What are the methods for testing and treating Mast Cell Activation Syndrome (MCAS)?

Testing for Mast Cell Activation Syndrome (MCAS)

The diagnosis of MCAS requires documentation of recurrent episodes of systemic symptoms affecting at least 2 organ systems, laboratory evidence of mast cell activation during symptomatic episodes, and response to medications targeting mast cell mediators. 1

Diagnostic Criteria

Clinical Presentation

• Episodic symptoms affecting multiple organ systems:
  • Cardiovascular: hypotension, tachycardia, syncope
  • Dermatologic: urticaria, flushing, pruritus
  • Respiratory: wheezing, nasal stuffiness
  • Gastrointestinal: nausea, vomiting, diarrhea, abdominal cramping
  • Neurological: cognitive dysfunction, headaches

Laboratory Testing

1. Serum Tryptase (Primary Test):

   • Collect at baseline AND during symptomatic episodes (within 1-4 hours after symptom onset)
   • Diagnostic threshold: >20% above baseline plus 2 ng/mL 2, 1
   • Example: If baseline is 5 ng/mL, a value >8 ng/mL during symptoms would be diagnostic

2. Urinary Mediator Testing (if tryptase is normal):

   • N-methylhistamine
   • 11β-prostaglandin F2α
   • Leukotriene E4 1, 3
   • Collect 24-hour urine sample during/after symptomatic episodes

3. Molecular Testing:

   • KIT D816V mutation testing (if tryptase >15 ng/mL)
   • TPSAB1 α-tryptase copy number testing to rule out hereditary α-tryptasemia 1

4. Bone Marrow Biopsy (in selected cases):

   • Consider if persistent tryptase >20 ng/mL
   • Mast cell immunophenotyping using flow cytometry and/or immunohistochemistry
   • Markers include CD117, CD25, CD2, and optionally CD30 2

Diagnostic Algorithm

1. Initial Evaluation:

   • Document episodic symptoms affecting ≥2 organ systems
   • Rule out other causes of mast cell activation (allergies, drugs, infections) 2
   • Obtain baseline serum tryptase level

2. During Symptomatic Episode:

   • Collect serum tryptase within 1-4 hours of symptom onset
   • Consider urinary mediator testing if available

3. Diagnostic Pathways:

   • If WHO criteria for systemic mastocytosis are met → Diagnose systemic mastocytosis
   • If not, but evidence of mast cell activation is present → Consider primary MCAS
   • If symptoms but no laboratory confirmation → Consider idiopathic MCAS/anaphylaxis

4. Confirmatory Testing:

   • Response to mast cell-targeted therapies (antihistamines, mast cell stabilizers)
   • Repeat laboratory testing during multiple episodes

Common Pitfalls in MCAS Diagnosis

• Missing collection windows for mediator levels (must be within 1-4 hours of symptoms)
• Relying solely on symptoms without laboratory confirmation
• Failing to establish baseline tryptase levels for comparison
• Not considering other diagnoses that can mimic MCAS 1

Referral Recommendations

If MCAS is suspected based on clinical and laboratory findings, patients should be referred to an allergy specialist or mast cell disease research center for comprehensive evaluation and management 2.

Treatment Considerations

For confirmed MCAS, Cromolyn Sodium has demonstrated efficacy in managing symptoms, particularly gastrointestinal manifestations (diarrhea, abdominal pain), with improvement also seen in cutaneous symptoms (urticaria, pruritus, flushing) 4.

Recent research indicates that MCAS may be over-suspected and under-confirmed, with only 2% of suspected cases meeting full diagnostic criteria in one prospective study 5, highlighting the importance of rigorous diagnostic evaluation.