Rheumatic fever

Definition

Acute rheumatic fever (ARF) is a non-suppurative, acute inflammatory complication of pharyngeal infection with group A streptococci (Streptococcus pyogenes). It causes combinations of arthritis, carditis, subcutaneous nodules, erythema marginatum and chorea. The late consequence is chronic rheumatic heart disease with valve damage.

Occurrence & epidemiology

• First episode possible at any age, most often between 5 and 15 years (peak of streptococcal pharyngitis); uncommon before 3 and after 21 years. A preceding symptomatic pharyngitis is recalled by only about two thirds.
• Worldwide incidence 8–51 per 100,000; below 10 per 100,000 in North America and Western Europe, higher in Eastern Europe, the Middle East, Asia, Africa, Australia and New Zealand; up to 50–250 per 100,000 in some indigenous populations.
• An estimated 39 million or more people worldwide live with rheumatic heart disease.

Aetiopathogenesis

• Molecular mimicry: M proteins of rheumatogenic streptococcal strains share epitopes with proteins of synovium, heart muscle and heart valves; the immune reaction is thus directed against the body's own tissue.
• Host factors: certain HLA class II antigens and the B-cell antigen D8/17; undernutrition, overcrowding and low socioeconomic status favour streptococcal infection.
• Only pharyngeal, not skin or other streptococcal infections trigger rheumatic fever.
• Heart: pancarditis from the inside out (endocardium and valves, myocardium, pericardium); in the acute phase most commonly mitral regurgitation, pericarditis and sometimes aortic regurgitation. In the chronic phase thickening, fusion and retraction of leaflets and chordae cause stenosis or regurgitation, most commonly as mitral stenosis and aortic regurgitation.

Clinical features

• Onset: typically about 2–3 weeks after the streptococcal infection.
• Migratory polyarthritis: the most common manifestation (about 35–66 % of children), often with fever; mainly affects ankles, knees, elbows and wrists; severe pain with comparatively little swelling; leaves no permanent damage.
• Carditis: in about 50–70 % of first episodes; valvulitis is the most consistent feature; subclinical valve involvement detectable only by echocardiography in up to 18 %. Typical is an apical holosystolic mitral regurgitation murmur; also tachycardia (especially during sleep), pericardial rub, cardiac enlargement, heart failure.
• Subcutaneous nodules: painless, on the extensor surfaces of large joints, in fewer than 10 % of children, usually together with arthritis and carditis.
• Erythema marginatum: serpiginous, flat or slightly raised, painless rash on the trunk and proximal limbs, in fewer than 6 % of children.
• Sydenham chorea: in about 10–30 % of children, often only months after the infection; rapid irregular movements, fluctuating grip strength ("milkmaid's grip"), grimacing, tongue darting, muscular hypotonia.
• General: fever of 38.5 °C or more, anorexia, malaise.

Histology

Characteristic are Aschoff bodies: granulomatous collections of leukocytes, myocytes and interstitial collagen, mainly in the myocardium; similar foci can be found in synovium and subcutaneous nodules. Erythema marginatum shows perivascular neutrophilic and mononuclear infiltrates of the dermis.

Diagnosis

Modified Jones criteria

Major criteria (low-risk population): carditis (clinical and/or subclinical), polyarthritis, chorea, erythema marginatum, subcutaneous nodules.

Minor criteria (low-risk population): polyarthralgia, ESR above 60 mm/h or CRP above 30 mg/l, fever of 38.5 °C or more, prolonged PR interval on the ECG.

Moderate- and high-risk populations: monoarthritis and polyarthralgia also count as major criteria; minor criteria are monoarthralgia, fever of 38.0 °C or more, ESR of 30 mm/h or more and/or CRP of 30 mg/l or more, and a prolonged PR interval. A low-risk population is one in which acute rheumatic fever occurs in no more than 2 per 100,000 school-age children per year or rheumatic heart disease is diagnosed in no more than 1 per 1000 people.

Diagnosis of a first episode requires 2 major or 1 major and 2 minor criteria plus evidence of preceding group A streptococcal infection (raised or rising antistreptolysin O or anti-DNase B titer, positive throat culture or positive rapid test). Sydenham chorea alone is sufficient if other causes have been excluded.

Investigations

• Detection of streptococcal infection: throat culture and rapid test are often already negative when rheumatic fever appears; antistreptolysin O and anti-DNase B titres peak 3–6 weeks after the pharyngitis. About 80 % of children with rheumatic fever have a markedly raised antistreptolysin O titre.
• Inflammatory markers: ESR typically above 60 mm/h, CRP above 30 mg/l and often above 70 mg/l; leukocytes 12,000–20,000/µl.
• ECG: prolonged PR interval in only about 35 % of children; higher-degree AV block uncommon; signs of pericarditis or chamber enlargement.
• Doppler echocardiography in all patients: also detects subclinical carditis. Pathological mitral regurgitation: seen in at least 2 views, jet length of 2 cm or more in at least one, peak velocity above 3 m/s, pansystolic. Pathological aortic regurgitation: seen in at least 2 views, jet length of 1 cm or more, peak velocity above 3 m/s, pandiastolic. Morphologically, among others, annular dilatation, chordal elongation, leaflet prolapse, nodular thickening of the leaflet edges.
• Troponin: normal values exclude marked myocardial damage.
• Joint aspiration when needed to exclude other causes of arthritis (cloudy fluid with neutrophils, culture negative).

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Rheumatic Fever
2. StatPearls: Acute Rheumatic Fever
3. Rheumatic fever – new diagnostic criteria, Reumatologia 2018

Cross-references