The natural history of gout can be divided into three distinct stages (Figure 44–1):
Acute and intermittent (or intercritical) gout.
Chronic tophaceous gout.
The natural history of gout progresses through three stages.
Although most untreated cases of gout progress to chronic tophaceous gout, the course varies considerably from one patient to another. Whereas some patients experience only one or two attacks of acute gouty arthritis during their lifetime, over 80% have a second flare within 2 years of the first. 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 10–30 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 (Figure 44–2). 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. The 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.
Acute gouty attack of the first metatarsophalangeal joint.
Symptoms resolve quickly with appropriate treatment, but even untreated, an acute attack resolves spontaneously over 1–2 weeks. With resolution of the attack, patients enter an interval termed the “intercritical period” when they are again completely asymptomatic. 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 and tophi increase in size. 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, radiographic contrast agents, and specific urate-lowering drugs (probenecid, allopurinol, febuxostat, and pegloticase). 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 (see above).
As gout continues to progress, the patient gradually enters the stage of chronic gouty arthritis. This is the result of a macrophage-driven chronic inflammatory response that surrounds tophi (see above) and 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 seen on radiographs prior to entry into this stage (Figure 44–3). 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.
Radiographic changes of gout.
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 have an elevated serum urate (>6.8 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.
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 underexcreters.
During an acute attack, the synovial fluid findings are consistent with moderate to severe inflammation (see Chapter 2). The leukocyte count usually ranges between 5 and 80,000 cells/mcL with an average between 15,000 and 20,000 cells/mcL. The cells are predominantly 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 in synovial fluid or aspirates of tophaceous deposits (Figure 44–4). These crystals appear as bright yellow needle-shaped objects when parallel to the axis 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.
Urate crystal ingested by a polymorphonuclear leukocyte in synovial fluid. This finding is pathognomonic for acute gouty arthritis.
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 (see Figure 44–3). Ultrasonography can also be used to make the diagnosis. The characteristic finding is a “double contour sign,” a superficial, hyperechoic band on the surface of the articular cartilage.
MRI and CT scans are also sensitive methods of detecting tophi and erosions.
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.