What is the diagnosis and treatment for a 13-year-old male patient with a history of streptococcal pharyngitis and suspected acute rheumatic fever (ARF) presenting with symptoms of rash, bone pain, and swelling, and at risk for Sydenham chorea?

Sydenham Chorea: Clinical Overview and Management

Definition and Pathophysiology

Sydenham chorea (SC) is a major manifestation of acute rheumatic fever (ARF), representing the most common cause of acquired chorea in children worldwide, resulting from an autoimmune response following Group A streptococcal (GAS) pharyngitis. 1, 2, 3

• SC develops through molecular mimicry, where antibodies and T-cells generated against streptococcal M-protein cross-react with structurally similar cardiac and neuronal tissue antigens, triggering autoimmune inflammation in genetically susceptible individuals 4
• The latency period between GAS pharyngitis and SC onset is typically 14-21 days, though at least one-third of cases result from asymptomatic streptococcal infections 1, 4
• SC accounts for approximately 96% of acute chorea cases presenting to hospitals in areas endemic for ARF 5

Clinical Presentation

Neurologic Features

• Motor manifestations: Involuntary, fleeting, irregular, nonrhythmic choreiform movements affecting face and extremities; chorea may be unilateral in 30% of cases 2, 5
• Associated neurologic symptoms: Dysarthria (67%), gait disturbance (51%), deterioration of handwriting (29%), behavior changes (46%), and headache (11%) 5
• Nonmotor symptoms: Obsessive-compulsive behavior and attention-deficit/hyperactivity disorder manifestations 2
• Severe presentation: Chorea paralytica, where muscle tone is so decreased that patients become bedridden 2

Cardiac Involvement

• Carditis occurs in 44% of SC patients and represents the primary source of morbidity 5
• All patients with suspected SC must undergo immediate echocardiography with Doppler to assess for pathological mitral and/or aortic regurgitation and document baseline cardiac status 4
• Other ARF manifestations are less common: arthritis (11%), erythema marginatum (3%), subcutaneous nodules (rare) 5

Diagnostic Approach

Laboratory Confirmation

• Elevated or rising anti-streptolysin O (ASO) titers and/or anti-DNase B antibodies confirm recent GAS infection in 99% of tested patients 4, 5
• ASO titers peak 3-6 weeks after pharyngitis and remain elevated for several months; anti-DNase B titers peak 6-8 weeks post-infection 1, 4
• Elevated acute phase reactants (ESR, CRP) and possible prolonged PR interval on ECG support the diagnosis 4

Neuroimaging Considerations

• Neuroimaging is NOT necessary for typical SC presentations and should be reserved only for atypical cases 5
• In a large retrospective study, neuroimaging was abnormal in only 8 of 32 MRI scans and 1 of 20 CT scans in SC patients, with findings being nonspecific and not aiding diagnosis 5
• Obtain neuroimaging only when: hemichorea is present, history suggests cerebrovascular event, or presentation is otherwise atypical for SC 5

Diagnostic Pitfalls

• Approximately 15% of school-age children are asymptomatic GAS carriers, making it challenging to distinguish true infection from carriage with concurrent viral pharyngitis 4
• SC can be misdiagnosed as a "fidgety" child or psychiatric manifestation 3
• Group C and G streptococcal pharyngitis present identically to GAS but do NOT cause ARF or SC 4

Treatment Protocol

Acute Phase Antimicrobial Therapy

Administer a full therapeutic course of penicillin to eradicate residual GAS, even if throat culture is negative at diagnosis 6, 4

• Penicillin V: 250 mg twice daily for children <27 kg; 500 mg 2-3 times daily for adolescents/adults for 10 days 1, 6
• Alternative for penicillin allergy: Azithromycin 500 mg once daily for 5 days or clarithromycin 250 mg twice daily for 10 days in adults 6
• Benzathine penicillin G: 600,000 units IM for patients <27 kg; 1,200,000 units IM for patients ≥27 kg as single dose 1

Symptomatic Treatment of Chorea

First-line treatment is valproic acid 2

• For patients not responding to valproic acid or presenting with severe chorea (including chorea paralytica), use risperidone 2
• Other dopamine receptor-blocking drugs such as haloperidol may be useful as alternatives 2
• For patients failing conventional therapy or not tolerating medications, consider immunosuppressive treatment with intravenous methylprednisolone followed by tapering oral prednisone 2
• Plasmapheresis and intravenous immunoglobulin are regarded as experimental treatments 2

Anti-inflammatory Therapy for Severe Carditis

• In cases with severe inflammation or cardiac involvement, consider corticosteroids such as prednisone at 1-2 mg/kg/day for 1-2 weeks 6
• For severe cases with significant cardiac involvement, intravenous methylprednisolone (1000 mg/day initially) may be considered, followed by oral prednisone 6

Secondary Prophylaxis: Critical for Prevention

Continuous antimicrobial prophylaxis must be initiated immediately upon ARF/SC diagnosis to prevent recurrences, as at least 20% of SC patients experience recurrent attacks 7, 2

Preferred Regimen

• Benzathine penicillin G 1,200,000 units IM every 4 weeks (600,000 units for patients <27 kg) is the gold standard, being approximately 10 times more effective than oral antibiotics 6, 7
• In high-risk populations or patients with recurrence despite adherence to the 4-week regimen, administer every 3 weeks 6

Alternative Oral Regimens

• Penicillin V 250 mg twice daily (less effective than IM benzathine penicillin) 6
• For penicillin allergy: erythromycin or first-generation cephalosporins (if no immediate-type hypersensitivity) 6

Duration of Prophylaxis (Based on Cardiac Involvement)

The duration depends critically on whether carditis occurred and whether residual heart disease persists:

• SC with rheumatic carditis and residual heart disease: 10 years after last episode OR until age 40 years (whichever is longer), often lifelong 6, 4, 7
• SC with rheumatic carditis but no residual heart disease: 10 years OR until age 21 years (whichever is longer) 6, 4
• SC without carditis: 5 years OR until age 21 years (whichever is longer) 6, 4

Critical Prophylaxis Considerations

• Never stop prophylaxis prematurely, as recurrent ARF worsens cardiac damage progressively 6, 4
• Prophylaxis should continue even after valve surgery, including prosthetic valve replacement 6
• Each recurrence of ARF potentially worsens rheumatic heart disease 4

Recurrence Patterns and Implications

• Recurrent SC occurs in 42% of patients, with episodes occurring 3 months to 10 years after the initial episode 8
• At recurrence, chorea is often the sole rheumatic sign, making diagnosis challenging 8
• Recurrence may represent either susceptibility to the movement disorder or permanent subclinical basal ganglia damage from the initial episode 8

Family and Contact Management

Obtain throat swab specimens from ALL household contacts of a child with ARF/SC, and treat positive contacts regardless of symptoms 4

• Family members should receive prompt treatment of any streptococcal infections 6
• This prevents transmission and potential ARF development in genetically susceptible family members 4

Prognosis and Long-term Monitoring

• SC is usually self-limited, with marked improvement often occurring within 1-2 weeks of treatment initiation 3
• Morbidity is primarily related to cardiac lesions rather than neurologic sequelae 2
• Obsessive-compulsive behavior associated with SC is typically not as severe as in other conditions like Tourette's syndrome 2
• The high risk of recurrent attacks (20%) and progressive cardiac damage necessitates lifelong vigilance and adherence to prophylaxis protocols 2