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

Treatment of Mast Cell Activation Syndrome (MCAS)

Start with H1 and H2 antihistamines as first-line therapy, add cromolyn sodium 200 mg four times daily if symptoms persist, and reserve omalizumab for refractory cases unresponsive to standard antimediator therapy. 1, 2

Stepwise Treatment Algorithm

First-Line: Antimediator Therapy

Begin with dual antihistamine blockade as the foundation of treatment 2:

• H1 antihistamines to control urticaria, pruritus, and flushing 2
• H2 antihistamines to address gastrointestinal symptoms and provide additional mediator blockade 2
• Add leukotriene receptor antagonists for patients with respiratory symptoms or inadequate response to antihistamines alone 2

Second-Line: Cromolyn Sodium

If symptoms persist despite antihistamine therapy, add cromolyn sodium oral solution 200 mg four times daily. 1

Cromolyn sodium is FDA-approved specifically for mastocytosis and provides:

• Improvement in diarrhea, abdominal pain, flushing, headaches, vomiting, urticaria, nausea, and itching 1
• Clinical benefit typically appears within 2-6 weeks of treatment initiation 1
• Efficacy comparable to combination therapy with chlorpheniramine plus cimetidine 1
• Benefits persist for 2-3 weeks after discontinuation 1

Third-Line: Additional Mediator-Targeting Agents

For patients with partial response, consider adding 2:

• Aspirin (if tolerated) to inhibit prostaglandin D2 synthesis 2
• Zileuton for leukotriene synthesis inhibition 2
• Corticosteroids for prolonged severe episodes, though not for routine maintenance 2

Fourth-Line: Omalizumab for Refractory Disease

For patients refractory to H1 antihistamines plus at least one other antimediator agent, add omalizumab. 3

Omalizumab dosing and outcomes:

• Most common effective dose: 150 mg every 2 weeks 3
• Higher doses (≥300 mg/month) associated with better complete response rates 3
• 61% of refractory patients achieve partial response, with 18% achieving complete response 3
• Effective for both clonal and nonclonal MCAS 3
• Successfully reduces anaphylaxis episodes and may allow glucocorticoid discontinuation 3

Emergency Management

All patients must carry epinephrine auto-injectors for acute mast cell activation episodes and anaphylaxis. 2

Advanced/Aggressive Disease Considerations

For patients with underlying systemic mastocytosis and severe symptoms 4, 5:

• Cytoreductive therapies are reserved for advanced/aggressive systemic mastocytosis 4
• KIT inhibitors (such as avapritinib) can achieve mast cell eradication in KIT D816V-positive disease, but must be balanced against potential side effects 5
• These targeted therapies are considered only in severely affected, therapy-refractory patients 4

Critical Pitfalls to Avoid

Do not diagnose MCAS without completing thorough medical evaluation to exclude autoimmune, neoplastic, or infectious diseases that may mimic mast cell activation. 6 Many patients referred for suspected MCAS have other unrelated conditions or comorbidities rather than true MCAS 6.

The stepwise approach is necessary because no method exists for predicting which treatment will control symptoms in individual patients 4. Treatment must target mast cell mediator effects in most patients, with the core strategy being symptom control through mediator blockade 4, 2.