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

Treatment of Mast Cell Activation Syndrome (MCAS)

The cornerstone of MCAS treatment is a combination of trigger avoidance, H1 and H2 antihistamines, mast cell stabilizers like oral cromolyn sodium, and emergency medications for acute reactions. 1

First-Line Treatment Approach

Trigger Avoidance

• Identify and avoid known triggers of mast cell activation:
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (aspirin, radiocontrast agents, specific anesthetics) 1, 2

Pharmacologic Management

Antihistamines

• H1 Antihistamines:

  • Nonsedating H1 antihistamines are preferred first-line
  • Can be increased to 2-4 times standard dose if needed
  • Target symptoms: pruritus, flushing, urticaria, dermatographism, tachycardia 1, 2
  • Caution: Sedating H1 antihistamines may cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 3

• H2 Antihistamines:

  • First-line for gastrointestinal symptoms
  • Help H1 antihistamines attenuate cardiovascular symptoms 1

Mast Cell Stabilizers

• Oral Cromolyn Sodium:
  • Particularly effective for gastrointestinal symptoms (bloating, diarrhea, abdominal cramps)
  • May improve neuropsychiatric manifestations
  • FDA-approved with clinical trials showing improvement in gastrointestinal symptoms within 2-6 weeks of treatment initiation 1, 4
  • Recommended dosing: Divided dosing with weekly upward titration to reach desired target dose 3

Acute Management of Mast Cell Activation Attacks

Emergency Medications

• Epinephrine:

  • All patients with history of systemic anaphylaxis should carry epinephrine autoinjectors
  • Use for severe reactions, especially hypotension or laryngeal angioedema
  • After using epinephrine, patients should be taken to emergency department while remaining in supine position 3, 1

• Bronchodilators:

  • Albuterol via nebulizer or metered-dose inhaler for bronchospasm symptoms 1

Additional Targeted Therapies

For Specific Symptoms

• Gastrointestinal Symptoms:

  • H2 antihistamines as first-line therapy
  • Oral cromolyn sodium for bloating, diarrhea, and cramps
  • Leukotriene receptor antagonists (e.g., montelukast) may help, especially with elevated urinary LTE4 levels 1, 2
  • Cyproheptadine (H1 antihistamine with antiserotonergic properties) may help 2

• Skin Symptoms:

  • Moisturizers to prevent dryness
  • Water-soluble sodium cromolyn cream for urticaria and pruritus
  • Topical corticosteroids for inflammation 1, 2

• Refractory Symptoms:

  • Aspirin may reduce flushing and hypotension in some patients, 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 3

  • Doxepin (potent H1 & H2 antihistamine with tricyclic antidepressant activity)

    • May reduce central nervous system manifestations
    • Caution: may cause drowsiness, cognitive decline, and increase suicidal tendencies in children and young adults with depression 3

  • Steroid taper/burst for refractory symptoms

    • Initial oral dosage of 0.5 mg/kg/day, followed by slow taper over 1-3 months
    • Consider 50 mg prednisone 13 hours, 7 hours, and 1 hour before radiologic or invasive procedures when MC activation has been problematic 3

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams
• Pre-anesthetic treatment including anxiolytics, H1 and H2 antihistamines, and possibly corticosteroids
• Use safer anesthetic agents: propofol, sevoflurane, isoflurane, fentanyl, remifentanil
• Avoid muscle relaxants atracurium and mivacurium 2

Pregnancy Management

• Multidisciplinary team including high-risk obstetrics, anesthesia, and allergy specialists
• Focus on trigger avoidance, prophylactic antihistamines, and as-needed corticosteroids 2

Common Pitfalls and Caveats

• Cognitive decline reported with anticholinergic H1 blockers, especially in elderly patients
• Pain should not be left untreated, as it can trigger mast cell activation 1
• Measure serum tryptase within 30-120 minutes of symptom onset during acute reactions for diagnostic confirmation 1, 2
• Eliminating additives in drugs by compounding them is not recommended 3

Prognosis and Treatment Duration

• No specific studies evaluating prognosis of patients with MCAS
• Treatment should be based on symptoms and increased levels of MC mediators
• Therapeutic intervention should be adjusted to fit each patient 3