Every Man a King: Henry VIII's Worst Affliction Is on the Rise in America

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Gout may sound like an 18th-century affliction, but the number of Americans suffering from the painful inflammatory condition has doubled in the past few decades.

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James Gillray's 1799 caricature, "The Gout" (Wikimedia Commons)

What do beer drinkers, chickens, crocodiles and orangutans have in common?

Well, for some evolutionary reason, humans, birds, reptiles and great apes lack a liver enzyme called uricase which breaks down and regulates uric acid, a normal waste product of the purines found in many foods, such as shellfish and organ meats. Brewers yeast and hops, essential ingredients of beer, are also high in purines.

Timothy E. Quan, staff physician at Eastern Connecticut Health Network (ECHN) and clinical assistant professor of medicine at Yale University, said that beer packs a "triple whammy" because of its purine-rich ingredients, the dehydration it causes and the way it decreases the kidneys' ability to get rid of uric acid.

Without uricase to break it down, it's up to the kidneys to eliminate uric acid in the urine. When they don't, uric acid salts, called urate, can form needle-like crystals that may collect in the kidneys and form kidney stones, and in the joints, tendons and surrounding tissue where they can cause gout.

The most common type of inflammatory arthritis among middle-aged and older men and, increasingly, women, gout is widely considered one of the most painful physical afflictions known to man. Even women have been known to say it's worse than childbirth.

Recognized throughout human history, gout's famous sufferers have included Alexander the Great, Charlemagne, King Henry VIII and "Piero The Gouty" of the famed Florentine Medici family. Benjamin Franklin at age 74 penned a dialogue in 1780 between himself and "Madam Gout," pleading to know, "What have I done to merit these cruel sufferings?" Gout replied, "Many things; you have ate and drank too freely, and too much indulged those legs of yours in their indolence."

Gout may seem so ... 18th century. But the number of people suffering from the disease here and now has been growing both domestically and abroad. "In the past few decades," according to a recent review published in Nature, "gout has approximately doubled in prevalence in the USA, and is also markedly increasing in prevalence in other countries with established and emerging economies."

That's right: The number of people afflicted with gout, the disease of Charlemagne and Henry VIII, has doubled in our lifetime.

Who is this cruel 'Madam Gout'?

An acute gout attack typically involves a red, tender, "hot," swollen joint. The most common place gout presents, oddly enough, is in the metatarsal-phalangeal joint at the base of the big toe of either foot. Other joints--such as the ankles, heels, knees, wrists and fingers--can also be affected.

H. Ralph Schumacher, professor of medicine at the University of Pennsylvania and editor-in-chief of the Journal of Clinical Rheumatology, explained that urate crystals probably collect in the big toes because the feet tend to be cooler than the rest of the body, and the big toes in particular endure a lot of wear and tear, which can allow crystals to form.

Schumacher said the only "absolute diagnosis" involves inserting a needle in the swollen joint--"with permission"--to look for the characteristic crystals of gout in the egg white-like synovial fluid that lubricates joints and tendon sheaths. "The diagnosis can then be suggested by the typical clinical picture," he said. "It should not be based on only the blood uric acid level."

A normal uric acid range is six parts or less per deciliter of blood. Although a high level of uric acid, or hyperuricemia, isn't considered dangerous, about 10 percent of people with it will develop gout at some point in their lives.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), as many as 80 percent of people with gout have a family history of the disease. It's far more common in men because the female hormone estrogen appears to protect women against hyperuricemia, at least until menopause.

Diet alone doesn't generally cause hyperuricemia and gout. Being overweight and sedentary, lead exposure, diuretic medications to eliminate excess fluid from the body, other medications (such as protease inhibitors used to treat HIV infection), even aspirin, can increase risk. Other health problems--such as high blood pressure or an underactive thyroid gland (hypothyroidism)--can also prevent the kidneys from properly ridding the body of excess uric acid. Two rare conditions, Kelley-Seegmiller syndrome and Lesch-Nyhan syndrome, also cause hyperuricemia.

Recent research suggests that fructose-sweetened soft drinks are not only ballooning up bodies and causing obesity-related health problems--including the so-called metabolic syndrome, type-2 ("adult onset") diabetes and high blood pressure--but increasing both male and female soda drinkers' uric acid concentrations as well.

Richard J. Johnson, a professor of medicine and head of the division of Renal Diseases and Hypertension at the University of Colorado-Denver, said there is "overwhelming" evidence that the fructose in high-fructose corn syrup--it's been called "metabolic poison"--increases the risk for gout. The use of HFCS in virtually all processed foods makes it hard to avoid, but has a great deal to do with the apparent uptick in gout cases in recent years.

"The classic thinking," said Johnson, "is that the rise in obesity itself may be responsible for the rise in uric acid." But epidemiological studies show that the rise in uric acid precedes the development of obesity and diabetes. "Therefore," he said, "it is likely that there are other reasons uric acid is increasing in our population. Our studies suggest that this is driven in part by the intake of sugar and high fructose corn syrup." He said his research also suggests that uric acid may have a role in causing hypertension and insulin resistance (diabetes).

"What is the horse and what is the cart?" asked Michael H. Pillinger, associate professor of medicine and biochemistry and molecular pharmacology at New York University and rheumatology chief at the Manhattan VA Medical Center. "There are metabolic effects when you take more fructose that promote hyperuricema," he said. "But all that caloric intake also leads to weight gain--and as you gain weight, you set up changes that also appear to promote hyperuricemia." He added, "Maybe everything is the cart, and everything the horse."

Gout be gone

So how do you avoid waking up one night--gout tends to attack during the night, when our body temperature is lower--shrieking in pain because even the touch of a downy-soft many-thread-count sheet can be agonizing?

For one thing, you can watch what you eat and drink. "It's a no-brainer," said Schumacher, "if you notice that something like a drinking binge brings on attacks, that you should try to avoid it. But most people do not associate having extra cookies that raise the fructose level with bringing on attacks."

The American College of Rheumatology in its forthcoming updated treatment guidelines "provides general guidance on what foods to avoid, limit or encourage," said UCLA associate clinical professor of medicine John Fitzgerald, one of the guideline authors, adding, "Foods containing high fructose are something specifically mentioned to avoid." Although not everything in the guidelines is "new and different," Fitzgerald said it's "important to remember these guidelines are not just for rheumatologists, but for primary physicians and family physicians," who actually see and treat more gout cases than rheumatologists, who tend to see the harder cases.

Non-steroidal anti-inflammatories (NSAIDs), such as indomethacin and ibuprofen, are the usual first-line treatment for a gout attack. For those with ongoing hyperuricemia and gout, allopurinol remains the standard medication used to regulate uric acid and prevent gout. Like every drug, this one can have serious consequences for some people. About 2 percent develop a drug rash known as "allopurinol hypersensitivity syndrome," and up to 10 percent experience such side-effects as gastrointestinal upset. Those of Han Chinese, Thai and Korean backgrounds, particularly if they already have kidney disease, have a greater risk of life-threatening reactions to allopurinol.

Oddly enough, starting a drug to lower uric acid can actually trigger a gout attack. In that case, colchicine  an ancient drug made from the autumn crocus, Colchicum autumnale, also known as "meadow saffron," has been the standard treatment. Other drugs also can be used, including febuxostat, which blocks production of uric acid, and pegloticase, which is given by injection and breaks down uric acid for patients who can't benefit from or tolerate the other medications.

There are also natural ways to prevent gout attacks. Avoiding dehydration by simply drinking water is a simple, safe and effective one. Drinking six or more cups of coffee per day appears to lower the risk of gout attacks in men over 40, those most at risk. Vitamin C supplements, milk and other dairy products also seem to offer protection.

Scott Zashin, clinical professor of medicine at the University of Texas and author of the newly published book Natural Arthritis Treatment, is enthusiastic about the effectiveness of tart cherries. Although it's uncertain whether cherries or products made from them can reduce uric acid, Zashin said "they may be useful for preventing acute gout attacks."

Of course when "Madam Gout" cracks her whip, your only thought is to end the pain, fast. Preventing further attacks, however, takes time. "Men tend to want things to happen fast and not be compliant," said Zashin. Subsequent gout attacks have a way of changing that. "The main thing," he said, "is patients have to recognize they have to be patient. It may take a year to get things under control."

You can't change the uricase-free way evolution made you. But you can choose to eat foods and drink beverages--in moderation, as Quan emphasized--and take the medication your doctor prescribes if you've already made Ms. Gout's unwelcome acquaintance. Unless, of course, excruciating pain is your thing.

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The author of Victory Deferred, John-Manuel Andriote has specialized in HIV/AIDS reporting since 1986. His research materials, correspondence, and recorded interviews are part of a special collection curated by the Smithsonian.

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