Lymphocytic Arteritis in Epstein–Barr Virus Vulvar Ulceration (Lipschütz Disease)

Abstract

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Lipschütz genital ulcer revisited: is juvenile gangrenous vasculitis of the scrotum the male counterpart?

“…In histopathology, the most common findings were lymphocytic arteritis and a submucosal scar, followed by venulitis, endarteritis obliterans, thrombosis, neutrophilic sebaceous adenitis and mucosal lymphoid hyperplasia . Neutrophils compromised half of the infiltrates in some specimens.…”

“…EBV infection has been documented in small‐vessel endothelium and smooth muscle adjacent to the ulcers as well as muscular vessel vasculitis. Vulvar ulceration associated with EBV reactivation has been described, but less clearly defined …”

“…Vulvar ulceration associated with EBV reactivation has been described, but less clearly defined. 25,26 Primary EBV infection is generally asymptomatic. Two patterns of EBV seroconversion are known: in developed countries of high hygiene standard, the peak is observed in children at 2-4 years and later at 14-18 years, while in countries with lower hygiene standards, the primary EBV infection is usually acquired in early childhood, almost by the age of 6 years.…”

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“…Clinicamente, a doença tem surgimento súbito, manifestando-se com grandes ulcerações dolorosas em vulva e terço inferior da vagina 7,8 . Geralmente com diâmetro maior que 1 cm e profunda, a UL apresenta borda avermelhada, padrão em espelho ou "kissing pattern", e centro necrótico com exsudado acinzentado ou preto-acinzentado 9,10 .…”

“…Geralmente com diâmetro maior que 1 cm e profunda, a UL apresenta borda avermelhada, padrão em espelho ou "kissing pattern", e centro necrótico com exsudado acinzentado ou preto-acinzentado 9,10 . O quadro clínico pode ainda ser constituído por alterações locais, como edema labial e adenopatia local, e sistêmicas, como febre, mal-estar geral, mialgia e odinofagia 7,8 . O eritema e o edema secundário podem ser importantes e a celulite deve ser considerada 9 .…”