From the Guidelines
Testing for Mast Cell Activation Syndrome (MCAS) involves several key steps to confirm the diagnosis, including blood and urine tests to measure mast cell mediators, a detailed symptom diary, a trial of mast cell stabilizing medications and antihistamines, and assessment of symptom improvement. The diagnosis of MCAS should be entertained in patients with an appropriate clinical and laboratory profile when other conditions have been excluded, as stated in the 2019 report by the AAAAI Mast Cell Disorders Committee Work Group 1. Patients with MCAS can have a variable clinical phenotype affecting multiple organ systems, and a key feature is recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 of the 4 organ systems listed, including cardiovascular, dermatologic, respiratory, and gastrointestinal systems 1.
The evaluation should include measuring mediator levels at baseline and during an acute episode, such as serum tryptase, 24-hour urine tests for N-methylhistamine, prostaglandin D2, and 11-beta-prostaglandin F2 alpha 1. If the laboratory findings correlate with the presence of symptoms, then appropriate therapies should be implemented, such as histamine-blocking agents or aspirin, and the symptoms should resolve with these therapies 1.
Some key points to consider when testing for MCAS include:
- Measuring mast cell mediators, such as serum tryptase and urinary prostaglandin D2 metabolites, during or shortly after symptomatic episodes 1
- Keeping a detailed symptom diary to document potential triggers and reactions affecting multiple body systems 1
- Initiating a trial of mast cell stabilizing medications and antihistamines to assess symptom improvement 1
- Temporarily discontinuing antihistamines and mast cell stabilizers before testing, if medically safe to do so, to ensure accurate results 1
- Ensuring samples are properly handled, such as keeping them cold and processing them promptly, to prevent degradation of mediators 1
It is essential to note that MCAS diagnosis requires meeting three criteria: typical symptoms affecting multiple organ systems, elevated mast cell mediators during symptomatic periods, and response to medications targeting mast cell mediators or their release 1. By following these steps and considering the latest evidence, clinicians can accurately diagnose and manage MCAS, improving patient outcomes and quality of life.
From the Research
Diagnostic Criteria for Mast Cell Activation Syndrome (MCAS)
The diagnosis of MCAS is defined by several criteria, including:
- Typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA) 2
- Increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis 2
- Response of MCA symptoms to antimediator therapy 2
- Episodic symptoms with mast cell mediators affecting two or more organ systems 3
- Laboratory data includes an increased validated urinary or serum markers of MCAS, documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/mL 3
Laboratory Tests for MCAS
Several laboratory tests can be used to diagnose MCAS, including:
- Serum tryptase levels 2, 3
- Urinary histamine metabolites 3
- 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 3
- Increased validated urinary or serum markers of MCAS 3
Classification of MCAS
MCAS can be classified into several categories, including:
- Primary or clonal mast cell disorders (MCDs) 4
- Secondary MCAS, characterized by normal mast cells (MCs) which are activated by external triggers 4
- Idiopathic form, when no trigger or genetic mutation can be identified 4
Challenges in Diagnosing MCAS
The diagnosis of MCAS can be challenging due to the non-specific clinical picture and the limited availability of laboratory tools 4, 5. Therefore, the diagnosis is often established after exclusion of other possible clinical entities 4.