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 avoidance of known triggers, and pharmacologic agents such as H1R antihistamines, H2R antihistamines, and mast cell stabilizers like cromolyn sodium, as outlined in the 2019 report by the AAAAI Mast Cell Disorders Committee Work Group 1.

Key Treatment Components

• Avoidance of known triggers is crucial in managing MCAS, as it can help prevent mast cell activation and subsequent symptoms.
• H1R antihistamines, such as nonsedating options, are generally preferred and can be increased to 2 to 4 times the standard dose, while sedating H1 antihistamines might be used but with caution due to potential cognitive decline, particularly in the elderly 1.
• H2R antihistamines can be used as first-line therapy for gastrointestinal symptoms and might help H1R antihistamines attenuate cardiovascular symptoms 1.
• Cromolyn sodium can reduce abdominal bloating, diarrhea, and cramps, and its benefit might extend to neuropsychiatric manifestations, with divided dosing and weekly upward titration recommended to improve tolerance and adherence 1.

Additional Considerations

• Other pharmacologic agents that may be considered include doxepin, aspirin, steroid taper/steroid burst, omalizumab, cysteinyl leukotriene inhibitor (eg, montelukast), and cyproheptadine, each with specific indications and precautions 1.
• Acute management strategies, such as epinephrine autoinjectors for patients with a history of systemic anaphylaxis or airway angioedema, and supine positioning for those with recurrent hypotensive episodes, are also essential components of MCAS treatment 1.

Personalized Approach

• Treatment of MCAS is highly individualized, requiring careful monitoring and adjustment based on symptom response, as the condition can affect multiple body systems and present differently in each patient.
• A low-histamine diet and identification of personal triggers, which can include certain foods, medications, temperature extremes, stress, and strong odors, are also important aspects of managing MCAS symptoms.

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.

The treatment for Mast Cell Activation Syndrome (MCAS) may involve the use of cromolyn sodium. Key points to consider:

• Dosage: 200 mg QID
• Benefits:
  • Clinically significant improvement in gastrointestinal symptoms
  • Improvement in cutaneous manifestations and cognitive function
• Onset of action: Clinical improvement occurred within 2-6 weeks of treatment initiation
• Duration of action: Benefits persisted for 2-3 weeks after treatment withdrawal 2

From the Research

Treatment Options for Mast Cell Activation Syndrome (MCAS)

• The treatment for MCAS focuses on modulating mast cell activation and the effects of the mediators, with many therapies being simple over-the-counter medications 3.
• Avoiding triggers is also an important part of the therapy 3.
• Some cases of MCAS may be refractory to treatment, but sunitinib, a multitargeted tyrosine kinase inhibitor, has been shown to be effective in achieving immediate, complete, sustained, non-toxic remission in life-threatening MCAS refractory to multiple agents including imatinib 4.
• H1-antihistamines have been found to be effective in the treatment of primary MCAS, with significant improvements in quality of life, symptom control, and reduction in itching and whealing 5.
• The diagnosis, classification, and management of MCAS can be complex, and a personalized approach is recommended, taking into account the etiology of mast cell activation, the number and releasability of mast cells, organs affected, and the type and consequences of comorbid conditions 6.

Medications Used to Treat MCAS

• Sunitinib: a multitargeted tyrosine kinase inhibitor 4.
• H1-antihistamines: such as rupatadine, azelastine, chlorpheniramine, hydroxyzine, and ketotifen 5.
• IgE-blocking antibodies: for patients with combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies, and sometimes hereditary alpha tryptasemia are detected 6.
• Anti-mediator-type drugs: for patients with severe MCA events 6.
• MC-targeting therapy: for patients with combined forms of MCAS 6.

Research Needs

• More research is needed to understand the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients 7.
• Further studies are required to develop an optimal management plan for MCAS, following the principles of personalized medicine 6, 7.
• Education for patients and health care providers on MCAS is necessary to improve diagnosis, treatment, and management of the condition 7.