First Case of Severe Enterovirus 71 Infection in Portugal

Abstract

To the Editors: In December 2011, a 17-month-old boy was admitted to a pediatric intensive care unit in Lisbon, Portugal, because of rapidly progressive acute flaccid paralysis, rhombencephalitis and coma. He had been diagnosed with hand-foot-mouth disease 3 days before admission. Leukocyte counts, C-reactive protein and serum glucose values were elevated. He was treated with acyclovir, ceftriaxone and ciprofloxacin. Due to this clinical severity, intravenous immunoglobulin and a pulse of methylprednisolone were administered. After 4 cardiac arrests, hypotension and pulmonary edema, he was managed with high frequency oscillatory ventilation, nitric oxide and inotropic support for 4 days. Cerebrospinal fluid cytochemical analysis was normal. Immunoelectrophoresis revealed intrathecal IgG production and an increased permeability pattern. Magnetic resonance imaging showed lesions in the medulla oblongata, pons, dentate nuclei of the cerebellum and spinal cord, suggesting enterovirus rhombencephalitis. An enterovirus was identified in the stool by reverse transcription-polymerase chain reaction, despite negative cerebrospinal fluid, as expected during enterovirus central nervous system infection, especially in severe cases.1 It was identified as C2 EV71, by sequencing of the partial nucleotide sequence of viral protein 1.1 No index case was found. His condition evolved to spastic tetraparesia and tracheostomy because of an absent gag reflex, with cavitation of the brainstem and cervical spinal cord lesions and diffuse brain stem and encephalic atrophy. EV71 neurologic disease includes acute flaccid paralysis, meningitis and rhombencephalitis. Cardiopulmonary complications, like neurogenic pulmonary edema, and cardiac collapse occur in a subset of children with rhombencephalitis, mostly in those younger than 5 years, associated with high mortality rate.1 Among survivors, neurodevelopmental sequelae are frequent. Prognostic factors are progressively being found, including central nervous system involvement, leukocytosis, hypotension and hyperglycemia, all of which were found in our case. Since 1969, several epidemics have been reported in the Asia-Pacific region. C2 EV71 was responsible for large outbreaks in Taiwan (1998) and Australia (1999). In the last 10 years, reported cases in Europe have been sporadic and mild, mainly C1 and C2 EV71. This is the first known case in Portugal and the most severe EV71 infection described in Europe in the last decade, since the 2 fatal cases in United Kingdom and France.2 The C2 strain in this case is related to strains circulating in other European countries and the Asian-Pacific region. EV71 infection therapy is mainly supportive. Epidemiologic studies in China implicated glucocorticoids, which block the innate immune response, as a risk factor for critical and fatal EV71 infections.3 However, children with critical EV71 infection have a high incidence of adrenal insufficiency, which can affect their prognosis. Glucocorticoids may be considered when this condition is identified or highly suspected.3 In our case, it was initially impossible to exclude acute disseminated encephalomyelitis. Therefore, glucocorticoid was used. Vaccine is the best option for controlling the disease.4 Paulo Venâncio, MD Marta Oliveira, MD Rita Silva, MD Carla Conceição, MD Maria João Brito, MD Pediatric Intensive Care Unit Hospital Dona Estefânia Centro Hospitalar Central (CHLC) Lisbon, Portugal