Rheumatic Fever Medication
- Author: Mark R Wallace, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD more...
Antibiotic treatment in patients who present with acute rheumatic fever (ARF) is necessary irrespective of the throat culture result. Such therapy probably does not alter the risk of developing rheumatic heart disease but at least minimizes the possible transmission of a rheumatogenic streptococcal strain.
Primary prophylaxis (treatment of streptococcal pharyngitis) dramatically reduces the risk of ARF and should be provided whenever a group A streptococcal pharyngitis is confirmed.
Secondary prevention is required to prevent additional streptococcal infections and is the critical step in management of ARF. Patients with a history of rheumatic fever are at a high risk of recurrent ARF, which may further the cardiac damage. The exact duration of chronic antimicrobial prophylaxis remains controversial, but the WHO guidelines are commonly used. There had been concern that sustained benzathine penicillin as secondary prophylaxis would lead to the development of resistant strains of Streptococcus viridans, but a recent study found no support for this hypothesis.
Rheumatic fever with carditis and clinically significant residual heart disease requires antibiotic treatment for a minimum of 10 years after the latest episode; prophylaxis is required until the patient is aged at least 40-45 years and is often continued for life.
Rheumatic fever with carditis and no residual heart disease aside from mild mitral regurgitation requires antibiotic treatment for 10 years or until age 25 years (whichever is longer).
Rheumatic fever without carditis requires antibiotic treatment for 5 years or until the patient is aged 18-21 years (whichever is longer).
Children given penicillin G benzathine at a dose of 1.2 million U IM q4wk experienced a recurrence rate of 0.4 cases per 100 patient-years of observation. ARF recurrence rates have been found to be even lower if penicillin is administered q3wk instead of q4wk. This regimen may be appropriate in patients with severe rheumatic heart disease. Weigh the benefits of a 3-week regimen against patient compliance and cost; compliance is often poor to start with, at least partially due to the pain of the injections. Long-term administration of oral penicillin may be used in lieu of the intramuscular route. Erythromycin or sulfadiazine may be used in patients who are allergic to penicillin.[1, 6]
Long-acting depot form of penicillin G. DOC for prophylaxis of streptococcal pharyngitis. Avoids compliance problems of oral regimens.
Phenoxymethyl derivative of penicillin G is acid-stable, enhancing oral bioavailability. Patient compliance is essential for effectiveness.
Macrolides inhibit protein synthesis, in contrast to penicillin cell wall effects. DOC for primary treatment of streptococcal pharyngitis in penicillin allergy. May use for secondary prophylaxis in patients allergic to penicillin.
Exerts bacteriostatic action through competitive antagonism with para-aminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid are not susceptible to the action of sulfonamides. Used in secondary prophylaxis of ARF.
Salicylates and corticosteroids are the mainstay of the anti-inflammatory treatment of ARF. Avoid anti-inflammatory drugs until diagnosis is confirmed, as they may mask symptoms essential to the diagnosis. Analgesics without anti-inflammatory properties (ie, codeine) are used for mild disease. Corticosteroids and salicylates cannot prevent or modify the development of subsequent rheumatic heart disease but are used for symptomatic relief. Some experts believe steroids are of value in patients with severe or fulminant carditis, but data are sparse.
Clinical or laboratory manifestations of rheumatic inflammation may recur upon cessation of anti-inflammatory therapy. Rebound occurs frequently with corticosteroids; hence, they require gradual tapering rather than abrupt cessation. Salicylates are usually continued for a month following corticosteroid discontinuance.
Used in patients with moderate-to-severe arthritis and carditis without heart failure. Treatment is administered for at least 8 wk.
Used in severe carditis and CHF. High-dose prednisone is administered for 2-3 wk, then tapered over 3 wk. IV corticosteroids are reserved for fulminant cases.
Cilliers AM. Rheumatic fever and its management. BMJ. 2006 Dec 2. 333(7579):1153-6. [Medline].
Stollerman GH. Rheumatic fever. Lancet. 1997 Mar 29. 349(9056):935-42. [Medline].
Bisno AL, Pearce IA, Stollerman GH. Streptococcal infections that fail to cause recurrences of rheumatic fever. J Infect Dis. 1977 Aug. 136(2):278-85. [Medline].
Shulman ST. Rheumatic heart disease in developing countries. N Engl J Med. 2007 Nov 15. 357(20):2089; author reply 2089. [Medline].
McDonald M, Currie BJ, Carapetis JR. Acute rheumatic fever: a chink in the chain that links the heart to the throat?. Lancet Infect Dis. 2004 Apr. 4(4):240-5. [Medline].
Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005. 366:155-68. [Medline].
Erdem G, Mizumoto C, Esaki D, Reddy V, Kurahara D, Yamaga K, et al. Group A streptococcal isolates temporally associated with acute rheumatic fever in Hawaii: differences from the continental United States. Clin Infect Dis. 2007 Aug 1. 45(3):e20-4. [Medline].
Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb. 39(1):31-9. [Medline].
Guilherme L, Kalil J. Rheumatic Heart Disease: Molecules Involved in Valve Tissue Inflammation Leading to the Autoimmune Process and Anti-S. pyogenes Vaccine. Front Immunol. 2013. 4:352. [Medline].
Veasy LG, Wiedmeier SE, Orsmond GS. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med. 1987 Feb 19. 316(8):421-7. [Medline].
Wallace MR, Garst PD, Papadimos TJ, Oldfield EC 3rd. The return of acute rheumatic fever in young adults. JAMA. 1989 Nov 10. 262(18):2557-61. [Medline].
Erdem G, Dodd A, Tuua A, Sinclair S, I'atala TF, Marrone JR, et al. Acute rheumatic fever in American Samoa. Pediatr Infect Dis J. 2007 Dec. 26(12):1158-9. [Medline].
Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005 Nov. 5(11):685-94. [Medline].
Carapetis JR. Rheumatic heart disease in developing countries. N Engl J Med. 2007 Aug 2. 357(5):439-41. [Medline].
Joseph N, Madi D, Kumar GS, Nelliyanil M, Saralaya V, Rai S. Clinical spectrum of rheumatic Fever and rheumatic heart disease: a 10 year experience in an urban area of South India. N Am J Med Sci. 2013 Nov. 5(11):647-52. [Medline].
Casey JD, Solomon DH, Gaziano TA, Miller AL, Loscalzo J. Clinical problem-solving. A patient with migrating polyarthralgias. N Engl J Med. 2013 Jul 4. 369(1):75-80. [Medline].
Atatoa-Carr P, Lennon D, Wilson N,. Rheumatic fever diagnosis, management, and secondary prevention: a New Zealand guideline. N Z Med J. 2008 Apr 4. 121(1271):59-69. [Medline].
Weiner SG, Normandin PA. Sydenham chorea: a case report and review of the literature. Pediatr Emerg Care. 2007 Jan. 23(1):20-4. [Medline].
Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Jani D, et al. Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med. 2007 Aug 2. 357(5):470-6. [Medline].
Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Sidi D, et al. Echocardiographic screening for rheumatic heart disease. Bull World Health Organ. 2008 Feb. 86(2):84. [Medline].
Vijayalakshmi IB, Vishnuprabhu RO, Chitra N, Rajasri R, Anuradha TV. The efficacy of echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol Young. 2008 Oct 10. 1-7. [Medline].
Sahin M, Yildirim I, Ozkutlu S, Alehan D, Ozer S, Karagöz T. Clinical features and mid- and long-term outcomes of pediatric patients with subclinical carditis. Turk J Pediatr. 2012 Sep-Oct. 54(5):486-92. [Medline].
Narula J, Kaplan EL. Echocardiographic diagnosis of rheumatic fever. Lancet. 2001 Dec 8. 358(9297):2000. [Medline].
Tubridy-Clark M, Carapetis JR. Subclinical carditis in rheumatic fever: a systematic review. Int J Cardiol. 2007 Jun 25. 119(1):54-8. [Medline].
Lopez-Benitez JM, Miller LC, Schaller JG, Moreno LM, de Canata ME. Erroneous diagnoses in children referred with acute rheumatic fever. Pediatr Infect Dis J. 2008 Feb. 27(2):181-2. [Medline].
Kaplan EL, Anthony BF, Chapman SS, Ayoub EM, Wannamaker LW. The influence of the site of infection on the immune response to group A streptococci. J Clin Invest. 1970 Jul. 49(7):1405-14. [Medline].
Ayoub EM, Nelson B, Shulman ST, Barrett DJ, Campbell JD, Armstrong G. Group A streptococcal antibodies in subjects with or without rheumatic fever in areas with high or low incidences of rheumatic fever. Clin Diagn Lab Immunol. 2003 Sep. 10(5):886-90. [Medline].
Wilson NJ, Voss L, Morreau J, Stewart J, Lennon D. New Zealand guidelines for the diagnosis of acute rheumatic fever: small increase in the incidence of definite cases compared to the American Heart Association Jones criteria. N Z Med J. 2013 Aug 2. 126(1379):50-9. [Medline].
Shivaram P, Ahmed MI, Kariyanna PT, Sabbineni H, Avula UM. Doppler echocardiography imaging in detecting multi-valvular lesions: a clinical evaluation in children with acute rheumatic fever. PLoS One. 2013. 8(9):e74114. [Medline].
Pereira BA, da Silva NA, Andrade LE, Lima FS, Gurian FC, de Almeida Netto JC. Jones criteria and underdiagnosis of rheumatic fever. Indian J Pediatr. 2007 Feb. 74(2):117-21. [Medline].
Voss LM, Wilson NJ, Neutze JM, Whitlock RM, Ameratunga RV, Cairns LM. Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Circulation. 2001 Jan 23. 103(3):401-6. [Medline].
Bilavsky E, Eliahou R, Keller N, Yarden-Bilavsky H, Harel L, Amir J. Effect of benzathine penicillin treatment on antibiotic susceptibility of viridans streptococci in oral flora of patients receiving secondary prophylaxis after rheumatic fever. J Infect. 2008 Apr. 56(4):244-8. [Medline].
Dale JB. Current status of group A streptococcal vaccine development. Adv Exp Med Biol. 2008. 609:53-63. [Medline].
Veasy LG. Time to take soundings in acute rheumatic fever. Lancet. 2001 Jun 23. 357(9273):1994-5. [Medline].
Ragupathi L, Herman J, Mather P. Late Recurrence of Rheumatic Fever. Am J Med Sci. 2015 Oct. 350 (4):342-3. [Medline].