Acyclovir is a widely used treatment for varicella-zoster virus (VZV) infections. It exhibits good tissue penetration, in- cluding within the cerebrospinal fluid (CSF), and is primarily excreted renally¹. Although acyclovir is generally well tolerated, systemic adverse effects may occur. The most common of these is acute renal failure, although neurotoxicity has also been reported^2,3. In particular, renal damage can result in drug accumulation, increasing the risk of neurotoxicity².

In this case report, a 55-year-old woman presented with painful grouped erythematous vesicles on her abdomen, left flank, and back that had developed 5 days prior. She was diagnosed with herpes zoster (Fig. 1). She had hypertension, end-stage renal disease, and vitiligo. Due to her creatinine clearance of 18 mL/min, intravenous acyclovir at a dosage of 5 mg/kg/day was administered for five days. On the third hospital day, the patient developed bilateral lower extremity weakness, blurred vision, dysarthria, dizziness, aggressive atti- tude, and disruptive behavior. The patient's psychosis was suspected to be delirium caused by administration of the medication, as the symptoms suddenly worsened. The Mini-Mental State Examination revealed disorientation, while brain magnetic resonance imaging showed no acute lesions. Attempts to perform a cerebrospinal tapping to rule out central nervous system infection were hindered by the patient's lack of cooperation. Repeated blood tests indicated a deteri- oration in creatinine clearance to 6 mL/min, three times worse than the previous assessment. Acyclovir treatment was ceased, and her symptoms significantly improved after three sessions of hemodialysis at two-day intervals. The im- mediate resolution of these symptoms upon discontinuation of acyclovir suggested a possible causal relationship with acyclovir neurotoxicity.

Figure 1. The patient's abdomen exhibited several grouped erythematous vesicles, characteristics of herpes zoster lesions.

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Neurotoxicity refers to a neuropsychiatric condition triggered by the administration of antiherpetic drugs such as acyclovir and valacyclovir. Age and renal dysfunction are identified as primary risk factors for neurotoxicity⁴. In this case, the neurotoxicity was thought to have occurred because of the patient's worsening creatinine clearance. The predominant symptom observed was disorientation, although other symp- toms such as altered consciousness, hallucinations, agitation, dysarthria, seizures, delirium, irritability, and delusion were also reported².

A condition that requires differentiation from neurotoxicity is viral encephalitis. While both conditions can present with the psychiatric symptoms of disorientation and alterations in consciousness, viral encephalitis commonly includes symptoms such as fever, headache, and neck stiffness. The diagnosis of viral encephalitis can be confirmed by polymerase chain reaction testing for positive VZV antibodies and pleocytosis in a CSF analysis⁵. Furthermore, a key distinction lies in the timing of symptom onset. Neurotoxicity typically manifests three days after antiviral administration, whereas viral encephalitis typically arises seven days after the appearance of skin lesions². Even though CSF analysis was not conducted in this study, the diagnosis of acyclovir neurotoxicity can be made based on the timing of psychiatric symptoms and disorientation, as well as the observed improvement following discontinuation of acyclovir and treatment with hemodialysis.

In conclusion, dermatologists should be vigilant regarding the potential neurological symptoms associated with acyclovir administration, particularly in patients with end-stage renal disease. Monitoring renal function is crucial in mitigating the risk of neurotoxicity.