What is the management approach for mast cell activation syndrome?

Management of Mast Cell Activation Syndrome (MCAS)

The first-line treatment for Mast Cell Activation Syndrome consists of H1 and H2 antihistamines, mast cell stabilizers like cromolyn sodium, and avoidance of identified triggers, with additional medications added in a stepwise approach based on symptom severity and organ system involvement. 1

First-Line Pharmacological Management

Antihistamines

• H1 antihistamines: Nonsedating options preferred for dermatologic manifestations, tachycardia, and abdominal discomfort 1
  • First-generation (sedating) H1 antihistamines should be used with caution, particularly in elderly patients, due to risk of cognitive decline and drowsiness 1
• H2 antihistamines: Famotidine and cimetidine for gastrointestinal symptoms and to enhance H1 antihistamine effects on cardiovascular symptoms 1

Mast Cell Stabilizers

• Oral cromolyn sodium: Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain) 2
  • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 2
  • Recommended administration: Divided dosing with weekly upward titration to improve tolerance 1
  • Patients should be counseled that benefits may take up to a month to appear 1

Emergency Medications

• Epinephrine autoinjectors: Essential for patients with history of systemic anaphylaxis or airway angioedema 1
  • Patients must be properly instructed on proper use and indications

Second-Line and Adjunctive Therapies

For Respiratory Symptoms

• Bronchodilators: Albuterol via nebulizer or metered-dose inhaler for bronchospasm 1
• Leukotriene modifiers: Montelukast and zafirlukast particularly helpful for bronchospasm and gastrointestinal symptoms, especially with elevated urinary LTE4 levels 1

For Refractory Symptoms

• Aspirin: Can reduce flushing and hypotension, especially with elevated urinary 11β-PGF2α levels 1

  • CAUTION: Contraindicated in those with allergic or adverse reactions to NSAIDs
  • Introduction should be done in a controlled clinical setting due to risk of triggering mast cell degranulation 1

• Corticosteroids: For refractory symptoms 1

  • Initial oral dosage: 0.5 mg/kg/day
  • Can be used prophylactically before procedures

• Omalizumab: Consider for patients with symptoms resistant to standard therapies 1

  • Binds free IgE, preventing binding to FcεRI
  • Case reports support its benefit in preventing anaphylaxis
  • Limitation: Expensive

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative teams 3, 1
• Pre-anesthetic treatment:
  • Anxiolytics (benzodiazepines)
  • Antihistamines (H1 and H2 blockers)
  • Consider corticosteroids
• Safer anesthetic options: 3
  • Induction: Propofol
  • Inhalational: Sevoflurane or isoflurane
  • Analgesics: Fentanyl or remifentanil
  • Local anesthetics: Lidocaine, bupivacaine
• Avoid: Muscle relaxants atracurium and mivacurium, succinylcholine 3
• Exercise caution with opiates (codeine, morphine) but don't withhold if needed for pain 3

Obstetric Management

• Multidisciplinary team including high-risk obstetrics, anesthesia, and allergy 3, 1
• Focus on symptom alleviation with medications that minimize fetal harm
• Standard approaches during pregnancy: 3
  • Avoidance of triggers
  • Prophylactic antihistamines
  • As-needed corticosteroids
  • Epinephrine on demand for anaphylaxis

Bone Health Management

For patients with osteopenia/osteoporosis: 3

• Supplemental calcium and vitamin D
• Bisphosphonates (with continued use of antihistamines)
• Consider anti-RANKL monoclonal antibody (e.g., denosumab) as second-line therapy for refractory bone pain

Monitoring and Treatment Assessment

• Evaluate treatment efficacy based on reduction in frequency and severity of symptoms 1
• Focus on morbidity, mortality, and quality of life outcomes
• In anaphylaxis events: Check serum tryptase level within 30–120 minutes of symptom onset 3

Common Pitfalls and Caveats

1. Mistaking MCAS for functional gastrointestinal disorders 4
2. Significant delays in diagnosis are common 4
3. Failure to recognize that multiple conditions can coexist in the same patient (e.g., hereditary alpha tryptasemia, mastocytosis, atopic diathesis) 5, 6
4. Not accounting for the multisystem nature of the disorder when developing treatment plans 7
5. Underappreciation of the need for multidisciplinary management 8

By following this stepwise approach to MCAS management with careful attention to symptom patterns and organ system involvement, clinicians can significantly improve quality of life and reduce morbidity for patients with this challenging condition.