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

Mast cell activation syndrome (MCAS) is characterized by recurrent, systemic episodes of mast cell mediator release, often resembling anaphylaxis and involving multiple organ systems.

To describe clinical, laboratory, and therapeutic characteristics of patients with non-clonal mast cell activation syndromes in a real-life cohort.

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.

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.

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.