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

**Authors:** Keri Allen, Alan Wang, Matthew A Hibdon, Robert Castro, John Greene

PMC · DOI: 10.7759/cureus.93215 · 2025-09-25

## TL;DR

This paper presents three cases of severe, hard-to-treat herpes infections in patients with weakened immune systems, highlighting unusual symptoms and treatment challenges.

## Contribution

The study contributes three unique case reports of acyclovir-resistant HSV in immunocompromised patients with atypical clinical features.

## Key findings

- Three immunocompromised patients presented with necrotizing cutaneous HSV infections resistant to standard antiviral therapy.
- Atypical HSV manifestations were observed in patients with hematologic malignancies or prior chemoradiation.
- The cases suggest the need for prolonged antiviral treatment and early resistance testing in managing such infections.

## Abstract

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.

## Linked entities

- **Chemicals:** acyclovir (PubChem CID 135398513), foscarnet (PubChem CID 3415)
- **Diseases:** acute myeloid leukemia (MONDO:0015667), anal squamous cell carcinoma (MONDO:0006082), multiple myeloma (MONDO:0009693)

## Full-text entities

- **Diseases:** AML (MESH:D015470), anal squamous cell carcinoma (MESH:D002294), multiple myeloma (MESH:D009101), hematologic malignancies (MESH:D019337), HSV infections (MESH:D006561)
- **Chemicals:** foscarnet (MESH:D017245), Acyclovir (MESH:D000212)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12553515/full.md

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Source: https://tomesphere.com/paper/PMC12553515