Search

Objectives: Inflammatory low back pain (IBP) is a typical feature of spondylarthritis (SpA). IBP can be caused by infections, drugs, and different malignancies. Among cancers, hematologic malignancies and solid tumors can cause IBD either paraneoplastically or through metastasis. In this study, we aimed to present the demographic and clinical characteristics of our patients who presented with IBP in the last 10 years and whose final diagnosis was malignancy., Methods: Thirty-four patients who presented with inflammatory low back pain in the last 10 years and were diagnosed with malignancy as the final diagnosis were included in the study. Thirty-six patients, diagnosed as axial SpA, with similar age-sex ratio of 1:1 from each center were included as the control group., Results: Hematologic malignancies were multiple myeloma, acute leukemia, and lymphoma in descending order. Solid tumors were breast cancer, lung cancer, bone tumors, prostate, colon, embryonal carcinoma, and malignancy of unknown primary. In malignancy-related low back pain, the hematologic/solid ratio was similar (18/16), the interval between symptom and diagnosis was shorter, and biomarkers' results such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum lactate dehydrogenase (LDH) levels were significantly higher than the control group., Conclusion: Malignancy-related low back pain differs from SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. Malignancies must be kept in mind in the differential diagnosis, and in order to validate our findings, the results of larger case series are needed, especially in terms of causative malignancies. Key Points • In malignancy-related inflammatory low back pain, the hematologic/solid ratio was similar, the interval between symptom and diagnosis was shorter, and acute phase reactant levels and LDH levels were significantly higher. • Malignancy-related inflammatory low back pain differs from axial SpA patients with a more severe clinical picture, higher acute phase reactants levels, and higher LDH values. • Malignancies must be kept in mind in the differential diagnosis of axial SpA., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background : Secukinumab is a monoclonal antibody against interleukin 17 approved for patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and psoriasis. Treating axSpA and PsA patients with a history of malignancy is a challenge. While initial results on the applicability of secukinumab in this patient group are positive, the number of studies on this topic remains limited. This study aimed to investigate the drug's survival time and the efficacy and safety of secukinumab treatment in this specific patient group. Methods : This retrospective study included 30 patients with a history of malignancy who were followed up in rheumatology outpatient clinics in 12 centers throughout Turkey and treated with secukinumab between May 2018 and March 2024 with a diagnosis of axSpA and PsA. Results: The mean follow-up time was 29.8 ± 19.3 months. The drug retention rate was 89.7% after 12 months and 80.6% after 24 months. The most common tumor in our study was papillary thyroid carcinoma ( n = 5, 16.7%). During follow-up, local tumor recurrence was observed in a patient with urothelial carcinoma of the bladder. Conclusions : In the largest cohort reported to date, treatment with secukinumab in axSpA and PsA patients with a history of malignancy was not shown to cause oncologic recurrence except for one local tumor recurrence. Drug retention rates were also high, and disease activation and function improved compared to baseline. Therefore, secukinumab could be a safe and effective option for this patient group.

Objective: In this study, our objective was to present real-life data on the incidence of inflammatory bowel disease (IBD) among patients receiving secukinumab treatment., Methods: The study consisted of 209 patients who had prior exposure to anti-tumor necrosis factor (TNF) or were biologically naive. Patients with a pre-existing history of IBD were excluded from the study., Results: Of the 209 patients in the study, 176 (84.3%) had ankylosing spondylitis, while 33 (15.7%) had psoriatic arthritis. 112 (53.6%) patients had prior exposure to at least one anti-TNF treatment before initiating secukinumab. IBD developed in 10 (4.8%) of the 209 patients. The incidence of IBD among patients who initiated secukinumab as their first biologic agent was 1%. For patients who had previously received any anti-TNF treatment and subsequently transitioned to secukinumab, the incidence of IBD was 8% (p=0.018, odds ratio (OR): 8.38, 95% CI: 1.04-67.45). A mean of 3.67 months (±4.3) after anti-TNF use, whereas IBD symptoms developed in the biologically naive patient after 15 months., Conclusion: Our study observed IBD incidence in 4.8% of patients using secukinumab. Patients who initiated secukinumab after previous anti-TNF treatment exhibited a significantly higher rate and risk of developing IBD. The onset of IBD occurred earlier in these patients (mean 3.67 months), whereas a single case of IBD showed a longer duration (15 months). Further studies with larger patient numbers are warranted to provide a more comprehensive understanding of our findings., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background/aim: The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19., Materials and Methods: In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews., Results: The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively., Conclusion: This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases., (© TÜBİTAK.)

Background: To investigate the impact of smoking on disease activity, treatment retention, and response in patients with ankylosing spondylitis (AS) treated with their first tumor necrosis factor-α inhibitor (TNFi)., Methods: AS patients who started their first TNFi treatment for the active axial disease (BASDAI ≥ 4) from TURKBIO Registry were included. Treatment response of smoker (current and ex-smokers) and nonsmoker (never smoker) patients were primarily evaluated as achievement of BASDAI50 or improvement in BASDAI at least 20 mm at 3 months and 6 months compared to baseline., Results: There were 322 patients with AS (60% male, 59% smoker, mean age: 38.3 years). The median follow-up time was 2.8 years (Q1- Q3: 1.3-3.8), and disease duration was 3.5 years (Q1-Q3: 0.7-8.2). Smokers had male predominance (p < 0.001), lower ESR (p = 0.03), higher BASDAI (p = 0.02), BASFI (p = 0.05), HAQ-AS (p = 0.007), and ASDAS-CRP (p = 0.04) compared with nonsmokers at baseline. In the multivariate analysis, male gender [OR 2.7 (95%CI 1.4-5), p = 0.002], and concomitant conventional synthetic disease-modifying antirheumatic drug use [OR 2.4 (95%CI 1.1-5.2), p = 0.03] were associated with better treatment response. There was an association of male gender [HR 2.4 (95%CI 1.6-3.7), p < 0.001], older age (≥30years) [HR 1.8 (95%CI 1.1-2.8), p = 0.01], and response to treatment [HR 1.8 (95%CI 1.2-2.9), p = 0.008] with better treatment retention. No impact of smoking status was found on treatment retention and response in univariate and multivariate analyses., Discussion: This study suggested that smoking was associated with poorer patient-reported outcomes in biologic naïve AS patients initiating their first TNFi treatment, but it had no impact on the TNFi treatment response and retention rate.

Background/aim: Adipose tissue produces several inflammatory mediators. Thus, obesity affects the disease course and the responses to the antirheumatic agents in inflammatory diseases. The aim of the study was to determine whether the body mass index (BMI) is involved in the response to rituximab in rheumatoid arthritis (RA)., Materials and Methods: This multicenter retrospective study included 206 RA patients who received rituximab from the Turkish Biologic (TURKBIO) registry between 2011 and the end of May 2017. Demographic and clinical data including age, sex, disease type, disease duration, and previous or current treatment with disease-modifying antirheumatic drugs (DMARDs) and biological drug durations are stored in the database. Patients with a BMI ≥30 kg/m 2 were classified as obese, and patients with a BMI <30 kg/m 2 were classified as nonobese. Kaplan-Meier survival analysis was performed to estimate the drug survival. The subgroups were compared using the log-rank test., Results: The mean BMI of 206 patients included in the study was 27.05 (17.2-43.4) kg/m 2 . There were 59 (28.6%) patients in the obese group and 147 (71.4%) patients in the nonobese group. The mean age, female percentage, and baseline disease activity score 28 (DAS28) were higher in the obese group than in the nonobese group. However, the ΔDAS28 at both 6 and 12 months were not significantly different between the groups (p = 0.785 and p = 0.512, respectively). Patient pain Visual Analogue Scale (VAS), patient fatigue VAS, and patient global VAS scores were also significantly higher at baseline in the obese group (p = 0.003, p = 0.006, and p = 0.006, respectively). However, no significant difference was found in terms of changes in patient pain VAS, patient fatigue VAS, patient global VAS and physician global VAS scores at 6 and 12 months compared to those at baseline. Rituximab treatment was ongoing for 71.2% of the obese and 63.3% of the nonobese patients (p = 0.279). The median drug survival duration was 77 months in the obese group and 62 months in the nonobese group (p = 0.053). The estimated drug survival rates for rituximab were not statistically significantly different in the obese and nonobese groups. Rituximab-related side effects were also similar between the groups., Conclusion: In obese and nonobese patients with RA, rituximab treatment exhibits similar side effects and similar long-term efficacy. These results suggest that obesity does not alter drug survival for rituximab and response rates, in RA and rituximab may be a favorable treatment agent in patients with RA and obesity., (© TÜBİTAK.)

Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that targets the IL-6 receptor. TCZ found to be efficacious and has a good tolerated safety profile in rheumatoid arthritis (RA) patients. The aim of this study was to describe the disease activity and retention rate in Turkish RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting. Secondary data obtained from adult RA patients' files was used in a multicenter and retrospective context. Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints with ESR (DAS28-ESR), and retention rates of TCZ were evaluated at related time points. 130 patients (87.7% female) with a mean age of 53 years (SD; 15.0) were included in the study. Mean RA duration was 14 years and median duration of follow-up was 18.5 months. Number of patients with ongoing TCZ treatment at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (< 2.8) and DAS28-ESR (< 2.6) scores were 61.5, 44.6, 30%, and 54.6, 40.8, 27.7%, respectively. Both CDAI and DAS28-ESR scores significantly improved at 6, 12 and 24 months (p < 0.001 for both). At 24 months, 23 patients (17.6%) discontinued TCZ, of whom majority (17/23) were due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93, 84.3, and 72.2%, respectively. In this real-world study, TCZ as a first-line biologic therapy was found to be efficacious and showing high retention rates. These real-world study results are in line with previous randomized studies., (© 2022. The Author(s).)

Objectives: This study aimed to evaluate the hepatitis B (HBV) and C (HCV) frequency and clinical characteristics among patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who receive biological treatments., Patients and Methods: The observational study was conducted with patients from the TReasure database, a web-based prospective observational registry collecting data from 17 centers across Türkiye, between December 2017 and June 2021. From this database, 3,147 RA patients (2,502 males, 645 females; median age 56 years; range, 44 to 64 years) and 6,071 SpA patients (2,709 males, 3,362 females; median age 43 years; range, 36 to 52 years) were analyzed in terms of viral hepatitis, patient characteristics, and treatments used., Results: The screening rate for HBV was 97% in RA and 94.2% in SpA patients. Hepatitis B surface antigen (HBsAg) positivity rates were 2.6% and 2%, hepatitis B surface antibody positivity rates were 32.3% and 34%, hepatitis B core antibody positivity rates were 20.3% and 12.5%, HBV DNA (deoxyribonucleic acid) positivity rates were 3.5% and 12.5%, and antibody against HCV positivity rates were 0.8% and 0.3% in RA and SpA patients, respectively. The HBsAg-positive patients were older and had more comorbidities, including hypertension, diabetes, and coronary artery disease. In addition, rheumatoid factor (RF) positivity was more common in HBsAg-positive cases. The most frequently prescribed biologic disease-modifying antirheumatic drugs were adalimumab (28.5%), etanercept (27%), tofacitinib (23.4%), and tocilizumab (21.5%) in the RA group and adalimumab (48.1%), etanercept (31.4%), infliximab (22.6%), and certolizumab (21.1%) in the SpA group. Hepatitis B reactivation was observed in one RA patient during treatment, who received rituximab and prophylaxis with tenofovir., Conclusion: The epidemiological characteristics of patients with rheumatic diseases and viral hepatitis are essential for effective patient management. This study provided the most recent epidemiological characteristics from the prospective TReasure database, one of the comprehensive registries in rheumatology practice., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

Objectives: The study aimed to investigate the variation of brain-derived neurotrophic factor (BDNF) levels following acute exercise in patients with rheumatoid arthritis (RA)., Patients and Methods: This cross-sectional study was conducted with 88 participants (25 males, 63 females; mean age: 45.1±8.3 years; range, 18 to 65 years) between July 2020 and May 2021. Of the participants, 44 were RA patients, and 44 were age-and sex-matched healthy controls. Aerobic exercise was utilized in all participants for a single session. Depression and anxiety levels were evaluated with the Beck Depression Inventory and Hospital Anxiety and Depression Scale. Blood samples were collected from all subjects before and immediately after the intervention., Results: Serum BDNF levels (both baseline and after exercise) were similar in the RA and control groups. Although serum BDNF levels significantly decreased in both groups after aerobic exercise (Wilcoxon rank p<0.05), ΔBDNF levels were significantly higher in the RA group than in the control group (p=0.047). Additionally, ΔBDNF levels were significantly correlated with the Hospital Anxiety and Depression Scale scores in the RA group (p<0.05) but not in the control group., Conclusion: A single bout of exercise may effectively decrease serum BDNF levels in patients with RA and healthy subjects. The long-term effect of exercise on BDNF levels should be investigated in prospective studies., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The coronavirus disease 2019 pandemic has been resulting in increased hospital occupancy rates. Rheumatic patients cannot still reach to hospitals, or they hesitate about going to a hospital even they are able to reach. We aimed to show the effect of the first wave of coronavirus disease 2019 pandemic on the treatment of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis or spondyloarthritis., Methods: Patients were divided into three groups as follows: pre-pandemic (Pre-p: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within 6 months before March 11, 2020); post-pandemic A (Post-p A: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the first 6 months after March 11, 2020); post-pandemic B (Post-p B: starting on biological disease-modifying anti-rheumatic drug therapy for the first time within the second 6 months)., Results: The number of rheumatoid arthritis patients in the Post-p A and B groups decreased by 51% and 48%, respectively, as compared to the Pre-p group similar rates of reduction were also determined in the number of spondyloarthritis patients. The rates of tofacitinib and abatacept use increased in rheumatoid arthritis patients in Post-p period., Conclusion: The number of rheumatoid arthritis and spondyloarthritis patients starting on biological disease-modifying anti-rheumatic drugs for the first time decreased during the first year of the coronavirus disease 2019 pandemic.

Objectives: Achilles tendinopathy can be noticed in both acromegaly and ankylosing spondylitis (AS). Acromegaly patients presenting with tendinopathy findings may be confused with AS findings. In this study, sonoelastrographic findings of Achilles tendon are explored in patients with AS and acromegaly., Methods: 25 patients with AS, 30 patients with acromegaly, and 18 healthy controls were enrolled in the study. Achilles tendon was evaluated by sonoelastography in all the study participants., Results: The thickness of Achilles tendon in neutral positions was higher in acromegaly patients than those in AS patients. The sonoelastography measurement of Achilles tendon was increased in acromegaly patients when compared to the control group and AS patients., Conclusion: The thickness of Achilles tendon can increase in patients with acromegaly and AS. However, the sonoelastographic features of Achilles tendon can be similar in patients with AS and acromegaly.

Objective: The aim of this study is to examine the changes in physical activity level, fatigue, depression, and sleep quality in patients with Behçet's disease during the COVID-19 pandemic., Methods: The study was designed as an online questionnaire applied to individuals who are being followed up with the diagnosis of Behçet's disease in the rheumatology department. Data were collected using multiple scales including International Physical Activity Questionnaire (IPAQ), Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), Pittsburg Sleep Quality Index (PSQI), and Visual Analogue Scale (VAS) to evaluate physical activity level, fatigue, depression, sleep quality, and pain, respectively., Results: Sixteen patients diagnosed with Behçet's disease were included in the study. No statistically significant difference was observed between the IPAQ, FSS, BDI, PSQI, and VAS assessment scores before COVID-19 and during COVID-19 period (P > .05 for all)., Conclusion: Thinking of the negative effects of aggressive clinical symptoms, Behçet's disease patients should be supported in physical activity and psychosocial status.

Objectives: This study aims to define serum levels of netrin-1 and netrin receptors in patients with fibromyalgia (FM) and osteoarthritis (OA)., Patients and Methods: This cross-sectional study was conducted with a total of 150 female participants (mean age: 47.2±16.1 years; range, 18 to 89 years) at Fırat University between June 2016 and December 2016. The participants were evaluated in three groups: the FM group with 50 patients, the OA group with 50 patients, and the control group, which included 50 healthy volunteers. Netrin-1, netrin receptors (DCC, UNC5B, and UNC5D), interleukin (IL)-6, IL-10, and IL-17 levels were analyzed by the enzyme-linked immunosorbent assay from the serum samples of the participants., Results: The level of serum netrin-1 was significantly lower in the FM group than in the control and OA groups (p<0.01 and p<0.001, respectively). However, the difference between patients with OA and healthy controls in terms of netrin-1 was not statistically significant (p>0.05). In addition, serum levels of netrin receptors and cytokines in the FM group were similar to the control group (p>0.05). However, serum DCC, UNC5D, IL-6, and IL-10 levels were higher in the OA group compared to the control group (p<0.001, p<0.05, p<0.01, and p<0.001, respectively)., Conclusion: Serum netrin-1 level is suppressed in FM, which suggests that netrin-1 is influential in FM pathogenesis., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2022, Turkish Society of Physical Medicine and Rehabilitation.)

Objective: TURKBIO registry, established in 2011, is the first nationwide biological database in Turkey. This study aimed to provide an overview of TURKBIO data collected by June 2018., Methods: The registry included adult patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-AxSpA), and psoriatic arthritis (PsA). Demographic and clinical features, disease activity markers, and other follow-up parameters, current and previous treat- ments, and adverse events were registered electronically at each visit using open-source software. The registration of patient-reported outcome measures was carried out electronically by the patients using touch screens., Results: TURKBIO registry included a total of 41,145 treatment series with biologicals. There were 2,588 patients with axSpA (2,459 AS and 129 nr-axSpA), 2,036 with RA, and 428 with PsA. The total number of patients, including those with other diagnoses, was 5,718. In the follow-up period, the number of patients and also visits steadily increased by years. The yearly mean number of visits per patient was found to be 2.3. Significant improvements in disease activity and health assessment parameters were observed following the biological treatments. Biologics were often given in combination with a con- ventional synthetic disease-modifying antirheumatic drug in patients with RA. Infections were the most commonly seen adverse events, followed by allergic reactions. Tuberculosis was observed in 12 patients, malignancy in 18, and treatment-related mortality in 31., Conclusion: TURKBIO provided a valuable real-life experience with the use of biologics in rheumatic diseases in Turkey.

Objective: The knowledge of physicians about complementary and alternative medicine (CAM) applications is limited. However, especially in chronic diseases, patients and their relatives can often refer to CAM applications. Rheumatic diseases are chronic in nature presenting with a wide clinical spectrum. Despite developing treatment options, achieving treatment goals may not always be possible. For this reason, patients seek different treatment and use traditional and complementary medicine. The aim of this study was to investigate causes, consequences, and the frequency of applying to CAM in rheumatic diseases., Methods: Ninety-five patients admitted to the rheumatology outpatient clinic were enrolled in the study. Health assessment questionnaire and short-form-36 were used to determine the quality of life of patients. Anxiety and depression symptoms were screened by the Hospital Anxiety and Depression scale, a questionnaire that was filled-in by the patients themselves. Also, patients were questioned about their place of residence, level of education, diagnosis, CAM modality types, application reasons, and outcomes. Chi-square test was used to analyze categorical data. Parametric data were analyzed using Student t-test, and nonparametric data were analyzed using Mann-Whitney U test., Results: Thirty-two of our patients had applied to CAM modalities (phytotherapy [34.45%], cupping therapy [21.8%], acupuncture [12.5%], hirudotherapy [12.5%], food supplement [12.5%], and ozone treatment [6.25%]). Only 31.3% of the patients informed their doctors about CAM applications. 47.8% of fibromyalgia patients and 29.2% of patients with inflammatory rheumatic diseases had applied to CAM. Gender, working status, income level, smoking, and alcohol habits were not associated with the application to CAM. However, none of the residents of the village, 14.3% of the residents of the district center, and 41.1% of the residents of the city center had applied to CAM modality. The rate of applying to CAM was 18.2% for those who cannot read and write. The application ratio of CAM is over 40% among secondary school, high school, and university graduates., Conclusion: Among patients with rheumatic diseases, application to CAM is quite common. Very few patients inform their physicians about applying to CAM. Contrary to what is presumed, the rate of applying CAM applications is lower among those living in rural areas and with low education levels.

Objective: To compare the clinical features, laboratory findings, and prognosis of Behçet's disease (BD) patients with and without Budd-Chiari syndrome (BCS)., Methods: This multicenter retrospective study investigated 61 (M/F: 41/20) patients with BD, having coexistent BCS, and 169 (M/F:100/69) BD patients as the control group without BCS from 22 different centers of Turkey diagnosed between 1990 and 2017., Results: Of the total 61 BD patients with BCS, the onset of the first symptom and the median age of diagnosis were earlier in contrast to BD patients without BCS (p = 0.005 and p = 0.007). Lower extremity deep vein and inferior vena cava (IVC) thrombosis were more common in patients with BCS (all; p < 0.01) compared to the control group. Mortality was significantly higher in BD-BCS patients with IVC thrombosis than in the controls (p = 0.004). Since most of the cases in our cohort had chronic and silent form of BCS, mortality rate was 14.8%, which was on the lower range of mortality rate reported in literature (14-47%). While all BD-BCS patients received immunosuppressive (IS) agents, only half of them received additional anticoagulant treatments. Among IS agents, interferon treatment was more frequently used in this cohort (19%), compared to other series reported in literature (2.3%)., Conclusion: To our knowledge, this is the largest series of BD patients with BCS. Our patients had earlier disease onset and diagnosis, higher frequency of IVC thrombosis, and higher mortality rate, compared to BD patients without BCS. Mortality was significantly higher in BD-BCS patients with IVC thrombosis compared to controls. Key Points • Mortality rate is higher in BD-associated BCS patients with IVC involvement. • Chronic and silent form of BD-associated BCS has a better prognosis. • The main treatment options are corticosteroids and immunosuppressive agents, whereas anticoagulant treatment remains controversial., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objective: Rheumatoid arthritis (RA) is a disabling inflammatory disorder. Ginger is used for food and medicine to treat arthralgia, sprains, and muscle aches. Anti-inflammatory effects of ginger have been observed. The aim of our study was to detect the effects of ginger on experimentally induced inflammatory arthritis., Methods: Female Wistar albino rats (n = 21) were randomly separated into three groups (control, arthritis, and arthritis + ginger). Arthritis was generated by an appropriate method using type 2 collagen and Freund's adjuvant (collagen-induced arthritis model). The ginger group was treated starting at the first collagen injection with ginger root extract for 32 days by oral gavage (50 mg/kg/daily). Interleukin (IL)-6, IL-17, tumor necrosis factor-α (TNF-α), sclerostin, dickkopf-related protein-1 (DKK-1), and obestatin serum levels were studied by enzyme-linked immunosorbent assay method. Tissue TNF-α, IL-17, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) levels were detected using the Western blot method., Results: Mean arthritis score and serum levels of TNF-α, IL-6, and IL-17 were significantly decreased in ginger group than in the arthritis group. Increased sclerostin serum level and decreased DKK-1 serum levels were detected in ginger group compared with arthritis group. The decreases of IL-17, TNF-α, COX-2, and NF-κB tissue levels were statistically significant in the ginger group compared with arthritis group. Histopathological evaluation of the ginger group showed a decrease in the inflammation score compared to arthritis group., Conclusion: It can be concluded that ginger has protective properties in the development of inflammatory arthritis. The antiarthritic acts of ginger are related to NF-κB activity and Wnt pathway. Thus, it may be suggested that ginger is a candidate to research in human RA treatment.

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings., Materials and Methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP –1, –3, and –13 levels in FLSs culture were determined by ELISA., Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP –1, –3, and –13 expressions from FLSs induced by IL-1β and TNF-α were increased, while dasatinib suppressed their productions from FLSs., Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aim: To evaluate treatment adherence and predictors of drug discontinuation among patients with inflammatory arthritis receiving bDMARDs within the first 100 days after the announcement of the COVID-19 pandemic., Materials and Methods: A total of 1871 patients recorded in TReasure registry for whom advanced therapy was prescribed for rheumatoid arthritis (RA) or spondyloarthritis (SpA) within the 3 months (6–9 months for rituximab) before the declaration of COVID-19 pandemic were evaluated, and 1394 (74.5%) responded to the phone survey. Patients’ data regarding demographic, clinical characteristics and disease activity before the pandemic were recorded. The patients were inquired about the diagnosis of COVID-19, the rate of continuation on bDMARDs, the reasons for treatment discontinuation, if any, and the current general disease activity (visual analog scale, [VAS])., Results: A total of 1394 patients (493 RA [47.3% on anti-TNF] patients and 901 SpA [90.0% on anti-TNF] patients) were included in the study. Overall, 2.8% of the patients had symptoms suggesting COVID-19, and 2 (0.15%) patients had PCR-confirmed COVID-19. Overall, 18.1% of all patients (13.8% of the RA and 20.5% of the SpA; p = 0.003) discontinued their bDMARDs. In the SpA group, the patients who discontinued bDMARDs were younger (40 [21–73] vs. 44 years [20–79]; p = 0.005) and had higher general disease activity; however, no difference was relevant for RA patients., Conclusion: Although the COVID-19 was quite uncommon in the first 100 days of the pandemic, nearly one-fifth of the patients discontinued bDMARDs within this period. The long-term effects of the pandemic should be monitored., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aim: Sjögren’s syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/β-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS., Materials and Methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically., Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group., Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/β-catenin pathway activities may be altered in case of glandular inflammation., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Purpose: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients., Design: Retrospective cohort study., Methods: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded., Results: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both)., Conclusion: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine the real-life efficacy, safety, and drug-retention rates of leflunomide (LEF) or methotrexate (MTX) as a synthetic DMARD used in combination with biological DMARDs for rheumatoid arthritis (RA)., Methods: The TReasure database is a web-based, prospective, observational cohort of RA and spondyloarthritis patients from 17 centres in different regions of Turkey and data entry was enabled since December 2017. Until May 2019, 2556 RA patients on biologic treatment were recorded. Demographic and RA-related data of 1526 patient either received LEF or MTX were compared, efficacy of both drugs compared by RA-disease activity composite indices. Reasons fordrug discontinuation also recorded. Drug retention rates were compared with Kaplan-Meier curves (log-rank test)., Results: Of 2556 RA patients 1526 (59.7%) were receiving concomitant LEF (n=646, 42.3%; median follow up 35 months) or concomitant MTX (n=880, 57.3%; median follow-up 32 months) at the time of initiation to their first bDMARDs. The LEF group were older and had longer disease duration, proportion of females and seropositive patients was higher in this group. In the LEF group, non-anti-TNF agents were used in higher rate. Remission rates, changes in composite indices and rate of comorbidities and adverse events were similar in both groups. The retention rate of LEF + non-anti-TNF b/tsDMARDs was higher compared to MTX + anti-TNF bDMARDs (p=0.002, log-rank). Rates of adverse events were similar in both groups., Conclusions: LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.

Objectives: This study aims to evaluate the effects of ocrelizumab (OCZ) on familial Mediterranean fever (FMF) attacks in multiple sclerosis (MS) patients with FMF (MS+FMF patients)., Patients and Methods: This retrospective observational study included 11 patients (2 males, 9 females; mean age 46.6±9.2; range, 22 to 55 years) with MS+FMF hospitalized between January 2016 and July 2019. Demographic, clinical, and laboratory parameters and patient reported outcomes were analyzed in patients treated with OCZ for 18 months., Results: Combining OCZ with colchicine in MS+FMF patients significantly reduced the frequency of FMF attacks (p=0.003) and the frequency of joint attacks (p=0.002). Consistent with the clinical improvement, the maximum serum C-reactive protein levels were significantly decreased after combination therapy compared to before combination therapy (p=0.003). MS+FMF patients reported that FMF disease activity improved after OCZ therapy (Visual Analog Scale [VAS] 74±9.6 vs. VAS 46.5±8.1 mm, p=0.003)., Conclusion: Ocrelizumab therapy led to a prominent decrease in the frequency of FMF attacks, alleviated functional impairment, and improved quality of life in MS+FMF patients., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021, Turkish League Against Rheumatism.)

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis., Materials and Methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund’s adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed., Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws., Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis., Competing Interests: The authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objective: Secukinumab, a new treatment agent, selectively neutralizes interleukin (IL)-17A. It is used in the treatment of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. It is known that the agents used in the treatment of rheumatic diseases have effects on hematological parameters. In this study, we aimed to determine whether hematological parameters are affected in secukinumab therapy in patients with AS and PsA., Methods: Thirty-six patients on secukinumab treatment were included in the study by scanning the database of our hospital. Data on patients' age, gender, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), uric acid, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine values, and additional drug treatments were recorded from our database. The 0- and 6-month values of patients were analyzed., Results: Sixteen males (44.4%) and 20 females (55.6%) were included in our study. The average age was calculated to be 39.8±8.9 years. Of these, 30 patients receiving secukinumab treatment were diagnosed with AS, and 6 patients were diagnosed with PsA. Twenty-three patients (63.9%) were continued with secukinumab treatment at the 6th month. When CBC, glucose, urea, creatine, AST, ALT, ESR, CRP, and uric acid values of the patients at 0 and 6 months were compared, there was no significant difference., Conclusion: In our study, no significant difference was found between 0 and 6 months in terms of CBC, AST, ALT, urea, creatinine, uric acid, glucose, CRP, and ESR levels in patients receiving secukinumab. However, an increase in hemoglobin values was observed in patients who continued the treatment. These results may suggest that secukinumab treatment has no negative effects on hematological parameters.

Background/aim: The Wnt/ß-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 μg/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/ß-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/ß-catenin pathway. Paricalcitol and the Wnt/ß-catenin pathway are candidates for research in human rheumatoid arthritis., (CC-BY 4.0)

Background/aim: The TReasure registry, created in 2017, is an observational multicenter cohort that includes inflammatory arthritis patients. This article reviews the methodology and objectives of the TReasure registry established to collect data from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients., Methodology: Fifteen rheumatology centers in Turkey will contribute data to the TReasure database. The actual proprietor of the database is the Hacettepe Rheumatology Association (HRD) and Hacettepe Financial Enterprises. Pharmaceutical companies that operate in Turkey (in alphabetical or er), Abbvie, Amgen, BMS, Celltrion Healthcare, Novartis, Pfizer, Roche, and UCB, support the TReasure registry. TReasure is a web-based database to which users connect through a URL (https://www.trials-network.org/treasure) with their unique identifier and passwords provided for data entry and access. TReasure records demographic and clinical features, comorbidities, radiology and laboratory results, measures of disease activity, and treatment data., Discussion: TReasure will provide us with various types of data, such as a cross-sectional view of the current nationwide status of the patients currently receiving these treatments, and retrospective data as much as allowed by the participating centers’ records. Finally, a high-quality prospective dataset will be built over the ensuing years from patients with a new diagnosis of RA or SpA.

Background/aim: Insulin-like growth factor (IGF)-I is a differentiation and growth factor. Antifibrotic action of octreotide has been reported in pulmonary fibrosis. The present study aimed to research the prophylactic and therapeutic potential of octreotide on a bleomycin (BLM)-induced experimental scleroderma model., Materials and Methods: Sixty Balb/c female mice were divided into 6 groups. Daily subcutaneous BLM (100 μg) was injected for 3 weeks in groups II and III and for 6 weeks in groups V and VI. Octreotide (100 μg/kg per day) was injected subcutaneously for the first 3 weeks in group III (prophylactic) and the second 3 weeks in group VI (therapeutic). Mice in groups I, II, and III were sacrificed at the end of the third week, while mice in groups IV, V, and VI were sacrificed at the end of the sixth week., Results: Repeated BLM applications increased dermal inflammatory cell counts and dermal thickness, and led to dermal fibrosis at both the third and sixth weeks. Moreover, mRNA expressions of TGF-β1 and IGF binding protein (IGFBP)-3 and -5 were higher in the BLM- injected sham groups. On the other hand, IGFBP-3 and -5 mRNA expressions were significantly decreased in both the prophylactic and therapeutic octreotide groups. Similarly, octreotide decreased dermal inflammatory infiltrations and dermal thickness., Conclusion: Octreotide has antifibrotic actions on experimentally induced dermal fibrosis. It can be suggested that IGF-I plays pathogenic roles, and octreotide is a candidate for research in the treatment of scleroderma.

Swelling in the salivary glands, particularly parotid glands, is observed in approximately one third of Sjögren's syndrome patients. However, such patients should be assessed in terms of causes such as malignancies, infections, amyloidosis, sarcoidosis, and other autoimmune diseases when parotid gland swelling is noted. It should be considered that the incidence of lymphoma increases in Sjögren's syndrome. Unilateral parotid swelling, especially if accompanied by severe pain and redness, should be monitored for suppurative bacterial infections. Brucellosis is a systemic disease that may involve one or multiple organs. It can appear with different clinical manifestations and nonspecific symptoms. Although local abscess formations secondary to brucellosis in different organs have been reported, no evidence for parotid involvement has yet been reported. In this study, a case with primary Sjögren's syndrome and parotid abscess secondary to brucellosis is presented.

Background/aim: The pathogenesis of Raynaud's phenomenon (RP) has not yet been fully elucidated. RP is characterized by exaggerated cold-induced vasoconstriction. Urotensin II (UII) is a potent vasoconstrictor. The aim of the present study was to evaluate plasma UII levels in both primary RP and secondary RP associated with systemic sclerosis (SSc).Materials and methods: Fifteen patients with primary RP, 30 patients with RP secondary to SSc, and 30 healthy controls (HC) were included in the study. Raynaud condition scores (RCS) were determined in the primary RP and SSc groups. Modified Rodnan skin score (MRSS) was determined for the SSc patients. Plasma UII level was analyzed by the ELISA method. Results: When compared to the HC group, plasma UII level was lower in the secondary RP group, but not in the primary RP group. Plasma UII level was not directly related to RCS in either the primary or secondary RP group. Moreover, it was not correlated with MRSS in the secondary RP group.Conclusion: The results of the present study suggest that UII is not associated with primary RP. Its level was lower in the secondary RP (SSc) patients. Therefore, it can be concluded that decreased UII level is related to SSc instead of RP.

Objectives: This study aims to examine the effects of sorafenib on a collagen-induced arthritis model., Materials and Methods: The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis., Results: Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone., Conclusion: Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Objectives: This study aims to determine the prophylactic and therapeutic efficacy of inhibition of Wnt/β-catenin signaling pathway with paricalcitol in an experimental scleroderma model created with bleomycin (BLM)., Materials and Methods: Sixty female BALB/c mice (8-week old and weighing 25 g to 30 g) were divided into six groups as prophylactic-early [group 1 (control I)], sham I (group 2), paricalcitol I (group 3), therapeutic-late [group 4 (control II)], sham II (group 5), and paricalcitol II (group 6) groups. Subcutaneous BLM (100 μg/day) injections were used to induce dermal fibrosis and paricalcitol (0.3 μg/kg/day) was applied subcutaneously to BLM-injected mice during the first three weeks for preventive interventions and in the second three weeks for therapeutic interventions. Tissue samples were harvested for subsequent pathological and real-time polymerase chain reaction analysis. Tissue transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions were determined by real-time polymerase chain reaction., Results: Repeated BLM applications increased the dermal inflammatory cell infiltration and dermal thickness, and led to dermal fibrosis, in both early and late stages. Similarly, transforming growth factor-beta 1, axin-1, and Wnt-2 expressions were significantly increased in the sham groups compared to the own control group (p<0.05 for all). Contrarily, prophylactic and therapeutic paricalcitol applications decreased the transforming growth factor-beta 1, axin-1, and Wnt-2 messenger ribonucleic acid expressions compared to the own sham group (p<0.05 for all). In addition, the regressions in dermal necro-inflammation and dermal fibrosis on pathological views were also observed in the paricalcitol applied groups., Conclusion: In this model, increased axin-1 and Wnt-2 messenger ribonucleic acid expressions suggest that Wnt/β-catenin pathway is active in dermal fibrosis., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Background/aim: Inflammatory back pain, spinal stiffness, and limited spinal mobility are characteristic features of ankylosing spondylitis (AS). Sleeping postures can affect and/or reflect sleeping disturbances. The aim of the study was to evaluate sleeping postures and sleep disturbances in patients with AS. Materials and methods: Seventy-seven patients with AS and 49 healthy controls were enrolled. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were applied to both groups. The most common sleeping postures were noted. Results: There was no significant difference between the groups in terms of sleeping postures. Total PSQI and ISI scores were higher in the AS group than in the controls (P = 0.004 and P = 0.038, respectively). The selection of sleeping postures of active and inactive patients were similar. The number of pillows used was not the same in the AS and control groups (P = 0.016). The frequency of customized bed use was higher in the AS group compared to the control group (P = 0.004). Conclusion: Sleep disturbances are more of a problem in patients with AS compared to healthy patients and in active AS patients compared to inactive ones. However, sleeping postures do not seem to affect either sleep disturbances or disease activity in patients with AS.

Background/aim: Gemcitabine (GEM) has antiproliferative effects on lymphocytes, which are potent pathogenic actors of rheumatoid arthritis (RA). The aim of the study was to investigate the therapeutic potential of GEM on collagen-induced arthritis (CIA)., Materials and Methods: Arthritis was induced by the intradermal injection of chicken type II collagen with incomplete Freund's adjuvant into albino Wistar rats. Doses of 5 and 20 mg/kg GEM were administered twice a week after the 14th day, which marked the onset the arthritis. Serum IL-17, TNF-α, malondialdehyde, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels and tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels were analyzed., Results: Histopathologically prevalent inflammation and cartilage/bone destruction were observed in the arthritis group. Moreover, in the arthritis group serum IL-17, TNF-α, and malondialdehyde levels were significantly increased while catalase, SOD, GPx, HO-1, and Nrf2 levels were significantly decreased. However, in the GEM-treated groups, decreased TNF-α, IL-17, and malondialdehyde levels; increased SOD, catalase, GPx, Nrf2, and HO-1 levels; and ameliorated perisynovial inflammation and cartilage/bone destruction were observed., Conclusion: GEM suppresses cytokine levels and enhances antioxidant activity. It also prevents cartilage/bone destruction in the CIA model. GEM may be a viable candidate for research into the treatment of RA.

Objective: Sirtuins (SIRTs) play a prominent role in metabolism, apoptosis, aging, inflammation, and epigenetics. Inflammation, apoptosis, and epigenetics are pathogenic issues in rheumatoid arthritis (RA). This study aimed to evaluate SIRT2 and SIRT3 mRNA expressions in patients with RA., Material and Methods: Fifty-four patients with RA and 26 healthy controls were enrolled. Disease activity was determined using the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (score of >2.6 was considered to be active). SIRT2 and SIRT3 mRNA expressions in the extracellular plasma were investigated by real-time PCR., Results: SIRT3 mRNA expression was higher in the RA group than in the healthy control group (4.64 fold, p<0.001), whereas SIRT2 mRNA expression was relatively lower in the RA group than in the healthy control group (0.55 fold, p=0.109). However, SIRT2 (1.73 fold, p=0.065) and SIRT3 (3.58 fold, p=0.051) mRNA expressions were relatively higher in patients with active RA than in those with inactive RA., Conclusion: In RA, SIRT3 mRNA expression is increased, whereas SIRT2 mRNA expression is decreased. Conversely, SIRT2 and SIRT3 mRNA expressions increase in active RA. Therefore, the fate of each SIRT may differ in RA., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Objective: Chronic inflammatory diseases are associated with altered body composition. Ghrelin has anti-inflammatory effects, and its level is altered in obesity and inflammatory diseases. The aim of the study was to evaluate the prevalence of obesity and ghrelin and obestatin levels in patients with Behçet's disease (BD)., Material and Methods: One hundred and forty-three (143) patients with BD and 112 healthy controls (HC) were enrolled. Participants were subdivided according to the body mass index (BMI) as lean (<18.5 kg/m 2 ), normal weight (18.5-24.9 kg/m 2 ), overweight (25-29.9 kg/m 2 ) and obese (≥30 kg/m 2 ). In addition to the routine evaluations (fasting blood glucose, lipid profile, and kidney and liver function tests), serum acylated-ghrelin (AG), unacylated-ghrelin (UAG), total ghrelin (TG) and obestatin levels were analyzed. Student's t-test and chi-square test were used for statistical analysis., Results: The prevalence of obesity was relatively lower in the BD group than in the HC group (12.6% vs. 20.5%, p=0.089). Serum ghrelin levels were similar in the BD and HC groups (p>0.05 for all) although the obestatin level was higher in the BD group compared to the HC group (p<0.001). Serum UAG, TG and obestatin levels were lower in obese BD patients (n=18) than non-obese BD patients (p=0.027, p=0.014 and p=0.001, respectively)., Conclusion: The obestatin level was high and the prevalence of obesity was low in the BD group. Moreover, obese BD patients had low obestatin levels. These results suggest that obestatin may protect BD patients from obesity., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Objective: Increased carotid arterial stiffness (CAS) is a predictor of subclinical early atherosclerosis as well as carotid intima-media thickness (cIMT). We aimed to determine CAS and cIMT in Behçet's disease (BD)., Material and Methods: BD (n=49) and rheumatoid arthritis (RA) (n=64) patients and healthy controls (HC) (n=40) were included in the study. cIMT was measured. CAS indices, including arterial compliance (AC), arterial distensibility (AD), Young's elastic modulus (YEM), Peterson's elastic modulus (Ep), and β stiffness index (βSI) were measured based on the diameter-pressure relationship., Results: When compared to the HC group, the mean cIMT was significantly higher in the RA group (p=0.033), but it was not higher in the BD group. The CAS indices, including AD, AC, Ep, and βSI were not significantly different among the study groups. Moreover, the cIMT and CAS indices were not significantly different between active (n=20) and inactive BD patients, and these indices were not correlated with the scores of disease activity. AD, AC and Ep were significantly lower in the BD patients with a positive pathergy reaction than in those with a negative reaction., Conclusion: These results suggest that BD does not directly lead to arterial stiffness or to an increase in cIMT., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Objective: Fibromyalgia (FM) is a chronic disease characterized by widespread pain. Somatic complaints associated with the cardiovascular system, such as chest pain and palpitations, are frequently seen in FM patients. P and QT dispersions are simple and inexpensive measurements reflecting the regional heterogeneity of atrial and ventricular repolarization, respectively. QT dispersion can cause serious ventricular arrhythmias. The aim of the present study was to evaluate QT dispersion and P wave dispersion in patients with FM., Material and Methods: The study involved 48 FM patients who fulfilled the established criteria and 32 healthy controls (HC). A standard 12-lead electrocardiogram was performed on all participants. QT dispersion was defined as the difference between the longest and the shortest QT intervals. Similarly, the differences between the shortest and longest P waves were defined as P wave dispersion., Results: The QT dispersion and corrected QT dispersion were shorter in the FM group compared with the HC group (p<0.001 for both). In terms of the P wave dispersion value, there was no significant difference between the FM and HC groups (p=0.088)., Conclusion: Longer QT and P wave dispersions are not problems in patients with FM. Therefore, it may be concluded that fibromyalgia does not include an increased risk of atrial and/or ventricular arrhythmias., Competing Interests: No conflict of interest was declared by the authors.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality., Objectives: The present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti-tumor necrosis factor (TNF) treatment on sleep quality and pattern., Methods: Fifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns., Results: When compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality., Conclusions: Sleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.

Background: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD., Methods: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission., Results: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course., Conclusion: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Genistein, a phytoestrogen, has anti-oxidant, anti-inflammatory, and anti-angiogenic properties. The aim of the present study is to evaluate the protective effect of genistein in bleomycin (BLM)-induced dermal fibrosis., Material and Methods: This study involved four groups of Balb/c mice (n=10 per group). Mice in three groups were administered BLM [100 μg/day in 100 μL phosphate-buffered saline (PBS)] subcutaneously for 4 weeks; the remaining (control) group received only 100 μL/day of PBS subcutaneously. PBS or BLM was injected into the shaved upper back. Two of the BLM-treated groups also received genistein (1 or 3 mg/kg/day, subcutaneously, to the dorsal front of neck). At the end of the fourth week, all mice were sacrificed and blood and tissue samples were obtained., Results: The BLM applications increased the dermal thicknesses, tissue hydroxyproline contents, α-smooth muscle actin-positive cell counts, and led to histopathologically prominent dermal fibrosis. The genistein treatments decreased the tissue hydroxyproline contents and dermal thicknesses, in the BLM-injected mice., Conclusion: Genistein has antifibrotic potential in BLM-induced dermal fibrosis model. However, its therapeutic potentials on human scleroderma require evaluation in future studies.

Objective: Bone scintigraphy is a highly sensitive method in the evaluation of sacroiliitis. Aim of this study is firstly to evaluate interobserver variation of partial and whole sacroiliac indicis, secondly investigation of clinical importance of these indicis in the diagnosis of sacroiliitis., Methods: Fourty-six subjects (24 female: 35.4±11.9; 22 male: 43.1±12.4) without sacroiliitis 45 subjects with low back pain (33 female: 43.3±11.5, 11 male: 35.5±17.2) were included in the study. For right (R) and left (L) whole indices (WSI) irregular region of interest (ROI), for partial indices superior (S) and inferior (I) rectangular ROI were used. For background activity, rectangular ROI was drawn from the sacral region. Indices were calculated from ratio of average counts of sacroiliac and background regions. Two independent observers calculated sacroiliac indices. Interobserver agreement was evaluated by Pearson analysis., Results: There was no significant interobserver difference (p>0.05). Significant correlation existed between all calculated indices. Among 45 patients with suspicion of sacroiliitis 15 had final diagnosis of sacroiliitis and all of the Tc-99m methilenediphosphonate planar and SPECT bone scintigraphy results of these patients were concordant with sacroiliitis. There were 8 false positive results in other 30 patients. Seven of these eight patients had normal index values. If the scintigraphy would be evaluated in conjuction with indicis the specificity would increase from 73% to 97% but sensitivity decreases from 100% to 80%. There was significant correlation between the observers calculated indicis (p<0.001)., Conclusion: Superior and inferior sacroiliac index values can be used with confidence. If we use sacroiliac index values to confirm positive results; index values can increase the specificity of bone scintigraphy.

Objective: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), chronic inflammatory diseases, demonstrate an increased incidence of cardiovascular manifestations and subclinical atherosclerotic disease. Salusin-α is a novel bioactive peptide that suppresses the formation of macrophage foam cells, and its serum level is significantly lower in patients with angiographically proven coronary artery disease. The aims of the study were to assess serum salusin-α level and its potential association with the predictors of atherosclerosis in SLE and SSc., Material and Methods: The study included 20 SLE and 22 SSc patients and 23 healthy controls (HC). All of the participants were female. Tumour necrosis factor-α (TNF-α), IL-6 and salusin-α levels, homeostasis model assessment for insulin resistance (HOMA-IR) index and common carotid intima-media thickness (IMT) were determined., Results: Salusin-α levels were lower and the IMTs were higher in the SLE and SSc groups than in the HC group. The salusin-α level was correlated with neither the disease activity scores nor cytokine levels and IMT in the SLE and SSc groups, although it was correlated with triglyceride level in the SLE group (r=-0.564, p=0.012), and with HOMA-IR index in the HC group (r=0.485, p=0.019)., Conclusion: The present preliminary study may support the idea that SSc leads to subclinical atherosclerosis, as in SLE. Moreover, it can be concluded that the decreased salusin-α levels in SLE and SSc may contribute to subclinical atherosclerosis. However, further studies with larger sample size are needed to demonstrate this contribution in SLE and SSc.

The involvement of the autonomic nervous system is less common than that of the central and peripheral nervous system in systemic lupus erythematosus (SLE) patients. However, its involvement can negatively affect the quality of life of the patient and cause life-threatening situations. In this study, autonomic function was evaluated in SLE patients who did not show any sign of autonomic involvement using R-R interval variation (RRIV) and sympathetic skin response (SSR) electrophysiological tests. SSR was used to evaluate the sympathetic nervous system, whereas RRIV was used for the parasympathetic nervous system. We included 23 SLE patients and 21 healthy volunteers in the study. Of the 23 SLE patients, 20 (86.9 %) were female and 3 (13.1 %) were male. The age range of the patients was between 19 and 52 years, with a mean age of 32.5 ± 9.1 years. Routine nerve conduction studies and autonomic tests were performed on patients in the electromyography (EMG) laboratory. Lower extremity SSR latencies were prolonged and a significant loss of amplitude was observed in comparison to the control group. Furthermore, deep-breath RRIV values for the patient group were significantly lower than that of the control group. Both sympathetic and parasympathetic nervous system involvement was seen in our study. In conclusion, EMG can reveal a possible underlying involvement in the absence of signs of autonomic involvement.

Objective: Systemic lupus erythematosus (SLE) patients have increased risk of coronary heart disease (CHD) that cannot be fully explained by the traditional risk factors. Metabolic alterations like oxidative stress and insulin resistance may be additional risk factors to contribute early and accelerated atherosclerosis in SLE. Our aim was to evaluate malondialdehyde (MDA) level, oxidative stress indicator, and homeostasis model assessment of insulin resistance (HOMA-IR), and possible relationship between oxidative stress and insulin resistance, in SLE., Methods: This cross-sectional controlled study included 30 SLE patients (SLE group) and 15 age- and sex-matched healthy controls (HC group). The SLE patients were classified into subgroups based on the disease activity index as active or inactive. Serum MDA, insulin, C-peptide, fasting blood glucose, lipid profile, acute phase reactants, tumor necrosis factor (TNF)-a, interleukin (IL)-6 and HOMA-IR were determined. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U and Pearson tests., Results: In the SLE group, TNF-a (7.9 [0.5-57.8] vs. 3.9 [0.3-6.3] pg/ml, p<0.01), IL-6 (9.2 [0.1-33.9] vs. 2.2 [0.1-4.8] pg/ml, p<0.01), MDA (2.3 [0.1-6.7] vs. 0.95 [0.5-2.96] nmol/ml, p<0.01) and C-peptide (1.9 [0.9-3.5] vs. 1.5 [1.1-2.4] ng/ml, p<0.01) levels were higher than in the HC group, while HOMA-IR index (1.7 [0.5-6.5] vs. 1.2 [0.8-2.9], p>0.05) was nonsignificantly higher. In the SLE group, MDA levels were correlated with insulin (r=0.614, p<0.05) and HOMA-IR (r=0.601, p<0.05)., Conclusion: In inflammatory diseases, relations between oxidative stress and insulin resistance, each of them triggers or enhances the other one, come to an impasse. In conclusion, this modifiable impasse might be important to prevent the development of atherosclerosis in SLE.