- Malcolm McDonald, PhD, FRACP, FRCPA
Malcolm McDonald, PhD, FRACP, FRCPA
- Associate Professor
- School of Medicine and Dentistry, James Cook University
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
Clinicians are universally aware of the common occurrence of fever caused by drugs, although reliable data on incidence are not available. Fever can be the sole manifestation of an adverse drug reaction in 3 to 5 percent of cases [1,2]. The risk of developing drug fever increases with the number of drugs prescribed, especially in older adult patients. Individuals with active HIV infection also appear to have an increased susceptibility to drug reactions of all types, including fever [3-5].
The recognition of drug fever is clinically important. Failure to recognize the etiologic relationship between a drug and fever often has undesired consequences including extra testing, unnecessary therapy, and longer hospital stays.
For the purpose of this discussion, drug fever is defined as "a disorder characterized by fever coinciding with administration of a drug and disappearing after the discontinuation of the drug, when no other cause for the fever is evident after a careful physical examination and laboratory investigation" . Others have applied definitions such as "the febrile response to a drug without cutaneous manifestations" , but, in our view, such a definition is overly restrictive. Data on drug fever are largely derived from hundreds of single case reports and a few small series. There are no controlled trials on this subject, and reporting bias may significantly distort our view.
The mechanisms of drug fever are multiple and, in many cases, are poorly or incompletely understood. However, most authorities classify drug-related fevers into five broad categories [1,2,7-9]:
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- Fever associated with hypersensitivity
- - Associations with specific agents
- Other antimicrobial agents
- - DRESS syndrome
- Fever due to altered thermoregulation
- Fever associated with drug administration
- Fever as an extension of the pharmacologic effect of a drug
- - Jarisch-Herxheimer reaction
- Fever due to an idiosyncratic reaction
- - Malignant hyperthermia
- - Neuroleptic malignant syndrome
- - Serotonin syndrome
- - Glucose-6-phosphate dehydrogenase deficiency
- Uncoupling oxidative phosphorylation
- GENERAL CLINICAL ISSUES
- Presence of rash
- Fever patterns
- Laboratory investigations
- Cessation of the drug(s)