From the Guidelines
The best test to confirm a diagnosis of Mast Cell Activation Syndrome (MCAS) is measurement of elevated mast cell mediators during symptomatic episodes, particularly serum tryptase, as well as 24-hour urine collections for N-methylhistamine, prostaglandin D2 or its metabolite 11β-prostaglandin F2α, and leukotriene E4, as recommended by the most recent and highest quality study 1. Ideally, tryptase should be measured during an acute flare and compared to a baseline level, with an increase of at least 20% plus 2 ng/mL being significant. These tests should be collected during symptomatic periods and properly handled (kept cold and processed promptly) to prevent degradation. It's essential to perform these tests while the patient is symptomatic and to temporarily discontinue medications that might interfere with results, such as antihistamines, if possible. Diagnosis typically requires evidence of mast cell mediator release, clinical symptoms consistent with mast cell activation affecting multiple organ systems, and response to medications targeting mast cell mediators. Since no single test is definitive, a combination of clinical presentation, laboratory findings, and therapeutic response is necessary for diagnosis, as supported by recent studies 1. Key clinical symptoms that may indicate MCAS include recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 organ systems, such as cardiovascular, dermatologic, respiratory, and gastrointestinal systems, as outlined in the study 1. The presence of specific symptoms during which levels of a mediator are increased and the clinical response to appropriate therapy are all prerequisites for the diagnosis of MCAS, as noted in the study 1. Furthermore, the measurement of PGD2 or its metabolite 11β-prostaglandin F2α can provide biochemical evidence for MC activation, as recommended by the European Competence Network on Mastocytosis consensus conference, and supported by the study 1. Overall, a comprehensive approach that incorporates clinical evaluation, laboratory testing, and therapeutic response is necessary to confirm a diagnosis of MCAS, as emphasized by the most recent and highest quality study 1.
From the Research
Diagnostic Tests for Mast Cell Activation Syndrome (MCAS)
To confirm the diagnosis of MCAS, several tests can be used, including:
- Serum tryptase level: an increase in serum tryptase from baseline during a mast cell activation episode is currently the most accepted biomarker measurement of mast cell release 2
- Urine mast cell mediators: such as histamine, cysteinyl leukotrienes, and prostaglandins, which can be collected at home and are non-invasive tests 2
- 24-hour urine 11β-prostaglandin2α: this test was found to be the most frequently elevated product in MCAS patients and had a strong correlation with symptoms such as flushing and pruritus 3
- Leukotriene E4: this metabolite showed the greatest average increase during episodes of MCAS and an acute/baseline increase of 1.3 or greater could be useful for corroborating a diagnosis of MCAS 4
Combination of Tests
Using a combination of these tests can help improve the diagnosis of MCAS, for example:
- Measuring 24-hour urine 11β-PGF₂α and serum tryptase levels can help avoid misdiagnosis and overinterpretation of MCAS symptoms 3
- A diagnostic algorithm that includes the assessment of clinical signs and symptoms, increase in tryptase level, and response to antimediator therapy can be used to diagnose MCAS 5
Urine Mediator Metabolites
The measurement of urine mediator metabolites, such as: