Gout's History

GOUT: An Historical Sketch

By: Thomas G. Benedek, M.D.

Gout is a disease that results from an imbalance between the production of uric acid (a break-down product of protein digestion), and the ability to excrete this substance, which is mainly a function of the kidneys. Why this imbalance and the resulting excess of uric acid in the blood, and often also in tissues, causes symptoms only intermittently is still being investigated.

Skeletal evidence of gout has been found in Egyptian mummies from possibly 4000 years ago. However, written evidence of the disease begins with the Hippocratic writings from about 400 BCE. One of these passages states: "Persons affected with the gout who are aged, have tophi in their joints, who have led a hard life, and whose bowels are constipated are beyond the power of medicine to cure." Of particular interest is the reference to "a hard life" because, from at least the 1^st century AD through the 20^th century, gout was thought to be a punishment for excesses of food, drink and debauchery.

Pain=podagra

The Greek term podagra literally means foot pain and it is true that, for unknown reasons, about two-thirds of early attacks of gout affect the big toe. But of course, the feet also suffer other painful ailments and, conversely, gout may affect any joint without inflaming a part of the foot. Therefore, podagra became a non-specific term for painful joints or arthritis. Many old descriptions of patients lack sufficient details to be confident that their diagnosis should have been gout, rather than some other disease. Indeed, by the 18^th century there are descriptions of "visceral gout" and "migratory gout" that could be any intermittently painful condition from migraine to a peptic ulcer, without any joint symptoms.

Hereditary Link

The hereditary predisposition to gout is stronger than for many other musculo-skeletal diseases. Therefore, the occurrence of suggestive symptoms in several members of a family increases the likelihood that the diagnosis is correct. A multi-generational example among French royalty is King Louis XIV, his father and grandfather. The strongest example within one generation is provided by children of the British King, George III. While he apparently never had an attack of gout, four sons and one daughter had the disease. (It would, however, be interesting to know the uric acid concentration of King George's blood.)

Classic Description from 17^th Century

The best early description of an acute attack of gout was made by the famous English physician, Thomas Sydenham, writing about himself in 1683. He also was one of the few medical writers who admitted to the lack of a reliable treatment. Indeed, while patients were blamed for contracting gout, the inadequacy of medicine in general was symbolized by its inability to cure this particular disease. Despite the use of many mainly herbal medications, used internally or as poultices, the basic therapy of that time continued to be diet modification.

Early Treatments

The 6^th century near-Eastern physician, Alexander of Tralles, has been alleged to have discovered a specific treatment for gout in the plant hermodactyl. If he did so, it was coincidental - like many physicians of that time he was looking for a better laxative. He included hermodactyl in several multi-ingredient prescriptions. His formulary has survived though.

Colchis was a community on the coast of the Black Sea from which Colchicum autumnale, the meadow saffron got its Latin name. Whether this species of crocus is identical with hermodactyl is uncertain. Over the centuries it was generally considered to be poisonous, among other symptoms causing severe diarrhea. The "rehabilitation" of medicinal colchicum is attributed to the 18^th century Viennese physician, Baron Anton Stoerk.

Just as Alexander of Tralles had included hermodactyl in his compound preparations, a late 18^th century French military officer, Nicolas Husson, concocted "Eau Medicinale" to treat various ailments, including gout. In 1814 John Want, a London physician, determined that the active ingredient of the French "medicine" was an extract of colchicum. "Eau medicinale" reached England in 1808 and in 1820 the first Pharmacopoeia of the United States included both syrup and wine of colchicum. Thus, a relatively specific drug treatment for gout was actually known, but neglected, before any of the pathophysiology of gout was discovered.

The microscopic appearance of sodium urate crystals obtained from tophi was described remarkably well by Antonij van Leeuwenhoek in 1679 and 1684. He assumed that the pain of gout is caused by needle shaped crystals poking into tissues. However, there was no advance in the understanding of the disease or its treatment before the development of chemistry in the 19^th century.

Breakthroughs in Treatment

The most important pioneer in the understanding of gout was Alfred B. Garrod, a London physician-investigator. He not only invented methods to test for uric acid, but also made fundamental observations about the metabolism of uric acid and its anatomic distribution in gout. Many investigators gradually improved the sensitivity of blood tests for uric acid, first proving that it is a normal constituent in blood and then that its concentration normally is lower in women, but increasing after menopause.

Treatments Today

Surprisingly, colchicine, as a liquid preparation, was used infrequently before 1936. It became the preferred therapy after it became available as a pill. It was logical to attempt to reduce the amount of uric acid in the body, but even an unpalatable low protein diet had only a slight effect. In the 1940s aspirin came into use to prevent gouty attacks because it is both analgesic and in a sufficiently large dosage increases uric acid excretion. There was nothing to prevent or counteract tophi until 1951, when probenecid was introduced. This, contrary to colchicine, significantly increases the excretion of uric acid, an effect with which low-dose aspirin interferes.

Allopurinol, introduced in 1963, is more effective than probenecid in diminishing uric acid. The drugs can be used together but rarely are. It does not affect the kidneys, but rather interferes with the production of uric acid by blocking the activity of two enzymes.

The treatment of gout today is potentially the most effective of any non-bacterial joint disease. Research on the development of even better means to lower uric acid in the body and advances in the understanding of the acute gouty attack continue today.

References

Gutman, A.B., Yu, T.-F: "Current principles of management in gout."
American Journal of Medicine, 1952; 13:744-759.

Hartung, E.F.: "History of the use of colchicine and related medicaments in gout."
Annals of the Rheumatic Diseases, 1954; 13:190-200.

Herrick, W.W., Tyson, T.L.: "Gout - A forgotten disease."
American Journal of the Medical Sciences, 1936; 192:483-488.

Marson, F.G.: "Studies in gout, with particular reference to the value of sodium salicylate in treatment."
Quarterly Journal of Medicine, 1953; 22:331-346.

McCarty, D.J.: "A historical note: Leeuwenhoek's description of crystals from a gouty tophus."
Arthritis & Rheumatism, 1970; 13:414-418.

Rodnan, G.P., Benedek, T.G.: "The early history of antirheumatic drugs."
Arthritis & Rheumatism, 13:145-165, 1970.

Sydenham, T.: "On Gout." Vol. II, 123-162 in: The Works of Thomas Sydenham.
London Sydenham Society, 1848. Reprint: Classics of Medicine Library, 1979.

Wallace, S.L.: "Benjamin Franklin and the introduction of colchicine into the United States."
Bulletin of the History of Medicine, 1968; 42:312-320.

Dr. Thomas Sydenham's 1683 description of an acute gout attack (translated from the Latin in 1850) is still referenced today. Dr. Sydeham was himself a gout sufferer.

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. This pain is like that of a dislocation, and yet the parts feel as if cold water were poured over them. Then follows chills and shiver and a little fever. The pain which at first moderate becomes more intense. After a time this comes to full height, accommodating itself to the bones and ligaments of the tarsus and metatarsus. Now it is a violent stretching and tearing of the ligaments-now it is a gnawing pain and now a pressure and tightening. So exquisite and lively meanwhile is the feeling of the part affected, that it cannot bear the weight of bedclothes nor the jar of a person walking in the room.

Source: Kelley's Textbook of Rheumatology, Sixth edition. 2001. Philadelphia, W.B. Saunders Company.
In editing - Dr. Thomas Benedek

Gout & Uric Acid Education Society