Mast Cell Activation Syndrome (MCAS): criteria, diagnostic pathways and current research

Mast cells belong to the innate immune system and sit wherever the body meets the outside world: skin, airways, gut mucosa and perivascular tissue. Their granules store more than 200 described mediators — among them histamine, tryptase, heparin, prostaglandin D2, leukotrienes and various cytokines. On activation they release these within seconds to minutes, while others are newly synthesised over hours.

Because those mediators bind receptors in almost every organ system, the literature describes a symptom pattern affecting several systems at once when activation is excessive — skin, gastrointestinal tract, circulation, airways and nervous system. That simultaneity is precisely why assignment to a single medical speciality so often fails.

Three terms must be distinguished, as studies do not use them synonymously: mastocytosis (clonal proliferation of mast cells, defined via the KIT D816V mutation and bone marrow findings), monoclonal mast cell activation syndrome (MMAS, partial clonal criteria) and mast cell activation syndrome (MCAS, non-clonal but pathologically increased activation). Anyone reading studies must first check which population was examined.

Two parallel sets of criteria currently exist for MCAS. So-called consensus-1 (Valent et al., Weiler et al. within the AAAAI) requires a strict triad: episodic symptoms in at least two organ systems, an objective rise in a mediator — classically serum tryptase by at least 20 % above the individual baseline plus 2 ng/ml within a defined window after an episode — and a response to mediator-targeted therapy.

Consensus-2 (Afrin et al., 2021, with a six-year update in 2026) argues that this tryptase window excludes too many affected people in practice, because tryptase is only one of many mediators and frequently stays within the reference range in MCAS. It therefore widens the mediator panel — to chromogranin A, prostaglandin D2, heparin, and urinary N-methylhistamine and leukotrienes — and weights a broader clinical pattern together with treatment response. Both frameworks are published, both are cited, and the debate remains open.

Pre-analytics are decisive in practice: several of these mediators are heat- and time-labile. Prostaglandin D2, heparin and N-methylhistamine require chilled collection, chilled centrifugation and prompt transport; a sample left at room temperature can produce a false negative. A normal baseline tryptase therefore does not exclude activation — and conversely, a persistently elevated baseline tryptase may reflect hereditary alpha-tryptasemia (TPSAB1 gene duplication), which must be considered separately.

Interpreting all of these findings belongs in specialist hands — typically allergology, haematology or specialised centres. This article describes the state of the professional debate only; it is not a guide to diagnosis or treatment.