Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease

Background In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. Methods We studied 154 children with virus-culture-confirmed EV71 infection . Children were divided into three groups: 11 patients with pulmonary oedem a; 38 patients with central nervous system (CNS) involvement and no pulmona ry oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. Findings Nine children with pulmonary oedema had hand, foot, and mouth dise ase, one had herpangina, and one had febrile illness with eight children wi th limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complicat ions recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12 4 [95% CI 2.6-60.1], p = 0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leu cocytosis, and limb weakness. Hyperglycaemia was tbe most significant progn ostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p = 0.003). Interpretation EV71 can cause hand. foot, and mouth disease, CNS involvemen t with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the m ost important prognostic factor.