Porth's Essentials of Pathophysiology, 4e

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Musculoskeletal Function

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Diagnosis and Treatment. Although hyperuricemia is the biochemical hallmark of gout, the presence of hyper- uricemia cannot be equated with gout because many per- sons with this condition never develop gout. A definitive diagnosis of gout can be made only when monosodium urate crystals are present in the synovial fluid or in tissue sections of tophaceous deposits. Synovial fluid analysis is useful in excluding other conditions, such as septic arthritis, pseudogout, and RA. 65–68 Diagnostic methods also include measures to determine if the disorder is related to overproduction or to underexcretion of uric acid. This is done through measurement of serum uric acid levels and collection of a 24-hour urine sample for determination of urate excretion in the urine. The objectives for treatment of gout include the ter- mination and prevention of the acute attacks of gouty arthritis and the correction of hyperuricemia, with con- sequent inhibition of further precipitation of sodium urate and absorption of urate crystal deposits already in the tissues. Pharmacologic management of acute gout is directed toward reducing joint inflammation. 65–68 Hyperuricemia and related problems of tophi, joint destruction, and renal problems are treated after the acute inflammatory process has subsided. Nonsteroidal anti-inflammatory drugs, particularly indomethacin and ibuprofen, are used for treating acute gouty arthritis. 68 Alternative therapies include colchicine and intra-articular deposition of cor- ticosteroids. Colchicine produces its anti-inflammatory effects by inhibition of leukocyte migration and phago- cytosis. Although the drug usually is given orally, a more rapid response is obtained when colchicine is given intra- venously. The acute symptoms of gout usually subside within 48 hours after treatment with oral colchicine has been instituted and within 12 hours after intravenous administration of the drug. The corticosteroid drugs have not been systemically studied, but can be useful in the treatment of acute gout limited to a single joint or bursa. Between acute attacks nonpharmacologic and phar- macologic measures are used to normalize uric acid lev- els as a means of reducing or preventing the frequency and severity of recurrence. 65–68 Nonpharmacologic meth- ods include maintenance of ideal weight, moderation in alcohol consumption, and avoidance of purine-rich foods (e.g., liver, kidney, sardines, anchovies, and sweet- breads). Avoidance of medications that inhibit renal excretion of uric acid (e.g., loop and thiazide diuretics, low-dose aspirin, and niacin) is also needed. Three classes of drugs may be used to lower the serum uric acid–xanthine oxidase inhibitors, uricosuric agents, and uricase agents. Xanthine oxidase inhibitors block the synthesis of uric acid. In this classification, the most commonly prescribed drug to lower urate levels is allo- purinol. Another xanthine oxidase inhibitor, febuxostat, is used for treatment in persons with a hypersensitiv- ity to allopurinol. The uricosuric agents (e.g., proben- ecid, sulfinpyrozone, and benzobromarone) prevent the tubular reabsorption of urate and increase its excretion in the urine. The serum urate concentrations are moni- tored to determine efficacy and dosage. Uricase agents convert insoluble uric acid to a soluble product that

A

Clinical Manifestations. The typical acute attack of gout is monoarticular and usually affects the first meta- tarsophalangeal joint. 65,66 The tarsal joints, insteps, ankles, heels, knees, wrists, fingers, and elbows also may be initial sites of involvement. Acute gout often begins at night and may be precipitated by excessive exercise, certain medications or foods, alcohol, or diet- ing. The onset of pain typically is abrupt, and redness and swelling are observed. The attack may last for days or weeks. Pain may be severe enough to be aggra- vated even by the weight of a bed sheet covering the affected area. In the early stages of gout after the initial attack has subsided, the person is asymptomatic, and joint abnor- malities are not evident. This is referred to as inter- critical gout. After the first attack, it may be months or years before another attack. As attacks recur with increased frequency, joint changes occur and become permanent. B FIGURE 44-13. (A) Gouty tophi of the hands appear as multiple rubbery nodules, one of which is ulcerated. (B) A cross-section of a digit demonstrates the trophaceous collection of toothpaste-like urate crystals. (From: Garcia RA, Klein MJ, Schiller AL. Bones and joints. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:1282.)