GOUT
Gout is one of the
crystal-induced arthropathies that is caused by precipitation of uric acid
crystals in the joint spaces, kidneys, and cutaneous locations. It is divided
into acute and chronic phases, which have different presentations and different
treatments. The human body’s immune reaction against the urate crystals causes
more damage than the crystals themselves. Gout has been described for centuries
and is clinically easily diagnosed. Medications, genetic predisposition, and
dietary habits all contribute to cases of gout. There are other crystal-induced
arthropathies that must be considered in the differential diagnosis of gout,
the most common being calcium pyrophosphate crystals.
Clinical Findings: Gout is a disease predominantly found in the
male population. Podagra is the classic presentation of an acute gouty attack.
Descriptions of podagra have been published in the medical literature for
centuries. It manifests as an acute monoarticular arthritis. The joint most
commonly affected is the metatarsophalangeal articulation of the great toe. The
clinical signs start as redness overlying the joint, swelling, warmth, and
severe pain. Podagra has often been described as one of the most painful
experiences a patient can perceive. A clue to the diagnosis is that the pain is
often so severe that it appears to be out of proportion to the clinical
picture. Patients complain of the slightest movement or touch; they are unable
to wear shoes or bear weight on the foot; and they often have trouble with
placement of a thin sheet over the affected joint. Acute attacks may be
frequent, and the need for therapy is quite apparent. If no treatment is
undertaken, an acute case of gout may last 7 days or longer. Any joint in the
body can be affected by acute gout, but the great toe is by far the most common
joint of involvement. Patients with acute gout have abnormal laboratory test
results that can help in the diagnosis. An increased white blood cell count
with a left shift is almost always seen. The markers of acute phase reactants
are elevated, including the erythrocyte sedimentation rate (ESR), ferritin, and
C-reactive protein.
The diagnosis can be made at the
bedside by joint aspiration and microscopic evaluation. The
affected joint is tapped with a fine-gauge needle and aspirated. The aspirate
is then evaluated under polarized microscopy. Needle-like, elongated crystals
of uric acid are seen freely within the synovial aspirate and also within the
leukocytes of patients with gout. Radiographs of the affected joint do not show
uric acid crystals and are likely to show only grossly abnormal soft tissue
swelling. The serum uric acid level in acute gout can be normal, slightly
elevated, or abnormally elevated; therefore, this test by itself is unreliable
in making the diagnosis.
Chronic gout, which is seen as a
sequela of multiple attacks of acute gout, leads to joint destruction and
chronic arthritis. Patients with chronic gout may also develop
acute episodes of gout. Patients with chronic gout are predisposed to the development
of tophaceous gout. This form of gout manifests as skin deposits of urate
crystals. It can occur in any location and is most often located within the
subcutaneous tissue. These tophi appear clinically as subcutaneous nodules,
often overlying the extensor joints, particularly the elbows, Achilles tendons,
and hands. For some reason, the ear is another area that is affected by tophi.
The nodules of tophi may become thinned and partially
translucent. The tophi may show an underlying yellowish appearance beneath the
skin, and occasionally the clumping of crystals is appreciated just underneath
the skin. With trauma, the nodules occasionally ulcerate, and crystals drain
from the tophi. Saturnine gout is a specific form of gout that has been found
to be caused by the consumption of ho emade moonshine that is contaminated with
lead.
Pathogenesis: Gout is caused by increased levels of uric acid
resulting from a decrease in secretion, an increase in production, or an
increase in dietary intake. Underexcretion of uric acid by the kidneys is
responsible for most cases of gout. This can result from genetic causes or from
use of medications that compete with the transport of uric acid, especially
alcohol and the loop diuretics. Uric acid is produced under normal circumstances
from the breakdown of purine nucleotides. Patients with the Lesch-Nyhan
syndrome have a defect in the hypoxanthine-guanine phosphoribosyltransferase
(HGPRT) enzyme, which is encoded by the gene HPRT1 and is critical in
the purine recycling pathway. This syndrome is seen in children and can lead to
severe neurological disease that is confounded by severe gout. Certain
chemotherapies cause severe immediate death of many leukocytes, resulting in
the release of a high concentration of uric acid that can overwhelm the body’s
normal mechanisms of removal, leading to gout. Foods found to have high
concentrations of uric acid should be avoided by patients with preexisting
gout, because they have been shown to exacerbate the disease.
Histology: Biopsies of gout are rarely performed, because
the clinical scenario is often diagnostic. When tissue of tophi is procured for
biopsy, it is best that it be fixed in alcohol, because formalin dissolves the
uric acid crystals, and they will not be seen on histological examination. The
diagnosis can still be made, because the needle-shaped, clefted areas left by
the dissolved crystals is characteristic. The crystals can be appreciated on
alcohol-fixed tissue, and they appear needle shaped and birefringent under
polarized light. The appearance of gout is much different from that of calcium
pyro- phosphate histologically, and there is usually no problem differentiating
the two conditions. The crystals of pseudogout are rhomboid shaped and weakly
birefringent.
Treatment: The therapeutic goal in acute gouty attacks is
to control the patient’s pain, and nonsteroidal antiinflammatory drugs (NSAIDs)
have long been the medications of choice. Indomethacin also has been widely
used for years. Aspirin should never be used in acute gout, because it can
transiently increase uric acid levels when initiated. Colchicine is another
medication that is used for the treatment of acute gouty attacks. Prednisone
can be used to decrease the acute inflammation, pain, and swelling. Medications
for the prophylactic treatment of gout are not used in acute episodes,
because they may make an acute attack worse. They have also been shown to cause
attacks of acute gout on rare occasions.
The most commonly used prophylactic
medications to help prevent future acute attacks in patients with chronic gout
are allopurinol and probenecid. Allopurinol is used exclusively for those
patients who overproduce uric acid, and probenecid is used
for those whose kidneys underexcrete uric acid. Up to one third of patients
started on allopurinol develop a cutaneous rash. If this happens, prompt
discontinuation is wise, because allopurinol can lead to a severe drug
hypersensitivity syndrome. Allopurinol works by inhibiting the purine breakdown
enzyme, xanthine oxidase. This ultimately decreases the amount of uric acid
produced from the breakdown of purine byproducts. Historically, allopurinol
was the first medication devised to inhibit a specific enzyme.
Tophi can be treated with the
long-term use of allopurinol or probenecid. Over time, the goal is to mobilize
the tissue uric acid and increase its excretion from the body. This can take
years. Individual tophi have been surgically removed to help increase range of
motion, f located around joints, or to improve cosmesis.
