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

Treatment of Mast Cell Activation Syndrome (MCAS)

The treatment of MCAS requires a stepwise approach focusing on trigger avoidance, prophylactic medications with H1 and H2 antihistamines as first-line therapy, and additional medications like cromolyn sodium for persistent symptoms. 1

First-Line Treatment Approach

Trigger Avoidance

• Identify and avoid known triggers of mast cell activation including:
  • Temperature extremes
  • Mechanical irritation
  • Alcohol
  • Certain medications (aspirin, radiocontrast agents, specific anesthetic agents)
  • Foods that trigger symptoms (individualized)

Prophylactic Medications

1. H1 Receptor Antihistamines

   • Nonsedating H1 antihistamines are preferred first-line (fexofenadine, cetirizine)
   • Can be increased to 2-4 times standard dosing for better symptom control
   • Target symptoms: flushing, pruritus, urticaria, tachycardia, abdominal discomfort 1
   • Caution with first-generation antihistamines (diphenhydramine, hydroxyzine) due to sedation and potential cognitive effects, especially in elderly patients

2. H2 Receptor Antihistamines

   • Ranitidine or other H2 blockers for gastrointestinal symptoms 1, 2
   • Particularly useful for abdominal pain, heartburn, and other GI manifestations
   • Also help H1 antihistamines attenuate cardiovascular symptoms

3. Cromolyn Sodium

   • Effective for gastrointestinal symptoms (diarrhea, abdominal pain, bloating) 3
   • Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3
   • Recommended dosing: 200 mg four times daily 3
   • Benefits may extend to neuropsychiatric manifestations 1
   • Divided dosing with weekly upward titration improves tolerance and adherence

Second-Line and Additional Therapies

For Persistent or Specific Symptoms

1. Leukotriene Modifiers

   • Montelukast (leukotriene receptor antagonist) or zileuton (5-lipoxygenase inhibitor)
   • Particularly helpful for bronchospasm or gastrointestinal symptoms
   • Most effective when urinary LTE4 levels are elevated 1

2. Aspirin

   • May reduce flushing and hypotension in some patients
   • Most effective in patients with elevated urinary 11β-PGF2α levels
   • Dosing may require increase up to 650 mg twice daily as tolerated
   • Contraindicated in patients with allergic or adverse reactions to NSAIDs 1

3. Doxepin

   • Potent H1 and H2 antihistamine with tricyclic antidepressant activity
   • Can help with central nervous system manifestations
   • Caution regarding drowsiness, cognitive effects, and potential increased suicidal tendencies in young adults with depression 1

4. Cyproheptadine

   • Sedating H1 antihistamine with antiserotonergic activities
   • Particularly helpful for gastrointestinal symptoms 1

5. Ketotifen

   • Sedating H1 antihistamine available as compounded medication in the US
   • Used for dermatologic, gastrointestinal, and neuropsychiatric symptoms 1

For Severe or Refractory Symptoms

1. Corticosteroids

   • Short-term use for severe flares (prednisone 0.5 mg/kg/day with slow taper over 1-3 months)
   • Premedication before procedures (50 mg prednisone at 13 hours, 7 hours, and 1 hour before procedures)
   • Long-term use limited by side effects 1

2. Omalizumab

   • Consider for prevention of anaphylactic episodes
   • Particularly useful for patients who cannot tolerate needed insect venom immunotherapy 1

Acute Management of Mast Cell Activation Attacks

1. Epinephrine Autoinjector

   • All patients with history of systemic anaphylaxis or airway angioedema should carry two autoinjectors
   • Instruct on proper use and when to administer 1

2. Supine Positioning

   • Patients with recurrent hypotensive episodes should be trained to assume supine position immediately 1

3. Bronchodilators

   • Albuterol via nebulizer or metered-dose inhaler for bronchospasm 1

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams
• Pre-anesthetic treatment with:
  • Anxiolytics (benzodiazepines)
  • Antihistamines (H1 and H2 blockers)
  • Consider corticosteroids 1
• Safer anesthetic agents include:
  • Propofol for induction
  • Sevoflurane or isoflurane for inhalation
  • Fentanyl or remifentanil for analgesia
  • Lidocaine or bupivacaine for local anesthesia 1
• Avoid muscle relaxants atracurium and mivacurium; rocuronium and vecuronium may be safer
• Avoid succinylcholine 1

Pregnancy Management

• Multidisciplinary team including high-risk obstetrician and anesthesiologist
• Avoidance of known triggers
• Prophylactic anti-mediator therapy (antihistamines, corticosteroids, epinephrine as needed)
• Interferon-alfa can be considered for pregnant women with severe refractory symptoms
• Avoid cladribine, imatinib, and midostaurin during pregnancy 1

Monitoring and Prognosis

• Clinical improvement typically occurs within 2-6 weeks of treatment initiation 3
• Benefits may persist for 2-3 weeks after treatment withdrawal
• Some patients with clonal MCAS may progress to systemic mastocytosis, though most follow an indolent course 1
• Therapeutic interventions should be adjusted based on symptoms and elevated mediator levels

By following this comprehensive treatment approach, most patients with MCAS can achieve significant symptom control and improved quality of life.