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急性リウマチ熱

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: 今井靖 自治医科大学 薬理学講座臨床薬理学部門・内科学講座循環器内科学部門

著者校正/監修レビュー済:2021/03/10
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

概要・推奨   

  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)
  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)
  1. 診断にはJones改訂診断基準(2015)を用いることが推奨される(推奨度1)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな ります。閲覧には ご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
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:
武井修治 : 特に申告事項無し[2021年]
監修:今井靖 : 講演料(第一三共株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行い、鑑別すべき疾患を追加した。

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. 抗菌薬で発症予防可能な疾患であり[1]、先進国での発生は激減し、わが国での年間患者数は17例にすぎない(2009年、小児慢性特定疾患治療研究事業に登録)。
  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[2]<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。

 
  1. 診断にはJones改定診断基準(2015)[3]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[4]
  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[5]<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1M)
  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

img1:  Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis.
 
 BMC Cardiovasc Disord. 2005 May 31;5(1):・・・
 
  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1RG)
  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[5]では、経口抗菌薬としては、ペニシリンV 40mg/kg/日(分3)またはアモキシシリン50mg/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12mg/kg/日(分1)5日間、クリンダマイシン20mg/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 

著者: Katharine A Robertson, Jimmy A Volmink, Bongani M Mayosi
雑誌名: 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  BMC Cardiovasc Disord. 2005 May 31;5(1):11. doi: 10.118・・・
著者: 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
雑誌名: 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  Circulation. 2015 May 19;131(20):1806-18. doi: 10.1161/・・・
著者: Michael A Gerber, Robert S Baltimore, Charles B Eaton, Michael Gewitz, Anne H Rowley, Stanford T Shulman, Kathryn A Taubert
雑誌名: 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  Circulation. 2009 Mar 24;119(11):1541-51. doi: 10.1161/・・・
著者: J R Carapetis, B J Currie
雑誌名: 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  Arch Dis Child. 2001 Sep;85(3):223-7.
著者: Stanford T Shulman, Elia M Ayoub
雑誌名: 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  Curr Opin Rheumatol. 2002 Sep;14(5):562-5.
著者: S E Swedo, H L Leonard, M Garvey, B Mittleman, A J Allen, S Perlmutter, L Lougee, S Dow, J Zamkoff, B K Dubbert
雑誌名: 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  Am J Psychiatry. 1998 Feb;155(2):264-71.
著者: S J Perlmutter, S F Leitman, M A Garvey, S Hamburger, E Feldman, H L Leonard, S E Swedo
雑誌名: 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  Lancet. 1999 Oct 2;354(9185):1153-8. doi: 10.1016/S0140・・・
著者: M A CREA, E A MORTIMER
雑誌名: Pediatrics. 1959 May;23(5):879-84.
Abstract/Text
PMID 13645124  Pediatrics. 1959 May;23(5):879-84.
著者: Yosef Uziel, Liat Perl, Judith Barash, Philip J Hashkes
雑誌名: 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  Pediatr Rheumatol Online J. 2011 Oct 20;9(1):32. doi: 1・・・
著者:
雑誌名: 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  World Health Organ Tech Rep Ser. 2004;923:1-122, back c・・・
著者: A M Cilliers, J Manyemba, H Saloojee
雑誌名: 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  Cochrane Database Syst Rev. 2003;(2):CD003176. doi: 10.・・・
著者: G V Herdy, A A Couto, J C Fernandes, M C de Olivaes, R Berger, V E Elias
雑誌名: 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  Arq Bras Cardiol. 1993 Jun;60(6):377-81.

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