Prolonged voriconazole treatment in a patient with chronic lymphocytic leukemia resulting in a litany of chronic overlapping toxicities

Voriconazole is a triazole antifungal with activity against a number of yeast and mold species including Candida, Aspergillosis, Fusarium, and Coccidioides. Invasive fungal infections are associated with high morbidity and mortality, prolonged treatment courses, and occasionally lifelong suppressive therapy. Voriconazole therapy can result in a number of acute toxicities that clinicians are frequently aware of including hepatotoxicity, visual disturbances, and hallucinations; however, there is limited experience with extended durations of voriconazole therapy. We describe the case of a 62-year-old man who developed Coccidioides meningitis as a result of prolonged neutropenia from treatment for chronic lymphocytic leukemia. He was initially treated with a number of different antifungal agents including voriconazole, liposomal amphotericin B, fluconazole, and itraconazole; however, he developed acute toxicity due to those agents. He was successfully re-challenged with voriconazole, and maintained therapeutic serum concentrations throughout treatment. As a result of prolonged voriconazole exposure of over 14 years, he has suffered a number of toxicities, most significantly including actinic keratosis, squamous cell carcinoma, and skeletal fluorosis. To our knowledge, this is the longest continuous use of voriconazole therapy currently in the literature.