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

Treatment Options for Mast Cell Activation Syndrome (MCAS)

The first-line treatment for MCAS consists of H1 and H2 antihistamines, with later-generation nonsedating H1 antihistamines often used at 2-4 times the standard FDA-approved doses for symptom control. 1, 2

First-Line Therapies

Antihistamines

• H1-receptor antihistamines are effective for dermatologic manifestations (flushing, pruritus, urticaria), tachycardia, and abdominal discomfort 1, 2
• Later-generation nonsedating H1 antihistamines (fexofenadine, cetirizine) are preferred over first-generation options and can be used at 2-4 times standard doses 1, 2
• H2-receptor antihistamines (famotidine, cimetidine) are recommended for gastrointestinal symptoms and to enhance the effect of H1 antihistamines on cardiovascular symptoms 1
• First-generation H1 antihistamines (diphenhydramine, hydroxyzine, chlorpheniramine) should be used cautiously due to sedation and potential cognitive decline, particularly in elderly patients 1

Mast Cell Stabilizers

• Oral cromolyn sodium is effective primarily for gastrointestinal symptoms (bloating, diarrhea, abdominal pain) 2, 3
• Should be started at low doses and gradually increased to 200 mg four times daily before meals and at bedtime 1
• Benefits may take 1-2 months to become apparent and persist for 2-3 weeks after discontinuation 1, 3
• May also help with neuropsychiatric manifestations 2

Second-Line Therapies

Leukotriene Modifiers

• Montelukast, zafirlukast (leukotriene receptor antagonists), or zileuton (5-lipoxygenase inhibitor) may reduce bronchospasm or gastrointestinal symptoms 1
• Most effective when used in conjunction with H1 antihistamines 1
• Particularly useful if urinary LTE4 levels are elevated 1, 2

Specialized Antihistamines

• Cyproheptadine (sedating H1 antihistamine with antiserotonergic properties) may help with gastrointestinal symptoms, diarrhea, and nausea 1
• Ketotifen (sedating H1 antihistamine) can be compounded in the US and may help with dermatologic, gastrointestinal, and neuropsychiatric symptoms 1

Anti-IgE Therapy

• Omalizumab has shown efficacy in refractory MCAS cases, with most patients (61%) achieving partial response and some (18%) achieving complete response 4
• Most effective at higher doses (≥300 mg/month) 4
• Can prevent anaphylactic episodes and allow discontinuation of systemic glucocorticoids in some patients 1, 4

Acute Management

Anaphylaxis Management

• Epinephrine autoinjector should be prescribed to patients with history of systemic anaphylaxis or airway angioedema 1, 2
• Patients should be instructed on proper use and when to administer 1
• Patients with recurrent hypotensive episodes should be trained to assume a supine position immediately 1
• Albuterol can be used via nebulizer or metered-dose inhaler for bronchospasm 1

Corticosteroids

• Short-term steroid bursts may be useful for refractory symptoms at an initial oral dose of 0.5 mg/kg/day with slow taper over 1-3 months 1
• Consider 50 mg prednisone 13 hours, 7 hours, and 1 hour before radiologic or invasive procedures when mast cell activation has been problematic 1
• Long-term use should be avoided due to side effects 2

Special Considerations

Aspirin Therapy

• May help attenuate refractory flushing and hypotensive episodes associated with prostaglandin D2 secretion 1
• Should be introduced in a controlled clinical setting due to risk of triggering mast cell degranulation 1
• Contraindicated in those with allergic reactions to NSAIDs 2

Perioperative Management

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

Common Pitfalls to Avoid

• Sedating H1 antihistamines can cause cognitive decline, particularly in elderly patients 1, 2
• Long-term steroid use should be avoided due to numerous adverse effects 2
• Aspirin should be introduced cautiously due to risk of triggering mast cell degranulation 1, 2
• Failure to recognize that symptoms may take 2-6 weeks to improve with treatments like cromolyn sodium 3
• Not prescribing epinephrine autoinjectors to patients with history of anaphylaxis 1, 2

Treatment Approach Algorithm

1. Start with antihistamines:

   • Second-generation H1 antihistamine (fexofenadine or cetirizine)
   • Add H2 antihistamine (famotidine or cimetidine) for gastrointestinal symptoms
   • Increase H1 antihistamine dose up to 2-4 times standard if needed 1, 2

2. Add mast cell stabilizer:

   • Oral cromolyn sodium for persistent gastrointestinal symptoms 1, 3

3. For inadequate response, add:

   • Leukotriene modifier (montelukast or zileuton) 1
   • Consider specialized antihistamines (cyproheptadine, ketotifen) for specific symptoms 1

4. For refractory cases:

   • Consider omalizumab, particularly for recurrent anaphylaxis 4
   • Short-term corticosteroids for severe flares 1
   • Cautious trial of aspirin in a controlled setting if prostaglandin-mediated symptoms predominate 1

5. Always provide:

   • Epinephrine autoinjector for patients with history of anaphylaxis 1, 2
   • Education on trigger avoidance and emergency management 2