What is gout? What is hyperuricemia?
Gout is a disease that results from an overload of uric acid in the
body. This overload of uric acid leads to the formation of tiny crystals
of urate that
deposit in tissues of the body, especially the joints. When crystals
form in the joints, it causes recurring attacks of joint
inflammation (arthritis).
Gout is considered a chronic and progressive disease. Chronic gout can
also lead to deposits of hard lumps of uric acid in the tissues,
particularly in and around the joints and may cause joint destruction,
decreased kidney function, and kidney stones (nephrolithiasis).
Gout has the unique distinction of being
one of the most frequently recorded medical illnesses throughout history. It is
often related to an inherited abnormality in the body's ability to process uric
acid. Uric acid is a breakdown product of purines that are part of many foods we
eat. An abnormality in handling uric acid can cause attacks of painful arthritis
(gout attack), kidney stones, and blockage of the kidney-filtering tubules with
uric acid crystals, leading to kidney failure. On the other hand, some people
may only develop elevated blood uric acid levels (hyperuricemia)
without having manifestations of gout, such as arthritis or kidney
problems. The state of elevated levels of uric acid in the blood without
symptoms is referred to as asymptomatic hyperuricemia. Asymptomatic
hyperuricemia is considered a precursor state to the development of
gout. The term gout refers the disease that is caused by an
overload of uric acid in the body, resulting in painful arthritic
attacks and deposits of lumps of uric acid crystals in body tissues.
Gouty arthritis is typically an extremely painful attack with a rapid
onset of joint inflammation. The joint inflammation is precipitated by
deposits of uric acid crystals in the joint fluid (synovial fluid) and
joint lining (synovial lining). Intense joint inflammation occurs as the
immune system reacts, causing white blood cells to engulf the uric acid
crystals and chemical messengers of inflammation to be released,
leading to pain, heat, and redness of the joint tissues. As gout
progresses, the attacks of gouty arthritis typically occur more
frequently and often in additional joints.
Who is affected by gout?
Approximately 5 million people in the United States suffer from gout.
(Did you know that none other than Benjamin Franklin had terribly
painful gouty arthritis?)
Gout is nine times more common in men than in women. It predominantly
attacks
males after puberty, with a peak age of 75. In women, gout attacks usually occur
after menopause.
While an elevated blood level of uric acid may indicate an increased
risk of gout, the relationship between hyperuricemia and gout is
unclear. Many patients with hyperuricemia do not develop gout
(asymptomatic hyperuricemia), while some patients with repeated gout
attacks have normal or low blood uric acid levels. In fact, the blood
level of uric acid often lowers during an acute attack of gout. Among
the male population in the United States, approximately 10% have
hyperuricemia. However, only a small portion of those with hyperuricemia
will actually develop gout.
What are gout causes and risk factors?
In addition to an inherited abnormality in handling uric acid, other risk
factors for developing gout include obesity, excessive weight gain (especially
in youth), moderate to heavy alcohol intake, high blood pressure, and abnormal
kidney function. Certain drugs, such as thiazide diuretics (hydrochlorothiazide
[Dyazide]), low-dose aspirin, niacin, cyclosporine, tuberculosis medications (pyrazinamide
and ethambutol), and others can also cause elevated uric acid levels in the
blood and lead to gout. Furthermore, certain diseases lead to excessive
production of uric acid in the body. Examples of these diseases include
leukemias, lymphomas, and hemoglobin disorders.
Interestingly, one study
demonstrated an increased prevalence of abnormally low thyroid hormone levels
(hypothyroidism) in patients with gout.
In patients at risk of developing
gout, certain conditions can precipitate acute attacks of gout. These conditions
include dehydration, injury to the joint, fever, excessive eating, heavy alcohol
intake, and recent surgery. Gout attacks triggered by recent surgery are
probably related to changes in the body-fluid balance as patients temporarily
discontinue normal oral fluid intake in preparation for and after their
operation.
What are gout symptoms and signs?
The small joint at the base of the big toe is the most common site of an
acute gout attack of arthritis. An acute attack of gouty arthritis at
the base of the big toe is medically referred to as podagra. Other
joints that are commonly affected include the ankles, knees, wrists,
fingers, and elbows. Acute gout attacks are characterized by a rapid
onset of pain in the affected joint followed by warmth, swelling,
reddish discoloration, and marked tenderness. Tenderness can be intense
so that even a blanket touching the skin over the affected joint can be
unbearable. Patients can develop fever with the acute gout attacks.
These painful attacks usually subside in hours to days, with or without
medication. In rare instances, an attack can last for weeks. Most
patients with gout will experience repeated attacks of arthritis over
the years.
Uric acid crystals can deposit in tiny fluid-filled sacs (bursae)
around the joints. These urate crystals can incite inflammation in the
bursae, leading to pain and swelling around the joints
(a condition called bursitis). In rare instances, gout leads to a more chronic type of joint inflammation that mimics rheumatoid arthritis.
In chronic (tophaceous) gout, nodular masses of uric acid crystals
(tophi) deposit in different soft-tissue areas of the body. Even though
they are most commonly found as hard nodules around the fingers, at the
tips of the elbows, in the ears, and around the big toe, tophi nodules
can appear anywhere in the body. They have been reported in unexpected
areas such as in the vocal cords or (rarely) even around the spinal
cord. When tophi appear in the tissues, the gout condition is felt to
represent a substantial overload of uric acid within the body.
How is gouty arthritis diagnosed?
Gout is suspected when a patient reports a history of attacks of painful
arthritis, particularly at the base of the toes. Ankles and knees are
the next most commonly involved joints in gout. Gout usually attacks one
joint at a time, while other arthritis conditions, such as systemic lupus and rheumatoid arthritis, usually attack multiple joints simultaneously.
The most reliable test for gout is finding uric acid crystals in a sample of the joint fluid obtained by joint aspiration
(arthrocentesis). Arthrocentesis is a common office procedure performed
under local anesthesia. Using sterile technique, fluid is withdrawn
(aspirated) from the inflamed joint using a syringe and needle. The
joint fluid is then analyzed for uric acid crystals and for infection.
Shiny, needle-like uric acid crystals are best viewed with a special
polarizing microscope. The diagnosis of gout can also be made by finding
these urate crystals from material aspirated from tophi nodules and
bursitis fluid. Although many doctors can do the procedure,
rheumatologists are specialists who are particularly trained in this
evaluation.
Sometimes, patients with a classic history and symptoms of gout can be
successfully treated and presumed to have gout without undergoing
arthrocentesis. However, establishing a firm diagnosis is still
preferable since other conditions can mimic gout. These include another
crystal-induced arthritis called pseudogout, psoriatic arthritis, rheumatoid arthritis, and even infection in the joint.
X-rays can sometimes be helpful and may show tophi-crystal deposits and bone damage as a result of repeated
bouts of inflammation. X-rays can also be helpful for monitoring the effects of chronic gout on the joints.
What is the treatment for gout?
There are two key concepts essential to treating gout. First, it is
critical to stop the acute inflammation of joints affected by gouty
arthritis. Second, it is important to address the long-term management
of the disease in order to prevent future gouty arthritis attacks and
shrink gouty tophi crystal deposits
in the tissues.
The treatment of an acute attack of gouty arthritis involves measures
and medications that reduce inflammation. Preventing future acute gout
attacks is equally as important as treating the acute arthritis.
Prevention of acute gout involves maintaining adequate fluid intake,
weight reduction, dietary changes, reduction in alcohol consumption, and
medications to lower the uric acid level in the blood (reduce
hyperuricemia).
Maintaining adequate fluid intake helps prevent acute gout attacks.
Adequate fluid intake also decreases the risk of kidney stone formation
in patients with gout. Alcohol is known to have diuretic effects that
can contribute to dehydration and precipitate acute gout attacks.
Alcohol can also affect uric acid metabolism to cause hyperuricemia.
Therefore, alcohol has two major effects that worsen gout by impeding
(slowing down) the excretion of uric acid from the kidneys as well as by
causing dehydration, both of which contribute to the precipitation of
uric acid crystals in the joints.
Gout diet
Dietary changes can help reduce uric acid levels in the blood. Since
purine chemicals are converted by the body into uric acid, purine-rich
foods are avoided. Examples of foods rich in purines include shellfish
and organ meats such as liver, brains, kidneys, and sweetbreads.
Researchers have reported, in general, that meat or seafood consumption
increases the risk of gout attacks, while dairy food consumption seemed
to reduce the risk. Protein intake or purine-rich vegetable consumption
was not associated with an increased risk of gout. Total alcohol intake
was strongly associated with an increased risk of gout (beer and liquor
were particularly strong factors). Fructose from the corn syrup in soft
drinks also increases the risk of gout.
Weight reduction can be helpful in lowering the risk of recurrent
attacks of gout. This is best accomplished by reducing dietary fat and
calorie intake, combined with a regular aerobic exercise program.
Gout medications
There are three aspects to the treatment of gout with medications. First, pain relievers such as acetaminophen (Tylenol) or other more potent analgesics are used to manage pain. Secondly, anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAIDS), colchicine,
and corticosteroids are used to decrease joint inflammation. Finally,
medications are considered for managing the chronic underlying metabolic
derangement that causes hyperuricemia and gout. This means treating the
elevated levels of uric acid in the blood with medications that reduce
these levels.
NSAIDS such as indomethacin (Indocin) and naproxen
(Naprosyn) are effective anti-inflammatory medications for acute gout.
These medications are tapered after the arthritis resolves. Common side
effects of NSAIDS include irritation of the gastrointestinal system,
ulceration of the stomach and intestines, and even intestinal bleeding.
People who have a history of allergy
to aspirin or nasal polyps should avoid NSAIDS because of the risk of
an intense allergic (anaphylactic) reaction. Colchicine
(Colcrys) for acute gout is administered by mouth to reduce inflammation
as well as to prevent gouty arthritis attacks while correcting
hyperuricemia with medications such as allopurinol (Zyloprim) or febuxostat
(Uloric). For acute attacks, it is given hourly or every two hours
until there is significant improvement in pain or the patient develops
gastrointestinal side effects such as severe diarrhea. For prevention, it is given once or twice daily. Other common side effects of colchicine include nausea and vomiting.
Corticosteroids such as prednisone,
given in short courses, are powerful anti-inflammatory agents for
treating acute gout. They can be administered orally or injected
directly into the inflamed joint. Corticosteroids can be prescribed to
patients who have accompanying kidney, liver, or gastrointestinal
problems. Long-term chronic use of corticosteroids is discouraged
because of serious long-term side effects.
In addition to medications for acute gout attacks, other drugs can be
taken over prolonged periods to lower blood uric acid levels. Lowering
blood uric acid levels reduces the risk of recurrent attacks of
arthritis, kidney stones, and kidney disease,
and also slowly dissolves hard tophi deposits. Medicines used to lower
blood uric acid level work either by increasing the kidney's excretion
of uric acid or by decreasing the body's production of uric acid from
the purines in foods. These medicines are generally not started until
after the inflammation from acute gouty arthritis has subsided because
they can worsen the attack. If they are already being taken prior to the
attack, they are continued and only adjusted after the attack has
resolved.
Probenecid (Benemid) and sulfinpyrazone
(Anturane) are medications that are commonly used to decrease uric acid
blood levels by increasing the excretion of uric acid into the urine.
Since these drugs can, in rare instances, cause kidney stones, they
should be avoided by those patients with a history of kidney stones.
These medications should be taken with plenty of fluid so as to promote
the rapid passage of uric acid out of the urinary system in order to
prevent kidney stone formation.
Allopurinol lowers the blood uric acid level by preventing uric acid
production. It actually blocks the metabolic conversion from purines in
foods to uric acid. This medication is used with caution in patients
with poor kidney function, as they are at a particular risk of
developing side effects, including severe rash and liver damage.
Febuxostat was approved by the U.S. Food and Drug Administration (FDA)
for the chronic management of hyperuricemia from gout in 2009.
Febuxostat has been shown to be more effective than allopurinol in
preventing acute attacks of gouty arthritis and is effective in
shrinking tophi deposits of uric acid in the tissues such as the
fingers, elbows, and ears. Because
febuxostat is not significantly metabolized by the kidneys, it may have
advantages over allopurinol in patients with underlying kidney disease.
While taking
febuxostat, patients have uric acid levels and liver function blood
tests monitored regularly.
Again, uric acid-lowering medications such as allopurinol and febuxostat
are generally not started in patients who are having acute attacks of
gout. These medications, when started during an acute attack, actually
can worsen the acute inflammation. Therefore, uric acid-lowering drugs
are usually instituted only after complete resolution of the acute
arthritis attacks, but if patients are already taking these medications,
they are maintained at the same doses during the acute attacks. In some
patients, increasing the dose of uric-acid-lowering medications can
precipitate gout attacks. In these patients, low doses of colchicine can
be given to prevent the precipitation of acute gout.
A new intravenous medication that is used to lower uric acid blood
levels in certain patients with chronic gout is PEGylated uricase
(pegloticase or Krystexxa). This infused medication (given every
two weeks) is to be considered only for those patients with gout that
has failed treatment with conventional uric-acid-lowering medications as
it can cause anaphylactic reactions and infusion reactions.
Pre-medicating with antihistamines and cortisone medications can
decrease the risk of these reactions.
It is essential to monitor the blood level of uric acid regularly once
uric-acid-lowering medications are used for optimal maintenance, as the
uric acid metabolism can change over time.
Home remedies which can alleviate the symptoms of acute gout include
resting and elevating the inflamed joint. Ice-pack applications can
sometimes make the inflammation worse by causing more uric acid to form
crystals in the involved area. Patients should avoid aspirin-containing
medications, when possible, because aspirin prevents kidney excretion of
uric acid.
What does the future hold for patients with gout and hyperuricemia?
Active research is ongoing in a variety of fields related to gout and
hyperuricemia. The management of the chronic gouty disease and its
relationship to improving blood pressure and kidney function is becoming
better defined.
Scientists recently reported that high animal protein intake slightly
increased the risk for gout. Others found that dietary calcium intake
may protect patients from getting gout attacks. Vitamin C may also lower
blood uric acid levels.
New medications to increase the elimination of uric acid in the urine
(such as benzbromarone) are being evaluated in clinical trials.
Researchers are also reporting on experimental drugs that can affect
chemical messengers involved in gouty inflammation called interleukins.
The optimal regimens for the treatment of acute gout attacks and chronic
gout conditions still require further long-term studies. Research
scientists will continue to develop less toxic and more effective
medications to battle this "scourge of the ages."
No comments:
Post a Comment