Authors: Theoharides TC, Tsilioni I, Ren H

PMID: 30884251 PMCID: PMC7003574 DOI: 10.1080/1744666X.2019.1596800


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, neuropsychiatric symptoms have been left out, and diagnostic criteria made stricter excluding most patients. Areas covered: 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, mycotoxins, release, secretion, tetramethoxyluteolin, and tryptase. Expert opinion: Conditions associated with elevated serum or urine levels of any mast cell mediator, in the absence of comorbidities that could explain elevated levels, should be considered ‘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.

Keywords: Activation; IL-37; IL-6; IgE; KIT mutation; antihistamines; autism spectrum disorder; brain fog; cytokines; inflammation; luteolin; mast cells; mastocytosis; mediators; myalgic encephalomyelitis/chronic fatigue syndrome; mycotoxins; tetramethoxyluteolin; tryptase.