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

Treatment for Mast Cell Activation Syndrome (MCAS)

The first-line treatment for Mast Cell Activation Syndrome is a combination of H1 and H2 receptor antihistamines, with later-generation nonsedating H1 antihistamines (such as fexofenadine and cetirizine) being preferred, which can be increased to 2-4 times the standard dose if needed. 1

First-Line Treatment Approach

Antihistamines

• H1 antihistamines:

  • Nonsedating options (preferred): Fexofenadine, Cetirizine
  • Can be increased to 2-4 times standard dose for better symptom control
  • Target symptoms: dermatologic manifestations, tachycardia, pruritus, flushing

• H2 antihistamines:

  • Options: Famotidine, Cimetidine
  • Target symptoms: gastrointestinal symptoms, cardiovascular symptoms
  • Prevent histamine-mediated acid secretion and blunt vasoactive effects

Mast Cell Stabilizers

• Cromolyn sodium:
  • Particularly effective for gastrointestinal symptoms (diarrhea, abdominal pain)
  • Also helps with cutaneous manifestations (urticaria, pruritus, flushing)
  • 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 deciding efficacy 1
  • Standard dose: 200 mg four times daily

Acute Management of Mast Cell Activation Attacks

• Epinephrine autoinjector: Essential for patients with history of anaphylaxis or airway angioedema
• Positioning: Supine position for hypotensive episodes
• Bronchodilators: Albuterol via nebulizer or metered-dose inhaler for bronchospasm
• Emergency care: If epinephrine is used, patient should be transported to emergency department while remaining supine 3

Second-Line Treatment Options

If first-line treatments are insufficient, consider adding:

Leukotriene Modifiers

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

Aspirin Therapy

• Can reduce flushing and hypotensive spells associated with PGD2 secretion
• Important caveat: Should 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 for Resistant Symptoms

Omalizumab

• Consider for patients with symptoms resistant to standard therapies
• Binds free IgE, preventing binding to FcεRI
• Particularly effective for preventing anaphylaxis in refractory cases
• Most common effective dose: 150 mg every 2 weeks
• Higher doses (≥300 mg/month) may be associated with complete response in some patients 4
• Majority of patients (61%) achieve at least partial response 4

Corticosteroids

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

Trigger Avoidance

• Identify and avoid triggers such as:
  • Insect venoms
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Medications (aspirin, radiocontrast agents, certain anesthetic agents) 3
  • For patients with venom sensitivity and history of anaphylaxis, consider lifelong venom immunotherapy

Special Considerations

Perioperative Management

• Higher risk of anaphylaxis during perioperative period
• Multidisciplinary management recommended (surgical, anesthesia, perioperative medical teams)
• Pre-anesthetic treatment: anxiolytic agents (benzodiazepines), antihistamines (H1 and H2 blockers), possibly corticosteroids
• Safer anesthetic agents: propofol, sevoflurane, isoflurane, fentanyl, remifentanil, lidocaine, bupivacaine
• Agents to avoid: muscle relaxants atracurium and mivacurium, succinylcholine 3

Pregnancy Management

• Multidisciplinary team approach (high-risk obstetrics, anesthesia, allergy)
• Focus on trigger avoidance, prophylactic antihistamines, as-needed corticosteroids, and epinephrine for anaphylaxis
• For severe refractory cases, interferon-alfa can be considered
• Avoid cladribine or tyrosine kinase inhibitors 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
• Note that urinary histamine levels and peripheral eosinophilia may not correlate with disease severity 2

Emerging Treatments

• KIT-targeting drugs are being investigated for mast cell eradication in certain cases, but must be balanced against potential side effects 5

By following this treatment algorithm and individualizing based on symptom predominance and response, most patients with MCAS can achieve significant improvement in quality of life and reduction in morbidity.