E. Novembre - Sezione SIAAIC Toscana

SIAIC Toscana-Emilia Romagna
San Marino
Allergia e mastocitosi in età pediatrica
Elio Novembre
Dipartimento di Scienze della Salute
AOU Meyer, Firenze
Cosa fare in questo bambino?
Ha 8 mesi, viene per una sospetta AA : a 6 mesi vomito e
orticaria dopo ingestione di una minestra con zucchina,
carota, finocchio semolino e 1 cucchiaio di parmigiano.
Portato al DEA e trattato con antiH1.
Ha anche maculo papule sul tronco e gli arti, da sempre
dicono i genitori, non prudono, ma talvolta si arrossano,
senza particolari fattori scatenanti. Lo visitiamo = ndn, in
particolare non organomegalia, solo alcune macule rossastre
su tronco e arti
Cosa fare in questo bambino?
Fa il prick: latte 0, uovo 2, merluzzo 0, grano 3,
soia 0, patata 0 , carota 0, mais 0, riso 0, Pbyp
zucchino 0
Vediamo se c’è il segno di Darier= positivo.
Visita dermatologica= Mastocitosi cutanea
(orticaria pigmentosa)
Prevalenza e insorgenza della
mastocitosi
- Prevalenza sconosciuta (circa 1/100000)
- Insorgenza
• 55% dei casi nei primi 2 aa
• 10% in bambini 2- 15 aa
• 35% dopo i 15 aa
- M=F
Clinical classification of cutaneous mastocytosis in children*
I Urticaria pigmentosa (70–90%)
II Mastocytoma (10–30%)
III Diffuse cutaneous mastocytosis (1–3%)
• Darier's sign positive in all forms.
Orticaria pigmentosa
Di solito lesioni multiple; sintomi lievi
• Macule, placche or noduli
• Interessamento viscerale e osseo raro and benigno
• Prurito, arrrossamento, diarrea occasionale
• Prognosi: buona, con risoluzione spontanea nell’ 80% dei casi
entro la pubertà
Mastocitoma
• Una
o due lesioni: noduli, placche o macule con frequente vescicolazione
• Prurito, flushing e diarrea rari
• Non interessamento viscerale o osseo
• Prognosi: molto buona con risoluzione spontanea nella grande maggioranza
di casi
Mastocitosi cutanea diffusa
Diffusa infiltrazione cutanea (pelle coriacea) , eritema, vescicole
• Frequenti arrossamenti, prurito, diarrea cronica, e complicanze come lo
shock ipovolemico, sanguinamento.
• Interessamento viscerale e osseo frequente e benigno
• Prognosi: discreta. Le bolle tendono a scomparire. Persistenza di orticaria,
iperpigmentazione e cute coriacea. La insorgenza neonatale può essere
correlata a esito fatale.
• Cosa fare in questo bambino?
- Allergia alimentare (grano, uovo?)
- Mastocitosi (Orticaria pigmentosa)
§
§ A skin biopsy is recommended unless the exam is unambiguous
Fried AJ Curr Asthma Report
Cosa fare in questo bambino?
Prescriviamo gli esami per sospetta mastocitosi cutanea
- emocromo completo con formula,
- test di funzionalità epatica,
- sideremia,
- dosaggio plasmatico della triptasi
- facciamo lo SCORMA
- I genitori rifiutano la biopsia
+ Unicap per gli allergeni sospetti
A Estensione= 1% (Mastocitoma solitario)
100%( Mastocitosi diffusa)
B Intensità= 1 lesione tipica valutata in base a
pigmentazione/ eritema, vescicolazione
segno di Darier (0-3)
8
C Segni soggettivi = 0-10
1
VALORI FRA 5.2 E 100
1
3
17.7
Heide R et al Clin Exp Dermatol 2008
Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease
severity parameters in childhood and adult cutaneous mastocytosis
R. : Heide et al
Clinical and Experimental Dermatology
Volume 34, Issue 4, pages 462–468, June 2009
METHODS:
The SCORMA Index in 64 patients (31 children and 33 adults) was compared with serum tryptase levels. The results
of the first visit at which SCORMA and tryptase were evaluated were analysed.
RESULTS:
There was a positive correlation between the SCORMA Index and serum tryptase levels, indicating the value of the
SCORMA Index in the assessment of mastocytosis with skin involvement.
CONCLUSION:
The results of this study showed that the SCORMA Index is a useful tool for evaluating the severity of cutaneous
mastocytosis. The correlation between the SCORMA Index and serum tryptase levels underlines the benefit of the
SCORMA Index as a clinical tool. Repeated SCORMA Index measurements can provide a rapid impression of changes
in the clinical state of mastocytosis. This is particularly relevant in children, because taking blood samples from this
group is much more difficult.
Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease severity
parameters in childhood and adult cutaneous mastocytosis
Heide et al Clinical and Experimental Dermatology 2008
Cosa fare in questo bambino?
Risultato esami:
- RAST grano 10, uovo 0.6
- Triptasi sierica = 5
Eseguiamo TPO uovo=ndn
Dimettiamo il pz solo con dieta di esclusione per
grano
Programmiamo un controllo dopo 6 mesi
Quale follow-up in questo bambino?
Allergia alimentare : monitoraggio clinico e
allergologico e individuazione tempi per TPO grano
Orticaria pigmentosa : monitoraggio clinico e della
triptasi
Storia naturale della mastocitosi
cutanea del bambino
La storia naturale della mastocitosi cutanea
è benigna. Nella maggior parte dei bambini
le lesioni cutanee tendono a scomparire con
la pubertà.
Hartmann K., et al. Int Arch Allergy Immunol 2002.
Brockow K. Immunol Allergy Clin North Am 2004.
Follow-up of paediatric
mastocytosis:a review of 180 patients
Ris. Com
Ris. Parz.
Nessuna mod.
Mastocitoma (27)
20 (74%)
5 (18%)
2 (7.5%)
Durata media (aa)
7.4
5.6
2.4
Orticaria pigmentosa (62)
35 (56%)
15 (24%)
12 (19.4%)
Durata media (aa)
10.2
7.1
2.8
Ben-Amitai D et al IMAJ 2005
Fattori di rischio nel bambino
• Elevata estensione delle lesioni cutanee
• Aumento valori triptasi basale
• Blistering diffuso
Brockow K. Immunol Allergy Clin North Am 2014
Allergia e mastocitosi nella età
pediatrica
Differences between Mast Cell Activation in Mastocytosis and during IgE-mediat ed
Allergic H ypersensitivity
Masto cytosis
Key cell
Recep tor
Me chan ism
Trig gers
Serum tr yp tas e after t he
clinical reactio n
Bas al se rum try pt ase
Skin te sts
Mast cell
C-kit r eceptor (D816V mutati on)
Non IgE-medi ated
Nonspecific (psychological,
pha rm acological, mechanica l
facto r s and t em per atu r e
cha nges )
Incre ased
Usually incre ased (>20 µg/ l) in
SM
Less t han 20 µg/ l in CM
Negative
IgE-me diate d Alle rgic
Hyper sen s itivity
Mast cell and bas ophil
Fc RI
IgE-cr oss-linki ng by aller gen
Specific (IgE antib ody)
Incre ased
Not incre ased
Positive
Mastocytosis and atopy: a study of 33 patients with
urticaria pigmentosa.
Thirty-three patients with histologically verified urticaria pigmentosa were studied for
coexisting atopic disease by means of history, skin prick testing with five common
inhalants and serological investigation for total IgE and specific IgE antibodies to five
common inhalants. The prevalence of atopy in urticaria pigmentosa was similar to
that observed in the normal Swiss population, both on the basis of history (7/33 = 21%)
and of positive skin prick tests to common inhalants (12/33 = 36%). However, total
serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a
control group of 52 Swiss blood donors of comparable age and sex distribution
(geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies
to common inhalants were also observed less frequently in urticaria pigmentosa patients
than in controls, although this difference was not statistically significant. Low total and
specific IgE values in patients with urticaria pigmentosa may be explained by increased
absorption of circulating IgE to abundant tissue mast cells.
Muller U et al, Allergy. 1990.
Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric
patients with mastocytosis in Spain: a study of the Spanish network on
mastocytosis (REMA).
-A questionnaire was given to 210 patients with mastocytosis (cutaneous mastocytosis (CM), n=8; indolent
-systemic mastocytosis (ISM), n=140 (125 with skin involvement); well-differentiated systemic mastocytosis
(WDSM), n=5; Isolated BM mastocytosis (BMM), n=3 and mastocytoma, n=1) to evaluate the history of asthma,
rhinitis, conjunctivitis,atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop infant
(aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done
to 72 patients.
RESULTS:
The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Allergic diseases
coexist in patients with mastocytosis with similar frequency as compared with the general population. The coexistence
of atopy does not influence mastocytosis-associated symptoms-
Gonzales de Olano D et al, Clin Exp Allergy. 2007
Mastocitosi e rischio di anafilassi
nella età pediatrica:
sono necessarie particolari
misure preventive?
Clinical classification of cutaneous mastocytosis in children*
I Urticaria pigmentosa (70–90%)
II Mastocytoma (10–30%)
III Diffuse cutaneous mastocytosis (1–3%)
• Darier's sign positive in all forms.
La mastocitosi al Meyer
Storia clinica ed esami diagnostici in pazienti con orticaria pigmentosa
Etˆ di comparsa
Biopsia
Triptasi ematica
Paziente 1
Prima visita
(etˆ )
2008 (4 mesi)
3 mesi
No
5
Paziente 2
2014 (24 mesi)
12 mesi
Si
5
Paziente 3
2013 (8,5 mesi)
1 mese
Si
4
Paziente 4
2012 (26 mesi)
1 mese
No
4,7
Paziente 5
2014 (12 mesi)
11 mesi
No
4
Paziente 6
2014 (64mesi)
3 mesi
No
5
Paziente 7
2014 (6 mesi)
6 mesi
No
5
Età pr ima visita (media) = 20,6 me si
Età di com par sa (media) = 5,3 mesi
Tript asi em atic a (media) = 4,6
AA= 1/7
SOD Allergologia- Servizio Dermatologia
La mastocitosi al Meyer
Storia clinica ed esami diagnostici in pazienti con mastocitoma
Etˆ di comparsa
Biopsia
Triptasi ematica
Paziente 1
Prima visita
(etˆ )
2012 (24 mesi)
Alla nascita
No
5
Paziente 2
2011 (11 mesi)
Alla nascita
No
6
Paziente 3
2012 (9 mesi)
8 mesi
No
5
Paziente 4
2014 (36 mesi)
24 mesi
No
3
Paziente 5
2012 (15 mesi)
3,5 mesi
No
6
Età pr ima visita (media) = 19 mesi
Età di com par sa (media) = 7,1 mesi
Tript asi em atic a (media) = 5
AA= 0/5
SOD Allergologia- Servizio Dermatologia
Biopsia cutanea bambino di 12 m con mastocitosi
cutanea
Dr. Greco- Prof. Buccoliero
Upper panel: clinical aspects of cutaneous mastocytosis (a line): left: A child with maculopapular cutaneous
mastocytosis: large red brown disseminated maculo-papules and plaques/middle: a child with diffuse cutaneous
mastocytosis: diffuse skin infiltration and bullae/right: an adult with urticaria pigmentosa: little red brown
disseminated macules. Middle panel: histological aspects of cutaneous mastocytosis (HES × 25) (b line): left:
mast cell infiltration around blood vessels with epidermal pigmentation/middle: dense mast cell infiltration
throughout the entire dermis/right: mast cell infiltration around blood vessels with vascular dilatation.
Lower panel: bivariate plots displaying flow cytometric data obtained from fresh peripheral blood samples (
c line): MC precursor previously identified as CD34-CD117 + circulating cells as illustrated in adult case (circle)
are absent in paediatric cases.
J Eur Acad Dermatol Venereol. 2014 Jul;28(7):967-71
Misure preventive
I Urticaria pigmentosa (70–90%)
Casi particolari
II Mastocytoma (10–30%)
No
III Diffuse cutaneous mastocytosis (1–3%)
SI ?
Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk
factors in 120 patients
In children, the extent (A, P < 0.01) and density of skin lesions (B, P < 0.01) did correlate with
anaphylaxis, but not in adults. Serum tryptase levels (C) were higher in children (P < 0.03) and
adults (P < 0.01) with anaphylaxis, but diaminooxidase levels did not correlate with anaphylaxis
(D)
Brockow K et al Allergy 2008
Bambina di 15 mesi . I genitori vivono a Parigi.
Padre con asma e allergia alimentare
Bronchiolite a 3 mesi, poi bronchiti asmatiformi, In terapia
con Flixotide.
Notata la presenza di 3 elementi maculosi sul tronco.
Fatta diagnosi di orticaria pigmentosa, consigliata dieta
priva di AIL + farmaci da evitare + precauzioni per anestesia.
SCORMA 26
Dosaggio triptasi= 4
IgE totali 22
RAST inalanti negativo
In childhood, the risk for anaphylactic episodes was limited to
children with extensive skin disease, but nonexistent for children
with mastocytoma or limited macular lesions.
Brockow K et al Allergy 2008
La prevenzione nella mastocitosi del
bambino
- Rischio di anafilassi durante anestesia
- Rischio di anfilassi da punture di insetti
-Evitare cause di degranulazione immunologica e non
immunologica del mastocita:
- alimenti istamino liberatori
- FANS
?
Anesthesia in children with mastocytosis--a case
based review
Reported complications of anesthesia in pediatric patients with mastocytosis
Source
Age (years)
Diagnosis
.
Coleman et al
James et al.
Damodar et al.
Carter et al.
4 and 5
No range given
14
0.5–20
UP
12 UP 3 mastocytoma
Extracutaneous mastocytoma
13 CM, 8 SM, one mastocytoma
Complications
None
Two rashes with codeine
Hypotension and bronchospasm
Flushing in two vomiting in four
UP, urticaria pigmentosa, GA, general anesthesia
Ahmad N et al, Paediatr Anaesth. 2009 Feb;19(2):97-107.
High prevalence of anaphylaxis in patients with systemic mastocytosis – a single‐
centre experience
- 84 pz adulti con MS
Gulen T et al. Clinical & Experimental Allergy 2013
Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk
factors in 120 patients
Parents of four children reported acute anaphylactic reactions after:
- food intake (n = 2),
- vaccination (n = 1),
- jump into cold water (n = 1),
- without identified cause (n = 6).
*In contrast to adult patients, hymenoptera stings played no part in eliciting
anaphylaxis in children with mastocytosis.
Brockow K et al Allergy 2008
Misure preventive nel bambino con mastocitosi
Children with extensive skin disease and especially active disease forming
blisters, should be anaesthetized with caution (same as in adult) .
Before more data on the tolerance of NSAIDs in children with
mastocytosis, a cautious approach is reasonable.
Bonadonna P et al COACI 2012
GRAZIE PER L’ATTENZIONE
Terapia della mastocitosi cutanea nel
bambino
.
Nelle forme più estese di mastocitosi cutanea o in presenza di una
sintomatologia da degranulazione mastocitaria sono molto utili gli
antistaminici anti-H1 e anti-H2 la cui efficacia nel controllo del
prurito, delle manifestazioni orticarioidi e degli eventuali flush è
stata dimostrata dall’esperienza clinica.
Nei pazienti con una mastocitosi cutanea diffusa o nelle forme
bollose intense può essere indicato l’uso di corticosteroidi .
In taluni casi è stato utilizzato Pimecrolimus in associazione con
antiH1.
Terapia della mastocitosi nel bambino
Il mastocitoma solitario raramente richiede un trattamento poiché
tali lesioni tendono alla regressione spontanea. Tuttavia i bambini
di età superiore ai 2 anni possono giovarsi dell’applicazione di
steroidi topici ad alta potenza, anche in occlusione, della
crioterapia o dell’escissione chirurgica.
Anaphylaxis in patients with mastocytosis: a study on history, clinical
features and risk factors in 120 patients
Therapy of anaphylaxis in patients with mastocytosis
Therapy
Epinephrine
Hospitalization
Antihistamines
Corticosteroids
No therapy
Children (%)
0
25
50
25
25
Adults (%)
11
25
61
46
36
Brockow K et al Allergy 2008
Allergy. 2008 Feb;63(2):226-32.
Anaphylaxis in patients with mastocytosis: a study on history, clinical features and
risk factors in 120 patients.
Brockow K1, Jofer C, Behrendt H, Ring J.
Abstract
BACKGROUND:
Excessive mast cell mediator release may lead to anaphylaxis in patients with mastocytosis. However,
the incidence, clinical features and trigger factors have not yet been analyzed.
METHODS:
To identify risk factors for anaphylaxis in mastocytosis, we determined cumulative incidence, severity,
clinical characteristics, and trigger factors for anaphylaxis in 120 consecutive patients (74 adults, 46
children;), and correlated these with disease severity of mastocytosis, skin involvement, basal total
serum tryptase, and diaminooxidase concentrations.
RESULTS:
The cumulative incidence of anaphylaxis in patients with mastocytosis was higher in adults (49%; P <
0.01) compared with that in children (9%). Only children with extensive skin involvement had
experienced anaphylaxis. In adults, anaphylaxis was correlated to the absence of urticaria pigmentosa
lesions (P < 0.03). Reactions occurred more frequently in adults with systemic (56%) when compared
with cutaneous mastocytosis (13%; P < 0.02). In adults, 48% of reactions were severe, and 38%
resulted in unconsciousness. Major perceived trigger factors for adults were hymenoptera stings (19%),
foods (16%), and medication (9%); however, in 26% of reactions, only a combination of different
triggers preceded anaphylaxis. Trigger factors remained unidentified in 67% of reactions in children
compared with 13% in adults. Patients with anaphylaxis had higher basal tryptase values (60.2 +/- 55
ng/ml, P < 0.0001) in comparison with those without (21.2 +/- 33 ng/ml), but not diaminooxidase levels.
CONCLUSION:
Adult patients and children with extensive skin disease with mastocytosis have an increased risk to
develop severe anaphylaxis; thus, an emergency set of medication including epinephrine is
recommended.
Cutaneous mastocytosis in children: a clinical analysis
of 71 cases
Patients with diffuse cutaneous mastocytosis: 2 years or longer follow-up and outcome
No.
Waters and Lacson 1957 1
Orkin et al.1970 (Review) 7
Onset
Follow-up time
Neonatal
5 years
1–9 months 2.5–10 years
Klaber 1976 1
Meneghin a 1980
6 m.
1
25 years
2 months
Leathery skin
56 years
Willenze et al. 1980
1
?
25 years
Oku et al.1990
2
1 neonatal
5 years
Present series
1
3
5 months
6 years
3–4 months 2–6 years
Outcome
Died of mast cell leukaemia
Regression of bullae, persistent cutaneous
infiltration
Dermographism
Multiple nodules, no hives, no bullae
Cutaneous tumours containing mast cells
Multiple nodules, no hives, no bullae Cutaneous
tumours containing mast cells
Hives, absence of bullae, hyperpigmentation
and leathery skin No bullae, no hives
Hyperpigmentation and leathery skin
Regression of bullae, persistent cutaneous
infiltration Dermographism
AE Kiszewski1, et al Journal of the European Academy of Dermatology and Venereology 2004
Clinical aspects of paediatric
mastocytosis:a review of 101 cases
Lange M et al JEADV 2013; 27:97-102
In conclusione in questo bambino la gestione allergologica
(test allergologici e test di tolleranza) è stata assolutamente
normale senza alcun “occhio di riguardo” per la concidente
mastocitosi.
Ma i bambini con mastocitosi hanno più frequentemente
allergie?
E’ necessario dare loro particolari diete o consigli per
situazioni a rischio?
Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients
with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA).
Thirty-six adult patients (22%) with a median age of 47 years (range; 23 to 74) had a history of
at least one anaphylactic episode. The percentage of males was significantly higher; 26 (72.2%)
vs. 10 (28.8%), P<0.001
According to the category of the disease, the prevalence of anaphylactic
symptoms in adults with ISM, was similar as compared with all the remaining groups; 32/140
(22.85%) vs. 4/23 (17.39%), respectively. Among the 36 adults with anaphylactic symptoms,
specific IgE against a known allergen was detected only in nine cases (25%). In the remaining
27 cases, in 15 no allergen was identified and in 12 cases clinical symptoms appeared after
exposure to a known trigger such as non-steroidal anti-inflammatory drugs (n=4), β-lactams (n=2)
– amoxcyllin/clavulanic, ampicillin –, hymenoptera sting (n=2), amynoglicosides (n=1) –
streptomycin –, phenylephrine (n=1), general anesthesia (n=1).
Gonzales de Olano D et al, Clin Exp Allergy. 2007 Oct;37(10):1547-55
Arch Med Sci. 2012 Jul 4;8(3):533-41. doi: 10.5114/aoms.2012.29409.
Mastocytosis in children and adults: clinical disease heterogeneity.
Lange M et al.
Mastocitosi cutanea diffusa