Hand, Foot and Mouth Disease and Kingella kingae Infections

To the Editors: Hand, foot and mouth disease (HFMD) is a childhood disease caused by human enteroviruses that affects particularly toddlers in the age of 6–23 months.1 HFMD is usually associated with benign and self-resolving aphthous ulcers and skin rash of the extremities that occur as epidemic waves in summer and in early fall, but also all year around as sporadic cases. Uncommonly, it leads to meningoencephalitis and cardiopulmonary complications. To our knowledge, osteoarticular infections secondary to HFMD have not been yet documented. Herein, we report a series of children who developed Kingella kingae infections following HFMD. From April to October 2013, 9 children ranging from 10 to 45 months old (mean age: 18.7 months) were diagnosed with K. kingae osteoarticular infections in the Department of Pediatric Orthopedics of the University La Timone Children’s Hospital, Marseille, France. Four cases were epidemic, and 5 were sporadic. Real-time PCR targeting the cpn60 gene of K. kingae was positive from osteoarticular samples (6/8), blood (1/8), and oropharynx (6/8),2 and K. kingae was also cultivated from peripheral blood in 1 case (Table 1). Among toddlers younger than 24 months (7/9), 5 presented with HFMD (71.4%) in the prior 3 weeks, and 2 with stomatitis (28.6%) leading to a painful mouth and feeding difficulties. No oral manifestations were found in the 2 children >23 months old. During the same period, the National Reference Center for Enteroviruses and Parechoviruses (CNREV-PEV) in Clermont-Ferrand, France, noticed an increased incidence of HFMD.TABLE 1: Reported Cases of Epidemic (E) and Sporadic (S) K. kingae Infections Secondary to Hand, Foot and Mouth Disease in Toddlers <24 MonthsWe retrospectively analyzed joint aspirations harvested from an 11 month-old girl who presented with arthritis secondary to HFMD, in whom first analysis performed by routine methods of cultures failed to detect bacteria. Joint aspirations and stool specimens were sent to the CNREV-PEV, and coxsackievirus-A6 infection was confirmed by enterovirus genome detection and genotyping from stool specimens. K. kingae genome was further detected by real-time PCR targeting the cpn60 gene from joint aspirations that were stored at –20°C for 2 years. K. kingae is an oropharyngeal commensal of toddlers recognized as the primary cause of osteoarticular infections in children <4 years old in developed countries, also with an increased attack rate in the 6–23 months group of age.3 Herpes simplex virus4 and rhinovirus have been previously identified in association with K. kingae infections. Coxsackievirus-A6 is an emerging and predominant causative agent of HFMD worldwide responsible for atypical rashes that can mimic herpetic and varicella-zoster infections.5 Given that HFMD virus initially replicates in the oropharynx at the onset of an infection suggests that oropharyngeal interplays at mucosal surfaces between some HFMD virus, K. kingae strains, and host cells might promote invasive infections. Our findings show that HFMD may trigger true osteoarticular infections and that coxsackievirus-A6 and K. kingae infections can be associated, therefore supporting a role for HFMD virus in the occurrence of K. kingae infections. Nawal El Houmami, MD Department of Pediatric Orthopedics University La Timone Children’s Hospital Aix-Marseille University Marseille, France Audrey Mirand, MD, PhD Laboratoire de Virologie Centre National de Référence des Enterovirus et Parechovirus-laboratoire associé CHU Clermont-Ferrand Clermont-Ferrand, France Grégory Dubourg, MD, PhD URMITE “Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes” UM63, CNRS 7278, IRD 198, Inserm 1095 Aix-Marseille University Marseille, France Derek Hung, MD Department of Microbiology Queen Mary Hospital University of Hong Kong Hong Kong, People’s Republic of China Philippe Minodier, MD Department of Pediatric Emergency Medicine University North Hospital Aix-Marseille University Marseille, France Jean-Luc Jouve, MD, PhD Department of Pediatric Orthopedics University La Timone Children’s Hospital Aix-Marseille University Marseille, France Rémi Charrel, MD, PhD Aix Marseille Université, IRD French Institute of Research for Development EHESP French School of Public Health, EPV UMR_D 190 “Emergence des Pathologies Virales” IHU Méditerranée Infection APHM Public Hospitals of Marseille Marseille, France Didier Raoult, MD, PhD Pierre-Edouard Fournier, MD, PhD URMITE “Unité de Recherche sur les Maladies Infectieuses et Tropicales, Emergentes” UM63, CNRS 7278, IRD 198, Inserm 1095 Aix-Marseille University Marseille, France