What is the differential diagnosis for knee pain in a pediatric patient following a viral illness?

Differential Diagnosis for Knee Pain in a Pediatric Patient Following Viral Illness

The most critical diagnosis to exclude immediately is septic arthritis, which requires urgent joint aspiration if the child has fever, elevated inflammatory markers (CRP >2.0 mg/dl), and age <5 years, as this combination predicts >90% probability of septic knee arthritis. 1

Immediate Life-Threatening Considerations

Septic Arthritis

• Septic arthritis is an orthopedic emergency requiring immediate diagnosis and treatment to prevent rapid cartilage destruction. 2
• Kingella kingae is the most common pathogen in children under 4 years of age. 2
• Hematogenous seeding is the most common route of infection. 2
• Key predictive factors: age <5 years AND CRP >2.0 mg/dl together predict >90% probability of septic arthritis in a child with painful swollen knee. 1
• If these criteria are absent, risk remains >15%, so joint aspiration should still be strongly considered. 1
• Concomitant osteomyelitis occurs in >50% of pediatric cases. 2

Multisystem Inflammatory Syndrome in Children (MIS-C)

• MIS-C must be considered in any child with fever and joint pain occurring 2-6 weeks after a viral illness, particularly with SARS-CoV-2 exposure. 3
• Clinical features include fever, mucocutaneous findings, myocardial dysfunction, gastrointestinal symptoms, and arthralgia/arthritis. 3
• Tier 1 screening includes: CBC with differential, complete metabolic panel, ESR, CRP, and SARS-CoV-2 PCR/serology. 3
• Proceed to Tier 2 evaluation if elevated ESR/CRP AND at least one of: lymphopenia, neutrophilia, thrombocytopenia, hyponatremia, or hypoalbuminemia. 3
• MIS-C is rare (2 per 200,000 individuals under age 21) but can decompensate rapidly. 3

Common Post-Viral Diagnoses

Benign Acute Childhood Myositis

• Presents as sudden onset bilateral lower extremity pain with refusal to walk or tiptoe gait during or immediately following viral illness recovery. 4
• Typically symmetric bilateral lower extremity involvement, not isolated to knee. 4
• Self-limited, resolving within 3 days. 4
• Creatine phosphokinase may be elevated; myoglobinuria is rare but warrants hospital admission. 4
• Management includes rest and analgesia with excellent prognosis. 4

Post-Viral Reactive Arthritis

• Multiple viruses cause post-infectious arthritis including parvovirus B19, rubella, alphaviruses, EBV, CMV, hepatitis B/C, and HIV. 5
• Parvovirus B19 and alphaviruses can cause prolonged arthritis that may be indistinguishable from rheumatoid arthritis. 5
• Typically occurs days to weeks after viral illness. 5

Critical Pitfall to Avoid

Referred Pain from Intra-Abdominal Pathology

• Acute appendicitis with abscess can present as isolated knee pain with fever and elevated inflammatory markers, mimicking septic arthritis. 6
• Blood cultures growing gastrointestinal organisms (e.g., Granulicatella adiacens) should prompt abdominal imaging. 6
• Consider abdominal ultrasound or CT if knee imaging is benign but clinical picture suggests infection. 6

Diagnostic Algorithm

Step 1: Immediate Risk Stratification

• Check vital signs, assess ability to bear weight, and examine for systemic signs. 3
• Obtain: CBC with differential, CMP, ESR, CRP, blood cultures. 3
• If age <5 years AND CRP >2.0 mg/dl: probability of septic arthritis >90% → proceed directly to joint aspiration. 1

Step 2: SARS-CoV-2 Screening (if applicable)

• Obtain SARS-CoV-2 PCR and serology if viral illness occurred 2-6 weeks prior. 3
• If positive with elevated inflammatory markers, evaluate for MIS-C with cardiac workup (EKG, troponin, BNP). 3

Step 3: Joint Aspiration Decision

• Perform arthrocentesis if any of the following: 3, 1
  • Age <5 years with CRP >2.0 mg/dl
  • Fever with inability to bear weight
  • Marked elevation in inflammatory markers (CRP >10 mg/dl)
  • Clinical suspicion remains despite negative initial screening
• Synovial fluid analysis: cell count with differential, Gram stain, culture. 1
• Percent PMN substantially improves diagnostic accuracy. 1

Step 4: Consider Alternative Diagnoses

• If knee imaging and aspiration are benign but blood cultures grow GI organisms, obtain abdominal imaging. 6
• If bilateral lower extremity pain with recent viral illness and normal inflammatory markers, consider benign acute myositis. 4
• Check viral serologies (parvovirus B19, EBV, CMV) if reactive arthritis suspected. 5

Step 5: Admission Criteria 3

• Abnormal vital signs (tachycardia, tachypnea)
• Respiratory distress
• Neurologic changes
• CRP >10 mg/dl
• Abnormal cardiac markers (troponin, BNP)
• Evidence of renal or hepatic injury
• Confirmed or highly suspected septic arthritis or MIS-C

Key Laboratory Interpretation

• ESR and CRP elevation are nonspecific but critical for risk stratification. 7, 1
• CRP rises and falls more rapidly than ESR with changes in inflammation. 7
• Age and sex affect normal ESR values (higher in women and older patients). 7
• In MIS-C, CRP values >10-20 mg/dl are common. 3