Acute rheumatic fever: Epidemiology and pathogenesis
- Allan Gibofsky, MD, JD, FACP, FCLM
Allan Gibofsky, MD, JD, FACP, FCLM
- Professor of Medicine and Public Health
- Weill Medical College of Cornell University
- Section Editors
- Robert Sundel, MD
Robert Sundel, MD
- Section Editor — Pediatric Rheumatology
- Associate Professor of Pediatrics
- Harvard Medical School
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
The potential complications of group A Streptococcus (GAS) pharyngeal infection include both suppurative (eg, cellulitis, otitis media, sinusitis) and inflammatory, nonsuppurative conditions. Acute rheumatic fever (ARF) is one of the nonsuppurative complications (others include scarlet fever, toxic shock syndrome, and acute glomerulonephritis [AGN]). There is a latent period of two to three weeks following the initial pharyngitis before the first signs or symptoms of ARF appear . The disease presents with various manifestations that may include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum.
The epidemiology and pathogenesis of ARF are reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of this disorder are discussed separately. (See "Acute rheumatic fever: Clinical manifestations and diagnosis" and "Acute rheumatic fever: Treatment and prevention".)
Other complications of streptococcal tonsillopharyngitis are also discussed separately. (See "Complications of streptococcal tonsillopharyngitis".)
In developing areas of the world, severe disease caused by group A Streptococcus (eg, ARF, rheumatic heart disease, glomerulonephritis, and invasive infections) is estimated to affect nearly 20 million people and is the leading cause of cardiovascular death during the first five decades of life . ARF can occur at any age, although most cases occur in children 5 to 15 years of age [3-5]. Worldwide, there are 470,000 new cases of ARF and 233,000 deaths attributable to ARF or rheumatic heart disease each year [2,6,7]. Most cases occur in developing countries and among indigenous groups .
The mean incidence of ARF is 19 per 100,000 worldwide , but it is lower (2 to 14 cases per 100,000) in the United States and other developed countries [10,11]. The lower incidence in developed countries is probably primarily due to improved hygienic standards (eg, improved housing, less household crowding, better education and employment) and in smaller part due to routine use of antibiotics for acute pharyngitis. From time to time, localized outbreaks of ARF occur [12-17]. These may be associated with specific strains of Streptococcus, though this alone cannot explain overall variations in the incidence of rheumatic fever . (See "Evaluation of acute pharyngitis in adults" and "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis".)
- RAMMELKAMP CH Jr, STOLZER BL. The latent period before the onset of acute rheumatic fever. Yale J Biol Med 1961; 34:386.
- Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis 2005; 5:685.
- Lawrence JG, Carapetis JR, Griffiths K, et al. Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia, 1997 to 2010. Circulation 2013; 128:492.
- Parnaby MG, Carapetis JR. Rheumatic fever in indigenous Australian children. J Paediatr Child Health 2010; 46:527.
- Seckeler MD, Barton LL, Brownstein R. The persistent challenge of rheumatic fever in the Northern Mariana Islands. Int J Infect Dis 2010; 14:e226.
- Carapetis JR. Rheumatic heart disease in developing countries. N Engl J Med 2007; 357:439.
- Zühlke LJ, Steer AC. Estimates of the global burden of rheumatic heart disease. Glob Heart 2013; 8:189.
- Noonan S, Zurynski YA, Currie BJ, et al. A national prospective surveillance study of acute rheumatic fever in Australian children. Pediatr Infect Dis J 2013; 32:e26.
- Tibazarwa KB, Volmink JA, Mayosi BM. Incidence of acute rheumatic fever in the world: a systematic review of population-based studies. Heart 2008; 94:1534.
- Miyake CY, Gauvreau K, Tani LY, et al. Characteristics of children discharged from hospitals in the United States in 2000 with the diagnosis of acute rheumatic fever. Pediatrics 2007; 120:503.
- Gordis L. The virtual disappearance of rheumatic fever in the United States: lessons in the rise and fall of disease. T. Duckett Jones memorial lecture. Circulation 1985; 72:1155.
- Stollerman GH. Rheumatic fever. Lancet 1997; 349:935.
- Veasy LG, Wiedmeier SE, Orsmond GS, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987; 316:421.
- Hoffman TM, Rhodes LA, Pyles LA, et al. Childhood acute rheumatic fever: a comparison of recent resurgence areas to cases in West Virginia. W V Med J 1997; 93:260.
- Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in the intermountain area of the United States. J Pediatr 1994; 124:9.
- Westlake RM, Graham TP, Edwards KM. An outbreak of acute rheumatic fever in Tennessee. Pediatr Infect Dis J 1990; 9:97.
- Hosier DM, Craenen JM, Teske DW, Wheller JJ. Resurgence of acute rheumatic fever. Am J Dis Child 1987; 141:730.
- Bisno AL. The resurgence of acute rheumatic fever in the United States. Annu Rev Med 1990; 41:319.
- Siegel AC, Johnson EE, Stollerman GH. Controlled studies of streptococcal pharyngitis in a pediatric population, 1: factors related to the attack rate of rheumatic fever. N Engl J Med 1961; 265:559.
- Whitnack E, Bisno L. Rheumatic fever and other immunologically-mediated cardiac diseases. In: Clinical immunology, Parker C (Ed), WB Saunders, Philadelphia 1980. Vol 2, p.894.
- Kaplan EL, Bisno AL. Antecedent streptococcal infection in acute rheumatic fever. Clin Infect Dis 2006; 43:690.
- DENNY FW, WANNAMAKER LW, BRINK WR, et al. Prevention of rheumatic fever; treatment of the preceding streptococcic infection. J Am Med Assoc 1950; 143:151.
- Markowitz M, Gerber MA. Rheumatic fever: recent outbreaks of an old disease. Conn Med 1987; 51:229.
- Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal pharyngitis: the case for penicillin therapy. Pediatr Infect Dis J 1994; 13:1.
- STOLLERMAN GH, LEWIS AJ, SCHULTZ I, TARANTA A. Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever. Am J Med 1956; 20:163.
- Bessen D, Jones KF, Fischetti VA. Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever. J Exp Med 1989; 169:269.
- Bessen DE, Sotir CM, Readdy TL, Hollingshead SK. Genetic correlates of throat and skin isolates of group A streptococci. J Infect Dis 1996; 173:896.
- Shulman ST, Stollerman G, Beall B, et al. Temporal changes in streptococcal M protein types and the near-disappearance of acute rheumatic fever in the United States. Clin Infect Dis 2006; 42:441.
- Johnson DR, Stevens DL, Kaplan EL. Epidemiologic analysis of group A streptococcal serotypes associated with severe systemic infections, rheumatic fever, or uncomplicated pharyngitis. J Infect Dis 1992; 166:374.
- Lee GM, Wessels MR. Changing epidemiology of acute rheumatic fever in the United States. Clin Infect Dis 2006; 42:448.
- STETSON CA, RAMMELKAMP CH Jr, KRAUSE RM, et al. Epidemic acute nephritis: studies on etiology, natural history and prevention. Medicine (Baltimore) 1955; 34:431.
- Anthony BF, Kaplan EL, Wannamaker LW, et al. Attack rates of acute nephritis after type 49 streptococcal infection of the skin and of the respiratory tract. J Clin Invest 1969; 48:1697.
- Kaplan EL, Johnson DR, Cleary PP. Group A streptococcal serotypes isolated from patients and sibling contacts during the resurgence of rheumatic fever in the United States in the mid-1980s. J Infect Dis 1989; 159:101.
- Read SE, Reid HF, Fischetti VA, et al. Serial studies on the cellular immune response to streptococcal antigens in acute and convalescent rheumatic fever patients in Trinidad. J Clin Immunol 1986; 6:433.
- Potter EV, Vincente JB, Mayon-WHite RT, et al. Skin infections and immunoglobulin A in serum, sweat, and saliva of patients recovered from poststreptococcal acute glomerulonephritis or acute rheumatic fever and their siblings. Am J Epidemiol 1982; 115:951.
- Erdem G, Mizumoto C, Esaki D, et al. Group A streptococcal isolates temporally associated with acute rheumatic fever in Hawaii: differences from the continental United States. Clin Infect Dis 2007; 45:e20.
- Potter EV, Svartman M, Mohammed I, et al. Tropical acute rheumatic fever and associated streptococcal infections compared with concurrent acute glomerulonephritis. J Pediatr 1978; 92:325.
- Kaplan EL, Anthony BF, Chapman SS, et al. The influence of the site of infection on the immune response to group A streptococci. J Clin Invest 1970; 49:1405.
- Bisno AL, Nelson KE. Type-specific opsonic antibodies in streptococcal pyoderma. Infect Immun 1974; 10:1356.
- 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; 4:240.
- McDonald MI, Towers RJ, Andrews RM, et al. Low rates of streptococcal pharyngitis and high rates of pyoderma in Australian aboriginal communities where acute rheumatic fever is hyperendemic. Clin Infect Dis 2006; 43:683.
- Cywes C, Stamenkovic I, Wessels MR. CD44 as a receptor for colonization of the pharynx by group A Streptococcus. J Clin Invest 2000; 106:995.
- van de Rijn I, Zabriskie JB, McCarty M. Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J Exp Med 1977; 146:579.
- Dale JB, Beachey EH. Epitopes of streptococcal M proteins shared with cardiac myosin. J Exp Med 1985; 162:583.
- Cunningham MW, McCormack JM, Fenderson PG, et al. Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein. J Immunol 1989; 143:2677.
- Cunningham MW, McCormack JM, Talaber LR, et al. Human monoclonal antibodies reactive with antigens of the group A Streptococcus and human heart. J Immunol 1988; 141:2760.
- Galvin JE, Hemric ME, Ward K, Cunningham MW. Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin. J Clin Invest 2000; 106:217.
- Faé KC, da Silva DD, Oshiro SE, et al. Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease. J Immunol 2006; 176:5662.
- Quinn A, Kosanke S, Fischetti VA, et al. Induction of autoimmune valvular heart disease by recombinant streptococcal m protein. Infect Immun 2001; 69:4072.
- Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 2003; 9:914.
- Cheadle WB. Harvean lectures on the various manifestations of the rheumatic state as exemplified in childhood and early life. Lancet 1889; 1:821.
- Wilson MG, Schweitzr MD, Lubschez R. The familial epidemiology of rheumatic fever. J Pediatr 1943; 44:468.
- Taranta A, Torosdag S, Metrakos JD, et al. Rheumatic fever in monozygotic and dizygotic twins. Circulation 1959; 20:778.
- GLYNN LE, HOLBOROW EJ. Relation between blood groups, secretor status and susceptibility to rheumatic fever. Arthritis Rheum 1961; 4:203.
- Ayoub EM, Barrett DJ, Maclaren NK, Krischer JP. Association of class II human histocompatibility leukocyte antigens with rheumatic fever. J Clin Invest 1986; 77:2019.
- Maharaj B, Hammond MG, Appadoo B, et al. HLA-A, B, DR, and DQ antigens in black patients with severe chronic rheumatic heart disease. Circulation 1987; 76:259.
- Guilherme L, Weidebach W, Kiss MH, et al. Association of human leukocyte class II antigens with rheumatic fever or rheumatic heart disease in a Brazilian population. Circulation 1991; 83:1995.
- Patarroyo ME, Winchester RJ, Vejerano A, et al. Association of a B-cell alloantigen with susceptibility to rheumatic fever. Nature 1979; 278:173.
- Khanna AK, Buskirk DR, Williams RC Jr, et al. Presence of a non-HLA B cell antigen in rheumatic fever patients and their families as defined by a monoclonal antibody. J Clin Invest 1989; 83:1710.
- Fuhlbrigge R, 2015. Personal communication.