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ID PMID Title PublicationDate abstract
32510714 Oral health-related quality of life in different rheumatic diseases. 2020 Nov OBJECTIVES: Aim of this cross-sectional study was to investigate oral health-related quality of life (OHRQoL) of patients with different rheumatic diseases. SUBJECTS AND METHODS: Patients with rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematodes (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and vasculitis were included. OHRQoL was assessed with the German short form of oral health impact profile (OHIP G14). Age, disease duration, leukocytes, c-reactive protein (CRP) and haemoglobin counts were considered as disease related parameters. RESULTS: A total of 356 patients, assigned to the groups RA (n = 218), SLE (n = 36), AS (n = 36), PsA (n = 33), vasculitis (n = 19) and SSc (n = 14) were included. The OHIP G14 sub-scale psychosocial impact differed significantly between groups (p = .02). The OHIP G14 sum score was also significantly different between groups (p < .01). A medium-sized correlation was found for CRP with OHIP G14 sum score within SLE group (r = .344, p = .04). A large correlation was detected for leukocytes within PsA group (r = .525, p < .01). The reliability of the applied OHIP G14 was high. CONCLUSION: Patients with rheumatic disease show a reduced OHRQoL, with several differences between the entities. Psychosocial aspects appear to be of relevance and should be considered in multidisciplinary dental care of these patients.
32445443 Biocompatible Nanovesicular Drug Delivery Systems with Targeting Potential for Autoimmune 2020 Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one's immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer's, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.
32215344 Orbital pseudotumor as the presenting symptom of Crohn's disease in a male child. 2020 Jun PURPOSE: This report will describe a case of orbital pseudotumor that is associated with underlying Crohn's disease in a pediatric patient. OBSERVATIONS: An 8-year-old male with a past medical history of chronic constipation who presented to the ophthalmologist in July 2017 with a 7-month history double vision, left upper lid ptosis, left abducens nerve palsy, and an abnormal thyroid test. The patient's family history was negative for any autoimmune disease including, juvenile idiopathic arthritis, rheumatoid arthritis, thyroid disease, type 1 diabetes mellitus or inflammatory bowel disease. Diagnosis of orbital pseudotumor of the left eye was made based on CT scan findings and he was then treated with a one-week course of oral prednisone. After resolution of his initial symptoms, he presented a month later with swelling in his left eye and was treated with a 6-month steroid taper with resolution of symptoms. In June 2018, the patient presented with swelling in his right eye and was treated with prednisone plus steroid sparing agents. Extraocular muscle biopsy was negative for IgG4 related disease, fungal infection, or malignant lymphoma and workup for sarcoidosis and granulomatosis with polyangiitis was unremarkable. In September 2018, the patient presented with bloody stools, diagnosed and treated for a perirectal abscess. Subsequent colonoscopy performed in January 2019 confirmed Crohn's disease. He is currently undergoing treatment with adalimumab and is in remission in terms of orbital pseudotumor. CONCLUSION AND IMPORTANCE: In conclusion, although the association between orbital pseudotumor and Crohn's disease is very rare, medical professionals should remember this connection when a patient presents with idiopathic orbital pseudotumor. To rule out this possibility, we recommend a thorough history of GI findings should be taken on the initial patient encounter. Crohn's disease may be an underlying cause of certain cases of orbital pseudotumor, and treatment and control of the underlying Crohn's disease may help to reduce recurrence rates of orbital pseudotumor. Additional studies need to be performed to better understand the association between the two diseases.
31682893 Pill or needle? Determinants of the preference for long-acting injection over oral treatme 2020 Mar 2 Although long-acting injection (LAI) is presented as first line treatment option for patients with psychosis, negative attitudes toward this galenic negatively impact the selection of this treatment option. However, these negative attitudes may not be confined to patients but also observed in the general population. A web-based study on 1807 participants was conducted during which participants imagined that they had a particular chronic illness based on clinical vignettes (mental illnesses: schizophrenia, depression; somatic illnesses: multiple sclerosis, rheumatoid arthritis). The frequency of relapse and the intensity of symptoms were experimentally manipulated in the vignettes. Participants rated their subjective distress associated with each vignette, their belief in the effectiveness of treatment, and their treatment preference regarding medication. We examined under which conditions LAI was preferred over pills. Statistical analyses were performed using Bayesian methods. Results showed that participants preferred LAI over pills in 40.5% to 50.8% of cases. LAI was more preferred for illnesses with low frequency of relapse, low subjective distress, and for somatic than for mental illnesses. The perceived advantage for LAI over pills and the belief about the better efficiency of LAI were the main factors that drove the preference for LAI. Keeping in mind some advantages of LAI, the public negative representations of injections might partially influence patients' prejudices against LAI. These attitudes should be named and discussed with the patients when LAI seems to represent a relevant therapeutic option.
32043830 Utility of Coronary Calcium Scoring (CCS) in Connective Tissue Disorders (CTDs) for the Ev 2020 Feb OBJECTIVE: To assess the current state of knowledge for the utility of coronary calcium scoring (CCS) in connective tissue disorders (CTDs) as it relates to the presence and quantification of coronary atherosclerosis. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search via PubMed, Embase, Scopus, Web of Science Core Collection, CINAHL, and Cochrane Database of Systematic Review retrieved 1019 studies (since database inception on May 7, 2018) from which 121 manuscripts were eligible for review. Inclusion criteria consisted of studies that investigated CCS in adults with respective CTDs. Studies were excluded if a complete manuscript was not written in English or was a case report. RESULTS: Thirty-one studies were included (27 with healthy age-/gender-matched control group for comparison and 4 without). CTDs analyzed in articles with control group: 11 rheumatoid arthritis (RA), 14 systemic lupus erythematosus (SLE), 4 systemic sclerosis (SSc), 1 idiopathic inflammatory myopathies (IIM), 1 Takayasu arteritis, and 1 psoriasis. Nine out of 11 RA studies, 12 out of 14 SLE studies, and 2 out of 4 SSc studies showed statistically significant increased CCS when compared with the control group. CTDs analyzed in studies without control group: two Kawasaki disease, one juvenile idiopathic arthritis (JIA), and one antiphospholipid syndrome (APS) article, which demonstrated increased coronary arterial calcium burden, however, without statistically significant data. CONCLUSION: CTDs, especially SLE and RA, are associated with higher CCS compared with the control group, indicating increased risk of coronary atherosclerosis. Our search did not elicit sufficient publications or statistically significant results in many other CTDs.
33190407 The necessity of patch testing in determining the causative drug of AGEP. 2021 Jul BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP)is a rare, severe skin reactionmainly caused by medications such as antibiotics, anti fungals, Calcium channel blockers and Anti malarias. Although it resolves spontaneously in most patients, systemic corticosteroids are neededin severe cases. AIMS: In order to determine the drug that is causing this condition, patch testing must be performed. Hydroxychloroquine is a medication that is used for the treatment of rheumatic and dermatologic conditions. And although it has been rarely seen to cause this reaction, we report a case of Hydroxychloroquine-induced (HCQ) AGEP which was confirmed by Patch testing. PATIENTS: A woman 49 years of age with an18 month history of mild, untreated Rheumatoid Arthritis experienced an acute episode of arthritis in her right elbow. Upon going to a rheumatologist, Prednisolone 5 mg BID and HCQ 200 mg daily were administered for a 30-day period. But after only 17 days of this treatment, the patient developed generalized erythema and painful pustular eruptions. Prednisolone dosage was changedto 7.5 mg per day andHCQ was discontinued one day afterthe appearance of eruptions. The diffuse erythema started improving a week after the patient's hospitalization.Considering the factthat our patient was receiving multiple potentially causative medications, patch testing was necessary to distinguish the drug responsible for this reaction. RESULTS: After the patch testing was done, HCQ-induced AGEP was confirmed. CONCLUSIONS: Patch testing is the gold standard of determining the responsible drug for an AGEP reaction. It should also be kept in mind that HCQ, although rarely, can cause this condition.
32833044 The role of xenobiotics in triggering psoriasis. 2020 Dec Psoriasis is a common inflammatory skin disease affecting approximately 2% of the world population. A complex interplay of genetic predisposition and risk factors contributes to the risk of its onset. Several xenobiotics have been implicated in the pathogenesis of psoriasis. Drugs are among the most investigated trigger factors; strong association with disease induction or exacerbation has been reported for β-blockers, lithium, NSAIDs and ACE inhibitors, all of which are commonly used in the management of various comorbidities in psoriasis patients. Furthermore, inhibitors of TNF have a well-documented potential for triggering new-onset psoriasis when used for other indications (e.g. Crohn's disease or rheumatoid arthritis), while post-marketing data have revealed the same association for ustekinumab. Several other drugs have been connected with psoriasis, but the evidence is less compelling. Smoking and alcohol have been reported to increase the risk for occurrence of psoriasis, but can also affect unfavorably the course of the disease and its response to treatment. Furthermore, exposure to secondhand smoke, especially in childhood, also mediates the risk. Emerging data now suggest that air pollution also has a detrimental effect on skin disease, including psoriasis, but this association needs further investigation. Understanding of the toxic effect of xenobiotics on the initiation and clinical course of psoriasis can contribute to its better control, as it can help with the avoidance of triggering factors and, in some cases, influence the success of pharmacological treatment. It, therefore, has an important place in the comprehensive management of psoriasis.
32560321 Prevalence of Migraine and Neuropathic Pain in Rheumatic Diseases. 2020 Jun 17 To investigate the physiopathology of pain in chronic inflammatory rheumatic diseases (CIRDs), we assessed the prevalence of migraine and neuropathic pain in 499 patients with CIRDs. We studied 238 patients with rheumatoid arthritis, 188 with spondyloarthritis (SpA), 72 with psoriatic arthritis (PsA), and 1 unclassified. Migraine was diagnosed according to IHS migraine diagnostic criteria. Neuropathic pain was diagnosed when patients scored at least 3 on the DN4 questionnaire. Participants completed a validated self-assessment questionnaire. Migraine prevalence was 34% (165/484), and it was highest in PsA. Risk factors for migraine were a high level of anxiety, female sex, young age, and TNF-alpha inhibitor treatment (OR = 1.90 (1.13-3.25)). Besides, high disease activity was a risk factor in SpA. Blood CRP level was not significantly associated with migraine. Of 493 patients with CIRDs, 21.5% had chronic pain with neuropathic characteristics. Compared to the French general population, these patients had significantly higher prevalences of migraine (two-fold) and neuropathic pain (three-fold). This study showed that migraine and neuropathic pain frequently occurred in patients with rheumatic diseases. Therefore, upon reporting residual pain, these patients should be checked for the presence of migraine or neuropathic pain, despite adequate clinical control of rheumatic disease.
33274023 Management of Gonarthrosis with a Rotating Hinge Prosthesis: Minimum 10-Year Follow-up. 2020 Dec BACKGROUND: The use of hinged designs is usually reserved for severe deformities or instability in contemporary total knee arthroplasty (TKA). Results have been mixed with some authors reporting relatively high incidences of complications. The aim of this study is to present the results of primary TKA performed with a hinged prosthesis with a minimum 10-year follow-up. We also examined the factors that influence survivorship of this prosthesis. METHODS: A total of 238 primary TKA procedures were performed using hinged prostheses. Indications included osteoarthritis, rheumatoid arthritis, posttraumatic deformity, and arthritis. Clinical outcomes were assessed using the Hospital for Special Surgery score. Radiologic assessment was performed at each follow-up. Survivorship was calculated based on the Kaplan-Meier method. All complications were documented. RESULTS: Mean follow-up was 13.5 years (standard deviation [SD], 3.4). Mean flexion at final review was 118° (SD, 20°). Fifty-four percent and 20% reported excellent and good functional scores, respectively. Survivorship was 94% at 13.5 years in patients over 60 years of age and 77% in patients less than 60 years of age. Survivorship in patients with preoperative varus deformity was 96% and that in valgus knees was 79%. CONCLUSIONS: The results of this study suggest that when rotating hinges are used for primary TKA, the best results are achieved in patients over 60 years old. The indications for this design in the setting of primary TKA include significant deformities, severe bone loss, and ligamentous laxity.
33108917 Small-molecule CSF1R kinase inhibitors; review of patents 2015-present. 2021 Feb INTRODUCTION: Colony stimulating factor 1 receptor (CSF-1R, also known as c-FMS kinase) is in the class III receptor tyrosine kinase family, along with c-Kit, Flt3 and PDGFRα. CSF-1/CSF-1R signaling promotes the differentiation and survival of myeloid progenitors into populations of monocytes, macrophages, dendritic cells and osteoclasts, as well as microglial cells and also recruits host macrophages to develop into tumor-associated macrophages (TAMs), which promote tumor progression and metastasis. AREAS COVERED: In the last 5 years, and recently stimulated by the approval of pexidartinib (Turalio™, Daiichi Sankyo) in 2019 for the treatment of tenosynovial giant cell tumors, there has been a large increase in activity (both journal articles and patent applications) around small molecule inhibitors of CSF1R. Features of this work have been the surprising diversity of chemical classes shown to be potent and selective inhibitors, and the breadth of disease states (cancer, arthritis, and 'cytokine storm' syndromes) covered by CSF1R inhibitors. All these aspects are covered in the following sections. EXPERT OPINION: The field has developed rapidly from 2014 to the present, with many different chemotypes proving to be potent inhibitors. The range of potential utilities of CSF1R inhibitors has also expanded to include dementia, ulcerative colitis/Crohn's disease, rheumatoid arthritis inflammation, and fibrosis.
33065756 Associations between pediatric asthma and adult non-communicable diseases. 2021 Feb BACKGROUND: To date, there is no comprehensive study examining how asthma diagnosed in childhood or adolescence is associated with diagnoses of subsequent non-communicable diseases (NCDs) during adulthood. Our study aimed to examine the associations between pediatric asthma and several adult NCDs, with temporality and long interval times between asthma and NCD diagnoses. METHODS: We used RAND Indonesian Family Life Survey Fifth Wave (IFLS5) fielded in 2014-2015, to study whether being diagnosed with pediatric asthma at 0-19 years of age was associated with increased risks of hypertension, diabetes, rheumatoid arthritis, stomach diseases, kidney diseases, and heart diseases or stroke diagnosed in adulthood. We used the weighted Poisson regression adjusting for age, sex, urbanicity, and insurance status to estimate risk ratios. Subgroup analyses were performed by sex and age of asthma and other NCD diagnoses. RESULTS: Pediatric asthma significantly increased risks of hypertension, diabetes, and stomach diseases diagnosed at 20 years of age or above. Males with pediatric asthma diagnosed at 0-10 years of age had significantly higher risk of hypertension, while females with pediatric asthma diagnosed at 0-10 years of age had significantly higher risks of diabetes and stomach diseases. Females with pediatric asthma diagnosed at 11-19 years of age had significantly higher risks of diabetes, arthritis, stomach diseases, and kidney diseases. We also found varying associations by age of NCD diagnosis. CONCLUSION: Our results suggest pediatric asthma is associated with increased risks of several adult NCDs, and these associations may vary by sex and age of asthma and other NCD diagnoses.
33019878 Proton magnetic resonance spectroscopy ((1)H-MRS) in rheumatic autoimmune diseases: A syst 2020 Dec BACKGROUND/PURPOSE: Proton magnetic resonance spectroscopy ((1)H-MRS) has been shown to be an important non-invasive tool to quantify neuronal loss or damage in the investigation of central nervous system (CNS) disorders. The purpose of this article is to discuss the clinical utility of (1)H-MRS in determining CNS involvement in individuals with rheumatic autoimmune diseases. METHODS: This study is a systematic review of the literature, conducted during the month of November and December of 2019 of articles published in the last 16 years (2003-2019). The search for relevant references was done through the exploration of electronic databases (PubMed/Medline and Embase). We searched for studied including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), juvenile idiopathic arthritis, rheumatoid arthritis (RA), psoriasis, Sjögren's syndrome (pSS), vasculitis and Behçet. Only studies published after 2003 and with more than 20 patients were included. RESULTS: We included 26 articles. NAA/Cr ratios were significant lower and Cho/Cr ratios increased in several brain regions in SLE, SS, RA, SSc. Associations with disease activity, inflammatory markers, CNS manifestations and comorbidities was variable across studies and diseases. CONCLUSION: The presence of neurometabolite abnormalities in patients without ouvert CNS manifestations, suggests that systemic inflammation, atherosclerosis or abnormal vascular reactivity may be associated with subclinical CNS manifestations. MRS may be a usefull non-invasive method for screening patients with risk for CNS manifestations.
33161563 Development of JAK inhibitors for the treatment of immune-mediated diseases: kinase-target 2020 Nov JAKs are a family of intracellular tyrosine kinases consisting of four members, JAK1, JAK2, JAK3, and TYK2. They are key components of the JAK-STAT pathway that transmit signals of many cytokines involved in the pathogenesis of numerous immune-mediated diseases and have been major molecular targets in developing new drugs for the treatment of such diseases. Some small-molecule inhibitors of JAKs have been approved by the FDA for rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease. Now, newer JAK inhibitors with isoform-selectivity among the four different JAKs are being developed, with the aim of improving clinical outcomes compared with earlier developed drugs with pan-JAK inhibition. Most of these selective inhibitors target the kinase domains of JAKs, functioning through the traditional inhibition mode of kinases; but recently those that target their pseudokinase domains, allosterically inhibiting the enzymes, have been under development. In this review, key characteristics, efficacy, and safety of FDA-approved and representative drugs in late stages of development are briefly described in order to provide clinical implications with respect to JAK inhibitor selectivity and future development perspectives. The recent development of pseudokinase-targeted inhibitors of JAKs is also included.
31699619 [Methotrexate in juvenile idiopathic arthritis. Adverse effects and associated factors]. 2020 Mar INTRODUCTION: Methotrexate (MTX) is the drug of choice for juvenile idiopathic arthritis. Its clinical efficacy is limited due to the development of adverse effects (AEs). PATIENTS AND METHODS: A retrospective observational study was conducted on the AEs associated with MTX therapy in children diagnosed with juvenile idiopathic arthritis followed-up in a tertiary hospital between 2008 and 2016. RESULTS: The study included a total of 107 patients, of whom 71 (66.3%) were girls (66.3%). The median age at diagnosis was 6.4 years (IQR 3.1-12.4), with a median follow-up of 45.7 months (IQR 28.8-92.4). There were 48 patients (44.9%) with oligoarthritis, and 26 children (24.3%) with rheumatoid-factor negative polyarthritis. Of these, 52/107 (48.6%) developed AEs, with the most frequent being gastrointestinal symptoms (35.6%) and behavioural problems (35.6%). An age older than 6 years at the beginning of therapy increased the risk of developing AEs, both in the univariate (OR=3.5; 95% CI: 1.5-7.3) and multivariate (12% increase per year) analyses. The doses used, administration route, or International League of Associations for Rheumatology (ILAR) classification, were not associated with the development of AEs. Twenty children required a dosage or route of administration modification, which resolved the AE in 11 (55%) cases. MTX was interrupted due to the development of AEs in 37/107 patients (34.6%), mainly due to increased plasma transaminases (n=14, 37.8%), gastrointestinal symptoms (n=9, 24.3%) and behavioural problems (n=6, 16.3%). CONCLUSIONS: MTX is the therapy of choice for patients with juvenile idiopathic arthritis, but 50% of the children develop some form of AE. Although the AEs are not severe, they lead to interruption of therapy in 35% of the children.
31641939 Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic 2020 Oct BACKGROUND: Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA). The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients. The relative expressions of miR-21, STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay. Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21. The expression of STAT3/p-STAT3 was measured by western blot, and the levels of interleukin (IL)-17A, p65, matrix metalloproteinases (MMP)-3, MMP-4 and receptor activator of nuclear factor-κB after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay. Finally, the miR-21 targeted STAT3 gene was detected by the dual-luciferase reported assay. RESULTS: The expression of miR-21 was significantly lower in JIA patients than in healthy control (P < 0.05). The level of STAT3 was increased in PBMCs of JIA group compared with control group (P < 0.05). Furthermore, the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 (r = - 0.5854/r = - 0.6134, P < 0.05). The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21. The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 (P < 0.05). RASFs were induced into osteoclasts using M-CSF. The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group (P < 0.05). CONCLUSIONS: We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control. MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3. MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.
32401103 Low glucocorticoids in stress-related disorders: the role of inflammation. 2020 Nov There is evidence that plasma cortisol concentration can be either increased or decreased in patients with depression and related anxiety and stress-related disorders; the exact pathophysiological mechanisms of this state are not almost clear. Several distinct theories were proposed and mechanisms, which could lead to decreased glucocorticoid signaling and/or levels, were described. However, there is a possible drawback in almost all the theories proposed: insufficient attention to the inflammatory process, which is undoubtedly present in several stress-related disorders, including post-traumatic stress disorder (PTSD). Previous studies only briefly mentioned the presence of an inflammatory reaction's signs in PTSD, without giving it due importance, although recognizing that it can affect the course of the disease. With that, the state of biochemical changes, characterized by the low glucocorticoids, glucocorticoid receptor's resistance and the signs of the persistent inflammation (with the high levels of circulating cytokines) might be observed not only in PTSD but in coronary heart diseases and systemic chronic inflammatory diseases (rheumatoid arthritis) as well. That is why the present review aims to depict the pathophysiological mechanisms, which lead to a decrease in glucocorticoids in PTSD due to the action of inflammatory stimuli. We described changes in the glucocorticoid system and inflammatory reaction as parts of an integral system, where glucocorticoids and the glucocorticoid receptor reside at the apex of a regulatory network that blocks several inflammatory pathways, while decreased glucocorticoid signaling and/or level leads to unchecked inflammatory reactions to promote pathologies such as PTSD. LAY SUMMARY This review emphasizes the importance of inflammatory reaction in the development of puzzling conditions sometimes observed in severe diseases including post-traumatic stress disorder - the decreased levels of glucocorticoids in the blood. Following the classical concepts, one would expect an increase in glucocorticoid hormones, since they are part of the feedback mechanism in the immune system, which reduces stress and inflammation. However, low levels of glucocorticoid hormones are also observed. Thus, this review describes potential mechanisms, which can lead to the development of such a state.
33243033 Costs of medication use among patients with juvenile idiopathic arthritis in the Dutch hea 2021 Oct Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype.Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, subtype) and medication use were extracted. Medication use and costs were reported as: 1) mean total annual costs; 2) between-patient heterogeneity in these costs; 3) duration of medication use; and, 4) costs over the treatment course.Results: The analysis included 691 patients. Mean total medication costs were €2,103/patient/year, including €1,930/patient/year (91.8%) spent on biologicals. Costs varied considerably between subtypes, with polyarticular rheumatoid-factor positive and systemic JIA patients having the highest mean costs (€5,020/patient/year and €4,790/patient/year, respectively). Mean annual medication costs over the patient's treatment course ranged from <€1,000/year (71.1% of patients) to >€11,000/year (2.5% of patients). Etanercept and adalimumab were the most commonly used biologicals. Cost fluctuations over the treatment course were primarily attributable to biological use.Conclusions: Polyarticular rheumatoid-factor positive and systemic JIA patients had the highest mean total annual medication costs, primarily attributable to biologicals. Costs varied considerably between subtypes, individuals, and over the treatment course.
32616563 Systemic lupus erythematosus and neutropaenia: a hallmark of haematological manifestations 2020 Jul OBJECTIVE: Systemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%-40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined. METHODS: 998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×10(6)/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia. RESULTS: 208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57-10.3)), lymphopaenia (OR 4.41 (2.51-11.5)) and low C3 (OR 1.91 (1.03-4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers. CONCLUSION: This study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren's disease.
32857280 Early-onset subclinical cardiovascular damage assessed by non-invasive methods in children 2021 Feb Chronic inflammation starting early in life and continuing into adulthood may predispose children with Juvenile Idiopathic Arthritis (JIA) to cardiovascular (CV) complications. To compare non-invasive CV risk markers- left ventricular mass index (LVMi), brachial artery flow mediated dilatation (FMD) and carotid artery intima-media thickness (CIMT) between patients with JIA and healthy controls. Measurements of LVMi, CIMT and FMD and lipid profile were compared between 4 and 18 year old 81 patients with JIA and 78 age and sex matched healthy controls. Among 81, 20 had systemic onset, 19 enthesitis related arthritis, 9 polyarticular rheumatoid factor (RF) + ve, 19 polyarticular RF -ve, 11 oligo-articular, and 3 un-differentiated JIA. FMD was significantly lower (p < 0.001), CIMT and LVMi significantly higher in patients (p ≤  0.001). CIMT showed positive correlation with blood pressure (p = 0.001), disease duration (p  ≤  0.001) and negative correlation with high density lipoprotein (HDL) (p ≤  0.001). FMD correlated positively with HDL (p = 0.006) and negatively with disease duration (p ≤  0.001). CIMT (p = 0.017) and FMD (p = 0.04) were significantly worse in active than inactive disease. Children with JIA have worse lipid profile, increased LVMi, CIMT, and reduced brachial artery FMD, suggestive of early cardiovascular dysfunction.
32531346 Sicca syndrome following immune checkpoint inhibition. 2020 Aug The recent approval of Immunologic checkpoint inhibitors as an effective therapeutic strategy against cancer came at the cost of toxicities mediated by an excessive activation of immune system against health tissues, including among others musculoskeletal and sicca complaints.The latter occur in the context of an entity reminiscent of Sjogren's syndrome, with distinct characteristics such as abrupt onset, male predominance, lower prevalence of autoantibodies and response to steroids.