How is mast cell activation syndrome (MCAS) managed?

Management of Mast Cell Activation Syndrome (MCAS)

The management of mast cell activation syndrome requires a stepwise approach focused on trigger avoidance, symptom prevention with antihistamines and mast cell stabilizers, and acute treatment with epinephrine for severe reactions. 1

Prevention Strategies

Trigger Identification and Avoidance

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

First-Line Pharmacologic Prevention

• H1-receptor antihistamines: Nonsedating H1 antihistamines (e.g., fexofenadine, cetirizine) are generally preferred and can be increased to 2-4 times the standard dose for symptom control 1
• H2-receptor antihistamines: Recommended as first-line therapy for gastrointestinal symptoms and to help H1 antihistamines attenuate cardiovascular symptoms 1
• Oral cromolyn sodium: FDA-approved for mastocytosis to reduce abdominal bloating, diarrhea, and cramps; benefits may extend to neuropsychiatric manifestations 1, 2
• Leukotriene modifiers: Montelukast or zileuton may reduce bronchospasm or gastrointestinal symptoms, particularly in patients with increased urinary LTE4 levels 1

Second-Line Pharmacologic Prevention

• Doxepin: A potent H1 and H2 antihistamine with tricyclic antidepressant activity that may reduce central nervous system manifestations, but can cause drowsiness and cognitive decline, particularly in elderly patients 1
• Aspirin: May reduce flushing and hypotension in some patients, particularly those with increased urinary 11β-PGF2α levels, but is contraindicated in those with allergic reactions to NSAIDs 1
• Cyproheptadine: A sedating H1 antihistamine with anticholinergic and antiserotonergic activities that may help with gastrointestinal symptoms 1
• Ketotifen: A sedating H1-receptor antagonist available as a compounded medication in the US 1

Refractory Cases

• Omalizumab: Case reports indicate prevention of anaphylactic episodes in some patients with MCAS or systemic mastocytosis 1
• Corticosteroids: Short-term use for refractory symptoms at an initial oral dosage of 0.5 mg/kg/day, followed by a slow taper over 1-3 months 1
• GLP-1 receptor agonists: Emerging evidence suggests potential benefit in refractory MCAS, though further research is needed 3

Acute Management

Anaphylaxis and Severe Reactions

• Epinephrine autoinjector: Patients with a history of systemic anaphylaxis or airway angioedema should be prescribed this device and instructed on proper use 1
• Supine positioning: Patients with recurrent hypotensive episodes should be trained to assume a supine position immediately 1
• Bronchodilators: Albuterol can be inhaled via nebulizer or metered-dose inhaler to treat bronchospasm 1
• Emergency medical attention: If epinephrine is used, the patient should be transported to the emergency department while remaining in the supine position 1

Organ-Specific Management

Gastrointestinal Symptoms

• H2-receptor antihistamines are first-line therapy 1
• Oral cromolyn sodium can reduce abdominal bloating, diarrhea, and cramps 1, 2
• Leukotriene modifiers may help with gastrointestinal symptoms 1
• Cyproheptadine may be beneficial for diarrhea and nausea 1

Skin Manifestations

• H1-receptor antihistamines for dermatologic manifestations like flushing, pruritus, urticaria 1
• Topical treatments may include water-soluble sodium cromolyn cream for urticaria and pruritus 1
• Topical corticosteroids for skin inflammation 1

Neuropsychiatric Symptoms

• Cromolyn sodium benefits may extend to neuropsychiatric manifestations 1
• Doxepin may reduce central nervous system manifestations 1

Special Considerations

Perioperative Management

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

Pregnancy Management

• Multidisciplinary approach including high-risk obstetrics, anesthesia, and allergy specialists 1
• Focus on trigger avoidance, prophylactic antihistamines, as-needed corticosteroids, and epinephrine for anaphylaxis 1
• Cytoreductive therapy with interferon-alfa can be considered for severe refractory cases, but cladribine or tyrosine kinase inhibitors are not recommended 1

Treatment Monitoring and Prognosis

• Treatment should be guided by symptoms and elevated mast cell mediator levels 1
• For example, 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 data from the Mayo Clinic cohort followed for more than 15 years showed no progression to mastocytosis 1
• Patients with indolent systemic mastocytosis generally have a normal life expectancy 1

Common Pitfalls to Avoid

• Sedating H1 antihistamines can cause drowsiness, impair driving ability, and lead to cognitive decline, particularly in elderly patients 1
• Aspirin should be used with caution and is contraindicated in those with allergic reactions to NSAIDs 1
• Long-term steroid use should be avoided due to side effects 1
• Eliminating additives in drugs by compounding is not recommended based on evidence from studies in chronic urticaria 1