American College Of Rheumatology/European League Against Rheumatism Research Articles

Tophaceous gout of the atlantoaxial joint: a case report

BackgroundTo report the occurrence of tophaceous gout in the cervical spine and to review the literature on spinal gout.Case presentationThis report details the occurrence of a large and clinically significant finding of tophaceous gout in the atlantoaxial joint of the cervical spine in an 82-year-old Caucasian man with a 40-year history of crystal-proven gout and a 3-month history of new-onset progressive myelopathy. The patient's American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria score was 15.0.ConclusionSpinal gout is more common than previously thought, and it should be considered in patients who present with symptoms of myelopathy. Diagnosis can be made without a tissue sample of the affected joint(s) with tools like the ACR/EULAR criteria and the use of the “diagnostic clinical rule” for determining the likelihood of gout. Early conservative management with neck immobilization and medical management can avoid the need for surgical intervention.

Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3): A Novel Marker for Lymphoma Development among Patients with Young Onset Sjogren's Syndrome.

Background: Primary Sjogren’s syndrome (SS) is an autoimmune disease with a strong predilection for lymphoma development, with earlier disease onset being postulated as an independent risk factor for this complication. Variations of the Leukocyte immunoglobulin-like receptor A3 (LILRA3) gene have been previously shown to increase susceptibility for both SS and non-Hodgkin B-cell lymphoma (B-NHL) in the general population. We aimed to investigate whether variations of the LILRA3 gene could predispose for lymphoma development in the context of SS. Methods: Study population, all of Greek origin, included 101 SS cases with a current or previous diagnosis of lymphoma (SS-lymphoma, SS-L) and 301 primary SS patients not complicated by lymphoma (SS-non-lymphoma, SS-nL). All SS patients fulfilled the 2016 SS American College of Rheumatology/European league against Rheumatism (ACR/EULAR) classification criteria. A total of 381 healthy controls (HC) of similar age/sex/race distribution were also included. On the basis of the age of SS onset and the presence or absence of adverse predictors for lymphoma development, SS patients were further stratified into younger (≤40 years) and older (>40 years) age of disease onset, as well as into high/medium and low risk groups. Polymerase chain reaction (PCR) was implemented for the detection of the following LILRA3 gene variants: homozygous non-deleted or functional wild type (+/+) heterozygous (+/−) and homozygous deleted (−/−). LILRA3 serum protein levels were quantitated by enzyme-linked immunosorbent assay (ELISA) in 85 individuals (29 SS-L, 35 SS-nL patients and 21 HC). Results: While no statistically significant differences were detected in the overall frequency of LILRA3 gene variants between SS-L, SS-nL and HC groups, LILRA3 serum protein levels were increased in the SS-L group compared to HC (1.27 ± 1.34 vs. 0.38 ± 0.34 ng/mL, p-value: 0.004). After stratification according to the age of SS onset and history of lymphoma, as well as the presence or absence of adverse predictors for lymphoma development, the prevalence of the functional LILRA3 gene variant was found to be significantly increased in the young onset SS-L group compared to the HC of similar age and sex distribution (100% vs. 82.9%, p = 0.03), as well as in the high/medium risk SS compared to the low risk SS (91.3 vs. 78.3%, p = 0.0012). Of note, young onset SS-L and SS-nL groups displayed higher LILRA3 serum levels compared to their older counterparts (p-values: 0.007 and 0.0005, respectively). Conclusion: The functional LILRA3 gene variant increases susceptibility to SS-related lymphoma development in patients with a disease onset of <40 years old, implying that genetically determined deranged immune responses in younger SS individuals could underly their pronounced risk for lymphoma development.

Performance of the 2019 EULAR/ACR systemic lupus erythematosus classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis

ObjectiveTo evaluate the performance of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in a cohort of patients with biopsy-confirmed lupus nephritis (LN) and their renal...

Efficacy of doxycycline as a combination therapy in the treatment of rheumatoid arthritis: a randomized controlled clinical trial

BackgroundThis single-center randomized open-label clinical trial evaluates the effectiveness of doxycycline as a combination therapy for active rheumatoid arthritis (RA) with methotrexate (MTX).Materials and methodsOne hundred and sixty RA patients were recruited who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Subjects were randomly allocated in a 1:1 ratio into one of two treatment arms; one group was maintained on MTX alone and the other group on MTX together with doxycycline orally 200 mg daily. Follow-up clinical response, erythrocyte sedimentation rate (ESR), levels of C-reactive protein (CRP), and disease activity score 28 (DAS28-CRP) after 3 months were done.ResultsThere was a significant difference regarding DAS28-CRP between the two groups (median (IQR) 4.26 (3.6–5) for those treated with MTX alone compared with 2.8 (2.37–3.5) for those treated with MTX together with doxycycline) (p = 0.005). A higher number of patients treated with doxycycline in combination with MTX achieved remission (40.5%) compared to patients who received MTX alone (13.5%). The levels of ESR and CRP were lower in patients treated with MTX and doxycycline and this was statistically significant (p = 0.005, p = 0.003 respectively).ConclusionDoxycycline as a cost-effective combination therapy with MTX can achieve higher rates of remission than MTX alone in RA patients without causing increase in the adverse events profile.Trial registrationClinical Trials.gov, NCT03194204. Registered on 21 June 2017

Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis

Objective: Few studies have investigated the efficacy of subcutaneous tocilizumab (TCZ-SC) on ultrasound-detected inflammation. This study aimed to explore the clinical efficacy of TCZ-SC treatment in rheumatoid arthritis (RA) patients and to evaluate the response by ultrasound compared to Composite Disease Activity Scores (CDAS). Method: This open-label, single-arm study enrolled RA patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs initiating TCZ-SC 162 mg once weekly for 24 weeks, with clinical assessments at baseline, 2, 4, 8, 12, 16, 20, and 24 weeks. Ultrasound examinations [semi-quantitative score (0–3) of 36 joints and four tendons] were performed at baseline, 4, 12, and 24 weeks. CDAS and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) response, and sum scores of ultrasound grey scale/Doppler were calculated. Changes during follow-up were explored by the Mann–Whitney test and correlations by Spearman’s rho. Results: In total, 133 patients (mean ± sd age 55.9 ± 12.0 years) were assessed clinically and 110 patients were also examined with ultrasound. All clinical and ultrasound scores decreased significantly after 4 weeks (p < 0.001). At 24 weeks there was EULAR good response in 87.7% and ACR 70% response in 47.4%. Ultrasound scores had no or low correlations with patient-reported outcomes. At 24 weeks, CDAS remission was achieved in 27.4–83.5% and a sum score Doppler of 0 was found in 53.3%. Conclusions: Clinical and ultrasound scores decreased rapidly. Ultrasound scores were not associated with patient-reported variables. Half of the patients reached ultrasound remission, while there were large discrepancies in the percentage of patients reaching remission based on different CDAS. Trial registration: Study ML28691, registered 28 January 2014, ClinicalTrials.gov identifier: NCT02046616

Polymyalgia rheumatica: A case series from Colombia and analysis of Latin America

ObjectivePolymyalgia rheumatica (PMR) is the most common inflammatory disease in patients over 50 years. Information about the disease in Latin America (LATAM) is scarce. We aimed to evaluate a group of Colombian patients with PMR and to conduct a systematic review of PMR in LATAM. MethodsA multicentric retrospective study was performed. Medical records of 256 PMR patients were evaluated. Patients were divided into two groups, those fulfilling the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR and those who did not (i.e., clinical diagnosis). A systematic literature review and meta regression was performed comparing Colombian vs LATAM patients. ResultsFrom 256 patients, 145 (56.6%) fulfilled the 2012 EULAR/ACR criteria, and 111 (43.3%) were classified by clinical diagnosis. Inflammatory bilateral shoulder pain, pelvic girdle aching, morning stiffness >45 min, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CPR), and Methotrexate (MTX) prescription were more common in the 2012 EULAR/ACR group. None of the included patients presented overt polyautoimmunity (PolyA), whereas up to 24% exhibited latent PolyA. In addition, these patients showed high frequency of malignancy (7.59%). In the meta regression analysis, Colombian patients exhibited lower ESR levels, and were less likely to develop giant cell arteritis (GCA) as compared to the rest of LATAM data. ConclusionPatients with PMR in LATAM exhibit similar phenotypes from other cohorts worldwide. Malignancy, GCA and latent PolyA should be considered in the routine clinical follow-up of patients with PMR.

Mild cognitive impairment and rheumatoid arthritis

AbstractBackgroundIncreasing evidence from the last ten years suggests that systemic inflammation may be associated with an increased risk of developing Alzheimer’s disease (AD). Some studies have found an association between rheumatoid arthritis (RA) and neurodegeneration with several finding increased incidence of mild cognitive impairment (MCI) in those with RA compared to healthy controls. This study aims to use preliminary data from the Rheumatoid arthritis, medication and memory study (RESIST) to investigate the prevalence of MCI in a population of patients with RA and explore the relationship between MCI and specific demographic and clinical characteristics.MethodThe Montreal Cognitive Assessment (MoCA) was used as a cognitive screening tool and was administered to subjects who were ≥55 years of age and had been diagnosed with RA according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. Demographic and clinical data was recorded at screening in face‐to‐face interviews and included age, gender, type of RA medication and date of RA diagnosis. 260 participants completed both screening and baseline visits as part of the RESIST longitudinal study, MoCA scores from baseline were analysed for these participants. Statistical analysis was used to provide descriptive statistics for our population and determine predictors of cognitive impairment.ResultA total of 636 participants (mean age 68.1, 67.5% female) were screened between May 2018 and December 2019. The mean MoCA for screened participants was 25.4, 45.3% of our population scored &lt;26 in the MoCA and were considered cognitively impaired. Age was negatively correlated to MoCA score and was the only significant predictor of cognitive impairment (p&lt;0.001). Gender, type of RA medication and duration of disease did not contribute to the regression model. The mean MoCA score was found to differ by 0.404 points between screening and baseline.ConclusionA large proportion of our participants scored below the proposed cut‐off for normal cognition in the MoCA suggesting at the high prevalence of MCI in older adults with RA. This may provide further support for the role of chronic inflammation in AD and questions whether it would be worthwhile introducing routine screening for MCI in rheumatology clinics.

Sexual dysfunction and its determinants in women with rheumatoid arthritis.

To evaluate sexual function in Tunisian women with rheumatoid arthritis (RA) and to examine factors that are predictors of female sexual dysfunction including sociocultural factors, disease activity, and psychological status. We conducted across-sectional study including 71women with aconfirmed diagnosis of RA according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria. Clinical and sociodemographic characteristics were collected. The participants were asked to complete the Female Sexual Function Index (FSFI), which contains 19questions, assessing six areas of female sexual function in the previous 4weeks. Sexual dysfunction was defined as an FSFI score less than or equal to 26.55. The psychosocial status was evaluated by the Hospital Anxiety and Depression (HAD) scale. Prevalence of sexual dysfunction and predictors of sexual difficulties were assessed. The prevalence of female sexual dysfunction in women with RA was 49.3%. All areas were altered especially desire (2.92 ± 1.3), arousal (3.27 ± 1.5), and orgasm (3.77 ± 1.5). In univariate analysis, sexual dysfunction was correlated with the age of patients (p = 0.049), the age of partners (p = 0.013), pain (p = 0.001), number of night awakenings (p = 0.02), morning stiffness (p = 0.010), tender joints (p = 0.05), disease activity score (DAS28 ESR) (p = 0.043), fatigue (p = 0.028), and Health assessment questionnaire (HAQ) (p = 0.02). In multivariate analysis, the age of patients and pain were predictive factors of sexual dysfunction. By analyzing each area of the FSFI score, the age of patients was the independent variable associated with desire. Tender joints were associated with lubrication and the age of partners with arousal, orgasm, and satisfaction. Our study suggests that rheumatoid arthritis has anegative impact on patients' sexuality. Age of patients and partners, pain, and tender joints appear to be the main factors influencing sexual function.

The prevalence of rheumatoid arthritis in middle-aged and elderly people living in Naqu City, Tibet, Autonomous Region of China

ObjectiveTo estimate the prevalence of rheumatoid arthritis (RA) in the Tibet Autonomous Region (China).MethodsA population-based cross-sectional survey was conducted on 1458 residents of Luoma Town, Tibet Autonomous Region, who were aged ≥ 40 years old. We interviewed participants using questionnaires, and rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and C-reactive protein (CRP) were determined. The identification of RA in this study was on the basis of criteria issued by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guideline.ResultsHerein, 782 participants completed all items of RA. The overall prevalence of RA was 4.86%, and the prevalence was higher in women than that in men (7.14% vs. 2.56%, p = 0.005). The age-standardized prevalence of RA was 6.30% (95% confidence interval (CI) 4.20–8.64%), which was 2.46% (95% CI 1.04%, 4.10%) and 9.59% (95% CI 5.93%, 13.77%) in men and women, respectively.ConclusionThe prevalence of RA is relatively higher in the Tibet than that in other areas of China.

Value of labial salivary gland histopathology for diagnosis of Sjögren's syndrome in patients with anti‐centromere antibody positivity

Although anti-centromere antibody (ACA)+ Sjögren's syndrome (SS) is considered a subtype of SS, it was not included in the recent American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) SS classification criteria. ACA+patients without anti-SS-A/Ro antibodies require salivary gland histopathology to fulfill the ACR/EULAR criteria for diagnosis of SS. We reviewed salivary gland histology among ACA+patients referred for the diagnosis of SS using the ACR/EULAR and Japanese criteria which does not require biopsy. Data from 147 ACA+patients with dry eyes and/or mouth who visited our department were retrospectively analyzed. Clinical, immunological, and histological data were collected and statistically analyzed. Sixty-five patients (44%) had undergone labial salivary gland biopsy. The frequency of dry mouth was higher in ACA+patients who had undergone labial salivary gland biopsy than in those who had not (P=.046), while there were no differences in biopsy rates between patients with and without sclerodactyly (P=.51). According to the current ACR/EULAR classification criteria, Greenspan grade of 3 or 4 for labial salivary gland histopathology is required in patients without anti-SS-A/Ro antibody for the diagnosis of SS. Four patients with Greenspan grades <3 and anti-SS-A/Ro antibody met the criteria for SS. In 54 patients in which the ACR/EULAR criteria were met, 53 patients were diagnosed with SS using the Japanese criteria. In ACA+/anti-SS-A/Ro- antibody patients, agreement between ACR/EULAR and Japanese criteria sets was excellent. For easily classifying ACA+patients as SS cases, salivary gland biopsy should be performed in ACA+patients with dry symptoms to identify ACA+ patients.

The diagnostic utility of rheumatoid factor and anticitrullinated protein antibody for rheumatoid arthritis in the Indian population

BackgroundThere is lack of Indian data on diagnostic utility of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) for diagnosis of rheumatoid arthritis (RA) and prevalence of these antibodies in patients with RA and the healthy population. The study was aimed to assess the diagnostic utility and prevalence of RF and ACPA at different titers in the Indian scenario. MethodAll the patients of RA fulfilling the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 classification criteria and age and gender-matched healthy controls were included in the study. RF and ACPA were measured by nephelometry and the enzyme-linked immunosorbent assay (ELISA) method, respectively. ResultOf 803 patients (291 men and 512 women) included, the RF was positive in 566 (70.5%) study patients. The ACPA was positive in 527 (71.7%) patients of 735 of them. Among 408 healthy controls, 45 (11%) were RF positive and 19 (4.7%) were ACPA positive.At the positive cutoff level, the RF had a specificity of 87.6% (95% confidence interval [CI] = 84.4–90.8; positive likelihood ratio [LR+] 5.7). Specificity at 2 and 3 times above the upper limit of normal (ULN) increased to 96.2% (95% CI = 94.3–98.1; LR+ 15.7) and 97.1% (95% CI = 95.5–98.7; LR+ 17.1), respectively.The specificity of ACPA at the positive cutoff level was 94.4% (95% CI = 92.2–96.6; LR+ 12.7), which increased to 98% (95% CI = 96.6–99.4), at 2xULN level. The likelihood ratio for ACPA at all cutoff levels measured was more than 10. ConclusionThe sensitivity and specificity of RF and ACPA in our study population are comparable with those of other studies. ACPA at lower titers may have sufficient diagnostic utility for RA in an appropriate clinical setting.

The Impact of Dysphagia in Myositis: A Systematic Review and Meta-Analysis.

(1) Background: Dysphagia is a clinical hallmark and part of the current American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) diagnostic criteria for idiopathic inflammatory myopathy (IIM). However, the data on dysphagia in IIM are heterogenous and partly conflicting. The aim of this study was to conduct a systematic review on epidemiology, pathophysiology, outcome and therapy and a meta-analysis on the prevalence of dysphagia in IIM. (2) Methods: Medline was systematically searched for all relevant articles. A random effect model was chosen to estimate the pooled prevalence of dysphagia in the overall cohort of patients with IIM and in different subgroups. (3) Results: 234 studies were included in the review and 116 (10,382 subjects) in the meta-analysis. Dysphagia can occur as initial or sole symptom. The overall pooled prevalence estimate in IIM was 36% and with 56% particularly high in inclusion body myositis. The prevalence estimate was significantly higher in patients with cancer-associated myositis and with NXP2 autoantibodies. Dysphagia is caused by inflammatory involvement of the swallowing muscles, which can lead to reduced pharyngeal contractility, cricopharyngeal dysfunction, reduced laryngeal elevation and hypomotility of the esophagus. Swallowing disorders not only impair the quality of life but can lead to serious complications such as aspiration pneumonia, thus increasing mortality. Beneficial treatment approaches reported include immunomodulatory therapy, the treatment of associated malignant diseases or interventional procedures targeting the cricopharyngeal muscle such as myotomy, dilatation or botulinum toxin injections. (4) Conclusion: Dysphagia should be included as a therapeutic target, especially in the outlined high-risk groups.

Relationship between change in physical activity and in clinical status in patients with idiopathic inflammatory myopathy: A prospective cohort study

ObjectiveThis study aimed to investigate the relationship between changes in clinical status on daily life physical activity (PA) in patients with idiopathic inflammatory myopathy (IIM). MethodsPatients with dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) or overlap myositis (OM) who presented either a new-onset or relapsing IIM, stable disease on maintenance therapy or were undergoing immunosuppressant tapering were included. Patients were evaluated at inclusion (V0), and at two follow-up visits (V1, 94±12 days from V0; V2, 96±17 days from V1). The American College of Rheumatology/European League against Rheumatism (ACR/EULAR) response criteria was recorded. PA assessed using 14-days raw accelerometry data gathered using a wrist-worn accelerometer after each visit (mean daily Euclidean norm minus 1 g (ENMO) was computed). ResultsFifty-five patients (16 OM, 27 IMNM and 12 DM) were included. At baseline, 67% of patients had an ENMO Z-score less than 1. At inclusion, ENMO mainly correlated with health assessment questionnaire score (HAQ, ρ=-0.51, p<0.01), manual muscle testing 8 (MMT8, ρ=0.42, p<0.01), creatinine level (ρ=0.41, p<0.01), and SF-36 physical functioning score (ρ=0.38, p<0.002). At follow-up, ENMO changes mainly correlated with changes in MMT8, HAQ, SF-36 fatigue, and depression score (all ρ>0.43, all p<0.001). Level of agreement between ACR/EULAR response criteria and changes in PA was 15, 45, and 90% for minimal (n = 13), moderate (n = 20), and major (n = 10) improvements, respectively. ConclusionBaseline PA levels and change in PA correlated with muscle strength and function, yet changes in PA were also influenced by psychological status. Only patients with major improvements on the ACR/EULAR criteria had significant increase in PA. Accelerometer may serve as an objective tool to define a clinically relevant real-life outcome.

New Classification Criteria for Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with highly variable clinical and immunological manifestations. Classification and diagnosis of SLE are complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. The 1997 update of the 1982 American College of Rheumatology (ACR) criteria for SLE has been widely used for classification of SLE. In order to improve clinical relevance and early diagnosis, the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) group suggested the 2012 SLICC criteria. These sets of classification criteria have unweighted lists of various serological and clinical findings typical of SLE, can be fulfilled by reaching a sum score of points. The only exception is biopsy-proven lupus nephritis with autoantibodies in the 2012 SLICC criteria. In an attempt to overcome limitations of the previous sets of SLE classification criteria, the new 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE have been recently published. The 2019 EULAR/ACR criteria include positive ANA at least once as obligatory entry criterion; followed by additive hierarchically clustered and weighted criteria. The structure and weighting of criteria constitute a paradigm shift in the classification of SLE. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%. This review attempts to delineate the history, performance and limitations of the current sets of SLE criteria.

THU0135 PATIENT GLOBAL ASSESSMENT LEVELS PRECLUDE THE MAJORITY OF RHEUMATOID ARTHRITIS PATIENTS OTHERWISE IN REMISSION, FROM REACHING THIS STATUS: SYSTEMATIC LITERATURE REVIEW AND META-ANALYSES INCLUDING 23,297 PATIENTS

Background: Based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based remission definition for rheumatoid arthritis (RA), the main reason for near-misses (failing Boolean remission solely due to one criterion >1) is a patient global assessment (PGA) >1/10.1-3 The frequency of this PGA-near-remission status has not been well established. Objectives: To synthesize the overall prevalence of ACR/EULAR Boolean-based remission and PGA-near-remission cross-sectionally in published studies, and to explore association with disease duration. Methods: We systematically searched PubMed database (from 1/jan/2011 till 15/jan/2020) for “Rheumatoid arthritis” AND Boolean [OR synonyms] AND PGA [OR synonyms], and carried out a hand search of the references of the included studies. Two reviewers independently assessed the study inclusion and extracted the data (n (%) of patients in each remission status, mean (SD) disease duration, and country/city). Studies were excluded if any of the four Boolean criterion was not considered (e.g. C-Reactive Protein not assessed), or if only patients with low disease activity or remission were selected. If different time assessments were provided, we selected the 1y follow-up, as the most common. Random effects meta-analyses of proportions with double arcsine transformation were performed (also by disease duration subgroups) using MEDCALC®. Heterogeneity was assessed by I2. Results: From 41 studies identified, 8 studies concerning 12 subsamples were analysed (n=23,297 patients; of which 22% had ≤2 years mean disease duration). The overall prevalence of Boolean remission was 12% (95%CI: 10-15%, p Conclusion: The overall prevalence of PGA-near-remission in patients with RA followed in clinical practice was 1/3 more prevalent than Boolean remission, a difference more pronounced in patients with established disease. Overall, over 61% of all RA patients otherwise in remission failed to satisfy the Boolean definition of remission solely due to a PGA>1. The use of PGA in the definition of treatment target exposes a substantial proportion of patients to the risk of overtreatment with immunosuppressive agents, while being deprived of the adjunctive therapy they probably need.

Genetic heterogeneity of pediatric systemic lupus erythematosus with lymphoproliferation.

Systemic lupus erythematosus (SLE) is a chronic, rare autoimmune disease. In recent years, multiple monogenic diseases with early onset autoimmunity and lymphoproliferation have been identified, such as autoimmune lymphoproliferative syndrome, rat sarcoma (RAS)-associated autoimmune leukoproliferative disease, signal transducer and activator of transcription 3 gain-of-function syndrome and interleukin-2 receptor α deficiency. Therefore, we performed whole-exome sequencing in children with SLE with lymphoproliferation to identify genes associated with these conditions.We enrolled 7 patients with SLE with lymphoproliferation from different families. Demographic data, clinical manifestations, laboratory and histopathologic findings, treatment, and outcome were documented. Whole-exome sequencing was performed in 7 patients and their families. Suspected variants were confirmed by Sanger sequencing. Protein levels were detected in patients with gene mutations by western blot.Four patients were male, and 3 were female. No consanguinity was reported within the 7 families. The average age at onset was 5.0 years (range: 1.2–10.0 years). The most common features were renal (7/7 patients) and hematologic (6/7 patients) involvement and recurrent fever (6/7 patients), while only 2 patients presented with skin involvement. Antinuclear antibodies at a titer of ≥1:320 were positive in all patients. All patients fulfilled four 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for the classification of SLE. We identified a somatic activating NRAS variant (c.38 A>G, p.G13C) in peripheral venous blood from 4 patients, at levels ranging from 8.8% to 42.8% in variant tissues that were absent from their parents. B cell lymphoma (BCL)-2-interacting mediator of cell death levels in peripheral blood mononuclear cells from 4 patients were markedly reduced, whereas those in the control were normal. Another 2 mutations, c.559C>T (p.Q187X) in the TNFAIP3 gene and c.3061G>A (p.E1021K) in the PIK3CD gene were detected in 2 patients.The SLE is a novel phenotype of somatic mutations in the NRAS gene and germline mutations in the PI3CKD gene. These genes, NRAS, TNFAIP3, and PIK3CD, should be considered candidates for children with SLE with lymphoproliferation. If patients with SLE and lymphoproliferation present with renal and hematologic involvement and recurrent fever, they need gene testing, especially male patients.

Application of the 2019 European League Against Rheumatism/American College of Rheumatology systemic lupus erythematosus classification criteria in clinical practice: a single center experience.

Originally developed as research tools, different classification criteria sets for systemic lupus erythematosus (SLE) are also used to diagnose SLE in routine clinical care. The recently developed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria set is noted to perform better than previous SLE classification criteria. This study applied the new criteria schema to a tertiary center SLE cohort, ascertained its performance, and identified the clinical characteristics of patients who did not fulfill these criteria. From the 217 patients who were included, 11 (5%) did not meet the new criteria, mainly because of the antinuclear antibody entry criterion, resulting in a diagnostic sensitivity of 94%. Within this group, we found that constitutional and renal manifestations were unusual. Additionally, specific SLE antibodies as well as hypocomplementemia were less likely to be present. We did not observe a statistically significant difference in outcomes between the two groups of patients (fulfilling vs. unfulfilling the new criteria). We conclude that the EULAR/ACR criteria may misclassify a small subset of SLE patients with milder disease. It is important to be cognizant of key clinical and serologic features of these patients and treat them accordingly to prevent further irreversible damage.

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic...

Testing different thresholds for patient global assessment in defining remission for rheumatoid arthritis: are the current ACR/EULAR Boolean criteria optimal?

ObjectivesThis study aimed to evaluate different patient global assessment (PGA) cut-offs required in the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean remission definition for their utility in rheumatoid...

Clinical efficacy and safety of tocilizumab in the treatment of seropositive rheumatoid arthritis patients in India

Background: Tocilizumab (TCZ) is a human interleukin (IL)-6 receptor (IL-6R) antibody which competitively inhibits IL-6 signal transduction. Clinical efficacy and safety of TCZ in the treatment of rheumatoid arthritis (RA) and other autoimmune conditions have been established. However, there is a lack of data on its use in the Indian population. Objective: The objective was to study the clinical efficacy and safety of TCZ in Indian patients with seropositive RA. Patients and Methods: This was a prospective, observational single-center study conducted at a tertiary care rheumatology center. All patients were more than 16 years of age, fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA, and had at least moderate disease activity as measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28-ESR) ≥3.2 at enrollment while on at least two disease-modifying antirheumatic drugs. Patients with latent tuberculous infection were excluded from the study. Six doses of TCZ were administered at 8 mg/kg body weight dose at four weekly interval and clinical response was assessed at each visit. Results: All 30 patients enrolled completed the study. Baseline DAS28-ESR was 5.03 (SD0.39) which improved to 2.4 (△-2.6; 95% confidence interval: 2.30–3.04; P Conclusions: TCZ is an effective and safe option for the treatment of seropositive RA.