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ID PMID Title PublicationDate abstract
30185371 Is rheumatoid arthritis an innocent bystander in female reproductive problems? A comparati 2018 Sep OBJECTIVE: Contrary to the old belief that rheumatoid arthritis (RA) is rare in sub-Saharan Africa, recent reports have increasingly recognized that the burden of the disease has probably been long under-appreciated in West Africa. Thus, fertility and other attributes of the reproductive lives among women with RA have not received research attention in Africa. We aimed to compare the fertility between married Nigerian women with and without RA. METHODS: A comparative study of 50 women with RA and 50 women without RA was conducted via the specialist rheumatology clinics at two teaching hospitals in Nigeria. The participants were aged 18 years or older. Patients with RA were recruited on the basis of the fulfillment of the 1987 American College of Rheumatology classification criteria for RA, whereas the control participants were age-matched to the patients. Using an interviewer-administered questionnaire, demographic and clinical information was collected from each participant. Clinical details at the time of diagnosis of RA were extracted from the hospital records of the patients. The patients were tested for rheumatoid factor and anti-cyclic citrullinated peptide antibody, and the disease activity was assessed using the Clinical Disease Activity Index. The functional status was determined using the Steinbrocker functional classification. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 20 (IBM Corp.; Armonk, NY, USA). The proportions of individuals with history of infertility, irregular menstruation, and menopausal states were compared between the two groups using χ(2) and Fisher's exact tests, whereas the durations of infertility and parities were compared using Mann-Whitney U and independent t-tests, respectively. RESULTS: A positive history of infertility was found in 22 (44%) patients and 14 (28%) controls (p=0.096), while 17 (34%) patients and 23 (46%) controls were found to be postmenopausal (p=0.221). History of irregular menstruation was present in 15 (30%) patients and 4 (8%) controls (p=0.005). The median duration of infertility was 60 (range: 16-132) months among the patients and 36 (range: 12-72) months among the controls (p=0.036), while the mean parity was 2.85±1.8 among the patients and 3.77±2.2 among the controls (p=0.027). A significant association was found between infertility and functional class as well as methotrexate treatment. CONCLUSION: Infertility is not uncommon among patients with RA, and like many aspects of rheumatic diseases, it may have been under-recognized in the Nigerian patients.
30506262 Intravenous anesthetic ketamine attenuates complete Freund's adjuvant-induced arthritis in 2019 Feb BACKGROUND: The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats. METHODS: The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence. RESULTS: The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9). CONCLUSION: Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.
29119480 Rheumatoid factor false positivity in patients with ANCA-associated vasculitis not having 2018 Oct We investigated the rate of rheumatoid factor (RF) false positivity at diagnosis and its influence on clinical and prognostic features and rheumatoid arthritis (RA) development during the follow-up in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients without RA or other medical conditions triggering RF false positivity. We reviewed the medical records of 128 AAV patients. We divided patients with AAV and each variant into two groups according to RF positivity and compared variables between the two groups. Odds ratio and cumulative relapse-free survival rate were obtained by multivariate logistic regression analysis and the Kaplan-Meier survival analysis, respectively. The mean age at diagnosis was 53.6 years and 41 patients were male. Of 128 AAV patients, 69 patients (53.9%) were classified as microscopic polyangiitis (MPA), 29 (22.7%) as granulomatosis with polyangiitis (GPA) and 30 (23.4%) as eosinophilic GPA (EGPA). The rate of RF false positivity was 39.1% in AAV patients. On univariate analysis, general, cutaneous and mucous and ocular manifestations and myeloperoxidase (MPO)-ANCA (or perinuclear (P)-ANCA) positivity were associated with RF false positivity in patients with AAV. On multivariate analysis, cutaneous manifestation was the only independent predictor of RF false positivity in EGPA patients. RF false positivity had no influence on cumulative relapse-free survival rate of AAV or RA development during the follow-up. RF false positivity rate was 39.1% in AAV patients and it was associated with cutaneous manifestation in EGPA patients at diagnosis, but not relapses of AAV or RA development during the follow-up.
31427051 Management of vaccination in rheumatic disease. 2018 Dec Autoimmune inflammatory rheumatic diseases (AIIRD) such as rheumatoid arthritis and spondyloarthritis, including psoriatic arthritis and ankylosing spondylitis are associated with an increased risk of infection due to a combination of the immunosuppressive effect of the AIIRD, comorbidities, and use of corticosteroids and the immunosuppressive effect of conventional synthetic disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts-) DMARDs, and biologic (b-) DMARDs. Many infections are preventable with vaccination. However, as the protective immune responses induced by vaccination may be impaired by immunosuppression, vaccination should be considered before the commencement of immunosuppression. Another opportune time to review vaccination status is when planning overseas travel, as destination-specific vaccines are often required. Although limited published data regarding vaccine efficacy in patients with AIIRD make prescriptive guidelines difficult, a vaccination history should be part of the initial workup in all patients with AIIRD. Unfortunately, this is often not done by rheumatologists. This paper encourages those caring for patients with AIIRD to regularly review vaccination status.
31093599 TNF Inhibitor-Induced Psoriasis: Proposed Algorithm for Treatment and Management. 2019 Apr Tumor necrosis factor a (TNF-α)-targeted therapies have expanded the therapeutic options for patients with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA) and have significantly improved patients' quality of life. Paradoxically, anti-TNF-α agents may induce psoriatic eruptions or worsen preexisting psoriatic skin disease. Currently, there is no standard approach for the management of TNF inhibitor-induced psoriasis. Here, we conduct a literature review on TNF inhibitor-induced psoriasis and introduce a novel treatment algorithm for maintaining otherwise effective anti-TNF therapy versus switching to a different class as appropriate in the management of patients with IBD, RA, psoriasis, or PsA.
29853972 Small Peptides Compound Isolated from Agkistrodon with Antiarthritic Effect in Collagen-In 2018 Agkistrodon in Chinese medicine has long been used as an effective treatment against rheumatoid arthritis (RA). The present research further investigated the effects of peptides extracted from the crude Agkistrodon on the RA rat model. Extracted peptides were separated by parameter-optimized ion-exchange chromatography (IEC), peptide fractions were further analysed by MALDI-TOF/TOF MS, and nano-LC-MS/MS acquired mass spectra were further characterized using Mascot software, which ranks the best matches in the NCBI database. RT-PCR results in RAW264.7 cells indicated that Agkistrodon peptide components had inhibitory effects against inflammatory cytokines. The therapeutic efficacy of Agkistrodon peptides was evaluated on the Wistar rats with collagen-induced arthritis. Symptom relief and reduced cartilage destruction and bone erosion were observed, which can be explained by the direct suppression of inflammatory cytokines in the joints. Agkistrodon peptides downregulate the expression of TNF-α, IL-1β, and IL-6, which may alleviate cartilage destruction and bone erosion, thus relieving symptoms of RA.
30284497 CCL25 chemokine-guided stem cell attraction: an assessment of possible benefits and risks. 2018 Oct Due to its chemoattraction potential on mesenchymal stromal cells of the CCL25/CCR9 axis, local application of CCL25 to severely damaged tissues may be a promising approach for regenerative therapies. Analysis of the given data revealed that CCL25/CCR9 signaling has a crucial role in regulation of an adult immune homeostasis. CCR9 expression variations resulted in dysfunctional immune response in colitis, rheumatoid arthritis and endometriosis. Regarding oncology, different neoplastic tissues exploit CCL25-dependent CCR9 signaling for either local proliferation or migration processes. The CCR9 pathway likely can trigger crosstalk between the Akt and NOTCH pathway and thus participate in the regulation of the neoplastic behavior. In conclusion, the designated application-tissue requires precise molecular analysis of possible CCR9 expression due to its proto-oncogenic characteristics.
29663162 Functional Defects of Treg Cells: New Targets in Rheumatic Diseases, Including Ankylosing 2018 Apr 16 PURPOSE OF REVIEW: This study aims to review the advances of Treg cell biology, the functional defects of Treg cells, and the potential strategies for the experimental, preclinical or clinical application of Treg cell therapy in the context of autoimmune/immune-mediated rheumatic diseases. RECENT FINDINGS: CD4(+)CD25(+) regulatory T (Treg) cells are a phenotypically and functionally heterogeneous subset of lymphocytes that prevent a variety of autoimmune diseases. As in many autoimmune diseases, the functional defects of Treg cells are supposed to play relevant roles in the pathogenesis and development of systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, and other autoimmune/immune-mediated rheumatic diseases. Consequently, manipulation and modulation of Treg cells represent a potent strategy for therapeutic benefit in many such diseases. A further understanding of the functional defects of Treg cells in rheumatic diseases will contribute to find new targets and therapies in rheumatic diseases, including ankylosing spondylitis.
30199605 Advances and challenges in targeting IRF5, a key regulator of inflammation. 2019 May Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors, originally implicated in antiviral responses and interferon production. However, studies conducted in different laboratories over the last decade have placed IRF5 as a central regulator of the inflammatory response. It has become clear that IRF5 contributes to the pathogenesis of many inflammatory and autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus. Given the role of IRF5 in physiology and disease, IRF5 represents a potential therapeutic target. However, despite a significant interest from the pharmaceutical industry, inhibitors that interfere with the IRF5 pathway remain elusive. Here, we review the advances made by various studies in targeting multiple steps of signalling leading to IRF5 activation with their therapeutic potential, and the possible complications of such strategies are discussed.
30349905 Multidisciplinary dentistry for transitional care patients. 2018 A growing patient population is adolescents and young adults who have had one or more serious medical problems and are aging into adulthood. This group of patients has unique medical needs, which has resulted in the development of a specialized area of medicine: transitional care medicine. The case reviews of two of these patients are described. Patient 1 was a 23-year-old man with hereditary pancreatitis. His genetic condition resulted in the need for pancreatic splenectomy and removal of part of his small bowel, resulting in insulin-dependent diabetes and malnutrition. These complex clinical issues and the challenges of chronic pain were further complicated by severe anxiety disorder and substance abuse. He presented to the University of Rochester Medical Center's Complex Care Center (CCC), an interdisciplinary clinic that provides care for adults with pediatric onset conditions, staffed with both dentists and physicians, with acute pain from a grossly decayed premolar tooth. His blood glucose measured > 500 mg/dL and he was experiencing an acute episode of anxiety. With the expertise and experience of center staff his care needs could be met. Patient 2 was a 32-year-old woman with chronic juvenile rheumatoid arthritis, drug-associated lupus, and mental health problems including depression. This condition requires her to be managed with broad spectrum immunosuppression to prevent joint inflammation that results in significant joint destruction and bone loss. She presented to the CCC with an abscessed molar tooth, which prevented her from receiving her required immunotherapy, IV tocilizamab. While monitored by on-site physicians, a center dentist could safely proceed with the extraction. These cases illustrate that, as the population of transitional care patients grows, general dentists can learn to work on-site with physicians and allied health per-sonnel to meet the need.
29922065 Current treatment options for psoriatic arthritis: spotlight on abatacept. 2018 Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, tendon sheaths, and entheses affecting patients with established skin psoriasis, or, less frequently, patients without a personal history of psoriasis with a positive familial history. Many treatment options are now available to deal with the different aspects of the disease, including traditional and biological disease-modifying antirheumatic drugs and the recently released targeted synthetic disease-modifying antirheumatic drugs. However, ~40% of patients still fail to achieve a meaningful clinical response to first-line biologic therapy advocating the development of novel medications. It is now well accepted that T-cells participate in the immunopathogenesis of several autoimmune diseases. For this reason, the potential intervention on T-cells represented an attractive therapeutic target for a long time, becoming a clinical reality with the development of abatacept. Abatacept is a biologic agent selectively targeting the T-cell costimulatory signal delivered through the CD80/86-CD28 pathway and was approved in December 2005 by the US Food and Drug Administration and in May 2007 by European Medicines Agency for the treatment of patients with rheumatoid arthritis in combination with methotrexate. Based on the relevant role of T-cells in PsA pathogenesis and following the positive results obtained in a phase III clinical trial, abatacept recently received approval for treatment of patients with PsA. In this review, we will focus on the current knowledge about the emerging role of abatacept in treatment of PsA.
29115552 Effects of daphnetin combined with Bcl2‑siRNA on antiapoptotic genes in synovial fibrobl 2018 Jan The aim of the present study was to investigate the effects of daphnetin combined with B cell lymphoma 2 (Bcl2)‑targeted small interfering (si)RNA (si‑Bcl2) on antiapoptotic genes in fibroblast‑like synoviocytes (FLS) in rats with collagen II‑induced arthritis (CIA). The roles of si‑Bcl2 and daphnetin were determined by measuring the expression levels of Bcl2. Protein and mRNA expression levels of Bcl2 in FLS were determined by flow cytometry and reverse transcription‑quantitative polymerase chain reaction. Apoptosis of FLS was also determined by flow cytometry. It was revealed that treatment with si‑Bcl2 or daphnetin alone resulted in downregulation of Bcl2 mRNA and protein expression. In addition, the mRNA expression levels of the signal transducer and activator of transcription 3 (STAT3), which transcriptionally regulates the activity of mitochondria, were reduced. The combination of si‑Bcl2 and daphnetin exhibited an enhanced effect on rheumatoid arthritis FLS (RAFLS), in which the apoptotic rate was significantly higher than either treatment alone. The results suggested that si‑Bcl combined with daphnetin may have an enhanced effect in promoting apoptosis of RAFLS derived from CIA rats, and a possible underlying molecular mechanism may function through the downregulation of Bcl2 expression and STAT3, which is located upstream of Bcl2 in the mitochondrial apoptotic pathway. The results of the present study are expected to provide theoretical and experimental basis for the treatment of RA and the medicinal development of daphnetin combined siRNA.
30510070 LACC1 Regulates TNF and IL-17 in Mouse Models of Arthritis and Inflammation. 2019 Jan 1 Both common and rare genetic variants of laccase domain-containing 1 (LACC1, previously C13orf31) are associated with inflammatory bowel disease, leprosy, Behcet disease, and systemic juvenile idiopathic arthritis. However, the functional relevance of these variants is unclear. In this study, we use LACC1-deficient mice to gain insight into the role of LACC1 in regulating inflammation. Following oral administration of Citrobacter rodentium, LACC1 knockout (KO) mice had more severe colon lesions compared with wildtype (WT) controls. Immunization with collagen II, a collagen-induced arthritis (CIA) model, resulted in an accelerated onset of arthritis and significantly worse arthritis and inflammation in LACC1 KO mice. Similar results were obtained in a mannan-induced arthritis model. Serum and local TNF in CIA paws and C. rodentium colons were significantly increased in LACC1 KO mice compared with WT controls. The percentage of IL-17A-producing CD4(+) T cells was elevated in LACC1 KO mice undergoing CIA as well as aged mice compared with WT controls. Neutralization of IL-17, but not TNF, prevented enhanced mannan-induced arthritis in LACC1 KO mice. These data provide new mechanistic insight into the function of LACC1 in regulating TNF and IL-17 during inflammatory responses. We hypothesize that these effects contribute to immune-driven pathologies observed in individuals carrying LACC1 variants.
29037819 Drug-Induced Paradoxical Vocal Fold Motion. 2018 Jan Vocal cord dysfunction, also known as paradoxical vocal fold motion (PVFM), is a disorder characterized by abnormal vocal cord adduction during inspiration. PVFM is commonly misdiagnosed as asthma because of the similarity of symptoms: cough, wheezing, chest pain, and dyspnea. We present the clinical vignette of a 36-year-old woman with juvenile rheumatoid arthritis and multiple adverse drug reactions who presented with recurrent episodes of unrecognized PVFM during skin testing for drug allergy, omalizumab treatment, and tocilizumab desensitization. Before the diagnosis of PVFM, these episodes were treated as anaphylaxis, including the administration of epinephrine. Once diagnosed and treated for PVFM, the patient did not present any further events and continued treatment for drug allergy. PVFM may be underreported in hypersensitivity reactions because of the similarity to Type 1-mediated respiratory symptoms and comorbid asthma.
32090197 Prognostic value of Sjögren's syndrome autoantibodies. 2018 Oct Sjögren's syndrome is in part considered an autoimmune disease because patient sera contain antibodies binding self-structures. In fact, in addition to anti-Ro (or SSA) and anti-La (or SSB), which are included in the classification criteria, there are a wide variety of autoantibodies found among these patients. We reviewed English-language MEDLINE sources. Anti-Ro and anti-La found among healthy individuals, including mothers giving birth to infants with neonatal lupus, predicts future connective tissue disease. Those with Sjögren's syndrome can be divided into two groups; patients with only exocrine gland involvement and those with systemic disease. The presence of anti-Ro/La is associated with systemic, extraglandular disease. Rheumatoid factor is also associated with extraglandular disease while anti-cyclic citrullinated peptide (CCP) is likely associated with inflammatory arthritis and progression to rheumatoid arthritis. Anti-mitochondrial antibodies are uncommon but predict progression to primary biliary cirrhosis. Cryoglobulinemia is found in excess among those with non-Hodgkin's lymphoma. Determination of autoantibodies on the sera of Sjögren's syndrome patients has prognostic implications for Sjögren's syndrome itself as well as associated diseases.
29808541 Comorbidities in vitiligo: comprehensive review. 2018 Oct Vitiligo is a common skin disorder characterized by idiopathic, progressive cutaneous hypomelanosis. Vitiligo is associated with several comorbid autoimmune, systemic, and dermatological diseases, primarily thyroid disease, alopecia areata, diabetes mellitus, pernicious anemia, systemic lupus erythematosus, rheumatoid arthritis, Addison's disease, inflammatory bowel disease, Sjögren's syndrome, dermatomyositis, scleroderma, ocular and audiological abnormalities, psoriasis, and atopic dermatitis. It is essential to increase awareness of these comorbidities in order to improve the disease burden and quality of life of patients with vitiligo. Herein, we review the association with the most frequent comorbidities associated with vitiligo.
30484671 Osteoporosis complicating some inborn or acquired diseases. 2018 Nov 28 Osteoporosis in chronic diseases is very frequent and pathogenetically varied. It complicates the course of the underlying disease by the occurrence of fractures, which aggravate the quality of life and increase the mortality of patients from the underlying disease. The secondary deterioration of bone quality in chronic diseases, such as diabetes of type 1 and type 2 and/or other endocrine and metabolic disorders, as well as inflammatory diseases, including rheumatoid arthritis - are mostly associated with structural changes to collagen, altered bone turnover, increased cortical porosity and damage to the trabecular and cortical microarchitecture. Mechanisms of development of osteoporosis in some inborn or acquired disorders are discussed.
29480896 From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current statu 2018 It is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed patients. It is important for improvement of RA therapy to understand when and what changes occur in patients developing RA. This is true for both seropositive and seronegative patients. Activation of the immune system as presented by autoantibodies, increased cytokine and chemokine production, and alterations within several immune cells occur during RA development. In this review we describe RA pathogenesis with a focus on knowledge obtained from patients with arthralgia, pre-RA and recently diagnosed RA. Connections are proposed between altered immune cells, cytokines and chemokines, and events like synovial hyperplasia, pain and bone damage.
29951326 The Risk of Immunosuppression: A Case of Salmonella Meningitis. 2018 Salmonella meningitis is a rare infection, particularly in adults. We report the case of a 75-year-old female with a history of rheumatoid arthritis on TNF-antagonist immunosuppressive therapy who initially presented to the hospital for management of back and leg pain and was ultimately diagnosed with bacterial meningitis secondary to Salmonella species infection. She was treated with ceftriaxone with slow improvement in neurological function. Though the source of infection was never clearly identified from multiple imaging studies, we suspect the severity of her presentation was due to her history of TNF-antagonist use.
30356664 The Development of Immunotherapy Strategies for the Treatment of Type 1 Diabetes. 2018 Optimized insulin therapies, increased use of continuous glucose monitoring/insulin pumps and most importantly the arrival of reliable closed loop systems will undeniably lead to a reduction in the burden of complications that arise from type 1 diabetes. However, insulin therapy will only ever treat the symptoms of the disease and will not alter the underlying pathology. The aim of immunotherapy treatment is to modulate the immune system, a strategy that has been successful in autoimmune conditions such as multiple sclerosis, rheumatoid arthritis and lupus. However, the success rate of immunotherapy treatment in type 1 diabetes has been low. There are several distinct stages of T1D development. In this review, we summarize the most important immunotherapeutic approaches tested thus far and focus on the characteristic features and unmet need within the different stages of the disease.