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

Treatment of Mast Cell Activation Syndrome (MCAS)

The first-line treatment for Mast Cell Activation Syndrome (MCAS) is a combination of H1 and H2 receptor antihistamines, targeting symptoms such as dermatologic manifestations, tachycardia, and gastrointestinal discomfort. 1

First-Line Treatment Approach

Antihistamine Therapy

• H1 Antihistamines:

  • Later-generation non-sedating H1 antihistamines (fexofenadine, cetirizine) are preferred
  • Can be used at 2-4 times standard doses for better symptom control
  • Target symptoms: flushing, pruritus, urticaria, tachycardia, abdominal discomfort 1

• H2 Antihistamines:

  • Famotidine, cimetidine
  • Particularly effective for gastrointestinal symptoms
  • Help H1 antihistamines attenuate cardiovascular symptoms 2

Mast Cell Stabilizers

• Oral Cromolyn Sodium:
  • FDA-approved for mastocytosis
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain)
  • Benefits seen within 2-6 weeks of treatment initiation
  • Should be taken for at least 1 month before assessing efficacy 3
  • Divided dosing with weekly upward titration improves tolerance 2

Acute Management of MCAS Attacks

• Epinephrine Autoinjector:

  • Essential for patients with history of systemic anaphylaxis or airway angioedema
  • Patients should be instructed on proper use 2, 1

• Positioning:

  • Supine positioning for hypotensive episodes
  • Use bedpan for diarrhea and emesis basin after rolling to side/abdomen 2

• Bronchodilators:

  • Albuterol via nebulizer or metered-dose inhaler for bronchospasm 2

Second-Line Treatment Options

• Leukotriene Modifiers:

  • Montelukast, zafirlukast (leukotriene receptor antagonists)
  • Zileuton (5-lipoxygenase inhibitor)
  • Particularly helpful for bronchospasm and gastrointestinal symptoms
  • Most effective when urinary LTE4 levels are elevated 2, 1

• Aspirin:

  • Can reduce flushing and hypotension, especially with elevated urinary 11β-PGF2α levels
  • Contraindicated in those with allergic/adverse reactions to NSAIDs
  • May require dosing up to 650mg twice daily
  • Should be introduced in controlled clinical setting 2, 1

Treatment of Resistant Symptoms

• Omalizumab:

  • Anti-IgE monoclonal antibody
  • Effective for preventing anaphylactic episodes in refractory cases
  • Most common effective dose is 150mg every 2 weeks
  • Higher doses (≥300mg/month) associated with better response rates
  • 75% of patients with refractory MCAS show at least partial response 4

• Corticosteroids:

  • For refractory symptoms
  • Initial oral dosage of 0.5 mg/kg/day
  • Slow taper over 1-3 months
  • Can be used prophylactically before procedures (50mg prednisone at 13,7, and 1 hour before procedures) 2, 1
  • Should be tapered quickly to limit adverse effects

Special Considerations

Perioperative Management

• Higher risk of anaphylaxis during surgery
• Multidisciplinary approach involving surgical, anesthesia, and perioperative teams
• Pre-anesthetic treatment with anxiolytics, antihistamines, and possibly corticosteroids
• Avoid muscle relaxants atracurium and mivacurium; rocuronium and vecuronium may be safer
• Propofol, sevoflurane, isoflurane, fentanyl, and remifentanil are generally safer anesthetic options 2

Pregnancy Management

• Multidisciplinary team including high-risk obstetrics, anesthesia, and allergy
• Focus on symptom alleviation with medications that minimize fetal harm
• Avoid triggers and use prophylactic antihistamines
• For severe cases, interferon-alfa can be considered
• Avoid cladribine or tyrosine kinase inhibitors 2

Treatment Pitfalls and Caveats

• First-generation (sedating) H1 antihistamines can cause cognitive decline, particularly in elderly patients 2, 1
• Cromolyn sodium may take weeks to show benefit; patients should be counseled about delayed onset of action 1
• Treatment efficacy should be assessed based on reduction in frequency and severity of symptoms 1
• Many patients have combined forms of MCAS (with allergies and other comorbidities), requiring comprehensive treatment approaches 5
• Gastrointestinal symptoms are often mistaken for functional disorders, leading to significant delays in diagnosis and appropriate treatment 6

By following this structured approach to MCAS treatment, focusing on symptom control through antihistamines and mast cell stabilizers first, then escalating to second-line and refractory treatments as needed, most patients can achieve significant improvement in quality of life and reduction in morbidity.