What is the recommended management of acute rheumatic fever, including anti‑inflammatory therapy, antibiotic treatment, and secondary prophylaxis?

Management of Acute Rheumatic Fever

Immediate Eradication of Group A Streptococcus

All patients with acute rheumatic fever must receive a full therapeutic course of penicillin to eradicate residual Group A Streptococcus, even if throat culture is negative at diagnosis. 1

• Oral penicillin V: 500 mg orally 2-3 times daily for 10 days in adults; 250 mg twice daily for children 1
• For penicillin-allergic patients: Azithromycin 500 mg once daily for 5 days, clarithromycin 250 mg twice daily for 10 days, or erythromycin 1, 2
• This initial treatment must be completed before transitioning to long-term prophylaxis 1

Anti-Inflammatory Therapy for Acute Phase

Aspirin remains the anti-inflammatory drug of choice for most patients with carditis. 3

• For severe inflammation or cardiac involvement: Consider corticosteroids such as prednisone at 1-2 mg/kg/day for 1-2 weeks 1
• For severe cases with significant cardiac involvement: Intravenous methylprednisolone (1000 mg/day initially) may be considered, followed by oral prednisone 1
• The choice between aspirin and corticosteroids depends on severity of cardiac involvement, with corticosteroids reserved for more severe presentations 1, 3

Secondary Prophylaxis: The Gold Standard

Intramuscular benzathine penicillin G (1.2 million units every 4 weeks) is the gold standard for secondary prophylaxis and is approximately 10 times more effective than oral antibiotics (0.1% vs 1% recurrence rate). 1, 4, 5

Primary Regimen

• Benzathine penicillin G: 1.2 million units intramuscularly every 4 weeks 1, 6, 5
• For high-risk populations or recurrence despite adherence: Consider administration every 3 weeks 1, 6, 4
• This intramuscular regimen reduces recurrence risk substantially (RR 0.07,95% CI 0.02 to 0.26) compared to oral antibiotics 1, 4

Alternative Oral Regimens (Less Effective)

• Oral penicillin V: 250 mg twice daily 6
• Sulfadiazine: 1 g orally once daily for adults; 0.5 g once daily for patients weighing ≤27 kg 6
• For penicillin allergy: Erythromycin orally twice daily 2

Duration of Secondary Prophylaxis: A Critical Decision

The duration is determined by the presence and severity of cardiac involvement during the initial episode, not current cardiac status. 7, 4

Rheumatic Fever WITH Carditis AND Residual Heart Disease

• Duration: 10 years after last attack OR until age 40 years (whichever is longer), sometimes lifelong 7, 1, 6
• Rationale: Patients with persistent valvular disease have the highest risk of complications from recurrence 7

Rheumatic Fever WITH Carditis BUT NO Residual Heart Disease

• Duration: 10 years after last attack OR until age 21 years (whichever is longer) 7, 1, 6, 4
• Key point: Even with normal echocardiographic findings now, the history of carditis mandates extended prophylaxis 4

Rheumatic Fever WITHOUT Carditis

• Duration: 5 years after last attack OR until age 21 years (whichever is longer) 7, 1, 6, 4

Special Circumstances

• Lifelong prophylaxis: Should be considered for patients at high risk of Group A Streptococcus exposure 7, 6
• After valve surgery: Prophylaxis must continue even after valve replacement, following the same duration guidelines 7, 6

Critical Pitfalls to Avoid

Never discontinue prophylaxis prematurely based solely on normal echocardiographic findings, as patients remain susceptible to Group A Streptococcus infection. 4

• At least one-third of rheumatic fever cases arise from asymptomatic Group A Streptococcus infections, making continuous prophylaxis critical even in asymptomatic patients 1, 4
• Recurrent rheumatic fever is associated with worsening of rheumatic heart disease 7
• Even when Group A Streptococcus pharyngitis is treated optimally, rheumatic fever can still occur in susceptible individuals 1
• Infection with Group A Streptococcus does not have to be symptomatic to trigger a recurrence 7

Endocarditis Prophylaxis Considerations

Current guidelines no longer recommend routine endocarditis prophylaxis for patients with rheumatic heart disease unless they have prosthetic valves or prosthetic material used in valve repair. 7, 6, 4

• For patients requiring endocarditis prophylaxis: If receiving penicillin prophylaxis, use an agent other than penicillin for dental procedures, as oral α-hemolytic streptococci likely have developed resistance 6
• Alternative agents: Amoxicillin for high-risk dental or surgical procedures (if not recently treated with penicillin), or clindamycin for immediate penicillin hypersensitivity 2
• Maintaining optimal oral health remains the most important component of preventing infective endocarditis 7, 6

Monitoring and Follow-Up

Serial echocardiographic evaluations are essential for detecting subclinical progression of valvular disease that may not be apparent on physical examination. 4

• Echocardiography confirms normal valvular function and documents the absence of mitral regurgitation 4
• People with early or mild rheumatic heart disease have the greatest capacity to benefit from intramuscular antibiotic prophylaxis (8.1% benefit) compared to no antibiotics (0.7%) 5

Adverse Events and Safety

Intramuscular benzathine penicillin G probably carries an increased risk of hypersensitivity reactions and local reactions compared to no antibiotics, but anaphylaxis and sciatic nerve injury remain rare. 5

• Hypersensitivity reactions: RR 137 (95% CI 8.51 to 2210) 5
• Local reactions: RR 29 (95% CI 1.74 to 485) 5
• Anaphylaxis: Peto OR 7.39 (95% CI 0.15 to 372) - may not differ significantly from no antibiotics 5
• Sciatic nerve injury: Peto OR 7.39 (95% CI 0.15 to 372) - may not differ significantly from no antibiotics 5