IGHE and allergic disease: Just as many risk factors have been identified for DENV patients that are associated with severe infection and vascular leakage, many factors can theoretically influence the degree of MC activation in vivo in response to a stimulus, including the stimulus concentration, the presence of pre-existing antibodies such as IgE and their concentration, and host-specific differences in the intracellular signaling and sensitization of MC that can result from genetic diversity or existing allergy.