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Volume 3 - Number 2/2012
’Italian Acn
A cura dell
e Board
2012
TEMBRE
14-15 SET
CON L’ADESIONE
NAPOLI
DEL PRESIDENTE DELLA REPUBBLICA
Presidente
G. Monfrecola
Presidente Onorario
F. Ayala
C
NAPOLI
14-15 Settembre 2012
.
.
F
Journal
of
Acne
and
Related
Diseases
European
Journal
of
Acne
and
Related
Diseases
European
Journal
of Acne
and
Related
Diseases
European
Volume 3, Number 2/2012
Volume
3, n.
2012
Volume
1, 2012
Volume
3,1,
n.3,
1,n.2012
WORK IN PROGRESS
LAVORI IN CORSO
Stefano Veraldi
As it can be seen in this issue of the European
Journal of Acne, the Italian Acne Club gains
“kudos” for the adherence of new Italian colleagues:
I wish to thank them for their support.
The importance of the international editorial board,
with several prestigious dermatologists, is great.
Some of them are coming from extra-european
countries (I wonder if it is now time to name our
journal as International Journal of Acne).
The activity of the Italian Acne Board keeps up:
a CD on oral isotretinoin is ready; a new book on
seborrhoeic dermatitis will be published very soon.
Furthermore, we are evaluating the possibility
of writing novel books on cosmetology
of acne and rosacea.
Lastly, I have some interesting news: in 2013,
the Acne Day will be held in Milan (the sooner,
the better). In consideration of the attendance of
several international dermatologists, it will be
named International Acne and Rosacea Days.
Come si può vedere in questo numero dello
European Journal of Acne, l’Italian Acne
Club aumenta di prestigio, grazie all’adesione
di nuovi colleghi, che desidero qui ringraziare.
Grande è anche l’importanza del nuovo board
editoriale internazionale, con vari prestigiosi
dermatologi, anche extra-europei (mi domando:
non è arrivato il momento di chiamare il giornale
International Journal of Acne?).
L’attività dell’Italian Acne Board continua: è pronto
un CD sull’isotretinoina orale; tra breve sarà
pubblicato un nuovo libro sulla dermatite seborroica e
saranno messi in cantiere un nuovo libro sulla
cosmetologia dell’acne e uno sulla rosacea.
Dulcis in fundo, anche se è un po’ prematuro,
ci saranno grandissime novità per quanto riguarda
l’Acne Day del 2013: sarà organizzato a Milano e,
in considerazione della partecipazione di numerosi
dermatologi stranieri, si chiamerà
International Acne and Rosacea Days.
Il lavoro, quindi, continua…
Volume 3, Number 2/2012
Editorial Board
Topical nicotinamide in acne: a critical review
Content
Stefano Veraldi, Giuseppe Micali, Mauro Barbareschi, Aurora Tedeschi, Rossana Schianchi
Editor
Stefano Veraldi Milano
Co-Editor
Mauro Barbareschi Milano
Scientific Board
Vincenzo Bettoli
Stefano Calvieri
Gabriella Fabbrocini
Giuseppe Micali
Giuseppe Monfrecola
Nevena Skroza
Annarosa Virgili
Ferrara
Roma
Napoli
Catania
Napoli
Roma
Ferrara
Managing Editor
Antonio Di Maio Milano
pag 21
Spa water for acne therapy
pag 27
Epidemiologia dell’acne: oltre i dati europei
pag 31
Acne e fotoprotezione
pag 37
Strategie per migliorare l’aderenza terapeutica nell’acne
pag 43
Follicular biopsy (FB) can be useful for monitoring therapeuthic
compliance in acne patients
pag 49
Counseling: adherence to therapy and quality of life
pag 54
Cosmetics and acne: a primer
pag 57
Silvia Alberti Violetti
Gabriella Fabbrocini, Maria Carmela Annunziata, Nevena Skroza, Vincenzo Bettoli,
Nayera Moftah, May el-Samahy, Zrinka Bucvic Mokos, Mauro Barbareschi,
Stefano Veraldi, Giuseppe Micali, Francesco Bruno, Giuseppe Monfrecola
Giuseppe Monfrecola, Rosanna Izzo
Gabriella Fabbrocini, Luigia Panariello, Valerio De Vita,
Dario Bianca, Maria Chiara Mauriello, Giuseppe Monfrecola
Gennaro Ilardi, Gabriella Fabbrocini, Nevena Skroza, Sara Cacciapuoti,
Ersilia Tolino, Claudio Marasca, Giuseppe Monfrecola
Gabriella Fabbrocini, Caterina Mazzella, Rosanna Izzo, Giuseppe Monfrecola
Aurora Tedeschi, Laura Guzzardi, Giuseppe Micali
Italian Acne Club
Mario Bellosta (Pavia), Enzo Berardesca (Roma), Carlo Bertana (Roma), Alessandro Borghi (Ferrara), Francesco Bruno (Palermo), Maria Pia De Padova (Bologna),
Paolo Fabbri (Firenze), Mario Maniscalco (Sciacca), Carlo Pelfini (Pavia), Mauro Picardo (Roma), Maria Concetta Potenza (Roma), Marco Romanelli (Pisa),
Alfredo Rossi (Roma), Rossana Schianchi (Milano), Patrizio Sedona (Venezia), Riccarda Serri (Milano), Aurora Tedeschi (Catania),
Antonella Tosti (Bologna/Miami), Matteo Tretti Clementoni (Milano)
International Editorial Board
Zrinka Bukvic Mokos (Zagreb, Croatia), Tam El Ouazzani (Casablanca, Morocco), May El Samahy (Cairo, Egypt), Uwe Gieler (Giessen, Germany),
Maite Gutierrez Salmerón (Granada), Marius-Anton Ionescu (Paris, France), Monika Kapinska Mrowiecka (Cracow, Poland), Nayera Moftah (Cairo, Egypt),
Nopadon Noppakun (Bangkok, Thailand), Gerd Plewig (Munich, Germany), Miquel Ribera Pibernat (Barcelona), Robert Allen Schwartz (Newark, Usa),
Jacek Szepietowski (Breslau, Poland), Shyam Verma (Ladodra, India)
Editorial Staff
Direttore Responsabile: Pietro Cazzola
Direttore Generale: Armando Mazzù
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European Journal of Acne and Related Diseases
Volume 3, n. 2, 2012
Stefano Veraldi 1, Giuseppe Micali 2, Mauro Barbareschi 1, Aurora Tedeschi 2,
Rossana Schianchi 3
1 Department of Anaesthesiology, Intensive Care and Dermatological Sciences, University of Milan, I.R.C.C.S. Foundation, Cà Granda
Ospedale Maggiore Policlinico, Milan, Italy; 2 Department of Surgical and Medical Sciences, Dermatology Section, University of
Catania, Italy; 3 European Institute of Dermatology, Milan, Italy
Topical nicotinamide in acne: a critical review
Stefano Veraldi
SUMMARY
Nicotinamide can be considered as
an effective drug for the treatment
of mild to moderate inflammatory
acne. Tolerability is excellent: no
cases of contact dermatitis were published so far.
Furthermore, topical nicotinamide lacks of photoaller-
gic or phototoxic potential: therefore, it can be used in
complete safety also in the summertime. When associated with 0.2% myrtacine, it is effective for prevention and
treatment of retinoid dermatitis.
Finally, topical nicotinamide can be used in association
with other topical anti-acne drugs.
Key words: Acne, topical nicotinamide.
Introduction
Nicotinamide (also known as niacinamide) is a water-soluble amide of nicotinic acid
(also known as niacin). They are similarly effective
because they can be converted into each other.
Other synonyms are vitamin B3 and vitamin pellagra preventing (vitamin PP).
Nicotinamide is a component of two very important enzymes involved in hydrogen transfer: nicotinamide adenine dinucleotide (NAD, coenzyme I)
and nicotinamide adenine dinucleotide phosphate
(NADP, coenzyme II) 1, 2. These two codehydrogenases supply hydrogen to the respiratory chain for
oxidation and energy production 3.
Toxicology
Nicotinamide is present in all living cells.
It is consumed in the diet: it is contained mainly in
the liver (5-25 mg of nicotinamide/100 g), beef,
kidney and fish (2-15 mg/100 g), and mushrooms
(3-5 mg/ 100 g) 4. Nicotinamide is therefore con-
sidered a safe compound. In fact, it is considered
by the Food and Drug Administration (FDA) as
'Generally Recognized as Safe' (GRAS) 5.
Several acute toxicity studies evaluated the safety of
nicotinamide in animal models. In mice, the LD50
for both subcutaneous and intraperitoneal injections
of nicotinamide is approximately 2 g/kg 5.
In rats, the LD50 for oral administration is 2.5-3.5
g/kg 5; LD50 for nicotinamide injected subcutaneously is 1.68 g/kg 5. Long term studies in male
Sprague-Dawley rats, using daily dosages of up to
600 mg/kg of nicotinamide injected intraperitoneally for five weeks, had only minimal effects,
resulting in a decrease in food intake and less
weight gain in a dose-dependent manner 5, 6. In all
instances, these dosages far exceed the dosages of
nicotinamide used clinically. Nicotinamide was
shown to have oncopreventive effects and no carcinogenic or cocarcinogenic effects 5, 7, 8.
Data on mutagenicity of nicotinamide are negative:
several studies demonstrated that many mutagens
act by reducing intracellular levels of nicotinamide
21
Volume 3, n. 2, 2012
in target cells 5. It was observed an increase in DNA
repair after treatment of mouse lymphocytes with
0.5-10 nmol/l solutions of nicotinamide 5.
Studies on the reproductive effects of nicotinamide
were carried out in several species. The drug has
not been shown to be teratogenic. Contrariwise, it
has protective effects in some animal models 9.
Several studies were conducted to evaluate the irritation and sensitization potential of 4% nicotinamide gel. In repeated insult patch tests, using a
modified Draize-Shelanski-Jordan protocol, 227
subjects were exposed to the drug for six weeks.
The results of this study demonstrated that 4%
nicotinamide gel was neither irritanting nor sensitizer 5. Furthermore, phototoxicity and photoallergy studies were performed in 25 patients. These
studies showed no evidence of phototoxicity or
photoallergy 5.
Pharmacokinetics
In vitro studies on percutaneous absorption of topically applied nicotinamide were performed 10, 11. Total absorption, expressed as percent of applied dosage, was 11.1 ± 6.2 in vivo 11.
Following oral administration, peak plasma concentrations are achieved at 1-3 hours, with peak
concentrations of 0.08-1.1 μmol/ml for doses of 16 g, respectively 12.
The drug is metabolized by intestinal bacteria and
the liver and is excreted in the urine 13, 14.
Mechanisms of action
The clinical activity of nicotinamide may
result from the presence of a pyridine ring in the
chemical structure 5.
Several theories were proposed for the mechanism
of action of topical nicotinamide in acne.
Nicotinamide acts in acne as anti-inflammatory
agent. It inhibits neutrophil chemotaxis 3, 5, 15, 16 and
synthesis of phosphodiesterase (PDE): the resultant
increase in cyclic AMP (cAMP) induces the inhibition of release of proteases from leukocytes and the
inhibition of lymphocyte transformation 3, 5, 17, 18.
22
Nicotinamide inhibits the synthesis of polyadenosinediphosphate-ribose-polymerase-1
(PARP-1), a nuclear enzyme contributing to DNA
repair, which, if overactivated, causes cell necrosis 3. PARP enhances nuclear factor-kB (NF-kB)mediated transcription, which plays a central role
in the expression of cytokines, adhesion molecules
and inflammatory mediators 3.
Nicotinamide inhibits the expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex-II (MHC-II), and the synthesis of interleukins (ILs) 1 and 12, tumor necrosis factor (TNF)- and macrophage migration inhibition factor (MIF) 3, 19. MIF inhibition may be
responsible for the steroid-sparing effect of nicotinamide, as MIF is upregulated by corticosteroids 3.
Propionibacterium (P.) acnes is implicated in the
inflammatory phase of acne. It has been shown that
it activates IL-8 synthesis by interacting with Tolllike receptor (TLR)-2 on the surface of keratinocytes. Some authors demonstrated that nicotinamide downregulates IL-8 gene expression at
transcriptional and post-transcriptional levels and
IL-8 protein synthesis in a dose-dependent manner,
through phosphorylation of the mitogen-activated
protein kinase (MAPK) and TLR-2 degradation. In
addition, nicotinamide decreases the half-life of
IL-8 mRNA by affecting its stability 16, 20.
Furthermore, nicotinamide acts as an electron
scavenger 3, 5, 15.
Finally, topical nicotinamide has a stabilizing
effect on epidermal barrier function [reduction in
transepidermal water loss (TEWL) and improvement in the moisture content of the horny layer] 21.
Nicotinamide leads to an increase in protein synthesis (e.g. keratin, filaggrin and involucrin) 21, has
a stimulating effect on ceramide synthesis 21,
speeds up the differentiation of keratinocytes, and
raises intracellular NADP levels 1.
The activity of nicotinamide on sebum excretion
rate (SER) was studied by Draelos et al. 22. A total
of 100 Japanese subjects were enrolled in a doubleblind, placebo-controlled study. Fifty subjects
applied a 2% nicotinamide moisturizer on the face
for 4 weeks and 50 subjects applied a placebo moisturizer for 4 weeks. SER measurements were taken
at baseline, week 2 and week 4. The group treated
Volume 3, n. 2, 2012
with nicotinamide demonstrated significantly lowered SER after 2 and 4 weeks of application 22.
A commercially available product of 4% nicotinamide oil-free cream contains an anti-bacterial
adhesive (ABA) substance: the latter is sucrose
stearate. This substance inhibits the adhesion of P.
acnes on cytoplasmic membrane of corneocytes of
the infra-infundibulum. Seven volunteers of both
genders with acne applied once a day on one forearm, for three days, a gel containing sucrose
stearate; the other forearm was considered as control. Corneocytes were isolated from the two forearms of each volunteer and incubated with P.
acnes. Bacterial adhesion to corneocytes was quantified by flow-cytofluorimetry: fluorescence intensity of corneocytes-bacteria complex was measured. ABA inhibited the adhesion of 50% P. acnes
in three patients and of 82 to 97% in four patients
23.
Clinical studies
The first clinical study on the activity and
tolerability of topical nicotinamide in acne was
published in 1995 by Shalita et al. 15. In this double-blind study, 4% nicotinamide gel was compared to 1% clindamycin gel in the treatment of
moderate inflammatory acne. Seventy-six patients
were randomly assigned to apply either nicotinamide (n = 38) or clindamycin (n = 38), twice
daily for eight weeks. Efficacy was evaluated at
weeks 4 and 8 using Physician's Global Evaluation,
Acne Lesion Counts and Acne Severity Rating.
After eight weeks, both treatments induced comparable (P = 0.19) beneficial results in the Physician's
Global Evaluation: 82% of the patients treated with
nicotinamide and 68% treated with clindamycin
improved. Both treatments induced statistically
similar reduction in acne lesions (papules and pustules: -60% nicotinamide versus -43% clindamycin:
P = 0.168), and acne severity (-52% nicotinamide
group versus -38% clindamycin group: P = 0.161).
These results demonstrated that nicotinamide is of
comparable efficacy to clindamycin 15.
Griffiths 24, in 1995, published the results of three
multicentre, randomized, double-blind, vehicle-
controlled studies which were carried out in United
Kingdom. A total of 969 patients with mild to
moderate inflammatory acne of the face were treated twice daily for 8-12 weeks with 4% nicotinamide gel (= 486 patients) or placebo (= 483
patients): 709 patients were considered evaluable
at the end of the study (356 patients in the nicotinamide group and 353 in the vehicle group). Three
clinical criteria of evaluation were used: acne
severity rating, physician’s global evaluation and
papule/pustule count. Acne severity rating:
patients treated with nicotinamide experienced
greater improvement over baseline at final visit
compared with vehicle (p = 0.013). Patients under
21 years of age showed significant improvement
(p = 0.009) with nicotinamide use compared with
vehicle, whereas there was no difference between
nicotinamide and vehicle in the over 21 age group
of patients. Physician’s global evaluation: a significantly greater improvement at final visit in the
group of patients treated with nicotinamide compared with the group treated with the vehicle (p =
0.016) was observed. A significant clinical
improvement was observed with nicotinamide
treatment in the pre-21 year age group only (p =
0.024). Papule/pustule count: in the group of
patients treated with nicotinamide, papule/pustule
count fell from 29.43 ± 0.77 at baseline to 15.40 ±
0.70 at final visit, compared with 29.34 ± 0.78 to
16.07 ± 0.69 in the vehicle group, e.g. a non significant (p = 0.16) difference between the two groups.
The high vehicle response observed in these
patients was most likely a consequence of the
hydro-alcoholic gel vehicle, which exerted some
therapeutic effect. Side effects were limited to
local erythema and dryness 24.
In 2003, two Indian studies were published 25, 26. In
the study by Dos et al. 25, eighty patients with
moderate acne were enrolled for the comparative
evaluation of 1% clindamycin phosphate (40
patients) versus 1% clindamycin phosphate and
4% nicotinamide gel (40 patients). This study did
not show any added advantage of clindamycin in
combination with nicotinamide over clindamycin
alone 25.
In the trial by Sardesai et al. 26, a total of 75
patients with inflammatory acne were divided into
23
Volume 3, n. 2, 2012
three groups. Group A was treated with 4% nicotinamide and 1% clindamycin, group B was treated
with 1% clindamycin and group C, which was considered to have resistance to local antibiotics due
to no response to treatment, was treated with the
combination. At the end of eight weeks, the results
were compared. It was concluded that addition of
nicotinamide was of not much value in treating
inflammatory acne 26.
Weltert et al. 27 carried out a double-blind clinical
trial in which 4% nicotinamide gel was compared
to 4% erythromycin gel. Two groups of 80 patients
each with moderate inflammatory acne of the face
were treated for eight weeks. The efficacy was
evaluated by means of retention and inflammatory
lesion count and clinical score of seborrhoea.
Nicotinamide and erythromycin led to equivalent
regression of inflammatory lesions: this was visible from the first month of treatment. Seborrhoea
score presented a more significant decrease in the
group treated with nicotinamide 27.
An Italian, multicentre, controlled, sponsor-free
study, carried out by the Italian Acne Board
(IAB) 28, demonstrated that 4% nicotinamide oilfree cream, applied twice daily for 12 weeks,
induced a significant clinical improvement (≥ 50%
from baseline) in 21 out of 64 patients (32.8%)
with mild to moderate acne. When nicotinamide
(applied once daily for 12 weeks) was associated
with 0.1% adapalene gel (applied once daily for 12
weeks), 54 out of 106 patients (50.9%) improved.
This group of patients was compared with another
group of 78 patients who were treated with adapalene (1 application/day for 12 weeks) and a moisturizer (1 application/day for 12 weeks). A significant clinical improvement was observed in 32 out
of 78 patients (41%). Acne severity and treatment
efficacy were evaluated by means of the Global
Acne Grading System (GAGS) 29. Results of these
three studies may be summarized as follows: a)
one-third of patients significantly improved with
nicotinamide alone. This improvement was sometimes (approximately in 15% of patients) slow (up
to three weeks). b) Tolerability was excellent.
Topical nicotinamide lacks of photoallergic or
phototoxic potential: therefore, it can be used in
complete safety also in the summertime. c) The
24
association nicotinamide-adapalene is more effective than the association adapalene-moisturizer: it
is possible that nicotinamide and adapalene possess a synergistic effect 28.
A multicentre, double-blind, randomized study was
conducted by clinical and biophysical non-invasive
measurements to evaluate the efficacy and tolerability of a 4% nicotinamide-phospholipidic (linoleic
acid rich-phosphatidylcholine) emulsion versus 1%
topical clindamycin phosphate, both applied once
daily for 12 weeks. The nicotinamide-phospholipidic association resulted slightly superior to clindamycin for all parameters studied (better compliance and global clinical improvement) 30.
Finally, a multicentre, prospective, non-randomized, open, parallel-group study will be soon published 31. Patients with mild to moderate acne, who
were treated with a topical retinoid for at least one
month and had developed skin irritation, were
assigned to one of the two following treatments:
0.2% myrtacine + 4% vitamin PP (n = 116) or a
simple emollient cream (n = 48). Myrtacine is an
ethanolic extract obtained from myrtle leaves. It
showed several pharmacological properties in
vitro: it inhibits keratinocyte proliferation, inhibits
the growth of P. acnes, decreases the synthesis of
pro-inflammatory mediators via the cyclo-oxigenase and lipo-oxigenase pathways, and decreases
lipase activity. Both treatments were administered
twice daily. Study endpoints were: improvement in
signs and symptoms of retinoid dermatitis, global
efficacy, reduction in acne severity, overall clinical
outcome, patient satisfaction and tolerability. At
day 28, the association myrtacine—vitamin PP significantly decreased signs (erythema, dryness/scaling and oedema) and symptoms (itching, stinging
and burning sensation) of retinoid dermatitis
(p < 0.01) compared with the simple emollient
cream. In addition, the association myrtacine—vitamin PP decreased acne severity in a significantly
greater proportion of patients (p = 0.023) and was
associated with a better clinical outcome (global
improvement: p < 0.001) compared with the simple emollient cream. The association myrtacine—
vitamin PP was also associated with greater patient
satisfaction and was better tolerated than the simple emollient cream.
Volume 3, n. 2, 2012
Conclusions
Results of clinical studies published so far
on the treatment of acne with topical nicotinamide
may be summarized as follows: a) nicotinamide
can be considered as an effective drug for the treatment of mild to moderate inflammatory acne; b)
tolerability is excellent: no cases of contact dermatitis due to topical nicotinamide were published
so far. Furthermore, topical nicotinamide lacks of
photoallergic or phototoxic potential: therefore, it
can be used in complete safety also in the summertime. When associated with 0.2% myrtacine, it is
effective for prevention and treatment of retinoid
dermatitis; c) topical nicotinamide can be used in
association with other topical anti-acne drugs,
although, to our knowledge, it was associated so far
only with adapalene and phosphatidylcholine.
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30. Morganti P, Berardesca E, Guarneri B, et al. Topical clindamycin 1% vs. linoleic acid-rich phosphatidylcholine and
nicotinamide 4% in the treatment of acne: a multicentre-randomized trial. Int J Cosmet Sci 2011; 33:467-76.
27. Weltert Y, Chartier S, Gibaud C, et al. Évaluation clinique
en double aveugle de l’efficacité d’un gel de nicotinamide 4%
(Exfoliac® NC Gel) versus gel d’érythromycine 4% dans la prise
en charge des acnés modérées à composante inflammatoire prédominante. Nouv Dermatol 2004; 23:385-94.
31. Veraldi S, Giovene GL, Guerriero C, Bettoli V. Efficacy and
tolerability of topical 0.2% myrtacine and 4% vitamin PP for
prevention and treatment of retinoid dermatitis in patients with
mild to moderate acne. Giorn Ital Dermatol Venereol 2012
(in press).
Volume 3, n. 2, 2012
Department of Pathophysiology and Transplantation, Università degli Studi di Milano - Fondazione IRCCS Ca' Granda - Ospedale
Maggiore Policlinico, Milan - Italy
SPA water for acne therapy
SUMMARY
Spa therapy, using mineral spring
and thermal mud has been widely
used in dermatology as complement of “classical” medicine to
treat a lot of skin diseases.
Acne is one of these, because of spa water, particularly
sulfuric-rich one, influences some its etiopathogenetic
factors.
In Italy, balneotherapy for acne (usually twelve sessions/year), is astonishingly paid by the public health,
but in literature there are no data that support a role of
this spa therapy in acne.
Key words: Balneotherapy, acne, acne therapy.
Dear Sir,
Spa therapy, based on the use of mineral
spring and thermal mud, has been widely used in
medicine. In dermatology, from the studies by Von
Hebra and Duhring about keratolytic effect of spa
waters, balneotherapy has been considered as complement of “classical” medicine to treat a lot of
diseases, especially psoriasis and atopic dermatitis 1. Acne is another disease of the skin that could
improve by means of spa waters. In Italy, balneotherapy for acne (usually twelve sessions/year),
is astonishingly paid by the public health, despite
of its dramatic situation according the economical
point of view.
I performed a systematic review in Pubmed,
EMBASE and Cochrane Library on balneotherapy
in the treatment of acne. Literature reports that balneotherapy, especially using sulfuric-rich spa
water, influences some etiopathogenetic factors of
acne, through a keratolytic effect and reduction of
sebum production: sulfur can break disulfide
bonds contained in keratins, shedding the corneocytes accumulated in sebaceous follicles 2; furthermore, in sebaceous glands, sulfur can decrease differentiation of sebocytes and sebum excretion 3.
Sulfur waters also possess antibacterial and antifungal properties, due to pentathionic acid produced by interaction between sulfur and oxygen
radicals in the deeper layers of the epidermis 5.
Furthermore, not only sulfuric waters, but also
other mineral waters, induce vasodilation, an analgesic influence on pain receptors, and inhibition of
the immune response 5, 6.
These data leaded to think that sulfuric waters were
the best ones for acne therapy; however, Karatsi 7
suggested that it isn’t know if only a single element
or component of a spa source makes more effective
one mineral water than another one, but probably it
is due to combination of multiple elements.
I found no randomized controlled trials about the
treatment of acne with balneotherapy. In addition,
27
Volume 3, n. 2, 2012
literature reports only few non-randomized studies
that supported an improvement of acne by means
of balneotherapy.
In particular, Argenziano et al. 3 demonstrated, in a
group of 45 patients, a reduction of sebum excretion, keratinocyte hyperproliferation and inflam-
mation. Shani et al8 reported a non-randomized
study on 86 patients treated in the Dead Sea with a
reduction in the number of comedones and pustules.
In conclusion, literature data do not support a role
of balneotherapy in acne.
References
1. Najeeba R, Arakkal FA. Spa therapy in dermatology. Indian
J Dermatol Venereol Leprol 2011; 77:128-34.
2. Hjorth N. Traditional topical treatment of acne. Acta Derm
Venereol (Stockh) 1980; 89:53-5.
3. Argenziano G, Delfino M, Russo N. Mud and baththerapy in
the acne cure. Clin Ter 2004; 155:121-5.
4. Matz H, Orion E, Wolf R. Balneotherapy in dermatology.
Dermatol Ther 2003; 16:132-40.
5. Nasermoaddeli A, Kagamimori S. Balneotherapy in medicine:
a review. Environ Health Prev Med 2005; 10:171-9.
28
6. Nappi G. Dermatologia. In: Nappi G, Medicina e clinica termale. 1st ed. Pavia: Ed. Selecta Medica, 2001; 115.
7. Karatsi P. The therapeutic properties of spa baths in the treatment of acne: Case studies. Epitheorese Klinikes Farmakologias
kai Farmakokinetikes 2010; 28:289-93.
8. Shani J, Seidl V, Hristakieva E, et al. Indications, contraindications and possible side-effects of climatotherapy at the Dead
Sea. Int J Dermatol 1997; 36:481-92.
12
BRE 20
M
E
T
T
SE
I 14-15
L
O
P
CON L’ADESIONE
A
rd N
DEL PRESIDENTE DELLA REPUBBLICA
a
o
B
e
n
c
’Italian A
ll
e
d
a
r
A cu
Presidente
G. Monfrecola
Coordinatore dei corsi
teorico-pratici
WWW.EDIZIONIZIINO.COM
G. Fabbrocini
Circolo
Ufficiali Esercito
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SEGRETERIA ORGANIZZATIVA
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www.newcongress.it [email protected]
EVENTO ACCREDITATO
Segreteria Scientifica
L. Panariello
C. Capasso
C. Mazzella
Italian Acne Board
M. Barbareschi
V. Bettoli
G. Fabbrocini
G. Micali
G. Monfrecola
N. Skroza
S. Veraldi
Presidente Onorario
F. Ayala
Relatori e moderatori
F. Ayala - Napoli
R.S. Auriemma - Napoli
N. Balato - Napoli
M. Barbareschi - Milano
M. Bellosta - Pavia
E. Berardesca - Roma
V. Bettoli - Ferrara
F. Bruno - Milano
S. Calvieri - Roma
N. Cameli - Roma
C. Cardinali - Prato
A. M. Colao - Napoli
M. P. De Padova - Bologna
M. Delfino - Napoli
O. De Pità - Roma
A. Di Landro - Bergamo
A. Di Pietro - Milano
M. El Samahy - Egitto
P. Fabbri - Firenze
G. Fabbrocini - Napoli
M. Gola - Firenze
T. Ionescu - Francia
M. Kapinska - Polonia
G. Lo Scocco - Prato
G. Micali - Catania
G. Monfrecola - Napoli
L. Panariello - Napoli
C. Pelfini - Pavia
A. Peserico - Padova
M. Picardo - Roma
G. Plewig - Germania
M. C. Potenza - Roma
C. Rigoni - Milano
A. Romani - Montecatini Terme
P. Romano - Roma
P. Santoianni - Napoli
N. Skroza - Roma
J. Szepietowski - Polonia
A. Tedeschi - Catania
M. Tretti Clementoni - Milano
S. Veraldi - Milano
Volume 3, n. 2, 2012
Gabriella Fabbrocini 1, Maria Carmela Annunziata 1, Nevena Skroza 2, Vincenzo Bettoli 3,
Nayera Moftah 4, May el-Samahy 5, Zrinka Bucvic Mokos 6, Mauro Barbareschi 7,
Stefano Veraldi 7, Giuseppe Micali 8, Francesco Bruno 9, Giuseppe Monfrecola 1
1 Dipartimento di Patologia Sistematica, Sezione di Dermatologia. Università di Napoli Federico II. Italy; 2 Dipartimento di
Dermatologia "Daniele Innocenzi". Università di Roma La Sapienza, Polo Pontino. Italy; 3 Dipartimento di Medicina Clinica e
Sperimentale, Sezione di Dermatologia. Ospedale Sant'Anna, Università di Ferrara, Italy; 4 Department of Dermatology, Faculty of
Medicine for Girls, Al-Azhar University, Cairo, Egypt; 5 Department of Venereology, Faculty of Medicine, Ain Shams University,
Cairo, Egypt; 6 University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine,
Zagreb, Croatia; 7 Istituto di Scienze Dermatologiche, Fondazione Osp. Maggiore di Milano Policlinico Mangiagalli e Regina Elena IRCCS Università degli Studi di Milano, Italy; 8 Clinica Dermatologica, Università di Catania. Italy; 9 Via Santa Sofia, 18 - 20122
Milano, Italy.
* IN COLLABORAZIONE CON LO IAB (Italian Acne Board) E IL MAB (Meditterranean Acne Board)
Epidemiologia dell’acne: oltre i dati europei
SUMMARY
Background. L'acne è una patologia dermatologica molto comune ed
è caratterizzata da un grande impatto sulla qualità della vita dei pazienti. Le differenti latitudini e le varie abitudini circa l’esposizione al sole possono cambiare radicalmente le caratteristiche della malattia; esistono tuttavia soltanto pochi
studi in letteratura che analizzano l’epidemiologia dell’acne a seconda della provenienza razziale.
Obiettivo. Il presente studio ha l'obiettivo di determinare
alcuni dati epidemiologici circa la patologia acneica, la
sua gravità e la sua gestione durante la stagione estiva tra
i vari gruppi etnici del bacino del Mediterraneo.
Materiali e metodi. Il campione analizzato è costituito da
285 pazienti acneici (168 italiani, 65 egiziani, 52 croati),
di età compresa tra i 12 e i 40 anni, e da 50 dermatologi
(30 italiani, 10 egiziani, 10 croati).
Un gruppo di dermatologi ha elaborato un questionario
destinato ai pazienti per ottenere alcuni dati epidemiologici e per valutare il loro atteggiamento nei confronti della
terapia estiva e un questionario per gli specialisti dermatologi al fine di analizzare la gestione e il trattamento dell’acne in estate.
Risultati. I pazienti italiani sono quelli che si fotoespongono per più tempo, mentre la maggior parte dei croati e
dei pazienti egiziani (sebbene nel 70% dei csi non usino
fotoprotezione) si espone per meno di 3 ore al giorno.
Farmaci specifici per il trattamento dell’acne sono utilizzati, durante l'estate, solo dal 50% dei pazienti, indipendentemente dalla loro origine. Il 90% dei dermatologi italiani e dei croati prescrivono sempre una protezione solare
mentre gli egiziani nel 50% dei casi la prescrivono solo se
il paziente è in trattamento con retinoidi.
Pazienti non lontani geograficamente presentano alcune
importanti differenze che si ripercuotono anche sulle abitudini prescrittive dei dermatologi.
Key words: Acne, epidemiologia, paesi mediterranei.
Introduzione
L'acne vulgaris è una delle patologie dermatologiche più comuni nella popolazione generale 1, ed è
caratterizzata da un elevato impatto sulla qualità
della vita dei pazienti 2. I dati epidemiologici non
sono completi e non risultano disponibili per tutti i
paesi. La prevalenza può raggiungere l'80% negli
adolescenti, soprattutto nei maschi 3-7. Sono presenti pochi studi in letteratura che mettono a confronto la prevalenza e le caratteristiche dell’acne
nei diversi gruppi razziali ed etnici. Recenti studi
hanno mostrato alcune differenze nel contenuto di
lipidi nello strato corneo e nei melanosomi nei
pazienti di diversa origine etnica ma, fino ad ora,
tutti i reperti, comprese le differenze nella dimensione dei pori e nella produzione di sebo, sembrano controversi 8, 9. Inoltre, la diversa latitudine e la
durata dell'esposizione solare dei pazienti può
cambiare radicalmente le caratteristiche della
malattia. Infatti, l'esposizione al sole può interferire nella patogenesi globale dell’acne. La produzio-
31
Volume 3, n. 2, 2012
Tabella 1.
Provenienza dei pazienti e dei dermatologi coinvolti nello studio.
Italia
Croazia
Egitto
Tot
Pazienti
168
52
65
285
Dermatologi
20
10
10
50
ne di sebo risulta aumentata 10, 11, il P.acnes viene
distrutto con un meccanismo fotodinamico 12, e il
processo di cheratinizzazione viene alterata 13, 14.
Un’attenta analisi delle caratteristiche della patologia acneica nei diversi tipi di pelle è importante per
un migliore accudimento del paziente e potrebbe
contribuire a ottimizzare le linee guida della terapia.
Il presente studio vuole descrivere alcuni dati epidemiologici sull'acne, la sua severità e la sua
gestione durante la stagione estiva tra i diversi
gruppi razziali ed etnici del Mediterraneo. In questo studio sono stati analizzati dati provenienti da
questionari di pazienti italiani, che hanno caratteristiche etniche tipiche dell’Europa occidentale, di
pazienti egiziani, un gruppo con caratteristiche sia
europeee sia africane, e di pazienti croati che
hanno alcune caratteristiche razziali in comune
con l'etnia asiatica. Un secondo obiettivo è stato
quello di esaminare l'approccio dei dermatologi di
origine italiana, croata ed egiziana al trattamento e
alla gestione dell'acne nel periodo estivo.
Materiali e metodi
Il presente studio è stato condotto, da dicembre
2010 a maggio 2012, presso l'Università di Napoli
"Federico II" - Dipartimento di Patologia
Sistematica - Divisione di Dermatologia, in
conformità con le linee guida etiche della
Dichiarazione di Helsinki del 1975 e ciascun
paziente ha partecipato volontariamente allo studio. Un gruppo di esperti dermatologi europei ha
elaborato un questionario da sottoporre ai pazienti
acneici per determinare alcuni dati epidemiologici
(sesso, età, gravità dell’acne ecc.), per valutare il
loro atteggiamento nei confronti della terapia nel
periodo estivo, nonché l'utilizzo di fotoprotezione.
Molte città italiane (Napoli, Milano, Roma,
32
Ferrara, Catania) sono state coinvolte nello studio
così come alcuni centri di riferimento europei per
l’acne come quello croato e quello egiziano.
È stato anche elaborato un questionario destinato
ai medici dermatologi per valutare il loro approccio alla gestione e trattamento dell’acne durante
l'estate nei diversi paesi.
Sono stati intervistati 285 pazienti (168 italiani, 65
egiziani, 52 croati), e 50 dermatologi (30 italiani,
10 egiziani, 10 croati) (Tabella 1).
Risultati
La fascia d'età più rappresentata tra i pazienti intervistati, è stata quella tra i 12 e i 18 anni (45%)
seguita da quella tra i 18 ei 25 (31%). Il gruppo tra
i 25 e i 40 anni è stato quello meno rappresentato
(23%). Il campione risulta composto da femmine
per il 64% e da maschi per il 36%.
Per quanto riguarda l'utilizzo di prodotti fotoprotettivi è stata rilevata una notevole differenza di
comportamento tra pazienti italiani, croati ed egiziani, probabilmente correlata ai diversi fototipi
predominanti nei vari paesi. Infatti, la maggior
parte dei pazienti egiziani (70%) non utilizza alcuna fotoprotezione (Figura 1). Nonostante questo,
Figura 1
Utilizzo di fotoprotezione.
Volume 3, n. 2, 2012
Figura 2
Per quanto tempo
ti esponi al sole
durante l’estate?
sono state evidenziate alcune differenze nelle
dichiarazioni dei pazienti intervistati riguardo alla
loro esposizione quotidiana al sole in estate: i
pazienti italiani sono quelli che si espongono per
più tempo (più di 3 ore al giorno), mentre la maggior parte dei croati e dei pazienti egiziani (sebbene non usino fotoprotezione) si espone per meno di
3 ore al giorno (Figura 2).
Farmaci e prodotti specifici per il trattamento dell’acne sono utilizzati, durante l'estate, solo dal 50%
dei pazienti, indipendentemente dalla loro origine
(Figura 3). In ogni caso, entrambi i gruppi di pazienti, sia quelli che interrompono sia quelli che proseguono la terapia, dichiarano di non riscontare un
peggioramento della malattia nei mesi estivi con
l'eccezione dei pazienti egiziani che dichiarano
Figura 3
Utilizzo di terapia anti acne durante l’estate.
(70%) di vedersi peggiorati in assenza di uno specifico trattamento anti-acne estivo. Per quanto riguarda i questionari compilati dagli specialisti, è stato
rilevato che le abitudini prescrittive, circa i prodotti
fotoprotettivi, dei dermatologi egiziani differiscono
Figura 4
Prescrizione filtri
solari ai pazienti
acneici.
33
Volume 3, n. 2, 2012
Figura 5
Terapie anti-acne
tollerate meglio in estate.
da quelle degli italiani e dei croati, poiché mentre il
90% degli italiani e dei croati indicano sempre una
protezione solare, gli egiziani nel 50% dei casi la
prescrivono solo se il paziente è in trattamento con
retinoidi (Figura 4).
La domanda sul prodotto meglio tollerato dai pazienti durante l'estate ha permesso di constatare che i dermatologi italiani e croati tendono a sospendere la prescrizione di farmaci preferendo consigliare l’uso di
cosmetici e OTC che sono meglio tollerati; questo non
accade in Egitto dove, forse a causa della predominanza di fototipi diversi, sono considerati ben tollerati
antibiotici topici e sistemici (Figura 5)
Considerazioni conclusive
Alla luce dei nostri risultati è evidente che tali
gruppi di pazienti, seppure non lontani geografica-
mente, hanno alcune differenze che si ripercuotono anche sulle abitudini prescrittive dei dermatologi. Gli italiani si espongono ma si fotoproteggono di più.
I croati vanno maggiormente sensibilizzati ad una
fotoprotezione mirata sebbene si espongano di
meno mentre gli egiziani vanno maggiormente informati in quanto pur sostenendo di non fotoesporsi e di non foto proteggersi, dimenticano di vivere
ad una latitudine che li fotoespone quasi tutto l’anno e che può modificare la storia naturale della
malattia e la compliance terapeutica.
Tale indagine da noi condotta in collaborazione
con i membri dello IAB (Italian Acne Board) e del
MAB (Mediterranean Acne Board) ha il merito di
veicolare informazioni sulle abitudini dei pazienti
e degli specialisti nelle varie nazioni consentendo
di aggiornare i dati epidemiologici e i percorsi diagnostico-terapeutici nel campo dell’acne.
Bibliografia
34
1. Halder RM, Grimes PE, McLaurin CI, et al. Incidence of
common dermatoses in a predominantly black dermatologic
practice. Cutis 1983; 32:388-390.
4. Gloor M, Eicher CH, Wiebelt H, Moser G. Soziologische
Untersuchungen bei der Acne vulgaris. Grosse Verlag Berlin
1978; 53(23):871-880.
2. Thomas DR. Psychosocial effect of acne. J Cutan Med Surg
2004; 8(Suppl. 4): 3–5.
5. Götz H, Zabel G. Acne vulgaris in 2, 249 high-school students. G Ital Dermatol Minerva Dermatol 1971; 46 (3):133-136.
3. Burton JL, Cunliffe WJ, Stafford I, Shuster S. The prevalence of acne vulgaris in adolescence. Br J Dermatol 1971; 85
(2):119-26.
6. Rademaker M, Garioch JJ, Simpson NB. Acne in schoolchildren: no longer a concern for dermatologists. BMJ 1989; 298
(6682):1217-1219.
Volume 3, n. 2, 2012
7. Schäfer T, Nienhaus A, Vieluf D, Berger J, Ring J.
Epidemiologiy of acne in the general population: the risk of
smoking. Br J
11. Suh DH, Kwon TE, Youn JI. Changes of comedonal
cytokines and sebum secretion after UV irradiation in acne
patients. Eur J Dermatol 2002; 12;139-44.
8. Richards GM, Oresajo CO, Halder RM. Structure and functions of ethnic skin and hair. Dermatol Clin 2003; 21:595-600.
12. Sigurdsson V, Knulst AC, Van Weelden H. Phototherapy of
acne vulgaris with visible light. Dermatology 1997; 194:256-60.
9. Berdaresca E, Maibach H. Ethnic skin: overview of structure
and function. J Am Acad Dermatol 2003; 48:S139-142.
13. Mills OH, Porte M, Kligman AM. Enhancement of comedogenic substances in ultraviolet radiation. Br J Dermatol 1978;
98:145-50.
10. Piérard-Franchimont C, Piérard GE, Kligman A. Seasonal
modulation of the sebum excretion. Dermatologica 1990;
181:21-2.
14. Piérard GE, Piérard-Franchimont C. Squamometry in acute
photodamage. Skin Res Technol 1995; 1:137-9.
35
Volume 3, n. 2, 2012
Giuseppe Monfrecola, Rosanna Izzo
Sezione di Dermatologia Clinica, Allergologica e Venereologica, Dipartimento di Patologia Sistematica, Università Federico II, Napoli
Giuseppe Monfrecola
Acne e fotoprotezione
SUMMARY
Una adeguata e corretta fotoprotezione è importante in tutti i soggetti, ma in particolar modo è necessaria nei pazienti acneici.
Nella valutazione degli effetti delle radiazioni solari sulla
cute acneica, si possono individuare sia effetti negativi
degli UV, quali favorire l’ipercheratinizzazione infundibolare, promuovere la secrezione sebacea, aumentare i
fenomeni di perossidazione lipidica e incrementare il potere comedogenico di alcune sostanze; sia effetti positivi degli UV, come ridurre la proliferazione del P.acnes
(UVB), proprietà antinfiammatorie (es. IL-1Ra, IL-10) e
aumentare i livelli di α-MSH con azione pigmentogena e
antinfiammatoria. I filtri solari per pazienti acneici sono
specificamente formulati per pelli acneiche: il tipo di filtro da utilizzare deve essere di tipo MEDIO (SPF15-20-5)
ALTO (SPF30-50); per quanto riguarda il tipo di veicolo,
al momento l’indicazione più favorevole e razionale sembra essere quella di un emulsione fluida tipo OLIO IN
ACQUA, eventualmente arricchita con sostanze naturali
con attività antinfiammatoria, sebostatica e lenitiva. I più
innovativi fotoprotettori per pelli acneiche si basano su di
un esclusivo sistema filtrante discriminante verso UVA e
UVB mentre preferiscono lasciare filtrare la luce blu che
dai recenti studi sembra espletare una potente azione
antibatterica sul P.acnes e sulla conseguente cascata antinfiammatoria. A tali filtri, con proprietà non comedogeniche e fotostabili, si è dimostrata particolarmente favorevole l’aggiunta di composti con attività antiacne specifici, quali l’Acetato di zinco e l’acido laurico e sostanze
antiossidanti, lenitive e disarrossanti, quali la vitamina E
e l’acido ferulico.
Key words: Acne, fotoprotezione, filtri solari, acido ferulico, acido laurico, vitamina E, zinco.
Introduzione
dall’atmosfera terrestre, prevalentemente dallo
Fin dai tempi antichi, il Sole e la luce
strato di ozono: esso blocca le radiazioni dotate di
solare sono stati associati, dagli esseri umani, all’igrande energia, incompatibili con la vita, quali i
dea di benessere fisico e psichico. Tutte le civiltà,
raggi X, gamma e cosmici, e i raggi ultravioletti C.
in qualche forma, hanno venerato il Sole come
Sulla nostra pelle arrivano, così, solo raggi ultrasimbolo divino di autorità e potere.
violetti di tipo A e B (UVA, UVB), le radiazioni
Nel nostro emisfero, in particolar modo nel pedello spettro visibile responsabili dei colori perceriodo estivo, i raggi solari raggiungono la superfipibili (VIS) e gli infracie terrestre, e quindi
Figura 1
rossi (IR) responsabili
anche la nostra pelle, in
Spettro solare.
del calore (Figura 1).
elevata concentrazione.
Una parte di questi ragÈ anche il momento in
gi viene riflessa dallo
cui tendiamo ad esporci
strato corneo, la restanmaggiormente alla luce
te parte viene assorbita
solare.
provocando modificaLa luce solare non è
zioni fisiologiche, benealtro che energia sotto
fiche (produzione della
forma di radiazioni eletvitamina D, innalzamentromagnetiche (REM).
to del tono dell’umore) e
Tali radiazioni sono fildi difesa (aumento della
trate, per la gran parte,
37
Volume 3, n. 2, 2012
dopo irradiazione 4. Infatti, come precedentemente ricordato, gli effetti dell’ UVA sono principalmente indiretti, mediati dai ROS, con frammentazione del DNA e perossidazione lipidica.
A livello sebaceo, la perossidazione dei lipidi
sebacei, comporta la produzione di isomeri
monoidrossiperossidati dello squalene, elemento fondamentale nel processo comedogenico 5, 6.
Infatti l’UV esalta il potere comedogenico di
alcune sostanze, come appunto lo squalene,
causando quindi ipercheratosi follicolare,
distensione dei follicoli con materiale simil-corneo, e aumento di volume dei microcomedoni 1.
produzione di melanina con conseguente comparsa dell’abbronzatura), ma anche alterazioni patologiche della struttura stessa della cute e del sistema
immunitario.
Acne e sole
Gli effetti delle radiazioni solari sulla cute
acneica possono essere schematizzati come segue:
•
•
38
Effetti sui cheratinociti: ipercheratinizzazione
infundibolare
La luce solare, sebbene nelle prime 24h-48h
provochi una inibizione della sintesi del DNA,
a distanza di un tempo > 48 h induce un notevole incremento della mitosi dei cheratinociti;
questi fenomeni potrebbero promuovere l’ostruzione infundibolare, che rappresenta uno
degli eventi più precoci della comedogenesi 1.
Gli effetti dell’UVB in tal senso sarebbero
molto più comedogenici dell’UVA; quest’ultimo, invece, agirebbe principalmente per via
indiretta attraverso l’interazione con i cromofori endogeni , la cui attivazione induce la produzione dei ROS, aventi come principali bersagli
i lipidi, le proteine e gli acidi nucleici.
Effetti sulle ghiandole sebacee: iperseborrea
Gli effetti dell’UV sulle ghiandole sebacee
sono ampiamente riportati in letteratura:
Lesnik e coll. hanno studiato gli effetti in vivo
degli UVB, evidenziando inizialmente la
necrosi dei sebociti ma, a distanza di 24-30 settimane, un effetto rebound con iperplasia delle
ghiandole sebacee e un aumento del numero
dei sebociti 2.
Akitomo et al. irradiando sebociti in vitro
hanno ottenuto risultati analoghi, osservando
che sebbene la proliferazione dei sebociti fosse
inibita dopo 2 giorni, il numero dei sebociti era
aumentato del 120/140% dopo 4 giorni e la
produzione di sebo era anch’essa aumentata
dopo una settimana 3.
Inoltre Yamazaki et al. hanno riportato che il
colesterolo7-idrossiperossido, marcatore di
perossidazione lipidica, aumenta notevolmente
•
Effetti sul Propionibacterium acnes
Studi condotti in vitro da Eluhr et al. hanno
rilevato che la crescita del P.acnes è significativamente inibita dagli UVB; al contrario gli
UVA non modificano la crescita di questo
microrganismo 7.
Il visibile (VIS), invece, sarebbe capace di attivare le porfirine sia endogene che batteriche
prodotte dal P.acnes, ovvero la Coproporfirina
III (attivata a 408 nm) e la Protoporfirina IX
(attivata a 415 e a 639 nm) (Figura 2).
•
Effetti antinfiammatori
L’UVA e il VIS sono capaci di esplicare importanti effetti antinfiammatori e immunommodulanti; studi in vitro su cellule HaCaT e hTERT,
irradiate con luce blu, hanno evidenziato inibizione di IL-1alfa. Inoltre l’UV determina un
Figura 2
Ghiandola sebacea.
Volume 3, n. 2, 2012
incremento sia della IL-10, potente citochina
con effetti antinfiammatori e immunosuppressivi, sia dell’ IL-1Ra, falso recettore che inibisce
competitivamente il legame dell’IL-1 con il suo
recettore naturale 8, 9.
•
Effetti su MSH
L’UV determina un incremento della sintesi di
MSH che, agendo sui cheratinociti, ha un’azione pigmentogena e antinfiammatoria. Tuttavia,
nei pazienti acneici, si devono considerare
anche i potenziali effetti del MSH sui sebociti,
nei quali si ha un incremento della sintesi di
squalene e una riduzione della secrezione di IL8 e di IL-1ß (Zouboulis et al.) 10; si deduce
quindi che l’MSH esplica da una parte un effetto antinfiammatorio e dall’altra un effetto lipogenico e comedogenico.
Riepilogando, quindi, gli effetti delle radiazioni
solari sulla cute acneica, si possono individuare sia
effetti negativi degli UV, quali:
1. Favorire l’ipercheratinizzazione infundibolare
2. Promuovere la secrezione sebacea.
3. Aumentare i fenomeni di perossidazione lipidica (es. colesterolo7-idrossiperossido).
4. incrementare il potere comedogenico di alcune
sostanze.
sia effetti positivi degli UV, come:
1. Ridurre la proliferazione del P.acnes (UVB).
2. Proprietà antinfiammatorie (es. IL-1Ra, IL-10)
3. Aumentare i livelli di -MSH con azione pigmentogena e antinfiammatoria.
Perché è importante la fotoprotezione
nei pazienti acneici?
Una adeguata e corretta fotoprotezione è
importante in tutti i soggetti, ma in particolar modo
è necessaria nei pazienti acneici, non solo per gli
effetti comedogenici dell’UV, ma anche per la prevenzione di tutti quei danni indotti dal sole (prevenzione di eritema, ustioni, fotodermatosi, fotoinvecchiamento e nella prevenzione di neoplasie
cutanee).
I criteri per la fotoprotezione topica prevedono sia
l’utilizzo di filtri ad azione chimica, con assorbimento delle radiazioni (acido aminobenzoico, cinnamati, salicilati, benzofenoni), sia filtri ad azione
fisica, che riflettono e disperdono le radiazioni
(biossido di titanio, ossido di zinco) (Tabella 1).
Indipendentemente dal tipo di filtro, un concetto
fondamentale nella fotoprotezione è dato dal fattore di protezione, o SPF (Sun Protecting Factor),
indicante cioè la capacità protettiva del filtro. Esso
si calcola come rapporto tra la minima dose eritemigena (MED) su cute protetta dal filtro e la MED
su cute non protetta. Tale parametro si riferisce
principalmente all’azione protettiva filtrante nei
confronti dell’UVB, ma non dell’UVA,
Al momento non esistono metodi universalmente
accettati e standardizzati per la determinazione del
fattore di protezione per gli UVA(UVA Protecting
Factor o UVA-PF).
Così come il calcolo dell'SPF per i filtri UVB si
basa sul confronto della MED tra la pelle protetta
e la pelle non protetta da filtro, anche per la valutazione dell'UVA-PF si rende necessaria l'indivi-
Tabella 1.
Principali classi di filtri chimici solari ed aree di assorbimento.
STRUTTURE CHMICHE
TIPO DI ASSORBIMENTO
PABA derivatives
UVB
Cinnamates
UVB
Benzyllidecamphor derivatives
UVB (Meroxyl SX:UVA)
Dibenzoilmethane derivatives
UVA
Benzophenones
UVB + UVA
Salicilates
UVB
39
Volume 3, n. 2, 2012
duazione di risposte cutanee misurabili specificamente indotte dagli UVA.
I filtri solari per pazienti acneici sono specificamente formulati per pelli acneiche: il tipo di filtro da utilizzare deve essere di tipo MEDIO (SPF15 – 20 –
25) ALTO (SPF30 – 50); per quanto riguarda il tipo
di veicolo, al momento l’indicazione più favorevole
e razionale sembra essere quella di un emulsione
fluida tipo olio-acqua, eventualmente arricchita con
sostanze naturali con attività antinfiammatoria,
sebostatica e lenitiva. Utilizzati anche i gel.
Nei pazienti acneici, va sottolineato l’uso obbligatorio di fotoprotettori nel caso in cui fossero prescritte terapie sistemiche, quali antibiotici (tetracicline) o pillole anticoncezionali per prevenire ed
evitare il rischio di fotosensibilizzazione e iperpigmentazione. La fotoprotezione è comunque da
consigliare anche durante il trattamento topico con
retinoidi, benzoilperossido e idrossiacidi. Si evince
dunque l’importanza di fotoprotettori sempre più
specifici e selettivi appositamente studiati per chi
ha una cute acneica o a tendenza acneica.
I più innovativi fotoprotettori per pelli acneiche si
basano su di un esclusivo sistema filtrante discriminante verso UVA e UVB mentre preferiscono
lasciare filtrare la luce blu che dai recenti studi sembra espletare una potente azione antibatterica sul
P.acnes e sulla conseguente cascata antinfiammatoria. A tali filtri, con proprietà non comedogeniche e
fotostabili, si è dimostrata particolarmente favorevole l’aggiunta di composti con attività antiacne specifici,quali l’acetato di zinco e l’acido laurico, la nicotinamide, lo zinco gluconato e sostanze antiossidanti, lenitive e disarrossanti, quali la vitamina E e l’acido ferulico, il ramnosio. D’altra parte sono note le
proprietà di molti dei composti descritti che fanno
intuire come il loro inserimento nel filtro solare
possa aumentare la compliance e la efficacia terapeutica dei pazienti con acne nel periodo estivo.
L’uso di antiossidanti come la vitamine E inibisce la
perossidazione lipidica di membrana, stabilizzandola, e proteggendo gli acidi grassi insaturi o ancora
l’acido ferulico che potenzia gli effetti di altri
antiossidanti come la vitamina C ed E. La nicotinammide espleta un potente effetto antinfiammatorio inibendo il rilascio di citochine mentre lo zinco
è un elemento metallico con attività batteriostatica
40
contro il P.acnes, in grado di inibire la chemiotassi
neutrofila e ridurre la produzione di TNF o ancora
l’aggiunta di acido laurico con potente effetto battericida che può modulare anche in questo caso l’attività antimicrobica con quello che ne consegue.
L’associazione, poi, di prodotti a base di ramnosio
che espletanto una potente azione sebo statica e
astringente possono aumentare l’efficacia terapeutica. La fotoprotezione dell’acneico diventa quindi
sempre piu’ un complemento terapeutico importante che puo’ consentire al dermatologo di avere il
controllo della patologia anche nel periodo estivo
(Figura 3).
Conclusioni
La fotoprotezione nei pazienti acneici con
prodotti appositi gioca un ruolo importante nel corso
del trattamento terapeutico. È opportuno dunque
chiarire al paziente che l’estate non porta ad un
miglioramento vero e duraturo; è importante non
interrompere completamente il trattamento, ma adeguarlo alla situazione estiva (in base a sesso, età,
tipo di acne, tipo di vacanza, etc.); è da sconsigliare
l’uso di idratanti non “dedicati”, utilizzando prodotti fotoprotettivi studiati per pelli acneiche (veicolo
O/A); la necessità di programmare una visita e un
adeguato trattamento subito dopo le vacanze.
Figura 3
Azione dello zinco.
Volume 3, n. 2, 2012
Bibliografia
1. Mills OH, Porte M, Kligman AM. Enhancement of comedogenic substances by ultraviolet radiation. Br J Dermatol 1978;
98(2):145-50.
(313 nm) and UVA1 (345-440 nm) radiation in vitro.
Photodermatol Photoimmunol Photomed 1997; 13(5-6):197201.
2. Lesnik RH, Kligman LH, Kligman AM. Agents that cause
enlargement of sebaceous glands in hairless mice. II.Ultraviolet
radiation. Arch Dermatol Res 1992; 284:106/8.
8. Krutmann J. Ultraviolet A radiation-induced immunomodulation: molecular and photobiological mechanism. Eur J
Dermatol 1998; 8(3):200-2.
3. Akitomo Y, Akamatsub H, Okanoc Y, et al. Effects of UV
irradiation on the sebaceous gland and sebum secretion in hamsters J Dermatol Sci 2003; 31(2):151-9.
9. Roberts JE Light and immunomodulation. Ann N Y Acad Sci
2000; 917:435-45.
4. Yamazaki et al Cholesterol 7-hydroperoxides in rat skin as a
marker for lipid peroxidation Biochem Pharmacol 1999;
58(9):1415-23.
5. Ekanayake Mudiyanselage S, Hamburger M, Elsner P, Thiele
JJ. Ultraviolet a induces generation of squalene monohydroperoxide isomers in human sebum and skin surface lipids in
vitro and in vivo J Invest Dermatol 2003; 120(6):915-22.
6. Chiba K, Yoshizawa K, Makino I, et al. Comedogenicity of
squalene monohydroperoxide in the skin after topical application J Toxicol Sci 2000; 25(2):77-83.
7. Eluhr, et al. The antimicrobial effect of narrow-band UVB
10. Zouboulis C, et al. Frontiers in sebaceous gland biology and
pathology Experiment Dermatol 17:542-551.
11. Capitanio B., Sinagra J. L Ruolo della clindamicina e dello
zinco acetato nella terapia topica dell’acne Ambulatorio
Acne/SSO di Dermatologia Pediatrica, Istituto San Gallicano,
Roma, Italia.
12. Strauss JS, Stranieri AM. Acne treatment with topical erythromycin and zinc: effect of Propionibacterium acnes and free
fatty acid composition. J Am Acad Dermatol 1984; 11(1):86-9.
13. Yang, et al. The Antimicrobial Activity of Liposomal Lauric
Acids Against Propionibacterium acnes Biomaterials 2009;
30(30):6035-40.
41
Volume 3, n. 2, 2012
Gabriella Fabbrocini, Luigia Panariello, Valerio De Vita, Dario Bianca,
Maria Chiara Mauriello, Giuseppe Monfrecola
Department of Systematic Pathology, Division of Clinical Dermatology, University of Naples Federico II, Naples, Italy
Strategie per migliorare
l’aderenza terapeutica nell’acne
SUMMARY
L’efficacia dei retinoidi topici nel
trattamento dell’acne è ampiamente
documentata, con un elevato livello
di evidenza clinica. Tuttavia, la loro
applicazione si accompagna ad un importante effetto collaterale: l’irritazione cutanea. Tale effetto è mal tollerato
dal paziente, il quale è indotto ad una prematura interruzione della terapia, che risulta, così, poco efficace.
Al fine di valutare quanto la compliance del paziente
acneico alla terapia sia migliorata dall’associazione di un
retinoide topico di prima generazione con un prodotto
topico dotato di maggiore tollerabilità ed efficace nelle
fasi meno gravi dell’acne, è stato condotto uno studio di
associazione alla tretinoina di un prodotto contenente
nicotinamide, retinolo e 7-deidrocolesterolo.
Sono stati selezionati 20 pazienti. Il protocollo prevede-
va l’applicazione della tretinoina su tutto il viso ogni
sera per 60 giorni, mentre di mattina su un emiviso
veniva applicato il prodotto in studio e sull’altro emiviso il solo veicolo.
Le valutazioni sono state eseguite mediante: Global
Acne Grading system, Reveal photo imaging system,
Colorimetro X-Rite 968®, questionario sulla tollerabilità compilato dal paziente.
I risultati hanno evidenziato che l’associazione di un
prodotto contenente nicotinamide, retinolo e 7-deidrocolesterolo e di tretinoina determina, da un lato, un miglioramento clinico superiore a quello ottenibile con il solo
retinoide e, dall’altro, una riduzione significativa degli
effetti collaterali del retinoide stesso, che rappresentano i
principali responsabili dell’interruzione volontaria della
terapia da parte del paziente.
Key words: Terapia topica; aderenza terapeutica; nicotinamide; retinolo; 7-deidrocolesterolo.
L’acne è una patologia cutanea cronica, a patogenesi multifattoriale, che mostra una prevalenza
variabile dal 50 al 93% tra gli adolescenti.
Essa è caratterizzata da iperplasia della ghiandola
sebacea, eccessiva produzione di sebo, ipercheratinizzazione follicolare e infiammazione, quest’ultima perpetuata dalla colonizzazione del follicolo
pilo-sebaceo da parte del Propionibacterium acnes.
Studi recenti hanno evidenziato il possibile ruolo
patogenetico svolto dal rimodellamento patologico
della matrice extracellulare ad opera delle metalloproteinasi (MMP) 1.
Le MMP sono un gruppo di endopeptidasi zincodipendenti che degradano selettivamente alcuni
componenti della matrice extracellulare così come
proteine non della matrice. Esse sono, quindi,
implicate nel rimodellamento tissutale, sia in condizioni fisiologiche che patologiche (ulcere,
infiammazione, metastatizzazione tumorale). Il
sebo di pazienti con acne è ricco di diversi tipi di
MMP, come MMP-1, MMP-9 e MMP-13, che sono
secrete dai cheratinociti e dai sebociti 2.
Inoltre, è stato dimostrato che il P. acnes è in grado
di indurre la produzione di pro-MMP2 attivando il
pathway NF-kB, che è un pathway ben noto per
l’induzione di diverse condizione infiammatorie 3.
Data, dunque, la complessa e multifattoriale patogenesi dell’acne, appare evidente come sia necessario un approccio terapeutico multi-target, basato
su prodotti topici costituiti da una combinazione di
principi attivi, ciascuno capace di intervenire su un
diverso fattore patogenetico.
L’efficacia dei retinoidi topici nel trattamento dell’acne è ampiamente documentata, con un elevato
livello di evidenza clinica. Essi sono in grado sia di
prevenire la formazione dei comedoni sia di indurne la regressione, nonché di espletare un marcato
effetto antinfiammatorio. Essi sono pertanto indicati nelle linee guida internazionali come terapia di
prima scelta non solo nell’acne comedonica, ma
43
Volume 3, n. 2, 2012
anche in quella papulo-pustolosa. Tuttavia, la loro
applicazione si accompagna ad un importante
effetto collaterale: l’irritazione cutanea, che si
manifesta con eritema, desquamazione e secchezza. Si tratta di un effetto mal tollerato dal paziente,
il quale è indotto ad una prematura interruzione
della terapia, che risulta, così, poco efficace.
Al fine di valutare quanto la compliance del paziente acneico alla terapia sia migliorata dall’associazione di un retinoide topico di prima generazione,
quale la tretinoina, con un prodotto topico dotato di
maggiore tollerabilità ed efficace nelle fasi meno
gravi dell’acne, è stato condotto uno studio di associazione ai retinoidi topici di un prodotto contenente nicotinammide, retinolo e 7-deidrocolesterolo.
In uno studio condotto da Emanuele et al. 4 sono
state dimostrate la sicurezza e l’efficacia di un prodotto topico combinato contente nicotinamide, retinolo e 7-deidrocolesterolo nel trattamento dell’acne.
Tale combinazione si è rivelata in grado di downregolare le MMP 1-2-9-14, l’interleuchina 6, la proteina-1 chemioattrattiva per i monociti (MCP1) e il fattore d’inibizione della migrazione dei macrofagi
(MIF) nelle aree cutanee affette da acne.
La scelta di tali molecole si basa su alcune evidenze scientifiche.
La nicotinamide, ovvero il derivato amidico della
vitamina B3, è stato ampiamente utilizzato, sia
topicamente che sistemicamente, in numerose
patologie cutanee infiammatorie, quali pemfigoide
bolloso, necrobiosi lipoidica e dermatite erpetiforme. Si è, inoltre, dimostrata efficace nel trattamento dell’acne 5.
Essa, infatti, agisce sulla componenente infiammatoria di tale patologia inibendo la produzione di
citochine pro-infiammatorie 6 e la chemiotassi dei
leucociti, nonchè downregolando l’espressione del
gene dell’IL-8 (la cui attivazione è stimolata dal P.
acnes), attraverso l’inibizione delle MAPK e il
pathway di NF-kb 7. La nicotinamide, applicata
topicamente su cute affetta da dermatite atopica, è
anche in grado di ridurre la perdita d’acqua transepidermica (TEWL) e si è dimostrata più efficace
della vaselina nell’esplicare un’azione idratante.
Essa stimola la sintesi di ceramidi, di acidi grassi
liberi e di colesterolo, migliorando, così, la funzione barrier della cute 8. Il retinolo, come gli altri pro-
44
dotti derivati dalla vitamina A, stimola la desquamazione dello strato corneo, favorisce la rimozione del
tappo di cheratina dal follicolo e mostra effetti antiinfiammatori nella cute affetta da acne 9.
Il 7-deidrocolesterolo, come gli altri analoghi e
derivati della vitamina D, ha mostrato effetti antiproliferativi e pro-differenziativi 10-11.
Sulla base di tali risultati, sono state valutate l’efficacia e la tollerabilità di un prodotto topico contenente
questi tre principi attivi rispetto a un placebo nel contrastare gli effetti collaterali della tretinoina e migliorare, così, l’aderenza dei pazienti acneici alla terapia.
Materiali e metodi
Tra ottobre 2011 e dicembre 2011, tra
tutti i pazienti afferenti presso l’ambulatorio di
Fisiopatologia cutanea e Dermatologia fisico strumentale che iniziavano terapia con tretinoina, sono
stati selezionati quelli di età compresa tra 14 e 30
anni, affetti da acne di grado lieve-moderato, con
prevalente localizzazione della patologia al volto.
Criteri di esclusione sono stati i seguenti: precedenti trattamenti con antibiotici orali, benzoilperossido e retinoidi orali; presenza di malattie endocrine, diabete mellito, malattie fisiche di grado
severo o gravidanza; uso di contraccettivi orali o
impiantabili, prednisone o altri steroidi.
Prima dell’inizio dello studio, ciascun partecipante
è stato informato sugli obiettivi e ha firmato un
consenso informato.
Tutti i pazienti hanno sospeso l’utilizzo di qualsiasi topico 2 settimane prima dell’inizio dello studio.
La composizione del prodotto topico che è stato
associato alla terapia con tretinoina topica è la
seguente: Nicotinamide 4%, Retinolo 1% e 7-deidrocolesterolo 0.5%.
Il protocollo prevedeva l’applicazione di un retinoide topico (acido retinoico tutto-trans o tretinoina) su tutto il viso ogni sera per 60 giorni, mentre
di mattina su un emiviso veniva applicato il prodotto in studio e sull’altro emiviso il solo veicolo.
Le valutazioni sono state effettuate all’inizio dello
studio (T0), dopo 30 giorni (T1) e dopo 60 giorni
(T2). Le metodiche sono state le seguenti:
– valutazione della gravità dell’acne mediante
Volume 3, n. 2, 2012
classificazione GAGS (Global Acne Grading
system);
– valutazione fotografica con immagini digitali
mediante Reveal photo imaging system (15
megapixel resolution •automatic focus •automated white balance correction • facial positions: left 45°, center 0°, right 45° );
– valutazione del colore della cute mediante
Colorimetro X-Rite 968® secondo il sistema
L*a*b*, raccomandato dalla Commission
Internationale de l’Eclairage. Si tratta di un
sistema tridimensionale di assi cartesiani in cui
l'asse L* individua le variazioni tra bianco e
nero, l'asse a* quelle fra rosso e verde e l'asse
b* quelle tra giallo e blu. Abbiamo utilizzato il
valore L* come indice di luminosità della pelle.
I valori possono andare da 0 (luminosità nulla,
pari al nero) a 100 (luminosità massima, pari al
bianco) e sono inversamente proporzionali al
grado di eritema e di infiammazione cutanea.
– valutazione della tollerabilità mediante un questionario sul grado di eritema, secchezza, bruciore, prurito, desquamazione in una scala da 0
(assenza di segni o sintomi) a 3 (valore massimo).
Tali valutazioni sono state effettuate su entrambi
gli emilati del viso dei pazienti, dopo accurata
detersione e in condizioni ambientali standard:
temperatura < 28° C, umidità < 80%.
Risultati
Sono stati inclusi nello studio 20 pazienti
(8 maschi, 12 femmine). L’età media è stata di 22.5
anni.
Tutti i pazienti arruolati hanno portato a termine lo
studio.
– Valori medi GAGS (test t di Student con
p < 0,05):
• T0 = 19
• T1 = 14,5
• T2 = 9,7
– Foto cliniche (Figure 1-4)
Figure 1
Figure 1
Emiviso trattato con il prodotto come tale.
Figure 2
Figure 2
Emiviso trattato con il solo veicolo.
45
Volume 3, n. 2, 2012
Figure 3
Figure 3
Figure 4
Figure 4
Eritema
46
Secchezza
Prurito
Bruciore
Desquamazione
Volume 3, n. 2, 2012
– Valori medi L* registrati mediante Colorimetro
X-Rite 968® (test t di Student con p < 0,05):
•
T0: emiviso trattato con il prodotto
come tale = 58,48; emiviso trattato con
il veicolo = 58,98
•
il veicolo = 58,38
•
il veicolo = 60,06
– Analisi dei questionari sulla tollerabilità: riduzione significativa e progressiva dell’eritema,
della secchezza, del prurito, del bruciore e della
desquamazione nell’emiviso trattato con il prodotto in studio. Tale riduzione è invece poco
significativa e limitata soltanto ad alcuni parametri, quali eritema, prurito e bruciore, nell’emiviso trattato con il veicolo.
Eritema
Secchezza
Prurito
Bruciore
Desquamazione
Discussione
L’utilizzo di terapie combinate nel trattamento dell’acne presenta un duplice vantaggio:
consente di agire su diversi target patogenetici e
può ridurre gli effetti collaterali tipici di alcune
classi di farmaci, come i retinoidi.
L’uso di questi ultimi, in particolare della tretinoina, è tuttavia limitato a causa dell’irritazione cutanea che generalmente essi provocano, definibile
clinicamente come una dermatite irritativa di grado
lieve. Ciò determina frequentemente una precoce
interruzione della terapia da parte del paziente, con
conseguente riduzione dell’efficacia terapeutica.
Tale problema può essere superato mediante l’associazione di un prodotto topico con effetto idratante e lenitivo, che consente di ridurre gli eventi
avversi, migliorando, così, l’aderenza del paziente
alla terapia.
Nel presente studio abbiamo testato la capacità di
un prodotto topico a base di nicotinamide, retinolo
e 7-deidrocolesterolo di migliorare la compliance
terapeutica di pazienti in trattamento con tretinoina
topica.
47
Volume 3, n. 2, 2012
Dai risultati ottenuti possiamo concludere che tale
prodotto presenta un ottimo profilo di sicurezza ed
efficacia:
– i valori medi del GAGS indicano un significativo miglioramento clinico già a T1, che prosegue,
poi, fino a T2. Ciò determina una maggiore soddisfazione del paziente, il quale osserva un più
rapido miglioramento della sua patologia;
– i valori di L* mostrano un significativo aumento della luminosità alla guancia dove è stato
applicato il prodotto in studio, mentre, dove è
stato applicato il solo veicolo, i valori sono
pressochè invariati da T0 a T2; ciò significa che
il prodotto in studio si è dimostrato capace di
ridurre il grado di eritema e di infiammazione
cutanea, diversamente da quanto verificatosi
con l’applicazione del solo veicolo.
– i dati del questionario sulla tollerabilità mostrano alla guancia trattata con il prodotto in studio
una riduzione o una scomparsa di tutti gli effetti collaterali causati dalla tretinoina; alla guancia controlaterale, invece, la riduzione dell’intensità degli effetti avversi è modesta e poco
significativa: essa potrebbe essere correlata ad
un fenomeno di naturale adattamento della cute
agli effetti collaterali del retinoide.
Da questi dati è opportuno considerare che nella
pratica clinica l’associazione di un prodotto contenente nicotinamide, retinolo e 7-deidrocolesterolo
e di tretinoina consente di mantenere costante l’aderenza del paziente alla terapia, in quanto determina, da un lato, un miglioramento clinico superiore a quello ottenibile con il solo retinoide e dall’altro una riduzione significativa degli effetti collaterali del retinoide stesso, che rappresentano i
principali responsabili dell’interruzione volontaria
della terapia da parte del paziente.
Bibliografia
1. Philips N, Auler S, Hugo R et al. Beneficial regulation of
matrix metalloproteinases for skin health. Enzyme Res 2011;
2011:427285.
2. Papakonstantinou E, Aletras AJ, Glass E, et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients
with acne and their regulation by isotretinoin. J Invest
Dermatol 2005; 125:673-684.
3. Choi JY, Piao MS, Lee JB, et al. Propionibacterium acnes
stimulates pro-matrix metalloproteinase-2 expression through
tumor necrosis factor-alpha in human dermal fibroblasts. J
Invest Dermatol 2008; 128:846-854.
4. Emanuele E, Bertona M, Altabas K, et al. Anti-inflammatory effects of a topical preparation containing nicotinamide,
retinol, and 7-dehydrocholesterol in patients with acne: a gene
expression study. Clin Cosmet Investig Dermatol 2012; 5:33-7.
5. Shalita AR, Smith JG, Parish LC, et al. Topical nicotinamide
compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Int J Dermatol 1995; 34:434-437.
6. Ungerstedt JS, Blombäck M, Söderström T. Nicotinamide is a
48
potent inhibitor of proinflammatory cytokines. Clin Exp
Immunol 2003; 131:48-52.
7. Grange PA, Raingeaud J, Calvez V, Dupin N. Nicotinamide
inhibits Propionibacterium acnes-induced IL-8 production in
keratinocytes through the NF-kappaB and MAPK pathways. J
Dermatol Sci 2009; 56(2):106-12.
8. Soma Y, Kashima M, Imaizumi A, et al . Moisturizing effects
of topical nicotinamide on atopic dry skin. Int J Dermatol 2005;
44:197-202.
9. Ruamrak C, Lourith N, Natakankitkul S. Comparison of
clinical efficacies of sodium ascorbyl phosphate, retinol and
their combination in acne treatment. Int J Cosmet Sci. 2009;
31(1):41-6.
10. Lehmann B, Querings K, Reichrath J. Vitamin D and skin:
new aspects for dermatology Exp Dermatol 2004; 13 Suppl
4:11-5.
11. Lehmann B. Role of the vitamin D3 pathway in healthy and
diseased skin--facts, contradictions and hypotheses. Exp
Dermatol 2009; 18(2):97-108.
Volume 3, n. 2, 2012
Gennaro Ilardi 1, Gabriella Fabbrocini 2, Nevena Skroza 3, Sara Cacciapuoti 2,
Ersilia Tolino 3, Claudio Marasca 2, Giuseppe Monfrecola 2
1 Department
of Biomorfological and Functional Sciences, Section of Pathological Anatomy and Citopathology, University of Naples
Federico II, Naples, Italy; 2 Department of Systematic Pathology, Division of Clinical Dermatology, University of Naples Federico II,
Naples, Italy; 3 Departement of Medico-Surgical Sciences and Biotechnologies. Corso della Repubblica, 04100, Latina, Italy.
Follicular biopsy (FB) can be useful for monitoring
therapeuthic compliance in acne patients
Nevena Skroza
SUMMARY
Follicular biopsy is a non-invasive
technique that allows to assess
quickly, accurately and noninvasively content of sebaceous follicles.
This technique can be useful to clarify some aspects of
comedogenesis and to monitor the efficacy of treatments in acneic patients. In this study we evaluate the
anticomedogenic effect of topical adapalene and benzoyl peroxide in acne treatment. In this open study a
total of 20 patients (16 females and 4 males) aged
between 18 and 40 years (mean age 30 years) with
mild/moderate acne were treated with topical adapalene and benzoyl peroxide.
The efficacy of the therapy was evaluated with Global
Acne Grading Sistem (GAGS), Global Efficacy on acne
lesions (GAIS), photographic documentation and follicular biopsy. The evaluation of the GAIS confirmed the
significant changes between T0 and T1, and was highlighted by stereomicroscopic examination of follicular
biopsies. Follicular biopsies seems to be the easiest and
less invasive method for efficacy evaluation of topical
cosmetics and drugs.
Key words: Follicular biopsy, adapalene and benzoyl peroxide.
Introduction
The study of the pilosebaceous follicles is
essential for understanding the pathophysiological
processe that occur in acne and for the evaluation of
comedogenesis. The alteration of keratinization in
the lower part of the sebaceous follicles seems to be
the first step for the development of microcomedones. This consists in an initial accumulation of
corneum material which leads to a follicular dilatation. Skin surface biopsy with cyanoacrylate was
introduced in 1971 by Marks and Dawber and subsequently renamed "follicular biopsy" by Kligman
1. It allows to assess quickly, accurately and noninvasively content of sebaceous follicles. Follicular
biopsy can be useful to clarify some aspects of
comedogenesis and this technique can monitor the
efficacy of treatments for patients with acne.
In this study we evaluate the anticomedogenic
effect of topical adapalene plus benzoyl peroxide
for the treatment of acne.
Materials and methods
Inclusion criteria
A total of 20 patients (16 females and 4 males)
aged between 18 and 40 years (mean age 30 years)
with mild/moderate acne were recruited with a
wash out from therapy almost of 4 weeks (Table 1).
Exclusion criteria
Patients with a known allergy to cosmetic products;
with chronic conditions present prior the enrolment.
49
Volume 3, n. 2, 2012
Table 1.
Inclusion and exclusion criteria.
INCLUSION CRITERIA
EXCLUSION CRITERIA
Prominent comedonal component
Known allergy to cosmetic products
Age between 18 and 40 years
Chronic conditions present prior to enrollment
Acne mild / moderate
Subjects already treated with other topical medications for acne
Wash out from 4 weeks
Participation in clinical studies which included the application of topical products on the face in the previous 4 weeks
Participation in clinical studies which included applying UV rays on your face in the previous 4 weeks
Alchol and drugs
Global Acne Grading Sistem (GAGS) and
Global Efficacy on acne lesions (GAIS)
At enrollment (T0) skin examination with assessment of the severity of acne using the Global
Acne Grading Sistem (GAGS) and Global Efficacy
on acne lesions (GAIS) were performed 2. Also at
time T1 the evaluation of acne lesions by lesion
count (GAGS) and of the overall effectiveness on
acne lesions (GAIS) was carried out. GAGS
system divides the face, chest and back into six
areas (forehead, each cheek, nose, chin and chest
and back) and assigns a factor to each area on the
basis of size, while the Global Aesthetic
Improvement Scale (GAIS) is a relative scale
where the investigator grades the overall clinical
improvement by comparing the patient's appearance at follow-up against a high magnification photograph taken prior to treatment.
Photographic documentation
Acquisition of digital photographic images (frontal
position, half face right and left) using Reveal
system (Canfield, USA) with 15 megapixel resolution, auto focus, correction and white balance,
flash light flash standard cross polarized light, processing brown spots and red areas. and a sample of
20 patients follicular biopsy was performed at T0
and after 60 days (T1).
Follicular biopsy (FB)
FB uses the bonding properties of cyanoacrylate
glue with proteins such as keratin. The liquid adhesive is applied under pressure and we wait its solidification by polymerization. A drop of cyanoacrylate is placed on the test area and covered by a
50
glass slide. The microscopic glass slide is then
applied on the top of the gel and pressed firmly
onto the skin for 3 minutes. The glass slide is gently removed, taking with it the upper part of the
stratum corneum 3. Thus the attached sample can
be examined preserved as present in vivo. The FB
was performed on the same area for both cheeks at
time 0 and time 1 (60 days after).
Cream application and evaluation of tolerability
The cream application was performed once a day,
during the period of the study. At time T1, 60 days
after initiation of therapy, dermatologists evaluated
some parameters such as tolerability, dryness,
desquamation, erythema, burning, itching. The
estimation of tolerability and cosmetic quality was,
however, also registered by some parameters such
as consistence, color after application, odor,
comfort of the skin after application, speed of
penetration and hydrating power.
Results
19 of 20 patients completed the study, one patient
drop out because he didn’t come back for the control. The evaluation of the GAGS (Severity of
lesions by means of Global Acne Grading System)
showed a reduction in lesion count of 43%
(Figures 1, 2A, 2B).
The evaluation of the GAIS (Global Efficacy on
acne lesions) confirmed the significance of the
change between T0 and T1, and was highlighted by
stereomicroscopic examination of follicular biopsies. The examination of the FB samples obtained
Volume 3, n. 2, 2012
Figure 1
GAGS
by stereomicroscopy analysis and the subsequent
numerical processing of the area occupied by
micro and macro comedones before (T0) and after
treatment (T1) showed a statistically significant
reduction of the lesions.
Our results showed a reduction of 56% between
time 0 (T0) and after 60 days of treatment (T1) for
the micro comedones. Considering the macro
comedones, the reduction is around 30% (Figures
3, 4, 5a, 5b).
B
A
Figure 2
Before (A) and after (B) treatment.
Figures 3, 4
Evaluation of the medium area (mm2) occupied by micro comedones at T0 (before treatment)
and at T1 (after the end of the treatment) on the right and left cheek.
Figure 3
We observed that the reduction is similar for all
skin areas, demonstrating the efficacy of the association among adapalene plus benzoyl peroxide to
Figure 4
fight the comedogenic process. The reduction of
30% of macrocomedones is a strong expression of
this effect because, as we expected, an increase of
51
Volume 3, n. 2, 2012
Figure 5
Stereomicroscopic
images A)
before and B)
after the
treatment.
A
B
macrocomedones would have been registered for
the high percentage at T0 of microcomedones. The
significant reduction can explain efficacy of this
formulation to block the comedogenesis process
and can explain clinical results.
As shown in Figure 5 we can observe that the
reduction of micro and macrocomedenes by FB is
higher respect to the reduction of GAGS, hypothesing that this non invasive technique can be useful
to better monitor clinical improvement in acne
patients (Figure 6).
The tolerability was evaluated by the dermatologist and by the patients: it was very good in 60% of
patients, good in 20%, 12% in average, only 8%
poor. It is important to underline that patients with
less value of tolerability, have had better results.
Erythema (that appeared in 8/20 patients) and
desquamation (that appeared in 4/20 patients)
when occurs can be an efficacy’s tool .
Discussion and conclusions
It's well known that microcomedones are
now considered the earliest lesions, not visible to
the naked eye, in the pathogenesis of acne vulgaris:
our results showed that follicular biopsy can be
useful to monitor therapy efficacy in acne patients.
The improvement registered in our study is very
significant, and it is stated by both index GAGS
and the GAIS.
In our study we evaluate the efficacy of the association of Adapalene 0.1% plus Benzoyl peroxide
52
Figure 6
Summary of clinical response to treatment.
2.5% by clinical and follicular biopsy analysis.
Adapalene is a derivative chemically stable of
naphthoic acid with activity similar of retinoids.
Studies on the biochemistry and pharmacology
have demonstrated that adapalene is active on the
pathological mechanisms involved in acne vulgaris 4. It is a potent modulator of cellular differentiation and keratinization and has anti-inflammatory
properties. Considering the mechanism of action,
adapalene binds the specific retinoic acid nuclear
receptors. Current evidence suggests that topical
adapalene normalizes the differentiation of follicular epithelial cells leading to a reduced formation of
microcomedones. In experimental models in vitro,
adapalene inhibits chemotactic responses (directional) and chemiokinetic (random) of human polymorphonuclear leukocytes and also the metabolism
of arachidonic acid to inflammatory mediators. In
Volume 3, n. 2, 2012
vitro studies have demonstrated the inhibition of
factors AP-1 and inhibition of the expression of
receptors of type-2 Toll. This profile suggests that
the cell-mediated inflammatory component present
in acne is reduced by adapalene. Benzoyl peroxide
plays an important role in the treatment of mild and
moderate, for keratolytic and bacteriostatic effects.
The oxidative action of Benzoyl peroxide promotes
the creation of an aerobic environment in the excretory duct of the sebaceous follicle, resulting in inhibition of anaerobic bacterial flora typical of acne. In
contrast to the topical antibiotics does not induce
the formation of resistant bacterial strains. Benzoyl
peroxide would also act with sebum suppressive
mode, resulting in a reduction in the size of sebaceous glands and with a decrease of seborrhea.
Both drugs can explain an important role to inhibit
comedogenesis process.
While it is well known their anti-inflammatory
properties, anticomedogenic effects can difficult to
detect. For this reason our results of CFB are very
important to set the use of these drugs also for acne
with predominant comedonal aspect.
In fact, the follicular biopsy was also used by other
authors to determine the potential of comedogenic
cosmetics 5; Thielitz A et al. 6 used this method to
analyze the changes induced by topical therapy in
the lipid composition of follicular infundibulum
and concluded that this method is suitable for the
detection of quantitative and qualitative changes in
the lipid profile induced by topical therapy. In light
of these findings, FB seems to be the easiest and
less invasive method for evaluation efficacy of topical cosmetics and drugs.
The data emerging from our results can give more
support to optimize the monitoring of acne therapy
on the basis of these findings. As in our experiences the consistence of reduction of micro and
macrocomedones open new research to understand
the efficacy of this association and can be useful in
this type of acne increasing the compliance of the
patients.
References
1. Mills Jr. OH, Kligman AM. The Follicular Biopsy
Dermatologica 1983; 167:57-63.
4. Mills OH, Klingman AM. A human model for assessing comedogenic substances, Arch Derm 1982; 118, 903.
2. Dréno B, Kaufmann R, Talarico S, et al. Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the
treatment of moderate to severe acne vulgaris: a multicentre,
randomized, double-blind controlled study. Br J Dermatol 2011;
165(2):383-90. doi: 10.1111/j.1365-2133.2011.10374.x. Epub
2011 Jul 6.
5. Thielitz A, Helmdach M, Röpke EM, Gollnick H: Lipid analysis of follicular casts from cyanoacrylate strips as a new method
for studying therapeutic effects of antiacne agents. Br J
Dermatol 2001; 145(1):19-27.
3. Pagnoni A, Kligman AM, el Gammal S, Stoudemayer T.
Determination of density of follicles on various regions of the
face by cyanoacrylate biopsy: correlation with sebum output. Br
J Dermatol 1994; 131(6):862-5.
6. Thiboutot DM, Weiss J, Bucko A, et al. Adapalene-BPO
Study Group. Adapalene-benzoyl peroxide, a fixed-dose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study. J Am Acad
Dermatol 2007; 57(5):791-9. Epub 2007 Jul 26.
53
Volume 3, n. 2, 2012
Gabriella Fabbrocini, Caterina Mazzella, Rosanna Izzo, Giuseppe Monfrecola
Department of Systematic Pathology, Division of Clinical Dermatology, University of Naples Federico II, Naples, Italy
Caterina Mazzella
Counseling: adherence to therapy and quality of life
SUMMARY
Acne is not only a problem of the
adolescents, because an high percentage of 30-40 years subjects can
be affected. The psychological
impact of acne is evident especially in timid and sensible
patients. Acne can be considered a social disease as it
affects patient’s psychology, compromising their self-confidence and their relationships. Counseling is an intervention of receiving, listening, understanding and clarification towards the patient with acne that is often confused,
stressed and suffering, especially when he has practiced
many therapies and they are affected by a long history of
acne. For this reason the Department of Dermatology of
University of Naples has created a personal project for
acne patient with the aim to educate them about their disease and understand the importance of the recommendations. We have created, besides, a new simple questionnaire that can improve the patient-doctor relationship and
better understand patient’s feelings. In our study 50
patients were recruited and this new questionnaire was
administered. The validity of questionnaire was studied
during a period of six months. Inclusion criteria were:
patients aged between 12 and 25 years with moderate
acne, severe acne and the presence of acne from 3
months. The patients were classified according to the
severity of acne (Global Acne Grading System) and they
were interviewed with our questionnaire which assesses
the QoL of patients with acne. This questionnaire allows
us to identify what type of feelings compromises the quality of life. Our results show that in 33% of patients acne
influences the quality of sleep; 75% of patients think that
acne has affected their health; 66% of patients are
depressed; 46% of patients do not feel accepted by society
and 86% of patients think that acne has impaired their
skin. Besides in 70% of patients acne has caused feelings
of shame, while in 80% of patients acne has compromised
serenity and happiness. The results obtained from our
experience both with this new questionnaire and the personalized project for acne patient have improved compliance and quality of life of the patients .
Key words: Acne, Counseling, compliance.
The prevalence of acne is highest
between 16 and 18 years, with an incidence ranging between 75% and 98%. Acne is not only a
problem of the adolescents, because an high percentage of 30-40 years subjects can be affected 1.
The psychological impact of acne is evident especially in timid and sensible patients; both their selfconfidence and their relationships are compromised. Acne can be considered a social disease as
it affects patient’s psychology 2. Counseling is an
intervention of receiving, listening, understanding
and clarification towards the patient. It is important
for the dermatologist understanding how young
patient live this distress 3.
In 2006, we interviewed 238 patients (160 F e 78
M; mean age: 20.86), showing that acne causes
significant distress (57%), and this is more evident
54
among women (66%). Discomfort is more evident
in twenty years patients, and in 47% of patients
compromise self-confidence with a reduction of
social life in 49% of cases.
Furthermore, the scars are a source of distress in
56% of patients and 45% of them do not like their
photographic image. 57% of women use cosmetics
to cover up acne about once a day and 21% of
patients, in both sexes, use sunlamps. Recent
french study shows beneficial effects of a medical
corrective make-up on the QoL of patients in various facial dermatoses 4. Poli F. et al. analyzed the
point of view of adolescents patients, using results
of questionnaire study in 852 french individuals 5.
A questionnaire was administered to youth by telephone helpline, most respondents (66.2%) had
experienced acne symptoms, which were mild in
Volume 3, n. 2, 2012
50.2% of cases and severe in 16% of cases. Often,
acne had been long-lasting (> 12 months in 49.6%
of cases). Many thought that gender, excess
weight, eating dairy products, and physical activity did not influence acne, and that frequent washing could improve acne. Eating chocolate and
snacks, smoking cigarettes, sweating, not washing,
touching/squeezing spots, eating fatty foods, using
make-up, pollution, and menstruation were
thought to worsen acne. The majority (80.8%) did
not believe acne to be a disease, but rather a normal phase of adolescence, yet 69.3% agreed it
should be treated. There was a preference for topical vs. systemic treatment. Many (38.6%) of the
respondents with acne had not consulted a physician. Almost two-thirds of respondents wanted
more information about acne. These data showed
that patient with acne is often confused, stressed
and suffering, especially when he has practiced
many therapies and they are affected by a long history of acne.
For this reason at outpatient of Department of
Dermatology of University of Naples we have created a personal project for acne patient. The importance of creating a personal project for acne patient
is based to the concept that to educate the patient
about their disease and understand the importance
of the recommendations can be helpful for its compliance. The personalized written action plan,
compiled by doctors and adapted to the specific
needs of each patient has this aim. The personalized project for acne patient explain them and to
their parents the progress of the disease, the possible treatments and its risks and benefits. From our
Figure 1
questionario acne
su paziente con GAGS 39.
55
Volume 3, n. 2, 2012
experience, providing brochures with these information both to parents and to patients can be useful for compliance and adherence treatment.
Written materials also can be effective tools for
reinforcing information and instructions provided
directly to the patients and parents in clinical
encounters. We provide a guide to home for parents in which there are the answers to the most
common parents’ questions, for example about the
causes of acne, the different type of acne (preadolescent and adult) and treatments (topical and oral)
and their side effects. We also provide the materials to the patient to explain simply what are the
actions to do during the day. In our experience,
parents often ask how to approach during the summer, what are the right recommendations and what
is truth or false about acne. The provided material
is not a substitute to relationship with the specialist, but an integral part of it. In conclusion, a personal project for the acne patient has the purpose
of improving both the observance of the treatment
and the quality of life of patients and their families.
In our experience the patients show a greater
adherence to therapy if we use their images
obtained from a Reveal photo imager system, to
assess the changes before and after treatment.
Evaluating with the patient the clinical improvement may help compliance to the therapy and
improve the quality of life. During clinical encounters we not only assess the severity of acne, but
also we evaluate the patient’s perception of the
disease.
For this reason, we have created a new simple
questionnaire can improve the patient-doctor relationship and better understand patient’s feelings
(Figure 1).
In our study 50 patients were recruited, and this
new questionnaire was administered. The validity
of questionnaire was studied during a period of six
months. Inclusion criteria were: patients aged
between 12 and 25 years with moderate acne,
severe acne and the presence of acne from 3
months. The patients were classified according to
the severity of acne (Global Acne Grading System)
and they were interviewed with our questionnaire
which assesses the QoL of patients with acne. The
first part of the questionnaire included questions
about sex and age, while the second part included
10 questions that evaluated, on a scale from 1 to
10, how acne influence on the quality of life in the
last month. This questionnaire allows us to identify what type of feelings compromises the quality
of life. Our results show that in 33% of patients
acne influences the quality of sleep; 75% of
patients think that acne has affected their health;
66% of patients are depressed; 46% of patients do
not feel accepted by society and 86% of patients
think that acne has impaired their skin. Besides in
70% of patients acne has caused feelings of shame,
while in 80% of patients acne has compromised
serenity and happiness. From our data and our
experience with this new questionnaire the personalized project for acne patient can improve compliance and quality of life of the patients .
References
1. White GM. Recent findings in the epidemiologic evidence,
classification, and subtype of acne vulgaris. J Am Acad
Dermatol 1998; 39:S34-7.
2. Fried RG, Wechsler A. Psychological problems in the acne
patient. Dermatol Ther 2006; 19(4):237-40.
3. Thiboutot D, Dréno B, Layton A. Acne counseling to improve
adherence. Cutis 2008; 81(1):81-6.
56
4. Peuvrel L, Quéreux G, Brocard A, et al. Evaluation of Quality
of Life after a Medical Corrective Make-Up Lesson in Patients
with Various Dermatoses. Dermatology 2012.
5. Poli F, Auffret N, Beylot C, et al. Acne as seen by adolescents:
results of questionnaire study in 852 French individuals. Acta
Derm Venereol 2011; 91(5):531-6.
Volume 3, n. 2, 2012
Aurora Tedeschi, Federica Dall’Oglio, Laura Guzzardi, Giuseppe Micali
Dermatology Clinic, University of Catania, Italy
Cosmetics and acne: a primer
Aurora Tedeschi
SUMMARY
A correct cosmetic approach plays
an important role in the management of patients with acne and
should not be underestimated, especially considering that most of the topical therapies may
cause stratum corneum barrier dysfunction. Indeed, cosmetics may help to minimize common side effects from
systemic agents such as retinoids or topical ones including benzoyl peroxide, retinoids, and antibiotics. If correctly prescribed and used, cosmetics may then have a synergist effect to the standard treatments for acne.
The most advanced cosmetics for acne may contribute to
obtain some clinical improvement better if associated to
standard medications. In this regard the dermatologist's
advice is very important.
Precise indications about cleansers, sebum controlling,
anti-inflammatory or corneolytic agents, as well moisturizers and photo-protective agents should be part of management of acne patients. Advices about shaving in males
and make-up/camouflage techniques in women should
also be provided.
In conclusion, an optimal cosmetic approach represents a
valuable support to conventional pharmacological therapy that however remains the main approach
Key words: Acne, cosmetics, topical treatment, cleansing, sebum controlling agents, anti-inflammatory agents,
corneolytics, moisturizers, photo-protective agents, shaving products, camouflage.
Introduction
Pharmacological treatments for acne
remain the principal approach and the use of cosmetics, if correctly prescribed, may contribute to
clinical improvement.
In Table 1 some general indications about cosmetic
use in acne patients are listed. In order to avoid cosmetics and/or procedures that may worsen acne, it
is necessary to teach patients to use the most
appropriate cosmetics, chosen in consideration of
ongoing pharmacological therapy as well as acne
type and severity 1.
Table 1.
General indications for the use
of cosmetics use in acne patients.
• Use appropriate cleanser, chosen in consideration of acne severity and
concurrent pharmacological therapy. Avoid aggressive or potent skin
cleansers.
• Wash the face twice daily with warm water; do not rub the face.
Remember that compulsive washing causes “acne detergicans”.
• Avoid the use of cleansing milk, especially in oily/ shiny skin, preferring
the use of water solutions that do not require rinse after use and are
well-tolerated.
• Avoid the use of astringents or toners, if not specifically recommended.
• Use a facial absorbing mask or scrub, 3-4 times a week, in oily skin and
comedonic acne.
Cosmetics and cosmeceutics
• Use the most appropriate sebum controlling or corneolytics agents in
consideration of acne type/ severity, avoiding overuse.
“Any preparation designed to be applied
to the body (face, hair, teeth) for the purpose of
cleansing, beautifying, promoting attractiveness,
or altering the appearance without affecting the
• Always use light and non-comedogenic moisturizers. During summer
avoid lengthy mid-day sun exposure and use appropriate photoprotection
indicated for acne skin.
57
Volume 3, n. 2, 2012
body’s structure or function is defined as cosmetic” 2, 3. Because of recent data show that many cosmetic products previously thought to be inert have
effects on the skin a new group of products, called
cosmeceuticals, has been introduced 4. They “may
have little pharmaceuticals activity and minimal
potential side effects and would be prescribed for
those indications in which cosmetics are usually
indicated” 5. The Federal Food, Drug and Cosmetic
Act does not recognize the “cosmeceutical” term,
for these reasons cosmeceuticals are still classified
either as drugs or cosmetics. In this article we will
discuss about cosmetics in general, even if for some
of them this term may seem restrictive.
Cosmetics and acne: background
In the last two decades many cosmetics
have been linked to the onset of some clinical forms
of acne. In particular, a type of acne, called “acne
cosmetica”, was related to the application of topical
products, especially greasy cosmetics able to induce
a comedogenic effect. This type of acne, clinically
characterized by tiny whiteheads clustering over the
cheeks, forehead and chin may also affect people
who are usually acne free 6-8. Its onset usually follows the use of some cosmetics for few weeks or
months and disappears when discontinued.
Comedogenicity is a slow process causing the
induction of whiteheads and blackheads that should
be distinguished by acnegenicity, that indicate a fast
process due to follicular irritation, inducing the production of papules and pustules 9. A substance not
comedogenic at low concentrations may become
comedogenic at higher concentration 6, 10.
Based on these considerations, cosmetics for acne
should be non comedogenic and non acnegenic.
Table 2.
Cosmetics for acne.
• Cleansers
• Sebum controlling agents
• Antinflammatory agents
• Corneolytics
• Moisturizers
• Photoprotective agents
• Shaving products
• Camouflage
Use of cosmetics in patients with acne
Different types of cosmetics can be used
in patients affected by acne and Table 2 lists the
various types of cosmetics for acne. Importantly,
most of them are formulated specifically for acne
skin and may contain some or a mixture of active
ingredients 11.
Hygiene and cleansing
Skin cleansing is an essential part of skin
care. It consists in a procedure that remove liposoluble, hydrosoluble and insoluble dirt through natural or synthetic surfactants 1. Several types of
cleansers are available with different mechanism
of action. Table 3 details mechanisms of cleansing
and types of cleansers available. Surfactants represent the most important group; they act decreasing
the surface tension resulting from skin dirt
removal. Table 4 lists the different types of surfactants, detailing advantages and disadvantages.
How choose the most appropriate cleanser? It is
important to note that the use of aggressive and
Table 3.
Type of cleansers and mechanism of cleansing.
58
Cleanser
Mechanism of action
Surfactants (natural soap and syndet)
Remove all type of dirt
Make up removers (cleansing milk, tonics, water solutions)
Remove liposoluble dirt
Astringent cleansers (paste or mud mask containing absorbent products)
Remove liposoluble dirt
Abrasive cleansers (vinyl mask and scrubs)
Remove insoluble dirt
Volume 3, n. 2, 2012
Table 4.
Different type of surfactants: advantages and disadvantages.
• Anionic surfactants are characterized by surface-active ion negative charged. Soap is the prototype of this category. They are excellent cleansers that remove
all type of dirt and are easy to wash. They also increase cutaneous pH that will return to normal levels after 4 hours.
• Cationic surfactants have positive charge on the surface-active ion. They have antimicrobic and antibacterial activity and most of them are used in hair
products because of their keratin affinity.
• Ampholitic surfactants characterized by both positive and negative charges that give variable tensioactive properties. They allow a mild cleansing.
• Non ionic surfactants are characterized by multiple small uncharged polar groups. They allow a mild cleansing.
• Syndet are obtained through a sophisticated manifacturing process in which weak organic acids are added to the formulation to obtain a pH close to normal
skin. They allow a mild cleansing and are more expensive than generic soap. Moreover, they may contain antiacne ingredients (10, 11) or moisturizers and
soothing agents.
strong cleansers, often used to remove the typical
acne patient’s skin oiliness, can cause erythema
and irritation (Figure 1). This habit should be
avoided since they may cause a paradoxal form of
acne called “acne detergicans”. This condition,
clinically characterized by papules, pustules and
comedones, is related to a paradoxal sebaceus
hypersecretion, that may result in increased chance
for growing pathogenic bacteria and skin infection.
The ideal cleanser for acne patients should be noncomedogenic, non-acnegenic, non irritating and
non-allergenic. Among the different surfactants
available, the so-called “natural soap” should be
avoided in acne patients because of their strongly
alkaline pH. Dermatologic bars and specifically
designed liquid, gel or foam cleansers, are synthetic surfactants, chemically different from natural
soaps, obtained through a sophisticated manufacturing process in which weak organic acids are
added to formulations in order to obtain a pH close
Figure 1
Erythema after
using aggressive
detergents.
to normal skin, so to provide a mild cleansing.
They may be enhanced with antiacne agents such
as benzoyl peroxide, sebum controlling or corneolytics substances as well as moisturizers and
soothing agents 12, 13. They are more expensive
than natural soaps. Among the different formulations, liquids are generally preferred to the solid
ones because they are milder and non irritating; gel
and foam formulations are in general well appreciated by youngsters 14.
Other syndets suitable for acne skin include surfatted soaps, rich in lanolin, almond oil and glycerol,
suggested by some authors, to improve the typical
xerosis observed during retinoid treatments and
lipid-free cleansers characterized by no fragrances,
colorants and preservatives substances, best if used
at the beginning of therapy in order to facilitate
cutaneous adaptation to treatments 2.
Among make-up removers, cleansing milk are the
most indicated for acne patients, reminding that they
require rinse with water or the subsequent use of
astringent lotions. Recent make-up remover formulations for acne include water solutions enhanced
with corneolytics or soothing agents. They are welltolerated and do not require rinse 15. Astringents or
toners are lotions containing alcohol or propylene
glycol. They are used after lipid free or milk
cleanser to remove other cleanser residues 9. The socalled “earth-based mask” containing absorbent
products such as clay, bentonite or kaolin, belongs to
this category of cleanser.
Finally, abrasive cleansers are mechanical exfoliants, including vinyl masks and scrubs that remove
insoluble dirt or induce a comedolytic effect 9, 15.
59
Volume 3, n. 2, 2012
Table 6.
Common antinflammatory agents for topical use.
• Nicotinamide
• Undecyl-ramnoside
Figure 2
Seborrhea in
patient with
comedonal acne.
• Zync
• Phytosphingosine
• Piroctone olamine
• Salicylic acid
• Sulfur derivatives
• Omega-3 and omega-6 fatty acids
• Resveratrol
Table 5.
Common sebum controlling agents for topical use.
• Carboxymethylcysteine lysine
• Derivatives of carboxylic acids
• Nicotinamide
• Piroctone olamine
• Pyridoxine hydrochloride
• Serenoa repens
topical or systemic pharmacological therapies for
acne have also an anti-inflammatory action and the
use of cosmetics with antinflammatory properties
may seems reasonable. Table 6 lists the most common antinflammatory agents found in cosmetic
products 18-19. In addition, the use of dietary supplement containing omega-3 and omega-6 fatty
acids could be an adjunctive treatment.
• Sulphur derivatives
Corneolytics
Sebum controlling agents
Sebum is produced by sebaceous glands
controlled by androgens. An overproduction of
sebum is frequently seen in acne patients (Figure 2).
Few drugs such as systemic retinoids, birth-control
pills, and spironolactone are indicated to regulate the
overproduction of sebum. Sebum-controlling agents
are cosmetic products used to absorb and retain
sebum 16. Their action seems mostly due to the presence of so-called “matifiant” agents, like metacrylate
copolymere mychrosphere 14. Their role on 5 reductase or on sebaceous glands activity need to be
further confirmed 17. Table 5 provides a list of substances with sebum controlling properties.
Antinflammatory agents
Recent understanding in the pathogenesis
of acne has suggested a pilot role of inflammatory
events in the development of acne lesions. Most of
60
Corneolytics are cosmetics that cause intercorneocyte cell detachment so to induce a
comedolytic effects. They include -hydroxyacids,
such as glycolic acid, lactic acid and citric acid;
hydroxyacids like salicylic acid, and -ketoacids
such as pyruvic acid in concentrations varying from
2% to 7% and up with glycolic acid as well as retinaldehyde and retinol, at concentration of 1% or
Figure 3
Comedones
and acne.
Volume 3, n. 2, 2012
Table 7.
Common corneolytics agents for topical use.
Table 8.
Common moisturizers agents for acne.
• Citric acid
• α-bisabolol
• Glycolic acid
• Aloe
• Lactic acid
• Enoxolone
• Mandelic acid
• Eau termale
• Pyruvic acid
• Jaluronic acid
• Salicylic acid
• Propylen Glycol
• Retinaldehyde
• Resveratrol
less 20, 21. This group of cosmetics is particularly
indicated for comedonal acne, making comedones
more superficial and at the same time smoothing the
skin (Figure 3).
They represent a valid and useful option for patients
that do not tolerate prescription topical retinoids and
during maintenance therapy 2, 22. The most common
corneolytics are listed in Table 7.
Moisturizers
Moisturizers are cosmetics designed to
hydrate the stratum corneum and make the skin soft
and sooth. The hydratation is an important issue in
acne patients considering that many treatments, such
as topical and systemic retinoids as well as benzoyl
peroxide, may cause skin xerosis (Figure 4).
Moisturizers for acne patients are mostly humec-
tants and emollients 1. Table 8 lists the most common moisturizers indicated in acne patients.
Specific lines of moisturizers indicated for patients
receiving oral isotretinoin, are available. Some of
them are designed to improve cheilitis, dry eyes or
nose-bleeding.
Photoprotective agents
UV radiation may have a mild anti-inflammatory effect, but it also promotes infundibular
hyperkeratosis. For these reasons acne tend to get
worse after returning from summer holidays 13.
Therefore, it is important to educate patients to
avoid lengthy mid-day sun exposure and the use of
products containing vegetables oils, considered as
comedogenic 10. Photoprotection is strongly recommended in all acne patients especially in those
taking oral/topical retinoids, oral antibiotics and
birth-control pills.
Shaving products
Figure 4
Desquamation
and erythema
after topical
retinoid
application.
In male patients with inflammatory acne,
daily shaving should not be recommended. Specific
non-irritating foams or gels enhanced by antibacterial agents such as triclosan and zync, along with the
use of non-comedogenic and soothing after shave
products should be suggested 13 in order to prevent
or minimize irritations or infections.
Camouflage
Camouflage, or corrective maquillage, is
a make-up technique able to minimize some unaes-
61
Volume 3, n. 2, 2012
Figure 5
Patient with moderate acne before (a)
and after (b) camouflage.
A
B
Figure 6
Patient with severe acne before (a)
and after (b) camouflage.
A
thetic post-inflammatory disorders such as hyperpigmentations typical of acne 2-9.
The benefit of covering inflammatory lesions with
designed corrective cosmetics has scientifically
been proven. Generic and commercial cosmetic
make-up is not indicated for acne patients because
of its potential comedogenic role 7, 23-26.
The approach to corrective cover cosmetics (CCC)
consists of two steps. The first one is a preliminary
clinical evaluation, through a questionary, in order to
evaluate need and realistic expectations for CCC 1.
The second one consists in the application of green
or yellow undercover, used, rispectively to minimize
62
B
inflammatory lesions and brownish hyperpigmented
spots. The most appropriate foundation color (liquid
or creamy formulations) is then applied and after this
a powder is gently pressed 1, 9, 27.
Lastly, additional colored facial cosmetics, including eye shadow, eyeliner, and mascara may be
applied to improve final appearance (Figures 5a5b, 6a-6b).
The use of cosmetics plays an undoubt role in the
management of acne. Their correct choice may
enhance the therapeutic outcome as well as patient's
compliance.
Volume 3, n. 2, 2012
References
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2. Toombs EL. Cosmetics in the treatment of acne vulgaris.
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of cosmetics. Hautarzt 2010; 61:126-131.
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17. Seiffert K, Seltmann H, Fritsch M, et al. Inhibition of
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63

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