Mast cell activation syndromes in clinical practice: diagnostic challenges, phenotypes, and real-life management.

Introduction: Mast cell activation syndrome (MCAS) is characterized by recurrent, systemic episodes of mast cell mediator release, often resembling anaphylaxis and involving multiple organ systems. Aim: To describe clinical, laboratory, and therapeutic characteristics of patients with non-clonal mast cell activation syndromes in a real-life cohort. Material and methods: This retrospective study included 21 adult patients fulfilling criteria for non-clonal mast cell activation syndromes, evaluated between 2015 and 2025 at a tertiary allergy and immunology centre in Istanbul, Türkiye. Demographic features, clinical manifestations, laboratory findings, and treatment responses were analysed. Results: Eighteen (85.7%) patients were female, with a mean age of 50.1 years. All experienced recurrent acute cutaneous symptoms, with gastrointestinal (42.9%), cardiovascular (61.9%), and respiratory (76.2%) involvement. Baseline serum tryptase levels were normal or mildly elevated, and all patients demonstrated an event-related "20% + 2 ng/ml" increase during follow-up. KIT D816V mutation was negative in peripheral blood in all patients and in bone marrow in 6 evaluated cases. No aberrant mast cell immunophenotype was detected in those undergoing bone marrow assessment. Based on available evaluation, 6 patients were classified as consistent with idiopathic (non-clonal) MCAS, whereas the remaining patients had comorbidities suggestive of secondary MCAS. Conclusions: Non-clonal mast cell activation syndromes remain diagnostically challenging and often require longitudinal evaluation. Omalizumab may serve as an effective adjunct therapy in patients with persistent symptoms. A phenotype-based approach is warranted.