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

Diagnostic Tests and Treatment for Mast Cell Activation Syndrome (MCAS)

The diagnosis of MCAS requires meeting all three criteria: recurrent symptoms affecting at least 2 organ systems, laboratory evidence of mast cell mediator release during symptomatic episodes, and response to antimediator therapy. 1

Diagnostic Criteria and Testing

Required Diagnostic Criteria

1. Recurrent symptoms consistent with mast cell activation affecting ≥2 organ systems:

   • Skin: flushing, urticaria, pruritus, angioedema
   • Gastrointestinal: diarrhea, nausea, vomiting, abdominal pain
   • Cardiovascular: hypotension, tachycardia, near syncope
   • Respiratory: wheezing, inspiratory stridor 2, 1

2. Laboratory evidence of mast cell mediator release during symptomatic episodes:

   • Serum tryptase: increase of >20% + 2 ng/mL from baseline (collect 1-4 hours after symptom onset)
   • 24-hour urine collection during symptomatic periods for:
     • N-methylhistamine
     • Prostaglandin D2 or its metabolite 11β-PGF2α (peaks 0-3 hours after episode)
     • Leukotriene E4 (LTE4) 2, 1

3. Response to antimediator therapy 2, 1

Additional Testing

• Peripheral blood or bone marrow testing for KIT mutation (especially D816V)
• TPSAB1 α-tryptase CNV testing for hereditary alpha tryptasemia 2

Important caveat: False negatives may occur in MCAS patients who don't show elevated tryptase during reactions. Heparin, chromogranin A, and plasma/urine histamine levels are not reliable markers for mast cell activation. 1

Treatment Algorithm

First-Line Therapy

1. H1 Antihistamines

   • Non-sedating options (fexofenadine, cetirizine)
   • Can increase to 2-4 times standard dose
   • Target symptoms: flushing, pruritus, urticaria, tachycardia 1

2. H2 Antihistamines

   • Options: famotidine, ranitidine, cimetidine
   • Use concurrently with H1 antihistamines
   • Target symptoms: abdominal discomfort, gastrointestinal and cardiovascular symptoms 1

3. Mast Cell Stabilizers

   • Cromolyn sodium: start low and gradually increase to 200 mg 4 times daily
   • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea)
   • FDA-approved for mastocytosis with documented improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching 1, 3

Second-Line/Targeted Therapy

1. Leukotriene Modifiers

   • For patients with elevated urinary LTE4 levels 2

2. Aspirin

   • For patients with flushing and hypotension, especially with increased urinary 11β-PGF2α levels
   • Contraindicated in those with allergic reactions to NSAIDs
   • May require dosing up to 650 mg twice daily 2, 1

3. Corticosteroids

   • For short-term management of severe symptoms
   • Initial oral dosage: 0.5 mg/kg/day with slow taper over 1-3 months
   • Not recommended for long-term use due to side effects 1

4. Omalizumab

   • For antihistamine-resistant symptoms
   • Particularly effective for recurrent anaphylaxis and skin symptoms 1

Emergency Management

• All MCAS patients should carry two epinephrine auto-injectors
• For anaphylaxis: administer intramuscular epinephrine immediately
• Patients should learn supine positioning for hypotensive episodes 1

Treatment Considerations

Individualized Approach

• Match treatment to specific mediator elevations:
  • Elevated urinary LTE4 → leukotriene antagonists
  • Elevated urinary PG metabolites → aspirin therapy 2

Monitoring

• Regular assessment of symptom control and medication efficacy
• Periodic laboratory evaluation during symptomatic episodes
• Adjustment of treatment regimen based on response 1

Prognosis

• Patients with indolent systemic mastocytosis demonstrate normal life expectancy
• Long-term follow-up of MCAS patients (>15 years) has not shown progression to mastocytosis 2

Clinical pitfall: MCAS is often underdiagnosed due to the heterogeneity of symptoms and overlap with other conditions. Collecting mediator samples during symptomatic episodes is crucial for diagnosis. Avoid relying solely on tryptase levels, as they may not be elevated in all MCAS patients.