Latest News in Rheumatology
3/14/2003
Age at Disease Onset and Diagnosis Delay in HLA-B27
Negative vs. Positive Patients With Ankylosing Spondylitis
HLA
Antigens May Influence the Age of Onset of Psoriasis and Psoriatic Arthritis
FDA Officials Argue Over Safety of New Arthritis Drug
Vitamin
D Helps Elderly Avoid Fractures
Bilateral
Anterior Toxic Optic Neuropathy and the Use of Infliximab
New
Database Gives Food Ingredient Details
Getting
Help With Prescription Drugs
Beating the System -- Ways to Protect Yourself in Three
Crucial Areas of Concern
In order to investigate differences between HLA-27 negative and HLA-B27
positive patients with AS, researchers Ernst Feldtkeller and colleagues from
around the world studied a total of 1080 patients with AS. They found the
following statistics.
Average age at disease onset:
HLA-B27 negative -- 27.7 years
HLA-B27 positive -- 24.8 years
Average age at diagnosis:
HLA-B27 negative -- 39.1 years
HLA-B27 positive -- 33.2 years
Average diagnosis delay:
HLA-B27 negative -- 11.4 years
HLA-B27 positive -- 8.5 years
Percentages with childhood disease onset (before the
age of 16 years):
HLA-B27 negative -- 7.6%
HLA-B27 positive -- 6.2%
Percentages of late onset (after the age of 40 years):
HLA-B27 negative -- 13%
HLA-B27 positive -- 5%
Acute anterior uveitis frequency (a potentially serious
complication of AS
involving the eye):
HLA-B27 negative -- 26%
HLA-B27 positive -- 41%
Average age at disease onset between males and females:
Males -- 25.7 years
Females -- 24.2 years
This study involved a much larger number of HLA-B27 negative
AS patients than had been previously studied. It confirms earlier reports
indicating a significantly older average age at disease onset and a less
frequent prevalence of acute anterior uveitis in HLA-B27 negative than in
HLA-B27 positive in AS. The frequency of late disease onset (after 40 years of
age) is significantly higher in HLA-B27 negative AS.
These researchers provide the first report on significant differences in the
distribution curves for the age at disease onset and for the age at diagnosis
between HLA-B27 negative and positive AS patients. The average delay between the
first spondyloarthritic symptoms and diagnosis is significantly longer in
HLA-B27 negative than in HLA-B27 positive AS. The frequency of juvenile disease
onset (before age 16) is nearly the same for both groups.
Interestingly, the researchers did not find a
difference between patients with primary AS and AS associated with psoriasis, inflammatory
bowel disease, or reactive arthritis.
An abstract for this study can be found online at: http://link.springer.de/link/service/journals/00296/contents/02/00237/s00296-002-0237-4ch002.html.
Researcher Ruben Quiero and colleagues sought to analyze whether HLA antigens influence the age of onset
of both psoriasis and psoriatic arthritis (PsA). They studied 135 patients with PsA (77 men; 58 women; average age 47 years),
and 50 patients with psoriasis alone were also recruited to analyze the role of
the HLA-Cw gene on disease susceptibility.
Average age of psoriasis onset in PsA patients:
HLA-Cw6 negative -- 32 years
HLA-Cw6 positive -- 23 years
Average age of PsA onset in PsA patients:
HLA-Cw6 negative -- 38 years
HLA-Cw6 positive -- 35 years
Average age of psoriasis onset in patients with psoriasis alone:
HLA-Cw6 negative -- 30 years
HLA-Cw6 positive -- 18 years
Average age of psoriasis onset in PsA patients:
HLA-B27 negative -- 32 years
HLA-B27 positive -- 24 years
Average age of PsA onset in PsA patients:
HLA-B27 negative -- 40 years
HLA-B27 positive -- 30 years
This study found that the HLA-Cw6 gene correlated well with a positive family
history of psoriasis among first-degree relatives -- 64% of patients with family
history of psoriasis were HLA-Cw6 positive, whereas only 30% of those without
family history were HLA-Cw6 positive.
Their results confirm the known association between HLA-Cw6, early onset psoriasis, and
positive family history (type 1 psoriasis). The association between HLA-B27 and
earlier onset ages for both psoriasis and PsA had not previously been
emphasized. They believe that HLA genes may determine not only disease
susceptibility, but also the age of disease onset in psoriasis and PsA.
An abstract for this study can be found online at: www.jrheum.com/abstracts/abstracts03/505.html
An eternal advisory panel to the US Food and Drug Administration, called the
Arthritis Advisory Committee, rejected calls from FDA safety experts to withdraw
a drug for rheumatoid arthritis from the market. The advisory committee found
that the benefits of the Aventis drug leflunomide (Arava) outweigh its rare side
effects, despite an internal FDA report that said that one in 200 users may be
at risk of serious acute liver injury.
The report from the FDA's Office of Drug Safety for the advisory committee's
meeting found that there was "an absence of documented long-term benefit
based on objective indices of functional ability/disability or delayed
mortality." It concluded that risks of leflunomide "greatly exceeded
its benefits". And because there are safer and more effective alternatives
on the market, the authors recommended the drug be immediately withdrawn.
Yet the recommendation was directly contradicted by senior FDA officials
because many of the reports linking the drug with acute liver injury were
confounded, inconclusive, or incomplete. One senior FDA officer, Dr. Lawrence
Goldkind, told the advisory panel than an exhaustive review of data, including
large health insurance databases covering more than 50,000 patients, indicated
that serious liver injury was a very rare side effect of the arthritis drug. He
claims there was no "consistent pattern" of toxicity, as seen with
other drugs.
The report can be viewed online at: www.fda.gov/ohrms/dockets/ac/03/briefing/3930b2.htm.
Prior studies have shown that a combination of vitamin D and calcium can
reduce fractures. But researchers in this new study wanted to see if vitamin D
alone would have the same effect. They point out that it is especially important
to prevent bone thinning and fractures in the elderly since breaking a hip can
cause death in many elderly people due to an increase in pneumonia or blood
clots from being immobilized in bed. Osteoporosis is also a known potential
complication for people with spondylitis. Results of this study were published
in the March issue of the British Medical Journal.
They studied more than 2,500 people 65 to 85 years old. Each person took
100,000 IU of vitamin D, which is a high dose compared with the normal dose of
400 IU, or a placebo every four months.
People who took vitamin D were 22% less likely to have a fracture during the
five-year study. They also were 33% less likely to have a fracture in areas of the
body that are commonly affected by osteoporosis, such as the hip, wrist,
vertebrae, and forearm.
There were no side effects of vitamin D and the cost was very small -- only
$1.59 a year. The researchers suggest further research into vitamin D as a way
of preventing fractures and believe that this could be a welcome addition to
potentially preventing osteoporosis and the serious health effects of this
disease.
Three cases of bilateral optic neuropathy were recently reported to the
Netherlands Pharmacovigilance Centre Lareb. Toxic optic neuropathy can result in
optic disc swelling and vision loss. Marcel P M ten Tusscher and colleagues
discuss the patients' experience and their use of infliximab (Remicade®).
Patient #1:
54 year old man with rheumatoid arthritis
Blurred vision 34 days after he was given a third dose of
infliximab
Also taking leflunomide, prednisone, naproxen, diazepam,
fluoxetine, famotidine,
metoprolol, and acetaminophen or codeine
20/30 vision in both eyes
Showed severe disc swelling, visual field defects, and
leakage to optic nerve heads
Treated with steroids but his vision did not recover
Patient #2:
62 year old woman with rheumatoid arthritis
Blurred vision 40 days after her third dose of infliximab
Also taking atenolol, enalapril or hydrochlorothiazide,
salicyclic acid, terfenadine,
and rofecoxib
20/80 vision in one eye
Showed slight swelling of the optic disc in right eye, marked
disc swelling with a
hemorrhage on the left eye, leakage, scotoma (blind spot),
etc.
Treated with methylprednisolone, but her vision failed to
improve
Patient #3:
54 year old man with rheumatoid arthritis
Loss in visual field two weeks after he was given the last of
three doses of
infliximab
Also taking prednisone, diclofenac, and omeprazole
20/400 vision in one eye
Showed disc swelling in both eyes, leakage, central defects,
scotoma, etc.
Vision decreased to 20/100
These three patients were diagnosed as having anterior optic neuropathy and
treated with steroids, but their conditions did not improve.
They reported symptoms after they had been given the third dose of infliximab,
suggesting that the effects of the drug may have increased with cumulative dose
or with time. Alternatively, the researchers suggest that rheumatoid arthritis
might be considered to be a risk factor for the anterior optic neuropathy.
Various drugs have been linked with optic neuropathy, but these drugs were
not used by their patients (with the exception of omeprazole, which was taken by
the third patient). It is questionable whether omeprazole causes optic
neuropathy, and their patient had used omeprazole for a long time without ocular
problems.
The paper can be found online at the British Medical Journal web site: http://bmj.com/cgi/content/full/326/7389/579.
The U.S. Department of Agriculture (USDA) has launched a new web site listing
the flavonoid content of foods ranging from beer to blueberries. It can be
found at www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.html.
Nutritionists say that flavonoids act as antioxidants, stopping the cell
damage caused by charged particles called free radicals. This cell damage may
lead to cancer, heart disease, and possibly a range of other diseases.
Researchers believe they are very important compounds found in food, and may be
part of the reason that eating fruits and vegetables can reduce the risk of
heart disease and cancer.
Different flavonoids may play a slightly different role in promoting health.
For example, some research shows that quercetin can limit the body's production
of histamine, which is the cause of allergic symptoms. Another example is beer
-- it contains virtually no flavonoids while red wine (long touted for its
healthful benefits) contains small amounts of several of them.
This web site will mostly be of use to researchers. It is comparable to one
that the USDA had posted for isoflavones, which are found in soy products and
which may be helpful in preventing heart disease.
For people who do not have prescription drug coverage information, there is a
new web site that provides information on getting more than 1,400 medications
free through patient assistance programs. People can go to the web site, fill
out a form, and receive a list of drug assistance programs for which they may
qualify. The web site, called www.HelpingPatients.org,
was announced by the Pharmaceutical Research and Manufacturers of America (PhRMA).
According to the PhRMA president Alan F. Holmer, "The pharmaceutical
industry has a long practice of providing prescription medications free of
charge to patients who might not be able to afford them. In 2002 alone, our
companies have helped more than 5 million patients get the medicines they
need."
PhRMA includes research-based pharmaceutical and biotechnology companies.
According to the March 2003 issue of the AARP (American Association of
Retired Persons) Bulletin newsletter, there are steps that people can
take to better navigate the American health care system.
Cost:
- If you are already retired and receiving coverage from your
former employer, find
out your future share of the cost and budget accordingly.
- Use generic drugs. Don't demand the latest drug you see
advertised on TV or in
a magazine.
- If you are eligible for Medicare and have trouble paying the
Part B premium
and the coinsurance, see if you are eligible for the
Medicare programs that will
help you pay these costs. Your state
insurance counseling program can tell
you how to apply.
- If you are eligible for health care through Veterans
Affairs, consider it. It
could be a way to get coverage for prescription drugs,
and the VA's
electronic medical record system helps improve the
quality of care
patients receive.
- If you are income is low, check out state programs that help
residents
pay for drugs. Ask your doctor about pharmaceutical assistance
programs
offered by drugmakers because these are based on
income.
Access:
- If you are thinking of retiring early, do not leave your job
unless you have
planned for continued insurance coverage until you are eligible
for Medicare.
- If you leave a job, you must elect COBRA health coverage in
order to obtain
your eligibility for an individual policy. If you have used up
your COBRA
benefits and attempt to buy new coverage within
63 days, you are eligible
for a policy regardless of any health problems you
have.
Quality:
- Keep a list of medications you are taking, including
over-the-counter drugs and
herbal supplements. Be sure all of your doctors
know what you are taking. If
you go to the hospital, give the
list to a hospital personnel when you are
admitted.
- If you or a family member is being transferred to a nursing
home from a hospital,
be sure you know what medications you are taking in
the hospital and that the
nursing home knows your regimen.
Medication errors can occur when patients
are transferred from one facility to
another.
- If you or a relative are in the hospital, ask for a copy of
your medical
administration record (the record that the hospital uses to keep
track of your
medications). Check to make sure that it matches
your own record of
medications you are taking.