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ID PMID Title PublicationDate abstract
20018030 Non-redundant summary scores applied to the North American Rheumatoid Arthritis Consortium 2009 Dec 15 After performing a genome-wide association study, it is often difficult to know which regions to follow up, especially when no one marker reaches genome-wide significance. Researchers frequently focus on their top N findings, knowing that true associations may be buried deeper in the list. Others focus on genes or regions that have multiple markers showing evidence of association. However, these markers are often in high linkage disequilibrium with one another (r2 > 0.80), which indicates that these additional markers are providing redundant information. I propose a novel method that identifies regions with multiple lines of evidence, by down-weighting the contribution of additional markers in proportion to pairwise linkage disequilibrium. I have used this non-redundant summary score in my analysis of the North American Rheumatoid Arthritis Consortium dataset released as part of Genetic Analysis Workshop 16. Three regions were identified that had a genome-wide empirical p-value less than 0.01, including one novel region on chromosome 20 near the KCNB1 and PTGIS genes.
20017976 Accommodating population stratification in case-control association analysis: a new test a 2009 Dec 15 It is well known that conventional association tests can lead to excessive false positives when there is population stratification. We propose a new test for detecting genetic association with a case-control study design. Unlike some other methods for handling population stratification, we treat the cases as a population and the controls as another one even though each of them may be a mixture of several sub-populations. A likelihood-ratio test is used to test whether the allele frequency of a testing single-nucleotide polymorphism in the case population is the same as that in the control population. This new test is applied to the Genetic Analysis Workshop 16 Problem 1 data on rheumatoid arthritis. Compared with the Pearson chi-square genotype test, the association strength of many single-nucleotide polymorphisms is decreased while the signal at the HLA region on 6p21 is maintained.
20018062 Identification of genes and haplotypes that predict rheumatoid arthritis using random fore 2009 Dec 15 Random forest (RF) analysis of genetic data does not require specification of the mode of inheritance, and provides measures of variable importance that incorporate interaction effects. In this paper we describe RF-based approaches for assessment of gene and haplotype importance, and apply these approaches to a subset of the North American Rheumatoid Arthritis Consortium case-control data provided by Genetic Analysis Workshop 16. The RF analyses of 37 genes identified many of the same genes as logistic regression, but also suggested importance of certain single-nucleotide polymorphism and genes that were not ranked highly by logistic regression. A new permutation method did not reveal strong evidence of gene-gene interaction effects in these data. Although RFs are a promising approach for genetic data analysis, extensions beyond simple single-nucleotide polymorphism analyses and modifications to improve computational feasibility are needed.
20017974 Simultaneous analysis of all single-nucleotide polymorphisms in genome-wide association st 2009 Dec 15 The availability of very large number of markers by modern technology makes genome-wide association studies very popular. The usual approach is to test single-nucleotide polymorphisms (SNPs) one at a time for association with disease status. However, it may not be possible to detect marginally significant effects by single-SNP analysis. Simultaneous analysis of SNPs enables detection of even those SNPs with small effect by evaluating the collective impact of several neighboring SNPs. Also, false-positive signals may be weakened by the presence of other neighboring SNPs included in the analysis. We analyzed the North American Rheumatoid Arthritis Consortium data of Genetic Analysis Workshop 16 using HLasso, a new method for simultaneous analysis of SNPs. The simultaneous analysis approach has excellent control of type I error, and many of the previously reported results of single-SNP analyses were confirmed by this approach.
21794638 [Biologics as first line therapy in the treatment of rheumatoid arthritis. A posture a fav 2009 Apr Changes in diagnosis and treatment of rheumatoid arthritis oblige us to question clinical practice. Evidence demonstrates that the combination of biologics and methotrexate in rapid increments leads to larger remission rates than methotrexate alone. The combination has a faster clinical response in activity, physical function, quality of life, fatigue and sleep. But the most significant effect of biologics is on radiographic progression. The reduction in radiological damage has a spectrum that goes from anti-TNF+methotrexate to anti-TNF monotherapy, being less with methotrexate, and independent from improvement in activity; it occurs with all of the anti-TNF drugs and with other targets with different mechanisms of action (anti-CD20, T cell costimulation inhibitors and anti IL-6). The clinical significance of this finding will be seen in the future, when more is known of its impact on the poor outcomes of RA patients. Because methotrexate is an excellent drug, it seems madness to say that all patients should receive biologics+methotrexate, but it is reasonable to consider that a subgroup must receive them from the start. The American College of Rheumatology recommends their use in patients with RA of less than 6 months since onset, with no previous exposure to methotrexate, persistent and elevated activity (<3 months) and poor prognostic factors or those with persistent and elevated activity (3-6 months) independent of poor prognostic factors, and if the patient "has insurance". A final thought would be: Is there a new treatment pyramid which has cost at its base now?
19790120 The prevalence of psoriatic arthritis in people with psoriasis. 2009 Oct 15 OBJECTIVE: To determine the prevalence of psoriatic arthritis (PsA) using the ClASsification criteria for Psoriatic ARthritis (CASPAR) for classification. METHODS: People with psoriasis were identified from the computerized morbidity indices of 2 large UK general practices, total population 22,500. Questionnaires were mailed to all 633 patients thus identified. Of the respondents, a 50% sample was assessed clinically and a proportion had blood samples and radiographs taken. Patients labeled as having psoriasis were also cross-referenced with a local secondary care morbidity index for PsA and rheumatoid arthritis. Figures for the prevalence of PsA were estimated from these data. RESULTS: One hundred sixty-eight questionnaires were returned (response rate 27%) and 93 people (55% of questionnaire respondents) were examined. Of these 93 people, 12 (4 of whom were cross-referenced to the hospital database) were thought to have PsA clinically, all fulfilling the CASPAR criteria for PsA. Six of the 93 examined patients did not have psoriasis or a family history of psoriasis and had no historical features or clinical signs of psoriasis on interview and examination. Extrapolating from the data of those people actually examined, the estimated (corrected) prevalence was 13.8% (95% confidence interval 7.1-24.1%). CONCLUSION: The estimated prevalence of PsA in this population, using the CASPAR criteria, was 13.8%. Misclassification of psoriasis and arthritis, and response bias, indicate that this is probably an overestimate.
19661549 Resistant cases of psoriatic arthritis: how to manage them. 2009 Aug Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2%-3% of the Caucasian population. Psoriatic arthritis (PsA), which occurs in up to one-third of patients with psoriasis, has a heterogeneous pattern expressed by various manifestations, including mono-oligoarthritis, an erosive and destructive polyarthritis indistinguishable from rheumatoid arthritis (RA), and spondyloarthropathy with axial involvement or enthesitis. Early detection of inflamed joints or axial involvement in patients with PsA is important in order to reduce inflammation and prevent joint destruction, deformity, and functional disability. The treatment of moderate-severe PsA has tended to include the same disease modifying antirheumatic drugs used to treat RA, but there is much less evidence supporting their efficacy and essentially none demonstrating that they slow radiographic joint destruction in PsA. A number of clinical trials have shown that tumor necrosis factor antagonists are generally safe and efficacious in the treatment of PsA, and can inhibit the progression of radiographic damage.
19493332 Locomotion and muscle mass measures in a murine model of collagen-induced arthritis. 2009 Jun 3 BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model. METHODS: CIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail. RESULTS: There is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass. CONCLUSION: The present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.
20209743 Characteristics of subjects self-reporting arthritis in a population health survey: distin 2009 Nov OBJECTIVES: Arthritis is a broad term covering disparate diseases with varying prognoses. Epidemiological surveys are important tools for arthritis research, but they either fail to specify arthritis subtypes or they provide self-reported arthritis data that are potentially misclassified. This limits their use for research about arthritis subgroups. This study describes and compares characteristics of subjects self-reporting subtypes of arthritis in a Canadian epidemiological survey. We also consider the feasibility of developing methods for distinguishing subtypes of arthritis in such population surveys. METHODS: Using data from 119,904 adult participants in the Canadian Community Health Survey (CCHS) cycle 3.1, we identified those self-reporting one of four subtypes of arthritis and compared the four groups with regard to socio-demographic status, lifestyle and health characteristics, medication use, health care utilization and functional outcomes. Cross-tabulations of weighted prevalence were estimated and tested for statistical significance using the chi-square test. RESULTS: Descriptive results showed very few distinguishing characteristics across self-reported arthritis subtypes on 34 investigated variables. Participants with osteoarthritis were more likely to be older and female than other groups. Statistical testing showed no difference between rheumatoid arthritis, osteoarthritis and "other" type of arthritis for physical activity level, health conditions, medication use, health care utilization and functional limitations. DISCUSSION: Characteristics of subjects who self-report different types of arthritis in a typical population health survey (CCHS) are not sufficiently dissimilar to justify valid data analyses and interpretation by arthritis subgroup. Future studies might focus on identifying and implementing supplemental questionnaire items in epidemiological population surveys.
19644903 Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of 2009 Aug 15 OBJECTIVE: To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. RESULTS: Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. CONCLUSION: Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term.
21108570 A case of bovine valve endocarditis caused by Engyodontium album. 2011 May We report the first case of Engyodontium album bioprosthetic valve endocarditis in a 44-year-old male with a history of juvenile rheumatoid arthritis. There is only one other report of Engyodontium album as a human pathogen. The present case supports the increased incidence of fungal endocarditis especially in patients receiving immunotherapy.
21290858 [Progressive pseudorheumatoid chondrodysplasia. Case report]. 2010 Nov We present the case of a 17-year-old patient suffering from progressive pseudorheumatoid chondrodysplasia from whom 2 total hip prostheses and 2 total knee prostheses were necessary. We have to do with a recessive autosomal genetic disorder characterized by a lysis of the articular cartilage. This leads to an early degeneration of the joints. The clinic is mainly characterized by various complaints such as joint pain, stiffness, limitation or swelling causing a significant motor disability from childhood. The first joints affected are situated in the hands, later followed by the hips, elbows and knees. The X-rays show severe, multifocal articular degenerative modifications which are unusual for the age. The genetic mutation concerns the WISP 3 gene actively expressed by articular chondrocytes and located on chromosome 6. The differential diagnosis is done with a series of rheumatologic disorders in children and autoimmune diseases. We mainly retain the juvenile rheumatoid arthritis. A symptomatic medical treatment can be undertaken first. However, given the evolving nature of the pathology, a joint replacement surgery is needed once the child's growth is finished (second decade of life).
21162916 [Malignant lymphoma associated with primary Sjögren's syndrome]. 2010 Oct 26 OBJECTIVE: To address the clinical features of malignant lymphoma (ML) occurring in primary Sjögren's syndrome (pSS), understand their similarities and differences and explore their risk factors. METHODS: Medical records of 17 cases of pSS/ML inpatients admitted to our hospital from January 1980 to August 2010 were systemically reviewed. And 163 cases were randomly selected as controls from 4485 pSS/nML inpatients at our hospital during the same period. RESULTS: There were 14 females and 3 m ales with the diagnostic age of pSS at (53 ± 13) years old. And the disease duration was (8 ± 9) years. There was no significant difference between two groups in three general aspects (P > 0.05). The gap between pSS and ML was (4 ± 4) years. Several significant differences existed between two groups (P < 0.05) in clinical features and laboratory findings: lymphadenopathy, parothydomegalia and leucopenia. The pathologic categories of ML in pSS/ML included NHL (n = 15) (14 cases of B-cell origin), HL (n = 1) and lymphosarcoma (n = 1). CONCLUSION: During the course of pSS, the occurrence of such manifestations as lymphadenopathy, parothydomegalia and leucopenia, etc.tends to have a complication of ML with a dominance of NHL. And a worse prognosis is expected.
20360662 Sjögren's syndrome: correlation between histopathologic result and clinical and serologic 2010 Apr AIM: Sjögren's syndrome (SS) represents a challenging illness to diagnose properly and, because of the serious complications such as lymphoma, it is important to reach a correct diagnosis in early stages. Aim of this retrospective study was to evaluate the correlation between histopathologic result of minor salivary gland biopsy and clinical and serologic parameters for the diagnosis of SS. METHODS: We evaluated 360 biopsies, taken from the lower lip, of 360 patients (18 males) on suspicion that they were suffering from SS. The Chisolm and Mason classification was used to state the diagnosis of SS. For each patient, the medical history and the symptoms were evaluated, and diagnostic tests were performed. The revised rules of the American-European Consensus Group Criteria were used to diagnose primary and secondary SS. For the statistical analysis we used the Chi(2) test; a difference of P<0.05 was considered significant. RESULTS: Considering the statistical correlation between a focal score > or =1 and the serological data, it was noted that a positive score was significantly correlated to all serological parameters examined (P<0.0001). A significant correlation was also found between a positive biopsy score and Schirmer's test and Rose Bengal test (P<0.0001). However, with regard to the clinical data, a significant correlation was found only for two parameters: xerostomia (P<0.0001) and parotid swelling (P<0.05). CONCLUSION: Minor salivary gland biopsies are of great diagnostic value in detecting SS. However, for the diagnosis of SS both clinical and serologic parameters should be considered. The data obtained from the present survey reveal that the serologic markers are more predictive than clinical parameters for a positive biopsy score.
19245858 Assessment of salivary gland function in Sjögren's syndrome: the role of salivary gland s 2009 Jul Salivary gland scintigraphy (SGS) is a non invasive method of salivary gland function assessment. This technique is easy to perform, reproducible and well tolerated by patients. Additionally, an abnormal salivary gland scintigraphy result is accepted by the American-European consensus group as a criterion for the diagnosis of Sjögren's syndrome. Scintigraphic evaluation of salivary gland function also plays an important role in therapeutic decision and patient follow-up. Schall's categorical classification is usually considered the standard method for salivary scintigraphy interpretation, though subjective and with limited capacity to discriminate borderline results. In order to improve the diagnostic accuracy of SGS, there has been an increasing interest in the quantification of glandular function. However, the debate on the most reliable and suitable parameters for the diagnosis of SS persists.
19811297 Whole body low dose irradiation improves the course of beginning polyarthritis in human TN 2009 May Rheumatoid arthritis (RA) displays a chronic inflammatory joint disease, accompanied by symmetric polyarthritis (PA) which evokes synovial inflammation, cartilage damage, and bone erosion. Patients with RA are routinely treated by immunosuppressive drugs. The therapy of inflammatory diseases and degenerative disorders with Low-dose radiotherapy (LD-RT) (single doses from 0.3 to 1.0 Gy) represents a low cost therapy with low toxicity, and is able to substitute at least in part treatment with drugs. The efficiency of LD-RT has already been proven in several animal models of inducible arthritis. In the present study we used a human TNF transgenic mouse model to examine the effects of LD-RT on PA. We observed a significant temporal improvement of the clinical progression of disease when mice were irradiated at the beginning of the disease. These data emphasize the role of LD-RT in clinical settings to treat patients with chronic and degenerative disorders and diseases.
20137605 [Characteristics of patients with primary Sjögren's syndrome and non-Hodgkin's lymphoma: 2009 Oct 27 OBJECTIVE: To characterize the clinical patterns of expression, laboratory serologic parameters and lymphomatous histological characteristics in patients with primary Sjögren's syndrome (pSS) who subsequently developed non-Hodgkin's lymphoma (NHL). METHODS: The authors analyzed 9 pSS patients (8 females, 1 male) who developed NHL. Five patients had received glucocorticoids, four of whom had received at least one immunosuppressive drugs (methotrexate, glucosidorum tripterygll totorum, cyclophosphamide and imuran). A protocol form was used to record the main characteristics of pSS and NHL. RESULTS: Eight patients fulfilled the American-European Consensus Criteria (AECC). The main SS manifestations were painless parotid enlargement (n = 7), six of whom were unilateral; the main immunologic features were positive rheumatoid factor (RF) in all examined patients and hyperimmunoglobulinemia (n = 7). The main manifestations of NHL were splenomegaly (n = 7) and lymphadenopathy (n = 5). The main histological subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma (n = 4) and diffuse large B cell lymphoma (n = 2). None of the patients with MALT lymphoma had a nodal primary location. Eight patients had an extranodal primary location, most frequently in salivary gland (n = 4) and lung (n = 4). CONCLUSION: Patients with pSS and NHL are clinically characterized by a high frequency of painless unilateral parotid enlargement, splenomegaly, lymphadenopathy, an immunologic pattern dominated by the presence of high-titer RF and hyperimmunoglobulinemia, a predominance of MALT lymphomas and an elevated frequency of primary extranodal involvement.
19306000 Portal vein thrombosis in adult-onset Still's disease: a case report and literature review 2009 Oct Adult-onset Still's disease (AOSD) is a systemic inflammatory disease in which a variety of thrombotic events may occur. However, to our knowledge, portal vein thrombosis (PVT), a potential cause of gastrointestinal bleeding, has not been described in the English literature. A previously well 47-year-old man diagnosed with AOSD showed a transient increase in serum transaminase level. A careful observation led to a prompt discovery of a re-increase in serum transaminase level and PVT that involved an entire left portal vein plus parts of supramesenteric vein. PVT resolved completely in 6 months, and the patient remained well for at least 1 year receiving anticoagulants plus an immunosuppressant that selectively inhibits guanosine monophosphate synthesis in the purine metabolism pathway. Thrombotic events, if not lethal, deteriorate the quality of life in AOSD patients. This report illustrates the spectrum of AOSD and underlines the need to include PVT in differential diagnosis if serum liver enzyme levels fluctuate.
19424660 An unusual case of autoimmune hepatitis in a patient with adult-onset Still's disease. 2010 Jan Adult-onset Still's disease (AOSD) is an autoimmune disease characterized by spiking fever, evanescent rash, arthritis, serositis, and liver involvement. Although autoimmune hepatitis (AIH) has been reported in association with various autoimmune diseases, AOSD-associated AIH is rare. We herein report an unusual case of AIH in a patient with AOSD.
20199209 A new kind of and reversible brainstem involvement in primary Sjögren's syndrome as an in 2010 Feb The prevalence of abnormalities on brain magnetic resonance imaging (MRI) varies in primary Sjögren's syndrome (pSS) patients and they are generally multiple hyperintense areas in the subcortical and periventricular white matter on T2-weighted and fluid-attenuated inversion recovery sequences. Here, we report brainstem involvement in a patient with pSS that was extensive on MRI, but reversible. The patient's outcome was positive. To our knowledge, a similar case has not previously been described.