error.
Finally, particular attention should be given to the therapeutic procedures made with an “off label” system, recurrent in
dermatology to evaluate the real necessity and safety. The
author will face this problem underlining the most frequent
risks in dermatology and proposing for each one a specific
strategy to prevent it, referred to the suitability of the programmed steps of the interventions, information and
informed consent to collaborate with the patient and finally
the technical-procedural activities.
References
1. DM 5 marzo 2003
2. www.dermatologialegale.it/news.php?id_news=26012004
3. Dimasi L. Professione a Rischio. “Club medici news” anno 7, Settembre –
Ottobre 2007; 7(5):12-14.
4. Taragin G. Medical Professional Liability Cit. in IORIO m.: la responsabilità
Professionale dell’operatore sanitario e la tutela assicurativa. Minerva
Medicina Legale 2001, 121, 217- 241.
5. G. De Panfilis, F. De Ferrari in: Aspetti medico-legali jn Dermatologia.
Prima Edizione by Mediserve s.r.l.
COMBINED LASER ND:YAG 1064 - IPL
TREATMENT: 10 YEARS OF EXPERIENCE
IN TECHNOLOGY DEVELOPMENT
S. Colaiuda
Various invasive and non-invasive methods for eliminating
varices are available, however, each of them has some limitations. The invasive technique known as sclerotherapy whose
rate of success depends on the doctor’s high technical accuracy and skills. There are also laser treatments but they have
shown limitations as regards the elimination of superficial
and small-diameter telangectasies and no effect on deeper
varices.
Our experience is based on the treatment of deep reticular
varices (up to 5 mm) and extended varices (up to 3 mm of
diameter) as well as of superficial telangectasies of the lower
limbs with a combined system using an IPL (Intense Pulse
Light) source and a Nd:Yag 1064 laser. We performed this
technique between 1997 and 2007 following a 3-stage clinical protocol (cardiovascular-blood-clinical and instrumental
screening).
The varix surface reduction was 80-90% after 3 treatments in
80% of patients. The use of an IPL source during the next 3
treatments enabled us to observe that the varix area had
totally disappeared in 90% of treated patients.
The excellent results observed during our 10-year experience
let us confirm the effectiveness of the combining the Nd-Yag
1064 with the I.P.L. source for a non-invasive treatment of
large and deep varices and superficial telangectasies of the
lower limbs. An outpatient treatment that is also very well
tolerated.
PHOSPHATIDYLCHOLINE AND ADIPOCYTES
M.D. Colombo
Phosphatidylcholine is the phospholipid that mainly constitutes the cell membrane. Phosphatidylcholine is also known as
1,2-diacil-sn-glycero-3-phosphocholine, Ptd Cho and lecithin.
The term lecithin has different meanings when it is used chemistry and biochemistry, rather than commercially. Chemically,
lecithin is phosphatidylcholine. Commercially, it is a natural
mixture of neutral and polar lipids. Phosphatidylcholine,
which is a polar lipid, is found in commercial lecithin in concentrations varying between 20% and 90%. Most of the commercial products of lecithin contain about 20% of phosphatidylcholine. Phosphatidylcholine is important for the composition of the cell membrane and to repair it. It is also the
main form of transport of choline. Choline is the precursor of
the acetylcholine neurotransmitter. Phosphatidylcholine has a
role in the export of very-low-density lipoprotein. The role of
phosphatidylcholine in maintaining the integrity of the cell
membranes is vital for all the basic biological processes. Such
processes are: the information flow within the cells from the
DNA and RNA to the proteins; the production in cellular energy and intracellular communication or transduction signal.
Phosphatidylcholine, especially the one rich of polyunsaturated acid fats, has a marked fluidification effect on cell membranes. The reduction of cell membrane fluidification and their
rupture, as well as the failure of the repair processes is associated with many diseases including liver and neurological
pathologies, various types of tumours and cell death.
Phosphatidylcholine has been used in medicine for over 50
years as a drug for a long series of pathologies and lately for its
anti-cholesterol and anti-triglyceride properties. Its action
involves the natural emulsification of fats, eliminating them by
transforming them into energy. For this reason, it is now more
than 10 years that it is injected subcutaneously as a powerful
lipolytic. It is presumed that this medication penetrates into the
adipocytes through the double lipidic layer, acting as an emulsifying/tensioactive agent. The modification of the lipids,
induced by the drug, occurs with the transformation of the
water-soluble products. This leads to their elimination because
not compatible with the liposoluble content of the adipocytic
cell. However, to date the full action mechanism of phosphatidylcholine on fatty deposits is still not totally clear.
A STUDY PROTOCOL FOR AN OPEN OBSERVATIONAL RETROSPECTIVE MULTICENTRIC
STUDY ON THE USE OF FORMULAS
CONTAINING PHOSPHATIDYLCHOLINE IN THE
TREATMENT OF LOCALISED ADIPOSITY
M.D. Colombo
The phosphatidylcholine (PC) is the most frequent phospholipid in the animal and vegetable world. It is an impor-
tant component of lecithin (10-20%). PC is made up of a
group of phosphates, 2 fatty acids and choline, and is a precursor of acetylcholine. Linoleum acid is the main fatty acid.
PC is the main structural component of the cellular membrane. About 40%-50% of the cellular membranes are compost of PC. Given its role in maintaining the cellular membrane whole it has the essential job of haemostatic regulation
of its fluidity.
PC is commercially produced in association with deoxycolic
biliary salt (DC) and an anti-microbic (benzilic alcohol). The
formula is similar to commercially available Essentiale and
Lipostabil which have vitamin E and vitamin B group additives.
The injection of PC is becoming one of the most popular
techniques in the treatment of localized adiposity.
Many open studies have reported promising results in the
treatment of: under eye bags, double chin, cheeks, hips, lipomas, lipodystrophy in HIV patients, especially for the buffalo hump and in other areas. As a result of these studies and
after the introduction of off label treatments for the xanthelasmas in 1988, many European, South American and South
African doctors began to treat localized adiposity with commercial products such as Essentiale and Lipstabil (Natterman
– Aventis) which contain PC.
Even if these products are used for the treatment of liver and
cardiovascular pathologies, they are not approved by the
FDA for aesthetic use and the Brazilian Ministry of Health
has recently prohibited the used of Lipstabil because of
insufficient documentation on safety and efficacy. For this
reason the idea of organizing a formal study under the
patronage of those dermatological societies accredited with
the task of experimenting in the field of aesthetic dermatology, who are able to demonstrate the efficacy and tolerability of this preparation in the reduction of localized adiposity.
Given the unique active mechanism on adipose tissue of this
product, we propose a retrospective study with a large number of patients with a precise codified treatment scheme to
demonstrate the real efficiency and tolerability of PC in the
reduction of localized adiposity.
The primary objective is:
• To evaluate in a cohort of patients affected with a medium
degree of localized adiposity the efficacy of the preparation
containing phosphatidylcholine (PC) in the reduction of
the same.
The secondary objectives are to:
• Evaluate the reduction of PEFS in the third and fourth
stages (according to Curri) in patients who have been
treated for localized adiposity with severe clinical picture
of PEFS.
• Evaluate the reduction of localized adiposity by way of
ultrasound (e.g. linear array from v7.5 MHz with Esaote
ultrasound AU3 partner) with a standardized measure of
positive results.
• Evaluate the anthropolycometric variations.
91
• Evaluate histological alterations (descriptive analysis) of
the biopsies carried out on a limited sample of the
patients.
• Evaluate the tolerability of the phosphatidylcholine containing preparation during the whole length of the study
through the collection of CRF on all the side effects etc.
• Evaluate the changes in the tape measure values of the
haematic lipidic picture.
Experimental design
Observational, retrospective and Multicentred.
BOTULINUM TOXIN: PHARMACOLOGY
M.D. Colombo
Botulinum is a drug: therefore, using it to smooth wrinkles is
a pharmacological treatment that needs precise rules to be
followed and the Specialist deontology and caution.
The patient must be suitably informed about approved indications, contraindications, possible optional treatments, and
side effects.
The physician needs to have an in-depth knowledge of the
botulinum pharmacology, the face anatomy, the previous
experiences in wrinkle-smoothing treatments (namely
fillers).
The injection technique is conceptually and practically very
different from the traditional filler injection technique: actually, the toxin is a protein that must be accurately injected in
the muscle in very low dosages and via a very thin face needle. This treatment leads to a temporary reduction of acetylcholine release, i.e. the chemincal mediator liberated at nerve
endings as neurotransmitter.
As a consequence, the muscles concerned relax, thus reducing the continuous muscle traction, often spontaneous and
non voluntary, of the upper skin tissues that gives that
frowned and angry expression. The relaxation effect is well
visible 3-7 days after the treatment and lasts on average 4
months.
Then, botulinum injections must be periodically repeated
not only to maintain the results but also to prevent other
expression lines from appearing again on the face.
The scientific international literature reports and confirms
that face rejuvenation treatments may be well associated to
other dermoplastic treatments such as chemical peelings,
biorevitalization, reabsorbable intradermal fillers and laser
resurfacing with very good results.
BOTOX AND COLLATERAL EFFECTS
M.D. Colombo
Botox is largely used all over the world. Nowadays, millions
of patients are treated with Botox not only for medical reasons, but also for aesthetic implications.
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It is a medicine with a very wide “therapeutic window”, easy to
use and with a low frequency of collateral effects.
But it is important to remember that Botox is a protein and
patients may risk an anaphylactic shock. Literature reports only
one case every 10,000 treatments, but in that case it is better to
be equipped with injectable cortisone and adrenaline.
AIFA, with a newsletter to all doctors, recommends other
interesting aspects about muscular weakness.
These problems are rare, most frequent in neurologic
patients where higher dosages are used.
The most common side-effects, also reported by the media,
are actually less serious and caused by a poor application or
by a wrong behaviour of the patient after the treatment.
All the side effects are completely reversible, causing a temporary discomfort to the patient but with a complete reestablishment.
USE OF BOTULIN IN THE LOWER THIRD
OF THE FACE
M.D. Colombo
In the clinical practice, botulin can be very useful to solve
some aesthetic problems without recurring to more invasive
techniques.
Infact, it is very important to face some particular requests
that can be treated with botulin, such as nasal wrinkles
(bunny lines), perioral wrinkles, raising of the mouth angle
to treat the depressor anguli oris; raising the nose tip, to correct a “gummy smile” or to treat deep zygous wrinkles. Also
the neck, especially platysma bands can be correct with some
suitable injections of botulin, so as the mandibular profile
with the technique called “Nefertitis”.
All these zones demand a good anatomic preparation and
physiologic movement can be faced only after seeing that it
is safe to use it in the upper portion of the face.
PHOTODYNAMIC THERAPY FOR SKIN CARE.
A HIGH VERSATILE METHOD: HAIR REMOVAL
C. Comacchi, GIRTEF (Gruppo Italiano Radiofrequenze
e Terapia Fotodinamica)
Most people ask for undesired hair removal mainly to solve
an esthetic problem since excessive hair growth may have a
major psychological and social impact.
Cutaneous photodynamic therapy (TFDc) is proving to be a
very effective therapy for the treatment of actinic keratosis
and epitheliomas as well as many skin conditions. Some
recent studies have emphasised its usefulness in the treatment of idiopathic hirsutism (IH) and hypertrichosis.
The goal of the study was an evaluation of TFDc effectiveness
in women with undesired hair:
• hypertrichosis with non-androgen dependent fair hair
and/or thin hair on the face and other areas of the body.
• mild-moderate androgen-dependent idiopathic hirsutism
of the face or other areas of the body.
Results from both clinical studies showed a significant reduction of undesired hair without re-growth at six/nine months
as from the end of the protocol.
CONDITIONS: EXPERIENCES WITH BLUE LIGHT
C.Comacchi, F. Bini, GIRTEF (Gruppo Italiano Radiofrequenze
e Terapia Fotodinamica)
Indications for photodynamic therapy for skin conditions
(PDT) with blue light are partly the same as those applied to
PDT with red light, while some clinical and practical advantages of this methodology are becoming increasingly convincing. The used blue light has a wave length of 470 nm
and the performed work is usually the same as that of the red
light, i.e. 100 joule. ALA application time is 60-75 minutes.
Exposure time (irradiation) is slightly less than 3 minutes.
The patient does not complain about any pain neither during nor after the treatment, not his/her skin looks particularly “stressed”, as skin rashes and edema are so minor that, only
for precautionary reasons, a soothing cream is applied after
the treatment. From a clinical point of view, results with the
application of blue light seem to occur faster, requiring less
sessions and providing more comfort for the patient: exceptionally good results can be obtained for acne, actinic keratosis and skin photodamages, already at 14 days. For more
superficial skin conditions, susceptible of photodynamic
treatment, with regard to red light, the advantage offered by
blue light is quite obvious also for the operator, as it requires
shorter application times. Due to intrinsic characteristics and
to its lower degree of penetration (dissipation of a more energetic light with same joule value on a smaller skin volume),
the blue light seems more efficient in terms of rapidity and
reduced number of sessions required to achieve the same
result and it also explains the complete absence of pain during the treatment (very few nervous terminations are
involved by blue light) and a much more limited erythematous reaction right after the treatment (less involvement of
vascularized skin layers).
VITILIGO THERAPY: AN APPROACH
PROPORTIONATE TO THE CLINICAL ACTIVITY
OF THE DISEASE
C. Comacchi, G. Menchini, GISV (Italian Group for the Study
and Treatment of Vitiligo)
In order to treat vitiligo there is no single or elective therapy,
but rather a series of therapies aimed at reducing the
immune reaction and at stimulating the residual reserve
melanocytes to multiply in order to recolor hypo/achromic
patches induced by the disease. The correct therapeutic protocol requires first of all examination by a dermatologist supported, if necessary, by other specialists (endocrinologist,
immunologist/allergist, psychologist, geneticist, ophthalmologist). This with the goal of identifying the “characteristics”
of vitiligo in each patient.
In fact, a dermatologist must assess:
1. activation index (VAI) in order to assess if vitiligo
is in a stationary phase, in regression or if the condition
is worsening;
2. genetic framework;
3. type and extent of vitiligo: widespread, acrofacial,
localized, segmented and seborrhoeic;
4. age of the patient;
5. patient’s phototype (skin color and hair assessment
on each patient);
6. association with other diseases;
7. Koebner’s reaction;
8. psychological involvement;
9. alterations in the quality of life.
These factors can also be assessed through blood tests aimed
at avoiding the presence of autoimmune diseases and help in
the identification of the most appropriate medical therapy.
We are convinced that only by following a rigorous investigation method we’ll be able to implement a therapeutic protocol aimed at providing real hope for improvement to
patients suffering from vitiligo.
Lectures
Mollet I, Ongenae K, Naeyaert JM. Origin, clinical presentation, and diagnosis
of hypomelanotic skin disorders. Dermatol Clin. 2007; 25(3):363-71, ix.
Rezaei N, Gavalas NG, Weetman AP, Kemp EH. Autoimmunity
as an aetiological factor in vitiligo. J Eur Acad Dermatol Venereol.
CUTANEOUS LYMPHOMAS CLINICAL
DIFFERENTIAL DIAGNOSIS
A. Costanzo
The increasingly common use of research methods, such as
immunohistochemistry and molecular analysis integrating
the routine histomorfological exam, has greatly contributed
to the development of the primitive cutaneous lymphoma
current concept. The relationship between the clinical and
pathologic picture and the immunophenotypic and genotypic characters has allowed to clearly distinguish the different
subgroups of the cutaneous lymphoma, thus offering valuable indications on the clinical course, the therapy and the
prognosis.
In addition, thanks to the new technologies, it is now possible to correctly distinguish the cutaneous lymphomas from
the several clinical entities of superimposable morphology
that are usually included in the differential diagnosis.
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This report will address the various possible types of differential diagnosis that should be used when suspecting a primitive cutaneous lymphoma and in the clinical, immunophenotypic and molecular criteria that enable a correct diagnosis.
TUMOURS OF THE CEPHALIC EXTREMITY:
STANDARD AND ADVANCED
MORPHOFUNCTIONAL RECONSTRUCTIONS
D. D’Angelo, L. Ligrone, L. Martora
Skin tumours represent about 10-15% of all the neoplasias
in man and account for about 1.6% of deaths. This pathology, even through its peak of incidence, involves individuals
between 60 and 80 years, in recent years there has been an
increased incidence in young and very young population.
From a histological point of view, malignant skin lesions in
85% of the cases are constituted by 85% Basocellular
Carcinomas, whereas Spinocellular Carcinomas are equal to
13%, Malignant Melanomas 1.5%, and rare tumours (mainly sarcomas) involve 0.5% of the cases.
With regard to the distribution of skin tumours, in 90% of
the cases (Baso- and Spinocellular) epitheliomas develop in
photoexposed areas, such as forehead, nose, cheeks, auricular and periorbital region. This percentage goes up to 100%
of the cases involving keratoacanthomas. Melanomas tend to
feel less the effects of actinic radiations, since most of these
lesions are found in covered areas: trunk and lower limbs.
Surgery for these lesions to date represents first choice treatment for all those lesions considered to be curable.
Obviously, such treatment involves a demolishing phase and
a reconstructive one and has to abide to some fundamental
principles:
1) Oncological radicality: the extirpation of the lesions has
to be sufficiently large so as to avoid local relapses.
2) Re-establishment of functionality: reconstruction has to
be performed above all with purpose of the functional
recovery of the treated part and/or system. So, all the tissular components sacrificed for the removal need to be
reconstructed.
3) Morphological re-establishment: reconstruction should
have the purpose of not just restoring the shape, abut also
the consistence and the colour of the demolished districts. Even for this reason, it is important that the reconstruction aims at reintegrating the tissues that have been
removed.
Authors report their own personal experience.
MAGISTERIAL READING “LIPOFILLING”
C. D’Aniello
The idea of using an autologous material as fat for filling up,
reshaping and changing the cutaneous surface, dates back to
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the beginning of 19th century. During the past century, several scientific researches on the use of adipose tissue as a filling
up product were made.
The lipofillling is a particular procedure that provides for the
use of autologous fat as a filling up product, instead of an
extraneous substance which can be a potential source of
allergic reactions or rejections.
The success of this procedure is due to the sample technique
and the transfer of adipocytes: the adipose tissue is sucked
where there is more than enough, thanks to some cannulas
linked to syringes and then it is injected in those body areas
to be treated. The tissue that has been transferred will firstly
take its nourishment thanks to the simple imbibition of well
vascularized tissues and then it will create new vascular connections; moreover, the transplanted adipose tissue shows
the presence of several adult stem cells in its context, which
are responsible of an overall improvement of the treated area
thanks to neoangiogenesis processes and fibroplastic proliferation.
The main indications are represented by postramautic outcomes, cicatricial outcomes due to burns, asymmetries of the
mammary edges (Poland Syndrome, breast augmentation,
mammary reconstruction), face volumetric augmentation,
radiodermatitis outcomes, atrophy due to corticosteroids
and antiretroviral drugs, facial congenital malformation. The
advantages of this technique are represented by the biocompatibility of the adipose tissue, by the easiness and the versatility of the procedure, by the scarce morbidity of the donating area and by the good results. The lipofilling has imposed
itself during the last few years in plastic surgery and it opens
up new horizons in the health field and in the scientific
research.
PEAT: APPLICATIONS IN PLASTIC
DERMATOLOGY
M.L. D’Errigo
The peloid is a particular crenotherapeutic means deriving
from the primary or secondary mixture of a solid natural
material (inorganic, organic or mixed) and water of various
nature and origin (mineral, sea, lagoon, lake).
In Italy, the crenotherapeutic use of peat is not very widespread, due to the prevailing use of mud, contrarily to what
happens in Central Europe, where slit and peat is more commonly used. Peat represents the first stage of carbonization of
vegetable substances, which from peat, to lignite turns into
fossil coal.
From the chemical point of view, peat is made up of the
remains of plants of various nature (sphagnum, grass, seaweed…) in different grades of decomposition. The maturation of this product in thermal water, for instance hypertonic sodium chloride water, make it very suitable to treat and
prevent many rheumarthropatic, dermatological and angio-
logical diseases. Peat can be applied under the form of a
compress (like all peloids) or masks, with a duration of
about 15 minutes. Indications for use in dermatology are
some primitive diseases such as seborrhoea, acne and skin
xeroses.
This precious product can be used to prepare cosmetic pro ducts that have a mineralizing, restoring and lenitive action.
The application of peat, followed by a bath in thermal water,
may induce the rearrangement of the microcirc u l a t o ry flows
and stimulate the activity of enzymes that make it effective for
the treatment of edematous-fibrosclerotic panniculopathy.
TISSULAR CHANGES DUE TO BIPOLAR
RADIOFREQUENCY IN SYNERGY WITH 900 nm
DIODE: BIOPTIC RESEARCH
F. De Angelis
This research wants to underline the effects produced by
bipolar ELOS® radiofrequency on collagen, dermatic and
hypodermic structures and annexes. Seven female patients
aged between 35 and 65 years have been selected. The
patients have been subjected to cutaneous biopsy through
punch of the left nasogenal sulcus before carrying out the
first treatment and then after one month (1st treatment), two
months (2nd treatment), three months (3rd treatment), six
months (check up) and after one year from the first treatment (check-up). The selected volunteers have resulted negative to pregnancy, collagen diseases, cheloids, photosensitivity, isotretinoin use or previous facial rejuvenating cosmetic treatments. The bioptic samples have been stained with
eosin hematoxylin to evaluate the morphological changes.
Specific antibodies for collagen I/III have been used to evaluate the induction of collagen neosynthesis.
PYRUVIC ACID (video)
M.P. De Padova
Pyruvic acid in alcoholic solution has been successfully used
for years now to treat several dermatological conditions with
the aim of provoking a limited and controlled destruction of
the epidermis and of the superficial layers of the skin in
order to eliminate or improve skin defects. However, today it
has become a more competitive product which can be used
in different conditions thanks to more innovative and less
irritating formulations which can also be combined to exfoliating substances.
It is an alpha-ketoacid with three carbon atoms, which is
present in nature, in apples, in fermented fruit and which
has keratolytic, sebostatic and antimicriobial characteristics.
Pyruvic acid acts as follows:
• On the skin, where it reduces the bond between keratinocytes and induces acantholysis.
• On the papillary dermis, where high concentrations can
provoke the separation between the dermis and the epidermis and induce an inflammatory reaction on the dermis, by releasing inflammatory mediators stimulating tissue repair through the formation of new collagen and elastic fibers.
• On hair follicles, where it can penetrate very deep and act
as a bacteriostatic substance (by reducing the local pH)
and a comedolytic agent (by reducing the cohesion
between keratinocytes and the wall of the sebaceous
gland).
The author reports the results on patients suffering from
papulopustular acne, rosacea, melasma and photoaging, suggesting that this peeling cannot replace the indicated treatments, but it has to be used to optimise their action.
The improvement obtained increases with the depth of the
lesion induced, but so do risks and possible side effects.
Therefore the post-peeling management has to be strictly
implemented and monitored.
VULVAR ALLERGIC CONTACT DERMATITIS
O. De Pità
The onset of genital lesions can generate considerable concern in the patient and, from a clinical point of view, it poses
relevant diagnostic and therapeutic remarks. Genital lesions
are, in fact, the sign of a wide range of diseases and their
accurate diagnosis depends on the complex evaluation of
epidemiological, personal, clinical and lab factors required
for the adoption of the correct therapeutic appro a c h .
Aetiology includes sexually transmitted diseases (STD, herpes, granulomas, amebiasis), non-STD related infections
(Candida, Tinea), inflammatory diseases (Psoriasis, Lichen),
autoimmune diseases (Behcet, Vitiligo), tumor-related diseases (Paget, Melanoma) and exogenous agents (irritants,
drugs). Furthermore, besides dermatological and/or infective
signs, an allergic mechanism should be considered and suspected when the lesions worsen despite treatments. Type I,
II, III and IV hypersensitivity reactions can, as a matter of
fact, all be responsible for the onset of genital lesions and
they can be sub-categorized in those related to sexual activity (allergy to seminal fluid, to spermicides, to latex) and in
those that are not sex-related (allergy to local remedies,
detergents, Ig-E mediated candidosis).
INTERACTIVE CASES: SMALL MELANOMAS
(< 5 mm IN DIAMETER)
P. De Simone
The Incidence of skin melanoma has progressively increased
throughout the world: in Italy there are 10-15 cases/100,000
inhabitants per year, in Australia 40 cases/100,000/inhabi-
95
tants per year. However, early diagnosis remains a fundamental objective for an effective secondary prevention. The
clinical application of the ABCDE criterion has successfully
contributed to the early detection of suspicious pigmented
lesions.
However, in the last few years, numerous cases of melanoma
with a diameter < 5 mm have been described; therefore the
D criterion from the above-mentioned acronym is being
questioned.
To this end, the authors present 506 histologically documented pigmented lesions with a diameter < 5 mm. Of these,
48/506 are melanomas. All the lesions have been studied
with digital epiluminescence videomicroscopy.
PEELING OF FACIAL SKIN
M. Dembinski
The definition of a chemical peel is the acceleration of the
exfoliation induced by the application of a corrosive and irritating chemical substance on the skin.
The mechanism is:
• the stimulation of epidermal multiplication through the
removal of the corneal layer;
• the destruction of the damaged cutaneous layers; and
• the induction of an inflammatory reaction which produces
neo collagen and elastin.
The classification is:
• very superficial and is the removal of the corneal layer;
• superficial, which provokes necrosis of part of the epidermis between the granular and basal layer;
• medium, which provokes necrosis of the epidermis and
penetrates the papillary dermis;
• deep – very deep, which provokes epidermal necrosis and
penetration of the reticular dermis.
The depth and intensity of the peeling depends on:
• the exfoliating agent used;
• the concentration in % and pH;
• the amount applied;
• the application technique (with or without occlusions);
• application time (neutraliser);
• skin preparation (scrubbing and/or peeling);
• skin type (Fitzpatrick).
The classification of the exfoliating agent:
• Very superficial is glycolic acid 30-50%, retinoic acid, salicylic acid, TCA 10%, Pyruvic acid, resorcinolyc acid 2030%,
• Medium glycolic acid 70-90% pH <2, TCA 30-50%
strengthened with CO , Jesner solution or AHA weekend
peel, chem. Lift (32% phenol);
• Deep 88% phenol, Gordon & Baker phenol formula;
• Phenol formula Fintsi-Exoderm.
Suitable pathologies for chemical peeling:
• Ageing skin both chrono- and photoageing;
2
96
• Hyperchromia and melasma;
• Active acne;
• Post acne scars;
• Pre-cancerous skin lesions.
Skin ageing peelings:
• superficial: for prevention-cure has a low impact on social
life, excellent tolerance, low cost, treatment cycles;
• medium: cure-prevention, medium impact on social life
(1-4 days);
• deep: cure, high impact on social life (7-9 days) high cost.
Superficial peeling:
• Glycolic acid in various concentrations and pH;
• Retinoic acid, Salicylic acid, Pyruvic Acid, Azlaic acid.
Medium peeling: A weekend peel is:
• Solution A is an exfoliating chemical agent (salicylic +
Resorcinolo + Lactic + undecylenic acids in a solution of
ethanol;
• Coraline Desmosponge of cellularia epphydatia Powder
dry coral from the red sea, which is rich in silicon oxide
and used as an abrasive agent;
• Solution B is an activating powder;
• Hydrogen peroxide = H O , dead sea salt,
• Aloe extract.
2
2
Weekend peel: treatment phases
Epidermal exfoliation after 72 hours
Advantages: Easy to use in outpatient setting. Light or no
burning sensation or pain. Applicable to all types of skin
(even olive skin) and on all parts of the body. Short recovery
time (72 hours or a weekend). Long lasting results and a
highly effective therapy. Safe with no risk or complications.
Chemilift® Phenol light at 32.7%
Peeling with average aggression which forms an epidermal
frost. The esfoliation is complete within 5-7 days. It can be
applied to limited areas of the face or all over. Phenol at
32.7% is the esfoliating agent. Transcutol® is the penetrating
agent. Penetration is progressive, reduction in intrinsic toxicity, tissue around the eyes can be treated without secondary
effects - for the patient: gel with carbonfluoride. Moisturiser,
transparent, non allergenic, gives a better final solution,
shorter post peeling, exclusion time from social life is less
than a week.
Phenol based deep peeling Exoderm®
Exoderm solution - Component mechanism
• Phenol (carbolic acid-c6 h5 OH) creates a breakdown in
the epidermal keratinic protein;
• Septisol and glycerine (acts as a surfactant) reduce the
superficial tension and dilute cutaneous sebum;
• Croton oil (acts as an irritant) causes local inflammation
which increases phenol penetration and the subsequent
formation of collagen fibre;
• Oils as diluting agent;
• A buffer to equalise the solution penetration into the skin.
APPLICATIONS OF THERMOGRAPHY
IN COSMETOLOGY
A. Di Carlo
Cosmetic preparations are able to change local skin conditions. If they are effective, they provide a subjective and objective sensation of smooth, soft and polished skin etc., that can
be referred to as “e u d e rm i a ”. These substances act by reducing
the thermal exchange between the environment and the skin
surface due to a chemical and physical effect. The resulting
increase in skin temperature induces a superficial vasodilatation and an increase in the exchange between capillary circ ulation and tissues, with the passage of salts, electrolytes, water
and nutrients into the dermis (the so-called greenhouse effect).
Thermography is a non invasive method to study microcirc ulation. It can selectively evaluate the papillary microcirculation
and its modifications induced by the cosmetic preparations,
face masks, etc. In fact, capillaroscopy only provides morphological and non hemodynamic data, while laser Doppler is
able to evaluate the overall skin flow (superficial+deep dermis). By using thermostimulation, it is then possible to evaluate thermal gradients that are much lower than 0.1 °C, which
is the upper limit of present thermographers.
Therefore thermography may have experimental applications
and can be used to evaluate cosmetic substances or preparations. It is designed to investigate the bioavailability and efficacy of new preparations and is particularly indicated in the
study of chrono- and photo-aging, of the percutaneous
absorption of cosmetic products and pharmacological
agents. In the clinical setting, it is used to study dermatological microangiopathies. The paper presents the experience of
the institute in this particular setting and some examples of
other possible applications of this technique.
EMODYNAMICS OF VENOUS CIRCULATION:
PHYSIOPATHOLOGY OF MICRO-CIRCULATION
A. Di Gioia
From an hemodynamic point of view, the venous circulation
system (macro and micro-circulation), is regulated by the
same laws of physics, the most important one being gravity.
Thus, what do we mean by Hemodynamics of the venous
system?
Hemodynamics of the venous system studies the parameters
required for the implementation of the venous function.
These parameters are: (1) The study of deep and surface
venous networks, (2) The study of the forces generated by
the cardiac pump (heart), torax-abdominal forces, valvemuscular forces of the calf and the plantar pump force
required to implement venous physiology.
The hemodynamic study allows accurate diagnosis and a
more suitable treatment of vein diseases both in macro and
in micro circulation.
In our opinion, the diagnosis of telangiectasis in the lower
limbs is essentially based on an accurate Hemodynamic picture.
As a result, in order to adopt a suitable therapeutic approach,
it is fundamental to use three key tools:
• Clinical observation of posture variations of telangiectasies
and their morphology;
• Use of a slide for microscope;
• Use of an Eco-Doppler device, with 7.5, 10, 13 MHz
probes.
As far as clinical observation is concerned, pertaining posture variations, telangiectasies usually shows three behaviors.
• Telangiectasies which are totally indifferent according to
posture variation,
• Telangiectasies which are more apparent when the patient
is standing,
• Telangiectasies which are more apparent when the patient
is lying on a couch.
F u r t h e r m o re, there is an almost constant association
between the response to teleangectasie, posture variation and
their morphology.
• Telangiectasies that are more apparent when the patient is
standing, often have an up-side down tree morphology.
• Telangiectasies that become visible with a similar posture
could, however less frequently, show small dots or spider
angiomas, and in this case the slide test shows a small central vein running perpendicular to the skin.
• Telangiectasis that are more apparent when the patient is
lying down are situated on the outer surface of the third
superior and on the inner surface of the third inferior of
the thigh, i.e. in the typical areas of cellulite, and they look
like simple linear telangiectasis with visible underlying
reticular veins.
Very often these simple and linear telangiectasis tend to converge towards a reticular vein located farther away until they
take the shape of a tree, but this time right-side up.
Finally, telangiectasis not showing posture changes, may
show simple and linear telangiectasis without any evident
underlying vein network, or spot shaped telangiectasis or
spider angioma. In this latter case, the slide test can demonstrate the presence of a central artery or nothing at all.
An Eco-Doppler test would reveal abnormal blood flows
both between the deep vein system and the superficial one
(reflux) also within the superficial venous system (deflux).
Such examination is advised in cases where telangiectasis is
better seen with the patient standing.
Once the diagnostic process has been completed, treatment
indication and programming must take into account that differeny types of telangiectasis have developed in different
emodynamic areas. This applies both to the type of chosen
treatment (laser or sclerosis) and to the general strategy
(cases with surgical treatment priority, cases with sclerotherapic treatment and cases that can be directly treated by laser
applications).
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PEELING WITH RETINOIDS
E. Di Lella
The efficacy of retinoid therapy in photo and chrono-ageing
carried out on both long-term and short-term studies, has
been amply reported in the literature. Retinoids in particular
retinoic acid studies are the most frequently reported on the
use for photo-ageing therapy. Retinoids causes an increase in
the epidermal turnover and in the cells of the basal layer. It
reduces the volume and secretion of sebaceous gland, the
proliferation and activity of fibroblasts, epidermal melanin
and the transfer of melanosomes to the keratinocytes.
When we choose to use retinoids we must linger a while on
the structure formulas, pharmacokinetics, histological
changes and on the most recent topical formulas which give
the best absorption and efficacy.
THE TIME AND PH-DEPENDENCES.
A NEW TOOL TO OPTIMIZE THE CLINICAL
EFFICACY OF ACTIVE INGREDIENTS
EMPLOYED IN THE SECTORS OF MEDICAL
AND AESTHETIC DERMATOLOGY
F. Di Pierro
It is well-known that modern dermatology makes use of
compounds obtained via extraction. Some of these extractive
derivatives are currently listed as medicinal specialties in
many countries of the world. Such compounds are characterized by interesting pharmacological properties for dermatology, both medical and aesthetic. The antioxidant, anti-collagenasic, pro-collagen, vaso-protective, endotheliumrestructuring and anti-fibrosis properties of most of these are
well-know. The level of pharmacological investigation on
such derivatives has allowed for many of them to expand the
knowledge on kinetic absorption, and therefore pharmacokinetics and pharmacodynamics. The analysis of this evidence has thrown light, thanks to good evidence-based medicine, some of the limitations that characterise most of these
derivatives: instability, poor oral bioavailability and early
curve of plasmatic extinction. Compounds, such as vine seed
leucocianidine, melilotus coumarin, pennywort selected
triterpenes, Ananas comusus bromeline or verbascoside and
Olea europea hydroxytyrosol (just to make some examples)
can be galenically “manipulated” to optimise the pharmacological performance. For this purpose, time-dependences
and pH-dependences constitute a valid tool that can be used
to improve the clinical efficacy of these active ingredients.
In this way, it is possible to increase the pharmacodynamics
of leucocianidine, reduce the effects of liver first-pass of
coumarin, improve AUC for Asiatic acid, protect bromeline
from gastric lysis and increase oral bioavailability of polyphenolic derivatives from Olea. Clinically, all this translates into
a more evident antioxidant and anti-collagenasic effect,
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increased pro-lympokinetic activity, a more evident synthesis
of collagen, a stronger anti-fibrosis action and a greater dermoprotective activity.
FILLER RELATED SIDE-EFFECTS
A. Di Pietro
Fillers represent one of the main methods to correct wrinkles
and modify face volumes. There are two types of fillers:
absorbable and permanent ones. Permanent fillers should be
avoided for a series of different negative reasons which can
easily occur. The most common event is persistent tumescence in the site of injection and the frequent appearance of
edema even years after the filler injection. Granulomas
(caused by a foreign body) are not rare and they can fistulate
causing subsequent permanent atrophic scars.
INJECTION TECHNIQUES (video)
A. Di Pietro
For many years, dermatologists have used dermal fillers to
fill wrinkles and face depressions. At the beginning, there
was not such a wide range of formulas as we have today:
therefore, after a careful evaluation, the choice of the plastic
dermatologist on the injection technique was aimed at producing a re-absorbable and biocompatible product and in
particular the best compliance with patients (slow-stretching
technique) and reduction of side effects (inflammatory reactions, erythema, haematoma…) giving a longer persistence
of the implantation. After a long experience, plastic dermatologists have identified new instructions (as well as the filling of wrinkles and face depressions, increase of lip and
cheekbone volume, correction of asymmetries…) to which
always new products and formulas have been added from
many manufacturing companies. Therefore, on top of the
traditional techniques (picotage, deep linear and tunnelisation …) experience has added other methods of implantation (paris-lips, overlap, rimage ….) regarding new instructions identified by the specialists, sometimes on the basis of
the patient’s demands or on always new advanced technologic formulas about dermal fillers introduced in outpatient
practice. We will analyse traditional techniques and new
techniques together with new instructions and objectives. In
conclusion, we will indicate new techniques with a biorivitalizing effect. This speech is equipped with short videos.
TOPICAL THERAPY
P.P. Di Russo
The incidence of cutaneous non melanoma tumours and
their forerunners is continually increasing. Surgical therapy
is at the moment the best treatment. There are some precancerous lesions such as actinic keratosis and superficial basal
cell carcinomas that respond well to local pharmacologic
therapy. We will examine some more or less recent topic
therapies (retinoids, 5-fluoruracile, diclofenac, imiquimod,
photodynamic therapy) and we will compare them considering indications, advantages and disadvantages.
These alternative therapies to surgery can become the first
choice in particular conditions due to the general status of
the patient, to the age, to the site and number of lesions, very
useful in some pathologies characterized by the presence of
multiple cutaneous tumours like Gorlin-Golts Syndrome.
SPA AND SKIN
G. Dituri
From thousand years ago spas are places where a unique
hydromineral and environmental property and irreproducibly
useful to prevent and care many cutaneous pathologies.
Spas arose as parks or very important architectural buildings,
generally in wide areas very important for their ecological,
natural and landscapes value and protected and far from pollution.
Spas are equipped with health and technique plants that utilize bioactive sources from water, peloids and from the habitat (climate, sun, caves, plants, sea etc.) and associated with
experienced doctors and other qualified health professionals.
Specialized institutes are animated by a new spirit under the
WHO definition indicating the fundamental concept of
“wellbeing”. Often they have an agreement with the National
Health System offering services on prophylaxis and diagnosis, health education programmes and research through scientific committees and study centres and promoting partnership with Universities and other research institutes.
The medical hydrology, under his new cover called Thermal
Medicine, is the branch that studies the applications and
thermal methods for many pathologies like skin diseases.
Infact, the skin has its anatomic and physiological characteristics and thanks to its easy access represents the best target
for preventive, curative and rehabilitative thermal treatments.
Today, many scientific studies are showing the positive
effects of the crenotherapy to treat psoriasis, atopic dermatitis, eczema, seborrheic dermatitis, acne, itch, angio-dermatitis and so on.
Furthermore, environment and thermal stay is different from
hospital stay, it represents the best place also for the psychological effects to treat old patients and children.
In conclusion, having the crenotherapy many favourable
characteristics to activate many vital functions and helping a
good general status of the tegumentary apparatus, spa can be
considered as the “health and wellbeing workshop” not only for
the skin but also for the whole body.
ACNE TREATMENT:
FROM CLASSIC TO INNOVATION
B. Dréno
In 2003, an international committee of physicians and
researchers in the field of acne, working together as the
Global Alliance to Improve Outcomes in Acne, developed
consensus guidelines for the treatment of acne. These guidelines were evidence based when possible but also included
the extensive clinical experience of this group of international dermatologists. As a result of the evaluation of available
data and the experience, significant changes occurred in the
management routines for acne. The greatest change arose on
the basis of improved understanding of acne pathophysiology. The recommendation now is that acne treatments should
be combined to target as many pathogenic factors as possible. A topical retinoid should be the foundation of treatment
for most patients with acne, because retinoids target the
microcomedo, the precursor to all acne lesions. Retinoids
also are comedolytic and have intrinsic antiinflammatory
e ffects, thus targeting 2 pathogenic factors in acne.
Combining a topical retinoid with an antimicrobial agent targets 3 pathogenic factors, and clinical trials have shown that
combination therapy results in significantly faster and greater
clearing as opposed to antimicrobial therapy alone. Oral
antibiotics should be used only in moderate-to-severe acne,
should not be used as monotherapy, and should be discontinued as soon as possible (usually within 8-12 weeks).
Because of their effect on the microcomedo, topical retinoids
also are recommended as an important facet of maintenance
therapy.
Concerning, procedural treatments, it is a field whose importance is increasing. Simple procedural treatments such as
comedone extraction and intralesional steroids have been
utilized for many years as adjunctive therapy for acne. In the
past 5 years, new technologies and procedures have become
available that present new options for the treatment of acne.
Objectives: The objective was to review, summarize, and
evaluate the key studies of procedural therapies for the treatment of acne as well as place them in perspective with current clinical practice.
Methods: Studies selected for evaluation had at least 10
patients and clear statements of purpose, acne severity,
patient selection, follow-up evaluations, previous and concurrent medications, treatment parameters, methods for
evaluating results, and adverse effects. All studies were complete and published (in English) in peer-reviewed journals.
Results and Conclusions: Earlier procedural therapies were
adjunctive to medical therapy, such as intralesional steroids,
chemical peels, and microdermabrasion. Newer methods
include radiofrequency, light or laser, and photodynamic
therapy that represent treatment alternatives for systemic
medications. Still early in their development, these new procedures provide an important, novel set of options for the
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treatment of acne. The most developed and studied therapies
are blue or blue/red light combinations, 1,450-nm diode
laser, and photodynamic therapy with 5-aminolevulinic acid
or indocyanine green.
PAPAYA MYTH OR REALITY
M. Enrico
With regard to the exceptional characteristics of fermented
papaya FPP (Fermented Papaya Preparation) it is necessary
to separate truth from legend. Unfortunately, the great
uproar triggered by the media in 2002 linked to the
improvement of the health conditions of Pope John Paul II,
hindered medical credibility for a long time. Advertisement
built around this event debased its image in the eyes of the
experts. Notwithstanding the therapy did not have magic
powers, but was based on concrete biochemical principles,
the mass media hailed the miraculous power, arousing
doubts and suspicion in many members of the scientific
community. Unfortunately, most physicians and pharmacists
have only but heard of FPP, and very few have had the
chance to study it in-depth with clinical trials.
Consequently, although everyone has been talking about
papaya for several years, the fundamental principles that
allow it to have a protective function are still not clearly
understood or poorly interpreted both by physician and the
public. These active principles offer great support to our
immune system and to the regulatory mechanisms of our
body, so that they may “work” in harmony and therefore prevent the onset of diseases. However, it is necessary to make
a distinction between the anti-oxidating characteristics of
this fruit at its natural state and those of the FPP commercialized as Immun’Age by the Osato Japanese Laboratories.
Thus, FPP is not a “miraculous powder” but a product of great
quality, effective, non-toxic, without side effects, can be used
naturally and without any risks, without claiming to be a
substitute for traditional therapies is a concrete help to prevent the inset of various diseases.
ACNE AND ROSACEA: A COMPARISON
P. Fabbri
For some decades already acne (a) and rosacea ( r) have been
considered as two different diseases with specific epidemiology, clinical features, morphology, development and
etiopathogenesis.
The main features enable us to make a clear-cut distinction
between the two diseases synthetically: onset occurring at
different ages (acne outbreaks earlier), proliferation or non
proliferation of comedos (that are typical in acne, but do not
appear in rosacea), eye inflammation (that is frequent in
rosacea, but does not appear in acne), development features
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(subsequent phases showing different morphological components), histopathological markers and anatomical and
functional involvement of the micro-vessels (typical of
rosacea).
The two diseases have also a different etiopathogenesis: different genetic makeup, different etiologic agents (or simply
triggering agents) (where the P. acnes plays an important etiologic role in acne only), induction mechanisms of skin
lesions which are partially immune-mediated in both diseases but cannot be overlapped.
Despite these differences, note that acne-related lesions may
appear on erythrosic facial tissue and that the coexistence of
a and r (acne with rosacea) is not a very rare event. However,
this condition requires special attention and treatments.
CLINICAL-HISTOLOGICAL ASPECTS
IN SKIN AGING
G. Ferranti
The hystopathological alterations correlated to skin aging
and especially the ones induced by UV light, can be viewed
as epithelial changes ranging from simple hyperkeratosis up
to dysplastic and neoplastic lesions and dermal changes. The
most significant change is the so-called solar elastosis that
shows well-defined hystopathological aspects and which is
the basic element to distinguish intrinsic aging (chronoaging) from extrinsic aging (photo-aging).
HYSTOLOGY OF SKIN EPITHELIAL TUMORS
G. Ferranti
In human oncology, skin epithelial tumors are the most common forms of neoplasia. A good correlation between
histopathological and clinical data can not only facilitate the
diagnosis but also improve the prognosis, thus adopting the
most adequate therapy. Skin epithelial tumors are generally
benign and this is correlated to early diagnosis and the
hystopathological identification of the type of cancer which
often requires very different therapeutic and preventive
approaches. The dermopathologist’s role is to make the diagnosis and to provide all the information to adopt the correct
treatment option.
DOES THE DYSPLASTIC NEVUS STILL EXIST?
THE ROLE OF THE DERMATOPATOLOGIST/
DERMATOSCOPIST
G. Ferranti
The histopathologist plays a major role in the diagnosis of
melanocyte lesions not only because such diagnosis is very
difficult, but also because the interpretation of such lesions
need specif clinical skills. As a matter of fact, these lesions are
skin neoplasias and therefore are exposed to traumas and
environmental changes to which other kinds of neoplasias
may not be exposed. Some external agents (sun, traumatisms, scratching, etc) may change the morphology of such
lesions which are therefore very difficult to interpret without
special skills in histopathology. In addition, nevi and
melanomas are also exposed to “endogenous” changes, namely the Sutton phenomenon and eczematization that may also
alter their codified histopathological features and make diagnosis very difficult.
PATHOLOGIES OF THE GENITAL MUCOSA:
HISTOLOGY AND CLINICAL CORRELATIONS
G. Ferranti
The role of the histopathologist in the diagnosis of the
pathologies of the genital mucosa is of great relevance. In
fact, as well as the numerous neoplasias that may appear in
these sites, it is opportune to remind the great importance
the many viral pathologies have and those that we may consider borderline with the skin. Thus it is necessary to have
great knowledge of the nosological schemes and classifications typical of dermatology in order to deal with the habitual diagnostic difficulties complicated by a tissular substrate
that often modifies not only the clinical picture, but also the
histopathological formulas.
Therefore, as well providing a more detailed neoplastic pictures and of the viral pathologies, the author suggests a classification according to the pattern of the inflammatory conditions, just like the classificative approach often adopted in
dermopathological diagnostics.
DERMATOSCOPY: HISTOPATHOLOGICAL
CORRELATIONS
G. Ferranti
With the codification of dermatoscopic diagnostics, the discipline of dermatology has acquired an important tool for the
study and diagnosis of pigmented lesions.
However, the morphological elements developed through
this new technique require a histopathological correlation
that would make them more significant so as to achieve a
more accurate diagnosis and a more reliable prognosis.
It is therefore appropriate to go through very quickly, what
are the main correlates between dermatoscopic images and
microscopic aspects.
The fundamental element in the dermatoscopic observation
of a pigmented lesion is given by the pigmentary network. It
is morphologically represented by melanin produced by the
melanocytes of the dermoepidermal junction. When this network is regular it is a sign that also the histological aspects
are regular and this means that we are dealing with a benign
lesion. Since the melanoma manifests precisely at the dermoepidermal junction, any modification of the pigmentary
network may correspond to all those architectural events that
entail a neoplastic progression of the pigmented lesion; gross
melanocytic thecae, the prevalence of single melanocytes
rather than those clustered in nests, the fusion of various thecae among themselves up to building structures resembling “a
b r i d g e” and the climbing of single neoplastic melanocytes
towards more superficial layers of the skin.
Another architectural element exclusively defined through
dermoscopy is the globular pattern: expression of
melanocytic thecae present in the papillary and sub-papillary
derma. Generally, this aspect strongly suggests a benign
lesion.
When well-codified structures are not detected (homogeneous and nodular pattern), the melanocytic elements are
found in the deeper portion of the derma, whereas they are
not found at the level of the dermoepidermal junction. Such
dermatoscopic aspects come up when you have a blue nevi
(dermal proliferation of hyperpigmented dendritic melanocytes), but also if you have nodular melanomas (neoplastic proliferation destroys the skin structures and changes the
various anatomical aspects). In reality these two patterns are
quite similar, but in the nodular form, it is possible to note
an architectural organization, although modified by neoplastic expansion; an example of this could be the verticalizing
component in the course of a superficial melanoma.
The red-bluish saccular structures represent dilated vessels
and proliferated by dermal haemangiomas that when they
present thrombi they could pose problems of differential
diagnosis with malign nodular neoplasias and chiefly with
melanoma. When at least three dermoscopic parameters,
necessarily including an irregular pigmented network, in a
single lesion it is possible to observe a composite pattern.
Often, this pattern is significantly correlated to a dysplastic
nevus or to a melanoma, generally quite thin.
These characteristics, known as global patterns, are to be
considered as intermediate morphological aspects between
clinical observation and histopathological study. There are
many other parameters that have a precise histological correlate, such as for instance punctiform pigmentations that are
the expression of aggregates of melanin in the more superficial portions of the skin.
Or the radial striae and pseudopods that are the expression
of a radial proliferation of atypical melanocytes. Of notable
interest are the whitish veil (dermatoscopic expression for
hyperkeratosis) and the bluish veil (dermatoscopic expression for regression phenomena).
Also the observation of vascular patterns: tree-like, commalike, crown-like, punctiform, etc. can be useful for the diagnosis and the prognosis.
This short and incomplete list of dermatoscopic parameters
that can be correlated with histopathology, allow to seize the
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importance of such correlation and how the two disciplines
have to be deeply understood by the specialist wishing to
approach this new method.
DERMOSCOPIC ASPECTS
OF KERATINOCYTIC TUMORS
A. Ferrari
According to a two-step algorythm for the differentiation of
skin pigmented lesions, the diagnostic criteria for melanocytic lesions are: a pigmented reticulum, striae, brown dots and
globules, a homogeneous bluish pigmentation and a parallel
pattern (for lesions on the palms and soles). Without these
criteria, it is possible to use other pigmented structures for
the differential diagnosis between melanocytic and non
melanocytic lesions. Non melanocytic lesions include epithelial and malignant lesions following the proliferation of keratinocytes in all skin structures, the epidermis and the
eccrine and apocrine pilosebaceous and sweat glands. The
most frequent lesions are characterised by the presence of
pigment such as seborrhoic keratosi and pigmented basalcell carcinoma. Corneal pseudocysts and comedo-like
defects are specific dermoscopic features of seborrhoic keratosis. When vasculature is present, it appears as fine hairpin structures surrounded by a whitish halo. Pigmented
basal-cell carcinoma is characterised by tree-leaf shaped
areas, multiple grey-blue dots, cart-wheel shaped areas, large
grey-blue ovoidal areas. In this type of cancer, there are other
features such as tree-like vessels and ulceration. Moreover, in
some cases, several morphological variants of skin vascular
structures observed with dermoscopy allow for the differential diagnosis between non pigmented tumors and
hypo/amelanotic melanoma, such as clear-cell achantoma,
keratoachantoma and Bowen’s disease. Clear-cell achantoma
is characterized by dot-like vessels arranged as a reticular
structure inside the lesion or as a pearl necklace; keratoachantoma is characterised by hair-pin vessels surrounded
by a whitish halo and generally located at the edge of the
lesion; Bowen’s disease generally appears as a squamous
plate with glomerular vessels inside the lesion. The presentation will discuss a selected series of keratinocytic lesions with
characteristic videodermoscopic features and some tumors
that are difficult to diagnose because of their atypical presentation.
LIPODOMIC PROFILE AND RADICALIC STRESS:
A MULTIDISCIPLINARY DERMATOLOGICAL
APPROACH
C. Ferreri
The field of dermatology is directly involved in the evaluation of the lipid composition of the cell membrane. Above all
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the membrane permeability and fluidity reflect the skin
resistance and it is well known that the poli-unsaturated
fatty acids are needed for health skin.
Such fatty acids are subject to decay by the action of free
radicals and the process of oxidation.
In fact the skin has a wide variety of anti-oxidant substances
and traps for radicals as a defence mechanism to preserve its
lipid composition. In this context diet has an important role
in the etiopathogenesis of many dermatological diseases for
the supply of balanced lipid components, vitamins and antioxidants.
Within this context a lipidomic approach has been added
(1) which is a discipline of lipid presence in living organisms, their structure, role, and the changes that occur in
physiological and pathological conditions. In “c h a n g e s” the
effects of nutrition and nutraceutics are included.
The approach applied to dermatology and other disciplines
starts with an analysis of fatty acids specifically the phospholipids in the ery t h rocytic membrane, an analysis which
makes use of a re f e rence library and recent information of
fatty acid structure the so called “trans fatty acids” which are
produced by radicalic stress according to recent research
results carried out on animal and human cellular models (24). This analysis must be combined with a clinical history
and gathered information from the patients by way of a
questionnaire, to trace a metabolic profile and the incorporation of lipids in the membrane personalised for each subject. With this personal lipidomic profile we can obtain
information for a precise individual strategy on the composition of the lipid membrane, which combines the adoption
of a diet with a nutraceutic supplement in order to take in
sufficient fatty acids where a deficiency exists as protection
against the oxidative and radicalic consumption in order to
establish a functional equilibrium amongst the lipid components.
This profile must be checked after 4-6 months of tre a t m e n t
as well as a clinical re-evaluation by the physician as a proof
of the patients pro g ress and would allow a therapy revision
or improvement.
The lipidomic approach has been applied in many cases of
dermatological diseases and here we report their outcome.
References
1. German, JB, Gillies, LA, Smilowitz, JT, Zivkovic, AM, Watkins, SM
Lipidomics and lipid profiling in metabolomics. Current Opinion Lipidology,
2007, 18, 66-71.
2. Ferreri C, Chatgilialoglu C. Geometrical trans lipid isomers: a new target
for lipidomics. ChemBioChem 2005, 6, 1722-1734.
3. Ferreri C, Kratzsch S, Brede O, Marciniak B, Chatgilialoglu C. Trans lipids
formation induced by thiols in human monocytic leukemia cells. Free Radical
Biol. Med. 2005, 38, 1180-1187.
4. Ferreri C, Angelini F, Chatgilialoglu C, Dellonte S, Moschese V, Rossi
P, Chini L. Trans fatty acids and atopic eczema/dermatitis syndrome: the
relationship with a free radical cis.trans isomerization of membrane lipids.
Lipids 2005, 40, 661-667.
COSMETOLOGY OF CELLULITIS
P. Fileccia
Cellulitis or edematous fibroscleotic panniculopathy is the
most widespread blemish of the lower limbs of the women of
our country: about 80% of Italian women declare to be
affected by this disorder and, differently from all other blemishes, from teleangectasies to stretch marks, all the groups we
have interviewed all say that ‘… I have always done something: I have applied such cream, constantly, but no results!’.
Cosmetology of cellulitis can be summarised in the following
brief, generalized statement, that before such an extraordinarily effective question no adequate reply is provided by the
topical products found on the market. We shall see a list of
the most valid and promising cosmetic treatments, making
the point on their effective role and we shall determine the
leading criteria to standardise and improve this category of
this greatly demanded dermocosmetics.
knowledge many plants have revealed to be rich of therapeutic active principles for the skin, other plants are
acknowledged to have supplementary properties of the complex superficial structure, playing a role that cannot be
replaced or reproduced by analogous synthetic substances.
The author will provide a selection of raw materials of vegetable nature that are mostly employed in cosmetics and
their activity will be assessed in the light of literature till now
produced. A choice of the complex method for the evaluation of the chain of the productive passages in natural cosmetics and especially in the biological one will be made,
because Europe and Italy want to harmonize it in order to
provide a concrete and serious response to the demand of an
educated public very heedful towards the good health of the
skin, but also towards the environment in which they live.
RAMAN SPECTROSCOPY AND LASER THERAPY
IN ORAL MUCOSAL LESIONS
G.M. Gaeta
PRE- AND POST-PEELING COSMETICS
P. Fileccia
Cosmetic treatments adopted before and after peeling are
definitely tailored according to the substance used to carry it
out, the type of skin it is performed on and to aims you
intend to achieve.
Generally speaking, pre-peeling treatment should be is started 2 or 3 weeks before peeling is performed: it is a fundamental procedure that enables to reduce the healing time,
ensure a more even distribution on the surface and in-depth,
reduce the risk of adverse events and tests the patient’s level
of toleration to the substance that will then be used for peeling. In addition, it allows to fidelize patients and not accept
those who are not adapt. The most frequently used agents
are, tretinoin, mild keratolytic products (glycolic acid or salicylic acid), combinations of depigmentating agents, photoprotectors with high SPF. Treatment has to be stopped 1-2
days before peeling. Post-peeling treatment is more common
to various types of peeling. Refreshing and disinfecting compresses are recommended, followed by the application of
emollients and especially in medium-deep peelings, steroids
of average potential and antibiotics. Maximum photoprotection is peremptory throughout the following month for
superficial peeling, and for 5-6 months for average-deep
peeling.
NATURAL COSMETOLOGY: FROM ANCIENT
DOCTRINES TO MODERN CHALLENGES
P. Fileccia
The use of plants as a source of raw materials useful for the
skin is a custom for man and even in the light of current
The use of lasers in odontostomatology determined a considerable improvement in treatment techniques designed for
oral mucosal and hard tissues lesions, enhancing healing
processes and improving post-surgery outcomes, with aesthetic results that can hardly be obtained through traditional
techniques and encouraging increased compliance by the
patient.
Mucosal resurfacing treatment in oral mucosa hyperkeratosis, reoccurring infections, treatment of fibromuscular tractions, excision of benign or malignant oral lesions, conservative and endodontic therapies, certainly represent one of
the main goals of laser-assisted dentistry.
Different laser light sources such as Erbium, Neodymium,
Diode, CO , are used in different applications in daily dentistry procedures.
In major surgery procedures, the CO laser is for sure the preferred laser thanks to its coagulative and penetration effect,
better accessibility in complex surgical sites with respect to
traditional surgery or very radical or invalidating techniques
(surgery procedures for oral and VADS dysplasia).
In minor oral surgery procedures (preprostethic, endodontic,
parodontal), for infective lesions, tooth decay removal, bone
remodeling surgery and for aesthetic purposes (resurfacing),
as well as for the capacity to operate with minimal heat
release (reduction or no anesthesia is required), Erbium laser
is an excellent tool. In minor oral surgery procedures,
endodontic sterilization for parodontology and bleaching,
Diode or Neodymium lasers are the most suitable tools.
In this seminar, following the description of the different
fields of application of laser light sources, and the relevant
use parameters, a practical session will take place with
demonstrations performed on patients suffering from different pathological conditions.
2
2
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ENDOSCOPIC REJUVENATION OF THE FACE
E. Gandolfi
The author describes the endoscopic rejuvenation technique
of the face in the light of the clinical cases collected between
March 1996 and November 2007 and on the technical evolution during the years.
The author explains the current trends with regard to the
association of the surgical endoscopic lifting and fat transplantation in the filling and firming of the third inferior
median of the face with Silhouette surgery of the last generation.
The author illustrates this technique associated with miniinvasive rejuvenation of the face, the side effects, the outcomes and complications.
VITILIGO AND THYROID: THE POINT OF VIEW
OF THE ENDOCRINOLOGIST
cerns both the merely functional thyroid and hypophysial
aspect (FT4, FT3 and TSH) and especially the immune status (AbTg and AbTPO).
The hypothyroidism therapy is naturally a replacement therapy with thyroid hormone (L-thyroxine) in order to normalize all the functional parameters of the hypophysis-thyroid
axis (FT4 and TSH) and it must be continued for all the
patient’s life, monitoring the patient’s clinical conditions and
functional status periodically.
During the therapy, particular attention should be put on the
semiotics referred by the patient that could lead the patient
to modify the dosage and this often can cause potentially
harmful blood disorders.
THE ROLE OF DERMOSCOPY
IN THE PIGMENTED PATHOLOGY
OF THE MUCOUS MEMBRANES
S. Gasparini
M. Gargani
Thyroid autoimmune pathologies represent the most frequent cause of the thyroid hormonal disorder (hypothyroidism). In adults, this dysfunction has a high prevalence
(0.6-0.8%) with a higher frequency in females (ratio F:M= 28/1), in the old age and in the areas with a lack of iodine.
Among the causes of hypothyroidism the most representative
is Hashimoto Thyroiditis, an organ-specific pathology on a
likely genetic base. Characteristics of this pathology are the
presence in the circle of specific anti-thyroglobulin autoantibodies (AbTg) and anti-thyroperoxidase (AbTPO).
The natural evolution of this pathology is towards the
atrophic form and so towards hypothyroidism. This particular kind of hormonal disorder can be part of a wide range of
autoimmune polyglandular syndromes and so with a combination with other pathologies, like the pernicious anaemia,
adrenal crisis (or Addisonian crisis), insulin-dependent diabetes mellitus.
Among the most frequent pathologies combined with the
autoimmune thyroiditis, it is important to remember vitiligo,
on the basis of the relevant frequency. Combination between
vitiligo and Hashimoto Thyroiditis shows a maximum prevalence in females with particular relevance after 40 years and
in presence of a familiar history of vitiligo.
Nevertheless, while the objective relevance of vitiligo does
not pose, to the expert eye, problems about a correct diagnosis, but this does not always happen for other thyroid
functional disorders and in particular for hypothyroidism. In
fact, in some cases, its seriousness can be underestimated
and so it is necessary to carry out a blood test, to make a correct diagnosis.
For this reason it would be better for the patient, on the basis
of the frequency of the combination between Hashimoto thyroiditis and vitiligo, to always do a blood test, which con-
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The pigmented lesions of the mucous and semi-mucous
membranes (prolabium, genital and anal semi-mucosa) often
pose serious interpretative problems, both from the clinical
and from the dermoscopic point of view. The diagnostic difficulties from the dermoscopic perspective are on one hand
linked to the troublesome use of the equipment for these
sites and on the other the rare number of cases reported in
literature.
The pigmented lesions that most often pose problems of differential diagnosis with melanomas (for the frequent clinical
similarity and the signalled possible correlations) are
melanoses.
Generally these lesions, found at the labial or genital level,
are characterized by the presence of a widespread background pigmentation on which it is possible to spot more
concentrated globular or linear-like brown-reddish, brown
or greyish pigmentations.
In melanoses that appear clinically suspect, thus simulating
a melanoma, such aspects appear irregular, they combine in
a disordered way and present prevalently grey-blackish
tones. In such cases, dermoscopic assessment is not enough
and a biopsy is needed.
In the event of a melanoma, as well as a major degree of
unhomogeneity in the distribution of the pigment, there
could be dermoscopic patterns that are indicative of similar
malignancies in other regions.
THE IMPORTANCE OF DERMATOSCOPY
IN FACIAL LESIONS
S. Gasparini
In elderly people or in those subjects with a pronounced
photoaging it is possible to identify several facial pigmented
lesions that require an accurate diagnosis in order to arrange
a diversified and suitable treatment. Many of these lesions
are simultaneously present and they show similar clinical
aspects. Malignant lentigo, solar lentigo (seborrheic keratosis
in its initial phase), lichenoid keratosis and actinic pigmented keratosis are lesions that often imply serious differential
diagnosis problems.
The need for suitable therapeutic treatment for these kind of
pathologies is linked to serious medical reasons, but it is also
induced by esthetical motivations. The development of modern pharmacological, instrumental and surgical therapeutic
tools is now able to satisfy those needs but, due to the presence of this wide range of available treatments, it is necessary
to identify the most suitable diagnosis in order to provide for
appropriate treatments for different kind of lesions.
Dermatoscopy seems to be a useful diagnostic method for
assessment and differential diagnosis of pigmented lesions of
the cephalic end, above all in those subjects with a pronounced photoaging.
Malignant lentigo is dermatoscopically characterized by the
presence of grey-blue points/globules and greyish pigmented
stripes that, gathering around follicles, lead to annular granular structures.
The gathering of these annular structures leads to the creation of a greyish pseudonetwork.
Another typical aspect is represented by follicles that are
asymmetrically pigmented and characterized by the presence
of annular hyperpigmentation, dark-blackish coloured.
When the above mentioned stripes begin to lengthen and to
cross themselves around follicles, the peculiar pattern of
malignant lentigo is created, that is rhomboidal dark-greyish
structures. In the most advanced phases it is possible to
notice peculiar areas or blue globules around follicles and
areas characterized by homogenous dark-greyish and blackish pigmentation that tend to block follicular openings.
Seborrheic keratosis and senile lentigo (which is an initial
macular keratosis) dermatoscopically present a yellow-darkish pseudonetwork, fingerprints structures and a typical
fragmented border.
According to medical literature, the patterns similar to malignant lentigo are quite always yellow-darkish and the rhomboidal structures are not present.
However sometimes it is possible to identify annular granular patterns with greyish shades and dark-greyish stripes
around follicles.
Actinic pigmented keratosis is often characterized by a
pseudonetwork made up by dark-greyish and sometimes
grey-blackish annular granular structures, thus simulating
the initial phase of malignant lentigo.
Dermatoscopy is giving a great contribution to the diagnosis
of these lesions, but sometimes it shows some limits, so it is
absolutely necessary to make a bioptic sample, when in
doubt. This sample should be made close to the lesion and
following dermatoscopic indications.
CONDITIONS AND HPV-RELATED DISEASES:
EXPERIENCE IN PROCTOLOGY
R. Gattai, B. Magini, P. Cappugi, P. Bechi
Introduction: Condyloma acuminatum is a quite common
sexually transmitted infection which, among the various
sites, could also develop in the perianal, anal and more rarely
in rectal areas. Diagnosis is usually easy, but there is no standard therapeutic procedure; electrocoagulation is the treatment of choice, but relapses are very high. Photodynamic
therapy (PDT) is a new procedure applied to a wide range of
neoplastic, pre-neoplastic and benign pathologies; among
these pathologies there is broad experience in the scientific
literature on condylomas affecting male and female external
genitals.
Patients and methods: A study is being conducted in our
Center (we currently have recruited 12 patients) on a PDT
treatment for anorectal and perianal relapsing condylomas.
The protocol envisages the application of a gel and the subcutaneous/submucous injection of 5-ALA, then, after 4
hours the patient is subjected to 635 nm wave length light
irradiation (90 Joule in 1.5 minutes). At the end of the photodynamic therapy, condyloma lesions are removed by electrocoagulation.
Conclusions: We will present preliminary data on our experience, with special focus on feasibility and tolerability of the
pro c e d u re; furthermore, we will analyze medium-term
results on relapses.
THE USE OF THE DERMOSCOPE
WITH SPITZ/REED NEVUSES
G. Giovene
In the field of skin melanocyte-based proliferation, epitheliod and/or spindle cell nevuses represent a peculiar clinicalhistological entity which stimulates a lot of interest and discussions among scholars. Since its first description, by
Sophia Spitz in 1948, it was immediately apparent how its
various bio-morphological expressions were not rarely similar to those of melanoma, representing for dermatologists
and histopathologists alike a very sensitive diagnostic and
prognostic problem.
Dermoscopy can provide a useful help to dermatologists in
identifying Spitz related lesions and in managing them.
According to our experience, there are two dermoscopic patterns for epitheliod and/or spindle cell nevuses:
• the symmetric globular pattern, with the typical Spitz
form, little pigmented, relatively common in childhood,
and
• the “starburst” symmetric pattern, which is typical of the
hyperpigmented Reed form, more common in adulthood.
Having said this, several variations can be identified in both
109
patterns, as well as additional criteria, which account for a
wide dermoscopic range of such proliferations.
The typical or atypical onset of the nevus, its regular or irregular shape can represent a distinctive criterion between
lesions that only need to be monitored and lesions that need
to be surgically removed immediately.
In any case, based on epidemiological observations, the age
factor is strongly affecting dermatologists’ attitudes towards
Spitz lesions: in fact, there is wide consensus on the opportunity of surgically removing Spitz nevuses in patients over
15, even if suspicious clinical-dermoscopic criteria are not
present; on the other hand, in patients under 15, dermatologists may make their decisions on typical Spitz/Reed nevuses with more discretionary power.
MINIMALLY INVASIVE BLEPHAROPLASTY
S. Grappolini
Blepharoplasty is designed to remove fatty pseudohernias
and excess skin that can cause blepharochalasis of the upper
lid. Clearly the correction of excess skin can be performed
with long incisions and more or less extensive scars.
Minimally invasive procedures are designed to correct fatty
p s e u d o h e rnias through a transconjuctival approach or
through a direct transcutaneous approach to the tip of the
fatty pseudohernia. Very small incisions are required to perform canthoplasty that is designed to modify the lateral canthus of the lids through cantholysis and its reinsertion in
another position...
DIFFERENTIAL DIAGNOSIS
OF ANDROGENETIC ALOPECIA
M. Guarrera
The diagnosis of androgenetic alopecia is essentially clinical
and only apparently easy. It is very important to look at the
case history of the patient, as it could also be useful for prognostic purposes. The clinical examination is required to
establish the alopecia severity and extent, together with diagnostic methodologies. These are non invasive methodologies, such as the “pull test”, the modified “wash test” and dermoscopy, which are all useful tools in differentiating the
diagnosis of this type of alopecia from other types, and first
of all from telogen effluvium.
picion on its presence, it does not provide sufficient elements
to draw an adequate in-depth diagnosis. Nevertheless, the
performance of some simple lab investigations would allow
the immediate diagnosis of the problem, avoiding the
patients to experience a series of consequences that would
jeopardize life duration and/or quality in the short or medium term.
To make this picture more complex – even though it is
already quite discouraging – we should add that if the doctor, for a series of reasons, is not adequately “informed” on the
subject, the lab analyst is not generally “equipped” for the
carrying out of tests aimed at the oxidative stress assessment
(for example isoprostanes, MDA, d-ROMs, TAS, etc). In the
meantime – paradoxically – therapists, pharmacists, trainers
and beauticians continue to prescribe and/or suggest antioxidant supplements to individuals that are potentially at risk
for oxidative stress.
Being aware of this actual problem, the purpose of this intervention is to provide a series of scientific evidences – now
consolidated in the international biomedical literature – to
support the concept that only a careful and adequate lab
assessment, based on specific biochemical and physiopathological knowledge, can allow the identification and the clear
definition of an oxidative stress condition and eventually
allow, when indicated, the monitoring of the antioxidant
therapy.
NAIL DISEASE IN CHILDREN
M. Iorizzo
The ungual apparatus develops itself during the ninth week
of embryonic life. At birth nails are completely grown and
their length is linked to the age of gestation and to the child’s
weight. A newborn baby’s nails are often thin and soft. Their
growth speed increases during childhood and it reaches the
adult value around 10 to 14 years of age.
Nails physiological and pathologic anomalias can appear in
children. They will be both presented, but a special attention
will be given to pathologic anomalies because they can represent a diagnostic aid in recognizing dermatologic and systemic diseases. This presentation is made of a quick guide
which sums up all the useful elements in a rapid identification of the most common ungual alterations and it gives synthetic indications on their possible treatment.
GLYCOLIC ACID
EFFICACY ASSESSMENT ON ANTIOXYDANT
FORMULATIONS. COMPARING METHODS
G.M. Izzo
E.L. Iorio
Glycolic acid has been the first alphahydroxyacid to be made
available to doctors to treat skin defects caused by different
dermoplastic diseases.
It was introduced about 15 years ago and it has allowed an
Oxydative stress does not have own symptoms, it does not
generate a real clinical profile, thus, if the doctor has no sus-
110
increasing number of doctors to perform peeling procedures.
After an initial boom, a period of decline has followed,
because of the false expectations of physicians and patients
betrayed by the inaccurate and rough information provided
by companies and the mass media.
At present, it can be correctly used mostly as an intradermal
chemical peeling, followed by the application of active substances able to correct different defects.
DIODE LASER: USES AND STRATEGIES
IN LOWER LIMB TELEANGIECTASIC
VARICOSE VEINS
G.M. Izzo
Among the different kinds of lasers, the Diode has recently
appeared and in particular a laser with a wavelength of 532
nm and 808 nm, which is able to treat red and blue teleangiectasis, as well as the small and filiform ones. However,
lower limb teleangiectasis can resist to this treatment, so it is
necessary to act in these fields:
• Modify the horny layer of epidermis;
• Modify red teleangiectases making them more sensitive to
laser;
• Perform the endolaser through a thin optical fibre than can
be inserted into needles 25 or 27G.
It is possible to modify the horny layer of epidermis thanks
to suitable therapies while it is possible to modify red
telengiectases through a sclerosing injection of hyperaemizing substances such as sodium salicylate, etc…
This report analyzes all these different possibilities of making
lower limb teleangiectasis more sensitive to diode lasers and
it also shows endolaser possibilities with 100 or 200 micron
fibres.
CHEMICAL PEELS: COMPLICATIONS
AND POSSIBLE REMEDIES
G.M. Izzo
The clinical application of peeling can cause undesired side
effects and complications. The speaker will present a selection images of all the possible complications which can arise
from an improper use of the various chemical agents available for peeling and will suggest possible therapeutic strategies to correct them.
MICROINVASIVE RHINOPLASTY TECHNIQUES
M. Klinger
The nose is constituted by cartilages, ligaments and complex
muscles with delicate anatomic relation and with aesthetic
and functional characteristics with a primary relevance.
Nasal surgery includes different interventions, more or less
invasive and aimed at different structures as septum-plastic
and turbine-plastic, bone correction and surgery of the dorsal structures, spike surgery.
The profile and bridge of the nose, of the nasal tip, of the
supra-tip and of the columella nasi as well as rotation of the
spike and variations of the nose-labial angles can be modified
with many techniques, affecting in an important way the aesthetic balance and the respiratory function.
Among the different approaches given, to use “close” techniques without columella cut, without delivery, through
bilateral intra-cartilage incision and retrograde undermining
allow a valid compromise between the control of the movement and low invasive surgery.
Best indication for the noses with a bulbous spike and rotation deficiency (typical of old faces), which are most suitable
for microinvasive surgery.
The intra-cartilaginous approach allows direct excision of the
cephalic portion of the lateral crura and an adequate access
to the dorsal structures with limited undermining. In particular, undermining of the periostium is reserved only for the
osteotomic lines. Such precaution is aimed at searching a
long-term efficacy and in the meanwhile a rapid functional
and aesthetic rehabilitation.
So, rhinoplasty is a micro-invasive technique not only for its
performance, but also for its rehabilitation period which will
be more rapid and characterized by a low morbidity.
CARBOXYTHERAPY IN NON-INVASIVE
AESTHETIC MEDICINE - MY EXPERIENCES
N. Koutna
Carboxytherapy (CO gas injections) has been used in balneotherapy for more than 70 years (1932-Spa Royat,
France).
During last 15 years, the method slowly has found its stable
place also in dermatology and aesthetic medicine, either as a
sole technique or as additional approach e.g. after liposuctions or in healing problematic wounds.
As normally strict balance between CO and O gases is established in human body, CO infusion to the tissue leads to
instant local changes – improvement of local oxygenation via
Bohr´s effect, increased blood supply, improved deformability of erythrocytes etc. – all resulting in improvement of cellular function and of local metabolism. There is also slight
lipolytic and lipoclastic effect and direct effect on fibroblasts
(still not explained in details), leading to collagen rebuilding
and neocollagenasis.
The method is surprisingly versatile, indicated every w h e re
when the basic effect – improvement of the trophics is useful.
In non-invasive aesthetic medicine carboxytherapy can be
used as a rejuvenation technique (face, neck and décolleté,
2
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2
2
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hands), for contouring (face, small body areas), in the treatment of cellulite, for improvement of scars and striae, after
liposuctions.
In dermatology the method can be very valuable in the treatment of wounds (incl. leg ulcers and diabetical wounds), for
effluvium and alopecias (even androgenetic alopecia in men),
for psoriasis and sclerodermias.
The method is safe and cheap, very rarely contraindicated,
but has also limitations: first, like any injection technique, it
is not primarily relaxing, but is well-tolerated by the majority of the clients and very appreciated, as the effects come relatively soon. However, the level of visible improvement is
sometimes slightly unpredictable, depending probably mainly on biological aging (ability of the cells to react). Therefore,
according to the state and indication carboxytherapy can be
combined with other techniques (superficial peels, botulotoxin, fillers, mesotherapy, light sources or electrolipolysis,
plastic surgery).
The results of my personal work with carboxytherapy (more
then 250 patients) will be the subject of the lecture, with
accent on some useful recommendations regarding the indication of the method and combinations with other techniques.
age dose was reduced, increasing the number sittings especially in the mandibular and paranasal area. Treatment tips
used for the transmission of the radiofrequency have been
geometrically modified to their own dimension over the
years. The results have been evaluated by comparing photographs, before and after, and with patient questionnaires
on the level of satisfaction, before and after one, three and six
months. No complications were reported.
Results: The immediate effects of the treatment were visible
in the pulled areas, particularly around the mandibular area
and eyebrows.
The maximum improvement of skin tissue and tone were
seen 8-12 weeks after treatment and continued for at least 612 months. Photographs are very important in patient evaluation of the treatment since change is not immediately evident. Multiple low energy sittings give the best results especially in young patients.
Conclusions: With a correct patient selection, the
Thermage® procedure has proven to be even more efficient
and safe. The new referral guidelines have notably increased
the level of satisfaction and compliancy of patients.
THE EVALUATION OF THE CAPACITY
OF MONO-POLAR RADIOFREQUENCY
IN REDUCTION OF WRINKLES
AND THE TREATMENT OF SAGGY SKIN:
WHAT HAS CHANGED DURING THE LAST
THREE YEARS
G. Leone
T. Lazzari
Background: Today’s patients seek a way to reduce wrinkles
and saggy skin but avoiding surgery. They hope to improve
their skin tone with laser treatment without post-treatment
negative side effects. The aim of this three year study is to
evaluate the efficiency of capacitive advanced radiofrequency
techniques in skin rejuvenation with non-invasive methods
over time.
Methods: From June 2004 to July 2007 more than 100
patients (age range 35 to 59) of various phototype, and with
moderate skin laxity (skin mobility not > 3 cm) (with specific exceptions), underwent facial treatment with mono-polar
advanced capacitive radiofrequency techniques which in
terms of volume heats and tightens tissue while protecting
the epidermis with a cooling spray. This procedure usually
requires more than one sitting. Patients reported pain from
the heat which was initially controlled with topical or
tronchular anaesthesia or sedation. The improvement of this
technique permitted the progressive reduction of anaesthetic
use allowing treatment to be performed in some cases without. Originally the energy used was the highest tolerated by
the patient but according to more recent guidelines the aver-
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THE ROLE OF PRO-BIOTICS
IN PHOTO PROTECTION
The role of free radicals and reactive oxygen species, is often
mentioned in the process of numerous pathologies (e.g. arterial sclerosis, inflammation and neoplasms) and ageing. Ever
increasing data suggests that free radicals, in particular oxygen free radicals, have a primary role in the development of
cutaneous photo-damage, photo-ageing and sun exposure
skin cancers. The skin is probable the more susceptible
organ to environmental oxidative stress since it is directly
exposed to ultraviolet radiation and to substances which are
able to generate ROS in the presence of oxygen.
Even though human skin has evolved and developed various
defence mechanisms to survive the insults of UV induced
oxidative stress, many oxidants can escape the system causing critical damage especially where the defence mechanisms
are already overloaded.
In order to create an equilibrium of anti-oxidant/pro-oxidant
in vivo, anti-oxidant activity can be increased through the
administration of exogenous anti-oxidants or to inhibit the
origins of reactive oxygen species by controlling the composition of cellular ions. This and other recently acquired information from the research into free radicals have opened new
possibilities for therapeutic trials with exogenous anti-oxidants. Furthermore it must be underlined that these anti-oxidants are much more efficient when they are systemically
administered and the antioxidant mixture with respect to
each single active substance has an integrated supplement
adds to the physiological anti-oxidant pool.
VULVAR INFECTIONS IN DERMATOSIS
P. Lippa
Vulvar infections are part of a set of vulvar symptoms of the
adjacent cutaneous area or of the rest of the skin, sometimes
associated to other similar symptoms affecting other mucous
membranes.
Even though the simplex, scleroatrophic and planus lichens
have a common denominator linked to their name, they are
completely different for their clinical, histological and pathogenetic aspects, thus they are considered distinct nosological
entities. However, many problems related to their interpretation exist, above all at vulvar level, because the tissular
anatomy of that area tends to express similar morphologies
in the different forms of the above mentioned lichens. An
iconographic collection of genital lichens in comparison to
the differential diagnoses and the diagnostic difficulties faced
during their interpretation are hereby presented.
The histological aid has often been useful, but it is not always
easy to perform it because it is barely accepted by patients.
Vulvar infections during the lichen phase can appear due to
spontaneous mycotic overinfection or caused by the use of
topical steroids or other immunosuppressants, or after the
mortification of vulvovaginal or adjacent cutaneous folds.
THE ORAL MUCOUS MEMBRANE
IN THE ELDERLY: A QUESTION OF TASTE
M. Lomuto
All the perceived sensations reach the deep gustative centres
(frontal-orbital cortex in primates) where they are elaborated
and merged into one signal: taste. In the elderly, there is a
physiological drop in their ability of perceiving fragrances
and tastes, in a significantly correlated manner between
them.
It is therefore evident how the different physiological, paraphysiological and/or simply pathological (candidial glossitis,
the burning mouth syndrome, the Sjögren’s Syndrome, etc.)
changes of the oral cavity and/or of the various organs
involved in degustation (hyposmia, phantosmia, parosmia,
dysosmia, reduced sight, dysausia, hypoacusia, etc.) mostly
frequent in the elderly, alter the gustative perception and
therefore can determine quali-quantitative variations in food
intake (up to refusal) and therefore of the nutritional conditions. This happens even more frequently when associated
with psychological disorders (Empty Nest Syndrome, loss of
the social role when retiring, feeling of marginalisation, etc.)
or physical disorders (senile dementia, Alzheimer, etc.).
It thus appears clear how taste changes, especially in the
elderly, cannot and must not be considered banal because it
could be an indication of the pathology of other organs or
systems (just think of the refusal of meat in presence of gastric carcinoma) or, however, a phenomenon capable of seriously determining the nutritional degree, given the close correlation between taste and nutritional choices.
COSMETOLOGY OF THE NAILS
S. Lorenzi
It is commonly observed that accepting or refusing various
types of food (solid and liquid) changes in time, according to
the various phases of life, thus influencing in a significant
way every person’s way of eating.
Tasting food, whether it is solid or liquid, is an extremely
complex action (still not fully understood), a global perception triggered by the combination, with summing or subtracting effects of signal coming from:
• Sensations from the mouth: taste (i.e. all the sensations
perceived by the taste receptors for sweetness, bitterness,
saltiness, acid);
• Smell: fragrance (sensation induced by external fragrance
molecules to stimulate the olfactory papillae of the nasal
cavities) and aroma (expression of the stimulation of the
olfactory papillae of the retronasal region by molecules
released by the food during mastication and/or dissolved
by the action of the saliva);
• Sight (especially the colour, recalling previous experiences
with the same sort of food, but also the its pleasant presentation);
• Tactile sensations (obtained by the pressure of food on the
hard palate during mastication);
• Auditory sensations;
• Undifferentiated chemical sensations.
In the last few years there are some cosmetic treatments
capable of curing temporary alterations and correct permanent malformations or deformities of the nails.
The application of sculptured nails is currently considered a
practical treatment for onychophagia and onychotillomania.
Nail reconstruction can also be chosen to hide the presence
of serious alterations of the lamina surface, post-traumatic
permanent, of nail pterigium and total absence of the nails.
All nail reconstruction techniques employ acrylic resins in
gel or powder, which are then directly applied and modelled
on the nail lamina that needs to be corrected.
Polymerization of the artificial “sculptured” nails is done with
chemical additives or by exposure to ultraviolet or visible
light.
If on one hand nail reconstruction may correct the aesthetic
conditions and aspect of the nail lamina, on the other this
could give rise to more or less serious undesirable effects.
The long use of sculptured nails can weaken the lamina, in
fact their continued application is not advisable. Traumatic
or irritative onycholysis is frequent.
Allergic reactions to acrylic resins are rarer. Luckily, serious
and permanent side-effects, such as paraesthesia of the fingers involved are very rare.
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ANTIOXIDANTS IN PRE AND POST TREATMENT
PROTOCOLS ON LARGE SKIN AREAS
A. Luci
Clinical and experimental studies have confirmed the efficacy of antioxidants in resurfacing and in other procedures on
large skin areas and in reducing adverse and undesired
effects.
Acute local and systemic oxidative stress can trigger bacterial and viral infections
Inflammatory cells and mainly activated granulocytes are
recruited on the inflamed skin from circulating blood and
the bone marrow.
They release extremely reactive oxygen and nitrogen species
that exacerbate the oxidative stress to cellular and non cellular targets and of the dermis and the epidermis.
In turn, the oxidation residues of cell membranes, the DNA
and extracellular polysaccharides stimulate gene expression,
protein synthesis, cell proliferation; in short, all the functions
that result in tissue regeneration.
As a result, antioxidants should be used with great determination as topical and mainly systemic agents not only to prevent viral infections but also as re-epithelising and antiinflammatory agents.
ERBIUM
G.I. Luppino
The desire to look younger is increasingly permeating our
society and the demand for new procedures that offer a
younger look is increasing all the time in a population that
wants to appear “more beautiful”.
Wrinkles, the signs of time of the face and hands, scars and
skin lesions in fact make you look older and alter the aesthetic aspect of our person.
Nowadays, it is possible to resolve these blemishes without
necessarily recurring to surgery, without deep anaesthesia
and without being hospitalized.
In the last few years, skin resurfacing lasers can be found on
the market and are useful in reducing the thermal radiation
damages and therefore are capable of producing a precise
skin photo-ablation, which is fundamental to obtain the best
level of skin rejuvenation.
The Erbium Laser (Er:YAG) has proven to be a particularly
effective for remodelling of the skin and of the superficial
derma. Tissue ablation takes place in a safe and controlled
manner, because thermal conduction on the surrounding tissues is minimum, thanks to the high affinity of this laser ray
with the water contained in the tissues. This allows to work
on the skin superficially, in a scarcely invasive manner and
therefore with little pain, rapid healing without complications and an excellent aesthetic result. Moreover, the collagen fibres of the derma are stretched and remodelled thus
116
giving the skin a smoother aspect. Thus the Erbium Laser
may be considered as an instrument for pure ablation or
vaporization. Due to its characteristic of having a very thin
ablation thickness, it is often said that the Erbium laser
should be used only for superficial treatment, and that for
deep resurfacing it is better to use a Co laser.
Actually, according to our experience, what we need is an
optimal resurfacing, so that wrinkles and acne scars are
removed respecting as much as possible the derma, thus
avoiding hypo-pigmented outcomes. To this aim, the Erbium
laser, with its limited ablative action in each passage and with
limited residual thermal damage, it can be considered as an
excellent instrument for a deeper use.
Recovery time following this sort of intervention is very
rapid: after a week it is possible to resume normal relational
activities by using common make-up. Erythema persists, in a
decreasing manner, for maximum 30-40 days. Aesthetic
results after only a month are excellent.
2
LASER PHYSICS AND BIOCHEMISTRY
G.I. Luppino
Applications of laser beams on human tissues have now been
validated for years, since now it is possible to treat specific
conditions which were impossible up to a few years ago (pigmented lesions, tattoos, hypertrichosis, photo-damages, vascular pathologies and blemishes). However, it is still very
important that the operator is aware of the main theoretic
principles when using lasers in a coherent manner. This is
necessary in order to avoid inappropriate therapeutic activities that with such instruments may produce very serious
side-effects.
The author outlines the main physical laws of lasers and the
way the laser beam interacts with human tissues.
In the last few years, attention has been dedicated to those
mechanisms that regulate healing after the laser treatment
and the subsequent achievement of the clinical effects.
The latter may be to collagen remodelling, immediately evident with ablative lasers, but probably also dependent on the
release of cellular cytokines.
In fact, the heat generated by the laser can induce a HRS
(Heat Shock Response) defined as temporary changes of cellular metabolism, which in a rapid and transitory manner
determines the productions of HSP 70 (Heat shock protein),
that can play a key role in the coordinated expression of TGF.
To all this, you need to add the biochemical implications, at
the expense of the mastocytic system.
In fact, the dermoplastic process of dermal remodelling takes
place correctly only with certain limits of laser stimulation,
associated to a precise and repeatable mastocytic tissue pattern. These elements certainly represent a model of scientific work and their clinical development, in the near future
will lead to a better understanding of the mechanisms that
regulate the interactions between laser and skin, and consequently the possibility to have a better practical control,
maximum respect of the skin surface and a more rapid healing process.
will be able to determine all those implications deriving from
the use of these lasers, such as evidently different erythemas,
oedemas, hyper- or hypopigmentation.
In fact, the wave length of the Er:YAG Laser has the maximum coefficient of absorption in the water found in the tissues, 14 times more than that of CO .
When using the Erbium:YAG Laser, it is possible to have a
better control of the depth and a have a better and earlier
estimation of any damage.
Tissue vaporization is not accompanied by carbonization and
it happens with only minimal dispersion of energy to the surrounding tissues and therefore with a minimum heat damage. In fact, the Er:YAG Laser diffuses about 5 µ for a 30-50
µ heat damage of CO pulsed. And if the Erbium Laser, at
least in the classic form, has also some limitations including
the need to perform multiple ablative passages, the sometimes troublesome management of abrasion and the lack of
deep stimulation of collagen genesis, they have tried to be
resolved by using a second generation Erbium:YAG called
VSP (Variable Square Pulse) with its characteristic pulsed
emissions at wave lengths varying between 100 and 1500
µsec. When using impulses around 100 µsec, the quantity of
energy discharged as heat will steadily become higher thus
allowing a better vessel coagulation, stimulate the deeper
portions of the derma and therefore act upon the collagen.
The author shall highlight the advantages and the limits of
this laser emission, also in terms of cost/benefit, as well as the
current and future developments of the Er:YAG systems with
varying impulses, especially with reference to the stimulation
of the derma, with minimal ablation (SMOOTH MODE), and
to the remodelling of collagen in the short- and long-term.
2
LASER 1450 AND ACNE DURING ITS ACTIVE
PHASE
G.I. Luppino
Acne is an inflammation of pilosebaceous unities of some
areas of our body, above all face, with more impact during
adolescence and on male patients. Even though acne pathophysiology is well known, acne is still a very widespread
pathology and often it has a disabling effect on the social life
of those who suffer it; moreover the needs derived from a
modern lifestyle induce patients to look for new, rapid and
effective solutions.
For some time, high technology systems are consolidated
means in acne treatment.
The Diode Laser (! = 1450 nm) seems to have good results
and safety requirements.
This particular kind of laser is widely accepted by patients
because it has a low impact on their lifestyles.
Patients can continue to carry out their activities as the laser
causes just an erythema that lasts only half an hour.
The Diode Laser 1450 phototerapy for the treatment of the
acne pathology can be used as an alternative to the usual
therapies or as an integral part of those therapeutic protocols
in which it is associated to consolidated treatments.
The preliminary results of a research involving twenty
patients suffering from papulopustolous acne and treated
with this particular laser are presented and the therapeutic
protocols, the methodology and the long-term and shortterm side effects.
ABLATIVE LASERS
G.I. Luppino
For years, skin with actinic damage has been treated by
removing the epidermis and a variable part of the derma
with chemical peelings and dermabrasion, methods that can
cause both ablation and stimulation of the derma, but which
do not allow to control the deepness of the treatment, which
is instead possible with the laser systems.
Modern classification allows to distinguish between ablative
and non-ablative lasers, according to their ability in eliminating portions of tissue.
With regard to coherent ablative emissions, there is the CO
laser and the Erbium Laser: YAG, which fundamentally differ for their wave length, which is 10600 nm for the first one
and 2940 nm for the second one. Just the emission difference, without counting the other physical characteristics,
2
2
“SUMMA”
M. Maggiorotti
Today, the citizen/patient feels lost among the conflicting
messages of most media about the unthinkable breakthroughs of medicine. However real these advances may be
they are still not available to all the population and often bolster expectations that remain unmet. At the same time, the
citizen/patient is perturbed by the news of other patients
falling victims of gross and inexcusable medical malpractice.
In such a situation, the patients may be allured by unscrupulous profit-seeking people who put forth the possibility of
making easy money through claims for damages against the
doctors and/or the hospitals that treated them.
Similarly, the citizens may become the object of the so-called
“defensive medicine”, i.e. a therapeutic choice that is rather
dictated by the doctor’s need to take precautions against possible lawsuits rather than by his/her scientific convictions.
Doctors are going through a very difficult situation; they are
under the scrutiny of the judiciary, not to mention the press.
Squeezed between the willingness to provide better care to
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patients and the decisions of administrative health care and
financial bodies that impose rules to be abided by when
making a therapeutic choice.
Similarly, the medical profession is faced with a real attack by
the media and the judiciary; we all know how many doctors
are too often frivolously accused of malpractice on the newspapers headlines. It is well known that most doctors who are
brought to trial are eventually acquitted as not guilty; however, the frustrations and stress of being tried will cause them
indelible moral and substantial pecuniary damage.
Another major problem affecting doctors is the termination
of the insurance policy. As a matter of fact, the Insurance
Companies, regardless of the doctor being proven liable or
not, terminate the insurance contract as soon as they receive
a claim for damages.
Furthermore, they add more and more burdensome clauses
and franchises to civil liability policies and complain about
loss of profits (as a result of questionable calculations that
consider the sums “put aside” for the accidents as losses). As
a consequence, insurance policies increase premiums exponentially to reassure the doctors whose contracts have been
terminated by another company. We have been so far as to
see a surgeon having trouble in finding a company that
assures him even though he/she is ready to pay for a premium that may exceed his/her monthly wage.
In December 2002, a group of doctors and friends and jurists
of Rome set up the AMAMI that is the acronym for
“Associazione per i Medici Accusati di Malpractice Ingiustamente” (the Association of Doctors wrongly accused of
malpractice), with a single “Mission”: fighting against groundless malpractice allegations – often addressed to the medical
profession – in order to restore a serene doctor-patient relationship.
The non profit Association is supported by a board of experts
working to raise awareness on the issue affecting doctors.
The Association has worked to spread its initiative and reach
the media with a view to avoiding misrepresentations of the
medical profession. Too often do the newspapers report stories about alleged malpractice that eventually turns out to be
absolutely ungrounded. The Association has decided to cast
a new light on the work of single doctors and, more generally, to raise awareness on an issue affecting many doctors
today. They are often victims of groundless charges stemming
from intentions that are far from being inspired by a sheer
desire for justice. AMAMI has spoken out through several
articles (88) published on the most important national newspapers as well as through TV and radio interviews (16). In
addition, until now A.M.A.M.I. has been presented during
85 high-level Congresses and Medical and Legal
Conferences.
Relations with Scientific Societies, Doctors’ Trade
Unions and Medical Associations
Experts from the various sectors of medicine and a legal
board of jurists and medical examiners.
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With over 35,000 members AMAMI is a major point of reference throughout the national territory since it is the most
representative medical association and the only one which
concretely deals with and fights against the phenomenon of
the so-called “frivolous lawsuits”.
With a view to achieving its goal and restore a serene doctor/patient relationship, AMAMI has set out various successful tools:
• Raising awareness about the issue affecting doctors;
• Partnerships with the Scientific Societies, the Doctors’
Trade Unions, Associations and Citizens’ representatives;
• First “Legal” Aid;
• Establishment of patient/doctor disputes observatory on a
regional base;
• Out-of-court settlements of doctor/patient litigations;
• Joint medical consultation and Permanent Conference of
Specialty;
• Government commitment to promote joint technical
advice;
• Question in Parliament about the insurance companies’
issue;
• Fund for the victims of medical malpractice;
• Free-of-charge legal aid to doctors during lawsuits for an
ungrounded malpractice case.
Several companies and medical trade unions have joined
AMAMI and registered all their members. Until now such
companies and associations are:
• SIRM (Italian Society of Medical Radiology);
• SICPRE (Italian Society of Plastic, Reconstructive
and Esthetic Surgery);
• SICVE (Italian Society of Vascular and Endovascular
Surgery);
• SIED (Italian Society of Digestive Endoscopy);
• SINch (Italian Society of Neurosurgery);
• SIU (Italian Society of Urology);
• FIO (Italian Federation of Oxygen-Ozone Therapy);
• Nuova ASCOTI (Trade Union Association of Italian
Orthopedists and Traumatologists);
• SNR (National Trade Union of Radiologists);
• UEC (Italian Association of Endocrinology Units);
• SPES (Trade Union of Health Care Emergency
Professionals).
In addition we have set up partnerships with SIOT (Italian
Society of Orthopedics and Traumatology) - FNOMCeO
(National Federation of the Surgeons and Dentists
Association) and in particular with the Medical Associations
of Palermo, Catania, Latina, Ascoli Piceno, Firenze, Savona,
Vicenza, Padua, Treviso, Taranto, Rieti and Belluno which
share our vision and have helped us very much to spread our
“Mission”.
Partnerships with the Citizens’ Associations
In the fight against ungrounded malpractice allegations,
AMAMI acts in the interest of the citizens. In this connection,
health care must be entrusted to doctors who have regained
the necessary confidence and security to make the right therapeutic choice for the patient based on their real scientific
convictions rather than on “frivolous lawsuit” fears.
The members of several citizens’ associations do share our
“Mission” and are supporting us in launching common
actions aimed at “healing” the unstable relation between doctors and their patients.
First “Legal” Aid
The national headquarters of AMAMI offer a phone (06
8082454 and fax line (06 8072351) and an email address
([email protected]) to all its members who wish to
contact a lawyer free-of-charge. The Service called “Pronto
Soccorso Legale” (First Legal Aid) is the result of some colleagues’ request to ask for advice and information in the
event of their receiving an unexpected damage claim or,
worse, a notification of investigation. Therefore, the First
Legal Aid Service aims at providing the doctor with the technical explanation of the event and at guiding him/her in the
right direction. Until now, the “Pronto Soccorso Legale” of
AMAMI has received 127 calls.
Establishment of a Litigation Observatory
In Italy, there is not a body aimed at collecting and disseminating data on doctors/patients litigations nor there is one to
provide feedback to hospitals and doctors who could take
corrective actions and prevent such events from occurring
accordingly.
Restore confidence within the community, and also among
those who have been occasionally victims of the so called
“defensive medicine”, i.e. the doctor seeking to protect him/herself against possible allegations and lawsuits instead of making
choices that are dictated by real scientific convictions.
This should also lead hospitals and health care centres to
undertake the right corrective actions in the interest of the
patient and to avoid that doctors may be driven by fears
when taking decisions but by the real needs of their patients.
AMAMI is voicing the need to establish a regional/national
Body which should collect all the damage claims and complaints for alleged malpractice.
Recently, the media overexposure has led to a misinterpretation of the Italian health care service as dysfunctional.
This requires us to shed light on the real quantitative and qualitative nature of the claims lodged against doctors and therefore, indirectly on the health care system as a whole. It is
known that many people still confuse dysfunctional with malpractice whereas things stand differently. As a matter of fact,
2/3 doctors, who are wrongly accused, are eventually acquitted as a result of an ungrounded damage claim legal action.
Until now, the number of medical mistakes reported by the
media has been nothing but the result of a free, arbitrary and
uncritical interpretation of ANIA figures (Associazione
Nazionale Imprese di Assicurazione – National Association
of Insurance Companies). Consequently, every damage claim
is considered as an accident.
This means that the claims against one or more doctors for
the same alleged mistake as well as all the claims that in any
case will be rejected or dismissed are all summed up. This
system of spreading data without any competent body crosschecking them in advance led both care-seeking patients and
doctors who work in hospitals to live like in “times of terror”
with the mass media reporting dreadful news like “90 deaths
in the hospitals every day”. If it was so we may easily reach
32,850 deaths per year, i.e. the number of victims caused by
an average-scale war.
These serious circumstances alone require that an observatory for the settlement of disputes between patients and doctors is established without further delays.
The Observatory should focus on three major areas
of activity:
1) Collecting all damage claims sent to hospitals or individual doctors
The competent regional council may issue a circular letter or
a directive calling for the following bodies to send any such
claim to the observatory in real time:
General and Health Care Directorates of both public and private hospitals, General Hospitals’ Management, etc. (since
risk management is a budget item);
Medical Associations which could inform and ask the individual members to actively participate in the initiative by sending
all relevant data and information about damage claims.
The accident departments of insurance companies and the
citizens may also be invited to forward the damage claims
received or submitted through a newsletter to be disseminated as much as possible via the mass media or other systems
of communication.
AMAMI and the citizens’ association would invite their members to cooperate effectively and actively by transmitting (via
a toll-free phone number) the damage claims submitted.
2) Data cross-check aimed at setting up a database in
compliance with the privacy regulations
Cataloguing the claims under different headings: type of dispute, calls received existence of the necessary and correct
legal-medical support to supplement each damage claim, etc.
3) Single dispute monitoring
Monitoring the dispute development up to the final outcome
of the legal proceedings and anonymous publication of the
data about the “real dispute”
Therefore, this Body shall receive calls and information from
all hospitals, doctors, medical associations, insurance companies and, on a voluntary basis, citizens too.
This will enable us:
1. to get the right data;
2. to get a positive feedback from all doctors who will be
informed about any event and be able to undertake corrective actions to prevent such events from occurring
again;
• to place special focus on the most critical health care sectors;
• to highlight excellence areas.
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Out-of-court settlement of patient/doctor litigations
and AMAMI Arbitration Agreement
As a rule, a lawsuit aimed at compensation for personal
injury may last several years of long and exhausting waiting
for both patients and doctors and cost dozens of thousand of
euros to the Government. With the Austrian and German
experiences in mind and in line with the other professions
we should call for a provision imposing an out-of-court settlement of such litigations. In this regard, a draft Text on outof-court settlement is now under discussion (provisions for
the promotion of out-of-court settlements 5492). Art. 6
imposes the obligation to try and settle the dispute between
a doctor and a patient out of a court up to a maximum
amount of 100,000 euros.
The text has been at a standstill in the Commission for
Justice since the 6th of April 2005, despite the favorable
opinions with remarks of the other Commissions. We are following the parliamentary process with great interest.
While waiting to know the result of the parliamentary
process that should lead to the approval of this longed-for
text another document is available to discourage ltigations:
the “AMAMI Arbitration Agreement”. Many colleagues are
already asking their patients to sign it and include it in their
clinical records. The use of this document regularly reduces
the need for ordinary legal actions and ensures that patients
get actual protection in case of malpractice in the shortest
time as possible. It also allows obtaining compensation for
the damages incurred within 180 days.
Joint Medical Consultation and Permanent Conference
of Specialty
(www.conferenzaspecialita.org - [email protected])
The development and super specialization of medicine as
well as an increasing number of damage claims, now more
than ever, impose to accurately assess the action of a doctor
sued for malpractice. This requires high-level and unchallengeable technical/scientifical advice for each specialty
involved in such a case. Too often, are trials hinged upon
poor technical/scientific advice that is eventually overridden.
The judges are sometimes faced with the problem of finding
experts as skilled as the doctor under investigation or even
more; in this connection, the representatives of several medical specialties have accepted to recommend such experts
throughout the national territory on a case by case basis and
“on demand”.
In the year 2004, the presidents of the Imprese Scientifiche
italiane gave their support to the establishment of the –
Conferenza Permanente di Specialità – a Body in charge of
recommending experts and “super experts” to prosecutors
and judges.
These experts should support the legal examiner in every
case of alleged malpractice throughout the national territory.
Several Prosecutor’s Offices and Civil Courts of different
Italian regions have expressed their satisfaction with this tool
and have used it in many occasions to ask for the names of
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such experts and super experts in support of the medical
examiner in a number of cases of alleged malpractice.
Until now many Specialties’ representatives have joined the
initiative:
- Allegra C. President SIAPAV (Angiology and vascular
disease)
- Bajetta E. President AIOM (Medical oncology)
- Beltrutti D. President IC-WSPC (Pathology of pain)
- Bormioli M. SICPRE President (Plastic surgery)
- Bracale G. SICVE President (Vascular surgery)
- Buccheri G. President SIMA (Anthroposophic medicine)
- Cannavò G. President Assoc. M. Gioia (Legal examiner)
- Carosi G. President SIMIT (Infectivology)
- Chiarella F. President ANMCO (Cardiology)
- Collice M. President SINCH (Neurosurgery)
- Cosentino F. President SIED (Digestive endoscopy)
- Cricelli C. President SIMG (General medicine)
- Dall’Osso T. President CIPe (Pediatrics)
- De Benedetto M. President SIOeCh CF (Otolaryngology)
- De Nicola U. President Nuova Ascoti (Orthopaedics trade
union)
- Del Sasso L. President SIOT (Orthopedics)
- Di Felice G. President ISSE (Surgical endoscopy)
- Di Pietro A. President ISPLAD (Dermatology)
- Fedele F. President SIC (Cardiology)
- Ferrari A.M. Secretary SIMEU (Emergency medicine)
- Forestieri P. President SICOB (Surgery of obesity)
- Lagalla R. President SIRM (Medical radiology)
- Leonardi M. President FIO (Oxigen-ozone therapy)
- Lucà F. Secretary SNR (Radiology trade union)
- Miccoli P. President UEC (Endocrinology)
- Mirone V. President SIU (Urology)
- Nappi O. President SIAPEC-IAP (Pathologic anatomy)
- Nardocci F. President SINPIA (Infant neuropsychiat.)
- Passaretti U. President SICM (Hand surgery)
- Seeberger G. President AIO (Odontology)
- Serra A. President SIIO (Oral infectivology)
- Tersigni R. President SIC (Surgery)
- Vitali E. President (SICCH) (Heart surgery)
- Zoccali C. President SIN (Nephrology)
Government engagement to promote joint technical advice
On AMAMI proposal on the 1st December 2004 the
Government accepted the agenda (during session n. 553 n.
9/4636 – bis – B/3 ) suggested by MPs Milanese –Baiamonte
and undertake to:
• Omissis… rule that the technical advice required by the
party/parties required to prepare a case for trial be always
provided by a professional specialized in the matter under
dispute and a legal examiner jointly. Such professional’s
scientific and technical expertise must equal or outdo that
of the doctor under investigation and his advice must be
sworn;
• to issue directives containing standard and objective criteria for the selection of advisors and experts by the prose-
cutors. – omissis – We are waiting for the promised legislation to be enacted.
Insurance Issues – Civil and Criminal Liability –
Question in Parliament
Over the last years one of the issues that has mostly affected
the doctor’s capacity to confidently carry out his/her professional work is the termination of the insurance policy. At present, in the sector of medical professional liability, a huge gap
has widened between civil and criminal case law. As regard
criminal law, 2 doctors out of 3 (after a long legal ordeal
which is very unlikely to be reparable) are acquitted of all
charges. Contrarily, civil courts are increasingly upholding
the patients’ claims for damage compensation. This trend has
led insurance companies – which are profit-making businesses – to take increasingly stringent precautionary measures. As a result, they have introduced a huge number of
vexatory clauses in the contracts for professional civil liability. These are the most damaging clauses to doctors:
• termination of the insurance policy upon reception of a
claim for damages (since the claim is considered as malpractice ipso-facto) irrespective of the outcome of the trial,
if any. More colleagues receiving a notification of investigation for one single event (that is likely to be dismissed) may
have their policies terminated because of the claims made..
• the transition from a regime of loss occurrence to claims
made with limited retroactivity. This means that should a
doctor have his/her insurance policy terminated, he/she
cannot ask for being reassured with a policy covering a
claim for an accident that occurred 3 years earlier ( even if
he/she had an insurance policy at the time of the accident).
• Aggregate maximum coverage for hospitals. That is to say:
the available insurance amount for the year that concerns
all the employees of the same hospital. Therefore, if a
claim is made late in the year it is very unlikely to have the
required coverage.
In October 2005, MPs Cola, Ercole, Francesca Martini,
Ricciotti, Porcu, Castellani, Lisi and Massidda submitted a
parliamentary question to the Minister of Pro d u c t i v e
Activities and the Minister of Health. We report hereby the
most relevant passages:
…In order to know – whereas AMAMI, in the person of its
president…. Has claimed that: …the Companies have
increased the premiums… Have included franchises, ...have
changed the insurance terms... Have denied compensation…
have applied the right to cancel …what actions they intend
to undertake to protect a so large category of professionals
whose mission is the health of the citizens…
Fund for the victims of Medical Malpractice
The results of medical science are sometimes invalidated by
absolutely unforeseeable and uncontrollable complications;
therefore the results do match or fail to achieve the patient
and doctor’s desired effects independently from the doctor’s
action. Complications may have various causes such as a different response of the body to therapies that prove success-
ful in 99% of patients but not in all of them. A typical example may be an infection associated to prosthesis implantation
despite intra and post-operative asepsis measures and the
administration of a proper antibiotic therapy following
surgery. We do believe that patients suffering from such complications must be compensated and do need to take a legal
action with an unncertain result against a doctor who is likely to be proven not guilty. In this connection, government’s
bodies should set up a compensation fund for the victims of
uncontrollable and unforeseeable medical and hospital complications based on the French model. We have the duty to
bring this issue forward in the most suited fora.
Prosecuting the promoters of ungrounded litigations
Too often are we involved in “litigations” that are very far
from seeking Justice but are exclusively grounded on the
plaintiff’s or the plaintiff’s supporters’ desires to make profit.
With a view to tackling this increasingly widespread trend,
we have decided to support our members, free-of-charge, in
case of ungrounded litigation followed by full acquittal. This
initiative has a double purpose: indemnifying the victim of
an infamous action and deter further such actions against
professionals. A verdict of not guilty must satisfy the following requirements in order for AMAMI to take action:
• the doctor must have been acquitted (or the appeal rejected) with final judgment;
• the legal action was undertaken (or the document drafted)
in contempt of scientific truth;
• there has been evidence of the doctor’s suffering pecuniary
and/or moral-psychological damage.
Therefore, we have proposed to prosecute the promoters of
an ungrounded legal action that resulted in the doctor’s
acquittal but brought him/her dishonor, stress and disgrace.
The damage compensation action is undertaken by one of
our member who is supported by the Association’s lawyers
and is always started off by a doctor who has been acquitted
with final judgment and believes that he/she has been the
victim of ungrounded accusations. Once the AMAMI
General Board has read the proceedings and heard the preliminary opinion by the Legal and Specialty Boards members, the G.B. decides whether to support the doctor in starting off a compensation procedure. If damages are recovered,
the Board upholds the judgment without asking any fee to
the doctor who will allocate a percentage of the amount fixed
by the judge to the Association’s fund. Until now 36 cases
have been examined and ended with an acquittal judgment.
Only in 6 cases out of 36, the Board decided to offer free
legal aid to the doctor seeking for damage compensation.
FILLERS: LEGISLATION AND CLASSIFICATION
A. Malasoma
Dermatologists have been using dermal fillers for years to
smooth wrinkles, lines and folds and restore lost volumes. In
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the past, the substances and formulations were not as amazingly varied as they are today. This may be a cause of confusion among dermatologists who wants to choose a filler and
that is all the more worsened by the fact that the products
have not the same legal status as drugs but they are considered “medical devices”. The author will try to shed light by
starting from the definition and the requirements for an ideal
filler and reach the conclusion that such a filler does not still
exist! Therefore, the best choice is to use fully reabsorbable
and biocompatible fillers such as hyaluronic acid, collagen,
hydroxyapatites, agarose, polylactic acid.
The author illustrates the main features of the various substances and try a classification of reabsorbable fillers. The
purpose is to enable dermatologists to understand the safety
level of the product as well as its specificity for the case to be
treated (type of inestetism, severity, skin type, localization,
combination with other treatments …).
PEELING WITH SALICILIC ACID
A. Malasoma
For some time now this type of peeling has been used with
excellent results in patients with medium to light acne since
it has an antibacterial and sebo regulatory effect. Today SA is
also equally effective in the treatment of mild skin ageing
(level 1 of the Mark Rubin scale) especially due to sun damage since it has a decisive Keratolytic and bland lightening
action. It can also be used for rosacea because it reduces erythrosis and has an antimicrobic effect. SA is absolutely the
safest acid available to use in such clinical cases as it has no
negative side effects. It give a superficial peeling which creates a strong scaling effect on the cornified layer and it regenerates the epidermis and penetrates the sebaceous follicles.
FANGO SHATUI: VANGUARD SINERGY
ACCORDING TO TRADITION
A. Malasoma, A. Parisi
SHATUI is the acronym for: SHaked Thermal Units
Included.
SHATUI mud derives from nanotechnology, a branch of
applied sciences and technology dealing with the design and
creation of objects that are no larger than a micron.
In order to put nanotechnology into practice you need to
have the skills to manipulate directly atoms or molecules,
with the primary aim of designing and experimenting
devices that are both highly functional and allow to reduce
dimensions.
Dermocosmetics of the future intends to apply this generic
knowledge specifically to the field of cosmetic technique and
set up or adjust the so-called nano-emulsions, in other words
polyphase heterogeneous systems where at least one phase is
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dispersed under the form of nano-particles, as large as
between 100 and 500 nanometres, in the continued external
phase. Any substance administered by means of nanotechnology acts more rapidly due to the increased bioavailability.
Plastic dermatology, so close to the thermal environment,
focusing in particular on healthy skin helping it become
nicer, could not have avoided dealing with nano-emulsions.
Adding nano-emulsions in thermal mud produces a triple
effect:
• Allows to personalise treatment according to the active elements contained in the nano-emulsions (exfoliating,
hydrating, nourishing, toning, etc.) according to the indications given by the specialist.
• Increases the benefits of the mud by facilitating the
absorption of the mineral salts it contains.
• Treatment becomes absolutely exclusive, considered the
enormous difference between the waters of the various
thermal springs throughout Italy.
Conclusion:
• Nano-emulsions increase the benefits of the mud by attribution a new and exclusive extra value to all the dermoaesthetic treatments carried out in the thermal centres.
• Emphasise the role of the specialist, who will be able to
personalise the activity of the mud by adding nano-emulsions containing specific active ingredients able to rapidly
correct a blemish.
CONDITIONS AND ACNE
L. Mavilia, P. Di Marco, G. Santoro
In 2006 an article by Wiegell and Wulf was published on Br
J Dermatol about the treatment of acne by photodynamic
therapy (PDT) using methyl aminolevulinate (MAL) and red
light. Authors performed a double treatment at 2 weeks
achieving good clinical results on the inflammatory component of acne. However, they said that patients reported serious side effects such as “moderate to severe pain during treatment and severe erythema, pustular eruptions and epithelial exfoliation” to the extent that 7 patients out of 19 rejected the second cycle of treatment and quitted the study. In October
2007, always on Br J Dermatol, we published the follow-up
at 12 weeks on 16 patients affected by acne of moderate to
severe degree. Due to relevant side effects reported in the literature, we decided to use a reduced amount of the drug,
mixing one part of MAL (Metvix – Galderma) and three parts
of moisturizing cream (Cetafil – Galderma) with the drug at
a 4% dilution. Patients reported a modest but sustainable
burning sensation during red light application and later on,
at three days from the treatment, they complained about
slight erythema and exfoliation. A second treatment was performed after one week and then follow-up visits were scheduled at 4, 8 and 12 weeks with the count of acne lesions. 11
patients required a third treatment after 4 weeks from the
first one, because the count of inflammatory lesions was not
exceeding 50% of the basal count. In females, the first treatment and eventually the third one coincided on purpose
with their pre-menstrual period. At the 12th week of followup, in agreement with the study of Wiegell and Wulf, we did
not notice any difference on non -inflammatory lesions,
while the lesion count was reduced by about 66% (range 5681%). All 16 patients reached the conclusion of the study
and no drop-offs were recorded. In conclusion, in our opinion, the use of a reduced concentration of photosensibilizing
agents and low light doses could be useful, it has the same
efficacy at lower costs in controlling PDT side effects in acne
patients, even if additional studies on a wider number of
patients will be necessary in order to identify the best protocol capable of establishing the right balance between good
efficacy and low side effects.
RADIOFREQUENCY
F. Mazzarella
Radiofrequency generators are gaining more and more
ground in dermatology not only by virtue of their well-know
surgical applications but also of the possibility of using them
in the treatment of a number of esthetics-related conditions.
A journey inside this relatively new field that starts from
some key concepts of electric current physics and, through
the interactions between current and the skin, leads to an
illustration of real applications in plastic dermatology.
CUTANEOUS PHOTODYNAMIC THERAPY:
DIFFICULT CASES
M. Menchini, A. Castelli
Photodynamic therapy is a non-invasive method that use
photosensitizers given through a topic or a systemic way,
which are activated by a light at an opportune wavelength
and determine photo-physical, photo-chemical and photobiologic effects which cause a cell death through necrosis or
apoptosis. Photodynamic therapy is used to treat some different dermatological pathologies, with an oncological or
inflammatory nature.
We have some official subscriptions (actinic keratosis, Bowen
disease, superficial basalioma) and some pathologies in
which photodynamic therapy can be used only as a second
choice.
We have selected some border cases:
• Pathologies with an official subscription but not so serious;
• Pathologies in which doesn’t exist an official subscription;
• Pathologies in which first choice is not applicable.
We will describe some emblematic clinical border cases on
the use of this method.
PROPOSAL FOR A CLINICAL INDEX
ON VITILIGO DISEASE ACTIVITY
G. Menchini, C. Comacchi, GISV (Gruppo Italiano
per lo Studio e la Terapia della Vitiligine)
Vitiligo is an auto-immune disease characterized by the formation of white or pale skin patches due to the focal disappearance of the epidermal melanocytes.
Even though 1% of the world population are effected by this
disease, indiscriminately of ethnic groups, an index of clinical evaluation has yet to be developed. The VAI (index of
Vitiligo activity) is based on the clinical signs of re and de
pigmentation of each patch which is given a score to reflect
the disease activity in each individual. The formulation of
this index is an enormous step ahead in the composition and
evaluation of therapy. The GISV therefore proposes a simplified and standardized formula for the translation of the
numeric scores attributed to a clinical picture, since it is fundamental to the therapeutic formula and mode for this disease as well as the evaluation-comparison by the scientific
community of each single therapy.
There is no single cure for vitiligo but rather multiple therapies which are all aimed at reducing the immune reaction
and at stimulating the residual melanocytic reserve to multiply in order to re-pigment the hypo or achromic patches typical of this disease.
A correct therapeutic protocol can only be formulated by a
thorough dermatological examination together with other
specialists (endocrinologist, immunologist/allergologist, psychologist, geneticist, ophthalmologist) in order to establish
the all vitiligo characteristics in each individual.
The dermatologist must evaluate:
• The activity index, stationary, in regression or worsening;
• The genetic picture;
• Type and how widespread: generalized, achro-facial,
localized, segmental or seborrhoeic;
• Patient age;
• Patient photo-type;
• Presence of other diseases;
• Presence of Koebner reaction;
• Psychological involvement;
• Changes in the quality of life.
Blood analysis should be carried out to exclude the presence
of other auto-immune diseases and to help in the choice of
the most appropriate medical therapy.
Lectures
Westerhof W, d’Ischia M. Vitiligo puzzle: the pieces fall in place.
Pigment Cell Res 2007 Oct; 20(5):345-59.
Mollet I, Ongenae K, Naeyaert JM. Origin, clinical presentation, and diagnosis
of hypomelanotic skin disorders. Dermatol Clin 2007 Jul; 25(3):363-71, ix.
Rezaei N, Gavalas NG, Weetman AP, Kemp EH. Autoimmunity as an
aetiological factor in vitiligo. J Eur Acad Dermatol Venereol 2007 Aug;
21(7):865-76. Review.
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Sehgal VN, Srivastava G. Vitiligo: compendium of clinico-epidemiological
features. Indian J Dermatol Venereol Leprol 2007 May-Jun; 73(3):149-56.
Boone B, Ongenae K, Van Geel N, Vernijns S, De Keyser S, Naeyaert JM.
Topical pimecrolimus in the treatment of vitiligo.Eur J Dermatol 2007 Jan-Feb;
17(1): 55-61. Epub 2007 Feb 27.
Kemp EH, Gavalas NG, Gawkrodger DJ, Weetman AP.. Autoantibody
responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun
Rev 2007 Jan; 6(3):138-42. Epub 2006 Oct 2.
STEM CELLS IN VITILIGO
S. Mercuri
Current vitiligo therapy does not offer a safe and effective
treatment to the problem.
Stem cells could represent a new therapeutic approach since
the first cases to be treated have shown a positive outcome.
With the correct technique stem cells can be used on
melanocytes and inserted into the affected zone.
After a few weeks, a visible improvement and resolution to
the achromatic patches have been documented in a good
percentage of cases.
COSMETIC LEGISLATION
P. Minghetti
In this report the definition of cosmetics and the relevant
using purpose differences between these products and drugs
or medical devices are presented. The procedures provided
by law for the manufacturing and the introduction of these
products on the market are briefly summarized.
NEW USE OF LUTEINE IN SKIN AGING
P. Morganti
Luteine with same chemical structure differentiates itself
from beta-carotene for the presence of 2 hydrossylic groups
present at terminal ionic ring level.
These characteristics, making the molecule more hydrophilic, provide it with special affinity towards the cell membrane and the interstitial liquid. Furthermore, the presence
of OH groups, not present in beta-carotene and in lycopene,
allow luteine to better react with singlet oxygen, especially in
aqueous systems identified in the ocular mucosa and in skin
lipidic lamellas.
Due to all these reasons, luteine is present in high concentrations especially in the macula lutea of the eye and on the
skin, where the double antioxidant and photoprotective
function takes place both against UVR and blue light.
Thanks to its molecular composition and to its efficacy as
active re-moisturizing and photoprotective principle, this
oxy-carotenoid is used as new principle in active antiaging
both in local and systemic applications. Together with the
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chemical-physical characteristics of luteine, new experimental data will be presented, demonstrating its efficacy when
used locally (cosmetic product) and at systemic level (supplement) in order to optimize early aged skin conditions.
SURGICAL TREATMENT
P. Mulas
In Italy, dermatology is not considered as a surgical branch,
but dermo-surgery must depend on the laws and responsibilities regarding a surgical branch to protect both patients
and those who do this job. Absolute subscription to a surgical treatment needs to make a histological test on the
removed lesion, while related subscription is the best therapeutic, functional and aesthetic result versus other treatments. As a result, not all the dermatologic lesions should be
treated surgically; the most important cutaneous lesions in
which we have an absolute subscription are: cutaneousmucous malignant lesions, pre-cancerous lesions and benign
lesions, malformations and inflammatory lesions if, as we
already said, we could obtain a better result with other treatments. We will describe necessary methods and surgical
instruments (suture, sterilization etc.) in a surgical treatment
of cutaneous lesions.
SHOCK WAVES IN THE TREATMENT
OF LOCALISED ADIPOSITY
S. Nava
Liposuction is used to improve the body contours and to
reduce localised adiposity and is certainly the most widely
used surgical technique in aesthetic surgery. This technique
has been used for ten years and gives excellent results with
loco-regional anaesthesia, sedation and regional anaesthesia.
Notwithstanding the improvements made with liposuction,
it is still subject to risk since it is an invasive therapy and
patients are not always happy with the results obtained and
the necessary and prolonged post surgical medication.
The recent introduction on the market of new electro-medical appliances using ultrasound, with a shock wave effect,
has revolutionised the approach to reducing localised adiposity and body contouring. Ultrasound destroys adipose
cells which liberates fatty acids obtaining the same result as
liposuction. The results are obtained by the lysis of selective
fat through the breakdown of the adipose membrane without
causing damage to the surrounding skin, blood vessels or the
peripheral nervous system. Fat removal happens through
physiological pathways for example through the lymphatic,
venous and immune systems. The triglycerides resulting
from cellular separation are dispersed in the interstitial fluid
where they are gradually taken by the venous or lymphatic
systems to the liver and metabolised within several hours or
days. The ability of the body to free itself from triglyceride
molecules is much greater than the amount of triglycerides
released as a consequence of the treatment. Debris from the
disintegrated cells is removed by normal inflammatory reaction, for example phagocytes and both by products from the
decomposition process are safely taken care of by the blood.
The safety of the Contour 1 treatment is demonstrated by
studies carried out in Israel and is approved by the Bioethic
Committee. It was tested on 60 women who underwent
abdomenoplasty and the subsequently treatment with
“Ultrashape”. Histology demonstrated the destruction of the
adipose tissue with no damage to the surrounding skin, connective tissue, blood vessels or nerve endings. Clinical observations did not reveal haematoma, cutaneous or subcutaneous petechia or alterations in the consistency of the skin.
Patients and Methods: From December 2006 to May 2007,
201 patients (170 f and 31m with an average age of 42.6 and
44.2 respectively) were treated 262 times with Contour 1.
The areas treated were:
Women: 80 - the abdomen, 72 - thighs, 17 - hips.
Men: 19 - the abdomen, 6 - hips, 7 - breast tissue (gynaecomastia).
778 doses were administered to the abdomen, 735 to the
thighs, 480 to hips in the women and 996 to the abdomen,
702 to the hips and 607 to breast tissue in men.
The results observed in terms of an average reduction were:
After 1 treatment:
Women: Abdomen 2.38 cm, thighs 1.40 cm, and hips 1 cm.
Men: Abdomen 1,73 cm, hips 1.03 cm and breast tissue
1.90 cm.
After 2 treatments:
Women: Abdomen 1.46 cm, thighs 0.80 cm and hips 1 cm.
Men: abdomen 1cm, hips 0.70 cm and breast tissue 1 cm.
The percentage of patients whose outcome was less than the
average was 4% abdomen, and 11.5% thighs. These patients
were only the women. Negative side effects were less than
2% and limited to erythemas in the treated areas but all had
a spontaneous resolution.
THE TREATMENT OF SKIN PRIMITIVE
LYMPHOMAS: THE ROLE OF THE
DERMATOLOGIST
S. Nisticò
The treatment of skin primitive lymphomas has the aim of
slowing down the progression of the disease and controlling
the symptoms. The therapeutic approach varies according to
the stage of the disease. In the early stages of Mycosis
Fungoides (Stages 1 a and b) this can be achieved with a topical steroid therapy, carmustine, meclorethamine, phototherapy and PUVA with good chances of complete response. The
discussion shall focus on new treatments, of exclusive dermatological pertinence, based on laser and monochromatic
excimer light, thus reporting the experience of the
Dermatological Clinic of the University of Rome “Tor Vergata”.
For the more infiltrated Mycosis Fungoides forms (Stage 2)
combined strategies are recommended (PUVA and Retinoids,
PUVA and Interferon Alpha, Retinoids and Interfero n
Alpha). In the event of relapses or widespread skin involvement, as well as Sézary Syndrome and in the most aggressive
forms of T-lymphomas, it is possible to use radiotherapy or
systemic chemotherapy. New approaches in the more
advanced stages include some new retinoids (Targretin),
antiblastics (Celix), or antimetabolites (Gemcitabine) systemically. For the B-cell forms of skin lymphomas, radiotherapy and surgical excision of the lesions represent the
treatments of choice; new approaches include the use of
intralesional interferon alpha and anti CD20 rituximab.
ATYPICAL/DYSPLASTIC NEVUS: A CLINICAL
OR AN HISTOLOGICAL CONCEPT?
G. Noto
The clinical appearance of several Clark nevuses seems to be
simply one of the aspects of subject phenotypes with high
relative melanoma risk, a risk that is genetically described
and jointly determined by environmental factors.
Among clinically atypical nevuses it is important to distinguish the dysplastic nevus, which has genetic implications
and which represents a high risk factor for melanoma, from
the dysplastic nevus which has no genetic implications and
which can be seen sporadically, for which the risk of developing melanoma would depend on the total number of
melanocyte nevuses, on the phototype and on environmental factors. The clinical-histological correlation of its atypical
character and of nevuses dysplasia does not seem consistent,
meaning that we can find clinically atypical nevuses but with
normal histopathology and vice versa.
About 70-85% of skin melanomas forms directly on healthy
skin, thus only 15-30% would develop on a pre-existing skin
lesion that we can identify as a clinical precursor. We still
have to establish if some of the precursors should be considered as pre-cancerous lesions or if the onset on top of another nevus is determined by a purely statistical percentage. A
responsible follow-up process would appear to be the clinical approach that could greatly ensure better prevention.
ATYPICAL OR DYSPLASTIC MELANOCYTIC
NEVUS: REMARKS ON THE FOLLOW-UP
AND TREATMENT
G. Noto
Atypical or dysplastic nevuses can be observed in individuals affected or not affected by melanoma and they can have
genetic implications or appear sporadically. Usually, they
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measure more than 5 mm in diameter, they are flat or with
elevation in the center. The color is dark or irregularly pigmented. From a clinical point of view, atypical or dysplastic
nevuses differ from acquired nevuses because they appear
during puberty or even childhood, showing a dynamic
behavior during adult life, and they continue to develop during the course of life, even after 40 years of age.
Histopatological criteria include the presence of an architectural disorder with asymmetry, subcutaneous fibroplasia
(concentric or lamellar), freckled melanocytic hyperplasia
with spindle cells or epithelioids aggregated in capsules of
irregular shape and size with formation of bridges between
the skin interpapillary ridges. A considerable nosological
problem on the concept of atypical/dysplastic nevuses with
no genetic implication is represented by the clinical-histological correlation which is often non consistent, i.e. it is possible to observe a clinically atypical nevus which, from an
histological point of view is normal, or viceversa. Thus, the
possibility of predicting hystological displasia on a clinical
base is quite limited.
Today, clinical evidence of the atypical/dysplastic nevus syndrome with genetic implications is no longer questioned.
The risk of developing a melanoma would be higher in individuals affected by atypical/dysplastic nevus syndrome with
genetic implications, but without a family history of
melanoma, while the risk would be much higher in individuals affected by atypical/dysplastic nevuses and with a family history of melanoma. Individuals with atypical sporadic
nevuses with no genetic implications have been included by
some authors among the individuals showing an increased
risk of melanoma, however in much lower percentages with
respect to individuals with dysplastic nevuses with genetic
implications. Thus it is important to distinguish atypical or
dysplastic nevuses, with genetic implications which represent a strong risk factor for melanoma, from the atypical/dysplastic nevuses without genetic implications which can be
observed sporadically, in the presence of which the risk of
melanoma would depend on the total number of melanocytic nevuses, on the phototype and on environmental factors.
PHOTODYNAMIC THERAPY:
TREATMENT OF EXTERNAL AND INTERNAL
GENITAL HERPES
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tissue and allowing a selective treatment. This application
principle is used in the treatment of florid condilomas of the
vulva, vagina and cervix, in vaginal flat condilomas and in
vegetal forms and flat condilomas of the penis, by using gel
ALA locally applicated and treated afterwards with red light.
Naturally, treatment is made after performing a biopsy and
HPV hybridization of the lesions to identify the oncogenic
level of the virus. The outcomes are interesting for the percentage of regression and for the outcomes (compared to
other techniques: laser and electric blade).
COMBINED TECHNIQUES
ON FACIAL REJUVENATION
R. Oddenino
Starting from some considerations on ageing and face morphology, the author describes some surgical methods which,
combined together, determine a general rejuvenation of the
face thanks to the correction of the single anatomic areas.
GENE ALTERATIONS
A. Pacifico
Ultraviolet radiations (UV) cause inflammation, erythema,
immunosuppression, photoaging, DNA impairment, gene
mutations and skin cancers. A number of studies showed that
alterations in tumor suppressor gene p53 play a major role in
the development of skin cancers. The protein p53, involved in
the programmed cell death processes (apoptosis), is the
genome “watchdog” and helps repair impaired DNA or eliminate the cells with excessively impaired DNA. Chronic exposure to UV radiations helps inactivate the DNA repair mechanisms and induces p53 mutations. Keratinocytes with accumulated p53 mutations caused by increased resistance to
apoptosis are permissive for clonal expansion and subsequently for the development of actinic keratosis and squamous
cell epitheliomas. Photo-induced mutations of p53 appear at a
v e ry early stage of cancerogenesis. However, stopping UV
exposure does not rule out the risk of developing a skin cancer even though its growth may be slower.
V. Nucci
PHOTODYNAMIC THERAPY IN SKIN
AND GENITAL WARTS
Photodynamic therapy (PTD) is based on the principle of
photodynamic reaction and therefore on the absorption of
luminous energy from a photosensitive substance (PS).
At present 5-aminlevulinic acid (ALA) is used which is not a
real photosensitizer but a photosensitizing preliminary application representing a intermediate product in our cells that
easily passes through altered cells and not through normal
cells, producing a photosensitivity primarily to the damaged
M. Papini
Skin warts are an extremely common pathology and can be
treated in many ways, from applications of salicylic acid or
other caustics, to cryotherapy and topical immunotherapy.
The probability of success of the various types of treatment
vary considerably and less than half of the individuals affected heal spontaneously. Some of the classic treatments, such
as applications of salicylic acid have low or moderate costs, but
have a modest therapeutic success, also in relation to the poor
compliance of the patient in applying the medication correctly. Other treatments, such as cryotherapy are painful and
require a lot of healing time after treatment and may cause
dyschromatic and/or cicatricial outcomes, especially when
lesions are located in aesthetically or functional sensitive
regions (face, perionichium). Immunomodulating treatments,
such as imiquimod, intralesional interferon, topical immunotherapy with SADBE or difenciprone have very high costs.
Photodynamic therapy (PDT) has proven to be effective in the
treatment of skin warts, with a rate of success ranging between
56% and 100% of the cases and in any case definitely higher
than those obtained with cryotherapy and with PDT-placebo.
PDT in the treatment of skin warts combines selectivity of
action with the absence of significant side-effects and scars or
unaesthetic outcomes. However, still relatively high costs
impose a more limited use for the time being, re s e rved only for
“diff i c u l t” cases, such as periungual locations, multiple lesions
and/or widespread, face lesions and other aesthetic sites in
individuals with coloured skin or those particularly sensitive
to dyschromatic or cheloid outcomes.
RADIO FREQUENCY AND OTHER
TECHNOLOGIES IN BLEMISHES
OF THE LOWER LIMBS
nations, for example France, have created a scientific base for
such treatment in order to regenerate their thermal
springs/bath facilities. We in Italy on the other hand, have
made limited use of our spring waters and facilities and
failed to exploit their wonderful characteristics and to recognise their true value in the treatment of skin diseases.
The dermatological surgeon has the task of repairing this situation by creating a synergy, a communication network
between the thermal locations scattered all over Italy, with
the express intention of exploiting the different thermal
properties and the wide choice of creno-therapeutic types,
from the use of peloides to that of the more famous water
therapies in dermatology for example, sulphur, calcic bicarbonate, carbonic and salsobromoidic with their anti-phlogistic and antiseptic action.
Our experience is with Salsobromoidic water, from Villa
Undulna (Terme della Versilia) which is used in the treatment of hyper-seborrhoea and irritable skin. We evaluated
the hydrocorneometrics, the sebometrics, the elastometrics
and the degree of erythema in patients affected with this
pathology before and after crenotherapy. Our next step will
be carry out a similar evaluation in patients who undergo
specific dermatological surgery, with a very precise post therapy protocol of crenotherapy versus the usual prescription of
common and tested dermocosmetics.
A. Pavesi
GENETIC COUNSELING
IN MELANOMA PATIENTS
The rationale for non ablative radio frequency will be discussed combined with infra red and vacuum and or laser
treatment and their results will subsequently be evaluated.
Even though the use of radio frequency in the treatment of
blemishes of the lower limbs is still in the pioneer stage,
there exists in the literature evidence on the efficacy of its use
in the treatment of cellulites and localised adiposity when
combined with an operator dependent mechanical massage
with an aspiration vacuum system of 200 mmbar (negative
pressure 750 mmHg) a radio frequency of 200 watts and
infra red (700-1500 nm).
The use of a mono-polar non ablative radio frequency of 6
MHz was approved by the FDA in 2006 to increase the skin
and subcutaneous tone and compactness in the lower limbs,
thighs and knees in particular.
K. Peris, M.C. Fargnoli
THE FIRST EXPERMENTAL APPROACHES
TO THERMAL WATER IN DERMATOLOGICAL
SURGERY
C. Pedrinazzi
The use of thermal water in aesthetic treatment has existed
for many years, but until now it has produced a relative poor
panorama of scientific papers. Our colleagues in other
Recent advances in molecular genetics have shown the
importance of high penetrance genes such as CDKN2A and
CDK4 (cell cycle regulation) and low penetrance genes such as
MC1R (skin pigmentation). Both types of genes have been
shown to contribute to melanoma predisposition. CDKN2A
is the most important susceptibility gene to melanoma that
has been identified so far: 20-40% of family melanoma
patients have shown germline mutations in C D K N 2 A.
Predictive factors of germline mutations in CDKN2A in
melanoma families are: i) a high number of family members
with melanoma, ii) diagnosis at young age, iii) development
of multiple melanomas and iv) family history of pancreatic
cancer.
These criteria are more stringent in geographic areas with
higher incidence of sporadic melanoma (e.g., Australia) visà-vis lower incidence areas (e.g., Europe) which suggests a
different distribution of genetic and/or environmental risk
factors. At present, the screening of gene CDKN2A is advisable in patients with at least one predictive factor. Screening
must be exclusively carried out within a research project and
accompanied by genetic counseling before and after the test.
Tests must be carried out by skilled staff only in order to
ensure that data are properly interpreted.
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THE WORLD MARKET OF BEAUTY:
TRENDS AND PROSPECTS
E. Perosino
The notion of “healthy skin” for the patient is very different
from what the dermatologist considers as “healthy” versus
“ill”. The patient perceives his/her skin as a good-looking or
bad-looking skin other than ill or healthy which is a philosophical way to bridge the gap between health and illness.
This perspective includes an array of intermediary steps
expressing a highly narcissistic trend that dates back to the
‘80s when outward appearance prevailed on the inner self.
In this regard the way we look outside inevitably passes
through the health of our skin.
The proof is that between 1980 and 2007 the world market
of beauty products shifted from about 1100 to 10000 million
euros. In 24 years, Italians have more than doubled their
budgets for beauty products and have gradually changed
their purchasing behaviors: the world of beauty has democratized, the consumers’ approach is more and more rational
and less and less emotional; perfumer’s shops have lost
ground to the profit of large distribution chains, first, and
pharmacies then, which has eventually brought about the
concept of “medicalized” beauty.
The dermatologist, who is specialized in the treatment of
skin, mucosa, etc, is even more frequently contacted to
address non-pathological conditions and to treat healthy
skins from a sheer cosmetic and esthetic point of view, or to
correct skin defects caused by either photo-aging/chronoaging or sebaceous glands and hair follicles.
IPL AND LASER: INDICATIONS
AND LIMITATIONS, THE CONCEPT
OF SELECTIVE PHOTOTHERMOLYSIS
E. Perosino
The fundamental concept that has brought about a revolution in the utilization of lasers in dermatology is the principle of selective photothermolysis, i.e. the possibility to
destroy specific pigmentary and vascular targets called chromophorous, totally sparing the surrounding structures. This
is possible if you are aware of and manage to exploit particular physical properties of laser and pulsed light technologies. Widely employed nowadays for non-ablative skin rejuvenation, we intend a set of non-surgical methods that contribute to the correction of face blemishes correlated to
“chrono” and “photoageing”.
These can be summarized in vascular, pigmented and dystrophic alterations and in alterations of skin tone and elasticity. The ultimate aims of photorejuvination are thus the elimination of the aforementioned vascular and pigmented blemishes and to act on the cellular component of the derma,
which by means of a thermal shock, is stimulated to produce
128
a major quantity of collagen, hyaluronic acid and elastin.
This treatment exploits the principle of selective photothermolysis, thus allowing, thanks to the specific characteristics
of the IPL systems, the employment of impulse sequences
opportunely adjusted according to the time of emission, the
number and the quantity of energy and obviously the appropriateness of choosing one or more wave lengths for each
treatment. In order to obtain the best possible result, also
dermocosmetological domiciliary and non-domiciliary protocols are implemented, which allow the skin to respond to
the thermal stimuli in the most rapid and effective way.
LASER SIDE EFFECTS
E. Perosino
If you do not need a laser: don’t use it!!!
Dr. Leon Gold, one of major high technology experts said
that a few years ago and contrary to what it may sound like
it is not trivial at all.
As a matter of fact, he emphasized that the use of any kind
of complex technology requires a good knowledge of the
basic and advanced laws of physics underlying that technology. Indeed, every wavelength used will have – theoretically
at least – its specific target and therefore a precise and foreseeable biological effect.
Hence, physics will help us understand each instrument correctly, foresee the most appropriate therapeutic use and last
but not least, the side effects.
Therefore, before using any kind of instrument, doctors shall
undergo a thorough theoretical training that may turn to be
difficult for some.
However, regular users of high technology know that some
side effects are sometimes hard to predict and that the same
doctor who made the treatment must take care of the patient
who develops side effects, also from the legal-medical point
of view.
REJUVENATION OF THE VULVA
E. Perosino
Skin and mucous membrane ageing are substantially tied to
two large categories of intrinsic and extrinsic factors. In the
ageing of the cutaneous-mucous membrane of the external
genital apparatus the hormonal changes related to the
menopause and pre-menopause are very significant. This
reduction of the hematic estrogen-progesterone production
causes a reduction in correspondent receptors and an
increase in androgenic activity.
The atrophic vulva (either senile or physiological) has a histologically proven progressive reduction of the dermis due to
reduced collagen production and a flattening of the dermalepidermal junction. Estrogen receptors are present in the
epidermis and basal layer of the epidermis and the fibroblasts in the dermis, which diminish along with the reduction
of plasmatic estrogens.
An ageing vulva is usually only noticed by the patient
through dryness and itching but often she fails to mention
other clinical aspects which are important to her sexual and
emotional life.
With the collaboration of the gynaecologist and dermatologist new therapeutic protocols are being developed: pharmacological, dermo-cosmetological and instrumental, to obtain
the best clinical and functional approach for the needs of
modern women.
References
Massobrio M., Ardizzoja M., Carmazzi C.M. , Fisiopatologia clinica
del climaterio femminile. Centro Scientifico Editore, Torino, 1998.
AA.VV. Premenopausa e Menopausa. Fisiopatologia, clinica e terapia. Editors:
A.R. Genazzani , M. Gambacciani. CIC Edizioni Internazionali Roma, 2000.
Erikssen P.S. and Rasmussen H. Low dose17b estradiol vaginal tablets in the
treatment of atrophic vaginitis: a double placebo controlled study. Eur J Obstet
Gynaecol Reprod Biol 44:137-44, 1992.
strated by Stegman’s histology studies). The depth of the tissue destruction is proportional to the potency of the solution
used, which is usually between 50% and 88%. The technique re q u i res a pre - t reatment pro c e d u re: the skin is
degreased with acetone and an anaesthesia must be applied
to deaden the nerves above and in between the eyes and
around the chin.
Phenol is applied to small areas with a 5-10 minute interval
to reduce cardio-toxicity. The skin becomes a compact frost
white and cold water compresses are applied causing erythema some minutes later.
The toxic effects on the heart are generally exaggerated and
are usually the result of an incorrect application and concentration. Skin complications include hyperpigementation
which is generally resolved spontaneously, while more rarely
scaring and hypopigmentation. These complications can be
easily avoided with a careful selection of patients and accurate photo-protection.
UNGUAL NAEVI
B.M. Piraccini
EPIDEMIOLOGY AND CLINICS
P. Piemonte
Basal cell carcinoma is the most frequent malignant skin cancer and the most frequent of all malignant neoplasia of our
organism. In the main European countries, it accounts for
about 70/100,000 cases per year while in some regions of the
United States it exceeds 200/100,000. Its malignancy is
localized and it rarely triggers metastasis; needless to say that
late diagnosis may entail mutilations.
Squamous cell carcinomas account for about 20-30% of skin
tumors and so they rank second after basal cell epitheliomas;
unlike the latter, they can trigger metastasis even if in most
cases they are not very aggressive. In the main European
countries, it accounts for about 10-20/100,000 cases per
year.
Besides epidemiological aspects, we will discuss clinical ones
and differential diagnostic methodologies for skin cancer
concerning keratinocytes, pre-cancerous lesions, such as
actinic keratosis in its different evolving forms, real in situ
carcinomas like the Bowen, and finally we will discuss several types of basal cell and squamous cell carcinomas.
PEELING WITH PHENOL
V. Pietrantonio
A chemical peel with phenol dates back 40 years and it is still
available since it is an effective treatment. Phenol irreversibly
denatures both membrane and structural protein causing a
controlled necrosis of the epidermis and dermis (demon-
Ungual naevi appear as a longitudinal pigmented band
(melanonychia) of variable colour which can range from
light to dark brown. They usually affect just one finger. The
melanonychia can be associated to a naevus of periungual
tissue. Dark naevi can be visible due to transparency through
the proximal nailfold (Hutchinson sign). It can happen in
children that ungual naevi grow clear through time.
THE MAGISTRATE’S PERSPECTIVE
I. Pisano
The author shall try to examine, from the viewpoint of legislation in force – with particular reference to the issues linked
to dermatology and plastic surgery – the professional responsibility of the physician, both as an independent worker and
as a public employee, briefly underlining the responsibilities
of the Head Physician and of the healthcare team, as well as
the compensation issues linked to civil responsibility and
professional insurance.
Recalling the previous presentations, we shall briefly outline
the concepts of “medical blame” and diligence, informed consent and burden of proof (onus probandi).
In particular, we shall examine the issue of the physician’s
penal responsibility for negligent serious and very serious
lesions to the person (article 590 of the criminal code) and
the case of negligent homicide.
Mention will be made to the so-called “defensive medicine”
and of the issues, both in the civil and criminal suits, connected to the risk of the choice of Technical Adviser on your
part or one appointed by the court.
129
BETA-CAROTENE IN PHOTOPROTECTION:
YES OR NO?
G. Politi
The presentation illustrates the rational use of beta-carotene
in photoprotection, in stimulating melanogenesis and in
neutralising ORs. A review of the literature is presented on
the harmful effects of beta-carotene in order to evaluate its
appropriate use.
SCLEROSANT THERAPY
G. Porcu
Sclerosant therapy of the lower extremity is an extremely efficacious therapy, easy and cheap to remove varicose veins in
the lower extremity, able to respond always to an increasing
demand (and often not outstanding) by the patients and, at
the same time, sourcing of an important professional satisfaction by the professional who makes it. After an introduction on the principle rules to follow recruiting patients to
reduce failure and complication at its lowest, we will show
materials and methods to make the sclerosant therapy on
varicose veins in relation to their calibre: type and concentration of the sclerosant substance, needles and syringes,
ways to injection, sclerosant mousse, post-treatment elastocompression. We will show through a video the real and
essential heart of this matter: techniques of endovasale injection in particular on the different methods who change in
relation to the calibre of the varicose vein to treat.
MEDICAL THERAPY FOR ANDROGENETIC
ALOPECIA AND TELOGEN EFFLUVIUM
A. Rebora
The fundamental principle for any therapy is the correct
diagnosis. So you need to understand if you are dealing with
a mere AGA or with an AGA complicated by acute or chronic TE. The therapeutic approach will be very different. In the
first case, minoxidil and/ finasteride would be the main aid.
In the second case, you first need to deal with TE that is what
worries the patient and tends to consider it the cause for the
loss of his hair. According to evidence based medicine there
are no drugs that can be recommended. Topical cortisones
and in some cases systemic cortisones can be used with partial success.
RISK MARKERS IN ALOPECIA: FERRITIN ROLE
M. Ribuffo
Even if the association between iron and alopecia reported
by Hard since 1963, only since the ‘90s did Rushton estab-
130
lished the role of the iron lack, measured by serum ferritin in
androgenic alopecia and in the AGA, in particular in women.
At that time, the role of ferritin in alopecia has been object of
intense debate in the international society, and more recent
studies have shown, the association between law levels of
ferritin and different kinds of alopecia (alopecia circumscripta, androgenic alopecia, telogen effluvium), notwithstanding
their different aetiology.
Some authors have purposed a “threshold hypothesis” so low
levels of ferritin can decrease the risk to develop different
kinds of alopecia.
In this sense, in patients with a high genetic predisposition
for androgenic alopecia or AGA, ferritin deficit does not represent an important triggering factor. On the contrary, in
patients with a low or medium genetic predisposition, the
deficit ceiling is decreased and represents an important risk
factor.
In these patients, the supplementation of iron (folic acid, B6
vitamin) could be a strategic therapy to control the risk and
the development of alopecia.
MALE COSMETOLOGY
L. Rigano
Our first impact with a person is visual. A pleasant aspect is
essential to improve social communication. The behavioural
shift nowadays involves both men an women, who increasingly use of cosmetic products, even though men are still
reluctant in using skin-care products. However, a series of
social factors are leading to the adoption of programs of cosmetic maintenance and treatment. For instance, performing
gymnastics regularly in gyms and wellness centres, or the
need of special care for the ageing skin, in a population
where one third is over 60 years old, and age which non
longer entails social and sentimental inactivity. Finally, the
professional competition with the younger generations,
which entails situations based on appearance comparisons.
All this has led also men to resort to creams and lotions in a
more programmed manner. Cosmetic industry immediately
conformed itself to this new market (although it has being
trying to push it for many years) with specific products and
adequate communication tools. New formulas in containers
specially designed to attract men, without undermining the
concept of masculinity. Men are more interested in the solutions (offered by the cosmetic product as a whole) to their
skin problems rather than in the particular active ingredient,
of which, for the time being, they do not have the culture.
But are we sure that men’s skin is so different that it needs
specific treatment products? Research on this aspect are few.
In dermatology, skin diseases are more or less equally distributed between men and women, apart from allergy to
nickel which is more frequent in women who wear costume
jewellery. However, healthy men’s skin have some particular
differences that deserve specific cosmetics, above all the skin
pH, usually more acid than that of women and secondly the
horny layer, which is thicker and therefore the active principles have more difficulty in going deep down. Then there is
the influence of the hormones, which is practically constant
and not cyclic and has prolonged effects both on the structure and on the average life of hair, rather than on the activity of the sebaceous glands. Then, the great number of piliferous glands which act as a funnel to the penetration of
ingredients in some areas. In the end, regular shaving, that
entails frequent skin renovation of the face and this facilitates
irritations.
All these characteristics require specific and balanced formative strategies, that should always take into account the social
role of men and their perception of the cosmetics world. In
the field of cosmetic media, there are new materials intended mainly for male-skin treatment: emollient oils easy to
massage and spread, not greasy, transparent and colourless,
such as hydrogenated polydecenes or meadow foam oil are
now replacing the traditional mineral and vegetable oils.
Meanwhile, after so much criticism against anti-cellulitis
products, men are becoming more and more fascinated by
these products to help sculpture abdominal muscles, face
scrub lotions and generous doses of self-tanners.
THE NEW FRONTIERS OF COSMETIC
SUBSTANCES
L. Rigano
Cosmetic innovation is under continuous pressure. The elements affecting it are the environmental impact, the increasing safety demand both for skin and body, the need for effectiveness guaranteed by scientific evidences and affordable
costs. Scientific development can offer new raw materials,
together with the use of natural organic or biological products. The environmental impact is no longer separated from
research and it requires simpler processes, ecological authentication, biodegradable chains, absence of solvents and
impurities, together with a reduction in emissions and a
lower energy consumption. Safety means, not only cosmetics, that do not inflame eyes or the mucosa, but also an
increase in the cutaneous compatibility and re-balancing.
The new frontier is atopics tolerability by children and the
elderly. All impurities should be under control and words
such as non-sensibilizing or non-comedogenic are requested.
Some explicative examples are the use of glyceryl and polysaccharide derivatives, that are replacing many ethoxylates
components in the emulsifiers field, or the use of hyaluronic
acid, with new syntheses that allow to obtain selected cuts
working as biological regulators and cutaneous skin messengers. The identification of active substances in traditional
vegetable extracts can serve as new scientific justifications to
ethnic medicine and cosmetics.
This field no longer offers just molecules…but organized
systems, that develop a mimesis of cutaneous structures,
drawing inspiration from skin biochemistry and lipidic integration. Multiple actions, epidermal repairing and integrated
transportation can now offer new opportunities to the development of effective and safe cosmetics.
PLASTIC DERMOCOSMESIS, MYTHS
AND NEW FRONTIERS: WOMEN FIGURE
BETWEEN PAST AND REALITY
C. Rigoni
I got you under my skin!
Skin is the privileged mean of communication between the
mind and the body, it is our window overlooking the world,
it is our boundary, it contains our body and it exposes us to
other people. However, it is also the biggest and most widespread organ of our body, featuring a very complicated functional and physiological system, which transmits all of our
perceptions.
In today’s world, where the collective interest is more oriented towards appearing and appearance, and where longevity
is a fact, there is a strong need to stay young from a mental
point of view, as well as from a physical one, and the skin
exalts every expectation. The contemporary art model has
now deleted the analogy old-ugly or old-mean, in the
attempt of giving the identity of a new ageless and timeless
beauty.
Charm and beauty are pursued at the risk of subjecting oneself to plastic surgery procedures that are often very questionable; however, dermatologists should always be regarded
as valid reference professionals. Thus it is inevitable that also
dermatologists have to comply with the needs of new
patients in the Third Millennium, for whom time has frozen
and apparently the biological clock does not exist anymore.
Dermatologists, just like psychiatrists do, should pay attention to social issues, to the body culture, but he should mainly focus on skin health and on protecting a specialty that is
authoritative and credible.
CO
2
M. Romagnoli
The technological instrumentation in dermatological units
has rapidly increase in the last few decades.
One of these instruments is CO laser (10600 nm), considered as a class 4 ablative lasers only for medical use. It is
surely one of the most versatile tools and with major applications in dermatology.
In fact, this instrument has different beam emission timings
that can be used to vaporise small skin neoformations, such
as common and seborrheic warts, sebaceous hyperplasias
2
131
and nevi and more cosmetic applications such as actinic
wrinkles, acne scars, lentigos.
One particular spot emission mode is capable of not covering the whole surface treated. For one year now, this technique has been used to treat fine wrinkles, sun spots and
actinic keratosis with a significant increase in compliance.
Rapid healing times have revamped the use of this instrument for cosmetic applications for which it had no longer
been used because of the high risk of complications and
down time.
The different applications of CO continuous wave, ultrapulsed and fractioned ultrapulsed laser will be explained
with its pros and cons.
2
SHOCK WAVES
M. Romagnoli
Shock waves have been used in medicine for sometime now
and in dermatology as a treatment for cellulites and saggy
skin. Their use differs from that of localised ultrasound since
shock waves acoustics have a single short impulse with a
raised amplitude.
The shock wave produces vessel dilation through the production of nitric oxide and the metabolic activation of tissues
as a result of energy development which changes the acoustic
impedance of the tissues.
MONOPOLAR RADIOFREQUENCY
and act mainly in the dermis. Radio frequencies work by
forming an electric field between the electrode and the skin.
The rapid alternation within this field provokes the displacement of the ionised molecules inside an electric field and
heat is produced by the resistance of the molecules to their
displacement. The depth of action, unlike the laser system
(which depends on the wave length) is proportional to the
sheaf dimension and has a reach of a 5-6 mm (as compared
to 0.2 mm in a 1064 nm laser) while heat production is proportional to tissue impedance but must remain within a safety range which is calculated before treatment begins. J. energy = I2 x R x t.
Radio frequency action heats the dermis and subcutaneous
tissue and produces a partial shortening of the collagen fibres
and this is usually immediately visible although sometimes it
can take up to a few days to appear. New collagen fibres and
tissue contracture (through the process of repair) will be produced and will be clinically visible about a month later and
will continue to improve for three months after treatment.
Ultrastructural histological studies support the idea that the
activation of the fibroblasts, endothelial cells and hematic
vessels from the liberation of cytokines and growth factors is
responsible for this phenomena and they also demonstrate
that there is an increase in the clinical production of collagen
fibres and tissue retraction in the treated areas.
We provide information on choosing suitable patients, the
use and addition of a new points system for a faster and less
uncomfortable treatment for tissue tightening and the most
recently FDA approvals for skin tightening on various areas
of the body.
M. Romagnoli
The research into a highly efficient and minimally invasive
system for skin rejuvenation is continually evolving.
Radio frequency is a highly efficient and minimally invasive
technique which has for sometime now been used in the
interruption of abnormal conditions in conductive fibres in
cardiac arrhythmia, for endovenous closure of the saphenous
vein, the ablation of prostatic carcinomas and for ligament
laxity. It is also used in many dermatosurgical procedures.
The safe use of radio frequency in skin rejuvenation has been
made possible through the development of a system which
inhibits the thermal damage of the epidermis but at the same
time allows heat to be transferred into the deep derma and
the subcutaneous tissue where laser systems and IPL are
unable to interact.
Skin rejuvenation with the mono-polar 6 MHz radio frequency has been made possible by the presence of a cooling
system before, during and after the emission of radio waves
which guarantees a high standard of safety on the epidermis.
Bipolar radio frequency treatment also exists, where the
depth of action is equal to half the distance between the positive and negative poles situated on the sheaf but unlike 6
MHz mono-polar treatment they require repeated sittings
132
NON ABLATIVE RADIO FREQUENCY
IN SKIN TIGHTENING
M. Romagnoli
The research into a highly efficient and minimally invasive
system for skin rejuvenation is continually evolving. Radio
frequency has already been used for some time now in the
field of medicine for example, in the interruption of anomalies in conductive fibres in cardiac arrhythmia, the endovenous closure of the saphena, the ablation of prostatic carcinoma and for ligament laxity as well as in many dermatosurgical procedures.
The pivotal point of this technology in its transfer to skin
rejuvenation is the idea that this is a totally safe system, in
that it impedes thermal damage of the epidermis but at the
same time allows heat to be transferred into the deep derma
and the subcutaneous tissue where laser systems and IPL are
unable to interact.
In the mono-polar radio frequencies MHz it is possible (skin
rejuvenation is possible through) with the presence of a cooling system before, during and after the emission of bipolar
radio frequencies where the depth of action in equal to half
of the distance between the positive and negative poles both
situated on the sheaf/bundle. These are different from the 6
Mhz mono-polar since they require repeated sittings and
react mainly on the dermis.
Radio frequencies work by forming an electric field between
the electrode and the skin. The rapid rotation within this
field provokes the displacement of the ionised molecules
inside an electric field and the resistance met by the molecules to their displacement causes heat production. The difference from a laser system where the action depth depends
on the wave length instead here it is the dimension of the
sheaf/bundle which determines the action depth.
The depth of action in this system is proportional to the
dimension of the sheaf/bundle which allows it to reach 5-6
mm (as compared to 0.2 mm in a laser 1064 nm) while the
production of heat is proportional to tissue impedance and
must remain in the safety range which is calculated before
patient treatment begins. J. energy = I2 x R x t. The rationale
for the radio frequency action is that heat reacts on the dermis and subcutaneous tissue producing a partial shortening
of the collagen fibres. This is usually immediately clinically
evident but can sometimes takes up to a few days after treatment to appear. There will also be production of new collagen fibres and tissue contracture (through the process of
repair) which will be clinically visible after about a month
and will continue to successively improve for three months
after treatment.
This phenomenon has been hypothesised to be caused by
the activation of the fibroblasts, endothelial cells and hematic vessels from the liberation of cytokines and growth factors.
This hypothesis is supported by ultrastructural histological
studies which demonstrate that beyond the increased clinical
production of collagen fibres there is also tissue retraction of
the treated areas.
We will speak about how to select suitable patients for this
treatment, technical evolution during the first year of use
with the introduction of a new points system which allows a
faster and less uncomfortable treatment for the tissue tightening and the most recent FDA approvals for skin tightening
in various areas of the body.
RADIO FREQUENCY UNIT AND OTHER
TECHNOLOGIES IN THE TREATMENT
OF LOWER LIMB BLEMISHES
M. Romagnoli
The rationale for non ablative radio frequency techniques
combined with infrared rays, a vacuum or a laser will be discussed and the results obtained from this therapy will be
evaluated.
Even though the use of radio frequency in this field is a pioneering treatment, evidence already exists on it’s efficacy with
cellulite and localised adiposity, when combined with: a
mechanical or human massage, an aspiration system with
200mmbar vacuum (750 mmHg negative pressure), 20 watt
radio frequency and 700-1500 infrared rays.
The use of 6Mz mono polare non ablative radio frequency
was approved by the FDA in February 2006 to increase skin
and subcutaneous tone and compactness of the lower limbs,
in particular of the thighs and knees.
THE ITALIAN STUDY GROUP
ON TECHNOLOGIES (GIST) THE RESULTS
OF THE USE OF MONO-POLAR 6 MHZ RADIO
FREQUENCY TREATMENT
M. Romagnoli
GIST was found through the need to compare the results of
mono polar 6MHz radio frequency users.
In particular the differences in methodology and results presented the need to understand the advantages and disadvantages of this treatment. With the results from a questionnaire
sent to 30 centres scattered all over Italy a polycentric study
with more than 2000 cases has been created. This is the
largest in the whole of Europe.
The study results and the starting point for these new guidelines will be projected to the audience.
SHOCK WAVE THERAPY IN DERMATOLOGY
FOR PEFS AND SAGGY SKIN
M. Romagnoli, A. Pavesi
Shock wave therapy in dermatology and aesthetic medicine.
Preliminary results in body shaping.
The use of shock waves is a new idea in dermatology and
aesthetic medicine. The treatment is easy to apply, non evasive, has no side effects and tangible results are visible after
only a few sittings.
The study performed was carried out on the assumption that
shock waves when aimed at subcutaneous tissue can
improve the blemishes caused by cellulite and saggy skin and
reduce the panniculus adiposus in localised adiposity.
12 patients affected with cellulites, saggy skin and/or localised
adiposity in various regions of the body were given 6 sittings
of shock wave treatment administered twice a week.
An objective evaluation was made with photographs, skin and
subcutaneous ectomography with bone landmarks, impedance metric and simple tape measure values, which were carried out before treatment was begun and again at the end.
Patient compliance was excellent due to both high treatment
tolerability during and after treatment and the positive
results obtained with relation to the time involved.
The results obtained, even though from a small group of
patients, were satisfactory from the aesthetic point of view
and without any adverse side effects. In particular they con-
133
firmed the results obtained from previous studies that the
subcutaneous skin was more compact after treatment and
reduced body volume.
SKIN TISSUE REPAIR IN DERMOCOSMETOLOGY
M. Romanelli, V. Dini
Every time there is breach in the skin and a wound is created, there is a sudden and immediate fall of the anatomic and
functional organization of the skin. This loss of continuity in
the skin triggers complex mechanisms with the aim of closing the breach involving both cells found in the skin as well
as cells of haematic origin.
The skin seems to play a key role in tissue repair stage. In
fact, the skin enters into a proliferative stage with the process
of reconstruction of the superficial layer (re-epithelialisation). In the sequence of the events leading to the repair of
the tissue, the role of the derma fully enters into action only
when, terminated the primary exudative and infiltrating phenomena typical of inflammation, the granulation tissue
begins to be formed by the dermal fibroblasts.
The formation of the granulation tissue represents the key
event of the second stage, known as proliferative, of the healing process and inevitably involves the onset on the following one, known as remodelling, marked by the progressive
reorganization of the matrix.
Scars are a medical issue with functional and cosmetic implications. Clinically, cicatricial tissue distinguishes itself from
normal skin for its abnormal colour, the irregular surface, the
presence of contraction of the area where it is found and for
the hardness of the tissue. The typical characteristics of a
pathological cicatrisation are: the continued production of
collagen; defective remodelling of cells and of the extracellular matrix; the presence of a widespread inflammatory infiltrate and the absence of elastic fibres.
The abnormal quantity of collagen found in these scars is
due to the loos of balance between synthesis and degradation. These structural differences with regard to eutrophic
scars account for the mechanical properties of cheloids, such
as a major fixedness, consistence and elastic resistance.
CLASSIFICATION AND DEPTH. GENERAL
TECHNIQUE: FACTORS INFLUENCING DEPTH
A. Romani
At present, Peeling is one of the most widely used outpatient
treatment options for several diseases and cosmetic defects
(face “refreshing”). The plastic dermatologist will evaluate the
defect to be corrected and can use many peeling substances
with a single component or with multiple components. The
aim is to perform a controlled peeling procedure to eliminate
the problem identified. The presentation analyses the char-
134
acteristics of each peeling substance and its efficacy, the
depth at which it acts and other variables.
The appropriate knowledge of peeling substances, their
behavior and effects on the skin is indispensible but often
not sufficient to correctly perform a peeling procedure.
What are the variables that may have an impact on peeling?
Chemical peeling is an outpatient dermoplastic treatment
and therefore, in most cases, it complements and does not
replace home topical and systemic therapies.
Before performing a chemical peeling it is crucial to evaluate:
1. the disease or skin defect (and whether it is indicated),
2. Possible contraindications,
3. The patient’s motivations,
4. The patient’s expectations in terms of the benefits that can
be obtained,
5. The patient’s compliance with post-peeling instructions,
6. The type of skin,
7. The need to combine dermocosmetic treatments and/or
pharmacological therapies.
In addition, it is very important to inform the patient about:
1. The benefits that can be realistically obtained on the basis
of the disease or of the skin defect,
2. The procedure,
3. The post-peeling course,
4. Possible implications,
5. Alternative treatment options.
Therefore it is clear that the deeper the action of the Peeling
substance, the stronger the skin stimulation, the greater the
benefits that can be obtained but also the complications.
That is why it is very important for this technique to be performer by an experienced plastic dermatologist who can
closely follows up the patient.
TISSUE INDUCTION: BIOSTIMULATION
WITH HYALURONIC ACID
A. Romani
In Plastic Dermatology there is an increasing availability of
new injectable solutions to treat wrinkles.
The introduction of a natural hyaluronic acid with a high
molecular weight and PDRNs has actually opened new methods to counter and prevent ageing and photoageing at the
level of the skin and has introduced the concept of biorevitalization and active photoprotection through a marked
restructuring action of tissues.
The author will examine the physiopathological basis of skin
ageing and photoageing and the fundamental role of
hyaluronic acid in the stimulation of fibroblasts, the scavenger action on free radicals with clinical and instrumental
results.
Natural bio-interactive hyaluronic acid and PDRNs have very
interesting characteristics, safe and versatile and can be an
integral part of any program of skin rejuvenation.
Long-acting biorevitalization, the cross-linked and picotage
techniques, sites, timing and ways of administration with the
support of a short video shall complete the presentation.
MORPHOLOGY, AGING AND CLASSIFICATION
OF WRINKLES
A. Romani
The most meaningful and visible sign of the shift from youth
to senescence is represented by the appearance of facial wrinkles.
If we take into consideration the concept of beauty compared
to a young skin, the importance of the outward appearance
in modern society based on image and the tendency to emarginate the old, we can understand how it is important to try
to “exorcise” aging above all trying to solve or weaken the
problem of wrinkles.
Dermatology and in particular Plastic Dermatology deals
with and takes care of the body as it exteriorly appears, thus
it has the task of scientifically evaluating and then putting
into practice the most suitable treatments aimimg to obtain
prevention and improvement of skin aging signs.
A wrinkle can be defined as a permanent and linear furrow
of the skin, with a variable depth.
In this presentation the causes that bring about the appearance of wrinkles are presented such as:
• Aging,
• Muscular and articular movements,
• Force of gravity,
• Night postures.
A morpho-evolutive classification of wrinkles, differentiated
with regard to areas and pathogenetic causes, is analyzed
according to age, lifestyle and possible corrections and intervention methods.
A “RESTORED” BODY
M.C. Romano
The body of a cancer patient often becomes a symbol of suffering through surgery, chemo and radiotherapy. More often
than not, these life saving therapies are extremely invasive
and surgery may leave very obvious scarring which can be
both maiming and disabling. Moreover it is nearly always
the case that further “beneficial” chemo or radio therapy is
given, notwithstanding its high toxicity and a host of negative side effects is given with the aim of washing away the
malignant cells so that the organism becomes more alive than
dead.
The skin is one of the most maltreated organs in cancer therapy with alopecia, folliculitis, early ageing from oxidative
stress and extensive and painful radio dermatitis to name but
a few side effects. Furthermore let us not forget that our skin
is what we show to the world and our peers, and we cannot
expect an already physically weakened patient to cope with
the psychological impact of a demoralising appearance.
The possibility of counteracting such side effects, without
interfering with the desired aim of these treatments must be
considered in the fight against cancer. The therapy to restore
life to a profoundly threatened organism must be accompanied by a dermal cosmetic control in order to resolve, reduce
and slow down skin damage, which would otherwise and
inevitably be suffered by a patient who already has to deal with
the side effects of the life saving therapy.
VIDEODERMATOSCOPIC ASPECTS
IN TRICOLOGICAL DIAGNOSIS
A. Rossi
Hair can be affected by many diseases, some of which should
be considered as typical of this structure and only limited to
it. Most of these diseases are systemic and hair alterations are
just an epiphenomenon of a generalised disorder. The aim of
this presentation is to illustrate the current techniques
designed to study hair. As for all the laboratory techniques,
there is a wide range of options such as simple and fast tests
that can be performed by any laboratory and/or by any doctor at a low cost, or more sophisticated and very expensive
techniques requiring very complex equipment and highlytrained personnel.
Today, one of the most frequently used tricological diagnostic tools is digital videodermatoscopy which has paved the
way to a series of revolutionary hair examination methods. In
fact, in the past, a series of empirical and time-consuming
methods were required.
Today instead, it is possible to obtain the same results with a
simple and standardised approach, storing a vast amount of
information on the health of the scalp and of the hair.
Thanks to these imaging techniques that make it possible to
look for different markers for the diagnosis and the followup of patients suffering from alopecia, the Dermatologist has
dramatically changed his approach to these patients.
Moreover, all patients’ clinical and instrumental files are
stored in an archive and can be quickly retrived to manage
their cases. In fact the system runs a management software
for patients suffering from alopecia, thus facilitating diagnosis. The authors will discuss the use of new technologies for
managing these patients.
EXPERIMENTAL EVALUATION OF THERMAL
WATER IN AESTHETIC PLASTIC DERMATOLOGY
F. Russo
As in various other medical disciplines, thermal medicine
has evolved in recent years through intense re s e a rch.
135
Nowadays the outlook is without a doubt extremely valid for
crenotherapy especially in the light of the necessity of a multidisciplinary approach to the research for new information,
types of treatment for chronic and socially more diffuse and
important pathologies, as for example osteoporosis or obesity, where integrated and sequential therapeutic strategies
have good prospects also in contributing to the slowing
down of the ageing process of the human tissue.
Let us not forget the continuous contribution from bio-molecular research which also indicates to the medical doctor at
the thermal springs the new physiopathological directives at
the base of the mechanism of action of the thermergic stimulus, that may be found in the very early studies on the
involvement of HSPs carried out by the Pisa School in the
crenotherapy sector.
LASER, IPL AND TELEANGIECTASIS
OF LOWER LIMBS
G. Scarcella
Sclerotherapy is the more safe and standardized method for
the treatment of lower limbs teleangiectases; during the last
few years some Laser Systems were conceived and they are
able to produce very good results in this kind of use.
In this report some of the principal lasers used for lower
limbs teleangiectases are reviewed, underlining benefits and
disadvantages in comparison to traditional methods.
VASCULAR LASER
G. Scarcella
Vascular cutaneous lesions are very common in dermatological practices and they are independent from patients’ gender
and age.
Up until recently vascular cutaneous lesions treatment was
very difficult and sometimes, please refer to Port Wine
Stains, almost impossible. Later, thanks to the appearance of
laser technology, it became simpler, but above all safer.
The first Laser System, which was designed according to the
Selective Photothermolysis principles, was the Pulse Dye vascular laser.
Before this kind of laser, other selective Laser Systems were
used for vascular pathologies, but they had a continuous or
almost continuous impulse, so they were not able to produce
a selective thermic damage. The use of these less specific
lasers was always associated with a high percentage of scars,
above all if the user had not selected the right laser parameters and patient’s phototype.
Nowadays, the use of pulse lasers, respecting Anderson and
Parrish Selective Photothermolysis, revolutionized vascular
cutaneous lesions treatment and makes it possible to obtain
unimaginable results.
136
THE FOOT FROM PATHOLOGY TO DECORATION
B. Scoppio
The foot, for its anatomical and functional structure, is an
essential organ for our daily activities and more and more
attention is being dedicated to its wellbeing that has a strong
impact on quality of life. In fact, it is exposed to physical,
chemical and biotic exogenous stimuli and therefore subject
to various skin and nail pathologies favoured by predisposing and/or triggering factors such as perspiration, soaking,
frequent body cleaning and environmental situations.
Physical threats involve traumatisms accounting for friction
blisters, tylomas and nail traumas, while low temperatures
are associated with chilblains and Raynaud’s Phenomenon.
Contact dermatitis often involves the extremities, induced by
chemical agents mainly deriving from sock and shoe dyes,
chrome in the leather, rubber, shoe glue, but also from paraphenylendiamine (PPD) and methacrylates. With the spreading fashion of temporary henna tattoos and nail reconstruction there is an increased risk for sensitization towards allergens such as PPD and methacrylates. Generally, adverse reactions triggered by temporary tattoos are not due to henna
itself, but to the substances added to enhance its colour and
duration.
In the various techniques of nail reconstruction, the materials and the glues employed are made with acrylicates, which
are substances that can cause sensitization reactions.
Then there are foot dermatoses due to bacterial, mycotic and
viral infections, such as plantar pitted keratolysis, interdigital mycosis, onychomycosis and vulgar warts, without leaving out those dermatological manifestations induced by sea
organisms, such as accidental stings of sea echini and weeverfish and treatments to cure and prevent these affections.
THE ITALIAN LEGISLATION
ON FOOD SUPPLEMENTS
S. Selletti
The author provides an overview of current legislation on the
marketing of food supplements in Italy following the transposition of the EU Directive 2002/46 in the national law.
However, the directive contains various items on the protection of public health, therefore the Italian legislation has
made use of the right to introduce specific references to the
national health care system during the transposition procedure.
On the one hand, this solution may not foster harmonization
between the various Member States but, on the other hand,
it undoubtedly allows for greater consumer’s protection.
The author illustrates the regulatory requirements to market
food supplements with reference to the functional regulatory requirements for market sale. He will then dwell upon the
types of products and their correct presentation, emphasiz-
ing that such substances can certainly be good for people’s
health and well-being but they cannot be compared nor can
they replace drugs. As a matter of fact, they can only be considered as adjuvants.
The author will also illustrate a few cases of legal relevance
with a view to providing useful information and principles to
the doctors participating in the Congress.
LASER LIPOLYSIS IN LOCAL ANESTHESIA
A. Serraglio
Lipolaser technique: Connect to the laser a 600 micron fibre ,
inserting the end of the fibre inside a cannula needle of 2 mm
diameter. Make the fibre come out of 1 cm from the cannula.
Now turn on the laser, program it in continuous mode of laser
energy emission and with a power varying from 5 to 10 W.
After having performed Klein tumescent local anesthesia,
introduce the cannula needle with the laser fibre and by slow
but continuous movements activate the laser emission, using
it for 3 to 5 seconds per area and then moving radially.
At the beginning the operator can notice a little resistance,
but later on the area becomes softer and the initial resistance
decreases.
Once fat is completely emulsified, it is possible to begin to
suck it.
1,2-2 mm diameter cannulas are used.
Benefits:
• It is a state of the art method which allows to emulsify the
most resistant fat.
• It is possible to use 1,2.2 mm cannulas and to make a
superficial microliposculpture.
• It is a rapid method with a very good joule effect due to
warmth emanated from the end of the laser at subcutaneous level with a following lifting effect.
• If used by experts, this technique allows to treat every
lipodystrophy, also the most resistant ones and quite
rapidly.
A tight bandage with a resilient sheath will follow, together
with one day of rest and then after eight days a lymphodrainage series twice a week.
Cases and short films.
senile and iatrogenic hypodermal dystrophy and gravitational aging, ptosis, loss of volumes (correction, modelling and
neocollagenogenesis tensioning effect of the face contours, of
the zygomatic region and of the oral and the chin regions).
PLLA could be defined as a “controllerd fibrosis”: PLLA is also
defined as a “Dermal Stimulatory Device”.
The paper focuses on the improvement and the enhancement of the implant techniques of this resorbable and
biodegradable biopolymer on the basis of a 7-year experience.
In addition it deals with the prevention and management of
possible undesirable side effects such as early and late nodules through the correct selection of patients and the management of late nodules and the combination of PLLA and
hyaluronic acid according to the face districts to be treated
and the type of wrinkles.
PHOTODYNAMIC THERAPY AND ACNE
F. Servello
Photodynamic therapy is based on the tissue’s photo-oxydation following the application of a selective photosensitizing
agent, i.e. 5-aminolevulinic acid that triggers the photodynamic reaction as a result of a light source application.
The treatment is indicated for actinic keratoses, nonmelanoma neoplasias, Bowen disease.
Vulgar acne is one of the most common disorders that we
find in our daily clinical practice.
PDT has reduced side effects and very good esthetic results
as regards the psychological problems linked to this condition. ALA is converted into protoporphirin IX, a powerful
photosensitizing agent that induces a prolonged suppression
of the gland function and a reduction of the microbian follicular flora in the sebaceous follicle and glands.
Assessment of effectiveness and benefits of PDT in the treatment of acne.
Description of the technique.
INSTRUMENTAL TECHNOLOGY
IN THE DIAGNOSIS OF MELANOMAS
I. Stanganelli
BIORESTRUCTURING WITH POLYLACTIC ACID
R. Serri
Poly-L-lactic acid (PLLA, Poly-L-Lactic Acid) is reconstituted
with sterile water from a minimum of an hour to a maximum
of some days before its use. It has to be injected in the deep
dermis-hypodermis with different techniques with respect to
traditional resorbable fillers.
In fact, with PLLA, it is necessary to treat the whole district
and not the individual wrinkle, in order to correct both the
In recent years, the introduction of dermoscopy (i.e. epiluminescence microscopy) has opened a new dimension in the
study of pigmented lesions and the identification of
melanomas in their early stage.
Dermoscopy is a non-invasive exam that allows to visualize
in vivo the structures of the skin, the dermoepidermal junction and the papillary derma not visible to the naked eye,
which present specific histological correlates. The most commonly used tool is the dermatoscope, a monocular with a
10x fixed magnification and very easy to use. Other devices
137
are the stereomicroscope, the videodermatoscope and digital
cameras with special lens.
The identification of specific diagnostic patterns linked to
the distribution of colours and to the presence of dermoscopic structures, suggest the degree of atypicalness o benignity of the lesion analysed. The considerable expansion of
this technique has made it difficult to establish a homogeneous standardization of terminology on the diverse morphological criteria visualized during dermoscopic observation. The most commonly uses dermoscopic classifications
are the pattern analysis, the rule of the dermoscopic ABCD,
the Menzies Method, the 7 point checklist and the stratification of the risk levels.
The implementation of the digital systems of dermoscopy
has opened up other applications, both in clinical practice
and in applied research. In fact, computerized technology
allows to make a mainly clinical use to monitor the evolution
of a melanocytic lesion (mole mapping), to create a database
in images and for the development of data communication.
Other applications include the support of dermoscopic pictures for a more precise correlation with histopathology and
the review of misclassified cases.
A very new diagnostic technique in vivo – quasi histological
– is confocal laser microscopy, which represents the future
challenge for an in vivo assessment of difficult lesions.
In the scope of automatic diagnosis, many groups have met
to work out the “magic” mathematical algorithm that would
help the clinician identify a melanoma.
Recent reviews have shown that the impact of diagnosis carried out with different techniques and with the support of
the computer is not significantly different from the diagnosis
of the expert clinician and appears to be independent from
the optical method employed to analyse the lesion (videomicroscope, digital stereomicroscope, video-camera, spectrophotometer).
However, studies published in literature present many biases that strongly suggest that the role of the computer is still
anchored to the field of research or to the object parameterization of clinical data.
Computers cannot substitute the dermatologist in the articulated diagnostic pathway of pigmented lesions.
on its biological characteristics and on inherent and extrinsic
elements, in particular the exposure to ultraviolet rays which
affect the dermatoscopic structures, and colours have been
studied following intense sun exposure and artificial ultraviolet radiations.
In practice, even if univocal dermatoscopic criteria in the
recognition of those parameters that can define a “lesion to be
stored for follow-up” are missing, the melanocytic nevi than
can hide a potential melanoma are:
1) nevi with peculiar hyperpigmentation;
2) nevi with peculiar hypopigmentation;
3) melanocytic nevi with black homogeneous pattern (without corneal lamella);
4) nevi with multifocal hypo/hyperpigmentation.
The surgical excision in the presence of the clinical-dermatoscopic “ugly-duckling” is highly recommended, because of the
contemporaneous presence of reticular, globular and homogeneous structures or because of the evident patient history
of recent changes. The follow-up should never be performed
in nodular lesions presenting atypical characters, because it
is not possible to exclude for certain a nodular melanoma.
In the case of multiple smooth atypical lesions, a continuous
dermatoscopic monitoring is advisable in order to evaluate
the possible symmetry changeability or the structural
changes.
Focal enlargement with a change in shape associated to
re g ression and/or colour changes (appearance of new
colours/asymmetry of the pigmentary pattern) is considered
as a suspicious element. Besides general changes in colour
and shape, it is important to evaluate those changes happened in dermatoscopic structures:
1) appearance of new structures: peripheral comedos, radial
stripes, pseudopods, whitish velum, grey-blue areas,
irregular and prominent pigmentary network;
2) changes of the network, such as thickening, irregularity
and lack of homogeneity.
Even though the digital monitoring allows to study the
development of a melanocytic lesion, the lack of clinical and
instrumental standards leads to several issues concerning the
real benefits and the limits of this method.
For these reasons this procedure requires caution and high
experience.
DIGITAL MONITORING
I. Stanganelli
TREATMENT OF CUTANEOUS AGING
D. Steiner
Digital applications in dermatoscopy have opened new perspectives in the treatment of patients at the risk of
melanoma, in melanocytic lesion monitoring and in applied
research.
Digital systems allow to store in a computer dermatoscopic
and clinical images of single nevi, thus permitting a detailed
follow-up of chromatic and structural changes during time.
The history of melanocytic lesions can vary and it depends
138
Safe, effective and little-aggressive procedures have increasingly been used in the treatment of cutaneous aging.
Botulinim Toxin is the best treatment for lines of expression.
The indications, the most important points, preparation of
the patients and their expectations will be addressed.
The new points that can shape and lift the face will be
shown.
The importance of an individualized program will also be
focused upon.
Complications and the duration will be discussed.
The technique of using fillers has also greatly evolved during
the last few years.
We will address the types of fillers, their indications and risks
and we will discuss the experience with hyaluronic acid and
polylactic acid.
The duration, effectiveness and complications of the fillers
will be addressed.
The pros and cons of definitive and non-definitive fillers will
be discussed.
Lastly, we will address the techniques used for combining
these procedures.
PRONOUNCED PROTECTIVE EFFECT
OF ANTI-STAT1 FLAVONOIDS
IN INFLAMMATORY DISEASES:
MOLECULAR MECHANISM OF ACTION
H. Suzuki
Flavonoids, bearing a common structure composed of 2phenylbenzopyrone with different number and position of
hydroxyl groups, exhibit a variety of beneficial effects in cardiovascular diseases. Although their therapeutic properties
have been attributed mainly to their antioxidant action, they
have additional protective mechanisms. Recently, we have
shown that epigallocatechin-3-gallate (EGCG) protects the
rat heart from ischemia/reperfusion (I/R)-induced damage by
inhibiting apoptosis and signal transducer and activator of
transcription 1 (STAT1) activation in card i o m y o c y t e s ,
although functional relationship between anti-STAT1 activity and antioxidant capacity of EGCG has been elusive. Here,
we have investigated the cardioprotective mechanisms of
naturally occurring, strong antioxidant flavonoids such as
quercetin, myricetin and delphinidin. Although all of them
protect the heart from I/R-injury, myricetin and delphinidin,
which are able to inhibit STAT1 activation, exert more efficient protective action than quercetin. Biochemical and computer modeling analysis were undertaken to study the direct
interaction between STAT1 and flavonoids with anti-STAT1
activity.
SENTINEL LYMPH NODE:
STATUS OF THE TECHNIQUE
attention of the entire scientific and research world during
the last few years.
Nowadays the status of the sentinel lymph node is recognized as the most important factor in this pathology, together with the Breslow thickness. This evidence is supported by
international clinical researches, such as MSLT I, thus widely accepted.
As every re v o l u t i o n a ry scientific discovery, the sentinel
lymph node technique has brought about several new issues
that basic research and many clinical studies are trying or
will try to resolve. After having demonstrated the prognostic
meaning, the therapeutic options based on the status of the
sentinel lymph node are being studied; for example the
MSLT II research, still ongoing, is trying to establish if it is
necessary to empty the lymph node basin of the positive sentinel lymph node or if a follow-up is feasible. Clinical
research is studying how to get important information from
the sentinel lymph node in order to make the diagnosis more
effective and surgery more conservative. The sentinel lymph
node technique has undergone many changes since its introduction, from the difficult visual research of coloured lymph
nodes to the easier research of radiomarked lymph nodes
and in the future several technical changes will occur.
Also the technique of searching tumoral cells inside lymph
nodes is undergoing many changes; for example alternative
methods to traditional microscopy (eosin hematoxylin), such
as RT-PCR, are being tested. Other researches are aimed at
trying to determine the status of the sentinel lymph node
through ultrasound techniques and without extirpating it.
Other researches are trying to discover the biological meaning of isolated tumor cells (ITC) inside the sentinel lymph
node; some maintain that they can act as a stimulus of the
immune system against the tumour. Moreover the study of
the sentinel lymph node could give important information
on tumor stem cells that can help creating drugs able to
block their growth and stop metastasis.
The sentinel lymph node technique is used for several
tumours, both superficial and deep, and clinical researches
are trying to verify the effectiveness of the above mentioned
technique in the various neoplasia.
Nowadays, with regards to the melanoma, the emptying of
the lymph node basin is still used in all those patients that
are not part of specific clinical researches.
MELATONIN AND HAIR CYCLE
A. Tosti
A. Testori
After the introduction of the sentinel lymph node technique
in 1992, we have witnessed several important changes in the
staging and research of melanoma, and more generally of
those cutaneous tumoral diseases that can give rise to lymph
nodal metastasis. This technique has undoubtly drawn the
The melatonin greatly affects hair cycle because it can both
prevent telogen and stimulate the anagen return of follicles.
This report describes the effects of melatonin on follicles and
it shows the result of a spontaneous research aimed at evaluating the long-term effectiveness of melatonin oral assumption in the treatment of female androgenic alopecia.
139
A CAREFUL TEST OF NAILS CAN SOMETIMES
GIVE USEFUL ELEMENTS FOR A PRECOCIOUS
DIAGNOSIS OF SOME SYSTEMIC PATHOLOGIES
A. Tosti
Clubbing
Clubbing is characterized by the spissitude of the ungual
phalanx flesh giving a drumstick appearance to the finger.
The nails appear rounded, with a watch glass like appearance
and with the angle between the proximal ungual fold and the
lamina is > 180°. The hyperplasia of the dermal fibre vascular tissue forms the nail base and is extremely mobile.
Clubbing can be idiopathic or as result of cardiovascular,
bronco-pulmonary or gastrointestinal pathologies.
Yellow nail syndrome
In this Syndrome nail growth is slow or stops completely.
The ungual lamina varies between pale yellow and greenish
yellow with an increased latero-lateral and antero-posterior
curvature. The cuticle is absent and onycholysis is frequently present.
The ungual changes are typically associated with lymphoedema and or chronic infections of the respiratory apparatus, and
is sometimes a condition related to a paraneoplasm.
Apparent leukonychia
White Terry Nails
Apparent Leukonychia hits the whole nails making an exception for a distal arch of 1-2 mm. Many authors consider it as
a pathgnomonic sign of the cirrhosis, but in reality is frequently observed also in healthy individuals.
Half and half nails
Apparent Leukonychia hits the half proximal part of the nail
presenting a deep red colour in the distal half. Frequently
associated with hyper-azotaemia is a ungual sing characteristic of a chronic nephritic insufficiency.
Muehrcke’s Lines
Apparent Leukonychia with multiple cross bands. Are a frequent side effect of anti-blastic chemotherapy and a typical
sign of hypo-albumin (Nephrosis Syndrome).
Bazex paraneoplastic acrokeratosis
This pathology is characterized by psoriasiform alterations of
the nails and of the periungual regions, of the face (nose,
auricle) and of the palmoplantar regions.
Bazex paraneoplastic acrokeratosis is a precocious sign of
neoplastic pathologies that more often hit the respiratory and
gastrointestinal system. Cutaneous phenomenon can go better or to regress removing the tumour.
Melanonychia
A striated Melanonychia with multiple bands or a cross
Melanonychia that hits more fingers can be observed in
patients affected by AIDS or rarely during endocrinopathies.
Ungual signs of collagenosis
Ungual fold capillaroscopic alterations
Examing capillary of the proximal ungual fold it is easy to
point out these alterations through a common ophthalmo-
140
scope\funduscope after putting a light stratum of immersion
oil on the fold. In Systemic Sclerosis and in dermatomyositis
it is typical to find a rarefying and a dilatation of capillary. In
Dermatomyositis these alterations are frequently associated
with cuticle haemorrhage. In Systemic Lupus Eritematosus
capillary density is normal but capillaries appear enlarged
and tortuous with a glomerule appearance.
Pterigium inversum unguis
This is a clinical typical sign of Sclerosis. The ungual wrinkle
disappear due to ischemic lesions of the hyponychium so
that hyponychium skin adheres to the ventral lamina surface.
Patient generally feels pain cutting his nails.
Medicine induced ungual alterations
Anti-neoplastic medicine often causing a Striated
Melanonychia, striated Leukonychia and or appare n t
Leukonychia.
Zidovudine (AZT) produce Melanonychia in high percentage
of treated patients. The development of a striated
Melanonychia can also be caused by a PUVA treatment.
Rarely PUVA therapy, like also a tetracycline therapy in the
summer, can cause photo-onycholysis.
Photo-onycholysis can also appear after therapeutic short
cycles. Ultraviolet radiations involved in the development of
this pathology are those included between 310 and 313 nm.
Photo-onycholysis can also arise after few weeks after the
end of the therapy hitting only the fingers of the hand. The
thumb is less subjected to ultraviolet radiations and for this
reason is almost always saved. In the photo-onycholysis lamina lateral bonds are not involved and often detachment is
preceded by pain.
FROM KAPOSI’S SARCOMA TO ANGIOSARCOMA
A. Tourlaki
Kaposi’s sarcoma is a proliferative disorder affecting vasal
endothelia; at skin level it shows through spots, nodules or
erythematic-purple plaques, usually located on lower limbs.
Except rare cases, its typical variation has a chronic course
which slowly aggravates but which is rarely a direct cause of
death.
Here we describe three patients affected by the typical
Kaposi’s sarcoma which, following long illness, showed one
or more atypical lesions, diagnosed as angiosarcomas
through histology tests.
In one of these cases, angiosarcoma was the cause of death,
while the other two cases, for whom the diagnosis of
angiosarcoma was only recently diagnosed, are kept under
observation. Angiosarcoma is a rare malignant tumor affecting the vasal endothelium and which, unlike the typical
Kaposi’s sarcoma, usually has a fatal prognosis.
Based on our experience, the Kaposi’s sarcoma can rarely
evolve into angiosarcoma, with a relevant modification of the
prognosis.
COSMESIS AND MORALITY: CONSIDERATIONS
BY A “MATURE” DERMATOLOGIST...
L. Valenzano
Cosmesis as Dermatology and Cosmetology, along with all
the subsequent diversifications (Esthetic Medicine,
Cosmetology, Corrective Dermatology, Plastic Dermatology,
etc.) is the result of the science’s interest towards the ancient
art of decorating the body and therefore paying attention to
one’s outward appearance: an ancient usage that is likely to
date back to the dawn of humanity since it is peculiar to
man. Its legitimacy, that was already encompassed in the various notion of caring for one’s appearance for oneself and the
others, was solemnly consecrated by the WHO definition of
health in 1984 as well as by other important official statements.
However, inasmuch as it has been recognized as an insuppressible human need, it cannot be separated from a moral
perspective that involves both the Doctor and the Patient.
In this connection, the experts of various scientific fields
have shown their interest towards the technical-scientific
aspects but also the more important ethical implications
related to Cosmesis.
type 38 HPV has a limited ability to transform in vitro and it
is well known that the E6 protein of the cutaneous HPV is
able to interact on the apoptic stimulus induced by UVB, by
means of the decay of the Bak protein cell, favouring the survival of the altered DNA cell.
The cutaneous HPV studies are still in the initial phase but
seem to indicate that some skin tumour sub-groups are in
part associated with an infection from such viruses. This and
other new information will add to our ability to prevent
these neoplasms by the production of specific vaccines.
IATROGENIC ACNE
S. Veraldi
The aetiopathogenetic role of corticosteroids, both topical
and sistemic, has been known for many years now.
Some drugs can cause acne or an acne-like eruption such as
vasodilators, amiodarone, pimecrolimus, cancer agents and
some biological drugs. Some vitamins of the B group, such as
B2 (or riboflavine), B6 (or pyridoxine) and B12 (or
cianocobalamine) can esacerbate persistent acne or cause
acne or acne-like eruptions, especially if they are used at
high doses.
THE ROLE OF HUMAN PAPILLOMAVIRUS
IN NON MELANOMA SKIN TUMOURS
DERMOCOSMETOLOGY FOR DARK SKIN
A. Venuti
S. Veraldi
Non melanoma skin tumours such a basil cell and squamous
cell carcinomas represent the most common form of neoplasms in the light skinned population. The incidence of
these tumours is already increasing because of the ageing
population and also the increased sun exposure of these
individuals. Besides the obvious factors of ageing and sun
exposure, the genetic make up of these subjects seem to be
an influential factor. Although the verruciform epidermal
dysplasia is a rare inherited disease, it is well known to be
related to the development of skin tumours by increasing the
susceptibility to infection of a particular virus through the
mutation of at least two genes EVER1 and EVER2. On the
basis of these tumour/viral infection association studies, the
papillomavirus, in particular the HPV-skin or beta-papillomavirus, seem to increase the susceptibility to skin cancer.
This is already held to be true in the case of the HPV mucosal or alpha papillomavirus which are defined as high risk for
example types 16 and 18, for gynaecological tumours.
The transformation mechanism of the cutaneous HPV seems
to differ from that of the mucous membrane virus and an
important co-factor is a deficiency in the immune system, as
can be seen in transplant patients taking anti-reject therapy.
However, when we speak of cutaneous HPV we are referring
to a virus which is substantially different from those affecting
the genitals with less carcinogenic strength. For example
Few years ago, at our Institute, we opened a clinic specialized in the diagnosis and treatment of infective, parasitic and
tropical skin diseases. Among other opportunities, this initiative allowed us to see several dark skin patients.
Light skins and dark skins have different anatomies. In dark
skins we see a surface hydro-lipidic film that is richer in fatty
acids, a more compact and thicker horny layer and
melanosomes present also in horny layer keratinocytes; furthermore, melanosomes are scattered and bigger in size. On
the contrary, there are no differences between light and dark
skins in terms of number, distribution and morphology of
melanocytes.
The dermis and the under skin layer show no relevant differences with regard to light skin. In dark skins, sebaceous
and sudoriparous glands are more widespread, they are more
numerous, bigger in size and hypersecreting. Hair is less
widespread and it usually has a curved or spiral shape, with
a flat and elliptic cut section. Nails are the same both for dark
and for light skins. Overall, dark skins differ from light skins
mainly in terms of color, which is due to the particular
anatomy of melanosomes.
This different anatomy assumes a different physiology, which
affects a different incidence and/or clinical onset of skin diseases. In the first case, we would like to mention rosacea (less
frequent on dark skins) and vitiligo (more frequent on dark
141
skins); in the second case, we will mention erythema: all dermatologists know that on light skins erythema shows as a
reddening area, ranging in color from pink to bright red,
which disappears when pressure is applied with a finger, but
not all dermatologists know that, on dark skins, erythema
has a grayish color.
The different clinical onset of diseases on dark skins require
that dermatologists perform a critical review of skin disease
interpretation methodology. The dermatologist again has to
face the problem of morphology of skin lesions that he
thought was acquired and final. Thus he will have to go back
to observation and classification of known dermatological
conditions, but showing new or atypical clinical onsets: this
phenomenon has been called as the Salgari 2 syndrome.
Furthermore, it should be reminded that diseases observed
on dark skins can also be seen on light skins: thus there are
no skin diseases that are solely specific of dark skins.
Another interesting aspect that has emerged over the years is
the one concerning integration. Quite simply, individuals with
dark skin who in the recent past used to go to the dermatologist for a disease, today they see the dermatologist for cosmetic issues. The shift from a “medical” need to a “cosmetic” need
is a symptom of integration between two cultures.
According to our experience, most people with dark skin
refer to a dermatologist for acne diagnosis and treatment, folliculitis, pigmentation alteration (ranging from vitiligo to
melasma), cicatrisation issues (hypertrophic scars and
keloids) and alopecia (often caused by chemical, heat and
mechanic trauma).
Thus Italian dermatologists must quickly comply with a new
culture and a new social environment.
MEDICAL PROFESSIONAL LIABILITY RISK
M.A. Volpi
The introductory paper on the legal configuration of the professional liability risk will illustrate the sources of law on
medical liability, starting from the right to protect health
enshrined in the Constitution up to the double provision of
articles 1176 c.c. (diligence of execution), 1218 c.c. (debtor’s
liability), 2043 c.c. (compensation for malpractice), 2230
c.c. (intellectual work done), 2236 (liability of health service
provider).
Therefore, the paper will illustrate the diligence duty and the
liability under and outside the terms of a contract as well as
the subjective aspects of liability (malice, slight and gross
negligence).
Then, a short overview will be provided on the means and
result obligations with special reference to the burden of the
proof in case of doctor-patient litigation.
Finally, the paper will illustrate the causal nexus with special
reference to the “condicio sine qua non” theory, the concurrence of causes and the omissive conduct and harmful event.
142
NANOTECHNOLOGIES IN DERMOCOSMESIS
H.S. Zadeh
Nanoemulsions are etherogeneous poly-phase systems in
which at least one phase is dispersed as nano-particles during the continuous external phase.
They are mainly micellar systems appearing “spontaneously”
when the same components of the emulsified etherogeneous
system are bound in properly proportioned quantities and
are mutually stable under a thermodynamic point of view. A
simple description of such dispersed systems may be the following: globules with very tiny diameter (10-200 nm) of a
liquid phase dispersed in another phase in a continuous
mode thanks to a quite high number of tensioactive agents.
There may be A/O or O/A nano-emulsified systems, however the common, essential chemical-physical condition for the
formation and stabilization of such systems is the low interface tension value during the O/A phase.
As a rule, in order to obtain this result, tensioactive agents
blends are used (primary and amphiphilic surface active
agents); they create an amphiphilic tensioactive crown on the
dispersed droplet surface and improve the thermodynamic
efficiency of the system since they lower the interface tension.
Nano-emulsions are the most stable and versatile theoretical
model on the application viewpoint as regards the application of technical devices in cosmetics, pharmaceutics and the
food liquid vehicles.
Indeed, in emulsified systems, the average size of phase
aggregates is measured in nanometers (10-9 m) with an average diameter between 100 and 500 nm. With such particles
size in the dispersed phase, the ratio between the internal
emulsified phase and the average radius of the particles
becomes so big that it considerably increases the mutual
electrostatic repulsions among nano-aggregates: this chemical-physical phenomenon results in a considerable increase
of kinetic stability and, more generally, in a chemical-physical stability of the emulsion. The tiny diameter of the particles reduces the matter’s capacity to interact with light, with
ultraviolet quantum (hv), to the extent that the resulting cosmetic emulsions appear translucid and transparent and take
the typical bluish Tyndall color, i.e. an opalescent blue.
This explains the need to have a considerable thermal and
kinetic energy to obtain such emulsions (vacuum homogenizing emulsifiers). The other variable, i.e. interface tension,
plays a major role since it interacts with surfactant agents
that can reduce the same energy between the dispersed/dispersing liquid interface and therefore proportionally reduces
the energy that the system must use to produce stable nanoemulsions.
The Stokes-Einstein law shows that the sedimentation rate
and therefore the instability of the emulsified system is proportional to the size of the particles in the dispersed phase.
Therefore, the emulsifying-surfactant chemical system is of
paramount importance to obtain nanostructured dispersions
with sustainable industrial processes.
The most recent advances in nanotechnology have led to the
development of a new nano-emulsifying raw material for
cosmetic-pharmaceutical usage that can produce nanoemulsions whose particles have an average size below 300 nm.
This raw material is the result of an innovative combination
of natural molecules including a Lipoaminoacid (Capryloyl
Glycine), an hydrolyzed protein (Potassium lauroyl wheat
aminoacids) and vegetal fat glycerides (Palm glycerides).
This cosmetic ingredient allows to obtain stable nanoemulsions without too much kinetic energy aimed at reducing the
interface tension of the dispersed phase micelles during
homogenization: in fact, with this new gel-type device we do
not need any homogenization power since there is almost no
interface tension in the nanoaggregates. Therefore there is a
spontaneous nano-dispersion of the gel-type blend just after
the very first phases of moderate mechanical emulsification
followed by slow incorporation of additional aqueous phase
which makes the bluish Tyndall color appear. This proves
that nanodispersion has taken place with the UV light
absorption.
This new raw material can be considered as “revolutionary”
under every aspect of new nano-colloidal dispersed systems
and their related cosmetic and dermocosmetic applications.
Indeed, it allows for extremely fluid nano-colloidal emulsions or dispersions with high chemical-physical stability. It
also allows to avoiding some of the most frequent and disastrous phenomena of instability that affect multi-phase systems such as sedimentation, creaming and coalescence of
fluid emulsions.
The vegetal origin of molecules forming the emulsifying
blend (Nanocream") and their exceptional synergy and efficiency in causing nano-colloidal dispersion without external
mechanical and/or thermal energy (no need of vacuum
homogenizers) during heterogeneous oil phases too and in
considerable quantities enhances the ability of the formulator not to use the most common and widespread ethoxylate
synthesis emulsifiers such as POE, PPG-derivatives and
esther phosphoric derivatives.
Nanocream" is mostly used in functional and dermatological cosmesis and in the preparation of fluid and hyperfluid
emulsified sprays for external usage (large skin areas: sprays,
lotions, etc.).
ORAL SUPPLEMENT, PREVENTION OF
PHOTOCARCINOGENESIS AND PHOTOAGEING:
NOVELTIES ON THE USE OF POLYPODIUM
LEUCOTOMOS EXTRACT
C. Zane
Solar radiation is considered to be the main environmental
harmful factor accounting for the sun burns, skin tumours
and photoageing.
The sun emits a wide spectrum of electromagnetic radiations
including ultraviolet, visible and infrared bands.
The erythemogenous and carcinogenous effects are directly
correlated with damages to the DNA, RNA, proteins and
other cellular constituents caused by UVB. Also UVA plays
an important role in the onset of such effects and it is correlated to an aerobe harm mediated by the formation of reactive species of oxygen, such as singlet oxygen, superoxide
anion and hydroxylic radicals which in turn cause photooxidative damage to DNA and to cell membranes.
Thus, both UVB and UVA are involved in the appearance of
short-term and long-term collateral effects.
In order to survive the attacks of UV radiations, the skin has
various in-built defence mechanisms out of which antioxidants (both non-enzymatic and enzymatic systems) play a
key role. Of the non-enzymatic systems, lipidic molecules
such as beta-carotene, a precursor of vitamin A, and tocopherol (vitamin E), mainly found in the cell membrane are
greatly involved in these defensive mechanisms. Among
water-soluble molecules, ascorbate is the most efficient
antioxidant.
Instead, dismutase (SOD), catalase, thioredoxin reductase,
glutathione peroxidise belong to enzymatic systems, as well
as glutathione reductase that restores the levels of reduced
glutathione.
Notwithstanding these defence mechanisms, the demand for
skin protection can be higher following considerable sun
exposure. Sun erythema occurs when the consumption of
sunscreens exceeds their regeneration thus leading to alteration of the cell functions. Some experimental data suggest
that the lack of antioxidants have a role in the onset of skin
tumours. Although, it is evident that the supplement of some
antioxidants may heighten the erythemogenous ceiling, their
protective role towards the carcinogenous effects of UV still
remains controversial.
Traduzioni a cura di Giuseppe D’Aleo.
Eventuali omissioni saranno pubblicate come errata corrige nel prossimo numero del Journal of Plastic Dermatology.
143
Istruzioni agli Autori
Obiettivo della rivista
Articoli in supplementi al fascicolo
Il Journal of Plastic Dermatology, organo
ufficiale dell’International-Italian Society of PlasticAesthetic Dermatology, si rivolge a tutti i dermatologi (e cultori della materia) che vogliono mantenersi aggiornati sia sugli aspetti patogenetici degli
inestetismi e dell’invecchiamento della cute, sia
sull’uso delle nuove tecnologie (laser, radiofrequenza, luce pulsata, ecc), delle sostanze esfolianti,
dei materiali iniettivi per la supplementazione dermica, dei dermocosmetici, degli integratori, ecc.
Il Journal of Plastic Dermatology pubblica, articoli
originali, casi clinici, rassegne, report congressuali
e monografie.
Payne DK, Sullivan MD, Massie MJ.
Women’s psychological reactions to breast cancer.
Semin Oncol 1996; 23 (Suppl 2):89
Preparazione degli articoli
Gli articoli devono essere dattiloscritti
con doppio spazio su fogli A4 (210 x 297 mm),
lasciando 20 mm per i margini superiore, inferiore
e laterali.
La prima pagina deve contenere: titolo, nome e
cognome degli autori, istituzione di appartenenza e
relativo indirizzo. La seconda pagina deve contenere un riassunto in italiano ed in inglese e 2-5
parole chiave in italiano ed in inglese.
Per la bibliografia, che deve essere essenziale, attenersi agli “Uniform Requirements for Manuscript submitted to Biomedical Journals” (New Eng J Med
1997; 336:309). Più precisamente, le referenze
bibliografiche devono essere numerate progressivamente nell’ordine in cui sono citate nel testo (in
numeri arabi tra parentesi). I titoli delle riviste devono essere abbreviate secondo lo stile utilizzato da
PubMed (la lista può essere eventualmente ottenuta
al seguente sito web: http://www.nlm.nih.gov).
Articoli standard di riviste
Parkin MD, Clayton D, Black RJ, Masuyer
E, Friedl HP, Ivanov E, et al. Childhood leukaemia in
Europe after Chernobil: 5 year follow-up. Br J Cancer
1996; 73:1006
Articoli con organizzazioni come autore
The Cardiac Society of Australia and New
Zealand. Clinical exercise stress testing. Safety and
performance guidelines. Med J Aust 1996; 164:282
144
Libri
Ringsven MK, Bond D. Gerontology and
leadership skill for nurses. 2nd ed. Albany (NY):
Delmar Publisher; 1996
Capitolo di un libro
Phillips SJ, Whisnant JP. Hypertension and
stroke. In: Laragh JH, Brenner BM, editors. Hypertension: pathophysiology, diagnosis, and management.
2nd ed. New York: Raven Press; 1995, p.465
Figure e Tabelle
Per favorire la comprensione e la memorizzazione del testo è raccomandato l’impiego di
figure e tabelle. Per illustrazioni tratte da altre pubblicazioni è necessario che l’Autore fornisca il permesso scritto di riproduzione.
Le figure (disegni, grafici, schemi, fotografie)
devono essere numerate con numeri arabi secondo
l’ordine con cui vengono citate nel testo ed accompagnate da didascalie redatte su un foglio separato.
Le fotografie possono essere inviate come stampe,
come diapositive, o come immagini elettroniche
(formato JPEG, EPS, o TIFF).
Ciascuna tabella deve essere redatta su un singolo
foglio, recare una didascalia ed essere numerata
con numeri arabi secondo l’ordine con cui viene
citata nel testo
Come e dove inviare gli articoli
Oltre al dattiloscritto in duplice copia, è
necessario inviare anche il dischetto magnetico
(formato PC o Mac) contenente il file con il testo e
le tabelle.
Gli articoli vanno spediti al seguente indirizzo:
Antonio Di Maio
Edizioni Scripta Manent
Via Bassini 41
20133 Milano
E-mail: [email protected]
[email protected]

2nd International Congress of Plastic Dermatology

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