Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
31846747 Citral-induced analgesia is associated with increased spinal serotonin, reduced spinal noc 2020 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Citral (3,7-dimethyl-2,6-octadienal) is the main component of Cymbopogon citratus (DC) Stapf, an herb with analgesic properties. Arthritic pain is the main unpleasant component of rheumatoid arthritis. The pharmacological approaches used to treat arthritic pain are often accompanied by adjuvant drugs or non-pharmacological treatments, showing a constant need in identifying new efficient analgesic drugs. AIM OF THE STUDY: To test the hypothesis that citral, which is a monoterpenoid compound with therapeutic properties, reduces nociception, spinal pro-nociceptive and pro-inflammatory signaling, and systemic oxidative stress in arthritic rats. MATERIALS AND METHODS: Complete Freund's adjuvant (CFA) was administrated in the left knee joint of rats. Oral treatment with citral was performed during eight days and mechanical allodynia was monitored during the period of treatment to evaluate the analgesic effect of citral. We assessed the levels of serotonin (5-hydroxytryptamine, 5-HT) in the lumbar dorsal horn of the spinal cord (DHSC) and the profiles of expression of the glycogen synthase kinase-3β (GSK3β), which is a 5-HT-regulated intracellular protein, and of the stress-activated protein kinase (SAPK)/jun N-terminal kinase (JNK) in the DHSC. Plasma levels of superoxide dismutase (SOD) were assessed as an indicator of oxidative stress. RESULTS: Administration of CFA induced mechanical allodynia associated with reduced spinal GSK3β phosphorylation, increased spinal SAPK/JNK phosphorylation, and increased plasma SOD levels. Oral administration of citral reversed mechanical allodynia, increased endogenous spinal 5-HT levels, reduced spinal SAPK/JNK phosphorylation, and reduced plasma SOD levels. CONCLUSION: Citral shows anti-nociceptive effects in an animal model of arthritic pain by modulating spinal nociceptive signaling.
31313244 Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Attenuate Collagen-Induced Arthriti 2020 Apr The aim of the study was to evaluate if gold-coated superparamagnetic iron oxide nanoparticles (AuSPION) magnetic-targeted to the arthritic articulation of collagen induced arthritis (CIA) rats are able to ameliorate rheumatoid arthritis without producing significant biological adverse effects in comparison to colloidal Au nanoparticles (AuC) and metotrexate (MTX). Male Wistar rats were divided into control; arthritic; AuSPION (150 μg kg(-1)); AuC (150 μg kg(-1)) and MTX (2.5 μg kg(-1)). Treatments were administered thrice every other day by the intraperitoneal route 15 min after all groups had a neodymium magnet coupled to the right ankle joint (kept for 1 h). Paw edema and body weight were measured weekly. Joint sections were evaluated by Haematoxylin & Eosin and immunohistochemistry (TNF-α, IL-1β). Biomarkers of oxidative stress were used to evaluate toxicity. Among the evaluated treatments, AuSPION led to significant clinical improvements (decreased edema and infiltration by leukocytes as well as less positively immunostained cells for both TNF-α and IL-1β in synovium) accompanied by a lack of toxicity as indicated by redox state and genotoxicity assays. Our results clearly indicate that the magnetic targeting of AuSPION suppresses joint edema and inflammation, cytokine expression as well as the redox imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats. The results demonstrate for the first time the potentiality of AuSPION administration under a magnetic field as an attractive alternative for future treatments of rheumatic diseases.
31852268 Infection risk in patients undergoing treatment for inflammatory arthritis: non-biologics 2020 Feb Introduction: Despite the therapeutic effectiveness of biologics targeting immune cells or cytokines in patients with inflammatory arthritis, which reflects their pathogenic roles, an increased infection risk is observed in those undergoing biological treatment. However, there are limited data regarding the comparison of infection risks in inflammatory arthritis patients treated with non-biologics (csDMARDs), biologics (bDMARDs), including tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors, or targeted synthetic (ts)DMARDs.Areas covered: Through a review of English-language literature as of 30 June 2019, we focus on the existing evidence on the risk of infections caused by bacteria, Mycobacterium tuberculosis, and hepatitis virus in inflammatory arthritis patients undergoing treatment with csDMARDs, bDMARDs, or tsDMARDs.Expert opinion: While the risks of bacterial and mycobacterial infection are increased in arthritis patients treated with csDMARDs, the risks are further higher in those receiving bDMARDs therapy, particularly TNF inhibitors. Regarding HBV infection, antiviral therapy may effectively prevent HBV reactivation in patients receiving bDMARDs, especially rituximab. However, more data are needed to establish effective preventive strategies for HBsAg-negative/HBcAb-positive patients. It seems safe to use cyclosporine and TNF inhibitors in patients with HCV infection, while those undergoing rituximab therapies should be frequently monitored for HCV activity.Abbreviations: ABT: abatacept; ADA: adalimumab; AS: ankylosing spondylitis; bDMARDs: biologic disease-modifying anti-rheumatic drugs; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: corticosteroids; CsA: cyclosporine A; csDMARDs: conventional synthetic disease-modifying anti-rheumatic drugs; CZP: certolizumab; DAAs: direct-acting antiviral agents; DM: diabetes mellitus; DOT: directly observed therapy; EIN: Emerging Infections Network; ETN: etanercept; GOL: golimumab; GPRD: General Practice Research Database; HBV: hepatitis B virus; HBVr: HBV reactivation; HBsAg+: HBsAg-positive; HBsAg-/anti-HBc+: HBsAg-negative anti-HBc antibodies-positive; HCV: hepatitis C virus; HCQ: hydroxychloroquine: IFX: infliximab; IL-6: interleukin-6; JAK: Janus kinase; LEF: leflunomide; LTBI: latent tuberculosis infection; mAb: monoclonal antibody; MTX: methotrexate; OR: odds ratio; PsA: psoriatic arthritis; PMS: post-marketing surveillance; RA: rheumatoid arthritis; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; SCK: secukinumab; SSZ: sulfasalazine; TOZ: tocilizumab; RCT: randomized controlled trial; RR: relative risk; RTX: rituximab; 3HP: 3-month once-weekly isoniazid plus rifapentine; TB: tuberculosis; tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs; UTK: ustekinumab; WHO: World Health Organization.
32772578 Nonunion and Reoperation Following Proximal Interphalangeal Joint Arthrodesis and Associat 2022 May BACKGROUND: Proximal interphalangeal joint (PIPJ) arthrodesis can provide reliable pain relief and restore hand function in patients with PIPJ arthritis. However, there is a paucity of literature on patient-specific preoperative risk factors that are associated with adverse outcomes after PIPJ arthrodeses. Therefore, the primary purpose of this study was to assess preoperative predictors of nonunion and reoperation after PIPJ arthrodesis. METHODS: This study identified all patients who underwent PIPJ arthrodesis at a single community practice between 1987 and 2013. The final analysis included 415 PIPJs treated with arthrodesis. The mean follow-up was 1.3 years. Data on preoperative diagnosis, demographics, comorbidities, and operative techniques were recorded, as well as the occurrence of nonunions and reoperations. Logistic regression models were used to identify independent risk factors of nonunion and reoperation. RESULTS: There were 40 nonunions (10%) and 62 reoperations (15%). Of the reoperations, there were 39 incidences of isolated hardware removal, 9 irrigation and debridement, 8 amputations, 5 revision arthrodeses, and 1 corrective osteotomy. The highest number of nonunions occurred in the traumatic diagnosis group (37%), followed by the rheumatoid group (23%) and the scleroderma group (15%). The highest number of reoperations occurred within the traumatic joint disorder group (40%), followed by the rheumatoid group (24%) and the scleroderma group (11%). Multivariate analysis revealed that male sex (P < .01) and hepatic disease (P = .03) were significant risk factors of nonunion. Male sex was also significantly associated with increased reoperation risk (P < .01). CONCLUSION: Risks of nonunions and reoperations after PIPJ arthrodeses are low; however, these findings may guide clinicians and patients in the preoperative decision-making process and help with targeted postoperative surveillance to mitigate these risks.
32923288 Reactive Arthritis in a 37-Year-Old Female With SARS-CoV2 Infection. 2020 Aug 12 We report the case of a 37-year-old female who presented for evaluation of acute 10/10 right hand pain, 12 days after testing positive for SARS-CoV2. The patient was admitted to the hospital due to the severity of her pain. As an inpatient, extensive workup by the medicine team and rheumatology revealed no structural, vascular, or neurogenic cause of her pain. The patient's blood work was unremarkable for elevations in lyme serology, antinuclear antibody (ANA), rheumatoid factor, and uric acid. It was determined that the cause of her pain was most likely reactive arthritis (ReA) secondary to her SARS-CoV2 infection. She was treated with voltaren gel, neurontin, and oral dilaudid as needed and discharged. Upon follow-up, her pain improved and she was prescribed a wrist splint, ultram, and occupational therapy for perceived wrist tendinitis. To our knowledge, this is the first description of a case of ReA caused by the SARS-CoV2 virus.
32849596 IL-27 Regulated CD4(+)IL-10(+) T Cells in Experimental Sjögren Syndrome. 2020 Interleukin 27 (IL-27) plays diverse immune regulatory roles in autoimmune disorders and promotes the generation of IL-10-producing CD4(+) T cells characterized by producing the immunosuppressive cytokine IL-10. However, whether IL-27 participates in pathological progress of Sjögren syndrome (SS) through regulating CD4(+)IL-10(+) T cells remains unknown. Here we aimed to explore the potential role of IL-27 and CD4(+)IL-10(+) T cells in the pathogenesis of SS. The IL-27 gene knockout non-obese diabetic (Il-27 (-/-)NOD) mice were generated and injected with exogenous IL-27. Exogenous injection of IL-27 and neutralization of IL-27 with anti-IL-27 antibody in NOD mice were performed. The histopathologic changes in submandibular glands, lacrimal glands and lung, salivary flow rate, and percentages of CD4(+)IL-10(+) T cells were determined. And, ovalbumin-immunized C57L/B6 mice were injected with IL-27 to detect the percentage of CD4(+)IL-10(+) T cells. In vitro, splenic naive T cells from C57L/B6 mice were cultured with IL-27 for 4 days to induce the differentiation of CD4(+)IL-10(+) T cells. In addition, IL-27, IL-10, and CD4(+)IL-10(+) T cells were determined in health control and SS patients. The results showed that Il-27 (-/-)NOD mice had more severe disease and lower level of CD4(+)IL-10(+) T cells than control mice. And IL-27 promoted the generation and differentiation of CD4(+)IL-10(+) T cells in vivo and in vitro significantly. In agreement with the findings in the SS-like mice, patients with SS showed lower levels of IL-27, IL-10, and CD4(+)IL-10(+) T cells. Our findings indicated that IL-27 deficiency aggravated SS by regulating CD4(+)IL-10(+) T cells. Targeting IL-27 and CD4(+)IL-10(+) T cells may be a novel therapy for patients with SS.
31491724 Interleukin-21-mediated suppression of the Pax3-Id3 pathway exacerbates the development of 2020 Jan Sjögren's syndrome (SS) is a systemic autoimmune disease with severe dysfunction of glandular secretory function mediated by T and B lymphocyte infiltration into the exocrine glands, including the salivary and lacrimal glands. Follicular helper T (Tfh) cells exacerbate the disease by causing B cell hyperactivity. Inhibitor of DNA binding 3 (Id3) deficiency causes activation of Tfh cells and is known to be a clinical manifestation of human SS disease. In this study, we investigated the mechanism of action of Pax3, which is reduced in SS and can interact with Id3, in NOD/ShiLtJ mice as an animal model of SS. Treatment with interleukin (IL)-21, a major cytokine secreted from Tfh cells, suppressed Pax3 and Id3 expression via STAT3 in splenic T cells in vitro. Administration of pCMV14-3xFlag PAX3 vector improved the severity of SS by reducing the number of Tfh cells in NOD/ShiLtJ mice. Application of IL-21R-Fc increased the number of Pax3- and Id3-positive cells in the salivary glands, while reducing the proportion of Tfh cells and IL-17-producing T cells in NOD/ShiLtJ mice. The salivary glands from SS patients showed decreased levels of Pax3 or Id3 expression compared with healthy controls. Our findings regarding reinforcement of the Pax3-Id3 signal pathway may facilitate the development of novel therapeutic strategies for SS.
32424031 Mixed methods study of clinicians' perspectives on barriers to implementation of treat to 2020 Aug OBJECTIVES: In treat to target (T2T), the patient is treated to reach and maintain specified and sequentially measured goals, such as remission or low disease activity. T2T in psoriatic arthritis (PsA) has demonstrated improved clinical and patient-reported outcomes and is recommended in European guidelines. However, most clinicians do not use T2T in PsA. This study examined the barriers and enablers to implementation in practice. METHODS: Sequential mixed methods comprising a qualitative design (interviews and focus group) to inform a quantitative design (survey). Qualitative data were analysed thematically, and quantitative statistics were analysed descriptively. RESULTS: Nineteen rheumatology clinicians participated in telephone interviews or a face-to-face focus group. An overarching theme 'Complexity' (including 'PsA vs Rheumatoid Arthritis', 'Measurement' and 'Resources') and an underpinning theme 'Changes to current practice' (including 'Reluctance due to organisational factors' and 'Individual determination to make changes') were identified. 153 rheumatology clinicians responded to an online survey. Barriers included limited clinical appointment time to collect outcome data (54.5%) and lack of training in assessing skin disease (35%). Enablers included provision of a protocol (86.4%), a local implementation lead (80.9%), support in clinic to measure outcomes (83.3%) and training in T2T (69.8%). The importance of regular audit with feedback, specialist PsA clinics and a web-based electronic database linked to hospital/national information technology (IT) systems were also identified as enablers. CONCLUSIONS: Implementation of T2T in PsA requires an integrated approach to address the support, training and resource needs of individual clinicians, rheumatology teams, local IT systems and service providers to maximise success.
32457913 Differential Diagnosis of Inflammatory Arthropathies by Musculoskeletal Ultrasonography: A 2020 Background: Differential diagnosis in early arthritis is challenging, especially early after symptom onset. Several studies applied musculoskeletal ultrasound in this setting, however, its role in helping diagnosis has yet to be clearly defined. The purpose of this work is to systematically assess the diagnostic applications of ultrasonography in early arthritis in order to summarize the available evidence and highlight possible gaps in knowledge. Methods: In December 2017, existing systematic literature reviews (SLR) on rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), polymyalgia rheumatica (PMR), calcium pyrophosphate deposition disease (CPPD), and gout were retrieved. Studies on ultrasound to diagnose the target conditions and detecting elementary lesions (such as synovitis, tenosynovitis, enthesitis, bone erosions, osteophytes) were extracted from the SLRs. The searches of the previous reviews were updated and data from new studies fulfilling the inclusion criteria extracted. Groups of reviewers worked separately for each disease, when possible diagnostic accuracy (sensitivities, specificities) was calculated from primary studies. When available, the reliability of ultrasound to detect elementary lesions was extracted. Results: For all the examined disease, recent SLRs were available. The new searches identified 27 eligible articles, with 87 articles included from the previous SLRs. The diagnostic performance of ultrasound in identifying diseases was addressed by 75 studies; in most of them, a single elementary lesion was used to define diagnosis, except for PMR. Only studies on RA included consecutive patients with new onset of arthritis, while studies on gout and CPPD often focused on subjects with mono-arthritis. Most of the remaining studies enrolled patients with a defined diagnosis. Synovitis was the most frequently detected lesion; clinical diagnosis was the most common reference standard. The diagnostic performance of ultrasound across different conditions was extremely variable. Ultrasound to identify elementary lesions was assessed in 38 studies in OA, gout and CPPD. Its performance in OA was very variable, with better results in CPPD and gout. The reliability of ultrasound was moderate to good for most lesions. Conclusions: Although a consistent amount of literature investigated the diagnostic application of ultrasound, in only a minority of cases its additional value over clinical diagnosis was tested. This SLR underlines the need for studies with a pragmatic design to identify the placement of ultrasound in the diagnostic pathway of new-onset arthritis.
32043398 Prevalence of sicca symptoms and Sjögren's syndrome in coeliac patients and healthy contr 2020 May Objective: There has been no previous study comparing the frequency of sicca symptoms and Sjögren's syndrome (SS) in coeliac patients (CPs) and healthy controls (HCs) using a tight screening method. The aim of this study was to compare the frequency of sicca symptoms and SS in HCs and CPs.Method: The study included 80 CPs and 100 HCs. This study was designed as a case-control study with four phases. The frequency of SS in CPs and HCs was defined according to the 2002 American-European Consensus Group (AECG) and 2012 American College of Rheumatology (ACR) classification criteria. The frequency of sicca symptoms and SS was compared between CPs and HCs.Results: Ocular and oral symptoms occurred in 22% and 26% of CPs, respectively, compared to 13% and 10% of HCs, respectively. Proportions with oral symptoms were statistically significantly different between CPs and HCs (p = 0.005), whereas there was no significant difference for ocular symptoms (p = 0.113). According to ACR and AECG criteria, the prevalence of SS was 3.8% and 5.0% in CPs and 3.0% and 2.0% in HCs, respectively.Conclusion: Although oral symptoms were more frequent in CPs than in HCs, the frequency of SS was not different between the groups. The increased frequency of oral symptoms may be related to reasons other than autoimmunity.
31634227 Association Between Early Sjögren Markers and Symptoms and Signs of Dry Eye. 2020 Mar PURPOSE: Animal models suggest that early markers of Sjögren syndrome (EMS)-antibodies against salivary protein 1, parotid secretory protein, and carbonic anhydrase 6 (CA6)-are more accurate signals of early Sjögren when compared with classic markers (anti-Ro and anti-La). To further understand the relationship between EMS and dry eye (DE), we compared symptoms and signs of DE in subjects who tested positive versus negative for EMS. METHODS: In this cross-sectional study, patients at the Miami Veterans Affairs Eye Clinic who were tested for EMS underwent a standard ocular surface examination. Indications for EMS testing included DE symptoms in combination with dry mouth symptoms, low tear production, corneal staining, or a Sjögren disease-associated autoimmune disease. Statistical tests performed were the χ test, Fisher exact test, independent sample t test, and Spearman correlation. RESULTS: Seventy-three percent of 44 patients tested positive for 1 or more EMS. CA6 IgG was most frequently elevated, followed by CA6 IgM and parotid secretory protein IgG. EMS-positive versus EMS-negative subjects were more likely to escalate DE treatment past artificial tears to topical cyclosporine (n = 32, 100% vs. n = 9, 75%, P = 0.02). There were no demographic or comorbidity differences between EMS-positive and EMS-negative subjects, and marker levels did not correlate with more severe tear film measures. CONCLUSIONS: Most of the individuals with DE tested positive for 1 or more EMS antibodies, including men and Hispanics. Future studies will be needed to understand how to incorporate EMS data into the care of an individual with DE.
30986119 Evaluation of the Efficacy and Safety of A Novel 0.05% Cyclosporin A Topical Nanoemulsion 2020 Apr 2 Purpose: To evaluate the efficacy and safety of a novel topical cyclosporin A 0.05% nanoemulsion in comparison with a conventional emulsion in primary Sjögren's syndrome dry eyes.Methods: Prospective, randomized, double-blinded study was conducted.Results: Corneal and conjunctival staining score was improved in both groups, with a faster change noted in the nanoemulsion group at 12 weeks (p < 0.05). Tear film break-up time was significantly improved in the nanoemulsion group at 12 weeks (p < 0.05), while ocular surface disease index score was improved in both groups without a difference at 12 weeks. Schirmer I value and goblet cell grade did not change in both groups. IL-6 and MMP-9 were significantly decreased in both groups at 12 weeks.Conclusions: Both nanoemulsion and conventional cyclosporin A improved ocular signs, symptoms, and conjunctival inflammation. However, the novel cyclosporin A nanoemulsion showed faster improvement of ocular surface staining scores than the conventional emulsion.
32630417 Pulmonary Involvement in a Mouse Model of Sjögren's Syndrome Induced by STING Activation. 2020 Jun 25 Sjögren's Syndrome (SS), a chronic autoimmune disorder affecting multiple organ systems, is characterized by an elevated type I interferon (IFN) response. Activation of Stimulator of Interferon Genes (STING) protein induces type I IFN and in mice, several features of SS, including anti-nuclear antibodies, sialadenitis, and salivary gland dysfunction. Since lung involvement occurs in one-fifth of SS patients, we investigated whether systemic activation of STING also leads to lung inflammation. Lungs from female C57BL/6 mice injected with the STING agonist 5, 6-Dimethylxanthenone-4-acetic acid (DMXAA), were evaluated for acute and chronic inflammatory responses. Within 4h of DMXAA injection, the expression of Ifnb1, Il6, Tnf, Ifng, and Mx1 was significantly upregulated. At 1 and 2 months post-treatment, lungs showed lymphocytic infiltration in the peri-bronchial regions. The lungs from DMXAA treated mice showed an increased expression of multiple chemokines and an increase in lymphatic endothelial cells. Despite STING expression in bronchial epithelium and cells lining the alveolar wall, bone marrow chimeras between STING knockout and wild type mice showed that STING expression in hematopoietic cells was critical for lung inflammation. Our results suggest that activation of the STING pathway might be involved in SS patients with concomitant salivary gland and lung disease.
32315325 Aberrant HLA-DR expression in the conjunctival epithelium after autologous serum treatment 2020 The aim of this study was to determine the effect of autologous serum (AS) eye drops on the density of human leucocyte antigen (HLA)-DR-positive epithelial cells and Langerhans cells on the ocular surface of patients with bilateral severe dry eye disease (DED) due to graft-versus-host disease (GvHD) or Sjögren's syndrome (SS). The study was conducted on 24 patients (48 eyes). AS was applied 6-10 times daily for 3 months together with regular artificial tear therapy. HLA-DR-positive cells were detected by direct immunocytochemistry on upper bulbar conjunctiva imprints obtained before and after treatment. The application of AS drops led to a statistically significant increase in the mean density of aberrant HLA-DR-positive conjunctival epithelial cells (p < 0.05) and HLA-DR-positive Langerhans cells (p < 0.05) in the GvHD group. Aberrant HLA-DR-positive epithelial cells in the SS group were decreased non-significantly. All patients reported a significant decrease in the Ocular Surface Disease Index (p < 0.01), which indicates improvement of the patient's subjective feelings after therapy. There was an expected but non-significant decrease of aberrant HLA-DR-positive conjunctival epithelial cells in the SS group only. However, the increased density of HLA-DR-positive cells, indicating slight subclinical inflammation, does not outweigh the positive effect of AS in patients with DED from GvHD.
32842840 Transverse myelitis associated with primary biliary cirrhosis: clinical, laboratory, and n 2022 Apr PURPOSE: Only five patients diagnosed with transverse myelitis (TM) associated with primary biliary cirrhosis (PBC) have been reported in the literature to date. We report two additional patients with TM associated with PBC at our hospital and review all seven cases. MATERIALS AND METHODS: An association between neuromyelitis optic spectrum disease (NMOSD) and PBC is reported for the first time in one of our patients. The second patient was diagnosed with TM associated with PBC without Sjögren's syndrome (SS). A literature review was performed using the PubMed database. RESULTS: All patients diagnosed with TM associated with PBC were female with a median age of 53 years. TM was associated with SS in 71.4% of the patients. Complete TM and incomplete TM were diagnosed in 71.4% and 28.6% of the patients. The erythrocyte sedimentation rate was increased in 83.3% of patients. All patients were positive for anti-mitochondrial antibodies. Other autoantibodies, including anti-nuclear antibodies, rheumatoid factor, anti-SSA antibody, were detected in some patients. Cerebrospinal fluid analysis was abnormal in 83.3% of patients. The spinal cord lesions involved more than three vertebral segments in 85.7% of patients. Glucocorticoids were administered in 85.7% of patients, and good responses were observed. CONCLUSIONS: The association between TM and PBC may be missed by neurologists. More attention should be paid to the association between NMOSD and PBC. Most patients show SS and may experience relapse, and there is a good rationale for early commencement of immunosuppressive therapy.
32064919 Economic impact of dry eye disease in Spain: A multicentre retrospective insurance claims 2021 Mar PURPOSE: To analyse the occurrence and cost of dry eye disease in Spain in the recent years. METHODS: A cross-sectional analysis based on anonymised data from an insurance claims database that includes data from 1997 to 2015 from public and private hospitals and healthcare centres; 36,081 patients were eligible for the study after duplicate elimination. Five ICD9 codes associated with dry eye were used for patient selection, including vitamin A deficiency with xerophthalmic scars of cornea, xerophthalmia due to vitamin A deficiency, keratoconjunctivitis sicca not specified as Sjögren's, dry eye syndrome and keratoconjunctivitis sicca Sjögren's disease. RESULTS: Over 88% of the patients were female, and the mean age was 66 years. Patients with keratoconjunctivitis sicca Sjögren's disease represented more than 89% of all patients and had the highest percentage of women. Both the annual number of patients and the number of admissions have increased exponentially since 1997 raising from 1079 to 3097 and from 1344 to 5938, respectively. The in-hospital length of stay was 9.6 (standard deviation = 11.6) days where more than 65% of the admissions were due to emergencies. Total costs were found to increase from €4.9 to €30.3 million during the study period; in parallel, there was an increase in the mean annual cost per patient, which was on average €7379. CONCLUSION: Disease incidence is likely to increase due to the influence of modern-day workplace, and it is important to take into account the high economic burden and the large decrease in quality of life in regards to Spanish society and health policies.
32250566 Predictive modeling of aspirin-triggered resolvin D1 pharmacokinetics for the study of Sjà 2020 Apr OBJECTIVES: Sjögren's syndrome (SS) is an autoimmune disease that causes chronic inflammation of the salivary glands leading to secretory dysfunction. Previous studies demonstrated that aspirin-triggered resolvin D1 (AT-RvD1) reduces inflammation and restores tissue integrity in salivary glands. Specifically, progression of SS-like features in NOD/ShiLtJ mice can be systemically halted using AT-RvD1 prior or after disease onset to downregulate proinflammatory cytokines, upregulate anti-inflammatory molecules, and restore saliva production. Therefore, the goal of this paper was to create a physiologically based pharmacokinetic (PBPK) model to offer a reasonable starting point for required total AT-RvD1 dosage to be administered in future mice and humans thereby eliminating the need for excessive use of animals and humans in preclinical and clinical trials, respectively. Likewise, PBPK modeling was employed to increase the range of testable scenarios for elucidating the mechanisms under consideration. MATERIALS AND METHODS: Pharmacokinetics following intravenous administration of a 0.1 mg/kg dose of AT-RvD1 in NOD/ShiLtJ were predicted in both plasma and saliva using PBPK modeling with PK-Sim® and MoBi® Version 7.4 software. RESULTS: The model provides high-value pathways for future validation via in vivo studies in NOD/ShiLtJ to corroborate the findings themselves while also establishing this method as a means to better target drug development and clinical study design. CONCLUSIONS: Clinical and basic research would benefit from knowledge of the potential offered by computer modeling. Specifically, short-term utility of these pharmacokinetic modeling findings involves improved targeting of in vivo studies as well as longer term prospects for drug development and/or better designs for clinical trials.
33216992 Pulmonary hypertension in connective tissue diseases, new evidence and challenges. 2021 Apr Pulmonary arterial hypertension is a lethal complication of different connective tissue diseases such as systemic sclerosis, mixed connective tissue disease and systemic lupus erythematosus. Although the treatment possibilities for patients with pulmonary arterial hypertension have increased in the last two decades and survival of patients with idiopathic pulmonary arterial hypertension has improved, the latter is not the case for patients with pulmonary arterial hypertension associated with connective tissue disease. In this narrative review, we review recent literature and describe the improvement of early diagnostic possibilities, screening modalities and treatment options. We also point out the pitfalls in diagnosis in this patient category and describe the unmet needs and what the focus of future research should be.
33055428 PTPN2 links colonic and joint inflammation in experimental autoimmune arthritis. 2020 Oct 15 Loss-of-function variants of protein tyrosine phosphatase non-receptor type 2 (PTPN2) enhance risk of inflammatory bowel disease and rheumatoid arthritis; however, whether the association between PTPN2 and autoimmune arthritis depends on gut inflammation is unknown. Here we demonstrate that induction of subclinical intestinal inflammation exacerbates development of autoimmune arthritis in SKG mice. Ptpn2-haploinsufficient SKG mice - modeling human carriers of disease-associated variants of PTPN2 - displayed enhanced colitis-induced arthritis and joint accumulation of Tregs expressing RAR-related orphan receptor γT (RORγt) - a gut-enriched Treg subset that can undergo conversion into FoxP3-IL-17+ arthritogenic exTregs. SKG colonic Tregs underwent higher conversion into arthritogenic exTregs when compared with peripheral Tregs, which was exacerbated by haploinsufficiency of Ptpn2. Ptpn2 haploinsufficiency led to selective joint accumulation of RORγt-expressing Tregs expressing the colonic marker G protein-coupled receptor 15 (GPR15) in arthritic mice and selectively enhanced conversion of GPR15+ Tregs into exTregs in vitro and in vivo. Inducible Treg-specific haploinsufficiency of Ptpn2 enhanced colitis-induced SKG arthritis and led to specific joint accumulation of GPR15+ exTregs. Our data validate the SKG model for studies at the interface between intestinal and joint inflammation and suggest that arthritogenic variants of PTPN2 amplify the link between gut inflammation and arthritis through conversion of colonic Tregs into exTregs.
33458661 Demodex Species Frequency and Risk Factors in Patients With Rheumatoid Arthritis. 2020 Sep OBJECTIVES: This study aims to investigate the presence of Demodex species in rheumatoid arthritis (RA) patients, to identify the risk factors for developing Demodex infestation, and to determine the effect of immunosuppressant drugs on Demodex mite infestations. PATIENTS AND METHODS: The study included 93 RA patients (16 males, 77 females; mean age 53.3±11.3 years; range, 27 to 83 years) and 76 healthy controls (19 males, 57 females; mean age 50.3±13.9 years; range, 19 to 86 years). Specimens were collected from face skin by using standardized sur- face skin biopsy. Demodex infestation was considered for ≥5 living parasites/cm2 of skin while Demodex mite presence was defined as any Demodex larvae, adults, or eggs found in the specimen. RESULTS: The frequencies of Demodex mite presence were 44% for the RA patients and 15.7% for the healthy controls (p<0.001). The rates of Demodex infestation were similar between the two groups (18.3% versus 7.9%, p=0.054). There were no statistically significant differences between the groups regarding skin type, skin care, epilation, body washing, use of a moisturizer, personal towel use, the number of residents at home, or whether there were pets at home or in proximity. Itching in eyes was higher in RA patients, but the frequency of other skin symptoms was not differ- ent from healthy controls. Logistic regression analysis indicated that the diagnosis of RA was an independent risk factor for Demodex mite presence in this study population. Disease activity and duration, use of corticosteroids, conventional disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs were not effective factors on Demodex mite presence in RA patients. CONCLUSION: Although Demodex mite presence was 3.5-fold higher in RA patients, the rate of Demodex infestation was similar to that of healthy controls.