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ID PMID Title PublicationDate abstract
25297553 Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with s 2015 Jan Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded.
20842515 Case report: successful use of short-term add-on tocilizumab for multirefractory systemic 2013 Mar We report on a 64-year-old woman with multirefractory flare of adult-onset Still's disease successfully treated with six-month course of add-on anti-interleukin 6 receptor antibody, tocilizumab. Before administration of tocilizumab, the combination therapy with 80 mg/day of prednisolone and cyclosporine or tacrolimus for five weeks, two courses of pulse methylprednisolone, and high-dose intravenous immunoglobulin could not control the disease. Add-on tocilizumab dramatically improved her disease state and enabled tapering of corticosteroid and tacrolimus. Furthermore remission has been maintained on low-dose corticosteroid and tacrolimus after withdrawal of tocilizumab. This case report suggests that short-term add-on tocilizumab might be a useful therapeutic option for patients with multirefractory flare of polycyclic systemic adult-onset Still's disease.
25457064 Salivary transforming growth factor alpha in patients with Sjögren's syndrome and reflux 2014 Nov INTRODUCTION: Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux. OBJECTIVE: To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls. METHODS: This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations. RESULTS: The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls. CONCLUSION: Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group.
24886995 Comparison of clinical efficacies of autologous serum eye drops in patients with primary a 2014 Jul PURPOSE: Autologous serum eye drops are considered to be safe and efficient for the treatment of dry eyes associated with Sjögren syndrome (SS). The purpose of this study was to compare the clinical efficacies of autologous serum eye drops in the management of primary and secondary SS. METHODS: Patients with primary (n = 20; 35 eyes) and secondary (n = 14; 27 eyes) SS dry eye were included. Serum concentrations of proinflammatory cytokines [tumor necrosis factor α, interleukin (IL)-1β, IL-6, and IL-8] were measured by a multiplex immunobead assay. The ocular symptom scores, ocular staining grades, and tear break-up time were evaluated before and after 4 weeks of 50% autologous serum eye drop application. RESULTS: At enrollment, patients with secondary SS had higher serum proinflammatory cytokine levels (tumor necrosis factor α, IL-1β, IL-6, and IL-8) than patients with primary SS (P < 0.01). After 4 weeks of autologous serum eye drop treatment, patients with primary SS had significantly improved ocular symptoms (P < 0.01), ocular surface staining grades (P < 0.01), and tear break-up time (P < 0.05). However, patients with secondary SS had no improvement (P > 0.05). CONCLUSIONS: Our results suggest that autologous serum eye drops might not be effective for the treatment of secondary SS because of elevated serum proinflammatory cytokine levels.
24797167 Use of a novel high-resolution magnetic resonance neurography protocol to detect abnormal 2014 May The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional "stocking-and-glove" distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system-the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain.We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients whose neuropathic pain resolved with intravenous immunoglobulin (IVIg) therapy had improvement of MRN DRG abnormalities.We have developed a novel MRN protocol that can detect DRG abnormalities in SS patients with neuropathic pain who do not have markers of peripheral neuropathy. We found that SS patients with MRN DRG abnormalities had statistically significant, increased IENFD on skin biopsy studies, which may suggest a relationship between trophic mediators and neuropathic pain. Given that our literature review has demonstrated that many SS neuropathic pain patients do not have a neuropathy, our findings suggest an important niche for this MRN DRG technique in the evaluation of broader subsets of SS neuropathic pain patients who may not have underlying neuropathies. The improvement of MRN DRG abnormalities in patients with IVIg-induced remission of neuropathic pain suggests that our MRN protocol may be capturing reversible, immune-mediated mechanisms targeting the DRG.
24023247 The EULAR Sjogren's syndrome patient reported index as an independent determinant of healt 2013 Dec OBJECTIVE: To investigate the significant determinants of health-related quality of life (HRQOL) and the association of the EULAR Sjögren's syndrome patient reported index (ESSPRI) with clinical parameters including HRQOL in Korean patients with primary Sjögren's syndrome (pSS) compared with non-SS sicca patients. METHODS: We prospectively analysed 104 pSS and 42 non-SS sicca patients. Clinical data including Short Form 36 (SF-36) scores, self-assessments for symptoms and ESSPRI were cross-sectionally collected. RESULTS: Although most self-assessments and HRQOL statuses were comparable, different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients. pSS patients with low HRQOL had significantly higher ESSPRI scores [P = 7.6 × 10(-6) for physical component summary (PCS) subgroups and P = 0.0015 for mental component summary (MCS) subgroups] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients (all P ≤ 0.0020). Moreover, in multivariate linear regression analyses, ESSPRI (P = 0.035) and depression (P = 4.1 × 10(-14)) were significantly correlated with the PCS and the MCS, respectively. However, in the non-SS sicca group, xerostomia inventory (XI) scores were higher in the low PCS subgroup (P = 0.031) and this correlated with five SF-36 scales (all P ≤ 0.046). XI scores (P = 0.0039) and anxiety (P = 7.9 × 10(-10)) were the main determinants of the PCS and MCS, respectively. CONCLUSION: HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients, although the groups had similar clinical symptoms and HRQOL reduction. Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients, ESSPRI is suggested to be disease-specific for pSS.
22971705 A case of solitary pulmonary nodular amyloidosis with Sjögren's syndrome. 2013 Patients with Sjögren's syndrome frequently have pulmonary involvement, but the involvement of nodular pulmonary lesions, including pulmonary amyloidosis, is rare. Most cases of pulmonary amyloidosis involve multiple nodules; solitary pulmonary nodular amyloidosis, as an associated condition of Sjögren's syndrome, is very rare.In our report, we present the case of an 80-year-old female with Sjögren's syndrome who was incidentally found to have a small solitary pulmonary nodule. The nodule showed high fluorodeoxyglucose uptake and contained areas of calcification. Because the probability that the nodular lesion was malignant could not be excluded, the tumor was excised using a thoracoscopic procedure; the final diagnosis was pulmonary nodular amyloidosis. Although most cases of pulmonary amyloidosis involve multiple nodules, amyloidosis should be considered in the differential diagnosis for a solitary pulmonary nodule in patients with Sjögren's syndrome.
22967808 Type III membranoproliferative glomerulonephritis in a patient with primary Sjögren's syn 2013 Feb Renal involvement in the form of glomerulonephritis in Sjögren's syndrome (SS) is less common and usually a latent sequel in the course of the disease. We report a patient with Type III membarnoproliferative glomerulonephritis (MPGN) with hypothyroidism, which precedes the onset of the clinical manifestation of SS. She received immunosuppressions consisting of i.v. cyclophosphamide and high-dose corticosteroid and subsequently oral corticosteroid resulting in complete remission of nephrotic syndrome. To our knowledge, this is the first report of successfully treated Type III MPGN associated with SS.
23452375 Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study 2013 Mar 2 BACKGROUND: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. METHODS/DESIGN: HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. TRIAL REGISTRATION: ISRCTN91859104.
24062461 NF-κB inhibitor targeted to activated endothelium demonstrates a critical role of endothe 2013 Oct 8 Activation of the nuclear transcription factor κB (NF-κB) regulates the expression of inflammatory genes crucially involved in the pathogenesis of inflammatory diseases. NF-κB governs the expression of adhesion molecules that play a pivotal role in leukocyte-endothelium interactions. We uncovered the crucial role of NF-κB activation within endothelial cells in models of immune-mediated diseases using a "sneaking ligand construct" (SLC) selectively inhibiting NF-κB in the activated endothelium. The recombinant SLC1 consists of three modules: (i) an E-selectin targeting domain, (ii) a Pseudomonas exotoxin A translocation domain, and (iii) a NF-κB Essential Modifier-binding effector domain interfering with NF-κB activation. The E-selectin-specific SLC1 inhibited NF-κB by interfering with endothelial IκB kinase 2 activity in vitro and in vivo. In murine experimental peritonitis, the application of SLC1 drastically reduced the extravasation of inflammatory cells. Furthermore, SLC1 treatment significantly ameliorated the disease course in murine models of rheumatoid arthritis. Our data establish that endothelial NF-κB activation is critically involved in the pathogenesis of arthritis and can be selectively inhibited in a cell type- and activation stage-dependent manner by the SLC approach. Moreover, our strategy is applicable to delineating other pathogenic signaling pathways in a cell type-specific manner and enables selective targeting of distinct cell populations to improve effectiveness and risk-benefit ratios of therapeutic interventions.
24893986 Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear fa 2014 Aug This study focused on the potential therapeutic effect of baicalin on collagen-induced arthritis (CIA) in rats and the underlying mechanisms. The CIA rats were injected with baicalin (50, 100, or 200 mg/kg) once daily for 30 days. The rats were monitored for clinical severity of arthritis, and joint tissues were used for radiographic assessment and histologic examination. We quantified tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in experimental animals and used Western blots to assess levels of protein abundance, phosphorylation, and acetylation of nuclear factor (NF)-κB p65 and sirtuin 1 (sirt1) protein expression in joint tissues. Human fibroblast-like synoviocytes from rheumatoid arthritis (HFLS-RA) were adopted in further mechanistic investigations. Baicalin intraperitoneal injection for 30 days dose-dependently blocked clinical manifestations of CIA, such as functional impairment and swollen red paws. Meanwhile, it alleviated collagen-induced joint inflammation injury and inhibited the secretion of TNF-α and IL-1β in both rat synovium and HFLS-RA. Further mechanistic investigations revealed that baicalin suppresses NF-κB p65 protein expression and phosphorylation in synovial tissue and human-derived synoviocytes. Moreover, the acetylation of NF-κB p65 was downregulated by baicalin, which negatively correlates with the baicalin-induced upregulation of sirt1 expression in the same conditions. The data indicate that CIA in rats can be alleviated by baicalin treatment via relieving joint inflammation, which is related to the suppression of synovial NF-κB p65 protein expression and the elevation of its deacetylation by sirt1.
24132362 Early follow-up of reverse total shoulder arthroplasty in patients sixty years of age or y 2013 Oct 16 BACKGROUND: Reverse shoulder arthroplasty (RSA) is an accepted treatment that provides reproducible results in the treatment of shoulder arthritis and rotator cuff deficiency. Concerns over the longevity of the prosthesis have resulted in this procedure being reserved for the elderly. There are limited data in the literature with regard to outcomes in younger patients. We report on the early outcomes of RSA in a group of patients who were sixty years or younger and who were followed for a minimum of two years. METHODS: A retrospective multicenter review of sixty-six patients (sixty-seven RSAs) with a mean age of 52.2 years was performed. The indications included rotator cuff insufficiency (twenty-nine), massive rotator cuff disorder with osteoarthritis (eleven), failed primary shoulder arthroplasty (nine), rheumatoid arthritis (six), posttraumatic arthritis (four), and other diagnoses (eight). Forty-five shoulders (67%) had at least one prior surgical intervention, and thirty-one shoulders (46%) had multiple prior surgical procedures. RESULTS: At a mean follow-up time of 36.5 months, mean active forward elevation of the arm as measured at the shoulder improved from 54.6° to 134.0° and average active external rotation improved from 10.0° to 19.6°. A total of 81% of patients were either very satisfied or satisfied. The mean American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) score for pain improved from 40.0 to 72.4 and 7.5 to 3.0, respectively. The ability to achieve postoperative forward arm elevation of at least 100° was the only significant predictor of overall patient satisfaction (p < 0.05) that was identified in this group. There was a 15% complication rate postoperatively, and twenty-nine shoulders (43%) had evidence of scapular notching at the time of the latest follow-up. CONCLUSIONS: RSA as a reconstructive procedure improved function at the time of short-term follow-up in our young patients with glenohumeral arthritis and rotator cuff deficiency. Objective outcomes in our patient cohort were similar to those in previously reported studies. However, overall satisfaction was much lower in this patient population (81%) compared with that in the older patient population as reported in the literature (90% to 96%).
25495344 Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation an 2014 Dec 12 BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articular cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclasts and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be a promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicates the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reported that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA model mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation of articular cartilage in RA model mice. RESULTS: We induced arthritis in mice by injection of anti-type II collagen antibodies and lipopolysaccharide (LPS). Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increased bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected with anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated with OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC1 did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articular cartilage from destruction in mice with arthritis. CONCLUSIONS: Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammation in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.
24789000 Adalimumab, etanercept, infliximab, and the risk of tuberculosis: data from clinical trial 2014 May This review evaluates the risk of tuberculosis (TB), adherence with recommendations for TB prevention, and host-related risk in patients with rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis receiving infliximab (IFX), adalimumab (ADA), and etanercept (ETN) through an analysis of phase III randomized controlled trials (RCT), postmarketing surveillance, and national registries. Ten (0.21%) TB cases occurred among 4590 patients in 16 RCT of IFX, 9 (0.12%) among 7009 patients in 21 RCT of ADA, and 4 (0.05%) among 7741 patients in 26 RCT of ETN. Overall, 19/23 (83%) TB cases occurred in patients with RA. Data from national registries and postmarketing surveillance showed an increased risk of TB in patients receiving any of the 3 anti-tumor necrosis factor (TNF) drugs, with a 3-4 times higher risk associated with IFX and ADA than with ETN. Deviations from recommended TB prevention procedures were observed in up to 80% of patients, and most registries did not include data on host-related risk factors for TB. TB occurrence was reduced in recent RCT but not in real-life practice. TB risk was lower for ETN than for monoclonal antibody anti-TNF agents. More complete data collection, including host-related TB risk factors, is advisable to avoid biased results.
24706840 Transglutaminase 2 is essential for adherence of Porphyromonas gingivalis to host cells. 2014 Apr 8 Porphyromonas gingivalis is the major causative agent of periodontitis, and it may also be involved in the development of systemic diseases (atherosclerosis, rheumatoid arthritis). P. gingivalis is found on and within oral and gingival epithelial cells following binding to surface components of host cells, which serve as receptors for the bacterium. Evidence is presented in this study that shows that transglutaminase 2 (TG2) plays a critical role in the adherence of P. gingivalis to host cells. Studies of confocal microscopy indicate colocalization of P. gingivalis with TG2 on the surface of HEp-2 epithelial cells, with clusters of TG2 seen at bacterial attachment sites. By silencing the expression of TG2 with siRNA in HEp-2 cells, P. gingivalis association was greatly diminished. The bacterium does not bind well to a mouse fibroblast cell line that produces low amounts of surface TG2, but binding can be restored by introduction of TG2 expressed on a plasmid. TG2 can form very tight complexes with fibronectin (FN), and the complementary binding sites of the two proteins are known. A synthetic peptide that mimics the main FN-binding sequence of TG2 blocks the formation of TG2-FN complexes and is highly effective in inhibiting adherence of P. gingivalis to host cells. These findings provide evidence of a role for cell-surface TG2 in bacterial attachment and subsequent internalization.
24600322 New onset of dermatomyositis/polymyositis during anti-TNF-α therapies: a systematic liter 2014 We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM) in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA), one by Crohn's disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD) were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors) was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA) with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.
23566679 B-cell targeted therapeutics in clinical development. 2013 B lymphocytes are the source of humoral immunity and are thus a critical component of the adaptive immune system. However, B cells can also be pathogenic and the origin of disease. Deregulated B-cell function has been implicated in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B cells contribute to pathological immune responses through the secretion of cytokines, costimulation of T cells, antigen presentation, and the production of autoantibodies. DNA-and RNA-containing immune complexes can also induce the production of type I interferons, which further promotes the inflammatory response. B-cell depletion with the CD20 antibody rituximab has provided clinical proof of concept that targeting B cells and the humoral response can result in significant benefit to patients. Consequently, the interest in B-cell targeted therapies has greatly increased in recent years and a number of new biologics exploiting various mechanisms are now in clinical development. This review provides an overview on current developments in the area of B-cell targeted therapies by describing molecules and subpopulations that currently offer themselves as therapeutic targets, the different strategies to target B cells currently under investigation as well as an update on the status of novel therapeutics in clinical development. Emerging data from clinical trials are providing critical insight regarding the role of B cells and autoantibodies in various autoimmune conditions and will guide the development of more efficacious therapeutics and better patient selection.
25163486 Comparison of cancer incidence among patients with rheumatic disease: a retrospective coho 2014 Aug 28 INTRODUCTION: Rheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. In the present study, we examined the relative incidence of several cancers in a single homogeneous cohort of patients with different RDs. METHODS: Patients (N = 3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM) or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs). RESULTS: During the follow-up period of 31,064 person-years, 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin's lymphoma (SIR for RA patients = 3.387, 95% confidence interval (CI) = 1.462 to 6.673; SIR for SLE patients = 7.408, 95% CI = 2.405 to 17.287). SLE patients also had a higher risk of cervical cancer (SIR = 4.282, 95% CI = 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR = 4.917, 95% CI = 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR = 30.529, 95% CI = 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR = 0.663, 95% CI = 0.327 to 0.998). The mean time between the RD and cancer diagnoses ranged from 0.1 to 16.6 years, with the shortest time observed in patients with DM (2.0 ± 2.1 years). CONCLUSIONS: Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RDs might be beneficial.
25092612 Obesity in autoimmune diseases: not a passive bystander. 2014 Sep In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.
24166363 [Interleukin-6 inhibition as a potential therapeutic target in rheumatic diseases]. 2014 Apr As a pro-inflammatory cytokine, the 21-kDa glycoprotein interleukin-6 (IL-6) plays a crucial role in the initiation of acute inflammation, as well in the perpetuation of a chronic inflammatory immune response. Thus, IL-6 might be involved in the pathogenesis of various autoimmune diseases. So far, the IL-6-rezeptor-antibody tocilizumab (TCZ, RoActemtra®) is the only approved drug for the treatment of IL-6-mediated disease, including rheumatoid arthritis (RA), systemic juvenile idiopathic (sJIA) and polyarticular juvenile arthritis (pJiA), as well as Castleman's disease (in Japan only). In recent years, an emerging number of case reports and small uncontrolled case series have reported on the successful treatment of various other chronic inflammatory diseases, which has resulted in the idea of a broad therapeutic potential for IL-6 blockade. Numerous IL-6 targets are currently in phase II/III study programs for RA as well as for other indications. This review focuses on the development of tocilizumab and other IL-6 targets as a therapeutic option for various diseases in rheumatology.