Atypical Presentations of Acyclovir-Resistant Herpes Simplex Virus in Immunocompromised Patients: A Case Series

Herpes simplex virus (HSV) infections in immunocompromised patients can have atypical presentations - anywhere from granulomatous to linear erosive lesions - and become refractory to standard therapy. We report three cases of necrotizing cutaneous HSV infection in immunocompromised patients with underlying hematologic malignancies or prior chemoradiation, all presenting with atypical and refractory manifestations of the disease. One case involved a 53-year-old female patient with relapsed/refractory acute myeloid leukemia (AML) who developed a necrotizing cutaneous HSV infection refractory to acyclovir and subsequently foscarnet. Two additional cases highlight similar cutaneous presentations of HSV, a patient with anal squamous cell carcinoma and a patient with multiple myeloma, underscoring the variability and severity of the disease in the setting of profound immunosuppression. These cases underscore the possible need for prolonged antiviral therapy, early resistance testing, and adjunctive treatment strategies in managing atypical HSV infections in severely immunocompromised patients. Further studies are needed to establish evidence-based protocols for such challenging cases.