Robert Ashman, MD
Division of Immunology
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
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
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
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
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
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
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
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
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
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
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
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
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
RE: Predictive factors-- Are no erosions after six months a
good sign? Or do you mean years? What's considered *rapid*
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.