Supplements Update on the Diagnosis and Treatment of Gout
Diagnosis of Gout: Clinical, Laboratory, and Radiologic Findings
SF Analysis. Even when the clinical appearance strongly suggests gout, the diagnosis must be confirmed by needle aspiration of the acutely inflamed joint or suspected tophus.18 During the 1960s, McCarty and Hollander described this method.4 A drop of SF should be examined promptly under routine light and polarizing light microscopy. SF is best examined while fresh. If MSU crystals cannot be identified on the wet preparation after 5 to 10 minutes, the remaining SF should be centrifuged and the pellet examined. This technique can increase yield if only a few crystals are present. Gouty tophi should be examined by smearing a small amount of tophaceous material onto a slide. A smear from gouty tophi will show a mass of brilliantly birefringent, needle-shaped crystals.
MSU crystals are needle-shaped and approximately 2 to 20 mm long. They exhibit strong negative birefringence under polarized light. They appear yellow when they are parallel to the axis of the slow vibration of the compensator and blue when lying perpendicular to the same axis.22 MSU crystals can be observed in more than 95% of patients with acute gouty arthritis.13 In some asymptomatic patients, MSU crystals are also detected in joints in which there is no inflammation,23,24 and this is thought to confirm the diagnosis. MSU crystals are largely intracellular during acute gouty attacks and the intercritical period, whereas they are mostly extracellular and free in the SF in chronic gout (Figure). SF leukocyte counts are elevated from 2000 to 100 000/mL in patients with acute gout.
SF should ideally be examined within 6 hours of arthrocentesis to reduce the rate of artifactual results. If microscopic examination is delayed, SF should be refrigerated.25 Postaspiration changes particularly affect cell counts. Changes in MSU crystals are less of a problem, and the crystals can usually still be identified, but become smaller, less numerous, and less birefringent with time.
Although demonstrating the presence of MSU crystals by aspiration of SF is the gold standard for the diagnosis of gout, there is great variability between examiners. Several studies have looked at the quality of SF identification. Of the 25 laboratories studied by Von Essen and Holtta, for instance, 19 identified all MSU crystals correctly.26 In a study by Hasselbacher, crystals were correctly detected in 39 of 50 samples.27 Petrocelli and associates found equally good results for MSU identification with gramstained and wet preparations of SF.28 Studies of the reproducibility of SF analyses, however, have shown that some laboratories perform very poorly.29,30 Crystal concentration is important in making the diagnosis.31 The higher the crystal load in the SF, the more likely it is that observers will obtain accurate results.
It is sometimes difficult to differentiate whether a patient with acute arthritis has gout or pseudogout. Pseudogout is one main form of calcium pyrophosphate dihydrate (CPPD) deposition disease, chronic arthritis being the other. Pseudogout gets its name because the clinical presentation of an acute attack is similar to that of gout (Table 3). Almost half of acute attacks of CPPD crystal deposition disease affect the knees, but the wrists, metacarpophalangeal joints, elbows, and shoulders may also be involved. Furthermore, some CPPD crystals may be difficult to distinguish from MSU crystals with a regular microscope. Under compensated polarized light, however, the difference between the 2 types of crystals is evident, and the correct diagnosis can be made. The CPPD crystals are rhomboid-shaped and have weakly positive birefringence, whereas MSU crystals are needle-shaped with strong negative birefringence.
SU Level. The diagnostic value of an SU level is limited. A normal SU level clearly does not exclude acute gout. Despite the fact that SU levels <8 mg/dL are considered normal in many hospitals, levels >6.8 mg/dL are above saturation level and may allow deposition of gouty crystals. SU levels can clearly either rise or fall with attacks and may even be below saturation levels for urate. As many as 42% of patients may have normal SU levels during bouts of acute gouty arthritis.32,33
Despite these limitations, SU levels will be elevated at some point in a patient with gout, and it is important to follow the SU level during the course of treatment. An elevated SU level alone, however, does not serve as the sole criterion for gout. Although sustained hyperuricemia is a risk factor for acute gouty arthritis, tophaceous gout, and uric acid nephrolithiasis, most patients with hyperuricemia will never have an attack of gout. No treatment is required for asymptomatic patients, but it is prudent to determine the cause of hyperuricemia and correct it if possible.
X-ray Film. Radiographic abnormalities are not sufficiently sensitive and specific for the diagnosis of gout.34 Only 45% of patients with gout manifest radiographic bone changes, and then only 6 to 8 years after the initial attack.34 Typical well-defined, "punched out," periarticular erosions with overhanging edges are not seen radiographically until 6 to 12 years after the initial acute attack.35,36 The radiographic changes indicate the chronicity of the disease process. The radiographic hallmarks of gout are normal mineralization, joint space preservation, sharply marginated erosions with sclerotic borders, overhanging edges, and asymmetric polyarticular distribution.
Computed Tomography (CT) Scans. CT techniques reveal MSU deposits in vitro as well as within the knee joint, whereas such deposits are not visible on plain radiographs.37 Increased attenuation of the x-ray beam of the CT scanner could be due to a high concentration of sodium nuclei in the MSU crystals. It is well known that CT scanning can readily diagnose stones of the urinary tract not visible on conventional radiographs.38 It can be assumed that such calculi are composed mainly of urate.
Magnetic Resonance Imaging (MRI). MRI is a useful method of determining the extent of disease in tophaceous gout and may provide information regarding the patterns of deposition and spread of MSU crystals. Tophi usually have low signal intensity on both TI- and T2-weighted images and a variable enhancement pattern on MRI.39
In a study comparing soft tissue and bony changes observed by clinical examination and plain radiographs with those observed by MRI, both plain radiographs and clinical examination were found to markedly underestimate the size and extent of soft tissue and osseous involvement by tophi compared with MRI findings.40
MRI also detects early subclinical tophaceous deposits and indicates that urate deposits appear to spread along compartmental and fascial planes as opposed to the traditional view of strict radial growth.
Ultrasound. Plain radiography, MRI, and scintigraphic findings on bone scan provide helpful diagnostic clues but are not useful in making a definite diagnosis of gout. Ultrasonography is a more reliable, noninvasive method for diagnosing gout.41 Ultrasonographic investigation can detect deposition of MSU crystals on cartilaginous surfaces, as well as tophaceous material and typical erosions. Future large prospective, randomized, controlled trials of patients with crystal-proved gout are needed to further evaluate the use of ultrasonography in diagnosing gouty arthritis.
Response to Treatment
Response to colchicine treatment is not an accurate tool to diagnose gout because patients with other inflammatory diseases such as psoriatic arthritis, pseudogout, and Bechet's arthritis, as well as those with gout, often respond favorably to colchicine.42-44
Heat and cold are adjuvant treatments for arthritis. In gouty arthritis, cold applications, in addition to being a useful adjuvant treatment, are helpful for discriminating patients with gout from other forms of inflammatory arthritis. Topical ice has been shown to help relieve joint pain in patients with gouty arthritis but not in patients with rheumatoid arthritis or other inflammatory arthridities.45,46
The presence of MSU crystals in SF or tophus remains the gold standard for the diagnosis of gout. Supportive data to make a diagnosis of gout include a typical clinical history of a sudden and severe exquisitely painful joint, most classically the first metatarsophalangeal joint; a history of underlying renal disease or use of medications that cause hyperuricemia; an elevated SU level; radiologic evidence suggestive of gouty arthritis; and a favorable response to colchicine treatment and topical cold applications.
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