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Dr. Maria Michailidou


                                                                    PODAGRA (GOUT)

Essentials of Diagnosis

Caused by deposition of uric acid crystals and usually associated with hyperuricemia. Usually begins as an intermittent, acute monoarthritis, especially of the first metatarsophalangeal joint. Over time, attacks become more frequent, less intense, and involve more joints. Diagnosed by demonstrating uric acid crystals in joint fluid. Extra-articular manifestations include tophi and renal stones. Arthritis responds to nonsteroidal anti-inflammatory drugs or colchicine.

General Considerations

The underlying basis for gout is an increased total body urate pool. This is generally manifested as hyperuricemia, which is defined as a serum urate concentration more than 7.0 mg/dL. The concentration of 7.0 mg/dL is important because fluids with urate content greater than that are supersaturated with urate, a condition that favors urate crystal precipitation.

At least 5% of asymptomatic Americans manifest hyperuricemia on at least one occasion during adulthood. Hyperuricemia may be even more common in Europe and in countries in the Far East.

The likelihood of developing symptomatic gout and the age at which that occurs correlates with the duration and magnitude of hyperuricemia. In one study, persons with urate levels between 7.0 and 8.0 mL/dL had a cumulative incidence of gouty arthritis of 3% while those with urate levels greater than 9.0 mL/dL had a 5-year cumulative incidence of 22%. Hyperuricemia alone is not sufficient for the diagnosis of gout, however, and asymptomatic hyperuricemia in the absence of gout is not a disease. It appears that clinical gout will develop in fewer than one in four hyperuricemic persons at any point.

Gout presents predominantly in men with a peak age of onset in the fifth decade. The incidence of gout in women approaches that of men only after they have reached age 60 years. The onset of disease in men prior to adulthood or in women before menopause is quite rare and is almost always due to an inborn error of metabolism or congenital condition. The prevalence of self-reported gout is estimated to be 13.6 per 1000 men and 6.4 per 1000 women.

Hyperuricemia can result from increased urate production, decreased uric acid excretion by the kidneys, or a combination of the two mechanisms. Fewer than 5% of patients with gout are hyperuricemic because of urate overproduction. These persons can be recognized because they excrete more than 800 mg of uric acid in their urine during a 24-hour period. Those who excrete less uric acid than 800 mg are hyperuricemic because of impaired renal excretion. Defining individuals as "over-producers" or "underexcreters" is helpful in predicting whether the hyperuricemia is associated with a variety of acquired or genetic disorders () and may be useful in some cases in determining the most appropriate treatment.

Clinical Findings

Symptoms and Signs

The natural history of gout can be divided into three distinct stages

1. Asymptomatic hyperuricemia.

2. Acute and intermittent (or intercritical) gout.

3. Chronic tophaceous gout.

Although most untreated patients with gout will progress to chronic tophaceous gout, the course varies considerably from one patient to another. Some patients experience only one or two attacks of acute gouty arthritis during their lifetime. It is quite unusual for tophi to develop in a patient with no history of acute gouty arthritis.

The initial episode of acute gouty arthritis usually follows 10 to 30 years of asymptomatic hyperuricemia, and there is no evidence that damage occurs to any organ system during that time. Just why and when the first attack of gout occurs in susceptible persons remains a mystery. Although some patients experience prodromal episodes of mild discomfort, the onset of a gouty attack is usually heralded by the rapid onset of exquisite pain associated with warmth, swelling, and erythema of the affected joint (. The pain escalates from the faintest twinges to its most intense level over an 8- to 12-hour period. Initial attacks usually affect only one joint and, in half the patients, the first attack involves the first metatarsophalangeal joint. Other joints frequently involved in the early stage of gout include the midfoot, ankle, heel, and knee. Wrist, fingers, and elbows are more typical sites of attacks later in the course of the disease. The intensity of the pain is such that patients cannot stand even the weight of a bed sheet on the affected part and most find it difficult or impossible to walk when the lower extremities are involved in an acute attack. The acute attack may be accompanied by fever, chills, and malaise. Cutaneous erythema associated with the attack may extend beyond the involved joint and resemble cellulitis. Desquamation of the skin may occur as the attack resolves.

Symptoms resolve quickly with appropriate treatment, but even untreated, an acute attack resolves spontaneously over 1 to 2 weeks. With resolution of the attack, patients enter an interval termed the "intercritical period" when they are again completely asymptomatic. The rare patient will not experience a second attack of gout but most will. Early in the intermittent stage, episodes of arthritis are infrequent and the intervals between the attacks vary from months to years. Over time, the attacks become more frequent, less acute in onset, longer in duration, and tend to involve more joints.

During the intercritical periods of acute intermittent gout, the previously involved joints are virtually free of symptoms. Despite this, monosodium urate crystal deposition continues. Urate crystals often can be identified in the synovial fluid despite the absence of symptoms and erosive changes indicative of bony tophi begin to appear on radiographs.

Although the reasons why acute gout develops when it does are not clear, attacks tend to be associated with rapid increases, and more often, decreases in the concentration of urate in synovial fluid. These concentrations mirror the fluctuations seen in the serum. Accordingly, a person may experience a sudden drop in the serum urate level, leading to an acute attack and, therefore, is found to be normouricemic when blood is tested at that time. Trauma, alcohol ingestion, and the use of certain drugs are known to trigger gout attacks as well. Gouty attacks not infrequently occur as a person is recovering from an alcoholic binge. Drugs known to precipitate attacks do so by rapidly raising or lowering serum urate levels. Candidate agents include diuretics, salicylates, and the urate-lowering drugs allopurinol and radiographic contrast agents. It is believed that these fluctuations in urate levels destabilize tophi in the gouty synovium. The sudden addition of urate to them may render them unstable, or the sudden lowering of the urate concentration may cause partial dissolution and instability. As the microtophi break apart, crystals are shed into the synovial fluid and the gouty attack is initiated by the ingestion of these crystals by polymorphonuclear leukocytes.

As gout continues to progress, the patient gradually enters the stage of chronic gouty arthritis. This usually develops after 10 or more years of acute intermittent gout. The transition to chronic gout is complete when the intercritical periods are no longer pain free. The involved joints are now persistently uncomfortable and may be swollen. Patients report stiffness or gelling sensations as well. Visible or palpable tophi may be detected on physical examination during this stage of gout, even though they may have been recognized by radiographs prior to entry into this stage ). The development of tophaceous deposits in individual patients varies; in general, they are a function of the duration and severity of the hyperuricemia, with a mean occurrence approximately 12 years after the onset of the first attack of gout in those not treated with urate-lowering drugs.

Laboratory Findings

Hyperuricemia remains the cardinal feature of gout. The usefulness of this laboratory finding in establishing the diagnosis of gout is limited. Whereas most patients with gout will have an elevated serum urate (greater than 7.0 mg/dL), levels may fall within the normal range on occasion; in fact, levels in the normal range are not uncommon during acute attacks, as described above. In addition, during the acute attack, the complete blood cell count may show a leukocytosis with increased polymorphonuclear leukocytes on the differential and elevations of the erythrocyte sedimentation rate and C-reactive protein. The greatest utility of measuring serum urate is in monitoring the effects of urate-lowering therapy.

During an acute attack, the synovial fluid findings are consistent with moderate to severe inflammation . The leukocyte count usually ranges between 5 and 80,000 cells/L with an average between 15,000 and 20,000 cells/L. The cells are predominately polymorphonuclear leukocytes.

The definitive diagnosis of gout is made by examination of synovial fluid or tophaceous material with compensated polarized light microscopy and identifying the characteristic monosodium urate crystals. These crystals appear as bright yellow needle-shaped objects when parallel to the access of slow vibration on the first-order compensator. When these crystals are perpendicular to that axis, they are blue. Crystals are usually intracellular and needle-shaped during acute attacks but may be small, blunted, and extracellular as the attack subsides or during intercritical periods.

The 24-hour urine uric acid measurement is not required in all patients with gout but is useful for determining potential causes of hyperuricemia (see above) as well as determining whether uricosuric therapy can be effective, since this form of therapy is effective only in underexcretors.

Imaging Studies

No radiographic abnormalities are present early in the disease course. In acute gouty arthritis, the only finding may be soft tissue swelling in the involved joint. Bony abnormalities indicative of deposition of urate crystals (microtophi) develop only after years of disease. These abnormalities are most frequently asymmetric and confined to previously symptomatic joints. The advanced bony erosions of advanced gout are often radiographically distinct. Typically, they are slightly removed from the joint space, have a rounded or oval shape, and are characterized by a hypertrophic calcified "overhanging edge." The joint space may be preserved or show osteoarthritic type narrowing.

Special Tests

Patients with gout often suffer from hyperlipidemia, glucose intolerance, hypertension, coronary artery disease, and obesity. Accordingly, it is appropriate to measure serum lipids and fasting blood sugars in patients with gout. Because renal dysfunction develops in many patients with hypertension and gout, it is appropriate to monitor serum creatinine levels as well.