ABSTRACT: Early and accurate gout diagnosis and disease management are essential. Making the clinical diagnosis takes into consideration the differential diagnosis supported by the use of clinical, serological, and diagnostic studies. Hyperuricemia is a serum uric acid level consistently higher than 6.8 mg/dL. Various imaging modalities have advantages over others in making the diagnosis. The impact of gout is underestimated, and diagnosis and management generally are poor. Everyday challenges include medication noncompliance, nonadherence, and nonconcordance. The contemporary approach to gout management is focused on controlling 3 distinctive phases of disease: acute flare, flare prophylaxis, and reduction of the body urate burden.
Hyperuricemia and gout have increased markedly in prevalence and clinical complexity over the past 2 decades. Early and accurate diagnosis and disease management are essential, because appropriate management limits systemic disease involvement, health care costs, unnecessary hospitalizations, workdays lost, and functional disability.
Making the clinical diagnosis of gout takes into consideration the differential diagnosis supported by the use of clinical, serological, and diagnostic studies. As with all diagnostic evaluations, the history and physical examination direct the process.
In this article, we describe the history and physical examination, the clinical features of an acute gout attack, laboratory testing, appropriate imaging studies, approaches to treatment, and various agents that may be effective. Included are recommendations for specialized management and referral to a rheumatologist for help in management.
History and physical examination
Understanding the predominance of gout in men is important for a complete evaluation (ratio, 20:1). The onset of gout in men usually is seen between age 35 and 50 years. In women, gout is seen largely after menopause; estrogen is uricosuric and plays a role in controlling urate levels.
Understanding patterns in affected joints also is important. The development of microtophi in cooler synovium and in the cartilage of distal extremity joints, olecranon bursa, and helix of the ear explains the predilection of lower extremities for gout flare. Urate is less soluble at temperatures below 37°C (98.6°F). Deeper, warmer structures become affected when the urate burden is great and over a long period. Urate precipitation also is favored by the absolute degree of supersaturation, plasma proteins, and abnormal aggrecans (eg, osteoarthritis [OA]), which reduce solubility.
Food and alcohol consumption both trigger acute flares and contribute to long-term management issues. Gout incidence is associated with daily intake of red meat and seafood, which have a high purine content, as well as consumption of alcohol, especially beer, which has the highest soluble purine content. High-purine-content vegetables did not seem to impact incidence of gout.1 There is a direct enzymatic link between increased intake of fructose (high-fructose corn syrup in artificial sweeteners) and elevated serum urate level2—a concern because fructose is ever more predominant in food. This links directly to the rise in obesity, a common denominator in the comorbidities of hyperuricemia, hypertension, hyperlipidemia, and atherosclerosis.
Increasing data indicate that gout and hyperuricemia alone are associated with increased cardiovascular disease (CVD) and mortality.3,4 Some authors argue that hyperuricemia is a biomarker for increased CVD, hypertension, and new-onset and progressive renal disease. Therefore, these comorbidities and the medications currently used to manage them are important to consider—they complicate the diagnosis as well as the management of acute, chronic, and recurrent gouty arthritis. Insufficient urate excretion can be iatrogenic with widely used therapies, such as diuretics, low-dose aspirin, niacin, cyclosporine, tacrolimus, antituberculosis drugs, and many antivirals.
The current diagnostic criteria for acute gouty arthritis are based on the 1977 American College of Rheumatology (ACR) criteria (Table 1). The ACR criteria for the classification of acute gout are inadequate for in-office diagnosis in about 20% of cases.5 New criteria currently are under development. European League Against Rheumatism (EULAR) recommendations for the diagnosis of gout highlight the value of synovial fluid crystal analysis (Table 2).
However, the classic description of acute gouty arthropathy stands: It is the very rapid onset of unilateral monarthritis with acute inflammation and severe pain. Often called podagra, it usually involves the midfoot or the first metatarsophalangeal joint. Patients who have this symptom complex often report previous episodes of the same symptoms. At first, these attacks are self-limited, resolving in 3 to 10 days. Also associated with classic acute gouty arthritis are periarticular or bursal erythema, followed by skin desquamation with resolution of attack as well as systemic symptoms, such as fever and leukocytosis. Uncharacteristic polyarticular involvement also may occur but often in the later stages of the disease.
These features can make the diagnosis difficult because similar signs and symptoms are seen in other acute processes, including septic arthritis, calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, OA, posttraumatic arthritis, and soft tissue injury.
Hyperuricemia is a serum uric acid (SUA) level consistently higher than 6.8 mg/dL. Note that during an acute gout flare, levels may be normal or only slightly elevated (lower than 8 mg/dL),6 often leading clinicians to a misdiagnosis and, ultimately, mismanagement. Also note that asymptomatic hyperuricemia is common and does not need to be managed unless there is systemic or joint involvement.
Because of these confounders, a joint aspiration must be completed for synovial fluid analysis if the diagnosis is at all indeterminate because it remains the gold standard for the diagnosis of gout. Musculoskeletal ultrasonography (MSUS) and dual energy CT (DECT) are beginning to challenge this standard—they are becoming useful alternative, noninvasive means to assess patients for the changes of acute, intermediate, and chronic gout.
No current diagnostic study can effectively differentiate between infectious and noninfectious causes of inflammatory arthritis other than aspiration and fluid analysis with cell count, Gram stain, and cultures. These are imperative for the most accurate diagnosis and directed management. The EULAR recommendations for the diagnosis highlight the value of synovial fluid analysis. Joint fluid is assessed with the use of a polarized microscope looking for negatively birefringent needle-shaped crystals.
During an acute gout flare, the joint aspirate is inflammatory. A useful rule of thumb when grossly evaluating synovial fluid is the inability to read print on paper through the fluid-filled tube—this would indicate aspirate with a leukocyte count into the inflammatory range of 1000 to 2000/µL. Aspirates with leukocyte counts higher than 1000 to 2000/µL are very cloudy. In an attempt to differentiate between gout and bacterial/septic arthritis, a leukocyte count with differential is just as important as Gram stain and culture. In gouty arthritis, the white blood cell (WBC) count typically is between 1000 and 50,000/µL, with less than 90% neutrophils; in septic arthritis, the WBC count typically is greater than 50,000/µL, with more than 90% neutrophils.
There is a direct inverse relationship between the amount of inflammation within the joint and the viscosity of the joint fluid. Crystal analysis is completed by assessment under a polarized light microscope, which requires only a minute amount of fluid.
Monosodium urate (MSU) crystals, which are precipitated in gout, are needle-shaped and strongly negative birefringent, meaning that they appear yellow when the long axis of the crystal is parallel to the red compensator and blue when it is perpendicular. In contrast, CPPD crystals have various shapes, although they primarily are rhomboid-shaped with weak positive birefringence. Additional crystal formations may be seen.
Previous corticosteroid injections may confuse the diagnosis because they appear as strongly positive birefringent crystals. During an acute attack, MSU crystals are seen both extracellularly and intracellularly as they are engulfed by the leukocyte (neutrophil). The fluid should be analyzed for at least 5 minutes over numerous fields to firmly rule out the presence of MSU crystals.7 For correct visualization of the aspirate, the handling of the sample is extremely important.
Plain radiography. This study demonstrates nonspecific soft tissue changes of swelling as well as more definitive changes characteristic of gout, including subcortical cysts, marginal “punched-out” erosions with overhanging edges (new cortical bone formation), and calcified tophi. The advantages are low cost, quickness, low radiation dose, in-office examination, and widespread availability. The disadvantages include a lack of sensitivity and specificity in early disease. After 5 years of flare activity, only about half of patients with gout have radiographic or erosive changes on plain radiographs.7,8
High-resolution CT. The advantages are superiority to plain radiography for detecting early disease and tophi changes. The disadvantages are high cost, high radiation exposure, moderate availability, and a lack of specificity.
DECT. The advantages of this newer diagnostic study are sensitivity and specificity for urate deposits, especially those in soft tissue and bone structures.9 The disadvantages: expensive and high radiation exposure.
MRI. This modality detects tophi with representative decreased signal in both T1- and T2-weighted images with variable enhancement.8 MRI is a useful examination when the presence of tophi is suspected but not proven. MRI often demonstrates greater-sized tophi than expected or appreciated on physical examination. The advantages are superiority to plain radiography in early detection and characterization of tophi and no radiation exposure. The disadvantages are less benefit than CT scanning, a lack of specificity for tophi, moderate availability, and high expense.
High-resolution (8 to16 MHz) MSUS. This can be a point of care technology for a quick and accurate bedside evaluation. It is sensitive for early detection of crystal deposits, seen as hyperechoic masses or linear bands in synovial or cartilage borders8 with the characteristic “double-contour” sign (representing MSU crystals layering the articular cartilage surface).
MSUS can differentiate between MSU crystal deposits and CPPD crystal deposits and is far more sensitive than plain radiography for early disease detection.8 The advantages are sensitivity and specificity, good early disease detection, low cost, widespread availability, portability, in-office use, and no radiation exposure. Because MSUS often is available for in-office services and does not use radiation, with a lower cost than CT and MRI, it is a popular choice with both patients and physicians.10 A disadvantage: a sonographer skilled in musculoskeletal evaluations and interpretation is required.
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• Terkeltaub R, Edwards NL. Gout: Diagnosis and Management of Gouty Arthritis and Hyperuricemia. 2nd ed. West Islip, NY: Professional Communications, Inc; 2011. This is a key resource that provides the most up-to-date review of gout diagnosis and treatment.