Diagnostic Approach for Severe Joint Pain

Initial Clinical Assessment

A 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, should be performed, according to the American College of Rheumatology 1, 2
Particular attention should be paid to age and gender of the patient, geographical area, functional status, duration of symptoms and morning stiffness, number and pattern of tender/swollen joints, and axial/entheseal involvement and extra-articular/systemic features, as recommended by the European League Against Rheumatism 3, 4

Inflammatory markers, such as Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), should be performed to assess inflammation, as suggested by the Infectious Diseases Society of America 5, 4
Complete blood count with differential should be performed to evaluate for infection, inflammation, or malignancy, according to the American College of Rheumatology 6, 7

Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA/anti-CCP) should be tested for suspected rheumatoid arthritis, as recommended by the American College of Rheumatology 8, 4
Antinuclear antibody (ANA) testing should be performed if connective tissue disease is suspected, according to the European League Against Rheumatism 4

Plain radiographs of affected joints should be performed at baseline to evaluate joint damage, erosions, and exclude alternative diagnoses, as suggested by the American College of Radiology 1, 9, 4
Consider ultrasound or MRI of affected joints if clinically indicated, such as persistent arthritis unresponsive to treatment, suspicion of metastatic lesions or septic arthritis, according to the European League Against Rheumatism 1, 3, 4

Arthrocentesis (joint aspiration) should be performed if septic arthritis or crystal-induced arthritis is suspected, as recommended by the Infectious Diseases Society of America 1, 10
Synovial fluid analysis should include total cell count and differential leukocyte count, crystal analysis for gout or pseudogout, and Gram stain and culture for infectious causes, according to the American College of Rheumatology 10, 5

Blood cultures should be performed if fever is present, symptoms have acute onset, or if bloodstream infection is suspected, as suggested by the Infectious Diseases Society of America 10, 5
Consider testing for viral hepatitis B, C, and tuberculosis, especially before starting immunosuppressive therapy, according to the American College of Rheumatology 1, 8

Patients with inflammatory arthritis should be monitored with serial rheumatologic examinations and inflammatory markers every 4-6 weeks after treatment initiation, as recommended by the American College of Rheumatology 1, 2
Consider repeat radiographs within 1 year to assess for disease progression, according to the European League Against Rheumatism 4

The American College of Rheumatology recommends using radiographs of the hands and feet as the initial imaging technique to detect lesions 11
The European League Against Rheumatism suggests that ultrasound and MRI are superior to clinical examination for detecting joint inflammation and should be considered for a more accurate assessment 11
MRI can detect bone marrow edema, which is a strong independent predictor of subsequent radiographic progression in early rheumatoid arthritis 11
Ultrasound and MRI can detect inflammation that predicts subsequent joint damage, even in cases of clinical remission 12

The assessment of disease activity should be based on clinical symptoms and radiological measures, including the presence of inflammatory signs and elevated inflammation markers if applicable 13
The American College of Rheumatology recommends considering the presence of symptoms and radiological activity when evaluating disease activity, and initiating treatment if inflammation is active 13

The presence of clinical symptoms and corresponding radiological disease activity should be considered as active inflammation and treatment should be initiated 13
The absence of clinical symptoms and radiological disease activity should be considered as inactive inflammation and treatment should not be started 13

The American College of Rheumatology notes that power Doppler activity has been found in 15-62% of patients in clinical remission according to DAS28, American College of Rheumatology, or simplified disease activity index criteria 12
MRI synovitis is present in 96% and bone marrow edema in 52% of patients in clinical remission 12

Ultrasound detects synovitis 2.18-fold more frequently than clinical examination in hands/wrists, and MRI detects synovitis 2.20-fold more frequently than clinical examination, according to the European League Against Rheumatism 14, 15
Ultrasound or MRI should be considered for more accurate detection of joint inflammation, particularly when clinical findings are equivocal or to confirm true remission, as recommended by the American College of Rheumatology 16, 14, 15
Ultrasound is superior for detecting tenosynovitis, with a 2.48-4.69 fold better detection rate than clinical examination, according to the European League Against Rheumatism 14, 15