Clinical Spectrum of Drug Hypersensitivity Reactions in Systemic Mastocytosis: Drug-Induced Anaphylaxis as a Unique...

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min-max: 8.59-200.00) overall, and 41.85 µg/L (min-max: 19.00-200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management.