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Published on: October 14, 2021
Characteristics and Therapeutic Strategies for Diffuse Cutaneous Mastocytosis
Paula Pernea1, Cecile Méni1,2, Julien Rossignol2,3
1Department of Dermatology, Reference Center for Rare Skin Disorders in Children, AP-HP, Necker Children's Hospital, Paris Centre University, Paris, France.
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.
Insights
Diffuse cutaneous mastocytosis (DCM) in children presents differently than maculopapular cutaneous mastocytosis, with increased risks of anaphylaxis and aggressive systemic forms. Treatments like tyrosine kinase inhibitors showed good efficacy and tolerance in pediatric patients.
Area of Science:
- Pediatric Hematology
- Dermatology
- Rare Diseases
Background:
- Diffuse cutaneous mastocytosis (DCM) is a rare, severe pediatric subtype of mastocytosis with extensive skin involvement.
- Limited comprehensive studies exist on the clinical and molecular features of pediatric DCM.
Purpose of the Study:
- To characterize the clinical, molecular, and treatment outcomes of pediatric patients with DCM.
- To compare DCM patient characteristics with those of maculopapular cutaneous mastocytosis (MPCM).
Main Methods:
- Retrospective analysis of 33 pediatric patients with clinical DCM presentation (1996-2023) at Necker Children's Hospital.
- Collected data included clinical presentation, laboratory results, and KIT sequencing from skin biopsies and bone marrow.
- Compared DCM cohort data with published pediatric MPCM findings.
Main Results:
- DCM patients had higher mean baseline serum tryptase levels (47.5 μg/L vs 7.4 μg/L), increased anaphylaxis risk (12.1% vs 2.4%), and more frequent association with aggressive systemic mastocytosis (ASM) (12.1% vs 0.9%) compared to MPCM.
- KIT codon 816 variants were found in 19.0% of patients, with all 4 cases associated with ASM.
- Systemic treatments (imatinib, midostaurin, sirolimus) were generally well-tolerated and effective; 86.6% of untreated patients showed spontaneous regression over 6 years.
Conclusions:
- Pediatric DCM presentation is distinct from MPCM, carrying a higher risk of anaphylaxis and ASM, consistently linked to the KIT D816V variant.
- Tyrosine kinase inhibitors and sirolimus demonstrate efficacy and tolerability in pediatric DCM, with treatment selection guided by KIT variant type.
- The findings highlight the importance of molecular profiling for guiding treatment and understanding prognosis in pediatric mastocytosis subtypes.
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