Acute Rheumatic Fever & Rheumatic Heart Disease

Trigger and mechanism

The antecedent infection. Acute rheumatic fever follows untreated pharyngitis caused by group A Streptococcus (S. pyogenes), after a latent period of about 2–4 weeks. It mainly affects children aged 5–15, and each new streptococcal throat infection can trigger a recurrence. Streptococcal skin infection (impetigo) can cause post-streptococcal glomerulonephritis but not rheumatic fever.

Molecular mimicry. Antibodies and T cells raised against streptococcal M protein, which is also the organism's chief antiphagocytic virulence factor, cross-react with host antigens: cardiac myosin, valve glycoproteins such as laminin, and neurons of the basal ganglia. The resulting antibody-mediated injury is a type II hypersensitivity reaction. The heart is never infected, so the valve lesions are sterile. Superantigen exotoxins, in contrast, cause streptococcal toxic shock, not rheumatic fever.

Diagnosis: the Jones criteria

Evidence of streptococcal infection. Throat cultures are often negative by the time symptoms begin. Prior infection is therefore documented by an elevated or rising antistreptolysin O (ASO) or anti-DNase B titer, or by a positive throat culture or rapid antigen test. Anti-DNase B stays elevated longer than ASO, which helps when chorea appears months later.

Minor criteria and the rule. The minor criteria are fever, arthralgia, elevated ESR or CRP, and a prolonged PR interval. With evidence of preceding streptococcal infection, a first attack requires 2 major criteria, or 1 major plus 2 minor. Isolated Sydenham chorea can establish the diagnosis on its own. A finding counts only once: arthralgia is not added as a minor criterion when arthritis is counted as major, and a prolonged PR interval is not added when carditis is counted.

Carditis in detail. Myocarditis with heart failure is the main cause of death in the acute phase. Valvulitis usually produces mitral regurgitation, heard as an apical holosystolic murmur, sometimes with aortic regurgitation. A soft apical mid-diastolic murmur during acute carditis (the Carey Coombs murmur) reflects inflamed mitral leaflets, not fixed stenosis.

Pathology

Aschoff bodies. The pathognomonic lesion of rheumatic carditis is the Aschoff body. It is an interstitial focus of fibrinoid necrosis surrounded by lymphocytes (mainly T cells), plasma cells, activated macrophages, and occasional multinucleated giant cells. These granuloma-like lesions heal by fibrous scarring. They should not be confused with Councilman bodies, which are apoptotic hepatocytes.

Anitschkow cells. These activated macrophages within Aschoff bodies have abundant cytoplasm and a central, slender, wavy ribbon of chromatin. The nucleus looks like a caterpillar when cut lengthwise and like an owl's eye in cross-section.

Valves and atrium. Small warty vegetations (verrucae) line the closure lines of inflamed leaflets. They are sterile and nondestructive, unlike the bulky vegetations of infective endocarditis. MacCallum plaques are patches of subendocardial thickening in the left atrium.

Chronic rheumatic heart disease

Mitral stenosis. Repeated attacks thicken and calcify the leaflets, fuse the commissures, and shorten, thicken, and fuse the chordae tendineae. Decades later the result is a narrow fish-mouth (buttonhole) mitral orifice. The mitral valve is involved in nearly all cases, the aortic valve in many, the tricuspid less often, and the pulmonic rarely. Auscultation reveals a loud S1 and an opening snap followed by a low-pitched mid-diastolic rumble at the apex.

Downstream effects. Left atrial pressure rises, causing pulmonary congestion. The left atrium then dilates, which predisposes to atrial fibrillation, and stasis in the dilated atrium forms mural thrombi that embolize to the brain and elsewhere. The left atrium is the most posterior chamber, so when enlarged it compresses the esophagus (dysphagia). It can also compress the left recurrent laryngeal nerve against the pulmonary artery (hoarseness, Ortner syndrome) and elevate the left main bronchus.

Treatment and prevention

The acute attack. Penicillin eradicates residual streptococci even if the throat culture is negative. Aspirin or other NSAIDs control the arthritis.

Secondary prophylaxis. Intramuscular benzathine penicillin G every 3–4 weeks prevents the recurrences that progressively scar the valves. Continuous prophylaxis is needed because repeat infections can be subclinical. Its duration depends on cardiac involvement:

Primary prevention. Treating streptococcal pharyngitis with penicillin or amoxicillin within 9 days of symptom onset prevents the first attack. Antibiotic prophylaxis before dental work is a separate measure that targets infective endocarditis, not rheumatic fever.