Mast cell activation syndrome (MCAS) is a group of rare disorders that presents with symptoms of excessive chronic mast cell activation. MCAS can be primary, secondary, or idiopathic. In primary MCAS, a clonal population of mast cells is present. Patients may fulfill the diagnostic criteria for systemic mastocytosis or, in cases of a low mast cell burden, they may not (monoclonal mast cell activation syndrome). Secondary MCAS is most commonly caused by immunoglobulin E (IgE)-mediated allergic disease but is sometimes caused by non-IgE-mediated causes such as drugs, venoms, or other inflammatory disorders.

The underlying pathophysiology of MCAS involves excessive systemic activation of mast cells, leading to degranulation and release of vasoactive mediators such as histamine and tryptase. These mediators cause an array of symptoms and signs including flushing, pruritus, urticaria and angioedema, nasal congestion and pruritus, bronchoconstriction and throat swelling, headache, and diarrhea. A severe complication of MCAS is systemic anaphylaxis. The disease is often episodic in nature, with symptoms waxing and waning over time. MCAS is most commonly found in White females. Symptoms often start in childhood and continue into adulthood if left untreated.