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PE22.4 | Acute Rheumatic Fever — SDL Guide

Learning Objectives

• Describe the aetiology and pathogenesis of acute rheumatic fever following Group A streptococcal pharyngitis
• Apply the 2015 revised Jones Criteria for diagnosis of ARF in high-risk populations including India
• Recognise the clinical features of carditis, migratory polyarthritis, Sydenham chorea, erythema marginatum, and subcutaneous nodules
• Outline the management of ARF including eradication therapy, anti-inflammatory treatment, and cardiac failure management
• Prescribe and counsel on secondary prophylaxis with benzathine penicillin G, including dose, frequency, and duration by severity

INSTRUCTIONS

Acute rheumatic fever is preventable and treatable, yet it remains the leading cause of acquired heart disease in children and young adults in India and other low- and middle-income countries. A single missed Group A streptococcal throat infection, not treated with penicillin, can trigger an autoimmune cascade that scars the mitral valve and leads to heart failure by age 30. Understanding the 2015 Jones criteria, recognising subclinical carditis, and prescribing the correct secondary prophylaxis regimen are skills that will directly prevent rheumatic heart disease in your community-level practice.

References

• Ghai Essential Pediatrics, 9th edition, Ch 14 — Acute Rheumatic Fever (textbook)
• Nelson Textbook of Pediatrics, 21st edition, Ch 464 — Acute Rheumatic Fever (textbook)
• IAP Guidelines on Rheumatic Fever and Rheumatic Heart Disease; AHA 2015 Jones Criteria Revision (guidelines)

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Version 2.0 | NMC CBUC 2024

Clinical Presentation of Acute Rheumatic Fever

Acute rheumatic fever presents 2–4 weeks after Group A streptococcal pharyngitis in a child typically aged 5–15 years, the age of peak streptococcal pharyngeal colonisation. The clinical features are those of a multi-system inflammatory disease affecting the heart, joints, skin, and central nervous system, and they are best understood through the Jones Criteria, which were specifically designed to capture the combination of features that characterises ARF rather than mimicking conditions. The cardinal presentation in India is a school-age child with fever, a migratory polyarthritis that is disproportionately painful relative to its physical appearance, and a newly audible cardiac murmur — this triad demands immediate consideration of ARF and its implications for the heart.

1. Carditis (most important major criterion — the only criterion with lasting sequelae):
Pancarditis involves pericardium (pericardial rub, chest pain), myocardium (tachycardia, impaired contractility, gallop), and most critically endocardium (valvulitis — most common manifestation). The mitral valve is most commonly affected (mitral regurgitation → apical pansystolic murmur radiating to axilla); the aortic valve is secondarily affected (aortic regurgitation → early diastolic murmur at left sternal border). The tricuspid and pulmonary valves are rarely affected. Valvulitis causes commissural fusion and leaflet thickening over time (rheumatic valve disease). The 2015 revised criteria allow subclinical carditis (echo-proven valvulitis without audible murmur) as a major criterion in high-risk populations — this is critical because subclinical carditis is common in India (up to 15–20% of ARF episodes).

2. Polyarthritis (most common major criterion):
A migratory polyarthritis affecting large joints (knees, ankles, elbows, wrists) in an asymmetric, additive-then-migratory pattern. Each joint is hot, swollen, exquisitely tender — the pain is characteristically disproportionate to the clinical signs (the child may refuse to walk). Crucially, arthritis in ARF resolves completely without joint damage, typically within 4 weeks, and responds dramatically to aspirin within 24–48 hours ('satisfying' aspirin response). In high-risk populations (Jones 2015 revision): monoarthritis alone qualifies as a major criterion because monoarthritis followed by dramatic aspirin response in a high-prevalence setting has a high positive predictive value.

3. Sydenham chorea (isolated major criterion — can occur months after the other features):
Sydenham chorea is an involuntary, purposeless, non-rhythmic movement disorder affecting the face, tongue, and limbs — the child cannot keep the tongue protruded steadily ('jack-in-the-box tongue'), handwriting deteriorates, and voluntary movements become clumsy. It is a late manifestation, appearing up to 6 months after the preceding streptococcal infection, and may occur in isolation without other features of ARF. It is self-limiting (weeks to months) but may recur with subsequent streptococcal infections.

4. Erythema marginatum (uncommon; <10% of cases):
A faint, evanescent, pink rash with pale centres and raised serpiginous red margins, occurring on the trunk and proximal limbs (never the face). It is transient — may be visible only after warming the skin or applying heat. Non-pruritic.

5. Subcutaneous nodules (rare; <5% of cases; occur with severe carditis):
Firm, non-tender nodules over bony prominences and tendons (occiput, vertebral spines, olecranon, patella, metatarsal heads). Freely mobile. They appear with severe carditis and are associated with a higher risk of RHD.

Major Jones Criteria in Acute Rheumatic Fever

Aetiology and Pathogenesis

Acute rheumatic fever is the consequence of an autoimmune response to Group A streptococcal (GAS) pharyngitis in a genetically susceptible individual. The key insight is that ARF is not caused by direct bacterial invasion of the heart or joints — the GAS infection itself is confined to the throat — but by a cross-reactive immune response where antibodies and T cells generated against streptococcal antigens mistakenly attack structurally similar host proteins. This principle of molecular mimicry explains both the pathology and the fundamental logic of prevention: eradicate GAS from the throat before the immune response matures, and ARF cannot occur. Three conditions are required for ARF to develop, and understanding each informs a different aspect of prevention and treatment strategy.

Aetiology — required conditions for ARF:

1. Group A Streptococcal pharyngitis: Only pharyngitis (NOT skin infection/impetigo) triggers ARF. This is because the pharyngeal immune response — with its abundant lymphoid tissue — generates the systemic autoimmune cascade. M protein, present on the streptococcal cell surface, is the primary virulence factor and molecular mimicry antigen.

1. Genetic susceptibility: Only ~3% of individuals with untreated GAS pharyngitis develop ARF, indicating that host genetics play a crucial modifying role. HLA class II alleles (DR2, DR4, DR7) are associated with susceptibility.

1. Immune dysregulation: B cells produce antibodies against GAS M protein; these cross-react with cardiac myosin (myocarditis), cardiac valve endothelium (valvulitis), brain basal ganglia (chorea), and joint synovium (arthritis). Molecular mimicry is the central mechanism.

Pathology of carditis:

• Aschoff body: the pathognomonic granulomatous lesion of rheumatic carditis — a central area of fibrinoid necrosis surrounded by histiocytes (Anitschkow myocytes with characteristic 'caterpillar' nuclei), giant cells, and lymphocytes. Found in the myocardium and pericardium.
• Valvulitis: the endocardial lining of valves becomes inflamed; small verrucae (warty vegetations) form along the line of valve closure, particularly the mitral valve. Repeated episodes cause progressive leaflet thickening, fusion of commissures, and shortening of chordae tendineae → mitral stenosis over years.
• Pericarditis: fibrinous pericarditis causes chest pain and pericardial friction rub; usually resolves without constriction.

Natural history:
Each GAS throat infection in a child with a prior history of ARF triggers a new episode of carditis, progressively damaging the valve with each episode. This is why secondary prophylaxis — preventing recurrent GAS infections — is the cornerstone of preventing RHD progression. The risk of carditis in recurrent ARF episodes is higher than in the first episode.

Acute Rheumatic Fever Pathogenesis

Diagnosis — 2015 Jones Criteria

The Jones Criteria, originally proposed in 1944 and most recently revised in 2015 by the American Heart Association, provide the diagnostic framework for ARF. The 2015 revision is particularly important for India and other high-risk populations because it introduced two-tier criteria — a more sensitive set for high-risk populations (where ARF is endemic, such as Australia's Indigenous communities and India) and the original stricter criteria for low-risk populations. India is classified as a high-risk population, so the high-risk criteria apply. The diagnosis requires fulfilling the criteria AND demonstrating evidence of a preceding GAS infection — the criteria alone, without microbiological or serological evidence of recent streptococcal infection, do not constitute a diagnosis of ARF.

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Diagnosis of ARF (2015 Jones Criteria — HIGH-RISK populations, applicable to India):

Diagnosis = 2 major criteria, OR 1 major + 2 minor criteria + EVIDENCE of preceding GAS infection.

Major criteria:
1. Carditis — clinical (new murmur, pericardial rub, cardiac failure) or echocardiographic (subclinical carditis: mitral/aortic regurgitation on echo without audible murmur). Echo for subclinical carditis is a new major criterion in the 2015 revision for high-risk populations.
2. Polyarthritis — or monoarthritis in high-risk populations (Jones 2015 revision)
3. Sydenham chorea — can be the sole basis for ARF diagnosis (lone chorea) when occurring in a child without another explanation, even without elevated inflammatory markers
4. Erythema marginatum — evanescent, non-pruritic, central clearing rash on trunk/proximal limbs (not face)
5. Subcutaneous nodules — firm, painless, over bony prominences; associated with severe carditis

Minor criteria:
1. Monoarthralgia (not monoarthritis — arthralgia = pain without objective findings; only applicable if arthritis is NOT a major criterion)
2. Fever — ≥38.0°C for high-risk populations (≥38.5°C for low-risk)
3. Elevated ESR — ≥60 mm/h (high-risk) OR elevated CRP ≥3.0 mg/dL
4. Prolonged PR interval — beyond age-appropriate upper limit on ECG (cannot be counted if carditis is a major criterion)

Evidence of preceding GAS infection (all require at least ONE):
• Elevated or rising ASO titre (>200 Todd units in children)
• Positive throat culture for Group A Streptococcus
• Positive rapid antigen test for GAS
• Elevated anti-DNase B titre

Special situations:
• Lone chorea: ARF can be diagnosed on the basis of chorea alone without fulfilling other criteria, as chorea typically appears late (months after the acute infection) when ASO titres may have normalised.
• Insidious carditis: if rheumatic carditis presents slowly without other features, diagnosis requires echo-documented RHD in a high-prevalence setting + clinical judgement.

Investigations in ARF:

Investigation	Finding in ARF	Significance
ASO titre	Elevated (>200 Todd units)	Evidence of preceding GAS
Throat culture	May be positive for GAS	Confirms active infection
ESR/CRP	Elevated	Minor criterion + disease activity
ECG	Prolonged PR interval	Minor criterion; monitor for heart block
Echocardiography	Mitral/aortic regurgitation	Diagnoses subclinical carditis; quantifies severity
Blood count	Neutrophilic leucocytosis	Non-specific acute inflammation