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1. GOUTY ARTHRITIS

ESSENTIALS OF DIAGNOSIS

  • Acute, monoarticular arthritis, often of the first MTP joint; recurrence is common.

  • Polyarticular involvement more common with longstanding disease.

  • Identification of urate crystals in joint fluid or tophi is diagnostic.

  • Dramatic response to NSAIDs.

  • With chronicity, urate deposits in subcutaneous tissue, bone, cartilage, joints, and other tissues.

General Considerations

Gout is a heterogeneous metabolic disease, often familial, associated with abnormal deposits of urate in tissues and characterized initially by a recurring acute arthritis, usually monoarticular, and later by chronic deforming arthritis. Urate deposition occurs when serum uric acid is supersaturated (ie, at levels greater than 6.8 mg/dL [404.5 mcmol/L]). Hyperuricemia is due to overproduction or underexcretion of uric acid—sometimes both. The disease is more common in Asian-Pacific populations, eg, a prevalence of over 10% has been reported in the Māori people. Primary gout has a heritable component, and genome-wide surveys have linked risk of gout to genes whose products regulate urate handling by the kidney. Secondary gout, which also may have a heritable component, is related to acquired causes of hyperuricemia, eg, medication use (especially diuretics, low-dose aspirin, cyclosporine, and niacin), myeloproliferative disorders, CKD, and lead poisoning (Table 22–4). Alcohol ingestion promotes hyperuricemia by increasing urate production and decreasing the renal excretion of uric acid. Finally, hospitalized patients frequently suffer attacks of gout because of changes in diet, fluid intake, or medications that lead either to rapid reductions or increases in the serum urate level.

Table 22–4.Common risk factors for gout.

About 90% of patients with primary gout are men, usually over 30 years of age. In women, the onset is typically postmenopausal. The characteristic lesion is the tophus, a nodular deposit of monosodium urate monohydrate crystals with an associated foreign body reaction. Tophi are found in cartilage, subcutaneous and periarticular tissues, tendon, bone, the kidneys, and elsewhere. Urates have been demonstrated in the synovial tissues (and fluid) during acute arthritis; the acute inflammation of gout is believed to be initiated by the ingestion of uncoated urate crystals by monocytes and synoviocytes. Once inside the cells, the gout crystals are processed through Toll-like receptors and activate NALP-3 inflammasomes that in turn release a variety of chemotactic agents and cytokines capable of mediating inflammation. The precise relationship ...

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