Phenotypic and Genotypic Characteristics of Mastocytosis Differ According to the Age of Disease’s Onset.

Mastocytosis is a heterogeneous group of disease with respect to clinical, biological and genotypic features, which may either occur during childhood or at the adult’s age. Adult’s mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutations, while pediatric’s disease is mostly limited to the skin and often resolves spontaneously during adolescence. No study has attended to compare characteristics of adult’s mastocytosis according to the age of disease’s onset. Among 155 adult patients with histologically proven cutaneous mastocytosis and complete phenotypic and genotypic data available recruited through the French mastocytosis network (AFIRMM), disease started before 15 years in 23 patients (15%) and later than 18 years in 132 patients (85%). We compared phenotypic and genotypic features of patients whose disease started during childhood (Group 1, n = 23) with those of 31 randomly allocated patients whose disease started at adult’s age (Group 2). Genotypic analysis was performed on skin biopsy by direct sequencing of c-kit exons 17 and 8 to 13 in which most of activating mutations are found.

According to the WHO classification, the percentage of systemic disease was similar in both groups (61 vs. 79%) in groups 1 and 2, respectively. Bone pain (57% vs. 23%) and flush (83% vs. 39%) differ between groups (p < 0.01). Bullous lesions were only observed in group 1 (14%) while telangiectasia macularis eruptiva perstans was only observed in group 2 (16%). Major asthenia, syncope, mood disturbances, anaphylactoid reactions, gastrointestinal and respiratory disturbances and blood cell count, serum tryptase and liver enzymes levels did not differ between groups. C-kit 816 mutations was found in 33% and 77% of patients in groups 1 and 2, respectively (p < 0.001). 45% of patients whose disease’s onset occurred before the age of 2 years vs. 7% of those whose disease’s onset occurred later during childhood presented with C-kit 816 mutation (p < 0.001). Other c-kit activating mutations were found in 29% and 3% (p < 0.001) and lack of c-kit activating mutation in 38% and 20% (p < 0.001) in groups 1 and 2, respectively. In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease’s onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.