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Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection. Purpose To create a deep neural network to detect MRI changes in sacroiliac joints indicative of axSpA. Materials and Methods This retrospective multicenter study included MRI examinations of five cohorts of patients with clinical suspicion of axSpA collected at university and community hospitals between January 2006 and September 2020. Data from four cohorts were used as the training set, and data from one cohort as the external test set. Each MRI examination in the training and test sets was scored by six and seven raters, respectively, for inflammatory changes (bone marrow edema, enthesitis) and structural changes (erosions, sclerosis). A deep learning tool to detect changes indicative of axSpA was developed. First, a neural network to homogenize the images, then a classification network were trained. Performance was evaluated with use of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

Background: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by microangiopathy, inflammation, fibrosis. Interstitial lung disease (ILD) is common among SSc patients. Objective: This study aims to define the clinical, laboratory, and serologic characteristics of SSc patients with ILD and to present the frequency of chest computed tomography features. Methods: Two hundred twenty-six SSc patients who applied to the Rheumatology Department between January 2007 and August 2019 were retrospectively examined. A total of 100 SSc patients with ILD (44.2%) were determined. Clinical, laboratory, and serological features of SSc patients with and without ILD were compared. Results : Both groups had similar characteristics in terms of age and sex. The duration of disease (p=0.001) and follow-up time (p=0.001) were longer in SSc patients with ILD. Multivariable logistic regression analysis indicated that the duration of disease (OR: 1.06 (1.01-1.13), p=0.029), presence of gastrointestinal system involvement (OR: 3.29 (1.28-8.46), p=0.013) and anti-SCL70-positivity (OR: 6.04 (2.35-15.49), p Conclusion: We have shown a relationship between anti-SCL70, disease duration, gastrointestinal system involvement, and ILD in SSc patients.

To describe the clinical characteristics of neuro-Behcet’s syndrome (NBS) and to define the factors associated with relapses and poor outcome. Among 2118 patients with Behcet’s syndrome who fulfilled the international study group criteria, 208 (9.8%) patients had NBS. Retrospective data of 125 NBS patients (55.5% male; mean age 37.2 ± 11.8 years) were analysed. We divided patients into two subgroups, either parenchymal (p-NBS) or non-parenchymal (np-NBS), according to international consensus recommendations for NBS. We assessed the predictor factors associated with relapse and poor outcome—which was defined as a modified Rankin score (mRS) ≥ 3 at last follow-up and/or death—using Cox and logistic regression analyses, respectively. In total, 79 (63.2%) patients presented with p-NBS and 46 (36.8%) presented with np-NBS. Ocular involvement was more common in p-NBS than np-NBS (55.7% vs. 37.0%, p = 0.04), whereas vascular involvement excluding cerebral vein thrombosis was more frequent in patients with np-NBS (19.0% vs. 52.2%, p

Objectives: To evaluate the demographic and clinical characteristics of patients with Behcet's syndrome (BS), and to define their associations with the presence of major organ involvement (MOI).Method: Medical records of 2118 patients (964 males, 1154 females) were analysed retrospectively. MOI was defined as the presence of at least one of vascular, eye, nervous, or gastrointestinal system involvement. Univariable and multivariable binary and ordinal logistic regression analyses were applied to assess the factors that were potentially associated with MOI.Results: The mean ± sd age at diagnosis was 30.5 ± 9.4 years. Genital ulcer and joint involvement were more common in females (both p < 0.001), while MOI was more frequent in males (p < 0.001). Genital ulcer (p < 0.001) and vascular involvement (p = 0.006) were more common in patients with a younger age at diagnosis, while joint involvement was more common in older patients. A total of 1097 patients (51.8%) had at least one MOI, 322 (15.2%) at least two MOIs, and 48 (2.3%) at least three MOIs. Male gender, smoking history, and absence of genital ulcer were significantly associated with MOI in multivariable binary logistic regression. Multivariable ordinal regression analyses confirmed the association between MOI and male gender and smoking, but not the protective effect of genital ulcers. In both regression analyses, we found no significant effects of age, human leucocyte antigen-B51, skin involvement, or joint involvement on MOI.Conclusion: Male gender and positive smoking history have a significant influence on the presence of MOI in patients with BS.

ObjectivesThis study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA).MethodsThe assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen’s kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores.ResultsAltogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen’s kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen’s kappa of 0.932 (95% CI 0.885 to 0.980).ConclusionsThe Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

Background Radiographs of the sacroiliac joints are commonly used for the diagnosis and classification of axial spondyloarthritis. The aim of this study was to develop and validate an artificial neural network for the detection of definite radiographic sacroiliitis as a manifestation of axial spondyloarthritis (axSpA). Methods Conventional radiographs of the sacroiliac joints obtained in two independent studies of patients with axSpA were used. The first cohort comprised 1553 radiographs and was split into training (n = 1324) and validation (n = 229) sets. The second cohort comprised 458 radiographs and was used as an independent test dataset. All radiographs were assessed in a central reading session, and the final decision on the presence or absence of definite radiographic sacroiliitis was used as a reference. The performance of the neural network was evaluated by calculating areas under the receiver operating characteristic curves (AUCs) as well as sensitivity and specificity. Cohen’s kappa and the absolute agreement were used to assess the agreement between the neural network and the human readers. Results The neural network achieved an excellent performance in the detection of definite radiographic sacroiliitis with an AUC of 0.97 and 0.94 for the validation and test datasets, respectively. Sensitivity and specificity for the cut-off weighting both measurements equally were 88% and 95% for the validation and 92% and 81% for the test set. The Cohen’s kappa between the neural network and the reference judgements were 0.79 and 0.72 for the validation and test sets with an absolute agreement of 90% and 88%, respectively. Conclusion Deep artificial neural networks enable the accurate detection of definite radiographic sacroiliitis relevant for the diagnosis and classification of axSpA.

Objectives The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool. Methods Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy. Results 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters). Conclusions Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA.

To determine the SpA prevalence and identify its associated factors in Crohn's disease (CD) patients receiving a systematically rheumatological and imaging assessment, including magnetic resonance imaging (MRI) of the sacroiliac joints and spine.CD patients either naive to biologics or without them for three months prior enrollment were recruited in a subgroup of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). A structured assessment of SpA manifestations was performed by a rheumatologist, including MRI of sacroiliac joints and spine. Demographic and clinical parameters including disease activity in CD (Harvey Bradshaw Index-HBI) and SpA (C-reactive protein - CRP, Bath Ankylosing Spondylitis Disease Activity Index, and Ankylosing Spondylitis Disease Activity Score) were collected. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the presence of SpA.A total of 103 patients with CD were included in the cohort. The mean CD disease duration was 1.3±2.4years and 95.1% were naïve to biologics. The most frequent musculoskeletal manifestation was back pain (65.0%), followed by chronic back pain (50.5%), and arthralgia (43.7%). Prevalence of SpA was 19.4% with slightly higher proportion of axial SpA than peripheral SpA, and higher proportion of radiographic axial SpA (7.4%) than non-radiographic axial SpA (2.8%). Changes in MRI compatible with axial SpA were found in 15 (14.7%) patients, of which 9 (81.1%) patients had the clinical diagnosis of axial SpA. HLA-B27 positivity (OR 9.02, CI 95% 2.29-35.55) and higher disease activity of CD as reflected by the HBI (OR 1.14, 95%CI 1.01-1.30) were significant and independently associated with the presence of SpA.SpA was present in nearly one out of five patients with CD and it was associated with the expression of HLA-B27 and a higher clinical activity of CD. Our findings raise awareness to rheumatologists and gastroenterologists on the high concomitance between both diseases and may help to reduce the delay in SpA diagnosis.

OBJECTIVE Behcet syndrome (BS) is a multisystemic chronic vasculitic disease. Among previous studies, although there are some that showed increased risk of subclinical atherosclerosis in BS, there are also others that showed the opposite. The objective of this study is to evaluate subclinical atherosclerosis in BS by using the cutoff value for intima-media thickness in the 2013 European Society of Cardiology/European Society of Hypertension guideline. METHODS We conducted a cross-sectional analysis of 100 BS patients and 30 healthy volunteers at a single center in a 4-month period. All ultrasound scans were performed in a blind manner to the clinical assessment, and they were carried out by the same researcher by a B-mode ultrasonography. RESULT When we grouped the patients based on the presence of subclinical atherosclerosis, the frequency of subclinical atherosclerosis in the BS patients was found to be higher than that in the healthy controls (32% and 7%, respectively; p = 0.006). When a cutoff is used for carotid intima-media thickness, increased atherosclerosis risk is observed in BS patients with vascular involvement (p = 0.043). CONCLUSIONS Although higher inflammation and increased atherosclerosis in vascular BS patients were expected, this situation was not supported much in previous studies. We think that this may have been caused by mere comparison of numerical data, and usage of a cutoff value could be more significant in distinguishing what is normal and what is abnormal as in several medical parameters.

Objectives To describe demographic and clinical characteristics of vascular involvement in patients with Behcet's syndrome (BS) and to evaluate associations with such involvement. Methods We retrospectively evaluated records of 2118 BS patients. In total, 460 patients diagnosed with superficial thrombophlebitis (ST) and/or major vascular events (venous and/or arterial involvements) were included in current analysis. Isolated ST with no accompanying deep venous thrombosis might be accepted as part of skin involvement; therefore, we defined two different outcomes for vascular involvement (“any vascular event” and “major vascular events”) and performed univariable and multivariable logistic regression to assess factors associated with these outcome variables. Results Overall, 68 (14.8%) patients had isolated ST, and 392 (85.2%) had major vascular events. The mean age of vascular BS was 33.8 (SD: 10.5) years and median follow-up was 13.9 (Q1–Q3: 8.3–22.9) years. The primary sites of major vascular events were deep venous thrombosis (n = 358, 77.8%), pulmonary arterial involvement (n = 66, 14.3%), extrapulmonary arterial involvement (n = 52, 11.3%), and intracardiac thrombosis (n = 14, 3.0%), respectively. Male sex was significantly associated with a higher risk for both outcome variables. When it was added to analysis, ST itself was the strongest explanatory variable that was associated with major vascular events in all multivariable models (ORs = 11.9, 12.0, 13.0, and 18.9). While HLA-B51 was significantly associated with any vascular event, there was no similar observation for major vascular events. Conclusion Male sex is a well-known risk factor for major vascular events in BS, but our study established that presence of ST was the strongest risk factor.

Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication.This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized.The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.

BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

To report the clinical characteristics of pulmonary artery involvement (PAI) in patients with Behçet's syndrome (BS) and to define the predictors of relapses.We performed retrospective analysis of BS patients with PAI who fulfilled international study group criteria. Among 460 patients with vascular Behçet's syndrome (VBS), 66 were diagnosed with PAI. For final analyses, 61 patients with PAI were included who had at least 2 follow-up visits (72.1% male, mean age at BS diagnosis 29.34 ± 10.1 years). The patient data were recorded. Relapse was defined as the reoccurrence of vascular event in any vascular structure. Factors associated with relapse were assessed by logistic regression analysis.There were no differences considering demographic and clinical features of the patients with and without PAI in the VBS group, except that intracardiac thrombosis was more common in the patients with PAI (19.7% vs 0.3%). Among 61 patients, 50 (82.0%) had isolated pulmonary artery thrombosis (PAT), whereas 11 (18.0%) had pulmonary artery aneurysm with or without PAT. Twenty-four (39.3%) patients experienced vascular relapse during median follow-up of 65.9 (Q1-Q3: 20.1-109.0) months. To define the factors associated with relapses, patients with isolated PAT were analysed. On multivariable logistic regression analysis, older age at BS diagnosis and anticoagulation usage seemed to be protective (OR: 0.92, 95% CI 0.86-1.02, OR: 0.34, 95% CI 0.09-1.33, respectively).Our results indicate a higher frequency of intracardiac thrombosis in BS patients with PAI and possible efficacy of anticoagulation usage in preventing relapses. Key Points • This study shows that intracardiac and intracranial thromboses are seen more frequently in patients with PAI and the prevalence of pulmonary artery thrombosis has been increasing in the case of PAI. Furthermore, our report indicates that anticoagulation might be effective in preventing further vascular relapses.

Background/aim High mobility group box- 1 (HMGB- 1) is a nuclear protein acting as a proinflammatory molecule. The serum HMGB- 1 levels were found elevated in chronic inflammatory diseases. In this cross-sectional study, serum HMGB- 1 levels in Behcet’s disease (BD) patients and healthy controls (HC) were studied. Also, its association with disease activity scores and clinical findings were evaluated. Materials and methods Ninety BD patients and 50 age-sex matched HC were included in the study. Disease activity scores were assessed by Behcet Disease Current Activity Form (BDCAF) and Behcet Syndrome Activity Score (BSAS). Serum HMGB- 1 levels were measured using a commercial ELISA kit. A p value of < 0.05 was considered to be statistically significant. Results Serum HMGB- 1 levels were significantly higher in BD than in HC (43.26 pg/mL and 16.73 pg/mL; p < 0.001, respectively). Serum HMGB- 1 levels were statistically significantly associated with presence of erythema nodosum (EN) and genital ulcers in the last one month prior to recruitment (p = 0.041 and p < 0.001, respectively). BDCAF and BSAS scores were positively correlated with serum HMGB- 1 level ( p = 0.03 and p = 0.02, respectively). Conclusion HMGB - 1 may play a role in the development of BD. Also, due to its positive correlation with disease activity indices, it can be used as a novel disease activity parameter in BD.

Background: data regarding outcome of Coronavirus disease 2019 (COVID-19) in patients with autoimmune hepatitis (AIH) are lacking. Patients and methods: we performed a retrospective study on AIH patients with COVID-19 from 34 centres in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity-score matched cohort of non-AIH patients with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase>2xupper limit of normal) during COVID-19 was also evaluated. Results: we included 110 AIH patients (80%,female) with a median age of 49 (range:18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (p=0.041; odds ratio (OR) 3.36[1.05-10.78]) while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (p=0.009; OR 0.26[0.09-0.71]). The rates of severe COVID-19 (15.5% vs 20.2% p=0.231) and all-cause mortality (10% vs 11.5%; p=0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (p, Italian Ministry of University; Research (MIUR)-Department of Excellence Project PREMIA; AMAF Monza ONLUS; AIRCS

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P&nbsp

Objective To evaluate the diagnostic value of SpA parameters and their combination for the diagnosis of axial SpA in patients with an a priori different probability of the diagnosis. Methods A total of 361 patients with chronic back pain and suspicion of axial SpA (181 referred by primary care physicians or orthopaedists, 180 recruited via an online screening tool) received a structured rheumatologic examination, which resulted into a diagnosis or exclusion of axial SpA. The prevalence of axial SpA indicating the pre-test probability was 40% in the physician-referred subgroup and 20% in the online screening subgroup. Sensitivities, specificities and likelihood ratios for SpA features were determined in both subgroups and the respective post-test probabilities of axial SpA were calculated. Results The relative diagnostic value of single SpA features varied substantially between the groups with different referral pathways. For instance, HLA-B27 positivity increased the probability of the presence of axial SpA by 35% to 55% in online-screened patients and by 22% to 62% in physician-referred patients. The absence of HLA-B27 resulted in a sharp decrease in the probability of the presence of axial SpA in physician-referred patients (from 40% to 6%). This decrease was less sharp in the online screening group (from 20% to 10%). These differences were especially relevant in patients with a small number (one to two) of positive SpA features. Conclusion The diagnostic value of SpA features varies in different patient populations, which should be considered in the diagnostic approach.

We read with great interest the case report by Kuwabara et al .1 With this comment, we want to share the case of a 38-year-old male patient with a long history of radiographic axial spondyloarthritis (r-axSpA)—with HLA-B27 positivity, peripheral joint involvement and skin psoriasis—complicated by Takayasu arteritis (TAK), showing a favourable response to a combination therapy of Tofacitinib (TOF) and methotrexate (MTX) with the readers of the ‘Annals of the Rheumatic Diseases’ . The r-axSpA was well-controlled under tumour necrosis factor alpha inhibiton with infliximab and MTX between 2013 and 2017 (figure 1). At the beginning of 2017, he presented a worsening of his disease with peripheral arthritis/enthesitis in addition to fatigue and myalgia of the neck and shoulder region. Therefore, in 2017/2018, the treatment was changed to golimumab, and then—due to persistent symptoms—to etanercept, secukinumab and certolizumab pegol and additionally MTX was switched to sulfasalazine (SSZ). All treatment courses failed to achieve an adequate disease control (figure 1). Additionally, the patient self-administered oral prednisolone (PSL) (between 50 and 15 mg daily) during that period. Figure 1 Treatment and CRP courses overview of the different treatment strategies and the CRP course over time. bDMARDs, biological disease modifying antirheumatic …

IntroductionPsoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA.Methods and analysesThis is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint.Ethics and disseminationThe study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted.Trial registration numberNCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.

Primary Sjögren syndrome (pSS) is usually encountered between the fourth and sixth decades. It is known that the age of onset in autoimmune diseases may affect the clinical features. In this study, we aimed to investigate the clinical and laboratory characteristics of early onset pSS patients.The data of 352 pSS patients were analyzed retrospectively. The patients were divided into two groups as those with the onset age of 35 or younger (early-onset) and those with the onset age of older than 35. The clinical, laboratory, and serological characteristics of the two groups were compared. p 0.05 was considered statistically significant.Forty patients in the group with an onset age of 35 or younger (11.4%) and 312 patients with an onset age of older than 35 (88.6%) were analyzed. The frequency of skin (22.5% vs 1.9%, p 0.001) and renal involvement (10% vs 2.2%, p = 0.026) was significantly higher in the early-onset group than the late-onset group. There was no significant difference between the two groups in terms of xerostomia, eye dryness, arthritis, and other systemic involvement. Anti-Ro52 positivity (p = 0.04), elevated serum IgG levels (p = 0.004), and low C4 (p = 0.002) presence were more frequent in the early-onset group.Consequently, it is seen that the clinical phenotype of early-onset pSS patients may be different to those with later onset. Especially the more frequent observation of poor prognostic factors at early-onset ages shows the necessity to monitor these patients more regularly.• The clinical and laboratory features of patients with early-onset primary Sjogren syndrome may differ from late-onset patients.

The management of spondyloarthritis (SpA) has substantially changed as a consequence of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). However, the treatment options in patients with axial SpA (axSpA) not responding to nonsteroidal anti-inflammatory drugs (NSAIDs) had been restricted to tumor necrosis factor alpha (TNFα) inhibitors for almost 15 years. With the approval of secukinumab, an interleukin (IL)-17A inhibitor, there is a new alternative in the treatment of axial SpA. In patients with psoriatic arthritis (PsA) not responding to conventional therapy with NSAIDs and conventional synthetic DMARDs, therapeutic options are more diverse. In addition to TNFα inhibitors and secukinumab, another IL-17A inhibitor ixekizumab, IL-12/23 blocker ustekinumab, phosphodiesterase-4 inhibitor apremilast, T-cell-mediated pathway inhibitor abatacept, and Janus kinase (JAK) inhibitor tofacitinib are the approved treatment. Nevertheless, there is still an unmet need for further treatment options in both axSpA and PsA. Further therapeutics, such as the dual IL-17A and F inhibitor bimekizumab, IL-17 receptor blocker brodalumab, and JAK inhibitors baricitinib, filgotinib and upadacitinib are in development for these indications. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab are further emerging drugs for PsA. Thus, the number of treatment options in SpA is likely to be increased over the next few years that make identification of optimal treatment strategies essential.

Post-operative hypoparathyroidism is a complication in patients who undergo thyroid surgery. Our study aimed to evaluate the incidence and causes of post-operative transient and permanent hypoparathyroidism in patients undergoing thyroid surgery.The data of 933 consecutive patients who underwent total thyroidectomy in a single center were retrospectively evaluated. The rate of post-operative hypoparathyroidism, clinicopathological features, and laboratory parameters during the post-operative first day, first month, and first year of patients with and without hypoparathyroidism were analyzed. Patients with hypoparathyroidism were classified as transient or permanent cases.The incidence of post-operative hypoparathyroidism was 22.7%, including transient (20.6%) and permanent (2.1%). In multivariable analysis, independent predictors of permanent hypoparathyroidism were as follows: surgery due to malignant thyroid disease, tumor multifocality, and pre-operative vitamin-D deficiency (VDD) (p0.001, 0.047, and 0.002, respectively). During the post-operative first month, the mean serum PTH levels were found to be 7.58 pg/mL, and they remained low on the post-operative first year in patients with permanent hypoparathyroidism.Surgery due to thyroid malignancy and VDD should be considered risk factors for permanent hypoparathyroidism in patients who undergo thyroid surgery. The post-operative first month is important in the prediction of permanent hypoparathyroidism.Hypoparathyroidism, Permanent, Transient.L’ipoparatiroidismo postoperatorio è una complicanza possibile della chirurgia della tiroide, e ci siamo proposti di studiarne incidenza transitoria o permanente, e cause, in 933 pazienti della nostra casistica di operati alla tiroide controllati retrospettivamente. Si tratta della casistica dei un singolo unico centro, e di una valutazione retrospettiva riguardante l’incidenza dell’ipoparatiroidismo postoperatorio, le caratteristiche clinico- patologiche del pazienti, ed i parametri di laboratorio del primo giorno postoperatorio, del primo mese e del primo anno di questi pazienti, senza o con ipoparatiroidismo, distinguendo in quest’ultimo gruppo l’ipoparatiroidismo transitorio o permanente. Come risultato abbiamo riscontrato un’incidenza di ipoparatiroidismo postoperatorio del 22,7% - rispettivamente 20,6% transitorio e 2,1% permanente. Con l’analisi multivariata i fattori indipendenti di previsione dell’ipoparatiroidismo sono risultati: interventi per patologia maligna, multifocalità del tumore, carenza preoperatoria di vitamina D (VDD) – rispettivamente p0,001; 0.047; 0.002). Durante il primo mese postoperatorio i livelli medi del PTH nel siero sono stati trovati essere 7,58 pg/ml, rimanendo bassi per tutto il primo anno postopertorio in caso di iperparatiroidismo permanente. In conclusione la chirurgia per patologia maligna e la carenza preoperatoria di vit D dovrebbero essere considerato fattori di rischio di ipoparatiroidismo postoperatorio nel pazienti candidati ad intervento chirurgico. Il primo mese postoperatorio è importante per la previsione dell’ipoparatiroidismo permanente.

Background/aim We aimed to assess the association between retinal vascular caliber (RVC) scores and disease activity in rheumatoid arthritis (RA) patients. Materials and methods Forty-seven RA patients, 32 systemic lupus erythematosus (SLE) patients, and 45 healthy people were enrolled. RA and SLE patients were subdivided into groups according to C-reactive protein (CRP) levels. RA patients were also grouped according to Disease Activity Score-28 (DAS-28). Fundus photography was performed for all patients. RVC was summarized as the central retinal artery and vein equivalents (CRAE and CRVE). Results Mean CRVE for RA patients was 213.3 ± 17.8 μm compared with 209.2 ± 14.1 μm for SLE and 217.5 ± 26.2 μm for the control group (P = 0.17). RVC scores did not differ between the CRP-high and CRP-low groups. As the RA disease activity increased, the widening of CRVE became more prominent and statistically significant. When the DAS-28 > 5.1 (CRVE, 220.4 (211.8–246.5) μm) group and DAS-28 ≤ 3.2 (CRVE, 214.4 (172.4–242.3) μm) group were compared, statistical significance was more pronounced (P = 0.03) than when comparing the DAS-28 > 3.2 and DAS-28 ≤ 3.2 groups (P = 0.05). Conclusions CRVE, which reflects systemic inflammation and possibly increased cardiovascular risk, was significantly increased in active RA patients. The association between retinal venular widening and disease activity, regardless of CRP, may be a sign that RA-related inflammation may have systemic vascular effects even with normal levels of CRP.

Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), mean platelet volume (MPV), and red cell distribution width (RDW) may potentially reflect inflammatory status in systemic autoimmune diseases. The aim of this study is to investigate the association between these proposed markers and disease manifestations, activity, and severity in systemic sclerosis (SSc). We conducted a cross-sectional study of 69 systemic sclerosis (SSc) patients and 50 healthy volunteers in a single center. Adult patients with SSc and healthy controls were compared in terms of NLR, MLR, MPV, RDW, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Venous blood samples were drawn after at least 8 h of fasting in the morning. Extension of skin fibrosis was evaluated by using modified Rodnan skin score (mRSS). Disease severity and activity were assessed by Medsger disease severity and European Scleroderma Trials and Research Group (EUSTAR) disease activity scores, respectively. Associations of disease manifestations, clinical, laboratory, and capillaroscopic findings, mRSS, and the disease activity and severity scores with the proposed hematological markers were evaluated. Multiple regression models were generated for significant associations. The neutrophil number was higher (p = 0.004) and lymphocyte number was lower (p

BACKGROUND/OBJECTIVE Interleukin (IL) 35 is a member of the IL-12 family. Studies show that IL-35 is an important anti-inflammatory cytokine and suppresses effector T-cell activity. In this study, we aimed to evaluate serum IL-35 levels in systemic sclerosis (SSc) patients and its potential relation with clinical findings. METHODS We conducted a cross-sectional analysis of 70 SSc patients and 29 healthy volunteers in a single center in 5 months' period. Extension of skin fibrosis was evaluated by using modified Rodnan skin score. Disease severity was assessed by Medsger disease severity scores. Serum IL-35 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Cloud-Clone Corp, Wuhan, China). The relationship between IL-35 levels and clinical and laboratory parameters was investigated. Mann-Whitney U test was used to compare parameters among the groups. Correlation was tested by Spearsman correlation coefficient. RESULTS Serum IL-35 levels was significantly higher in SSc patients (8.69 [interquartile range, 29.33] pg/mL) than in healthy controls (7.11 [interquartile range 7.53] pg/mL; p < 0.001). There was no significant relationship between serum IL-35 levels and organ involvement. There was a negative correlation between serum IL-35 levels and Medsger disease severity score (Rho, -0.333; p = 0.006), modified Rodnan skin score (Rho, -0.307; p = 0.010), and C-reactive protein (Rho, -0.294; p = 0.015). There was no relationship between IL-35 and disease duration and erythrocyte sedimentation rate. CONCLUSIONS Our study revealed that IL-35 levels were higher in SSc patients, and in contrast to previous studies, it was the first study that showed that IL-35 levels did not increase in SSc patients with pulmonary fibrosis.

Interleukin-6 (IL-6), IL-15, and heat shock protein 72 (Hsp72) are molecules that have significant metabolic effects on glucose and fat metabolism and a cell’s stress response. The aim of this study is to determine serum levels of these molecules in runners after a long-distance trail run. Serum IL-15 levels after such endurance events have not been investigated yet. Blood samples were collected from 37 athletes (11 female, 26 male) before and after a 35-km trail run, with a total climb of 940 m. Serum was obtained from the samples, and IL-6, IL-15, and Hsp72 levels were measured from using the sandwich ELISA method. The athletes completed the race in 308.3 ± 37.4 min on average. After the race, the mean serum IL-6, IL-15, and Hsp72 concentrations increased 13.2-fold, 2.22-fold, and 1.6-fold, respectively (p < 0.001, p < 0.001, and p = 0.039, respectively). This is the first study to demonstrate the increase in serum IL-15 levels following an acute endurance exercise. In addition to IL-15, we report that IL-6 and soluble Hsp72 levels also increased significantly following a 35-km trail run. Since these molecules are involved in regulating glucose and fat metabolism, significant increases of IL-6, IL-15, and soluble Hsp72 may have health benefits that may be associated with long-distance trail runs, which are becoming more popular worldwide.

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

AIM To evaluate the relationship between serum adenosine deaminase (ADA) levels and histological features in patients with autoimmune hepatitis (AIH). METHODS A total of 80 subjects (52 AIH cases and 28 healthy controls) were included in the study. Patients were diagnosed according to the simplified criteria suggested by the International Autoimmune Hepatitis Group. All of the cases had been diagnosed with AIH between 2010-2015 at Hacettepe University, Department of Gastroenterology. Serum blood samples were collected and stored at -80 °C until the biochemical estimation of ADA activity. The diagnosis of patients was confirmed by liver biopsy. Serum ADA > 20 U/L was considered to be high level. RESULTS Mean serum ADA levels were significantly higher in AIH patients than those in healthy controls (25.4 ± 9.6 U/L vs 12.8 ± 2.2 U/L, P < 0.001). Serum ADA levels > 20 U/L were found in 63.5% AIH patients and in 0% healthy controls (P < 0.001). Mean serum ADA levels were significantly increased in each stage of histological activity: 15.2 ± 3.5 U/L for patients with mild interface hepatitis, 23.1 ± 10.0 U/L for patients with moderate interface hepatitis and 30.9 ± 7.0 U/L for patients with severe interface hepatitis (P < 0.001). Correlation analysis showed that there was a positive association between serum ADA levels and histological activity (r = 0.71, P < 0.001). Receiver operating characteristic analysis suggested that 24.5 U/L was the optimum cut-off point of ADA level for severe interface hepatitis (sensitivity 88%, specificity 85.2%, area under the curve: 0.88). CONCLUSION Because of the positive correlation with inflammatory activity, serum ADA level may be a potential biomarker for predicting or monitoring histological activity in patients with AIH.

25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH. Serum 25(OH)D levels were quantified in 68 therapy naive AIH patients and 34 healthy controls. Mean serum 25(OH)D levels were significantly lower in AIH compared to healthy controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p

Background Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is used to describe the coexistence of both diseases, with either a sequential or a simultaneous presentation in the same patient. Available studies have focused on the simultaneous form, whereas there is limited information on sequential PBC-AIH. We carried out a retrospective study of patients who sequentially developed PBC-AIH overlap syndrome. Methods The medical data of 1065 patients diagnosed with PBC (n=483) and AIH (n=582) were retrospectively analyzed. Results A sequential development of PBC-AIH was observed in 19 (1.8%) patients after a mean of 6.5 (1-14) years of follow-up. AIH developed in 12 (2.5%) PBC patients, whereas PBC occurred in seven (1.2%) patients with AIH. The baseline serologic and histological findings of patients who developed PBC-AIH were similar to those of patients with typical PBC or AIH. Eighteen patients were treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppression after the diagnosis of PBC-AIH was established. One patient showed a spontaneous resolution of hepatitic flare under UDCA therapy. Biochemical remission was achieved in 16 patients, whereas three progressed to decompensated cirrhosis and required liver transplantation. Conclusion The sequential overlap of PBC-AIH can occur during the follow-up of patients with pure PBC or AIH. In our cohort, we could not identify any factors that predicted the development of this rare condition. The combination of UDCA and immunosuppression seems to be an appropriate therapy in the setting of PBC-AIH.