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ID PMID Title PublicationDate abstract
32501889 Increased immediate early gene activation in the basolateral amygdala following persistent 2020 Jul 10 Chronic pain results in a variety of neural adaptations, many of which are maladaptive and result in hypersensitivity to pain. In humans, this hypersensitivity can be debilitating and treatment options are limited. Fortunately, there are numerous animal models that mimic clinical populations and have the potential to aid in the evaluation of underlying mechanisms and ultimately the development of better treatments. One of these is the complete Freund's adjuvant (CFA)-model of chronic inflammatory pain. In rodents, this model requires the injection of CFA into the hindpaw, muscle, or joint, which induces inflammation similar to what might be found in individuals with rheumatoid arthritis or tendonitis. While the mechanistic effects CFA on the spinal cord are well established, less is known about the effects of CFA on the brain. Thus, in this study, neuronal activation, as measured by c-Fos immunocytochemistry, in brain regions important to control of pain was evaluated. Animals that received CFA treatment, and tested 3 days later for mechanical allodynia and edema, had an increase in the number of c-Fos immunopositive cells in the basolateral amygdala, but not in any of the other brain regions that were evaluated. Given that the basolateral amygdala is known to be important for pain-related emotional responses, these data suggest that the CFA-model may provide an opportunity to further explore how pain affects this brain region at a mechanistic level, which in turn may shed light on what may be occurring in clinical populations.
32332272 The Influence of Hand Dominance on the Degree of Deformities in Patients With Systemic Lup 2020 Oct BACKGROUND/OBJECTIVE: Joint deformities in Jaccoud arthropathy (JA), associated with systemic lupus erythematosus (SLE), can lead to a reduction in articular function and an impaired quality of life. There is controversy in the literature as to whether hand dominance contributes to deformities observed in rheumatoid arthritis and other forms of rheumatism. The purpose of this study was to assess whether hand dominance has any influence on the degree of deformity or joint range of motion in patients with JA associated with SLE. METHODS: This was a pilot cross-sectional study of 22 female patients (mean age, 46.18 ± 12.61 years) with both SLE and JA. Each patient's hand grip and hand and wrist joint range of motion were assessed by the same examiner. The Wilcoxon test was used to compare the median values of the angles and muscular strength found between the sides. RESULTS: All the study participants were right-side dominant. The median muscle strength of the right and left hands was 13.25 kilogram-force (KgF) (range, 7.00-18.00 KgF) and 10.50 KgF (range, 7.50-17.25 KgF), respectively. Both the fingers of the right and left hands had a median ulnar drift of 10.00°; however, their ranges differed (right, 4.50° to 20.00°; left: 0.00° to 15.50°). No statistically significant differences were found in the extension angulation of the proximal interphalangeal joints or the flexion of the distal interphalangeal joints of the second to fifth fingers, between the dominant and nondominant hands. CONCLUSIONS: Hand dominance does not seem to influence the degree of JA deformities in patients with SLE.
32332073 The microbiome in rheumatology: Where are we and where should we go? 2020 Jun From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.
32328321 Reactivation of Epstein-Barr Virus Presenting as Massive Splenomegaly after Initiation of 2020 Epstein-Barr virus infection is most commonly asymptomatic in the acute setting, where the end result of infection is the adoption of a viral latency phenotype. The virus can reactivate later in life leading to the abnormal proliferation of the infected B, T, or NK cells. Hereby, we report a 71-year-old female with seronegative rheumatoid arthritis who presented with massive splenomegaly, pancytopenia, and positivization of antibodies against double-stranded deoxyribonucleic acid (dsDNA) after initiation of the anti-tumor necrosis factor (TNF) golimumab. The diagnosis of EBV-associated lymphoproliferative disorder (LPD) was demonstrated by elevation of the plasmatic EBV viral load. Withdrawal of the anti-TNF and treatment with the anti-CD20 antibody rituximab were able to revert the clinical abnormalities. EBV-associated LPDs are described after initiation of other anti-TNF agents, such as infliximab, but no reports of golimumab-associated EBV LPD are found in the literature. The mechanisms for this occurrence are not clear, but these are known to involve expression of a panel of viral proteins specific to the viral latency phenotypes.
32319265 Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targetin 2020 Sep 1 Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.
32226694 A Comparison of Four Cardiovascular Risk Assessment Instruments in Saudi Patients. 2020 Feb 24 Introduction Several cardiovascular risk calculators are available online to measure the probability of developing cardiovascular disease (CVD) without defining the appropriate population. In the current study, four risk assessment instruments were investigated with Saudi Arabian patients with CVD to identify the instrument with the best predictability. The chosen instruments were the Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation (SCORE), American College of Cardiology/American Heart Association (ACC/AHA) Atherosclerotic Cardiovascular Disease Risk Estimator, and the United Kingdom score which is called QRISK(®). Methods Saudi patients, 40 years and older, with acute coronary syndrome, were recruited. Data related to age, gender, ethnicity, height, weight, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL), smoking status, diabetes mellitus, rheumatoid arthritis, chronic kidney disease, atrial fibrillation, heart attack in a first-degree relative, and use of antihypertensive treatment were recorded. Results Out of 129 patients, the ACC/AHA had higher predictability with low risk (26.3%) and high risk (66.7%) groups. The QRISK(®) was highly applicable (95.3%); however, the SCORE was not considered applicable (22.5%). Conclusion The QRISK(®) is easy to implement and applicable in a population-based study, but the ACC/AHA is superior in predicting individuals with a high risk of CVD.
32208940 An evaluation of baricitinib as a therapeutic option for adult patients with moderate to s 2020 Jun INTRODUCTION: Moderate-to-severe AD burdens a large proportion of AD patients and may represent an inadequacy of treatment options available for resistant disease. AREAS COVERED: This review provides an overview of the therapies for moderate-to-severe AD in late-stage development and in the clinic, and focuses on baricitinib as an emerging therapeutic option. Baricitinib is an orally available selective JAK1/JAK2 inhibitor that is approved for use in the treatment of moderate-to-severe rheumatoid arthritis (RA). Baricitinib decreases AD lesions, disease severity, and improves quality of life. Overall, the small molecule inhibitor is well tolerated. However, its black-box warnings in the RA population raise a concern for its long-term safety. EXPERT OPINION: Baricitinib is a promising treatment modality for moderate-to-severe AD. Its primary advantage over dupilumab, the revolutionary biologic agent approved for AD, is that patients prefer an oral medication over an injection. However, providers will likely prescribe an injectable over an oral medication if baricitinib has an unfavorable safety profile. Insurance coverage of baricitinib will also have a major role in clinical use. Baricitinib will likely face competition from other JAK inhibitors in the future; however, it will have an advantage if it becomes the first FDA-approved medication of its kind for resistant AD.
32206866 [Biologicals and small molecules for systemic lupus erythematosus]. 2020 Apr Targeted treatment is a rheumatologist's dream, which, with the advent of biologicals and more recently small molecules, has become true for rheumatoid arthritis and is about to translate into reality for systemic lupus erythematosus (SLE). Belimumab, the first biological approved for SLE, is now also available in a subcutaneous formulation. It is notable that this drug achieved the primary endpoint in four independent trials and demonstrated substantial reduction of organ damage accrual. The B cell depletion with antibodies against CD20 remains clinically relevant and of interest for future developments and the combination of both approaches (belimumab and anti-CD20) is an exciting idea. Blockade of the type I interferon receptor with anifrolumab was effective in a phase 3 trial and blocking interleukin-12 and interleukin-23 with ustekinumab is currently being tested in a phase 3 clinical trial. The old ideas of blocking tumor necrosis factor (TNF) and interleukin‑6 have also not yet been forgotten. More novel approaches comprise Janus kinase (Jak) inhibition with positive phase 2 data for baricitinib and soon inhibition of Bruton's tyrosine kinase (BTK) as well as proteasome inhibitors. The treatment of SLE could therefore soon become much more varied.
32070817 A successful surgical treatment of a closed rupture of flexor digitorum superficialis in s 2020 INTRODUCTION: Isolated closed rupture or avulsion of the flexor digitomm superficialis (FDS) tendon at its insertion is a rare diagnosis. It can be related to a pathology such as rheumatoid arthritis, bony abnormalities, tenosynovitis, fractures, or tuberculosis. A review of the literature identified only few cases of closed avulsion or rupture of FDS tendons nonpathologically. We hope this report will help to gather more experience for the surgical intervention in a delayed presentation of ruptured flexor digitorm superficialis tendon. The work has been reported in line with the SCARE criteria. PRESENTATION OF CASE: We report a case of 48-year-old surgeon who sustained a trauma to her left middle finger. The patient presented three months after injury with complaints of pain and decreased range of motion of involved digit. Patient was treated conservatively and after failure of conservative treatment surgical intervention was done with complete tendon excision and capsulotomy of Proximal interphalangeal joint. Patient retained full range of motion and pain subsided. DISCUSSION: Isolated closed avulsions or rupture of the FDS tendon is a challenging entity in hand surgery in diagnosis and treatment. Nonsurgical treatment with splinting and physiotherapy might help to prevent flexion deformity. The surgical treatment include tenolysis, flexor digitorum superficialis tendon excision, and in selected patients capsulotomies of involved joints. CONCLUSION: A review of the literature identified only few cases of closed avulsion of FDS tendons nonpathologically. Early diagnosis and intervention can prevent sequel of flexion contracture.
32061815 Minocycline, focus on mechanisms of resistance, antibacterial activity, and clinical effec 2020 Sep OBJECTIVES: The increasing crisis regarding multidrug-resistant (MDR) and extensively drug-resistant microorganisms leads to appealing therapeutic options. METHODS: During the last 30 years, minocycline, a wide-spectrum antimicrobial agent, has been effective against MDR Gram-positive and Gram-negative bacterial infections. As with other tetracyclines, the mechanism of action of minocycline involves attaching to the bacterial 30S ribosomal subunit and preventing protein synthesis. RESULTS: This antimicrobial agent has been approved for the treatment of acne vulgaris, some sexually transmitted diseases and rheumatoid arthritis. Although many reports have been published, there remains limited information regarding the prevalence, mechanism of resistance and clinical effectiveness of minocycline. CONCLUSION: Thus, we summarize here the currently available data concerning pharmacokinetics and pharmacodynamics, mechanism of action and resistance, antibacterial activity and clinical effectiveness of minocycline.
31988808 Identification of key biomarkers and immune infiltration in the synovial tissue of osteoar 2020 BACKGROUND: Osteoarthritis (OA) is the most common chronic degenerative joint disease and is mainly characterized by cartilage degeneration, subcartilage bone hyperplasia, osteophyte formation and joint space stenosis. Recent studies showed that synovitis might also be an important pathological change of OA. However, the molecular mechanisms of synovitis in OA are still not well understood. OBJECTIVE: This study was designed to identify key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis. MATERIALS AND METHODS: The gene expression profiles of GSE12021, GSE55235 and GSE55457 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional enrichment analyses were performed. A protein-protein interaction network (PPI) was constructed, and module analysis was performed using STRING and Cytoscape. The CIBERSORT algorithm was used to analyze the immune infiltration of synovial tissue between OA and normal controls. RESULTS: A total of 106 differentially expressed genes, including 68 downregulated genes and 38 upregulated genes, were detected. The PPI network was assessed, and the most significant module containing 14 hub genes was identified. Gene Ontology analysis revealed that the hub genes were significantly enriched in immune cell chemotaxis and cytokine activity. KEGG pathway analysis showed that the hub genes were significantly enriched in the rheumatoid arthritis signaling pathway, IL-17 signaling pathway and cytokine-cytokine receptor interaction signaling pathway. The immune infiltration profiles varied significantly between osteoarthritis and normal controls. Compared with normal tissue, OA synovial tissue contained a higher proportion of memory B cells, naive CD4+ T cells, regulatory T cells, resting dendritic cells and resting mast cells, while naive CD4+ T cells, activated NK cells, activated mast cells and eosinophils contributed to a relatively lower portion (P > 0.05). Finally, the expression levels of 11 hub genes were confirmed by RT-PCR. CONCLUSION: The hub genes and the difference in immune infiltration in synovial tissue between osteoarthritis and normal controls might provide new insight for understanding OA development.
31965913 Lessons from precision medicine in rheumatology. 2020 Apr Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common autoimmune rheumatic diseases that vary in severity, clinical presentation, and disease course between individuals. Molecular and genetic studies of both diseases have identified candidate genes and molecular pathways that are linked to various disease outcomes and treatment responses. Currently, patients can be grouped into molecular subsets in each disease, and these molecular categories should enable precision medicine approaches to be applied in rheumatic diseases. In this article, we will review key lessons learned about disease heterogeneity and molecular characterization in rheumatology, which we hope will lead to personalized therapeutic strategies.
31608507 Inflammasomes in the pathophysiology of autoinflammatory syndromes. 2020 Mar Inflammasomes are a specialized group of intracellular sensors that are key components of the host innate immune system. Autoinflammatory diseases are disorders of the innate immune system that are characterized by recurrent inflammation and serious complications. Dysregulation of the inflammasome is associated with the onset and progression of several autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic fever syndrome, familial Mediterranean fever, rheumatoid arthritis, and systemic lupus erythematosus. In this review, we discuss the involvement of various inflammasome components in the regulation of autoinflammatory disorders and describe the manifestations of these autoinflammatory diseases caused by inflammasome activation.
31567595 Self-reported Health Diagnoses and Demographic Correlates With Kratom Use: Results From an 2020 May/Jun OBJECTIVES: To determine whether diagnosed pre-existing health conditions correlate with Kratom demographics and use patterns. METHODS: A cross-sectional, anonymous US national online survey was conducted among 8049 Kratom users in October, 2016 to obtain demographic, health, and Kratom use pattern information. RESULTS: People who use Kratom to mitigate illicit drug dependence self-reported less pain and better overall health than individuals who used Kratom for acute/chronic pain. Self-reported improvements in pre-existing mental health symptoms (attention deficit and hyperactivity disorder/attention deficit disorder, anxiety, bipolar disorder, post-traumatic stress disorder, and depression) attributed to Kratom use were greater than those related to somatic symptoms (back pain, rheumatoid arthritis, acute pain, chronic pain, fibromyalgia). Demographic variables, including female sex, older age, employment status, and insurance coverage correlated with increased likelihood of Kratom use. CONCLUSIONS: Kratom use may serve as a self-treatment strategy for a diverse population of patients with pre-existing health diagnoses. Healthcare providers need to be engaging with patients to address safety concerns and potential limitations of its use in clinical practice for specific health conditions.
33569065 Therapies Targeting Trained Immune Cells in Inflammatory and Autoimmune Diseases. 2020 The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.
33425968 Case Report: Composite Angioimmunoblastic T-Cell Lymphoma and Epstein-Barr Virus-Positive 2020 Immunosuppressants are widely used to treat patients with rheumatoid arthritis (RA), and their adverse effects have been known to cause other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). We report a patient with RA who had been treated with methotrexate (MTX) and tacrolimus (TAC) and who developed whole body lymphadenopathy. We simultaneously confirmed angioimmunoblastic T-cell lymphoma (AITL) through a right cervical lymph node biopsy and Epstein-Barr virus-positive B-cell lymphoproliferative disorder (EBV-positive B-LPD) through a bone marrow examination. After cessation of immunosuppressant therapy, both LPDs completely disappeared. Patients with AITL are occasionally reported to develop B-cell lymphoma through reactivation of the EBV, which leads to clonal expansion in the microenvironment. Immunohistochemistry results revealed that both LPD components were positive for EBV-encoded RNA. Moreover, in this patient, the plasma EBV DNA level was found to be high; therefore, EBV infection was a probable etiology. Synchronous coexistence of AITL and B-LPD as an OIIA-LPD has rarely been reported. This case report is the first to discuss the disappearance of both LPDs on withdrawal of immunosuppressants only. AITL occasionally accompany B-LPD; however, this composite lymphoma comprised AITL and B-LPD, and OIIA-LPDs should not be overlooked.
33290287 Current Approach for the Diagnosis and Management of Noninfective Scleritis. 2020 Dec 7 Scleritis is a rare, vision-threatening inflammation of the sclera that is often associated with life-threatening systemic illnesses. Rheumatoid arthritis remains the most common associated systemic rheumatic disease and the commonest systemic association of scleritis. Granulomatosis with polyangiitis is the most common cause of vasculitis-associated scleritis. The etiopathogenesis of scleritis remains unclear, but can be immune complex-mediated or due to a local delayed hypersensitivity reaction. Scleritis can involve either the anterior or posterior sclera, and has a wide spectrum of clinical presentations. Among the subtypes of scleritis, necrotizing scleritis has an increased risk of complications and is more commonly associated with anterior uveitis and peripheral ulcerative keratitis. Posterior scleritis is often not diagnosed or missed due to its subtle clinical signs and protean manifestations. Meticulous history taking, detailed ocular examination, and a targeted array of investigations with a multi-disciplinary approach to find any underlying systemic disease are crucial for the management of a case of scleritis. Corticosteroids remain the mainstay of short-term treatment of scleritis; mild to moderate scleral inflammation may respond well to treatment with nonsteroidal antiinflammatory drug or topical corticosteroid. Corticosteroid-sparing immunosuppressive therapies are useful in cases with an inadequate response or failure to provide long-term control of inflammation, and to prevent recurrence of scleritis. Biologic agents are increasingly used in the management of scleritis, not responding to the conventional therapies. This review provides an overview of the various subtypes of scleritis and its systemic associations and evaluates current trends in the diagnosis and management of noninfective scleritis.
33217802 Systemic sclerosis and risk of cardiovascular disease: A PRISMA-compliant systemic review 2020 Nov 20 BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder leading to extensive fibrosis and microvascular injury. Macrovascular disease is well documented in other autoimmune rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. However, the link is unclear between SSc and macrovascular disease, particularly atherosclerotic cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between SSc and CVD. METHODS: A thorough literature search was conducted in the Cochrane, Embase, Medline, and PubMed to identify all cohort studies comparing the risk of CVD with and without SSc. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of cardiovascular end points were calculated. The risk of bias of included studies was assessed by the Newcastle-Ottawa scale. RESULTS: Seven cohort studies with a total of 14,813 study participants were included. In a comparison of SSc patients versus non-SSc controls, the pooled HR for cardiovascular disease was 2.36 (95% CI 1.97-2.81); for peripheral vascular disease was 5.27 (95%CI 4.27-6.51); for myocardial infarction was 2.36 (95% CI 1.71-3.25); and for stroke was 1.52 (95% CI 1.18-1.96). CONCLUSION: This meta-analysis revealed that SSc was associated with an increased risk of CVD. Clinicians who manage patients with SSc should be aware of the increased cardiovascular burden and undertake preventive measures.
33193357 Intestinal Dysbiosis in, and Enteral Bacterial Therapies for, Systemic Autoimmune Diseases 2020 Recent studies have shown that a number of common autoimmune diseases have perturbations of their intestinal microbiome (dysbiosis). These include: Celiac Disease (CeD), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Sjogren's Syndrome (SS), and Type 1 diabetes (T1D). All of these have intestinal microbiomes that are different from healthy controls. There have been numerous studies using animal models of single probiotics (monoclonal) or mixtures of probiotics (polyclonal) and even complete microbiota transfer (fecal microbial transfer-FMT) to inhibit or delay the onset of autoimmune diseases such as the aforementioned common ones. However, proportionally, fewer clinical trials have utilized monoclonal therapies or FMT than polyclonal therapies for treating autoimmune diseases, even though bacterial mono-therapies do inhibit the development of autoimmune diseases and/or delay the onset of autoimmune diseases in rodent models of those autoimmune diseases. In this review then, we review the previously completed and currently ongoing clinical trials that are testing bacterial therapies (FMT, monoclonal, and polyclonal) to treat common autoimmune dseases and discuss the successes in using bacterial monotherapies to treat rodent models of these common autoimmune diseases.
33162485 Triglyceride Deposit Cardiomyovasculopathy with Massive Myocardial Triglyceride which Was 2021 Apr 15 The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy ((1)H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using (1)H-MRS noninvasively.