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Acute rheumatic fever and rheumatic heart disease

Nature Reviews Disease Primers volume 2, Article number: 15084 (2016) Cite this article

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Abstract

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances — including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life — give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

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Figure 1: The global burden of RHD.
Figure 2: Generation of a cross-reactive immune response in ARF.
Figure 3: Manifestations of ARF in the joints.
Figure 4: Molecular and cellular basis of Sydenham's chorea.
Figure 5: Skin manifestations of ARF.
Figure 6: The GAS cross-reactive immune response in the heart.
Figure 7: Localization of Sydenham's chorea-derived antibodies and tyrosine hydroxylase in the brains of transgenic mice.
Figure 8: Expression of VCAM1 by the valvular endothelium.
Figure 9: Immunohistochemistry of infiltration of CD4+ T cells into the valve of the left atrium in ARF.
Figure 10: Echocardiogram from child with severe mitral regurgitation.
Figure 11: Echocardiogram from child with severe mitral stenosis.

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Acknowledgements

M.W.C. was supported by grants HL35280 and HL56267 from the National Heart, Lung and Blood Institute, the American Heart Association and the Oklahoma Center for the Advancement of Science, all in the USA.

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Authors and Affiliations

  1. Telethon Kids Institute, the University of Western Australia, PO Box 855, West Perth, 6872, Western Australia, Australia

    Jonathan R. Carapetis & Rosemary Wyber

  2. Princess Margaret Hospital for Children, Perth, Western Australia, Australia

    Jonathan R. Carapetis

  3. Children's National Health System, Washington, District of Columbia, USA

    Andrea Beaton & Craig Sable

  4. Department of Microbiology and Immunology, Biomedical Research Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Madeleine W. Cunningham

  5. Heart Institute (InCor), University of São Paulo, School of Medicine, São Paulo, Brazil

    Luiza Guilherme

  6. Institute for Immunology Investigation, National Institute for Science and Technology, São Paulo, Brazil

    Luiza Guilherme

  7. Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

    Ganesan Karthikeyan

  8. Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

    Bongani M. Mayosi & Liesl Zühlke

  9. Department of Paediatrics, the University of Melbourne, Melbourne, Victoria, Australia

    Andrew Steer

  10. Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

    Andrew Steer

  11. Green Lane Paediatric and Congenital Cardiac Services, Starship Hospital, Auckland, New Zealand

    Nigel Wilson

  12. Department of Paediatrics, University of Auckland, Auckland, New Zealand

    Nigel Wilson

  13. Department of Paediatric Cardiology, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa

    Liesl Zühlke

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  1. Jonathan R. Carapetis
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  2. Andrea Beaton
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  3. Madeleine W. Cunningham
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  9. Nigel Wilson
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  10. Rosemary Wyber
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  11. Liesl Zühlke
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Contributions

Introduction (J.R.C.); Epidemiology (J.R.C.); Mechanisms/pathophysiology (J.R.C., L.G. and M.W.C.); Diagnosis, screening and prevention (A.B., A.S., C.S. and J.R.C.); Management (J.R.C. and N.W.); Quality of life (J.R.C., L.Z. and R.W.); Outlook (B.M.M., G.K. and J.R.C.); overview of Primer (J.R.C.).

Corresponding author

Correspondence to Jonathan R. Carapetis.

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Competing interests

G.K., L.Z., A.S., J.R.C., A.B., N.W., L.G., C.S., R.W. and B.M.M. have no conflict of interest. M.W.C. has financial interest in and is Chief Scientific Officer of Moleculera Labs, a company offering diagnostic testing for neurological disorders.

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Carapetis, J., Beaton, A., Cunningham, M. et al. Acute rheumatic fever and rheumatic heart disease. Nat Rev Dis Primers 2, 15084 (2016). https://doi.org/10.1038/nrdp.2015.84

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