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

Treatment for Mast Cell Activation Syndrome (MCAS)

First-line treatment for MCAS includes H1 and H2 antihistamines, with nonsedating H1 antihistamines generally preferred, targeting symptoms such as dermatologic manifestations, tachycardia, and abdominal discomfort. 1

First-Line Treatments

1. H1 Antihistamines:

   • Nonsedating H1 antihistamines are preferred for most patients
   • First-generation H1 antihistamines should be used with caution, particularly in elderly patients, due to risk of cognitive decline 1

2. H2 Antihistamines:

   • Examples: famotidine and cimetidine
   • Target gastrointestinal symptoms
   • Help H1 antihistamines attenuate cardiovascular symptoms 1

3. Oral Cromolyn Sodium:

   • Specifically for gastrointestinal symptoms
   • Inhibits sensitized mast cell degranulation by blocking calcium ions from entering mast cells 2
   • Benefits typically seen within 2-6 weeks of treatment initiation
   • Patients should be counseled to take it for at least 1 month before determining efficacy 1

Second-Line and Adjunctive Treatments

1. Leukotriene Modifiers:

   • Examples: montelukast and zafirlukast
   • For bronchospasm and gastrointestinal symptoms
   • Especially beneficial when urinary LTE4 levels are elevated 1

2. Aspirin:

   • Reduces flushing and hypotension
   • Most effective when urinary 11β-PGF2α levels are elevated
   • CAUTION: Introduction should be done in a controlled clinical setting due to risk of triggering mast cell degranulation
   • Contraindicated in those with allergic or adverse reactions to NSAIDs 1

3. Corticosteroids:

   • For refractory symptoms
   • Initial oral dosage of 0.5 mg/kg/day
   • Can be used prophylactically before procedures 1

4. Omalizumab:

   • For patients with symptoms resistant to standard therapies
   • Binds free IgE, preventing binding to FcεRI
   • Note: Expensive treatment option 1

Emergency Medications

1. Epinephrine Autoinjectors:

   • Essential for patients with history of systemic anaphylaxis or airway angioedema 1

2. Bronchodilators:

   • Example: albuterol
   • For bronchospasm via nebulizer or metered-dose inhaler 1

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative teams
• Pre-anesthetic treatment with anxiolytics, antihistamines, and possibly corticosteroids
• Safer anesthetic options include:
  • Propofol for induction
  • Sevoflurane or isoflurane for inhalational anesthesia
  • Fentanyl or remifentanil for analgesia
  • Lidocaine and bupivacaine for local anesthetics 1

Diagnostic Approach to Guide Treatment

• Treatment should be tailored based on specific mediator elevations:
  • If increased urinary LTE4 levels: leukotriene antagonists recommended
  • If increased urinary PG metabolite levels: aspirin treatment may help 3

Treatment Assessment

• Efficacy should be evaluated based on reduction in frequency and severity of symptoms
• Focus on morbidity and mortality outcomes 1

Pitfalls and Caveats

1. Diagnostic Confusion:

   • MCAS is often misdiagnosed; thorough evaluation is necessary to exclude other conditions (autoimmune, neoplastic, or infectious) 4
   • Distinguish between primary MCAS (KIT-mutated, clonal mast cells), secondary MCAS (underlying inflammatory disease/allergy), and idiopathic MCAS 5

2. Treatment Considerations:

   • Avoid muscle relaxants atracurium and mivacurium, and succinylcholine during anesthesia 1
   • Exercise caution with opiates such as codeine and morphine, but do not withhold if needed for pain management 1
   • Eliminating additives in drugs by compounding is not supported by evidence 1

3. Monitoring:

   • In anaphylaxis events, check serum tryptase level within 30–120 minutes of symptom onset 1
   • Some patients with clonal MCAS can progress to systemic mastocytosis, requiring monitoring 3

MCAS treatment requires a personalized approach based on symptom presentation and mediator profiles, with the primary goal of reducing morbidity and mortality through appropriate mediator-targeting therapies.