今日の臨床サポート 今日の臨床サポート

著者: 武井修治 鹿児島大学大学院医歯学総合研究科(小児科)

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2024/05/15
参考ガイドライン:
  1. American Heart Association(https://www.heart.org/en): Circulation 2009, 119:1541-51.
患者向け説明資料

改訂のポイント:
  1. 病態について、加筆した。
  1. A群レンサ球菌関連抗体の測定法の変更に伴う正常上限値の記載を変更した。
  1. ASOは以前は毒素中和反応法で測定され、抗体価はTodd単位で示されていたが、現在ではラテックス凝集比濁法での測定が一般化してIU/mLで表記されている。そのため、改訂版ではこの検査法による正常上限値の記載を変更し、先行感染の判断に関する記載を修正した。また従来からA群レンサ球菌関連抗体としてASOに加えて、ASKとDNAase-Bの検査が行われてきたが、わが国ではASKやDNAase-Bは商業ベースでは測定されなくなり、臨床現場で測定する機会がなくなった。しかし海外ではASOとDNAase-Bが利用されているため、この二つの正常上限値を年齢別に記載した表に差し替え、関連する文献を追記した。
  1. 疫学調査(患者数)を更新した。
  1. 患者発生数について、2017年に報告された2010~2015年の疫学調査(323施設)のdataに更新した。ただこの報告での症例数は少ないため、臨床所見の頻度については多数例で検討した従来のものを残した。
  1. COVID-19パンデミックの影響を加筆した。

概要・推奨   

病態
  1. A群レンサ球菌と宿主組織とのmolecular mimicry(分子類似性)による免疫学的交差反応と考えられており、菌が保有するM蛋白とヒトの心筋や弁膜組織、N-アセチル-β-D-グルコサミンと大脳基底核神経細胞の抗原類似性が報告されている。
  1. 一卵性双生児での発症リスクや家族集積性の報告から、発症には遺伝学的背景が関与することが推定されており、自然免疫系と獲得免疫系の経路にかかわる複数の候補遺伝子が報告されている。
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病態・疫学・診察 

疾患情報(疫学・病態)  
  1. 急性リウマチ熱とは、A群レンサ球菌感染2~3週後に続発する全身性炎症性疾患で、性差はなく5~15歳に好発する。
  1. 先行感染から10日間の抗菌薬投与で発症予防が可能なため[1]、先進国での発生は激減しており、わが国の323施設で2010年~2015年の間に発生した患者数は44例である[2]
  1. COVID-19パンデミック期には発生数が減少[3]したことから、マスクや手洗いなどの感染予防対策の重要性が示唆された。
  1. 急性期には、発熱とともに移動性多関節炎(70%)、心炎(50%)、輪状紅斑(10%)(<図表>)、皮下結節(5%)が出現し、精神症状や舞踏病(5%)は遅れて出現する[4]<図表>
  1. 心炎は心内膜炎であり、僧帽弁や大動脈弁に弁膜障害を残す(リウマチ性心疾患)。
 
リウマチ性心疾患にみられた弁膜肥厚

リウマチ性心疾患患者の疣贅様に肥厚・突出した心弁膜。リウマチ熱では心内膜炎が50~60%にみられ、治療の遅れや不十分な治療では僧帽弁や大動脈弁を中心に機能障害を残す。

出典

Petty Ross E, Laxer Ronald M, et al:Textbook of Pediatric Rheumatology, 7th Edition,2016. p577. FIGURE 44-6.
 
  1. 診断にはJones改定診断基準(2015)[5]が用いられる。<図表>
  1. 急性期の治療では抗菌薬と抗炎症薬が用いられるが、心炎や重症舞踏病には抗炎症薬としてステロイド薬が用いられる[6]
  1. A群レンサ球菌の再感染で再発しやすく、再発すればリウマチ性心疾患のある例では弁膜障害が進行するため、抗菌薬による長期の予防内服が必要である[7]<図表>
 
  1. A群レンサ球菌感染症に罹患した場合、続発症であるリウマチ熱の発症予防目的で10日間の抗菌薬療法を行うべきである(推奨度1、M)
  1. まとめ:リウマチ熱の発症予防に関し、咽頭炎の患者を対象としたA群レンサ球菌を想定した抗菌薬療法の有効性に関するいくつかの大規模コホート研究があるが、それらを統合したメタ解析においても、抗菌薬療法の有効性が明らかとなった[1]。(<図表>
  1. 代表事例:1950~1961年に行われた10件のコホート研究(対象7,665例)を対象としたメタ解析では、抗菌薬によるリウマチ熱の予防効果は、全体では70%(RR=0.32、95%CI=0.21-0.48)、ペニシリン系抗菌薬に限ったコホート研究では80%(RR=0.20、95%CI=0.11-0.36)であった。
  1. 結論:このことから、A群レンサ球菌性咽頭扁桃炎が疑われる例では、抗菌薬の使用がリウマチ熱の発症を減らすことが明らかとなり、特にペニシリン系抗菌薬の10日間投与が勧められている。
 
抗菌薬によるリウマチ熱の発症予防

1950~1965年に行われた10のコホート研究では、A群レンサ球菌感染症が想定される咽頭炎患者7,665例において、抗菌薬によるリウマチ熱の予防効果は、コホート研究全体では70%(RR=0.32、95%CI=0.21-0.48)、ペニシリン系抗菌薬に限ったコホート研究では80%(RR=0.20、95%CI=0.11-0.36)であった。

出典

Katharine A Robertson, Jimmy A Volmink, Bongani M Mayosi
Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis.
BMC Cardiovasc Disord. 2005 May 31;5(1):11. doi: 10.1186/1471-2261-5-11. Epub 2005 May 31.
Abstract/Text BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever.
METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966-2003), EMBASE (1966-2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever.
RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21-0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11-0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately USD 46 in South Africa.
CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.

PMID 15927077
 
  1. リウマチ熱の発症予防目的の抗菌薬としては、ペニシリン系抗菌薬が推奨される(推奨度1、RG)
  1. まとめ:抗菌薬によるリウマチ熱発症予防のための抗菌薬としてはペニシリン系抗菌薬の服用が推奨されている。しかしアレルギー等でペニシリン系抗菌薬が使えない場合はマクロライド系抗菌薬、狭域のセファロスポリン系抗菌薬が代用される。(<図表>
  1. 代表事例の説明・結論:米国心臓協会(American Heart Association、AHA)によるリウマチ熱予防のための治療ガイドライン[7]では、経口抗菌薬としては、ペニシリンV 40 mg/kg/日(分3)またはアモキシシリン50 mg/kg/日(分1)が推奨され、ペニシリンアレルギー等で使えない症例では、クラリスロマイシン15mg/kg/日(分2)、アジスロマイシン12 mg/kg/日(分1)5日間、クリンダマイシン20 mg/kg/日(分3)などのマクロライド系抗菌薬の使用が推奨されている。
  1. 追記:わが国では経口ペニシリンG(バイシリンG)が使用されてきたが、安価なために配置されている医療機関は少なくなった。その意味での代替薬としては、FDAが承認しているアモキシシリン(パセトシン)が使いやすい。
問診・診察のポイント  
問診で確認すべきこと:
  1. 先行(2~3週前)するA群レンサ球菌感染症の存在

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文献 

Katharine A Robertson, Jimmy A Volmink, Bongani M Mayosi
Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis.
BMC Cardiovasc Disord. 2005 May 31;5(1):11. doi: 10.1186/1471-2261-5-11. Epub 2005 May 31.
Abstract/Text BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever.
METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966-2003), EMBASE (1966-2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever.
RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21-0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11-0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately USD 46 in South Africa.
CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.

PMID 15927077
Satoshi Sato, Yoji Uejima, Eisuke Suganuma, Tadamasa Takano, Yutaka Kawano
A retrospective study: Acute rheumatic fever and post-streptococcal reactive arthritis in Japan.
Allergol Int. 2017 Oct;66(4):617-620. doi: 10.1016/j.alit.2017.04.001. Epub 2017 Apr 22.
Abstract/Text BACKGROUND: Acute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA) are immune-mediated consequences of group A streptococcal pharyngitis. ARF has declined in developed nations. No prevalence survey of PSRA has been conducted. This study evaluated the incidence and characteristics of ARF and PSRA in Japanese children.
METHODS: From 2010 to 2015, ARF and PSRA were evaluated using clinical data retrospectively collected by chart review from 528 hospitals.
RESULTS: From 323 hospitals (61% response rate), 44 cases of ARF and 21 cases of PSRA were reported. Patients with ARF and/or PSRA were mainly from large cities in Japan. The mean age of ARF occurrence was 8.5 years, and the ratio of female/male patients was 16:28. Major manifestations in the acute phase included carditis, 27 cases (61.4%); polyarthritis, 22 cases (50%); erythema marginatum, 7 cases (15.9%); Sydenham chorea, 3 cases (6.8%); and subcutaneous nodules, 1 case (2.3%). Twenty-one (58.3%) patients had migratory arthritis. During the follow-up period, 6 patients (13.6%) showed mild carditis. For PRSA, the mean age was 8.2 years, and the ratio of female/male patients was 12:9. Six (28.6%) patients had monoarthritis, and 4 (19%) patients had migratory arthritis. No patient had carditis.
CONCLUSIONS: Although ARF and PSRA are rare in the Japanese pediatric population, substantial numbers of patients with both conditions were identified in this study. We observed a high incidence of arthritis and carditis in ARF patients. No PSRA case was complicated with carditis. General pediatricians need to have updated information about ARF and PSRA, even in industrialized countries.

Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.
PMID 28442182
Fuat Laloğlu, Naci Ceviz
Changes in the frequency and clinical features of acute rheumatic fever in the COVID-19 era: a retrospective analysis from a single center.
Rev Assoc Med Bras (1992). 2022 Sep;68(9):1313-1317. doi: 10.1590/1806-9282.20220620.
Abstract/Text OBJECTIVE: Coronavirus disease 2019 (COVID-19) pandemic resulted in significant changes in the frequency of many diseases. In this study, we aimed to investigate the changes in the frequency and clinical features of acute rheumatic fever (ARF) in this period and determine the effect of health measures taken against COVID-19 on this change.
METHODS: The cases with initial attack of ARF between January 2016 and March 2022 in Ataturk University, Division of Pediatric Cardiology, were determined from the clinic's database, and case per month ratios were calculated for each period, retrospectively. Also the frequency of the clinical manifestations was compared among patients before and during the outbreak.
RESULTS: Frequency of the major clinical manifestations among patients before and during the outbreak was similar. On average, the number of cases reported per month in the years 2016, 2017, 2018, and 2019 are, respectively, 1.75, 2, 2.25, and 2.58. In the first 3 months of 2020, the average number of cases reported per month was 3.67. After the advent of the pandemic, in the period from April to December 2020 and from January to September 2021, an average of 0.56 and 0.22 cases were reported per month, respectively. The frequency of clinical features between patients diagnosed before and during the outbreak was similar.
CONCLUSIONS: Our results indicated an important decrease in frequency of ARF, but no change in the clinical features of the disease during the COVID-19 pandemic. It is thought that this is the result of health measures taken for COVID-19. Children with an increased risk of acute rheumatic fever should be encouraged in terms of wearing mask, social distance, and cleaning, especially during the seasons when upper respiratory tract infections are common. Thus, a permanent decrease in the incidence of ARF and its recurrences may be achieved.

PMID 36228264
Gerber MA: Rheumatic fever. Nelson’s Textbook of Pediatrics, 17ed, Saunders, 2003; 874-879.
Michael H Gewitz, Robert S Baltimore, Lloyd Y Tani, Craig A Sable, Stanford T Shulman, Jonathan Carapetis, Bo Remenyi, Kathryn A Taubert, Ann F Bolger, Lee Beerman, Bongani M Mayosi, Andrea Beaton, Natesa G Pandian, Edward L Kaplan, American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young
Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association.
Circulation. 2015 May 19;131(20):1806-18. doi: 10.1161/CIR.0000000000000205. Epub 2015 Apr 23.
Abstract/Text BACKGROUND: Acute rheumatic fever remains a serious healthcare concern for the majority of the world's population despite its decline in incidence in Europe and North America. The goal of this statement was to review the historic Jones criteria used to diagnose acute rheumatic fever in the context of the current epidemiology of the disease and to update those criteria to also take into account recent evidence supporting the use of Doppler echocardiography in the diagnosis of carditis as a major manifestation of acute rheumatic fever.
METHODS AND RESULTS: To achieve this goal, the American Heart Association's Council on Cardiovascular Disease in the Young and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee organized a writing group to comprehensively review and evaluate the impact of population-specific differences in acute rheumatic fever presentation and changes in presentation that can result from the now worldwide availability of nonsteroidal anti-inflammatory drugs. In addition, a methodological assessment of the numerous published studies that support the use of Doppler echocardiography as a means to diagnose cardiac involvement in acute rheumatic fever, even when overt clinical findings are not apparent, was undertaken to determine the evidence basis for defining subclinical carditis and including it as a major criterion of the Jones criteria. This effort has resulted in the first substantial revision to the Jones criteria by the American Heart Association since 1992 and the first application of the Classification of Recommendations and Levels of Evidence categories developed by the American College of Cardiology/American Heart Association to the Jones criteria.
CONCLUSIONS: This revision of the Jones criteria now brings them into closer alignment with other international guidelines for the diagnosis of acute rheumatic fever by defining high-risk populations, recognizing variability in clinical presentation in these high-risk populations, and including Doppler echocardiography as a tool to diagnose cardiac involvement.

© 2015 American Heart Association, Inc.
PMID 25908771
大国真彦:リウマチ熱の診断および内科的治療基準(1974年).厚生省研究班報告.リウマチ1975; 15:185-189.
Michael A Gerber, Robert S Baltimore, Charles B Eaton, Michael Gewitz, Anne H Rowley, Stanford T Shulman, Kathryn A Taubert
Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics.
Circulation. 2009 Mar 24;119(11):1541-51. doi: 10.1161/CIRCULATIONAHA.109.191959. Epub 2009 Feb 26.
Abstract/Text Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by combining clinical judgment with diagnostic test results, the criterion standard of which is the throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice, because it is cost-effective, has a narrow spectrum of activity, and has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. For penicillin-allergic individuals, acceptable alternatives include a narrow-spectrum oral cephalosporin, oral clindamycin, or various oral macrolides or azalides. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The recommended duration of prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or a macrolide or azalide are acceptable alternatives in penicillin-allergic individuals. This report updates the 1995 statement by the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. It includes new recommendations for the diagnosis and treatment of GAS pharyngitis, as well as for the secondary prevention of rheumatic fever, and classifies the strength of the recommendations and level of evidence supporting them.

PMID 19246689
Alsaeid K, Cassidy JT: Acute rheumatic fever and post-streptococcal reactive arthritis. Cassidy JT, Petty RE, Laxer RM, Lindsley CB, eds; Textbook of Pediatric Rheumatology, 6th Ed. Saunders, ELSEVIER, 2011; 600-614.
J R Carapetis, B J Currie
Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever.
Arch Dis Child. 2001 Sep;85(3):223-7.
Abstract/Text AIMS: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries.
METHODS: The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively.
RESULTS: Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions.
CONCLUSIONS: Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

PMID 11517105
Andrew C Steer, Suzanna Vidmar, Roselyn Ritika, Joseph Kado, Michael Batzloff, Adam W J Jenney, John B Carlin, Jonathan R Carapetis
Normal ranges of streptococcal antibody titers are similar whether streptococci are endemic to the setting or not.
Clin Vaccine Immunol. 2009 Feb;16(2):172-5. doi: 10.1128/CVI.00291-08. Epub 2008 Dec 3.
Abstract/Text Group A streptococcal (GAS) serology is used for the diagnosis of post-streptococcal diseases, such as acute rheumatic fever, and occasionally for the diagnosis of streptococcal pharyngitis. Experts recommend that the upper limits of normal for streptococcal serology be determined for individual populations because of differences in the epidemiology of GAS between populations. Therefore, we performed a study to determine the values of the upper limit of normal for anti-streptolysin O (ASO) and anti-DNase B (ADB) titers in Fiji. Participants with a history of GAS disease, including pharyngitis or impetigo, were excluded. A total of 424 serum samples from people of all ages (with a sample enriched for school-aged children) were tested for their ASO and ADB titers. Reference values, including titers that were 80% of the upper limit of normal, were obtained by regression analysis by use of a curve-fitting method instead of the traditional nonparametric approach. Normal values for both the ASO titer and the ADB titer rose sharply during early childhood and then declined gradually with age. The estimated titers that were 80% of the upper limit or normal at age 10 years were 276 IU/ml for ASO and 499 IU/ml for ADB. Data from our study are similar to those found in countries with temperate climates, suggesting that a uniform upper limit of normal for streptococcal serology may be able to be applied globally.

PMID 19052157
Stanford T Shulman, Elia M Ayoub
Poststreptococcal reactive arthritis.
Curr Opin Rheumatol. 2002 Sep;14(5):562-5.
Abstract/Text Poststreptococcal reactive arthritis (PSRA) refers to a poststreptococcal arthritic condition that does not fulfill the Jones Criteria for diagnosis of acute rheumatic fever. Clinical features include additive rather than migratory arthritis that responds relatively poorly to salicylates and nonsteroidals; persistence for mean of 2 months; elevated acute phase reactants; and laboratory (usually serologic) evidence of recent group A streptococcal infection. PSRA is not associated with HLA-B27 but rather with HLA-DRB1*01. Because up to 6% of PSRA patients develop mitral valve disease, it is recommended that antistreptococcal prophylaxis be administered for 1 year and then discontinued if there is no evidence of cardiac involvement.

PMID 12192255
S E Swedo, H L Leonard, M Garvey, B Mittleman, A J Allen, S Perlmutter, L Lougee, S Dow, J Zamkoff, B K Dubbert
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases.
Am J Psychiatry. 1998 Feb;155(2):264-71.
Abstract/Text OBJECTIVE: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS]) infections (PANDAS).
METHOD: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities.
RESULTS: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for tics; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course was characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children; there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure.
CONCLUSIONS: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies.

PMID 9464208
S J Perlmutter, S F Leitman, M A Garvey, S Hamburger, E Feldman, H L Leonard, S E Swedo
Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood.
Lancet. 1999 Oct 2;354(9185):1153-8. doi: 10.1016/S0140-6736(98)12297-3.
Abstract/Text BACKGROUND: In children, exacerbations of tics and obsessive symptoms may occur after infection with group A beta-haemolytic streptococci. If post-streptococcal autoimmunity is the cause of the exacerbations, then children might respond to immunomodulatory treatments such as plasma exchange or intravenous immunoglobulin (IVIG). We studied whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms.
METHODS: Children with severe, infection-triggered exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including Tourette syndrome, were randomly assigned treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (saline solution given in the same manner as IVIG). Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, tics, anxiety, depression, and global function.
FINDINGS: 30 children entered the study and 29 completed the trial. Ten received plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma exchange groups showed striking improvements in obsessive-compulsive symptoms (mean improvement on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%], respectively), anxiety (2.1 [31%] and 3.0 [47%] improvement on National Institute of Mental Health anxiety scale), and overall functioning (2.9 [33%] and 2.8 [35%] improvement on National Institute of Mental Health global scale). Tic symptoms were also significantly improved by plasma exchange (mean change on Tourette syndrome unified rating scale of 49%). Treatment gains were maintained at 1 year, with 14 (82%) of 17 children "much" or "very much" improved over baseline (seven of eight for plasma exchange, seven of nine for IVIG).
INTERPRETATION: Plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. Further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies.

PMID 10513708
M A CREA, E A MORTIMER
The nature of scarlatinal arthritis.
Pediatrics. 1959 May;23(5):879-84.
Abstract/Text
PMID 13645124
Yosef Uziel, Liat Perl, Judith Barash, Philip J Hashkes
Post-streptococcal reactive arthritis in children: a distinct entity from acute rheumatic fever.
Pediatr Rheumatol Online J. 2011 Oct 20;9(1):32. doi: 10.1186/1546-0096-9-32. Epub 2011 Oct 20.
Abstract/Text There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question.

PMID 22013970
Rheumatic fever and rheumatic heart disease.
World Health Organ Tech Rep Ser. 2004;923:1-122, back cover.
Abstract/Text Rheumatic heart disease poses a major challenge to public health and is the most prevalent heart disease in children. The major determinants of rheumatic fever and rheumatic heart disease are poverty, malnutrition, overcrowding, poor housing, and a shortage of health-care resources. Although cost-effective strategies for the prevention and control of these diseases are available, they remain underutilized in most developing countries. A World Health Organization Expert Consultation reviewed the current scientific knowledge of rheumatic fever and rheumatic heart disease, as well as medical and public-health practices, and revised the Jones diagnostic criteria for rheumatic fever and rheumatic heart disease. This revision facilitates the diagnosis of: primary episodes of rheumatic fever, recurrent attacks of rheumatic fever in patients with or without rheumatic heart disease, rheumatic chorea, insidious onset rheumatic carditis and chronic rheumatic heart disease. The present report provides practical recommendations for an evidence-based approach to the prevention and management of rheumatic fever and rheumatic heart disease. It also provides practical guidance for implementing cost-effective programmes for controlling these diseases. The report will be of interest to clinicians, policy-makers and public-health professionals.

PMID 15382606
大国真彦:リウマチ熱の診断および内科的治療基準(1974年).厚生省研究班報告.リウマチ, 1975; 15:185-189.
A M Cilliers, J Manyemba, H Saloojee
Anti-inflammatory treatment for carditis in acute rheumatic fever.
Cochrane Database Syst Rev. 2003;(2):CD003176. doi: 10.1002/14651858.CD003176.
Abstract/Text BACKGROUND: Rheumatic heart disease remains the most important cause of acquired heart disease in developing countries. Although the prevention of rheumatic fever and the management of recurrences is well established the optimal management of active rheumatic carditis is still unclear.
OBJECTIVES: To assess the effects of anti-inflammatory agents such as aspirin, corticosteroids and immunoglobulin for preventing or reducing further heart valve damage in patients with acute rheumatic fever.
SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Issue 4, 2000), MEDLINE (1966 to April 2002), EMBASE (1998 to November 2002), LILACS (1998 to November 2002), Index Medicus (1950 to December 2000) and references lists of identified studies.
SELECTION CRITERIA: Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins) with placebo or controls, or comparing any of the anti-inflammatory agents with one another, in patients with acute rheumatic fever diagnosed according to the Jones, or modified Jones criteria. The presence of cardiac disease one year after treatment was the major outcome criteria selected.
DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality.
MAIN RESULTS: Eight randomised controlled trials involving 996 people were included. Several steroidal agents viz. ACTH, cortisone, hydrocortisone, dexamethasone and prednisone, and intravenous immunoglobulin were compared to aspirin, placebo or no treatment in the various studies. Six of the trials were conducted between 1950 and 1965, whilst the remaining two were done in the last 10 years. Overall there was no significant difference in the risk of cardiac disease at one year between the corticosteroid-treated and aspirin-treated groups (relative risk 0.87, 95% confidence interval 0.66 to 1.15). Similarly use of prednisone (relative risk 1.78, 95% confidence interval 0.98 to 3.34) or intravenous immunoglobulins (relative risk 0.87, 95%confidence interval 0.55 to 1.39) when compared to placebo did not reduce the risk of developing heart valve lesions at one year.
REVIEWER'S CONCLUSIONS: There is no benefit in using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessment of cardiac outcomes.

PMID 12804454
G V Herdy, A A Couto, J C Fernandes, M C de Olivaes, R Berger, V E Elias
[Pulse therapy (high doses of venous methylprednisolone) in children with rheumatic carditis. Prospective study of 40 episodes].
Arq Bras Cardiol. 1993 Jun;60(6):377-81.
Abstract/Text PURPOSE: To use corticosteroids in a shorter period to treat rheumatic carditis, keeping the patient in the hospital; and verify the time interval of normalization of rheumatic activity tests with this method.
METHODS: In 36 patients (40 episodes) intravenous methyl-prednisolone (1g/day) was administered. The number of series ranged from two to four, according to severity of the disease. The ages ranged from 6 to 17 years old, all of them fulfilled the criteria of Jones for diagnosis of rheumatic fever. They were submitted to treatment to eradicate the streptococcus, worms, PPD and dental focus extraction, before use of corticosteroids.
RESULTS: In all patients the signals and symptoms of heart failure improved. In six cases occurred complications during pulse therapy that were easily controlled with clinical measures. Two series of methylprednisolone were used in 10 children, three in nine and four in 21 episodes. Eight patients were sent to valve replacement. The interval of time that laboratory tests of rheumatic activity became negative was 41.2 +/- 13.3 days.
CONCLUSION: Using this IV corticotherapy it was possible decrease the amount of days of this medication, keeping the patient in the hospital. In this way we eliminate the problem of interruption of the treatment. There was not significative difference between oral and IV corticotherapy in order to the laboratory tests become negative.

PMID 8279976
宮崎 博: リウマチ熱および小児溶レン菌関連疾患の各種溶レン菌抗体に関する研究.医学研究, 1985; 55: 200-204.
渡邉言夫: リウマチ熱.小児の膠原病, 渡邉言夫編, 永井書店, 1994; 21-36.
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、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐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。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※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、実際の保険適応の査定において保険適応及び保険適応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応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:
武井修治 : 特に申告事項無し[2024年]
監修:五十嵐隆 : 特に申告事項無し[2024年]

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