Mast cell activation syndrome

Mast cell activation syndrome (MCAS) is a rare condition that is characterized by recurrent sudden-onset episodes of severe systemic symptoms associated with the release of mast cell mediators. In many cases the recurrent episodes present as anaphylaxis.

Acute episodes of MCAS-associated anaphylaxis must be managed according to the usual emergency protocol, with immediate administration of intramuscular epinephrine (adrenaline) alongside an ABCDE approach to assess the need for supplemental oxygen, intravenous fluids, and airway management.

A diagnosis of MCAS is confirmed by evidence of a significant rise in a mast cell marker (e.g., serum tryptase) during acute episodes and a positive clinical response to a medication that targets a mast cell mediator. It is important to then evaluate the MCAS subtype: primary (clonal), secondary (usually associated with IgE-dependent allergy), or idiopathic.

Treatment involves trigger identification and avoidance together with a stepwise approach to long-term pharmacotherapy, starting with an antihistamine (H1 antagonist) and H2 antagonist. Add-on options include a leukotriene receptor antagonist, cromolyn, and omalizumab. Patients with refractory primary (clonal) MCAS may require cytoreductive therapy. Lifelong immunotherapy is recommended for individuals with sensitivity to Hymenoptera venom.

​MCAS is a rare condition defined by severe, episodic reactions to mast cell-derived mediators.[1]Valent P, Akin C. Doctor, I think I am suffering from MCAS: Differential diagnosis and separating facts from fiction. J Allergy Clin Immunol Pract. 2019 Apr;7(4):1109-14. https://www.jaci-inpractice.org/article/S2213-2198(18)30819-5/fulltext http://www.ncbi.nlm.nih.gov/pubmed/30961836?tool=bestpractice.com ​ For a diagnosis of MCAS to be confirmed:[2]Valent P, Akin C, Arock M, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224511 http://www.ncbi.nlm.nih.gov/pubmed/22041891?tool=bestpractice.com [3]Weiler CR, Austen KF, Akin C, et al. AAAAI Mast Cell Disorders Committee Work Group report: Mast cell activation syndrome (MCAS) diagnosis and management. J Allergy Clin Immunol. 2019 Oct;144(4):883-96. https://www.jacionline.org/article/S0091-6749(19)31116-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/31476322?tool=bestpractice.com

• There must be recurrent, acute episodes of symptoms/signs associated with secreted mast cell mediators that affect two or more organ systems at the same time

• A transient rise in a mast cell mediator (e.g., tryptase) must be confirmed during these acute episodes, and

• The symptoms must respond to drugs that either target released mast cell mediators or suppress mast cell activation (e.g., antihistamine, H2 antagonist, leukotriene receptor antagonist, cromolyn).

In most cases, MCAS presents with recurrent episodes of anaphylaxis.[4]Gülen T, Akin C. Anaphylaxis and mast cell disorders. Immunol Allergy Clin North Am. 2022 Feb;42(1):45-63. https://www.sciencedirect.com/science/article/pii/S0889856121000825?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/34823750?tool=bestpractice.com