Herpes Simplex Virus Vasculitis and Herpes Vegetans in an Immunocompromised Host

Background: Herpes simplex virus (HSV) infection in immunocompromised individuals can present with severe and atypical manifestations, particularly in patients with hematologic malignancies undergoing chemotherapy or stem cell transplantation. Among these, HSV-induced vasculitis is a rare but serious complication characterized by vascular endothelial invasion, thrombosis, and hemorrhagic complications. In addition, herpes vegetans, a hyperkeratotic and verrucous variant, is an uncommon cutaneous presentation seen in immunosuppressed patients. The combination of vasculitis and atypical HSV skin lesions presents a diagnostic challenge and can lead to significant morbidity if unrecognized. Methods: We present a case report of HSV vasculitis in a patient with relapsed acute myeloid leukemia (AML) following allogeneic stem cell transplantation (alloSCT). A comprehensive literature review was conducted using PubMed and Google Scholar to identify similar cases and review management strategies. Results: A 53-year-old female with relapsed FLT3-TKD-mutated AML post-alloSCT developed neutropenic fever, mucositis, and a painful hypertrophic nodular lesion on the lower sacral area, which was tender and minimally draining. Despite broad-spectrum antimicrobial therapy, she experienced progressive multiorgan failure. Infectious workup revealed HSV vasculitis confirmed via biopsy, alongside evidence of myositis and cellulitis on imaging. The patient’s cutaneous lesions exhibited features of herpes vegetans, with verrucous and ulcerative characteristics suggestive of persistent viral replication and immune dysregulation. Given concerns for antiviral resistance, treatment was escalated from valacyclovir to foscarnet. The patient subsequently developed candidemia, worsening encephalopathy concerning for HSV encephalitis versus hemophagocytic lymphohistiocytosis (HLH)-associated neurological involvement, and progressive hepatic failure. Due to poor prognosis, she was transitioned to comfort measures and discharged to hospice. Conclusions: This case illustrates the rare coexistence of HSV vasculitis and herpes vegetans in an immunocompromised host. It underscores the importance of maintaining a high index of suspicion for atypical HSV presentations, especially in patients with hematologic malignancies and prolonged immunosuppression. Early biopsy, resistance testing, and consideration of alternative antivirals such as foscarnet are essential to improving outcomes, although prognosis remains poor in disseminated cases.