Abstract
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.
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Article info
Footnotes
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.
Identification
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© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
