Symptoms

Signs and Symptoms

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

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

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