Rheumatic fever

Overview

Acute rheumatic fever (ARF) is an immune-mediated inflammatory disease that follows a throat infection with group A beta-haemolytic streptococcus (Streptococcus pyogenes). It affects the heart, joints, skin and brain.

It is mainly a disease of children and young adults in low- and middle-income countries, including Pakistan, where overcrowding and limited access to treatment of sore throats keep it common. Its importance lies in the heart: repeated attacks lead to chronic rheumatic heart disease, the main cause of mitral stenosis.

Aetiology

• Group A streptococcal pharyngitis (sore throat or scarlet fever). Streptococcal skin infection (impetigo) leads to post-streptococcal glomerulonephritis, not rheumatic fever.
• Only a small proportion of untreated throat infections lead to ARF.
• Latent period: symptoms start 2–3 weeks after the sore throat.
• Risk factors: poverty, overcrowding, poor access to healthcare, genetic susceptibility, previous rheumatic fever (recurrences are common).
• Incidence has fallen greatly in wealthy countries with better hygiene and antibiotic use.

Pathogenesis

• Molecular mimicry: antibodies and T cells made against the streptococcal cell-wall M protein cross-react with cardiac myosin and other host proteins (laminin in valves, synovium, basal ganglia neurons).
• It is not caused by direct infection of the heart or by a toxin. Throat cultures are often negative by the time ARF appears.

Pathology

• Pancarditis: inflammation of endocardium, myocardium and pericardium.
• Aschoff bodies: focal areas of fibrinoid necrosis surrounded by lymphocytes, macrophages and Anitschkow cells ("caterpillar" or owl-eye nuclei). They are characteristic of rheumatic carditis.
• Verrucous vegetations: small, sterile, warty lesions along the lines of valve closure.
• MacCallum plaque: thickened patch on the posterior left atrial wall.
• Chronic stage: fibrosis, commissural fusion, thickened and shortened chordae ("fish-mouth" valve).

Clinical features

The illness typically begins with fever, malaise and joint pain a few weeks after a sore throat.

Major manifestations

Minor manifestations

• Fever.
• Arthralgia (not counted if arthritis is used as a major criterion).
• Raised ESR or CRP; raised white cell count.
• Prolonged PR interval on ECG (not counted if carditis is used as a major criterion).
• Previous rheumatic fever or rheumatic heart disease.

Diagnosis

Modified Jones criteria

Evidence of recent group A streptococcal infection, PLUS:

• 2 major criteria, or
• 1 major + 2 minor criteria.

Exceptions: Sydenham chorea or indolent (slowly developing) carditis alone may be enough, because they appear long after the infection when strep evidence may have faded.

Evidence of streptococcal infection

• Raised or rising antistreptolysin O (ASO) titre (the commonest test); anti-DNase B is an alternative.
• Positive throat culture for group A streptococcus (or rapid antigen test).
• Recent scarlet fever.

Investigations

Differential diagnosis

• Septic arthritis, reactive arthritis, juvenile idiopathic arthritis, SLE.
• Infective endocarditis (fever plus murmur).
• Viral arthritis, sickle cell crisis, leukaemia.
• Other causes of chorea (drugs, Wilson disease, SLE, Huntington disease).

Management

Acute attack

• Admit; bed rest while there is active carditis or heart failure; gradual mobilisation as ESR/CRP settle.
• Eradicate the streptococcus: penicillin (oral penicillin V course or a single IM benzathine penicillin injection); erythromycin or clarithromycin if allergic. Give it even if the throat swab is negative.
• Arthritis and fever: aspirin or other NSAIDs; they relieve symptoms quickly but do not prevent later heart damage.
• Severe carditis: some experts give high-dose prednisolone, although good evidence of benefit is lacking.
• Heart failure: diuretics, ACE inhibitors, rest; urgent valve surgery rarely.
• Chorea: a calm environment; dopamine-blocking drugs (e.g. haloperidol) or other agents for severe movements; it settles over weeks to months.

Secondary prophylaxis (prevention of recurrence)

The most important long-term step, because each new attack adds more valve damage.

• Benzathine penicillin G intramuscularly every month (preferred; better adherence), or daily oral penicillin V.
• Erythromycin if allergic to penicillin.
• Duration (Kumar and Clark): until the age of 20, or for 10 years after the most recent attack, whichever is longer.
• Longer courses are advised when carditis or established valve disease is present (often into middle age, sometimes lifelong).

Primary prevention

• Prompt diagnosis and penicillin treatment of streptococcal sore throat prevents most first attacks.
• Better housing and less overcrowding.

Complications and prognosis

• Acute: heart failure from severe carditis, pericardial effusion, arrhythmia.
• Chronic rheumatic heart disease: more than half of patients who have carditis go on to develop chronic valve disease, typically 10–20 years later.
  • Mitral valve is most often affected (mitral stenosis is the classic late lesion; MR is commoner in the acute and early phase).
  • Aortic valve next (often with mitral disease); tricuspid less often; pulmonary rarely.
• Complications of rheumatic valve disease: AF, stroke, infective endocarditis, heart failure, pulmonary hypertension, problems in pregnancy.
• Arthritis and chorea leave no permanent damage; only the heart is scarred.

Quick revision

• ARF = autoimmune reaction 2–3 weeks after group A strep throat infection (molecular mimicry, M protein).
• Major: carditis, migratory polyarthritis, Sydenham chorea, erythema marginatum, subcutaneous nodules.
• Minor: fever, arthralgia, raised ESR/CRP, prolonged PR, previous rheumatic fever.
• Diagnosis: strep evidence (ASO, throat culture, scarlet fever) + 2 major or 1 major + 2 minor; chorea alone can suffice.
• Carditis: apical pansystolic (MR), Carey Coombs mid-diastolic, pericarditis, heart failure.
• Aschoff bodies with Anitschkow cells are characteristic.
• Treat: penicillin, aspirin/NSAIDs, ± steroids for severe carditis, haloperidol for severe chorea.
• Prophylaxis: monthly IM benzathine penicillin until 20 or 10 years after last attack (longer with carditis).
• Late result: rheumatic mitral stenosis.

Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).

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