What are the diagnostic tests for Mast Cell Activation Syndrome (MCAS)?

Diagnostic Testing for Mast Cell Activation Syndrome (MCAS)

The diagnosis of Mast Cell Activation Syndrome requires a three-pronged approach: typical clinical symptoms affecting multiple organ systems, laboratory evidence of increased mast cell mediators during symptomatic episodes, and response to anti-mediator therapy. 1

Clinical Criteria

• MCAS presents with recurrent episodes of systemic symptoms affecting at least 2 of 4 organ systems concurrently 1:

  • Cardiovascular: hypotension, tachycardia, syncope or near syncope
  • Respiratory: wheezing, shortness of breath, inspiratory stridor
  • Dermatologic: flushing, urticaria, pruritus, angioedema
  • Gastrointestinal: diarrhea, nausea with vomiting, crampy abdominal pain

• Common triggers include hot water, alcohol, drugs, stress, exercise, hormonal fluctuations, infection, and physical stimuli 1

Laboratory Testing

Primary Diagnostic Tests

• Serum tryptase measurement 1:

  • Collect baseline tryptase level when patient is asymptomatic
  • Collect tryptase level during or within 1-4 hours after symptomatic episodes
  • Diagnostic criterion: increase of ≥20% plus 2 ng/mL above baseline during symptomatic episodes

• Bone marrow biopsy and aspirate 1:

  • Indicated to rule out systemic mastocytosis
  • Includes molecular testing for KIT D816V mutation
  • Mast cell immunophenotyping using flow cytometry (CD117, CD25, CD2) and/or immunohistochemistry

Additional Mediator Testing

• Urine tests for mast cell mediators 2, 3:
  • N-methylhistamine (histamine metabolite)
  • Leukotriene E4 (LTE4)
  • 2,3-dinor-11beta-prostaglandin F2 alpha (PGD2 metabolite)
  • Collect during symptomatic episodes and compare to baseline

Diagnostic Algorithm

1. Initial evaluation 1:

   • Document episodic symptoms affecting multiple organ systems
   • Rule out other causes of symptoms
   • Measure baseline serum tryptase

2. During symptomatic episodes 1, 4:

   • Collect serum tryptase 1-4 hours after symptom onset
   • Collect urine for mast cell mediator testing
   • Document response to anti-mediator therapy

3. Diagnostic confirmation 1:

   • Confirm symptoms affect ≥2 organ systems concurrently
   • Verify tryptase increase ≥20% plus 2 ng/mL above baseline
   • Document response to anti-mediator medications (H1/H2 antihistamines, leukotriene antagonists, mast cell stabilizers)

4. Classification 1:

   • Primary MCAS: clonal mast cells but not meeting criteria for systemic mastocytosis
   • Secondary MCAS: mast cell activation due to allergies, drugs, or infections
   • Idiopathic MCAS: no identifiable cause

Common Pitfalls to Avoid

• Do not diagnose MCAS based solely on non-specific symptoms like fatigue, fibromyalgia-like pain, or chronic back pain without laboratory confirmation 1, 5

• Avoid missing the episodic nature of true MCAS - persistent symptoms suggest alternative diagnoses 5

• Ensure proper timing of mediator testing - samples must be collected during symptomatic episodes 4, 6

• Do not confuse MCAS with related conditions like hereditary alpha-tryptasemia, Ehlers-Danlos syndrome, or POTS, which may coexist but are distinct entities 1, 5

• Recognize that serum tryptase may not always be elevated in MCAS, necessitating testing of other mediators 2, 3

Referral Recommendations

• Patients with suspected MCAS should be referred to specialists with expertise in mast cell disorders for comprehensive evaluation 1

• For patients with confirmed MCAS, referral to an allergy specialist or mast cell disease research center is recommended for additional testing and management 1