长期管理的重点是保证对二级预防的依从性。二级预防临床有效且成本效益好。[102]Tompkins DG, Boxerbaum B, Liebman J. Long-term prognosis of rheumatic fever patients receiving regular intramuscular benzathine penicillin. Circulation. 1972 Mar;45(3):543-51.http://circ.ahajournals.org/content/45/3/543.longhttp://www.ncbi.nlm.nih.gov/pubmed/5012243?tool=bestpractice.com[103]Tompkins RK, Burnes DC, Cable WE. An analysis of the cost-effectiveness of pharyngitis management and acute rheumatic fever prevention. Ann Intern Med. 1977 Apr;86(4):481-92.http://www.ncbi.nlm.nih.gov/pubmed/403842?tool=bestpractice.com
世界卫生组织 (WHO) 将风湿热的二级预防定义为“对于既往有风湿热发作,或者确诊风湿性心脏病的患者,持续应用特定的抗生素。目的是预防 A 族链球菌在上呼吸道定植或感染以及风湿热反复发作。”[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/
最有效的抗生素是青霉素,最有效的给药方法是每 3-4 周肌内注射长效苄星青霉素。[96]Stollerman GH. Rheumatic fever and streptococcal infection. New York: Grune & Stratton; 1975.[97]Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002;(3):CD002227.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002227/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12137650?tool=bestpractice.com
肌内注射苄星青霉素可使链球菌性咽炎减少 71%-91%,并使复发性风湿热减少 87%-96%。[97]Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev. 2002;(3):CD002227.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002227/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12137650?tool=bestpractice.com
二级预防可以降低风湿性心脏病的临床严重程度和死亡率,如果患者能坚持 10 年以上,则能使风湿性心脏病逆转约 50%-70%。[94]Feinstein AR, Stern EK, Spagnuolo M. The prognosis of acute rheumatic fever. Am Heart J. 1964 Dec;68:817-34.http://www.ncbi.nlm.nih.gov/pubmed/14235961?tool=bestpractice.com[95]Sanyal SK, Berry AM, Duggal S, et al. Sequelae of the initial attack of acute rheumatic fever in children from north India. A prospective 5-year follow-up study. Circulation. 1982 Feb;65(2):375-9.http://circ.ahajournals.org/content/65/2/375.longhttp://www.ncbi.nlm.nih.gov/pubmed/7053897?tool=bestpractice.com 国际上认可的苄星青霉素剂量与急性发作期间根除链球菌的使用剂量相同。[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/[104]Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics. 1995 Oct;96(4 Pt 1):758-64.http://www.ncbi.nlm.nih.gov/pubmed/7567345?tool=bestpractice.com 不同的权威机构推荐的肌内注射频率和二级预防持续时间有所不同。WHO 并未特别指定注射频率应每 3 周或每 4 周一次。一些专家建议对高风险患者(中度到重度心脏炎或有急性风湿热的既往突破病例)应每 3 周注射一次,因为有证据表明,这种方法能减少急性风湿热的复发次数。[105]Lue HC, Wu MH, Hsieh KH, et al, Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs. J Pediatr. 1986 Feb;108(2):299-304.http://www.ncbi.nlm.nih.gov/pubmed/3511209?tool=bestpractice.com 二级预防治疗的持续时间是由多个因素决定的,包括年龄、自上次急性风湿热发作以来的时间和疾病的严重程度。推荐的预防治疗持续时间也在不同的临床指南中存在差异。[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/[49]RHDAustralia (ARF/RHD writing group); National Heart Foundation of Australia; Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd ed). 2012 [internet publication].http://www.rhdaustralia.org.au/arf-rhd-guideline[99]Heart Foundation of New Zealand. New Zealand guidelines for rheumatic fever: diagnosis, management and secondary prevention of acute rheumatic fever and rheumatic heart disease: 2014 update. 2014 [internet publication].https://www.heartfoundation.org.nz/resources/acute-rheumatic-fever-and-rheumatic-heart-disease-guideline[100]Working Group on Pediatric Acute Rheumatic Fever and Cardiology Chapter of Indian Academy of Pediatrics, Saxena A, Kumar RK, et al. Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease. Indian Pediatr. 2008 Jul;45(7):565-73.http://www.indianpediatrics.net/july2008/565.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/18695275?tool=bestpractice.com 对于未确诊的全心炎患者,WHO 和印度指南推荐二级预防持续至最后一次发作后 5 年,或直至 18 岁(以时间较长者为准),[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/[100]Working Group on Pediatric Acute Rheumatic Fever and Cardiology Chapter of Indian Academy of Pediatrics, Saxena A, Kumar RK, et al. Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease. Indian Pediatr. 2008 Jul;45(7):565-73.http://www.indianpediatrics.net/july2008/565.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/18695275?tool=bestpractice.com而澳大利亚和新西兰的指南推荐,对于所有风湿热患者,包括那些未患全心炎的患者,至少要进行 10 年的预防治疗或直至 21 岁,以时间较长者为准。[49]RHDAustralia (ARF/RHD writing group); National Heart Foundation of Australia; Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd ed). 2012 [internet publication].http://www.rhdaustralia.org.au/arf-rhd-guideline[99]Heart Foundation of New Zealand. New Zealand guidelines for rheumatic fever: diagnosis, management and secondary prevention of acute rheumatic fever and rheumatic heart disease: 2014 update. 2014 [internet publication].https://www.heartfoundation.org.nz/resources/acute-rheumatic-fever-and-rheumatic-heart-disease-guideline 对于患有全心炎(轻度二尖瓣反流或治愈的全心炎)的患者,WHO 推荐二级预防持续到最后一次发作后 10 年或直到 25 岁(以时间较长者为准)。对于患有中度或重度瓣膜病的患者,包括已接受或需要进行瓣膜手术的患者,WHO 推荐终身接受二级预防治疗,澳大利亚指南推荐至少持续至 30 岁(新西兰)或 35 岁(澳大利亚)或直至 40 岁(严重风湿性心脏病)。[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/[49]RHDAustralia (ARF/RHD writing group); National Heart Foundation of Australia; Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd ed). 2012 [internet publication].http://www.rhdaustralia.org.au/arf-rhd-guideline[99]Heart Foundation of New Zealand. New Zealand guidelines for rheumatic fever: diagnosis, management and secondary prevention of acute rheumatic fever and rheumatic heart disease: 2014 update. 2014 [internet publication].https://www.heartfoundation.org.nz/resources/acute-rheumatic-fever-and-rheumatic-heart-disease-guideline
已证实青霉素过敏的患者应接受每日两次口服红霉素治疗。[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/ 在妊娠期可安全使用青霉素。[1]World Health Organization. Rheumatic fever and rheumatic heart disease: report of a WHO Expert Consultation. 2004 [internet publication].http://www.who.int/cardiovascular_diseases/publications/trs923/en/ 肌内注射苄星青霉素被认为对抗凝治疗患者也足够安全。
心内膜炎预防治疗
关于抗生素预防对于治疗心内膜炎的有效性,缺乏国际性专家共识。虽然这在英国是不推荐的,[106]National Institute for Health and Care Excellence. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. July 2016 [internet publication].https://www.nice.org.uk/guidance/cg64 美国心脏协会 (American Heart Association, AHA) 最新指南的结论为,在口腔科或外科手术前,为预防感染性心内膜炎,可推荐某些类型心脏瓣膜病患者(包括人工心脏瓣膜、环形瓣环成形术)使用抗生素进行预防治疗。[107]Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017 Jun 20;135(25):e1159-95.https://www.ahajournals.org/doi/10.1161/CIR.0000000000000503http://www.ncbi.nlm.nih.gov/pubmed/28298458?tool=bestpractice.com 在澳大利亚和新西兰,风湿性心脏病患者患心内膜炎的风险大大增加。[108]Baskerville CA, Hanrahan BB, Burke AJ, et al. Infective endocarditis and rheumatic heart disease in the north of Australia. Heart Lung Circ. 2012 Jan;21(1):36-41.http://www.ncbi.nlm.nih.gov/pubmed/21924682?tool=bestpractice.com 因此,澳大利亚国家心脏基金会 (National Heart Foundation of Australia) 和澳大利亚新西兰心脏学会 (Cardiac Society of Australia and New Zealand) 推荐,如果使用青霉素进行二级预防治疗,则可以在进行口腔科操作前给予克林霉素,剂量为 15 mg/kg(最大剂量 600 mg),口服或静脉单剂给药。[49]RHDAustralia (ARF/RHD writing group); National Heart Foundation of Australia; Cardiac Society of Australia and New Zealand. Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease (2nd ed). 2012 [internet publication].http://www.rhdaustralia.org.au/arf-rhd-guideline
对于风湿性心脏病患者,特别是严重心脏受累和心力衰竭的患者,推荐接种肺炎球菌和流感疫苗。