Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
12022325 Differences in the profiles of circulating levels of soluble tumor necrosis factor recepto 2002 May OBJECTIVE: To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity. METHODS: Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity. RESULTS: Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions. CONCLUSION: The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.
15479355 Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with 2004 Oct 15 BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. AIM: To survey side-effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A computerized search using the term 'azathioprine' or 'imuran' was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine-toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine-induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.
15186274 Variations in histological patterns of interstitial pneumonia between connective tissue di 2004 Jun AIMS AND METHODS: Pulmonary parenchymal disease is common in patients with connective tissue disorders (CTDs). However, most reports precede recognition of non-specific interstitial pneumonia (NSIP). We have therefore reviewed 54 lung biopsies from 37 patients with polymyositis/dermatomyositis (PM/DM) (n = 13), Sjögren's syndrome (n = 5), rheumatoid arthritis (n = 17) and systemic lupus erythematosus (SLE) (n = 2) to assess the overall and relative frequencies of patterns of interstitial pneumonia and their impact on prognosis. RESULTS AND CONCLUSIONS: NSIP was the most common pattern with an overall biopsy prevalence of 39% and patient prevalence of 41%. There was variation in prevalence between individual CTDs, with PM/DM commonly showing organizing pneumonia (n = 5), rheumatoid arthritis showing follicular bronchiolitis (n = 6) and Sjögren's syndrome showing chronic bronchiolitis (n = 4). These patterns presented either separately or in association with NSIP, occasionally with different patterns in biopsies from separate lobes. Only four patients showed a pattern of usual interstitial pneumonia (UIP): two with rheumatoid arthritis and one each with PM/DM and SLE. Overall mortality was 24%, the most frequently associated pattern being fibrotic NSIP (n = 5). In nine cases, pulmonary presentation preceded the systemic manifestation of the CTDs. When patients with CTDs present with chronic interstitial lung disease, the most common pattern is NSIP, although there is variation in pattern prevalence between individual disorders and patterns of interstitial pneumonia frequently overlap. These data suggest a different biology for intestitial pneumonias in CTDs when compared with the idiopathic interstitial pneumonias where UIP is the most common pattern. Mortality is similar to that seen in idiopathic NSIP and, coupled with pulmonary presentation occurring prior to the systemic manifestation of disease, this may have a bearing on the origin of some cases of putative idiopathic NSIP.
11927204 Self-rated health, chronic diseases, and symptoms among middle-aged and elderly men and wo 2002 Apr The objective was to study the association between chronic diseases, symptoms, and poor self-rated health among men and women and in different age groups, and to assess the contribution of chronic diseases and symptoms to the burden of poor self-rated health in the general population. Self-rated health and self-reported diseases and symptoms were investigated in a population sample of 6,061 men and women aged 35-79 years in Värmland County in Sweden. Odds ratios (OR) and population attributable risks (PAR) were calculated to quantify the contribution of chronic diseases and symptoms to poor self-rated health. Depression, neurological disease, rheumatoid arthritis, and tiredness/weakness had the largest contributions to poor self-rated health in individuals. Among the elderly (65-79 years), neurological disease and cancer had the largest contribution to self-rated health in men, and renal disease, rheumatoid arthritis, and cancer in women. Among the middle-aged (35-64 years), depression and tiredness/weakness were also important, especially in women. From a population perspective, tiredness/weakness explained the largest part of poor self-rated health due to its high prevalence in the population. Depression and musculoskeletal pains were also more important than other chronic diseases and symptoms at the population level. Even though many chronic diseases (such as neurological disease, rheumatoid arthritis, and cancer) are strongly associated with poor self-rated health in the individual, common symptoms (such as tiredness/weakness and musculoskeletal pains) as well as depression contribute more to the total burden of poor self-rated health in the population. More preventive measures should therefore be directed against these conditions, especially when they are not consequences of other diseases.
14528510 Prevalence of antibodies against alpha-fodrin in Sjögren's syndrome: comparison of 2 sets 2003 Oct OBJECTIVE: To compare the prevalence of antibodies against alpha-fodrin in Sjögren's syndrome (SS) classified according to San Diego and European Community Study Group (ESG) criteria. METHODS: The prevalence and mean concentrations of IgA and IgG autoantibodies against alpha-fodrin were determined and compared in patients with SS classified either according to San Diego criteria or to criteria of the ESG by ELISA. RESULTS: IgA antibodies against alpha-fodrin were detected in 88% and IgG antibodies against alpha-fodrin in 64% and either of these antibodies in 93% of 85 patients classified according to San Diego criteria. Antibodies against Ro were present in 38% of these sera. IgA antibodies against alpha-fodrin were detected in 61%, IgG antibodies against alpha-fodrin in 51%, and any of these antibodies in 73% of 51 patients classified according to the ESG criteria. The mean concentrations of both IgA and IgG antibodies against alpha-fodrin that seem to correlate with disease activity were higher in patients classified according to the San Diego criteria. CONCLUSION: Antibodies against alpha-fodrin are detectable in almost all sera obtained from patients with SS classified according to the San Diego criteria and are significantly more prevalent than antibodies against Ro. The lower prevalence of the autoantibodies in patients classified according to the ESG criteria reflects the lower specificity of these criteria for SS.
12209037 The role of interleukin-10 promoter polymorphisms in the clinical expression of primary Sj 2002 Sep OBJECTIVE: To analyse the role of polymorphisms of the interleukin-10 promoter region in the epidemiologic, clinical and immunologic characteristics of patients with primary Sjögren's syndrome (SS). METHODS: Sixty-three consecutive patients (59 women and four men; mean age 57 yr; range 20-83 yr) were studied in our Unit. All patients fulfilled four or more of the modified diagnostic criteria for SS proposed by the European Community Study Group in 1996. As controls, 150 healthy volunteers were recruited from the medical and laboratory staff working in our hospital. All the samples from patients and controls were analysed by PCR amplification and direct sequencing. RESULTS: The frequency of the interleukin-10 (IL-10) GCC haplotype was higher (0.48 vs 0.34, P=0.006) and the frequency of the IL-10 ACC haplotype lower (0.25 vs 0.39, P=0.005) in patients with primary SS compared with healthy controls. In the genotype analysis, the frequency of the GCC/ATA genotype was higher (29 vs 11%, P=0.001) and that of the ACC/ACC genotype lower (3 vs 12%, P=0.044) in patients with primary SS compared with healthy controls. GCC-carriers showed an earlier onset of the disease (48.06+/-14.98 yr vs 57.53+/-14.20 yr, P=0.034). The existence of systemic involvement (defined by cutaneous vasculitis, peripheral neuropathy, renal and/or pulmonary involvement) was more frequent in carriers of the GCC haplotype, although the difference did not reach statistical significance (40 vs 27%, P=0.278). No significant differences in the haematologic (hypergammaglobulinaemia, elevated ESR) and immunologic (ANA, RF, anti-Ro/SS-A and anti-La/SS-B antibodies) parameters were observed in carriers of the GCC haplotype. CONCLUSION: We describe an abnormal distribution of IL-10 promoter haplotypes in patients with primary SS compared with healthy controls. This consists of a predominance of the GCC haplotype, mainly related to a higher frequency of the heterozygote haplotype GCC/ATA. The presence of the GCC haplotype does not originate a different immunologic pattern but leads to an earlier onset of primary SS.
15529948 Alterations of the sympathovagal balance evaluated by heart rate variability in a rare cas 2004 Jul We present a rare case of adult Still's disease with cardiac involvement (myocarditis and coronary arteritis). The autonomic nervous system function was evaluated by heart rate variability (HRV) analysis performed by 24-hour electrocardiographic recording during the acute phase of the disease and the remission (after 1 month and 1 year). The HRV parameters were studied in the time (standard deviation of all NN intervals-total power - SDNN, square root of the mean of the sum of the squares of the differences between adjacent NN - RMS-SD and HRV index) and frequency domains (low frequency, high frequency, and low frequency/high frequency). The results of the analysis of the HRV highlight that in the acute phase of the disease with cardiac involvement the autonomic nervous system is globally altered, with modifications of the sympathovagal balance, due to impairment of the parasympathetic component. This trend tends to persist in the short period (1 month), but seems to resolve completely within 1 year. An altered sympathovagal balance should be considered as a possible marker of vasculitis-related ischemia.
11850593 Association Between FcgammaR IIa and IIIa polymorphism and clinical manifestations in Kore 2002 Feb High-dose intravenous immunoglobulins alter the disease activity of adult-onset Still's disease (AOSD). Because activation status of FcgammaR is possibly dependent on their genetic polymorphisms, we investigated whether the polymorphisms of FcgammaR IIa and IIIa are risk factors, and affect the clinical features of AOSD. Genomic DNA was extracted from 36 patients and from 197 healthy controls. Polymerase chain reaction for FcgammaR IIa and IIIa using the allele-specific primers and direct sequencing of FcgammaR IIIa polymorphic site were performed. The frequencies of FcgammaR IIa/IIIa genotype between patients with AOSD and controls were not different. The allelic frequencies of FcgammaR IIa/IIIa between patients with AOSD and controls were not different, either. However, the FcgammaR IIa-R/R131 genotype was associated with a higher concentration of hemoglobin (p=0.04) and stable liver function (p=0.009) than the other genotypes. The FcgammaR IIIa-F/F176 genotype was associated with significantly lower titers of serum ferritin (p=0.025), and higher serum albumin (p=0.037) and cholesterol (p=0.014) concentrations than the other genotypes. This study suggest that the FcgammaR IIa and IIIa polymorphisms might not be genetic risk factors for AOSD in Korean, but contribute to the activity of disease. FcgammaR IIa-R/R131 and IIIa-F/F176 genotypes, low-binding genotypes for IgG2a and G1, may have more protective effects in acute stage of the disease than the other genotypes.
15112192 Collapsing glomerulopathy in adult still's disease. 2004 May Idiopathic collapsing glomerulopathy is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis characterized clinically by a male and Afro-Caribbean racial predominance, proteinuria (often nephrotic range), and rapid progression to end-stage renal failure. Pathologically, the typical changes are global glomerular collapse leading to obliteration of glomerular capillary lumina, hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial changes. A secondary form with almost identical pathologic features is described in association with human immunodeficiency virus infection. We describe a female patient who presented with multisystemic manifestations, including high spiking fever, arthralgias, lymphadenopathy, striking hyperferritinemia, and impaired renal function with proteinuria. Renal biopsy showed classic collapsing glomerulopathy. A diagnosis of adult Still's disease was made on the basis of Yamaguchi's criteria. The patient was treated with steroids, resulting in remission of the rheumatological condition closely paralleled by remission of proteinuria and renal function, thereby strongly suggesting a causative link between adult Still's disease and collapsing glomerulopathy in this patient. We propose that collapsing glomerulopathy ought to be considered in adult Still's disease with unexplained renal insufficiency or proteinuria.
15034959 [Collagen diseases and recurrent meningitis in an 88 year old patient]. 2004 Recurrent aseptic meningitis (RAM) infrequent in elderly patients and generally secondary to drugs. Its association with rheumatologic diseases is also seldom reported in the elderly. Sjögren Syndrome (SS) sometimes affects the central nervous system, but the association between recurrent meningitis and SS is rare, specially in this age-group. We present an 88 year-old auto-valid patient, with a history of xerostomia, xerophthalmia, Raynaud, dysphagia, and recurrent parotid enlargement. In 2001 she developed a lymphocytic meningitis with a complete remission. A year later, she developed again an aseptic lymphocytic meningitis. We ruled out infectious causes. We found a FAN titer 1/160 with a nucleolar-mottled pattern, positive anti Ro and anti RNP antibodies and a positive lupus anticoagulant. We confirmed the ocular dryness and the lip biopsy was compatible with the diagnosis of SS. She had a good outcome with a complete remission without treatment in 10 days. We believe that this is a case of mixed connective tissue disease (MCTD) with predominant symptoms of SS, that developed a recurrent meningitis in its pure form. MCTD and SS should be considered in the differential diagnoses of RAM, also in the elderly.
12424971 [A case of Sjögren's syndrome with heat intolerance induced by generalized anhidrosis as 2002 Feb A 60-year-old man was admitted to our hospital because of heat intolerance induced by generalized anhidrosis. There were no abnormal findings on physical and neurological examinations except for anhidrosis. Reflex sweating to pilocarpine and acetylcholine was absent. Skin biopsy revealed no abnormalities of the sweat glands and ducts. Laboratory tests showed elevated levels of serum IgG and rheumatoid factor. Anti-nuclear antibodies, and antibodies to Sjögren's syndrome A and B were positive. Ocular examination revealed the presence of keratoconjunctivitis sicca. The pathological findings of minor salivary gland specimen confirmed a diagnosis of Sjögren's syndrome. This case suggests that generalized anhidrosis could be caused by the antigen-antibody reaction for the cholinergic receptor of sweat gland.
12353347 Primary Sjögren's syndrome with protein-losing gastroenteropathy: report of two cases. 2002 Jul Protein-losing gastroenteropathy is a rare complication in autoimmune diseases, especially in Sjögren's syndrome. We report two cases of primary Sjögren's syndrome, one in a 37-year-old female and another in a 50-year-old female, both of whom presented with peripheral edema. Protein-losing gastroenteropathies of the stomach and small intestine in the first patient and of the small intestine only in the second patient were demonstrated by abdominal Tc-99m labeled albumin abdominal scintigraphy and pathologic findings. Results of gastrointestinal tract biopsies from both patients showed chronic inflammatory cell infiltrations without lymphangiectasis or vasculitis. The patients were successfully treated with corticosteroids. Results of follow-up Tc-99m labeled albumin scintigraphy were well correlated with clinical improvement and the increase in serum albumin. Sjögren's syndrome should be considered as a cause of protein-losing enteropathy. Tc-99m labeled albumin abdominal scintigraphy is helpful in diagnosing the condition, locating the protein-losing sites, and monitoring the treatment outcome, especially in cases where protein loss occurs in the stomach.
15194588 Incidence of primary Sjogren's syndrome in Slovenia. 2004 Jul OBJECTIVE: To determine the annual incidence of primary Sjögren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.
11914812 Primary Sjögren's syndrome initially manifested by optic neuritis: MRI findings. 2002 Apr We herein describe the MRI findings in a patient clinically diagnosed with primary Sjögren's syndrome (SjS) initially manifested by retrobulbar optic neuritis. A 63-year-old woman suddenly had left ocular pain and progressive visual disturbance. MR T2-weighted images revealed hyperintensity in the left optic nerve, with swelling. Contrast-enhanced T1-weighted images showed no abnormal enhancement. Follow-up MRI 6 months after admission revealed no significant changes in the affected optic nerve. To our knowledge, optic neuritis as a complication of SjS has been reported in ten patients [1, 2, 3, 4, 5, 6] and MRI findings in only one of them [6]. We thought MR images were useful for visualizing optic nerve involvement in SjS and observing its course.
15651280 [A case of multiple pulmonary infarctions associated with Sjögren's syndrome and antipsyc 2004 Nov A 56-year-old woman presented with complaints of general malaise and left chest pain. Chest radiography and CT scanning revealed multiple nodules and infiltrations in both lung fields. Her symptoms diminished and the extent of some of the lung shadows decreased spontaneously. However, since new shadows appeared later in other parts of the lung, she was admitted to our hospital on September 3. A transbronchial lung biopsy was not adequate for diagnosing a particular disease. But thoracoscopic lung biopsy specimens revealed necrosis with localized pleural fibrosis, and so a diagnosis of pulmonary infarction was made. The patient did not have any underlying disease or coagulation abnormalities, but Sjögren's syndrome and an antipsychotic agent were suspected to be background factors.
14631125 High frequency of primary Sjögren's syndrome in Taiwanese patients presenting as relapsin 2004 Primary Sjögren's syndrome (PSS) with central nervous system involvement may mimic the manifestations of multiple sclerosis (MS). The prevalence of PSS in MS patients varies in the published literature (0-16.6%), but has not yet been investigated in Asia, having a much lower MS prevalence than Western countries. Twelve consecutive patients presenting with a relapsing-remitting MS-like syndrome were recruited to assess the presence of PSS according to the American-European consensus group criteria. Six patients (50%) fulfilled the diagnostic criteria of PSS. The preliminary result suggests that PSS is an important differential diagnosis in patients with MS-like syndrome in Taiwan. The prevalence of 'pure MS' in Taiwan might be even lower than expected. A further large-scale study is warranted to confirm this finding in Taiwan as well as other Asian countries.
12847443 Primary Sjögren syndrome in childhood: report of a case and review of the literature. 2003 Jul Sjögren syndrome (SS) in childhood is a rare and possibly underdiagnosed condition. The purpose of this study is to report a case of primary SS (PSS) in a 4-year-old Venezuelan girl and to review the pertinent literature. The patient presented with bilateral recurrent parotid enlargement, predominantly on the right side. She did not complain of dry mouth or eyes; however, decreased stimulated salivary flow rate and positive Schirmer and rose bengal tests were obtained. Sialography, sonograms, and a computed tomography scan of the parotid glands revealed pathologic changes consistent with SS. Anti-SS-A and anti-SS-B antibodies were present. Evaluation for antibodies against cytomegalovirus, Epstein-Barr virus, and HIV rendered negative results. Histopathologic examination of incisional biopsies of the right parotid and labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. Taken together, these findings are consistent with the diagnosis of juvenile PSS. The salient features of this rare disease are summarized on the basis of a comprehensive review of the epidemiologic, clinical, and serologic findings of the previously reported cases of PSS in children.
11886973 Miller Fisher syndrome in adult onset Still's disease: case report and review of the liter 2002 Feb Adult-onset Still's disease (AOSD) is a multi-system inflammatory disorder characterized by high spiking fevers, evanescent salmon-coloured rash, arthralgias or arthritis, hepatosplenomegaly, lymphadenopathy and sore throat. There is no specific test or combination of tests that can establish the diagnosis of AOSD and patients may present with other systemic involvement including neurological manifestations in 7-12% of cases. We present a complex case of a patient with AOSD who developed the Miller-Fisher variant of Guillain-Barré syndrome. This immunological disorder of the nervous system has not been described in association with AOSD before. We also review the literature on other neurological manifestations in AOSD. AOSD mimics different disease processes and its multi-system manifestations may complicate the picture further.
12380368 Juvenile rheumatoid arthritis. 2002 Aug Progress in achieving international consensus concerning the classification of juvenile idiopathic arthritis has been made, although further refinement and validation of these criteria is needed. It is hoped that this will facilitate more effective international collaboration in the study of these diseases, because much remains to be learned about genetic susceptibility, causation, pathogenesis, and treatment. Attention to the unique aspects of chronic arthritis in children such as impaired growth and macrophage activation syndrome may help to reduce disease-related morbidity and mortality. New biologic agents have substantially enhanced the treatment of JRA. The identification of reliable predictors of disease course and outcome is important in the rational and timely application of new therapies.
12904917 Inter- and intrareader variability in the interpretation of two radiographic classificatio 2003 Oct OBJECTIVE: To evaluate the inter- and intrareader variability for interpretation of a modified Larsen's radiographic classification system for juvenile rheumatoid arthritis (JRA) focused on osteochondral lesions and a conventional Larsen's classification system, compared to a reference MR scoring system of corresponding images. MATERIALS AND METHODS: Seventy-five radiographs of 60 children with JRA, performed within a short interval of time from the MR examinations, were independently evaluated by three experienced radiologists, three diagnostic imaging residents and three rheumatologists, in two separate sessions, according to the two different classification methods, blinded to the corresponding MR images. RESULTS: The inter- and intrareader concordance rates between the two radiographic classification systems and the MR-related radiographs were respectively poor and poor/moderate. The interobserver range of weighted kappa values for the conventional and the modified Larsen's system respectively was 0.25-0.37 vs 0.19-0.39 for radiologists, 0.25-0.37 vs 0.18-0.30 for residents and 0.19-0.51 vs 0.17-0.29 for rheumatologists. The intrareader rate ranged from 0.17-0.55 for radiologists, 0.2-0.56 for residents, and 0.14-0.59 for rheumatologists. CONCLUSION: Although the proposal of a new radiographic classification system for JRA focused on osteochondral abnormalities sounds promising, the low inter- and intrareader concordance rates with an MR-related radiographic system makes the clinical applicability of such a radiographic system less suitable.