Target Health Blog


March 25, 2019


Microscope photograph of spiked rods of uric acid crystals found in a synovial fluid sample illuminated with polarized light. Formation of uric acid crystals in the joints is associated with gout.
Photo credit: Bobjgalindo - Own work, CC BY-SA 4.0,

In 1683, Thomas Sydenham, an English physician, described its occurrence in the early hours of the morning and its predilection for older males:

Gouty patients are, generally, either old men or men who have so worn themselves out in youth as to have brought on a premature old age - of such dissolute habits none being more common than the premature and excessive indulgence in venery and the like exhausting passions. The victim goes to bed and sleeps in good health. About two o'clock in the morning he is awakened by a severe pain in the great toe; more rarely in the heel, ankle, or instep. The pain is like that of a dislocation and yet parts feel as if cold water were poured over them. Then follows chills and shivers and a little fever. The night is passed in torture, sleeplessness, turning the part affected and perpetual change of posture; the tossing about of body being as incessant as the pain of the tortured joint and being worse as the fit comes on.

Gout affects about 1 to 2% of the Western population at some point in their lives. It has become more common in recent decades. This is believed to be due to increasing risk factors in the population, such as metabolic syndrome, longer life expectancy, and changes in diet. Older males are most commonly affected. Gout was historically known as "the disease of kings" or “rich man's disease“. It has been recognized at least since the time of the ancient Egyptians. Dutch scientist Antonie van Leeuwenhoek first described the microscopic appearance of urate crystals in 1679. In 1848, English physician Alfred Baring Garrod identified excess uric acid in the blood as the cause of gout.

Gout is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint. Pain typically comes on rapidly, reaching maximal intensity in less than twelve hours. The joint at the base of the big 1) ___ is affected in about half of cases. It may also result in tophi, kidney stones, or urate nephropathy. Gout is due to persistently elevated levels of uric acid in the 2) ___. This occurs from a combination of diet, other health problems, and genetic factors. At high levels, uric acid crystallizes and the crystals deposit in joints, tendons, and surrounding tissues, resulting in an attack of gout. Gout occurs more commonly in those who regularly eat meat or seafood, drink beer, or are overweight. Diagnosis of gout may be confirmed by the presence of crystals in the joint fluid or in a deposit outside the joint. Blood uric acid levels may be normal during an attack.

Treatment with nonsteroidal anti-inflammatory 3) ___ (NSAIDs), steroids, or colchicine improves symptoms. Once the acute attack subsides, levels of uric acid can be lowered via lifestyle changes and in those with frequent attacks, allopurinol or probenecid provides long-term prevention. Taking vitamin C and eating a diet high in low-fat dairy products may be preventive. Gout can present in multiple ways, although the most usual is a recurrent attack of acute inflammatory 4) ___ (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. This is mainly due to lower body temperature. Other symptoms may rarely occur along with the joint pain, including fatigue and a high fever.

Long-standing elevated uric acid levels (hyperuricemia) may result in other symptoms, 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.The crystallization of uric 5) ___, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. Underexcretion of uric acid by the kidney 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. Dietary causes account for about 12% of 6) ___, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast. Chicken and potatoes also appear related. Other triggers include physical trauma and surgery.

Studies in the early 2000's found that other dietary factors are not relevant. Specifically, moderate consumption of purine-rich vegetables (e.g., beans, peas, lentils, and spinach) are not associated with gout. Neither is total consumption of protein. Alcohol consumption is strongly associated with increased risk, with 7) ___ presenting somewhat less of a risk than beer or spirits. The eating or drinking of coffee, vitamin C, and dairy products, as well as physical fitness, appear to decrease the 8) ___. Peanuts, brown bread, and fruit also appear protective. This is believed to be partly due to their effect in reducing insulin resistance. Gout is partly genetic, contributing to about 60% of variability in uric acid level. 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 commonly complicated by gout include lead poisoning, kidney failure, hemolytic anemia, psoriasis, solid organ transplants and myeloproliferative disorders such as polycythemia. A body mass index greater than or equal to 35 increases male risk of gout threefold. Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on 9) ___ function.

Diuretics have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk. Other medications that increase the risk include niacin, aspirin (acetylsalicylic acid), ACE inhibitors, angiotensin receptor blockers (except losartan), beta blockers, ritonavir, and pyrazinamide. The immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout, the former more so when used in combination with hydrochlorothiazide. A number of medications are useful for preventing further episodes of gout, including allopurinol, probenecid, febuxostat, and colchicine. Long term medications are not recommended until a person has had two attacks of gout, unless destructive joint changes, tophi, or urate nephropathy exist. It is not until this point that medications are cost-effective. They are not usually started until one to two weeks after an acute flare has resolved, due to theoretical concerns of worsening the attack. They are often used in combination with either an NSAID or colchicine for the first three to six months. While historically it is not recommended to start allopurinol during an acute attack of gout, this practice appears acceptable. Allopurinol blocks uric acid production, and is the most commonly used agent. Long term therapy is safe and well tolerated, and can be used in people with renal impairment or urate stones, although hypersensitivity occurs in a small number of individuals.

Febuxostat is only recommended in those who cannot tolerate allopurinol. There are concerns about more deaths with febuxostat compared to allopurinol. Probenecid appears to be less effective than allopurinol and is a second line agent. Probenecid may be used if under secretion of uric acid is present (24-hour urine uric acid less than 800 mg). It is, however, not recommended if a person has a history of kidney stones. Pegloticase is an option for the 3% of people who are intolerant to other medications. It is a third line agent. Pegloticase is given as an intravenous infusion every two weeks, and reduces uric acid levels. Pegloticase is useful decreasing tophi but has a high rate of side effects and many people develop resistance to it. In 2016 it was withdrawn from the European market. Lesinurad reduces blood uric acid levels by preventing uric acid absorption in the kidneys. It was approved in the United States for use together with allopurinol, among those who were unable to reach their uric acid level targets. Side effects include kidney problems and kidney 10) ___.

ANSWERS: 1) toe; 2) blood; 3) drugs; 4) arthritis; 5) acid; 6) gout; 7) wine; 8) risk; 9) kidney; 10) stones

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