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

Treatment of Mast Cell Activation Syndrome (MCAS)

The treatment of Mast Cell Activation Syndrome requires a stepwise approach with H1 and H2 antihistamines as first-line therapy, followed by mast cell stabilizers and leukotriene modifiers for persistent symptoms. 1

First-Line Treatment

Antihistamines

• H1 antihistamines: Later-generation non-sedating options are preferred
  • Fexofenadine or Cetirizine at 2-4 times standard dosing
  • Target symptoms: dermatologic manifestations (urticaria, pruritus), tachycardia, angioedema 1
• H2 antihistamines: Used in conjunction with H1 blockers
  • Famotidine or cimetidine
  • Target symptoms: gastrointestinal complaints, cardiovascular symptoms 1

Mast Cell Stabilizers

• Cromolyn sodium: FDA-approved for mastocytosis
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain)
  • Also helps with cutaneous manifestations and cognitive function
  • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 2
  • Patients should be counseled that onset of action can be delayed and should take it for at least 1 month before assessing efficacy 1

Acute Management

• Epinephrine autoinjector: Essential for patients with history of systemic anaphylaxis or airway angioedema 1
• Supine positioning: Recommended for hypotensive episodes 1
• Bronchodilators: Albuterol via nebulizer or metered-dose inhaler for bronchospasm 1

Second-Line Treatment (For Persistent Symptoms)

Leukotriene Modifiers

• Montelukast or zafirlukast (leukotriene receptor antagonists)
• Zileuton (5-lipoxygenase inhibitor)
• Target symptoms: dermatologic manifestations, bronchospasm, gastrointestinal symptoms 1

Prostaglandin Inhibitors

• Aspirin: Can reduce flushing and hypotensive episodes associated with PGD2 secretion
• Important caveat: Must be introduced in a controlled clinical setting due to risk of triggering mast cell degranulation
• Contraindicated in patients with allergic or adverse reactions to NSAIDs 1

Treatment of Resistant Symptoms

Biologics

• Omalizumab: Binds free IgE, preventing binding to FcεRI
  • Case reports support its benefit in preventing anaphylaxis
  • Expensive but effective option for refractory cases 1

Corticosteroids

• For refractory symptoms, initial oral dosage of 0.5 mg/kg/day
• Should be tapered as quickly as possible (over 1-3 months) to limit adverse effects 1

Advanced Therapies for Clonal MCAS

• Tyrosine kinase inhibitors: For patients with clonal MCAS (with KIT mutations)
  • Midostaurin: Multikinase inhibitor with activity against wild-type and D816V KIT
  • Masitinib: Effective against wild-type KIT and Lyn tyrosine kinases
  • Avapritinib: More selective D816V KIT inhibitor showing promising results 3

Avoidance Strategies

• Identify and avoid triggers of mast cell activation
• Common triggers include:
  • Temperature extremes (hypothermia or hyperthermia)
  • Physical trauma
  • Certain medications
  • Emotional stress 3

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams
• Pre-anesthetic treatment with:
  • Anxiolytic agents (benzodiazepines)
  • Antihistamines (H1 and H2 blockers)
  • Corticosteroids
• Safer anesthetic agents include:
  • Propofol (induction)
  • Sevoflurane or isoflurane (inhalational)
  • Fentanyl or remifentanil (analgesics)
  • Lidocaine, bupivacaine (local anesthetics)
• Avoid muscle relaxants atracurium and mivacurium (rocuronium and vecuronium may be safer) 3

Pregnancy Management

• Multidisciplinary team approach including high-risk obstetrics, anesthesia, and allergy specialists
• Focus on symptom alleviation with medications safe during pregnancy
• Avoid triggers and use prophylactic antihistamines
• For severe cases refractory to conventional therapy, interferon-alfa can be considered
• Tyrosine kinase inhibitors not recommended during pregnancy 3

Treatment Monitoring

• Assess efficacy based on reduction in frequency and severity of symptoms
• Focus on morbidity, mortality, and quality of life outcomes
• Consider tailoring treatment based on specific mediator elevations:
  • If increased urinary LTE4 levels: Use leukotriene antagonists
  • If increased urinary PG metabolite levels: Consider aspirin 3

Prognosis

• No specific studies evaluating prognosis of patients with MCAS
• Some patients with clonal MCAS can progress to systemic mastocytosis
• Patients with indolent systemic mastocytosis generally have normal life expectancy 3