Abstract
Patients with vulval aphthae, also termed Lipschütz ulcers, often present to genitourinary medicine clinics. Typically, these ulcers present as acute, painful, vulval ulcers in young women and adolescents. The aetiology is unknown, and often these ulcers are accompanied by flu-like symptoms. Previous case reports have linked such lesions to acute viral infections such as Epstein–Barr virus, cytomegalovirus and influenza A. We report the first case of influenza B virus and adenovirus infections associated with this presentation.
Case report
A 15-year-old girl presented to our London genitourinary medicine (GUM) clinic with a four-day history of painful genital ulceration and flu-like symptoms. Her family doctor had started aciclovir (200 mg 5 × daily) for presumed primary herpes simplex (HSV) infection. There was no history of any sexual or genital contact. Her only significant history was of recurrent orolabial cold sores, the aetiology of which was unclear.
Physical examination revealed three tender, well-demarcated, shallow vulval ulcers, measuring up to 1 cm diameter and affecting both labia minora. There were several intraoral aphthous-looking oral ulcers, with pharyngitis, cervical and inguinal lymphadenopathy. Speculum examination was not performed.
Initial management included continuation of aciclovir to cover possible HSV infection, topical lidocaine gel for ulcer analgesia and supportive therapy for flu-like symptoms. At review, five days later, the ulcer swab had tested negative for HSV DNA by in-house polymerase chain reaction (PCR)-based assay. The ulcers had improved but systemically she remained unwell; rhinorrhoea was especially prominent. A throat swab was taken for respiratory panel PCR: strong positive influenza B RNA and weak positive adenovirus DNA were detected. Serology showed HSV-1 which could explain her previous presumed herpes labialis (HSV-2 negative), and Epstein–Barr virus (EBV) IgG antibodies (EBV IgM not detected), but no cytomegalovirus (CMV) or syphilis antibodies. The original ulcer swab tested negative for influenza B RNA and adenovirus DNA.
Discussion
Patients with vulval aphthae or Lipschütz ulcers often present to GUM clinics. Other terminology of these ulcers includes ‘reactive non-sexually related acute genital ulcers’ (RNSRAGU). Typically, these ulcers present as acute, painful, vulval ulcers with a clean or fibrinous base in young women and adolescents, mostly affecting the labia minora, although there are case reports of necrotic ulceration also. 1 The aetiology is unknown, and often these ulcers are accompanied by flu-like symptoms. 2
When occurring in non-sexually active girls, such lesions have been linked to acute viral infections such as EBV, influenza A and CMV.3–5 With regard to EBV, case reports have detected EBV directly from ulcer swabs and biopsy specimens via PCR. Some hypotheses include immune complex deposition produced during acute EBV infection causing a type III hypersensitivity reaction. Other hypotheses suggested that EBV-linked genital ulceration may be a type of complex aphthosis, which may explain ulcers in association with other infections such as influenza and CMV. 6
To date, there have been no case reports associated with influenza B virus. Adenovirus has only rarely been reported in the literature, 7 with no reports documenting the presence of both viruses in a single patient. Adenovirus is a common infection and can be persistently detectable for months after initial infection. This may have accounted for the weak positive result, the significance of which remains unclear. The absence of pathogens detected in the ulcer swab suggests that such lesions may be acute aphthae triggered by systemic infections in susceptible individuals rather than a direct local cytopathic effect of the virus, as suggested with EBV. HSV infection is often suspected, though autoinoculation of HSV remains clinically rare, and misdiagnosis of HSV may carry significant stigma and distress, especially in young patients. Therefore, a broader differential must be considered, including numerous viral infections and rarer systemic diseases such as Behcet’s, with appropriate virological investigations to exclude other triggering causes of genital ulceration in non-sexually active girls.
Footnotes
Acknowledgements
The authors thank their patient and the staff at the Lloyd Clinic, Guy’s Hospital.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.