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

Treatment for Mast Cell Activation Syndrome (MCAS)

First-line treatment for Mast Cell Activation Syndrome (MCAS) consists of non-sedating H1 antihistamines (such as cetirizine or fexofenadine) at doses up to 2-4 times the standard dose, combined with H2 receptor antihistamines (such as famotidine) for gastrointestinal symptoms. 1

First-Line Pharmacological Management

Antihistamines

• Non-sedating H1 antihistamines target skin manifestations (flushing, pruritus), tachycardia, and abdominal discomfort 1
• Dosing can be increased to 2-4 times the standard dose for better symptom control 1
• H2 receptor antihistamines (famotidine, ranitidine, cimetidine) are particularly effective for gastrointestinal symptoms and can enhance the cardiovascular effects of H1 antihistamines 1

Mast Cell Stabilizers

• Oral cromolyn sodium is effective for reducing abdominal bloating, diarrhea, and cramps 1
• Cromolyn sodium works by inhibiting mast cell degranulation and blocking calcium ions from entering mast cells, thereby preventing mediator release 2
• May also provide benefit for neuropsychiatric manifestations 1

Second-Line Treatments

• Leukotriene modifiers (montelukast, zileuton) can reduce bronchospasm and gastrointestinal symptoms, especially in patients with elevated urinary LTE4 levels 1
• Aspirin may help reduce flushing and hypotension in patients with elevated urinary 11β-PGF2α levels, but requires careful monitoring due to potential adverse effects 1

Acute Management of Mast Cell Activation

• Epinephrine autoinjectors are essential for patients with a history of systemic anaphylaxis or airway angioedema 1
• Patients should assume a supine position during hypotensive episodes 1
• Bronchodilators like albuterol can be used for bronchospasm via nebulizer or metered-dose inhaler 1

Trigger Avoidance

• Identifying and avoiding known triggers is crucial for MCAS management 1
• Common triggers include:
  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications 1

Special Considerations

Gastrointestinal Symptoms

• Gastrointestinal symptoms are frequently reported in MCAS patients and often misdiagnosed as functional gastrointestinal disorders 3
• These may present as irritable bowel syndrome, dyspepsia, chronic nausea, and heartburn 3

Perioperative Management

• Requires a multidisciplinary approach with pre-anesthetic treatment including anxiolytics, antihistamines, and possibly corticosteroids 1
• Certain muscle relaxants should be avoided 1

Skin Care

• Avoid skin dryness
• Use moisturizers
• Apply water-soluble sodium cromolyn cream for urticaria and pruritus 1

Common Pitfalls and Caveats

• Inadequate antihistamine dosing: Standard doses are often insufficient for MCAS; doses typically need to be increased to 2-4 times standard dosing 1
• Focusing only on histamine: MCAS involves multiple mediators beyond histamine, so treatment targeting only histamine pathways may be insufficient 1, 4
• Medication interactions: Cognitive effects of anticholinergic antihistamines should be carefully considered, especially in elderly patients 1
• Delayed diagnosis: Patients with MCAS often experience significant delays in diagnosis, particularly when presenting with gastrointestinal symptoms 3
• Limited evidence base: There is an urgent need for large, well-designed clinical trials investigating the effectiveness of second-generation H1-antihistamines in MCAS treatment 5

Treatment Algorithm

1. Start with antihistamines:

   • H1 antihistamine (non-sedating): Begin with standard dose, increase up to 2-4 times if needed 1
   • Add H2 antihistamine for gastrointestinal symptoms 1

2. Add mast cell stabilizers:

   • Oral cromolyn sodium for persistent gastrointestinal and neuropsychiatric symptoms 1, 2

3. For inadequate response, add second-line agents:

   • Leukotriene modifiers for respiratory or persistent GI symptoms 1
   • Consider aspirin for flushing/hypotension (with careful monitoring) 1

4. Provide emergency management plan:

   • Epinephrine autoinjector prescription and training 1
   • Written action plan for acute episodes 1

5. Implement trigger avoidance strategies based on patient-specific triggers 1