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Objective: The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies., Methods: We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed., Results: We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP., Conclusion: LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders., (Copyright © 2011 by the American College of Rheumatology.)

Objective: To determine the clinical usefulness of spinal mobility measurements used for ankylosing spondylitis (AS) to assess spinal involvement in patients with psoriatic arthritis (PsA)., Methods: We assessed 100 patients with PsA and 103 patients with AS. Patients were classified as having axial PsA if they had grade 2 or higher unilateral sacroiliitis in the presence of spinal symptoms. All PsA patients, without taking the degree of joint involvement into consideration, were evaluated using several measurements for AS. Spinal measurements were compared with axial and peripheral forms of PsA, and the ability of the techniques to discriminate between the 2 forms of PsA was analyzed using the Mann-Whitney U test and the area under the receiver operating characteristic (ROC) curve. A logistic regression model was used to determine the best measurements for evaluating axial PsA. Finally, the results of measurements for axial PsA were compared with those for AS., Results: Of the 100 PsA patients, 46 met the classification criteria for axial PsA, which presented more severe spinal measurement assessments compared with peripheral PsA. Modified Schober test, lumbar side flexion, chest expansion, and cervical rotation measurements performed best under the ROC curve. Modified Schober test, lumbar side flexion, and cervical rotation were the more suitable measurements for assessing axial PsA. There were only minor differences between axial PsA and AS., Conclusion: The spinal measurements used to evaluate AS performed well to assess spinal involvement in PsA. These measurements, notably the modified Schober test, lumbar side flexion, and cervical rotation, should be used in daily clinical practice to assess PsA patients with spinal involvement.

Objective: Osteoarthritis (OA) is a degenerative rheumatic disease that is associated with extracellular matrix degradation and chondrocyte apoptosis in the articular cartilage. The role of mitochondria in degenerative diseases is widely recognized. We undertook this study to evaluate mitochondrial function in normal and OA chondrocytes and to examine age-related changes in mitochondria., Methods: Mitochondrial function was evaluated by analyzing respiratory chain enzyme complexes and citrate synthase (CS) activities as well as changes in mitochondrial membrane potential (Delta Psi m). The activities of mitochondrial respiratory chain complexes (complex I: rotenone-sensitive NADH-coenzyme Q(1) reductase; complex II: succinate dehydrogenase; complex III: antimycin-sensitive ubiquinol cytochrome c reductase; and complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from OA and normal cartilage. Delta Psi m was measured by JC-1 using flow cytometry. Statistical analysis was performed using the Mann-Whitney U test and Student's t-test as well as several models of multiple linear regression., Results: OA articular chondrocytes had reduced activities of complexes II and III compared with cells from normal cartilage. However, the mitochondrial mass was increased in OA. Cultures of OA chondrocytes contained a higher proportion of cells with de-energized mitochondria. We found no relationship between mitochondrial function and donor age either in normal or in OA chondrocytes., Conclusion: These findings suggest the involvement of mitochondrial function in the pathophysiology of OA. Cartilage degradation by OA and cartilage aging may be two different processes.

Objective: To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA)., Methods: A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single-therapy disease-modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen., Results: Four of the 43 patients (9.3%) who had been receiving long-term, well-tolerated treatment with MTX (mean +/- SD 375.5 +/- 159.5 days, range 227-561 days) developed AFTR shortly (mean +/- SD 25.7 +/- 13.6 days, range 17-46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 +/- 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR., Conclusion: The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single-drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.