What is Rheumatic Fever
Rheumatic fever is an inflammatory illness that occurs as a delayed sequela of group A streptococcal pharyngitis, typically developing 2-3 weeks after the initial throat infection in genetically susceptible individuals. 1
Definition and Pathophysiology
Rheumatic fever is a non-suppurative, immunologically mediated inflammatory disease that affects multiple organ systems following untreated or inadequately treated group A Streptococcus (GAS) pharyngeal infection. 2, 3, 4 The disease represents a classic example of molecular mimicry, where antibodies generated against streptococcal antigens cross-react with host tissues, particularly affecting the heart, joints, brain, and skin. 2, 4
Clinical Features and Diagnosis
Major Criteria (Jones Criteria)
The diagnosis relies on the modified Jones criteria, requiring evidence of preceding GAS infection plus either two major criteria OR one major plus two minor criteria: 1, 5
Major manifestations include:
- Carditis (most serious, can lead to permanent valve damage)
- Polyarthritis (migratory, affecting large joints)
- Chorea (Sydenham's chorea - involuntary movements)
- Subcutaneous nodules
- Erythema marginatum (characteristic rash) 1, 5
Minor Criteria
- Previous rheumatic fever or rheumatic heart disease
- Arthralgia (joint pain without objective inflammation)
- Fever
- Elevated inflammatory markers (ESR, CRP, or leukocytosis)
- Prolonged PR interval on ECG 1
Laboratory Confirmation
Supporting evidence of preceding streptococcal infection is mandatory and includes: 1
- Elevated antistreptolysin-O (ASO) or other streptococcal antibodies
- Positive throat culture for group A Streptococcus
- Recent scarlet fever
Critical caveat: No specific laboratory test exists for diagnosing rheumatic fever itself—diagnosis is clinical based on the Jones criteria. 1 The exception is Sydenham chorea or low-grade carditis discovered after a long latent period, where streptococcal evidence may be absent. 1
Acute Management
Eradication of Streptococcal Infection
Administer a full therapeutic course of penicillin to eradicate residual GAS, even if throat culture is negative at diagnosis: 6, 7
- Oral penicillin V: 250 mg twice daily for children; 500 mg 2-3 times daily for adolescents/adults for 10 days 6, 7
- For penicillin allergy: Erythromycin or first-generation cephalosporins (if no immediate-type hypersensitivity) 6, 7
- Alternative for adults: Azithromycin 500 mg once daily for 5 days or clarithromycin 250 mg twice daily for 10 days 7
Anti-inflammatory Therapy
Anti-inflammatory agents provide dramatic clinical improvement but do not prevent subsequent rheumatic heart disease development. 2 In severe cases with significant cardiac involvement, corticosteroids such as prednisone at 1-2 mg/kg/day for 1-2 weeks may be considered, though controlled studies have failed to demonstrate improved long-term prognosis. 7, 2
Secondary Prophylaxis (Most Critical Component)
Continuous antimicrobial prophylaxis is essential because recurrent rheumatic fever worsens cardiac damage progressively, and at least one-third of cases result from asymptomatic GAS infections. 6, 8, 9
Preferred Regimen
Benzathine penicillin G 1.2 million units intramuscularly every 4 weeks is the gold standard, providing approximately 10 times greater protection than oral antibiotics (0.1% vs 1% recurrence rate). 1, 7, 8, 9 In high-risk populations or patients with recurrence despite adherence to the 4-week regimen, administer every 3 weeks. 7, 8
Alternative Oral Regimens (Less Effective)
Duration of Prophylaxis (Stratified by Cardiac Involvement)
For patients with carditis and residual heart disease: Continue for at least 10 years after the last episode OR until age 40 years (whichever is longer), often lifelong. 1, 6, 7, 8
For patients with carditis but no residual heart disease: Continue for 10 years OR until age 21 years (whichever is longer). 1, 6, 7, 8
For patients without carditis: Continue for 5 years OR until age 21 years (whichever is longer). 7, 8
Critical Pitfalls to Avoid
Never discontinue prophylaxis prematurely based solely on normal echocardiographic findings—patients remain susceptible to recurrent GAS infection that will worsen cardiac damage. 8 Prophylaxis must continue even after valve surgery, including prosthetic valve replacement. 7, 8
Do not assume that successful treatment of the initial streptococcal pharyngitis eliminates risk—even when GAS pharyngitis is treated optimally, rheumatic fever can still occur in susceptible individuals. 6, 7 Antibiotics must be started within 9 days of symptom onset to effectively prevent acute rheumatic fever. 8
Recognize that infection with group A Streptococcus does not have to be symptomatic to trigger recurrence—this is why continuous (not episodic) prophylaxis is essential rather than simply treating acute pharyngitis episodes. 1, 6
Epidemiology and Public Health Impact
Rheumatic heart disease remains the largest global cause of cardiovascular disease in young people (age < 25 years), particularly in developing countries with overcrowded living conditions and inadequate sanitation. 8, 9, 4 In the United States, acute rheumatic fever has been uncommon since the 1970s, though cases increased after 1987. 1