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gout: More Than a Pain in the Toe
out (from the Latin gutta; drop) accounts for approximately 5% of all cases of arthritis (inflammation of a joint) and annually affects nearly 750,000 people. It is characterized by formation of uric acid crystals in joints or soft tissue. The incidence of gout continues to rise and affects males between the ages of 40 and 50 years at a higher rate compared to women. Uric acid levels are usually lower in women until they reach menopause when values become relatively equal. Gout is rare in children and young adults. Patients with organ transplants may be more susceptible to the condition because of the immunosuppressive medications they are receiving. Several other drugs can increase uric acid levels by reducing its removal through the kidneys. Increases in uric acid can also result in tophi (chalky deposits that can be felt under the skin) and kidney stones (nephrolithiasis). Cancer patients may have high levels of uric acid that can precipitate and cause kidney failure. This issue of WellAware will review the causes, clinical presentation, and management of gouty arthritis.
Causes and Clinical Presentation of Gout
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Gout is associated with an abnormally high level of uric acid in the blood (hyperuricemia). Uric acid is a byproduct of purine metabolism and is normally dissolved in the blood and excreted in the urine. Purines are essential constituents of all cells. In most persons with gout, uric acid is not readily eliminated by the kidneys and results in hyperuricemia. It subsequently can deposit in joints and tissues. High levels of uric acid do not always produce symptoms while persons with normal uric acid levels can experience an acute gouty attack. Hyperuricemia often, but not always, results in the formation of needle-like uric acid crystals that deposit in the joint and produce pain, redness, swelling, stiffness and inflammation. Symptoms of gout typically occur at night and often initially affect the big toe; this condition is referred to as podagra. The disease can occur in other joints, for example the ankle, heel, wrists, elbows, etc. An attack
of gouty arthritis usually affects only one joint per event. Episodes are sporadic in nature and commonly arise without warning. They often resolve without treatment in 3-10 days. At this point, the joint is apparently normal. A condition known as pseudogout presents with the same signs and symptoms as gout, but is caused by precipitation of calcium phosphate crystals, not uric acid. There are several risk factors for developing gout including genetics, sex, age, obesity, diet, excessive alcohol consumption, and exposure to lead. Diseases such as kidney failure and hypertension are often associated with hyperuricemia and gouty arthritis. Lastly, medications such as diuretics (furosemide, hydrochlorothiazide, metolazone etc), lowdose aspirin, some drugs used in treating tuberculosis, niacin, cyclosporine, and levodopa can increase uric acid levels. As stated earlier, hyperuricemia may be associated with no patient complaints or result in a variety of acute or chronic conditions. Table I includes the various stages or conditions associated with an increase in uric acid levels.
Diagnosis Hyperuricemia is defined as a serum uric acid value of greater than 6.8 mg per 100 mL. Remember, elevated levels do not necessarily mean that individuals will develop gouty attacks or any other complication. A presumptive diagnosis of gout can be made if there is severe inflammation in a single joint, the patient is hyperuricemic and they respond to administration of colchicine. Historically, the gold standard for diagnosis is aspiration or removal of joint fluid followed by microscopic evaluation. Uric acid crystals have a unique appearance and can specifically be identified by the physician.
Treatment The variety of medications available for the management of gout is limited; however, they are generally quite effective in both treating acute gouty attacks as well as preventing their recurrence. Non-steroidal anti-inflammatory drugs (NSAIDs) and continued on back
gout: More Than a Pain in the Toe colchicine are the agents commonly used to treat the pain and inflammation of an acute gouty attack. With the exception of patients suffering from kidney failure, a history of peptic ulcer disease, or those treated with anticoagulants, NSAIDs are the preferred therapy for relieving acute symptoms of gout. Colchicine, derived from a plant, has been used for generations for the treatment of acute gout. New treatment guidelines suggest a dose of two tablets at the beginning of an attack followed by one tablet one hour later. Because of adverse effects, colchicine is no longer considered the drug of choice for treating acute gout. On occasion, physicians may prescribe a short course of steroids such as prednisone during acute attacks. Symptoms can often be reduced after only a few hours. The medications used for the prevention of gouty attacks include allopurinol (Zyloprim) and probenecid. Allopurinol has been available since the 1960s and is quite effective in reducing uric acid levels in patients with gout as well as other conditions associated with hyperuricemia. Doses of the drug should be reduced in patients with kidney disease. Allopurinol has been implicated in a number of significant drug interactions. Febuxostat (Uloric) was approved by the Food and Drug Administration earlier this year and reduces uric acid levels in a manner similar to allopurinol. Probenecid, on the other hand, is used when the body excretes reduced amounts of uric acid. It decreases uric acid levels, but is not indicated for treatment of an acute attack. These preventative measures tend to be life-long therapies.
Along with pharmacological treatments, there are non-drug measures that can be taken to prevent or reduce gouty attacks. It is helpful to avoid alcohol and purine-rich foods (organ meats such as brains, liver and kidneys, anchovies, salmon, sardines, herring, asparagus and mushrooms), drink plenty of water and other fluids, and eat low-fat dairy products and complex carbohydrates. Bed rest, application of ice packs to affected joints, and reducing the amount of weight applied to the joint from clothing or bedding may also significantly decrease joint symptoms during an acute attack. Gout is a disease that has been described since biblical times. A better understanding of the condition and available therapies have allowed for continued improvement in its management.
Additional information on newsletter topics: Pharmaceutical Information Center 412-396-4600 email@example.com Questions about screenings or programs: Christine O’Neil, Pharm.D, B.C.P.S. 412-396-6417
Newsletter Contributors John G. Lech, Pharm.D David N. Ombengi, Pharm.D Lauren N. Lettrich, Pharm.D. Candidate Kyle B. Zaffino, Pharm.D. Candidate
Elevated uric acid levels in the blood with no other symptoms; treatment is normally not necessary.
Acute gouty arthritis
Deposits of uric acid crystals in joint spaces with abrupt onset of swelling, pain, and inflammation. Resolution usually occurs within 3-10 days even without treatment.
Period between acute attacks and absent of symptoms.
Chronic tophaceous gout
Develops over a period of years. May cause permanent damage to joints and sometimes the kidneys. Advancement to this stage usually does not occur in the majority of patients receiving treatment.
Table II: Common Treatment Options for Gout
A publication of: Mylan School of Pharmacy Center for Pharmacy Care Pharmaceutical Information Center (PIC)
URL: http://2.bp.blogspot.com/_3GeLPlID5vs/SI_dM02JK6I/ AAAAAAAAAEE/voCj-08bjPU/s400/The_gout_james_gillray.jpg
Table I: Stages of Gout
Febuxostat (Uloric) Colchicine Indomethacin (Indocin)* Naproxen (Naprosyn) Sulindac (Clinoril) Prednisone Methylprednisolone (Medrol)
use Prevention of gouty attacks
Treatment of acute attacks
Possible Adverse Effects Rash (sometimes severe), itching, liver disease, nausea, diarrhea Headache, nausea, vomiting, loss of appetite, sore gums, fever Rash, nausea, heart disease Diarrhea, nausea, vomiting, neuropathy, abdominal pain (must avoid excessive dosage!) Abdominal pain, nausea, rash, fluid retention, heartburn, kidney disorders, ringing in the ears, heart disease Nausea, abdominal pain, fluid retention, osteoporosis, increase in blood glucose, cataracts
* These are the only NSAIDs approved by the FDA for gout; however, others have been used as well.
For more information, please visit the following Web sites: • http://www.mayoclinic.com/print/gout/DS00090/DSECTION=all&METHOD=print • http://www.niams.nih.gov/Health_Info/Gout/default.asp • http://www.arthritis.org/disease-center.php?disease_id=42 • http://familydoctor.org/online/famdocen/home/common/pain/disorders/372.printerview.html
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