Acute rheumatic fever

doi:10.1016/S0140-6736(05)66874-2

The Lancet

Volume 366, Issue 9480, 9–15 July 2005, Pages 155-168

https://doi.org/10.1016/S0140-6736(05)66874-2 Get rights and content

Summary

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.

Section snippets

Epidemiology

According to WHO,⁹ at least 15·6 million people have RHD, 300 000 of about 0·5 million individuals who acquire ARF every year go on to develop RHD, and 233 000 deaths annually are directly attributable to ARF or RHD. However, these estimates are based on conservative assumptions, so the true disease burden is likely to be substantially higher. Furthermore, the overall quality of epidemiological data from developing countries is poor, particularly with respect to research documenting the

Pathogenesis

Although the pathogenesis of ARF and RHD remains somewhat elusive, ARF is clearly the result of an exaggerated immune response to specific bacterial epitopes in a susceptible host (figure 2).

Clinical features and diagnosis

The main clinical features of ARF are outlined in the Jones Criteria,¹¹¹ which were established in 1944 and then modified,¹¹² revised twice,113, 114 and updated (panel)¹¹⁵ by the American Heart Association. Every revision increased the specificity but decreased the sensitivity of the criteria,8, 116, 117 largely in response to the steadily declining incidence of ARF in developed countries. In regions of the world where ARF is endemic or epidemic, however, and where the risk associated with

Treatment

Not all treatments for ARF have been tested in randomised controlled trials. Some are based on anecdotal evidence, common sense, and proven safety. For example, penicillin is considered mandatory for the eradication of possibly persistent group A streptococcus infection of the upper respiratory tract, though this treatment has not been shown to alter the cardiac outcome after 1 year in controlled studies.147, 148 Similarly, long-term bed rest accelerated recovery from carditis and reduced the

Prevention

The overall lack of effective treatments for ARF means that any reduction of the burden of ARF and RHD will most likely come from new initiatives in prevention. Primary prevention of ARF has focused on antibiotic treatment of symptomatic pharyngitis caused by group A streptococcus. A course of antibiotics started within 9 days of the onset of a sore throat caused by group A streptococcus prevents most subsequent cases of ARF.165, 166, 167, 168 Table 3 lists the most frequently-used antibiotic

Conclusion

ARF has fallen off the radar of many doctors in developed countries, yet remains a daily challenge to doctors who work in developing countries. In this Seminar, we have attempted to present clinical aspects of ARF from the perspective of those who work with populations that bear the brunt of this disease. Further advances in our knowledge of ARF will, by necessity, come from developing countries. We hope that the next generation of researchers, teachers, and experts will also come from these

Search strategy and selection criteria

To ensure that the latest articles were reviewed, we searched our own reference libraries, the Cochrane Library (all dates), and MEDLINE (2000–2004) with the search terms “rheumatic fever” or “rheumatic heart disease”. We selected relevant articles published in any language and included several review articles or book chapters because they provide comprehensive overviews that are beyond the scope of this Seminar.

References (204)

L Gordis et al.
Studies in the epidemiology and preventability of rheumatic fever, 2: socio-economic factors and the incidence of acute attacks
J Chron Dis
(1969)
GH Stollerman
Rheumatic fever
Lancet
(1997)
MM Zaman et al.
Does rheumatic fever occur usually between the ages of 5 and 15 years?
Int J Cardiol
(1998)
I Ben-Dov et al.
Acute rheumatic fever in adults over the age of 45 years: an analysis of 23 patients together with a review of the literature
Semin Arthritis Rheum
(1980)
HA Majeed et al.
Acute rheumatic fever and the evolution of rheumatic heart disease: a prospective 12 year follow-up report
J Clin Epidemiol
(1992)
GH Stollerman
Rheumatogenic streptococci and autoimmunity
Clin Immunol Immunopath
(1991)
ER Brandt et al.
Can class I epitope of M protein be a diagnostic marker for rheumatic fever in populations endemic for group A streptococci?
Lancet
(1998)
AL Bisno et al.
Molecular basis of group A streptococcal virulence
Lancet Infect Dis
(2003)
MG Wilson et al.
The familial epidemiology of rheumatic fever: genetic and epidemiologic studies
J Pediatr
(1943)
G DiSciascio et al.
Rheumatic fever in children
Am Heart J
(1980)

G Simonini et al.

Lack of association between the HLA-DRB1 locus and post-streptococcal reactive arthritis and acute rheumatic fever in Italian children

Semin Arthritis Rheum

(2004)

G Hernandez-Pacheco et al.

MHC class II alleles in Mexican patients with rheumatic heart disease

Int J Cardiol

(2003)

HT Chou et al.

Association between transforming growth factor-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease

Am Heart J

(2004)

A Berdeli et al.

Involvement of immunoglobulin FcgammaRIIA and FcgammaRIIIB gene polymorphisms in susceptibility to rheumatic fever

Clin Biochem

(2004)

E Kemeny et al.

Tissue distribution of antigen(s) defined by monoclonal antibody D8/17 reacting with B lymphocytes of patients with rheumatic heart disease

Clin Immunol Immunopathol

(1994)

BM Feldman et al.

Diagnostic use of B cell alloantigen D8/17 in rheumatic chorea

J Pediatr

(1993)

S Kaur et al.

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients

Int J Cardiol

(1998)

EV Potter et al.

Tropical acute rheumatic fever and associated streptococal infections compared with concurrent acute glomerulonephritis

J Pediatr

(1978)

M McDonald et al.