tetano
Editor, Senior Moderator
Autopsy Findings in Children with Hand, Foot, and Mouth Disease
N Engl J Med 2012; 367:91-92July 5, 2012
Article
To the Editor:
From May 2008 through July 2010, an epidemic of hand, foot, and mouth disease occurred in Guangxi, China. During the epidemic, some children died of progressive cardiorespiratory failure. Postmortem pathological examinations were performed for 14 patients. Reverse-transcriptase–polymerase-chain-reaction assays of various specimens (throat swabs or stool samples) were performed to detect enterovirus 71, coxsackievirus A17, and pan-enterovirus messenger RNA. Assays for enterovirus 71 were positive in 12 patients. Assays to detect coxsackievirus A17 were positive in 1 patient, and assays to detect other enteroviruses were positive in 1 patient.
The major manifestations of the disease included fever and rash. Neurologic manifestations were noted in all patients. A startle response, myoclonic jerks, and limb trembling were the most frequent early manifestations of neurologic involvement and indicated deterioration due to the illness. As the patients' disease progressed, seizure and coma developed, and death occurred within 1 hour to 5 days after hospitalization. Autopsy of the 14 patients showed that the brain, especially the brain stem, was most severely involved (Figure 1Figure 1Photomicrographs of Brain-Biopsy Specimens Obtained from Patients with Hand, Foot, and Mouth Disease.); these findings are consistent with the neurotropism of enteroviruses.1-3
The respiratory symptoms were mild at the beginning of illness. Shortly after the deterioration associated with neurologic involvement, 11 of 14 patients had pulmonary edema or pulmonary hemorrhage. All lung specimens showed large amounts of pink fluid in the alveolar space combined with mild lymphocytic inflammation and focal pulmonary hemorrhage without diffuse lung damage (see Fig. 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org); these findings are different from those associated with influenza A (H1N1) virus infection.4
Acute heart failure is another severe complication of hand, foot, and mouth disease. In 13 of 14 patients, peripheral hypoperfusion and tachycardia were reported. An elevated level of creatine kinase MB (CK-MB) was detected in 11 patients, and an elevated level of troponin I was detected in 4 patients; this suggests a degree of cardiac damage.5 However, 12 of 14 cardiac specimens showed mild congestion and edema without inflammation, necrosis, or hemorrhage (Fig. 2 in the Supplementary Appendix); these findings indicate that circulatory dysfunction was of neurogenic origin, but it was not caused by myocarditis.
We also analyzed the relationship between the cardiac histologic findings and the serologic markers. In one patient with slightly elevated levels of CK-MB and troponin I, a cardiac specimen showed slight inflammation. In three patients with moderately increased CK-MB levels with elevated levels of troponin I, pathological examination showed neither myocardial inflammation nor necrosis. However, histopathological examination of a biopsy specimen obtained from one patient showed focal necrosis and degeneration of the myocardium, even though the levels of CK-MB and troponin I were normal. Therefore, CK-MB and troponin I may not be predictors of myocarditis related to hand, foot, and mouth disease.
Min Jiang, M.D.
Dan Wei, M.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
Wei-Lin Ou, M.D.
Affiliated Hospital of Guilin Medical College, Guilin, China
Kun-Xiong Li, M.D.
Dian-Zhong Luo, M.D., Ph.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
Yun-Qian Li, M.D.
Affiliated Hospital of Guilin Medical College, Guilin, China
E Chen, M.D.
Yulin Second People's Hospital, Yulin, China
Guang-Min Nong, M.D., Ph.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
ngm8525@hotmail.com
Drs. Jiang, Wei, and Ou contributed equally to this letter.
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
http://www.nejm.org/doi/full/10.1056/NEJMc1110981
N Engl J Med 2012; 367:91-92July 5, 2012
Article
To the Editor:
From May 2008 through July 2010, an epidemic of hand, foot, and mouth disease occurred in Guangxi, China. During the epidemic, some children died of progressive cardiorespiratory failure. Postmortem pathological examinations were performed for 14 patients. Reverse-transcriptase–polymerase-chain-reaction assays of various specimens (throat swabs or stool samples) were performed to detect enterovirus 71, coxsackievirus A17, and pan-enterovirus messenger RNA. Assays for enterovirus 71 were positive in 12 patients. Assays to detect coxsackievirus A17 were positive in 1 patient, and assays to detect other enteroviruses were positive in 1 patient.
The major manifestations of the disease included fever and rash. Neurologic manifestations were noted in all patients. A startle response, myoclonic jerks, and limb trembling were the most frequent early manifestations of neurologic involvement and indicated deterioration due to the illness. As the patients' disease progressed, seizure and coma developed, and death occurred within 1 hour to 5 days after hospitalization. Autopsy of the 14 patients showed that the brain, especially the brain stem, was most severely involved (Figure 1Figure 1Photomicrographs of Brain-Biopsy Specimens Obtained from Patients with Hand, Foot, and Mouth Disease.); these findings are consistent with the neurotropism of enteroviruses.1-3
The respiratory symptoms were mild at the beginning of illness. Shortly after the deterioration associated with neurologic involvement, 11 of 14 patients had pulmonary edema or pulmonary hemorrhage. All lung specimens showed large amounts of pink fluid in the alveolar space combined with mild lymphocytic inflammation and focal pulmonary hemorrhage without diffuse lung damage (see Fig. 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org); these findings are different from those associated with influenza A (H1N1) virus infection.4
Acute heart failure is another severe complication of hand, foot, and mouth disease. In 13 of 14 patients, peripheral hypoperfusion and tachycardia were reported. An elevated level of creatine kinase MB (CK-MB) was detected in 11 patients, and an elevated level of troponin I was detected in 4 patients; this suggests a degree of cardiac damage.5 However, 12 of 14 cardiac specimens showed mild congestion and edema without inflammation, necrosis, or hemorrhage (Fig. 2 in the Supplementary Appendix); these findings indicate that circulatory dysfunction was of neurogenic origin, but it was not caused by myocarditis.
We also analyzed the relationship between the cardiac histologic findings and the serologic markers. In one patient with slightly elevated levels of CK-MB and troponin I, a cardiac specimen showed slight inflammation. In three patients with moderately increased CK-MB levels with elevated levels of troponin I, pathological examination showed neither myocardial inflammation nor necrosis. However, histopathological examination of a biopsy specimen obtained from one patient showed focal necrosis and degeneration of the myocardium, even though the levels of CK-MB and troponin I were normal. Therefore, CK-MB and troponin I may not be predictors of myocarditis related to hand, foot, and mouth disease.
Min Jiang, M.D.
Dan Wei, M.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
Wei-Lin Ou, M.D.
Affiliated Hospital of Guilin Medical College, Guilin, China
Kun-Xiong Li, M.D.
Dian-Zhong Luo, M.D., Ph.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
Yun-Qian Li, M.D.
Affiliated Hospital of Guilin Medical College, Guilin, China
E Chen, M.D.
Yulin Second People's Hospital, Yulin, China
Guang-Min Nong, M.D., Ph.D.
First Affiliated Hospital of Guangxi Medical University, Nanning, China
ngm8525@hotmail.com
Drs. Jiang, Wei, and Ou contributed equally to this letter.
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
http://www.nejm.org/doi/full/10.1056/NEJMc1110981