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

Treatment of Mast Cell Activation Syndrome (MCAS)

The primary treatment for Mast Cell Activation Syndrome consists of H1 and H2 antihistamines, mast cell stabilizers like cromolyn sodium, and avoidance of identified triggers, with epinephrine autoinjectors for those with history of anaphylaxis. 1

First-Line Treatments

• Antihistamines:

  • Nonsedating H1 antihistamines (e.g., fexofenadine, cetirizine) are preferred and can be increased to 2-4 times the standard dose for symptom control 1
  • H2 antihistamines are first-line therapy for gastrointestinal symptoms and help H1 antihistamines attenuate cardiovascular symptoms 2, 1
  • Caution with sedating H1 antihistamines as they can cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 2, 1

• Mast Cell Stabilizers:

  • Oral cromolyn sodium is effective for gastrointestinal symptoms (diarrhea, abdominal pain, bloating) with benefits extending to neuropsychiatric manifestations 1, 3
  • Clinical improvement with cromolyn sodium typically occurs within 2-6 weeks of treatment initiation and persists for 2-3 weeks after treatment withdrawal 3

• Trigger Avoidance:

  • Identify and avoid known triggers including insect venoms, temperature extremes, mechanical irritation, alcohol, and certain medications (e.g., aspirin, radiocontrast agents, specific anesthetic agents) 1
  • For patients with insect venom sensitivity and history of systemic anaphylaxis, lifelong venom immunotherapy is recommended 1

Second-Line and Adjunctive Treatments

• Leukotriene Modifiers:

  • Montelukast or zileuton may reduce bronchospasm or gastrointestinal symptoms, particularly in patients with increased urinary LTE4 levels 2, 1

• Aspirin:

  • May reduce flushing and hypotension in some patients, particularly those with increased urinary prostaglandin metabolite levels 2, 1
  • Contraindicated in those with allergic or adverse reactions to NSAIDs 2

• Other Medications:

  • Doxepin (potent H1 & H2 antihistamine with tricyclic antidepressant activity) may reduce central nervous system manifestations but can cause drowsiness and cognitive decline 2
  • Omalizumab has shown benefit in preventing anaphylactic episodes in some patients 2
  • Cyproheptadine (sedating H1 antihistamine with anticholinergic and antiserotonergic activities) may help with gastrointestinal symptoms 2

Acute Management

• Epinephrine:

  • Patients with history of systemic anaphylaxis or airway angioedema should be prescribed an epinephrine autoinjector and instructed on proper use 2, 1
  • If epinephrine is used, the patient should be transported to the emergency department while remaining in the supine position 1

• Positioning:

  • Patients with recurrent hypotensive episodes should be trained to assume a supine position immediately 2, 1

• Bronchodilators:

  • Albuterol can be inhaled via nebulizer or metered-dose inhaler to treat bronchospasm 2, 1

• Corticosteroids:

  • May be useful for refractory symptoms at an initial oral dosage of 0.5 mg/kg/day, followed by a slow taper over 1-3 months 2
  • Side effects limit enthusiasm for long-term use 2, 1

Special Considerations

Perioperative Management

• Multidisciplinary management involving surgical, anesthesia, and perioperative medical teams is recommended 2, 1
• Pre-anesthetic treatment with anxiolytics (benzodiazepines), antihistamines (H1 and H2 blockers), and possibly corticosteroids 2, 1
• Safer anesthetic agents include propofol, sevoflurane, isoflurane, fentanyl, remifentanil, lidocaine, and bupivacaine 2, 1
• Avoid muscle relaxants atracurium and mivacurium (rocuronium and vecuronium may be safer) and succinylcholine 2, 1

Pregnancy Management

• Multidisciplinary approach including high-risk obstetrics, anesthesia, and allergy specialists 2
• Focus on trigger avoidance, prophylactic antihistamines, as-needed corticosteroids, and epinephrine for anaphylaxis 2
• For severe cases refractory to conventional therapy, interferon-alfa can be considered 2

Bone Health

• For patients with osteopenia/osteoporosis:
  • Supplemental calcium and vitamin D 2
  • Bisphosphonates (with continued use of antihistamines) 2
  • Anti-RANKL monoclonal antibody (e.g., denosumab) as second-line therapy for patients with bone pain not responding to bisphosphonates 2

Treatment Monitoring and Prognosis

• Treatment should be guided by symptoms and elevated mast cell mediator levels 1
• If a patient has increased urinary LTE4 levels, leukotriene antagonists are recommended; if urinary prostaglandin metabolite levels are increased, aspirin might help 1
• Some patients with clonal MCAS can progress to systemic mastocytosis, though long-term follow-up data shows limited progression 1, 4
• Treatment response should be monitored regularly, with medication adjustments based on symptom control 1, 5

Common Pitfalls to Avoid

• Failing to identify and address specific triggers for individual patients 1, 6
• Using sedating antihistamines in elderly patients or those who need to drive 2, 1
• Long-term steroid use without monitoring for side effects 2, 1
• Overlooking gastrointestinal symptoms that may be mistaken for functional disorders 7
• Not recognizing that MCAS may coexist with other conditions, requiring a personalized treatment approach 4, 6