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

From the Guidelines

Treatment for mast cell activation syndrome (MCAS) should involve a multi-faceted approach targeting symptom control and mast cell stabilization, with H1 antihistamines like cetirizine (10mg daily) or fexofenadine (180mg daily) as first-line treatments, often combined with H2 blockers such as famotidine (20mg twice daily) to address gastrointestinal symptoms, as recommended by the most recent guidelines 1.

Key Treatment Components

• H1 antihistamines: cetirizine (10mg daily) or fexofenadine (180mg daily) to relieve symptoms caused by secreted histamine 1
• H2 blockers: famotidine (20mg twice daily) to address gastrointestinal symptoms and help H1R antihistamines attenuate cardiovascular symptoms 1
• Mast cell stabilizers: cromolyn sodium (200mg four times daily before meals) to prevent mast cell degranulation and reduce symptoms such as diarrhea, abdominal pain, nausea, and vomiting 1
• Leukotriene modifiers: montelukast (10mg daily) may be added for more severe symptoms, particularly if urinary LTE4 levels are increased 1
• Low-dose aspirin (81mg daily) may be beneficial for some patients, but requires careful monitoring due to the risk of triggering reactions in certain individuals 1
• Corticosteroids like prednisone (typically 40-60mg with taper) may be necessary during acute flares 1

Lifestyle Modifications

• Identifying and avoiding personal triggers (certain foods, temperature extremes, stress, alcohol, NSAIDs) is crucial in managing MCAS symptoms 1
• Maintaining good sleep hygiene and managing stress through techniques like meditation can help reduce symptom severity 1
• Dietary approaches often involve an initial elimination diet followed by careful reintroduction of foods to identify and avoid trigger foods 1

Acute Management

• Epinephrine autoinjector should be prescribed for patients with a history of systemic anaphylaxis or airway angioedema, and patients should be instructed on how and when to use it 1
• Supine positioning and bronchodilators like albuterol may be necessary for patients experiencing recurrent hypotensive episodes or bronchospasm 1

From the FDA Drug Label

Four randomized, controlled clinical trials were conducted with Cromolyn Sodium Oral Solution (Concentrate) in patients with either cutaneous or systemic mastocytosis; two of which utilized a placebo-controlled crossover design, one utilized an active-controlled (chlorpheniramine plus cimetidine) crossover design, and one utilized a placebo-controlled parallel group design Clinically significant improvement in gastrointestinal symptoms (diarrhea, abdominal pain) were seen in the majority of patients with some improvement also seen for cutaneous manifestations (urticaria, pruritus, flushing) and cognitive function The benefit seen with Cromolyn Sodium Oral Solution (Concentrate) 200 mg QID was similar to chlorpheniramine (4 mg QID) plus cimetidine (300 mg QID) for both cutaneous and systemic symptoms of mastocytosis.

Treatment for Mast Cell Activation Syndrome:

• Cromolyn sodium (PO) may be considered for the treatment of mast cell activation syndrome, as it has shown clinically significant improvement in gastrointestinal symptoms and some improvement in cutaneous manifestations and cognitive function 2.
• The recommended dosage is 200 mg QID, with clinical improvement occurring within 2-6 weeks of treatment initiation and persisting for 2-3 weeks after treatment withdrawal.

From the Research

Treatment Options for Mast Cell Activation Syndrome

• Medications used to manage symptoms of MCAS include:
  • H1 and H2 antihistamines to block mediator receptors 3, 4
  • Leukotriene receptor blockade to inhibit mediator synthesis 3
  • Aspirin and zileuton to inhibit mediator synthesis 3
  • Sodium cromolyn to inhibit mediator release 3
  • Anti-IgE therapy 3
• Acute episodes of mast cell activation can be treated with epinephrine, and prolonged episodes may be addressed with corticosteroids 3
• Patients with clonal mast cell syndromes may require a reduction in the number of mast cells to prevent severe symptoms, including anaphylaxis and/or progression to aggressive diseases 3
• Second-generation H1-antihistamines, such as rupatadine, have been shown to be effective in improving quality of life and symptom control in patients with cutaneous and systemic mastocytosis 4
• Sunitinib, a multitargeted tyrosine kinase inhibitor, has been reported to be effective in treating life-threatening MCAS refractory to multiple agents, including imatinib 5

Diagnostic Criteria and Response to Treatment

• The diagnosis of MCAS is defined by three criteria: typical clinical signs and symptoms, increase in tryptase level, and response to antimediator therapy 6
• Patients with MCAS may have a range of symptoms, including abdominal pain, diarrhea, flushing, dermatographism, memory and concentration difficulties, and headache 7
• Response to treatment with anti-MC mediator medications can be assessed based on established criteria, and patients may experience complete or major regression in symptoms while taking these medications 7