Reference Article
3-11 RHEUMATIC FEVER
In many developing countries, rheumatic heart disease remains the leading cause of heart disease among children and young adults.
In developed countries many young physicians have never seen a patient with rheumatic fever (RF). They find themselves making decisions about whether cephalosporins, rather than penicillin therapy alone, constitute appropriate primary prevention therapy, and whether or not antibiotics are necessary for pharyngitis.
This seminar emphasizes the importance of early diagnosis and reporting of a patient with RF, because such a patient can introduce into the community strains of group A streptococci that are capable of causing the disease. These strains are known, appropriately, as rheumatogenic.

Diagnostic criteria:
Have not changed since the Jones criteria were introduced in the 1950s.
Polyarthritis of RF generally occurs early in the rheumatic attack, at a time when streptococcal antibodies are at their peak concentration. The absence of a substantial increase in antibodies (eg, antistreptolysin O and anti-DNase), is a useful negative predictor for RF.
Carditis is a pancarditis that is invariably associated with murmurs of valvulitis. Isolated myocarditis or pericarditis that is not associated with murmurs should not ordinarily be diagnosed as rheumatic in origin. Thus, a rheumatic carditis can be easily diagnosed by auscultation.
Sydenhams chorea, when florid, is easily recognized—erratic, jerky, purposeless movements, fleeting local muscular weakness, emotional liability, and personality changes. There are no confirmatory laboratory or imaging tests. Diagnosis is based entirely on clinical signs. If mild, chorea is commonly over looked and attributed by teachers and parents to behavioral and emotional disorders, restlessness, and clumsiness.

Epidemiology:
Group-A streptococci have been identified as the sole etiologic agent. But not all group-A streptococci cause the disease. (A fact that is still not widely appreciated.) Extra pharyngeal infections with group-A (pyodermas and soft tissue infections) are not rheumatogenic. And not all pharyngeal infections lead to RF. Some serotypes of group A strep do not cause RF. Some M serotypes have been clearly associated with RF (M 5 & 18). A subclass of surface proteins on rheumatogenic M serotypes cross react with heart tissue, synovium, and brain. Susceptibility to recurrences of RF might result from an acquired autoimmune response to an initial pharyngeal infection with a rheumatogenic strain of group-A streptococci. The response is amplified by subsequent bouts of infection. Progress in identifying the antigenic M-peptides promises development of a vaccine to prevent RF.
Recurrence of RF as well as primary attacks all but disappeared in certain populations long after penicillin prophylaxis has stopped. This occurs after rheumatogenic strains have also disappeared.
Some strains are nephritogenic (causing glomerulonephritis) — generally those with primary tropism for the skin. There is a clear separation of the microbiology of the two diseases.
While the decline in RF has been attributed mainly to socioeconomic advances and prophylactic penicillin, there has been no decline in incidence or prevalence of streptococcal pharyngitis. The decline was the result of the disappearance of rheumatogenic strains.
Rheumatogenic strains are highly contagious. Rapid transmission occurs by close person-to-person contact.

Treatment:
For the present, most physicians choose to use corticosteroids rather than salicylates simply because they are more effective anti-inflammatory treatment for relief of symptoms. It has not been determined, however, whether corticosteroids reduce the frequency of rheumatic heart disease.
The reviewer considers corticosteroids not to be appropriate for most cases of RF. They should be given to only a small minority of patients for whom the powerful suppression of inflammation achieved by corticosteroids may seem beneficial.

Prevention:
Has remained largely unchanged. Epidemics of RF in army and navy bases have been terminated by giving all personnel 1 200 000 U penicillin G benzathine (bicillin-LA).
Primary prevention: In communities with a high prevalence of RF, penicillin G benzathine is usually the first choice, because of poor compliance with 10-day regimens of oral penicillin. In developed countries, where the threat of RF is diminished, oral penicillin V has become the norm. Throat cultures or tests for group-A antigen on throat swabs provide a useful negative predictive test. In settings where RF is rare, negative tests can exclude at least 90% of patients with sore throats from the requirement for antibiotic therapy. False positive tests are the result of non-group-A strep, previous group-A infections, or subclinical acquisition of throat-colonizing strains. Treatment of these infections with low doses of penicillin, however unnecessary, may do little harm, whereas an assault on them with broad-spectrum antibiotics may contribute to the emergence of common pharyngeal strains that are resistant to most antibiotics, such as S pneumoniae.
About 6-29% of patients treated with recommended regimens continue to carry group-A streptococci after clinical recovery. But by this time group-A streptococci have rapidly lost M protein and virulence, and thus their threat to contacts. Pharyngeal carriage persisting after adequate penicillin therapy does not pose a threat in populations from which rheumatic fever has disappeared.

Secondary prevention:
A monthly injection of 1 200 000 U penicillin G benzathine is the most effective regimen for patients at greatest risk for recurrence. After 5 years, prophylaxis can be safely stopped—when the original strains of rheumatogenic streptococci have disappeared from the community.

Lancet March 29, 1997; 349: 935-942 Narrative review from Boston Univ. Mass.

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