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Introduction:
For as long as scientists have studied rheumatic disease,
bacterial infections have been believed to trigger certain
types of arthritis. The strongest support for this theory is
seen in ReA and IBD arthritis. In ReA, bacterial infections of
the intestines, genitals, and upper respiratory tract
typically precede the onset of arthritis, while in arthritis
related to IBD (Crohn�s disease, ulcerative colitis),
bacteria in the intestines is believed to invade the
bloodstream and trigger arthritis.
In ReA, bacterial forms of diarrhea known as
dysentery, sexually transmitted diseases such as
gonorrhea or chlamydia, or the common �strep
throat� have all been found to trigger joint inflammation.
While well recognized, only a small minority of individuals
contracting such illnesses develop ReA. When investigating
these conditions, researchers have found no evidence for an
active infection, but it appears that following the infection,
the immune system recognizes something in the body that is
similar to the bacteria and begins attacking it. It is also
noteworthy that some patients with human immunodeficiency
virus (HIV) infection are at risk for developing ReA.
IBD arthritis develops in up to 20% of those with
Crohn�s disease or ulcerative colitis. Joint involvement tends
to correlate with the level of intestinal inflammation in
ulcerative colitis, but for some reason not in Crohn�s
disease. Arthritis has also been described in association with
other intestinal disorders such as celiac disease,
Whipple�s disease, and a recently described
condition known as collagenous colitis.
All of these conditions fall into the category of
illnesses known as spondyloarthropathies (spon-di-lo-ar-thr�w-pa-thees),
which include ankylosing spondylitis (AS) and
psoriatic arthritis (PsA) (see related sections).
These forms of arthritis tend to involve the spine and/or a
small number of additional joints as well as the areas around
joints where tendons and ligaments attach. All of these
conditions are also associated to some extent with a gene
known as HLA-B27.
Features of ReA:
Typically, joint symptoms and swelling begins about 2 to 4
weeks after the triggering infection, although sometimes this
infection is unrecognized. The joints most commonly affected
are located below the waist (i.e. � knees, ankles, and feet),
typically in an asymmetric pattern, with different joints
being affected on each side. Less commonly, arthritis may
occur in the hands, wrists, elbows, or shoulders, resembling
rheumatoid arthritis (RA). When spinal symptoms are present,
the sacroiliac joint, located below the waist at the
junction of the spine and pelvis, is typically involved.
Tendinitis, particularly of the heel, may also be a dominant
feature of ReA.
Inflammation in other parts of the body also commonly
occurs. The most common manifestation is conjunctivitis,
commonly referred to as �pink eye.� Redness, irritation,
excessive tearing, and crusting of the eyelashes are typical
symptoms. Less commonly, a deeper inflammation of the eye
known as iritis may occur, which is usually more
painful, results in more blurring of vision, and may result in
vision loss if not treated. Inflammation of the genital
region, including the urethra, penis, testicles, prostate
gland, or cervix, may also occur in the absence of an active
infection. Burning with urination, discharge from the urethra,
and a scaly rash in the genital region are symptoms or
findings that may be present. Mouth ulcers and a scaly rash on
the palms or soles resembling psoriasis (known as
keratoderma blenorrhagicum) are other commonly observed
features of ReA.
The outcome of ReA is variable. While up to 1/3 of
patients recover completely from their joint symptoms within 2
years, over 15% have recurring or chronic joint inflammation,
and most of the remaining patients have continued joint pain
in the absence of signs of inflammation. While less commonly
seen than in RA, deforming changes of the joints may occur in
ReA and become an ongoing source of pain and limitation in
function.
Features of IBD Arthritis:
The arthritis in patients with IBD occurs slightly more
commonly in the spine than in other joints. As in those with
ReA, the sacroiliac joint is the most frequent location that
becomes inflamed. This joint may be involved on x-rays without
the patient having symptoms, but lower back pain is frequently
seen. Sacroiliac inflammation may begin either before or after
the IBD is diagnosed, and bowel and lower back symptoms do not
seem to correlate well or mirror each other.
In contrast to spinal arthritis, inflammation in other
joints may correlate more closely with disease activity in the
bowel. The most common joints involved include the knuckle and
finger joints of the hands, the knees, the ankles, the elbows,
and the shoulders. The upper limbs are involved more
frequently in patients with IBD than in ReA, and a greater
number of joints tend to become inflamed in these patients
overall. While joint damage may occur, the inflammation does
not typically produce destruction of the bone or joint.
Because patients with IBD are at risk for joint infections as
well as loss of blood supply to the bones (a complication
known as avascular necrosis), an acutely swollen or
painful joint should be investigated accordingly to rule out
these problems.
Other complications of IBD occurring in other parts of
the body include iritis, red nodules over the shins known as
erythema nodosum, painful ulcerations of the skin known
as pyoderma gangrenosum, sores in the mouth known as
aphthous ulcers, and complications involving the liver.
While all of these features have been well described in IBD
patients, they all occur in less than 20% of these individuals
and are less frequently seen than the arthritis described
above.
Diagnosis: Both ReA and IBD arthritis
are best diagnosed by carefully examining the joints for
swelling, tenderness, limited motion, and other signs of
inflammation. Arthritis fitting the patterns described above
in a patient with a known recent infection or either known or
suspected IBD should raise the suspicion for these disorders.
For patients with abnormal skin findings, oral ulcers, eye
inflammation, genital involvement, or other features common to
either ReA or IBD, the diagnosis is further supported.
X-rays of involved joints, particularly the pelvis if
sacroiliac disease is suspected, can provide additional
evidence for these forms of arthritis. While x-rays are often
normal initially and may remain normal throughout the course
of the disease (particularly in IBD patients), joint films may
demonstrate erosions or joint damage suggesting the need for
more aggressive treatment or provide evidence for another
explanation for the patient�s joint symptoms.
Laboratory testing is of less value in the diagnosis of
both ReA and IBD arthritis. While both conditions are usually
associated with elevations in markers of inflammation, these
findings are not specific and can be seen in a number of
inflammatory conditions. The HLA-B27 gene can be measured, but
this finding is not necessary to establish the diagnosis of
either condition. While the presence of this gene may be
helpful in supporting the diagnosis, a significant percentage
of individuals with ReA and IBD arthritis lack this finding,
and a negative test certainly does not rule out these forms of
arthritis. Crohn�s disease patients may exhibit antibodies to
a yeast known as Saccharomyces cerevisiae, and
ulcerative colitis patients may demonstrate anti-neutrophil
cytoplasmic antibodies (ANCA), but once again these tests
are frequently negative and do not need to be ordered in every
patient.
The procedures required to diagnose IBD are beyond the
scope of this discussion, but in general the diagnosis is made
by endoscopy, a procedure where a lighted flexible tube
is inserted through the rectum to look into the colon, or by
barium studies done in the x-ray department. Other
specialists, such as gastroenterologists or surgeons, are
usually more involved in the diagnosis and treatment of the
bowel component of the disease.
Therapy: As in many forms of arthritis,
the treatment of ReA and IBD arthritis depends on the severity
of the joint involvement and the potential for causing damage.
In patients with IBD, many of the therapies that treat the
bowel disease will also treat the joint disease, but we will
focus our discussion on the treatment of IBD arthritis.
Non-steroidal anti-inflammatory drugs (NSAIDs)
are useful in treating joint symptoms and may be sufficient in
mild cases of either ReA or IBD arthritis. Examples of drugs
in this category include ibuprofen, naproxen, and indomethacin,
the latter being a preferred drug by many physicians for
spondyloarthropathies. One problem with these agents in IBD is
that they have the potential to aggravate gut inflammation in
addition to placing patients at risk for damage to the lining
of the stomach or ulcers. Newer NSAIDs that are �COX-2
selective� greatly reduce the risk of stomach damage and may
also cause less exacerbation of bowel inflammation, but this
issue has not been addressed in well-designed studies as of
yet.
Corticosteroids such as prednisone are effective
for treating flares of IBD, but are less effective in treating
associated arthritis or ReA. Injections of steroids directly
into inflamed joints or soft tissues may, however, be
effective in controlling acute symptoms accompanying arthritis
or tendinitis flares.
Sulfasalazine (SSZ) is a well-established
treatment for inflammatory bowel disease and is often helpful
in treating joint inflammation in these patients as well as
those with ReA who do not respond to NSAIDs. SSZ is
slow-acting, taking effect in 2-3 months but often providing
more consistent relief of symptoms than NSAIDs alone. The most
common side effects are nausea, abdominal discomfort, and
allergic reactions, but less common side effects, such as a
drop in white blood cells and elevated liver enzymes, must be
monitored while taking SSZ.
Antibiotics given to patients with ReA may reduce
the severity or duration of arthritis, but they are more
effective in doing so if targeting a specific infection. Both
tetracycline-based antibiotics (doxycycline, e.g.) and
ciprofloxacin have been shown to be beneficial when
given over a period of three months in ReA triggered by
genital infections and infectious diarrhea, respectively.
While the studies yield somewhat mixed results, it is
reasonable to treat a recognized triggering infection with
appropriate antibiotic therapy.
Immune suppressing drugs such as methotrexate
(MTX), and azathioprine (AZA) may be
useful in certain patients. There are few well-designed
studies examining their specific effects on these types of
arthritis, but since they are frequently used in treating IBD,
many have made the observation that the joint symptoms also
improve in these patients. The effectiveness of these agents
in treating ReA is variable and may be greater in treating
inflammatory arthritis in joints other than the spine. Before
starting a patient with ReA on one of these medications,
checking for exposure to HIV infection is prudent, as these
patients are at greater risk for side effects. For more
details regarding side effects of these drugs, see
Medications section or the Rheumatoid Arthritis
section, where they are covered in greater detail.
Tumor necrosis factor (TNF) antagonists
have represented a major advance in the treatment of
spondyloarthropathies and IBD. These drugs block the effects
of TNF, a protein involved in inflammation in various parts of
the body and have been used extensively in RA. While more
studies have documented their benefit in treating patients
with AS and PsA, they appear to be useful in treating ReA and
IBD arthritis.
The drugs in this class that are currently in use
include etanercept (trade name Enbrel),
infliximab (trade name Remicade), and adalimumab
(trade name Humira). Enbrel and Humira are
administered by weekly or every two week injections,
respectively, and Remicade is given by intravenous infusion
every 8 weeks. While some evidence exists that each agent
benefits patients with spondyloarthropathy in general, only
Remicade seems to be beneficial for the bowel disease in
patients with IBD.
Because TNF antagonists suppress the immune system,
infections must be monitored while taking these therapies, and
exposure to tuberculosis should be assessed by performing a
skin test prior to starting on of these drugs. Injection site
reactions, infusion reactions, worsening of heart function in
patients with heart failure, and worsening of disease in
patients with multiple sclerosis are additional potential side
effects.
Given the above risks and the cost of these
medications, TNF antagonists are not for every patient with
ReA or IBD arthritis, but in those with severe or resistant
disease, they represent a major advance in therapy. The
physician and patient working together can best decide which
combination of the above treatments is most appropriate for
each individual with ReA or IBD-associated arthritis. |
