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What Causes Rheumatoid Arthritis?

Posted Aug 24 2008 1:49pm
ANNOUNCER: Rheumatoid arthritis is a common disease of the immune system. Although the exact cause is unknown, researchers believe that a combination of factors are involved.

ERIC RUDERMAN, MD: We know there are genes that are associated with it. We also know that it runs in families, and so if someone has rheumatoid arthritis, it's very likely or common that someone else in their family will have rheumatoid arthritis, or sometimes another autoimmune disease.

ANNOUNCER: Researchers have identified specific genetic markers involved in immune function.

ALISA KOCH, MD: One of the main associations is HLA-DR4, and this is a specific genetic marker within which the disease susceptibility region can be found. And we believe that patients are at higher risk for developing rheumatoid arthritis if they have such a disease susceptibility marker.

ANNOUNCER: Environmental factors also appear to be a contributing cause of the disease. These might be a particular infection, periodontal disease or even smoking.

CLIFTON O. BINGHAM, MD: The patient has the right priming of their immune system and then the right set of outside forces come to play, this might be an infection that we haven't identified, it may be outside environmental triggers that we don't yet understand. But what happens is there's a confluence of these things that all come together at the wrong time for the particular patient that begin to activate the immune system.

ANNOUNCER: Immunological factors also play a role. A normal immune system protects the body from bacteria and viruses, while in rheumatoid arthritis, a misdirected immune response contributes to the disease.

ERIC RUDERMAN, MD: The best analogy would be to think about getting a cut on your skin. If you get a cut on your skin and it gets infected, it gets red, it gets swollen. And what's happening there is your immune system is bringing all sorts of inflammatory types of cells into that area to help get rid of the infection. And when the infection is cleared, either on its own or with the help of an antibiotic, those cells tend to go away, and the swelling and the redness goes away, and it heals. In rheumatoid arthritis, it's as if your joints are recruiting all these inflammatory cells from the body into the joint to fight off an infection that we can't find, and it never goes away, and so it's not as if it heals. The inflammation keeps going. It stays there. And that sets the whole cascade in motion that becomes rheumatoid arthritis.

ANNOUNCER: Proteins called cytokines drive the process.

ERIC RUDERMAN, MD: There's a cytokine called interluekin-1, and there's another cytokine called tumor necrosis factor, or TNF, and they're made by cells in the joint, picked up by other cells, and they seem to be an important factor in continuing the inflammatory process. And so when we look at people with rheumatoid arthritis, we see higher levels of these cytokine proteins in the joint tissues, in the fluid in the joints, and even in their blood.

ALISA KOCH, MD: Additionally, these cytokines will recruit other inflammatory cells, such as the lymphocytes, the T lymphocytes and the B lymphocytes into the joint tissue, and those cells will then proceed to proliferate and the B cells will make antibody, which can then later be detected in the joint fluid, the synovial fluid. The cytokines also have effects on blood vessels, so that they can cause the blood vessels to grow and proliferate.

CLIFTON O. BINGHAM, MD: This is all seen, clinically, by symptoms, such as joint swelling, warmth and tenderness. This is all being driven by these chemicals.

ANNOUNCER: While it is difficult to predict the course of the disease, certain factors play a role in how severe it may become.

ERIC RUDERMAN, MD: There are certain markers, markers of active inflammation, markers that include how many joints are involved, certain antibodies, like the rheumatoid factor or the CCP test, that, if they're there, tell me that that person is more likely to have very aggressive disease. They're not one-to-one, so there are people who have some of these markers that are associated with bad disease who may not in fact end up having bad disease. But when we see those, we're even more concerned about making sure we start treatment so that we prevent what we assume are likely to be the consequences.

ANNOUNCER: Doctors say that regardless of the cause, early diagnosis and aggressive treatment are essential.

STEVEN ABRAMSON, MD: We all agree now that this can be a devastating disease that should be treated early, and that once the damage has begun to accumulate in the joints, it's much harder to reverse. In fact, we're not sure that medicines can restore the cartilage and bone, but we have very good evidence now that they prevent the damage to the bone and cartilage, and that's the fundamental cause of disability.

ANNOUNCER: New treatments are offering patients improved outcomes.

STEVEN ABRAMSON, MD: We learned in the 1970s that the life expectancy was reduced by 10 to 15 years from simply having rheumatoid arthritis. So we've become much more aggressive in the past 25 years and have seen for the first time during this period that we can slow the progression of the disease, reduce disability, improve function, get people back to work. We rarely see people in wheelchairs anymore, and I think there's been a real revolution because of better treatments.

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