Drug fever: a narrative review

Abstract

Drug fever is an adverse drug reaction accompanied by a febrile response and is a common problem among clinicians, hence an updated knowledge of drug fever is important. A consensus regarding the definition of drug fever is lacking. Thus, descriptions of drug fever in previous literature are often inconsistent. In this narrative review, we summarized various features of drug fever, including its definition, epidemiology, risk factors, clinical presentation, diagnosis, treatment and prognosis, based on the earliest literature. Recent advances in information technology have encouraged researchers to use pharmacovigilance databases for clinical and pharmacological research. We outlined how a pharmacovigilance database, along with recently developed research methods, could be used to research drug fever.

Keywords: drug adverse reactions; drug fever; narrative review.

Fig. 1. Venn diagram schema of the definition of drug fever

Drug fever in this review is highlighted in red and circled by a dark red line. Drug fever by the narrowest definition excludes skin manifestation and is circled by a white line. Abbreviations: ADRs, adverse drug reaction; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal syndrome; DIHS, drug-induced hypersensitivity syndrome; DRESS, drug reaction with eosinophilia and systemic symptoms; SLE, systemic lupus erythematosus; RS3PE, remitting seronegative symmetrical synovitis with pitting edema; CDI, Clostridioides difficile infection.

Fig. 2. An example of two-by-two contingency table in disproportionality analysis

To calculate the risk of azathioprine (AZA)-induced drug fever and compare the risk with other drugs, data of the whole population with AZA and other drug administrations are necessary; however, such data are unavailable. However, the number of spontaneously reported cases of AZA and other drug administrations with drug fever and ADR other than drug fever is available in the pharmacovigilance database. Researchers can create a two-by-two contingency table from these data. The proportional reporting ratio (PRR) can be calculated from the table using the formula. If the PRR exceeds a certain value, AZA and drug fever may occur.