Characteristics and Therapeutic Strategies for Diffuse Cutaneous Mastocytosis

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.