Acute Rheumatic Fever¶
Chapter 371 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Acute rheumatic fever (ARF) is an autoimmune reaction triggered by group A streptococcal (GAS) infection, leading to multisystem inflammation.
- Key clinical features include polyarthritis, carditis, chorea, erythema marginatum, and subcutaneous nodules. Carditis is the most significant complication, leading to rheumatic heart disease (RHD).
- Diagnosis relies on the Jones criteria, combining clinical manifestations and evidence of preceding GAS infection (e.g., elevated ASO titers).
- Secondary prophylaxis with benzathine penicillin G is critical to prevent recurrence, especially in high-risk populations.
- Echocardiography is essential for staging RHD and monitoring valvular damage progression.
1. DEFINITION & OVERVIEW¶
Acute rheumatic fever (ARF) is a multisystem inflammatory disease caused by an autoimmune response to group A streptococcal (GAS) infection. It primarily affects children aged 5–14 years and can lead to rheumatic heart disease (RHD), a major cause of acquired heart disease in low- and middle-income countries (LMICs).
Table 371-1: Staging of Rheumatic Heart Disease by Echocardiography¶
| Stage | Clinical Risk | Echocardiographic Features |
|---|---|---|
| Stage A | Minimal risk of progression | Mild MR/AR without morphologic features |
| Stage B | Moderate/high risk of progression | Mild valvular regurgitation + ‡1 morphologic feature (£20 years) or ‡2 morphologic features (>20 years) |
| Stage C | High risk of clinical complications | Moderate/severe MR/AR, MS/AS, pulmonary hypertension, decreased LV systolic function |
| Stage D | Established clinical complications | Cardiac surgery, heart failure, arrhythmia, stroke, infective endocarditis |
1.1 Global Burden¶
ARF and RHD are diseases of poverty, historically common in all countries but now more prevalent in LMICs. Over 40 million people are affected by RHD globally, with >300,000 annual deaths. Sub-Saharan Africa, Pacific nations, and South Asia bear the highest burdens.
1.2 Pathogenesis¶
ARF is driven by molecular mimicry between GAS M protein and human cardiac/myocardial antigens. Genetic susceptibility (e.g., HLA class II alleles) and environmental factors (e.g., streptococcal skin infections) contribute to disease development.
2. EPIDEMIOLOGY¶
ARF is most common in children aged 5–14 years, with recurrence rates higher in adolescents. RHD peaks in 25–40-year-olds. No clear gender association for ARF, but RHD is more common in females. Risk factors include overcrowding, poor hygiene, and lack of secondary prophylaxis.
2.1 Demographics¶
ARF incidence is highest in LMICs, with 95% of cases and deaths occurring in developing countries. Sub-Saharan Africa, Pacific nations, and South Asia have the highest burdens.
2.2 Risk Factors¶
Overcrowded living conditions, asymptomatic streptococcal infections, poor access to healthcare, and lack of secondary prophylaxis increase risk. Skin infections are increasingly implicated as a source of GAS.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
ARF is caused by an autoimmune response to GAS infection. Molecular mimicry between M protein and human antigens drives inflammation. Genetic factors (e.g., HLA class II alleles) and environmental triggers (e.g., streptococcal skin infections) contribute to susceptibility.
3.1 Organism Factors¶
Group A streptococcus (GAS) is the causative agent. M-serotypes 1, 3, 5, 6, 14, 18, 19, 24, 27, and 29 are most commonly associated with ARF, though newer evidence suggests more serotypes are rheumatogenic.
3.2 Host Factors¶
Genetic susceptibility (e.g., HLA class II alleles, IGHV4-61*02), immunologic determinants (e.g., TNF, mannose-binding lectin), and inherited susceptibility (44% concordance in monozygotic twins) play key roles.
4. CLINICAL FEATURES¶
ARF presents with polyarthritis, carditis, chorea, erythema marginatum, and subcutaneous nodules. Carditis is the most significant complication, leading to RHD. Symptoms typically appear 2–4 weeks after GAS infection.
4.1 Cardiac Involvement¶
Mitral valve involvement is most common, with regurgitation, thickening, and calcification. Myocardial inflammation may cause P-R interval prolongation and heart failure.
4.2 Joint Involvement¶
Polyarthritis (knees, ankles, hips, elbows) is common, with migratory, hot, swollen joints. Monoarthritis may occur, especially in early stages.
4.3 Neurological Manifestations¶
Sydenham’s chorea (involuntary movements) is common in females. Other features include emotional lability and obsessive-compulsive traits.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include other autoimmune disorders, viral infections, and non-rheumatic causes of joint pain or heart failure. Key differentiators include the temporal relationship to GAS infection and characteristic clinical features.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis relies on the Jones criteria (Table 371-2), combining clinical features and evidence of GAS infection. Echocardiography is critical for staging RHD (Table 371-1). Serologic tests (ASO, anti-DNase B) and throat swabs are used to confirm GAS infection.
Table 371-2: Jones Criteria for ARF Diagnosis¶
| Category | Major Criteria | Minor Criteria |
|---|---|---|
| Initial ARF | 2 major or 1 major + 2 minor | Fever ‡38.5°C, arthralgia, prolonged PR interval, elevated ESR/CRP |
| Recurrent ARF | 2 major or 1 major + 2 minor | Fever ‡38°C, arthralgia, prolonged PR interval, elevated ESR/CRP |
Table 371-3: Testing and Monitoring in Acute ARF¶
| Investigation | Details |
|---|---|
| ECG | Monitor for PR interval prolongation, arrhythmias |
| Echocardiogram | Assess valvular damage and cardiac function |
| CBC | Check for anemia, leukocytosis |
| CRP/ESR | Inflammatory markers |
| Streptococcal serology | ASO, anti-DNase B titers |
| Throat/swab | Confirm GAS infection |
6.1 Diagnostic Criteria¶
Jones criteria: Major criteria (carditis, arthritis, chorea, erythema marginatum, subcutaneous nodules); minor criteria (fever, arthralgia, prolonged PR interval, elevated ESR/CRP).
6.2 Laboratory Tests¶
Anti-streptolysin O (ASO), anti-DNase B titers, ESR, CRP, and throat/swab cultures. Urinalysis for streptococcal antigens may be used in resource-limited settings.
7. MANAGEMENT & TREATMENT¶
Treatment includes antibiotics for GAS infection, anti-inflammatory drugs (salicylates/NSAIDs) for symptoms, and secondary prophylaxis with benzathine penicillin G. Glucocorticoids may be used in severe cases of carditis or chorea.
7.1 Acute Management¶
Antibiotics (penicillin V or benzathine penicillin G) to eradicate GAS. Salicylates/NSAIDs for arthritis/chorea. Glucocorticoids may be used in severe carditis or refractory chorea.
7.2 Secondary Prophylaxis¶
Long-term benzathine penicillin G (1.2 million units every 4 weeks) to prevent recurrence. Alternatives include oral penicillin V or erythromycin for penicillin-allergic patients.
7.3 Heart Failure Management¶
Diuretics, ACE inhibitors, and beta-blockers for heart failure. Echocardiography for monitoring valvular damage progression.
8. PROGNOSIS & COMPLICATIONS¶
Untreated ARF lasts ~12 weeks. With treatment, recovery occurs within 1–2 weeks. Complications include RHD, heart failure, stroke, and infective endocarditis. Prognosis is poor without secondary prophylaxis.
8.1 RHD Progression¶
RHD may progress to severe valvular dysfunction, requiring surgical intervention. Staging (Table 371-1) guides management and prognosis.
8.2 Long-Term Outcomes¶
Patients with RHD require lifelong monitoring. Mortality is high in untreated cases, but secondary prophylaxis significantly reduces recurrence risk.
9. SPECIAL CONSIDERATIONS¶
ARF is more common in LMICs due to poor living conditions and limited healthcare access. Prevention strategies include improving hygiene, reducing overcrowding, and implementing register-based RHD control programs.
9.1 Pregnancy¶
ARF during pregnancy can complicate maternal and fetal outcomes. Prophylaxis should continue during pregnancy.
9.2 Pediatrics¶
Children are most affected; early diagnosis and prophylaxis are critical. Echocardiography is essential for detecting subclinical RHD.
10. KEY POINTS & CLINICAL PEARLS¶
ARF is a preventable disease. Early recognition of GAS infection and prompt treatment with antibiotics reduce recurrence risk. Secondary prophylaxis with benzathine penicillin G is the cornerstone of long-term management. Echocardiography is vital for staging RHD and guiding treatment decisions.