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MEDICAL BIOLOGY: ON GOUT

Gout was the first form of arthritis recognized to be caused by the deposition of crystals (urate) in the joints and periarticular tissues. The term "gout" is derived from the Latin "gutta", a drop. It is applied to crystal-deposit arthritis because of the false belief in ancient times that the disease was caused by drops of bad "humor". The term "humor", in turn, refers to the ancient Greek theory of four body humors: blood, yellow bile, black bile, and phlegm.

The term "gout" is currently defined as a disorder of purine metabolism, occurring especially in men, characterized by a raised by variable blood uric acid level and severe recurrent acute arthritis of sudden onset resulting from deposition of crystals of sodium urate in connective tissues and articular cartilage. Most cases of gout are inherited, resulting from a variety of abnormalities of purine metabolism.

The following points are made by Robert A. Terkeltaub (New Engl. J. Med. 2003 349:1647):

1) Gout is a common medical problem, affecting at least 1 percent of men in Western countries, with a male:female ratio ranging from 7:1 to 9:1.(1) Humans do not express the enzyme uricase, which degrades uric acid, an end product of purine nucleotide catabolism.(2) Consequently, statistically normal uric acid levels in men and premenopausal women (7 mg per deciliter [416 micromol per liter] and 6 mg per deciliter [357 micromol per liter], respectively) are close to the limits of urate solubility (approximately 7 mg per deciliter at 37 deg C) in vitro, imposing a delicate physiologic urate balance.(3)

2) Hyperuricemia is central to gout but does not inevitably cause disease.(4,5) A serum urate level of at least 9 mg per deciliter was associated with an annual incidence of gouty arthritis of 4.9 percent in a cohort of healthy men; the incidence was 0.5 percent among those with a serum urate level of 7 to 8.9 mg per deciliter (529 micromol per liter) and 0.1 percent among those with urate levels below 7 mg per deciliter.(5) Predictors of the development of clinical gout, other than the serum urate level, include hypertension, the use of thiazides and loop diuretics, obesity, and a high alcohol intake, all of which appear to contribute in an additive manner to the risk of gout.(5)

3) Uric acid urolithiasis is common in the presence of excessive production and excretion of urate. Overproduction of urate and persistently acid urine (which may be more prevalent in patients with gout) also increases the risk of calcium oxalate urolithiasis.(1) Clinically evident interstitial nephropathy, which is directly promoted by medullary deposition of monosodium urate at a physiologic pH, has become uncommon in Western countries, probably as a consequence of improved pharmacologic management of gout and increased use of nondiuretic therapies for hypertension.

4) The classic symptoms of gouty arthritis are recurrent attacks of acute, markedly painful monoarticular or oligoarticular inflammation, but polyarthritis and chronic arthritis can occur.(4) Thus, the differential diagnosis of gouty arthritis is broad.(4) A definitive diagnosis requires the direct identification of urate crystals in the joint and the exclusion of infection. Serum urate levels are frequently normal during attacks of acute gout.

References (abridged):

1. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994. Am J Kidney Dis 2002;40:37-42

2. Wu X, Wakamiya M, Vaishnav S, et al. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci U S A 1994;91:742-746

3. Bomalaski JS, Holtsberg FW, Ensor CM, Clark MA. Uricase formulated with polyethylene glycol (uricase-PEG 20): biochemical rationale and preclinical studies. J Rheumatol 2002;29:1942-1949

4. Wortmann RL. Gout and hyperuricemia. Curr Opin Rheumatol 2002;14:281-286

5. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia: risks and consequences in the Normative Aging Study. Am J Med 1987;82:421-426

New Engl. J. Med. http://www.nejm.org

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