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Letters to the Editor

Hand, Foot and Mouth Disease and Kingella kingae Infections

El Houmami, Nawal MD; Mirand, Audrey MD, PhD; Dubourg, Grégory MD, PhD; Hung, Derek MD; Minodier, Philippe MD; Jouve, Jean-Luc MD, PhD; Charrel, Rémi MD, PhD; Raoult, Didier MD, PhD; Fournier, Pierre-Edouard MD, PhD

Author Information
The Pediatric Infectious Disease Journal: May 2015 - Volume 34 - Issue 5 - p 547-548
doi: 10.1097/INF.0000000000000607
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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
TABLE 1:
Reported Cases of Epidemic (E) and Sporadic (S) K. kingae Infections Secondary to Hand, Foot and Mouth Disease in Toddlers <24 Months

We 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

REFERENCES

1. Xing W, Liao Q, Viboud C, et al. Hand, foot, and mouth disease in China, 2008-12: an epidemiological study. Lancet Infect Dis. 2014;14:308–318
2. Ceroni D, Dubois-Ferriere V, Cherkaoui A, et al. Detection of Kingella kingae osteoarticular infections in children by oropharyngeal swab PCR. Pediatrics. 2013;131:e230–e235
3. Dubnov-Raz G, Scheuerman O, Chodick G, et al. Invasive Kingella kingae infections in children: clinical and laboratory characteristics. Pediatrics. 2008;122:1305–1309
4. Amir J, Yagupsky P. Invasive Kingella kingae infection associated with stomatitis in children. Pediatr Infect Dis J. 1998;17:757–758
5. Flett K, Youngster I, Huang J, et al. Hand, foot, and mouth disease caused by coxsackievirus a6. Emerg Infect Dis. 2012;18:1702–1704
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