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

From the Guidelines

The treatment for Mast Cell Activation Syndrome (MCAS) should prioritize a multi-faceted approach, including H1 antihistamines, H2 antihistamines, mast cell stabilizers, and avoidance of triggers, as recommended by the most recent guidelines 1. The goal of treatment is to control symptoms, stabilize mast cells, and improve quality of life.

• First-line treatments include: + H1 antihistamines, such as cetirizine (10mg daily) or loratadine (10mg daily), which can be increased to 2 to 4 times the standard dose if necessary 1 + H2 antihistamines, such as famotidine (20mg twice daily) or ranitidine (150mg twice daily), which can help with gastrointestinal symptoms and cardiovascular symptoms 1
• Mast cell stabilizers, such as sodium cromolyn (200mg 3-4 times daily before meals), can help reduce abdominal bloating, diarrhea, and cramps, and may also benefit neuropsychiatric manifestations 1
• For more severe symptoms, leukotriene modifiers, such as montelukast (10mg daily), may be added 1
• During acute flares, corticosteroids, such as prednisone (typically 40-60mg daily, tapered over 1-2 weeks), can provide relief 1
• Identifying and avoiding triggers is equally important, including certain foods, medications, temperature extremes, strong odors, and stress, as recommended by recent studies 2, 3
• Dietary modifications, such as following a low-histamine diet, can also help manage symptoms 1 These medications work by blocking histamine receptors, stabilizing mast cell membranes to prevent degranulation, or inhibiting inflammatory mediators released during mast cell activation. Regular follow-up with healthcare providers is essential to monitor response and adjust treatment as needed, taking into account the latest guidelines and recommendations 1, 4, 5.

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 (MCAS) may include:

• Cromolyn sodium (PO) 200 mg QID, which has shown clinically significant improvement in gastrointestinal symptoms and some improvement in cutaneous manifestations and cognitive function 6
• Chlorpheniramine (4 mg QID) plus cimetidine (300 mg QID), which has shown similar benefits to cromolyn sodium for both cutaneous and systemic symptoms of mastocytosis 6 Clinical improvement may occur within 2-6 weeks of treatment initiation and persist for 2-3 weeks after treatment withdrawal 6

From the Research

Treatment Options for Mast Cell Activation Syndrome (MCAS)

• The treatment for MCAS involves modulating mast cell activation and the effects of the mediators, which can be achieved through various medications and therapies 7.
• H1-antihistamines have been shown to be effective in treating primary MCAS, with significant improvements in quality of life, symptom control, and reduction in itching and whealing 8.
• Other treatment options include: + Blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade) + Inhibition of mediator synthesis (aspirin, zileuton) + Mediator release (sodium cromolyn) + Anti-IgE therapy + A combination of these approaches 9.
• Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids 9.
• Cromolyn Sodium has been shown to differentially regulate human mast cell and mouse leukocyte responses to control allergic inflammation, and may be a useful treatment option for MCAS 10.

Management of Symptoms

• Gastrointestinal symptoms, such as irritable bowel syndrome, dyspepsia, chronic or cyclical nausea, and heartburn, are common in MCAS patients and can be refractory to symptom-targeted prescription medications 7.
• Avoiding triggers and using over-the-counter medications can help manage symptoms 7.
• Patients with clonal mast cell syndromes may need a reduction in the number of mast cells to prevent severe symptoms, including anaphylaxis and/or progression to aggressive diseases 9.

Research Needs

• There are many gaps in knowledge about MCAS, resulting in confusion about this clinical syndrome 11.
• Further research is needed to understand the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients, as well as to identify effective treatment options and management strategies 11.