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リウマチ熱の診療手順

リウマチ熱の診療手順を示す。初発例や再発例の診断にはJonesの改定診断基準(2015)を用いる。
治療では、心炎による弁膜障害を防ぐことが重要であり、ステロイド薬が用いられる。また、ペニシリン系抗菌薬はリウマチ熱の発症予防と再発予防に重要であり、前者では10日間、後者では心炎の有無や弁膜障害の有無で投与期間が決定される。
出典
img
1: 著者提供

輪状紅斑

リウマチ熱の急性期に約10%の頻度で出現する一過性の皮疹である。体幹、四肢近位部の内側などに好発し、中心部は正常な色調で、周囲の輪状の紅斑は温めると潮紅する。
出典
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1: Petty Ross E, Laxer Ronald M, et al:Textbook of Pediatric Rheumatology, 7th Edition,2016. p577. FIGURE 44-5.

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
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1: Petty Ross E, Laxer Ronald M, et al:Textbook of Pediatric Rheumatology, 7th Edition,2016. p577. FIGURE 44-6.

リウマチ熱の主症状

出現時期や持続期間は先行感染からの週数で、各症状の出現頻度はグラフの高さで示す。輪状紅斑(erythema marginatum)は、急性期以降も比較的長い期間にわたって一過性に出現する。舞踏病(chorea)は急性期からみられることもあるが、通常は先行感染から3カ月ほどで出現することが多い。
出典
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1: Petty Ross E, Laxer Ronald M, et al:Textbook of Pediatric Rheumatology, 7th Edition,2016. p575. FIGURE 44-4.

Jonesの改訂診断基準(2015)

リウマチ熱に対する診断基準として、Jonesの改定診断基準(2015)が用いられる。診断には、先行するA群レンサ球菌感染症があり、かつ主症状2項目以上、または主症状1項目+副症状2項目以上が必要である。再発の場合においても、A群レンサ球菌の先行感染が必須で、更に主症状2項目以上、または主症状1項目+副症状2項目以上、または副症状3項目以上を満たすことが診断に必要である。診断基準の適応には注意が必要であり、例えば主症状として多関節炎がある場合、副症状として関節痛を採用しない。
・画像(心エコー検査の評価基準):心エコー検査によるリウマチ性弁膜炎の評価[ID0609]
出典
imgimg
1: 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.
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.
Circulation. 2015 May 19;131(20):1806-18. doi: 10.1161/CIR.00000000000...

リウマチ熱発症予防のための抗菌薬療法(A群レンサ球菌感染症の治療)

リウマチ熱の予防には、先行するA群レンサ球菌感染症にける10日間のペニシリン系抗菌薬の投与が有用である。わが国では経口のペニシリンG(バイシリンG)60~120万単位やアモキシシリン(パセトシン)が用いられている。アレルギーでペニシリン系抗菌薬を使えない場合には、マクロライド系抗菌薬や狭域のセファロスポリン系抗菌薬が代用される。
出典
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1: 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.
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.
Circulation. 2009 Mar 24;119(11):1541-51. doi: 10.1161/CIRCULATIONAHA....

A群レンサ球菌関連抗体の正常上限抗体価(IU/mL)

ASO:anti-streptolysin O、ADNase: anti-deoxyribonuclease
 
先行感染の証明には抗体測定が有用であり、学童期ではASO 300 IU/mL以上を目安にする。単回測定で500 IU/mL以上の場合は先行感染ありと判断して良いが、年齢を考慮してもASOが正常上限値以下の場合は回復期のペア血清で4倍以上の抗体価の増加を確認する。なお、わが国ではASOのみ測定可能だが、海外ではADNase-Bも利用されている。
 
出典
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1: Steer AC, Vidmar S, Ritika R, et al. Normal ranges of streptoccal antibody titiers are similar whether streptococci are endemic to the setting or not. Clin Vaccine Immunol 2009, 16:172-175.

ARF関節炎の鑑別点

リウマチ熱の主症状ごとに、それぞれの鑑別診断を示す。舞踏病では発熱や関節炎などの急性期より遅れて発症し、また明確な急性期症状を欠くことがあり、多様な疾患を鑑別する必要がある。
出典
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1: Poststreptococcal reactive arthritis.
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.
Curr Opin Rheumatol. 2002 Sep;14(5):562-5.

心エコー検査によるリウマチ性弁膜炎の評価

出典
imgimg
1: 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.
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.
Circulation. 2015 May 19;131(20):1806-18. doi: 10.1161/CIR.00000000000...

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
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1: Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis.
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.
BMC Cardiovasc Disord. 2005 May 31;5(1):11. doi: 10.1186/1471-2261-5-1...

リウマチ熱の主症状からみた鑑別診断

リウマチ熱の主症状ごとに、それぞれの鑑別診断を示す。舞踏病では発熱や関節炎などの急性期より遅れて発症し、また明確な急性期症状を欠くことがあり、多様な疾患を鑑別する必要がある。
出典
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1: Acute rheumatic fever.
著者: Jonathan R Carapetis, Malcolm McDonald, Nigel J Wilson
雑誌名: Lancet. 2005 Jul 9-15;366(9480):155-68. doi: 10.1016/S0140-6736(05)66874-2.
Abstract/Text: Acute rheumatic fever (ARF) and its chronic sequela, rheumatic heart disease (RHD), have become rare in most affluent populations, but remain unchecked in developing countries and in some poor, mainly indigenous populations in wealthy countries. More than a century of research, mainly in North America and Europe, has improved our understanding of ARF and RHD. However, whether traditional views need to be updated in view of the epidemiological shift of the past 50 years is still to be established, and improved data from developing countries are needed. Doctors who work in populations with a high incidence of ARF are adapting existing diagnostic guidelines to increase their sensitivity. Group A streptococcal vaccines are still years away from being available and, even if the obstacles of serotype coverage and safety can be overcome, their cost could make them inaccessible to the populations that need them most. New approaches to primary prevention are needed given the limitations of primary prophylaxis as a population-based strategy. The most effective approach for control of ARF and RHD is secondary prophylaxis, which is best delivered as part of a coordinated control programme.
Lancet. 2005 Jul 9-15;366(9480):155-68. doi: 10.1016/S0140-6736(05)668...

予防投与期間

リウマチ熱に罹患した個体はA群レンサ球菌に対する感受性が高いため、再感染するとリウマチ熱を再発しやすい。また、リウマチ性心疾患を残した例では、再発により弁膜障害が進行する。したがって、再発予防のために抗菌薬の長期投与が行われるが、その投与期間は心炎の有無により、また心炎例では弁膜障害の有無で決められている。
出典
imgimg
1: 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.
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.
Circulation. 2009 Mar 24;119(11):1541-51. doi: 10.1161/CIRCULATIONAHA....

リウマチ熱の診療手順

リウマチ熱の診療手順を示す。初発例や再発例の診断にはJonesの改定診断基準(2015)を用いる。
治療では、心炎による弁膜障害を防ぐことが重要であり、ステロイド薬が用いられる。また、ペニシリン系抗菌薬はリウマチ熱の発症予防と再発予防に重要であり、前者では10日間、後者では心炎の有無や弁膜障害の有無で投与期間が決定される。
出典
img
1: 著者提供

輪状紅斑

リウマチ熱の急性期に約10%の頻度で出現する一過性の皮疹である。体幹、四肢近位部の内側などに好発し、中心部は正常な色調で、周囲の輪状の紅斑は温めると潮紅する。
出典
img
1: Petty Ross E, Laxer Ronald M, et al:Textbook of Pediatric Rheumatology, 7th Edition,2016. p577. FIGURE 44-5.