rheumatoid%20arthritis
RHEUMATOID ARTHRITIS

Rheumatoid arthritis is a systemic autoimmune rheumatic disorder of unknown etiology.
It is the most common form of inflammatory arthritis.
Patient usually complains of joint pain and/or swelling with morning stiffness that lasts for more than an hour.

Goals of treatment are clinical and radiological remission of disease and to reduce functional limitations and permanent joint damage.

Rheumatoid%20arthritis Diagnosis

Classification

New Classification Criteria for Rheumatoid Arthritis

  • Developed by the American College of Rheumatology (ACR) Board of Directors and European League Against Rheumatism (EULAR) Executive Committee
  • Can be applied to patients at more than one point in the evolution of their signs and symptoms
  • Limited only to patients with clinical synovitis in at least 1 joint and synovitis not secondary to other disease
  • A total score of ≥6/10 is needed to classify a patient as having definite rheumatoid arthritis
  • Number and site of involved joints
    • 5 points for >10 joints, including at least 1 small joint1
    • 3 points for 4-10 small joints1
    • 2 points for 1-3 small joints1
    • 1 point for 2-10 large joints (eg shoulders, elbows, hips, knees, ankles)
  • Serological abnormality (at least 1 test result is needed)
    • 3 points for high-positive [>3x upper limit of normal (ULN)] rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA)
    • 2 points for low-positive (≤3x ULN) RF or ACPA
  • Acute-phase reactants abnormality (at least 1 test result is needed)
    • 1 point for abnormal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)
  • Symptom duration
    • 1 point for ≥6 weeks

1Eg metacarpophalangeal (MTP) joints, proximal interphalangeal (PIP) joints, 2nd-5th metatarsophalangeal (MTP) joints, thumb interphalangeal joint, wrists

Physical Examination

Physical Findings

  • Joint pain and swelling are the key features of rheumatoid arthritis
  • Limited or restricted range of motion 
  • Hand and foot involvements are common in the early course of rheumatoid arthritis
    • Symmetric polyarthritis involving the interphalangeal thumb joints, MCP and/or PIP joints of the hands and the MTP joints of the feet strongly suggests rheumatoid arthritis
  • Deformities due to joint and tendon destruction are late manifestations of rheumatoid arthritis:
    • Ulnar deviation or drift
    • Radial deviation of wrist
    • Boutonnière and swan-neck deformities
    • Hammer toes
    • Joint ankylosis (uncommon)
    • Genu varus or valgus may also be seen secondary to erosion of femoral condyles and tibial plateau

Evaluation

Severity of Disease

  • Rheumatoid arthritis can be characterized as mild, moderate or severe which is best applied to untreated patients

Mild Disease

  • Patients meet the criteria for rheumatoid arthritis, have <6 inflamed joints, with absence of extra-articular involvement and evidence of bone erosions or cartilage loss on X-ray

Moderate Disease

  • Patients have 6-10 inflamed joints
  • Presence of some of the following: Elevated ESR and/or CRP, positive RF and/or ACPA, appearance of inflammation as well as minimal joint space narrowing and small peripheral erosions on X-ray, absence of extra-articular disease

Severe Disease

  • Patients have >20 inflamed joints, elevated ESR and/or CRP
  • Presence of ≥1 of the following clinical features: Anemia of chronic disease and/or hypoalbuminemia, positive RF and/or ACPA, appearance of bone erosions and cartilage loss on X-ray, presence of extra-articular disease

Laboratory Tests

Rheumatoid Factor (RF)

  • Present in approximately 60-80% of patients with rheumatoid arthritis
  • Not recommended in monitoring patients with rheumatoid arthritis but useful in diagnosis especially if measured with ACPA
    • Presence of both RF and ACPA show a more severe disease
  • RF titers rarely change with disease activity

Anti-citrullinated Protein Antibody (ACPA)

  • Shows similar diagnostic sensitivity as RF but with higher specificity rate of approximately 95-98%
  • Not recommended in monitoring patients with rheumatoid arthritis

Acute Phase Reactants

  • Inflammatory markers ESR and CRP are not specific for rheumatoid arthritis but reflect the degree of synovial inflammation
  • Monitoring of these acute phase reactants can be used to assess disease activity

Complete Blood Count (CBC)

  • May show anemia of chronic disease, leukocytosis and thrombocytosis

Imaging

X-ray

  • Commonly used to assess the presence of joint damage secondary to rheumatoid arthritis
  • Early changes include soft-tissue swelling and juxta-articular demineralization
  • Later changes involve erosions through the cortex of the bone and around the margins of the joint
  • Decreased sensitivity if taken during the 1st 6 months of the course of the disease

Magnetic Resonance Imaging (MRI)

  • More sensitive than standard radiography for detecting bone destruction
  • Detects bone erosions and subclinical synovitis earlier in the course of the disease
  • May be used in patients with suggestive cervical myelopathy

Ultrasonography

  • Alternative method to estimate the degree of inflammation and volume of inflamed tissue
  • As with MRI, shows features of joint inflammation that are not physically evident (eg subclinical synovitis for suspected rheumatoid arthritis) and detects bone erosions in early disease
  • May also be used to assess joints for intra-articular steroid injections
  • Should not be used for routine disease activity monitoring in adults with rheumatoid arthritis

Assessment of Disease Activity

  • Several indices are developed to assess disease activity which are useful in monitoring the response to therapy and in defining remission
  • Preferred rheumatoid arthritis disease activity measurements by ACR for regular clinical use include the Disease Activity Score in 28 Joints (DAS28) with ESR or CRP Level, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index, Patient Activity Scale-II, and Routine Assessment of Patient Index Data 3
  • Scores are categorized to low, moderate and high disease activity

Disease Activity Score 28 (DAS28)

  • Assesses the patient’s rheumatoid arthritis disease by measuring the following:
    • Number of swollen joints in the hands (interphalangeal thumb joints, MCP and/or PIP joints), wrists, shoulders, knees, elbows and feet (2nd to 5th MTP joints)
    • Serum ESR and CRP
    • Visual Analogue Score to analyze patient’s global assessment of disease activity on the day of examination
  • The results are combined and assessed based on the total score:
    • <2.6: Disease remission
    • 2.6-3.2: Low disease activity
    • 3.2-5.1: Moderate disease activity
    • >5.1: High disease activity

Clinical Remission

  • The goal of treatment is clinical remission (reached after 6 months of therapy) or if unlikely, at least a low disease activity 
    • Modify treatment if improvement is inadequate (<50% of disease activity) after 3 months of therapy

Definition of Remission in Rheumatoid Arthritis Clinical Trials

  • Two definitions proposed by the ACR/EULAR to define clinical remission in rheumatoid arthritis include the following, suggested to be used in clinical trials as an outcome measure:
    • 1 Boolean-based definition
    • 1 based on a composite index of rheumatoid arthritis activity
  • Boolean-based definition - may be done at any time point, patient should have all of the following:
    • Tender joint count ≤1 (include feet and ankles in the evaluation of the joints)
    • Swollen joint count ≤1 (include feet and ankles in the evaluation of the joints)
    • CRP ≤1 mg/dL
    • Patient global assessment ≤1 (on a scale of 0-10): Based on the patient’s current feeling about their disease
  • Index-based definition - at any time point, patient should have a SDAI score of ≤3.3
  • Sustained remission is ≥6 months according to the ACR/EULAR Boolean- or index-based definition 
  • Persistent remission according to ACR/EULAR is associated with the lowest flare risk and dose tapering 

Poor Prognostic Factors

  • High count of swollen joints
  • Evidence of early erosions
  • Presence of RF and/or ACPA, particularly at high levels
  • High levels of acute phase reactants
  • Moderate or high disease activity persisting despite treatment with conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) (csDMARDs) based on composite measures including joint counts
  • Treatment failure with ≥2 csDMARDs
  • Other factors such as female gender, older age, smoking history and presence of obesity or anemia

 

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