Mast cells are closely associated with epithelium, serving as sentinels responsible for the recognition of tissue injury and coordination of the initial inflammatory response. Upon detection of the injured cell content, mast cells then tailor the release of preformed and newly produced chemical mediators to the detected challenge, via an array of pathogen receptors. In addition to
immunoglobulin E receptor-triggered mast cell activation, commonly referred to as allergic or atopic disorders, non-
immunoglobulin E receptor mediated mast cell activation follows engagement of
toll-like receptors,
immunoglobulin G receptors, and
complement receptors. Upon containment of the extrinsic challenge, acute
inflammation is downregulated, and repair of the injured tissue ensues. The mast cell compartments must return to a baseline steady state to remain tolerant towards
self-antigens and harmless entities, including environmental conditions, to prevent unnecessary immune activation and chronic
hypersensitivity disorders. Over the past 50 years, an increasing number of patients are experiencing episodes of aberrant mast cell activation, not associated with
allergen-specific
mast cell disease or
systemic mastocytosis. This led to proposed diagnostic criteria of
mast cell activation syndrome.
Mast cell activation syndrome is a heterogeneous disorder, defined by a combination of (1) recurrent symptoms typical of mast cell activation, (2) an increase of validated mast cell derived mediators, and (3) response to treatment with mast cell stabilizing or mast cell mediator-targeted
therapies. Onset of
mast cell activation syndrome ostensibly reflects the loss of tolerance in the mast cell compartment to nonthreatening entities and nonhazardous environmental conditions. The etiology of chronic mast cell dysregulation and associated intolerance to
self-antigens or harmless entities is not well understood, but a growing number of studies point to exposure of the epithelial borders, which leads to inappropriate or excessive mast cell activation or impaired resolution of acute
inflammation following neutralization of the identified pathogen.
CASE PRESENTATION: CONCLUSION:
Mast cell activation disease causes problems of increased complexity in children and adults. The increased prevalence and severity of
mast cell activation disease has been attributed to dramatic changes in our lifestyles and modern living environments. These changes likely impact the integrity of the epithelial barriers, leading to loss of tolerance in the mast cell compartment. Here, we present a case of a nonatopic, 74-year-old female who developed
mast cell activation disease after exposure to a potent environmental toxin.
Mast cell activation disease commonly involves several organ systems, with patients often referred to a succession of different specialists. This results in delayed diagnosis and suboptimal care. Instead, early recognition of
mast cell activation disease would lead to better outcomes. We review the literature, describing the diagnostic criteria for
mast cell activation disorders that can improve recognition of this multiorgan system syndrome. Further research is needed into the interaction of epithelial barrier disruption and the dysregulation of the immune system.