Criteria for the regression of pediatric mastocytosis
Published online: April 1, 2021
Mastocytosis corresponds to a heterogeneous group of neoplastic conditions characterized by the accumulation of mast cells (MCs) in 1 or more organs. Adults tend to have persistent, systemic mastocytosis, whereas MC infiltration in children is usually limited to the skin and typically regresses after several years. The clinical manifestations of mastocytosis are related to the clonal accumulation of MCs and the effects of mediators released from the MCs [mast cell activation symptoms (MCASs)]. In more than 85% of both adult and pediatric cases, KIT mutations are present, with the KIT D816V mutation being present in most affected adults but in only half the affected children. Although it has been hypothesized that the mutational differences observed between pediatric and adult cases explain (at least in part) the regression of cutaneous mastocytosis (CM), the underlying mechanisms have not yet been identified. The objectives of this retrospective study of a large cohort of well-characterized patients with pediatric onset mastocytosis were to (1) identify the clinical, biological, and molecular factors associated with spontaneous CM regression in children and (2) analyze the correlation between MCASs and the skin lesion regression.
Between January 1, 1996, and December 31, 2018, a total of 610 patients consulted for pediatric onset mastocytosis at the French National Reference Center. Two hundred and seventy-two of them had suffered from pediatric-onset mastocytosis for at least 8 years, and so were selected for long-term follow-up. The study variables were assessed twice: at disease onset (during a consultation) and at a study visit (a “phone interview” or a clinical examination). Clinical data, the baseline serum tryptase level, the KIT sequence, and the progression of MCASs and CM were recorded.
The male-to-female ratio was 1.23, and 115 patients (42.3%) had congenital mastocytosis. Twenty- three patients (8.5%) had familial mastocytosis (ie, at least 1 first- degree parent with mastocytosis). Two hundred eleven (77.6%) patients presented with maculo-papular CM, 46 (16.9%) with mastocytoma, and 15 (5.5%) with diffuse CM. MCASs were frequent in patients with CM (71.7%) and appeared not to be related to the extent of skin involvement (except for pruritus and flushing). The KIT gene was sequenced (using a skin biopsy sample) in 66 patients (24.3%): 28 of these 66 (42.4%) carried a mutation in codon 816 (exon 17), 28 (42.4%) carried a KIT mutation outside codon 816, and 10 (15.2%) had a WT KIT gene. CM regressed in 210 of the 272 included patients (77.2%; mean time to regression, 6.10 years). The rare cases of aggressive systemic mastocytosis were symptomatic from the outset. Congenital mastocytosis and the KIT D816V mutation were associated with CM regression (odds ratio, 0.48, P [ .031, and 0.173, P [ .031, respectively). Aggravation of MCASs over time was correlated with the persistence of skin lesions. However, the MCASs became more intense in 19% of the patients with MCASs at baseline and CM regression, justifying long-term follow-up in this setting.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.