Gout is one of the crystal-induced arthropathies that is caused by precipitation of uric acid crystals in the joint spaces, kidneys, and cutaneous locations. It is divided into acute and chronic phases, which have different presentations and different treatments. The human body’s immune reaction against the urate crystals causes more damage than the crystals themselves. Gout has been described for centuries and is clinically easily diagnosed. Medications, genetic predisposition, and dietary habits all contribute to cases of gout. There are other crystal-induced arthropathies that must be considered in the differential diagnosis of gout, the most common being calcium pyrophosphate crystals.
Clinical Findings: Gout is a disease predominantly found in the male population. Podagra is the classic presentation of an acute gouty attack. Descriptions of podagra have been published in the medical literature for centuries. It manifests as an acute monoarticular arthritis. The joint most commonly affected is the metatarsophalangeal articulation of the great toe. The clinical signs start as redness overlying the joint, swelling, warmth, and severe pain. Podagra has often been described as one of the most painful experiences a patient can perceive. A clue to the diagnosis is that the pain is often so severe that it appears to be out of proportion to the clinical picture. Patients complain of the slightest movement or touch; they are unable to wear shoes or bear weight on the foot; and they often have trouble with placement of a thin sheet over the affected joint. Acute attacks may be frequent, and the need for therapy is quite apparent. If no treatment is undertaken, an acute case of gout may last 7 days or longer. Any joint in the body can be affected by acute gout, but the great toe is by far the most common joint of involvement. Patients with acute gout have abnormal laboratory test results that can help in the diagnosis. An increased white blood cell count with a left shift is almost always seen. The markers of acute phase reactants are elevated, including the erythrocyte sedimentation rate (ESR), ferritin, and C-reactive protein.
The diagnosis can be made at the bedside by joint aspiration and microscopic evaluation. The affected joint is tapped with a fine-gauge needle and aspirated. The aspirate is then evaluated under polarized microscopy. Needle-like, elongated crystals of uric acid are seen freely within the synovial aspirate and also within the leukocytes of patients with gout. Radiographs of the affected joint do not show uric acid crystals and are likely to show only grossly abnormal soft tissue swelling. The serum uric acid level in acute gout can be normal, slightly elevated, or abnormally elevated; therefore, this test by itself is unreliable in making the diagnosis.
Chronic gout, which is seen as a sequela of multiple attacks of acute gout, leads to joint destruction and chronic arthritis. Patients with chronic gout may also develop acute episodes of gout. Patients with chronic gout are predisposed to the development of tophaceous gout. This form of gout manifests as skin deposits of urate crystals. It can occur in any location and is most often located within the subcutaneous tissue. These tophi appear clinically as subcutaneous nodules, often overlying the extensor joints, particularly the elbows, Achilles tendons, and hands. For some reason, the ear is another area that is affected by tophi. The nodules of tophi may become thinned and partially translucent. The tophi may show an underlying yellowish appearance beneath the skin, and occasionally the clumping of crystals is appreciated just underneath the skin. With trauma, the nodules occasionally ulcerate, and crystals drain from the tophi. Saturnine gout is a specific form of gout that has been found to be caused by the consumption of ho emade moonshine that is contaminated with lead.
Pathogenesis: Gout is caused by increased levels of uric acid resulting from a decrease in secretion, an increase in production, or an increase in dietary intake. Underexcretion of uric acid by the kidneys is responsible for most cases of gout. This can result from genetic causes or from use of medications that compete with the transport of uric acid, especially alcohol and the loop diuretics. Uric acid is produced under normal circumstances from the breakdown of purine nucleotides. Patients with the Lesch-Nyhan syndrome have a defect in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme, which is encoded by the gene HPRT1 and is critical in the purine recycling pathway. This syndrome is seen in children and can lead to severe neurological disease that is confounded by severe gout. Certain chemotherapies cause severe immediate death of many leukocytes, resulting in the release of a high concentration of uric acid that can overwhelm the body’s normal mechanisms of removal, leading to gout. Foods found to have high concentrations of uric acid should be avoided by patients with preexisting gout, because they have been shown to exacerbate the disease.
Histology: Biopsies of gout are rarely performed, because the clinical scenario is often diagnostic. When tissue of tophi is procured for biopsy, it is best that it be fixed in alcohol, because formalin dissolves the uric acid crystals, and they will not be seen on histological examination. The diagnosis can still be made, because the needle-shaped, clefted areas left by the dissolved crystals is characteristic. The crystals can be appreciated on alcohol-fixed tissue, and they appear needle shaped and birefringent under polarized light. The appearance of gout is much different from that of calcium pyro- phosphate histologically, and there is usually no problem differentiating the two conditions. The crystals of pseudogout are rhomboid shaped and weakly birefringent.
Treatment: The therapeutic goal in acute gouty attacks is to control the patient’s pain, and nonsteroidal antiinflammatory drugs (NSAIDs) have long been the medications of choice. Indomethacin also has been widely used for years. Aspirin should never be used in acute gout, because it can transiently increase uric acid levels when initiated. Colchicine is another medication that is used for the treatment of acute gouty attacks. Prednisone can be used to decrease the acute inflammation, pain, and swelling. Medications for the prophylactic treatment of gout are not used in acute episodes, because they may make an acute attack worse. They have also been shown to cause attacks of acute gout on rare occasions.
The most commonly used prophylactic medications to help prevent future acute attacks in patients with chronic gout are allopurinol and probenecid. Allopurinol is used exclusively for those patients who overproduce uric acid, and probenecid is used for those whose kidneys underexcrete uric acid. Up to one third of patients started on allopurinol develop a cutaneous rash. If this happens, prompt discontinuation is wise, because allopurinol can lead to a severe drug hypersensitivity syndrome. Allopurinol works by inhibiting the purine breakdown enzyme, xanthine oxidase. This ultimately decreases the amount of uric acid produced from the breakdown of purine byproducts. Historically, allopurinol was the first medication devised to inhibit a specific enzyme.
Tophi can be treated with the long-term use of allopurinol or probenecid. Over time, the goal is to mobilize the tissue uric acid and increase its excretion from the body. This can take years. Individual tophi have been surgically removed to help increase range of motion, f located around joints, or to improve cosmesis.