What is the treatment for mast cell activation syndrome?

Treatment of Mast Cell Activation Syndrome (MCAS)

The first-line treatment for mast cell activation syndrome consists of H1 and H2 antihistamines, with nonsedating H1 antihistamines (such as fexofenadine and cetirizine) often used at 2-4 times standard doses for optimal symptom control. 1

First-Line Medications

• H1 antihistamines reduce dermatologic manifestations (flushing, pruritus), tachycardia, and abdominal discomfort 2

  • Nonsedating H1 antihistamines (fexofenadine, cetirizine) are preferred and can be used at 2-4 times standard doses 1
  • First-generation H1 antihistamines (diphenhydramine, hydroxyzine) should be used with caution, especially in elderly patients, due to sedation and cognitive decline risks 2

• H2 antihistamines (ranitidine, famotidine) are recommended for:

  • Gastrointestinal symptoms 1, 3
  • Enhancing the effect of H1 antihistamines for cardiovascular symptoms 1

• Oral cromolyn sodium is FDA-approved for mastocytosis and helps with:

  • Gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting) 4
  • May also improve flushing, headaches, urticaria, and itching 4
  • Potential benefits for neuropsychiatric manifestations 1

Second-Line and Adjunctive Treatments

• Leukotriene modifiers:

  • Montelukast or zileuton may reduce bronchospasm and gastrointestinal symptoms 2, 1
  • Particularly helpful if urinary LTE4 levels are elevated 2

• Specialized antihistamines for specific symptoms:

  • Cyproheptadine (H1 antihistamine with antiserotonergic activity) may help with gastrointestinal symptoms 2
  • Ketotifen (sedating H1 antihistamine) can be compounded for dermatologic, gastrointestinal, and neuropsychiatric symptoms 2

• Aspirin therapy:

  • May help if prostaglandin metabolite levels are increased 1
  • Use with caution as it's contraindicated in those with allergic reactions to NSAIDs 1, 5

Acute Management

• Epinephrine autoinjector:

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

• Immediate interventions during acute episodes:

  • Assume supine position for hypotensive episodes 2, 1
  • Albuterol via nebulizer or inhaler for bronchospasm 2
  • Transport to emergency department while maintaining supine position if epinephrine is used 1

• Corticosteroids for severe episodes:

  • Initial oral dosage of 0.5 mg/kg/day with slow taper over 1-3 months for refractory symptoms 2
  • Consider 50 mg prednisone at 13 hours, 7 hours, and 1 hour before procedures when MC activation has been problematic 2
  • Long-term use should be avoided due to side effects 1

Advanced Therapies

• Omalizumab:

  • Case reports show prevention of anaphylactic episodes in some MCAS patients 2
  • Particularly helpful for those who cannot tolerate needed insect venom immunotherapy 2

• KIT-targeting drugs:

  • Emerging research suggests potential for mast cell eradication in certain cases 6
  • Currently more applicable to mastocytosis than non-clonal MCAS 6

Prevention Strategies

• Identify and avoid known triggers including: 1

  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (radiocontrast agents, specific anesthetic agents)

• For patients with insect venom sensitivity and history of systemic anaphylaxis, consider lifelong venom immunotherapy 1

Special Considerations

Perioperative Management

• Requires multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams 1
• Pre-anesthetic treatment with anxiolytics, antihistamines (H1 and H2), and possibly corticosteroids 1
• Safer anesthetic agents include propofol, sevoflurane, isoflurane, fentanyl, remifentanil, lidocaine, and bupivacaine 1
• Avoid muscle relaxants atracurium and mivacurium; rocuronium and vecuronium may be safer 1

Common Pitfalls to Avoid

• Misdiagnosing symptoms as functional gastrointestinal disorders when they may be MCAS 7
• Focusing only on histamine and tryptase when other mediators may be involved 8
• Using sedating antihistamines in elderly patients or those prone to cardiovascular events 2
• Long-term steroid use without considering side effects 1

Treatment Monitoring

• Guide therapy based on symptoms and elevated mast cell mediator levels 1, 9
• If urinary LTE4 levels are increased, use leukotriene antagonists 1
• If urinary prostaglandin metabolite levels are increased, consider aspirin (with appropriate precautions) 1

MCAS treatment requires a targeted approach based on the specific mediators involved and symptoms presented. The foundation of therapy remains antihistamines and mast cell stabilizers, with additional medications added based on symptom profile and laboratory findings.