Mast Cell Activation Syndrome

Mast cell activation syndrome (MCAS) is a clinical syndrome of severe, recurrent, episodic mast-cell mediator release. The pattern is usually multisystem: flushing or urticaria may occur with abdominal cramping or diarrhoea, wheezing or throat tightness, tachycardia, presyncope, or hypotension. Mast-cell mediators increase vascular permeability, relax vascular smooth muscle, constrict bronchial smooth muscle, and alter gastrointestinal motility, so one activation event can produce findings in several systems at once. Tryptase is a serine protease stored in mast-cell secretory granules. At rest, mast cells continuously release monomeric pro-tryptase, which contributes to the person’s baseline concentration. Degranulation releases mature tetrameric tryptase and produces a temporary rise. Commercial serum assays report total tryptase, including alpha and beta isoforms and pro- and mature forms; they cannot identify whether activation was IgE-mediated or non-IgE-mediated. MCAS is not synonymous with an elevated baseline tryptase, chronic allergy, or a suspected “mast-cell trigger.” Consensus diagnosis requires all three elements: 1. Severe, recurrent, episodic symptoms consistent with systemic mast-cell activation and involving at least two organ systems. 2. Objective biochemical evidence of mast-cell mediator release during an episode. 3. Improvement...