What are the laboratory tests for diagnosing rheumatic fever?

Laboratory Workup for Rheumatic Fever

The laboratory workup for diagnosing rheumatic fever must include evidence of preceding Group A Streptococcal infection plus inflammatory markers, with anti-streptolysin O (ASO) titer being the primary serological test. 1, 2

Evidence of Preceding Streptococcal Infection

• Anti-streptolysin O (ASO) titer

  • Begins to rise approximately 1 week after infection
  • Peaks between 3-6 weeks post-infection
  • Normal values vary by age (higher in children than adults)
  • Upper normal limit for children aged 5-15 years: 239-515 IU/mL 2

• Anti-DNase B antibody

  • Important when ASO is negative but clinical suspicion remains high
  • Rises 1-2 weeks after infection
  • Peaks 6-8 weeks post-infection 2

• Other streptococcal antibodies

  • Antihyaluronidase
  • Antideoxyribonuclease B
  • Antistreptokinase antibodies 3

• Throat culture

  • Gold standard for detecting current GAS infection
  • May be negative if performed weeks after the initial infection 1

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR)

  • Low-risk populations: ≥60 mm in first hour
  • Moderate/high-risk populations: ≥30 mm/h 1
  • Almost never normal in ARF (except isolated chorea) 1

• C-reactive protein (CRP)

  • Should be ≥3.0 mg/dL
  • Commonly >7.0 mg/dL depending on laboratory method
  • Values should always be higher than the upper limit of normal 1
  • Rises and falls more quickly than ESR (useful for monitoring treatment response) 3

• Complete blood count

  • Leukocytosis (>10,000 white blood cells/mm³) 1
  • Anemia may be present 1

Cardiac Assessment

• Electrocardiogram (ECG)

  • To detect prolonged PR interval (minor criterion)
  • Must account for age variability 1

• Echocardiography with Doppler

  • Essential for documenting clinical or subclinical carditis
  • Detects valvular regurgitation (mitral or aortic)
  • More sensitive than auscultation for detecting mild valvular involvement 2, 4

Newer Potential Markers

• Neutrophil-to-lymphocyte ratio (NLR)
• Platelet-to-lymphocyte ratio (PLR)
• Monocyte-to-lymphocyte ratio (MLR)
  • All three are significantly higher in patients with rheumatic heart disease
  • Correlate positively with ESR and CRP levels
  • May help in diagnosis and monitoring disease progression 5

Interpretation Considerations

• Normal ESR and CRP

  • Should prompt reconsideration of ARF diagnosis
  • Exception: patients with isolated chorea may have normal inflammatory markers 1

• Common Pitfalls

  • Misinterpreting elevated titers as indicating acute rather than recent past infection
  • Failing to consider age-specific normal values for ASO
  • Relying solely on ASO without considering anti-DNase B when ASO is negative 2
  • Overtreatment based on isolated elevated ASO without clinical correlation 2

Laboratory Testing Algorithm

1. Initial testing:

   • ASO titer
   • ESR and CRP
   • Complete blood count
   • ECG
   • Throat culture (if recent infection suspected)

2. If ASO negative but clinical suspicion high:

   • Add anti-DNase B testing

3. For cardiac assessment:

   • Echocardiography with Doppler (even with normal auscultation)

4. For monitoring:

   • Serial ESR and CRP measurements
   • Repeat echocardiography to assess valvular changes

Remember that laboratory tests must be interpreted in the context of clinical findings using the revised Jones criteria, which differ between low-risk and moderate/high-risk populations 1.