What is the diagnostic work-up and treatment for a patient presenting with joint aches and fever?

Work-up of Joint Aches with Fever

For a patient presenting with joint aches and fever, immediately perform arthrocentesis with synovial fluid analysis (cell count, Gram stain, culture, and crystal analysis) to rule out septic arthritis, which is a medical emergency requiring urgent treatment to prevent joint destruction and mortality. 1, 2

Immediate Clinical Assessment

History and Physical Examination

• Document fever pattern: High-spiking fevers (>39°C) that are quotidian or double quotidian, peaking in late afternoon/evening, suggest Adult-Onset Still's Disease (AOSD) 3
• Assess ability to bear weight: Inability to bear weight on the affected limb significantly increases likelihood of bacterial infection (osteomyelitis, septic arthritis, or intramuscular abscess) 2
• Examine all peripheral joints for tenderness, swelling, and range of motion, plus spine and entheseal sites 1
• Look for characteristic rash: Evanescent salmon-pink maculopapular eruption on proximal limbs/trunk accompanying fever suggests AOSD 3
• Check for extra-articular features: Sore throat (68-92% in AOSD), lymphadenopathy, splenomegaly, serositis 3

Joint Distribution Pattern

• Symmetric polyarthritis affecting knees, wrists, ankles suggests inflammatory arthritis 3, 1
• Oligoarthritis with fever may indicate reactive arthritis or peripheral spondyloarthritis 4, 5
• Carpal/pericapitate involvement is more typical of AOSD than rheumatoid arthritis 3

Urgent Laboratory Investigations

First-Line Blood Tests

• Complete blood count with differential: Leukocytosis >15×10⁹/L (especially >20×10⁹/L) strongly suggests infection or AOSD; pancytopenia suggests hemophagocytic syndrome 3, 2
• Inflammatory markers:
  • ESR >36 mm/hr associated with osteomyelitis/septic arthritis 2
  • CRP >60 mg/L strongly associated with bacterial infection 2
  • ESR and CRP are elevated in virtually all AOSD patients 3
• Blood cultures if fever present or acute onset to identify bacteremia source 1, 6

Synovial Fluid Analysis (Critical)

• Perform arthrocentesis immediately if septic arthritis or crystal arthropathy suspected 1
• Synovial fluid studies must include:
  • Total cell count and differential leukocyte count 1
  • Gram stain and culture for bacterial infection 1, 6
  • Crystal analysis for gout or pseudogout 1

Common pitfall: Delaying arthrocentesis in febrile patients with joint pain can result in irreversible joint damage from untreated septic arthritis 6

Autoimmune and Serologic Testing

• Rheumatoid factor (RF) and anti-CCP antibodies if rheumatoid arthritis suspected 1
• Antinuclear antibody (ANA) if connective tissue disease suspected 1
• HLA-B27 testing if spondyloarthritis suspected (especially with axial/spine involvement or reactive arthritis pattern) 3, 4
  • Note: HLA-B27 is less frequently positive in febrile spondyloarthritis patients (52% vs 77% in non-febrile) 4

Pre-Treatment Screening

• Test for viral hepatitis B, C, and latent/active tuberculosis before initiating any DMARD or immunosuppressive therapy 3, 1

Imaging Studies

Initial Imaging

• Plain radiographs of affected joints at baseline to evaluate for joint damage, erosions, and exclude alternative diagnoses 1
• Chest radiograph if systemic symptoms present or tuberculosis suspected 3

Advanced Imaging (When Indicated)

• Ultrasound or MRI should be performed if: 3, 1
  • Persistent arthritis unresponsive to treatment
  • Suspicion for metastatic lesions or septic arthritis
  • Clinical findings are equivocal
  • Need to confirm true remission
• MRI detects synovitis 2.20-fold more frequently than clinical examination and can identify bone marrow edema predicting radiographic progression 1
• Ultrasound is superior for detecting tenosynovitis (2.48-4.69 fold better than clinical examination) 1

Clinical pearl: In febrile spondyloarthritis patients, consider simple sacroiliac joint radiograph as part of initial evaluation 4

Differential Diagnosis Considerations

Infection (Rule Out First)

• Septic arthritis: Pre-existing joint disease (especially rheumatoid arthritis) increases risk during bacteremia 6
• Osteomyelitis: Consider if inability to bear weight, CRP >60 mg/L, ESR >36 mm/hr 2
• Reactive arthritis: Often follows genitourinary or gastrointestinal infection 4

Inflammatory Arthritis

• Adult-Onset Still's Disease: Triad of high-spiking fever, characteristic rash, and arthritis/arthralgias 3
• Peripheral spondyloarthritis: Can present with fever and severe systemic inflammatory response mimicking infection (leukocytosis, thrombocytosis, high ESR/CRP) 4, 5
• Psoriatic arthritis: May present with fever in 3.8% of cases 4

Critical Warning Signs

• Hemophagocytic syndrome: Pancytopenia with fever requires prompt immunosuppressive treatment 3
• Myocardial involvement: Check troponin if chest pain or cardiac symptoms present 3

Follow-up Monitoring

• Serial rheumatologic examinations with inflammatory markers every 4-6 weeks after treatment initiation 3, 1
• Repeat radiographs within 1 year to assess for disease progression 1
• Monitor CK, ESR, CRP if myositis suspected 3

Important caveat: The initial ED diagnosis is consistent with definitive diagnosis only 42% of the time in pediatric patients with fever and extremity pain, emphasizing need for thorough workup and follow-up 2. In febrile spondyloarthritis patients, only 7.7% initially visit rheumatology compared to 59% of non-febrile patients, leading to delayed diagnosis 4