Robert Ashman, MD
Professor
Division of Rheumatology

The University of Iowa

Peer Review Status: Internally Peer Reviewed
First Published: May 2000
Last Revised: September 2004

I am a director of the Rheumatology Division at University of Iowa Health Care. We are going to be talking today about arthritis and other diseases that affect the joints, muscles, and bones or cause inflammation. I would be happy to begin answering your questions now.

How does rheumatoid arthritis differ from other forms of arthritis?

Rheumatoid arthritis is the most common form of inflammatory arthritis. In rheumatoid arthritis, the lining of the joints becomes inflamed, almost as if they were infected, except, there is no evidence of any actual infection. Because there is no infection, the body is not able to stop the inflammation by itself. So we have to use various anti-inflammatory medications in order to stop the inflammation. There are about 30 recognized forms of inflammatory arthritis that your doctor needs to distinguish from rheumatoid arthritis. The treatment of inflammatory arthritis of different kinds has much in common, but there are differences, so accurate diagnosis is useful. Rheumatoid arthritis is different from osteoarthritis, which is the main non-inflammatory form of arthritis.

Are there any dietary concerns that could help with rheumatoid pain?

No. There are several books that have been written with conflicting claims about the best diet for rheumatoid arthritis. No food or combination of foods has ever been shown to affect rheumatoid arthritis with one exception: if you eat very large quantities of oily fish, that will decrease inflammation. After the research study that showed this was completed, none of the patients wanted to continue the diet because they didn't want to smell like fish. Other dietary changes that have been suggested have never been proven to have an effect. However, weight loss, if the patient is obese, is very helpful because it takes the pressure off joints.

What causes arthritis?

That would depend on the type of arthritis that you are talking about. When there is inflammation in the lining of the joint, the inflammation causes the joint to hurt. Extra fluid may form in the joint, the joint lining may swell, and the range of motion may be less until the inflammation is treated. There are many possible causes for inflammation that can add together to cause an inflammatory arthritis, but, in most cases, the cause is not known. Bacterial infection can cause acute arthritis with inflammation, which constitutes an emergency. Gout can cause an acute arthritis that needs to be distinguished from infection. When we get to non-inflammatory causes like osteoarthritis, the primary problem seems to be wear and tear of cartilage, which can be accelerated by an injury, by previous inflammation, or even by normal aging. The genes you inherit affect both kinds of arthritis. Some types of arthritis can run in families.

What are the symptoms of arthritis?

The symptoms of arthritis are pain in the joints. When the arthritis is non-inflammatory, the pain is worse with use and usually worse at the end of the day. When the pain is due to inflammation, frequently pain and stiffness are greatest in the morning or after a long period of rest. They are relieved by heat and gentle exercise. Of course, the most important symptom of arthritis is decreased function, sometimes caused by pain, and sometimes because the joint does not move properly. The treatment is directed to reducing inflammation, reducing pain and stiffness, but also to improving function.

Do most people just live with the pain? What are some of the most aggressive types of treatments?

I will assume that the questioner was referring to rheumatoid arthritis, an inflammatory form. We have a large selection of anti-inflammatory drugs that we can use, and we are able to escalate the attack on arthritis to the point where we can make the inflammation substantially improve in over 95 percent of patients with rheumatoid arthritis. It would take the rest of the hour to describe all of these medications to you. What I tell my patients is that if you don't get a good result with the medicine and dose that I prescribe, we can either change the dose or change the medicine or add a new medicine until the inflammation goes away. With non-inflammatory arthritis, like osteoarthritis, pain control and physical therapy to improve range of motion and strength are equally important. An anti-inflammatory medication is much less important.

How do drugs like aspirin, ibuprofen, naprosyn, and the coxibs work?

These are non-steroidal anti-inflammatory agents that work on an enzyme called cyclooxygenase. There are two forms of this enzyme. Aspirin and similar medications inhibit both enzymes. Coxibs (Celebrex, Vioxx, Bextra) inhibit only one enzyme. Because of that, they avoid some of the side-effects that are seen with aspirin and similar medications, especially the effect on bleeding and on the stomach lining. None of the research has shown that coxibs work better for arthritis than earlier cheaper medications; however, they have the advantage of producing fewer stomach ulcers. For that reason, they are often used in people who have a tendency to form stomach ulcers on other medications. There also is less risk of bleeding in people who are on anticoagulants with coxibs than with aspirin. Notice that I said the risk is less; I didn't say it was absent. For people who lack these special risks, the nonselective meds may work as well as the more expensive, highly advertised coxibs.

What causes arthritis in kids?

The major type of arthritis in children is called juvenile chronic arthritis. It is an inflammatory arthritis. Its cause has not been determined; in fact, it is probably several different diseases.

I take a non-steroidal, which works like a charm! Sometimes when I get a headache, I would also like to take some acetaminophen. Can you mix them?

Yes, you can take acetaminophen with an anti-inflammatory medication. However, it is not wise to take two non-steroid anti-inflammatory medications simultaneously, because most of the time you get better relief with one drug at an optimal dose.

Why do changes in weather affect arthritis?

No one has described why changes in weather affect arthritis. Most patients describe that weather changes do affect their arthritis, but they disagree as to what kind of weather changes are helpful and what kinds make it worse. In other words, I have had patients who have moved to the upper Midwest from Arizona because their arthritis is better in a moist, cold climate and others who live here who want to leave for Arizona because they think a hot, dry climate will be better.

What are some of the other "joint diseases"?

Arthritis means that there is pain in the joint, and most diseases of the joint cause either pain or limitation of motion, so we use the term arthritis to cover all of them. We have mentioned rheumatoid, osteo, infectious arthritis and gout. Other important categories are ankylosing spondylitis, an inflammation of the spine, reactive arthritis, psoriatic arthritis and lupus. In each case of these forms, arthritis is associated with inflammation in other parts of the body.

Does glucosamine really help rebuild cartilage? Is it safe? Is it better with or without Chondroitin added? What dosage is best?

Glucosamine is a constituent of cartilage, kind of like a brick is a constituent of a brick wall. When you eat glucosamine, it is digested and does not go to build up cartilage. However, clinical trials have shown that there is osteoarthritis pain in patients who take glucosamine. This effect commonly takes three to six months less to develop, even in patients who describe less pain in taking these medications. There is one trial showing that the cartilage loss is slower. The evidence for the use of chondroitin sulfate is not as convincing, but neither of these has been shown to cause harm. I don't know any clinical trial that establishes an optimal dose but 1500 mg of glucosamine per day was used in the trials.

I read that RA aggressiveness decreases after the first years? Is this true?

Generally not. Rheumatoid arthritis is most commonly a progressive disease where more joints become involved over time. We are reluctant to diagnose rheumatoid arthritis in patients who have had less than about two months of symptoms. Some patients with rheumatoid arthritis will show spontaneous decrease in inflammation, but this usually happens after ten or more years of disease, so we can't wait for that. Our treatment of rheumatoid arthritis is much more aggressive today than it was ten years ago. This is because of increased appreciation for destruction that even a couple of months of inflammation can cause and because of better medications for controlling inflammation. The earlier inflammation is suppressed, the less the joint destruction and disability.

Is there a predictive factor then for how bad it may become?

Yes. The pace at which new joints become involved is a predictive factor. A minority of patients with rheumatoid arthritis have only a few joints involved or a pattern of intermittent activity. This predicts that they will have a good outcome. However, most patients have progressive disease, which predicts a worse outcome. The rapid development of defects in the bone near the joints that are inflamed, predicts a bad outcome. In general, the patients who have a positive rheumatoid factor blood test have a worse outcome than the 25 percent that do not develop rheumatoid factor.

My father has RA, and I had an episode when I was 19. I am now 23, and haven't had a reccurrence. Is there any chance that it is in permanent remission?

Yes, there is a good chance that it could be a permanent remission. It turns out that several viruses can cause an arthritis resembling rheumatoid arthritis. This goes away within six months or less, never to recur. You may have had this kind of arthritis. Alternatively, you may have a delayed recurrence, but the longer you go without a recurrence, the greater is the chance that you won't have one.

How is the usual case of rheumatoid arthritis treated?

We generally begin with weekly methotrexate, which is efective in about 75% of cases. Methotrexate has the advantage that we have 40 years of experience with it, and so we know its side effects and how to avoid them. The key to avoiding the two most serious side effects is to do monthly blood tests for blood cells and liver function. These tests give advanced warning as to which patients are likely to have side effects. It is important to avoid alcohol and pregnancy while on methotrexate. It takes 6 to 8 weeks for a given dose of methotrexate to have its full effect. If there is no effect, the dose can be raised or other drugs added. If the blood tests warn of trouble ahead, we change to a different drug. Finding the lowest dose that works in an individual patient is very valuable for avoiding side effects. Once that dose is determined, it is often effective for many years. The frequency with which rheumatoid arthritis breaks through methotrexate is very low so usually remission can be sustained with methotrexate.

What is the latest research being done regarding rheumatoid arthritis?

There is a great deal of research being done on arthritis. In inflammatory arthritis, some of the most exciting research comes from studying the cells of the immune system that create inflammation. More than 20 years of research in molecular immunology has begun to pay off in the development of new medications that interrupt specific pathways of inflammation, while leaving other functions of the immune system intact. Drugs like Enbrel, Remicade, and Humira are examples of drugs that arose from basic immunology research. We hope that there will be many others in the future that stop inflammation by different means. Today we can treat the most difficult cases of rheumatoid arthritis with combinations of medications like the cancer specialists have learned to do. Several effective combinations have already been tested and shown to be relatively safe and are in use. We are witnessing a revolution in the way we treat arthritis.

Can the inflammation of arthritis be aggravated by the monthly menstrual cycle?

There are hormone changes that can affect the intensity of inflammation and also fluid shifts that can increase the swelling of joints at different times in the menstrual cycle. While some patients clearly describe fluctuations in symptoms, many other patients do not.

RE: Predictive factors-- Are no erosions after six months a good sign? Or do you mean years? What's considered *rapid* deterioration?

I have seen patients with rheumatoid arthritis who have progressed so rapidly that they have become disabled within a matter of weeks. This early progression can be reversed with strong anti-inflammatory therapy in most cases. Erosions by six months would certainly be a bad sign. More commonly, it takes one or two years to form erosions. On the other hand, if you have rheumatoid arthritis for as long as five years and no erosions or deformities have occurred, that is generally a good sign.

Do you recommend Enbrel for RA for use along with MTX? How about for early sero-positive RA?

Remicade, Humira, and Enbrel are the new "biologic" medications. They are more effective than methotrexate and are used in patients who have failed to respond to methotrexate. If they were inexpensive, there would probably be more use in early rheumatoid arthritis. Because of their expense, most patients with rheumatoid arthritis are unable to afford them, and insurance companies insist that patients must fail to improve with the less expensive medications before they will agree to pay for a "biologic" treatment. If, in the future, biologics become much less expensive, they might be used much more. However, the question about long-term side effects with biologics requires that they be studied over a period of many years before we can be certain about their long-term safety. Having said that, I have had good results, in general, when adding a biologic to methotrexate.