Rheumatoid arthritis
From Standard of Care
Chronic systemic disease with articular and extra-articular manifestations.
Hallmark is symmetrical inflammatory polyarthritis affecting small proximal diarthrodial joints.
Most common cause of adult inflammatory arthritis.
Conventional radiography is the standard measure of structural joint damage.
Characteristic laboratory abnormality is a positive rheumatoid factor, a circulating autoantibody against the Fc fragment of immunoglobulin G (IgG).
Affects 1 in every 100 people.
Associated with increased comorbidity and premature mortality.
Women:male 3:1.
Affects about 1% of the U.S. population.
Increased incidence in women related to increased prevalence before menopause.
About 70% of patients women.
Smoking a risk factor, and a predictor of disease severity.
Susceptibility linked with a region on chromosome 2q.
Arg620→Trp variant of the intracellular phosphate gene PTPN22 associated with the disease.
Elevated IL-6 contribute to anemia and fatigue associated with rheumatoid arthritis.
Twins studies reflect a genetic contribution to the disease and sibling of patients with seropositive disease have a 5-10 times increased risk of developing the disease than the general population.
Associated with an increased risk of death when severe, with advanced joint disease, functional limitations, disabilities, and extraarticular manifestations.
Burden of comorbidity is higher than expected associated compared to people of the same age and sex.
Peak age of onset is between fourth and fifth decades but can begin at any time.
1987 American Rheumatism Association classification criteria:
- Morning stiffness lasting greater than 1 hour for more than 6 weeks - Swelling in 3 or more joints for more than 6 weeks - Swelling in hand joints for more than 6 weeks - Symmetrical joint swelling for more than 6 weeks - Erosions or decalcification seen on hand x-rays - Rheumatoid nodules - Presence of serum rheumatoid factor
Interaction of T-cells and macrophages in joints plus their cytokines that drives the illness by stimulating the synovium to become hyperplastic and hypertrophic.
The growing inflammatory synovium and degrading enzymes, such as collagenase erode bone and cartilage and connective tissues within the joint capsule.
The synovium lining layer has an increased number of cells and the sublining is infiltrated with inflammatory cells, including lymphocytes, mast cells and macrophages.
Cells in the synovium produce cytokines that, with locally produced autoantibodies drive the chronic inflammatory process.
A3 adenosine receptor (A3AR) overexpressed in synovial tissue and peripheral blood mononuclear cells of patients and stimulation of the receptor decrease production of TNF-alpha.
Mortality in severe end-stage disease is comparable to three-vessel coronary artery disease or stage IV Hodgkin's disease.
Drug of choice since the 1990's is methotrexate but combination therapy is better.
Most cases are sporadic but concordance rates in monozygotic twins range from 15-30%.
Monozygotic twins have an increased concordance rate of rheumatoid arthritis compared to dizygotic twins.
Estimated that hereditability accounts for 60% of the role in etiology.
Patients with rheumatoid arthritis are more likely to be related to each other than are patients without rheumatoid arthritis, with the familial component extending beyond the primary family.
HLA-DR4 associated with aggressive disease, extraarticular processes and Felty's syndrome.
Interaction with IL-6 and other cytokines, immune cells, synovial fibroblasts and osteoclasts associated with signs and symptoms of rheumatoid arthritis including, cartilage destruction, bone degradation and pannus formation.
Interleukin-6 (IL-6) found in abundance in rheumatoid synovium and markedly elevated in the serum of patients rheumatoid arthritis.
IL-6 levels correlate with rheumatoid disease stage, severity of joint destruction and many systemic manifestations of RA.
Extraarticular manifestations include: rheumatoid nodules, skin ulcers, episcleritis, pleuropericarditis, vasculitis, lymphadenopathy, peripheral neuropathy, and Sjogren syndrome.
Rheumatoid arthritis not associated with uveitis.
Rheumatoid nodules in the lungs are most common in patients with rheumatoid factor and also have subcutaneous nodules.
Pulmonary manifestations include pulmonary nodules, interstitial fibrosis, pleural effusions, bronchiectasis, bronchiolitis, pulmonary hypertension and rarely vasculitis.
Significant joint destruction can occur within 2 years of the onset of disease.
2 years is a reasonable time in which to divide erosive from nonerosive rheumatoid arthritis, i.e. patients who have nonerosive disease by 2 years are unlikely to show subsequent erosive damage.
Up the 70% of patients have radiographic damage within the first 3 years after the onset of symptoms.
All anti-TNF (tumor necrosis factor) agents have clinical and radiologic benefits in early arthritis.
Combination therapy of anti-TNF agents and methotrexate have better response rates than either agent alone.
Patients with disease present less than 1 year have a significant likelihood of responding to treatment than individuals who have the disease duration of greater than 10 years.
One year ACR 20 response rate 35-57% for methotrexate.
One year ACR 20 response rate for leflunomide (Arava) about 45%.
One year ACR 20 response rate for etanercept (Enbrel) of 72% and ACR 50 of 49% at two years.
70% have no erosions of joints at two years with etanercept.
Predisposes to infections and increased risk of lymphoma.
Patients are a greater risk for cardiovascular morbidity and mortality.
Goal of therapy is to maximize control of the disorder within 2 years of diagnosis to prevent irreversible damage.
Hands are affected in virtually all patients.
The wrists, metacarpophalangeal joints, and proximal interphalangeal joints are most commonly involved.
Extra-articular manifestations predicted by severe joint disease, a positive antinuclear antibody, assay, IgA rheumatoid factor, rheumatoid nodules, and some HLA_DR haplotypes.
Therapeutic intervention early in the disease can lead to decreased joint damage and this particularly true if treated aggressively with combinations of medications.
Intensive weight bearing exercises improve aerobic conditioning and muscle strength in patients with RA without increase in disease activity.
The presence of antibodies to cyclic citrullinated peptides (CCP) is highly predictive of developing rheumatoid arthritis.
Patients with early polyarthritis positive for anti-CCP antibodies have a 93% chance of developing classic rheumatoid arthritis in 3 years.
One third of rheumatoid factor negative patients have a positive anti-cyclic citrullinated peptide antibody test.
Some patients present with sudden onset of episodic and transient monoarthritis or oligoarthitis without residual joint disease referred to as palindromic arthritis.
May present with glomerulonephritis and rheumatoid vasculitis both of which have active urinary sediment.
