今日の臨床サポート

パルボウイルスB19感染症(含む伝染性紅斑/リンゴ病)

著者: 堀越裕歩 東京都立小児総合医療センター 感染症科

監修: 細川直登 亀田総合病院

著者校正済:2021/11/17
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. 健常者、非妊婦の感染の場合、臨床診断のみで経過観察または対症療法自然治癒する(推奨度2
  1. 妊婦の感染の場合、胎児に影響が及ぶことがあるので産婦人科医にコンサルトする(推奨度1
  1. 造血が亢進している溶血性貧血の基礎疾患がある場合、aplastic crisisをきたすことがあるので、バイタルの確認、血液検査を行う(推奨度1
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
堀越裕歩 : 特に申告事項無し[2021年]
監修:細川直登 : 未申告[2021年]

改訂のポイント:
  1. 定期レビューを行い、感染ルートの加筆を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. パルボウイルスB19感染症とは、気道分泌物から飛沫感染で拡がる感染症で、他に母子で子宮内の垂直感染、非常に稀に血液製剤による感染がある。
  1. 小児では不顕性感染、伝染性紅斑(別名リンゴ病)、思春期・成人では関節炎、肝炎を発症する。
  1. 伝染性紅斑は、7~10日前に先行する感冒症状があり、両頬に紅斑が出現、そのあとに四肢に網目状紅斑を来す疾患である。体幹に網目状紅斑が出ることもある。
  1. 通常予後はよい疾患であるが、aplastic crisis、胎児水腫など重症化することがある。
  1. 通年性でみられることが多く、局地的や数年おきの流行がみられる。
  1. 小児期にほとんどの者が感染をし、ピークは5歳から9歳に多く、0歳から4歳がこれに続く。
  1. 成人期には、小児と異なり伝染性紅斑の典型像をとらないことが多く、診断が難しい。
  1. 骨髄の赤芽球前駆細胞に感染して赤血球の造血を止めるため、基礎に溶血性貧血疾患などがある場合に骨髄無形性発作(aplastic crisis)を起こしショックになることがある。日本人では遺伝性球状赤血球症が多く、未診断のこともあり、aplastic crisisを起こして診断されることもある。常染色体優性遺伝がほとんどで貧血の家族歴の聴取が参考になる。
  1. 免疫不全者で慢性貧血、妊婦で流産や胎児水腫がある。まれに心筋炎、脳炎・脳症を引き起こすことがある。
 
参考文献:[1][2]
問診・診察のポイント  
  1. 周囲での流行状況の有無、他の発疹性疾患の鑑別のため予防接種歴と罹患歴を問診する。

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文献 

著者: Herwig Lackner, Petra Sovinz, Martin Benesch, Stephan W Aberle, Wolfgang Schwinger, Sandrin Schmidt, Volker Strenger, Sonja Pliemitscher, Christian Urban
雑誌名: Pediatr Infect Dis J. 2011 May;30(5):440-2. doi: 10.1097/INF.0b013e3182014958.
Abstract/Text Of 1059 children, 35 children with various hemato-oncologic diseases were diagnosed with parvovirus B19 infection. The clinical spectrum included 11 immunocompromised patients presenting with prolonged pancytopenia, 7 patients with delayed hematologic recovery after stem cell transplantation, 5 patients with parvovirus B19 as possible cause of severe aplastic anemia or myelodysplastic syndrome, and 12 children with hemolytic anemia and transient aplastic crisis.

PMID 21502929  Pediatr Infect Dis J. 2011 May;30(5):440-2. doi: 10.109・・・
著者: Richard Kellermayer, Howard Faden, Mauro Grossi
雑誌名: Pediatr Infect Dis J. 2003 Dec;22(12):1100-1. doi: 10.1097/01.inf.0000101783.73240.4a.
Abstract/Text The records of 22 children with parvovirus B19-induced aplastic crisis were reviewed. The group consisted of 16 children with sickle cell hemoglobinopathies and 6 with hereditary spherocytosis. Children presented to the hospital 0.5 to 8 days (mean, 2.4 days) after the onset of symptoms. The children with sickle-cell disease presented earlier (mean, 1.4 days) than did children with hereditary spherocytosis (mean, 5 days; P = 0.02. Fever was the most common symptom, occurring in 73% of children. Rash did not occur in either group. Reticulocyte counts began to rise 1 week after onset of illness associated with a rise in parvovirus B19-specific IgG antibody. These data suggest that parvovirus B19 infection in children with sickle-cell hemoglobinopathies and heredity spherocytosis differs from infection in normal children.

PMID 14688575  Pediatr Infect Dis J. 2003 Dec;22(12):1100-1. doi: 10.1・・・
著者: Tadasu Nunoue, Koichi Kusuhara, Toshiro Hara
雑誌名: Pediatr Infect Dis J. 2002 Dec;21(12):1133-6. doi: 10.1097/01.inf.0000040714.21336.84.
Abstract/Text OBJECTIVE: To clarify the relation between the time of parvovirus B19 (B19) infection in pregnancy and fetal outcome, including the viral persistence in the fetus.
METHODS: Among 57 pairs showing serologic and/or virologic evidence of maternal and fetal B19 infection between 1986 and 1999 in Japan, 13 maternal-fetal pairs with the time of maternal B19 infection documented were retrospectively evaluated for fetal outcome and viral persistence.
RESULTS: Nonimmune hydrops occurred at 23, 21 and 26 gestational weeks (gw) in three fetuses as a result of their mothers' symptomatic infection (erythema infectiosum) at 3, 16 and 19 gw, respectively. Spontaneous abortion without hydrops and intrauterine growth retardation resulting in small-for-gestational age (SGA) classification occurred in two fetuses whose mothers had developed erythema infectiosum at 5 and 16 gw, respectively. Eight fetuses were asymptomatic as a result of their mothers' infection at 6, 9, 12, 15, 18, 23, 23 and 33 gw, respectively. B19 DNA was detected in neonatal serum in all nine cases tested.
CONCLUSION: Maternal B19 infection throughout gestation including the early stage after fertilization caused fetal infection that persisted until intrauterine fetal death with or without nonimmune hydrops or until the neonatal period after birth.

PMID 12488663  Pediatr Infect Dis J. 2002 Dec;21(12):1133-6. doi: 10.1・・・
著者: Albert J Eid, Robert A Brown, Robin Patel, Raymund R Razonable
雑誌名: Clin Infect Dis. 2006 Jul 1;43(1):40-8. doi: 10.1086/504812. Epub 2006 May 12.
Abstract/Text BACKGROUND: Infections with parvovirus B19 (PVB19) can cause significant morbidity in transplant recipients.
METHODS: To characterize the epidemiology and clinical spectrum of posttransplant PVB19 infection, we reviewed all cases at our institution during a 16-year period, summarized the data from 91 cases published in the medical literature, and performed longitudinal molecular surveillance for PVB19 DNAemia among 47 solid organ and hematopoietic stem cell transplant recipients.
RESULTS: The median time to onset of PVB19 disease was 7 weeks after transplantation. Anemia, leukopenia, and thrombocytopenia were present in 98.8%, 37.5%, and 21.0% of patients, respectively. Hepatitis, myocarditis, and pneumonitis were also reported in association with PVB19 disease. Allograft tissue loss or dysfunction was observed at the time of PVB19 disease in 10% of cases. At the onset of disease, PVB19 IgM serological test results were negative in 29% of cases. Almost all patients (96%) with anti-PVB19 IgM had a positive PVB19 polymerase chain reaction assay result. Intravenous immunoglobulin was the most commonly used treatment modality. Three of 98 patients died of myocarditis and cardiogenic shock associated with PVB19 disease. Molecular surveillance throughout the first year after transplantation did not reveal PVB19 DNAemia in 47 anemic solid organ and hematopoietic stem cell transplant patients.
CONCLUSIONS: PVB19 is a rare but clinically significant infection that manifests as refractory anemia during the posttransplantation period. The use of polymerase chain reaction for diagnosis is particularly helpful in immunosuppressed transplant patients who may fail to mount antibodies against PVB19 during active infection.

PMID 16758416  Clin Infect Dis. 2006 Jul 1;43(1):40-8. doi: 10.1086/50・・・
著者: Erik D Heegaard, Kevin E Brown
雑誌名: Clin Microbiol Rev. 2002 Jul;15(3):485-505.
Abstract/Text Parvovirus B19 (B19) was discovered in 1974 and is the only member of the family Parvoviridae known to be pathogenic in humans. Despite the inability to propagate the virus in cell cultures, much has been learned about the pathophysiology of this virus, including the identification of the cellular receptor (P antigen), and the control of the virus by the immune system. B19 is widespread, and manifestations of infection vary with the immunologic and hematologic status of the host. In healthy immunocompetent individuals B19 is the cause of erythema infectiosum and, particularly in adults, acute symmetric polyarthropathy. Due to the tropism of B19 to erythroid progenitor cells, infection in individuals with an underlying hemolytic disorder causes transient aplastic crisis. In the immunocompromised host persistent B19 infection is manifested as pure red cell aplasia and chronic anemia. Likewise, the immature immune response of the fetus may render it susceptible to infection, leading to fetal death in utero, hydrops fetalis, or development of congenital anemia. B19 has also been suggested as the causative agent in a variety of clinical syndromes, but given the common nature, causality is often difficult to infer. Diagnosis is primarily based on detection of specific antibodies by enzyme-linked immunosorbent assay or detection of viral DNA by dot blot hybridization or PCR. Treatment of persistent infection with immunoglobulin reduces the viral load and results in a marked resolution of anemia. Vaccine phase I trials show promising results.

PMID 12097253  Clin Microbiol Rev. 2002 Jul;15(3):485-505.
著者: Deborah M Feldman, Diane Timms, Adam F Borgida
雑誌名: Clin Lab Med. 2010 Sep;30(3):709-20. doi: 10.1016/j.cll.2010.04.009. Epub 2010 Jun 15.
Abstract/Text Several infections in adults warrant special consideration in pregnant women given the potential fetal consequences. Among these are toxoplasmosis, parvovirus B19, and cytomegalovirus. These infections have an important effect on the developing fetus depending on the timing of infection. This article reviews the modes of transmission as well as maternal and neonatal effects of each of these infections. In addition, recommended testing, fetal surveillance, and treatment where indicated are outlined.

Copyright 2010 Elsevier Inc. All rights reserved.
PMID 20638583  Clin Lab Med. 2010 Sep;30(3):709-20. doi: 10.1016/j.cll・・・
著者: Mario Berth, Eugene Bosmans
雑誌名: Clin Vaccine Immunol. 2009 Mar;16(3):372-5. doi: 10.1128/CVI.00380-08. Epub 2008 Dec 30.
Abstract/Text During an outbreak of parvovirus B19 we collected serum samples from 68 nonpregnant patients in the region of Antwerp (Belgium). Fifty-seven (84%) of the parvovirus B19 immunoglobulin M (IgM)-positive sera had a positive result for Epstein-Barr virus (EBV) IgM by Liaison testing, 61 (90%) had a positive result for herpes simplex virus (HSV) IgM, 20 (29%) samples were positive for cytomegalovirus IgM, and 15 (22%) had a positive result for Borrelia burgdorferi sensu lato IgM. As assay interference was suspected, sera were further investigated by using additional infectious-disease serology tests and by performing various interference elimination procedures. We could show that the EBV IgM and HSV IgM results were false positives due to aspecific IgM reactions with the solid phase. All samples were also analyzed by a modified Liaison EBV IgM assay, based on the addition of polyvinylpyrrolidone and polyvinyl alcohol to the dilution buffer, which partially eliminated this type of assay interference. Although the Liaison is a very convenient, automated immunoassay platform, this study demonstrates the potential for improvement of mainly the EBV IgM and HSV IgM tests.

PMID 19116304  Clin Vaccine Immunol. 2009 Mar;16(3):372-5. doi: 10.112・・・
著者: Simon Bredl, Annelie Plentz, Jürgen J Wenzel, Heiko Pfister, Johannes Möst, Susanne Modrow
雑誌名: J Clin Virol. 2011 Jun;51(2):115-20. doi: 10.1016/j.jcv.2011.03.012. Epub 2011 May 6.
Abstract/Text BACKGROUND: Acute parvovirus B19 (B19V) infection is characterized by high-level viremia. Antibodies against the capsid proteins VP1 and VP2 may complex with B19V-particles thereby becoming undetectable in diagnostic tests.
OBJECTIVES: We intended to obtain data on the frequency of false-negative serology in acute B19V-infection.
STUDY DESIGN: 129 plasma or serum samples of healthy blood donors and of patients with suspected B19V-infection were analyzed for B19V-DNA by qPCR and VP1/VP2-specific IgG and IgM by ELISA. Eleven of these samples were derived from four pregnant women with previous contact to B19V-infected individuals. Using acidic conditions virus/antibody-complexes were disrupted and detected by WesternLine and ELISA.
RESULTS: 83/118 samples were derived from acutely infected individuals displaying viremia (10(3)-10(12)geq/mL). In 24/83 viremic samples (28.9%) VP1/VP2-specific IgM and IgG were undetectable in ELISA, but could be demonstrated to be complexed with B19V-particles. Each 7/83 (8.4%) was IgM-positive/IgG-negative and IgM-negative/IgG-positive, in 45/83 samples (54.2%) IgG and IgM could be detected. 35 samples did not contain B19V-DNA; five of these were from seronegative persons. Analyzing consecutive sera derived from four pregnant women, B19V-DNA was demonstrated in 10/11 samples, B19V-specific IgG- and IgM-antibodies were detectable in 10/11 and 4/11 samples, respectively. In 2/4 women seroconversion was observed, but IgM was not detected in 50% of the samples. B19V-specific IgG but not IgM was detectable in 2/4 women.
CONCLUSION: Acute B19V-infection cannot be diagnosed by exclusive analysis of B19V-specific antibodies. Only the combination of assays for detection of B19V-DNA and antibodies enables correct serodiagnosis.

Copyright © 2011 Elsevier B.V. All rights reserved.
PMID 21530386  J Clin Virol. 2011 Jun;51(2):115-20. doi: 10.1016/j.jcv・・・
著者: Martin Enders, Gunnar Schalasta, Carola Baisch, Andrea Weidner, Laura Pukkila, Leena Kaikkonen, Hilkka Lankinen, Lea Hedman, Maria Söderlund-Venermo, Klaus Hedman
雑誌名: J Clin Virol. 2006 Apr;35(4):400-6. doi: 10.1016/j.jcv.2005.11.002. Epub 2005 Dec 5.
Abstract/Text BACKGROUND: Over 95% of fetal complications (fetal hydrops and death) occur within 12 weeks following acute parvovirus B19 (B19) infection in pregnancy. Therefore, weekly fetal ultrasound monitoring is generally recommended for this time period. However, in the majority of women, typical symptoms of acute infection (rash or arthropathy) are absent, and during epidemics, B19 infection may be diagnosed incidentally by antibody screening of women at risk.
OBJECTIVE: To assess the diagnostic value of currently available molecular and serological methods for reliable diagnosis of primary B19 infection in pregnancy.
STUDY DESIGN: Large panels of well-characterized acute-phase or convalescent sera were used to investigate the ability of a VP2 IgM EIA, a Light-Cycler-based B19-DNA PCR, a VP1-IgG avidity EIA and two VP2-IgG epitope-type specificity [ETS] EIAs to pinpoint the time of primary B19 infection in pregnancy.
RESULTS: The duration of low-level IgM positivity varied greatly (range 4-26 weeks). Samples collected within the first 2 weeks of infection showed high-level viremia (mean 1.75 x 10(8) geq/ml). During follow-up, low-level DNAemia (mean 9.7 x 10(4)geq/ml) persisted for at least 18 weeks in 91% (20/22) of patients. Considering the first 12 weeks after onset of disease the window of greatest risk for fetal complications, the "acute" phase was extended to cover this full period. In this case, performing the avidity and ETS-EIA sequentially, the positive predictive value was 100% in patients showing concordant avidity and ETS-EIA results.
CONCLUSIONS: In the presence of low IgM titres and/or low-level DNAemia the use of supplementary serological assays such as VP1-IgG avidity EIA and VP2-ETS-EIA is advisable for restriction or avoidance of unnecessary fetal ultrasound examinations or invasive diagnostics; and in general for strengthening the reliability of B19 serodiagnosis of pregnant women.

PMID 16332455  J Clin Virol. 2006 Apr;35(4):400-6. doi: 10.1016/j.jcv.・・・
著者: N Frickhofen, J L Abkowitz, M Safford, J M Berry, J Antunez-de-Mayolo, A Astrow, R Cohen, I Halperin, L King, D Mintzer
雑誌名: Ann Intern Med. 1990 Dec 15;113(12):926-33.
Abstract/Text OBJECTIVE: To determine the role of B19 parvovirus in red cell aplasia of patients infected with human immunodeficiency virus type 1 (HIV-1).
DESIGN: Uncontrolled clinical trial, with assay of serum, peripheral blood cells, and bone marrow for virus using DNA hybridization and immunocytochemistry techniques; these assays were then correlated with clinical findings, results of immunoassays for antivirus antibodies, and with immunoglobulin (Ig) therapy.
SETTING: Government medical referral center, and university and private hospitals.
PATIENTS: Seven patients with pure red cell aplasia and serologic evidence of infection with HIV-1.
MEASUREMENTS AND MAIN RESULTS: All patients had giant pronormoblasts in the bone marrow (present in transient aplastic crisis caused by acute B19 parvovirus infection). High concentrations of B19 parvovirus were demonstrated in sera, in several cases in samples separated by weeks or months. Viral DNA and capsid protein were present in the bone marrow of three patients studied, and active viral replication was detected by southern analysis. There was no antivirus IgG in capture immunoassay and no or very low levels of antivirus IgM. The patients did not have symptoms of fifth disease, the illness caused by this virus in immunologically normal persons. Six patients were treated with a regimen of intravenous commercial immunoglobulin. In all cases, this therapy resulted in rapid reduction in serum virus concentrations and full recovery of erythropoiesis. Relapses in two cases were predicted by DNA hybridization studies, and these cases were successfully retreated.
CONCLUSIONS: The B19 parvovirus is a remediable cause of severe chronic anemia in HIV-infected patients. Recognition of and therapy for parvovirus in this population will avoid erythrocyte transfusion and should prevent transmission of the virus to other persons, including immunosuppressed persons and women of child-bearing age.

PMID 2173460  Ann Intern Med. 1990 Dec 15;113(12):926-33.
著者: G Kurtzman, N Frickhofen, J Kimball, D W Jenkins, A W Nienhuis, N S Young
雑誌名: N Engl J Med. 1989 Aug 24;321(8):519-23. doi: 10.1056/NEJM198908243210807.
Abstract/Text
PMID 2548098  N Engl J Med. 1989 Aug 24;321(8):519-23. doi: 10.1056/N・・・

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