Abstract Background Voriconazole is a first-line antifungal for invasive aspergillosis and other mold infections. While hepatotoxicity, visual disturbances, and QTc prolongation are well-known adverse effects, drug-induced fever is rare and underrecognized, particularly in immunocompromised patients with multiple comorbidities. Early identification is essential to avoid unnecessary diagnostic testing, prolonged hospitalization, and misattribution to persistent infection. Case A 71-year-old male with rheumatoid arthritis (treated with rituximab and leflunomide), severe COPD with emphysema, and recently diagnosed multiple myeloma presented with worsening dyspnea and chronic cough. He had recurrent pneumonia and required home oxygen (2-5 L/min). CT imaging revealed bilateral cavitary lung lesions with probable aspergilloma, chronic interstitial changes, and honeycombing. Bronchoscopy with BAL grew Aspergillus fumigatus. He was started on voriconazole 200 mg PO twice daily, with LFT and QTc monitoring. Within 24 hours, he developed a fever up to 101.2 °F, persisting for 9 days despite stable pulmonary status, no new infectious foci, negative cultures, and no evidence of line or wound infection. After excluding other infectious or inflammatory causes, voriconazole-induced fever was suspected. The antifungal was switched to isavuconazonium (Cresemba). Fever resolved within 72 hours, and the patient remained afebrile through discharge, completing a 6-week course. Discussion Voriconazole-induced fever is rare but should be considered when persistent fever develops shortly after therapy initiation, particularly when:lThe patient is immunocompromised, increasing the baseline risk for infectious feverlCultures and imaging are stable or improvinglOther potential sources (lines, urinary tract, wounds, GI tract) are excludedEarly recognition avoids unnecessary investigations, prolonged hospitalization, and inappropriate therapy changes. Switching to an alternative azole, such as isavuconazonium, is often effective and well tolerated. This case is notable for high-risk comorbidities (RA, COPD, multiple myeloma, prior immunosuppression) in which distinguishing drug-induced fever from infection progression is challenging. Conclusion V oriconazole can cause persistent fever in immunocompromised patients, mimicking ongoing infection. Clinicians should maintain high suspicion when fever develops after initiation, particularly with improving or stable infectious lesions. Prompt recognition and therapy adjustment can lead to rapid resolution and reduced morbidity. Keywords:Voriconazole; drug-induced fever; immunocompromised; Aspergillus fumigatus; rheumatoid lung disease; isavuconazonium; pulmonary aspergillosis This abstract is funded by: none
Ashfaq et al. (Fri,) studied this question.