Evaluation and diagnosis of mast cell–associated disorders

Mast cells likely evolved to promote health and survival of their hosts, but these pathways and mechanisms have facilitated the development of immediate hypersensitivity reactions in humans. Holistically, mast cell activation is best conceived of as summative event having multiple inputs, with antigen-dependent immunoglobulin E (IgE)-mediated hypersensitivity being an important component. Patients with inappropriate mast cell activation, frequently independent of classical IgE-mediated allergic disease(s), are said to have mast cell–associated disorders (MCADs), that in some individuals result from clonal expansion of mast cells. A number of biomarkers and genetic tests have been developed that aid in confirmation of these clinical diagnoses. However, significant limitations remain in diagnostic modalities and management options for patients with suspected MCADs. Here we discuss human mast cells in an historical and evolutionary context and provide a clinical and genetic background for MCADs, as well as a practical approach for their evaluation and diagnosis.