MCAS testing

MCAS testing can be challenging because mast-cell mediators may rise during an episode and then return towards baseline. The timing of testing is therefore important, and results should be interpreted alongside the clinical picture. The mediators used, the significance of changes from an individual’s baseline and the thresholds required for diagnosis remain areas of ongoing research and debate. No single mediator test can confirm or exclude MCAS on its own. A raised result may provide evidence of mast-cell activation but is not specific to MCAS, while a normal result does not necessarily rule it out.

Blood tests

Serum tryptase is the most established routinely available marker of systemic mast-cell activation. An event-related rise compared with the individual’s baseline, commonly assessed using the 20% + 2 formula, has an important role within some diagnostic frameworks. Testing is most informative when an acute sample is collected within a few hours of symptom onset and compared with a later baseline sample, usually taken 24–48 hours after symptoms have resolved. Baseline tryptase may be normal in people with MCAS, and the absence of a qualifying rise does not by itself exclude mast-cell involvement or MCAS.

Urinary mediator tests

Other mast-cell-derived mediators may provide evidence of mast-cell activation. These can include urinary N-methylhistamine, leukotriene E4 and prostaglandin D2 and relevant metabolites. These markers may be useful where tryptase is normal or inconclusive, although their diagnostic thresholds and validation are less established than for tryptase. Results should be interpreted in the context of symptoms, timing of sampling, baseline values and the wider diagnostic assessment. Our leaflet on urine testing may be a helpful resource.