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ID PMID Title PublicationDate abstract
33044800 Temporal Relationship Between Juvenile Idiopathic Arthritis Disease Activity and Uveitis D 2022 Mar OBJECTIVE: To determine whether there is a temporal association between arthritis and uveitis activity among children with juvenile idiopathic arthritis-associated uveitis (JIA-U). METHODS: Uveitis and arthritis data from patients with JIA-U age ≤21 years were collected from July 2013 to December 2019 at a tertiary care center. Arthritis activity was assessed at each rheumatology visit, and the primary outcome was the presence of active uveitis at ophthalmologic examination within 45 days of the rheumatology visit. Repeated-measures logistic regression was used to evaluate the temporal association between any uveitis activity within 45 days of arthritis activity. Models were adjusted for demographic-, disease-, and treatment-related factors. RESULTS: A total of 98 patients were included: 81 (83%) female, 67 (69%) antinuclear antibody positive, 59 (60%) oligoarticular, and 13 (13%) enthesitis-related arthritis (ERA) subtypes. There were 1,229 rheumatology visits, with a median of 13 visits per patient (interquartile range 7-18). Concordance between arthritis and uveitis activity was observed 73% of the time (694 of 947). There was an independent temporal association between uveitis and arthritis activity (odds ratio 2.47 [95% confidence interval 1.72-3.54]; P < 0.01), adjusted for demographic and disease characteristics. Use of combination biologic and nonbiologic disease-modifying antirheumatic drugs, female sex, HLA-B27 positivity, and ERA and polyarticular (rheumatoid factor negative) subtypes were associated with decreased odds of active uveitis at any time point. CONCLUSION: In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity. These novel results suggest that an arthritis flare should prompt an expedited referral to the ophthalmologist.
35426539 Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulat 2022 Jun Methotrexate (MTX), the first-line drug for the treatment of rheumatoid arthritis (RA), can cause considerable toxicity, which limits effective dosage regimens. Moreover, it has rapid clearance, which leads to poor patient compliance. To mitigate such challenges, this study aimed to validate the use of MTX-loaded chitosan nanoparticles (NPs) in treating Freund's complete adjuvant (FCA) arthritis in rats. Healthy Wistar rats (n = 30) were divided into five groups. The first group served as healthy control, while the second group served as arthritic control. Group 3 was administered methotrexate, while groups 4 and 5 were MTX-loaded NP-treated groups. NPs were prepared by solvent evaporation method and characterized by zeta size, potential, polydispersity index (PDI), and Fourier-transform infrared spectroscopy. NPs were 190 nm in size, and PDI was 0.25, confirming the uniform distribution of NPs. A significant increase in paw thickness was noted up to the 21st day of the study, which was reversed by a high dose of MTX-loaded NPs. MTX NPs significantly reduced the level of pro-inflammatory markers, including TNF-α and IL-6, along with improving control of oxidative stress biomarkers. The findings of biochemical, haematological, radiological, and histopathological investigations further confirmed amelioration of necrosis and cellular infiltration. It can be concluded that MTX-loaded chitosan NPs are promising candidates for treating FCA-induced arthritis in a rat model.
35566580 Fatigue and Associated Factors in an Immune-Mediated Inflammatory Disease Population: A Cr 2022 Apr 27 Fatigue is a main symptom of chronic diseases, including immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD) and inflammatory arthritis (IA); however, the pathophysiological mechanisms are not completely understood. The aim of this study was to assess the prevalence of fatigue and the associated factors in an IMIDs population. A control group, IBD, and IA patients, were enrolled. The PROMIS(®) fatigue questionnaire was used to evaluate the symptoms. Information on demographics, anthropometrics, disease characteristics, and medications was collected for each participant. A total of 471 subjects (137 with IBD, 103 with IA, and 206 controls) were enrolled. IBD and IA patients reported greater fatigue than controls (p < 0.001, each). In univariate regression, patients with anxiety and depression were more likely to report fatigue (p = 1.40 × 10(-9) and p = 3.80 × 10(-11), respectively). Males, holding a high school diploma, and being employed were inversely correlated to the domain (p = 1.3 × 10(-5); p = 0.003 and p = 0.005, respectively). The use of steroids and disease activity determined increased fatigue (p = 0.014 and p = 0.019; respectively). In the multivariate analysis, anxiety and depression remained associated (p = 0.002 and p = 1.3 × 10(-5), respectively). IMIDs patients present increased fatigue compared with healthy subjects. Anxiety and depression are the main associated factors, suggesting a psychological component of the symptom; thus, a holistic management should be established.
35358376 Pain sensitization as a potential mediator of the relationship between sleep disturbance a 2022 Mar 31 OBJECTIVE: Many patients with rheumatoid arthritis (RA) suffer from sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. In this study, we examined the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain. METHODS: We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying anti-rheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and non-articular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System®. We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors. RESULTS: Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5-unit in sleep disturbance = 0.32, 95% confidence interval [CI] 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect. CONCLUSION: Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.
35178101 Yunnan Baiyao Ameliorates Rheumatoid Arthritis in Rats by Shifting the Th17/Treg Cell Bala 2022 Yunnan Baiyao (YNB) is a traditional Chinese medicine that possesses anti-inflammatory effects. Previously, we have demonstrated the effects of YNB in rheumatoid arthritis (RA) animal models; however, the underlying mechanisms are unclear. In the present study, we aimed to investigate the effects of YNB on the T-helper (Th)17/T-regulatory (Treg) cell balance in a collagen-induced arthritis rat model orally administrated YNB or methotrexate, a widely used therapeutic agent for treating RA. Our results showed that YNB treatment significantly decreased the voix pedis thickness and joint functionality scores and alleviated joint histopathology in these rats. These YNB-induced effects were achieved by decreasing the number of Th17 cells and increasing that of Treg cells in the spleen. Moreover, the interleukin- (IL-) 17 level considerably decreased in the serum of YNB-treated rats, whereas the IL-10 level significantly increased. Furthermore, YNB could inhibit RANKL-induced osteoclast formation by regulating the tumor necrosis factor receptor-associated factor 6/NF-κB/nuclear factor of the activated T-cell pathway. In summary, our study shows that YNB exhibits antiarthritic activity by decreasing the ratio of Th17/Treg cells, regulating the cytokine balance, and inhibiting osteoclast activation, providing an experimental basis that supports the use of this traditional Chinese medicine for the clinical treatment of RA.
35614292 MANTA and MANTA-RAy: Rationale and Design of Trials Evaluating Effects of Filgotinib on Se 2022 May 25 INTRODUCTION: The phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases. Here we describe the methods and rationale for these studies. METHODS AND RATIONALE: The MANTA and MANTA-RAy studies included men (aged 21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases, respectively. Participants had no history of reproductive health issues, and the following semen parameter values (≥ 5th percentile of World Health Organization reference values) at baseline: semen volume ≥ 1.5 mL, total sperm/ejaculate ≥ 39 million, sperm concentration ≥ 15 million/mL, sperm total motility ≥ 40% and normal sperm morphology ≥ 30%. Each trial included a 13-week, randomized, double-blind, placebo-controlled period (filgotinib 200 mg vs placebo, up to N = 125 per arm), for pooled analysis of the week-13 primary endpoint (proportion of participants with ≥ 50% decrease from baseline in sperm concentration). All semen assessments were based on two samples (≤ 14 days apart) to minimize effects of physiological variation; stringent standardization processes were applied across assessment sites. From week 13, MANTA and MANTA-RAy study designs deviated owing to disease-specific considerations. All subjects with a ≥ 50% decrease in sperm parameters continued the study in the monitoring phase until reversibility, or up to a maximum of 52 weeks, with standard of care as treatment. Overall conclusions from MANTA and MANTA-RAy will be based on the totality of the data, including secondary/exploratory measures (e.g. sperm motility/morphology, sex hormones, reversibility of any effects on semen parameters). CONCLUSIONS: Despite the complexities, the MANTA and MANTA-RAy studies form a robust trial programme that is the first large-scale, placebo-controlled evaluation of potential impacts of an advanced IBD and rheumatic disease therapy on semen parameters. TRIAL REGISTRATION: EudraCT numbers 2017-000402-38 and 2018-003933-14; ClinicalTrials.gov identifiers NCT03201445 and NCT03926195.
35469843 Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study. 2022 Apr 22 BACKGROUND: Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited. OBJECTIVE: We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD. METHODS: Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. We compared baseline prevalence and incidence after diagnosis of autoimmune conditions in 173,709 children and adults with new-onset AD and 694,836 age-, sex-, and general practitioner practice-matched controls. Outcomes were a composite of any autoimmune condition (Crohn disease, ulcerative colitis, celiac disease, pernicious anemia, type 1 diabetes, autoimmune hypothyroidism, Graves disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren syndrome, vitiligo, alopecia areata, and multiple sclerosis) and each individual autoimmune condition. RESULTS: Preexisting autoimmune conditions were more common in people diagnosed with AD compared to controls (composite 5.8% vs 4.3%). Excluding people with preexisting autoimmune disease, there was an association between AD and incidence of new-onset autoimmune disease (composite adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.23-1.34). Risk was highest for more severe AD (aHR 1.99; 95% CI 1.77-2.23) than moderate AD (aHR 1.33; 95% CI 1.19-1.49) or mild AD (aHR 1.22; 95% CI 1.16-1.28). People with AD were at significantly increased risk of developing psoriatic arthritis, Sjögren syndrome, Crohn disease, vitiligo, alopecia areata, pernicious anemia, ulcerative colitis, rheumatoid arthritis, and hypothyroidism (aHR range 1.17-2.06), but not other autoimmune conditions. CONCLUSION: People with AD have an increased risk of multiple autoimmune conditions, especially those with more severe AD.
35640489 Validation studies of rheumatoid arthritis patient-reported outcome measures in population 2022 May 19 BACKGROUND: Existing patient-reported outcome measures (PROMs) in rheumatoid arthritis (RA) may be limited in their applicability to populations that are at risk for inequities. We conducted a systematic review to identify and rate evidence in the validation studies for PROMs in populations at risk for inequity. METHODS: A systematic review of MEDLINE and EMBASE was completed. The search strategy was developed to identify measurement property studies for PROMs of interest (selected pain, disease activity, global evaluation and quality of life scales) in patients with RA. We identified experimental, observational, and qualitative studies reporting analysis of feasibility, construct validity and discriminant ability metrics for populations at risk for inequity by various factors including race, ethnicity, culture or language; employment status; sex and gender identity; education level; socioeconomic status; social support; age; health literacy and disability. These were rated based on the OMERACT Summary of Measurement Properties Equity table. RESULTS: From 19,786 titles and abstracts screened, we identified 14 unique studies reporting validation metrics for pain (n = 3), DAS28-ESR or DAS28-CRP (n = 2), ACR20 (n = 1), patient global assessment (n = 2), EQ5D (n = 4), and PROMIS® (n = 3) by race (n = 10 studies), age (n = 6 studies), sex (n = 5 studies), education level (n = 2 studies), and disability, literacy, employment status, social support level and socioeconomic status (n = 1 study each). Five studies reported on feasibility, 12 reported construct validity metrics, and 4 studies reported on discriminant validity metrics. All studies by culture or language were rated as having good measurement property metrics. There was limited assessment of measurement property metrics for other populations at risk for inequity. CONCLUSION: Our study highlights important gaps in patient representation in rheumatology research for accepted outcome measures. New outcome measures being developed for research purposes and clinical practice should ensure and report representation of patients from populations at risk for inequities in the testing of metrics of feasibility, construct validity and discriminant ability metrics.
33859345 TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-l 2022 Feb Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.
34970731 Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysi 2022 Apr INTRODUCTION: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. METHODS: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. RESULTS: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. CONCLUSIONS: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. TRIAL REGISTRATION NUMBERS: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.
35281745 Bone erosion in inflammatory arthritis is attenuated by Trichinella spiralis through inhib 2022 Mar 18 Helminths and helminth-derived products hold promise for treating joint bone erosion in rheumatoid arthritis (RA). However, the mechanisms of helminths ameliorating the osteoclastic bone destruction are incompletely understood. Here, we report that Trichinella spiralis infection or treatment with the excreted/secreted products of T. spiralis muscle larvae (MES) attenuated bone erosion and osteoclastogenesis in mice with collage-induced arthritis (CIA) through inhibiting M1 monocyte/macrophage polarization and the production of M1-related proinflammatory cytokines. In vitro, MES inhibited LPS-induced M1 macrophage activation while promoting IL-4-induced M2 macrophage polarization. Same effects of MES were also observed in monocytes derived from RA patients, wherein MES treatment suppressed LPS-induced M1 cytokine production. Moreover, MES treatment attenuated LPS and RANKL co-stimulated osteoclast differentiation from the RAW264.7 macrophages through inhibiting activation of the NF-κB rather than MAPK pathway. This study provides insight into the M1 subset as a potential target for helminths to alleviate osteoclastic bone destruction in RA.
34791526 Geographical variability in the relationship between synoptic weather type and emergency d 2022 Mar Bodily pain plagues populations across the globe. Past studies have discovered some links between synoptic weather types and different kinds of pain. These relationships are essential as they can aide in treatment and potentially prevention of pain. In this study, the role of geographical characteristics on the relationships between synoptic weather type and pain were looked at. North Carolina was separated into three geographic sections: Appalachian Mountains, Piedmont Plateau, and Coastal Plain. Over a 7-year period, synoptic weather types and emergency department (ED) visits for various kinds of pain (migraine, fibromyalgia, rheumatoid arthritis, osteoarthritis, and general back pain) were collected. Bootstrapped confidence intervals of the mean number of population-adjusted ED visit rates (per 100,000 persons), for the different synoptic weather types, were compared across the different geographic regions. In the plateau region, Moist Tropical and Moist Moderate weather types were often linked to the highest rates of ED visits, while Polar weather types were frequently associated with the fewest visits. The mountainous portion of the state displayed similar patterns between synoptic weather types and the different forms of pain, with migraine and fibromyalgia being the exceptions. Few statistically significant relationships were noted for the coastal region.
35317281 MicroRNA-10b promotes arthritis development by disrupting CD4(+) T cell subtypes. 2022 Mar 8 Rheumatoid arthritis (RA) is an inflammation-involved disorder and features the disruption of CD4(+) T lymphocytes. Herein, we describe that microRNA-10b-5p (miR-10b) promotes RA progression by disrupting the balance between subsets of CD4(+) T cells. MiR-10b-deficient mice protected against collagen antibody-induced arthritis (CAIA) model. RNA sequencing results indicated that disordered genes in miR-10b(-/-) CAIA model are closely associated with CD4(+) T cells differentiation. Moreover, miR-10b mimics promoted Th1/Th17 and suppressed Th2/Treg cells differentiation, whereas miR-10b inhibitor induced contrary effects. In addition, GATA3 and PTEN was confirmed as two targets of miR-10b, and GATA3 siRNA could increase Th1 and reduce Th2 cells meanwhile PTEN siRNA could increase Th17 and decrease Treg cells. Furthermore, miR-10b inhibitor significantly ameliorated collagen-induced arthritis (CIA) development by attenuating the dysfunctional CD4(+) T cell subpopulations. The present findings suggest that miR-10b could disrupt the balance of CD4(+) T subsets, while suppressed miR-10b could attenuate the severity of experimental arthritis, which provided us a novel mechanistic and therapeutic insight into the RA.
35054124 The Role of Interleukin 18/Interleukin 18-Binding Protein in Adult-Onset Still's Disease a 2022 Jan 15 Interleukin 18 (IL-18) is a pro-inflammatory cytokine of the IL-1 family, whose activity is tightly controlled at the level of production, as well as signalization. Notably, it is buffered by its natural inhibitor, IL-18 binding protein (IL-18BP), which is massively present in circulation in normal and in most pathological conditions, thus preventing harmful pro-inflammatory systemic effects of IL-18. IL-18 has long been considered to be involved in the pathophysiology of various inflammatory diseases. However, a first clinical trial using recombinant IL-18BP for the treatment of rheumatoid arthritis and psoriasis gave disappointing results. Direct measurements of unbound, bioactive, free form of circulating IL-18 demonstrated that IL-18 was more specifically involved in adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) but also in their most severe complication, macrophage activation syndrome (MAS). More importantly, administration of recombinant IL-18BP to patients with AOSD, and sJIA with MAS, showed promising results. This review summarizes available data regarding IL-18 and IL-18BP in AOSD and sJIA in mouse models and humans and shows the importance of IL-18/IL-18BP imbalance in these conditions, leading to the conclusion that IL-18, particularly free IL-18, may be a useful biomarker in these diseases and an interesting therapeutic target.
35249483 Relationship between Gut Microbiota and Bone Health. 2022 Mar 4 Gut microbiota (GM) are microorganisms that live in the host gastrointestinal tract, and their abundance varies throughout the host's life. With the development of sequencing technology, the role of GM in various diseases has been increasingly elucidated. Unlike earlier studies on orthopedic diseases, this review elucidates the correlation between GM health and bone health, and discusses the potential mechanism of GM effects on host metabolism, inflammation, and ability to induce or aggravate some common orthopedic diseases such as osteoarthritis, osteoporosis, rheumatoid arthritis, etc. Finally, the prospective methods of GM manipulation and evaluation of potential GM-targeting strategies in the diagnosis and treatment of orthopedic diseases are reviewed.
32644520 Collagen-Vascular Disease Associated With Interstitial Lung. 2022 Jan Collagen vascular disease encompasses a diverse group of immunologically mediated entities that share overlapping clinical and histopathologic features as well as manifest in characteristic patterns of interstitial lung disease. The collagen vascular diseases which commonly affect the pulmonary system include rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), polymyositis (PM), dermatomyositis (DM), mixed connective tissue disease (MCTD), and Sjogren’s syndrome (SS). The degree of lung involvement and spectrum of thoracic findings vary among the disorders, may be seen with clinically early or late disease, and portends certain patient outcomes. Identification of pulmonary involvement has important therapeutic and prognostic implications. Collagen vascular disease may be associated with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), diffuse alveolar damage (DAD), and lymphocytic interstitial pneumonia (LIP).
32119399 Epidermolysis Bullosa Acquisita. 2022 Jan Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune blistering disease of the skin and mucous membranes. EBA is caused by autoantibodies to type VII collagen, a major component of anchoring fibrils in the dermal-epidermal junction (DEJ). These anchoring fibrils are responsible for attaching the epidermis to the underlying dermis, and binding of autoantibodies to type VII collagen subsequently leads to detachment of the epidermis, resulting in skin fragility, blisters, erosions, scars, milia, and nail loss. Clinically, patients can present with various phenotypes. The mechanobullous and bullous pemphigoid-like forms of EBA are the two most common presentations. The classic mechanobullous EBA resembles dystrophic epidermolysis bullosa (EB) with bullae and erosions occurring at sites of trauma. The inflammatory forms of EBA present with clinical manifestations similar to other autoimmune blistering disorders, including bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP). EBA has been reported in association with several systemic diseases, including inflammatory bowel disease, thyroiditis, rheumatoid arthritis, hepatitis C infection, and diabetes mellitus.
28613696 Anorexia and Cachexia. 2022 Jan Cachexia is a significant loss of muscle and adipose tissue. It occurs in patients with advanced cancer, chronic obstructive pulmonary disease, chronic infection including AIDS and tuberculosis, chronic heart failure, and rheumatoid arthritis. Increases in pro-inflammatory factors characterize cachexia. There is a decreased quality of life, decreased tolerance to surgical or medical interventions, and shortened survival. The frequency and intensity of cachexia differ among cancers; patients with gastrointestinal, pancreatic, and lung cancers are more likely affected by cachexia than other tumors. By contrast, cachexia is relatively uncommon in patients with breast, sarcomas, and hematological malignancies. Cachexia is not simple starvation where fat stores replace glucose as the primary fuel. Cancer causes a change in metabolism as opposed to an energy deficit, so conventional nutritional support is not sufficient.
35575484 The Management of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis. 2022 May 16 INTRODUCTION: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder associated with an increased incidence and prevalence of cardiovascular disease (CVD), including myocardial infarction and heart failure. In addition to traditional risk factors, evidence suggests inflammation is critical to the pathophysiology of both conditions. Despite the association being well-recognised, challenges remain in managing cardiovascular risk in RA. AREAS COVERED: This manuscript analyses the association between CVD and RA andexplores the limitations in evaluating cardiovascular risk in RA with available risk assessment tools. The authors review and discuss the optimal management of traditional risk factors such as hypertension and dyslipidaemia and contemporary risk factors such as inflammation and analyse the cardiovascular impact of RA medications. EXPERT OPINION: Analysis points to the critical role of inflammation in the pathogenesis of RA and CVD. It is well established that conventional disease-modifying anti-rheumatic drugs (DMARDs) improve cardiovascular outcomes; however, underlying risk often remains underappreciated. The authors suggest there remains an opportunity to improve mortality and morbidity with the early recognition and identification of at-risk populations and the timely initiation of appropriate cardiovascular and anti-inflammatory medications. More research is necessary into the role that imaging may play in stratifying risk and in the longer-term cardiovascular impact of biological DMARDs.
35110134 Serum interleukin-6 in seropositive rheumatoid arthritis and response to tocilizumab: An o 2022 Jan OBJECTIVE: There is no clinically useful biomarker as a predictor of response to any class of biological disease-modifying antirheumatic drugs (bDMARD). Serum interleukin-6 (IL-6) has a major role in the pathogenesis of rheumatoid arthritis (RA) and its serum level in patients of RA may predict response to treatment with IL-6 receptor (IL-6R) antagonist tocilizumab. METHODS: Biological DMARD naïve patients of seropositive RA, fulfilling American College of Rheumatology/European League Against Rheumatism classification criteria 2010, were treated with 06 doses of tocilizumab (8mg/kg) at monthly interval. Baseline and post-treatment serum IL-6 levels were measured and correlated with response to treatment measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28 ESR) after treatment. RESULTS: The study included 34 patients and 26 (70%) of them achieved DAS-28 remission (DAS28 ESR < 2.6). The baseline serum IL-6 did not correlate with post-treatment DAS28 ESR (R -0.197, P = .264). Though, statistically not significant (P = .085) more patients with comparatively lower baseline serum IL-6 attained DAS28 remission (16 out of 17, P = .085). There was an increase in the serum IL-6 level (median 40.5pg/ml [IQR 130.2] to 72.6pg/ml [IQR 162.5]) after tocilizumab treatment and the change in IL-6 level also did not correlate with post-treatment DAS28 ESR (R -0.240, P = .172). CONCLUSION: Higher number of patients with comparatively lower serum IL-6 level attained DAS28 remission in this study; however, it was not statistically significant. It requires further evaluation in larger studies to make any conclusion on the role of serum IL-6 as a predictor of response to tocilizumab in seropositive RA.