BMJ  2003;327:631-632 (20 September), doi:10.1136/bmj.327.7416.631

Editorial

Treating acute rheumatic fever

So many years, and yet we do not know if steroids should be used

Rheumatic fever is a delayed complication of pharyngeal infection with group haemolytic streptococci. Susceptible individuals develop a diffuse inflammatory disease of the heart, joints, brain, blood vessels, and subcutaneous tissue. Carditis is the most serious manifestation of the disease. It may culminate in chronic valvular disease and can lead to heart failure and ultimately death. The incidence of acute rheumatic fever has declined in industrialised countries since the 1950s. However, a resurgence of the disease has been noted, and new epidemics have been reported in the United States.¹ Acute rheumatic fever continues to be an important cause of acquired heart disease in developing countries where it is an endemic disease.² Open heart surgery may be needed to repair or replace heart valves in patients with severely damaged valves, the cost of which is exorbitant and a drain on the meagre health resources of poor countries.

Because of substantial evidence pointing to the inflammatory nature of the disease anti-inflammatory agents such as corticosteroids and aspirin are used for its treatment. The treatment is, however, controversial. Several current textbooks recommend the use of corticosteroids in patients with acute rheumatic fever and heart failure.^3-5 In contrast other authors say that heart failure in patients with active rheumatic carditis occurs as a result of a haemodynamically severe valvular lesion that can be corrected only surgically and not by giving steroids.⁶

Substantial contrary evidence points, however, against treating patients who have acute rheumatic fever with corticosteroid agents to prevent the complications of carditis. This evidence against corticosteroids is based largely on randomised controlled studies performed 40-50 years ago and analysed in a recent Cochrane review.⁷ Eight randomised controlled trials describing outcomes in patients given anti-inflammatory agents were identified in this meta-analysis. All studies assessed cardiac outcomes in the form of clinically significant heart murmurs diagnosed on auscultation or the presence of incompetence of the aortic or mitral valve diagnosed by using echocardiography at least one year after treatment with anti-inflammatory agents. Several corticosteroid agents—namely adrenocorticotrophic hormone, cortisone, hydrocortisone, dexamethasone and prednisone—and intravenous immunoglobulin were compared with aspirin, placebo, or no treatment in the various studies. Three of the studies showed a higher risk of cardiac disease at one year after treatment with corticosteroids compared with aspirin. Only one study showed some advantage for aspirin, although statistically insignificant, in reducing the risk of cardiac disease compared with prednisone (relative risk 1.71, 95% confidence interval 0.92 to 3.19).

Overall no significant difference was seen in the risk of cardiac disease at one year between the groups treated with corticosteroids or with aspirin (0.87, 0.66 to 1.15). Similarly, use of prednisone (1.78, 0.98 to 3.34) or intravenous immunoglobulin (0.87, 0.55 to 1.39) compared with placebo did not reduce the risk of developing lesions to the heart valve at one year. No trials compared aspirin with placebo in patients with carditis in the presence of acute rheumatic fever; the efficacy of aspirin has therefore not been established. The reporting of secondary outcomes such as a reduction in the erythrocyte sedimentation rate and C reactive protein was too varied and inconsistent to analyse adequately. Corticosteroids seem superior to aspirin in the rate at which the erythrocyte sedimentation rate drops, but this is not a compelling reason to choose one drug over the other.

Although newer non-steroidal anti-inflammatory agents such as naproxen⁸ and high dose methylprednisone⁹ have been used to treat patients with acute rheumatic fever in more recent studies, the outcomes have not been tested in a randomised and controlled manner.

Ultimately there is no conclusive evidence to indicate that the use of corticosteroids in patients with acute rheumatic fever will prevent heart disease in the long term. It is sad that in this modern day era we have not found an effective treatment for a disease with an infectious origin that has such devastating consequences, particularly for patients who live in poor developing countries. Further randomised controlled studies examining corticosteroids with less outdated formulations—for example, prednisone and intravenous methylprednisone—are warranted. The availability and use of echocardiography and other newer technologies will help greatly in providing more precise, valid, and objective assessment of changes in cardiac lesions in future randomised controlled trials.

CH Baragwanath Hospital, PO Box 2588, Northcliff, 2115, Johannesburg, South Africa (amcilliers{at}icon.co.za)

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Competing interests: None declared.

References

1. Veasy LG, Wiedmeier SE, Orsmond GS, Ruttenberg HD, Boucek MM, Roth SJ, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med 1987;316: 421-7.[Abstract]
2. Olivier C. Rheumatic fever—is it still a problem? J Antimicrob Chemother 2000;45(suppl 13): s13-21.
3. Abraham MT, Cherian G. In: Chatterjee K, Cheitlin MD, Karliner J, Parmley WM, Rapaport E, Scheinman M, eds. Cardiology: an illustrated text/reference. New York: Gower Medical Publishing, 1991: 10.98-10.116.
4. Ayoub EM. In: Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP, eds. Moss and Adams' heart disease in infants, children, and adolescents: including the fetus and the young adult. 5th ed. Baltimore: Williams and Wilkins, 1995: 1400-16.
5. El-Said GM, El-Rafaee MM, Sorour KA, El-Said HG. In: Garson A, Bricker JT, Fischer DJ, Neish SR, eds. The science and practice of pediatric cardiology. 2nd ed. Baltimore: Williams and Wilkins, 1998: 1691-724.
6. Kingsley RH, Pocock WA. In: JB Barlow, ed. Prospectives on the mitral valve, 1987: 227-45.
7. Cilliers AM, Manyemba J, Saloojee H. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev 2003;(2): CD003176 [GenBank] .
8. Uziel Y, Hashkes PJ, Kassem E, Padeh S, Goldman R, Vollach B. The use of naproxen in the treatment of children with rheumatic fever. J Pediatr 2000;137: 269-71.[CrossRef][ISI][Medline]
9. Herdy GVH, Pinto CA, Olivaes MC, Carvalho EA, Tchou H, Cosendey R, et al. Rheumatic carditis treated with high doses of pulse therapy methylprednisolone. Arq Bras Cardiol 1999;72: 604-6.

Rapid Responses:

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