What is the diagnostic workup for Rheumatoid Arthritis (RA)?

From the Guidelines

The workup for rheumatoid arthritis (RA) should begin with a thorough clinical history and physical examination, focusing on joint pain, stiffness, swelling, and functional limitations, and patients should be referred to a rheumatologist within 6 weeks after the onset of symptoms. According to the 2016 update of the EULAR recommendations for the management of early arthritis 1, a definite diagnosis should only be made after a careful history taking and clinical examination, which should also guide laboratory testing and additional procedures. The clinical examination is the method of choice for detecting arthritis, which may be confirmed by ultrasonography 1.

Key Components of the Workup

• Laboratory testing should include a minimal panel of C reactive protein (CRP)/erythrocyte sedimentation rate (ESR), full blood cell count, transaminase levels, renal function, and urine analysis, as proposed by Combe et al. in 2017 1
• Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP) are specific markers for RA, while ESR and CRP indicate inflammation levels
• Imaging studies, such as plain radiographs, ultrasound, or MRI, may be useful for detecting early synovitis and erosions
• Synovial fluid analysis may be performed if joint effusion is present to exclude other conditions like gout or infection

Importance of Early Referral and Treatment

• Early referral to a rheumatologist is essential for prompt diagnosis and treatment initiation, as early intervention with disease-modifying antirheumatic drugs (DMARDs) can prevent joint damage and improve long-term outcomes 1
• Methotrexate is considered the anchor drug and should be part of the first treatment strategy in patients at risk of persistent disease, unless contraindicated 1
• The main goal of DMARD treatment is to achieve clinical remission, and regular monitoring of disease activity, adverse events, and comorbidities should guide decisions on choice and changes in treatment strategies 1

From the FDA Drug Label

The efficacy and safety of RITUXAN were evaluated in two randomized, double-blind, placebo-controlled studies of adult patients with moderately to severely active RA who had a prior inadequate response to at least one TNF inhibitor Patients were 18 years of age or older, diagnosed with active RA according to American College of Rheumatology (ACR) criteria, and had at least 8 swollen and 8 tender joints.

The workup for Rheumatoid Arthritis (RA) includes:

• Diagnosing active RA according to American College of Rheumatology (ACR) criteria
• Having at least 8 swollen and 8 tender joints
• Evaluating the patient's response to prior treatments, such as TNF inhibitors
• Assessing the patient's ACR response, including components such as:
  • Tender Joint Count
  • Swollen Joint Count
  • Physician Global Assessment
  • Patient Global Assessment
  • Pain
  • Disability Index (HAQ)
  • CRP (mg/dL) 2

From the Research

Rheumatoid Arthritis Workup

• The workup for rheumatoid arthritis (RA) involves a combination of clinical evaluation, laboratory tests, and imaging studies 3, 4, 5, 6.
• The diagnosis of RA should be considered in patients with at least one joint with definite swelling that is not better explained by another disease 3, 4.
• Laboratory tests that support a diagnosis of RA include:
  • Rheumatoid factor (RF) 3, 4, 5, 7
  • Anti-citrullinated protein antibody (anti-CCP) 3, 4, 5, 7
  • Elevated C-reactive protein (CRP) level 3, 4, 5, 6
  • Elevated erythrocyte sedimentation rate (ESR) 3, 4, 5, 6
• Initial laboratory evaluation should also include a complete blood count with differential and assessment of renal and hepatic function 4.
• Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis 4, 6.

Diagnostic Criteria

• The likelihood of a RA diagnosis increases with the number of small joints involved 4.
• Symmetrical small joint polyarthritis, morning stiffness, and constitutional symptoms are characteristic features of RA 6.
• Extra-articular manifestations are common and may affect multiple body systems 3, 6.

Laboratory Tests

• Laboratory tests provide valuable information for diagnosing and managing RA, but they have limitations and cannot serve as a gold standard for diagnosis and management in all individual patients with RA 5.
• More than 30% of patients with RA have negative tests for RF or anti-CCP antibodies, and 40% have a normal ESR or CRP 5.
• The use of decision tools, such as the Leiden clinical prediction rule for undifferentiated arthritis, may facilitate early diagnosis of RA 6.