Acute Rheumatic Fever

Acute rheumatic fever (ARF) is a systemic inflammatory connective tissue disease. It develops as a delayed complication of group A β-hemolytic streptococcal (GAS) pharyngitis or tonsillitis.

ARF is a post-infectious, immune-mediated condition. It most commonly affects the heart (carditis), joints (migratory polyarthritis), the central nervous system (Sydenham chorea), and the skin. The most serious long-term consequence is rheumatic heart disease (RHD), an acquired valvular heart disease due to valvular damage.

Aetiology and Pathophysiology

ARF is not caused by ongoing streptococcal infection. Instead, it results from an aberrant autoimmune response triggered by GAS. It typically occurs 2–4 weeks after an episode of GAS pharyngitis/tonsillitis.

The pathogenesis is driven by molecular mimicry. Streptococcal antigens (particularly M protein) share structural similarities with host proteins, especially in the cardiac muscle (myocardium), heart valves, synovium, and neuronal tissue. As a result, antibodies and immune cells generated against the streptococcus may cross-react with host tissues and provoke inflammation. The hallmark histologic feature of rheumatic carditis is the formation of Aschoff bodies (rheumatic nodules) in the myocardium.

Clinical significance

ARF is diagnosed using the Jones criteria, which include major and minor clinical manifestations. Evidence of a preceding group A streptococcal infection is required, for example, an elevated or rising antistreptolysin O (ASO) titer and/or a positive throat culture (or rapid antigen test).

Major Jones criteria:

• Carditis: inflammation involving all three layers of the heart (pancarditis). It may present with tachycardia, new murmurs, and chest pain; severe cases can progress to heart failure. This is the most serious manifestation.
• Migratory polyarthritis: inflammation of large joints (knees, ankles, elbows). Symptoms “migrate”: pain and swelling resolve in one joint and then appear in another.
• Sydenham chorea (chorea minor): CNS involvement with involuntary, rapid, irregular movements (hyperkinetic movements), muscle weakness, and emotional lability.
• Erythema marginatum: a characteristic pink, annular rash on the trunk and limbs.
• Subcutaneous rheumatic nodules: painless, firm nodules over bony prominences.

Treatment of the acute phase includes antibiotic therapy to eradicate GAS. This is combined with anti-inflammatory therapy: NSAIDs for arthritis and glucocorticoids for carditis. Long-term management centers on secondary prophylaxis: regular, prolonged administration of long-acting intramuscular penicillin (typically benzathine penicillin G; trade names vary by country) to prevent recurrent attacks and limit progression of cardiac damage.

Differential Diagnosis

Because ARF is multisystem, it requires a broad differential diagnosis. Migratory polyarthritis in ARF should be distinguished from other causes of arthritis, especially reactive arthritis and juvenile idiopathic arthritis (JIA). In contrast to many other causes, the arthritis of ARF typically improves rapidly and completely with aspirin or other NSAIDs. Carditis should be differentiated from viral myocarditis, and chorea from other hyperkinetic movement disorders. The presence of multiple major Jones criteria in the setting of confirmed preceding streptococcal infection makes ARF the most likely diagnosis.