What is acute rheumatic fever?

Acute Rheumatic Fever (ARF)

Acute rheumatic fever is an inflammatory, autoimmune disease that occurs as a delayed complication of pharyngeal infection with group A streptococcus, characterized by five major manifestations: carditis, arthritis, chorea, erythema marginatum, and subcutaneous nodules, which typically develop 2-3 weeks following the infection. 1

Definition and Pathophysiology

Acute rheumatic fever is a non-suppurative, immunologically mediated inflammatory response that follows group A streptococcal pharyngitis after a latency period of 2-3 weeks 2, 1. The disease represents one of the classic examples of a pathogenic trigger leading to autoimmune manifestations, where the body's immune system attacks its own tissues due to molecular mimicry between streptococcal and human proteins.

Clinical Manifestations

ARF is characterized by five major manifestations:

1. Carditis: Inflammation of the heart that can affect the endocardium, myocardium, or pericardium, potentially leading to valvular damage
2. Arthritis: Typically migratory and transient, affecting large joints with rapid response to anti-inflammatory treatment
3. Sydenham's Chorea: Involuntary, purposeless movements with emotional lability
4. Erythema Marginatum: Transient, non-pruritic rash with clear centers and rounded edges
5. Subcutaneous Nodules: Firm, painless nodules over bony prominences

Diagnosis

Diagnosis of ARF requires evidence of preceding group A streptococcal infection plus either:

• 2 major manifestations, OR
• 1 major and 2 minor manifestations 1

Minor manifestations include:

• Fever
• Arthralgia
• Elevated acute phase reactants (ESR, CRP)
• Prolonged PR interval on ECG

For recurrent ARF, a lower threshold may be sufficient: 2 major OR 1 major and 2 minor OR 3 minor manifestations 1.

Epidemiology and Impact

ARF and rheumatic heart disease affect nearly 20 million people worldwide and remain leading causes of cardiovascular death during the first five decades of life in developing regions 2, 3. In many countries, rheumatic heart disease causes more hospital admissions than congenital heart conditions 4.

Treatment

Treatment of ARF consists of:

1. Eradication of Group A Streptococcus:

   • Penicillin is the first-line treatment (Class I, LOE A) 5, 1
   • Options include oral penicillin V or intramuscular benzathine penicillin G
   • For penicillin-allergic patients: macrolides, azalides, narrow-spectrum cephalosporins, or clindamycin 5, 1

2. Symptomatic Management:

   • Aspirin or other NSAIDs for arthritis/arthralgia
   • Corticosteroids may be considered for moderate to severe carditis
   • Supportive care for chorea

Prevention

Primary Prevention

Primary prevention involves proper identification and adequate antibiotic treatment of group A streptococcal pharyngitis 5, 1:

• Throat culture is the gold standard for diagnosis
• Full 10-day course of penicillin is required to prevent ARF

Secondary Prevention

Secondary prevention is crucial for patients who have had ARF to prevent recurrences and worsening cardiac damage 5, 1:

• Continuous antimicrobial prophylaxis is recommended (Class I, LOE A)
• Penicillin is the agent of choice, with sulfadiazine or macrolides as alternatives for penicillin-allergic individuals
• Duration of prophylaxis depends on:
  • Presence of carditis and residual heart disease
  • Time since last attack
  • Risk of group A streptococcal exposure

Duration of Secondary Prophylaxis 5:

• With carditis and residual heart disease: 10 years or until 40 years of age (whichever is longer), sometimes lifelong
• With carditis but no residual heart disease: 10 years or until 21 years of age (whichever is longer)
• Without carditis: 5 years or until 21 years of age (whichever is longer)

Complications

The most significant complication of ARF is rheumatic heart disease (RHD), which can result from a single severe episode or multiple recurrent episodes 3. RHD primarily affects the mitral and aortic valves, potentially leading to heart failure and premature death if not properly managed.

Special Considerations

• Family members of ARF patients should be evaluated and treated if positive for group A streptococcus 1
• At least one-third of ARF cases result from asymptomatic streptococcal infections 1
• Group C and G streptococci can cause pharyngitis with similar clinical features to group A streptococci, but their association with ARF is not well established 5

ARF remains a significant public health challenge in resource-limited settings, requiring continued vigilance in diagnosis, treatment, and prevention strategies to reduce its global burden.