Although the overall incidence of acute rheumatic fever and rheumatic heart disease is low in most areas of the United States, they are the leading causes of cardiovascular death during the first five decades of life in developing countries. This disparity serves as a reminder of the importance of continued vigilance to prevent these diseases. The American Heart Association (AHA) recently updated its recommendations on the prevention of rheumatic fever.

Primary Prevention of Rheumatic Fever

Group A streptococcus (GAS) infections of the pharynx are the precipitating cause of rheumatic fever. Proper diagnosis and adequate antibiotic treatment of GAS infections can prevent acute rheumatic fever in most cases.

DIAGNOSIS OF STREPTOCOCCAL PHARYNGITIS

Acute pharyngitis is caused much more often by viruses than by bacteria. However, differentiation of GAS pharyngitis from other causes of acute pharyngitis is often difficult because none of the clinical findings suggestive of GAS infection is specific enough on its own for diagnosis (Table 1). A history of recent exposure is helpful in making the diagnosis, as is an awareness of the prevalence of GAS infections in the community.

If clinical and epidemiologic findings suggest GAS infection, microbiologic confirmation with a throat culture or rapid antigen detection test (RADT) is required. The diagnosis of GAS pharyngitis is more easily excluded than confirmed, so testing usually is unnecessary in patients with findings suggestive of a viral origin. Treatment is indicated for patients with acute pharyngitis who have a positive throat culture or RADT. However, because of the low sensitivity of many RADTs, a negative test does not exclude GAS infection, and a throat culture usually should be performed. The exception is in adults, in whom the incidence of GAS pharyngitis and the risk of acute rheumatic fever are low. In this population, diagnosis of GAS pharyngitis can be made on the basis of an RADT alone, without confirmation of negative results by a throat culture.

Antistreptococcal antibody titers reflect past—not present—immunologic events and therefore cannot be used to determine whether a patient with pharyngitis and GAS in the pharynx is truly infected or merely a streptococcal carrier. When present, elevated or increasing antistreptococcal titers can confirm a recent GAS infection and are valuable in identifying a preceding GAS infection in a patient suspected of having rheumatic fever.

TREATMENT OF STREPTOCOCCAL PHARYNGITIS

Primary prevention of rheumatic fever requires adequate therapy for GAS pharyngitis. In selecting a treatment regimen, physicians should consider bacteriologic and clinical effectiveness, ease of adherence to the recommended regimen (i.e., dosing frequency, duration of therapy, and palatability), cost, spectrum of activity of the selected agent, and potential adverse effects.

Intramuscular penicillin G benzathine, oral penicillin V potassium, and oral amoxicillin are the recommended antimicrobial agents for the treatment of GAS pharyngitis in persons without penicillin allergy (Table 2). GAS resistance to penicillin has never been documented, and penicillin prevents primary attacks of rheumatic fever even when started nine days after illness onset. Patients are no longer considered contagious after 24 hours of antibiotic therapy.

Penicillin V potassium is preferred over penicillin G benzathine because it is more resistant to gastric acid. However, penicillin G benzathine should be considered in patients who are unlikely to complete a 10-day course of oral therapy, in those with personal or family histories of rheumatic fever or rheumatic heart failure, and in those with environmental factors that put them at risk for rheumatic fever (e.g., crowded living conditions, low socioeconomic status).

OTHER RECOMMENDATIONS

Because most patients with GAS pharyngitis respond well to antimicrobial therapy, posttreatment throat cultures are indicated only in those who remain symptomatic, who have recurrent symptoms, or who have had rheumatic fever previously.

With the exception of persons who have had or whose family members have had rheumatic fever, repeated courses of antibiotics are typically not indicated in asymptomatic persons who continue to harbor GAS after appropriate therapy.

Although acute infections with group B and C beta-hemolytic streptococci can appear similar to GAS pharyngitis, rheumatic fever has not been documented as a complication of these infections.

Secondary Prevention of Rheumatic Fever

Recurrent rheumatic fever is associated with worsening or development of rheumatic heart disease. Prevention of recurrent GAS pharyngitis is the most effective method of preventing severe rheumatic heart disease. However, a GAS infection does not have to be symptomatic to trigger a recurrence, and rheumatic fever can recur even when a symptomatic infection is treated optimally. Therefore, prevention of recurrent rheumatic fever requires continuous antimicrobial prophylaxis rather than recognition and treatment of acute episodes of GAS pharyngitis.

SECONDARY PROPHYLAXIS

Continuous prophylaxis is recommended in patients with well-documented histories of rheumatic fever and in those with evidence of rheumatic heart disease (Tables 3 and 4). Prophylaxis should be initiated as soon as acute rheumatic fever or rheumatic heart disease is diagnosed. To eradicate residual GAS, a full course of penicillin should be given to patients with acute rheumatic fever, even if a throat culture is negative.

Continuous antimicrobial prophylaxis provides the most effective protection from recurrences of rheumatic fever. Because the risk of recurrence depends on many factors, physicians should determine the appropriate duration of prophylaxis on a case-by-case basis while also considering the presence of rheumatic heart disease. Patients who have had rheumatic carditis, with or without valvular disease, are at high risk of recurrences and are likely to have increasingly severe cardiac involvement with each episode. These patients should receive long-term antibiotic prophylaxis well into adulthood, and perhaps for life. Patients with persistent valvular disease should receive prophylaxis for 10 years after the last episode of acute rheumatic fever or until 40 years of age, whichever is longer. At that time, the severity of valvular disease and the potential for exposure to GAS should be determined, and continued prophylaxis (possibly lifelong) should be considered in high-risk patients.

In the United States, an injection of penicillin G benzathine every four weeks is the recommended prophylactic regimen for secondary prevention in most circumstances. In certain populations, administration every three weeks is justified because serum drug levels may fall below a protective level before four weeks after the initial dose. A three-week dosing regimen is recommended only for patients who have recurrent acute rheumatic fever despite adherence to a four-week regimen. The advantages of penicillin G benzathine should be weighed against the inconvenience to the patient and the pain of injection, which causes some patients to discontinue prophylaxis.

Successful oral prophylaxis depends on patient adherence to the prescribed regimen. Patients should be given careful, repeated instructions about the importance of compliance to the dosing regimen. Even with optimal patient compliance, the risk of recurrence is higher in patients receiving oral prophylaxis than in those receiving injections of penicillin G benzathine. Therefore, oral regimens are more appropriate for patients at lower risk of recurrent rheumatic fever.

Bacterial Endocarditis

The AHA no longer recommends prophylaxis for infective endocarditis in most patients with rheumatic heart disease. The exceptions are patients with prosthetic valves or valves repaired with prosthetic material, patients with previous endocarditis or specific forms of congenital heart disease, and cardiac transplant recipients who develop cardiac valvulopathy. In these patients, an agent other than penicillin should be used to prevent infective endocarditis, because alpha-hemolytic streptococci have likely developed resistance to penicillin.

Poststreptococcal Reactive Arthritis

Poststreptococcal reactive arthritis (PSRA) may occur after an episode of GAS pharyngitis in patients who do not have any other major criteria of acute rheumatic fever. PSRA generally follows a symptom-free interval of about 10 days after the GAS pharyngitis, is cumulative and persistent, involves the large and small joints and the axial skeleton, and does not respond to aspirin therapy. In contrast, arthritis associated with rheumatic fever occurs two to three weeks after an episode of GAS pharyngitis, is migratory and transient, involves only the large joints, and responds rapidly to aspirin therapy.

Although all patients with PSRA have serologic evidence of a recent GAS infection, GAS is isolated in no more than one half of these patients who have a throat culture. Because valvular heart disease can develop in patients with PSRA, secondary prophylaxis should be administered for up to one year after symptom onset, and these patients should be observed for several months for clinical evidence of carditis. If such evidence is not observed, prophylaxis can be discontinued. However, if valvular disease is detected, the patient should be classified as having had acute rheumatic fever, and secondary prophylaxis should be continued.

PANDAS

It has been proposed that an autoimmune response after a streptococcal infection may result in obsessive-compulsive disorder or tics in some children. This concept, known as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), is controversial, and the current evidence suggests that it should be considered a yet-unproven hypothesis. Until a causal relationship has been established between PANDAS and GAS infections, routine laboratory testing for GAS is not recommended to diagnose this disorder, and long-term prophylaxis or immunoregulatory therapy is not recommended.