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Introduction Acquired factor XIII (FXIII) inhibitor is a rare but possibly underdiagnosed bleeding disorder. To date, less than one hundred cases have been reported, but the number has increased rapidly in recent years, especially in Japan. Because of the rarity of this disorder, no treatment guidelines are available. In some reports, physicians treated the bleeding with cryoprecipitate or factor XIII concentrate and eradicated the inhibitor with various immune suppressants. Methods From January 2015 to December 2018, we collected consecutive patients diagnosed as having acquired FXIII inhibitor. FXIII activity and inhibitor were measured by a fluorescent factor XIII assay using isopeptidase reaction catalyzed by activated factor XIII and the Bethesda method, respectively. Factor XIII antigen was measured by latex-enhanced immunoassay. Results We found five adult patients with detectable FXIII inhibitor. Four of them were older than 70. Two had systemic lupus erythematosus. All the patients presented with ecchymosis and intramuscular hematoma. No life-threatening bleeding was observed. Delayed diagnosis was common with varied time periods needed to achieve a correct diagnosis. All bleedings were treated and improved by cryoprecipitate. Steroids were given to all patients and cyclophosphamide, rituximab, and other immune suppressants were also used. FXIII inhibitor was totally resolved in three, partially resolved in one, and persisted in one patient. Conclusion We documented five patients with acquired FXIII inhibitor, found over 4 years. The most common presentations were ecchymosis and intramuscular hematomas. Cryoprecipitate was effective in controlling most bleeds. Steroid, cyclophosphamide and rituximab were effective in eradicating inhibitor in some patients.

Background: Dactylitis is a characteristic feature of psoriatic arthritis (PsA). However, early diagnosis of mild dactylitis is challenging and image examination, such as ultrasonography (US), can be helpful. Objectives: We aimed to compare the clinical diagnosis of dactylitis made by the dermatologist and ultrasonographic diagnosis by the rheumatologist. Methods: Consecutive patients diagnosed with peripheral PsA seen in the dermatologic clinics were referred to the same dermatologist for evaluation of dactylitis. Consecutive patients with and without clinical dactylitis were diagnosed in 19 and 19 patients, respectively, by the referred dermatologist. All patients were then referred to an experienced rheumatologist unaware of the clinical diagnosis for sonographic examination of all 20 digits. Dactylitis under US was diagnosed when both proximal and distal parts of a digit were at least 0.25 mm larger than the contralateral digit. Results: For the clinical dactylitis group, 7 (36.8%) patients had more dactylitis diagnosed by US than clinically, and 2 (10.5%) patients had no dactylitis diagnosed by US. For the clinically no dactylitis group, 4 (21.1%) patients had no diagnosis of dactylitis by US, and most of these patients (78.9%) were diagnosed with dactylitis under US by the rheumatologist. More digits affected by dactylitis were found for both groups, although no statistically significant differences were found, probably due to the small sample size. Conclusion: The results revealed concordance between the dermatologist and rheumatologist for clinical dactylitis but not for patients without dactylitis. For PsA patients, US is more sensitive and useful for early dactylitis diagnosis in a dermatologic clinic.

Objectives The aim of this study was to compare ultrasound (US) grading and laboratory measures in patients with rheumatoid arthritis. Methods Two-hundred four patients with rheumatoid arthritis who received US evaluation for synovitis were included after excluding those using tocilizumab. Ultrasound grading of synovial hypertrophy (SH) and power Doppler (PD) at the most severe site were recorded. An assessment of the correlation of laboratory measures and US grading was conducted by reviewing the electronic medical records. Results High-titer anti–cyclic citrullinated peptide (anti-CCP) antibodies positivity was associated with SH grade ≥2 (odds ratio [OR], 6.00; 95% confidence interval [CI], 1.78–20.2) and PD grade ≥2 (OR, 5.56; 95% CI, 1.82–16.9). Recent C-reactive protein (CRP) levels ≥0.3 mg/dL were associated with SH grade ≥2 (OR, 3.13; 95% CI, 1.38–7.10) and PD grade ≥2 (OR, 2.38; 95% CI, 1.31–4.31). Anti-CCP antibody levels correlated with US scores better than the levels of CRP with higher Spearman ρ correlation coefficients. Most of the patients with recent CRP levels

Background Rituximab is known to be associated with a high resolved hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation in rheumatic patients receiving rituximab is limited. Aims To assess the HBV reactivation in HBsAg-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcomes and factors associated with HBV reactivation were analyzed. Results After a median follow-up period of 3.3 years, 21 patients developed HBV reactivation, among which 17 patients were positive for anti-HBc and 4 were negative. Thirteen patients had clinical hepatitis flare, while 8 patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, and undetectable serum anti-HBs level at rituximab initiation were associated with HBV reactivation. There was no significant difference in the HBV reactivation risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBV reactivation (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas, patients with negative anti-HBc, especially those without vaccination at birth, were still at risk for HBV reactivation after receiving rituximab. Regular monitoring of HBV serology should be considered for all HBsAg-negative patients receiving rituximab for autoimmune diseases.

Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy review and meta-analysis to determine the performance of anti-DFS70 antibodies in patients with a positive anti-nuclear antibody (ANA) test result to exclude SARD. We searched PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 22 February 2021, and included studies examining the diagnostic accuracy of anti-DFS70 antibodies in patients with a positive ANA test result. The results were pooled using a hierarchical bivariate model and plotted in summary receiver operating characteristic curves. R software and Stata Statistical Software were used for the statistical analysis. Eight studies with 4168 patients were included. The summary sensitivity was 0.19 (95% confidence interval: 0.12–0.28) and the specificity was 0.93 (95% confidence interval: 0.88–0.96). The area under the curve was 0.69 (95% confidence interval: 0.64–0.72). The meta-regression analysis showed that targeting only ANA-associated rheumatic disease was associated with higher specificity. In addition, the studies with a non-SARD prevalence of

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by persistent joint synovial inflammation and swelling, leading to cartilage damage and bone erosion. This retrospective, longitudinal study is to evaluate the treatment patterns of biologic-naïve RA patients receiving index biologic disease-modifying antirheumatic drug (bDMARD) and tofacitinib by the data of Taiwan National Healthcare Insurance Claims and the Death Registry between 2012 and 2017. Drug survival and treatment patterns were determined by investigating the occurrence of switching and discontinuation from index treatment. At baseline, 70.0% of patients used tumor necrosis factor inhibitors (TNFi) bDMARD with the majority taking etanercept (27.0%) or adalimumab (26.2%). During the follow-up period, 40.0% (n = 3,464) of index users switched (n = 1,479) or discontinued (n = 1,985) the treatment with an average incidence rate of 0.18 per patient-year. Among the six index treatment groups, drug survival was the lowest for adalimumab and highest for tocilizumab. When compared with etanercept, only adalimumab had a higher cumulative probability of switching/discontinuation (adjusted HR = 1.17, 95% CI: 1.08–1.28), whereas golimumab, non-TNFi bDMARDs and tofacitinib were significantly less probable to switch or discontinue. For patients switching the index treatment, tocilizumab (31.2%) and tofacitinib (23.4%) were the main regimens being switched to. In addition, 48.2% of patients who discontinued the index treatment received further retreatment, and 63.8–77.0% of them were retreated with same agent. In conclusion, this population-based study found that TNFi were the preferred agents as the index treatments during 2012–2017. Non-TNFi and tofacitinib were more common second-line agents being switched to. Nearly half of discontinued patients received retreatment, with a majority receiving the same agent.

Progressive multifocal leukoencephalopathy (PML) is a rare viral demyelinating disease of central nervous system. Immunosuppression is a significant risk factor for the disease. Previously, PML developed more commonly in patients of hematological malignancy and acquired immune deficiency syndrome (AIDS). In the era of biological disease modifying anti-rheumatic drugs, PML is more frequently reported in patients of autoimmune diseases. However, for its rarity and unspecific clinical presentations, accurate diagnosis and immediate immune restoration might be difficult in clinical practice, and the outcome might thus be miserable. Herein we present a 27-year-old lady of systemic lupus erythematosus (SLE) – rheumatoid arthritis overlap syndrome with suspected involvement of central nervous system. Neuropsychiatric SLE was suspected first. However, after intensive immunosuppressive treatment, the condition kept deteriorating. An alternative diagnosis was thus considered. PML was suspected for her immunosuppressive status and suggestive radiological findings, and the diagnosis was confirmed by a polymerase chain reaction of JC virus from cerebrospinal fluid. After restoring the immune status by decreasing the dose of immunosuppressants, the condition of the patient improved significantly. We report this case to raise the importance of clinical alertness for the rare but possibly underdiagnosed disease. Keywords: Antirheumatic agents, Rheumatoid arthritis, Immunosuppressive agents, Progressive multifocal leukoencephalopathy, Systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006–2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

Introduction Considering the progressive nature of axial spondyloarthritis (axSpA), it is important to determine whether tumor necrosis factor alpha (TNFα) inhibitors have an effect on early inflammatory and structural lesions detected using magnetic resonance imaging (MRI). Methods A search of MEDLINE/PubMed for full-text, English-language articles on randomized controlled trials (RCTs) of adalimumab, certolizumab, etanercept, golimumab, or infliximab published since January 2007 was conducted in February 2018 and again in December 2018. The collected articles reported on inflammatory or fatty lesion progression in the spine or sacroiliac joint (SIJ), determined using MRI, in a population that included at least 40% of patients with early axSpA, defined as non-radiographic axSpA. Results Of the 105 articles retrieved, 19 were included in this review, of which the majority were on etanercept (n = 11). A majority of selected articles included information on inflammatory lesions (SIJ 15/19; spine 12/19). All five TNFα inhibitors showed benefits on inflammation, assessed by MRI, in patients with early axSpA for up to 204 weeks of treatment. Structural progression in SIJ and the spine was assessed in 6/19 and 3/19 articles, respectively, with mixed evidence on benefits of TNF-inhibitor treatment. Conclusions In conclusion, treatment with TNFα inhibitors reduces MRI-evident inflammatory lesions in the SIJ and spine of patients with early axSpA for up to 4 years. There is less evidence of benefits on structural lesions. Additional studies are required to determine whether TNFα-inhibitor therapy can limit or delay radiological progression in patients with early axSpA. Funding Pfizer.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855, p &lt, 0.001) and CRP (Spearman’s ρ = 0.838, p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322, 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.

Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by immune dysregulation, chronic inflammation, vascular endothelial cell dysfunction, and progressive tissue fibrosis of the skin and internal organs. Moreover, increased cancer incidence and accelerated aging are also found. The increased cancer incidence is believed to be a result of chromosome instability. Accelerated cellular senescence has been confirmed by the shortening of telomere length due to increased DNA breakage, abnormal DNA repair response, and telomerase deficiency mediated by enhanced oxidative/nitrative stresses. The immune dysfunctions of SSc patients are manifested by excessive production of proinflammatory cytokines IL-1, IL-6, IL-17, IFN-α, and TNF-α, which can elicit potent tissue inflammation followed by tissue fibrosis. Furthermore, a number of autoantibodies including anti-topoisomerase 1 (anti-TOPO-1), anti-centromere (ACA or anti-CENP-B), anti-RNA polymerase enzyme (anti-RNAP III), anti-ribonuclear proteins (anti-U1, U2, and U11/U12 RNP), anti-nucleolar antigens (anti-Th/T0, anti-NOR90, anti-Ku, anti-RuvBL1/2, and anti-PM/Scl), and anti-telomere-associated proteins were also found. Based on these data, inflamm-aging caused by immune dysfunction-mediated inflammation exists in patients with SSc. Hence, increased cellular senescence is elicited by the interactions among excessive oxidative stress, pro-inflammatory cytokines, and autoantibodies. In the present review, we will discuss in detail the molecular basis of chromosome instability, increased oxidative stress, and functional adaptation by deranged immunome, which are related to inflamm-aging in patients with SSc.

We read with great interest the article by Petri et al demonstrating that higher hydroxychloroquine (HCQ) blood levels were associated with lower risk of thrombotic event in patients with systemic lupus erythematosus (SLE). (1) A mean blood level of 1068 ng/mL and a most recent level of 1192 ng/mL and above had a protective effect. The dose response implied a therapeutic threshold of HCQ. However, a previous study indicated a range of HCQ blood level from 1177 to 3513 ng/mL predicted later development of HCQ retinopathy. (2) Obviously, there's a great overlap between the protective level from thrombosis and toxic level of retinopathy. The optimal therapeutic range is so narrow (1068 to 1177 ng/mL) that dose titration to target this level would be difficult in clinical practice. It seems that the dilemma of avoiding retinopathy while maintaining the benefit of HCQ still exists.

Aim We evaluated the safety of baricitinib in an East Asian (EA) patient population with moderate-to-severely active rheumatoid arthritis (RA), through an integrated sub-analysis of data from the overall baricitinib RA clinical program. Methods Data from EA patients who received any dose of baricitinib from five completed studies (1 Phase 2, 4 Phase 3) and an ongoing long-term extension study were pooled up to 1 September, 2016. Exposure-adjusted incidence rates (EAIR) and incidence rates (IRs), both per 100 patient-years (PY), were calculated. Results This analysis included 740 EA patients with 1294 PY of total baricitinib exposure (maximum 3.5 years). Overall, 109 patients discontinued baricitinib due to adverse events (AEs); EAIR: 8.4. No deaths were reported in this cohort. Serious AEs were reported by 125 patients (EAIR: 9.7). Serious infections were the most common serious AEs (n = 53, IR: 4.15). IR of herpes zoster infection was 6.2; the majority of events were of mild-to-moderate severity. Three cases (IR: 0.23) of tuberculosis were reported. The IRs of malignancy (excluding non-melanoma skin cancer) was 0.99 and EAIR specifically of lymphoma was 0.1. The IR of major adverse cardiovascular events was 0.26, and deep vein thrombosis was reported in four patients (EAIR: 0.3). Two cases of gastrointestinal perforations (EAIR: 0.2) were reported. Conclusion Integrated data show that baricitinib is well-tolerated in EA patients with moderate-to-severely active RA in the context of demonstrated efficacy, which is generally consistent with safety results of the overall study population.

Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects.

Background: Multiple comorbidities, including rheumatoid arthritis (RA), have been reported to be associated with psoriasis. Objective: This study aimed to determine the prevalence and the clinical features of RA among patients with psoriasis in a tertiary referral center. Methods: Between January 2000 and December 2013, all patients coded with psoriatic disease (ICD-9 CM 696.0 OR ICD-9 CM696.1) and RA (ICD-9 CM 714.0) in a tertiary medical center were enrolled. Results: There were 10,844 patients and 9073 patients with psoriatic disease and RA identified by diagnostic codes, respectively. Among patients with psoriasis, 111 patients had claim-based diagnosis of RA (1.02%). By reviewing medical records and telephone interview or clinic visits, 25 of the 111 patients (0.23%) was identified unequivocally as having concurrent RA. Among them, 17 (68%) were female and 16 (64%) patients developed arthritis prior to the onset of psoriasis with a mean lag of 6.3 years (1–19 years); 8 (32%) had psoriasis skin lesions prior to the onset of arthritis with a mean lag of 6.9 years (3–20 years); 1 (4%) had skin lesions and arthritis in the same time; 17 (68%) patients also fulfilled the CASPAR classification criteria for psoriatic arthritis. The mean age of onset for arthritis was 49.6 years old. Conclusions: The prevalence of RA in psoriasis might be overestimated in some previous studies using claimed database. Patients with concurrent RA and psoriasis showed a comparable age of onset and male to female ratio, but had more axial involvements compared to patients without psoriasis.

Raynaud's phenomenon (RP) is the earliest and most common clinical manifestation in patients with systemic sclerosis (SSc) and its related diseases containing anti-TOPO-1 and/or anti-CENP-B autoantibodies in the sera. However, the cause-effect relationship between the two autoantibodies and RP remains elucidation. Sera containing anti-CENP-B and anti-TOPO-1 autoantibodies were obtained from SSc-related diseases manifesting RP. The polyclonal auto-antibodies were purified from pooled sera by affinity chromatography. Mouse monoclonal anti-CENP-B and anti-TOPO-1 were purchased. Calf pulmonary arterial endothelial cells (CPAE) were incubated with 40% patient sera, purified polyclonal antibodies or mouse monoclonal antibodies for 1-6 days. The vascular endothelial biomarkers von Willebrand factor (vWF), thrombomodulin (CD141) and 6-keto-prostaglandin F1α (6-keto-PGF1α), cell viability marker ATP, and cell necrosis/lysis marker LDH in the culture supernatants were measured by ELISA. The cell senescence biomarker β-galactosidase and telomere content in the cells were stained by the respective kit. The classical p53-p21 senescence pathway was detected by Western blot. We found that 40% anti-CENP-B or anti-TOPO-1-containing sera without heat-inactivation and mouse monoclonal antibodies suppressed 6-keto-PGF1α production, increased β-galactosidase, and decreased relative telomere content. The cell senescence effects were proved not via p53-p21 pathway. The pathognomonic anti-CENP-B and anti-TOPO-1 autoantibodies in SSc-related diseases accelerate vascular endothelial cell senescence and functional impairment inducing RP. The real signaling pathway for autoantibody-induced cell senescence remains exploration.

Objective The non-criteria neuropsychiatric manifestations of antiphospholipid syndrome include headache, dizziness, vertigo, seizure, depression and psychosis. There were still no objective methods qualified to detect the early central nervous system involvement in non-criteria antiphospholipid syndrome. We evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory insufficiency in the brains of patients with antiphospholipid antibodies and neuropsychiatric symptoms but without thromboembolism. Materials and methods Patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms composed the case group; patients without antiphospholipid antibody served as the control group. Subjects with a history of thromboembolism or autoantibodies to extractable nuclear antigens were excluded. All patients received Tc-99m ECD SPECT studies and were classified by the number of positive antiphospholipid antibodies they carried. The heterogeneity of brain perfusion was defined as the coefficient of variation of the SPECT signals. Analysis of variance (ANOVA) was applied to evaluate the differences between the groups. Results Total 60 adult patients were included in this study. There were 54 patients in the case group and 6 patients in the control group. The mean age was 38.3 ± 11.5 years. There were 52 women and 8 men. There was no significant difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation to the number of antiphospholipid antibodies (P = 0.01). Conclusions This is the first study demonstrating that Tc-99m ECD SPECT can early detect the increased heterogeneity of brain circulation in non-criteria antiphospholipid antibody carriers.

Systemic lupus erythematosus (SLE) is an archetype of systemic autoimmune disease, characterized by the presence of diverse autoantibodies and chronic inflammation. There are multiple factors involved in lupus pathogenesis, including genetic/epigenetic predisposition, sexual hormone imbalance, environmental stimulants, mental/psychological stresses, and undefined events. Recently, many authors noted that “inflammaging”, consisting of immunosenescence and inflammation, is a common feature in aging people and patients with SLE. It is conceivable that chronic oxidative stresses originating from mitochondrial dysfunction, defective bioenergetics, abnormal immunometabolism, and premature telomere erosion may accelerate immune cell senescence in patients with SLE. The mitochondrial dysfunctions in SLE have been extensively investigated in recent years. The molecular basis of normoglycemic metabolic syndrome has been found to be relevant to the production of advanced glycosylated and nitrosative end products. Besides, immunosenescence, autoimmunity, endothelial cell damage, and decreased tissue regeneration could be the results of premature telomere erosion in patients with SLE. Herein, the molecular and cellular bases of inflammaging and cardiovascular complications in SLE patients will be extensively reviewed from the aspects of mitochondrial dysfunctions, abnormal bioenergetics/immunometabolism, and telomere/telomerase disequilibrium.

Thymic malignancies cause alterations in the immune system. Thymomas are known to be associated with paraneoplastic syndrome and autoimmunity, including myasthenia gravis, systemic lupus erythematosus, inappropriate antidiuretic hormone secretion, pure red cell aplasia, pernicious anemia, pemphigus, and autoimmune thyroid diseases. However, paraneoplastic syndrome has rarely been observed in patients with thymic carcinoma. The management of patients with paraneoplastic autoimmune disease is difficult, and treatment of the underlying malignancy is important. Herein, we present a case of thymic carcinoma who developed systemic sclerosis 3 years after the initial diagnosis during disease progression.

Since the development of the ultrasound machine, musculoskeletal ultrasound (MSUS) has become widely used in rheumatology practice. This tool allows important information to be obtained for several diseases, such as the early detection of synovial proliferation, effusion, and bone erosion in rheumatoid arthritis, the recognition of enthesitis or dactylitis in spondyloarthropathies, and visual guidance for invasive procedures, such as biopsies, injections, or aspirations. In addition, the use of MSUS in research has increased steadily over the past decade. In this review, we provide a brief introduction and an overview of the clinical application of MSUS in rheumatic diseases.

Background Previous studies in Taiwan utilizing the Taiwan’s National Health Insurance Database (NHIRD) have estimated the direct healthcare costs of RA patients, but they have not focused on patients on bDMARDs, or considered patients’ response to therapy. Objectives The objective of this study was to estimate the rate of inadequate response for patients newly treated with biologic disease-modifying antirheumatic drugs (bDMARDs) as well as their costs and resource use. Methods Data were from the catastrophic illness file within the NHIRD from 1/1/2009 to 12/31/2013. Patients with RA, which was categorized by the presence of a catastrophic illness card, that were previously bDMARD-naive, were included in this study if they initiated their first bDMARD during the index period. The index period included all of 2010, a pre-index period consisting of the index date– 365 days, and a follow-up period including the index date to 365 days post-index, were also included. Previously biologically-naive patients were indexed into the study on the date of their first claim for a bDMARD. A validated algorithm was used to examine the rate of inadequate response (IR) in the biologically-naive cohort of patients. Inadequate responders met one or more of the following criteria during their year of follow-up: low adherence (proportion of days covered

Background/purpose Sjogren's syndrome (SS) is characterized by diminished exocrine secretions with the resultant symptoms of dry mouth and dry eye. As genetic predisposition and ethnicity may alter the effectiveness of drug treatment, evaluation of the efficacy and safety of the secretagogue pilocarpine hy-drochloride in the treatment of xerostomia in patients with SS in different populations is needed. Methods Forty-four patients with SS were enrolled in this double-blind, placebo-controlled trial. Patients were randomized to receive 5 mg pilocarpine (Salagen) or placebo tablet four times daily for 12 weeks. Global evaluation and subjective responses of patients were assessed by questionnaires with visual analog scales and categorical checkboxes. Saliva production was also measured by modified Saxon's test. Results Pilocarpine treatment significantly improved global assessment of dry mouth, symptoms associated with dry mouth (mouth comfort, ability to sleep and ability to speak), and saliva production compared to placebo. The drug was well tolerated and the most common adverse effect was sweating (5/23, 21.7%) resulting from the muscarinic agonist action of the drug. No serious drug-related adverse effect was found in this study. Conclusion The results of this study suggest that therapy with 5 mg pilocarpine four times daily is effective, safe and well tolerated for the relief of oral symptoms in patients with SS in Taiwan.

Discovertebral erosion with pseudoarthrosis is a well-known complication in ankylosing spondylitis but it is seldom mentioned in psoriatic arthritis. We report a 53-year-old woman with an 8-year history of pso-riatic arthritis who developed severe low back pain followed by sudden onset of numbness in the lower limbs, weakness and dysesthesia. Abnormal contour of L1 and L2 vertebrae and intervertebral disc space was noted during radiologic examination. Pseudoarthrosis was suspected based on extensive osseous re-sorption and reactive sclerosis about the discovertebral junction on magnetic resonance imaging study. She underwent emergency operation due to spinal instability with neurologic deficit. Pseudoarthrosis was confirmed intraoperatively. No evidence of infection or neoplasms was found. This case shows that pseudoarthrosis can be complicated in patients with psoriatic arthritis, and this possibility should be considered in patients with previously quiescent disease.

AIM The study intended to determine the specific ultrasonographic features of acute arthritis with periarticular bone erosions caused by acute osteomyelitis (OM), rheumatoid arthritis (RA) and gouty arthritis (GA). METHOD We included 33 patients (seven with acute OM, 18 with RA flares, and eight with GA attacks) having acute monoarthritis or oligoarthritis, and receiving ultrasound (US) examinations in the acute stage. The US images were rated by three rheumatologists blinded to the diagnosis. The median scores of their evaluation of the subcutaneous tissue, periosteum, and synovium were compared. Interrater reliability was calculated using Cronbach's alpha. RESULTS The highest mean grade of subcutaneous edema appeared in patients with acute OM, and grade 2 edema was more frequent than patients with RA and GA (P = .003 and P = .026, respectively; α = .869). The prevalence of subcutaneous power Doppler signal was also higher in patients with acute OM than in those with RA and GA (P

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 25 juin 2014

We investigated whether premature telomeric loss occurred in peripheral polymorphonuclear neutrophils (PMN) as well as mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE). We measured the telomere length of MNC and PMN in 60 SLE patients and 26 sex-, race - and age-matched healthy volunteers by Southern blotting with chemiluminescence method. The possible predisposing factors associated with telomere change were also analysed. We found the telomere length of MNC and PMN shortened with age in different degrees in both SLE and control groups. Compared to the control group, the telomere length was shortened in both SLE-MNC (6.08 kb in SLE versus 6.71 kb in control, P = 0.0008) and PMN (6.24 kb in SLE versus 6.75 kb in control, P = 0.0025). The average reduction in telomere length in SLE patients was equivalent to a premature senescence of 16.5 years in MNC and 13.4 years in PMN. In addition, the accelerated telomere shortening was more prominent in SLE patients younger than 45 years old. SLE disease activity (SLEDAI) contributed remarkably to the accelerated telomere erosion, at least in PMN. Moreover, the telomere length of MNC was significantly shorter than PMN in the same SLE patients with leukopenia and lymphopenia. These data suggested that MNC and PMN from patients with SLE displayed premature and accelerated telomere shortening that SLE is an independent factor for it. Lupus (2007) 16, 265—272.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 7 janvier 2015

Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear neutrophil (PMN) but also react with primed PMN to exert the inflammatory process in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated vasculitis and the related mechanism, PMN was cultured with monoclonal antibody MPO-ANCA and PR3-ANCA to determine the function of phagocytosis, Interleukin- 8 (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN could be significantly increased by lipopolysaccharide (LPS) and TNF-alpha, but not by IL-8 or GRO-alpha. The PMN-stimulating activity of ANCA was demonstrated by enhancing phagocytosis, IL-8 production, and glucose uptake that was more prominent by MPO-ANCA. The PMN stimulation by ANCA was not through protein kinase, H2O2, or superoxide anion radicals as their inhibitors exerted no effect on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN apoptosis and increased TRAIL production. These results demonstrate that activation-induced cell death (AICD) mechanism could be initiated in PMN with existence of ANCA. In conclusion, MPO-ANCA is more potent in stimulating PMN than PR3-ANCA. ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA.

BackgroundIf a patient has inflammatory bowel disease (IBD) and enthesitis, he/she can be classified as having peripheral spondyloarthritis according to criteria set by the Assessment of Spondyloarthritis International Society. In Taiwan, IBD patients visiting outpatient clinics can present without joint symptoms, so the prevalence of these musculoskeletal manifestations may be underestimated. We conducted this study to evaluate enthesitis by ultrasonography (US) in IBD patients, and compared these data with healthy controls (HCs).Materials and methodsFourteen IBD patients and 14 HCs underwent independent clinical and ultrasonographic examination of both legs at five entheseal sites. The Glasgow Ultrasound Enthesitis Scoring System (GUESS) was used to assess the degree of enthesitis in the two groups. The total score of enthesitis was calculated on the basis of US findings. All US examinations were undertaken by an experienced rheumatologist blinded to clinical and laboratory findings.ResultsTwo hundred and eighty entheses in 14 patients and 14 HCs were examined by US, which revealed 42/140 (30%) and 21/140 (15%) abnormal entheseal sites in patients and controls, respectively. The GUESS score was significantly higher in IBD patients than in HCs (p