Hydroxychloroquine Does Not Cause Increased Fever Risk
Patients taking hydroxychloroquine are not at increased risk of developing fever—this premise is incorrect. Hydroxychloroquine is an immunomodulatory and anti-inflammatory medication that, if anything, may suppress rather than promote febrile responses 1, 2.
Why This Misconception Exists
The confusion likely stems from misunderstanding hydroxychloroquine's role in treating infections that present with fever:
- Hydroxychloroquine treats chronic Q fever (not acute): The CDC recommends doxycycline plus hydroxychloroquine for chronic Q fever endocarditis, where fever is a symptom of the underlying infection, not a drug side effect 3, 4
- The fever comes from the infection, not the medication: In chronic Q fever, patients have persistent infection requiring 18-24 months of combination therapy; any fever present is from C. burnetii, not hydroxychloroquine 3, 4
Actual Effects on Fever Response
Hydroxychloroquine may actually reduce the ability to mount a normal fever:
- Immunomodulatory suppression: Long-term hydroxychloroquine use can alter normal febrile responses to infections or inflammatory triggers through sustained immunomodulation 2
- Masked infections: Patients on chronic hydroxychloroquine therapy may not develop fever as a warning sign of infection, potentially masking disease flares that would normally present with elevated temperature 2
- Clinical monitoring required: Regular monitoring for non-temperature indicators of infection is crucial in patients who may not mount typical febrile responses while on hydroxychloroquine 2
Common Adverse Effects (Not Fever)
The actual adverse effects of hydroxychloroquine include 3, 5, 6:
- Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea (most common reason for discontinuation) 3
- Cardiac: QT prolongation, ventricular arrhythmias, cardiomyopathy (life-threatening) 3, 5
- Ocular: Irreversible retinal toxicity requiring baseline and periodic ophthalmologic examinations 3, 5
- Hematologic: Hemolysis in G6PD deficiency patients 3, 4
- Dermatologic: Photosensitivity (especially when combined with doxycycline), severe skin reactions 3, 5
- Metabolic: Severe hypoglycemia 5
Clinical Context for Fever in Hydroxychloroquine Users
When patients on hydroxychloroquine develop fever, consider:
- Underlying infection: Evaluate for bacterial, viral, or other infections that would cause fever independent of medication 2
- Disease flare: In rheumatic disease patients, fever may indicate disease activity, not drug effect 1, 2
- Drug fever is not characteristic: Fever is not listed among the common or serious adverse effects in FDA labeling or major guidelines 5, 3
Key Pitfall to Avoid
Do not attribute fever in hydroxychloroquine users to the medication itself—investigate for underlying infections or disease activity that may be partially masked by the drug's immunomodulatory effects 2.