Acute Rheumatic Fever (ARF) - Short Answer Guide

1. ETIOLOGY

• Only ~3-6% of any population is genetically susceptible to ARF after GAS infection
• HLA class II allele polymorphisms and TNF/mannose-binding lectin variants confer susceptibility
• 44% concordance in monozygotic twins (vs 12% dizygotic) - confirms strong genetic component
• Occurs most in children aged 5-14 years; recurrences remain common into young adulthood

Source: Harrison's Principles of Internal Medicine 22E, Goldman-Cecil Medicine

2. PATHOPHYSIOLOGY

Flowchart

GAS Pharyngitis / Skin Infection
          ↓
 M-protein antigens processed by
   innate immune antigen-presenting cells
          ↓
   T-cell activation (humoral + cellular)
          ↓
  MOLECULAR MIMICRY
  (Streptococcal antigens mimic human proteins)
          ↓
Cross-reactive antibodies bind cardiac endothelium
→ VCAM-1 upregulation → lymphocyte recruitment
→ Endothelial lysis + complement activation
→ Release of laminin, keratin, tropomyosin peptides
          ↓
  Cross-reactive T cells invade heart
  (epitope spreading amplifies damage)
          ↓
 ┌─────────────────────────────────────────┐
 │         TISSUE INJURY BY LOCATION       │
 ├──────────────┬──────────────────────────┤
 │ Heart        │ Antibody binding +        │
 │              │ T-cell infiltration       │
 │              │ → CARDITIS (pancarditis)  │
 ├──────────────┼──────────────────────────┤
 │ Joints       │ Immune complexes          │
 │              │ → ARTHRITIS               │
 ├──────────────┼──────────────────────────┤
 │ Basal ganglia│ Antibody binding          │
 │              │ → CHOREA                  │
 ├──────────────┼──────────────────────────┤
 │ Skin/SC      │ Delayed hypersensitivity  │
 │              │ → Erythema marginatum,    │
 │              │   Subcutaneous nodules    │
 └──────────────┴──────────────────────────┘

Source: Harrison's 22E, Goldman-Cecil Medicine

3. REVISED JONES CRITERIA (2015 AHA Update)

Requires: Evidence of preceding GAS infection PLUS fulfillment of criteria below

Diagnostic Rule

Major Criteria

Minor Criteria

Low-risk: ARF incidence <2/100,000 school-age children/year OR RHD prevalence ≤1/1000/year

4. CLINICAL FEATURES (Frequency)

5. INVESTIGATIONS

Flowchart

Suspected ARF
      ↓
┌─────────────────────────────────────────┐
│  CONFIRM GAS INFECTION                  │
│  • Throat swab culture                  │
│  • Anti-streptolysin O (ASO) titre      │
│  • Anti-DNase B (ADB) titre             │
│  • Rapid strep antigen test             │
└────────────────┬────────────────────────┘
                 ↓
┌─────────────────────────────────────────┐
│  ACUTE PHASE REACTANTS / INFLAMMATION   │
│  • ESR                                  │
│  • CRP                                  │
│  • CBC (leukocytosis, normocytic anemia)│
└────────────────┬────────────────────────┘
                 ↓
┌─────────────────────────────────────────┐
│  CARDIAC INVESTIGATIONS                 │
│  • ECG → prolonged PR interval          │
│  • Echocardiogram → valvulitis,         │
│    subclinical carditis, regurgitation  │
└────────────────┬────────────────────────┘
                 ↓
┌─────────────────────────────────────────┐
│  EXCLUDE ALTERNATIVES (as indicated)   │
│  • ANA, dsDNA, anti-CCP (reactive       │
│    arthritis, lupus, JIA)               │
│  • Blood cultures (septic arthritis)    │
│  • Synovial fluid aspirate              │
│  • Gonorrhoeae / Chlamydia PCR          │
│  • Viral serology (parvovirus B19,      │
│    CMV, hepatitis)                      │
│  • Pregnancy test                       │
│  • UEC / creatinine (before NSAIDs)     │
└─────────────────────────────────────────┘

6. MANAGEMENT

Flowchart

CONFIRMED ARF
      ↓
 HOSPITALIZE + BED REST
      ↓
┌───────────────────────────────────────────────┐
│  STEP 1: ERADICATE GAS                        │
│  • Benzathine penicillin G IM:                │
│    - ≤27 kg: 600,000 units single dose        │
│    - >27 kg: 1.2 million units single dose    │
│  • OR Oral penicillin V 500 mg BD x 10 days   │
│  • OR Amoxicillin 50 mg/kg/day x 10 days      │
│  • Penicillin allergy: Azithromycin/macrolide  │
└───────────────────────┬───────────────────────┘
                        ↓
┌───────────────────────────────────────────────┐
│  STEP 2: TREAT MANIFESTATIONS                 │
│                                               │
│  ARTHRITIS / FEVER:                           │
│  • Aspirin 50-100 mg/kg/day in 4-5 doses      │
│    (max 4-8 g/day) x 2-4 weeks                │
│  • OR Naproxen 10-20 mg/kg/day BD             │
│    (preferred - safer, less GI side effects)  │
│                                               │
│  CARDITIS (mild-moderate):                    │
│  • Treat heart failure: diuretics,            │
│    ARBs, fluid restriction, bed rest          │
│                                               │
│  CARDITIS (severe):                           │
│  • ± Corticosteroids (prednisolone)           │
│    [limited evidence; used empirically]       │
│                                               │
│  CHOREA:                                      │
│  • Usually self-limiting (weeks-months)       │
│  • Carbamazepine or haloperidol if severe     │
│  • IVIg only for refractory severe chorea     │
└───────────────────────┬───────────────────────┘
                        ↓
┌───────────────────────────────────────────────┐
│  STEP 3: SECONDARY PROPHYLAXIS                │
│  • Benzathine penicillin G 1.2 million units  │
│    (600,000 units if ≤27 kg) IM every 4 weeks │
│  • Duration (see table below)                 │
└───────────────────────────────────────────────┘

Secondary Prophylaxis Duration Table

Oral alternatives: Penicillin V 250 mg BD or erythromycin 250 mg BD (penicillin allergy)

Management Summary Table

Key Mnemonics

• Carditis
• Arthritis (migratory)
• Sydenham's chorea
• Erythema marginatum
• Subcutaneous nodules

• Long PR interval
• Elevated ESR/CRP
• Arthralgia
• Pyrexia (fever ≥38.5°C)

Sources: Harrison's Principles of Internal Medicine 22E, Goldman-Cecil Medicine, Tintinalli's Emergency Medicine, Rheumatology 2-Volume Set (Elsevier 2022)

Glasgow Coma Scale (GCS) in Pediatrics

Q1. What is the GCS and why is it modified for children?

Q2. Modified GCS for Infants/Children (<2 years) vs Standard (>2 years)

Full Comparison Table

Total score = Eye + Verbal + Motor; Range: 3 (worst) - 15 (best)

Q3. Interpretation / Severity Classification

• GCS ≤14 = increased risk for intracranial injury in children
• GCS ≤13 = neuroimaging (CT head) generally indicated
• GCS ≤8 = indication for endotracheal intubation to protect airway

Q4. AVPU Scale (simpler alternative - PALS recommended)

The AVPU score is currently recommended by Pediatric Advanced Life Support (PALS) guidelines as it is faster, simpler, and has good validation in children.

Q5. Key Differences - Pediatric vs Adult GCS (Flowchart)

ASSESS CHILD'S CONSCIOUSNESS
         ↓
Is child VERBAL / >2 years?
         ↓
  YES                NO (Infant / preverbal)
   ↓                          ↓
Standard GCS            Modified Pediatric GCS
Verbal: Oriented,       Verbal: Coos/babbles,
  Confused,               Irritable cry,
  Inappropriate,          Cries to pain,
  Incomprehensible,       Moans, No response
  None
Motor: Obeys commands   Motor: Spontaneous movement
       Localizes pain          Withdraws to touch
       (same below)            (same below)
         ↓
  Score 3-15
         ↓
  Mild ≥13 | Moderate 9-12 | Severe ≤8

Q6. Clinical Significance in Pediatrics

Q7. Limitations of GCS in Children

• Poor interobserver reliability in young children
• Cannot be applied to sedated/intubated patients accurately
• Verbal component is unreliable in preverbal/crying children
• Does not accurately predict outcome in individual patients
• AVPU preferred in the emergency setting for speed

Q8. Memory Aid

"EMV" = Eyes, Motor, Verbal

• Babbles = 5
• Irritable cry = 4
• Cries to pain = 3
• Moans to pain = 2
• No response = 1

Sources: Tintinalli's Emergency Medicine (Comprehensive Study), Rosen's Emergency Medicine - Goldman-Cecil Medicine