Tetsushi Yoshikawa, Masahiro Ohashi, Fumi Miyake, Ayano Fujita, Chie Usui, Ken Sugata, Sadao Suga, Shuji Hashimoto, Yoshizo Asano
Exanthem subitum-associated encephalitis: nationwide survey in Japan.
Pediatr Neurol. 2009 Nov;41(5):353-8. doi: 10.1016/j.pediatrneurol.2009.05.012.
Abstract/Text
We sought to clarify clinical features of exanthem subitum associated-encephalitis/encephalopathy, generally caused by primary human herpesvirus-6 infection in Japan. A two-part questionnaire was sent to hospitals between January 2003-December 2004. Of 3357 questionnaires, 2357 (70.2%) were returned, and 2293 (68.3%) were eligible for analysis. Eighty-six cases of exanthem subitum-associated encephalitis/encephalopathy were reported. Seventy-seven (89.5%) of 86 patients were diagnosed with human herpesvirus-6 infection by virologic examination. Although 41 (50.6%) of 81 patients had no sequelae, 38 (46.9%) had neurologic sequelae. Moreover, two fatal cases (2.5%) were reported. Pleocytosis was evident in only 4 (7.5%) of 53 patients, and cerebrospinal fluid protein levels were within normal range (23.4 +/- 14.6 mg/dL S.D.) in all patients. Human herpesvirus-6 DNA was detected in 21 (53.8%) of 39 patients. Abnormal computed tomography findings were a predictor of neurologic sequelae (P = 0.0097). As a consequence of this survey, we estimate that 61.9 cases of exanthem subitum-associated encephalitis occur every year. The disease prognosis was unexpectedly poor.
F Barah, P J Vallely, M L Chiswick, G M Cleator, J R Kerr
Association of human parvovirus B19 infection with acute meningoencephalitis.
Lancet. 2001 Sep 1;358(9283):729-30. doi: 10.1016/S0140-6736(01)05905-0.
Abstract/Text
To find out the incidence and clinical presentation of parvovirus B19 meningoencephalitis, we tested samples of cerebrospinal fluid from 162 patients (one from each patient) with undiagnosed meningoencephalitis, who presented between March, 1997, and March, 1998 (an outbreak period) using nested PCR for B19 genes. Seven patients were positive; an incidence of 4.3%. Five additional cases of meningoencephalitis were detected from other years. Three patients with underlying disorders (haemophagocytic lymphohistiocytosis, Cockayne's syndrome, and Turner's syndrome) died. Neurological sequelae were observed in three surviving patients, all of whom had had striking abnormalities detected on brain scans done during the acute phase.
C C Huang, C C Liu, Y C Chang, C Y Chen, S T Wang, T F Yeh
Neurologic complications in children with enterovirus 71 infection.
N Engl J Med. 1999 Sep 23;341(13):936-42. doi: 10.1056/NEJM199909233411302.
Abstract/Text
BACKGROUND: Enterovirus 71 infection causes hand-foot-and-mouth disease in young children, which is characterized by several days of fever and vomiting, ulcerative lesions in the oral mucosa, and vesicles on the backs of the hands and feet. The initial illness resolves but is sometimes followed by aseptic meningitis, encephalomyelitis, or even acute flaccid paralysis similar to paralytic poliomyelitis.
METHODS: We describe the neurologic complications associated with the enterovirus 71 epidemic that occurred in Taiwan in 1998. At three major hospitals we identified 41 children with culture-confirmed enterovirus 71 infection and acute neurologic manifestations. Magnetic resonance imaging (MRI) was performed in 4 patients with acute flaccid paralysis and 24 with rhombencephalitis.
RESULTS: The mean age of the patients was 2.5 years (range, 3 months to 8.2 years). Twenty-eight patients had hand-foot-and-mouth disease (68 percent), and 6 had herpangina (15 percent). The other seven patients had no skin or mucosal lesions. Three neurologic syndromes were identified: aseptic meningitis (in 3 patients); brain-stem encephalitis, or rhombencephalitis (in 37); and acute flaccid paralysis (in 4), which followed rhombencephalitis in 3 patients. In 20 patients with rhombencephalitis, the syndrome was characterized by myoclonic jerks and tremor, ataxia, or both (grade I disease). Ten patients had myoclonus and cranial-nerve involvement (grade II disease). In seven patients the brain-stem infection produced transient myoclonus followed by the rapid onset of respiratory distress, cyanosis, poor peripheral perfusion, shock, coma, loss of the doll's eye reflex, and apnea (grade III disease); five of these patients died within 12 hours after admission. In 17 of the 24 patients with rhombencephalitis who underwent MRI, T2-weighted scans showed high-intensity lesions in the brain stem, most commonly in the pontine tegmentum. At follow-up, two of the patients with acute flaccid paralysis had residual limb weakness, and five of the patients with rhombencephalitis had persistent neurologic deficits, including myoclonus (in one child), cranial-nerve deficits (in two), and ventilator-dependent apnea (in two).
CONCLUSIONS: In the 1998 enterovirus 71 epidemic in Taiwan, the chief neurologic complication was rhombencephalitis, which had a fatality rate of 14 percent. The most common initial symptoms were myoclonic jerks, and MRI usually showed evidence of brainstem involvement.
Kimberly M Molina, Xiomara Garcia, Susan W Denfield, Yuxin Fan, William R Morrow, Jeffrey A Towbin, Elizabeth A Frazier, David P Nelson
Parvovirus B19 myocarditis causes significant morbidity and mortality in children.
Pediatr Cardiol. 2013 Feb;34(2):390-7. doi: 10.1007/s00246-012-0468-4. Epub 2012 Aug 8.
Abstract/Text
Although parvovirus B19 (PVB19) currently is the most common cause of viral myocarditis, limited pediatric data exist. Whereas other viruses infect cardiomyocytes, PVB19 targets coronary endothelium, leading to myocardial ischemia and dysfunction. A retrospective review investigated patients with polymerase chain reaction (PCR)-verified PVB19 myocarditis at Texas Children's Hospital and Arkansas Children's Hospital (January 2005 to August 2008). The primary end points of the study were transplant-free survival and circulatory collapse (death, mechanical support, or transplantation). For the 19 patients identified (age, 6 months to 15 years), the most common presenting symptoms were respiratory and gastrointestinal. At admission, all the patients demonstrated ventricular dysfunction requiring inotropic support (median ejection fraction, 24 %; median left ventricle end-diastolic diameter [LVEDD] z-score, 4.6). Whereas T-wave abnormalities were common, ST elevation was evident in five patients (two died and three required transplantation). Serum B-type natrietic peptide was elevated in all 12 patients tested (range, 348-8,058 pg/ml), and troponin I was high in 7 of 9 patients (range, 0.04-14.5 ng/ml). Of the 15 patients with circulatory collapse, nine received mechanical support, eight underwent successful transplantation, and five died. Only six patients (32 %) experienced transplant-free survival, and five patients had full recovery of function at discharge. In the transplant-free survival group, ST changes on presenting electrocardiography were less likely (p = 0.03), and the admission LVEDD z-score tended to be lower (3.3 vs 5.6; p = 0.08). In children, PVB19 myocarditis causes significant mortality and morbidity. Although mechanical intervention can support patients in the initial stage of decompensated heart failure, patients with PVB19 myocarditis often demonstrate persistent dysfunction requiring medical therapy and transplantation.
大橋 正博, 吉川 哲史, 三宅 史, 菅田 健, 須賀 定雄, 浅野 喜造：小児感染免疫18（4）：385─392，2006 突発疹関連脳炎脳症の全国調査.
Aleisha Hatakka, Julianne Klein, Runtao He, Jessica Piper, Edward Tam, Andrew Walkty
Acute hepatitis as a manifestation of parvovirus B19 infection.
J Clin Microbiol. 2011 Sep;49(9):3422-4. doi: 10.1128/JCM.00575-11. Epub 2011 Jul 6.
Abstract/Text
There are few reports in the literature of hepatitis as a manifestation of parvovirus B19 infection. We describe a case of parvovirus B19-associated acute hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in a liver biopsy specimen. Parvovirus B19 infection should be considered in the differential diagnosis of patients presenting with acute hepatitis.
Elena Bozzola, Alberto E Tozzi, Mauro Bozzola, Andrzej Krzysztofiak, Diletta Valentini, Annalisa Grandin, Alberto Villani
Neurological complications of varicella in childhood: case series and a systematic review of the literature.
Vaccine. 2012 Aug 24;30(39):5785-90. doi: 10.1016/j.vaccine.2012.05.057. Epub 2012 Jun 5.
Abstract/Text
Although varicella has usually an uncomplicated course in early childhood, several neurological complications may occur. We conducted a study to review the type and the rate of varicella neurological complications in a case series of hospitalized immunologically healthy children over nearly a 8 year period. We also systematically reviewed data from the literature to estimate the rate of varicella neurological complications. In our case reports, the proportion of neurological complications among all those hospitalized for varicella was of 21.7% (CI 17.9-26%). The pooled prevalence of neurological complications resulting from the systematic review of the literature identifies the likelihood of such complications in the range of 13.9-20.4%. Although neurological complications of chickenpox do not frequently result in permanent sequelae, they represent significant determinants of prolonged hospital stay and of other indirect costs. The obtained results may be useful for estimating costs associated with hospitalization from varicella in cost-benefit analysis for immunization.
Copyright © 2012 Elsevier Ltd. All rights reserved.
C Ziebold, R von Kries, R Lang, J Weigl, H J Schmitt
Severe complications of varicella in previously healthy children in Germany: a 1-year survey.
Pediatrics. 2001 Nov;108(5):E79.
Abstract/Text
OBJECTIVE: Varicella is a common infectious disease, usually benign and self-limited, and complications are believed to be rare. The purpose of this study was to describe the epidemiology of severe varicella complications in immunologically healthy children in Germany.
METHODS: Information on any admission of children with a severe complication associated with chickenpox was solicited throughout 1997 from all 485 pediatric hospitals in Germany using an established surveillance system. The case definition included nonimmunocompromised individuals who were up to 16 years of age and hospitalized with neurologic complications, bacterial superinfections, or hematologic complications.
RESULTS: The response rate to the surveillance questionnaire during the observation period was high: 93.4%. Of the 153 reported cases, 119 met the case definition. There was a seasonal distribution of reported complications with a peak in March. The majority of complications occurred in preschool-age children with a maximum age of 4 years. No gender predominance was found with a distribution of 56 female and 63 male patients. Multiple entries for complications were allowed. The most frequent complications were neurologic, which were reported in 73 children (61.3%); cerebellitis was the leading diagnosis (n = 48), followed by encephalitis (n = 22), meningitis (n = 2), and central facial palsy (n = 1). A total of 46 (38.6%) infectious complications were identified. Superinfections of the skin were present in 31 (26.0%), pyogenic arthritis was present in 5 (4.2%), osteomyelitis was present in 4 (3.3%), necrotizing fasciitis was present in 3 (2.5%), orbital cellulitis was present in 2 (1.6%), and pneumonia was present in 1 (0.8%). Streptococcus pyogenes was the leading cause of bacterial infections (18 cases [15.1%]), with invasive disease in 6 patients (8.4%) and linked to 4 of 8 cases with defect healing. Infectious complications were reported in the majority in younger children up to 4 years of age, whereas neurologic complications occurred more frequently in an older age range. Five children experienced thrombocytopenia or severe anemia. There was no bleeding disorder, no fatality, and no case of Reye syndrome reported during the 1-year observation period. In total, 8 (6.7%) of 119 patients reported having long-term sequelae, 6 attributable to infectious complications and 2 to persistent deficits after neurologic complications.
CONCLUSION: This is the first prospective nationwide study of severe complications of varicella in immunologically healthy children. Related to 14 025 867 children up to the age of 16, a crude incidence of severe chickenpox complications of 0.85/100 000 could be calculated [corrected]. The actual hospitalization rate attributable to complicated chickenpox is probably much higher, because this calculation refers to a population theoretically at risk and not the truly susceptible individuals. The results of this study demonstrate considerable morbidity with a comparatively high rate of encephalitis, osteomyelitis, and pyogenic arthritis. Although infectious complications were present in only 38.6% of the reported cases, they contributed disproportionately to the cases with chronic sequelae. Looking at these cases in more detail, S pyogenes involvement was identified as the major risk factor for invasive disease with an unfavorable long-term outcome. varicella-zoster virus, chickenpox/epidemiology, chickenpox/complications, encephalitis, cellulitis, osteomyelitis, necrotizing fasciitis, group A beta-hemolytic streptococci, Europe.
Eiichi Ishii, Shouichi Ohga, Shinsaku Imashuku, Masaki Yasukawa, Hiroyuki Tsuda, Ikuo Miura, Ken Yamamoto, Hisanori Horiuchi, Kenzo Takada, Koichi Ohshima, Shigeo Nakamura, Naoko Kinukawa, Kazuo Oshimi, Keisei Kawa
Nationwide survey of hemophagocytic lymphohistiocytosis in Japan.
Int J Hematol. 2007 Jul;86(1):58-65. doi: 10.1532/IJH97.07012.
Abstract/Text
Hemophagocytic lymphohistiocytosis (HLH), a disorder of the mononuclear phagocyte system, can be classified into two distinct forms: primary HLH (FHL) and secondary HLH. To clarify the epidemiology and clinical outcome for each HLH subtype, we conducted a nationwide survey of HLH in Japan. Since 799 patients were diagnosed in 292 institutions of Japan between 2001 and 2005, the annual incidence of HLH was estimated as 1 in 800,000 per year. Among them, 567 cases were actually analyzed in this study. The most frequent subtype was Epstein-Barr virus (EBV)-associated HLH, followed by other infection- or lymphoma-associated HLH. Age distribution showed a peak of autoimmune disease- and infection-associated HLH in children, while FHL and lymphoma-associated HLH occurred almost exclusively in infants and the elderly, respectively. The 5-year overall survival rate exceeded 80% for patients with EBV- or other infection-associated HLH, was intermediate for those with FHL or B-cell lymphoma-associated HLH, and poor for those with T/NK cell lymphoma-associated HLH (<15%). Although this nationwide survey establishes the heterogeneous characteristics of HLH, the results should be useful in planning prospective studies to identify the most effective therapy for each HLH subtype.
川崎病（MCLS、小児急性熱性皮膚粘膜リンパ節症候群）診断の手引き 厚生労働省川崎病研究班作成改訂5版.
麻疹の検査診断の考え方 国立感染症研究所感染症情報センター麻しん対策技術支援チーム 平成24年3月16日 [Internet]. [cited 2016 Jan 25]. Available from: http://www.mhlw.go.jp/stf/shingi/2r98520000025gxs-att/2r98520000025h3x.pdf
