BackgroundGout is due to monosodium urate (MSU) crystal deposition after chronic hyperuricemia. Although MSU crystal deposition can occur in every joint and peri-articular structure, spine involvement is scarcely reported. Dual energy computed tomography (DECT) is a performant tool to assess urate deposits, especially in deep structures such as intervertebral discs and apophyseal joints.Objectivesto describe spinal DECT features of urate monosodium deposits compared to peripheral joint DECT.MethodsPatient with gout diagnosis (MSU crystal identification by polarized microscopy or fulfilling “Nijmegen's criteria” (1)) who had undergone DECT were included from November 2012 to June 2016. Images were analyzed by a trained musculoskeletal radiologist. For each DECT, clinical and biochemical characteristics of each patient were collected retrospectively.Results22 patients (men 77%), mean age 62.5 years and mean BMI 28.4 kg/m2 were included. Mean gout duration was 108.0±114.4 months, mean of last available serum uric acid level was 520±193 μmol/l, and 15 patients had at least one clinical tophus. Mean estimated glomerular filtration rate (MDRD formula) was 47±27 ml/min/1.73 m2. One patient was on hemodialysis and one had received kidney transplant.A total of 39 DECT has been performed: 28 of peripheral joints and 11 of the spine (9 lumbar, 1 sacroiliac and 1 cervical). Spinal DECT were done in 10 patients to explore recurrent inflammatory pain (n=3 lumbar, 1 cervical and 1 buttock) or mechanical back pain (n=2 lumbar). 4 spinal DECT were performed in asymptomatic patients with extended peripheral tophi. Spinal MSU crystal deposits were disclosed by DECT in 83% (5/6) and 25% (1/4) of symptomatic and asymptomatic patients, respectively. In all painful patients, MSU crystal deposition was considered as a likely explanation of spinal symptoms. MSU crystal depositions was identified in apophyseal joints (n=5), cervical intervertebral disc (n=1) and yellow or interspinous ligaments (n=4). All involved apophyseal joints were eroded (figure 1). No vertebral bone erosion was observed. Calcification of spinal tophus was observed in 4 patients. DECT identified peripheral deposits in 15/18 (83.3%) patients. In peripheral DECT, bone erosions were observed in 71.4% and joint effusion in 32.1% of DECT positive peripheral joints. MSU crystal depositions were observed in tendons, cartilages or synovial membranes in 82.1% of positive DECT joints and in soft tissues in 64.3% of positive patients. MSU crystal deposits were calcified in 7 cases.ConclusionsMSU crystal depositions at the spine are present in 60% of patients in this retrospective DECT study. DECT can represent a performing imaging procedure for their detection in symptomatic patients. Further studies are needed to assess the clinical utility of DECT of the spine in gout.References Janssens HJ, Fransen J, van de Lisdonk EH, et al. A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med 2010;170:1120–6. Disclosure of InterestNone ...
BackgroundInterleukin 6 (IL-6) plays a crucial role in many rheumatic diseases, including osteoarthritis (OA) [1]. In cartilage, IL-6 activates chondrocyte catabolism by increasing the production of matrix-degrading enzymes, including matrix metalloproteinase 3 (MMP-3) and MMP-13, but it could have other roles.ObjectivesWe aimed to identify new biological processes regulated by IL-6 in cartilage.MethodsRNA-seq analysis (Illumina HiSeq platform) was used to determine biological pathways associated with IL-6/IL-6R (100 ng/ml) stimulation in mouse primary articular chondrocytes. Results were further validated by qPCR and western blot analysis. The effect of stimulation with CC chemokine ligand 2 (CCL2; 10 ng/ml), CCL7 and CCL8 (100 ng/ml) was investigated in vitro and ex vivo in mouse femoral head cartilage explants. The impact of targeted inhibition of CCL2 or CCL7 by siRNA or blockade of their common receptor CCR2 by a specific antagonist (RS-504393) was determined in IL-6–treated chondrocytes and/or cartilage explants.ResultsTranscriptomic analysis revealed overrepresentation of multiple functional clusters of genes in IL-6–stimulated chondrocytes, with strongly increased expression of signalling molecules and especially cytokines. Two of the 10 top genes upregulated by IL-6 were Ccl7 (log2 fold change [FC] 2.33, adjusted p-value [padj] =3.35x10-62) and Ccl2 (log2 FC 1.85, padj =9.10x10-26), which encode for CCR2 ligands. qPCR and western blot validations confirmed these results and revealed that IL-6 stimulation also increased the mRNA level of Ccl8, another CCR2 ligand not identified by RNA-seq analysis. CCL2 and CCL7 but not CCL8 activated extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase signalling and increased MMP-3 and MMP-13 production and activation. CCR2 blockade but not the specific inhibition of CCL2 or CCL7 by siRNA, greatly abrogated the IL-6–induced catabolism in vitro and ex vivo.ConclusionsWe identified 2 chemokines, CCL2 and CCL7, as key targets of IL-6 in chondrocytes. Although their main role is to mediate monocyte/macrophage recruitment to the joint, their receptor, CCR2, is also strongly involved in IL-6–induced cartilage catabolism. These results suggest a novel mechanism by which CCL2/CCR2 and CCL7/CCR2 signalling could be involved in rheumatic diseases, especially OA [2].References Latourte A, Cherifi C, Maillet J, et al. Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis Published Online First: 27 Oct 2016. doi:10.1136/annrheumdis-2016–209757.Raghu H, Lepus CM, Wang Q, et al. CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis. Ann Rheum Dis Published Online First: 13 Dec 2016. doi:10.1136/annrheumdis-2016–210426. Disclosure of InterestNone declared
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