What is acute rheumatic fever?

Acute Rheumatic Fever (ARF)

Acute rheumatic fever is an autoimmune disease triggered by group A streptococcal pharyngitis that affects multiple organ systems including the heart, joints, and central nervous system, occurring approximately 2-3 weeks after the initial infection and diagnosed using the Jones Criteria. 1

Epidemiology and Significance

• ARF affects nearly 20 million people worldwide
• It remains a leading cause of cardiovascular death during the first five decades of life in developing regions 1
• Disproportionately affects those in low- and middle-income countries and indigenous populations in wealthy nations 2
• Incidence has been declining even before widespread antibiotic use, but still affects approximately 19 per 100,000 children globally 3

Pathophysiology

The core mechanism involves molecular mimicry:

• Structural similarities between group A streptococcal (GAS) antigens and human tissues lead to cross-reactivity
• Antibodies produced against streptococcal components recognize and bind to similar epitopes in human tissues
• This cross-reactivity results in autoimmune damage to multiple organ systems 1
• The disease typically develops 2-3 weeks after the initial GAS throat infection
• At least one-third of ARF cases result from asymptomatic streptococcal infections 1

Clinical Manifestations and Diagnosis

Diagnosis requires evidence of preceding GAS infection plus clinical manifestations according to the Jones Criteria:

Major Manifestations

1. Carditis: Inflammation of the heart affecting valves (particularly mitral and aortic)

   • Presents with new murmurs, heart failure, or pericarditis
   • Can lead to long-term rheumatic heart disease

2. Arthritis:

   • Typically migratory and transient
   • Usually affects large joints
   • Responds rapidly to anti-inflammatory treatment

3. Chorea (Sydenham's Chorea):

   • Characterized by involuntary, purposeless movements
   • Emotional lability
   • May occur without other manifestations

4. Erythema Marginatum:

   • Transient, non-pruritic, pink rash with clear centers and rounded edges
   • Primarily on trunk and proximal extremities

5. Subcutaneous Nodules:

   • Firm, painless nodules over bony prominences
   • Usually associated with carditis 1

Minor Manifestations

Include fever, arthralgia, elevated inflammatory markers, and prolonged PR interval on ECG 1

Diagnostic Requirements

• Initial ARF: 2 major manifestations OR 1 major and 2 minor manifestations
• Recurrent ARF: 2 major OR 1 major and 2 minor OR 3 minor manifestations
• All require evidence of preceding GAS infection 1, 3

Prevention

Primary Prevention

• Proper identification and adequate antibiotic treatment of GAS pharyngitis
• Full 10-day course of penicillin required to prevent ARF 1

Secondary Prevention

• Continuous antimicrobial prophylaxis for patients who have had ARF
• Prevents recurrences and worsening cardiac damage
• Duration depends on:
  • Presence of carditis and residual heart disease
  • Time since last attack
  • Risk of GAS exposure
• May continue for 10 years or until 40 years of age for those with carditis and residual heart disease 1

Treatment

1. Eradication of GAS:

   • Penicillin is first-line treatment (10-day course)
   • For penicillin-allergic patients: narrow-spectrum cephalosporins, clindamycin, or macrolides/azalides 1

2. Symptomatic management:

   • Aspirin or other NSAIDs for arthritis/arthralgia
   • Corticosteroids may be considered for moderate to severe carditis 1

Complications

• Rheumatic heart disease (RHD) is the most serious long-term complication
• Can result from a single severe episode or multiple recurrent episodes 4
• Valvular heart disease, particularly affecting mitral and aortic valves
• Recurrences significantly increase the risk of severe cardiac damage 1

Clinical Pitfalls and Caveats

• Significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-streptococcal reactive arthritis 3
• No laboratory gold standard exists; diagnosis is entirely clinical 5
• No treatments have been definitively shown to reduce progression to rheumatic heart disease 5
• Family members of ARF patients should be evaluated and treated if positive for GAS 1
• Group C and G streptococci can cause similar pharyngitis but their association with ARF is not well established 1