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

Treatment of Mast Cell Activation Syndrome (MCAS)

The first-line treatment for MCAS should begin with a combination of H1 and H2 antihistamines, with non-sedating H1 antihistamines as the preferred initial therapy, targeting symptoms such as dermatologic manifestations, tachycardia, and abdominal discomfort. 1

Pharmacological Management

First-Line Medications

1. Antihistamines

   • H1 antihistamines: Non-sedating options (e.g., fexofenadine, cetirizine) are preferred and often used at 2-4 times the standard FDA-approved doses 2, 1
   • H2 antihistamines: Particularly effective for gastrointestinal symptoms and can enhance the cardiovascular symptom control of H1 antihistamines 2
   • Caution: First-generation (sedating) H1 antihistamines can cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 2

2. Mast Cell Stabilizers

   • Cromolyn sodium: Highly effective for gastrointestinal symptoms (bloating, diarrhea, cramps) and may benefit neuropsychiatric manifestations 2, 1
   • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3
   • Start at the lowest dose and gradually increase to 200 mg 4 times daily before meals and at bedtime 1

Second-Line Medications

1. Leukotriene Modifiers

   • Montelukast or other leukotriene receptor antagonists are most effective for respiratory and dermatologic symptoms 1
   • Most beneficial when urinary LTE4 levels are elevated 2, 1
   • Work best in conjunction with antihistamines 1

2. Aspirin

   • May reduce flushing and hypotension, particularly in patients with increased urinary prostaglandin metabolites 2, 1
   • Caution: Contraindicated in those with allergic reactions to NSAIDs; may trigger mast cell degranulation in some patients 2, 1
   • Clinical improvement might require dosing up to 650 mg twice daily 2

3. Other Options

   • Doxepin: Potent H1 and H2 antihistamine with tricyclic antidepressant activity; may reduce CNS manifestations but can cause drowsiness and increase suicidal tendencies in younger patients 2
   • Cyproheptadine: Sedating H1 antihistamine with anticholinergic and antiserotonergic activities; helpful for gastrointestinal symptoms 2

Acute Management

1. Epinephrine Autoinjector

   • Essential for patients with history of systemic anaphylaxis or airway angioedema 2, 1
   • Patients should carry two autoinjectors 1

2. Corticosteroids

   • For refractory symptoms: Initial oral dosage of 0.5 mg/kg/day, followed by slow taper over 1-3 months 2, 1
   • For procedures: Consider 50 mg prednisone at 13 hours, 7 hours, and 1 hour before radiologic or invasive procedures 2
   • Not recommended for long-term use due to side effects 2, 1

3. Emergency Measures

   • Supine positioning for recurrent hypotensive episodes 2, 1
   • Albuterol via nebulizer or metered-dose inhaler for bronchospasm 2, 1

Advanced Therapies

1. Omalizumab
   • Can prevent anaphylactic episodes in some patients 2
   • Particularly helpful for those who cannot tolerate needed insect venom immunotherapy 2

Treatment Approach Algorithm

1. Initial Treatment:

   • Start with non-sedating H1 antihistamine + H2 antihistamine
   • Add cromolyn sodium for gastrointestinal symptoms

2. If inadequate response after 4-6 weeks:

   • Increase H1 antihistamine dose (up to 4x standard dose)
   • Add leukotriene modifier if respiratory or skin symptoms persist

3. For persistent symptoms:

   • Consider aspirin (if no NSAID allergy)
   • Consider doxepin or cyproheptadine (with caution in elderly)

4. For severe, refractory symptoms:

   • Short course of corticosteroids
   • Consider omalizumab for recurrent anaphylaxis

Common Pitfalls and Considerations

• Medication triggers: Many drugs can trigger MCAS symptoms; review all medications carefully 1, 4
• Procedure preparation: Premedication protocol for procedures/surgery should include anxiolytic agents, H1 and H2 blockers, and corticosteroids 1
• Monitoring: Document symptom improvement with treatment and repeat mediator testing to assess biochemical response 1
• Misdiagnosis: Consider alternative diagnoses if no response to appropriate therapy after 8-12 weeks 1, 5
• Combined forms: Most severe MCA events occur in combined forms of MCAS, where multiple factors are present, requiring combination therapy 4

Special Considerations

• Bone health: Implement calcium and vitamin D supplementation for patients on long-term antihistamine therapy 1
• Comorbidities: Address associated conditions including autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which may impact GI symptoms 6