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The effects of caffeine and coffee, agents widely alleged to provoke flushing in patients with erythematotelangiectatic rosacea, were investigated. Neither caffeine nor coffee at 22 degrees C led to flushing reactions. Both coffee at 60 degrees C and water at 60 degrees C led to flushing reactions with similar temporal characteristics and of similar intensities. It is concluded that the active agent causing flushing in coffee at 60 degrees C is heat, not caffeine.

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The mechanisms of flushing reactions are pharmacologically and physiologically heterogeneous. Flushing may result from agents acting directly on the vascular smooth muscle or may be mediated by vasomotor nerves. Vasomotor nerves may lead to flushing as a result of events at both peripheral and central sites. In susceptible persons, frequent, intense flushing leads to a cluster of physical signs (rosacea). Flushing provoked by alcohol has been associated with ethnic sensitivity, a possible predisposition to alcoholism, various disulfiramlike agents, one type of diabetes mellitus, and the carcinoid syndrome and other types of neoplasia. Flushing reactions also occur during the menopause, after glutamate ingestion, and in response to oral thermal challenges.