What is the treatment for mast cell activation syndrome?

Treatment for Mast Cell Activation Syndrome (MCAS)

The treatment of mast cell activation syndrome requires a stepwise approach focused on avoidance of triggers and anti-mediator drug therapy, with H1 and H2 antihistamines forming the cornerstone of management. 1

First-Line Treatment Approach

Trigger Avoidance

• Identify and avoid known triggers of mast cell activation
• Common triggers include:
  • Certain medications
  • Temperature extremes
  • Physical stress
  • Emotional stress
  • Alcohol
  • Certain foods

Anti-Mediator Pharmacotherapy

H1-Antihistamines

• First choice: Second-generation (non-sedating) H1 antihistamines
  • Fexofenadine, cetirizine, loratadine
  • Can be increased to 2-4 times standard dosing 1
  • Target symptoms: flushing, pruritus, urticaria, tachycardia, abdominal discomfort

H2-Antihistamines

• Famotidine, ranitidine, cimetidine
• Target symptoms: abdominal pain, heartburn, gastrointestinal symptoms
• Can enhance effectiveness of H1 blockers for cardiovascular symptoms 1

Mast Cell Stabilizers

• Cromolyn sodium (oral formulation)
  • FDA-approved for mastocytosis 2
  • Particularly effective for gastrointestinal symptoms: diarrhea, abdominal pain, nausea, vomiting 2
  • May also improve flushing, headaches, urticaria, and itching 2
  • Administration: Start with low doses and gradually increase; divided dosing improves tolerance 1

Second-Line and Adjunctive Treatments

Leukotriene Modifiers

• Montelukast (leukotriene receptor antagonist)
• Zileuton (5-lipoxygenase inhibitor)
• Most beneficial for respiratory and gastrointestinal symptoms, especially with elevated urinary LTE4 levels 1

Additional Options

• Aspirin: May reduce flushing and hypotension, particularly in patients with elevated urinary prostaglandin metabolites

  • Caution: Contraindicated in patients with NSAID sensitivity
  • May require doses up to 650mg twice daily 1

• Cyproheptadine: Sedating H1 antihistamine with antiserotonergic properties

  • Particularly helpful for gastrointestinal symptoms and nausea 1

• Ketotifen: Sedating H1 antihistamine available as compounded medication

  • Used for dermatologic, gastrointestinal, and neuropsychiatric symptoms 1

Management of Acute Exacerbations

For Severe Reactions/Anaphylaxis

• Epinephrine autoinjector: Essential for patients with history of systemic anaphylaxis
  • Patients should be prescribed two devices and trained on proper use 1
• Supine positioning during hypotensive episodes
• Albuterol for bronchospasm 1

For Refractory Symptoms

• Corticosteroids: For severe flares unresponsive to other treatments

  • Initial oral dose: 0.5 mg/kg/day with slow taper over 1-3 months
  • Consider 50 mg prednisone 13 hours, 7 hours, and 1 hour before procedures when mast cell activation has been problematic 1
  • Long-term use limited by side effects

• Omalizumab: Consider for prevention of recurrent anaphylactic episodes 1

  • Particularly useful in patients who cannot tolerate needed insect venom immunotherapy

Special Considerations

Perioperative Management

• Multidisciplinary approach involving surgical, anesthesia, and perioperative medical teams 1
• Pre-anesthetic treatment with:
  • Anxiolytic agents (benzodiazepines)
  • H1 and H2 antihistamines
  • Consider corticosteroids 1
• Safer anesthetic agents (though evidence is anecdotal):
  • Propofol for induction
  • Sevoflurane or isoflurane for inhalation
  • Fentanyl or remifentanil for analgesia
  • Rocuronium or vecuronium if muscle relaxants needed 1
• Avoid: atracurium, mivacurium, and succinylcholine 1

Pregnancy Considerations

• Managed by multidisciplinary team including high-risk obstetrics 1
• Focus on symptom control with medications safe during pregnancy
• For severe refractory cases during pregnancy, interferon-alfa may be considered
• Avoid cladribine, imatinib, and midostaurin during pregnancy 1

Advanced/Refractory Disease Management

For patients with systemic mastocytosis or refractory MCAS not responding to standard therapy:

• Cytoreductive therapy options (for systemic mastocytosis):
  • Midostaurin
  • Cladribine
  • Imatinib (if KIT D816V mutation negative)
  • Interferon-alfa ± prednisone 1

Monitoring and Follow-up

• Regular assessment of symptom burden and quality of life
• For patients with systemic mastocytosis: H&P and labs every 6-12 months
• DEXA scan every 1-3 years for patients with osteopenia/osteoporosis 1

Common Pitfalls to Avoid

• Using sedating antihistamines in elderly patients (risk of cognitive decline) 1
• Withholding analgesics during procedures (pain can trigger mast cell activation) 1
• Failing to provide epinephrine autoinjectors to patients at risk for anaphylaxis
• Misdiagnosing MCAS symptoms as functional gastrointestinal disorders 3
• Overdiagnosis of MCAS without thorough evaluation for other conditions 4