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

Treatment for Mast Cell Activation Syndrome (MCAS)

The primary treatment for Mast Cell Activation Syndrome consists of antimediator therapy including H1 and H2 antihistamines, mast cell stabilizers like cromolyn sodium, and carrying emergency epinephrine for severe reactions. 1

First-Line Treatment Approach

Antimediator Medications

1. H1 Antihistamines

   • Non-sedating options (first choice): Fexofenadine or cetirizine
   • Can be increased to 2-4 times standard dose for better symptom control
   • For nighttime symptoms: Consider adding sedating antihistamine (e.g., hydroxyzine 10-25 mg) 1

2. H2 Antihistamines

   • Options: Famotidine, ranitidine, or cimetidine
   • Particularly helpful for gastrointestinal and cardiovascular symptoms
   • Should be used concurrently with H1 antihistamines for enhanced effect 1

3. Mast Cell Stabilizers

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

Emergency Medications

• Epinephrine: All MCAS patients should carry two epinephrine auto-injectors, especially those with history of anaphylaxis 1
• Emergency action plan should be created for severe reactions 1

Second-Line Treatments

1. Leukotriene Modifiers

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

2. Aspirin

   • Consider for patients with flushing and hypotension, particularly those with increased urinary 11β-PGF2α levels
   • Contraindicated in those with allergic reactions to NSAIDs
   • May require dosing up to 650 mg twice daily (use with caution) 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

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

Advanced/Refractory Cases

For patients with systemic mastocytosis with inadequate response to antimediator therapy:

1. Cytoreductive Therapy options:

   • Midostaurin
   • Cladribine
   • Imatinib (only if KIT D816V mutation negative or unknown)
   • Interferon (alfa-2b, peginterferon alfa-2a, or peginterferon alfa-2b) ± prednisone 3

2. Consider KIT inhibitors for severe cases:

   • Recent data suggest that long-term treatment with agents effectively inhibiting KIT function can result in mast cell eradication and symptom improvement 4

Management of Specific Situations

Surgery/Procedures

• Multidisciplinary management with surgical, anesthesia, and perioperative medical teams
• Use of benzodiazepines, antihistamines, and corticosteroids before procedures
• Caution with opioids (can trigger mast cell activation)
• Have emergency medications available 3

Pregnancy

• Multidisciplinary team including high-risk obstetrician and anesthesiologist
• Avoid known triggers
• Use prophylactic anti-mediator drugs (corticosteroids, antihistamines, epinephrine)
• Interferon-alfa can be considered for pregnant women with severe symptoms
• Avoid cladribine, imatinib, and midostaurin during pregnancy 3

Monitoring and Follow-up

• Regular assessment of symptom control and medication efficacy
• For indolent systemic mastocytosis:
  • History and physical, labs every 6-12 months
  • DEXA scan every 1-3 years for patients with osteopenia/osteoporosis 3
• Periodic laboratory evaluation during symptomatic episodes to confirm mast cell activation 1

Common Pitfalls and Caveats

1. Delayed diagnosis: MCAS is often mistaken for functional gastrointestinal disorders 5

2. Medication adjustments needed for organ 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

3. Trigger avoidance is crucial: Patients should be counseled about potential triggers of mast cell activation 3, 1

4. Inadequate treatment: Many patients are undertreated with only standard doses of antihistamines, when higher doses or combination therapy may be needed 6

5. Lack of high-quality evidence: Most treatment recommendations are based on expert opinion rather than controlled clinical trials 7