Acute Rheumatic Fever & RHD

Acute rheumatic fever (ARF) is a delayed, immune-mediated, non-suppurative inflammatory sequel to a group A beta-haemolytic streptococcal (GABHS) pharyngitis. It is a multisystem disease affecting the heart, joints, brain, skin and subcutaneous tissue, but its single most important consequence is rheumatic heart disease (RHD) — chronic, often progressive valvular damage that remains the commonest cause of acquired heart disease in children and young adults in India. For NEET PG, this topic is a perennial favourite: examiners test the Modified Jones Criteria (2015 revision), the pathological hallmark (Aschoff body), the predilection for the mitral valve, and the schedule and duration of benzathine penicillin secondary prophylaxis. The disease typically strikes children aged 5–15 years, peaks in lower socioeconomic strata with overcrowding, and characteristically follows the streptococcal sore throat by a latent period of 2–4 weeks.

A useful framing sentence: ARF "licks the joints but bites the heart" — the arthritis is transient and fully reversible, while the carditis can scar valves for life. Understanding this single line orients the whole topic, because almost every high-yield fact maps onto the contrast between fleeting acute inflammation and permanent fibrotic sequelae.

Etiology & Pathogenesis

The trigger is GABHS pharyngitis (Streptococcus pyogenes), specifically the rheumatogenic M-protein serotypes (e.g., M types 1, 3, 5, 6, 18, 24). A critical exam point: only throat infection causes ARF; streptococcal skin infection (impetigo/pyoderma) causes post-streptococcal glomerulonephritis (PSGN) but not ARF. The classic distinction:

Feature	Acute Rheumatic Fever	Post-strep Glomerulonephritis
Triggering site	Pharyngitis only	Pharyngitis or skin (pyoderma)
Latent period	2–4 weeks	1–2 weeks (throat), 3–6 weeks (skin)
Recurrences	Common (prophylaxis needed)	Rare
Long-term sequel	RHD (valvular)	Usually full renal recovery
Key antibody	ASO (throat), anti-DNase B	Anti-DNase B (skin), ASO (throat)

Pathogenesis — molecular mimicry: Antibodies and CD4+ T cells raised against streptococcal M-protein and the group-A carbohydrate (N-acetyl-glucosamine) cross-react with host antigens. Cross-reactive targets include cardiac myosin and the valvular endothelial protein laminin, the brain's basal ganglia (causing Sydenham chorea), and synovium. Antibody binding to the valve endothelium upregulates VCAM-1, recruiting CD4+ T cells that drive the inflammatory cascade. There is a strong genetic susceptibility linked to HLA-DR7 and the B-cell alloantigen D8/17.

Pathology — the Aschoff body: The pathognomonic lesion is the Aschoff body (Aschoff nodule), a focus of fibrinoid necrosis surrounded by lymphocytes, plasma cells and the characteristic Anitschkow cells — activated macrophages with a central wavy "caterpillar" chromatin bar (hence "caterpillar cells"); when multinucleated they are called Aschoff giant cells. Aschoff bodies are most often found in the myocardium (perivascular) and are the hallmark of rheumatic carditis. MacCallum plaques are areas of subendocardial thickening, classically in the left atrium.

High-yield: Anitschkow cells = "caterpillar cells"; Aschoff body is the pathognomonic lesion of rheumatic carditis and the most specific histological finding. It can persist for years and is the basis of "smouldering" rheumatic activity.

Rheumatic carditis is a pancarditis — it involves endocardium (valves), myocardium and pericardium. Valvulitis produces small, sterile, verrucous vegetations along the lines of valve closure (contrast with the larger, friable, destructive vegetations of infective endocarditis and the sterile vegetations on both surfaces in Libman-Sacks endocarditis of SLE).

Modified Jones Criteria (2015 revision)

Diagnosis of a first episode requires evidence of preceding GABHS infection PLUS either 2 major OR 1 major + 2 minor manifestations. Recurrent ARF can be diagnosed with 2 major, OR 1 major + 2 minor, OR 3 minor manifestations (with evidence of preceding strep).

The landmark 2015 AHA revision introduced risk-stratified criteria, recognising that the older criteria under-diagnosed disease in endemic populations (which includes India). Populations are stratified into low-risk (ARF incidence ≤2/100,000 school-age children/yr or all-age RHD prevalence ≤1/1000/yr) and moderate-to-high-risk (everyone else — India falls here).

	Major criteria	Minor criteria
Low-risk population	Carditis (clinical and/or subclinical), Arthritis (polyarthritis only), Chorea, Erythema marginatum, Subcutaneous nodules	Polyarthralgia; Fever ≥38.5°C; ESR ≥60 mm/hr and/or CRP ≥3.0 mg/dL; Prolonged PR interval
Moderate/high-risk (incl. India)	Carditis (clinical and/or subclinical by echo), Arthritis (monoarthritis or polyarthritis; polyarthralgia may also count), Chorea, Erythema marginatum, Subcutaneous nodules	Monoarthralgia; Fever ≥38°C; ESR ≥30 mm/hr and/or CRP ≥3.0 mg/dL; Prolonged PR interval

Key 2015 changes worth memorising for the exam:

• Subclinical carditis (valvulitis detected only on Doppler echocardiography, with no auscultable murmur) is now accepted as a major criterion. This is one of the most frequently tested updates.
• In high-risk populations, monoarthritis and even polyarthralgia count as the major "arthritis" criterion; monoarthralgia can serve as a minor criterion.
• Lower thresholds for fever (≥38°C) and ESR (≥30 mm/hr) in high-risk groups.
• A manifestation cannot be counted as both major and minor in the same patient (e.g., arthritis used as major cannot also have arthralgia counted as minor).

Mnemonic for major criteria — "JONES" / heart shape ♥ "CASES":

• J (♥) — joints (migratory polyarthritis)
• O (looks like the heart) — carditis (O = the heart)
• N — nodules (subcutaneous)
• E — erythema marginatum
• S — Sydenham chorea

Evidence of preceding streptococcal infection (required, except for indolent chorea or low-grade carditis presenting late): elevated or rising ASO (antistreptolysin O) titre, elevated anti-DNase B, a positive throat culture or rapid antigen test for GABHS, or a recent scarlet fever. ASO peaks at ~3–6 weeks; anti-DNase B peaks later (~6–8 weeks) and is more useful when chorea presents late. A throat culture is often negative by the time ARF manifests because of the latent period.

High-yield: Three situations allow ARF diagnosis without strictly fulfilling Jones criteria — (1) Sydenham chorea alone, (2) indolent carditis presenting insidiously, and (3) recurrence in a patient with established RHD with good supporting evidence.

Clinical Features

Onset is typically 2–4 weeks after the sore throat. The five major manifestations:

1. Migratory polyarthritis (~70%, most common major manifestation): Affects large joints — knees, ankles, elbows, wrists — in a fleeting, asymmetric, "migratory" pattern, each joint inflamed for a few days then resolving. It is exquisitely responsive to salicylates/NSAIDs (dramatic response within 24–48 h is almost diagnostic) and never causes deformity. Beware: if NSAIDs are given too early they can mask the migratory pattern (forme fruste).

2. Carditis (~50%, the most serious): A pancarditis. The earliest and commonest valve affected is the mitral valve → mitral regurgitation produces an apical pansystolic murmur radiating to the axilla. A mid-diastolic flow murmur at the apex (Carey-Coombs murmur) reflects relative mitral stenosis from valvulitis. Aortic regurgitation (early diastolic murmur at left sternal border) is the next commonest. Features of carditis: new significant murmur, cardiomegaly, congestive heart failure, pericarditis (friction rub, effusion, chest pain). The tricuspid and pulmonary valves are rarely involved.

High-yield: Order of valve involvement — Mitral > Aortic >> Tricuspid > Pulmonary. Isolated aortic or right-sided valve disease should make you doubt a rheumatic etiology.

3. Sydenham chorea (St. Vitus dance, ~10–30%): A late, often isolated manifestation appearing 1–6 months after infection (long latency, so ASO may have normalised — use anti-DNase B). Features: involuntary, purposeless, non-rhythmic movements, emotional lability, milkmaid's grip (irregular hand-grip pressure), pronator sign (arms pronate when held overhead), and darting/serpentine tongue. More common in females. Self-limiting (weeks to months) but a strong predictor of future RHD.

4. Erythema marginatum (<6%): Evanescent, non-pruritic, pink macules with serpiginous, well-demarcated margins and central clearing, over the trunk and proximal limbs (never the face); blanches on pressure and worsens with heat.

5. Subcutaneous nodules (<5%): Small, firm, painless, mobile nodules over extensor surfaces and bony prominences (elbows, knees, occiput, spine). They strongly correlate with severe carditis.

Erythema marginatum and subcutaneous nodules are the least common but most specific major criteria.

Investigations

There is no single confirmatory test; diagnosis is clinical (Jones). Investigations support the diagnosis, document streptococcal infection, and assess carditis severity.

• Evidence of strep infection: ASO titre (rising/elevated, >200 Todd units in adults, >330 in children is suggestive), anti-DNase B, throat swab culture, rapid antigen detection test.
• Acute-phase reactants: ESR and CRP elevated (minor criteria; useful to monitor activity and decide when to stop bed rest/anti-inflammatories). Note ESR may be low if CHF coexists.
• ECG: Sinus tachycardia; prolonged PR interval (first-degree AV block) is a minor criterion. Other findings: 2nd/3rd-degree block, ST-T changes of pericarditis.
• Echocardiography (Doppler): Now central — detects subclinical carditis (valvular regurgitation jets meeting morphological + Doppler criteria), quantifies regurgitation/stenosis, pericardial effusion and ventricular function. The WHF (World Heart Federation) criteria are used for echo-based RHD screening.
• Chest X-ray: Cardiomegaly, pulmonary congestion if heart failure.
• Throat culture is frequently negative by presentation owing to the latent interval.

Test	What it shows	Exam pearl
ASO titre	Recent strep (throat)	Peaks 3–6 wk; may be normal in late chorea
Anti-DNase B	Recent strep	Peaks later; best for chorea presenting late
ESR / CRP	Active inflammation	Minor criterion; monitors disease activity
ECG	Prolonged PR	Minor criterion; "PR prolongation ≠ carditis"
Echo-Doppler	Subclinical valvulitis	Major criterion (2015); MR most common jet

Management & Secondary Prophylaxis

Management has three arms: eradicate the streptococcus, suppress inflammation, treat complications, then prevent recurrence.

Stepwise approach:

Step 1 — Eradicate GABHS → give a course of penicillin to all patients regardless of throat culture result → single IM benzathine penicillin G 1.2 million units (6 lakh units if <27 kg) → OR oral penicillin V for 10 days → OR oral azithromycin/erythromycin if penicillin-allergic.

Step 2 — Anti-inflammatory therapy → for arthritis without carditis or mild carditis, give aspirin 80–100 mg/kg/day (children) in divided doses → for moderate-to-severe carditis with CHF/cardiomegaly, give oral corticosteroids (prednisolone 1–2 mg/kg/day) for 2–3 weeks then taper, with aspirin overlap during the taper to prevent rebound.

Step 3 — Treat heart failure / carditis → bed rest and graded ambulation → diuretics, ACE inhibitors, digoxin (cautiously) for CHF → valve surgery only for refractory severe regurgitation.

Step 4 — Manage chorea → usually supportive; for disabling chorea use valproate or carbamazepine (preferred over haloperidol/older agents) → a quiet environment.

Step 5 — Initiate secondary prophylaxis (begins immediately, even before discharge).

High-yield: Salicylates/steroids are symptomatic — they reduce inflammation and joint pain but do NOT prevent or reduce the incidence of subsequent RHD. Only penicillin prophylaxis prevents recurrence and protects the valves.

Secondary prophylaxis — the single most exam-relevant management point. The agent of choice is benzathine penicillin G IM every 3–4 weeks (every 3 weeks in high-incidence settings such as India):

Regimen	Dose	Notes
Benzathine penicillin G (IM) — DOC	1.2 MU (12 lakh) every 3–4 wk; 6 lakh if ≤27 kg	Best compliance/efficacy; 3-weekly in high-risk India
Penicillin V (oral)	250 mg twice daily	Compliance-dependent, less effective
Sulfadiazine (oral)	0.5 g (<27 kg) / 1 g (>27 kg) once daily	Alternative if penicillin-allergic
Erythromycin (oral)	250 mg twice daily	If allergic to both penicillin and sulfa

Duration of secondary prophylaxis (memorise the table — directly asked):

Category	Duration of prophylaxis
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 valvular disease (persistent RHD)	10 years or until age 40 (whichever is longer); often lifelong
After valve surgery / severe RHD	Lifelong prophylaxis

High-yield: The longer of the two limits always applies. "No carditis → 5 yr/age 21; carditis no damage → 10 yr/age 21; carditis with damage → 10 yr/age 40 or lifelong."

Primary prevention = prompt treatment of GABHS pharyngitis with a full course of penicillin within 9 days of symptom onset, which prevents the first attack of ARF. Primordial prevention addresses overcrowding, poverty and access to care. A licensed Strep A vaccine remains investigational.

Infective endocarditis prophylaxis: Note that current AHA guidelines do not recommend routine IE antibiotic prophylaxis for RHD/native valve disease before dental procedures (reserved for prosthetic valves, prior IE, certain congenital lesions). Secondary penicillin prophylaxis (for ARF) and IE prophylaxis are different concepts — a classic distractor.

Complications / Valvular Sequelae

The dreaded outcome is chronic rheumatic heart disease, developing over years from recurrent or severe carditis.

• Mitral stenosis (MS) — the commonest chronic valvular lesion of RHD and almost always rheumatic in origin. Produces a mid-diastolic rumble with presystolic accentuation, loud S1, opening snap at the apex; isolated MS is virtually pathognomonic of rheumatic disease. More common in females.
• Mitral regurgitation — the commonest lesion in acute carditis and in children.
• Aortic regurgitation / stenosis — next most frequent; combined mitral + aortic disease is typical.
• Atrial fibrillation from left atrial enlargement (MS) → predisposes to left atrial thrombus and systemic/cerebral embolism.
• Pulmonary hypertension and right heart failure from long-standing MS.
• Infective endocarditis on damaged valves.
• Congestive heart failure — leading cause of death in ARF/RHD.
• MacCallum patch in the left atrium; chronic valves show fibrosis, commissural fusion, leaflet thickening and a "fish-mouth"/"buttonhole" mitral orifice with chordal shortening.

High-yield: Isolated, "pure" mitral stenosis with an opening snap in a young Indian adult = rheumatic until proven otherwise. The shorter the A2–opening snap interval, the more severe the stenosis.

Differentials

• Juvenile idiopathic arthritis (JIA): persistent (not migratory) arthritis, poor/slow NSAID response, no carditis.
• Septic arthritis / reactive arthritis: usually monoarticular, suppurative, positive cultures.
• Post-streptococcal reactive arthritis (PSRA): shorter latency (<10 days), arthritis is additive/persistent and NOT migratory, poor aspirin response, lacks other Jones features — does not require long prophylaxis (though some give 1 year and reassess).
• Infective endocarditis: fever, new murmur, positive blood cultures, large vegetations, embolic phenomena.
• SLE: Libman-Sacks (verrucous) endocarditis, malar rash, ANA/anti-dsDNA positive, multisystem.
• Viral myocarditis / pericarditis: carditis without valvulitis or migratory arthritis.
• Sickle cell / leukaemia / serum sickness: can mimic arthralgia + fever.
• Lyme disease and gonococcal arthritis in relevant settings.

Recently asked / exam angle

• Subclinical carditis on echo is a MAJOR criterion (2015 revision) — one of the most repeated recent stems.
• In a moderate/high-risk population (India), monoarthritis counts as a major manifestation and monoarthralgia as a minor one — frequently tested as a single-best-answer twist.
• Aschoff body / Anitschkow ("caterpillar") cells = pathognomonic of rheumatic carditis — classic histology question.
• Duration of benzathine penicillin prophylaxis by carditis status — recurrent table-based MCQ (10 yr or up to age 40 for RHD).
• Anti-DNase B (not ASO) is the antibody of choice when Sydenham chorea presents late.
• Salicylates do not prevent RHD — only penicillin prophylaxis does (commonly worded as "which reduces valvular damage").
• Mitral valve is the most commonly affected; isolated mitral stenosis is the commonest chronic sequel.
• ARF follows throat infection only; PSGN follows skin or throat — paired-comparison stem.
• Migratory polyarthritis responds dramatically to aspirin and never deforms joints.
• Carey-Coombs murmur (mid-diastolic, apical) of acute mitral valvulitis.

Rapid revision

• ARF = immune sequel to GABHS pharyngitis only, latent period 2–4 weeks, ages 5–15 years.
• Pathogenesis = molecular mimicry (M-protein/myosin/laminin); HLA-DR7, D8/17 marker.
• Aschoff body with Anitschkow "caterpillar" cells = pathognomonic; MacCallum patch in left atrium.
• Jones 2015: 2 major OR 1 major + 2 minor (+ evidence of strep) for a first attack; subclinical carditis is now major.
• Major = JONES (Joints/migratory polyarthritis, ♥carditis, Nodules, Erythema marginatum, Sydenham chorea).
• High-risk (India): monoarthritis = major, monoarthralgia = minor, fever ≥38°C, ESR ≥30.
• Mitral > Aortic >> Tricuspid > Pulmonary; MR acute, MS the commonest chronic lesion.
• Sydenham chorea is late (1–6 mo), female-predominant; use anti-DNase B; treat with valproate/carbamazepine.
• Treat: benzathine penicillin to eradicate strep; aspirin for arthritis, steroids for severe carditis.
• Aspirin/steroids relieve symptoms but do NOT prevent RHD — only prophylaxis does.
• Secondary prophylaxis = benzathine penicillin G 1.2 MU IM q3–4 weeks; durations 5/age-21, 10/age-21, 10/age-40-or-lifelong.
• Primary prevention = treating strep throat within 9 days; "licks the joints, bites the heart."