Gout and Pseudogout Workup

  • Author: Bruce M Rothschild, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Mar 26, 2012
 

Approach Considerations

Arthrocentesis of the affected joint is mandatory for all patients with new onset of acute monoarthritis and is very strongly recommended for those with recurrent attacks whose diagnosis has never been proven by microscopic visualization of crystals. Tophi also may be aspirated for crystal analysis under polarizing microscopy.

A prior history of gout or pseudogout does not rule out the possibility of acute septic arthritis. In fact, the latter is more common in patients with a history of crystal-induced arthritis. Septic arthritis must be diagnosed and treated promptly, because irreversible damage can occur within 4-6 hours, and the joint can be completely destroyed within 24-48 hours.

Send joint fluid for fluid analysis, including cell count and differential, Gram stain, culture and sensitivity, and microscopic analysis for crystals. If crystals are seen, their shape and appearance under polarized light can aid in diagnosis.

In gout, crystals of monosodium urate (MSU) appear as needle-shaped intracellular and extracellular crystals. When examined with a polarizing filter, they are yellow when aligned parallel to the slow axis of the red compensator, but they turn blue when aligned across the direction of polarization (ie, they exhibit negative birefringence). Negatively birefringent urate crystals are seen on polarizing examination in 85% of specimens.

Microscopic analysis in pseudogout shows calcium pyrophosphate (CPP) crystals, which appear shorter than MSU crystals and are often rhomboidal. Under a polarizing filter, CPP crystals change color depending upon their alignment relative to the direction of the red compensator. They are positively birefringent, appearing blue when aligned parallel with the slow axis of the compensator and yellow when perpendicular.

In crystal arthritis, the WBC count in the synovial fluid is usually 10,000-70,000/µL. However, it may be as low as 1000/µL or as high as 100,000/µL.

Even in the presence of crystals in the joint fluid, blood cultures are indicated if any sign of systemic toxicity is present. Septic arthritis can occur in patients with active crystalline arthropathy.

Gouty attacks are triggered by crystal formation in synovial fluid. They are not related to serum levels of uric acid. Thus, an elevated serum uric acid level does not prove the diagnosis of acute gout, although hyperuricemia is present in 95% of cases, and a normal level does not exclude the diagnosis. Renal uric acid excretion should be measured in high-risk patients, including those with renal calculi, strong family history of gout, and first attack before age 25 years.

Pseudogout attacks can be triggered by many metabolic abnormalities. Thus, patients who have an initial attack of arthritis with CPP crystals should have a workup including a chemistry screen; magnesium, calcium, and iron levels; and thyroid function tests.

The WBC count in peripheral blood is usually elevated, with a left shift during acute attacks. Erythrocyte sedimentation rate (ESR) usually is elevated during acute attacks.

Imaging studies of the affected joint or joints are indicated. Patients with new onset of acute gout usually have no radiographic findings. In established disease, radiographs reveal punched-out erosions or lytic areas with overhanging edges.

MRI is capable of detecting crystal deposits but is not part of any routine evaluation for acute arthritis. MRI can be very useful in determining the extent of the disease and may help in the differential diagnosis. Indium-111–labeled leukocyte scans, usually used to identify infectious foci, also reveal intense accumulation in affected joints in gout.[67]

Patients with pseudogout usually have degenerative joint changes and may have calcifications in the soft tissues, tendons, or bursae.

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Synovial Fluid Analysis

When a patient presents with acute inflammatory monoarticular arthritis, aspiration of the involved joint is critical to rule out an infectious arthritis and to attempt to confirm a diagnosis of gout or pseudogout based on identification of crystals. Minute quantities of fluid in the shaft or hub of the needle are sufficient for synovial fluid analysis.

See the image of tophaceous gout fluid below.

Gout. Fluid obtained from a tophaceous deposit in Gout. Fluid obtained from a tophaceous deposit in a patient with gout.

Urate crystals are shaped like needles or toothpicks with pointed ends. Under polarizing light microscopy, urate crystals are yellow when aligned parallel to the axis of the red compensator and blue when aligned across the direction of polarization (ie, they exhibit negative birefringence). Finding negatively birefringent urate crystals firmly establishes the diagnosis of gouty arthritis.

See the images of urate crystals below.

Gout. Needles of urate on polarizing microscopy. Gout. Needles of urate on polarizing microscopy. Gout. Strongly negative birefringent, needle-shapeGout. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from an acutely inflamed joint.

Pseudogout crystals (calcium pyrophosphate) are rod-shaped with blunt ends and are positively birefringent. Thus, pseudogout crystals are blue when aligned parallel to the slow ray of the compensator and yellow when they are perpendicular.

Crystals need to be distinguished from birefringent cartilaginous or other debris. Debris may have fuzzy borders and may be curved, whereas crystals have sharp borders and are straight.

Corticosteroids injected into joints have a crystalline structure that can mimic monosodium urate crystals. They can be either positively or negatively birefringent.

The sensitivity of a synovial fluid analysis for crystals is 84%, with a specificity of 100%. If gout remains a clinical consideration after negative analysis findings, the procedure can be repeated in another joint or with a subsequent flare. Crystals may be absent very early in a flare.

While the sensitivity is inferior, urate crystals can be identified from synovial fluid aspirated from previously inflamed joints that are not currently inflamed. Such crystals are generally extracellular.

Synovial fluid should also be sent for cell count. During acute attacks, the synovial fluid is inflammatory, with a WBC count greater than 2000/µL (class II fluid) and possibly greater than 50,000/µL, with a predominance of polymorphonuclear neutrophils.

Synovial fluid glucose levels are usually normal, whereas they may be depressed in septic arthritis and occasionally in rheumatoid arthritis. Measurement of synovial fluid protein has no clinical value.

Crystalline arthritis and infectious arthritis can coexist. Indeed, infectious arthritis is more common in previously damaged joints, which may occur in patients with chronic gouty arthritis. Consequently, in patients with acute monoarticular arthritis, send synovial fluid for Gram stain and culture and sensitivity.

The pathologic specimens need to be processed anhydrously. Monosodium urate is water soluble and dissolves in formalin; therefore, only the ghosts of urate crystals may be seen if formalin is used. Alcohol-fixed tissue is best for identification of urate crystals.

Once a diagnosis of gout is established based on confirmation of crystals, do not need repeat aspiration of joints with subsequent flares is not necessary unless infection is suggested or the flare does not respond appropriately to therapy for acute gout.

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Serum Uric Acid

Measurement of serum uric acid is the most misused test in the diagnosis of gout. The presence of hyperuricemia in the absence of symptoms is not diagnostic of gout. In addition, as many as 10% of patients with symptoms due to gout may have normal serum uric acid levels at the time of their attack. Thus, the correct diagnosis of gout can be missed if the joint is not aspirated. Remember that situations that decrease uric acid levels can trigger attacks of gout. In such cases, the patient's prior medical records may reveal prior elevations of uric acid.

Approximately 5-8% of the population has elevated serum uric acid levels (>7 mg/dL), but only 5-20% of patients with hyperuricemia develop gout. Thus, an elevated serum uric acid level does not indicate or predict gout. As noted above, gout is diagnosed based on the discovery of urate crystals in the synovial fluid or soft tissues. More importantly, some patients with infectious arthritis present with a hot swollen joint and an elevated serum uric acid level and are at risk of being mismanaged if their synovial fluid is not aspirated to rule out septic arthritis.

Asymptomatic hyperuricemia should generally not be treated. However, patients with levels higher than 11 mg/dL and overexcretion of uric acid are at risk for renal stones and renal impairment; therefore, renal function should be monitored in these individuals.[68] In one study, ultrasound identified urate crystal deposition in 11 of 26 individuals having asymptomatic gout for 2-28 years (average, 6.2 y), affecting the knee in 9 individuals and the first metatarsal phalangeal joint in 6. These results document that asymptomatic gout may not be as innocuous as once perceived.[69]

The level of serum uric acid does correlate with risk for developing gout. The 5-year risk for developing gout is approximately 0.6% if the level is less than 7.9 mg/dL, 1% if 8-8.9 mg/dL, and 22% if higher than 9 mg/dL.

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Urinary Uric Acid

A 24-hour urinary uric acid evaluation is generally performed if uricosuric therapy is being considered. If patients excrete more than 800 mg of uric acid in 24 hours while eating a regular diet, they are overexcretors and thus overproducers of uric acid. These patients (approximately 10% of patients with gout) require allopurinol instead of probenecid to reduce uric acid levels.

Patients who excrete more than 1100 mg in 24 hours should undergo close renal function monitoring because of the risk of stones and urate nephropathy.

In patients in whom probenecid is contraindicated (eg, those with a history of renal stones or renal insufficiency), a 24-hour urine test of uric acid excretion does not need to be performed because the patient clearly will need allopurinol.

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Blood Studies

Obtaining an accurate measure of the patient's renal function before deciding on therapy for gout is important, since the serum creatinine evaluation alone can underestimate renal dysfunction in elderly patients or in patients with low muscle mass.

Glucose measurement is useful because patients with gout are at an increased risk of developing diabetes mellitus. Liver function studies are important because abnormal results may affect the selection of therapy.

The WBC count may be elevated in patients during the acute gouty attack, particularly if it is polyarticular.

Hypertriglyceridemia and low high-density lipoproteins are associated with gout.

Pseudogout attacks can be triggered by many metabolic abnormalities. Thus, patients who have an initial attack of arthritis with CPP crystals should have a workup including a chemistry screen; magnesium, calcium, and iron levels; and thyroid function tests.

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Radiography

Plain radiographs may show findings consistent with gout, but these findings are not diagnostic. Early in the disease, radiographs are often normal or show only soft-tissue swelling. Radiographic findings characteristic of gout, which generally do not appear within the first year of disease onset, consist of punched-out erosions or lytic areas with overhanging edges, as shown in the image below.

Gout. Radiograph of erosions with overhanging edgeGout. Radiograph of erosions with overhanging edges.

Erosions with overhanging edges generally are considered pathognomonic for gout but also can be found in amyloidosis, multicentric reticulohistiocytosis, and type IIA hyperlipoproteinemia.

Haziness suggestive of tophi can be seen in late gout, and tophi may calcify. Characteristics of erosions that are typical of gout but not of rheumatoid arthritis include the following:

  • Maintenance of the joint space[70, 71]
  • Absence of periarticular osteopenia
  • Location outside the joint capsule

Another characteristic of erosions typically of gout is sclerotic borders, sometimes called cookie-cutter or punched-out borders. In addition, erosions in gout may be distributed asymmetrically among the joints, with strong predilection for distal joints, especially in the lower extremities. (See the images below.)

Gout. Plain radiograph showing typical changes of Gout. Plain radiograph showing typical changes of gout in the first metatarsophalangeal joint and fourth interphalangeal joint. Gout. Plain radiograph showing chronic tophaceous Gout. Plain radiograph showing chronic tophaceous gouty arthritis in the hands.
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Ultrasonography

At the first attack, sites affected with gout are typically anechoic on ultrasonography. Later, diffuse enhancement may be evident at superficial cartilage margins.[72] Chondrocalcinosis show up as a thin, hyperechoic band parallel to hyaline cartilage and punctuated pattern on fibrocartilage.

Ultrasonographic findings in established gout include the following:[73, 74, 75]

  • A "double contour" sign, consisting of a hyperechoic, irregular line of monosodium urate crystals on the surface 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
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Computed Tomography

Plain radiographs and CT are complementary for recognizing erosions in gout.[76] Dual-energy CT, using a renal stone color-coding protocol, assesses chemical composition, labeling urate deposits in red.[77]

In a study comparing identification of nephrolithiasis in gout patients by CT imaging versus a history of urinary tract calculus, 62% of the patients with CT-documented scans had no history of urolithiasis. In 383 male patients with primary gout, CT scanning confirmed nephrolithiasis in 103 (26.9%), whereas the history of urinary tract calculus was positive in only 65 (17%) patients. The authors concluded that an accurate prevalence of urolithiasis cannot be determined by patients' histories.[78]

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Magnetic Resonance Imaging

MRI is not part of any routine evaluation for acute arthritis. MRI evidence of edema is minimal in gout, unless concomitant osteomyelitis is present.[79] However, MRI with gadolinium is recommended to evaluate any tendon sheath involvement and when osteomyelitis is in the differential diagnosis. Large deposits of crystals may be seen in bursae or ligaments.

Tophi usually have low or intermediate signal intensity on T1-weighted spin echo images. Signal intensity also tends to be low on T2-weighted images. In the absence of inflammation, the tophi are sharply delineated. Presence of inflammation results in increased perilesional signal intensity. Tophi and the surrounding area of inflammation enhance with gadolinium.[80]

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Contributor Information and Disclosures
Author

Bruce M Rothschild, MD  Professor of Medicine, Northeastern Ohio Universities Colleges of Medicine and Pharmacy; 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, and Society of Skeletal Radiology

Disclosure: Nothing to disclose.

Coauthor(s)

Anne V Miller, MD  Assistant Professor 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, and International Society for Clinical Densitometry

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.

Mark L Francis, MD  Consulting Staff, Arthritis and Osteoporosis Associates of New Mexico

Mark L Francis, MD is a member of the following medical societies: American College of Rheumatology, Illinois State Medical Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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.

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

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

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

  4. Knapp CM, Constantinescu CS, Tan JH, McLean R, Cherryman GR, Gottlob I. Serum uric acid levels in optic neuritis. Mult Scler. Jun 2004;10(3):278-80. [Medline].

  5. Klein R, Klein BE, Tomany SC, Cruickshanks KJ. Association of emphysema, gout, and inflammatory markers with long-term incidence of age-related maculopathy. Arch Ophthalmol. May 2003;121(5):674-8. [Medline].

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

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

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

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

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

  11. Terkeltaub RA, Dyer CA, Martin J, et al. Apolipoprotein (apo) E inhibits the capacity of monosodium urate crystals to stimulate neutrophils. Characterization of intraarticular apo E and demonstration of apo E binding to urate crystals in vivo. J Clin Invest. Jan 1991;87(1):20-6. [Medline].

  12. Terkeltaub R, Smeltzer D, Curtiss LK, et al. Low density lipoprotein inhibits the physical interaction of phlogistic crystals and inflammatory cells. Arthritis Rheum. Mar 1986;29(3):363-70. [Medline].

  13. 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. Sep 2005;52(9):2936-46. [Medline].

  14. 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. Jul 1989;16(7):971-6. [Medline].

  15. 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. Sep 1993;36(9):1274-85. [Medline].

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

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

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

  19. 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. Jul 2004;50(7):2273-80. [Medline].

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

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

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

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

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

  25. 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].

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

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

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

  29. 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. Oct 2011;63(10):3136-41. [Medline].

  30. 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. Sep 2008;35(9):1859-64. [Medline].

  31. Mould-Quevedo J, Peláez-Ballestas I, Vázquez-Mellado J, Terán-Estrada L, Esquivel-Valerio J, Ventura-Ríos L, et al. [Social costs of the most common inflammatory rheumatic diseases in Mexico from the patient's perspective]. Gac Med Mex. May-Jun 2008;144(3):225-31. [Medline].

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

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

  34. Rothschild BM, Heathcote GM. Characterization of gout in a skeletal population sample: presumptive diagnosis in a Micronesian population. Am J Phys Anthropol. Dec 1995;98(4):519-25. [Medline].

  35. 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. May 1995;38(5):628-32. [Medline].

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

  37. 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). Oct 2008;47(10):1567-70. [Medline].

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

  39. Yarom A, Rennebohm RM, Strife F, Levinson JE. Juvenile gouty arthritis. Two cases associated with mild renal insufficiency. Am J Dis Child. Oct 1984;138(10):955-7. [Medline].

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

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

  42. 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. Jun 2008;27(6):585-91. [Medline].

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

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

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

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

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

  48. [Best Evidence] 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). Jan 2010;49(1):141-6. [Medline].

  49. 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. Nov 2006;44(11):692-4. [Medline].

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

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

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

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

  54. 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. Apr 2011;70(4):597-604. [Medline].

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

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

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

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

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

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

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

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

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

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

  65. 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].

  66. 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. Jul 12 2010;170(13):1120-6. [Medline].

  67. Palestro CJ, Vega A, Kim CK, Swyer AJ, Goldsmith SJ. Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy. J Nucl Med. May 1990;31(5):682-4. [Medline].

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

  69. 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. Jan 2012;71(1):157-8. [Medline].

  70. 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].

  71. 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. Aug 2009;68(8):1290-5. [Medline].

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

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

  74. 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. Jan 13 2011;[Medline].

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

  76. 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. Aug 2009;68(8):1290-5. [Medline].

  77. 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..

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

  79. 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. Nov 2011;38(11):2475-81. [Medline].

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

  81. Rothschild B, Yakubov LE. Prospective 6-month, double-blind trial of hydroxychloroquine treatment of CPDD. Compr Ther. May 1997;23(5):327-31. [Medline].

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

  83. 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].

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

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

  86. 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. Oct 2010;62(10):3064-76. [Medline].

  87. 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.

  88. 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. Aug 2004;31(8):1575-81. [Medline].

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

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

  91. [Best Evidence] 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. Oct 2006;65(10):1312-24. [Medline].

  92. 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. Apr 2010;62(4):1060-8. [Medline].

  93. 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. Aug 2011;63(8):2226-37. [Medline].

  94. 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.

  95. [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. Feb 1991;18(2):264-9. [Medline].

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

  97. 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. Dec 2011;63(12):4002-6. [Medline].

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

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

  100. 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. Oct 2001;60(10):981-3. [Medline].

  101. Fels E, Sundy JS. Refractory gout: what is it and what to do about it?. Curr Opin Rheumatol. Mar 2008;20(2):198-202. [Medline].

  102. Fam AG, Dunne SM, Iazzetta J, et al. Efficacy and safety of desensitization to allopurinol following cutaneous reactions. Arthritis Rheum. Jan 2001;44(1):231-8. [Medline].

  103. Walz-LeBlanc BA, Reynolds WJ, MacFadden DK. Allopurinol sensitivity in a patient with chronic tophaceous gout: success of intravenous desensitization after failure of oral desensitization. Arthritis Rheum. Oct 1991;34(10):1329-31. [Medline].

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

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

  106. 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. Aug 17 2011;306(7):711-20. [Medline].

  107. Emmerson BT, Gordon RB, Cross M, et al. Plasma oxipurinol concentrations during allopurinol therapy. Br J Rheumatol. Dec 1987;26(6):445-9. [Medline].

  108. 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. Jun 2005;52(6):1843-7. [Medline].

  109. 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].

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

  111. Schumacher HR Jr, Sundy JS, Terkeltaub R, Knapp HR, Mellis SJ, Stahl N, et al. Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: Results of a phase II randomized, double-blind, placebo-controlled trial. Arthritis Rheum. Mar 2012;64(3):876-84. [Medline].

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

  113. Dalbeth N, Horne A, Gamble GD, Ames R, Mason B, McQueen FM, et al. The effect of calcium supplementation on serum urate: analysis of a randomized controlled trial. Rheumatology (Oxford). Feb 2009;48(2):195-7. [Medline].

  114. 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). Feb 2009;48(2):188-94. [Medline].

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

  116. 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. Sep 2008;58(9):2882-91. [Medline].

  117. Becker MA, Schumacher HR Jr, Wortmann RL, et al. . A phase 3 study comparing the safety and efficacy of oral febuxostat and allopurinol in subjects with hyperuricemia and gout. Arthritis Rheum. 2004;50:4103-4..

  118. Fam AG. Should patients with interval gout be treated with urate lowering drugs?. J Rheumatol. Sep 1995;22(9):1621-3. [Medline].

  119. Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: a clinical trial and review of the literature. Semin Arthritis Rheum. Jun 1990;19(6):329-36. [Medline].

  120. Konatalapalli RM, Demarco PJ, Jelinek JS, Murphey M, Gibson M, Jennings B, et al. Gout in the axial skeleton. J Rheumatol. Mar 2009;36(3):609-13. [Medline].

  121. Mayer MD, Khosravan R, Vernillet L, Wu JT, Joseph-Ridge N, Mulford DJ. Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment. Am J Ther. Jan-Feb 2005;12(1):22-34. [Medline].

  122. Primatesta P, Plana E, Rothenbacher D. Gout treatment and comorbidities: a retrospective cohort study in a large US managed care population. BMC Musculoskelet Disord. May 20 2011;12:103. [Medline]. [Full Text].

  123. Siegel LB, Alloway JA, Nashel DJ. Comparison of adrenocorticotropic hormone and triamcinolone acetonide in the treatment of acute gouty arthritis. J Rheumatol. Jul 1994;21(7):1325-7. [Medline].

  124. Singh JA, Hodges JS, Asch SM. Opportunities for improving medication use and monitoring in gout. Ann Rheum Dis. Aug 2009;68(8):1265-70. [Medline].

  125. Song EF, Xiang Q, Ren KM, Hu JC, Wu F, Gong MF, et al. Clinical effect and action mechanism of Weicao Capsule in treating gout. Chin J Integr Med. Jun 2008;14(2):103-6. [Medline].

  126. Wu EQ, Yu AP, Guerin A, et al. The costs of treatment failure gout: a claims-based analysis. ACR/ARHP Scientific Meeting 2009. Accessed January 28, 2010. Available at http://acr.confex.com/acr/2009/webprogram/Paper16451.htm.

 
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Gout. Acute podagra due to gout in an elderly man.
Gout. Tophaceous deposits in ear.
Gout. Tophaceous deposits on elbow.
Gout. Chronic tophaceous gout in an untreated patient with end-stage renal disease.
Gout. Fluid obtained from a tophaceous deposit in a patient with gout.
Gout. Strongly negative birefringent, needle-shaped crystals diagnostic of gout obtained from an acutely inflamed joint.
Gout. Plain radiograph showing typical changes of gout in the first metatarsophalangeal joint and fourth interphalangeal joint.
Gout. Plain radiograph showing chronic tophaceous gouty arthritis in the hands.
Gout. Radiograph of erosions with overhanging edges.
Gout. Needles of urate on polarizing microscopy.
 
 
 
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