Sydenham Chorea

Sydenham chorea is an acquired autoimmune movement disorder that follows group A streptococcal infection and is a major manifestation of acute rheumatic fever. It causes chorea, hypotonia, emotional lability and obsessive compulsive features, mostly in children.

It occurs in about 20 to 30% of patients with acute rheumatic fever, and is commonest in low and middle income regions where rheumatic fever remains endemic. Onset is between 5 and 15 years, with a female predominance after puberty.

Latency. Chorea appears 1 to 8 months (sometimes up to 6 months or more) after the streptococcal infection, often when other signs of rheumatic fever have faded; carditis is present in about 60 to 80%.

Course. Chorea usually remits within 2 to 6 months (mean about 4 months), but may last 2 years; recurrences occur in about 20 to 30%, often with pregnancy or oestrogen containing contraception.

Pathophysiology.

Antibodies to group A streptococcal carbohydrate cross-react with neuronal antigens in the basal ganglia (such as lysoganglioside and dopamine D2 receptors), causing neuronal dysfunction.

Molecular mimicry and T cell activation lead to the inflammation in the caudate and putamen.

• Chorea (generalised or hemichorea), motor impersistence ("milkmaid grip", darting tongue), hypotonia and clumsiness.
• Emotional lability, irritability, anxiety, obsessive compulsive behaviour and attention problems, sometimes before the chorea.
• Worsening with stress and abolition in sleep.
• Carditis (murmur, heart failure), arthritis, erythema marginatum or nodules in some.

Red flags.

• Heart failure, a new murmur, or chest pain (carditis).
• Severe chorea (paralytic chorea) with inability to eat, walk or speak.
• Psychosis or severe obsessive compulsive symptoms.
• Pregnancy associated chorea (chorea gravidarum).

• Clinical diagnosis: chorea with evidence of recent streptococcal infection is not required to be proven if chorea is the only major feature, with other causes excluded.
• Throat swab, anti-streptolysin O and anti-DNase B titres; inflammatory markers may be normal.
• Echocardiography for all patients to detect carditis, and ECG for conduction abnormality.
• MRI of the brain if features are atypical; tests to exclude Wilson disease, systemic lupus erythematosus, antiphospholipid syndrome, thyroid disease, drugs and Huntington disease.

Differential diagnosis. Systemic lupus erythematosus and antiphospholipid syndrome, Wilson disease, Huntington disease, chorea gravidarum, drug induced chorea, thyrotoxicosis, tic disorders, PANDAS and benign hereditary chorea.

• Eradicate streptococcus: phenoxymethylpenicillin 500 mg orally twice daily for 10 days in adults and in children over 27 kg (250 mg twice daily in children under 27 kg). Maximum 1 g daily for this use. Monitor for rash and anaphylaxis. Avoid in penicillin allergy; reduce the frequency in severe renal impairment (creatinine clearance under 10 mL/min). In allergy: azithromycin 500 mg orally on day 1, then 250 mg daily for 4 days (children 12 mg/kg once daily for 5 days, maximum 500 mg), with ECG monitoring if QT-prolonging drugs are taken.
• Secondary prophylaxis: benzathine benzylpenicillin 1.2 million units intramuscularly every 4 weeks (every 3 weeks in high risk settings; 600,000 units for children under 27 kg). Continue for at least 5 years after the last attack or until age 21, whichever is later; for carditis, 10 years or until age 40 for mild carditis, and lifelong for severe valve disease. Monitor for rash and injection site reactions. Avoid in penicillin allergy; in allergy use erythromycin 250 mg orally twice daily.
• Rest, a calm environment, safety measures and school support.
• Mild chorea needs no drug. For disabling chorea, sodium valproate in children: 10 to 15 mg/kg orally daily in 2 divided doses, increased to a usual 20 to 30 mg/kg daily. Maximum 60 mg/kg daily. Monitor liver function, platelets and ammonia. Avoid in liver disease, mitochondrial disease and urea cycle disorders; contraindicated in girls and women of childbearing potential unless a pregnancy prevention programme is in place.
• Carbamazepine as an alternative in boys and in girls when valproate is unsuitable: 5 mg/kg orally daily in 2 divided doses, increased every week to a usual 10 to 20 mg/kg daily. Maximum 1000 mg daily in children under 15 years. Monitor sodium, blood count and liver function; check HLA-B*1502 in at risk Asian ancestry; stop at the first rash.
• Severe or refractory chorea: prednisolone 1 mg/kg orally daily (maximum 60 mg) for 2 weeks, then tapered over 2 to 4 weeks. Monitor blood pressure, glucose, mood and infection. Avoid with active untreated infection; use caution in diabetes and hypertension.
• Treat carditis and heart failure with cardiology input.
• Treat obsessive compulsive symptoms with psychological therapy, and review mood.

Monitoring. Review every 2 to 4 weeks during chorea, then 3 monthly; echocardiography at diagnosis and during follow up; check adherence to prophylaxis.

Referral and escalation. Paediatric neurology and cardiology for all patients; psychiatry for severe behavioural symptoms.

Special groups. Adolescent girls and pregnancy: recurrence risk with oestrogens, so avoid oestrogen containing contraception and counsel; valproate is avoided. Low income settings: ensure access to long term prophylaxis.