Abstract

Monkeypox virus (MPXV), a member of the Orthopoxviridae family, can cause rare but severe infections that can pose significant challenges in immunocompromised individuals. We present a case series of three immunocompromised patients (age range = 53-64, mean = 57 years old), who contracted MPXV infection with atypical cutaneous manifestations. Immunohistochemistry utilizing a novel monoclonal antibody confirmed the presence of virus in the tissue. All three patients exhibited some degree of immunosuppression, including poorly controlled HIV infection, history of renal transplant on multiple immunomodulatory medications, and recently diagnosed diffuse large B-cell lymphoma with concurrent, advanced HIV infection in Patients 1, 2, and 3 respectively. Lesional skin from these patients revealed necrosis of the epidermis and dermis with abundant neutrophils. Ballooning degeneration of the follicular epithelium was present, along with keratinocytes displaying a ground glass appearance, intracytoplasmic inclusions, and multinucleation. Immunohistochemistry using the recombinant mouse monoclonal antibody against A29, a heparin-binding protein mediating virion cell fusion, showed nuclear and cytoplasmic dot-like staining within the epithelium that displayed viral cytopathic changes. The antibody displays some cross-reactivity with homologous proteins in other poxviruses. All three patients received confirmatory diagnoses by lesional PCR skin swabs and recovered with oral tecovirimat. We are presenting the cases to highlight the histopathologic features associated with MPXV infection and the availability of an immunohistochemical assay that should be considered in other high-risk patients with similar clinicopathologic findings to confirm the presence of MPXV infection, especially in the context of negative immunostains for other viruses, such as HSV or VZV.