ESSENTIALS OF DIAGNOSIS
Acute, monarticular arthritis, often of the first MTP joint; recurrence is common.
Polyarticular involvement more common in patients with longstanding disease.
Identification of urate crystals in joint fluid or tophi is diagnostic.
Dramatic therapeutic response to NSAIDs.
With chronicity, urate deposits in subcutaneous tissue, bone, cartilage, joints, and other tissues.
Gout is a metabolic disease of a heterogeneous nature, often familial, associated with abnormal deposits of urate in tissues and characterized initially by a recurring acute arthritis, usually monarticular, 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 especially common in Pacific islanders, eg, Filipinos and Samoans. Primary gout has a heritable component, and genome-wide surveys have linked risk of gout to several genes whose products regulate urate handling by the kidney. Secondary gout, which 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, plasma cell myeloma, hemoglobinopathies, chronic kidney disease, hypothyroidism, psoriasis, sarcoidosis, and lead poisoning (Table 20–4). 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 20–4.Origin of hyperuricemia.
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; indeed, 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 ...