The Case of Brian H.
Are his presenting symptoms hematologic in origin or indicative of a rheumatologic disorder, necessitating a consult between the treating physician and a rheumatologist?
GOUT AS A LIKELY DIAGNOSIS
The Third National Health and Nutrition Examination Survey (NHANES III) estimated the prevalence of gout in the US population to be 5.1 million between 1988 and 1994.10 During that period, gout affected more than 3 million men older than 40 and 1.7 million women older than 40, making this disease more common than RA and the most common form of inflammatory arthritis in adult men.10
The prevalence of gout in men increases with advancing age. Women have an increased risk of developing gout after menopause, and the incidence of gout becomes approximately equal between the genders after age 60 (Figure 1).10
Acute gouty arthritis most commonly begins with involvement of a single joint or multiple joints in the lower extremities, most commonly the first metatarsophalangeal (ie, podagra), midtarsal, ankle, or knee joints. However, similar to hemophilic arthropathy, any joint in the feet, ankles, knees, hands, wrists, or elbows may be involved. Pain, erythema, and swelling often begin in the early morning and increase and peak within 24 to 48 hours. The pain is severe, and patients often cannot wear socks or touch bedsheets during flare-ups.11 Occasionally, a gout attack triggers a systemic inflammatory response manifesting with fevers, leukocytosis, elevated sedimentation rates, and elevated C-reactive protein (CRP) and may be difficult to distinguish from acute septic arthritis.
12 Attacks typically subside within 5 to 7 days, even without treatment.11
Hyperuricemia is considered the most important risk factor for the development of gout.13 Numerous other risk factors include genetics, dietary factors (eg, meat and seafood consumption), alcohol consumption (especially beer and spirits), metabolic syndrome, hypertension, obesity, diuretic use, and chronic renal disease.
Gout is an inflammatory crystal arthropathy caused by altered purine metabolism, often leading to hyperuricemia.
12 Hyperuricemia is defined as the serum urate level, in body fluids, above which urate precipitates into monosodium urate (MSU) crystals. A urate level >6.8 mg/dL is considered hyperuricemia.12 When the local solubility limits of uric acid are exceeded, MSU crystals may be deposited in the joints, kidneys, and soft tissues. However, gout may also occur in the presence of normal serum uric acid levels. Pathogenic effects include arthritis, soft tissue masses (ie, tophi), nephrolithiasis, and urate nephropathy.11
Classification criteria to aid in the diagnosis of gout have been proposed by the American College of Rheumatology, and a consensus panel of experts from the European League Against Rheumatism (EULAR) has reviewed the evidence and made recommendations for diagnosing gout.14 Published clinical gout diagnostic (CGD) criteria: (1) >1 attack of acute arthritis, (2) mono/oligoarthritis attacks, (3) rapid progression of pain and swelling (<24 h), (4) podagra, (5) erythema, (6) unilateral tarsitis, (7) probable tophi, and (8) hyperuricemia.15
The main differential diagnosis of acute gout is pseudogout (calcium pyrophosphate deposition disease [CPPD]), other crystalline diseases, septic arthritis, atypical rheumatoid arthritis, trauma, OA, reactive arthritis, and fracture. The differential diagnosis should be considered based on the history and clinical presentation.
Synovial fluid analysis via aspiration of the affected joint is considered the gold standard for confirming a diagnosis of gout or other crystal-induced diseases and ruling out septic arthritis.11,12 Synovial fluid analysis offers a valuable diagnostic tool for evaluating any patient with acute monoarthritis. Once the fluid is aspirated, it can be examined grossly for color and turbidity. In general, transparent synovial fluid in the syringe is more suggestive of a noninflammatory condition, whereas fluid that appears turbid or purulent is more suggestive of inflammation or infection (eg, RA, septic arthritis). However, gross appearance alone is not diagnostic.12
To confirm or rule out infection, the fluid needs to be processed for Gram stain and culture. It is possible to have concomitant gout and septic arthritis. On microscopic examination, the number of white blood cells (WBCs) per high-power field can be estimated. The WBC count may be a useful adjunct in estimating the degree of inflammation present. With gout, synovial fluid analysis reveals leukocytosis, a nonspecific finding of inflammatory arthritis including infectious and crystalline causes.12 Synovial fluid WBC counts will usually be greater than 2000/mm3, and may be as high as
50,000/mm3.14 Crystal analysis is done with a microscope that is equipped to examine compensated polarized light. An accurate diagnosis can be made by a trained observer detecting and identifying MSU crystals (gout) or CPPD crystals (pseudogout). MSU crystals are strongly negatively birefringent and appear lancet-shaped when viewed under compensated polarized light.12 CPPD crystals are weakly birefringent and rhomboid or rod-shaped. CPPD crystals are more difficult to find and may be missed if the analysis is not done by a trained examiner. In addition to shape and birefringence, MSU and CPPD differ in color depending on the axis of orientation with respect to the polarizer. When the axis of the MSU crystal is parallel to the polarizer, it appears yellow; when perpendicular, it appears blue. The CPPD crystal is the reverse of that, so when the CPPD crystal is parallel, it appears blue, and when perpendicular, it appears yellow (Table 1).12
Recently, a method using dual-energy CT scanning of the affected joint has become available. This technology allows gouty crystals to appear as green pixelations when in and around the joint.17 In addition, ultrasound may be utilized in some circumstances to diagnose gouty arthritis and tophi, if any are present. There is a characteristic appearance, a so-called "double contour sign," that presents.18 These techniques allow for the diagnosis noninvasively, an obvious advantage in patients with coagulopathies.