What is the approach to diagnose a fever of rheumatological cause?

Diagnosing Fever of Rheumatological Cause

The diagnosis of fever of rheumatological origin requires application of the Jones criteria for acute rheumatic fever, with careful attention to major and minor manifestations while excluding other causes of fever. 1, 2

Major Manifestations to Evaluate

• Carditis - Can be clinical (murmurs, heart failure) or subclinical (detected by echocardiography). Echocardiographic criteria for pathological mitral regurgitation include jet in 2 planes, >1 cm, holosystolic, with velocity >2.5 m/s. 1, 2

• Arthritis - In low-risk populations, only polyarthritis is considered a major criterion, while in moderate/high-risk populations, monoarthritis or polyarthritis qualify. The arthritis is typically migratory, affecting large joints. 1, 2

• Chorea - Characterized by involuntary, purposeless movements that disappear during sleep. Other neurological disorders must be excluded. Evidence of preceding streptococcal infection may be difficult to document due to the long latent period. 1, 2

• Skin Findings - Look for erythema marginatum (evanescent, pink rash with pale centers and rounded margins, usually on trunk) or subcutaneous nodules (firm, painless protuberances on extensor surfaces of joints). 1, 2

Minor Manifestations to Assess

• Fever - In low-risk populations, fever ≥38.5°C is considered significant, while in moderate/high-risk populations, fever ≥38°C qualifies. The widespread use of antipyretics necessitates a detailed history. 1

• Arthralgia - In patients without arthritis as a major criterion, polyarthralgia is considered a minor criterion in low-risk populations, while monoarthralgia is a minor criterion in moderate/high-risk populations. 1, 2

• Laboratory Findings - Elevated acute phase reactants: ESR ≥60 mm/h and/or CRP ≥3.0 mg/dL in low-risk populations; ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL in moderate/high-risk populations. Normal values should prompt reconsideration of the diagnosis. 1, 2, 3

• ECG Changes - Prolonged PR interval (first-degree heart block) after accounting for age variability. This is a well-established minor criterion but insufficient alone for diagnosis. 1, 3

Diagnostic Algorithm

1. Document preceding Group A Streptococcal infection - Essential for diagnosis unless in cases of chorea or recurrent disease. 2, 4

2. Apply Jones criteria based on risk population:

   • Initial attack: 2 major manifestations OR 1 major plus 2 minor manifestations 1, 2
   • Recurrent attack: 2 major OR 1 major and 2 minor OR 3 minor manifestations 1

3. Perform echocardiography with Doppler - Recommended for all suspected cases to detect subclinical carditis. 2, 3

4. Consider differential diagnoses - Exclude infectious endocarditis, post-streptococcal reactive arthritis, Lyme disease, and other causes of fever. 1, 5

Special Considerations

• In cases of diagnostic uncertainty but high clinical suspicion, consider offering 12 months of secondary prophylaxis followed by reevaluation. 1, 2

• For recurrent symptoms in patients with history of rheumatic fever, look for evidence of streptococcal infection; if absent and echocardiography shows no valvulitis, symptoms may not be related to rheumatic fever. 1, 2

• In patients with fever of unknown origin where rheumatological cause is suspected but Jones criteria are not met, consider early FDG-PET/CT to identify the source of inflammation. 6, 5

• Adult-onset Still's disease, systemic lupus erythematosus, and vasculitides should be considered in the differential diagnosis of fever of rheumatological origin not meeting criteria for acute rheumatic fever. 7, 5

Common Pitfalls

• Failure to distinguish between physiological and pathological valvular regurgitation on echocardiography. Pathological regurgitation must meet specific criteria regarding jet length, velocity, and completeness of Doppler envelope. 1

• Overlooking the possibility of isolated congenital mitral or aortic valve abnormalities, which can mimic rheumatic valvulitis. 1

• Misdiagnosing post-streptococcal reactive arthritis (PSRA) as acute rheumatic fever. PSRA typically has prolonged symptoms and arthritis that doesn't respond promptly to salicylates. 1, 2

• Failing to recognize that normal ESR and CRP levels should prompt reconsideration of ARF diagnosis, as these values are almost never normal in ARF except in isolated chorea. 1, 3