LEARNING OBJECTIVES
1. Recognize the clinical setting of acyclovir-induced neurotoxicity. 2. Diagnose and manage acyclovir-induced neuroxicity.
CASE
A 46 year-old woman with AIDS (recent CD 4 + lymphocyte count 145 per mL & plasma HIV RNA level <400 copies per mL) and ESRD on continuous ambulatory peritoneal dialysis (CAPD) presented with pain in her right thigh for three months. Doppler ultrasounds were negative for deep venous thrombosis on two different tests. She had been in stable health without recent opportunistic infections. Her past medical history was significant for a history of shingles, orolabial herpes simplex disease, pancreatitis secondary to nucleosides, Candida esophagitis, and asthma. Her physical exam revealed an edematous right thigh and a tender 3 × 5 cm irregular ecchymotic area present on her lateral thigh near a small shallow ulcer. A small vesicle has preceded the ulcer. Laboratory data included a white blood cell count of 8.1K with 74% neutrophils; blood urea nitrogen of 74 mg/dL; creatinine of 15.7 mg/dL; and creatinine kinase 1,303 U/L. The Alveolar-arterial gradient was 71053.25 mmHg. Computerized Tomography of the right lower extremity with contrast and multiplanar 3D reconstructions revealed no abscess. Empiric therapy with intravenous acyclovir 5 mg/kg/day was empirically started on hospital day 2. The next day the patient developed delirium and hypoxemia. The arterial blood gas revealed a pH 7.21, PaCO2 67 mmHg, PaO2 163, HCO3 27 mmol/L, O2 saturation 97.8% on 100% oxygen via a non-rebreathable mask. Chest radiography demonstrated pulmonary edema. Cultures of the peritoneal fluid, bronchoalveolar lavage, blood, and spinal fluid, were all negative. The skin biopsy demonstrated findings consistent with calciphylaxis and pressure necrosis and the absence of viral inclusions. Acyclovir was discontinued on the sixth hospital day and a serum acyclovir level 12 hours after stopping the acyclovir was 5.5 mcg/mL (reported therapeutic peak range of 0.40–2.0 mcg/mL). Twenty-four hours after stopping the acyclovir the patient became alert and was extubated within 48 hours. Given all of these findings, the patient was diagnosed with acyclovir-induced respiratory depression.