From the Guidelines
Mast cell activation syndrome (MCAS) is diagnosed through a combination of clinical symptoms, laboratory tests, and response to treatment, requiring evidence of recurrent symptoms involving multiple organ systems, laboratory documentation of mast cell mediator release during symptomatic periods, and improvement with medications that target mast cell mediators. The diagnosis of MCAS involves a comprehensive approach, including:
- Clinical symptoms: recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 organ systems, such as cardiovascular, dermatologic, respiratory, and gastrointestinal systems 1
- Laboratory tests: elevated levels of mediators like tryptase, histamine, prostaglandins, or leukotrienes in blood or urine samples collected during flares, with a 20% increase in serum tryptase during an episode compared to baseline being particularly significant 1
- Response to treatment: improvement with medications that target mast cell mediators, such as H1 and H2 antihistamines, mast cell stabilizers, or leukotriene inhibitors 1
- Diagnostic criteria: recurrent symptoms, laboratory documentation of mast cell mediator release, and response to targeted therapeutic interventions, as outlined in the algorithm for diagnosing MCAS 1
- Ruling out other diseases: differential diagnosis to exclude other conditions that may present with similar symptoms, such as mastocytosis, hereditary alpha-tryptasemia, and other disorders 1
A thorough medical history review and physical examination, with attention to triggers like foods, medications, environmental factors, stress, or temperature changes, are also essential in the diagnosis of MCAS 1. Skin or tissue biopsies may be performed to rule out mastocytosis, a related but distinct condition 1.
The most recent and highest quality study, published in 2019 in the Journal of Allergy and Clinical Immunology, provides a comprehensive overview of the diagnosis and management of MCAS, including the clinical, laboratory, and therapeutic criteria for primary MCAS 1.
In summary, the diagnosis of MCAS requires a comprehensive approach, including clinical symptoms, laboratory tests, and response to treatment, as well as ruling out other diseases through differential diagnosis.
From the Research
Diagnostic Criteria for Mast Cell Activation Syndrome
The diagnosis of mast cell activation syndrome (MCAS) is based on several criteria, including:
- Typical clinical signs and symptoms of acute, recurrent (episodic), and systemic mast cell activation (MCA) 2, 3, 4, 5
- Increase in tryptase level to >20% + 2 ng/mL within 1-4 hours after onset of the acute crisis, or baseline serum tryptase levels that are persistently above 15 ng/mL 2, 3, 4, 5
- Response of MCA symptoms to antimediator therapy, including H1 and H2 histamine receptor antagonists, anti-leukotrienes, or mast cell stabilizers 2, 3, 4, 5
- Increase in other mast cell-derived mediators, such as histamine or PGD2, or their urinary metabolites 2, 4
Laboratory Tests
Laboratory tests that support the diagnosis of MCAS include:
- Validated urinary or serum markers of mast cell activation, such as an increase in the marker above the patient's baseline value during symptomatic periods on more than two occasions 2, 4
- 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 2, 4
- Baseline serum tryptase levels that are persistently above 15 ng/mL, or documentation of an increase of the tryptase level above baseline value on one occasion 2, 4
Classification and Diagnosis
The classification of MCAS requires highly sensitive and specific methodological approaches for the assessment of clonal bone marrow mast cells at low frequencies 3. A diagnostic algorithm has been proposed, focusing on the practical evaluation and management of patients with suspected MCAS 3, 5. The Spanish Network on Mastocytosis score has been used successfully as a predictive model for selecting MCAS candidates for bone marrow studies based on a high probability of an underlying clonal mast cell disorder 3.