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. 2025 Aug 1;161(8):855-862.
doi: 10.1001/jamadermatol.2025.1488.

Characteristics and Therapeutic Strategies for Diffuse Cutaneous Mastocytosis

Paula Pernea  1 , Cecile Méni  1   2 , Julien Rossignol  2   3 , Hélène Aubert  4 , Sébastien Barbarot  4 , Nathalia Bellon  1 , Anne-Claire Bing-Lecointe  5 , Julie Bonigen  1 , Anne-Claire Bursztejn  6 , Delphine Carré  7 , Alice Phan  8 , Eve Puzenat  9 , François Skowron  10 , Pierre Vabres  11 , Anne Welfringer-Morin  1 , Philippe Drabent  12 , Sylvie Fraitag  12 , Nicolas Garcelon  13 , Julie Agopian  14   15 , Patrice Dubreuil  14   15 , Stéphanie Mallet  16 , Stéphane Barete  17 , Michel Arock  18 , Olivier Hermine  2   3 , Christine Bodemer  1   2 , Laura Polivka  1   2 ; CEREMAST network; and the
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Characteristics and Therapeutic Strategies for Diffuse Cutaneous Mastocytosis

Paula Pernea et al. JAMA Dermatol. .

Abstract

Importance: Diffuse cutaneous mastocytosis (DCM) is a rare and severe subtype of pediatric mastocytosis, characterized by extensive skin involvement. Comprehensive studies on the clinical and molecular features of DCM remain limited.

Objective: To describe the clinical, molecular, and treatment-related characteristics and outcomes of a cohort of pediatric patients with a clinical presentation of DCM.

Design, setting, and participants: This retrospective study analyzed pediatric patients with a clinical presentation of DCM from January 1996 to October 2023 at Necker Children's Hospital in Paris, France.

Main outcome and measures: Data on clinical presentation, laboratory results, and KIT sequencing from skin biopsies and bone marrow, if available, were collected and analyzed. These data were compared with previously published findings from a pediatric cohort with maculopapular cutaneous mastocytosis (MPCM).

Results: The study included 33 pediatric patients, 18 (54.5%) of whom were male, with a clinical presentation of DCM, including 4 with aggressive systemic mastocytosis (ASM) and 29 with DCM. The mean (SD) age at the onset of the first clinically significant signs was 2.2 (2.2) months. A disease-revealing massive bullous eruption was noted in 9 patients (27.2%). Compared to MPCM, patients with a clinical presentation of DCM had a higher mean baseline serum tryptase level (47.5 μg/L [SD, 38.7; range, 5.0-178.0 μg/L] vs 7.4 μg/L [SD, 6.4; range, 1-45.2]; P < .001), a higher prevalence of anaphylaxis (4 [12.1%] vs 5 [2.4%]; P = .02), and a more frequent association with ASM (4 [12.1%] vs 2 [0.9%]; P = .004). KIT codon 816 variants were identified in 4 patients (19.0%), other KIT variants in 14 patients (66.7%), and wild-type KIT in 3 patients (14.3%). All 4 patients with KIT codon 816 variants had ASM. Seven patients (21.2%) received early systemic treatment (imatinib, midostaurin, or sirolimus depending on the type of KIT variants), starting at a mean (SD) age of 80.8 (135.6) months and continuing for a mean (SD) of 4.0 (2.6) years, with generally good tolerance and efficacy. Of the 15 patients without systemic treatment for more than 6 years, 13 (86.6%) exhibited spontaneous regression.

Conclusion and relevance: In this cohort study, DCM presentation differs significantly from MPCM, with a higher risk of anaphylaxis and aggressive systemic forms, the latter being consistently associated with the KIT D816V variant. Tyrosine kinase inhibitors and sirolimus were generally effective and well tolerated in this pediatric population, with the choice of treatment depending on the type of KIT variants.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Polivka reported grants from the Bettencourt Schueller Foundation. Dr Rossignol reported grants from Blueprint Medicines, personal fees from Blueprint Medicines, and grants from MSD outside the submitted work. Dr Garcelon reported personal fees from Takeda and nonfinancial support from John Modell Foundation outside the submitted work. Dr Arock reported personal fees from Blueprint Medicines, grants from Thermo Fisher, and personal fees from AB Science during the conduct of the study. Dr Hermine reported grants from AB Science, grants from BMS, and grants from Blueprint outside the submitted work. No other disclosures were reported.

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