Gout (also known as podagra when it involves the big toe) is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected (~50% of cases). However, it may also present itself as tophi, kidney stones, or urate nephropathy. It is caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues.
Diagnosis is confirmed clinically by the visualization of the characteristic crystals in joint fluid. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine improves symptoms. Once the acute attack has subsided, levels of uric acid are usually lowered via lifestyle changes, and in those with frequent attacks allopurinol or probenecid provide long-term prevention.
Gout has increased in frequency in recent decades affecting approximately 1–2% of the Western population at some point in their lives. The increase is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy and changes in diet. Gout was historically known as "the disease of kings" or "rich man's disease".
Signs and symptoms
Gout presenting in the metatarsal-phalangeal joint of the big toe. Note the slight redness of the skin overlying the joint.
Gout can present in a number of ways, although the most usual is a recurrent attack of acute inflammatory arthritis (a red, tender, hot, swollen joint). The metatarsal-phalangeal joint at the base of the big toe is affected most often, accounting for half of cases. Other joints, such as the heels, knees, wrists and fingers, may also be affected. Joint pain usually begins over 2–4 hours and during the night. The reason for onset at night is due to the lower body temperature then. Other symptoms that may occur along with the joint pain include fatigue and a high fever.
Long-standing elevated uric acid levels (hyperuricemia) may result in other symptomatology, including hard, painless deposits of uric acid crystals known as tophi. Extensive tophi may lead to chronic arthritis due to bone erosion. Elevated levels of uric acid may also lead to crystals precipitating in the kidneys, resulting in stone formation and subsequent urate nephropathy.
Cause
Hyperuricemia is the underlying cause of gout. This can occur for a number of reasons, including diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%. About 10% of people with hyperuricemia develop gout at some point in their lifetimes. The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the risk is 0.5% per year, while in those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year.
Lifestyle
Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggers include physical trauma and surgery. Recent studies have found dietary factors once believed to be associated are in fact not, including the intake of purine-rich vegetables and total protein. The consumption of coffee, vitamin C and dairy products as well as physical fitness appear to decrease the risk This is believed to be partly due to their effect in reducing insulin resistance.
Genetics
The occurrence of gout is partly genetic, contributing to about 60% of variability in uric acid level. A few rare genetic disorders, including familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity, and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.
Medical conditions
Gout frequently occurs in combination with other medical problems. Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance and abnormal lipid levels occurs in nearly 75% of cases. Other conditions which are commonly complicated by gout include: polycythemia, lead poisoning, renal failure, hemolytic anemia, psoriasis, and solid organ transplants. A body mass index greater than or equal to 35 increases a male's risk of gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function. Lesch-Nyhan syndrome is often associated with gouty arthritis.
Medication
Diuretics have been associated with attacks of gout. However, a low dose of hydrochlorothiazide does not seem to increase the risk.[ Other medicines that have been associated include niacin and aspirin (acetylsalicylic acid). Cyclosporine is also associated with gout, particularly when used in combination with hydrochlorothiazide, as are the immunosuppressive drugs ciclosporin and tacrolimus.
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