Recent advances in our understanding of mast cell activation – or should it be mast cell mediator disorders?

Abstract

An increasing number of patients present with multiple symptoms affecting many organs including the brain due to multiple mediators released by mast cells. These unique tissue immune cells are critical for allergic reactions triggered by immunoglobulin E (IgE), but are also stimulated (not activated) by immune, drug, environmental, food, infectious, and stress triggers, leading to secretion of multiple mediators often without histamine and tryptase. The presentation, diagnosis, and management of the spectrum of mast cell disorders are very confusing. As a result, specialists have recently excluded neuropsychiatric symptoms, and made the diagnostic criteria stricter, at the expense of excluding most patients. A literature search was performed on papers published between January 1990 and November 2018 using MEDLINE. Terms used were activation, antihistamines, atopy, autism, brain fog, heparin, KIT mutation, IgE, inflammation, IL-6, IL-31, IL-37, luteolin, mast cells, mastocytosis, mediators, myalgic encephalomyelitis/chronic fatigue syndrome, mycotoxins, release, secretion, tetramethoxyluteolin, and tryptase. Conditions associated with elevated serum or urine levels of any mast cell mediator, in the absence of any comorbidity that could otherwise explain such increases, should be considered mast cell activation disorders, or better yet be collectively termed ‘Mast Cell Mediator Disorders (MCMD).’ Emphasis should be placed on the identification of unique mast cell mediators, and development of drugs or supplements that inhibit their release.