What is the treatment for Mast Cell Activation Syndrome (MCAS)?

Treatment of Mast Cell Activation Syndrome (MCAS)

The most effective treatment for Mast Cell Activation Syndrome involves a stepwise approach starting with H1 and H2 antihistamines, followed by mast cell stabilizers like cromolyn sodium, with additional targeted medications based on specific symptoms. 1

First-Line Pharmacological Treatment

Antihistamines

• H1 antihistamines:

  • Start with non-sedating options like fexofenadine or cetirizine
  • May increase to 2-4 times standard dose for better symptom control
  • For nighttime symptoms, consider adding a sedating antihistamine (e.g., hydroxyzine 10-25 mg) 1

• H2 antihistamines:

  • Should be added concurrently with H1 antihistamines
  • Options include famotidine, ranitidine, or cimetidine
  • Particularly helpful for gastrointestinal and cardiovascular symptoms 1

Mast Cell Stabilizers

• Cromolyn sodium:
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain, nausea)
  • May also benefit neuropsychiatric manifestations
  • Starting dose: gradually increase to 200 mg 4 times daily before meals and at bedtime
  • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 1, 2

Second-Line and Adjunctive Treatments

For Specific Symptoms

• Leukotriene receptor antagonists (e.g., montelukast):

  • Useful for skin and gastrointestinal symptoms refractory to other treatments 1

• Aspirin:

  • Consider for patients with flushing and hypotension
  • Particularly those with increased urinary 11β-PGF2α levels
  • May require dosing up to 650 mg twice daily
  • CAUTION: Contraindicated in those with allergic reactions to NSAIDs 1

• Corticosteroids:

  • For short-term management of severe symptoms only
  • 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

• Omalizumab:

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

Anaphylaxis Management

• Emergency protocol:

  • Immediate administration of intramuscular epinephrine
  • Follow ABC approach (Airway, Breathing, Circulation)
  • Consider IV antihistamines and hydrocortisone
  • CRITICAL: Don't delay epinephrine - it should be the first medication administered 1

• All patients should have:

  • Emergency action plan
  • Epinephrine auto-injector prescription
  • Training on supine positioning for hypotensive episodes 1

Non-Pharmacological Management

Trigger Avoidance

• Identify and avoid personal triggers including:
  • Certain foods
  • Temperature extremes
  • Stress
  • Physical overexertion 1

Medication Timing

• Adjust timing to ensure highest drug levels when symptoms are anticipated 1

Monitoring and Follow-Up

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

Special Considerations

Renal Impairment

• Reduce cetirizine dose by half in moderate renal impairment
• Avoid cetirizine and levocetirizine in severe renal impairment
• Use loratadine and desloratadine with caution in severe renal impairment 1

Bone Health

• Consider calcium and vitamin D supplementation
• Consider bisphosphonates with continued antihistamine use for patients with osteopenia/osteoporosis 1

Diagnostic Criteria (Important for Treatment Monitoring)

MCAS diagnosis requires all three criteria:

1. Recurrent symptoms affecting at least 2 organ systems
2. Laboratory evidence of mast cell mediator release during symptomatic episodes
3. Response to antimediator therapy 1

Essential mediators to measure include:

• N-methylhistamine
• Prostaglandin D2 or its metabolite 11β-PGF2α
• Leukotriene E4 (LTE4)
• Serum tryptase (baseline and 1-4 hours after symptom flares) 1

Treatment Efficacy

Clinical studies have shown that cromolyn sodium 200 mg QID provides similar benefits to combination therapy with chlorpheniramine plus cimetidine for both cutaneous and systemic symptoms of mastocytosis. Benefits typically persist for 2-3 weeks after treatment withdrawal 2.