C h a p t e r 4 4
Disorders of the Skeletal System: Metabolic and Rheumatic Disorders
1131
the hips and knees are involved. Muscle-strengthening
exercises may help protect the joint and decrease pain.
Several dietary supplements are available and adver-
tised as beneficial for OA, but few have undergone rigor-
ous testing. The most widely used supplements for OA
are glucosamine and chondroitin sulfate. A recent mul-
ticenter trial funded by the National Institutes of Health
found that glucosamine and chondroitin (alone or in
combination) were no better than placebo in reducing
pain in the total group of persons with knee pain, but
that the combination may be effective in those with mod-
erate to severe pain.
63
Topical capsaicin may have some
pain-relieving effect in osteoarthritic knees and hands.
Oral medications are aimed at reducing inflammation
or providing analgesia. The mainstay of treatment for
mild osteoarthritis is acetaminophen. When acetamino-
phen fails to control symptoms , or if the symptoms are
moderate to severe, NSAID therapy is recommended.
Intra-articular corticosteroid injections may be used
when other treatment measures have been unsuccessful
in adequately relieving symptoms.
60,61
They are espe-
cially helpful in persons who have an effusion of the
joint. Injections usually are limited to no more than three
times a year in the same joint because their use is thought
to accelerate joint destruction. Viscosupplementation is
based on the hypothesis that joint lubrication is abnor-
mal in OA.
64
Hyaluronate is injected into the joint
weekly for 3 to 5 weeks.
Surgery is considered when the person is having severe
pain and joint function is severely reduced.
60
Procedures
include arthroscopic lavage and débridement, bunion
resections, osteotomies to change alignment of the knee
and hip joints, and decompression of the spinal roots
in osteoarthritic vertebral stenosis. Total hip replace-
ments have provided effective relief of symptoms and
improved range of motion for many persons, as have
total knee replacements, although the latter procedure
has produced less-consistent results. Joint replacement is
available for the first carpometacarpal joint. Arthrodesis
(surgical stiffening of a joint) is used in advanced disease
to reduce pain; however, this results in loss of motion.
Crystal-Induced Arthropathies
Crystal deposition in joints produces arthritis. In gout,
monosodium urate or uric acid crystals are found in the
joint cavity. Another condition in which calcium pyro-
phosphate dihydrate crystals are found in the joints
sometimes is referred to as
pseudogout
or
chondrocal-
cinosis.
A brief discussion of pseudogout is found in the
section on rheumatic diseases in the elderly.
Gout
Gout is actually a group of diseases known as the
gout
syndrome.
66–68
It includes acute gouty arthritis with
recurrent attacks of severe articular and periarticular
inflammation; tophi or the accumulation of crystalline
deposits in articular surfaces, bones, soft tissue, and
cartilage; gouty nephropathy or renal impairment; and
uric acid kidney stones.
The term
primary gout
is used to designate cases in
which the cause of the disorder is unknown or an inborn
error in metabolism and is characterized primarily by
hyperuricemia and gout. Primary gout is predominantly
a disease of men, with a peak incidence in the fourth to
sixth decade. In secondary gout, the cause of the hyper-
uricemia is known but the gout is not the main disorder.
Asymptomatic hyperuricemia is a laboratory finding
and not a disease. Most persons with hyperuricemia do
not develop gout.
Pathogenesis.
The pathogenesis of gout resides in an
elevation of serum uric acid levels. Uric acid is the end
product of purine (adenine and guanine from DNA and
RNA) metabolism.
3,4
The elevation of uric acid and the
subsequent development of gout can result from over-
production of purines, decreased salvage of free purine
bases, augmented breakdown of nucleic acids as a result
of increased cell turnover, or decreased urinary excre-
tion of uric acid. Primary gout, which constitutes 90%
of cases,
3
may be a consequence of enzyme defects that
result in an overproduction of uric acid, inadequate
elimination of uric acid by the kidney, or a combina-
tion of the two. In most cases, the reason is unknown.
In secondary gout, hyperuricemia may be caused by
increased breakdown of nucleic acids, as occurs with
rapid tumor cell lysis during treatment for lymphoma
or leukemia. Other cases of secondary gout result from
chronic kidney disease. Some of the diuretics, including
the thiazides, can interfere with the excretion of uric
acid.
An attack of gout occurs when monosodium urate
crystals precipitate in the joint and initiate an inflam-
matory response. Synovial fluid is a poorer solvent
for uric acid than plasma. Moreover, uric acid crys-
tals are even less soluble at temperatures below 37°C,
and typically are deposited in peripheral areas of the
body, such as the great toe, where the temperatures are
cooler than other parts of the body.
3
With prolonged
hyperuricemia, crystals and
microtophi
(i.e., small,
hard nodules with irregular surfaces that contain crys-
talline deposits of monosodium urate) accumulate
in the synovial lining cells and in the joint cartilage.
The released crystals are chemotactic to leukocytes
and also activate complement. Phagocytosis of urate
crystals by polymorphonuclear leukocytes occurs and
leads to polymorphonuclear cell death with the release
of lysosomal enzymes. As this process continues, the
inflammation causes destruction of the cartilage and
subchondral bone.
Repeated attacks of acute arthritis eventually lead to
chronic arthritis and the formation of the large, hard
nodules called
tophi
3,4
(Fig. 44-13). They are found
most commonly in the synovium, olecranon bursa,
Achilles tendon, subchondral bone, and extensor sur-
face of the forearm and may be mistaken for rheu-
matoid nodules. Tophi usually do not appear until 10
years or more after the first gout attack. This stage of
gout, called
chronic tophaceous gout,
is characterized
by more frequent and prolonged attacks, which often
are polyarticular.
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