Stanley B. Cohen, MD: Rheumatoid arthritis is an autoimmune disorder where the inflammatory cells attack the joints, as well as other organs. It’s primarily a muscular-skeletal disease, but it’s associated with systemic features such as fatigue, possibly low-grade fever, weight loss, and so forth. And what we know from a great deal of basic and clinical research is that there’s an inflammation of the lining of the joints; synovium becomes inflamed.
The synovium is a membrane, which lubricates the joints and is generally a fatty tissue with small blood vessels. But, with rheumatoid arthritis, it’s almost like tumors induce overgrowth. You get neovascularization, new blood vessels, and you’re full of cells—activated T cells, B cells, and macrophages which reduce inflammatory peptides and also stimulate the growth of the synovium, so it proliferates and eats into the cartilage and the bone.
We know that synovial osteoclasts cause the erosions and structural damage that occur with rheumatoid arthritis. So, in summary, it’s an autoimmune disease with multiple arms in the immune system upregulated. We don’t know, unfortunately, even after all these years, what the trigger is for the disease. We know there’s a genetic background, the DR4 locus, which plays a role in seropositive rheumatoid arthritis, but we don’t know what actually triggers the disease.
If a patient presents with inflammatory arthritis, we need to evaluate them to see if they have rheumatoid arthritis or one of several other forms of inflammatory arthritis, such as psoriatic arthritis or lupus, or a noninflammatory arthritis, such as osteoarthritis. Rheumatoid arthritis is classically a symmetrical polyarthritis. If one wrist is involved, the other wrist is involved; one knee, the other knee; although, there are plenty of exceptions.
The diagnostic workup relies heavily on the patient’s history and physical, like all of internal medicine diseases, and generally we then do laboratory tests and x-rays to confirm the diagnosis. So, in a patient with rheumatoid arthritis, by the time we finished analyzing their history and physical, we would have well been able to discern if they had an inflammatory arthritis. And then, we need to try to figure out what type of inflammatory arthritis they have.
We will check laboratory tests to include a rheumatory factor and cyclic citrullinated peptide antibodies, or CCP antibodies, along with acute phase reactants, such as sed rates (erythrocyte sedimentation) and CRPs (C-reactive protein). And if these are abnormal or positive, then we can make a diagnosis.
We have several features that allow us to differentiate between low- and high-risk patients. A high-risk patient is someone who has CCP antibody positivity, and to a lesser degree, rheumatoid factor positivity. They are at greater risk of disease progression, structural damage, and nonmuscular skeletal manifestations of the disease, whether or not that is what we used to see­—pericarditis, pleurisy, things of that nature, or sensorimotor neuropathy.
Patients who have elevated sed rates and CRPs, and patients who have baseline structural damage on x-rays, are at higher risk for disease progression. We also know that factors such as socioeconomic status and education—a poor socioeconomic status in a lesser educated patient—have a worse prognosis as well. There have been some conflicting results with studies on gender. Some suggest that men may have a worse prognosis, but that has not been substantiated. So, generally, seropositive patients with structural damage are at higher risk, and those are patients who should be treated aggressively from the onset.