What is the treatment for mast cell activation syndrome?

Treatment of Mast Cell Activation Syndrome (MCAS)

The treatment of mast cell activation syndrome requires 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
• Common triggers include:
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (aspirin, radiocontrast agents, specific anesthetics)

Pharmacologic Management

Core Medications

1. H1-Receptor Antihistamines

   • Nonsedating H1 antihistamines are preferred first-line
   • Can be increased to 2-4 times standard dose if needed
   • Sedating antihistamines (e.g., diphenhydramine) may cause drowsiness and cognitive decline, particularly in elderly 1

2. H2-Receptor Antihistamines

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

3. Oral Cromolyn Sodium

   • FDA-indicated for mastocytosis 2
   • Particularly effective for gastrointestinal symptoms (bloating, diarrhea, abdominal cramps)
   • May also improve neuropsychiatric manifestations
   • Recommended administration: divided dosing with weekly upward titration 1

Additional Medications Based on Symptoms

• Leukotriene Inhibitors (montelukast or zileuton)

  • For bronchospasm or persistent gastrointestinal symptoms
  • Particularly useful if urinary LTE4 levels are elevated 1

• Aspirin

  • May reduce flushing and hypotension in some patients
  • Particularly effective in those with elevated urinary 11β-PGF2α levels
  • Use with caution; contraindicated in those with allergic reactions to NSAIDs 1

• Doxepin

  • Potent H1 and H2 antihistamine with tricyclic antidepressant activity
  • May reduce central nervous system manifestations
  • Caution: can cause drowsiness, cognitive decline, and may increase suicidal tendencies in younger patients with depression 1

Acute Management of Mast Cell Activation Attacks

Emergency Medications

• Epinephrine autoinjector

  • All patients with history of systemic anaphylaxis should carry two autoinjectors
  • Use for severe reactions, especially hypotension or laryngeal angioedema 1

• Albuterol

  • For bronchospasm symptoms
  • Can be administered via nebulizer or metered-dose inhaler 1

Emergency Management Steps

1. Assume supine position for hypotensive episodes
2. Administer intramuscular epinephrine for severe reactions
3. Use inhaled bronchodilators for bronchospasm
4. Consider corticosteroids for prolonged episodes
5. Seek emergency care after epinephrine use 1

Special Considerations

Perioperative Management

• Higher risk of anaphylaxis during surgical procedures
• Recommendations:
  • Multidisciplinary approach involving surgical, anesthesia, and perioperative teams
  • Pre-anesthetic treatment with anxiolytics, antihistamines, and possibly corticosteroids
  • Avoid temperature extremes and unnecessary trauma
  • Safer anesthetic agents: propofol, sevoflurane, isoflurane, fentanyl, remifentanil
  • Avoid muscle relaxants atracurium and mivacurium; rocuronium and vecuronium may be safer 1

Pregnancy Management

• Multidisciplinary approach with high-risk obstetrics, anesthesia, and allergy specialists
• Focus on symptom management with medications safe during pregnancy
• Avoid triggers and use prophylactic antihistamines
• For severe refractory cases, interferon-alfa may be considered
• Avoid cladribine and tyrosine kinase inhibitors during pregnancy 1

Treatment for Specific Symptoms

Skin Symptoms

• Moisturize to prevent dryness
• Water-soluble sodium cromolyn cream for urticaria and pruritus
• Topical corticosteroids
• For diffuse lesions: zinc sulfate baths or sterile gauze 1

Gastrointestinal Symptoms

• H2 antihistamines as first-line therapy
• Oral cromolyn sodium for bloating, diarrhea, and cramps
• Cyproheptadine may help with gastrointestinal symptoms 1, 3

Bone Health

For patients with osteopenia/osteoporosis:

• Calcium and vitamin D supplementation
• Bisphosphonates (continue antihistamines)
• For refractory bone pain: consider interferon-alfa or denosumab 1

Common Pitfalls and Caveats

• Failure to recognize MCAS leads to significant delays in diagnosis and appropriate treatment 3
• Cognitive decline has been reported with anticholinergic H1 blockers, especially in elderly patients 1
• Pain should not be left untreated, as it can trigger mast cell activation 1
• Aspirin therapy requires caution due to potential for triggering reactions in some patients 1
• Diagnostic workup during acute reactions is crucial: measure serum tryptase within 30-120 minutes of symptom onset 1

The management of MCAS requires ongoing assessment of symptom burden and quality of life, with treatment adjustments based on response. While research on newer targeted therapies is ongoing 4, the current approach focusing on mediator blockade and mast cell stabilization remains the cornerstone of treatment.