Clinical Manifestations

Signs and Symptoms
  • Joint pain
  • Morning stiffness lasting >1 hr
  • Myalgia, fatigue, weight loss, low-grade fever, depression
  • Typically involves the joints of the fingers, wrists, toes
  • Upper & lower extremity joints are also affected (eg shoulders, elbows, knees & ankles)
  • Syndrome of polymyalgia rheumatica may occasionally be present
Physical Findings
  • Joint pain & swelling are the key features of early rheumatoid arthritis
  • Hand & foot involvements are common in the early course of RA
    • Symmetric polyarthritis involving the metacarpophalangeal, metatarsophalangeal, &/or proximal interphalangeal (PIP) joints of the hands strongly suggest RA
  • Deformities due to joint & tendon destruction are late manifestations of RA:
    • 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



  • Based on clinical signs & symptoms, lab results & imaging features
New Classification Criteria for RA:
  • 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 w/ 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 RA
  • 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) 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 wk
Differential Diagnoses
  • Systemic diseases
    • Rheumatic fever
    • Infective endocarditis
    • Still’s disease
    • Sarcoidosis
  • Other connective tissue syndromes
    • Scleroderma
    • Systemic lupus erythematosus
    • Systemic vasculitides
  • Spondyloarthropathies
    • Psoriatic arthritis
    • Reactive arthritis
  • Infectious arthritis
  • Crystal-induced arthritis
  • Endocrinopathies
  • Fibromyalgia
  • Osteoarthritis
  • Hemochromatosis
  • Paraneoplastic syndromes
Lab Exams
  • Rheumatoid factor (RF)
    • Present in approx 60-80% of patients w/ RA
    • Not recommended in monitoring patients w/ RA but useful in diagnosis esp if measured w/ ACPA
    • RF titers rarely change w/ disease activity
  • Anti-citrullinated protein antibody (ACPA)
    • Shows similar diagnostic sensitivity as RF but w/ higher specificity rate of approx 95-98%
  • Acute phase reactants
    • ESR & CRP are not specific for RA but reflect the degree of synovial inflammation
    • Monitoring of these acute phase reactants can be used to assess disease activity
  • CBC
    • May show anemia of chronic disease, leukocytosis & thrombocytosis
  • Synovial fluid analysis
    • Shows characteristics of inflammatory fluid w/ 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 RA
    • 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 mth 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
  • Ultrasonography
    • Alternative method to estimate the degree of inflammation & volume of inflamed tissue
    • As w/ MRI, shows features of joint inflammation that is not physically evident, & detect bone erosions in early disease
    • May also be used to assess metatarsophalangeal joints & for intra-articular steroid injections
1 Eg metacarpophalangeal joints, PIP joints, 2nd-5th metatarsophalangeal joints, thumb interphalangeal joint, wrists


Clinical Remission

  • Two definitions are proposed by the American College of Rheumatology/European League Against Rheumatism to define clinical remission in RA
    • These are suggested to be used in clinical trials as an outcome measure
Definition of Remission in RA Clinical Trials
  • Boolean-based definition - may be done at any time point, patient should have all of the ff:
    • 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, SDAI, 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 RA 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