Acute Rheumatic Fever (ARF)

Definition

Epidemiology

• Most common in children 5-15 years of age
• Males and females equally affected
• Rheumatic heart disease (the sequela) is more prevalent in women and peaks in the 3rd-4th decades of life
• ARF develops in about 1.6-2.5% of patients after infection with rheumatogenic streptococcal strains
• Higher incidence in developing countries and crowded living conditions

Pathobiology (Molecular Mimicry)

Clinical Manifestations

Arthritis

• Migratory polyarthritis - though additive pattern is also seen, especially in adults
• Knees (76%), ankles (50%), elbows/wrists (12-15%) most common
• Tenderness disproportionate to physical findings
• Responds rapidly to NSAIDs - lack of response should prompt reconsideration of diagnosis
• Synovial fluid: sterile with lymphocyte predominance
• Never radiographically destructive (Jaccoud's arthropathy can occur after recurrences)

Carditis (Pancarditis)

• Affects pericardium, myocardium, and endocardium
• Mitral valve involved in almost all cases; aortic valve in ~20-30%
• Most common murmurs:
  • Mitral regurgitation - high-pitched, blowing, holosystolic apical murmur
  • Carey-Coombs murmur - low-pitched, apical, mid-diastolic flow murmur
  • Aortic regurgitation - high-pitched, decrescendo diastolic murmur
• Heart failure occurs in 5-10% of first attacks - most life-threatening complication
• Subclinical carditis detectable only by Doppler echocardiography is an important 2015 addition to the Jones criteria

Chorea (Sydenham's Chorea / St. Vitus Dance)

• Involuntary, non-rhythmic, purposeless movements of body, limbs, and face
• Usually more pronounced on one side
• Stops during sleep

Skin Manifestations

• Erythema marginatum: pink, non-pruritic, blanching macules/papules spreading in a serpiginous pattern on trunk and proximal limbs
• Subcutaneous nodules: 0.5-2 cm, painless, over bony prominences or extensor tendons

Diagnosis - Revised Jones Criteria (2015, Updated for Doppler Era)

For Initial ARF:

• 2 major criteria, OR
• 1 major + 2 minor criteria

For Recurrent ARF:

• 2 major, OR 1 major + 2 minor, OR 3 minor criteria

Major Criteria

Minor Criteria

Labs

• Elevated ESR, CRP
• Normochromic, normocytic anemia
• Leukocytosis
• Prolonged PR interval on ECG
• Echocardiogram should be performed in all confirmed/suspected ARF cases

Treatment

1. Eradication of GAS (Acute)

• IM benzathine penicillin G 1.2 million units (single dose)
• Oral penicillin V or amoxicillin as alternatives

2. Anti-inflammatory Therapy

• NSAID/steroid therapy duration: 2-4 weeks for mild carditis; up to 2-3 months for severe
• NSAIDs should continue for 1-2 weeks beyond normalization of inflammatory markers

3. Secondary Prophylaxis (Mandatory)

• ARF without carditis: 5 years or until age 21 (whichever is longer)
• ARF with carditis, no residual heart disease: 10 years or until age 21
• ARF with carditis + persistent valve disease: 10 years or until age 40, sometimes lifelong

Prognosis

• Arthritis and chorea are self-limiting with no permanent sequelae
• Carditis is the major determinant of long-term morbidity - can lead to chronic rheumatic heart disease with mitral stenosis, mitral regurgitation, or aortic valve disease
• Risk of carditis recurrence is highest within the first few years; every recurrent ARF attack risks additional valve damage
• The 2024 WHO guidelines on RHD highlight that handheld echocardiography for subclinical carditis detection and uninterrupted benzathine penicillin G prophylaxis are the key strategies for reducing RHD burden in endemic regions

Clinical Approach: 28F with Raised ASO Titres (×2), Elevated CRP, Phalangeal Pain

Why This Presentation Needs Careful Workup

1. Phalangeal (small joint) arthritis - ARF typically causes large-joint migratory polyarthritis (knees, ankles, wrists). Small joint involvement is not a classic feature of ARF.
2. 28-year-old woman - peak ARF age is 5-15 years. A 28-year-old woman with small joint pain fits the demographic of early rheumatoid arthritis (RA) far more closely.
3. Raised ASO alone does not diagnose ARF - ASO can be elevated in many conditions and may just reflect a recent/past streptococcal exposure.

Step 1 - Assess Jones Criteria Status

Step 2 - Investigations to Order (Parallel Workup)

A. To Complete ARF Assessment

B. To Exclude Other Causes of Phalangeal Arthritis (Critical)

Step 3 - Key Differential Diagnoses to Consider

1. Post-Streptococcal Reactive Arthritis (PSRA) - Top Differential

2. Early Rheumatoid Arthritis

• Young woman + symmetric small joint (phalangeal) arthritis + elevated CRP = classic RA presentation
• ASO can be coincidentally elevated from a recent throat infection and does not exclude RA
• Anti-CCP is highly specific (>90%) and can be positive years before clinical RA

3. Systemic Lupus Erythematosus (SLE)

• Young woman, arthritis (often phalangeal), elevated CRP
• Must rule out with ANA/anti-dsDNA

4. Parvovirus B19 Arthropathy

• Symmetric small joint arthritis in women of childbearing age, self-limiting
• Check IgM serology

Step 4 - Clinical Assessment (Do Now)

• Careful joint examination: Is this truly phalangeal (PIP/DIP/MCP)? Are large joints (knees, ankles) also involved even mildly?
• Cardiac auscultation: Any new murmur?
• Skin: Erythema marginatum, subcutaneous nodules?
• Neurological: Any involuntary movements (chorea)?
• Fever: Temperature chart

Step 5 - Management Based on Findings

If ARF Confirmed (Jones criteria met on full workup):

• Hospitalise
• IM Benzathine Penicillin G 1.2 million units (GAS eradication)
• NSAIDs (naproxen or aspirin) for arthritis
• Echocardiography for carditis assessment
• Start secondary prophylaxis: Benzathine Penicillin G 1.2 million units IM every 4 weeks

If PSRA (no carditis, no other major Jones criteria):

• NSAIDs for arthritis (note: response may be incomplete unlike ARF)
• Short-course antibiotic prophylaxis initially recommended while monitoring for carditis
• Serial echocardiography over the following months
• If no carditis develops after 1 year, prophylaxis may be discontinued
• Treat any active GAS throat infection

If RA / SLE / Other:

• Refer to rheumatologist for disease-modifying therapy
• Do not start secondary penicillin prophylaxis

Summary - Immediate Next Steps (Priority Order)

1. Echocardiogram - single most important test; rules in/out carditis
2. ECG - PR interval
3. Anti-CCP + RF + ANA - screen for RA/SLE (very important in this demographic)
4. Anti-DNase B - strengthen or weaken the GAS link
5. ESR, CBC
6. Parvovirus B19 IgM
7. Hand X-rays
8. Throat swab for GAS

Bottom line: Raised ASO × 2 + elevated CRP + phalangeal arthritis in a 28-year-old woman does not meet Jones criteria for ARF. PSRA and early RA are equally (or more) likely. A full targeted workup - especially an echo and anti-CCP - is mandatory before labelling this as "rheumatic fever."

Antibiotic Management for This Patient

Goal 1 - Eradication of GAS (Acute / Immediate)

Drug of Choice: Benzathine Penicillin G (IM)

Why IM benzathine penicillin G is preferred over oral: single dose ensures complete compliance, achieves reliable eradication, and immediately transitions into prophylaxis without a separate prescription.

Goal 2 - Secondary Prophylaxis (Prevent Recurrence)

If ARF is confirmed (Jones criteria met + carditis on echo):

If PSRA only (no Jones criteria, no carditis on echo):

• Give the acute eradication course (IM benzathine PenG or oral Pen V × 10 days)
• Start short-term prophylaxis while awaiting echo results and monitoring for delayed carditis
• If no carditis develops at 1 year follow-up - prophylaxis can be discontinued
• NSAIDs for arthritis (naproxen preferred)

Practical Summary for This Patient Right Now

Step 1 (TODAY):
→ IM Benzathine Penicillin G 1.2 million units - single dose
  (clears GAS + starts prophylaxis in one shot)

Step 2 (Within 48 hrs):
→ Echo result determines whether to continue monthly IM prophylaxis

Step 3 (Ongoing):
→ If carditis confirmed: continue BPG 1.2 MU IM every 4 weeks
→ If no carditis (PSRA): review at 1 year, consider stopping

Note on penicillin allergy: If allergic, use oral azithromycin 250 mg/day. Cephalosporins can be used for acute eradication but are not recommended for long-term prophylaxis due to less evidence in this setting.

Revised Clinical Picture

What the Current Data Tells You

Antibiotic Decision in Pregnancy

1. GAS Eradication (Give This)

2. Secondary Prophylaxis - Hold or Start?

• Do not start long-term monthly prophylaxis yet
• Give the single eradication dose of IM benzathine penicillin G
• Monitor clinically - if carditis develops later, start prophylaxis
• If PSRA confirmed at follow-up with no carditis at 1 year - prophylaxis not required

Monthly benzathine penicillin G throughout pregnancy is acceptable and safe if ARF/carditis were confirmed, but it is not indicated here.

The Bigger Problem: NSAIDs for Arthralgia in Pregnancy

What to Use Instead for Pain in This Patient:

Summary: What to Do Right Now

1. ANTIBIOTIC:
   → IM Benzathine Penicillin G 1.2 million units - single dose (safe in pregnancy)
   → No long-term prophylaxis needed (no carditis, Jones criteria not met)

2. PAIN RELIEF:
   → Paracetamol 500-1000 mg TDS as first line
   → Avoid NSAIDs if in 3rd trimester / >28 weeks
   → If <28 weeks and pain uncontrolled: short course naproxen acceptable

3. WORKUP STILL NEEDED:
   → Anti-CCP, RF, ANA (RA/SLE - critical in a young pregnant woman)
   → Parvovirus B19 IgM (causes small joint arthritis in women of childbearing age)
   → Gestational age - determines what analgesia you can use
   → Repeat echo in 1 month to watch for delayed carditis development

4. REFER:
   → Rheumatology (if RA/SLE suspected)
   → Maternal-fetal medicine/high-risk OB (for monitoring)

Key message: ARF is not diagnosed here - do not give long-term penicillin prophylaxis. The immediate priority is eradicating GAS (single IM benzathine PenG), safe analgesia with paracetamol, and completing the workup to find the actual cause of phalangeal arthritis - especially RA and parvovirus, which are far more likely in this demographic.