A serum urate level greater than approximately 6.8 mg/dL, the saturation point of urate in biological fluids, is the underlying cause of gout. Hyperuricemia, along with other factors (detailed below), over time can result in the deposition of monosodium urate crystals into the joints. Gouty attacks are thought to occur by the abrupt release of these crystals into the joint space, where they may initiate an acute inflammatory reaction recognized as acute gouty arthritis. The acute attack is self-limited, but crystals remain in the joint and low-grade, often subclinical, inflammation persists even between acute attacks. Although acute attacks can be treated with anti-inflammatory medications, the underlying cause of the disease can be treated only by lowering the serum urate level.
CRYSTAL DEPOSITION AND THE DEVELOPMENT OF GOUT
Asymptomatic hyperuricemia is not a disease but rather is the underlying factor that can predispose to gout. A serum urate level of approximately 6.8 mg/dL is the concentration at which monosodium urate crystals begin to precipitate.1,2 Although this level is based on in vitro studies, it suggests a reasonable biological threshold for clinicians assessing patients for hyperuricemia. It should be noted that there are often no manifestations of gout during an extended period of hyperuricemia even though urate crystals are beginning to deposit into joints. The higher the serum urate level, the more likely that crystals will deposit into joints.
Predisposition is not causation
In the Normative Aging Study, 22% of men who had serum urate levels greater than 9 mg/dL developed gout during a 5-year period—a much higher rate than among men with serum urate levels less than 9 mg/dL.3 Nevertheless, a full 78% of the men in this study with serum urate levels greater than 9 mg/dL did not develop gout over the 5-year period, illustrating that while hyperuricemia predisposes to gout, it does not automatically cause gout.
Contributing factors beyond serum urate
Other factors, when combined with hyperuricemia, contribute to crystal deposition and the development of gout.
Trauma or irritation. Patients with hyperuricemia tend to have monosodium urate crystal deposition at sites of trauma or irritation. The first metatarsophalangeal joint is often affected, at least in part because it is a site of mechanical stress. Likewise, mechanical irritation from leaning on the elbow may cause crystals to deposit in the olecranon bursa.
Lower temperatures favor crystal deposition,1,4 which may explain why the helix of the ear and the foot are often sites of crystal deposition and tophus development. Both temperature and mechanical effects probably play a role in crystal deposition, however, as gouty attacks tend to occur at the first metatarsophalangeal joint, not at the interphalangeal joints of the foot, which are at a lower temperature.
Previous disease. Crystals also deposit with an increased incidence in previously diseased joints. The Heberden node is a good example.5 A patient with osteoarthritis in the fingers may experience dramatically increased pain and swelling because of a gout flare superimposed on an osteoarthritic joint.