The mechanism of mast cell activation may involve IgE and non-IgE-mediated triggers, clonal mast cell diseases, or may be idiopathic, and can be altered by various factors including, but not limited to, hormonal status, stress, genetic factors, mast cell burden, and simultaneous exposure to more than 1 factor.[21] The sudden release of biologically active mediators into the bloodstream is responsible for the allergic responses. Here, IGHE is linked to maculopapular cutaneous mastocytosis.