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ID PMID Title PublicationDate abstract
21686590 Deterioration of the liver biochemistry due to reactivation of chronic hepatitis B during 2009 To report a hepatitis B virus (HBV) reactivation during the treatment of etanercept for rheumatoid arthritis (RA).The chronological course of a patient with RA who developed HBV reactivation associated with etanercept treatment was recorded.A Taiwanese woman with RA was treated by etanercept. A severe deterioration of liver biochemistry occurred soon after the start of the biologicals because of the previously unrecognised HBV carrier status. The condition was successfully alleviated by oral lamivudine administration.In the prevalent area of HBV, viral titre monitoring and pre-emptive antiviral treatment may be fundamentally important to avoid serious complications of HBV reactivation whenever a new treatment modality such as biologicals is started for patients with RA.
19956437 Triptolide induces anti-inflammatory cellular responses. 2009 Mar 5 Tripterygium wilfordii Hook F. has been used for centuries in traditional Chinese medicine to treat rheumatoid arthritis, an autoimmune disease associated with increased production of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha. Triptolide is a compound originally purified from T. wilfordii Hook F. and has potent anti-inflammatory and immunosuppressant activities. In this study, we investigated the effect of triptolide on the global gene expression patterns of macrophages treated with lipopolysaccharide (LPS). We found that LPS stimulation resulted in >5-fold increase in expression of 117 genes, and triptolide caused a >50% inhibition in 47 of the LPS-inducible 117 genes. A large portion of the genes that were strongly induced by LPS and significantly inhibited by triptolide were pro-inflammatory cytokine and chemokine genes, including TNF-alpha, IL-1beta, and IL-6. Interestingly, LPS also induced the expression of micro-RNA-155 (miR-155) precursor, BIC, which was inhibited by triptolide. Confirming the cDNA array results, we demonstrated that triptolide blocked the induction of these pro-inflammatory cytokines as well as miR-155 in a dose-dependent manner. Profound inhibition of pro-inflammatory cytokine expression was observed at concentrations as low as 10-50 nM. However, triptolide neither inhibited the phosphorylation or degradation of IkappaBalpha after LPS stimulation, nor affected the DNA-binding activity of NF-kappaB. Surprisingly, we found that triptolide not only inhibited NF-kappaB-regulated reporter transcription, but also dramatically blocked the activity of other transcription factors. Our study offers a plausible explanation of the therapeutic mechanism of T. wilfordii Hook F.
21887155 An unusual cause of apareunia. 2009 A 49-year-old woman with history of rheumatoid arthritis presented with worsening pelvic pain. A pelvic computed tomography (CT) scan demonstrated a fracture and a lytic expansile lesion within the right superior and inferior pubic rami. The diagnosis of "insufficiency fractures secondary to rheumatoid arthritis" was established. Six months later, she started describing pain and fullness sensation in the vagina which eventually led to a complete apareunia. An x ray confirmed healing of the previous fractures, fracture of both left superior and inferior pubic rami, and an upwards shift of the right hemi-pelvis. Conservative management was chosen. Twelve months later, no improvement occurred and she was still apareunic. A "corrective osteotomy surgery" was performed and the displaced pubic rami and ischial tuberosities were remodelled bilaterally through a vertical incision over each labia majora. These bones were partially excised until an adequate vaginal opening was established. Her symptoms have impressively resolved with complete reverse of the apareunia.
21829425 Analgesics are not always the culprits: isolated gastric fundal varices as the cause of re 2009 The most common cause of upper gastrointestinal bleeding in patients with systemic rheumatic diseases is non-steroidal drug use; this is the case with COX-2 inhibitors, especially when used concomitantly with corticosteroids. Bleeding from varices is unusual in the absence of liver disease. We present an interesting case of a patient with systemic lupus erythematosus, rheumatoid arthritis and polymyositis overlap syndrome with recurrent upper gastrointestinal bleeds from isolated fundal gastric varices and a normal liver.
20476896 Adalimumab for the treatment of rheumatoid arthritis. 2009 Jan Rheumatoid arthritis (RA) is characterized by massive synovial proliferation resulting in joint destruction and deterioration in quality of life. TNF-alpha has been implicated in the central pathogenesis of RA, and its blockade? by anti-TNF-alpha monoclonal antibodies (infliximab and adalimumab) and the soluble TNF-alpha receptor (etanercept) has caused a paradigm shift in the treatment of RA. Adalimumab can be used alone or concomitantly with methotrexate, but the combination of both is significantly superior to monotherapy with adalimumab. Adalimumab can not only ameliorate the signs and symptoms of the disease, but can also inhibit the progression of joint destruction and improve quality of life. Approximately 50% of patients with early, aggressive RA receiving combination therapy with adalimumab and methotrexate can be introduced into disease remission (disease activity score < 2.6). Adalimumab is even effective in patients with RA treated previously with other biologics. Long-term treatment with adalimumab is safe and well tolerated in patients with RA.
19092833 Is there a role for everolimus in the treatment of RA? 2009 Feb The past decade has seen remarkable advances in the treatment of rheumatoid arthritis. Although this is good news for the majority of patients, one consequence is that the environment for the development of new drugs has become difficult as a result of high expectations for efficacy. Nevertheless, there remains a subgroup of patients with rheumatoid arthritis who are not candidates for treatment with the newer biologic agents and in whom oral DMARDs have certain advantages. A recent report by Bruyn et al. suggests that the proliferation-signal inhibitor everolimus could have unique properties, in addition to a convenient once-daily oral dosing schedule, that might fit this niche in the therapeutic armamentarium. Further studies are required, however, to confirm the disease-modifying effects and adverse event profile of this drug.
22216379 The Trends of DMARDS prescribed in Rheumatoid Arthritis Patients in Malaysia. 2009 Oct OBJECTIVES: To evaluate the trends of disease-modifying anti-rheumatic drugs (DMARDs) used in the treatment of rheumatoid arthritis (RA). METHODS: Patients who fulfilled the ACR criteria for RA from 1995 to 2006 and who attended the Rheumatology clinic at Ipoh Hospital were selected and their records were evaluated to determine the changing trends in the use of DMARDs. RESULTS: 128 patients with RA were identified. The most commonly prescribed DMARD as monotherapy was sulphasalazine (47.7%), followed by methotrexate (35.9%) and hydroxychloroquine. Methotrexate and sulphasalazine were the most frequently prescribed DMARDs, of which the use of methotrexate has increased 6 folds from 1997 to 2007 and the use of sulphasalazine remains around 30% to 50%. The combination of methotrexate with leflunomide has significantly increased in usage by 4 folds during the study period whilst methotrexate with sulphasalazine combination usage had slightly declined. CONCLUSION: DMARDs are still the cornerstone in the treatment of RA. Changes in the trend and aggressive use of DMARDs has been markedly influenced by the patient's awareness of early treatment, the incapacitating damage, availability of recently introduced leflunomide and the advancement of current recommended treatment protocol.
19519959 Capturing real-life patient care in psoriatic arthritis and its risks: the challenge of an 2009 Studies based on registries continue to inform us of many relevant issues in the treatment of arthritic conditions and constitute more than just a supplement of clinical trial data. We can learn about long-term aspects of therapies beyond the scope of most clinical trials and about larger-scale toxicity. The downsides need to be considered in the interpretation of the results and include mainly the biases that are inherent when routine clinical practice is just observed and not steered by a protocol. However, using steered protocols in practice not only would facilitate post hoc analyses of clinical effectiveness, but (as we have learned from research in rheumatoid arthritis) can also improve outcomes of our patients.
20018063 Detecting significant single-nucleotide polymorphisms in a rheumatoid arthritis study usin 2009 Dec 15 Random forest is an efficient approach for investigating not only the effects of individual markers on a trait but also the effect of the interactions among the markers in genetic association studies. This approach is especially appealing for the analysis of genome-wide data, such as those obtained from gene expression/single-nucleotide polymorphism (SNP) array experiments in which the number of candidate genes/SNPs is vast. We applied this approach to the Genetic Analysis Workshop 16 Problem 1 data to identify SNPs that contribute to rheumatoid arthritis. The random forest computed a raw importance score for each SNP marker, where higher importance score suggests higher level of association between the marker and the trait. The significance level of the association was determined empirically by repeatedly reapplying the random forest on randomly generated data under the null hypothesis that no association exists between the markers and the trait. Using random forest, we were able to identify 228 significant SNPs (at the genome-wide significant level of 0.05) across the whole genome, over two-thirds of which are located on chromosome 6, especially clustered in the region of 6p21 containing the human leukocyte antigen (HLA) genes, such as gene HLA-DRB1 and HLA-DRA. Further analysis of this region indicates a strong association to the rheumatoid arthritis status.
28925311 Combining effects of polymorphism of tumor necrosis factor α 5'-flanking region and HLA-D 2009 Apr We examined whether polymorphisms upstream of the TNF-α gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and RF) were evaluated every 2 months for 2 years. Radiological progression in hands/wrists and feet was evaluated every 6 months for 2 years using Larsen's score. HLA-DRB1 genotype was determined by PCR-RFLP method. The genotypes for -1031, -863, and -857 single-nucleotide polymorphisms in the upstream 5'-flanking region of TNFA were determined by a PCR-preferential homoduplex formation assay in patients with RA and 265 healthy controls. Four TNFA alleles (U01, U02, U03, and U04) were identified. The frequency of individuals with U02 was significantly higher in patients than in controls (P = 0.0025). Radiographs of hands/wrists/feet were available for 72 patients after 1 year and for 73 patients after 2 years. When the HLA-DRB1 genotype was analyzed simultaneously, patients possessing U02 without an HLA-DRB1 shared epitope (SE) (U02+SE-) showed the lowest progression of Larsen's score (12 months). There was no difference in the level of ESR, CRP, or RF at the first visit among U02+SE+, U02+SE-, U02-SE+, and U02-SE- groups. The combination of the polymorphism of the TNFA upstream promoter region and HLA-DRB1 allele was associated with radiological progression in the early stage of RA.
20584513 Effect of neuromuscular electrical stimulation in a patient with Sjogren's syndrome with d 2010 May Severe dysphagia in a 54 year-old woman with Sjogren's syndrome with involvement of multiple cranial nerves significantly improved after treatment with neuromuscular electrical stimulation (NMES) in combination with a swallowing rehabilitation program. The swallowing response was assessed in real time using a videofluoroscope. Immediate improvement in the tongue retraction force, clearing of the valleculae, increase in laryngeal elevation and shortening of pharyngeal transit time were noted during stimulation. The patient returned to independent oral feeding after 46 sessions of NMES. After follow-up for 1 year, we found that the patient maintained adequate oral feeding and did not show signs of pulmonary complications.
20484581 Diadenosine polyphosphates in tears of Sjogren syndrome patients. 2010 Nov PURPOSE: To analyze the levels of diadenosine tetraphosphate (Ap(4)A) and diadenosine pentaphosphate (Ap(5)A) in tears of subjects with Sjögren syndrome and to compare them with those in a control group. METHODS: Twelve subjects with a diagnosis of Sjögren syndrome and 20 healthy control subjects were invited to participate in the present study. Schirmer strips were used to measure tear secretion (Schirmer I test) and to collect tears. Ap(4)A and Ap(5)A were measured by high-pressure liquid chromatography (HPLC), and a dry eye questionnaire (DEQ) was used to evaluate dry eye symptomatology. RESULTS: The mean concentrations of Ap(4)A and Ap(5)A in the Sjögren syndrome group were 2.54 ± 1.02 and 26.13 ± 6.95 μM, respectively. This group of patients was divided in two subgroups: four patients with normal tear production and eight patients with low tear production. Concentrations of Ap(4)A, and Ap(5)A in patients with normal tear production (Schirmer test result, 12.3 ± 1.2 mm) were 0.47 ± 0.20 and 8.03 ± 3.27 μM, respectively. In the patients with low tear production (Schirmer test result, 1.0 ± 0.3 mm), the concentrations were 4.09 ± 1.36 and 39.51 ± 8.46 μM, respectively and in the control group, 0.13 ± 0.03 and 0.04 ± 0.02 μM, respectively. CONCLUSIONS: Patients with Sjögren syndrome have abnormally elevated concentrations of diadenosine polyphosphates, indicating that these compounds could be used in the diagnosis of this disease.
21118342 Type 1 diabetes associated with Hashimoto's thyroiditis and juvenile rheumatoid arthritis: 2010 Dec Autoimmune diseases are initiated by interaction between genetic and environmental factors and caused by the loss of immunologic tolerance to self-antigens. They cluster within families and individuals, but the aggregation in a triad is quite rare. We report a case of a young girl affected by three organ-specific autoimmune disorders, from which type 1 diabetes developed first, then Hashimoto's thyroiditis and juvenile rheumatoid arthritis were diagnosed. Hitherto unreported detailed genetic studies included genotyping of HLA class II, CTLA4, and PTPN22 gene regions. These genes have been associated with autoimmunity in general and some of their variants confer increased risk to all three diseases. Our results - with the limitation of reporting only on a single patient - contribute to the complex genetic background of these clustering organ-specific autoimmune diseases and the analysis of further similar cases might help to reveal how the major and minor genetic factors determine the individual clinical phenotype.
19561361 EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disea 2010 Jun OBJECTIVE: To develop a disease activity index for patients with primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). METHODS: Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific 'domains' contributing to disease activity. For each domain, features of disease activity were classified in three or four levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0-10 physician global assessment (PhGA) scale, each expert scored the disease activity of five patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain. RESULTS: All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.001). Compared with 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true. CONCLUSIONS: The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardised evaluation of primary SS should facilitate clinical research and be helpful as an outcome measure in clinical trials.
20483052 Efficacy of abatacept in a refractory case of adult-onset Still's disease. 2010 Mar Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder, characterized by spiking fever, skin rash, and arthritis. First-line treatment consists of corticosteroids. Methotrexate is commonly used in resistant cases or as a steroid-sparing drug. The availability of biologic drugs in the rheumatic diseases, such as anti-TNFs and IL-1ra, has allowed to treat very refractory cases of AOSD and provided new clues for the pathophysiology. However, anakinra and anti-TNFs may also fail or may be contraindicated in AOSD, and other treatment strategies are then necessary. Given that T cell activation may be a relevant part of the AOSD pathophysiology, abatacept, CTLA4IgFc, was administered in a 57-year-old man with AOSD failing traditional DMARDs and to anti-IL-1 and anti-TNF therapies, with a good outcome.
19847590 Adult onset Still's disease diagnosed concomitantly with occult papillary thyroid cancer: 2010 Feb Adult onset Still's disease (AOSD) is an inflammatory disease of unknown etiology, characterized by spiking fever, evanescent salmon pink maculopapular rash, arthritis, and leukocytosis with neutrophilia. Malignant lymphoma is one of the most important differential diagnoses of AOSD. AOSD has been reported as one of paraneoplastic syndromes associated with breast cancer. We report a rare case of occult papillary thyroid cancer (PTC) diagnosed coincidently with AOSD. A 32-year-old woman was diagnosed with AOSD according to the diagnostic criteria of Yamaguchi as follows: leukocytosis with neutrophilia, high fever with 39 degrees C and above, arthralgia/arthritis, sore throat, liver dysfunctions, and lymphadenopathy. Excisional biopsy of cervical lymph node showed metastatic papillary carcinoma, and immunohistochemical staining for thyroglobulin and thyroid transcription factor-1 was strongly positive. There was no evidence of focal lesion in the thyroid glands. To our knowledge, this is the first report of adult onset Still's disease diagnosed concomitantly with occult PTC.
19074185 Patient-reported outcomes in primary Sjogren's syndrome: comparison of the long and short 2009 Feb OBJECTIVES: The long-form 64-item Profile of Fatigue and Discomfort--Sicca Symptoms Inventory (PROFAD-SSI) questionnaire was developed as a patient-reported assessment tool for use in primary SS (PSS) and other rheumatic disorders. In this study, we assess whether the (shorter and more practical) 19-item PROFAD-SSI-SF (short form) gives similar results and whether a still briefer version using visual analogue scales (VASs) is feasible. METHODS: Questionnaire surveys comprising the long and short versions of the PROFAD-SSI were mailed to 43 patients with PSS and 50 patients with RA, who were asked to complete these contemporaneously as well as repeating the process 1 month later. PSS patients also completed a series of VASs comprising fatigue and sicca domains of the SSI. RESULTS: Surveys were returned from 35 PSS patients and 35 RA patients. All domains of the long- and short-form PROFAD-SSI showed strong correlations (Spearman rho between 0.779 and 0.996, P < 0.01). Factor analysis generally confirmed the previously validated domain structure with Cronbach's alpha = 0.99. The PROFAD-SF somatic fatigue domain correlated more strongly with a fatigue VAS than did the mental fatigue domain. The SSI-SF domain scores correlated with equivalent VAS scores. CONCLUSION: The long- and short-form PROFAD-SSI questionnaires correlate closely suggesting that the PROFAD-SF is valid as an outcome tool. Preliminary data also suggest that an even briefer form with compression of the domains into single VAS is also feasible.
20482595 Primary Sjögren's syndrome activity and damage indices comparison. 2010 Jul BACKGROUND: Significant differences exist in outcome measures developed to assess patients with primary Sjögren's Syndrome (pSS). In this review, we have compared proposed indices. METHODS: Three activity - SSDAI (SS Disease Activity Index), SCAI (Sjögren's Systemic Clinical Activity Index) and ESSDAI (EULAR SS Disease Activity Index) - and two damage indices - SSDDI (SS Disease Damage Index) and SSDI (SS Damage Index) have been analysed. Assessment 'tools' for perspectives of outcome (PROFAD - Profile of Fatigue and Discomfort, SF-36 - Medical Outcomes Study Short-Form 36-item questionnaire and ESSPRI - EULAR Sjögren's Syndrome Patients Reported Index) were also considered. RESULTS: SSDAI and ESSDAI are global scores. SCAI is a composite score. Validity is a limitation for SSDAI and SCAI. ESSDAI is complemented by ESSPRI for the assessment of subjective features. It is more accurate in detecting changes in activity. Damage indices differ with respect to observation period and external validation but both have low content validity. Main limitations for all indices are: inclusion of patients with mainly mild stable disease and lack of information about the completion time of the forms. CONCLUSIONS: All indices demonstrate a potentially useful benefit but further, larger studies are needed to assess reliability and sensitivity to change, to validate their use in clinical trials. Improvement in our knowledge of pathophysiology and clinical evolution of pSS is important to address unresolved issues: whether to include prognostic factors for an adverse outcome, an agreed definition of flare and most notably the distinction between activity and damage.
19836323 [Hypokalemic paralysis revealing Sjögren's syndrome associated with auto-immune thyroidit 2010 Feb We report a case of 36-year-old woman, admitted for hypotonic tetraparesis. Laboratory tests revealed severe hypokalaemia, acidosis, hyperchloremia and alkaline urinary pH allowing the diagnosis of distal tubular acidosis. Additional investigations led to the diagnosis of primary Sjögren's syndrome associated with Hashimoto's thyroïditis. The evolution was favorable under potassium citrate alkalinisation, the corticosteroid therapy and hormonal substitution. Based on this observation, the pathogenesis of distal tubular acidosis during auto-immune diseases (Sjögren's syndrome, monoclonal hypergammaglobulinemia, hypothyroidism) was discussed as well as its consequences and management.
22076178 B-cell pathology in juvenile idiopathic arthritis. 2010 Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.