Mast Cell Activation Syndrome (MCAS) Management

First-Line Preventive Medications

The American Academy of Allergy, Asthma, and Immunology recommends H1 antihistamines as the primary preventive therapy, with nonsedating second-generation agents preferred at standard doses, which can be increased to 2-4 times the standard dose for refractory symptoms 1, 2
H2 antihistamines should be used as first-line therapy for gastrointestinal symptoms and may help H1 antihistamines attenuate cardiovascular symptoms 1
Sedating H1 antihistamines may be used but carry risks of drowsiness, impaired driving ability, and chronic cognitive decline, particularly in elderly patients 1, 2

Doxepin is a potent H1 and H2 antihistamine with tricyclic antidepressant activity that may reduce central nervous system manifestations, though it carries similar cognitive risks as sedating antihistamines and may increase suicidal tendencies in children and young adults with depression 1, 3
Aspirin may reduce flushing and hypotension in patients with elevated urinary 11β-PGF2α levels, but is contraindicated in those with allergic or adverse reactions to NSAIDs 1, 3

Epinephrine autoinjector is essential for patients with history of systemic anaphylaxis or airway angioedema, administered intramuscularly for hypotensive episodes, laryngeal angioedema, or bronchospasm 2, 3
Albuterol treats bronchospasm symptoms 1
Supine positioning is critical for hypotensive episodes and should be maintained during transport to emergency department 2, 3

Midostaurin, cladribine, imatinib, and interferon-alpha preparations are options for patients with aggressive systemic mastocytosis, smoldering systemic mastocytosis with severe refractory symptoms, or mast cell leukemia 4

Identification and avoidance of triggers is the first step in prevention 2, 3
Benzodiazepines, H1 and H2 antihistamines, and corticosteroids are recommended perioperatively to reduce frequency and severity of mast cell activation symptoms 5
Opioids should be used with caution as they can trigger mast cell activation, though should not be withheld since pain itself triggers degranulation; fentanyl and remifentanil are safer alternatives 5