Often called the "disease of kings" because of its association with the rich foods and copious alcohol once available only to aristocrats, gout is staging a middle-class comeback as American society grows older and heavier.
The rising tide of gout — an extremely painful arthritis of the big toe and other joints — is leading the pharmaceutical industry to rediscover what it had considered a disease of the past. Companies are now racing to improve upon decades-old generic drugs that do not work well for everyone.
Already this year the Food and Drug Administration has approved the first new gout drug in more than 40 years, a product called Uloric from Takeda Pharmaceutical.
Another new drug, Krystexxa, made by Savient Pharmaceuticals of East Brunswick, N.J., will be reviewed for possible approval by an F.D.A. advisory committee on Tuesday.
And several other companies are testing drugs in clinical trials.
"It's kind of like the forgotten disease," said Barry D. Quart, chief executive of one of those companies, Ardea Biosciences of San Diego.
Ardea discovered accidentally that an AIDS drug it was developing might work against gout. Now the company has shifted its focus to gout, envisioning annual sales of $1 billion if its drug is successful.
That would mean a huge increase in spending on gout medicines, which had sales of only $53.4 million last year, according to IMS Health, a health care information company. Uloric, the drug from Takeda, sells a daily pill for at least $4.50 compared with 10 to 50 cents for the most commonly used generic, allopurinol.
It is estimated that two million to six million Americans have gout. Although the disease becomes more common as people age, some men develop gout in their 40s and 50s, or even younger. It is three to four times as common in men as in women, in part because estrogen is thought to protect premenopausal women from the illness.
Various studies suggest that the number of cases in this country has as much as doubled in the last three decades.
"We have accumulated a lot of people with severe disease," said Dr. Robert A. Terkeltaub, section chief of rheumatology at the Veterans Affairs Medical Center in San Diego and a consultant to some of the companies developing gout drugs. And the typical case these days, is "not going to be someone who looks like Henry VIII," he said. "Now it's going to be some 80-year-old lady with congestive heart failure."
One of the severe cases is Mr. Matthews, who had controlled his disease for many years with the generic allopurinol. But when he developed renal problems in 2006, he stopped taking allopurinol because it can be harmful to those with bad kidneys. After that, Mr. Matthews was bedridden or in a wheelchair and in such excruciating pain in many of his joints that he said he contemplated suicide.
"It was like having a toothache so bad you can't stand it, all over your body," he said.
Mr. Matthews, 76, says he found relief as a participant in a clinical trial of Savient's Krystexxa, the drug now up for review by the F.D.A.
Gout is caused by the buildup of a chemical called uric acid in the blood. Uric acid is formed by the breakdown of purines, which are components of DNA, RNA and some other important molecules in the body.
Some types of meat and fish, as well as beer, are particularly rich in purines and can raise the risk of gout. There is also evidence that sugary soft drinks raise the risk.
When uric acid levels get too high, the chemical can form needlelike crystals that accumulate in joints.
In the early stages of the disease, gout attacks, which can last several days and are excruciating, occur only rarely. But over time, the frequency increases and people can develop disfiguring and disabling lumps of the chalky white crystals, called tophi. Michael Clayton of Atlanta, who has severe gout, said he had to quit a job as general manager of a restaurant after customers complained about the tophi on his hands, which sometimes oozed liquid resembling Wite-Out.
Many doctors and patients treat only gout attacks. They use either pain relievers like naproxen, steroids or colchicine — a crocus plant derivative that has been used for centuries.
Many of the new drugs lower uric acid levels in the blood, meaning they can prevent gout attacks and keep the disease under control.
A problem in getting doctors to prescribe chronic treatment for gout is that many patients are reluctant to admit they have the disease because of its association with gluttony.
"It's part of society's view of gout that this is something self-inflicted," said Dr. N. Lawrence Edwards, professor of medicine at the University of Florida.
So the industry is trying to spread the word that genetics and other factors, not just diet, contribute to gout. Takeda and Savient bankroll the Gout and Uric Acid Education Society, which is led by Dr. Edwards and was formed in 2005 to raise awareness of the disease.
Another reason that gout is shedding its image as a disease of the past is preliminary evidence — though still far from proof — that high uric acid levels might also contribute to modern-day ills like hypertension, obesity, heart disease, kidney impairment and diabetes.
In one small study published last year, treatment with allopurinol reduced high blood pressure in adolescents.
Right now, it is estimated that 15 million to 20 million Americans have elevated uric acid levels, known as hyperuricemia. But they do not have gout symptoms and are therefore not treated.
If further studies prove that high uric acid levels contribute to other diseases, though, then "hyperuricemia" could be defined as a disease in its own right and millions of people might one day take drugs to lower uric acid levels, much as they now do to lower cholesterol.
Paul Hamelin, president of Savient, said, "There's a huge amount of ground that nobody's ever plowed yet."