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

From the Guidelines

The initial treatment for Mast Cell Activation Syndrome (MCAS) should involve a stepwise approach using antihistamines as first-line therapy, with H1 antihistamines such as nonsedating options being generally preferred and can be increased to 2 to 4 times the standard dose, as recommended by the AAAAI Mast Cell Disorders Committee Work Group report 1. The treatment approach typically starts with H1 antihistamines to control symptoms like hives, itching, and flushing, and may be combined with H2 antihistamines to address gastrointestinal symptoms.

• Key considerations include:
  • Starting with lower doses and gradually increasing as tolerated, due to potential sensitivity in MCAS patients
  • Identifying and avoiding personal triggers such as certain foods, temperature extremes, strong odors, or emotional stress
  • Regular monitoring and adjustment of treatment based on symptom control
  • Potential addition of mast cell stabilizers like oral cromolyn sodium or leukotriene modifiers like montelukast for more severe symptoms The goal of treatment is to block histamine receptors and stabilize mast cells to prevent the inappropriate release of inflammatory mediators that cause MCAS symptoms, with treatment typically being long-term 1.
• Important factors to consider when selecting antihistamines include:
  • Preference for nonsedating H1 antihistamines to minimize cognitive decline, particularly in the elderly population
  • Potential benefits of combining H1 and H2 antihistamines for comprehensive symptom management
  • Individualized treatment plans based on patient-specific symptoms and triggers.

From the FDA Drug Label

Cromolyn Sodium Oral Solution (Concentrate) is indicated in the management of patients with mastocytosis. Use of this product has been associated with improvement in diarrhea, flushing, headaches, vomiting, urticaria, abdominal pain, nausea, and itching in some patients. Four randomized, controlled clinical trials were conducted with Cromolyn Sodium Oral Solution (Concentrate) in patients with either cutaneous or systemic mastocytosis; The initial treatment for Mast Cell Activation Syndrome (MCAS) may involve the use of cromolyn sodium (PO), as it has been indicated in the management of patients with mastocytosis and has shown improvement in various symptoms, including gastrointestinal and cutaneous manifestations 2 2.

• Key benefits of cromolyn sodium (PO) include:
  • Improvement in gastrointestinal symptoms, such as diarrhea and abdominal pain
  • Improvement in cutaneous manifestations, such as urticaria, pruritus, and flushing
• Treatment initiation and duration of response:
  • Clinical improvement occurred within 2-6 weeks of treatment initiation
  • Benefits persisted for 2-3 weeks after treatment withdrawal

From the Research

Initial Treatment for Mast Cell Activation Syndrome (MCAS)

The initial treatment for MCAS typically involves a stepwise, individual-based approach in pharmacotherapy options, as there is currently no method for predicting the best available approach to control symptoms in individual patients with MCAS 3.

• The core component of the treatment in most patients is to control symptoms caused by mast cell mediator release, whereas cytoreductive therapies are mainly reserved for patients with advanced/aggressive systemic mastocytosis 3.
• Histamine receptor blockers and other mediator-targeting drugs can usually control mild and transient MCA-related symptoms 4.
• In severe cases, an MCA syndrome (MCAS) may be diagnosed, and treatment may involve targeted therapies aiming at blocking mutant KIT variants and/or downstream signaling pathways, which are currently being developed and may be considered in severely affected, therapy-refractory patients 3, 5.
• Omalizumab has been used as an alternative treatment option for patients with refractory MCAS, with most patients experiencing a partial response and some achieving a complete response 6.
• Continuous diphenhydramine infusion and imatinib have also been used in the treatment of MCAS, with promising outcomes in some cases 7.

Treatment Options

• Medications that stabilize mast cells, target mediators, or interfere with mediator effects are often prescribed for MCAS patients 5.
• KIT inhibitors, such as avapritinib, may be used to eradicate tissue mast cells and decrease serum tryptase levels in patients with KIT D816V-positive mastocytosis 5.
• The use of KIT inhibitors must be balanced against their potential side effects 5.

Diagnostic Algorithm

A diagnostic algorithm has been proposed to suspect and document or exclude MCAS, and to guide the investigating care providers to consider the principal diagnoses that may underlie MCAS, namely, severe allergy and systemic mastocytosis accompanied by severe MCA 4.