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

Treatment of Mast Cell Activation Syndrome

Start with H1 antihistamines as first-line therapy, add H2 antihistamines for gastrointestinal symptoms, and ensure every patient has an epinephrine autoinjector for emergency use. 1, 2

First-Line Preventive Treatment

H1 Antihistamines (Primary Therapy)

• Begin with nonsedating second-generation H1 antihistamines at standard doses (such as cetirizine) to control itching, flushing, skin rashes, and tachycardia 1, 2
• Doses may need to be increased to 2-4 times the standard FDA-approved dose for adequate symptom control in refractory cases 1, 2
• Alternative H1 options include diphenhydramine and hydroxyzine, though these sedating agents carry risks of drowsiness, impaired driving, and chronic cognitive decline, particularly in elderly patients 1, 2
• Monitor for cardiotoxicity when using high-dose H1 antihistamines 1

H2 Antihistamines (Add for GI Symptoms)

• Add H2 antihistamines (famotidine or ranitidine) if gastrointestinal symptoms persist despite H1 antihistamines alone 1, 2
• Combined H1 and H2 therapy is particularly effective for controlling severe pruritus and wheal formation when monotherapy fails 1
• H2 blockers may also help attenuate cardiovascular symptoms 2

Mast Cell Stabilizers

• Cromolyn sodium oral solution is FDA-approved for mastocytosis and has demonstrated improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching 3
• Clinical improvement typically occurs within 2-6 weeks of treatment initiation at 200 mg four times daily 3
• Benefits persist for 2-3 weeks after treatment withdrawal 3

Emergency Management

Epinephrine Autoinjector (Mandatory)

• Every MCAS patient must have an epinephrine autoinjector prescribed and caregivers trained in its use 1, 2
• Administer intramuscularly immediately for hypotension, wheezing, laryngeal edema, cyanotic episodes, or recurrent anaphylactic attacks 1, 2
• Maintain supine positioning during hypotensive episodes and throughout transport to the emergency department 2

Acute Symptom Management

• Albuterol treats bronchospasm symptoms 2
• Have emergency medications (epinephrine, corticosteroids, additional antihistamines) readily available 4

Second-Line and Adjunctive Therapies

Doxepin

• A potent H1 and H2 antihistamine with tricyclic antidepressant activity that may reduce central nervous system manifestations 2
• Use cautiously due to cognitive risks similar to sedating antihistamines and potential increased suicidal tendencies in children and young adults with depression 2

Aspirin

• May reduce flushing and hypotension in patients with elevated urinary 11β-PGF2α levels 2
• Contraindicated in those with allergic or adverse reactions to NSAIDs 2

Perioperative Management

• Pretreat with benzodiazepines, H1 and H2 antihistamines, and corticosteroids perioperatively to reduce frequency and severity of mast cell activation symptoms 2

Trigger Avoidance and Lifestyle Modifications

• Identification and avoidance of triggers is the first step in prevention 2
• Control temperature exposure, as mast cells are activated by hot temperatures and to a lesser extent cold temperatures 1
• Rational use of baths, showers, swimming pools, and air conditioning can decrease symptoms and reduce antihistamine requirements 1
• Avoid anxiety and stress, as they trigger mast cell activation 1

Pain Management Considerations

• Opioids should be used with caution but not withheld, as pain itself triggers mast cell degranulation 4, 2
• Fentanyl and remifentanil are safer opioid alternatives compared to morphine or codeine 4, 1, 2
• IV administration is generally preferred over oral administration to ensure reliable drug delivery and minimize gastrointestinal exposure 4
• Consider pretreatment with antihistamines (H1 and H2 blockers) and mast cell stabilizers before administering opioids 4

Advanced/Cytoreductive Therapies

• Reserved for aggressive systemic mastocytosis, smoldering systemic mastocytosis with severe refractory symptoms, or mast cell leukemia 2
• Options include midostaurin, cladribine, imatinib, and interferon-alpha preparations 2
• KIT inhibitors like avapritinib may result in virtual eradication of tissue mast cells in KIT D816V-positive mastocytosis, though use must be balanced against potential side effects 5

Critical Clinical Pearls

• Pain itself can trigger mast cell activation, creating a challenging cycle where inadequate pain control worsens MCAS symptoms 4
• A multidisciplinary approach involving allergy specialists and pain management experts is recommended 4
• Educate parents, caregivers, pediatricians, teachers, school nurses, and daycare workers about the diagnosis, treatment, and potential risks 1
• The long-term prognosis for children is favorable, with symptoms usually improving significantly after the first 6 to 18 months, and many experiencing spontaneous resolution as they grow older 1