Low Prevalence of Idiopathic Mast Cell Activation Syndrome Among 703 Patients With Suspected Mast Cell Disorders

Idiopathic mast cell activation syndrome (iMCAS) is characterized by severe, episodic systemic mast cell (MC) activation and mediator-related symptoms, an event-related increase in serum tryptase levels, and response to MC-targeted therapies in the absence of underlying IgE-mediated allergy or clonal MC disorder. Studies indicating its prevalence using evidence-based diagnostic criteria are lacking.

To assess the prevalence and clinical and laboratory features of patients with iMCAS.

We conducted a retrospective evaluation of data from 703 consecutive patients (aged ≥18 years) referred to our center based on suspicion of having MC disorders. Patients underwent a thorough clinical workup including patient history, allergy tests, KIT D816V mutation analysis, and/or bone marrow investigation. Disease activity was prospectively assessed during follow-up visits.

We identified 31 patients with confirmed iMCAS. Furthermore, hereditary α-tryptasemia was detected in three patients with baseline tryptase levels greater than 8 ng/mL. The most common clinical presentation during MCAS episodes was mucocutaneous symptoms in patients with iMCAS, especially urticaria or angioedema. However, these symptoms were less prevalent in patients with clonal MCAS (P = .015). The duration of diagnostic delay was significantly longer in patients with iMCAS compared to those with clonal MCAS (P = .02).

The overall prevalence of iMCAS was 4.4% in the entire cohort, which indicates that iMCAS is an uncommon condition. To accurately diagnose iMCAS, it is crucial to evaluate suspected patients using the three diagnostic MCAS criteria. This involves performing a comprehensive allergy work-up including laboratory tests and ultrasensitive mutation analysis of KIT D816V. Subsequently, recommended diagnostic algorithms should be applied.