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ID PMID Title PublicationDate abstract
32315078 Rare genetic variants in systemic autoimmunity. 2020 Jul Autoimmune disease is a substantial cause of morbidity and is strongly influenced by genetic risk. Extensive efforts have characterized the overall genetic basis of many autoimmune diseases, typically by investigation of common variants. While these common variants have modest effects and may cumulatively predispose to disease, it is also increasingly apparent that rare variants have significantly greater effect on phenotype and are likely to contribute to autoimmune disease. Recent advances have illustrated the next fundamental step in elucidating the genetic basis of autoimmunity, moving beyond association to demonstrate the functional consequences of these variants.
32110205 Transformation of Seborrheic Keratosis into Bowenoid Actinic Keratosis via Three Steps of 2020 Jan We report a case of seborrheic keratosis (SK) that transformed into bowenoid actinic keratosis (AK) via three steps of histological change in a 77-year-old woman. The patient presented with a multiple-year history of a brownish lesion on the right cheek. She reported that some months earlier she had noted a pinkish lesion developing within the brownish lesion. She had also been treated with several immunosuppressants for rheumatoid arthritis for many years. Physical examination revealed a nodule measuring 13 × 12 mm on the lateral side of the right upper cheek. The lesion comprised three regions: a brownish hyperkeratotic region in the upper portion; a pinkish region in the lower portion; and a slightly dented, band-like region between the other two regions. Histopathologically, the specimen consisted of four zones: SK comprising basaloid cells; SK composed of squamoid cells; atrophic AK; and bowenoid AK. The zones of SK with basaloid cells and squamoid cells clinically corresponded to the brownish hyperkeratotic region. Atrophic and bowenoid AK zones corresponded to the dented, band-like region and pinkish region, respectively. Collectively, the nodular skin lesion was diagnosed as SK associated with atrophic and bowenoid AK within the SK lesion. The present case suggests that bowenoid AK developed from SK by malignant transformation via three steps of histological change. The facts that our patient had received treatment with several immunosuppressants and that no other AK lesions were evident around the AK support the notion that in this case, bowenoid AK developed from SK by malignant transformation.
33426233 Extracellular microvesicles that originated adipose tissue derived mesenchymal stem cells 2020 Dec INTRODUCTION: Mesenchymal stem cells (MSCs) are promising therapeutic tools in regenerative medicine. In particularly adipose tissue derived MSC (AMSC) has powerful potential for the therapeutics of rheumatoid arthritis (RA) because these cells can control immune balance. RA systemically occurs autoimmune disease. Interestingly, IL-1 receptor antagonist deficient (IL-1ra(-/-)) mice induce inflammation in joints like RA. In RA therapy, although AMSC improves the inflammation activity, it is little known to play roles of extracellular microvesicles (EV) for improvement of RA. To clarify the MSC-derived EVs are involved amelioration mechanisms for RA by themselves, we examined the functional effects of development for RA by AMSC-EVs. METHODS: We isolated AMSCs derived mice adipose tissue and purified EVs from the culture supernatant of AMSCs. To examine whether EVs can improve RA, we administrated EVs or AMSCs to IL-1ra knockout mice as RA model mice. We analyzed EVs-included factor by western blot methods and RA improvement effect by ELISA. RESULTS: In this study, we showed that the swellings of joints on mice in wild type AMSC and that in AMSC-EVs decreased than that in IL-1ra(-/-) mice-AMSC-EVs and in none-treated. We detected IL-1ra expression in AMSC-EVs in wild type mice but not that in IL-1ra(-/-) mice. Proinflammatory cytokine expression changes in mice showed in AMSCs and AMSC-EVs, but no apparent differences cytokine expressions were detected in IL-1ra(-/-) mice. CONCLUSIONS: In this study, we concluded that MSCs might improve RA by the transferring of factors such as IL-1ra, which are included their MSC derived- EVs.
33257237 Economic Impact of Obstetric Events on Women of Reproductive Age Living With Psoriatic Art 2020 Nov 27 OBJECTIVE: To estimate the annual cost associated with obstetric events in women of reproductive age with immune-mediated inflammatory diseases, from the perspective of the National Healthcare System. METHODS: A cost-analysis was developed to estimate the impact associated with obstetric events in women of reproductive age with psoriasis (PSO), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). The analysis considered complications during fertility and conception, in pregnancy and in the postpartum. All parameters were validated and agreed by a multidisciplinary expert panel. Unitary costs (€, 2019) were obtained from national, local databases. RESULTS: During fertility and conception, an annual cost per patient of €229 was estimated for a preconception consultation in a patient with PSO, of €3,642 for a preconception consultation in patients with PsA, RA and axSpA and €4,339 for assisted reproduction. Women with complications in pregnancy had an annual cost per patient of €1,214 for a miscarriage in the first trimester, €4,419 for a late miscarriage in the second trimester, €11,260 for preeclampsia €3,188 for restricted intrauterine growth and €12,131 for threat of premature delivery. In the postpartum, an annual cost per patient of €120,364, €44,709, and €5,507 were estimated associated with admissions to neonatology of premature infants of <28, 28-32 and 33-37 weeks, respectively. CONCLUSIONS: This analysis provides insight on the economic burden of complications associated with women of reproductive age for immune-mediated diseases (PSO, PsA, RA, axSpA). Individualization of treatment, additional and close monitoring may reduce the risk and burden of these complications.
33299792 Epstein-Barr virus (EBV) induced pneumonitis in an immunocompetent adult: A case report. 2020 Epstein Barr Virus (EBV) is one of the herpes viruses that is responsible for causing infectious mononucleosis, lymphomas, and carcinomas primarily in immunocompromised individuals. We present a case of EBV-induced pneumonitis in an immunocompetent female, successfully treated with steroids. The patient is a 70 year-old female with a history of infectious mononucleosis in her teens who presented to the emergency room with worsening shortness of breath, associated with cough and fever. She underwent extensive work up and her serologic workup revealed positive anti-EBV antibodies, pointing towards the diagnosis of EBV induced pneumonitis. EBV-induced Pneumonitis is a very rare entity and is especially hardly seen among immunocompetent individuals. This interesting case shows that in this new era of viral pneumonias, EBV induced pneumonitis should be considered among differentials when dealing with lung infections. Prompt initiation of treatment with steroids or antiviral medication may result in complete recovery. The choices among treatment options can be individualized according to the severity of disease, course of disease progression, and side effect profile of medications. In our case we were able to successfully treat the patient with high dose steroids only.
33141244 [Diagnosis, treatment and prophylaxis of herpes zoster]. 2020 Dec In the case of reduced cellular immunity the previously dormant varicella zoster virus (VZV) causes the characteristic belt-shaped vesicular exanthema of herpes zoster. The initial clinical symptoms of herpes zoster are often non-specific and may lead to initial misdiagnosis. A common complication of herpes zoster is postherpetic neuralgia (PHN) but secondary hematogenic dissemination is only rarely observed. In addition to general factors, such as advanced age and female gender, inflammatory rheumatic diseases and their immunosuppressive treatment are important risk factors for the occurrence of herpes zoster. Antiviral therapy initiated in the first 72 h after the onset of exanthema reduces acute symptoms and the risk of complications. The subunit inactivated vaccine, which has been available since 2018, is highly effective and relatively well-tolerated but randomized controlled trials in patients with drug-induced immunosuppression for inflammatory rheumatic diseases are still pending.
32234852 Remitting seronegative symmetrical synovitis with pitting oedema after surgical remission 2020 Mar 31 A 64-year-old woman with refractory cellulitis in the lower legs was referred for inadequate glycaemic control. Physical examination revealed cushingoid features including central obesity. CT of the abdomen revealed a right adrenal mass that was positive on (131)I-adosterol imaging. Findings on endocrine evaluation confirmed a diagnosis of Cushing's syndrome, which was cured with a right adrenalectomy. Two months after surgery, the patient complained of pain and marked swelling of the hands during hydrocortisone replacement therapy (20 mg per day) given for postoperative adrenal insufficiency. Laboratory examination was unremarkable. However, contrast-enhanced T2-weighted MRI of the hands revealed enhanced signals surrounding the flexor tendons, leading to a diagnosis of remitting seronegative symmetrical synovitis with pitting oedema. Prednisolone (15 mg per day) was then initiated, and the symptoms disappeared within a few days. This case illustrates the possibility that successful treatment of Cushing's syndrome may trigger emergence of a glucocorticoid-responsive disease.
32020443 Correction to: Association of rheumatoid arthritis-related autoantibodies with pulmonary f 2020 Apr The publisher regrets that the two sections under the Results omitted inadvertently on the original published version of the above article.
31900502 Fibromyalgia interferes with disease activity and biological therapy response in inflammat 2020 Jun Fibromyalgia is one of the numerous comorbidities that may accompany inflammatory rheumatic diseases. Concomitant fibromyalgia in inflammatory rheumatic conditions can interfere with symptomatology, disease activity and overall management plan. The aim of the present narrative review article was to discuss the current evidence on (i) the prevalence/frequency of comorbid fibromyalgia in inflammatory rheumatic conditions, (ii) the role of fibromyalgia on disease activity, (iii) the impact of concomitant fibromyalgia on biological disease-modifying antirheumatic treatment outcomes and (iv) potential effectiveness of biological disease-modifying antirheumatic drugs on fibromyalgia-related symptoms among patients with inflammatory rheumatic diseases. A literature search was conducted through PubMed/MEDLINE Cochrane and Web of Science databases by using relevant keywords and their combinations. Studies representing different geographical areas of the world revealed that frequency rates of fibromyalgia are higher in inflammatory rheumatic diseases than those in the general population. Comorbid fibromyalgia interferes not only with the disease activity scores but also with the treatment outcomes and management plan. Further evidence is warranted in order to determine the potential benefits of biological disease-modifying antirheumatic drugs on fibromyalgia-related symptoms in patients with inflammatory rheumatic diseases.
33154972 Rheumatic Musculoskeletal Diseases and COVID-19 A Review of the First 6 Months of the Pand 2020 In December 2019, a cluster of severe pneumonia was observed in China, with the subsequent discovery of a new beta-coronavirus (SARS-CoV-2) as the causative agent. The elicited disease COVID-19 is characterized by fever, dry cough, myalgia, or fatigue and has a favorable outcome in the majority of cases. However, in some patients COVID-19 leads to severe pneumonia and sepsis with subsequent respiratory failure and gastrointestinal, hematological, neurological, and cardiovascular complications. A higher risk of infection is intrinsic to active rheumatic and musculoskeletal diseases (RMD) and the use of biological disease modifying anti-rheumatic drugs (DMARDs). With an increasing number of reports on COVID-19 in RMD patients, we are beginning to appraise their risks. In this review, we summarize the published cases of COVID-19 infections in RMD patients, including patients with inflammatory arthritis and connective tissue diseases as well as anti-phospholipid syndrome and Kawasaki syndrome. Overall, patients with inflammatory arthritis do not seem to be at a higher risk for infection or a severe course of COVID-19. Risk for critical COVID-19 in patients with systemic inflammatory diseases such as SLE or vasculitis might be increased, but this needs further confirmation. Furthermore, we summarize the data on DMARDs used to fight SARS-CoV-2 infection and hyperinflammation.
32989481 Complementary and Alternative Medicine Use in Psoriatic Arthritis Patients: a Review. 2020 Sep 28 PURPOSE OF REVIEW: While complementary and alternative medicine (CAM) use is prevalent in the general population and is known to be used in systemic rheumatic disease such as rheumatoid arthritis and systemic lupus erythematosus, its use in psoriatic arthritis (PsA) is less well-studied. The purpose of this review was to identify published data describing the use of CAM in patients with PsA. RECENT FINDINGS: PsA patients report frequent use of CAM. Diet is believed to affect disease activity, and dietary approaches are used by patients to mitigate symptoms. Dietary supplements have been studied, especially fatty acids, with some positive results. Herbal remedies show promise, but more and better studies are needed, including evaluating medical cannabis. Studies of some the most commonly used CAM, such as acupuncture and massage, are conspicuously absent. CAM use is common among patients with PsA. There is, however, a significant knowledge gap, and there is a critical need for rigorous research to ensure safe and effective use of CAM for these patients.
32256686 Pien Tze Huang alleviate the joint inflammation in collagen-induced arthritis mice. 2020 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Pien Tze Huang (PZH) is a Chinese patent medicine with anti-inflammatory and immunomodulatory effects. However, whether PZH could be used in RA therapy is still unknown. Therefore, this study aimed to explore the therapeutic effect and the potential mechanism of PZH on collagen-induced arthritis (CIA) mice. METHODS: Male DBA/1J mice were used to establish an animal model of CIA and then treated with different doses of PZH for 4 weeks. The therapeutic effect of PZH on CIA mice was evaluated by arthritis score, pathological staining, and detecting the levels of inflammatory factors in serum and joints. To investigate its possible mechanism, the activity of NF-κB signaling pathway, NLRP3 inflammasome and the level of A20 were detected. RESULTS: The results showed that PZH could alleviate the erythema and swelling of hind paws of CIA mice, improve the pathological conditions of joint and decrease the production of IL-1β, IL-6 and IL-17 in serum and joints. Furthermore, PZH could significantly inhibit the activity of NF-κB signaling pathway and NLRP3 inflammasome in the ankle joint of CIA mice compared with the model group. It also increased the level of A20 in the ankle joint of CIA mice. CONCLUSION: This study indicated that PZH could alleviate the joint inflammation of CIA mice, and the mechanism might be related to the regulation of NF-κB signaling pathway and NLRP3 inflammasome.
32160704 Downregulation of Hypoxia-Inducible Factor-1α by RNA Interference Alleviates the Developm 2020 Mar 6 Rheumatoid arthritis (RA) is the most common type of autoimmune arthritis. Hypoxia-inducible factor-1α (HIF-1α) as a transcription factor in response to hypoxia suggests that it could be a potential therapeutic target for the treatment of RA. In this study, we assessed whether the HIF pathway blockade attenuates the manifestations of RA in the collagen-induced arthritis (CIA) rat model. We constructed a short hairpin RNA (shRNA) lentiviral expression vector targeting HIF-1α (pLVX-shRNA-HIF-1α) and to achieve HIF-1α RNA interference. Quantitative RT-PCR, immunofluorescence staining, and western blot were used to detect the expressions of HIF-1α, vascular endothelial growth factor (VEGF), phsopho (p)-p65, and p-IКBɑ mRNA and protein, respectively. Micro-computed tomography was used to investigate joint morphology at different time points after CIA induction. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to monitor the expression of inflammatory cytokines. In vitro analyses revealed that pLVX-shRNA-HIF-1α effectively inhibited the expression of HIF-1α and VEGF and led to the activation of p-65 and p-IКBɑ, as well as decreased proinflammatory cytokine expression in cell culture. Inhibition of HIF-1α in rats decreased signs of a systemic inflammatory condition, together with decreased pathological changes of RA. Moreover, downregulation of HIF-1α expression markedly reduced the synovitis and angiogenesis. In conclusion, we have shown that pharmacological inhibition of HIF-1 may improve the clinical manifestations of RA.
33363853 Intraoral localized methotrexate-associated lymphoproliferative disorders concurrent with 2020 Dec Intraoral localized methotrexate-associated lymphoproliferative disorders can cause antiresorptive agent-related osteonecrosis of the jaw associated with infection due to its immunological abnormalities and ulcer formation.
33188932 DNA methylation signatures of autoimmune diseases in human B lymphocytes. 2021 Jan B lymphocytes play key roles in adaptive and innate immunity. In autoimmune diseases, their participation in disease instigation and/or progression has been demonstrated in both experimental models and clinical trials. Recent epigenetic investigations of human B lymphocyte subsets revealed the importance of DNA methylation in exquisitely regulating the cellular activation and differentiation programs. This review discusses recent advances on the potential of DNA methylation to shape events that impart generation of plasma cells and memory B cells, providing novel insight into homeostatic regulation of the immune system. In parallel, epigenetic profiling of B cells from patients with systemic or organo-specific autoimmune diseases disclosed distinctive differential methylation regions that, in some cases, could stratify patients from controls. Development of tools for editing DNA methylation in the mammalian genome could be useful for future functional studies of epigenetic regulation by offering the possibility to edit locus-specific methylation, with potential translational applications.
32735158 Anti-TNF biosimilars in rheumatology: the end of an era? 2021 Jan INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) have revolutionized the treatment of rheumatic diseases. Whilst extremely efficacious, the original TNFi also carried a high acquisition cost that limited their use. 'Biosimilar' TNFi's, developed on expiry of the patents for the biooriginators, have comparable efficacy and safety, are less expensive and provide the potential to improve access to these effective therapies in a more cost-effective manner. AREAS COVERED: The background and development of TNFis, their biosimilars and follow on 'copycat' drugs are discussed, together with their use in both developed and developing countries, focusing on the potential to enhance access to effective targeted therapies. EXPERT OPINION: Bridging the economic gap to facilitate universal access to anti-TNF biosimilars has been largely unsuccessful, driving the development of copycat mimics in developing countries. Meanwhile, the more recent introduction of targeted synthetic disease-modifying drugs has provided cheaper, equally effective treatments for rheumatic diseases that are conveniently delivered by mouth. We review the TNF biosimilars in rheumatic diseases, their role in a rapidly evolving treatment landscape, and speculate about the future for this iconic therapeutic class.
32249021 Exercise and inflammation. 2020 Apr Based on current knowledge deriving from studies in animals and humans (the general population and patients with non-communicable diseases), there is biological plausibility that exercise may have anti-inflammatory effects. This may be particularly important for patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMDs). The present review discusses the current state-of-the-art on exercise and inflammation, explores how exercise can moderate inflammation-dependent RMD outcomes and the most prevalent systemic manifestations and addresses the relationship between the dosage (particularly the intensity) of exercise and inflammation. We conclude that present data support potential beneficial effects of exercise on inflammation, however, the evidence specifically in RMDs is limited and inconclusive. More targeted research is required to elucidate the effects of exercise on inflammation in the context of RMDs.
33402867 Sex effect on the correlation of immunoglobulin G glycosylation with rheumatoid arthritis 2020 Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects females more than males with a presence of autoantibodies. Immunoglobulin G (IgG) produced by adaptive arm has 2 functional domains, Fc and Fab. The Fc domain binds Fc gamma receptors and C1q proteins of the innate arm. Therefore, the IgG Fc domain serves as a bridge between the innate and adaptive arms and is regulated by an evolutionarily conserved N-glycosylation with variable structures. These glycans are classified as agalactosylated G0, monogalactosylated G1, and digalactosylated G2, which are further modified by core-fucosylation (F) and bisecting N-acetylglucosamine (B) moieties such as G0F and G0FB. Interestingly, proinflammatory G0F is shown to be regulated by estrogen in vivo. Here, it is hypothesized that the regulation of G0F by estrogen contributes to sex dichotomy in RA by setting up the level of IgG-dependent inflammation and therefore, RA disease activity (Das28-CRP3). To investigate this hypothesis, IgG glycosylation was characterized in serum samples from active RA patients (n = 232) and healthy controls (n = 232) by serum N-glycan analysis using the high performance liquid chromatography. According to the results, the IgG Fc glycan phenotype originates predominantly from the structure of G0F, and both G0F and G0FB correlate with Das28-CRP3 in females, but not in males. In conclusion, IgG G0F-dependent inflammation differs in males and females, and these differences point to the differential regulation of inflammation by sex hormone estrogen via IgG glycosylation.
33364931 The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progress 2020 Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia-the principle immune cells of the brain-characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.
33145088 Thoracic imaging finding of rheumatic diseases. 2020 Sep In the era of Precision Medicine, diagnostic imaging plays a key role in initial diagnosis and treatment response assessment in thoracic manifestation of various rheumatic disorders; resulting in increased dependency on imaging for treatment planning. Chest radiographs serve as a good initial screening tool for assessment of emergent and urgent thoracic conditions, e.g., pneumothorax, pulmonary edema, consolidation and pleural effusions. Cross-sectional imaging techniques, e.g., computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) are most commonly utilized to evaluate more detailed pulmonary and mediastinal manifestations of rheumatic conditions. Magnetic resonance imaging (MRI) and ultrasound are most commonly used in cardiovascular, neural and musculoskeletal structures. This review article aims to highly key common thoracic imaging findings of rheumatic disorders, highlighting imaging test of choice for the particular disorder.