From the Guidelines
Diagnosing mast cell activation syndrome (MCAS) requires a comprehensive approach involving clinical evaluation, laboratory testing, and ruling out other conditions, with the diagnosis typically following three main criteria: recurrent symptoms consistent with mast cell mediator release affecting multiple organ systems, documented increases in mast cell mediators during symptomatic periods, and response to medications that target mast cell mediators. The diagnostic process for MCAS involves several key steps, including:
- Clinical evaluation: Patients should keep a detailed symptom diary noting triggers and reactions, and clinicians should look for recurrent episodes of systemic anaphylaxis with concurrent involvement of at least 2 organ systems, as described in the study by 1.
- Laboratory testing: Serum tryptase, 24-hour urine tests for N-methylhistamine, prostaglandin D2, and 11-beta-prostaglandin F2 alpha, and blood tests for histamine levels may be ordered, as suggested by 1.
- Ruling out other conditions: Doctors will typically rule out mastocytosis, allergic disorders, autoimmune diseases, and endocrine disorders, as these conditions can have similar symptoms to MCAS, as noted in 1.
- Treatment trials: Antihistamines (H1 blockers like cetirizine 10mg daily and H2 blockers like famotidine 20mg twice daily) or mast cell stabilizers (such as cromolyn sodium 200mg four times daily) may be used as both diagnostic and therapeutic tools, as described in 1. The diagnostic process often requires multiple specialists, including allergists/immunologists, gastroenterologists, and hematologists, and can be challenging and time-consuming, as there is no single definitive test for MCAS, and symptoms can fluctuate significantly, as highlighted in 1 and 1.
From the Research
Diagnostic Criteria for Mast Cell Activation Syndrome
To diagnose mast cell activation syndrome (MCAS), the following criteria are considered:
- Presence of typical symptoms, such as urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, and nasal stuffiness 2, 3, 4, 5
- Elevation of serum tryptase levels, with an increase of 20% plus 2 ng/mL above the individual's baseline 6
- Response to anti-mediator treatment, including H1/H2 receptor antagonists, anti-leukotrienes, or mast cell stabilizers 2, 3, 4, 5
Laboratory Tests for MCAS
Laboratory tests that support the diagnosis of MCAS include:
- Increased validated urinary or serum markers of mast cell activation, such as tryptase, histamine, or PGD2 3, 4
- Documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions 3, 4
- Baseline serum tryptase levels that are persistently above 15 ng/mL 3, 4
- 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha 3, 4
Classification of MCAS
MCAS can be classified into three categories:
- Primary MCAS, where KIT-mutated, clonal, mast cells are detected 2
- Secondary MCAS, where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found 2
- Idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated mast cells are identified 2
Practical Considerations for Diagnosing MCAS
Practical considerations for diagnosing MCAS include:
- Recognizing the variability of symptoms, which can range from mild to severe to life-threatening 2, 5
- Considering the presence of comorbidities, which can make diagnosis and treatment difficult 5
- Using a combination of clinical symptoms, laboratory tests, and response to treatment to establish a diagnosis of MCAS 2, 3, 4, 5