Clinical manifestations of hyperuricemia and gout

ACUTE GOUT FLARES: PAINFUL, UNPREDICTABLE, HIGHLY LIKELY TO RECUR

Acute flares of gouty arthritis are characterized by warmth, swelling, redness, and often severe pain. Pain frequently begins in the middle of the night or early morning. Many patients will describe awakening with pain in the foot that is so intense that they are unable to support their own weight. Patients may report fever and a flulike malaise. Fever and constitutional features are sequelae of the release of cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 following phagocytosis of crystals and activation of the intracellular inflammasome complex.⁷ Untreated, the initial attack will usually resolve in 3 to 14 days. Subsequent attacks tend to last longer and may involve more joints or tendons.

Where flares occur

It has been estimated that 90% of first attacks are monoarticular. However, the first recognized attack can be oligoarticular or even polyarticular. This seems particularly true in postmenopausal women and in transplant recipients. Gout attacks initially tend to occur in the lower extremities: midfoot, first metatarsophalangeal joint, ankle, or knee. Over time, gout tends to include additional joints, including those of the upper extremities. Axial joints are far less commonly involved. The initial (or subsequent) attack may be in the instep of the foot, not a well-defined joint. Patients may recall “ankle sprains,” often ascribed to an event such as “stepping off the curb wrong,” with delayed ankle swelling. These may have been attacks of gout that were not recognized by the patient and thus not reported to his or her physician. Bunion pain may be incorrectly attributed to gout (and vice versa). Therefore, we need to accept the limitations of historical recognition of gout attacks.

Acute flares also occur in periarticular structures, including bursae and tendons. The olecranon bursa, the tendons around the ankle, and the bursae around the knee are among the locations where acute attacks of gout can occur.

Risk of recurrence and implications for treatment

Based on historical data, the estimated flare recurrence rate is approximately 60% within 1 year after the initial attack, 78% within 2 years, and 84% within 3 years. Less than 10% of patients will not have a recurrence over a 10-year period. Untreated, some patients with gout will continue to have attacks and accrue chronic joint damage, stiffness, and tophi. However, that does not imply that published outcome data support treating every patient with urate-lowering therapy following an initial gout attack or even several attacks. There are no outcome data from appropriately controlled, long-term trials to validate such a treatment approach. Nonetheless, in some gouty patients, if hyperuricemia is not addressed, morbidity and joint damage will accrue. The decision as to when to intervene with urate-lowering therapy should be individualized, taking into consideration comorbidities, estimation of the likelihood of continued attacks, the impact of attacks on the patient’s lifestyle, and the potential complications of needing to use medications to treat acute attacks.

INTERCRITICAL PERIODS: CRYSTAL DEPOSITION CONTINUES SILENTLY

Immediately after an attack of gout, patients may be apt to have another if anti-inflammatory therapy is not provided for a long enough period, ie, until several days after an attack has completely resolved. Subsequently, there may be a prolonged period before another attack occurs. During this time, uric acid deposits may continue to increase silently. The factors that control the rate, location, and degree of ongoing deposition in a specific patient are not well defined. Crystals may still be found in the synovial fluid of previously involved joints until the serum urate level is reduced for a significant period to a level significantly less than 6.8 mg/dL.⁸

ADVANCED GOUT: DIFFERENTIATION FROM RHEUMATOID ARTHRITIS IS KEY

Tissue stores of urate may continue to increase if hyperuricemia persists at biologically significant levels (> 6.8 mg/dL). Crystal deposition can cause chronic polyarthritis. Some patients, especially as they age, develop rheumatoid factor positivity. Chronic gout, involving multiple joints, can mimic rheumatoid arthritis. Patients can develop subcutaneous tophi in areas of friction or trauma. These tophi, as well as periarticular ones, can be mistaken for rheumatoid nodules. It is unclear why only some people with hyperuricemia develop tophi. The presence of urate crystals in the aspirate of a nodule (tophus) or synovial fluid will distinguish gout from rheumatoid arthritis. Radiographs can also be of diagnostic use.

Unlike radiographic findings in rheumatoid arthritis, in gout there is a prominent, proliferative bony reaction, and tophi can cause bone destruction away from the joint. There may be a characteristic “overhanging edge” of proliferating bone surrounding a gout erosion (see Figure 3 in preceding article by Schumacher). These radiographic findings, although distinct from those of rheumatoid arthritis, can be confused with psoriatic arthritis, which also can be erosive with a proliferative bone response. Gout, however, is less likely to cause joint space narrowing than is either psoriatic arthritis or rheumatoid arthritis.

Intradermal tophi (Figure 1) are asymptomatic and frequently not recognized, yet are not that rare in severe untreated gout. Such tophi may be particularly common in transplant patients and appear as white or yellowish deposits with the overlying skin pulled taut.

POSTSCRIPT: GOUT IS NOT SO EASILY RECOGNIZED AFTER ALL