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ID PMID Title PublicationDate abstract
30916218 Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well a 2019 Mar 25 Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57-0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45-2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15-1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32-3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56-2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32-0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.
31511227 Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analy 2019 Nov OBJECTIVES: To provide the level and trends of prevalence, incidence and disability adjusted life years (DALYs) for rheumatoid arthritis (RA) in 195 countries from 1990 to 2017 by age, sex, Socio-demographic Index (SDI; a composite of sociodemographic factors) and Healthcare Access and Quality (an indicator of health system performance) Index. METHODS: Data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2017 were used. GBD 2017 modelled the burden of RA for 195 countries from 1990 to 2017, through a systematic analysis of mortality and morbidity data to estimate prevalence, incidence and DALYs. All estimates were presented as counts and age-standardised rates per 100 000 population, with uncertainty intervals (UIs). RESULTS: Globally, the age-standardised point prevalence and annual incidence rates of RA were 246.6 (95% UI 222.4 to 270.8) and 14.9 (95% UI 13.3 to 16.4) in 2017, which increased by 7.4% (95% UI 5.3 to 9.4) and 8.2% (95% UI 5.9 to 10.5) from 1990, respectively. However, the age-standardised rate of RA DALYs per 100 000 population was 43.3 (95% UI 33.0 to 54.5) in 2017, which was a 3.6% (95% UI -9.7 to 0.3) decrease from the 1990 rate. The age-standardised prevalence and DALY rates increased with age and were higher in females; the rates peaked at 70-74 and 75-79 age groups for females and males, respectively. A non-linear association was found between age-standardised DALY rate and SDI. The global age-standardised DALY rate decreased from 1990 to 2012 but then increased and reached higher than expected levels in the following 5 years to 2017. The UK had the highest age-standardised prevalence rate (471.8 (95% UI 428.9 to 514.9)) and age-standardised incidence rate (27.5 (95% UI 24.7 to 30.0)) in 2017. Canada, Paraguay and Guatemala showed the largest increases in age-standardised prevalence rates (54.7% (95% UI 49.2 to 59.7), 41.8% (95% UI 35.0 to 48.6) and 37.0% (95% UI 30.9 to 43.9), respectively) and age-standardised incidence rates (48.2% (95% UI 41.5 to 55.1), 43.6% (95% UI 36.6 to 50.7) and 36.8% (95% UI 30.4 to 44.3), respectively) between 1990 and 2017. CONCLUSIONS: RA is a major global public health challenge. The age-standardised prevalence and incidence rates are increasing, especially in countries such as Canada, Paraguay and Guatemala. Early identification and treatment of RA is vital especially among females, in order to reduce the ongoing burden of this condition. The quality of health data needs to be improved for better monitoring of disease burden.
30545212 Gluten-free diet in non-celiac patients: beliefs, truths, advantages and disadvantages. 2019 Jun A gluten-free diet is the safest treatment for the treatment of patient with celiac disease (CD) and other gluten-related disorders. However, in the last years, gluten-free diet is one of the most popular diet followed by the general population and by patients affected from others clinical conditions, such as non-celiac gluten sensitivity (NCGS), irritable bowel syndrome (IBS), autism, neurological, psychiatric and rheumatologic diseases and for improving sports practice. This review highlights some questions about the appropriateness of following this trend answering to some questions such as how safe are the current gluten-free products, what are the benefits and side effects of gluten-free diet and what are clinical conditions that might benefit from gluten avoidance.
31329968 Centre effects and case-mix in early rheumatoid arthritis observational cohorts: a narrati 2019 Nov 1 OBJECTIVES: Observational cohort studies in early RA are a key source of evidence, despite inconsistencies in methodological approaches. This narrative review assesses the spectrum of methodologies used in addressing centre-level effect and case-mix adjustment in early RA observational cohort studies. METHODS: An electronic search was undertaken to identify observational prospective cohorts of >100 patients recruited from two or more centres, within 2 years of an RA or early inflammatory arthritis diagnosis. References and author publication lists of all studies from eligible cohorts were assessed for additional cohorts. RESULTS: Thirty-four unique cohorts were identified from 204 studies. Seven percent of studies considered centre in their analyses, most commonly as a fixed effect in regression modelling. Reporting of case-mix variables in analyses varied widely. The number of variables considered in case-mix adjustment was higher following publication of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement in 2007. CONCLUSION: Centre effect is unreported or inadequately accounted for in the majority of RA observational cohorts, potentially leading to spurious inferences and obstructing comparisons between studies. Inadequate case-mix adjustment precludes meaningful comparisons between centres. Appropriate methodology to account for centre and case-mix adjustment should be considered at the outset of analyses.
30513021 Decreased Gene Expression of Epstein-Barr Virus-Induced Gene 3 (EBI-3) may Contribute to t 2019 May BACKGROUND: Interleukin-35 (IL-35) is a member of the IL-12 family of heterodimeric cytokines produced by regulatory T (Treg) cells. This immunosuppressive cytokine can prevent exaggerated inflammatory responses like those responsible for the development of rheumatoid arthritis (RA). This study aims to determine the correlation between the gene expression of Epstein-Barr virus-induced gene 3 (EBI-3) and IL-12A (p35) subunits of IL-35 in peripheral blood leukocytes with immunological and clinical parameters in RA patients. METHODS: We recruited 47 patients with RA and 44 healthy subjects. The disease activity score-28 (DAS-28) was assessed by an expert rheumatologist and the plasma levels of neopterin and anti-cyclic citrullinated peptide (anti-CCP) was measured using ELISA method also Serum rheumatoid factor (RF) was assessed by the agglutination test. For the evaluation of IL-12A and EBI-3 gene expression, we used qPCR. RESULTS: We did not find any significant correlation between the gene expression of IL-35 subunits and DAS-28. There was a negative correlation between the plasma levels of neopterin and the gene expression of EBI-3 (p = 0.004). Inversely, we found a positive correlation between plasma level of anti-CCP and neopterin (p < 0.001) also between RF and DAS-28 (p = 0.001). CONCLUSION: Regarding the significant negative correlation between EBI-3 gene expression and plasma levels of neopterin, it can be concluded that the altered gene expression of EBI-3 may play a role in the pathogenesis of RA.
30551369 Ankylosing spondylitis and mesenchymal stromal/stem cell therapy: a new therapeutic approa 2019 Jan Ankylosing spondylitis (AS) is an inflammatory rheumatoid disease categorized within spondyloarthropathies (SpA) and manifested by chronic spinal arthritis. Several innate and adaptive immune cells and secreted-mediators have been indicated to play a role in AS pathogenesis. Considering the limitations of current therapeutic approaches (NSAIDs, glucocorticoids, DMARDs and biologic drugs), finding new treatments with fewer side effects and high therapeutic potentials are required in AS. Mesenchymal stem cells (MSCs) with considerable immunomodulatory and regenerative properties could be able to attenuate the inflammatory responses and help tissue repair by cell-to-cell contact and secretion of soluble factors. Moreover, MSCs do not express HLA-DR, which renders them a favorable therapeutic choice for transplantation in immune-mediated disorders. In the present review, we describe immunopathogenesis and current treatments restrictions of AS. Afterwards, immunomodulatory properties and applications of MSCs in immune-mediated disorders, as well as recent findings of clinical trials involving mesenchymal stem cell therapy (MSCT) in ankylosing spondylitis, will be discussed in detail. Additional studies are required to investigate several features of MSCT such as cell origin, dosage, administration route and, specifically, the most suitable stage of disease for ideal intervention.
30915372 Efficient Therapeutic Function and Mechanisms of Human Polyclonal CD8(+)CD103(+)Foxp3(+) R 2019 OBJECTIVE: To investigate the potential therapeutic effect in a rheumatoid arthritis model of stable human CD8(+) regulatory T cells (hCD8(+)Tregs) induced by TGF-β1 and rapamycin (RAPA) in vitro. METHODS: Human CD8(+)T cells were isolated from human peripheral blood mononuclear cells and induced/expanded with TGF-β1 and RAPA along with anti-CD3/28 beads and IL-2 in vitro and harvested as hCD8(+)Tregs. The phenotypes, suppressive characteristics, and stability of the hCD8(+)Tregs in an inflammatory microenvironment were examined in vitro. Human CD8(+)Tregs were transfused into an acollagen-induced arthritis (CIA) mouse model, and their therapeutic effects and related mechanisms were investigated. RESULTS: Human CD8(+)Tregs induced by TGF-β1/RAPA showed high expression of Foxp3 and CD103, exhibited vigorous suppression ability, and were stable in inflammatory microenvironments. In CIA mice, the clinical scores, levels of anti-collagen IgG antibody, and cartilage destruction were significantly reduced after adoptive transfusion with hCD8(+)Tregs. Moreover, hCD8(+)Treg treatment significantly reduced the number of Th17 cells, increased the number of CD4(+)IFN-γ (+)T cells, and produced self CD4(+)Foxp3(+)Tregs in vivo. In an in vitro cell coculture assay, hCD8(+)Tregs significantly inhibited mouse CD4(+) effector T cell proliferation, induced mouse CD4(+)Foxp3(+)Treg and CD4(+)IFN-γ (+)Th1 cell production, reduced Th17 cell development, and downregulated CD80/86 expression on mature DCs (mDCs). CONCLUSION: TGF-β1/RAPA can induce hCD8(+)Tregs with stable suppressive characteristics, which could significantly alleviate the severity of CIA based on their stable suppressive ability in an inflammatory microenvironment and further influence the function of other downstream cell subtypes. Human CD8(+)Tregs might be a therapeutic strategy for rheumatoid arthritis.
31378114 Check-control of inflammation displayed by bone marrow mesenchymal stem cells in rheumatoi 2019 Sep Background: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.
31501349 Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microch 2019 Sep 24 HLA class II genes provide the strongest genetic contribution to rheumatoid arthritis (RA). HLA-DRB1 alleles encoding the sequence DERAA are RA-protective. Paradoxically, RA risk is increased in women with DERAA(+) children born prior to onset. We developed a sensitive qPCR assay specific for DERAA, and found 53% of DERAA(-/-) women with RA had microchimerism (Mc; pregnancy-derived allogeneic cells) carrying DERAA (DERAA-Mc) vs. 6% of healthy women. DERAA-Mc quantities correlated with an RA-risk genetic background including DERAA-binding HLA-DQ alleles, early RA onset, and aspects of RA severity. CD4(+) T cells showed stronger response against DERAA(+) vs. DERAA(-) allogeneic cell lines in vitro, in line with an immunogenic role of allogeneic DERAA. Results indicate a model where DERAA-Mc activates DERAA-directed T cells that are naturally present in DERAA(-/-) individuals and can have cross-reactivity against joint antigens. Moreover, we provide an explanation for the enigmatic observation that the same HLA sequence differentially affects RA risk through Mendelian inheritance vs. microchimeric cell acquisition.
31619597 Pulmonary Intravascular Large B-cell Lymphoma in a Patient Administered Methotrexate for R 2020 Feb 1 A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.
31202880 Rapid profiling of alkaloid analogues in Sinomenii Caulis by an integrated characterizatio 2019 Sep 10 Alkaloids, the principal constituents in the caulis of Sinomenium acutum, have gained an increasing interest over the past decades since they are widely employed as a clinical treatment for rheumatoid arthritis. In the present study, an integrated characterization strategy by combining mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension (DFIBE) was firstly proposed for rapid profiling of alkaloids in Sinomenii Caulis (SC) via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The rectangular MDFSC window could more accurately screen the target alkaloids of different types, and the DFIBE could facilitate the acquisition of characteristic fragment ions for structural elucidation of alkaloids. High-performance liquid chromatography (HPLC) fingerprints with principal component analysis (PCA) and hierarchical clustering analysis (HCA) was established for identifying the chemical markers and simultaneous determination of sinomenine, magnoflorine, menisperine, stepharanine and ehydrodiscretine. A total of 91 alkaloids, including 82 targeted ones (26 morphinans, 22 aporphines, 20 protoberberines and 14 benzylisoquinolines) were unambiguously identified or tentatively characterized in SC, and 14 of them were reported for the first time. Sinomenine and magnoflorine could be selected as chemical markers to evaluate the quality of SC from different localities. In conclusion, the proposed method provided a potential approach for chemical profiling and holistic quality control of herbal medicines.
30771237 Development and Validation of an (18) F-Fluorodeoxyglucose-Positron Emission Tomography Wi 2019 Aug OBJECTIVE: Clinical joint count assessment is important for detecting synovitis but its reliability is a subject of controversy. This study was undertaken to assess the correlation of positron emission tomography (PET)-derived parameters in 68 joints with disease activity and to compare the reliability of joint counts between PET with computed tomography (CT) and clinical assessment in patients with rheumatoid arthritis (RA). METHODS: We enrolled 91 patients with active RA (69 in a development group and 22 in a validation group) who underwent concurrent (18) F-fluorodeoxyglucose ((18) F-FDG)-PET-CT and clinical disease activity evaluation. PET-derived parameters were compared with disease activity assessed using clinical joint count parameters. A Disease Activity Score (DAS) using counts of PET-positive joints was developed, and then validation studies were performed in an independent group. RESULTS: The number of PET-positive joints (of 28 and 68 joints) was significantly correlated with the swollen joint count (SJC) and tender joint count (TJC) and the DAS in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). Intraobserver and interobserver reliability of PET for the affected joint counts were excellent. Interobserver reliability between nuclear medicine physicians and rheumatologists was good for the SJC and TJC in both 28 joints and 68 joints. After multivariate analyses, including ESR and patient's global assessment of disease activity (PtGA) in addition to PET-derived parameters, the PET/DAS was derived as (0.063 × number of PET-positive joints in 28 joints) + (0.011 × ESR) + (0.030 × PtGA). A significant correlation between the PET/DAS and the DAS28-ESR was confirmed in the validation group (P < 0.001). CONCLUSION: PET-CT could serve as a sensitive and reliable method in the evaluation of disease activity in RA patients, and may be applicable as a research tool, particularly in clinical trials.
30707326 MiR-5571-3p and miR-135b-5p, derived from analyses of microRNA profile sequencing, correla 2019 Jun OBJECTIVES: This study aimed to investigate microRNA (miRNA) expression profiles in synovium tissues of rheumatoid arthritis (RA) patients by RNA sequencing and to evaluate the values of dysregulated miRNAs in RA diagnosis and monitoring. METHODS: Thirty RA patients who underwent knee arthroscopy and 30 controls with knee trauma who underwent surgery were consecutively recruited, and synovium tissue samples of both groups were obtained during surgeries. In the exploration part, miRNA and mRNA expression profiles of 3 RA samples and 3 control samples were detected using RNA sequencing then followed by bioinformatic analyses. In the validation part, 5 candidate miRNA levels were detected by quantitative polymerase chain reaction (qPCR) in 30 RA patients and 30 control patients. RESULTS: In the exploration part, 78 miRNAs and 1582 mRNAs were upregulated while 40 miRNAs and 1295 mRNAs were downregulated in synovium tissue samples of RA patients compared with those of controls. Furthermore, enrichment analyses revealed that these dysregulated miRNAs and mRNAs were mainly implicated in immune activities and inflammatory diseases such as leukocyte migration, complement activation, and RA. In the validation part, qPCR assay revealed that miR-5571-3p and miR-135b-5p expressions were increased in RA patients compared with those in controls and disclosed good predictive values for RA risk with high area under the curves (AUCs). Besides, both miR-5571-3p and miR-135b-5p levels were positively correlated with disease activity and inflammation level of RA. CONCLUSIONS: Analyses of miRNA expression profiles by sequencing indicate that miR-5571-3p and miR-135b-5p correlate with increased RA risk and activity.
29369795 Cardiovascular magnetic resonance characterization of myocardial and vascular function in 2019 Jan BACKGROUND: Rheumatoid arthritis (RA) is a multisystem, autoimmune disorder and confers one of the strongest risks for cardiovascular disease (CVD) morbidity and mortality. OBJECTIVE: To assess myocardial function and vascular stiffness in RA patients with and without cardiovascular risk factors (CVRFs) using cardiovascular magnetic resonance (CMR). METHODS: Twenty-three RA patients with no CVRFs (17 female, mean age 52 ± 13 years), 46 RA patients with CVRFs (32 female, mean age 53 ± 12), 50 normal controls (32 female, mean age 50 ± 11 years), and 13 controls with CVRFs (7 female, mean age 55 ± 7 years), underwent CMR at 1.5 Tesla, including evaluation of left ventricular (LV) ejection fraction, strain, and vascular elasticity (aortic distensibility [AD] and pulse wave velocity [PWV]). Disease activity and duration were recorded for each patient. Subjects with known symptomatic CVD were excluded. RESULTS: LV volumes, mass, and ejection fraction were similar in the four groups. RA patients with CVRFs showed the greatest abnormality in mid short-axis circumferential systolic strain, peak diastolic strain rate, and vascular indices. RA patients without CVRFs showed a similar degree of vascular dysfunction and deformational abnormality as controls with CVRFs. AD and total PWV correlated with myocardial strain and RA disease activity. On multivariate regression analysis, strain was related to age, RA disease activity, AD, and PWV. CONCLUSION: CMR demonstrates impaired myocardial deformation and vascular function in asymptomatic RA patients, worse in those with CVRFs. Subclinical cardiovascular abnormalities are frequent and appear to be incremental to those due to traditional CVRFs and likely contribute to the excess CVD in RA.
31276446 Adherence to biological therapies in patients with chronic inflammatory arthropathies. 2019 Jul 1 INTRODUCTION: The aims of the study were to quantify adherence, determine the factors that can  predict adherence and identify the consequences of poorer adherence in patients with chronic  inflammatory arthropathies treated with biological therapies in daily clinical practice. METHOD: A descriptive, observational and retrospective study was carried out. Patients with  rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who started a biologic therapy  between 1 January 2009 and 31 December 2016 were included. Variables related to socioeconomic  status, the disease, the biological therapy and hospital resources were included. Adherence was  calculated by using the medication possession ratio. RESULTS: Three hundred and sixty-two patients and 423 lines of biological therapy were included.  Mean age ± standard deviation was 50.3 ± 13.9 years, and 228 (53.9%) were women. The  percentage of adherent patients was 187 out of 216 (87%) in rheumatoid arthritis, 91 out of 107  (85%) in ankylosing spondylitis and 84 out of 100 (84%) in psoriatic arthritis. Greater adherence was  associated with more frequent visits to the pharmacy service (odds ratio 1.2, 95% confidence  interval: 1.1-1.3 [p = 0.001]) and poorer adherence with a failure to attend scheduled appointments  at the rheumatology clinic (odds ratio 0.2, 95% confidence interval: 0.1-0.9 [p = 0.030]). There were  no differences between  adherent and non-adherent patients in terms of the number of hospital resources used. CONCLUSIONS: There are no differences in adherence to biological therapies among patients with  chronic inflammatory arthropathies. Adherence correlates with attendance at outpatient  appointments, but this does not imply an increase in the use of hospital resources.
30892622 Association between socioeconomic status and comorbidities among patients with rheumatoid 2019 Sep 1 OBJECTIVES: We examined the association between socioeconomic status (SES) and comorbidity distribution among patients with RA. METHODS: Information on comprehensive health status of 1088 RA patients (weighted n = 612 303) was obtained from the 2007-2015 Korea National Health and Nutrition Examination Survey database. SES components were household equivalence income, education and area of residence. To minimize confounding by age, patients were stratified by median age (63 years). Age-adjusted odds ratio (OR) with 95% confidence interval (95% CI) was estimated, comparing weighted prevalence of individual comorbidities between low and high SES groups in each age stratum. RESULTS: Among RA patients aged <63 years (mean 49 years, 70% female), we observed age-adjusted associations of depression (OR 2.13, 95% CI 1.01, 4.53), depressive mood (OR 2.68, 95% CI 1.54, 4.65), suicide ideation (OR 3.01, 95% CI 1.79, 5.07), diabetes (OR 3.09, 95%CI 1.31, 7.29), obesity (OR 2.04, 95% CI 1.30, 3.20), hypertriglyceridemia (OR 2.36, 95% CI 1.28, 4.34) and osteoarthritis (OR 2.12, 95% CI 1.13, 3.99) with low income, of suicide ideation with low education (OR 2.25, 95% CI 1.14, 4.44), but no association of any comorbidities with area of residence. Unhealthy behavior patterns were comparable between low- and high-income groups but patients with low income reported a numerically higher rate of failed access to necessary healthcare services. We did not find any association between SES and comorbidities among those aged ⩾63 years (mean 72 years, 83% female). CONCLUSION: Among Korean RA patients aged <63 years, socioeconomic inequalities of multiple comorbidities in mental, cardiometabolic and musculoskeletal systems were found.
31761884 Development of Disseminated Tuberculosis with Intestinal Involvement due to Adalimumab Adm 2020 Mar 15 Treatment of latent tuberculosis infection (LTBI) reduces the probability of reactivation of tuberculosis associated with anti-tumor necrosis factor (TNF) α inhibitors, but no chemoprophylaxis is completely protective. We herein report a woman with rheumatoid arthritis who developed disseminated tuberculosis with intestinal involvement during adalimumab administration despite LTBI treatment. Tuberculosis reactivation was not detected in sputum or urine but was detected from the terminal ileal mucosa. Detection of intestinal tuberculosis is rare in patients being treated with anti-TNFα therapy after LTBI treatment. As anti-TNFα inhibitors have become more common, the rate of reactivation of tuberculosis, including intestinal tuberculosis, has increased in patients being treated for LTBI.
30719581 ALPL mutations in adults with rheumatologic disorders and low serum alkaline phosphatase a 2019 Sep Tissue-nonspecific alkaline phosphatase (ALP), encoded by ALPL, is important for bone homeostasis and interacts with collagen type I. In the present study, we sequenced ALPL and a panel of collagen type I-related genes in 24 adults (age 22-80 years; 20 female) with persistently low serum ALP (< 40 U/L) and a range of rheumatologic symptoms. We found heterozygous pathogenic or likely pathogenic variants in ALPL in 14 (58%) of these individuals. In addition, 7 study participants had potentially damaging heterozygous variants of uncertain significance in genes related to collagen type I. Patients who were positive for ALPL variants had similar age and serum ALP levels to patients in whom no ALPL variants were detected, but had higher serum pyridoxal-5-phosphate concentrations (median 214 nmol/L vs. 64 nmol/L; p = 0.02; U test). In summary, heterozygous ALPL variants are frequent in individuals with rheumatologic symptoms and low ALP serum activity. It is possible that variants in genes that are involved in collagen type I production have a modifying effect on the clinical consequences of such ALPL variants.
31094242 Anti-TNF biosimilars in psoriasis: from scientific evidence to real-world experience. 2020 Dec Tumor necrosis factor (TNF) inhibitors account for a large proportion of drugs used to treat psoriasis and are indicated first-line options in certain settings. Several biosimilar drugs based on the anti-TNF agents adalimumab, infliximab, and etanercept are now available for use in patients with psoriasis. The favorable cost differential of biosimilars is expected to improve access to biologic therapy for biologic-naive psoriasis patients, who are often undertreated. Also, substantial cost savings can be made if patients are switched to biosimilars. To date, most clinical testing of anti-TNF biosimilars approved for use in psoriasis has been performed in patients with rheumatoid arthritis, and the results extrapolated to psoriasis. Although this may initially raise concerns for clinicians looking to start their psoriasis patients on biologic treatment with a biosimilar or switch from an original biologic to a biosimilar, the process of extrapolation is tightly regulated and scientifically justified. Furthermore, available real-world evidence of the safety and efficacy of anti-TNF agents in patients with psoriasis complements clinical trial data in patients with rheumatoid arthritis. When equipped with the appropriate knowledge, clinicians should have confidence to use biosimilars for the treatment of psoriasis.
31768994 Rare Finding of Bilateral Pseudoangiomatous Stromal Hyperplasia of the Breast: A Case Repo 2019 Dec 20 A 49-year-old woman, with a medical history of rheumatism, was admitted to our hospital with chief complaints of bilateral enlargement and redness of breasts. She underwent weekly breast examinations. Mammography findings were reported as category 3 for both breasts. Breast ultrasonography, magnetic resonance imaging, and chest contrast computed tomography revealed a massive tumor in the left BD region, however, there were no findings for suspected malignancy. Needle biopsy did not yield histologically malignant cells in both breasts. Mammary interstitium was edematous, and capillary-like slit structures were observed. The stroma stained with alcian blue and destained with hyaluronidase treatment. Since the stroma tested positive for vimentin, calponin, and CD34 and negative for CD31, the patient was diagnosed as (PASH). Because both breasts had similar diagnosis based on histopathologic findings, bilateral mastectomy was performed. Details about the origin of bilateral PASH are unknown but it may be related to the development of rheumatoid arthritis. Additionally, systemic autoimmune diseases like rheumatism may be the reason for repeated contraction and enlargement of PASH.