Enteroviral infection mimicking primary herpetic stomatitis in four children

Abstract

In autumn 2000 and 2001, four young immunocompetent children were admitted to our paediatric emergency ward for vesicular stomatitis, typical of primary herpes virus infection, and subsequently found to have a coxsackie A16-like virus. None of them had hand-foot-andmouth disease nor herpangina. Primary herpetic gingivostomatitis, herpangina or aphthous stomatitis are difficult to diagnose on the basis of oral lesions alone and virological investigations are important in this clinical context to avoid unnecessary anti-herpes treatment. We describe four herpetiform stomatitis cases due to coxsackie virus A16 (CVA-16). When they are implicated in symptomatic manifestations, enteroviruses, Picornaviridae family, cause a variety of distinctive and difficult to diagnose clinical syndromes. When they are associated with meningoencephalitis, a treatment would be important [1,5]. Virological investigations are not systematically undertaken when the central nervous system is not affected. In enteroviral infections like hand-foot-and-mouth disease, oral lesions are more consistently present than skin lesions [2]. Thus, illnesses may be mistakenly identified as herpes simplex virus (HSV) infection or aphthous stomatitis and treated accordingly (Fig. 1). Two children, aged 2 and 3 years respectively, were admitted to hospital with disseminated lesions of gingivostomatitis, deglutition pain, fever, and cervical adenopathy which led to the clinical diagnosis of primary HSV infection. Because of anorexia, intravenous acyclovir treatment and antiseptic mouth rinse were initiated. After 1 day of treatment, one patient developed some vesicles on the hands and feet, an involvement of a coxsackie virus was then assumed. The two children became apyretic 48 h later and recovered from eating difficulties. Two other patients were not admitted to hospital. They were seen in the emergency ward with fever, deglutition pain concomitant with an erosive and erythemathosous palate, gum and tongue lesions. One patient had cutaneous eruptions on the legs. A herpetic infection was suspected in both patients. A buccal mucosal sample was analysed in all four children. They all gave a cytopathic response in MRC-5 fibroblasts. Immunofluorescence examination of trypsinised cell cultures was negative with an enterovirus monoclonal antibody and with HSV-1 and HSV-2 monoclonal antibodies. All four cell cultures were, however, positive for enterovirus RNA by RT-PCR targeting the 5’ non coding region. The four cultured strains were untypeable by seroneutralisation. They were identified as CVA-16 using sequencing after another RT-PCR targeting a variable VP1–2A capsid region of the enteroviral genome [4]. Viruses are the most common causes of stomatitis, in particular the HSV (herpes gingivostomatitis), coxsackie virus (herpangina, hand-foot-and-mouth disease) and Epstein Barr virus (infectious mononucleosis). The main enteroviral cause of stomatitis and ulcerative lesions in the anterior mouth is the CVA-16, frequently in the context of hand-foot-and-mouth disease [3]. Enteroviruses and HSV are easily isolated from vesicles. For a more rapid diagnosis, molecular amplification or immunofluorescence (HSV only) can be performed. These cases highlight the importance of virological investigations in a clinical context of herpetiform stomatitis. It should help adequate management of this clinical entity avoiding intravenous acyclovir administration in case of enterovirus stomatitis. S. Vallet (&) AE M.-C. Legrand AE B. Picard Virology Laboratory, Department of Microbiology EA 3882 Biodiversity and Microbial Ecology, CHU Morvan, 2 avenue Foch, 29609 Brest Cedex, France E-mail: Sophie.Vallet@univ-brest.fr Tel.: +33-2-98223308 Fax: +33-2-98223987