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 & radiological remission of disease and to reduce functional limitations & permanent joint damage.


New Classification Criteria for Rheumatoid Arthritis:

  • Developed by the American College of Rheumatology (ACR) Board of Directors & European League Against Rheumatism (EULAR) Executive Committee
  • Can be applied to patients at more than one point in the evolution of their signs & symptoms
  • Limited only to patients with clinical synovitis in at least 1 joint & synovitis not secondary to other disease
  • A total score of ≥6/10 is needed to classify a patient as having definite rheumatoid arthritis
  • Number & 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) rheumatoid factor or anti-citrullinated protein antibody
  • 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 joints, proximal interphalangeal (PIP) joints, 2nd-5th metatarsophalangeal joints, thumb interphalangeal joint, wrists

Physical Examination

Physical Findings

  • Joint pain & swelling are the key features of early rheumatoid arthritis
  • Hand & foot involvements are common in the early course of rheumatoid arthritis
    • Symmetric polyarthritis involving the metacarpophalangeal, metatarsophalangeal, &/or proximal interphalangeal (PIP) joints of the hands strongly suggest rheumatoid arthritis
  • Deformities due to joint & tendon destruction are late manifestations of rheumatoid arthritis:
    • Ulnar deviation or drift
    • Boutonnière & swan-neck deformities
    • Hammer toes
    • Joint ankylosis (uncommon)
    • Genu varus or valgus may also be seen secondary to erosion of femoral condyles & tibial plateau


Severity of Disease

  • May be used as the basis for the treatment approach
  • 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 & 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 erythrocyte sedimantation rate (ESR) &/or C-reactive protein (CRP), positive rheumatoid factor (RF) &/or anti-citrullinated protein antibody (ACPA), appearance of inflammation as well as minimal joint space narrowing & small peripheral erosions on X-ray, absence of extra-articular disease

Severe Disease

  • Patients have >20 inflamed joints, elevated erythrocyte sedimentation rate &/or C-reactive protein
  • Presence of ≥1 of the following clinical features: anemia of chronic disease &/or hypoalbuminemia, positive rheumatoid factor &/or anti-citrullinated protein antibody, appearance of bone erosions & cartilage loss on X-ray, presence of extra-articular disease

Laboratory Tests

Laboratory Examinations

  • Rheumatoid factor (RF)
    • Present in approximately 60-80% of patients with rheumatoid arthritis (RA)
    • Not recommended in monitoring patients with rheumatoid arthritis but useful in diagnosis especially if measured with anti-citrullinated protein antibody (ACPA)
    • Rheumatoid factor titers rarely change with disease activity
  • Anti-citrullinated protein antibody (ACPA)
    • Shows similar diagnostic sensitivity as rheumatoid factor but with higher specificity rate of approximately 95-98%
  • Acute phase reactants
    • Erythrocyte sedimentation rate (ESR) & C-reactive protein (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 & thrombocytosis
  • Synovial fluid analysis
    • Shows characteristics of inflammatory fluid with low glucose, low C3 & C4 complement levels
      • Synovial fluid glucose, complement or protein levels are not routinely measured due to their limited clinical use
    • Important to determine the total cell count


Imaging Studies

  • X-ray
    • Commonly used to assess the presence of joint damage secondary to rheumatoid arthritis
    • Early changes include soft-tissue swelling & juxta-articular demineralization
    • Later changes involve erosions through the cortex of the bone & 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 earlier in the course of the disease
    • May be used in patients w/ suggestive cervical myelopathy
  • Ultrasonography
    • Alternative method to estimate the degree of inflammation & volume of inflamed tissue
    • As with MRI, shows features of joint inflammation that is not physically evident, & detect 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 w/ rheumatoid arthritis

Clinical Remission

  • Two definitions are proposed by the American College of Rheumatology/European League Against Rheumatism to define clinical remission in rheumatoid arthritis
    • These are suggested to be used in clinical trials as an outcome measure

Definition of Remission in Rheumatoid Arthritis Clinical Trials

  • Boolean-based definition - may be done at any time point, patient should have all of the following:
    • Tender joint count ≤1 (include feet & ankles in the evaluation of the joints)
    • Swollen joint count ≤1 (include feet & 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 & on physician’s assessment of the patient’s current disease activity
  • Index-based definition - at any time point, patient should have a Simplified Disease Activity Index (SDAI) score of ≤3.3

Assessment of Disease Activity

  • Several indices are developed to assess disease activity which are useful in monitoring the response to therapy & in defining remission
  • Scores are categorized to low, moderate & high disease activity
  • Eg Disease Activity Score in 28 points, Simplified Disease Activity Index, Clinical Disease Activity Index, Rheumatoid Arthritis Disease Activity Index, PAS of PASII, Routine Assessment Patient Index Data

Disease Activity Score 28 (DAS28)

  • Assesses the patient’s rheumatoid arthritis disease by measuring the following:
    • Number of swollen joints in the hands, wrists, shoulders, knees & elbows
    • Serum erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP)
    • Visual Analogue Score to analyze patient’s assessment on their level of pain & discomfort on the day of examination
  • The results are combined & 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
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