Abstract
Genital ulcers are caused by not only sexually transmitted infections (STIs), but also have other aetiologies. Epstein–Barr virus (EBV) infection can be associated with non-sexually-related acute genital ulcers. Evaluation by polymerase chain reaction (PCR) can avoid misdiagnosis when serological tests of EBV show atypical patterns or are otherwise inconclusive. An 11-year-old girl was transferred because of dysuria and painful genital ulcers. She had been well until 6 days before visiting when she presented with high fever and genital pain. She subsequently defervesced, but the pain increased, leading to the disclosure of the genital lesion. Although she denied sexual activity, further medical interviews and investigations were conducted repeatedly to her and her parents, with suspicion of child abuse. Physical examination revealed bilateral, deep and well-defined ulcers located on the labia majora (Fig. 1a), oral aphthae (Fig. 1b) and purulent discharge from an ear fistula (Fig. 1c). She did not present with any signs and symptoms of infectious mononucleosis (including pharyngitis, adenopathy and splenomegaly). Routine laboratory tests were unremarkable: liver function tests were normal, and there was no atypical lymphocytosis. Acyclovir was initiated for clinical suspicion of herpes simplex virus (HSV), and azithromycin and ceftriaxone were empirically administered for possible sexually transmitted bacteria. The oral aphthae and ulcerative ear fistula healed within a week, and the genital ulcers and dysuria resolved after another week. These signs and symptoms did not recur during follow-up. Seven months later, EBV serologies remained inconclusive, and EBV DNA in her peripheral blood became undetectable by PCR. Laboratory tests confirmed negative HSV-IgM/IgG titres examined 2 and 24 days after the transfer. HSV-PCR assays of the serum and swab specimens from the genital and oral lesions were negative. No other findings were indicating STIs. We excluded syphilis. Laboratory tests confirmed negative rapid plasma reagin and Treponema pallidum antibody haemagglutination test. Serology assays for EBV taken 2 days after transfer revealed an atypical profile, as follows: viral capsid antigen (VCA)-IgG 1:80, VCA-IgM negative and Epstein–Barr nuclear antigen (EBNA)-IgG negative. These data showed indeterminant results; however, PCR confirmed the presence of EBV DNA in oral and genital lesions as well as high EBV DNA copy numbers in plasma. Therefore, we diagnosed acute genital ulcers as being a result of EBV infection. The most common cause of acute genital ulcers is STIs in a sexually active female, and HSV is a common pathogen.1 In children who are not sexually active, abuse must first be suspected when seeing genital ulcers. At the same time, other infectious aetiologies, such as EBV and cytomegalovirus infections, should be considered as a common cause of non-sexually-related acute genital ulcers.2 In our case, serological tests for EBV antibodies were inconclusive. The presence of VCA-IgG without VCA-IgM and EBNA-IgG indicates either acute or past infection. However, it is known that VCA-IgM may present only in a very short duration or at low concentrations in acute infection and EBNA-IgG may not become detectable in up to 5% of patients with past infection.3 EBV DNA could be detected coincidentally in a patient with other diseases. However, EBV DNA was the only DNA detected from swab specimens of the oral lesion, genital legion and her plasma. She had 1000 copies/mL of EBV DNA in plasma, which is rarely seen in both immunocompetent and immunocompromised children without EBV disease. Repeated unnecessary medical interviews and examinations lead to a physical and emotional burden on both patients and their families. When the causes of genital ulcers are unclear after serological evaluation, PCR tests for EBV, and cytomegalovirus in addition to HSV, can help pursue the true causes. We are deeply grateful to Drs Mari Mitsui and Mitsuru Kubota who gave insightful comments and suggestions.
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