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ID PMID Title PublicationDate abstract
19371503 Generalized anxiety disorder and medical illness. 2009 Patients with generalized anxiety disorder (GAD) often have multiple medical comorbidities. The adrenal system and genetic and environmental factors are intermediaries between anxiety and medical illnesses such as chronic pain conditions and gastrointestinal, cardiovascular, endocrine, and respiratory disorders. Medical disorders associated with anxiety include migraine, rheumatoid arthritis, peptic ulcer disease, irritable bowel syndrome, coronary heart disease, hyperthyroidism, diabetes, asthma, and chronic obstructive pulmonary disorder. Compared to people with pain conditions without GAD, individuals with pain conditions and GAD experience and register pain differently; they also have increased awareness of symptoms. Comorbid medical illnesses may influence treatment choice for GAD. Treatment of anxiety in young patients with GAD needs to be long-term to decrease vulnerability to medical conditions.
19269784 A case of systemic amyloidosis following ankylosing spondylitis associated with congestive 2009 May Secondary (amyloid A [AA]) amyloidosis is a systemic disease characterized by amyloid deposition in many organs, leading to impaired function. Although cardiac involvement may occur with AA amyloidosis, significant deposition of amyloid in the heart is considered an infrequent observation and is rarely the cause of death. It occurs in 5% of patients with poorly controlled chronic inflammatory disease, mainly rheumatoid arthritis, ankylosing spondylitis, and familial Mediterranean fever. The authors report a case of AA amyloidosis diagnosed by rectal and skin biopsies, with cardiac involvement demonstrated by typical echocardiographic features in the presence of low voltage on electrocardiography.
19190623 Certolizumab pegol--what role does this new TNF inhibitor have in the treatment of RA? 2009 Mar The efficacy and safety of a new tumor necrosis factor inhibitor, certolizumab pegol, in active rheumatoid arthritis has now been assessed in three phase III, multicenter, randomized, double-blind, placebo-controlled clinical trials. This commentary focuses on the paper by Keystone et al., in which patients were followed for the longest duration. This study, which compared two doses of subcutaneous certolizumab pegol with placebo in patients with active RA receiving methotrexate, showed no advantage of 400 mg over 200 mg certolizumab pegol over 52 weeks, after induction with 400 mg. The nature of the patients enrolled in this study, trial design and possible safety issues are discussed, as is whether this trial can teach us anything about tumor necrosis factor inhibitors in general. On the basis of the results from this study, certolizumab pegol does not represent a major addition to our armamentarium, but because of the slightly different mechanism of action and structure of this drug, and the apparently acceptable therapeutic effects over one year, it is, nevertheless, welcome.
18979499 A polygenic model for integration of linkage and pathway information. 2009 Apr We introduce an approximate model for linkage curves which accommodates the polygenic structure of complex diseases and accounts for the simultaneous action of closely located genes. The model is extended so that information on biological pathways can be integrated. Using data on rheumatoid arthritis, we describe some of the many applications which the model allows: it can be used to test for residual linkage in the presence of already established loci, to derive a global test for linkage, to test for the relevance of a gene list in terms of linkage and to help in candidate gene prioritization by integration of gene-pathway annotation data.
21250424 [Update on total hip arthroplasty]. 2010 Dec 22 Total hip arthroplasty (THA) is one of the most common surgical procedures performed by orthopedic surgeons. Frequent indications for THA include osteoarthrosis of the hip joint that can be primary origin or secondary to dysplasia or traumatic origin, as well as fractures of the femoral neck in active patients. Other common indications include rheumatoid arthritis and osteonecrosis of the femoral head. It is a surgical intervention giving very good results giving patients pain relief and mobility with a success rate in more than 90% of cases. The point of this article is to inform the medical community on the actual situation of hip prosthetics in fields including epidemiology, clinical results, indications, contraindications, different types of prosthetic materials as well as surgical approaches.
18798316 Oral histoplasmosis: an unusual presentation. 2009 Feb BACKGROUND: Histoplasmosis is a localized or systemic fungal infection which may present as an acute primary or "reactivation" infection in the setting of immunosuppression. Tumor necrosis factor alpha (TNF-alpha) antagonists, used in the management of rheumatoid arthritis and Crohn disease, have been linked to reactivation of quiescent histoplasmosis. Microscopically, granulomas are either not evident or are infrequent in histoplasmosis when associated with TNF antagonist therapy presumably due to the suppression of macrophage activity. METHODS AND RESULTS: This article describes an unusual presentation of oral histoplasmosis in a 75-year-old-woman patient on TNF-alpha antagonist, namely infliximab. Microscopically, cellular atypia resulted in a work-up to rule out lymphoma. Gomori's methenamine silver stain demonstrated Histoplasma capsulatum leading to a diagnosis of histoplasmosis. She was treated successfully with itraconozole. CONCLUSION: This is the first reported case, insofar as the authors are able to determine, of oral histoplasmosis, in a patient undergoing treatment with infliximab.
21107087 IgG4-related disease: a cross-sectional study of 114 cases. 2010 Dec IgG4-related disease has been identified in various organs, but whether or not there are organ-specific characteristics related to the etiologic factors is still unknown. Here, we carried out a cross-sectional study of 114 patients with IgG4-related disease. On the basis of the location of the lesions, the patients were classified into 5 groups: head and neck (n=23), thoracic (n=16), hepatic and pancreatobiliary (n=27), retroperitoneal (n=13), and systemic (n=35). All groups had similar clinicopathologic features in various aspects. However, there were some organ-specific features: for example, the proportion of the female patients was significantly higher in the head and neck group, serum IgG4 concentrations were significantly higher in the head/neck and systemic groups, and all kidney lesions were associated with extrarenal disease. Unique pathologic features were dense fibrosis in dacryoadenitis, numerous lymph follicles in sialadenitis and dacryoadenitis, and obliterative arteritis in lung lesions. In addition, an epithelioid granuloma and rheumatoid nodule were noted within IgG4-related lesions in 2 patients, 1 each with a history of tuberculosis and rheumatoid arthritis, respectively. Malignant tumors (2 lung cancers and 1 malignant lymphoma) were identified after the diagnosis of IgG4-related disease in 3 patients, all in the systemic group. In conclusion, this study showed organ-specific features of IgG4-related disease. Further study is necessary to conclude whether these features reflect different manifestations of a single disease entity or suggest different underlying etiologic factors.
20017963 Representation of genetic association via attributable familial relative risks in order to 2009 Dec 15 The results from association studies are usually summarized by a measure of evidence of association (frequentist or Bayesian probability values) that does not directly reflect the impact of the detected signals on familial aggregation. This article investigates the possible advantage of a two-dimensional representation of genetic association in order to identify polymorphisms relevant to disease: a measure of evidence of association (the Bayes factor, BF) combined with the estimated contribution to familiality (the attributable sibling relative risk, lambdas). Simulation and data from the North American Rheumatoid Consortium (NARAC) were used to assess the possible benefit under several scenarios. Simulation indicated that the allele frequencies to reach the maximum BF and the maximum attributable lambdas diverged as the size of the genetic effect increased. The representation of BF versus attributable lambdas for selected regions of NARAC data revealed that SNPs involved in replicated associations clearly departed from the bulk of SNPs in these regions. In the 12 investigated regions, and particularly in the low-recombination major histocompatibility region, the ranking of SNPs according to BF differed from the ranking of SNPs according to attributable lambdas. The present results should be generalized using more extensive simulations and additional real data, but they suggest that a characterization of genetic association by both BF and attributable lambdas may result in an improved ranking of variants for further biological analyses.
20952683 A role for lymphotoxin in primary Sjogren's disease. 2010 Nov 15 The etiology of salivary gland injury in primary Sjögren's disease is not well understood. We have previously described a mouse model of Sjögren's disease, IL-14α transgenic (IL14αTG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin α (LTA) in the pathogenesis of Sjögren's disease in IL14αTG mice. IL14αTG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14αTG mice were crossed with LTA(-/-) mice, the IL14αTG.LTA(-/-) mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14αTG and IL14αTG.LTA(-/-) mice produced similar amounts of IFN-α and had similar deposition of autoantibodies in their salivary glands. Both IL14α and IL14α/LTA(-/-) mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-κB2 in their spleens. These studies suggest that LTA plays a critical role in the local rather than systemic inflammatory process of Sjögren's disease. Furthermore, local production of soluble LTA in the salivary glands of IL14αTG mice is necessary for the development of overt Sjögren's disease. Autoantibody deposition alone is not sufficient to produce salivary gland dysfunction. We also demonstrate that LTA is increased in the salivary gland secretions and sera of patients with Sjögren's disease, further strengthening the biological relevance of the IL14αTG model to understanding the pathogenesis of human disease.
20302639 Anticentromere antibody positive Sjögren's Syndrome: a retrospective descriptive analysis 2010 INTRODUCTION: A subgroup of patients with primary Sjögren's Syndrome (SS) and positive anticentromere antibodies (ACA) were recognized as having features intermediate between SS and systemic sclerosis (SSc). Our goal was to describe this group clinically and serologically and define its tendency to evolve to full blown SSc. METHODS: Among 535 patients with primary SS we identified 20 ACA positive (ACA+/SS). We compared them to 61 randomly selected ACA negative SS patients (ACA-/SS), 31 ACA positive SSc patients with sicca manifestations [SSc/(+) sicca] and 20 ACA positive SSc patients without sicca manifestations [SSc/(-) sicca]. RESULTS: Prevalence of ACA among SS patients was 3.7%. Cases and controls did not differ in sex ratio and age at disease onset. ACA+/SS patients had a lower prevalence of dry eyes, hypergammaglobulinaemia, anti-Ro and anti-La antibodies and a higher prevalence of Raynaud's phenomenon and dysphagia compared to ACA-/SS patients. They also had lower prevalence of telangiectasias, puffy fingers, sclerodactyly, Raynaud's phenomenon, digital ulcers and gastroesophageal reflux in comparison to both of the SSc subgroups and a lower prevalence of dyspnoea and lung fibrosis compared to the SSc/(+) sicca subgroup. Two patients originally having ACA+/SS evolved to full blown SSc. Four deaths occurred, all among SSc patients. Kaplan Meier analysis showed a significant difference between cases and controls in time from disease onset to development of gastroesophageal reflux, telangiectasias, digital ulcers, arthritis, puffy fingers, xerostomia, hypergammaglobulinaemia and dysphagia. CONCLUSIONS: ACA+/SS has a clinical phenotype intermediate between ACA-/SS and SSc and shows little tendency to evolve to SSc.
20098080 Perniosis: clinical and histopathological analysis. 2010 Feb Perniosis are inflammatory cutaneous lesions, located on acral skin, which present in association with cold exposure. They can appear as an idiopathic dermatosis or with an underlying autoimmune disease. The use of cutaneous biopsy to distinguish between both types is controversial. We analyze the histological findings in 9 cases of idiopathic perniosis (IP) and compare them with those obtained from 11 cases of perniosis associated with an autoimmune disease (autoimmune perniosis). The most frequent histopathological features observed in cases of IP were a lymphocytic infiltrate with perivascular (8 cases, 89%) and perieccrine distribution (6 cases, 66%), dermal edema (5 cases, 55%), and necrotic keratinocytes (5 cases, 55%), whereas those found in perniosis associated with an autoimmune disease were lymphocytic infiltrate with perivascular distribution (11 cases, 100%) but without perieccrine distribution (3 cases, 27%), vacuolation of the basal layer (7 cases, 63%), and necrotic keratinocytes (5 cases, 45%). The only significant difference between both groups was the perieccrine distribution of the lymphocytic infiltrate in cases of IP, which, as mentioned in previous studies, could be considered a histopathological clue to differentiate both types of perniosis.
18942022 IgA rheumatoid factor in primary Sjogren's syndrome. 2009 Jan OBJECTIVE: To assess the serum level of immunoglobulin A rheumatoid factor (IgA-RF) in patients with primary Sjogren's syndrome (pSS) and study the association with immunological and clinical factors. METHODS: Sera from 97 pSS patients diagnosed according to the preliminary European criteria and 100 controls were analysed for IgA-RF in a cross-sectional study design. RESULTS: IgA-RF was detected in serum of 25.8% of the pSS patients and in 1% of the controls. In patients with positive vs. negative IgA-RF, the focus scores in biopsy of the minor salivary glands were 4.41 and 1.43 (p<0.0001), respectively. There was a correlation between positive IgA-RF and positive antinuclear antibodies (ANA) (r = 0.263, p<0.009), IgM-RF (r = 0.70, p<0.0001), anti-SSA/SSB (r = 0.73, p<0.0001), and a high serum level of IgG (r = 0.59, p<0.0001). The presence of renal disease was higher in IgA-RF-positive vs. negative pSS patients (20.0% vs. 5.6%, p = 0.047). The serum level of the hormone prolactin (PRL) correlated to the serum level of IgA-RF (r = 0.31, p = 0.026). CONCLUSIONS: The presence of IgA-RF in patients with pSS is closely associated with the presence of autoantibodies, and with focus scoring in biopsies of the salivary glands. IgA-RF is associated with renal disease in pSS but we found no correlation to other extraglandular manifestations.
20880057 Clinical features of liver dysfunction in collagen diseases. 2010 Nov AIM:   Liver dysfunction is not rare in patients with collagen disease. We sought to elucidate the clinical features of liver dysfunction in the presence of collagen disease. METHODS:   We analyzed the frequency and causes of liver dysfunction in 607 patients (rheumatoid arthritis [RA], n = 220; systemic lupus erythematosus [SLE], n = 164; systemic sclerosis [SSc], n = 47; Sjögren's syndrome [SjS], n = 44; Behçet's disease, n = 43; polymyositis/dermatomyositis [PM/DM], n = 27; vasculitis syndrome, n = 25; mixed connective tissue disease [MCTD], n = 21; and adult-onset Still's disease [AOSD], n = 16). RESULTS:   Liver dysfunction was observed in 238 (39.2%) of 607 patients showing collagen disease. Patients with AOSD (81.3%), PM/DM (51.9%) and vasculitis syndrome (48.0%) frequently displayed liver dysfunction. Liver dysfunction in collagen diseases results from many causes; drug-induced liver injury (26.1%), fatty liver (7.6%), viral hepatitis (1.3%), autoimmune hepatitis (4.2%), primary biliary cirrhosis (15.9%) and the collagen disease itself (15.5%). Conversely, primary biliary cirrhosis was a leading cause in SSc (76.1%) and SjS (70.0%). Liver dysfunction in collagen disease tended to be mild. In addition, alanine aminotransferase levels correlated positively with ferritin levels in AOSD (R = 0.708, P < 0.05). Moreover, alkaline phosphatase levels correlated positively with C reactive protein levels in vasculitis syndrome (R = 0.833, P < 0.05). CONCLUSION:   Liver dysfunction in the presence of collagen disease has various causes, and dysfunction associated with collagen disease reflects the activity of the collagen disease itself.
21794580 [A comparison of leflunomide and subcutaneous methotrexate in the treatment of rheumatoid 2009 Mar OBJECTIVE: To compare, in the Spanish setting, two drugs for adults with rheumatoid artritis (RA): leflunomide and subcutaneous methotrexate (SC). The high price of methotrexate SC compared with traditional presentations of methotrexate justifies conducting an economic evaluation comparing it with leflunomide. METHODS: The analysis considered the annual costs of the drugs and their effectiveness, measured with a Number Needed to Treat (NNT) approach, considering both the ACR20 and ACR50 criteria for effectiveness. Data about efficacy and dosage were derived from the clinical trial US310, a randomized, doble-blinded controlled trial, which compared efficacy and safety of leflunomide (20mg/daily) vs placebo vs methotrexate (7.5-15mg/weekly) in 482 patients with active RA. Data about use of medical resources for drug monitoring (visits to rheumatologists and diagnostic procedures) were derived from the manufacturers' summary of product characteristics. Direct costs (drugs and monitoring) were obtained from two Spanish databases. The analysis has been performed under the Spanish National Health System perspective. RESULTS: Using the ACR20 criteria, the NNT with leflunomide and methotrexate are 4 (95% CI, 2.56-7.71) and 5 (95% CI, 3.03-14.3) respectively. Using the ACR50 criteria, NNT are 4 (95% CI, 2.72-6.54) and 7 (95% CI, 4.03-19.3). In the case of leflunomide, annual treatment costs per patient-year equals 1,793.30€; in the case of methotrexate total treatment costs amounts to 2,149.20€. CONCLUSIONS: Combining these results the cost of a controlled patient according to ACR20 would amount 7,173€ for leflunomide and 10,746€ for methotrexate SC. Results considering ACR50 are 7,173€ and 15,044€ for leflunomide and methotrexate respectively.
20924410 The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. 2010 Nov Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.
20874646 Alternatives to calcineurin inhibition in renal transplantation: belatacept, the first co- 2010 Sep In the early 1990s, Linsley and colleagues produced a soluble fusion protein, comprising of the extracellular domain of cytotoxic T lymphocyte antigen (CTLA)4 and the human IgG1 Fc domain. Since then, several hundreds of scientific publications have demonstrated that CTLA4-Ig blocks CD28-mediated co-stimulation and suppresses unwanted T cell-mediated responses in animal models of transplantation, autoimmunity and inflammation. In the past two decades, Bristol-Myers Squibb Co. has developed abatacept, a CTLA4-Ig molecule for treating psoriasis and rheumatoid arthritis, and belatacept, a second-generation, higher affinity CTLA4-Ig molecule for use in kidney transplantation. Belatacept represents a new class of transplantation immunosuppressants and potentially offers clinicians a breakthrough therapy to preserve kidney function in the long term and reduce the side effects of current immunosuppressive therapies.
20850425 IL-7 and lymphopenia. 2011 Jan 14 Interleukin-7 (IL-7) is a growth and anti-apoptotic factor for T-lymphocytes, with potential for clinical use in the treatment of immunodeficiencies due to loss of T-cells. Lymphopenia induced by disease (HIV infection, hemodialysis or Idiopathic CD4+ lymphopenia) or by treatment (high dose chemotherapy or depleting antibodies) for cancer or auto-immune diseases results in increased circulating levels of IL-7 which decline with T-cell recovery, however, the mechanism of such response remains to be elucidated. Furthermore, IL-7 is a major player in the regulation of peripheral T-cell homeostasis and as such is an important candidate cytokine for therapy aimed at improving T-cell reconstitution following lymphopenia. Anti- IL-7 is on the other hand proposed to treat conditions where IL-7 may play a more direct role in pathogenesis such as autoimmune disease like Rheumatoid Arthritis, Multiple Sclerosis or Inflammatory Bowel disease.
20667920 Scrub typhus associated macrophage activation syndrome. 2010 Oct Macrophage activation syndrome (MAS) is a rare phenomenon that occurs either primarily or secondary to a multitude of conditions, including juvenile rheumatoid arthritis most commonly, and other infections like enteric fever and tuberculosis. It has been reported as an extremely rare complication of scrub typhus with no cases presented from India. We report three cases of scrub typhus presenting with confirmed MAS between January 2007 and December 2007 to a tertiary care hospital in South India. All three patients had clinical and laboratory evidence for scrub typhus and MAS. All the patients responded promptly to antibiotics and made an uneventful recovery. These three patients are presented to highlight the importance of considering scrub typhus in patients with MAS following acute febrile illnesses.
20587340 A molecular Trojan horse: hijacking the bone marrow to treat autoimmune diseases. 2010 Jun Autoimmune diseases such as multiple sclerosis, type 1 diabetes, systemic sclerosis, and rheumatoid arthritis affect approximately 5% of the population and are characterized by a destructive immune response directed to self-tissues. Treatments are often designed to dampen the immune system and are therefore associated with unwanted side effects. A major challenge is to find a cure that does not compromise normal immune function. From our understanding of how the immune system develops, it is clear that mechanisms designed to eliminate or maintain control over self-reactive clones are critical for normal health. These key concepts form the crux of many experimental strategies currently aimed at abrogating the autoimmune response. In this review, we focus on the strategy of harnessing the bone marrow compartment through genetic manipulation directed at promoting ectopic autoantigen expression. Our experience with this strategy is presented in the context of reports in the literature and we argue for the potential benefit of translating this approach to the treatment of human autoimmune disease.
20536447 Thymosin beta4 and its posttranslational modifications. 2010 Apr Thymosin beta(4) as well as the other members of the beta-thymosin family are important G-actin sequestering peptides. The chemical properties, the biosynthesis, and posttranslational modifications (PTMs) of these peptides are discussed. During biosynthesis of thymosin beta(4) the initiator methionine is removed and the N-terminus is acetylated. Research on proteomics revealed several acetylated lysine residues and two phosphorylated threonine residues. The enormous number of phosphorylable and acetylable sites in the human proteome raises the question about the biological significance of these PTMs in the context of beta-thymosins. Presently, this question cannot be answered because neither the concentration of these modified beta-thymosins in cells is known nor the consequences of the modifications on the biological function(s) of beta-thymosins have been studied yet. Thymosin beta(4) is also posttranslationally modified by transglutaminase forming covalent bonds with other molecules. Prolyl oligopeptidase generates ac-SDKP from thymosin beta(4). The concentration of C-terminal peptide fragments of thymosin beta(4) is elevated in the blood of patients with rheumatoid arthritis.