What is the recommended workup and treatment for a patient suspected of having Mast Cell Activation Syndrome (MCAS)?

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

The diagnosis of MCAS requires fulfillment of three specific criteria: recurrent symptoms involving at least two organ systems, documented elevation of mast cell mediators during symptomatic episodes, and response to medications targeting mast cell mediators. 1

Diagnostic Criteria for MCAS

Step 1: Clinical Symptoms Assessment

Look for recurrent symptoms affecting at least two of these organ systems concurrently:

• Cardiovascular: Hypotension, tachycardia, syncope/near-syncope
• Respiratory: Wheezing, shortness of breath, inspiratory stridor
• Dermatologic: Flushing, urticaria, pruritus, angioedema
• Gastrointestinal: Diarrhea, nausea with vomiting, crampy abdominal pain 1

Step 2: Laboratory Testing

During symptomatic episodes, obtain:

• Serum tryptase: Must show increase >20% + 2 ng/mL above baseline (measured when patient is asymptomatic)
• Other mediator tests when appropriate:
  • 24-hour urinary N-methylhistamine
  • 24-hour urinary prostaglandin D2 or 11β-prostaglandin F2α
  • 24-hour urinary leukotriene E4 1

Step 3: Bone Marrow Evaluation

Consider bone marrow biopsy if:

• Persistently elevated baseline serum tryptase (>20 ng/mL)
• Positive peripheral blood KIT D816V mutation
• High REMA or NIH score suggesting possible clonal mast cell disorder 1

Step 4: Classification

Determine MCAS subtype:

• Primary MCAS: KIT mutation detected (clonal mast cells)
• Secondary MCAS: Underlying allergic/inflammatory condition identified
• Idiopathic MCAS: No identifiable cause or clonality 1, 2

Treatment Algorithm

First-Line Therapies

1. H1 antihistamines: For pruritus, flushing, urticaria
2. H2 antihistamines: For gastrointestinal symptoms
3. Mast cell stabilizers:
   • Oral cromolyn sodium: Particularly effective for gastrointestinal symptoms including diarrhea, abdominal pain, nausea, and vomiting 3
   • Improvement typically occurs within 2-6 weeks of treatment initiation 3

Second-Line Therapies

1. Leukotriene modifiers: For respiratory symptoms and flushing
2. Aspirin: For prostaglandin-mediated symptoms (only after ruling out aspirin sensitivity)
3. Corticosteroids: Short courses for acute flares

Severe/Refractory Cases

1. Omalizumab: For IgE-mediated symptoms
2. Cytoreductive therapies: For primary MCAS with aggressive features
   • Interferon-alfa
   • Tyrosine kinase inhibitors (e.g., midostaurin) 1

Emergency Management

• Epinephrine autoinjector: For anaphylactic episodes
• Emergency action plan for severe reactions

Avoidance Strategies

Identify and avoid triggers such as:

• Heat, temperature changes
• Alcohol
• Certain medications
• Physical stimuli (pressure, friction)
• Emotional stress
• Exercise
• Specific foods if identified 1

Common Pitfalls in MCAS Management

1. Overdiagnosis: Many patients referred for suspected MCAS actually have other conditions. Complete thorough evaluation before diagnosing MCAS 4.

2. Inadequate mediator testing: Samples must be collected during symptomatic episodes and properly handled to avoid false negatives.

3. Failure to establish baseline tryptase: Without baseline measurement, interpretation of elevated tryptase during reactions is difficult.

4. Overlooking comorbidities: Patients with MCAS often have other conditions requiring specific management.

5. Surgical considerations: Patients with MCAS have higher perioperative anaphylaxis risk. Premedication with anxiolytics, antihistamines, and possibly corticosteroids is recommended 1.

By following this structured approach to diagnosis and treatment, clinicians can effectively identify and manage patients with true MCAS while avoiding misdiagnosis in those with other conditions presenting with similar symptoms.