What investigations should be ordered for a patient presenting with severe joint pain?

Diagnostic Approach for Severe Joint Pain

The essential investigations for severe joint pain should include a complete rheumatologic history and examination, inflammatory markers (ESR/CRP), autoantibody testing (RF, ACPA, ANA), and plain radiographs of affected joints, with consideration of joint aspiration if septic or crystal arthritis is suspected. 1

Initial Clinical Assessment

• Complete rheumatologic history and thorough physical examination of all peripheral joints for tenderness, swelling, and range of motion, as well as examination of the spine 1
• Particular attention should be paid to:
  • Age and gender of the patient 1
  • Geographical area (relevant for endemic infectious causes) 1
  • Functional status 1
  • Duration of symptoms and morning stiffness 1
  • Number and pattern of tender/swollen joints 1
  • Axial/entheseal involvement and extra-articular/systemic features 1

First-Line Laboratory Investigations

• Inflammatory markers: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be performed to assess inflammation 1, 2
• Complete blood count with differential to evaluate for infection, inflammation, or malignancy 1, 3
• Basic metabolic panel to assess renal function 4, 3
• Liver function tests to evaluate hepatic function 4, 3
• Urinalysis to screen for renal involvement in systemic diseases 1, 3

Autoimmune and Serologic Testing

• Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA/anti-CCP) for suspected rheumatoid arthritis 1, 2
• Antinuclear antibody (ANA) testing if connective tissue disease is suspected 1, 2, 5
• HLA-B27 testing if symptoms suggest reactive arthritis, ankylosing spondylitis, or other spondyloarthropathies 1, 2
• Consider additional autoantibody tests if specific connective tissue diseases are suspected 1, 5

Imaging Studies

• Plain radiographs of affected joints should be performed at baseline to evaluate joint damage, erosions, and exclude alternative diagnoses 1, 2
• For hands, wrists, and feet, radiographs are particularly important as the presence of erosions is predictive for the development of rheumatoid arthritis 1
• Consider ultrasound or MRI of affected joints if clinically indicated (e.g., persistent arthritis unresponsive to treatment, suspicion of metastatic lesions or septic arthritis) 1, 2
• MRI of hands and wrists could be considered when rheumatoid arthritis is suspected but diagnosis is uncertain 1

Joint Fluid Analysis

• Arthrocentesis (joint aspiration) should be performed if septic arthritis or crystal-induced arthritis is suspected 1, 2
• Synovial fluid analysis should include:
  • Total cell count and differential leukocyte count 1, 2
  • Crystal analysis for gout or pseudogout 1, 2, 3
  • Gram stain and culture for infectious causes 1, 2

Additional Investigations Based on Clinical Suspicion

• Blood cultures if fever is present, symptoms have acute onset, or if bloodstream infection is suspected 1
• Consider testing for viral hepatitis B, C, and tuberculosis, especially before starting immunosuppressive therapy 1, 4
• Synovial biopsy is not routinely recommended but can provide information for differential diagnosis, especially in patients with persistent monoarthritis 1

Common Pitfalls and Caveats

• Laboratory tests in rheumatology are not diagnostic of any particular disease and should only be used to refine the diagnosis based on clinical findings 5, 6
• Overuse of "arthritis panels" without clinical context can lead to false positives and unnecessary concern 3, 5, 6
• Withholding antimicrobial therapy for at least 2 weeks prior to joint fluid collection increases the likelihood of recovering an organism in suspected infection 1
• Advanced imaging studies such as bone scans, leukocyte scans, MRI, CT, and PET scans should not be routinely used but reserved for specific clinical scenarios 1
• Early recognition of inflammatory arthritis is critical to avoid erosive joint damage 1

Follow-up Monitoring

• Patients with inflammatory arthritis should be monitored with serial rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation 1, 2
• Consider repeat radiographs within 1 year to assess for disease progression 1
• Consider early referral to a rheumatologist if there is joint swelling (synovitis) or if symptoms persist 1