Drag Fever (Part 1 of 2)

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Abstract
Review with 207 references. It is to be expected with the increasing use of many new and old therapeutic agents that drug fever will become more common. Ability to recognize drug fever appearing alone or in combination with other manifestations of drug allergy will become increasingly important. With rare exceptions, reliance must be placed at present upon detection of drug fever by its clinical characteristics, as there is no generally applicable in vitro test for detection of the drug allergic person. Drug fever, attributed to hypersensitivity, develops in the same way as other immunologic reactions. The patient developing drug fever when treated for the first time, or previously unsensitized, will have a gradually increasing fever beginning on the 7th to 10th day of treatment, and discontinuance of the drug is followed by prompt return of temperature to normal. If the patient is previously sensitized, or if rechallenged after having had a febrile reaction to a drug, the temperature may rise abruptly, often with a chill, when a single dose of the drug is administered. In other words, the occurrence of drug fever follows the same chronology as the occurrence of serum sickness or other classically allergic reactions. Other reactions may develop with drug fever, including urticaria, angioedema, immunologic thrombocytopenia, etc. Passive transfer of blood from a patient with known drug allergy to a non-allergic recipient has, at least in a few instances, resulted in drug fever following administration of the drug to the recipient. The methods of value in recognition and management of drug fever, and the importance of drug fever as an occasional premonitory sign of more serious allergic reactions are described. Simple substances such as drugs usually become antigenic only after conjugation with protein, and a brief discussion of the immunochemical considerations in drug allergy, with specific reference to drug fever is presented. There are few instances in which a drug or its degradation product has been identified as an important antigenic determinant, or in which the immunologic processes in the allergic reaction to drugs have been delineated. This is in part attributable to the unavailability of a satisfactory in vitro model for characterization of the allergic reaction. Further elucidation of the mechanisms of drug allergy will be required before a better understanding of drug fever is possible. Experimentally, both immediate and delayed hypersensitivity reactions have been associated with the production of fever. The pathogenesis of hypersensitivity fever closely resembles the pathogenesis of fever due to other pyrogenic reactions. The hypersensitivity reaction appears to be responsible for inducing the elaboration of an endogenous pyrogen, transferable from the febrile animal to a normal animal with plasma. This pyrogen probably is produced by granulocytes, as this is the only cell known to elaborate a pyrogenic substance in vitro. The absence of satisfactory evidence indicating the elaboration of a pyrogen from other cell types, suggests that the granulocyte is an important reactive component not only in immediate hypersensitivity but in delayed hypersensitivity reactions as well.