Introduction
Drug fever is an adverse drug reaction characterized by fever coinciding with the administration of a drug and disappearing after discontinuation of the offending agent. It accounts for up to 10% of cases evaluated for Pyrexia of Unknown Origin (PUO). Recognizing drug fever avoids prolonged hospitalization, redundant lab tests, and inappropriate antimicrobial escalation.
Pathophysiologic Mechanisms
Drug fever can arise through several mechanisms:
Hypersensitivity Reactions: T-cell mediated or immune complex-driven systemic response (Most common).
Altered Thermoregulation: Increased metabolic heat production (e.g., Thyroid hormones) or reduced heat dissipation (e.g., Anticholinergics).
Administration-Related: Endotoxin contamination or local phlebitis.
Pharmacological Action: Jarisch-Herxheimer reaction following antimicrobial treatment for spirochetal infections.
Common Offending Medications
| Class | Specific Agents |
| Antimicrobials | Beta-lactams (Penicillins, Cephalosporins), Sulfonamides, Vancomycin, Amphotericin B. |
| Cardiovascular Agents | Methyldopa, Quinidine, Procainamide, Hydralazine. |
| Anticonvulsants | Phenytoin, Carbamazepine, Phenobarbital. |
| Other Drugs | Allopurinol, Heparin, NSAIDs, Chemotherapeutic agents. |
Key Clinical Features
Relative Bradycardia (Faget Sign): Pulse rate remains inappropriately low despite high fever (though not universal).
Patient Appearance: Patients often appear paradoxically well despite high fevers ($> 39.0^\circ\text{C}$).
Associated Signs: Rash (maculopapular) in 20–30% of cases; mild eosinophilia on CBC.
Timeline: Can occur days to months after drug initiation (median time frame: 7 to 10 days).
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| DIAGNOSTIC ALGORITHM FOR DRUG FEVER |
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| 1. Suspect drug fever in PUO with no clear infectious source. |
| 2. Review medication administration record (MAR) timeline. |
| 3. Discontinue non-essential or suspected culprit drugs. |
| 4. Observe temperature response: Defervescence typically occurs |
| within 48 to 72 hours post-discontinuation. |
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