Technical Abstract: This study evaluates bullous cutaneous reactions and sequential histopathology in an individual sensitized to bed bug bites in an effort to better understand the allergic response and histology associated with these bites. There was a progression of the inflammatory response across time ranging from an urticarial-type reaction with edema, mast cell degranulation, and a mixed cellular infiltrate at 0.5h to an inflammatory vasculopathy with a mixed celluar infiltrate by 6h. By 24h, there was a destructive, necrotizing, eosinophil-prominent vasculitis. The mast cells were focally degranulated in several of the specimens where they correlated with edema. An unusual component of these reactions was the prominent infiltration of CD68+ histocytes. To our surprise, bullous reactions in this individual evolved over time into cutaneous vasculitis that favored, in part, a delayed hypersensitivity mechanism.