Pseudolymphomatous reaction to varicella zoster virus vaccination: role of viral in situ hybridization

Abstract

Herpes zoster (shingles) is the result of a reactivation of the varicella zoster virus (VZV). Many adults obtain a VZV vaccine in order to prevent zoster. Non-specific injection site reactions and generalized herpes eruptions have been reported to occur, especially in immunocompromised patients. However, these are most often anatomically generalized reactions and histopathologically resemble typical herpes infections. We report a 61-year-old female on immunosuppressant medications for rheumatoid arthritis who presented with a subcutaneous nodule at the site of a recent herpes zoster vaccination. Histopathological examination revealed a dense nodular and interstitial mononuclear infiltrate throughout the mid and deep dermis with extension into the superficial subcutaneous fat. Immunohistochemical staining revealed an admixture of T-cells and B-cells, with a predominance of T-cells. These findings are consistent with a pseudolymphoma (PL), a reactive inflammatory disorder that can resemble cutaneous lymphoma and has rarely been described in herpes infections and post-herpetic scars. In situ hybridization studies for VZV were performed and highlighted occasional deep fibroblasts with nuclear positivity for VZV DNA. A review of post-vaccination reactions and herpes-related PL is discussed with emphasis on using in situ hybridization in establishing the diagnosis.

Histological Spectrum of Cutaneous Herpes Infections

“…3 Similarly, Resnik et al 14 reviewed 45 cases that exhibited characteristic epithelial changes of herpes infection and found lymphocyte atypia in 71% of cases (32 of 45). 18 Herpes can also incite a CD56-positive rich infiltrate, mimicking CD56-positive NK-/T-cell lymphoma, a form of non-Hodgkin lymphoma. 3,14-17 Expression of CD30 is classically associated with cutaneous lymphoproliferative disorders, a spectrum of diseases ranging from lymphomatoid papulosis to anaplastic large-cell lymphoma.…”

Drug‐induced cutaneous pseudolymphoma: A systematic review of the literature

“…While the exact pathogenesis of the disease remains unclear, recent studies suggest that drugs responsible for causing CPL can weaken immune function by interfering with immunosurveillance leading to abnormal lymphocyte proliferation, increased suppressor T‐cell activity and hypogammaglobulinaemia 8–14 …”

“…Some features of DRESS syndrome are fever, haematological abnormalities (eosinophilia), systemic symptoms, lymphadenopathy and morbilliform eruption. In our study, we did not include DRESS reactions following a drug intake because we aimed to elucidate localized CPL caused by drugs 5–12 …”

“…While the exact pathogenesis of the disease remains unclear, recent studies suggest that drugs responsible for causing CPL can weaken immune function by interfering with immunosurveillance leading to abnormal lymphocyte proliferation, increased suppressor T-cell activity and hypogammaglobulinaemia. [8][9][10][11][12][13][14] Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is now considered different from drug-induced CPL. Some features of DRESS syndrome are fever, haematological abnormalities (eosinophilia), systemic symptoms, lymphadenopathy and morbilliform eruption.…”

“…In our study, we did not include DRESS reactions following a drug intake because we aimed to elucidate localized CPL caused by drugs. [5][6][7][8][9][10][11][12] This study aimed to perform a systematic review to summarize the demographic, clinical, histopathological and immunopathological characteristics as well as comorbidities, treatments and outcomes of patients with druginduced pseudolymphoma.…”