siaic toscana-emilia romagna san marino · persistenza di orticaria, iperpigmentazione e cute...

Allergia e mastocitosi in età pediatrica

Elio Novembre

Dipartimento di Scienze della Salute

AOU Meyer, Firenze

SIAIC Toscana-Emilia Romagna San Marino

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

Vediamo se c’è il segno di Darier= positivo.

Fa il prick: latte 0, uovo 2, merluzzo 0, grano 3, soia 0, patata 0 , carota 0, mais 0, riso 0, Pbyp zucchino 0

Visita dermatologica= Mastocitosi cutanea (orticaria pigmentosa)


Prevalenza e insorgenza della mastocitosi

• 55% dei casi nei primi 2 aa• 10% in bambini 2- 15 aa• 35% dopo i 15 aa

- Prevalenza sconosciuta (circa 1/100000)- Insorgenza

- 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.


- Allergia alimentare (grano, uovo?)

- Mastocitosi (Orticaria pigmentosa)

Fried AJ Curr Asthma Report 2013

§

§ A skin biopsy is recommended unless the exam is unambiguous

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


Heide R et al Clin Exp Dermatol 2008

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)

C Segni soggettivi = 0-10

VALORI FRA 5.2 E 100

8

1

1

3

17.7

Serum tryptase and SCORMA (SCORing MAstocytosis) Index as disease severity parameters in childhood and adult cutaneous mastocytosis

R. : Heide et al Clinical and Experimental DermatologyVolume 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


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 mastocitosicutanea 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

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

Ris. Com Ris. Parz. Nessuna mod.

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 Hypersensitivity

Mastocytosis IgE-me diated Alle rgic Hyper sen sitivity

Key cell Mast cell Mast cell and basophil Recep tor C-kit r eceptor (D816V mutation) Fc RI Mechanism Non IgE-medi ated IgE-cross-linki ng by aller gen Triggers Nonspecific (psychological,

pha rm acological, mechanica l facto rs and t em peratu re cha nges )

Specific (IgE antib ody)

Serum tr yptas e after t he clinical reaction

Incre ased Incre ased

Basal serum try ptase Usually incre ased (>20 µg/ l) in SM Less than 20 µg/ l in CM

Not incre ased

Skin te sts Negative Positive

Mastocytosis and atopy: a study of 33 patients with urticaria pigmentosa.

Muller U et al, Allergy. 1990.

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.

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).

Gonzales de Olano D et al, Clin Exp Allergy. 2007

-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-

Mastocitosi e rischio di anafilassi nella età pediatrica:

sono necessarie particolari misure preventive?

Clinical classification of cutaneous mastocytosis in children*




• Darier's sign positive in all forms.

Storia clinica ed esami diagnostici in pazienti con orticaria pigmentosa

Prima visita (etˆ )

Etˆ di comparsa Biopsia Triptasi ematica

Paziente 1 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 6 2014 (64mesi) 3 mesi No 5


Età pr ima visita (media) = 20,6 me si Età di com parsa (media) = 5,3 mesi Tript asi em atica (media) = 4,6

La mastocitosi al Meyer

SOD Allergologia- Servizio Dermatologia

AA= 1/7

Storia clinica ed esami diagnostici in pazienti con mastocitoma

Prima visita (etˆ )

Etˆ di comparsa Biopsia Triptasi ematica

Paziente 1 2012 (24 mesi) Alla nascita No 5

Paziente 2 2011 (11 mesi) Alla nascita No 6



Paziente 5 2012 (15 mesi) 3,5 mesi No 6

Età pr ima visita (media) = 19 mesi Età di com parsa (media) = 7,1 mesi Tript asi em atica (media) = 5

La mastocitosi al Meyer

SOD Allergologia- Servizio Dermatologia

AA= 0/5

Biopsia cutanea bambino di 12 m con mastocitosicutanea

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

Casi particolari

No

SI ?

Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients

Brockow K et al Allergy 2008

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)

Bambina di 15 mesi . I genitori vivono a Parigi.

Padre con asma e allergia alimentareBronchiolite 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 dietapriva di AIL + farmaci da evitare + precauzioni per anestesia.

SCORMA 26

Dosaggio triptasi= 4IgE totali 22RAST inalanti negativo

In childhood, the risk for anaphylactic episodes was limited tochildren with extensive skin disease, but nonexistent for childrenwith mastocytoma or limited macular lesions.


- 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

La prevenzione nella mastocitosi del bambino

?

Reported complications of anesthesia in pediatric patients with mastocytosis

Source Age (years) Diagnosis Complications.Coleman et al 4 and 5 UP NoneJames et al. No range given 12 UP 3 mastocytoma Two rashes with codeineDamodar et al. 14 Extracutaneous mastocytoma Hypotension and bronchospasmCarter et al. 0.5–20 13 CM, 8 SM, one mastocytoma Flushing in two vomiting in four

UP, urticaria pigmentosa, GA, general anesthesia

Anesthesia in children with mastocytosis--a case based review

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

Gulen T et al. Clinical & Experimental Allergy 2013

- 84 pz adulti con MS



- 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.

Parents of four children reported acute anaphylactic reactions after:

Bonadonna P et al COACI 2012

Misure preventive nel bambino con mastocitosi

Before more data on the tolerance of NSAIDs in children with mastocytosis, a cautious approach is reasonable.

Children with extensive skin disease and especially active disease formingblisters, should be anaesthetized with caution (same as in adult) .

GRAZIE PER L’ATTENZIONE

. 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 cutanea nel bambino

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.

Therapy of anaphylaxis in patients with mastocytosis

Therapy Children (%) Adults (%)Epinephrine 0 11Hospitalization 25 25Antihistamines 50 61Corticosteroids 25 46No therapy 25 36



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.

AbstractBACKGROUND: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. Onset Follow-up time OutcomeWaters and Lacson 1957 1 Neonatal 5 years Died of mast cell leukaemiaOrkin et al.1970 (Review) 7 1–9 months 2.5–10 years Regression of bullae, persistent cutaneous

infiltrationKlaber 1976 1 6 m. 25 years Leathery skin DermographismMeneghin a 1980 1 2 months 56 years Multiple nodules, no hives, no bullae

Cutaneous tumours containing mast cellsWillenze et al. 1980 1 ? 25 years Multiple nodules, no hives, no bullae Cutaneous

tumours containing mast cellsOku et al.1990 2 1 neonatal 5 years Hives, absence of bullae, hyperpigmentation

and leathery skin No bullae, no hives Hyperpigmentation and leathery skin

1 5 months 6 yearsPresent series 3 3–4 months 2–6 years 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 assolutamentenormale 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 persituazioni 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).

Gonzales de Olano D et al, Clin Exp Allergy. 2007 Oct;37(10):1547-55

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<0.001According 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), -lactams (n=2)β – amoxcyllin/clavulanic, ampicillin –, hymenoptera sting (n=2), amynoglicosides (n=1) – streptomycin –, phenylephrine (n=1), general anesthesia (n=1).

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

siaic toscana-emilia romagna san marino · persistenza di orticaria, iperpigmentazione e cute...

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