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Purpose: To identify bilateral hand and wrist findings of synovial inflammation associated with progression to rheumatoid arthritis (RA) in very-early-RA cohort (VERA) (duration, <3 months) and early-RA cohort (ERA) (duration, <12 but >3 months), to test tenosynovitis as a magnetic resonance (MR) imaging additional parameter for improving diagnostic accuracy of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, and to evaluate the symmetry of joint and tendon involvement., Materials and Methods: With institutional review board approval and informed consent, 32 women and three men (mean age, 45 years) with untreated recent-onset inflammatory arthritis participated in this prospective study and underwent MR imaging of both wrists and hands. After 12-month follow-up, 25 patients fulfilled the criteria for RA (10 VERA and 15 ERA patients). Ten patients did not fulfill the criteria for RA (non-RA [control] group). Possible associations between synovitis for each joint and tendon and RA diagnosis at 12 months were tested (univariate logistic regression analysis). Diagnostic performance of the ACR/EULAR RA classification criteria was evaluated (receiver operating characteristic curve analysis). Asymmetry prevalence (all joints and tendons in the analysis) was calculated., Results: Tenosynovitis of the extensor carpi ulnaris (odds ratio, 3.21) and flexor tendons of the second finger (odds ratio, 14.61) in VERA group and synovitis of the radioulnar joint (odds ratio, 8.79) and tenosynovitis of flexor tendons of the second finger (odds ratio, 9.60) in ERA group were significantly associated with progression to RA (P < .05). Consideration of tenosynovitis improved areas under the receiver operating characteristic curve of ACR/EULAR criteria performance for the diagnosis of RA from 0.942 (P < .0001; sensitivity, 52%; specificity, 100%) to 0.972 (P < .0001; sensitivity, 76%; specificity, 100%), with cutoff score of 6 or greater. Asymmetry was found in 80.0% (62 of 77) (VERA patients) and 69.3% (106 of 153) (ERA patients) of joint or tendon pairs (P < .05)., Conclusion: Tenosynovitis is an imaging finding in early RA, and its inclusion as a scoring criterion might contribute for a better diagnostic performance of the 2010 ACR/EULAR classification; early RA is an asymmetric disease., (© RSNA, 2012)

Pachydermodactyly is a superficial benign fibromatosis of unknown etiology; it is rare, more frequent in adolescent males, and characterized by painless swelling of the proximal interphalangeal joints(PIP) of the hands. Histologic examination of the skin shows epidermal hyperplasia and increased number of dermal fibroblasts and collagen fibers.We report the case of a 16-year-old adolescent boy who presented swelling of the lateral and dorsal regions of all the metacarpophalangeal and PIP joints of the left hand and PIP and metacarpophalangeal joints of the second and fifth fingers of the right hand, with 3 years of evolution and no arthritis or functional impairment. Results of complementary diagnostic examinations were normal, with the exception of hand ultra sound that showed skin thickening, without synovial proliferation or joint effusion. Skin biopsy confirmed pachydermodactyly. The patient under went aesthetic surgery with good outcome, without recurrence.This rare condition should be distinguished from idiopathic juvenile arthritis and other entities such as knuckle pads syndrome.

Introduction: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known., Method: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively., Results: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients., Conclusions: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

Objectives: Characterize Osteoarticular Brucellosis in the University Hospital of Coimbra (HUC) in the past decade., Material and Methods: A retrospective study of the cases diagnosed between January/2000 and December/2009 in the HUC., Results: Ninety patients were admitted with the dia-gnosis of brucellosis in our hospital, of whom 44 (49%; 18 men; 26 women, mean 49.5 years) had osteoarticular complications. Twenty-five (45%) patients had a positive epidemiological context. The most frequent clinical manifestation was local pain (73%) followed by polyarthralgias and constitutional symptoms. The C-reactive protein was the inflammatory marker most often increased (82%). The Rose Bengala test was positive in 42 patients, and a Wright's sero-aglutination above than 1/160 was detected in 28 patients. An etiologic agent was isolated in 28 (64%) patients, with 70% of positive blood cultures. The imaging procedure of choice was magnetic resonance imaging (MRI) (46%). The osteo-articular manifestation most frequent was spondylodiscitis (57%) with a lumbosacral involvement in 40%. All patients completed antibiotic therapy. One patient underwent surgery to drain the abscess. Patients had an average length of admission of 28.3 days, with a good outcome in 60%, and a reasonable outcome in 20%, despite 20% of the patients lost follow-up., Conclusions: Brucellosis is a disease of obligatory declaration not eradicated in Portugal, with a great impact on socio-economic and public health. So, this epidemiological knowledge of brucellosis cases, allows an early intervention and therapy.

Reactivation of infection with hepatitis B virus (HBV) is a potentially serious complication of immunosuppression, which can be identified and efficiently prevented. There have been an increasing number of cases of HBV reactivation in patients receiving immunosuppression in the context of rheumatic diseases such as rheumatoid arthritis or systemic lupus erythematosus. The recommendations in this area should be individualized taking into account two aspects: immunosuppressive regimens used (high or low risk of reactivation) and the different stages of HBV infection: chronic hepatitis B, inactive HBV carrier, occult hepatitis B infection defined by HB surface antigen (HBsAg) negative and antibody anti-HB core (anti-HBc) positive. In patients with rheumatic diseases that will start high-risk immunosuppressive drugs, we propose a universal screening with serological tests for hepatitis B (HBsAg, anti-HBs and anti-HBc). Patients with chronic hepatitis B (HBsAg positive, HBV DNA ≥ 2000 IU/ml, elevated ALT) should initiate antiviral therapy. Inactive HBV carriers (HBsAg positive, HBV DNA <2000 IU / ml, normal aminotransferases) exposed to high risk immunosuppressive therapy should undergo prophylaxis of HBV reactivation. Prophylaxis should be started 2 to 4 weeks before the beginning of immunosuppressive therapy and maintained for at least 6 to 12 months after its suspension. It is recommended to use entecavir or tenofovir as first line antiviral agents. In inactive HBsAg carriers under low-risk immunosuppressive therapy and patients with HBsAg negative/anti-HBc positive (HBV infection in the past), the strategy should be monitoring of viral reactivation with aminotransferases and HBV DNA determination in every 6 months.

Objective: CD8+ T cells are part of the T cell pool infiltrating the synovium in rheumatoid arthritis (RA). However, their role in the pathogenesis of RA has not been fully delineated. Using the K/BxN mouse model of spontaneous chronic arthritis, which shares many similarities with RA, we studied the potential of CD8+ T cell depletion with monoclonal antibodies (mAb) to stop and reverse the progression of experimental arthritis., Methods: CD8+ T cells from the blood and articular infiltrate of K/BxN mice were characterized for cell surface phenotypic markers and for cytokine production. Additionally, mice were treated with specific anti-CD8 mAb (YTS105 and YTS169.4), with and without thymectomy., Results: CD8+ T cells from the peripheral blood and joints of K/BxN mice were mainly CD69+ and CD62L-CD27+ T cells expressing proinflammatory cytokines (interferon-γ [IFNγ], tumor necrosis factor α [TNFα], interleukin-17a [IL-17A], and IL-4), and granzyme B. In mice receiving anti-CD8 mAb, the arthritis score improved 5 days after treatment. Recovery of the CD8+ T cells was associated with a new increase in the arthritis score after 20 days. In thymectomized and anti-CD8 mAb-treated mice, the arthritis score improved permanently. Histologic analysis showed an absence of inflammatory infiltrate in the anti-CD8 mAb-treated mice. In anti-CD8 mAb-treated mice, the serologic levels of TNFα, IFNγ, IL-6, and IL-5 normalized. The levels of the disease-related anti-glucose-6-phosphate isomerase antibodies did not change., Conclusion: These results indicate that synovial activated effector CD8+ T cells locally synthesize proinflammatory cytokines (IFNγ, TNFα, IL-17, IL-6) and granzyme B in the arthritic joint, thus playing a pivotal role in maintaining chronic synovitis in the K/BxN mouse model of arthritis.

Objective: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc)., Methods: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs., Results: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable., Conclusion: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Objectives: To determine the frequency of ovarian failure in pre-menopausal women after cyclophosphamide (cyc) treatment for systemic lupus erythematosus (SLE); identify risk factors for this complication; estimate the occurrence and viability of pregnancy during and after treatment., Methods: Review of the data of women treated with intravenous cyc in the department of Rheumatology of Hospitais da Universidade de Coimbra, updated by interview. Information on demographic features; gynaecologic and obstetrical history; characteristics of the disease; duration and side effects of treatment were obtained. Ovarian failure was defined as a lack of menses for, at least, four months and the diagnosis was confirmed by hormonal measurements., Results: Nineteen pre-menopausal women were treated with intravenous cyc in our department. The mean age at the time of cyc initiation was 28.4 years. Lupus nephritis was the most common indication for cyc treatment (89.5%). The mean number of pulses was 9.3 over a period of 16.8 months. The mean cumulative dosage was 6.973 mg. Three patients developed ovarian failure. Those women were older than the others (P=0.0016). One patient became pregnant while on treatment. Two women delivered healthy children after cyc withdrawal., Conclusion: Ovarian failure developed in 15.8% of our patients. As described in the literature, the age at cyc initiation appears to be a determinant risk factor. Pregnancy may occur during cyc therapy, and thus, an effective contraception is mandatory. After cyc withdrawal, pregnancy is possible with a favourable outcome.

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10(-10) M to 10(-6) M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

The innervation of normal and rheumatoid human synovium was studied by immunofluorescence microscopy. Antibodies against the general neuronal marker protein gene product (PGP) 9.5 and specific neuropeptides were used. We observed sensory nerves containing substance P (SP) and calcitonin gene related peptide (CGRP) as well as autonomic sympathetic fibers immunoreactive for neuropeptide tyrosine (NPY), its C terminal peptide (C-PON) and the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). Three subpopulations of nerve fibers labelled with SP and CGRP were identified: some stained for SP or CGRP only and others contained both peptides. NPY/C-PON and TH labelled predominantly perivascular nerves. Quantification of immunostained nerves revealed a significantly decreased innervation of rheumatoid synovia. The densities of both PGP 9.5 and neuropeptide containing nerves were lower in all rheumatoid samples. Our results are compatible with a local release of neuropeptides into joint fluid and point to a disturbed neuronal control of rheumatoid synovial tissue.