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Gout and Pseudogout

  • Author: Bruce M Rothschild, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jan 31, 2016
 

Practice Essentials

Gout and pseudogout are the 2 most common crystal-induced arthropathies. Gout (see the image below) is caused by monosodium urate monohydrate crystals; pseudogout is caused by calcium pyrophosphate crystals and is more accurately termed calcium pyrophosphate disease.

Gout. Acute podagra due to gout in elderly man. Gout. Acute podagra due to gout in elderly man.

Signs and symptoms

Symptoms of gout or pseudogout include the following:

  • Podagra (initial joint manifestation in 50% of gout cases and eventually involved in 90%; also observed in patients with pseudogout and other conditions)
  • Arthritis in other sites – In gout, the instep, ankle, wrist, finger joints, and knee; in pseudogout, large joints (eg, the knee, wrist, elbow, or ankle)
  • Monoarticular involvement most commonly, though polyarticular acute flares are not rare, and many different joints may be involved simultaneously or in rapid succession
  • In gout, attacks that begin abruptly and typically reach maximum intensity within 8-12 hours; in pseudogout, attacks resembling those of acute gout or a more insidious onset that occurs over several days
  • Without treatment, symptom patterns that change over time; attacks can become more polyarticular, involve more proximal and upper-extremity joints, occur more often, and last longer
  • In some cases, eventual development of chronic polyarticular arthritis that can resemble rheumatoid arthritis

Physical findings may include the following:

  • Involvement of a single (most common) or multiple joints
  • Signs of inflammation – Swelling, warmth, erythema (sometimes resembling cellulitis), and tenderness
  • Fever (also consider infectious arthritis)
  • Migratory polyarthritis (rare)
  • Posterior interosseous nerve syndrome (rare)
  • Tophi in soft tissues (helix of the ear, fingers, toes, prepatellar bursa, olecranon)
  • Eye involvement – Tophi, crystal-containing conjunctival nodules, band keratopathy, blurred vision, anterior uveitis (rare), scleritis

Complications of gout include the following:

  • Severe degenerative arthritis
  • Secondary infections
  • Urate or uric acid nephropathy
  • Increased susceptibility to infection
  • Urate nephropathy
  • Renal stones
  • Nerve or spinal cord impingement
  • Fractures in joints with tophaceous gout

See Presentation for more detail.

Diagnosis

Studies that may be helpful include the following:

  • Joint aspiration and synovial fluid analysis
  • Serum uric acid measurement (though hyperuricemia is not diagnostic of gout)
  • 24-hour urinary uric acid evaluation
  • Blood studies (including white blood cells [WBCs, triglyceride, high-density lipoprotein, glucose, and renal and liver function tests)

Plain radiographs may show findings consistent with gout. Erosions with overhanging edges are generally considered pathognomonic for gout (though also found in other diseases). Characteristics of erosions typical of gout include the following:

  • Maintenance of the joint space
  • Absence of periarticular osteopenia
  • Location outside the joint capsule
  • Sclerotic (cookie-cutter, punched-out) borders
  • Asymmetric distribution among the joints, with a strong predilection for distal joints, especially in the lower extremities

Ultrasonographic findings in established gout include the following:

  • A “double-contour” sign, consisting of a hyperechoic, irregular line of MSU crystals on the surface of articular cartilage overlying an adjacent hyperechoic bony contour
  • “Wet clumps of sugar,” representing tophaceous material, described as hyperechoic and hypoechoic heterogeneous material with an anechoic rim
  • Bony erosions adjacent to tophaceous deposits

Other imaging modalities that may be considered include the following:

  • Computed tomography (CT) – Complementary to plain radiography for recognizing erosions in gout
  • Magnetic resonance imaging (MRI) – MRI with gadolinium is recommended when tendon sheath involvement must be evaluated and when osteomyelitis is in the differential diagnosis

See Workup for more detail.

Management

Gout is managed in the following 3 stages:

  • Treating the acute attack
  • Providing prophylaxis to prevent acute flares
  • Lowering excess stores of urate to prevent flares of gouty arthritis and to prevent tissue deposition of urate crystals

Acute treatment of proven crystal-induced arthritis is directed at relief of the pain and inflammation. Agents used in this setting include the following:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin
  • Corticosteroids
  • Colchicine (now less commonly used for acute gout than it once was)
  • Adrenocorticotropic hormone (ACTH)
  • Combinations of drugs (colchicine plus NSAIDs, oral corticosteroids plus colchicine, intra-articular steroids plus colchicine or NSAIDs)

Therapy to control the underlying hyperuricemia generally is contraindicated until the acute attack is controlled (unless kidneys are at risk because of an unusually heavy uric acid load).

Long-term management of gout is focused on lowering uric acid levels. Agents used include the following:

  • Allopurinol
  • Febuxostat
  • Probenecid

Because these agents change serum and tissue uric acid levels, they may precipitate acute attacks of gout. This undesired effect may be reduced by prophylaxis with the following:

  • Colchicine or low-dose NSAIDs
  • Low-dose prednisone (if patients cannot take colchicine or NSAIDs)

Other therapeutic agents that may be considered include the following:

  • Uricase and pegloticase
  • Vitamin C
  • Anakinra
  • Fenofibrate

Nonpharmacologic measures that may be warranted are as follows:

  • Avoidance or restricted consumption of high-purine foods
  • Avoidance of excess ingestion of alcoholic drinks, particularly beer
  • Avoidance of sodas and other beverages or foods sweetened with high-fructose corn syrup
  • Limited use of naturally sweet fruit juices, table sugar, and sweetened beverages and desserts, as well as table salt
  • Maintenance of a high level of hydration with water (≥8 glasses of liquids daily)
  • A low-cholesterol, low-fat diet, if such a diet is otherwise appropriate for the patient
  • Weight reduction in patients who are obese

See Treatment and Medication for more detail.

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Background

Gout and pseudogout are the two most common crystal-induced arthropathies. Gout is caused by monosodium urate monohydrate crystals; pseudogout is caused by calcium pyrophosphate (CPP) crystals and is more accurately termed calcium pyrophosphate disease (CPPD). (See Pathophysiology and Etiology.) Gout is one of the oldest diseases in the medical literature,[1, 2] known since the time of the ancient Greeks. Pseudogout, which may be clinically indistinguishable from gout, was recognized as a distinct disease entity in 1962.

Crystal deposition can be asymptomatic, but gout and CPPD can develop into debilitating illnesses marked by recurrent episodes of pain and joint inflammation that result from the formation of crystals within the joint space and deposition of crystals in soft tissue.[3, 4, 5] If untreated, these disorders can lead to joint destruction and, in the case of uric acid crystals, renal damage.

Elevated serum uric acid levels are the principal risk factor for developing gout. lIn study that compared 993 patients with asymptomatic hyperuricemia and 4,241 normouricemic patients, the odds ratio (OR) for developing gout was 32 times higher in the hyperuricemic group than in the normouricemic group. The risk was most striking in men with severe hyperuricemia, in whom the OR for developing gout was 624.8.[6]

Although gout is associated with hyperuricemia, gout attacks are triggered not by a particular level of uric acid but typically by acute changes in the level of uric acid. All individuals with gout have hyperuricemia; however, hyperuricemia is also found in patients taking diuretics and even in those taking niacin or low doses of aspirin.

Gout may be either primary or secondary (see Etiology). Primary gout is related to underexcretion or overproduction of uric acid, often associated with a mix of dietary excesses or alcohol overuse and metabolic syndrome. Secondary gout is related to medications or conditions that cause hyperuricemia, such as the following[7] :

  • Myeloproliferative diseases or their treatment
  • Therapeutic regimens that produce hyperuricemia
  • Renal failure
  • Renal tubular disorders
  • Lead poisoning
  • Hyperproliferative skin disorders
  • Enzymatic defects (eg, deficient hypoxanthine-guanine phosphoribosyl transferase, glycogen storage diseases)

Gout is definitively diagnosed on the basis of demonstration of urate crystals in aspirated synovial fluid, in the absence of another etiology for arthritis. Classic radiographic findings are highly suggestive (see Workup).

Advances in early diagnosis and the availability of definitive treatment have significantly improved the prognosis of gout, as evidenced by the declining incidence of disabling chronic tophaceous gout. However, tophaceous gout may still develop because of misdiagnosis, poor management, medication intolerances, or poor patient adherence.

Gout is managed in the following 3 stages:

  • Treating the acute attack
  • Providing prophylaxis to prevent acute flares
  • Lowering excess stores of urate

Treatment of gout is important to relieve pain; to prevent disease progression; and to prevent deposition of urate crystals in the renal medulla or uric acid crystals in the renal collecting system, which may produce kidney stones or urate nephropathy.[8] (See Treatment.)

Management of pseudogout also involves treatment of the acute attack and prophylaxis. Treatment of the acute phase of pseudogout follows the same approaches as are used in gout, and colchicine is effective for prophylaxis. In contrast with gout, however, no specific therapeutic regimen exists to treat the underlying cause of CPP crystal deposition in pseudogout, except in cases associated with disorders such as hemochromatosis or hyperparathyroidism. (See Treatment.)

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Pathophysiology

Gout can be considered a disorder of metabolism that allows uric acid or urate to accumulate in blood and tissues. When tissues become supersaturated, the urate salts precipitate, forming crystals. In addition, the crystals also are less soluble under acid conditions and at low temperatures, such as occur in cool, peripheral joints (eg, the metatarsophalangeal joint of the big toe).

Urate initially precipitates in the form of needlelike crystals. The light-retarding (phase-shifting) characteristics of urate crystals allow them to be recognized by polarizing microscopy (see the image below).

Gout. Needles of urate crystals seen on polarizing Gout. Needles of urate crystals seen on polarizing microscopy.

Many conditions and drugs have been associated with an increase in plasma (and subsequent synovial) urate levels, particularly metabolic syndrome. A genetic predisposition for hyperuricemia exists; except in rare genetic disorders, however, the development of gout in hyperuricemic individuals appears to be mediated by environmental factors.[9, 10, 11]

The CPP crystals that produce pseudogout comprise a combination of inorganic pyrophosphate and calcium. The inorganic pyrophosphate is produced in large part by ectonucleotide phosphodiesterase pyrophosphatase (ENPP1), a catalytic enzyme found in chondrocytes of cartilage, and the pyrophosphate is exported potently by the membrane transporter ANKH.

A genetic predisposition exists for pseudogout. However, aging, some metabolic diseases (eg, hyperparathyroidism, hemochromatosis, and hypomagnesemia), and any process that leads to osteoarthritis also can be associated with subsequent CPP crystal deposition and pseudogout.

The presence of urate crystals in the soft tissues and synovial tissues is a prerequisite for a gouty attack. However, these crystals can also be found in synovial fluid or on the cartilage surface in the absence of joint inflammation.

A gout attack may be triggered either by release of crystals (eg, from partial dissolution of a microtophus caused by changing serum urate levels) or by precipitation of crystals in a supersaturated microenvironment (eg, release of urate as a consequence of cellular damage). In either situation, it is believed, naked urate crystals then interact with intracellular and surface receptors of local dendritic cells and macrophages, triggering a danger signal to activate the innate immune system.[12]

This interaction may be enhanced by immunoglobulin G (IgG) binding.[13, 14] Triggering of these receptors, including Toll-like receptors, followed by intracellular signaling by the NLRP3 inflammasome, results in the release of interleukin (IL)-1β, which in turn initiates a cascade of proinflammatory cytokines, including IL-6, IL-8, neutrophil chemotactic factors, and tumor necrosis factor (TNF)-α.[15, 16] Neutrophil phagocytosis leads to another burst of inflammatory mediator production.

Subsidence of an acute gout attack results from multiple mechanisms, including the clearance of damaged neutrophils, change in the properties of urate crystals, and the production of anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1RA), IL-10, and transforming growth factor (TGF)-β.[14, 17, 18, 19]

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Etiology

Gout develops in the setting of excessive stores of uric acid in the form of monosodium urate. Uric acid is an end-stage by-product of purine metabolism. Humans remove uric acid primarily by renal excretion. When excretion is insufficient to maintain serum urate levels below the saturation level of 6.8 mg/dL, hyperuricemia may develop, and urate can crystallize and deposit in soft tissues.

About 90% of patients with gout develop excess urate stores because of an inability to excrete sufficient amounts of uric acid in the urine (underexcretion). Most of the remaining patients either overconsume purines or produce excessive amounts of uric acid endogenously (overproduction). A few have impaired intestinal elimination of uric acid.

In rare cases, overproduction of uric acid is the result of a genetic disorder, such as the following[20] :

Overproduction of uric acid may also occur in disorders that cause high cell turnover with release of purines that are present in high concentration in cell nuclei. These disorders include myeloproliferative and lymphoproliferative disorders, psoriasis, and hemolytic anemias. Cell lysis from chemotherapy for malignancies, especially those of the hematopoietic or lymphatic systems, can raise uric acid levels, as can excessive exercise and obesity.

Causes of secondary gout due to underexcretion of uric acid include renal insufficiency, lead nephropathy (saturnine gout), starvation or dehydration, certain drugs, and chronic abuse of ethanol (especially beer and hard liquor). These disorders should be identified and corrected, if possible.

Certain comorbid conditions are associated with a higher incidence of gout, including the following[21, 22] :

  • Hypertension
  • Diabetes mellitus
  • Renal insufficiency
  • Hypertriglyceridemia
  • Hypercholesterolemia
  • Obesity
  • Anemia

Foods that are rich in purines include anchovies, sardines, sweetbreads, kidney, liver, and meat extracts. Consumption of fructose-rich foods and beverages (eg, those sweetened with high-fructose corn syrup) is associated with an increased risk of gout in both men and women.[23, 24]

Genetics

The heritability of serum urate levels is estimated at 63%.[25] Genome-wide association studies (GWAS) have identified several candidate loci associated with chronically elevated serum urate concentrations and gout.[26, 27, 28, 29]

In particular, 3 genes are noted to have a strong association with hyperuricemia. The locus with the strongest evidence of association is the glucose transporter 9 (GLUT9) gene, commonly referred to as the solute carrier 2A9 (SLC2A9), the product of which alters the renal excretion of uric acid. Some of the variants are associated with a protective effect, whereas others convey a higher risk of gout.[30]

The urate transporter 1 (URAT1) gene is involved with the urate-organic anion exchanger. Several mutations in this gene have been associated with gout.

Polymorphisms in the ABCG2 gene, which is located on chromosome 4 and codes for an intestinal urate transporter, are strongly associated with high serum uric acid concentrations and gout. Elevation of uric acid levels is greater in men than in women with the minor allele of rs2231142 in ABCG2.[26, 28]

Although genetic factors have been strongly associated with hyperuricemia, environmental and other state-of-health factors are responsible for the majority of the gout burden in developed countries.[30, 31] A study of 514 male twin pairs did show a strong concordance in hyperuricemia among monozygotic (MZ) twins (53%) as compared with dizygotic (DZ) twins (24%), but it did not show a significant difference between MZ and DZ twins with regard to the lifetime prevalence of gout.[11]

Causes of gout flares

Individual gout flares are often triggered by acute increases or decreases in urate levels that may lead to the production, exposure, or shedding of crystals. Changes in urate levels can result from acute alcohol ingestion, acute overindulgence in foods high in purines, rapid weight loss, dehydration, or trauma.

Similarly, flares can be precipitated by additions of or changes in dosage of medications that raise or lower uric acid levels. Medications that increase uric acid levels via effects on renal tubular transport include loop and thiazide diuretics, niacin, low-dose aspirin, and cyclosporine A.[32, 33, 34] Agents that lower levels of uric acid include radiocontrast dyes, xanthine oxidase inhibitors (eg, allopurinol and febuxostat), and uricosurics (eg, probenecid).

Pseudogout

Although the pathophysiology, clinical presentation, and acute-phase treatment of gout and pseudogout are very similar, the underlying causes of the 2 diseases are very different. Many cases of pseudogout in elderly people are idiopathic, but pseudogout has also been associated with trauma and with many different metabolic abnormalities, the most common of which are hyperparathyroidism and hemochromatosis.

Risk factors for pseudogout include use of loop diuretics (but not thiazide diuretics) and proton pump inhibitors, which cause hypomagnesemia.[34] Pseudogout attacks have been reportedly induced by etidronate disodium therapy and angiography.[35, 36]

Pseudogout has been recognized as having an underlying genetic component; however, comorbid conditions (such as osteoarthritis) and environmental factors are thought to play a much stronger role.[37] Some disorders that can lead to secondary pseudogout, such as hemochromatosis, do have a clear genetic cause. These patients should be properly evaluated and counseled.

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Epidemiology

United States statistics

Gout affects 8.3 million people in the United States; prevalence among adults is estimated to be 3.9%, on the basis of data from the 2007-2008 National Health and Nutrition Examination Survey (NHANES).[38] Prevalence is approximately 20% in patients with a family history of gout. It is estimated that more than 2 million people in the United States take medication to decrease serum uric acid levels.

Gout has become increasingly common in the United States as the population has grown older and heavier.[39] From 1990 to 1999, the incidence rose 40%.[40] Estimates for the number of US adults with self-reported gout in the previous year rose from 2.1 million in 1995 to 3 million in 2008.[10] In 2008, gout accounted for 174,823 emergency department (ED) visits in the US, or approximately 0.2% of all ED visits.[41]

The frequency of pseudogout varies with age. The annual incidence of acute attacks of arthritic pain and swelling is about 1.3 per 1000 adults, but nearly 50% of adults develop radiographic changes typical of CPPD by age 80 years.

Attacks of gout have been noted to occur more frequently in the spring and less frequently in the winter. The reason for this is unknown.

International statistics

Gout has a worldwide distribution. The prevalence varies widely from country to country. Regional differences may reflect environmental, dietary, and genetic influences.[42]

In the United Kingdom from 2000 to 2007, the incidence of gout was 2.68 per 1000 person-years—4.42 in men and 1.32 in women, and increasing with advancing age.[43] In Italy, the prevalence of gout rose from 6.7 per 1000 population in 2005 to 9.1 per 1000 population in 2009, increasing with age and 4 times higher in men.[44] In the Maori people of New Zealand, studies from the 1970s found that 0.3% of men and 4.3% of women were affected.[45, 46]

Sex- and age-related demographics

Gout has a male predominance.[24, 47] The estimated prevalence of gout is 5.9% in men and 2% in women.[38] This difference is largely a consequence of age at onset; estrogenic hormones have a mild uricosuric effect, and gout is therefore unusual in premenopausal women. For pseudogout, the male-to-female ratio is approximately 50:50.

The predominant age range of gout is 30-60 years. Usually, uric acid levels are elevated for 10-20 years before the onset of gout. In men, uric acid levels rise at puberty, and the peak age of onset of gout in men is in the fourth to sixth decade of life. However, onset may occur in men in their early 20s who have a genetic predisposition and lifestyle risk factors.[48] In women, uric acid levels rise at menopause, and peak age of onset is in the sixth to eighth decade of life.

The rate of gout is almost 5 times higher in persons aged 70-79 years than in those younger than 50 years.[49] The higher prevalence of gout in elderly persons may also reflect an increased prevalence of metabolic syndrome, high rates of diuretic treatment for hypertension and chronic heart failure, and the use of low-dose aspirin.[50]

Earlier onset of gout occurs in patients with renal insufficiency or a genetic abnormality of purine metabolism (eg, hypoxanthine-guanine phosphoribosyltransferase deficiency or phosphoribosylpyrophosphate synthetase superactivity). Cyclosporine A can cause an accelerated form of gout, even in premenopausal women, that can present after only a few years of hyperuricemia, particularly if the patient is also receiving diuretics.

Race-related demographics

Gout has an increased prevalence in some populations but is rare in others. For example, the frequency of gout is higher in populations such as the Chamorros and Maori and in the Blackfoot and Pima tribes. Many Maori and other Polynesian women have a genetic defect in renal urate handling that places them at risk for hyperuricemia and gout.[51] However, racial differences may at least in part reflect differences in diet, which has a large influence on the clinical expression of gout.

In the United States, the incidence of gout is 3.11 per 1000 person-years in African Americans and 1.82 per 1000 person-years in whites; the excess risk can be partly explained by a higher frequency of incident hypertension.[52] In contrast, clinically recognized gout is extremely rare among blacks living in Africa.[53]

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Prognosis

Gout is associated with considerable morbidity, with acute episodes often causing incapacitation. However, gout that is treated early and properly carries an excellent prognosis if patient adherence to treatment is good.

With early treatment, gout should be totally controlled. If attacks recur, successful uric acid adjustment (requiring lifelong use of urate-lowering medication) usually suppresses further activity. During the first 6-24 months of urate-lowering therapy, acute attacks of gout often occur more frequently.[54, 55]

Chronic injury to intra-articular cartilage leaves the joints more susceptible to subsequent joint infections. Draining tophi can become secondarily infected. Untreated chronic tophaceous gout can lead to severe joint destruction and, rarely, renal impairment. Deposition of monosodium urate crystals in the kidney can result in inflammation and fibrosis, leading to reduced renal function or chronic nephropathy.[56] Rarely, gout can produce spinal cord impingement when deposition in tissues produces a local mass.

Acute attacks of pseudogout usually resolve within 10 days. Prognosis for resolutions of acute attacks is excellent. Some patients experience progressive joint damage with functional limitation. CPPD also can cause chronic arthritis that can resemble osteoarthritis or rheumatoid arthritis.

Hyperuricemia and gout are associated with an increased overall likelihood of mortality. Whether this is directly attributable to hyperuricemia or gout or to gout-associated diseases (eg, insulin resistance, type 2 diabetes mellitus, abdominal obesity, hypercholesterolemia, or hypertension) has been much debated.[57, 58, 59]

Although no evidence has shown that gout or hyperuricemia causes any of these disorders, elevated urate levels have been shown to correlate with elevated blood pressure in adolescents.[60] Among middle-aged men, hyperuricemia is a significant independent risk factor for death from cardiovascular disease.[61] A meta-analysis found an independent association between gout and cardiovascular mortality as well as all-cause mortality.[59]

In a 2010 study, Kuo et al demonstrated that gout, but not hyperuricemia, is associated with higher risk of death from all causes and cardiovascular diseases. Analysis of 1383 deaths among 61,527 Taiwanese subjects showed in individuals with gout compared with those who had normal uric acid levels, the hazard ratio (HR) of all-cause mortality was 1.46 and the adjusted HR of cardiovascular mortality was 1.97. Among individuals with hyperuricemia, the HR of all-cause mortality was 1.07 and the adjusted HR of cardiovascular mortality was 1.08.[62]

An analysis of nationwide data on more than 200,000 English patients indicates that individuals with gout are at increased risk for both heart attack and stroke. The rate ratio for myocardial infarction in patients with gout was 1.82. Rate ratios for stroke were 1.71 for all stroke, 1.68 for ischemic stroke, 1.69 for hemorrhagic stroke, and 2.00 for stroke of unspecified type. Risks were elevated in both men and women and were higher in the younger age groups.[63, 64]

Risk for vascular disease is increased in patients with gout, particularly women, according to a retrospective cohort study from the United Kingdom that included 8386 patients with gout and 39,766 matched controls. Multivariate analysis showed that women with gout had a 25% increased risk for any vascular event compared with women without gout (hazard ratio [HR], 1.25) and increased risks for any coronary heart disease (HR, 1.25) and peripheral vascular disease (HR, 1.89).[65, 66]

Men with gout, compared with those without gout, had a small but significantly increased risk for any vascular event (hazard ratio [HR], 1.06) and an increased risk for any coronary heart disease (HR, 1.08) and peripheral vascular disease (HR, 1.18). Unlike women, men with gout were not at greater risk for angina, transient ischemic attack, or stroke.[65, 66]

 

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Patient Education

Patients with severe hyperuricemia should avoid foods with high purine content. Moderation in food and alcohol consumption is advised. Early recognition of acute gout attacks is critical, in that intervention with medication is much more effective earlier in the attack.

For patient education information, see the Arthritis Center, as well as Gout. Online information and pamphlets on gout are also available from the Arthritis Foundation.

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Contributor Information and Disclosures
Author

Bruce M Rothschild, MD Professor of Medicine, Northeast Ohio Medical University; Adjunct Professor, Department of Biomedical Engineering, University of Akron; Research Associate, University of Kansas Museum of Natural History; Research Associate, Carnegie Museum

Bruce M Rothschild, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Rheumatology, International Skeletal Society, New York Academy of Sciences, Sigma Xi, Society of Skeletal Radiology

Disclosure: Nothing to disclose.

Coauthor(s)

Mark L Francis, MD Professor of Medical Education, Department of Medical Education, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center

Mark L Francis, MD is a member of the following medical societies: American College of Physicians, Phi Beta Kappa

Disclosure: Nothing to disclose.

Anne V Miller, MD Chief, Rheumatology Division; Assistant Professor of Internal Medicine, Department of Medicine, Division of Rheumatology, Southern Illinois University School of Medicine

Anne V Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Richard W Allinson, MD Associate Professor, Department of Ophthalmology, Texas A&M University Health Science Center; Senior Staff Ophthalmologist, Scott and White Clinic

Richard W Allinson, MD, is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Andrew A Dahl, MD Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine

Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Paul E Di Cesare, MD, FACS Professor and Chair, Department of Orthopedic Sugery, University of California, Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Joseph Kaplan, MD, MS, FACEP Attending Physician, Department of Emergency Medicine, Martin Army Community Hospital, Fort Benning

Joseph Kaplan, MD, MS, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Jegan Krishnan, MBBS, FRACS, PhD Professor, Chair, Department of Orthopedic Surgery, Flinders University of South Australia; Senior Clinical Director of Orthopedic Surgery, Repatriation General Hospital; Private Practice, Orthopaedics SA, Flinders Private Hospital

Jegan Krishnan, MBBS, FRACS, PhD, is a member of the following medical societies: Australian Medical Association, Australian Orthopaedic Association, and Royal Australasian College of Surgeons

Disclosure: Nothing to disclose.

Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of Cleveland

Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sriya K M Ranatunga, MD, MPH Associate Professor, Department of Clinical Medicine, Southern Illinois University School of Medicine

Disclosure: Nothing to disclose.

Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

References
  1. Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004 Apr 17. 363(9417):1277-81. [Medline].

  2. Choi HK, Curhan G. Gout: epidemiology and lifestyle choices. Curr Opin Rheumatol. 2005 May. 17(3):341-5. [Medline].

  3. Currie WJ. The gout patient in general practice. Rheumatol Rehabil. 1978 Nov. 17(4):205-17. [Medline].

  4. Martinon F, Glimcher LH. Gout: new insights into an old disease. J Clin Invest. 2006 Aug. 116(8):2073-5. [Medline]. [Full Text].

  5. So A. Gout in the spotlight. Arthritis Res Ther. 2008. 10(3):112. [Medline]. [Full Text].

  6. Duskin-Bitan H, Cohen E, Goldberg E, Shochat T, Levi A, Garty M, et al. The degree of asymptomatic hyperuricemia and the risk of gout. A retrospective analysis of a large cohort. Clin Rheumatol. 2014 Apr. 33(4):549-53. [Medline].

  7. Edwards NL. Treatment-failure gout: a moving target. Arthritis Rheum. 2008 Sep. 58(9):2587-90. [Medline].

  8. Bluestone R, Waisman J, Klinenberg JR. The gouty kidney. Semin Arthritis Rheum. 1977 Nov. 7(2):97-113. [Medline].

  9. Bleyer AJ, Hart TC. Genetic factors associated with gout and hyperuricemia. Adv Chronic Kidney Dis. 2006 Apr. 13(2):124-30. [Medline].

  10. Reginato AM, Mount DB, Yang I, Choi HK. The genetics of hyperuricaemia and gout. Nat Rev Rheumatol. 2012 Oct. 8(10):610-21. [Medline]. [Full Text].

  11. Krishnan E, Lessov-Schlaggar CN, Krasnow RE, Swan GE. Nature versus nurture in gout: a twin study. Am J Med. 2012 May. 125(5):499-504. [Medline].

  12. Liu-Bryan R, Scott P, Sydlaske A, et al. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005 Sep. 52(9):2936-46. [Medline].

  13. Nagase M, Baker DG, Schumacher HR Jr. Immunoglobulin G coating on crystals and ceramics enhances polymorphonuclear cell superoxide production: correlation with immunoglobulin G adsorbed. J Rheumatol. 1989 Jul. 16(7):971-6. [Medline].

  14. Ortiz-Bravo E, Sieck MS, Schumacher HR Jr. Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. Arthritis Rheum. 1993 Sep. 36(9):1274-85. [Medline].

  15. Akahoshi T, Murakami Y, Kitasato H. Recent advances in crystal-induced acute inflammation. Curr Opin Rheumatol. 2007 Mar. 19(2):146-50. [Medline].

  16. Martinon F. Mechanisms of uric acid crystal-mediated autoinflammation. Immunol Rev. 2010 Jan. 233(1):218-32. [Medline].

  17. Terkeltaub RA. What stops a gouty attack?. J Rheumatol. 1992 Jan. 19(1):8-10. [Medline].

  18. Yagnik DR, Evans BJ, Florey O, et al. Macrophage release of transforming growth factor beta1 during resolution of monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2004 Jul. 50(7):2273-80. [Medline].

  19. Lioté F, Ea HK. Recent developments in crystal-induced inflammation pathogenesis and management. Curr Rheumatol Rep. 2007 Jun. 9(3):243-50. [Medline].

  20. Richette P, Bardin T. Gout. Lancet. 2010 Jan 23. 375(9711):318-28. [Medline].

  21. Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011 Mar. 23(2):192-202. [Medline].

  22. McAdams-Demarco MA, Maynard JW, Coresh J, Baer AN. Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study. Arthritis Res Ther. 2012 Aug 20. 14(4):R193. [Medline]. [Full Text].

  23. Choi HK, Willett W, Curhan G. Fructose-rich beverages and risk of gout in women. JAMA. 2010 Nov 24. 304(20):2270-8. [Medline].

  24. Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ. 2008 Feb 9. 336(7639):309-12. [Medline]. [Full Text].

  25. Yang Q, Guo CY, Cupples LA, Levy D, Wilson PW, Fox CS. Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study. Metabolism. 2005 Nov. 54(11):1435-41. [Medline].

  26. Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008 Dec 6. 372(9654):1953-61. [Medline]. [Full Text].

  27. Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet. 2008 Jan. 82(1):139-49. [Medline]. [Full Text].

  28. Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009 Jun. 5(6):e1000504. [Medline]. [Full Text].

  29. Merriman TR. Population heterogeneity in the genetic control of serum urate. Semin Nephrol. 2011 Sep. 31(5):420-5. [Medline].

  30. Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008 Apr. 40(4):437-42. [Medline].

  31. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med. 1987 Mar. 82(3):421-6. [Medline].

  32. Hall AP, Barry PE, Dawber TR, McNamara PM. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med. 1967 Jan. 42(1):27-37. [Medline].

  33. Lin HY, Rocher LL, McQuillan MA, Schmaltz S, Palella TD, Fox IH. Cyclosporine-induced hyperuricemia and gout. N Engl J Med. 1989 Aug 3. 321(5):287-92. [Medline].

  34. Rho YH, Zhu Y, Zhang Y, Reginato AM, Choi HK. Risk factors for pseudogout in the general population. Rheumatology (Oxford). 2012 Nov. 51(11):2070-4. [Medline]. [Full Text].

  35. Watanabe H, Yamada S, Anayama S, Sato E, Maekawa S, Sugiyama H, et al. Pseudogout attack induced during etidronate disodium therapy. Mod Rheumatol. 2006. 16(2):117-9. [Medline].

  36. Taggarshe D, Ng CH, Molokwu C, Singh S. Acute pseudogout following contrast angiography. Clin Rheumatol. 2006 Feb. 25(1):115-6. [Medline].

  37. Ciancio G, Bortoluzzi A, Govoni M. Epidemiology of gout and chondrocalcinosis. Reumatismo. 2012 Jan 19. 63(4):207-20. [Medline].

  38. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011 Oct. 63(10):3136-41. [Medline].

  39. Kim KY, Ralph Schumacher H, Hunsche E, Wertheimer AI, Kong SX. A literature review of the epidemiology and treatment of acute gout. Clin Ther. 2003 Jun. 25(6):1593-617. [Medline].

  40. Terkeltaub RA. Gout: Recent advances and emerging therapies. Rheumatic Disease Clinics Update. 2008;3(1):1-9.:

  41. Garg R, Sayles HR, Yu F, Michaud K, Singh J, Saag KG, et al. Gout-related health care utilization in US emergency departments, 2006 through 2008. Arthritis Care Res (Hoboken). 2013 Apr. 65(4):571-7. [Medline].

  42. Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z, et al. Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol. 2008 Sep. 35(9):1859-64. [Medline].

  43. Cea Soriano L, Rothenbacher D, Choi HK, García Rodríguez LA. Contemporary epidemiology of gout in the UK general population. Arthritis Res Ther. 2011 Mar 3. 13(2):R39. [Medline]. [Full Text].

  44. Trifirò G, Morabito P, Cavagna L, Ferrajolo C, Pecchioli S, Simonetti M, et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis. 2013 May. 72(5):694-700. [Medline].

  45. Reed D, Labarthe D, Stallones R. Epidemiologic studies of serum uric acid levels among Micronesians. Arthritis Rheum. 1972 Jul-Aug. 15(4):381-90. [Medline].

  46. Rose BS. Gout in Maoris. Semin Arthritis Rheum. 1975 Nov. 5(2):121-45. [Medline].

  47. Choi HK, De Vera MA, Krishnan E. Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology (Oxford). 2008 Oct. 47(10):1567-70. [Medline].

  48. Olaniyi-Leyimu BY. Consider gout in patients with risk factors, regardless of age. Am Fam Physician. 2008 Jul 15. 78(2):176. [Medline].

  49. Fravel MA, Ernst ME. Management of gout in the older adult. Am J Geriatr Pharmacother. 2011 Oct. 9(5):271-85. [Medline].

  50. Singh H, Torralba KD. Therapeutic challenges in the management of gout in the elderly. Geriatrics. 2008 Jul. 63(7):13-8, 20. [Medline].

  51. Simmonds HA, McBride MB, Hatfield PJ, Graham R, McCaskey J, Jackson M. Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling. Br J Rheumatol. 1994 Oct. 33(10):932-7. [Medline].

  52. Hochberg MC, Thomas J, Thomas DJ, Mead L, Levine DM, Klag MJ. Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum. 1995 May. 38(5):628-32. [Medline].

  53. Mody GM, Naidoo PD. Gout in South African blacks. Ann Rheum Dis. 1984 Jun. 43(3):394-7. [Medline]. [Full Text].

  54. Schumacher HR, Taylor W, Joseph-Ridge N, Perez-Ruiz F, Chen LX, Schlesinger N, et al. Outcome evaluations in gout. J Rheumatol. 2007 Jun. 34(6):1381-5. [Medline].

  55. Becker MA, MacDonald PA, Hunt BJ, Lademacher C, Joseph-Ridge N. Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy. Nucleosides Nucleotides Nucleic Acids. 2008 Jun. 27(6):585-91. [Medline].

  56. Yü T, Talbott JH. Changing trends of mortality in gout. Semin Arthritis Rheum. 1980 Aug. 10(1):1-9. [Medline].

  57. Forman JP, Choi H, Curhan GC. Uric acid and insulin sensitivity and risk of incident hypertension. Arch Intern Med. 2009 Jan 26. 169(2):155-62. [Medline]. [Full Text].

  58. Kim SY, De Vera MA, Choi HK. Gout and mortality. Clin Exp Rheumatol. 2008 Sep-Oct. 26(5 Suppl 51):S115-9. [Medline].

  59. Lottmann K, Chen X, Schädlich PK. Association between gout and all-cause as well as cardiovascular mortality: a systematic review. Curr Rheumatol Rep. 2012 Apr. 14(2):195-203. [Medline]. [Full Text].

  60. Feig DI, Johnson RJ. The role of uric acid in pediatric hypertension. J Ren Nutr. Jan/2007. 17(1):79-83. [Medline].

  61. Krishnan E, Svendsen K, Neaton JD, et al. Long-term cardiovascular mortality among middle-aged men with gout. Arch Intern Med. 2008 May 26. 168(10):1104-10. [Medline].

  62. Kuo CF, See LC, Luo SF, Ko YS, Lin YS, Hwang JS, et al. Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology (Oxford). 2010 Jan. 49(1):141-6. [Medline].

  63. Janeczko L. Gout Tied to Higher Risk of Heart Attack and Stroke. Medscape Medical News. Available at http://www.medscape.com/viewarticle/813367. Accessed: November 4, 2013.

  64. Seminog OO, Goldacre MJ. Gout as a risk factor for myocardial infarction and stroke in England: evidence from record linkage studies. Rheumatology (Oxford). 2013 Sep 17. [Medline].

  65. Barclay L. Gout Linked to Increased Vascular Disease Risk. Medscape Medical News. Available at http://www.medscape.com/viewarticle/830663?nlid=64464_2224&src=wnl_edit_medp_rheu&spon=27. Accessed: September 8, 2014.

  66. Clarson LE, Hider SL, Belcher J, Heneghan C, Roddy E, Mallen CD. Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink. Ann Rheum Dis. 2014 Aug 27. [Medline].

  67. Lin SH, Hsieh ET, Wu TY, Chang CW. Cervical myelopathy induced by pseudogout in ligamentum flavum and retro-odontoid mass: a case report. Spinal Cord. 2006 Nov. 44(11):692-4. [Medline].

  68. Puig JG, Michan AD, Jimenez ML, et al. Female gout. Clinical spectrum and uric acid metabolism. Arch Intern Med. 1991 Apr. 151(4):726-32. [Medline].

  69. Meyers OL, Monteagudo FS. Gout in females: an analysis of 92 patients. Clin Exp Rheumatol. 1985 Apr-Jun. 3(2):105-9. [Medline].

  70. Macfarlane DG, Dieppe PA. Diuretic-induced gout in elderly women. Br J Rheumatol. 1985 May. 24(2):155-7. [Medline].

  71. Kramer HM, Curhan G. The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III, 1988-1994. Am J Kidney Dis. 2002 Jul. 40(1):37-42. [Medline].

  72. Marchini GS, Sarkissian C, Tian D, Gebreselassie S, Monga M. Gout, stone composition and urinary stone risk: a matched case comparative study. J Urol. 2013 Apr. 189(4):1334-9. [Medline].

  73. Taniguchi Y, Yoshida M, Tamaki T. Posterior interosseous nerve syndrome due to pseudogout. J Hand Surg Br. 1999 Feb. 24(1):125-7. [Medline].

  74. Dalbeth N, Schauer C, Macdonald P, Perez-Ruiz F, Schumacher HR, Hamburger S, et al. Methods of tophus assessment in clinical trials of chronic gout: a systematic literature review and pictorial reference guide. Ann Rheum Dis. 2011 Apr. 70(4):597-604. [Medline].

  75. Stocker SL, Graham GG, McLachlan AJ, Williams KM, Day RO. Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout. J Rheumatol. 2011 May. 38(5):904-10. [Medline].

  76. Chehab MR, Goyal J, Schlesinger N. Tophaceous Pustule-like Rash in a Patient with Gout. J Rheumatol. 2012 Jan. 39(1):194-5. [Medline].

  77. Coassin M, Piovanetti O, Stark WJ, Green WR. Urate deposition in the iris and anterior chamber. Ophthalmology. 2006 Mar. 113(3):462-5. [Medline].

  78. Slansky HH, Kubara T. Intranuclear urate crystals in corneal epithelium. Arch Ophthalmol. 1968 Sep. 80(3):338-44. [Medline].

  79. Bernad B, Narvaez J, Diaz-Torné C, Diez-Garcia M, Valverde J. Clinical image: corneal tophus deposition in gout. Arthritis Rheum. 2006 Mar. 54(3):1025. [Medline].

  80. MCWILLIAMS JR. Ocular findings in gout; report of a case of conjunctival tophi. Am J Ophthalmol. 1952 Dec. 35(12):1778-83. [Medline].

  81. Morris WR, Fleming JC. Gouty tophus at the lateral canthus. Arch Ophthalmol. 2003 Aug. 121(8):1195-7. [Medline].

  82. Fishman RS, Sunderman FW. Band keratopathy in gout. Arch Ophthalmol. 1966 Mar. 75(3):367-9. [Medline].

  83. Julkunen H, Heinonen OP, Pyörälä K. Hyperostosis of the spine in an adult population. Its relation to hyperglycaemia and obesity. Ann Rheum Dis. 1971 Nov. 30(6):605-12. [Medline]. [Full Text].

  84. KOSKOFF YD, MORRIS LE, LUBIC LG. Paraplegia as a complication of gout. J Am Med Assoc. 1953 May 2. 152(1):37-8. [Medline].

  85. Nguyen C, Ea HK, Palazzo E, Lioté F. Tophaceous gout: an unusual cause of multiple fractures. Scand J Rheumatol. 2010. 39(1):93-6. [Medline].

  86. Janssens HJ, Fransen J, van de Lisdonk EH, van Riel PL, van Weel C, Janssen M. A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med. 2010 Jul 12. 170(13):1120-6. [Medline].

  87. Barthelemy CR, Nakayama DA, Carrera GF, Lightfoot RW Jr, Wortmann RL. Gouty arthritis: a prospective radiographic evaluation of sixty patients. Skeletal Radiol. 1984. 11(1):1-8. [Medline].

  88. Dalbeth N, Clark B, Gregory K, Gamble G, Sheehan T, Doyle A, et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis. 2009 Aug. 68(8):1290-5. [Medline].

  89. Fodor D, Albu A, Gherman C. Crystal-associated synovitis- ultrasonographic feature and clinical correlation. Ortop Traumatol Rehabil. 2008 Mar-Apr. 10(2):99-110. [Medline].

  90. de Ávila Fernandes E, Kubota ES, Sandim GB, Mitraud SA, Ferrari AJ, Fernandes AR. Ultrasound features of tophi in chronic tophaceous gout. Skeletal Radiol. 2011 Mar. 40(3):309-15. [Medline].

  91. Fernandes EA, Lopes MG, Mitraud SA, Ferrari AJ, Fernandes AR. Ultrasound characteristics of gouty tophi in the olecranon bursa and evaluation of their reproducibility. Eur J Radiol. 2011 Jan 13. [Medline].

  92. Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007 Jul. 46(7):1116-21. [Medline].

  93. Loffler C, Sattler H, Peters L, Loffler U, Uppenkamp M, Bergner R. Distinguishing gouty arthritis from calcium pyrophosphate disease and other arthritides. J Rheumatol. 2015 Mar. 42(3):513-20. [Medline].

  94. Naredo E, Uson J, Jiménez-Palop M, Martínez A, Vicente E, Brito E, et al. Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout?. Ann Rheum Dis. 2014 Aug. 73(8):1522-8. [Medline].

  95. Pineda C, Amezcua-Guerra LM, Solano C, Rodriguez-Henríquez P, Hernández-Díaz C, Vargas A, et al. Joint and tendon subclinical involvement suggestive of gouty arthritis in asymptomatic hyperuricemia: an ultrasound controlled study. Arthritis Res Ther. 2011 Jan 17. 13(1):R4. [Medline]. [Full Text].

  96. Ottaviani S, Juge PA, Aubrun A, Palazzo E, Dieudé P. Sensitivity and Reproducibility of Ultrasonography in Calcium Pyrophosphate Crystal Deposition in Knee Cartilage: A Cross-sectional Study. J Rheumatol. 2015 Aug. 42 (8):1511-3. [Medline].

  97. De Miguel E, Puig JG, Castillo C, Peiteado D, Torres RJ, Martín-Mola E. Diagnosis of gout in patients with asymptomatic hyperuricaemia: a pilot ultrasound study. Ann Rheum Dis. 2012 Jan. 71(1):157-8. [Medline].

  98. Dalbeth N, Clark B, Gregory K, Gamble G, Sheehan T, Doyle A, et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis. 2009 Aug. 68(8):1290-5. [Medline].

  99. Al-Arfaj AM, Nicolaou S, Eftekhari A, Munk P, Shojani K, Reid G, et al. Utility of dual energy computed tomography (DECT) i8n tophaceous gout. Ann Rheum Dis. 2008;58:S878.

  100. Ward IM, Scott JN, Mansfield LT, Battafarano DF. Dual-Energy Computed Tomography Demonstrating Destructive Calcium Pyrophosphate Deposition Disease of the Distal Radioulnar Joint Mimicking Tophaceous Gout. J Clin Rheumatol. 2015 Sep. 21 (6):314-7. [Medline].

  101. Shimizu T, Hori H. The prevalence of nephrolithiasis in patients with primary gout: a cross-sectional study using helical computed tomography. J Rheumatol. 2009 Sep. 36(9):1958-62. [Medline].

  102. Poh YJ, Dalbeth N, Doyle A, McQueen FM. Magnetic Resonance Imaging Bone Edema Is Not a Major Feature of Gout Unless There Is Concomitant Osteomyelitis: 10-year Findings from a High-prevalence Population. J Rheumatol. 2011 Nov. 38(11):2475-81. [Medline].

  103. McQueen FM, Doyle A, Reeves Q, Gao A, Tsai A, Gamble GD. Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. Rheumatology (Oxford). 2014 Jan. 53(1):95-103. [Medline].

  104. Oostveen JC, van de Laar MA. Magnetic resonance imaging in rheumatic disorders of the spine and sacroiliac joints. Semin Arthritis Rheum. 2000 Aug. 30(1):52-69. [Medline].

  105. [Guideline] Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012 Oct. 64(10):1431-46. [Medline].

  106. [Guideline] Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: Therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012 Oct. 64(10):1447-61. [Medline].

  107. Goodman A. Urate-Lowering Cuts Complications From Gout. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814057. Accessed: November 18, 2013.

  108. Rashid N, Levy GD, Wu YL, Zheng C, Koblick R, Cheetham TC. Patient and clinical characteristics associated with gout flares in an integrated healthcare system. Rheumatol Int. 2015 Nov. 35 (11):1799-807. [Medline]. [Full Text].

  109. Reber P, Crevoisier X, Noesberger B. Unusual localisation of tophaceous gout. A report of four cases and review of the literature. Arch Orthop Trauma Surg. 1996. 115(5):297-9. [Medline].

  110. Schapira D, Stahl S, Izhak OB, Balbir-Gurman A, Nahir AM. Chronic tophaceous gouty arthritis mimicking rheumatoid arthritis. Semin Arthritis Rheum. 1999 Aug. 29(1):56-63. [Medline].

  111. Shogan CP, Folio CL. Tophaceous gout and rheumatoid arthritis awareness. J Am Osteopath Assoc. 2008 Jul. 108(7):352; author reply 352-3. [Medline].

  112. Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi H. Low-dose aspirin use and recurrent gout attacks. Ann Rheum Dis. 2014 Feb 1. 73(2):385-90. [Medline].

  113. Schumacher HR, Berger MF, Li-Yu J, Perez-Ruiz F, Burgos-Vargas R, Li C. Efficacy and tolerability of celecoxib in the treatment of acute gouty arthritis: a randomized controlled trial. J Rheumatol. 2012 Sep. 39(9):1859-66. [Medline].

  114. Medsafe Pharmacovigilance Team. Colchicine: lower doses for greater safety. Available at http://www.medsafe.govt.nz/profs/puarticles/colchdose.htm. Accessed: October 3, 2008.

  115. Nuki G. Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. Curr Rheumatol Rep. 2008 Jul. 10(3):218-27. [Medline].

  116. Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006 Oct. 65(10):1312-24. [Medline].

  117. Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW. High versus low dosing of oral colchicine for early acute gout flare: Twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. 2010 Apr. 62(4):1060-8. [Medline].

  118. Terkeltaub RA, Furst DE, Digiacinto JL, Kook KA, Davis MW. Novel evidence-based colchicine dose-reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P-glycoprotein inhibitors. Arthritis Rheum. 2011 Aug. 63(8):2226-37. [Medline].

  119. FDA takes action to stop the marketing of unapproved injectable drugs containing colchicine. US Food and Drug Administration. Available at www.fda.gov/bbs/topics/news/2008/new01791.html. Accessed: September 30, 2008.

  120. Roddy E. Hyperuricemia, gout, and lifestyle factors. J Rheumatol. 2008 Sep. 35(9):1689-91. [Medline].

  121. Perez-Ruiz F, Herrero-Beites AM, Carmona L. A two-stage approach to the treatment of hyperuricemia in gout: The "Dirty Dish" hypothesis. Arthritis Rheum. 2011 Dec. 63(12):4002-6. [Medline].

  122. Yu T. The efficacy of colchicine prophylaxis in articular gout--a reappraisal after 20 years. Semin Arthritis Rheum. 1982 Nov. 12(2):256-64. [Medline].

  123. [Guideline] Wallace SL, Singer JZ, Duncan GJ, et al. Renal function predicts colchicine toxicity: guidelines for the prophylactic use of colchicine in gout. J Rheumatol. 1991 Feb. 18(2):264-9. [Medline].

  124. Markel A. Allopurinol-induced DRESS syndrome. Isr Med Assoc J. 2005 Oct. 7(10):656-60. [Medline].

  125. Singer JZ, Wallace SL. The allopurinol hypersensitivity syndrome. Unnecessary morbidity and mortality. Arthritis Rheum. 1986 Jan. 29(1):82-7. [Medline].

  126. McAdams DeMarco MA, Maynard JW, Baer AN, Gelber AC, Young JH, Alonso A, et al. Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: the Atherosclerosis Risk in Communities cohort study. Arthritis Rheum. 2012 Jan. 64(1):121-9. [Medline]. [Full Text].

  127. Stamp LK, Taylor WJ, Jones PB, Dockerty JL, Drake J, Frampton C, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis Rheum. 2012 Aug. 64(8):2529-36. [Medline].

  128. Vázquez-Mellado J, Morales EM, Pacheco-Tena C, et al. Relation between adverse events associated with allopurinol and renal function in patients with gout. Ann Rheum Dis. 2001 Oct. 60(10):981-3. [Medline].

  129. Riedel AA, Nelson M, Joseph-Ridge N, Wallace K, MacDonald P, Becker M. Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims. J Rheumatol. 2004 Aug. 31(8):1575-81. [Medline].

  130. Rees F, Jenkins W, Doherty M. Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study. Ann Rheum Dis. 2012 Jun 7. [Medline].

  131. Hair PI, McCormack PL, Keating GM. Febuxostat. Drugs. 2008. 68(13):1865-74. [Medline].

  132. Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008 Nov 15. 59(11):1540-8. [Medline].

  133. Becker MA, Schumacher HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005 Dec 8. 353(23):2450-61. [Medline].

  134. Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010. 12(2):R63. [Medline]. [Full Text].

  135. Jackson RL, Hunt B, MacDonald PA. The efficacy and safety of febuxostat for urate lowering in gout patients 65+ years of age. BMC Geriatr. 2012 Mar 21. 12:11. [Medline]. [Full Text].

  136. Wells AF, MacDonald PA, Chefo S, Jackson RL. African American patients with gout: efficacy and safety of febuxostat vs allopurinol. BMC Musculoskelet Disord. 2012 Feb 9. 13:15. [Medline]. [Full Text].

  137. Chohan S, Becker MA, MacDonald PA, Chefo S, Jackson RL. Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. Arthritis Care Res (Hoboken). 2012 Feb. 64(2):256-61. [Medline].

  138. Zurampic (lesinurad) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals. December, 2015. Available at [Full Text].

  139. Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C, RDEA594-203 Study Group. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis. 2016 Jan 7. 7 (6):433-42. [Medline]. [Full Text].

  140. Bieber JD, Terkeltaub RA. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis Rheum. 2004 Aug. 50(8):2400-14. [Medline].

  141. Committee for Medicinal Products for Human Use (CHMP). Krystexxa (pegloticase). European Medicines Agency. Available at http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002208/human_med_001591.jsp&mid=WC0b01ac058001d124. January 25, 2016; Accessed: January 30, 2016.

  142. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011 Aug 17. 306(7):711-20. [Medline].

  143. Huang HY, Appel LJ, Choi MJ, et al. The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial. Arthritis Rheum. 2005 Jun. 52(6):1843-7. [Medline].

  144. So A, De Smedt T, Revaz S, et al. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007. 9(2):R28. [Medline].

  145. Lee YH, Lee CH, Lee J. Effect of fenofibrate in combination with urate lowering agents in patients with gout. Korean J Intern Med. 2006 Jun. 21(2):89-93. [Medline].

  146. So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum. 2010 Oct. 62(10):3064-76. [Medline].

  147. Lowry F. FDA Panel Says No to Canakinumab for Gout Attacks. Medscape Medical News. Available at http://www.medscape.com/viewarticle/745076. Accessed: February 9, 2011.

  148. Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology (Oxford). 2009 Feb. 48(2):188-94. [Medline].

  149. Sundy JS, Becker MA, Baraf HS, Barkhuizen A, Moreland LW, Huang W, et al. Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study. Arthritis Rheum. 2008 Sep. 58(9):2882-91. [Medline].

  150. Savient Pharmaceuticals, Inc. Krystexxa Prescribing Information. Available at http://www.krystexxa.com/hcp/default.aspx.

  151. Kelly JC. Gout risk high in those with psoriasis, psoriatic arthritis. Medscape Medical News. March 28, 2014. [Full Text].

  152. Merola JF, Wu S, Han J, Choi HK, Qureshi AA. Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis. 2014 Mar 20. [Medline].

  153. Wilson ME, Wan SH, Beyder A, Osborn TG, Beckman TJ. Acute polyarticular gout presenting as delirium. J Clin Rheumatol. 2013 Jun. 19(4):221-2. [Medline].

 
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Gout. Acute podagra due to gout in elderly man.
Gout. Tophaceous deposits in ear.
Gout. Tophaceous deposits on elbow.
Gout. Chronic tophaceous gout in untreated patient with end-stage renal disease.
Gout. Fluid obtained from tophaceous deposit in patient with gout.
Gout. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from acutely inflamed joint.
Gout. Plain radiograph showing typical changes of gout in first metatarsophalangeal joint and fourth interphalangeal joint.
Gout. Plain radiograph showing chronic tophaceous gouty arthritis in hands.
Gout. Radiograph of erosions with overhanging edges.
Gout. Needles of urate crystals seen on polarizing microscopy.
Gout. Hematoxylin and eosin (H&E) stain, low power, showing abundant pale pink areas surrounded by histiocytes and multinucleated giant cells.
Gout. H&E stain, high power, showing that most urate crystals have been dissolved but that some pale brown-gray crystals did survive processing.
Pseudogout. H&E stain, high power, under polarized light to highlight rhomboidal crystals.
H&E stain, medium power, of pseudogout with pale pink fibrocartilage in upper portion and purple crystals of calcium pyrophosphate in lower portion.
Pseudogout. H&E stain, high power, of calcium pyrophosphate crystals, demonstrating their rhomboidal structure.
 
 
 
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