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ID PMID Title PublicationDate abstract
31431961 An audit of the use of hydroxychloroquine in rheumatology clinics. 2018 OBJECTIVE: The aim was to audit the use, indications, complications and patient information regarding HCQ treatment in rheumatology clinics in a tertiary referral centre. METHODS: During a 9-month period, we identified all patients prescribed HCQ and attending rheumatology clinics in one hospital. We established: (i) the indication for HCQ; (ii) the prevalence of HCQ overdosing based on absolute body weight (ABW); (iii) documentation of warning of risk of retinal toxicity; (iv) systemic and ocular co-morbidities; (v) ocular symptoms during treatment; and (vi) reasons for stopping HCQ. RESULTS: We identified 427 patients (104 male and 323 female). The cumulative dose of HCQ was lower in RA (median 365 g; range 6-1752 g) compared with SLE (450 g; 66-1788 g) (P = 0.105). The median duration of HCQ therapy was 4 years (range 0.1-13 years); 28% of patients with RA and 29% with SLE continued HCQ beyond 5 years. After adjusting for ABW and renal function, 10% (31/312) had been prescribed doses exceeding recommendations. Formal documentation of counselling on ocular complications was found in only one-third of patients. Three cases of HCQ retinopathy were identified (all of whom had RA). CONCLUSION: HCQ therapy is being used for >5 years in 29% of patients with rheumatic diseases, with higher than recommended doses in ∼10% of patients. We recommend more rigorous scrutiny of the use of HCQ to reduce the risk of retinopathy.
30585183 Main Oral Manifestations in Immune-Mediated and Inflammatory Rheumatic Diseases. 2018 Dec 25 Oral manifestations are frequent in patients with rheumatic diseases. The aim of this review is to offer readers practical advice concerning the onset, diagnosis and treatment of the main oral manifestations encountered in rheumatological and dental clinics. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, periodontal disease, and dysphagia may be the first expression of a number of rheumatic diseases. Some of these manifestations are aspecific and very frequent, such as oral aphthosis, which can be the first manifestation in patients with systemic lupus erythematosus; some are potentially dangerous, such as jaw claudication during the course of giant cell arteritis; and some are very rare but peculiar, such as strawberry-like gingivitis in patients with granulomatosis with polyangiitis. Other oral manifestations are due to adverse reactions to disease-modifying anti-rheumatic drugs. Oral alterations in rheumatic diseases are frequently overlooked in clinical practice, but their prompt recognition not only allows the local lesions to be appropriately treated, but also makes it possible to identify an underlying systemic disease.
29849649 Association between Rheumatoid Arthritis and Respiratory Allergic Diseases in Korean Adult 2018 Rheumatoid arthritis (RA) and allergic diseases are result of a poor functioning immune system, giving dominance to either T-helper 1 (Th1) or T-helper 2 (Th2) diseases, respectively. Studies have stated that there seems to be a relationship present between the immune response subsets. This study was designed to examine the association between RA and respiratory allergic diseases in Korean adults. The study utilized the KNHANES 2013-2015 data and excluded individuals diagnosed with RA before being diagnosed with allergic diseases, using age at clinical diagnosis. Total of 253 RA patients were matched 1 : 1 with non-RA patients by a propensity score, using sex and age as matched variables. Multivariate conditional logistic regression analyses were used to evaluate for association between RA and respiratory allergic diseases in the matched 506 participants. RA was associated with an increased risk of prevalence of respiratory allergic diseases with an OR of 1.51 (95% CI, 1.31-1.75), adjusted for socioeconomic demographic variables. The adjusted OR for prevalence of RA among participants with prevalence of asthma and allergic rhinitis was as follows: 3.12 (95% CI, 2.77-3.51) and 1.39 (95% CI, 1.16-1.67). Participants with prevalence of asthma in particular had an increased risk of developing prevalence of RA. Based on our findings, Th1 and Th2 diseases may indeed coexist, and one pathway may stimulate or contribute towards the onset of the other.
29492586 From blood coagulation to innate and adaptive immunity: the role of platelets in the physi 2018 Jun Thrombosis and cardiovascular complications are common manifestations of a variety of pathological conditions, including infections and chronic inflammatory diseases. Hence, there is great interest in determining the hitherto unforeseen immune role of the main blood coagulation executor-the platelet. Platelets store and release a plethora of immunoactive molecules, generate microparticles, and interact with cells classically belonging to the immune system. The observed effects of platelet involvement in immune processes, especially in autoimmune diseases, are conflicting-from inciting inflammation to mediating its resolution. An in-depth understanding of the role of platelets in inflammation and immunity could open new therapeutic pathways for patients with autoimmune disorders. This review aims to summarize the current knowledge on the role of platelets in the patomechanisms of autoimmune disorders and suggests directions for future research.
29112329 In Vitro and In Vivo Investigation of Potential for Complex CYP3A Interaction for PF-00251 2018 Mar The dissociated agonists of the glucocorticoid receptor are a novel class of agents in clinical development for rheumatoid arthritis. PF-04171327 (fosdagrocorat) is a phosphate ester prodrug of PF-00251802 (dagrocorat), a selective high-affinity partial agonist of the glucocorticoid receptor, which is further metabolized to PF-04015475. This study evaluated the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of PF-00251802 and PF-04015475 in vitro and used model-based prediction approaches to estimate clinical impact. PF-00251802 is a reversible inhibitor of several CYPs, but modeling has suggested no clinically relevant interaction. PF-00251802 and PF-04015475 are time-dependent inhibitors and inducers of CYP3A in vitro; PF-00251802 is also a time-dependent inhibitor of CYP2D6. Model-based prediction suggested the potential for weak inhibition of CYP3A in vivo. A clinical DDI study was conducted with midazolam, a sensitive CYP3A substrate. A phase 1 open-label, multiple-dose study evaluated the effect of PF-04171327 on midazolam pharmacokinetics and safety in 12 healthy volunteers. Administration of midazolam alone or concomitantly with PF-04171327 resulted in equivalent pharmacokinetic profiles (AUC(inf) , 21.17 vs 20.28 ng·h/mL, respectively), indicating that PF-04171327 had no net effect on CYP3A activity in vivo. These findings support the further development of PF-00251802 and PF-04171327 as potential treatments for patients with rheumatoid arthritis (NCT00987038).
30030655 Characterizing the Relation Between Expression QTLs and Complex Traits: Exploring the Role 2018 Sep Measurement of gene expression levels and detection of eQTLs (expression quantitative trait loci) are difficult in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be high, which would allow for inference of eQTL functioning in the brain via eQTLs detected in readily accessible tissues, e.g. whole blood. Applying Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantified the enrichment in polygenic signal of blood and brain eQTLs in genome-wide association studies (GWAS) of 11 complex traits. We looked at eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium and two other large representative studies, and found no tissue-specific eQTL effects. Next, we integrated the GTEx eQTLs with regions associated with tissue-specific histone modifiers, and interrogated their effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects of eQTLs located inside regions bearing modification H3K4me1 on schizophrenia, but not rheumatoid arthritis, and not tissue-specific. Finally, we extracted eQTLs associated with tissue-specific differentially expressed genes and determined their effects on rheumatoid arthritis and schizophrenia, these analysis revealed limited enrichment of eQTLs associated with gene specifically expressed in specific tissues. Our results pointed to strong enrichment of eQTLs in their effect on complex traits, without evidence for tissue-specific effects. Lack of tissue-specificity can be either due to a lack of statistical power or due to the true absence of tissue-specific effects. We conclude that eQTLs are strongly enriched in GWAS signal and that the enrichment is not specific to the eQTL discovery tissue. Until sample sizes for eQTL discovery grow sufficiently large, working with relatively accessible tissues as proxy for eQTL discovery is sensible and restricting lookups for GWAS hits to a specific tissue for which limited samples are available might not be advisable.
29141196 ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis- 2018 Feb 5 Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis. Our results revealed that acid (pH 6.0) decreased the cell viability and induced apoptosis of articular chondrocytes. PcTx1 and APETx2 combination significantly attenuated acidosis-induced chondrocyte cytotoxicity due to inhibit apoptosis, and this role could be enhanced by ASIC2a overexpression compared with the PcTx1 and APETx2 combination alone group. Moreover, both the [Ca(2+)](i) levels and the levels of phosphorylated ERK1/2 as well as p38 were further reduced in acidosis-induced chondrocytes after ASIC2a overexpression in the presence of PcTx1 and APETx2. Furthermore, ASIC2a overexpression also reduced acid-induced the expression of ASIC1a. In addition, ASIC2a overexpression further promoted the PcTx1 and APETx2-increased levels of type II collagen in acidosis-induced chondrocytes. Taken together, the current data suggested that ASIC2a overexpression might enhance the anti-apoptotic and protective role of PcTx1 and APETx2 against acid-induced rat articular chondrocyte apoptosis by regulating ASIC1a expression and the [Ca(2+)](i) levels and at least in part, suppressing p38 and ERK1/2 MAPK signaling pathways.
30323570 Factors influencing the use of biologic therapy and adoption of treat-to-target recommenda 2018 OBJECTIVE: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. METHODS: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or ≥2 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). RESULTS: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-naïve patient was prompted by worsening of the disease. In the RA diagnosis <2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis ≥2 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis <2 years subset than in the RA diagnosis ≥2 years subset (65% vs 77% satisfied, respectively; P<0.0001). CONCLUSION: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted.
29524605 Redox-sensitive signaling in inflammatory T cells and in autoimmune disease. 2018 Sep Reactive oxygen species (ROS) are byproducts of oxygen metabolism best known for their damaging potential, but recent evidence has exposed their role as secondary messengers, which regulate cell function through redox-activatable signaling systems. In immune cells, specifically in T cells, redox-sensitive signaling pathways have been implicated in controlling several functional domains; including cell cycle progression, T effector cell differentiation, tissue invasion and inflammatory behavior. T cells from patients with the autoimmune disease rheumatoid arthritis (RA) have emerged as a valuable model system to examine the functional impact of ROS on T cell function. Notably, RA T cells are distinguished from healthy T cells based on reduced ROS production and undergo "reductive stress". Upstream defects leading to the ROS(low) status of RA T cells are connected to metabolic reorganization. RA T cells shunt glucose away from pyruvate and ATP production towards the pentose phosphate pathway, where they generate NADPH and consume cellular ROS. Downstream consequences of the ROS(low) conditions in RA T cells include insufficient activation of the DNA repair kinase ATM, bypassing of the G2/M cell cycle checkpoint and biased differentiation of T cells into IFN-γ and IL-17-producing inflammatory cells. Also, ROS(low) T cells rapidly invade into peripheral tissue due to dysregulated lipogenesis, excessive membrane ruffling, and overexpression of a motility module dominated by the scaffolding protein Tks5. These data place ROS into a pinnacle position in connecting cellular metabolism and protective versus auto-aggressive T cell immunity. Therapeutic interventions for targeted ROS enhancement instead of ROS depletion should be developed as a novel strategy to treat autoimmune tissue inflammation.
29127458 Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an anta 2018 Feb PURPOSE: The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis. The safety, pharmacokinetics and pharmacodynamics of BI 655064, a novel humanised antagonistic anti-CD40 monoclonal antibody, were investigated in this first-in-human trial. METHODS: Healthy male subjects (n = 72) were randomised 3:1, within each BI 655064 dose group, to single intravenous (IV; 0.2-120 mg) or subcutaneous (SC; 40-120 mg) doses of BI 655064 or placebo. Safety, plasma exposure, CD40 receptor occupancy and CD40L-induced CD54 upregulation were assessed over 12 weeks. RESULTS: Adverse events (AEs) were reported in 43% of subjects (n = 31). Frequency and intensity of AEs were generally similar between BI 655064 and placebo and showed no dose relationship. The most frequent AEs were headache and nasopharyngitis. One mild rash and one local reaction occurred with SC BI 655064; two serious AEs were reported, both judged unrelated to BI 655064. Pharmacokinetic evaluation demonstrated a more than proportional increase in plasma exposure relative to BI 655064 dose, with a terminal half-life between 4 h and 4 days IV and approximately 5 days SC; doses ≥ 20 mg IV and 120 mg SC showed > 90% CD40 receptor occupancy and inhibition of CD54 upregulation, which lasted 7 days in the 120 mg IV and SC groups. CONCLUSIONS: Single doses up to 120 mg BI 655064 IV and SC were well tolerated and showed a high potential to block the CD40-CD40L pathway, supporting further clinical development of BI 655064 in patients with autoimmune disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01510782.
29037480 Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurp 2018 Feb Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also responsible for several haematological malignancies, including myeloproliferative neoplasms and acute lymphoblastic leukaemia. Accumulating evidence links adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), an energy sensor and regulator of organismal and cellular metabolism, with the suppression of immune and inflammatory processes. Recent studies have shown that activation of AMPK can limit JAK-STAT-dependent signalling pathways via several mechanisms. These novel findings support AMPK activation as a strategy for management of an array of disorders characterised by hyper-activation of the JAK-STAT pathway. This review discusses the pivotal role of JAK-STAT signalling in a range of disorders and how both established clinically used and novel AMPK activators might be used to treat these conditions.
29303013 Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis sympt 2018 Apr BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. AIM: This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. RESULTS: The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. CONCLUSIONS: These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.
28735448 Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthri 2018 Apr Andrographolide, a diterpenoid lactone obtained from plant Andrographis paniculata, is used in South Asian countries to relieve various inflammatory symptoms. To study the effects of this agent, the impact of andrographolide on production of inflammatory mediators were delineated in mouse peritoneal macrophages (PMϕ). Inflammatory mediators like nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin-6 and related molecular mechanisms of andrographolide-mediated inhibition of enzymes/transcription factors were studied. In addition, the in vivo anti-inflammatory activity of andrographolide was evaluated in an adjuvant-induced arthritis rat model. The results indicated that andrographolide clearly inhibited the production of NO and TNF-α in lipopolysaccharide-activated PMϕ in a dose-related manner. Immunoblot analyses revealed that andrographolide suppressed activation of both inducible NO synthase and cyclo-oxygenase-2 by directly targeting nuclear transcription factor (NF)-κB. Complete Freund's Adjuvant-induced paw edema in rats was also significantly inhibited by andrographolide treatment. From the data, we concluded that andrographolide imparted anti-inflammatory effects by suppressing two key inflammatory enzymes and a signaling pathway that mediates expression of variety of inflammatory cytokines/agents in situ. It is plausible that eventually, after further toxicologic characterization, andrographolide might be useful as a drug for the clinical treatment of various inflammatory diseases like rheumatoid arthritis or diseases associated with joint pain.
30248434 The P2X7 Receptor, Cathepsin S and Fractalkine in the Trigeminal Subnucleus Caudalis Signa 2018 Nov 1 Temporomandibular joint (TMJ) is frequently involved with rheumatoid arthritis with a high prevalence that could result in a chronic pain state. Once the disease is established in the joint, the antigen-specific immune reaction initiates a neuro-immune cascade of events that causes sensitization of the central nervous system. This study establishes animal experimental models that evaluate the chronicity of albumin-induced arthritis hypernociception in the TMJ. Antigen-induced arthritis was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund's. Intra-articular injection of mBSA (10 µg/TMJ/week) during 3 weeks resulted in a persistent inflammatory hypernociception which was characterized by an inflammatory episode characterized by the increased of lymphocytes, macrophages and pro-inflammatory interleukins IL-12 and IL-18. The persistent model of inflammatory hypernociception induced by arthritis in the TMJ elicited protein levels of P2X7 receptors, cathepsin S and fractalkine in the trigeminal subnucleus caudalis. Overall, the results of the present work suggest that a persistent inflammatory hypernociception of albumin-induced arthritis in the TMJ leads to the activation of the central nervous system signaling by P2X7/cathepsin S/fractalkine pathway.
30039181 Evaluation of opioid use among patients with back disorders and arthritis. 2018 Nov PURPOSE: Long-term opioid use for chronic pain has increased, but limited evidence exists on its benefits. Evaluation of long-term benefits in pain is based on patient-reported measures such as health-related quality of life (HRQoL). This study examined the long-term effects of opioid use on HRQoL and its subdomains in patients with back pain or arthritis by comparing opioid users to non-opioid users for three metrics: (1) any opioid use, (2) duration of opioid use, and (3) average daily morphine equivalent dose. METHODS: A nationally representative sample of cancer-free adults with chronic back pain or arthritis was selected. Using the 12-Item Short Form Survey, HRQoL measures of Mental Component Score (MCS), Physical Component Score (PCS), and individual subdomains were assessed at baseline and 1 year later. Opioid users were matched to non-opioid users in a 1:1 greedy match using propensity scores estimated based on many patient demographics and baseline HRQoL measures. RESULTS: At year one, PCS was significantly lower among opioid users, mostly driven by bodily pain subdomain; MCS was not different. Short-term opioid users (< 1 month) had higher MCS while long-term users (≥ 1 month) had lower PCS. Low-dose [< 20 morphine milligram equivalents (MME)/day] opioid use was associated with lower PCS, while no difference was found between high dose (≥ 20 MME/day) and non-opioid users. However, most differences were not clinically significant. CONCLUSIONS: Long-term opioid use is not associated with improvements in HRQoL. Clinicians should carefully evaluate the need for opioid use, especially long-term use in managing chronic back pain and arthritis.
28916184 Role of the IL-12/IL-35 balance in patients with Sjögren syndrome. 2018 Jul BACKGROUND: An interferon signature is involved in the pathogenesis of primary Sjögren syndrome (pSS), but whether the signature is type 1 or type 2 remains controversial. Mouse models and genetic studies suggest the involvement of T(H)1 and type 2 interferon pathways. Likewise, polymorphisms of the IL-12A gene (IL12A), which encodes for IL-12p35, have been associated with pSS. The IL-12p35 subunit is shared by 2 heterodimers: IL-12 and IL-35. OBJECTIVE: We sought to confirm genetic association of the IL12A polymorphism and pSS and elucidate involvement of the IL-12/IL-35 balance in patients with pSS by using functional studies. METHODS: The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French control subjects. Functional studies were performed on sorted monocytes, irrespective of whether they were stimulated. IL12A mRNA expression and IL-12 and IL-35 protein levels were assessed by using quantitative RT-PCR and ELISA and a multiplex kit for IL-35 and IL-12, respectively. RESULTS: We confirmed association of the IL12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in patients with pSS carrying the risk allele (P = .016). Serum levels of IL-12p70 were greater in patients than control subjects (P = .0001), especially in patients with more active disease (P = .05); conversely, IL-35 levels were decreased in patients (P = .0001), especially in patients with more active disease (P = .05). In blood cellular subsets both IL12p35 and EBV-induced gene protein 3 (EBI3) mRNAs were detected only in B cells, with a trend toward a lower level among patients with pSS. CONCLUSION: Our findings emphasize involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease.
30619636 Periodontal pathogens and the association between periodontitis and rheumatoid arthritis i 2018 Dec PURPOSE: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. METHODS: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. RESULTS: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). CONCLUSIONS: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.
29449025 [Prospective, monocentric, uncontrolled study of efficacy, tolerance and adherence of cycl 2018 Feb PURPOSE: To evaluate the efficacy, tolerability and treatment adherence of Ikervis(®) (Santen, SAS) (ciclosporine 0.1 %) for first line therapy or following treatment with Restasis(®) (Allergan, Inc.) (ciclosporine 0.05 %) for severe dry eye syndrome. MATERIAL AND METHODS: A prospective, monocentric, uncontrolled study was conducted between January 2012 and March 2015 on 110 eyes of 55 patients with severe dry eye on first line therapy or previously treated with Restasis(®) who required the introduction of Ikervis(®). Patients' quality of life was assessed before and after treatment was started using a standardized questionnaire (Ocular Surface Disease Index(©) [OSDI]), clinical efficacy was quantified at the slit lamp, by measurement of the Break Up time Test (BUT) and the Oxford classification. Tolerability and adherence to treatment were measured using a simple questionnaire. RESULTS: A total of 72 eyes of 37 patients were included. Etiologies of dry eye syndrome were dominated by Sjögren syndrome (32 %) and severe ocular surface conditions (48 %). The mean age was 57.7 years (±17.45) and mean follow-up was 458 days (±292). The mean BUT increased by 2.043seconds [1.522-2.563] (P<0.0001). Corneal/conjunctival involvement evaluated by the Oxford classification was also improved with a difference in level of 1.68 [1.290-2.071] (P<0.0001). Ocular Surface Disease Index(©) (OSDI) decreased by 21.7 [16.372-27.024] (P<0.0001). Treatment tolerability was moderate, with more than 50 % of patients experiencing pain on instillation. Overall satisfaction with treatment was good, with more than 60 % of patients feeling better after initiation of treatment. CONCLUSION: Ikervis(®) is an effective treatment of severe dry eye. Its indications tend to evolve towards less severe dry eye. However, the tolerability profile remains poor, and an improvement in this would be desirable.
30017867 Customary practices in the monitoring of dry eye disease in Sjogren's syndrome. 2018 Oct PURPOSE: Diagnostic testing for dry eye disease (DED) in Sjogren's syndrome (SS) is well described. Little is published about monitoring this systemic autoimmune DED. We analyzed the SS related DED tests used in North American optometric practices and compared academic settings to private practice settings. METHODS: A retrospective chart review of 123 SS charts from 6 optometric practices in North America was conducted. Testing done during the first examination following a SS diagnosis was recorded on Research Electronic Data Capture (REDCap) database. The complete data file was reviewed and testing type and methodology were compared. RESULTS: Symptoms of DED (98.4% of charts),meibomian gland dysfunction (76.4% of charts), corneal staining with fluorescein (75.6% of charts) and anterior blepharitis (73.2% of charts) were the most frequently recorded variables. Clinicians used different methodologies to measure and grade these variables. Private practitioners were more likely to use symptom questionnaires and grading scales and to describe anterior blepharitis. Academic settings were more likely to record TBUT and tear meniscus height. CONCLUSIONS: The monitoring of DED in SS is not uniform in optometric offices across North America. Creating accepted standards of testing will improve the ability of clinicians and researchers to communicate and understand the course of DED in SS.
30475093 Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca 2019 May AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of β(2)-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up. CONCLUSIONS: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms.