What is the relationship between Mas-related G-protein coupled receptor X2 (MRGPRX2) and urticaria?

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Last updated: April 22, 2025View editorial policy

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From the FDA Drug Label

The mechanism by which these effects of omalizumab result in an improvement of chronic spontaneous urticaria (CSU) symptoms is unknown. There is no information about MRGPRX2 urticaria in the provided drug label. The FDA drug label does not answer the question.

From the Research

MRGPRX2 urticaria is a distinct form of chronic urticaria that should be treated with second-generation H1 antihistamines, such as cetirizine (10mg daily) or fexofenadine (180mg daily), with the option to increase the dose up to four times the standard dose if needed, as supported by the most recent study in 2023 1.

Key Points

  • MRGPRX2 urticaria is caused by the activation of the Mas-related G protein-coupled receptor X2 found on mast cells, leading to direct mast cell activation rather than IgE-mediated mechanisms.
  • Treatment should focus on avoiding identified triggers and using second-generation H1 antihistamines as the first line of treatment.
  • For patients with inadequate response, omalizumab (300mg subcutaneous injection every 4 weeks) may be added, and in severe cases, cyclosporine (3-5mg/kg/day in divided doses) can be considered.
  • The condition can be triggered by medications, certain foods, and environmental factors, and patients should maintain a symptom diary to help identify patterns.

Mechanism and Diagnosis

  • MRGPRX2-mediated urticaria involves direct mast cell activation, which explains why some patients experience reactions to multiple, chemically unrelated drugs.
  • Skin testing may be negative despite clear clinical reactions to certain substances, making diagnosis challenging.
  • Recent studies, such as the one published in 2024 2, have provided updated insights into the structure, expression, and biology of MRGPRX2, which can help understand conditions and diseases attributed to its activation and/or overexpression.

Treatment and Management

  • The treatment approach should prioritize avoiding identified triggers and using pharmacological interventions to manage symptoms.
  • Second-generation H1 antihistamines are the preferred initial treatment, with the option to increase the dose or add other medications like omalizumab or cyclosporine as needed.
  • Patients should be advised to maintain a symptom diary to help identify patterns and triggers, and to work closely with their healthcare provider to adjust their treatment plan as necessary.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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