Gout: Update on Some Pathogenic and Clinical Aspects
Section snippets
Pathogenesis of urate crystal deposition and tophus
Uric acid is a weak acid (pKa 5,8) that is present mainly as urate, the ionized form, at physiologic pH. As urate concentrations increase in physiologic fluids, urate can crystallize as a monosodium salt in oversaturated tissues, mainly within and around joints, but also in the skin or other structures, such as spinal ligaments and fibrous tissues [1]. The physiochemical properties of monosodium urate (MSU) cause crystals to precipitate in body fluids if the concentration is greater than 6.8
Pathogenesis of urate crystal-induced inflammation
MSU crystals are capable of directly triggering, amplifying, and sustaining an intense inflammatory response, a so-called “acute attack,” because of their ability to activate humoral and cellular inflammatory components. The pathogenic inflammatory pathways of MSU crystal-induced inflammation recently have been reviewed [1], [2], [3]. Sequential cellular activation is postulated from in vivo studies focusing on tissue pathology analysis [4], [5]: MSU crystals first are released in the joint
Diagnosis of gout
Diagnosis of gout relies on the association of acute attacks, presence of tophus, hyperuricemia, and, in some advanced diseases, chronic and destructive arthropathies. Classification of gout is a different issue that is approached partly with the (former) American Rheumatism Association preliminary criteria [59]. To date, however, there are no diagnostic recommendations or evidenced-based medicine recommendations for gout. This gap will be filled by a task force of the European League Against
Common clinical aspects
Acute gout attacks occur mainly in the lower extremities, starting at the foot joint, as has been known for centuries. Podagra is located by definition in the first MTP joint. As the disease progresses, other joints may be involved, including the knee and hip joint or upper limb. Podagra is more common in men, and women show a higher frequency of upper limb joint involvement [63]. The most common diagnoses of arthritis in the first MTP joint are crystal-induced synovitis, septic arthritis,
Imaging
Radiographs are not useful for the diagnosis of acute gout except for differential diagnosis. A pseudopodagra can be observed in apatite or CPPD deposit. Also, when young patients present with subacute or acute pain under the first MTP after a walk, a sesamoid necrosis or fracture of the first MTP should be discussed and a specific radiograph prescribed (Walter-Muller view).
In chronic disease evolving to destructive arthropathy, the radiologic hallmark of tophus is well known (Fig. 2).
Outcome and evaluation of gout
As new treatments are developed, there are no well-established outcome measures or data on follow-up and outcome of gout cohorts, including patients treated long-term, regarding chronic joint clinical and radiologic symptoms or quality of life. The Outcome Measure in Rheumatoid Arthritis Clinical Trials (OMERACT) has begun developing sets of outcome criteria that will be discussed at their meeting in Malta in May, 2006. Clinical issues remain as do imaging aspects related to tophus detection by
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This work was supported by grants from the INSERM, the ARPS, and the ART.