Anaphylaxis is a common feature of mastocytosis patients, particularly with Hymenoptera venoms. Hence, it is hypothesized that mastocytosis patients may have an increased susceptibility to developing drug-induced anaphylaxis (DIA). Patients and medical practitioners are therefore concerned when there is a need to use various drugs. However, this issue has not been systematically investigated. Our study aimed to investigate the prevalence and clinical characteristics of anaphylaxis to various types of drugs among mastocytosis patients. A retrospective study was conducted among 470 consecutive patients (≥ 18 years) with confirmed clonal mast cell diseases recruited from two independent mastocytosis reference centers. All patients underwent a comprehensive, individualized allergy workup with evaluation of the (self)reported drug hypersensitivity. Overall prevalence of DIA was 6.3% accounting for 1/3 of the confirmed drug hypersensitivity reactions. Non-steroidal anti-inflammatory drugs (NSAIDs) were the most common elicitors of DIA (56%), followed by perioperative agents (23%) and antibiotics (13%). Anaphylactic reactions were severe in most cases with 43% of patients experiencing hypotensive syncope. All drug-related hypersensitivity reactions occurred before mastocytosis was diagnosed. The prevalence of DIA in mastocytosis tends to be higher than in general population, but is overall low. However, its severity is more pronounced. Our results suggest that mastocytosis patients with a prior reaction to drugs should undergo a thorough allergy workup. Well-tolerated drugs can be further used without specific precautions.

The KIT D816V mutation is a hallmark of clonal mast cell disease (cMCD) including systemic mastocytosis. cMCD diagnosis is frequently delayed because of variable symptoms until confirmatory bone marrow biopsy is performed. Screening techniques for KIT D816V variant in peripheral blood (PB) may facilitate diagnosis. Prevalence of KIT D816V in patients with anaphylaxis or mast cell activation (MCA) symptoms is unknown. We sought to determine the prevalence of KIT D816V in PB of patients with anaphylaxis or systemic MCA symptoms. The PROSPECTOR trial (NCT04811365) included patients with anaphylaxis or systemic MCA symptoms who had (1) moderate to severe anaphylaxis to Hymenoptera sting, (2) 20% + 2 ng/mL increase in tryptase level over the baseline level during moderate to severe anaphylaxis with cardiovascular involvement, and/or (3) involvement of both the cardiovascular system and 1 or more other organ systems with basal serum tryptase (BST) levels greater than or equal to 8 ng/mL. KIT D816V in PB, hereditary α-tryptasemia (HaT), and BST levels were centrally evaluated. Of the 381 enrolled patients, 179, 76, and 203 were in groups 1, 2, and/or 3, respectively. Fifteen patients (4%) had detectable KIT D816V in PB; 12 of 15 (80%) had BST levels less than 20 ng/mL. Most patients with KIT D816V (11 of 15 [73%]) had Ring-Messmer grade III/IV anaphylaxis. Fourteen additional patients with BST levels greater than 11.4 ng/mL, no HaT, and local follow-up were diagnosed with cMCD, totaling 29 of 381 patients (8%) with cMCD in the PROSPECTOR trial. The overall prevalence of HaT was 36% (138 of 381). The PROSPECTOR trial demonstrated a meaningful KIT D816V prevalence in patients with anaphylaxis or systemic MCA symptoms; more frequent and sensitive screening for KIT D816V is needed in this patient population.