What are the recommended tests and treatments for Mast Cell Activation Syndrome (MCAS) and mitochondrial dysfunction?

Testing for Mast Cell Activation Syndrome (MCAS) and Mitochondrial Dysfunction

For suspected MCAS, diagnostic testing should include serum tryptase levels collected at baseline and 1-4 hours following symptom flares, with increases of 20% above baseline plus 2 ng/mL necessary to demonstrate evidence of mast cell activation. 1

Diagnostic Approach for MCAS

Initial Assessment

• Consider MCAS testing in patients who present with episodic symptoms affecting multiple organ systems:
  • Visceral and somatic pain
  • Pruritus, flushing, sweating, urticaria, angioedema
  • Wheezing, tachycardia
  • Abdominal cramping, vomiting, nausea, diarrhea
  • Neurological complaints
  • Symptoms involving 2 or more physiological systems 1

Laboratory Testing for MCAS

1. Primary Test:

   • Serum tryptase levels:
     • Collect at baseline (when asymptomatic)
     • Collect 1-4 hours after symptom flares
     • Diagnostic increase: ≥20% above baseline plus 2 ng/mL 1, 2

2. Additional Testing (typically performed by allergy specialists):

   • 24-hour urine collection for:
     • N-methylhistamine
     • Prostaglandin D2 or its metabolite 11β-PGF2α
     • Leukotriene E4 (LTE4) 2

3. Tissue Evaluation:

   • CD-117 immunohistochemical staining of duodenum or ileum biopsies
   • Note: Mast cell counts per high power field are controversial as diagnostic criteria 1

Next Steps After Initial Testing

• If MCAS diagnosis is supported through clinical and/or laboratory features, refer to an allergy specialist or mast cell disease research center for additional testing 1
• For suspected systemic mastocytosis, consider bone marrow biopsy with immunohistochemistry for mast cell tryptase, CD117, and CD25 1

Testing for Mitochondrial Dysfunction

Current guidelines do not specifically address testing for mitochondrial dysfunction in the context of MCAS. This represents a gap in the current evidence base.

Treatment Approach for MCAS

First-Line Medications

1. H1 Antihistamines:

   • Non-sedating options (fexofenadine, cetirizine)
   • May increase to 2-4 times standard dose for better control 2

2. H2 Antihistamines:

   • Famotidine, ranitidine, cimetidine
   • Particularly helpful for gastrointestinal and cardiovascular symptoms 2

3. Mast Cell Stabilizers:

   • Cromolyn sodium:
     • FDA-approved for mastocytosis
     • Particularly effective for gastrointestinal symptoms
     • Recommended dosing: gradually increase to 200 mg 4 times daily before meals and at bedtime 2, 3
   • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3

Additional Treatment Options

• Leukotriene receptor antagonists (montelukast) for refractory skin and GI symptoms 2
• Aspirin for flushing and hypotension (contraindicated in those with NSAID allergy) 2
• Short-term corticosteroids for severe symptoms 2
• Omalizumab for antihistamine-resistant symptoms 2

Emergency Management

• All MCAS patients should carry two epinephrine auto-injectors 2
• For anaphylaxis, administer intramuscular epinephrine immediately 2

Common Pitfalls to Avoid

1. Misinterpreting symptoms as MCAS without completing thorough medical evaluation 4
2. Failing to consider other clinically relevant conditions (autoimmune, neoplastic, infectious) 4
3. Delaying epinephrine administration in anaphylaxis 2
4. Not adjusting medication timing to ensure highest drug levels when symptoms are anticipated 2
5. Failing to consider medication adjustments for patients with renal or hepatic impairment 2

Long-term Management

• Regular assessment of symptom control and medication efficacy
• Periodic laboratory evaluation during symptomatic episodes
• Development of an emergency action plan for severe reactions 2
• Patient education on supine positioning for hypotensive episodes 2

By following this structured diagnostic and treatment approach, clinicians can appropriately identify and manage patients with MCAS, improving their morbidity, mortality, and quality of life outcomes.