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

Treatment for Mast Cell Activation Syndrome (MCAS)

The cornerstone of MCAS treatment is a stepwise approach using antihistamines (H1 and H2 blockers), mast cell stabilizers, and medications targeting specific mediators, along with trigger avoidance. 1

First-Line Therapy

• H1 antihistamines: Nonsedating options (fexofenadine, cetirizine) are preferred and can be used at 2-4 times the standard dose for symptom control 2, 1

  • First-generation H1 antihistamines should be used cautiously, especially in elderly patients, due to risk of cognitive decline 2

• H2 antihistamines: First-line therapy for gastrointestinal symptoms and can help H1 antihistamines attenuate cardiovascular symptoms 2, 1

• Oral cromolyn sodium: Effective for reducing abdominal bloating, diarrhea, and cramps; benefits may extend to neuropsychiatric manifestations 2, 1, 3

  • Mechanism: Inhibits sensitized mast cell degranulation by indirectly blocking calcium ions from entering mast cells 3
  • Divided dosing with weekly upward titration improves tolerance and adherence 2

• Trigger identification and avoidance: Critical component of management 1

  • Common triggers include insect venoms, temperature extremes, mechanical irritation, alcohol, and certain medications 1, 4

Second-Line and Adjunctive Therapy

• Leukotriene modifiers: Montelukast or zileuton may reduce bronchospasm or gastrointestinal symptoms, particularly in patients with increased urinary LTE4 levels 2, 1, 5

• Aspirin: May reduce flushing and hypotension in some patients, particularly those with increased urinary prostaglandin metabolites 2

  • Use with caution and contraindicated in those with allergic reactions to NSAIDs 2, 1

• Doxepin: A potent H1 and H2 antihistamine with tricyclic antidepressant activity that may reduce central nervous system manifestations 2, 1

  • May cause drowsiness and cognitive decline, particularly in elderly patients 2

• Omalizumab: Case reports indicate prevention of anaphylactic episodes in some patients with MCAS 2, 5

• Cyproheptadine: A sedating H1 antihistamine with anticholinergic and antiserotonergic activities that may help with gastrointestinal symptoms 2

Acute Management

• Epinephrine autoinjector: Patients with history of systemic anaphylaxis or airway angioedema should be prescribed this device and instructed on proper use 2, 1

• Supine 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

  • Can also be used prophylactically before procedures (50 mg prednisone at 13 hours, 7 hours, and 1 hour before procedures) 2

Special Considerations

Perioperative Management

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

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

Treatment Monitoring

• Treatment should be guided by symptoms and elevated mast cell mediator levels 1, 6
• If a patient has increased urinary LTE4 levels, leukotriene antagonists are recommended; if urinary prostaglandin metabolite levels are increased, aspirin might help 1, 5

Common Pitfalls to Avoid

• Misdiagnosis as functional gastrointestinal disorders, leading to treatment delays 7, 4
• Using sedating H1 antihistamines in elderly patients, which can cause cognitive decline 2, 1
• Long-term steroid use should be avoided due to side effects 1
• Failure to recognize associated conditions like autonomic dysfunction, small fiber neuropathy, and connective tissue disorders that may impact symptoms 4
• Not distinguishing between primary (clonal), secondary (reactive), and idiopathic MCAS, which affects treatment approach 6, 8