Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis.

Frozen shoulder is a common fibroproliferative disease characterized by the insidious onset of pain and restricted range of shoulder movement with a significant socioeconomic impact. The pathophysiological mechanisms responsible for chronic inflammation and matrix remodeling in this prevalent fibrotic disorder remain unclear; however, increasing evidence implicates dysregulated immunobiology. IL-17A is a key cytokine associated with inflammation and tissue remodeling in numerous musculoskeletal diseases, and thus, we sought to determine the role of IL-17A in the immunopathogenesis of frozen shoulder. We demonstrate an immune cell landscape that switches from a predominantly macrophage population in nondiseased tissue to a T cell-rich environment in disease. Furthermore, we observed a subpopulation of IL-17A-producing T cells capable of inducing profibrotic and inflammatory responses in diseased fibroblasts through enhanced expression of the signaling receptor IL-17RA, rendering diseased cells more sensitive to IL-17A. We further established that the effects of IL-17A on diseased fibroblasts was TRAF-6/NF-κB dependent and could be inhibited by treatment with an IKKß inhibitor or anti-IL-17A antibody. Accordingly, targeting of the IL-17A pathway may provide future therapeutic approaches to the management of this common, debilitating disease.

Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation.

OBJECTIVE: To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target. METHODS: First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1ß to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system. RESULTS: We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD. CONCLUSION: Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA.

Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease.

OBJECTIVES: Increasing evidence suggests that inflammatory mechanisms play a key role in chronic tendon disease. After observing T cell signatures in human tendinopathy, we explored the interaction between T cells and tendon stromal cells or tenocytes to define their functional contribution to tissue remodelling and inflammation amplification and hence disease perpetuation. METHODS: T cells were quantified and characterised in healthy and tendinopathic tissues by flow cytometry (FACS), imaging mass cytometry (IMC) and single cell RNA-seq. Tenocyte activation induced by conditioned media from primary damaged tendon or interleukin-1ß was evaluated by qPCR. The role of tenocytes in regulating T cell migration was interrogated in a standard transwell membrane system. T cell activation (cell surface markers by FACS and cytokine release by ELISA) and changes in gene expression in tenocytes (qPCR) were assessed in cocultures of T cells and explanted tenocytes. RESULTS: Significant quantitative differences were observed in healthy compared with tendinopathic tissues. IMC showed T cells in close proximity to tenocytes, suggesting tenocyte-T cell interactions. On activation, tenocytes upregulated inflammatory cytokines, chemokines and adhesion molecules implicated in T cell recruitment and activation. Conditioned media from activated tenocytes induced T cell migration and coculture of tenocytes with T cells resulted in reciprocal activation of T cells. In turn, these activated T cells upregulated production of inflammatory mediators in tenocytes, while increasing the pathogenic collagen 3/collagen 1 ratio. CONCLUSIONS: Interaction between T cells and tenocytes induces the expression of inflammatory cytokines/chemokines in tenocytes, alters collagen composition favouring collagen 3 and self-amplifies T cell activation via an auto-regulatory feedback loop. Selectively targeting this adaptive/stromal interface may provide novel translational strategies in the management of human tendon disorders.

Vancomycin Wrap for Anterior Cruciate Ligament Surgery: Molecular Insights.

BACKGROUND: The use of the vancomycin wrap to pretreat the hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown in popularity since it was first described in 2012 and has significantly reduced rates of postoperative infection. However, it remains unknown if this antibiotic treatment affects the molecular composition of the graft. PURPOSE: To establish whether treatment with vancomycin at 5 mg/mL, the most commonly used concentration, alters the molecular function of the hamstring graft in ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Surplus hamstring tendon collected after routine ACLR surgery was used for in vitro cell culture and ex vivo tissue experiments. Vancomycin was used at 5 mg/mL in RPMI or saline diluent to treat cells and tendon tissue, respectively, with diluent control conditions. Cell viability at 30, 60, and 120 minutes was assessed via colorimetric viability assay. Tendon cells treated with control and experimental conditions for 1 hour was evaluated using semiquantitative reverse transcription analysis, immunohistochemistry staining, and protein quantitation via enzyme-linked immunosorbent assay for changes in apoptotic, matrix, and inflammatory gene and protein expression. RESULTS: Vancomycin treatment at 5 mg/mL significantly reduced tenocyte viability in vitro after 60 minutes of treatment (P < .05); however, this was not sustained at 120 minutes. Vancomycin-treated tendon tissue showed no significant increase in apoptotic gene expression, or apoptotic protein levels in tissue or supernatant, ex vivo. Vancomycin was associated with a reduction in inflammatory proteins from treated tendon supernatants (IL-6; P < .05). CONCLUSION: Vancomycin did not significantly alter the molecular structure of the hamstring graft. Reductions in matrix protein and inflammatory cytokine release point to a potential beneficial effect of vancomycin in generating a homeostatic environment. CLINICAL RELEVANCE: Vancomycin ACL wrap does not alter the molecular structure of the ACL hamstring graft and may improve graft integrity.

Short-Term Western Diet Intake Promotes IL-23‒Mediated Skin and Joint Inflammation Accompanied by Changes to the Gut Microbiota in Mice.

We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.

Attenuation of Dupuytren's fibrosis via targeting of the STAT1 modulated IL-13Rα1 response.

Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren's disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren's as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease.

Differential Requirement for CCR6 in IL-23-Mediated Skin and Joint Inflammation.

CCR6 is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CCR6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. CCR6-knockout mice were resistant to IL-23-induced skin inflammation but exhibited no changes in joint inflammation compared with wild-type mice. Depletion of neutrophils protected wild-type mice from skin and joint disease without suppressing T helper type 17 cytokine expression. In contrast, mice lacking γδ T cells showed a partial reduction in neutrophilic recruitment and a significant decrease in IL-17A expression in skin and paw tissue. Thus, in an IL-23-mediated model that allows concurrent assessment of both skin and joint disease, we showed that CCR6 is critical for inflammation in the skin but not in the joint. Furthermore, our data suggest that neutrophils and γδ T cells are key effector cells in IL-23-mediated skin and joint inflammation in mice.

Fibroblast activation and inflammation in frozen shoulder.

INTRODUCTION: Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the fibroblast compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder. METHODS: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Fibroblast activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1ß upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR. RESULTS: Immunohistochemistry demonstrated increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM). CONCLUSIONS: These results show that fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease.

Alarmins in Frozen Shoulder: A Molecular Association Between Inflammation and Pain.

BACKGROUND: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. PURPOSE: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects. STUDY DESIGN: Controlled laboratory study. METHODS: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients with unstable shoulders (control). The samples were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry using antibodies against alarmin molecules including high-mobility group protein B1 (HMGB1), interleukin 33, S100A8, S100A9, and the peripheral nerve marker PGP9.5. Immunoreactivities were rated in a blinded fashion from "none" to "strong." Immunohistochemical distribution within the capsule was noted. Before surgery, patient-ranked pain frequency, severity, stiffness, and the range of passive shoulder motion were recorded and statistically analyzed. RESULTS: Compared with control patients, patients with frozen shoulder had greater frequency and severity of self-reported pain ( P = .02) and more restricted range of motion in all planes ( P < .05). H&E-stained capsular tissue from frozen shoulder showed fibroblastic hypercellularity and increased subsynovial vascularity. Immunoreactivity of alarmins was significantly stronger in frozen shoulder capsules compared with control capsules ( P < .05). Furthermore, the expression of the alarmin molecule HMGB1 significantly correlated ( r > 0.9, P < .05) with the severity of patient-reported pain. CONCLUSION: This study demonstrates a potential role for key molecular danger signals in frozen shoulder and suggests an association between the expression of danger molecules and the pain experienced by patients.

Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis.

OBJECTIVES: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. METHODS: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. RESULTS: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1ß), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. CONCLUSION: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders.

Arteritis de Takayasu: ¿infrecuente o poco diagnosticada? / Takayasu's arteritis: infrequent or underdiagnosed?

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A propósito del fenómeno de Raynaud / On Raynaud’s phenomenon

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Vasculitis de Jacob Churg y Lotte Strauss. Descripción de 9 casos / Churg-Strauss Vasculitis. Description of 9 cases

Introducción El síndrome de Churg-Strauss (SCS) es una vasculitis que afecta a vasos de pequeño y mediano calibre, caracterizándose clínicamente por afectación predominante del aparato respiratorio, asma y eosinofilia periférica y anatomopatológicamente por la presencia de granulomas y la infiltración tisular por eosinófilos. Objetivos En el presente trabajo se detallan las características de una serie de 9 pacientes con SCS diagnosticados en un centro universitario de referencia. Pacientes y métodos Estudio retrospectivo: entre 1984 y 2007 se diagnosticaron 9 pacientes con SCS en nuestro centro. De todos ellos se obtuvieron de forma retrospectiva datos epidemiológicos, clínicos, analíticos, estudios anatomopatológicos y tratamiento recibido. Resultados De estos 9 pacientes, 7 eran hombres. La edad media en el momento del diagnóstico fue de 51 años (rango 23–76 años). Ocho de los pacientes tenían antecedente de asma bronquial. Las manifestaciones clínicas más frecuentes fueron las cutáneas (66%), musculoesqueléticas (66%), del sistema nervioso periférico (55%) y las pulmonares (55%). Todos presentaban eosinofilia periférica. Los anticuerpos anticitoplasma de neutrófilo (ANCA) fueron positivos en 6 pacientes (66%), la mayor parte de ellos con patrón perinuclear en inmunofluorescencia (p-ANCA). Todos los pacientes recibieron tratamiento con glucocorticoides y 8 de ellos requirieron, además, tratamiento inmunosupresor, principalmente ciclofosfamida. Conclusiones En este trabajo se presentan 9 pacientes diagnosticados de SCS. Las manifestaciones clínicas no difieren de las observadas en el resto de series publicadas. Sin embargo, en esta serie se observa una mayor positividad de ANCA. La mayoría de los pacientes fueron tratados con glucocorticoides e inmunosupresores, debiéndose individualizar el tratamiento de cada paciente según el grado de afectación (AU)

Introduction Churg-Strauss Síndrome (SCS) is a necrotizing vasculitis affecting small to medium-sized vessels, characterized by lung involvement, asthma and peripheral blood eosinophilia, and pathologically by the presence of granulomas and eosinophilic infiltrates. Objectives This report analizes the characteristics of 9 patients with SCS diagnosed in an university referral center. Patients and methods Retrospective study. Between 1984 and 2007 nine patients with SCS were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment required were retrospectively analyzed. Results Nine patients (7 males). The mean age at the time of diagnosis was 51 years (range 23–76 years). Eight of these patients had history of asthma. The more frequent organs involved were the skin (66%), musculoesqueletical system (66%), peripheral nervous system (55%) and the lung (55%). All patients presented peripheral eosinophilia. ANCA positivity was demonstrated in 6 patients (66%), most of the patients with the p-ANCA pattern. All patients were treated with corticosteroids, and in 8 immunosupressant treatment was required, mainly cyclophosphamide. Conclusions In this report, 9 patients with SCS are presented. Clinical characteristics are similar with the observed in other reports. We observed a major positivity of ANCA. Most of the patients were treated with corticosteroids and inmunosupresants, but the treatment should be tailored depending on the involvement of the patient (AU)

Mujer joven con artritis intermitente / Young woman with relapsing arthritis

Mujer de 28 años con episodios autolimitados de artritis intermitente de rodilla de 48 a 72h de duración, los cuales se repetían cada 2 semanas de forma periódica. El estudio inmunológico fue negativo así como el estudio radiológico. Posteriormente se realizó artroscopia de rodilla sin llegar a un diagnóstico definitivo. Se discuten, a continuación, las diferentes causas de reumatismos intermitentes(AU)

A 28-years old lady complains of self-limited episodes of relapsing knee arthritis of 48–72h of duration every 2 weeks. Immunological profile was all negative. At the same time, radiological images did not reveal any abnormality. She underwent to knee arthroscopy, however, a definite diagnosis was not reached. We discuss the differential diagnosis of relapsing arthritis(AU)

[Young woman with relapsing arthritis]. / Mujer joven con artritis intermitente.

A 28-years old lady complains of self-limited episodes of relapsing knee arthritis of 48-72h of duration every 2 weeks. Immunological profile was all negative. At the same time, radiological images did not reveal any abnormality. She underwent to knee arthroscopy, however, a definite diagnosis was not reached. We discuss the differential diagnosis of relapsing arthritis.

[Churg-Strauss Vasculitis. Description of 9 cases]. / Vasculitis de Jacob Churg y Lotte Strauss. Descripción de 9 casos.

INTRODUCTION: Churg-Strauss Síndrome (SCS) is a necrotizing vasculitis affecting small to medium-sized vessels, characterized by lung involvement, asthma and peripheral blood eosinophilia, and pathologically by the presence of granulomas and eosinophilic infiltrates. OBJECTIVES: This report analizes the characteristics of 9 patients with SCS diagnosed in an university referral center. PATIENTS AND METHODS: Retrospective study. Between 1984 and 2007 nine patients with SCS were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment required were retrospectively analyzed. RESULTS: Nine patients (7 males). The mean age at the time of diagnosis was 51 years (range 23-76 years). Eight of these patients had history of asthma. The more frequent organs involved were the skin (66%), musculoesqueletical system (66%), peripheral nervous system (55%) and the lung (55%). All patients presented peripheral eosinophilia. ANCA positivity was demonstrated in 6 patients (66%), most of the patients with the p-ANCA pattern. All patients were treated with corticosteroids, and in 8 immunosupressant treatment was required, mainly cyclophosphamide. CONCLUSIONS: In this report, 9 patients with SCS are presented. Clinical characteristics are similar with the observed in other reports. We observed a major positivity of ANCA. Most of the patients were treated with corticosteroids and inmunosupresants, but the treatment should be tailored depending on the involvement of the patient.

Artritis séptica politópica: análisis de 19 casos / Polyarticular septic arthritis: analysis of 19 cases

Objetivo: El 15% de las artritis sépticas corresponde a formas poliarticulares, si bien son escasas las series publicadas. Evaluamos las características de los enfermos con artritis séptica poliarticular recogidos en un servicio de reumatología. Material y método: Análisis retrospectivo de las artritis piógenas con afección oligoarticular o poliarticular. Se incluye únicamente a los enfermos con aislamiento del germen en el líquido articular. Se analizan las variables clínicas, analíticas y radiológicas de la serie. Resultados: Se registraron 19 casos (14 varones y 5 mujeres) con una media de edad de 55 años. La media del tiempo hasta el diagnóstico fue 6 días. La articulación afectada con mayor frecuencia fue la rodilla, seguida del tobillo. La media de focos infecciosos por paciente fue 3 (intervalo, 2-6). Los factores de riesgo más frecuentes fueron la diabetes mellitus, la insuficiencia renal crónica, la hepatopatía crónica, la gota y la artritis reumatoide. Los gérmenes aislados fueron Staphylococcus aureus (47%), S. agalactiae (21%) y bacilos gramnegativos. Los hemocultivos fueron positivos en el 52,6%, y el 15,8% presentó shock séptico. La gammagrafía con 99Tc mostró la afección politópica cuando fue realizada. La duración media del tratamiento antibiótico fue 46±27 días. La evolución fue satisfactoria en el 52,6% y tórpida en el 26%, con mortalidad del 15,8% (3 casos). Se realizó artrotomía en el 21%. Conclusiones: La presencia de oligoartritis o poliartritis no excluye el diagnóstico de artritis infecciosa. Entre los factores de riesgo destacan las artropatías inflamatorias previas. S. aureus es el microorganismo causal más frecuente. La morbilidad y la mortalidad de esta forma de infección articular son importantes, por lo que debe mantenerse un alto índice de sospecha y realizar una exploración sistemática de todas las articulaciones (AU)

Objective: Polyarticular septic arthritis accounts for 15% of all septic arthritis, but there are few references in the literature. We describe characteristics of patients with polyarticular septic arthritis in a rheumatology service. Patients and method: Retrospective analysis of patients with septic arthritis involving more than one joint. Only patients with positive culture of synovial fluid were included. Clinical, analytical and radiological variables are reviewed. Results: 19 patients (14 male) had a polyarticular infection. Mean age was 55 years. Mean time from onset to diagnosis was 6 days. The knee was the most commonly involved joint, followed by ankle. The mean number of joints involved per patient was 3. Risk factors included diabetes, chronic renal or hepatic disease, gout and rheumatoid arthritis. Most commonly isolated agents were S. aureus (47%) and S. agalactiae (21%). Blood cultures were positive in 52,6% and 15.8% had septic shock. Scintygraphic bone scan showed a polyarticular uptake. Mean duration of antibiotic therapy was 46±27 days. Clinical outcome was good in 52,6%, complicated in 26%, and mortality rate was 15.8% (3 cases). Joint debridement was performed in 21%. Conclusions: Multiple joint involvement does not exclude the diagnosis of septic arthritis. Inflammatory arthritis is an important risk factor. S. aureus in the main infectious agent. The morbidity and mortality of this condition are important, so we need to maintain a high index of suspicion for the condition (AU)