Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM

Background: Indolent systemic mastocytosis (ISM) without skin lesions (ISMs-) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs+). Interestingly, in almost one-half of ISMs- patients, MC-mediator release episodes are triggered exclusively by insects. Objective: We aimed to determine the clinical and laboratory features of ISMs- associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. Methods: A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs(-), 72 ISMs- triggered by other factors (otherISMs(-)), 56 ISMs+, and 64 nonclonal MC activation syndrome, were studied. Results: Compared with otherISMs(-) and ISMs+ patients, insectISMs(-) cases showed marked male predominance (78% vs 53% and 46%; P < .001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 mu g/L; P <= .009). Moreover, insectISMs(-) less frequently presented BM MC aggregates (46% vs 70% and 81%; P <= .001), and they systematically showed MC-restricted KIT mutation. Conclusions: ISMs- patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs- and ISMs+ patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors.