Rheumatoid Arthritis
Epidemiology
There is an annual incidence of around 0.4 per 1000 in female and 0.2 per 1000 in males. The incidence may be rising. The prevalence is 0.4-1% with geographical variation. The strongest risk factor is smoking.
Pathology
In the synovial tissue, there is recruitment and retention of inflammatory cells, the formation of villous projections, and the generation of pannus tissue that invades and destroys cartilage and bone. The pathology occurs in stages. Mechanisms that initiate disease are distinct from those that perpetuate disease. In chronic synovitis there are interactions of cell types native to the joint and inflammatory cells are recruited. Cytokine "networks" are established. Angiogenesis occurs and this is promoted by mediators that include growth factors, proinflammatory cytokines, chemokines, matrix components, cell adhesion molecules, proteases, and others. Enzymatic destruction of the cartilage matrix occurs. Osteoclasts contribute to articular bone resorption.
Clinical Features
The preclinical phase is defined by an RA-related autoimmunity without clinically apparent inflammatory arthritis. This RA-related autoimmunity can be triggered initially outside the joints in a mucosal site. The RA-related autoantibodies that include RF and anti-CCF can be used to identify those at risk of developing RA in the future.
In clinically apparent disease, the typical features are morning stiffness along with swelling in the wrists, PIPJs and MCPJs. The early diagnosis is critical, however many cases of early arthritis are not RA.
Anti-CCP antibodies occur earlier than RF and are more specific than the latter.
Extra-articular features may occur including constitutional symptoms, distinct organ manifestations, and severe multiorgan disease. Systemic features may have a poor prognosis, especially the presence of vasculitis and rheumatoid lung disease.
Imaging
Symmetric bilateral RA is commonly seen in the hands and feet, but asymmetric disease is frequently found in large joints. The earliest radiographic changes occur in the hands and feet: tissue swelling, erosions, and diffuse joint space narrowing. Radiographic evidence of disease in the large joints is most common in the elbow, shoulder, and knee. Sacroiliac joint disease is uncommon. Rare late-term complications are atlantoaxial subluxation and basilar invagination. The best view for atlantoaxial subluxation is a lateral film of the cervical spine in flexion. For basilar invagination MRI and CT are best. Ultrasound and MRI are increasingly commonly used to detect subclinical disease.
Antibodies
Most autoantibodies are not joint-specific. Autoantibodies are present in the earliest stages of disease, and there may be years before clinical disease manifestation.
Rheumatoid factors (RFs) are autoantibodies to the Fc portion of IgG. High-titre IgM-RF and IgA-RF are associated with erosive and more severe disease. Anti-citrullinated citrullinated protein antibodies (anti-CCPs) are autoantibodies to atigens containing the unusual amino acid citrulline. They are more specific than RF, and similar to high-titre RF are associated with erosive RA.
Assessment
Assessment involves prognosticating the disease process. The key features of disease process are joint swelling and tenderness, the acute-phase response, pain, patient global assessment, and evaluator global assessment. Clinical disease activity using composite measures is of at least similar validity to ultrasonographic assessment without any clinical benefit. Disease activity is the immediate target of therapeutic intervention. The ultimate goal is optimal disease outcome which encompasses health-related quality of life. The proxy measure for disease outcome is radiographic damage. Function can be assessed with the Health Assessment Questionnaire or direct functional performance tests. Function is influenced by disease activity as well as joint damage. Any functional disability from joint damage is irreversible.
Diagnostic Criteria
Target population (those who should be tested): Patients
Classification criteria for RA (score-based algorithm: add score of categories A–D; a score of ≥6/10 is needed to classify a patient as having definite RA)[Note 3] | |
| A. Joint involvement[Note 4] | Score |
|---|---|
| 1 large joint[Note 5] | 0 |
| 2–10 large joints | 1 |
| 1–3 small joints (with or without involvement of large joints)[Note 6] | 2 |
| 4–10 small joints (with or without involvement of large joints) | 3 |
| >10 joints (at least 1 small joint)[Note 7] | 5 |
| B. Serologic results (at least 1 test result is needed for classification[Note 8] | Score |
| Negative RF and negative ACPA | 0 |
| Low-positive RF or low-positive ACPA | 2 |
| High-positive RF or high-positive ACPA | 3 |
| C. Acute-phase reactants (≥1 test result is needed for classification)[Note 9] | Score |
| Normal CRP and normal ESR | 0 |
| Abnormal CRP or abnormal ESR | 1 |
| D. Duration of symptoms[Note 10] | Score |
| <6/wk | 0 |
| ≥6/wk | 1 |
|
ACPA, Anti–citrullinated protein antibody; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate. | |
Criteria Notes
- ↑ The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of rheumatoid arthritis (RA) with a history compatible with prior fulfillment of the 2010 criteria should be classified as having RA. Patients with long-standing disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA.
- ↑ Differential diagnoses vary among patients with different presentations but may include conditions such as systemic lupus erythematosus, psoriatic arthritis, and gout. If it is unclear about the relevant differential diagnoses to consider, an expert rheumatologist should be consulted.
- ↑ Although patients with a score of <6 of 10 are not classifiable as having RA, their status can be reassessed, and the criteria might be fulfilled cumulatively over time.
- ↑ Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. Distal interphalangeal joints, first carpometacarpal joints, and first metatarsophalangeal joints are excluded from assessment. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement.
- ↑ “Large joints” refers to shoulders, elbows, hips, knees, and ankles.
- ↑ ∥“Small joints” refers to the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists.
- ↑ In this category, at least one of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed elsewhere (e.g., temporomandibular, acromioclavicular, sternoclavicular).
- ↑ “Negative” refers to international unit (IU) values that are less than or equal to the upper limit of normal (ULN) for the laboratory and assay; “low-positive” refers to IU values that are higher than the ULN but three times or less the ULN for the laboratory and assay. Where rheumatoid factor (RF) information is available only as positive or negative, a positive result should be scored as low positive for RF.
- ↑ Normal and abnormal is determined by local laboratory standards.
- ↑ “Duration of symptoms” refers to patient self-report of the duration of signs or symptoms of synovitis (e.g., pain, swelling, tenderness) of joints that are clinically involved at the time of assessment regardless of treatment status.
Management
Early diagnosis and treatment are critical for optimal outcomes. At the earliest opportunity DMARDs +/- glucocorticoids should be used. The disease activity is monitored regularly until a target is reached, which is ideally remission. A proportion of patients can achieve remission in early RA without medication, however DMARDs are effective in slowing or stopping RA progression and are the mainstays of treatment. Effective management also reduces the risk of complications including cardiovascular disease and cancers. Eventual withdrawal of DMARDs is potentially possible in some patients but there is a high risk of relapse.
