What is the first‑line management of acute rheumatic fever, including antibiotic and anti‑inflammatory therapy?

Treatment of Acute Rheumatic Fever

For acute rheumatic fever, immediately administer a full 10-day course of penicillin to eradicate Group A Streptococcus (even if throat culture is negative), provide anti-inflammatory therapy with high-dose aspirin (or corticosteroids if severe carditis is present), and initiate lifelong secondary prophylaxis with intramuscular benzathine penicillin G 1.2 million units every 4 weeks. 1, 2

Antibiotic Therapy for GAS Eradication

First-Line Regimens

• Oral Penicillin V: 250 mg twice daily for 10 days (children <27 kg) or 500 mg 2-3 times daily for 10 days (adolescents/adults ≥27 kg) 1, 2
• Intramuscular Benzathine Penicillin G: Single injection of 600,000 units (<27 kg) or 1.2 million units (≥27 kg) 2

Penicillin-Allergic Patients

• Erythromycin or first-generation cephalosporins (if no immediate-type hypersensitivity to β-lactams) 3, 1
• Azithromycin 500 mg once daily for 5 days or clarithromycin 250 mg twice daily for 10 days are acceptable alternatives 1

Critical Timing Consideration

• Treatment can be initiated up to 9 days after symptom onset and still prevent rheumatic fever complications 3
• Administer penicillin immediately at diagnosis, even if throat culture is negative, to eradicate residual streptococci 1, 4

Anti-Inflammatory Therapy

For Arthritis and Mild Carditis

• High-dose aspirin (acetylsalicylic acid): 75-100 mg/kg/day divided into multiple doses for 4-6 weeks 2, 4
• Rheumatic fever arthritis responds rapidly to aspirin, typically resolving within days 2, 4

For Severe Carditis or Pancarditis

• Corticosteroids (prednisone 1-2 mg/kg/day for 1-2 weeks) should be considered when severe cardiac inflammation is present 1
• In severe cases with significant cardiac involvement, intravenous methylprednisolone (1000 mg/day initially) may be used, followed by oral prednisone 1

Secondary Prophylaxis (Prevention of Recurrence)

Gold Standard Regimen

Benzathine penicillin G 1.2 million units intramuscularly every 4 weeks is the gold standard and provides approximately 10 times greater protection than oral antibiotics (0.1% vs 1% recurrence rate). 3, 1, 2

• In high-risk populations or patients with recurrence despite adherence, administer every 3 weeks 3, 1
• High-risk populations include children, adolescents, parents of young children, teachers, healthcare workers, military recruits, and economically disadvantaged populations 2

Alternative Oral Regimens (Less Effective)

• Penicillin V potassium: 250 mg orally twice daily 3
• Sulfadiazine: 1 g orally once daily (for penicillin-allergic patients) 3, 2
• Macrolide antibiotics: Variable dosing (for patients allergic to both penicillin and sulfadiazine) 3

Duration of Secondary Prophylaxis

Cardiac Status	Duration	Citation
Rheumatic fever WITHOUT carditis	5 years or until age 21 (whichever is longer)	[3,1,2]
Carditis WITHOUT residual valvular disease	10 years or until age 21 (whichever is longer)	[3,1,2]
Carditis WITH residual valvular disease	10 years or until age 40 (whichever is longer), often lifelong	[3,1,2]

Critical Pitfalls and Caveats

Why Continuous Prophylaxis is Essential

• At least one-third of rheumatic fever cases result from asymptomatic GAS infections, making primary prevention impossible in these scenarios 1, 2, 4
• GAS infection does not need to be symptomatic to trigger recurrent rheumatic fever 3, 1, 2
• Even when symptomatic GAS pharyngitis is treated optimally, rheumatic fever can still occur in susceptible individuals 1
• Each recurrence of rheumatic fever worsens cardiac valve damage progressively 3, 4

Prophylaxis Must Continue After Valve Surgery

• Secondary prophylaxis is required even after valve replacement, including prosthetic valve implantation 3, 1

Household Contact Management

• Obtain throat swab specimens from all household contacts of a patient with acute rheumatic fever 4
• Treat all positive contacts regardless of symptoms to prevent transmission 4

Medications to Avoid

• Tetracyclines: High prevalence of resistant strains 3
• Sulfonamides and trimethoprim-sulfamethoxazole: Do not eradicate GAS 3
• Older fluoroquinolones (ciprofloxacin): Limited activity against GAS 3
• Newer fluoroquinolones (levofloxacin, moxifloxacin): Unnecessarily broad spectrum and expensive 3

Drug Interaction Warning

• Do not prescribe macrolide antibiotics with cytochrome P450 3A inhibitors (azole antifungals, HIV protease inhibitors, some SSRIs) due to QT prolongation risk 3, 1

Distinguishing Post-Streptococcal Reactive Arthritis (PSRA)

PSRA differs from acute rheumatic fever and requires different management 4:

• Appears approximately 10 days after pharyngitis (vs. 14-21 days for ARF) 4
• Does not respond readily to aspirin (unlike ARF arthritis) 4
• Tends to be cumulative, persistent, and may involve small joints or axial skeleton 4
• Observe for several months for evidence of carditis and consider secondary prophylaxis for up to 1 year 4