Positive Rheumatoid Factor Research Articles

Evaluating the Clinical Utility of Testing for Autoimmune Disorders in the Setting of Leukopenia/Neutropenia in an Ambulatory Hematology Clinic.

Introduction:Leukopenia (WBC count of <3.8K/uL) and/or neutropenia (<1.8K/uL, both institutional lab cutoffs), are commonly encountered by physicians on routine blood testing on otherwise healthy patients. This finding, whether incidental or not, often leads to hematology referrals. A broad work up may be pursued in an attempt to find a definitive diagnosis. We conducted this study to assess the utility of testing for anti-nuclear antibody (ANA) as well rheumatoid factor (RF) in patients with leukopenia/neutropenia and whether or not a positive serology led to a rheumatologic diagnosis.Methods:After obtaining institutional review board approval, we searched for outpatient hematology consults with a diagnosis of leukopenia and/or neutropenia using ICD-9 and ICD-10 diagnostic codes between 2005-2015 at Henry Ford Hospital. Data points included demographics and antibody serology. Patients were excluded if they had a known hematologic disorder, known rheumatologic disorder or were on active chemotherapy. A positive ANA or RF were considered if titers were >1:80 or RF >14 IU/mL, respectively as these are institutional cutoffs. Complete blood counts were reviewed for patients who were not excluded based on above criteria. Hematology and rheumatology notes were reviewed looking for symptoms suggestive of autoimmune conditions or if an alternative diagnosis was made.Results:A total of 561 patients were seen in our outpatient clinic during the 10 year interval with an associated diagnostic code for leukopenia/neutropenia.199 were excluded due to incomplete data or inadequate follow up period, 35 patients for known malignancy, 14 for known rheumatologic disorder, and 122 for being on active chemotherapy. The remaining 191 patients were reviewed for data analysis. Patient demographics are summarized in table 1.A total of 116 patients (61%) were tested for ANA, of which 27 (23%) were positive. 22 of those 27 (81%) patients were referred to rheumatology, 6 of which were diagnosed with rheumatologic diseases (22%). RF was tested in 110 patients (58%), of which 15 were positive (14%) all were referred to rheumatology, and 5(42%) were diagnosed with rheumatologic diseases. Test results, referral rate and rheumatologic diagnosis are listed in table 2.The majority of patients who were diagnosed with rheumatologic disorders had associated findings suggestive of underlying disease (3 patients with systemic lupus erythematosus (SLE) had mild thrombocytopenia (100-150K/uL), 1 patient with mixed connective tissue disease had Raynaud's phenomenon, 3 patients with rheumatoid arthritis (RA) had arthralgias and 1 had myalgias, all with correlating physical exam or radiographic findings).Other alternative diagnoses for leukopenia/neutropenia included drug induced, viral and bacterial infections, hematologic malignancies, ethnic neutropenia, transient leukopenia, and idiopathic.Conclusion:Ambulatory hematology consults for leukopenia/neutropenia are a common occurrence in practice. Our study showed that 11 patients out of 191 (6%) were found to have an associated rheumatologic disorder, with the majority having other signs/symptoms or associated lab abnormalities suggestive of autoimmune disease. This study shows that testing for ANA and RF in patients with leukopenia/neutropenia are of limited clinical utility in asymptomatic patients with no other lab abnormalities and it should not be part of a routine work up unless directed by symptoms. Primary care providers need to screen for other abnormalities (symptoms/clinical findings) in order to identify patients that would benefit most from subspecialty referral. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Perforating Rheumatoid Nodule Mimicking Malignant Soft-tissue Mass of the Forearm.

Rheumatoid nodule1, one of the most characteristic manifestations of rheumatoid arthritis (RA), occurs in approximately 30% of patients, is generally associated with positive rheumatoid factor, smoking, and high disease activity2, and occurs in some patients with specific genotypes receiving methotrexate (MTX)3 An 83-year-old woman with a history of anticitrullinated protein antibody-positive RA treated by oral MTX, as well as gout, was hospitalized for a growing tumor of her right forearm.

OP0215 MENTAL HEALTH, SLEEP AND COGNITION CHARACTERISTICS IN RHEUMATOID ARTHRITIS AND ASSOCIATIONS WITH RHEUMATOID FACTOR STATUS IN THE UK BIOBANK

Background:There are significant gaps in the literature regarding sleep, mental health, and cognition for people with rheumatoid arthritis (RA) despite being important aspects of patients’ overall quality of life. Similarly, there is a lack of understanding about the role of rheumatoid factor (RF) on these domains.Objectives:The aim of the current study was to characterize mental health, cognition, and sleep variables in people with RA and to compare these associations in people with positive RF (RF+) and negative RF (RF-) in a large population cohort.Methods:This cross-sectional study used baseline data from the UK Biobank cohort (n= 502,506) to compare people with and without RA and people that are RF+ versus RF- on a variety of sociodemographic, lifestyle, illness-related factors and depression, neuroticism, performance on cognitive tests and sleep-related factors. Logistic regression analyses were also performed to determine whether RF seropositivity was associated with mental health, cognition, and sleep variables. We adjusted for the covariates of age, sex, ethnicity, deprivation index, smoking status, BMI and alcohol intake.Results:In this sample 5,907 people self-reported having RA (1.17%), of which 74% were RF- and 26% were RF+. There were significant differences (p &lt; 0.05) between people with and without RA for depression, neuroticism, nap during the day, getting up in the morning, insomnia, reaction time, fluid intelligence and prospective memory. There were significant differences (p &lt; 0.05) between RF+ and RF- people for depression, neuroticism, sleep duration, nap during the day, getting up in the morning, insomnia, and reaction time. In the unadjusted regression analyses neuroticism (B=-0.06, SE= 0.01, p &lt; 0.001), sleep duration (B=0.02, SE= 0.005, p &lt; 0.001), nap during the day (OR=1.28, 95% CI: 1.02-1.65, p &lt; 0.05) and reaction time (B=4.55, SE=0.53, p&lt; 0.001) were significantly associated with RF status. After adjusting for covariates, only sleep duration (B=0.01, SE=0.005, p&lt; 0.01) remained significant.Conclusion:The current study suggests that RA diagnosis and RF status are associated with differences in mental health, sleep, and cognition, highlighting the importance of addressing these aspects in clinical settings and future research.Disclosure of Interests:None declared

AB0200 TRENDS IN THE CHOICE OF FIRST BIOLOGIC AND TARGETED SYNTHETIC DMARD IN RHEUMATOID ARTHRITIS PATIENTS: 20-YEARS JOURNEY OF HUR-BIO REAL-LIFE REGISTRY

Background:In the last 20 years, there have been extraordinary improvements and practice-changing developments in the management of rheumatoid arthritis (RA). Exploring the pathogenetic mechanisms first enabled clinicians to use anti-tumor necrosis factor (TNF) alpha agents, then drugs targeting different molecules. Parallel to these developments, treatment guidelines have been changed accordingly. Meanwhile, how these developments have been reflected into the real-word practice is a question of interest.Objectives:In this study, we aimed to explore the first biologic agent trends of our 20-years of single-center experience.Methods:HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single center biological disease modifying anti-rheumatic drug (DMARD) registry since 2005. Patients who were started biologics before 2005 were registered retrospectively. In brief; demographic data, treatment-related data (including adverse events) and disease-related data of RA patients have been recorded in HUR-BIO. Until the end of the 2020, 21 different rheumatologists contributed to the development of HUR-BIO. In this study, distribution of the first-line biologic agents was calculated according to 5-year periods starting from the 2001. Also, demographic and serologic data of RA patients were reported.Results:A total of 2080 RA patients was registered in HUR-BIO by the end of 2020. Of these patients, 79.5% was female. Mean age at the starting of bDMARD was 53.3 ± 17.8 years. Rate of rheumatoid factor and anti-cyclic citrullinated peptide positivity was 67.6% and 61.0%, respectively. 65 (3.2%), 335 (16.1%), 858 (41.2%) and 822 (39.5%) patients were prescribed with their first bDMARD in 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively. There was a trend towards the increasing prescription of non-Anti-TNF bDMARDs over time.Table 1.Distribution of first biologic DMARDs in RA patients according to 5-years periods2001-20052006-20102011-20152016-2020TotalAdalimumab15 (23.1)111 (33.0)187 (21.8)153 (18.6)466 (22.4)Etanercept30 (46.2)154 (45.8)229 (26.7)54 (6.6)467 (22.4)İnfliximab20 (30.8)58 (17.3)64 (7.5)7 (0.9)149 (7.1)Golimumab0037 (4.3)43 (5.2)80 (3.8)Certolizumab0037 (4.3)68 (8.3)105 (5.0)Anti-TNF65 (100)323 (96.4)554 (64.5)325 (39.5)1267 (60.9)Tofacitinib006 (0.7)212 (25.8)218 (10.5)Tocilizumab009 (1.0)102 (12.4)111 (5.3)Rituximab012 (3.6)136 (15.8)84 (10.2)232 (11.1)Abatacept00153 (17.8)99 (12.0)252 (12.1)Non-Anti-TNF012 (3.6)304 (35.5)497 (60.5)813 (39.1)Total65 (100)335 (100)858 (100)822 (100)2080 (100)Approval years of drugs in Turkey; Infliximab: 2003, etanercept:2004, adalimumab: 2005, golimumab: 2013, certolizumab: 2014, abatacept: 2010, tocilizumab: 2013, rituximab:2009, tofacitinib: 2015,Conclusion:Real-life practice in RA seems consistent with treatment guidelines. Use of non-Anti-TNF bDMARDs becoming more frequent year-by-year. Jak kinase inhibitor has rised through the last 5 years. Next decade may be the years of Jak kinases inhibitors.Disclosure of Interests:None declared

Predictors of drug survival for biologic and targeted synthetic DMARDs in rheumatoid arthritis: Analysis from the TRA Clinical Electronic Registry

In this study we aimed to identify the predictors of drug survival for biologic and targeted synthetic DMARDs (bDMARDs and tsDMARDs) among patients with rheumatoid arthritis (RA) in a real-world setting. Data from RA patients receiving bDMARDs and tsDMARDs between 2007 and 2019 were extracted from the Taiwan Rheumatology Association Clinical Electronic Registry (TRACER). Patients were categorized into tumor necrosis factor-alpha (TNF-α) inhibitors, non-TNF-α inhibitors, and tofacitinib groups. The primary outcome was 3-year drug retention and the causes of bDMARDs and tsDMARDs discontinuation were recorded. Baseline demographic data before the initiation of bDMARDs and tsDMARDs treatment were analyzed to identify the predictors of 3-year drug survival. A total of 1,270 RA patients were recruited (TNF-α inhibitors: 584; non-TNF-α inhibitors: 535; tofacitinib: 151). The independent protective factors for 3-year drug survival were positive rheumatoid factor (RF) (HR: 0.48, 95% CI: 0.27-0.85, p = 0.013) and biologics-naïve RA (HR: 0.61, 95% CI: 0.39-0.94, p = 0.024). In contrast, positive anti-citrullinated protein antibody (ACPA) (HR: 2.24, 95% CI: 1.32-3.79, p = 0.003) and pre-existing latent tuberculosis (HR: 2.90, 95% CI: 2.06-4.09, p<0.001) were associated with drug discontinuation. RA patients treated with TNF-α inhibitors exhibited better drug retention, especially in the biologics-naïve subgroup (p = 0.037). TNF-α inhibitors were associated with lower cumulative incidence of discontinuation due to inefficacy and adverse events (both p<0.001). Baseline RF and ACPA positivity in abatacept-treated patients were associated with a better 3-year drug survival. However, negative ACPA levels predicted superior drug survival of TNF-α inhibitors and tofacitinib. In conclusion, bio-naïve status predicted better drug survival in TNF-α inhibitors-treated RA patients. RF and ACPA positivity predicted better abatacept drug survival. In contrast, ACPA negativity was associated with superior TNF-α inhibitors and tofacitinib survival.

Frequency of Cardiovascular Manifestation in Patients With Rheumatoid Arthritis.

IntroductionRheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease. The increased inflammatory burden in RA may result in atherosclerosis, myocardial infarction (MI), and subsequent mortality. In this study, we will determine the frequency of cardiovascular manifestation in RA patients through history, laboratory workup, and echocardiography.MethodsThis cross-sectional study was conducted in the rheumatology unit of a tertiary care hospital in Pakistan. Three hundred and twenty-two (n=322) participants with a previously confirmed diagnosis of RA were enrolled in this study via consecutive convenient non-probability sampling.ResultsCardiovascular manifestations were present in 188 (58.3%) participants. More participants had positive rheumatoid factor (82.9% vs. 32.8%; p-value: < 0.0001) in RA patients with cardiovascular manifestation compared to RA patients without cardiovascular manifestation. Patients with cardiovascular manifestations have a significantly higher C-reactive protein (CRP; 10.21 ± 2.81 mg/L vs. 8.17± 2.01 mg/L; p value: < 0.0001) and erythrocyte sedimentation rate (ESR; 16.2 ± 3.14 mg/L vs. 15.1 ± 2.99 mg/L; p value: 0.0017).ConclusionIn this study, patients with a cardiovascular manifestation had a higher frequency of patients with rheumatoid factor, higher mean values of CRP and ESR. The early diagnosis and management of cardiac manifestations would aid in controlling the severity of the disease and the overall mortality.

Troubling Tenosynovitis: When a Serious Sign Persists

A 42-year-old woman was admitted to the hospital with 5 days of diffuse joint pain and swelling associated with prolonged morning stiffness and intermittent fevers up to 38.7°C. The review of systems was negative for rashes, mouth sores, pleuritic chest pain, alopecia, dysuria, vaginal discharge, diarrhea or vomiting, cough or shortness of breath, recent travel, sick contacts, or tick exposure. Her medical history was significant for a 2-year history of an undifferentiated connective tissue disease, which presented with inflammatory arthritis, palpable skin rashes (biopsy showed immunoglobulin G and immunoglobulin M granular deposition along the basement membrane zone, suggestive of a connective tissue disease), positive antinuclear antibodies, positive SS-A and SS-B, low total complement, low C3 and C4, and positive rheumatoid factor with negative anticyclic citrullinated peptide antibodies.

Association of Rheumatoid Arthritis with Diabetic Comorbidity: Correlating Accelerated Insulin Resistance to Inflammatory Responses in Patients

Over the past two decades, with advancement of medical research and technology, treatments of many diseases including chronic disorders like rheumatoid arthritis (RA) have been revolutionized. Treatment and management of RA has been refined by advances in understanding its pathologic mechanisms, the development of drugs which target them and its association with various other chronic comorbidities like diabetes. Diabetes prevalence is closely associated with RA since elevated insulin resistance have been observed with RA. It is also associated with inflammation caused due to pro-inflammatory cytokines like tumour necrosis factor α and interleukin 6. Inflammation encourages insulin resistance and also stimulates other factors like a high level of rheumatoid factor in the blood leading to positivity of rheumatoid factor in RA patients. The degree of RA inflammation also tends to influence the criticality of insulin resistance, which increases with high activity of RA and vice versa. Markers of glucose metabolism appear to be improved by DMARDs like methotrexate, hydroxychloroquine, interleukin 1 antagonists and TNF antagonist while glucocorticoids adversely affect glycemic control especially when administered chronically. The intent of the present review paper is to understand the association between RA, insulin resistance and diabetes; the degree to which both can influence the other along with the plausible impact of RA medications on diabetes and insulin resistance.

Seropositive juvenile rheumatoid arthritis: analysis of the spectrum of clinical manifestations and therapy according to a retrospective study

Seropositive juvenile rheumatoid arthritis (JRA) is the rarest subtype of juvenile idiopathic arthritis (JIA) that is the equivalent of RA in adults and is manifested mainly by a symmetric polyarticular lesion, rapid structural disease progression with the formation of intraarticular erosions, the presence of positive rheumatoid factor (RF), and/or anti-cyclic citrullinated peptide (CCP) antibodies.Objective: to analyze demographic, clinical, and laboratory features of seropositive JRA and drug therapy according to a retrospective 10-year study.Patients and methods. The retrospective study enrolled patients diagnosed with seropositive JRA confirmed according to the ILAR classification, who were treated at the Childhood Rheumatology Department, V.A. Nasonova Research Institute of Rheumatology, from 2010 to 2020. Demographic indicators, data from clinical, laboratory, and instrumental examinations, and performed therapy were assessed.Results and discussion. The investigation enrolled 70 patients, amounting to 6.5% of the total number of patients with all clinical types of JIA. Among them, there was a great preponderance of girls (88.6%); the ratio of boys to girls was 1:7.8. The median age of onset of JRA was 12.2 [7.0; 14.0] years; the median duration of disease at diagnosis verification was 6 [4; 12] months; the median number of active joints at diagnosis of JRA was 16.5 [10.75; 23.25]; oligoarthritis was identified in 11.2% of patients at disease onset (within the first 6 months). During the first year of the disease, radiographic Stages II, III, and IV were defined in 42.9, 50, and 7.1%, respectively. Positive RF was found in 94.3% of patients; there was positivity for anti-CCP antibodies in 78.6%, a combination of positivity for RF and anti-CCP antibodies in 72.9%; only positive anti-CCR antibodies were seen in 5.7%. The median ESR at diagnosis verification was 29 [19.75; 44.5] mm/h; that of CRP was 15.0 [6.9; 34.4] mg/l. The extra-articular manifestations of the disease were found in 18 patients (25.7% of the total number of patients): fever in 5 (7.2%); lymphadenopathy in 17 (24.3%); lung damage in 3 (4.3%); rheumatoid nodules in 2 (2.9%); pericarditis in 1 (1.4%) patient, and uveitis in 1 (1.4%). Sjögren's syndrome was diagnosed in 25.7% of patients; autoimmune thyroiditis in 8.6%. A family history of autoimmune diseases was recorded in 22.8%. Nonsteroidal anti-inflammatory drugs and glucocorticoids were used in 97.1 and 48.6% of patients; respectively; the patients received synthetic disease-modifying antirheumatic drugs (sDMARDs): only methotrexate (MTX) [n=55 (78.6%)], sequentially 2 sDMARDs [n=10 (14.3%)], 3 sDMARDs [n=5 (7.1%)]; biological agents (BAs) [n=66 (94.2%)]. During the first year of the disease, Biological therapy was initiated because of the rapid progression of the erosive process in 78.6% of patients. 64.3% of children took one BA, 18.6 and 7.1% received two and three BAs, respectively. Abatacept (ABC) as the first BA was used most often (45.7%). The reasons for revision of therapy were its secondary inefficiency in most cases and serious adverse reactions in 4 patients (ABC- and infliximab-related infusion reactions in 2 cases and conversion of tubercular tests in 2). The differences in the anti-CCP antibody detection rate were statistically insignificant in the group that used only one BA effectively long and in the group that needed to switch to another BA. When choosing a BA, preference was given to tocilizumab or rituximab (RTM) in patients with seropositive JRA in the presence of systemic manifestations, and high clinical and laboratory activities and to RTM or ABC in those with detected Sjögren's syndrome.Conclusion. Seropositive JRA is a rare subtype of JIA that has an initially unfavorable course. Most patients require early aggressive therapy, including MTX and a BA due to the rapid progression of erosive arthritis. The presence of systemic manifestations and/or Sjögren's syndrome plays a defining role in choosing a specific BA. The presence of anti-CCP antibodies does not affect the selection or change of a BA.

Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study.

The aim of this multicenter, retrospective study was to clarify the retention rates of sarilumab (SAR), baricitinib (BAR), and tofacitinib (TOF) in patients with rheumatoid arthritis (RA). Patients treated with either SAR (n = 62), BAR (n = 166), or TOF (n = 185) (females, 80.9%; age, 61.0 years; disease duration, 11.1 years; rheumatoid factor positivity, 84.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone dose, 5.3 mg/day [47.0%] and methotrexate dose, 8.8 mg/week [58.4%]; biologics- or Janus kinase inhibitors-switched cases 78.4%) were included. The reasons for drug discontinuation were classified into 4 major categories (lack of effectiveness, toxic adverse events, non-toxic reasons, and remission) by each attending physician. The drug retention rate was estimated at 18 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling. The discontinuation rates of SAR, BAR, and TOF for the corresponding reasons were as follows, respectively: lack of effectiveness (15.7%, 15.6%, and 21.5%; P = 0.84), toxic adverse events (15.8%, 12.1%, and 12.3%; P = 0.35), non-toxic reasons (10.9%, 7.7%, and 6.8%; P = 0.35), and remission (0.0%, 2.8%, and 0.0%; P = 1.0). The overall retention rates excluding non-toxic reasons and remission were as follows: 68.8% for SAR, 72.5% for BAR, and 66.7% for TOF (P = 0.54). After adjustment by potent confounders, SAR, BAR, and TOF showed similar discontinuation rates due to lack of effectiveness and toxic adverse events. Key Points • This is the first retrospective multicenter study that aimed to clarify the retention rates and reasons for discontinuation of SAR, BAR, and TOF in patients with RA.

14-3-3η Protein as a Potential Biomarker in Juvenile Idiopathic Arthritis.

The 14-3-3η (eta) protein was evaluated as a biomarker in a cohort of patients with juvenile idiopathic arthritis (JIA), as well as disease- and healthy-controls, to determine its potential clinical utility. In this case-control study, levels of 14-3-3η protein were evaluated in archival specimens from patients with JIA, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), as well as healthy pediatric controls. Just over 200 patients were evaluated, using specimens banked between 1990 and 2011. Comparisons were made to complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-nuclear antibody (ANA) positivity. 14-3-3η at levels 0.2 ng/mL or higher was considered positive. Fisher’s exact tests, odds ratios, 95% confidence intervals, and p-values were reported. 14-3-3η positivity was seen in all included JIA subtypes. The rate of positivity was the highest in RF-positive (pos) polyarticular JIA. In the disease and healthy controls, lower rates of positivity were observed. The frequency of 14-3-3η positivity among RF-positive and RF-negative (neg) polyarticular JIA patients, especially at values ≥0.5 ng/mL (associated with poor outcomes in adults), was also highest. Several JIA patients with 14-3-3η positivity developed RF and anti-CCP positivity later in their disease. Significant levels of 14-3-3η can be found in approximately 30% of RF-pos and RF-neg patients with polyarticular JIA. This protein may represent a new biomarker for polyarticular JIA, particularly RF-neg polyarticular JIA.

Clinical significance of serum survivin in rheumatoid arthritis patients: Relation to disease activity, functional status and radiological damage

Aim of the workTo measure the levels of serum survivin in rheumatoid arthritis (RA) patients and to assess its relation to disease activity, functional impairment, and radiological damage. Patients and methodsThis study included 58 RA patients and 34 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), modified Larsen radiological score and serum survivin level were assessed. ResultsThe mean age of the patients was 43.5 ± 11.5 years; 43 females and 15 males (F:M 2.9:1) with a mean disease duration of 2.6 ± 1.13 years. RF was positive in 79% Survivin level was significantly increased in patients compared to the controls (171.8 ± 74.4 pg/ml vs. 98.7 ± 16 pg/ml, p < 0.001) and in those with activity (203.1 ± 69.1 pg/ml) compared to those in remission (102.1 ± 12.1 pg/ml). Survivin level tended to be higher in females (177.1 ± 79.5 pg/ml) compared to males (156.4 ± 57 pg/ml) (p = 0.36) and was significantly higher in those with positive RF (183 ± 75.9 pg/ml) compared to those with a negative test (128.6 ± 50.5 pg/ml) (p = 0.02). A significant correlation was detected between survivin and disease duration, DAS28, ESR, CRP, VAS, HAQ, RF, and modified Larsen scores (p < 0.001). On univariate logistic regression the RF, HAQ, modified Larsen and survivin level were significant predictors but were insignificant on multivariate analysis. ConclusionIn RA patients the serum survivin is significantly increased compared to the controls. The disease activity, functional impairment, and radiological joint damage were associated with these high concentrations.

Excess mortality persists in patients with rheumatoid arthritis.

To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA). Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population. Over the observation period, 225 deaths were reported. Total age- and sex-adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44-1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C-reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities. The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself.

Disease-modifying drug retention rate according to patient age in patients with early rheumatoid arthritis: analysis of the ESPOIR cohort.

Physicians are sometimes hesitant to use disease-modifying antirheumatic drugs (DMARDs) in elderly patients with rheumatoid arthritis (RA), as they are deemed too fragile, although there are no sufficient scientific evidence. We aimed to compare DMARD treatment retention in early RA patients from the ESPOIR cohort, according to age upon inclusion. Overall, treatment retention was evaluated as the percentage of patients whose DMARDs were not stopped, with stratification by age group: < 50, 50-64, and > 65years. Survival curves were measured using the Kaplan-Meier method. Of the entire ESPOIR cohort (n = 813), 7% were > 65years old. Methotrexate (MTX) was used by 521 patients, and was the sole DMARD for 198 patients. MTX treatment retention appeared better in patients > 65years old compared to < 50years old [HR 0.45 (0.25; 0.81); p = 0.008, n = 195/198] with adjustment on sex, smoking, positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, body mass index, changes in DAS28 and corticosteroid treatment. The proportion of patients using etanercept (n = 111), and this drug's retention rate, did not differ according to patient age. The proportion of patients treated with adalimumab (n = 104) was significantly higher in patients < 50years old (p = 0.003), and treatment retention was marginally better among younger patients [HR 1.68 (0.88; 3.22), p = 0.12]. Within the ESPOIR cohort, DMARD retention did not appear to differ according to age-except for better retention of MTX treatment in patients 50-64years old, and of adalimumab in patients < 50years old.

The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negative rheumatoid arthritis patients.

Background:Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs).Methods:A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies.Results:Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (rs = 0.39), RF and ACPAs, (rs = 0.3) and RF and anti-CarP, (rs = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF.Conclusion:Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.

LAMP3 (CD208) Expression in Squamous Cell Carcinoma and Epithelial Dysplasia of the Oral Cavity and Clinicopathological Characteristics of Unfavorable Prognosis.

This study aimed to evaluate LAMP3 (CD208) gene expression in oral squamous cell carcinoma (OSCC) and dysplastic oral epithelium by quantitative real-time polymerase chain reaction (qPCR) and compare LAMP3 expression in different disease grades and stages. In this study, 60 OSCC and dysplastic oral epithelium samples were obtained from the Mashhad University of Medical Sciences together with their demographic and clinicopathological documents. LAMP3 expression was measured by qPCR. LAMP3 expression was significantly greater in OSCC than in dysplasia samples (P=0.001), in grade III OSCC than in grades I and II, and also greater in advanced than in early OSCC disease stage (P=0.001). The significantly greater LAMP3 expression in OSCC than in dysplastic epithelium indicates a role for LAMP3 in carcinogenesis in oral mucosa. Our results suggest LAMP3 may be useful as an anticancer target and/or to predict disease pathogenesis in OSCC patient's cells.

The clinical significance of anti-DFS70 autoantibodies and its correlation with Vitamin D levels.

This study aims to investigate the clinical significance of anti-dense fine speckled 70 (DFS70) autoantibodies and its association with systemic autoimmune rheumatic diseases (SARD) related autoimmune markers and Vitamin D levels. The study group consisted of 281 (mean age±SD: 45.31±15.89 years; 88.3% female) anti-DFS70 autoantibody-positive patients. All patients' sera in the study group were tested by ANA HEp-2 indirect immunofluorescent antibody (IIF) and immunoblotting (IB) methods (Euroimmun AG, Lübeck, Germany). Anti-DFS70 antibody-positive patients were divided into two subgroups. Anti-DFS70 antibody-positive patients with SARD were assigned as Group 1 (n=43), anti-DFS70 antibody-positive patients without SARD were assigned as Group 2 (n=238). A control group with anti-DFS70 negative patients with SARD were assigned as Group 3 (n=49, mean age±SD: 49.86±12.08; 79.6% female). The clinical characteristics, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), neutrophil/lymphocyte ratio, thrombocyte/lymphocyte ratio (TLR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and 25-hydroxyvitamin D3 (25OHD3) levels were compared between three groups. The majority (61.9%) of anti-DFS70 antibody positive patients had no specific diagnosis. Other systemic diseases were detected as allergic diseases (10.0%), hematological abnormalities (5.0%), thyroid diseases (3.6%), gastrointestinal system diseases (1.8%), malignancies (1.4%), and infections (1.1%). ESR, CRP levels, and TLR were lower in Group 2 than Groups 1 and 3 (p<0.05). RF and anti-CCP positivity rates were lower in Group 2 when compared with Groups 1 and 3 (p<0.05). 25OHD3 levels did not differ between three groups (p=0.103). We observed that anti-DFS70 autoantibody may be associated with organ-specific autoimmune diseases, allergic diseases, and hematological disorders. Therefore, it is essential to evaluate these pathologies in patients positive for anti-DFS70 antibodies.

Targetoid lesions in a patient with systemic lupus erythematosus

Rowell Syndrome is a rare presentation of lupus erythematosus manifesting as an eruption of erythema multiforme-like papules and plaques with immunological findings of positive rheumatoid factor, speckled antinuclear antibodies, and/or anti-Ro/La antibodies. This case highlights the unusual and highly debated presentation of Rowell Syndrome in a 66-year-old woman with newly-appearing erythematous, targetoid plaques in the setting of previously diagnosed systemic lupus erythematosus. Skin biopsy revealed histological features of full-thickness epidermal necrosis with focal sub-epidermal separation and a superficial perivascular lymphocytic infiltrate interpreted to favor Rowell Syndrome given her clinical history and presentation. Although no standard treatment exists, a prednisone taper and topical corticosteroids proved effective initially, with complete resolution at six months on mycophenolate mofetil and belimumab.

Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody

OBJECTIVE To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjogren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study

Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.