Severe Pulmonary Hemorrhage in Herpangina

To the Editors: Herpangina is a common infectious disease of childhood caused by enteroviruses (EV): Coxsackievirus A2, 4, 5, 6, 8, 10, 16 and Enterovirus A71 (EV-A71).1 The clinical manifestations of herpangina include fever, sore throat and herpes in the pharynx and isthmus. The minority have serious complications, such as encephalitis, meningitis, pulmonary hemorrhage, pulmonary edema and cardiopulmonary failure.1,2 Although coxsackievirus A6 (CV-A6) has become the dominant pathogen of herpangina in some regions of China,2,3 severe cases caused by CV-A6 are rare. We present an extremely rare case of CV-A6 severe herpangina complicated with pulmonary hemorrhage. A 4-years and 7-months old boy was admitted to our hospital with a history of fever and vomiting for 1 day, cough and dyspnea for half a day, mechanical ventilation for 8 hours, and extracorporeal membrane oxygenation (ECMO) support for 3.5 hours. One day before admission, the child presented to a local hospital with high fever, vomiting, herpes in the isthmus and no rash on the hands, feet or hips. Thirteen hours before admission, the child developed a cough, pink frothy sputum and dyspnea. Nasal catheter oxygen, gamma globulin and methylprednisolone treatments did not work. Eight hours before admission, he developed severe dyspnea, pale complexion, unconsciousness, rapid heart rate, low blood pressure and poor peripheral circulation. Three hours before admission, the boy was placed on ECMO and transferred to our hospital. The patient received the EV71 vaccine. Blood tests revealed blood lactate (7.5 mmol/L), B-type natriuretic peptide precursor (21,768 pg/mL), creatine kinase isoenzyme (16.130 ng/mL) and troponin T (0.515 ng/mL). Echocardiography showed a large left ventricle, left ventricular ejection fraction 24%. Head magnetic resonance imaging and computed tomography, electroencephalogram and the cerebrospinal fluid examinations were normal. The CV-A6 nucleic acid test was positive. The diagnosis was CV-A6 severe herpangina, cardiopulmonary failure and pulmonary hemorrhage. After comprehensive treatment with ECMO, mechanically assisted ventilation, methylprednisolone anti-inflammatory agent, intravenous immunoglobulin shock therapy, anti-infection therapy, vasoactive drugs and other agents, cardiopulmonary function was restored, and the boy was discharged 14 days later. The specific mechanism of severe herpangina complicated with pulmonary hemorrhage is unclear, pulmonary hemorrhage is preceded by and closely associated with the central nervous system involvement. Severe herpangina with pulmonary hemorrhage may be related to neurogenic pulmonary edema, cardiac dysfunction, increased vascular permeability and cytokine storms.4 As an important part of modern pediatric intensive care, ECMO has been used to support gas exchange in children with severe acute respiratory failure who fail mechanical ventilation.5 ECMO for severe cardiopulmonary failure provides gas exchange and systemic circulation. In this case, when the patient developed severe pulmonary hemorrhage and routine mechanical ventilation could not maintain vital signs, the use of ECMO effectively avoided irreversible organ damage and saved the patient’s life.