Diagnosis and management of mast cell activation syndrome (MCAS) in Canada: a practical approach

An increasing number of patients are presenting to allergists with concerns about mast cell activation syndrome (MCAS), often in the context of persistent, unexplained, multisystem symptoms. This review aims provide a practical, stepwise approach to the diagnosis and management of MCAS, based on the consensus criteria established by the European Competence Network on Mastocytosis-American Initiative on Mast Cell Diseases, an international consortium of leading experts in mast cell disorders endorsed by major scientific organizations. The first step is to evaluate whether the clinical presentation is consistent with MCAS, recognizing that the prototypical presentation is idiopathic anaphylaxis. Symptoms should be severe, episodic, typical of mast cell activation, and involve at least two organ systems. The next step is to exclude secondary causes of mast cell activation, particularly cofactor-dependent food allergy and nonsteroidal anti-inflammatory drug hypersensitivity. Objective evidence of mast cell activation must then be obtained, preferably by identifying an acute increase in serum tryptase (on a sample drawn within four hours of an episode) compared to baseline. Alternatively, urinary metabolites of mast cell mediators can be assessed by comparing baseline values with those obtained 3-6 h post-event. Importantly,elevated baseline values in serum tryptase or urinary metabolites are not diagnostic of MCAS, nor do normal values exclude the diagnosis. In patients with idiopathic anaphylaxis, evaluation for a clonal mast cell disorder is recommended. This includes measuring baseline serum tryptase, testing for the KIT p.D816V mutation in peripheral blood (using high-sensitivity assays, if available), and calculating a mast cell clonality prediction score. A bone marrow biopsy should be considered for those with a high probability of mast cell clonality. Management includes instructing patients to treat acute episodes with an epinephrine auto-injector, particularly when anaphylaxis criteria are met. For patients with recurrent episodes, prophylactic therapy may be initiated, starting with H1-antihistamines and stepping-up as needed. While most patients have a favourable clinical course, some may require multiple medications to prevent or attenuate episodes. Future research should focus on validating and refining diagnostic and therapeutic strategies. In clinical practice, expanding access to key diagnostic tools-such as urinary mediator assays, sensitive KIT mutation testing, and tryptase genotyping-would facilitate and improve care of those patients.