Arthritic pain and disability are at or near the top of the list of reasons adult patients seek medical attention. At least 47.8 million US residents have arthritis. In Europe, the magnitude of the problem is similar, affecting 8 million in the United Kingdom and 108 million across the continent. Osteoarthritis is by far the most common form of arthritis. In a regional UK study, nearly half of adults 50 years or older reported some form of osteoarthritic knee pain over a 1-year period. Among the arthritides, gout is notable for the agonizing nature and unique pathogenesis of the pain it generates. Gout is the most common cause of inflammatory arthritis among men and postmenopausal women. Because of the atypical nature of some of its clinical manifestations, gout can present serious diagnostic challenges for practicing physicians. In recent years, knowledge about gout's pathogenesis, pathophysiology, and differential diagnosis has advanced on a broad front. Genetic variants within a newly identified transport gene, SLC2A9, have been associated with a low fractional excretion of uric acid and the presence of gout in several population samples. The SLC2A9 gene encodes glucose transporter 9—a unique hexose and high-capacity urate transporter. In addition, human ATP-binding cassette, subfamily G2 (ABCG2), encoded by the ABCG2 gene, has been found to mediate renal urate secretion. Introduction of a mutation encoded in a model system by a common single nucleotide polymorphism, rs2231142, resulted in a 53% reduction in urate transport rates compared with wild-type ABCG2. Based on a large population study, it has been estimated that at least 10% of all gout cases in white persons may be attributable to this single nucleotide polymorphism causal genetic variant. Of the various categories of arthritis, the crystal-induced arthropathies, gout and pseudogout, are manifested by acute inflammation and tissue damage arising from deposition in joints and periarticular tissues of monosodium urate (MSU), calcium pyrophosphate dehydrate, or basic calcium phosphate crystals. The innate immune system rapidly detects invading pathogenic microbes and nonmicrobial “danger signals” such as MSU crystals. When these crystals are deposited in synovial tissues, NLR proteins (NOD-like receptors) form multiprotein complexes known as inflammasomes that trigger secretion of inflammation-producing cytokines like interleukin-1β and interleukin-18. Usually, gout can be diagnosed by medical history, physical examination, and presence of hyperuricemia (urate >416 μmol/L). However, a urate concentration less than 416 does not by itself rule out gout. Confirmation of the diagnosis by identification of typical MSU crystals in aspirated synovial fluid is definitive. Analysis of joint fluid is mandatory to rule out septic arthritis, which can rapidly become lethal. Because of its special ability to identify and quantitate urate deposits in peripheral tissues, dual-energy computed tomography should prove valuable in the differential diagnosis of gout. Gout mimics a variety of illnesses; for example, spinal gout may masquerade as metastatic cancer, epidural abscess, and nerve compression syndrome.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Metabolism - Clinical and Experimental
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The burden of musculoskeletal conditions at the start of the new millennium. World Health Organization, Geneva2003
- Projections of US prevalence of arthritis and associated activity limitations.Arthritis Rheum. 2006; 54: 226-229
- The costs of arthritis.Arthritis Rheum. 2003; 49: 101-113
- The prevalence of pain and pain interference in a general population of older adults: cross-sectional findings from the North Staffordshire Osteoarthritis Project (NorStOP).Pain. 2004; 110: 361-368
- Osteoarthritis as a public health problem: the impact of developing knee pain on physical function in adults living in the community: (KNEST 3).Rheumatology. 2007; 46: 877-881
- Epidemiology of gout.CCJM. 2008; 75: S9-S12
- Epidemiology, risk factors, and lifestyle modifications for gout.
- A prescription for lifestyle change in patients with hyperuricemia and gout.Curr Opin Rheumatol. 2010; 22: 165-172
- SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.Nat Genet. 2008; 40: 437-442
- Recent insights into the pathogenesis of hyperuricemia and gout.Hum Mol Genet. 2009; 18: R177-184
- Facilitative glucose transporter 9, a unique hexose and urate transporter.Am J Physiol Endocrinol Metab. 2009; 297: E831-835
- Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.Proc Natl Acad Sci U S A. 2009; 106: 15501-15506
- Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout.Proc Natl Acad Sci U S A. 2009; 106: 10338-10342
- Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study.Am J Med. 1987; 82: 421-426
- Crystal-associated arthritis.Clin Geriatr Med. 1998; 14: 495-513
- The influence of temperature on the solubility of monosodium urate.Arthritis Rheum. 1972; 15: 189-192
- Intracellular innate immunity in gout arthritis: role of NALP3 inflammasome.Immunol Cell Biol. 2010; 88: 20-23
- The inflammasomes: guardians of the body.Ann Rev Immunol. 2009; 27: 229-265
- Recent advances in crystal-induced acute inflammation.Curr Opin Rheumatol. 2007; 19: 146-150
- Macrophage release of transforming growth factor beta1 during resolution of monosodium urate monohydrate crystal–induced inflammation.Arthritis Rheum. 2004; 50: 2273-2280
- High-density lipoproteins down-regulate CCL2 production in human fibroblast-like synoviocytes stimulated by urate crystals.Athritis Res Ther. 2010; 12 ([Epub ahead of print]): R23
- “On gout” vol. II, 123-162.in: The works of Thomas Sydenham. Sydenham Society, London1848 ([Reprint: Classics of Medicine Library, Atlanta, 1979])
- Serum urate during acute gout.J Rheumatol. 2009; 36: 1287-1289
- Identification of urate crystals in gouty synovial fluid.Ann Int Med. 1961; 54: 452-460
- Bacterial septic arthritis in adults.Lancet. 2010; 375: 845-855
- Rare coexistence of gouty and septic arthritis: a report of 14 cases.Clin Exp Rheumatol. 2009; 27: 902-906
- Dual-energy CT as a potential new diagnostic tool in the management of gout in the acute setting.AJR Am J Roentgenol. 2010; 194: 1072-1078
- Dual energy CT—a new perspective in the diagnosis of gout.Rofo. 2010; 182: 261-266
- Crystal arthritis. Gout and pseudogout in the geriatric patient.Geriatrics. 2004; 59: 25-30
- Gout in the axial skeleton.J Rheumatol. 2009; 36: 609-613
- Thoracic spinal gout mimicking metastasis.Hong Kong Med J. 2009; 15: 143-145
- Tophaceous gout of the lumbar spine mimicking an epidural abscess: MR features.AJNR Am J Neuroradiol. 1996; 17: 1949-1952
- Spinal cord compression due to tophaceous vertebral gout: a case report and literature review.Rev Med Interne. 1999; 20: 253-257
- Pancreatic gout masquerading as pancreatic cancer in a heart transplant candidate.J Heart Lung Transplant. 2009; 28: 1112-1113
- Gouty tophus simulating soft tissue tumor in a heart transplant recipient.Skeletal Radiol. 1997; 26: 626-628
- Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis.Ann Rheum Dis. 2009; 68: 1602-1608
- MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals.J Clin Invest. 2006; 116: 2262-2271
Publication of this article was supported by the Collège International de Recherche Servier (CIRS).
STATEMENT OF CONFLICT OF INTEREST: The author has nothing to disclose.
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.