Paediatrics chapters
Rheumatic fever and secondary prophylaxis
Acute rheumatic fever after a group A streptococcal sore throat: how it damages the heart, the major and minor Jones criteria, the tests that support the diagnosis, aspirin and steroid treatment, and how long penicillin prophylaxis must continue.
- Rheumatic fever is a delayed, non-suppurative immune reaction 2-4 weeks after group A streptococcal pharyngitis, mostly at 5-15 years; antibodies against streptococcal M protein cross-react with heart, joints, skin and brain.
- Diagnose with the Jones criteria: 2 major, or 1 major + 2 minor, plus evidence of recent strep infection; majors are carditis, migratory polyarthritis, chorea, erythema marginatum, subcutaneous nodules.
- Treat with penicillin to clear strep, aspirin for arthritis and mild carditis, prednisolone for carditis with cardiomegaly or failure, then long-term secondary prophylaxis with benzathine penicillin.
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Overview
Acute rheumatic fever (ARF) is a delayed, non-pus-forming inflammatory illness that follows pharyngitis with group A beta-haemolytic streptococcus (GAS). It affects the heart, joints, brain, skin and subcutaneous tissue. Joints, skin and brain recover fully; the heart may be scarred for life as rheumatic heart disease (RHD). It remains an important, preventable cause of heart disease (Nelson), though Akbar notes its incidence is falling in Pakistan.
The illness is preventable: treating strep throat prevents first attacks, and regular penicillin prophylaxis prevents recurrences; the risk of permanent heart damage rises with each recurrence.
Epidemiology and risk factors
- First attack usually at 5-15 years; rare under 4 years.
- No sex difference, except chorea is commoner in girls.
- Linked to poverty, overcrowding, poor housing and poor access to healthcare.
- Only a small fraction of untreated strep throats (about 1-5% with rheumatogenic strains) lead to ARF.
- Skin infections are unlikely to cause ARF; streptococcal infection can instead be followed by glomerulonephritis.
- After one attack, the risk of recurrence with another strep throat is high: about 50% in the first year, falling to about 10% after several years.
- Akbar quotes an annual incidence of about 50 per 100,000 children, falling in Pakistan.
Pathophysiology and immunological basis
- Molecular mimicry: antibodies and T cells raised against streptococcal components (M protein, group A cell wall carbohydrate, hyaluronate capsule) cross-react with similar molecules in heart valves, myocardium, joints and brain (basal ganglia).
- This explains the latent period of 1-5 weeks (average about 3) between sore throat and illness (Akbar; Nelson gives 2-6 weeks); a direct toxin theory (streptolysin O) cannot explain this delay.
- In the heart all three layers are inflamed (pancarditis). The valves take the lasting damage: thickened, oedematous cusps with small nodules on the mitral leaflets, and later chronic progressive valve disease, particularly stenosis.
ARF follows throat infection only, and only after a delay of weeks. A child with sore throat and arthritis on the same day does not have ARF.
Clinical features and major manifestations
Migratory polyarthritis (about 75%)
- The commonest major manifestation.
- Large joints: knees, ankles, wrists, elbows, shoulders (roughly in that order).
- Migratory: as one joint settles, another flares.
- Joints are hot, red, swollen and very tender; the child refuses to move them.
- Responds almost at once to salicylates.
- Heals completely, no deformity.
- Severity of arthritis is inversely related to severity of carditis.
Carditis (about 50-60%)
- Can cause palpitations, chest pain or breathlessness, but is often silent.
- Valvulitis:
- Apical pansystolic murmur of mitral regurgitation, radiating to the axilla (commonest).
- Carey Coombs murmur: soft apical mid-diastolic murmur from narrowing of the mitral valve by thickened, oedematous cusps; a definite sign of mitral valvulitis.
- Early diastolic murmur at the base in aortic valvulitis.
- Myocarditis: tachycardia out of keeping with fever (high sleeping pulse), soft S1, gallop, cardiomegaly, heart failure.
- Pericarditis: chest pain, friction rub, effusion.
- The 2015 revision accepts subclinical carditis (valvulitis seen on echo without a murmur) as meeting the carditis criterion.
Sydenham chorea (about 10-15%)
- Late manifestation; may appear up to 6 months after the strep infection, often when other signs have gone.
- Commoner in girls.
- Never occurs together with arthritis; may coexist with carditis.
- Sudden, jerky, purposeless, non-repetitive movements, mainly of the trunk and proximal limbs.
- Hypotonia, clumsy gait, slurred speech, poor handwriting, emotional lability (laughing and crying).
- Outstretched hands show wrist flexion with finger hyperextension.
- Self-limiting (1 week to over 2 years); rarely leaves lasting neurological damage.
Erythema marginatum (about 1%)
- Pink, serpiginous, ring-shaped rash with pale centres and spreading edges.
- On the trunk and proximal limbs; evanescent (comes and goes), with edges that join or overlap; non-itchy and brought out by warmth (Nelson).
Subcutaneous nodules (under 1%)
- Firm, painless, about 1 cm, freely mobile.
- Over extensor surfaces and bony prominences (elbows, knees, knuckles, ankles), scalp, scapula and spine.
- Strongly linked with severe carditis.
JONES: Joints (migratory polyarthritis), O (a heart-shaped O for carditis), Nodules, Erythema marginatum, Sydenham chorea.
Modified (revised) Jones criteria
| Major manifestations | Minor manifestations |
|---|---|
| Carditis (clinical or subclinical on echo) | Fever |
| Polyarthritis (migratory) | Arthralgia |
| Sydenham chorea | Raised ESR or CRP |
| Erythema marginatum | Prolonged PR interval on ECG |
| Subcutaneous nodules |
Plus evidence of preceding GAS infection: positive throat culture or rapid strep antigen test, or raised or rising ASO (or other antistreptococcal antibody) titre.
Diagnosis of a first attack: 2 major, or 1 major + 2 minor, plus evidence of recent GAS infection.
Exceptions:
- Chorea alone is enough once other causes are excluded; no strep evidence needed.
- Insidious or late-onset carditis with no other explanation; no strep evidence needed.
- Recurrence in a child with known RHD or past ARF: one major, or fever, arthralgia or raised acute-phase reactants, with evidence of recent strep infection, supports a presumptive diagnosis.
If arthritis is counted as a major criterion, arthralgia cannot also be counted as a minor one (Nelson).
9-year-old, fever 38.5 °C, migratory arthritis of knees and ankles, ESR 80, ASO raised, no murmur, normal echo
Major: polyarthritis (1). Minor: fever, raised ESR (2). Arthralgia not counted (arthritis already used)
1 major + 2 minor + evidence of recent strep infection = acute rheumatic feve
Investigations
| Test | Finding and use |
|---|---|
| ESR | Raised in active disease; used to monitor activity; may be falsely raised by anaemia and fall in heart failure |
| CRP | Raised; not affected by anaemia; falls with control of inflammation |
| ASO titre | Raised in about 85%; above about 200 Todd units is suggestive, a single value of 500 units indicates recent infection, about 333 is borderline (then add another antibody test) |
| Anti-DNase B | Second antibody test; anti-hyaluronidase is a third choice |
| Throat swab | GAS grown in only a minority by the time ARF appears |
| FBC | Mild anaemia, neutrophil leucocytosis |
| ECG | Prolonged PR (above 0.18 s) is the earliest sign; longer QT; second-degree or complete block; ST-T changes of myocarditis or pericarditis |
| Chest X-ray | Cardiomegaly from failure or effusion |
| Echocardiography | Valvulitis (including subclinical), regurgitation, effusion, ventricular function; follow-up of valve damage |
About one third of children with ARF recall no sore throat, which is why antibody titres matter.
Differential diagnosis
- Arthritis: juvenile idiopathic arthritis, septic arthritis, reactive arthritis (Shigella, Salmonella, Yersinia), post-streptococcal reactive arthritis, SLE, sickle cell crisis, leukaemia.
- Carditis: innocent murmur, viral myocarditis or pericarditis, infective endocarditis, Kawasaki disease, congenital heart disease, mitral valve prolapse.
- Chorea: Wilson disease, Huntington chorea, cerebral palsy, tics, hyperactivity.
Management
1. Rest
- Until signs of inflammation settle (normal pulse and temperature; ESR is the best activity marker).
- Roughly 1-2 weeks for arthritis alone, 2-4 weeks with mild carditis, and several months with moderate to severe carditis.
- Restrict salt if there is heart failure.
2. Eradicate streptococci (in every case)
- Benzathine penicillin single IM injection, 6-12 lac units (0.6-1.2 million units), or a 10-day course of oral penicillin or amoxicillin.
- Penicillin allergy: azithromycin (5 days), erythromycin (10 days) or clindamycin.
- Then start secondary prophylaxis.
3. Anti-inflammatory treatment
| Situation | Drug |
|---|---|
| Arthritis, or carditis without cardiomegaly or failure | Aspirin 50-70 mg/kg/day in four doses for 3-5 days, then about 50 mg/kg/day for 3 weeks, then half that for another 2-4 weeks |
| Carditis with more than minimal cardiomegaly and/or heart failure | Prednisolone 2 mg/kg/day in divided doses for 2-3 weeks, then half the dose for 2-3 weeks, then tapered; start aspirin (50 mg/kg/day for about 6 weeks) as the steroid is tapered to prevent rebound |
- Aspirin and steroids relieve symptoms but do not cure or prevent valve damage.
- Salicylism: vomiting, tinnitus, gastric irritation, hyperventilation (respiratory alkalosis, later metabolic acidosis), hypoglycaemia, bleeding; reduce or stop.
4. Heart failure
Heart failure is an indication for corticosteroids, diuretics or digoxin, with bed rest and salt restriction. Severe failure from a badly damaged valve that does not respond to medical treatment may need valve repair or replacement.
5. Chorea
- Quiet surroundings; protect from injury.
- Phenobarbital (drug of choice in Akbar); if it fails, haloperidol or chlorpromazine. Anti-inflammatory drugs are usually not needed.
- Chorea still needs secondary prophylaxis.
Complications
- Chronic rheumatic heart disease: mitral valve most often, then aortic, then tricuspid. Mitral regurgitation comes first; mitral stenosis follows in 2-10 years.
- Heart failure in the acute attack (myocarditis, valve regurgitation).
- Pericardial effusion; arrhythmias and heart block.
- Later: infective endocarditis on damaged valves and valve failure needing surgery.
- Recurrences, each adding valve damage.
Prognosis
- Joints and chorea recover completely; outcome depends on the heart.
- Worse with severe initial carditis and with each recurrence; children with carditis in the first attack usually get carditis again in a recurrence.
- About 50-70% of children with mild carditis recover without lasting heart disease.
Prevention
Primary prevention
- Treat GAS pharyngitis promptly; penicillin started within 9 days of the sore throat prevents ARF.
- Improve housing and reduce overcrowding; better access to care.
Secondary prophylaxis
Drugs:
- Benzathine penicillin IM, 6-12 lac units (Nelson: 1.2 million units) every 28 days (Nelson): the most effective option because adherence is assured.
- Oral penicillin twice daily (dose by local protocol); Nelson notes oral regimens are generally less effective than the injection.
- Penicillin allergy: erythromycin 250 mg twice daily; sulfadiazine 0.5 g/day under 30 kg and 1 g/day over 30 kg; or another macrolide.
Duration:
| Category | Duration |
|---|---|
| ARF without carditis | 5 years or until age 21, whichever is longer |
| ARF with carditis but no residual valve disease | 10 years or until age 21, whichever is longer |
| ARF with carditis and residual valve disease | 10 years or until age 40, whichever is longer; sometimes lifelong |
Each new GAS throat infection carries about a 50% risk of recurrence in a child who has had ARF, and heart damage worsens with each recurrence, so continuous prophylaxis is essential.
Expect: GAS throat infection (not skin) with a latent period of weeks; age 5-15; molecular mimicry with M protein; the five major and four minor Jones criteria and how to combine them; chorea and indolent carditis as exceptions to strep evidence; migratory large-joint arthritis that responds to aspirin and leaves no damage; Carey Coombs murmur and mitral involvement; chorea in girls, late, never with arthritis; nodules with severe carditis; prolonged PR as minor; ASO interpretation; aspirin for arthritis and prednisolone for carditis with cardiomegaly or failure; phenobarbital for chorea; benzathine penicillin and the prophylaxis duration table.
Quick revision
- ARF follows GAS pharyngitis after 1-5 weeks; ages 5-15; mimicry with M protein.
- Majors: carditis, migratory polyarthritis, chorea, erythema marginatum, nodules. Minors: fever, arthralgia, raised ESR/CRP, long PR.
- 2 major or 1 major + 2 minor, plus strep evidence (not needed for chorea or indolent carditis).
- Arthritis 75%, carditis 50-60%, chorea 10-15%, erythema marginatum about 1%, nodules under 1%.
- Mitral valve most affected; Carey Coombs mid-diastolic murmur in acute carditis.
- Aspirin for arthritis and mild carditis; prednisolone 2 mg/kg/day for carditis with cardiomegaly or failure.
- Prophylaxis: 5 yrs/21; 10 yrs/21; 10 yrs/40 or lifelong.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why does rheumatic fever not follow streptococcal skin infection?
Akbar notes that skin infections are unlikely to produce rheumatic fever; the rheumatogenic strains act through throat infection, while streptococcal infection can instead lead to glomerulonephritis.
Can rheumatic fever be diagnosed without a raised ASO titre?
Yes, when the only finding is Sydenham chorea or slowly developing carditis with no other cause, because these appear long after the infection when antibody levels may have fallen.
Why is benzathine penicillin preferred for secondary prophylaxis?
A single deep injection gives long-lasting penicillin levels, so it does not depend on the child remembering daily tablets, and recurrence rates are lowest with it.
Which children with rheumatic fever get steroids instead of aspirin?
Those with carditis plus more than minimal cardiomegaly or heart failure; arthritis and mild carditis are treated with aspirin.