The role of albumin-to-globulin ratio in undifferentiated arthritis: Rheumatoid arthritis versus primary Sjögren syndrome

Objectives: This study aims to compare initial albumin-to-globulin ratio (AGR) in patients with rheumatoid arthritis (RA) and primary Sjögren syndrome (pSS) presenting with undifferentiated arthritis (UA) and to investigate whether there was a difference in terms of AGR between the two patient groups and healthy controls. Patients and methods: Between January 2019 and December 2019, a total of 177 patients including 96 RA (10 males, 86 females; mean age: 53.6±10.8 years; range, 21 to 74 years) and 81 pSS (5 males, 76 females; mean age: 53.2±14.1 years; range, 23 to 79 years) and 82 healthy controls (20 males, 62 females; mean age: 50.5±13.6 years; range, 20 to 79 years) were included in this case-control study. Demographic characteristics, albumin, and globulin levels of all participants were recorded. The AGR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-citrullinated protein antibodies (ACPA) were assessed. Results: The mean AGR was 1.50±0.16 in the control group, 1.48±0.24 in the RA group, and 1.30±0.23 in the pSS group, indicating a significant difference between the pSS and the other two groups (p<0.001). The receiver operating characteristic analysis revealed that the cut-off value for AGR was 1.39 (area under the curve=0.736) with a sensitivity of 0.642 and a specificity of 0.646 (p<0.001). The ESR and CRP values were higher (p<0.001), and ANA (p<0.001) and RF (p=0.003) positivity were lower in the RA group, compared to the pSS group. Conclusion: This study findings indicate that AGR is a helpful tool in the differential diagnosis of RA and pSS presenting with UA at the time of admission, and Sjögren syndrome should be considered in case of AGR ≤1.39.

Pregnancy outcomes between pregnant systemic lupus erythematosus patients with clinical remission and those with low disease activity: A comparative study

Objectives: This study aims to compare pregnancy outcomes between systemic lupus erythematosus (SLE) patients who attained clinical remission based on the Definition of Remission in SLE (DORIS) and those with lupus low disease activity based on Low Lupus Disease Activity State (LLDAS). Patients and methods: Between January 1993 and June 2017, a total of 90 pregnancies (one twin pregnancy) from 77 patients (mean age: 6.9±4.8 years; range, 17.9 to 37.3 years) were included in the study. The clinical remission and the LLDAS groups were modified into modified clinical remission and LLDAS groups, respectively by omitting Physician Global Assessment (PGA). The clinical SLE disease activity index (cSLEDAI) score was used for LLDAS. Results: Pregnancies in 49 patients occurred, when they were in modified clinical remission and in 57 in modified LLDAS. There was no significant difference in demographic characteristics, disease activity, or medication received at conception between the two groups. Pregnancy outcomes were similar between the modified clinical remission and the modified LLDAS groups in terms of successful pregnancy (83.67% vs. 84.21%), full-term births (38.78% vs. 38.60%), fetal losses (16.33% vs. 15.79%), spontaneous abortions (14.29% vs. 14.04%), small for gestational age infants (18.37% vs. 19.30%), low birth weight infants (42.86% vs. 40.35%), maternal complications (46.94% vs. 49.12%), and maternal flares (36.73% vs. 40.35%). The agreement of pregnancy outcomes was very high between the two groups (91.11% agreement). Conclusion: Pregnancy outcomes in SLE patients who achieved modified clinical remission and modified LLDAS were comparable.

Vasculitis induced by biological agents used in rheumatology practice: A systematic review

Objectives: Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology. Patients and methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents. Results: Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal. Conclusion: Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.

Is COVID-19 multisystem inflammatory syndrome a new variant of Kawasaki Disease?

Objectives: In this systematic review, we aimed to evaluate the clinical features, therapeutic options, and outcomes of children with multisystem inflammatory syndrome in children (MIS-C) and to investigate whether MIS-C is a new variant of Kawasaki disease. Materials and methods: Adhering to PRISMA principles, we searched for eligible studies between December 2019 and June 2020 through the following databases: PubMed, ISI Web of Science, SCOPUS, and Science Direct. Studies including original data of patients aged <21 years with MIS-C and descriptions of clinical signs, laboratory or radiological investigations were selected. Results: A total of 84 studies were identified, for which 48 were eligible for full screening and only 13 studies (n=657) met our inclusion criteria. More than 70% of patients with MIS-C tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The most common symptoms were gastrointestinal (80 to 100%) and most patients presented with fever for >4 days. Mucocutaneous manifestations are similar to Kawasaki disease presented in up to 64% in some studies. Almost all patients had significant elevations in inflammatory markers, and up to 50 to 100% had elevated troponin suggesting myocardial damage. Intravenous immunoglobulin (IVIG) was administered to 60% of patients in 12 studies and 80 to 100% in five studies. Steroids were administered to 10 to 95% of patients. The overall mortality rate was 0.9%. Conclusion: The temporal association between novel coronavirus disease 2019 (COVID-19) onset and Kawasaki-like disease and MIS-C suggests a causal link. Both syndromes have similar cascades of symptoms and hyperinflammation, which likely explain their response to the same immunomodulatory agents. However, it is unclear yet why some children appear more susceptible to develop MIS-C.

Transition readiness in adolescents with juvenile idiopathic arthritis and their parents: Our single-center experience

Objectives: We aimed to identify characteristics of juvenile idiopathic arthritis (JIA) patients associated with good self-management skills in the transition readiness process and to investigate the readiness of JIA patients and their families for the transition into the adult healthcare system. Patients and methods: Between March 2021 and June 2021, a total of 44 JIA patients (9 males, 35 females; median age: 15.1 years; range, 12.3 to 19.3 years) admitted to the pediatric rheumatology outpatient and inpatient clinics and their parents were included. Transition Readiness Assessment Questionnaire (TRAQ) was cross-culturally adapted. The TRAQ was administered to all JIA patients and their parents at one point. Demographic and clinical data were collected. Results: Fourteen (31.8%) of 44 JIA patients had a concomitant disease, while 10 (22.7%) of them had uveitis. Eleven (25%) of them had a family history of autoimmune diseases. In total, 21 (47.7%) of JIA patients were receiving biologics. There was a strong correlation between older age and total TRAQ scores among patients (ρ=0.799, p<0.001) and a moderate correlation between older patient age and total TRAQ scores among parents (ρ=0.522, p<0.001). Patient and parent total TRAQ scores were strongly correlated (ρ=0.653, p<0.001). There was no significant association of JIA patient characteristics (JIA disease subtypes, disease duration, gender, concomitant diseases, uveitis, family history of autoimmune diseases, number of hospitalizations, and treatment with biologics) with TRAQ scores and JIA patients' and parents' readiness for transition. Conclusion: Transition readiness of JIA patients increases with advancing age. There is no significant difference between transition readiness for JIA patients and their parents.

Prediction of subclinical left ventricular dysfunction by speckle-tracking echocardiography in patients with anti-neutrophil cytoplasmic antibody--associated vasculitis

Objectives: This study aims to evaluate left ventricular functions using speckle-tracking echocardiography (STE) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Patients and methods: Between June 2018 and July 2019, a total of 31 AAV patients (17 males, 14 females; median age: 53 years; range, 47 to 62 years) and 21 healthy controls (11 males, 10 females; median age: 56 years; range, 46 to 60 years) were included in the study. Clinical and biochemical characteristics of all participants were recorded. All participants underwent conventional and two-dimensional STE. The receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of serum N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) that predicted subclinical left ventricular dysfunction. The Spearman correlation analysis was used to determine the correlation between left ventricular global longitudinal strain (LV-GLS) and NT-pro-BNP. Results: The LV-GLS was lower in AAV patients (19.3% vs. 21.7%, respectively; p=0.014). NT-pro-BNP was negatively correlated with LV-GLS (p=0.005, r=0.401). Conclusion: Subclinical left ventricular dysfunction can be detected by STE in patients with AAV who have free of clinically overt cardiovascular disease. The LV-GLS is negatively correlated with serum NT-pro-BNP levels.

Measuring the impact of an educational intervention in rheumatoid arthritis: An open-label, randomized trial

Objectives: This study aims to determine whether patients with active rheumatoid arthritis (RA), either starting on or changing biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), demonstrate better self-management safety skills three months after receiving a multidisciplinary educational intervention compared to patients receiving usual care. Patients and methods: Between October 2015 and October 2018 , this open-label, randomized-controlled trial included a total of 107 RA patients (27 males, 80 females; mean age: 60.2±10.4 years; range, 54 to 71 years) who were on treatment or in whom treatment was changed with a biological or targeted synthetic DMARD. The patients were randomized into two groups: Group 1 (n=57) received additional intervention with educational DVD and one teleconference session and Group 2 (n=55) received usual care and were offered the intervention at three months. All patients underwent a final visit at six months. At each visit, the patients completed the BioSecure questionnaire measuring the self-care safety skills, a behavioral intention questionnaire, and the Beliefs about Medicines Questionnaire (BMQ). Results: No significant difference was observed in the Biosecure score at three months between the two groups (p=0.08). After pooling the first three-month data in Group 1 and the last three-month data in Group 2, the mean score of the BioSecure questionnaire increased to 7.10±0.92 in the group receiving educational intervention (p<0.0001). This increase was maintained at six months in Group 2 (p=0.88). The rate of appropriate behavioral intention increased over time (76% at baseline and 85% at six months for both groups). There was no significant change in the BMQ (p=0.44 to 0.84). Conclusion: The development of an educational DVD followed by a teleconference seem to improve self-care safety skills of the patients in practical situations.

The comparison of effects of balneotherapy, water-based and land-based exercises on disease activity, symptoms, sleep quality, quality of life and serum sclerostin level in patients with ankylosing spondylitis: A prospective, randomized study

Objectives: This study aims to compare the effects of balneotherapy, water-based exercise (WBE), and land-based exercise (LBE) on disease activity, symptoms, sleep quality, quality of life, and serum sclerostin level (SSL) in patients with ankylosing spondylitis (AS). Patients and methods: Between January 2019 and January 2020, a total of 60 patients (35 males, 25 females; mean age: 40.9±11.2 years; range, 18 to 55 years) who were diagnosed with AS were randomly divided into the balneotherapy (n=20), WBE (n=20), and LBE (n=20) groups (20 sessions of treatment in groups of five to six patients). The patients were evaluated before treatment and at 4 and 12 weeks using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Ankylosing Spondylitis Quality of Life (ASQoL) Scale, Fatigue Severity Scale (FSS), and Pittsburg Sleep Quality Index (PSQI), and SSL were measured. Results: Statistically significant improvements in the BASDAI, BASFI, MASES, BASMI, ASQoL, FSS, and ASDAS-CRP scores were observed in all groups at 4 and 12 weeks of follow-up (p<0.05). A significant improvement in sleep latency was seen in the balneotherapy and WBE groups. Changes in SSL were not statistically significant in any group (p>0.05). Conclusion: Balneotherapy, WBE, and LBE are effective in the treatment of AS, and the beneficial effects may last for at least 12 weeks.

Dysregulation of complement factor H in juvenile-onset systemic lupus erythematosus patients

Objectives: This study aims to evaluate the expression pattern of factor H in peripheral blood and the frequency of factor H autoantibodies in plasma of juvenile-onset systemic lupus erythematosus (jSLE) patients compared to healthy controls. Patients and methods: Between March 2019 and October 2019, a total of 30 healthy individuals (3 males, 27 females; mean age: 26±7.4 years; range, 18 to 40 years) and 65 jSLE patients (age of onset ≤16 years) (2 males, 63 females; mean age: 23.4±7 years; range, 15 to 38 years) were included. Factor H expression pattern was examined in blood of all subjects using quantitative real-time polymerase chain reaction and the frequency of factor H autoantibodies was estimated in plasma using enzyme-linked immunosorbent assay. Results: Factor H expression was significantly downregulated in jSLE patients compared to healthy controls (p<0.01). A significant underexpression of factor H was observed in jSLE patients with nephritis compared to those without nephritis (p<0.03), while there was no association of factor H expression levels with any of the other clinical and serological features, disease activity or disease damage index of patients. Only 5% of jSLE patients were positive for factor H autoantibodies without any correlations with the clinical data or disease activity of patients. Conclusion: Our study results suggest that factor H expression can be dysregulated in jSLE patients.

LncRNA cardiac autophagy inhibitory factor is downregulated in rheumatoid arthritis and suppresses the apoptosis of fibroblast-like synoviocytes by promoting the maturation of miRNA-20a

Objectives: In this study, we aimed to investigate the effects of LncRNA cardiac autophagy inhibitory factor (CAIF) and miR-20a on the apoptosis of synovial cells in rheumatoid arthritis (RA) and the regulatory mechanism. Patients and methods: Between May 2018 and March 2020, a total of 62 RA patients (24 males, 38 females; mean age: 55.2±4.9 years; range, 42 to 68 years) and 62 controls (24 males, 38 females; mean age: 55.3±4.8 years; range, 41 to 68 years) were included in this study. Plasma samples were collected from all participants. The expression levels of CAIF, mature miR-20a, and miR-20a precursor in these plasma samples were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Correlations were analyzed using linear regression analysis. Overexpression of CAIF was achieved in human fibroblast-like synoviocytes (HFLSs) and the expression levels of mature miR-20a and miR-20a precursor were determined using RT-qPCR. Cell apoptosis was analyzed by cell apoptosis assay. Results: The CAIF was downregulated in RA and positively correlated with the expression of mature miR-20a. In HFLSs, LPS treatment resulted in downregulation of both CAIF and miR-20a in a dose-dependent manner. In HFLSs, overexpression of CAIF did not affect the expression of miR-20a precursor, but upregulated the expression of mature miR-20a. Cell apoptosis analysis showed that overexpression of CAIF and miR-20a inhibited the apoptosis of HFLSs induced by LPS. The combination of overexpression of CAIF and miR-20a showed a stronger effect. Conclusion: The CAIF may suppress the apoptosis of HFLSs in RA by promoting the maturation of miR-20a.