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Objective We aimed to assess patients with axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) for disease activity and serum markers of endothelial dysfunction. Methods We studied 161 patients (123 males, 38 females) with axSpA: 153 with ankylosing spondylitis and 8 with non-radiographic axSpA, and 30 healthy controls (HC). We collected: age; sex; disease duration; extra-articular symptoms (IBD and acute anterior uveitis), comorbidities; human leukocyte antigen B27 status; and treatment. We measured serum interleukin (IL)-6, interleukin-18, IL-23, vascular endothelial growth factor (VEGF) epidermal growth factor (EGF), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), and fetuin-A levels. Results IBD was diagnosed in 19 (11.8%) patients with axSpA. Compared to patients with axSpA without IBD, those with IBD had higher serum C-reactive protein (CRP) level (p = 0.05), erythrocyte sedimentation rate (ESR) (p = 0.005), and serum ET-1 levels (p = 0.01). In patients with axSpA and IBD, ET-1 levels correlated positively with CRP level (p = 0.006) and ESR (p = 0.02), and ADMA levels with visual analog scale scores (p = 0.01). Patients with axSpA and IBD had higher serum levels of IL-6 (p = 0.01), IL-18 (p = 0.005), and ADMA (p = 0.01) and lower serum levels of fetuin-A (p = 0.01) than did controls. Conclusions Patients with axSpA and IBD had higher levels of disease activity, as assessed by ESR and CRP and ET-1 levels, than did patients with axSpA without IBD. Compared to HC, patients with axSpA and IBD had increased IL-18, ADMA levels and decreased fetuin-A level.

IntroductionThe aim of the study was to evaluate the impact of disease activity, selected serum cytokines, and therapy on metabolic syndrome (MetS) components in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.Material and methodsWe studied 46 SAPHO patients (40 women, 6 men). We recorded age, sex, disease duration, arthritis localization, type of skin changes, bone scintigraphy results, comorbidities, BASDAI, VAS, and treatment. We measured erythrocyte sedimentation rate, C-reactive protein, lipid profile, serum IL-6, IL-18, IL-23, endothelin-1, vascular endothelial growth factor, and epidermal growth factor (EGF).Results97.8% of patients had sternoclavicular joint arthritis, 91.3% of patients palmoplantar pustulosis. In 65.2% of SAPHO patients skin changes and arthritis started simultaneously. Apart from non-steroidal anti-inflammatory drugs, patients were treated with methotrexate (41.3%), sulfasalazine (41.3%), and antibiotics (39.1%). 19.5% of patients met MetS criteria. Serum IL-23 correlated positively with total cholesterol (TC; p = 0.02) and high-density lipoprotein cholesterol (HDL-C) (p = 0.01) in the SAPHO group. There was a negative correlation between HDL-C and BASDAI (p = 0.02). Patients treated with methotrexate had higher triglyceride (p = 0.01) and low-density lipoprotein cholesterol (LDL-C) (p = 0.01) levels. There was a negative correlation between TC and EGF (p = 0.03). Increased prevalence of autoimmune diseases and depression was observed in SAPHO patients.ConclusionsSerum IL-23 protects, whereas methotrexate treatment stimulates selected components of the MetS in patients with SAPHO syndrome.

Idiopathic retroperitoneal fibrosis, or Ormond’s disease, is a rare syndrome which is in essence the deposition of pathological fibrous tissue in the retroperitoneal space. In most cases, it is initially asymptomatic, but as the disease progresses, clinical symptoms develop. The main complaint are abdominal pain and symptoms resulting from the involvement of ureters, arterial and venous vessels. Diagnosis is based on computed tomography or magnetic resonance imaging, demonstrating a fibrotic tissue mass accumulated in the retroperitoneal space. Due to the typically late presentation of clinical symptoms, a diagnosis is difficult and is often made after complications occur. In our article, we present the case of a 71-year-old patient in whom coexisting ankylosing spondylitis and retroperitoneal fibrosis were diagnosed 15 years after non-specific abdominal pain occurred.

The long-term mortality in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is unexpectedly decreased or at least not increased regardless of several mortality risk factors that these diseases share with other chronic immune-mediated rheumatic diseases. The genetic and immunological profile of PMR/GCA patients is unique, therefore, the hypothesis that this profile provides some survival advantage to PMR/GCA patients should be considered. The longevity is a phenomenon that was demonstrated to be familial. The familial aggregation of longevity can be studied by analysis of life expectancy in family members. Here we test the hypothesis of the aggregation of an increased longevity in the families of PMR/GCA patients. We compared the age of death of 358 parents of 179 PMR and GCA patients with corresponding data retrieved from 506 parents of 253 randomly collected age and sex-matched controls. The number of nonagenarian (≥ 90-year -old) mothers of PMR/GCA patients was significantly higher (OR = 2.34, 95%CI 1.11–11.95, p p = 0.003). Our data suggest the familial aggregation of nonagenarians in PMR/GCA patients.

Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2–212, 32% &lt, 4 weeks, 29% 5–12 weeks, 26% 13–28 weeks, 13% with &gt, 28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with “good” therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. Conclusions: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.

The existence of polymyalgia rheumatica (PMR) with normal inflammatory indices at the time of diagnosis still represents a diagnostic conundrum. According to the literature, some patients with PMR following immune checkpoint inhibitory therapy had normal values of both erythrocyte sedimentation rate and C-reactive protein concentrations at the time of diagnosis. In this short communication we investigated the possibility that in some patients with PMR the main pathogenic mechanism is constituted by inhibition of some checkpoints, such as programmed death receptor-1, programmed death ligand 1, and “cytotoxic” lymphocyte antigen 4. In these patients, the pathogenetic mechanisms underlying PMR can act much more upstream than commonly suggested. Also, we addressed the question of whether these patients should be considered as affected by PMR-like syndromes or by PMR subset.

Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. Methods This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud’s symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. Results In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (β = 2.854, p

Objective The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. Methods In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. Results Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (− 2.7 and − 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. Conclusion CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. ClinicalTrials.gov identifier NCT02149121. Electronic supplementary material The online version of this article (10.1007/s40259-018-00331-4) contains supplementary material, which is available to authorized users.

Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a constellation of dermatological and osteoarticular symptoms. The pathogenesis of SAPHO is unknown, but infectious, genetic, immunological and environmental factors may play a role. SAPHO is classified along two different spectrums: pustulo-psoriatic hyperostotic spondyloarthritis and chronic recurrent multifocal osteomyelitis. The typical skin lesions are palmoplantar pustulosis and acne. The sign of arthritis is involvement of the anterior chest wall, most often the sternoclavicular joints. There are no standard treatment recommendations, but nonsteroidal anti-inflammatory drugs, sulfasalazine, methotrexate, antibiotics and biological drugs can be considered.

Silent vasculitis may accompany polymyalgia rheumatica (PMR), resulting in complications such as vision deterioration. Reduced visual field is a possible manifestation. A 66-year-old man was diagnosed with PMR and treated accordingly (prednisone maximum 15 mg/day) at a tertiary center, with resolution of his symptoms. After 18 months, he suddenly experienced right eye vision loss. Visual field of his left eye was peripherally limited (Figure 1). Color Doppler ultrasound …

INTRODUCTION ANCA-associated vasculitides (AAV) is a group of rare disorders where inflammation and damage of the small blood vessels lead to dysfunction of the supplied organs. In severe flares of the disease patients may require intensive care unit (ICU) admission and treatment. The study aims to characterize Polish patients with AAV who were admitted to the ICU and compare them to the others. MATERIAL AND METHODS An observational, retrospective study based on the POLVAS - registry of Polish adult patients with AAV was carried out. Patients admitted to the ICU (ICU group) were identified and compared with the patients who did not require ICU admission (non-ICU group). Characteristics and comparison between groups were made using standard statistic descriptive methods. RESULTS 30 patients admitted to the ICU were identified among 573 cases included in the registry. All patients in the ICU group with available data were ANCA positive. The clinical manifestations related to the ICU admission were respiratory, renal and central nervous system involvement. The treatment regimen for remission induction was similar in both groups. Almost half of the patients in the ICU-group (48.3%) required dialysis, whereas in the non-ICU group it was 21.8% (P = 0.01). Infections were also more frequent in the ICU group (72.4% vs. 36.9% P < 0.001). The mortality rate among patients who needed ICU treatment was significantly higher when compared to the rest of the patients (53.6% vs. 7.8%; P < 0.001). CONCLUSIONS In the Polish AAV cohort one in twenty patients required ICU admission. This group was characterized by multiple organ involvement and high mortality.

Evidence from over 10 years of clinical experience demonstrates that biosimilar medicines approved in the European Union can be used for all their registered indications as safely as their originators and with no negative impact on therapeutic efficacy. The debate on the use of biosimilars in rheumatology focuses specifically on the safety of switching between biosimilars and reference products. Studies conducted to date, including randomised double-blind and open-label extension trials, have not demonstrated any significant differences in therapeutic efficacy or safety between patients switched from one medicine to another and those who were continued on a single medicine. According to the latest recommendations for the use of biosimilars in rheumatic diseases, developed by an international task force in 2017, there is no clinical evidence that a single switch from an originator to a biosimilar medicine is associated with any significant risk for patient safety or reduction in therapeutic efficacy.

Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The presented article discusses the mechanism of action and the clinical application of tofacitinib. Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with biological drugs already available.

Objectives: Report on one-year results from the Polish Spondyloarthritis Initiative registry (PolSPI), containing the cross-sectional analysis of clinical and imaging data as well as database methodology. Material and methods: The PolSPI registry includes patients with axial (axSpA) and peripheral (perSpA) spondyloarthritis according to ASAS classification criteria, and/or patients with ankylosing spondylitis according to modified New York criteria, psoriatic arthritis according to CASPAR criteria, arthropathy in inflammatory bowel disease, reactive arthritis, juvenile spondyloarthritis or undifferentiated spondyloarthritis. Epidemiologic data and history of signs, symptoms and treatment of spondyloarthritis are collected and assessment of disease activity is performed. Radiographic images of sacroiliac joint, cervical and lumbar spine, and results of bone densitometry are collected. Every 6 months blood samples for inflammatory markers, and for long-term storage are taken. Results: During a one-year period from September 2015 to August 2016, 63 patients were registered on an electronic database; 44 (69.8%) of patients were classified as axial spondyloarthritis (axSpA) and 19 (30.2%) as peripheral spondyloarthritis (perSpA) according to ASAS criteria. Statistically significant differences between axSpA and perSpA were discovered in the percentage of HLA-B27 antigen occurrence (92.6% and 50%, respectively), BASDAI (2.8% and 4.1%, respectively), DAS 28 (2.66% and 4.03%, respectively), percentage of peripheral arthritis (20% and 88.8%, respectively), enthesitis (26.7% and 70.6%, respectively), dactylitis (6.7% and 88.9%, respectively), as well as extra-articular symptoms: acute anterior uveitis (26.7% and 5.6% , respectively) and psoriasis (6.9% and 55.6%, respectively). Patients with axSpA had significantly higher mean grade of sacroiliac involvement according to New York criteria, higher mSASSS score, and lower T-score in femoral neck in bone densitometry. Conclusions: At the early stage of the disease patients with axSpA compared to those with perSpA, have more advanced structural damage of sacroiliac joints and spine, and lower bone mineral density in the femoral neck. In the upcoming years the PolSPI registry will prospectively follow-up patients with SpA, recording response to treatment and carrying out research on interaction of inflammation and bone remodelling.

The myxoma makes 80–90% of benign cardiac neoplasms. The first symptom in 50% of patients is an embolism resulting from relocation of tumor fragments or blood clots into the bloodstream. Elevated values of acute phase proteins in these patients are results of non-specific immune response to an antigen causing the disease. Interleukin 6 (IL-6) plays a role in this reaction, modifying inflammatory response by: influence on lymphocyte T differentiation, lymphocyte B to plasmocyte transformation, and stimulation of the liver to produce acute phase proteins. Elevated IL-6 is found in 80% of patients with diagnosed myxoma, which causes it to be an important marker in diagnostic and post-operational monitoring. The role in non-specific inflammatory response played by IL-6 in myxoma and autoimmune disorders was a cause of many diagnostic mistakes. Available literature does not suggest a coincidence of cardiac myxoma and systemic sclerosis. This is why we would like to present a case report, with special regard to correlation between IL-6 values and activity/stage of diagnosed disorders.

Career situation of first and presenting author Assistant. Introduction Vascular abnormalities are common complications in rheumatic patients. Their background is multifactorial and still is a subject of the debate. Objectives This study was designed to evaluate the significance of selected noninvasive imaging indices, immunological and genetic biomarkers in diagnosis of vascular lesions in rheumatic diseases. Methods The study group included 288 patients with systemic connective tissue diseases (SCTD). The noninvasive evaluation of vascular lesions was made on the basis of carotid intima-media thickness (cIMT), ankle brachial index (ABI), high resistance index (HRI) and ulnar artery intraluminal diameter (UAID) measurements using HDI 3500 (ATL). We analyzed more than 100 variables: autoantibodies, inflammatory and angiogenic markers, genetic polymorphisms and classical risk factors for atherosclerosis. Statistical analysis was performed with STATA 11 including: chi2Yates, chi2Pearson and rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results Macroangiopathy was influenced by selected autoantibodies including antiphospholipid (OR=4.4; 95% CI:1.1–20.7) and anti-endothelial cell (OR=6.6; 95% CI:1.6–28.3) as well as inflammatory biomarkers (OR=3.6; 95% CI:1.1–11.8). The analysis of genetic polymorphisms showed especially an important impact of VEGF 2578 AA genotype on atherosclerosis development (OR=4.8; 95% CI:1.1–21.1). Angiogenic biomarkers were strongly associated with prothrombotic risk (OR=22.8; 95% CI:2.3–230.6). The analysis of relations between imaging indices and vascular manifestations revealed significant association of cIMT with cardiovascular (OR=52.9; 95% CI:7.0–1012.7) and cerebrovascular disease (OR=4.0; 95% CI:1.0–15.3). There was significant reverse correlation between ABI and peripheral vascular disease (R=−0.33; p=0.001). HRI values significantly correlated with thromboembolic disorders (R=−0.29; p=0.03). Finaly, UAID was notably related to microangiopathic complications (p Conclusions The protocol for vascular lesions diagnosis in SCTD should be based on the combination of imaging and laboratory biomarkers. Immunological and inflammatory factors are crucial in diagnostics of vascular involvement in rheumatic diseases. IMT and ABI showed a high prognostic value and can be used for the general cardiovascular risk stratification. Disclosure of Interest None declared.

Author(s): Deodhar, Atul; Gensler, Lianne S; Sieper, Joachim; Clark, Michael; Calderon, Cesar; Wang, Yuhua; Zhou, Yiying; Leu, Jocelyn H; Campbell, Kim; Sweet, Kristen; Harrison, Diane D; Hsia, Elizabeth C; van der Heijde, Desiree | Abstract: ObjectiveTo evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti-tumor necrosis factor [anti-TNF]-naive patients and patients with inadequate response or intolerance to anti-TNF, respectively); study 3 patients had nonradiographic axial SpA.MethodsIn all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3.ResultsFor study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies.ConclusionIn these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.

Purpose The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients’ cohort. Materials and methods Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. Results There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0–8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18–14.0) and 2000 mg (1500–2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01–1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68–4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10–2.71). Conclusions Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

Atherosclerosis (ATS) is a multifactorial disease which may be considered an immune/inflammatory response of intima to tissue damage. Systemic autoimmune rheumatic diseases (SARDs) are a heterogeneous group of disorders characterized by an immune response against self-antigens based on the interaction between genetic predisposition, dysregulation of the immune system, and environmental factors. Various SARDs are associated with accelerated and often premature ATS. Traditional risk factors alone fail to fully account for this phenomenon; thus it has been attributed to complex interactions between traditional risk factors and factors associated with the disease process and its treatment. As cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality in SARDs, there is an immense need for an improved CVD prevention in this patients group. Noninvasive imaging assessment of vascular pathophysiology as well as selected biomarkers can help to improve risk assessment.

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the broad clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Unfortunately the clinical classification, ANCA specificity or genetic characteristics alone is not able to categorize AAV patients in a satisfactory manner. As a consequence advanced statistical techniques were used to identify and stratify AAV subphenotypes [1, 2]. Here we have analyzed influence of the ANCA type on clinical manifestations and demographic characteristics in various types of AAV, based on data from the POLVAS registryObjectives:We decided to retrospectively analyze a large cohort of Polish AAV patients deriving from several referral centers – members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS) – and concentrate on demographic and clinical characteristics of anti-PR3 and anti-MPO positive patients regardless of their clinical diagnosis.Methods:We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016. Patients were enrolled by 9 referral centers. We analyzed dichotomous variables: gender; ANCA status – anti-PR3+ or anti-MPO+, ANCA negative; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves and polytomous variable (number of relapses), supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever)[3].Results:MPO-positive patients (both GPA and EGPA phenotype) were older at the time of diagnosis with a substantial percentage diagnosed > 65 years of age, and with high rate of renal involvement. Interestingly, while in the whole group of patients diagnosed with EGPA male to female ratio was 1:2, the MPO+ EGPA patients showed M:F ratio of 1:1.The analysis of ANCA negative AAV reveled significant differences in GPA, ANCA negative group is characterized with significantly lower frequency of renal involvement compared to rest GPA (11,5% vs 63,7%) pConclusion:ANCA specificity is indispensable as a separate variable in any clinically relevant analysis of AAV subcategories. MPO+ group is characterized by older age at time of diagnosis, male to female ration 1:1, kidney involvement, and shows more homogenous clinical phenotype than PR3+ AAV patients. In our group ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9. https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Biedroń G, Wawrzycka-Adamczyk K, Bazan-Socha S, Ćmiel A, Zdrojewski Z et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2020 Sep 1. Epub PMID: 32896241.[3]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:None declared

Background:Rituximab (RTX) is a B cell depleting monoclonal antibody with proven efficacy in the treatment of ANCA-associated vasculitis (AAV). The infectious complications occur in 15-25%.Objectives:We aimed to assess the frequency and risk factors of infections in patients with AAV receiving RTX among Polish patients.Methods:7 tertiary referral centers experienced in the treatment of vasculitis completed a questionnaire regarding AAV patients treated with RTX.Results:Among 49 patients included in the analysis (47 with GPA, 2 with MPA; 36/73% men; mean age at diagnosis 42,45±14,9 yrs., mean age on RTX initiation 46,14±14,72 yrs.,) at least one infection occurred in 20 patients (40.82%) after mean time of 16,65±16,01 weeks since the administration of RTX. Patients were followed for a mean time of 26,88±21,94 months. There were no differences in the incidence of infectious complications by gender, age, BMI, smoking status, severity of the disease, activity of the disease (BVAS), time from diagnosis to RTX initiation, carriage of staphylococcus aureus in the upper respiratory tract, total dose of CYC before RTX treatment. We didn’t observe severe hypogammaglobulinemia or neutropenia after RTX treatment. 40% of the observed infections occurred during the first month, 35% between second and sixth month of follow-up, while 25% were observed between 6 and 12 months after the RTX initiation. Of the 20 patients who developed infection, 12 (24.5%) had further infections. Antibiotic prophylaxis with trimethoprim–sulfamethoxazole was administered in 40 out of 49 (81.63%). Upper respiratory tract infection was the most common infectious complication (n=11), followed by lower respiratory tract (n=4), soft tissues (n=4) and urinary tract infections (n=4), lacrimal gland abscess (n=2) and abdomen (n=1). In cases with a positive microbial result Staphylococcus aureus (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=1), Candida (n=1) and others (n=6) were identified. No fatalities were recorded and only 3 patients had severe infection with the necessity of prolonged treatment.Conclusion:Despite the high number of infections in our group treated with RTX, most of them were not severe. Upper respiratory tract was the most common site of infection.Disclosure of Interests:None declared

Background:The long-term mortality in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is unexpectedly decreased (1,2,3,4) or at least not increased regardless increased mortality risk factors that these diseases share with other systemic inflammatory disorders.Objectives:We aimed to test the hypothesis on aggregation of increased longevity in families of PMR/GCA patients because the family members of long-lived subjects have a survival advantage.Methods:After questioning our patients we compared age of death of 358 parents of 179 PMR and GCA patients with corresponding data retrieved from 506 parents of 235 randomly collected age and sex matched controls.Results:We found the number of nonagenarian (≥90 year old) mothers of PMR/GCA patients significantly higher vs controls. Both nonagenarian parents were found in 6 patients (3.35%) and in none of the controls. Decreased number of nonagenarian fathers of our patients remains unexplained.Table 1.Number of nonagenarians (.90 years olds) in parents of PMR/GCA patientsParents agePMR/GCA (N=179)Controls (N=253)OR95%CIpMothers148 (82.68%)243 (96.05%)≥9031 (17.32%)10 (3.95%)2.341.11-11.95Fathers≥90161 (89.94%)18 (10.06%)203 (80.24%)50 (19.76%)0.450.24-0.830.0064One of parents≥90136 (75.98%)43 (24.02%)193 (76.28%)60 (23.72%)1.020.63-1.630.9412Both parents≥90173 (96.65%)6 (3.35%)253 (100.00%)0 (0%)8.772.26-405.100.003Mothers of female patients≥90105 (84%)20 (16%)149 (97%)4 (3%)7.12.27-29.190.0001Mothers of male patients≥9043 (80)11 (20%)94 (94%)6 (6%)4.011.25-13.970.0066N - number of all parentsConclusion:Confirming our findings in a wider studies would imply a need of including some genetic or behavioural factors to explain PMR/GCA survival advantage.References:[1]Garen T, Lerang K, Hoffmann-Vold AM, et al. Mortality and causes of death across the systemic connective tissue diseases and the primary systemic vasculitides. Rheumatology (Oxford) 2019;58:313-20.[2]Bengtsson BA, Malmvall BE. Prognosis of giant cell arteritis including temporal arteritis and polymyalgia rheumatica. A follow-up study on ninety patients treated with corticosteroids. Acta Med Scand 1981;209:337-45.[3]Andersson R, Malmvall BE, Bengtsson BA. Long-term survival in giant cell arteritis including temporal arteritis and polymyalgia rheumatica. A follow-up study of 90 patients treated with corticosteroids. Acta Med Scand 1986;220:361-4.[4]Gonzalez-Gay MA, Blanco R, Abraira V et al Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality. J Rheumatol 1997;24:21716.Acknowledgments:o professor Maciej Markiewski for revision of the manuscriptDisclosure of Interests:Marcin Milchert Consultant of: Sanofi, Roche, Marek Brzosko: None declared

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus there is an unmet need for phenotype identification especially among patients with granulomatosis with polyangiitis GPA, patients with microscopic polyangiitis MPA group seems to be more uniform. Recently, based on previous clustering analysis and clinical, histopathological, serological and prognostic aspects three subcategories of AAV have been proposed and named as: non-severe AAV, severe PR3-AAV and severe MPO-AAV [1].Objectives:In line with these attempts to subcategorize AAV we decided to use latent class analysis (LCA) on a large multicenter cohort of polish AAV patients from POLVAS [2] registry to identify potential new subphenotypes or confirm already proposed ones.Methods:Latent Class Analysis (LCA) approach was used as a model based clustering method of objects described by dichotomous (e.g., gender; ANCA status – cANCA, pANCA; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves) and polytomous (number of relapses) variables supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever).Results:Results of LCA on our AAV group returned four class model of AAV subphenotypes, confirming existence of the previously proposed by Mahr at al. [1] and revealed fourth – previously not described clinically relevant subphenotype. To this fourth class - belong patients only with GPA, diagnosed at young age, with multiorgan involvement, high relapse rate and relatively high risk of death.Table 1.AAV subcategorization – summary of clinical characteristics and ANCA specificityLCA Class 1LCA Class 2LCA Class 3LCA Class 4No of patients13019410297AAV typeMainly GPAMainly GPAmainly MPAOnly GPAAge at diagnosisMiddle ageMiddle ageOldYoungMale/female ratio1:22:11:11:1Main organ involvementENT, respiratory, eyeRenal, respiratory, ENTRenal, respiratory, skinMultiorgan involvementRelapse rateintermediateintermediatelowhighModified class description (based on ref. [1])Non severe AAVSevere PR3 AAVSevere MPO AAVSevere non-renalPR3 AAVConclusion:Based on multiple clinical and serological variables LCA methodology identified 4-class subphenotypes model of AAV. Fourth-class is a new clinically important subphenotype including exclusively PR3-positive young AAV patients with multiorgan involvement, high risk of relapse and distinct mortality.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9.https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, i in. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:Krzysztof Wójcik: None declared, Adam Ćmiel: None declared, Anna Masiak: None declared, Zbigniew Zdrojewski: None declared, Radoslaw Jeleniewicz: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Iwona Brzosko: None declared, Marek Brzosko: None declared, Piotr Głuszko: None declared, Małgorzata Stasiek: None declared, Małgorzata Wisłowska: None declared, Joanna Kur-Zalewska: None declared, Marta Madej: None declared, Anna Hawrot-Kawecka: None declared, Hanna Storoniak: None declared, Barbara Bułło-Piontecka: None declared, Alicja Dębska-Ślizień: None declared, Eugeniusz Kucharz: None declared, Katarzyna Jakuszko: None declared, Jacek Musiał: None declared

Systemic lupus erythematosus (SLE) is a rheumatic disease with unclear pathogenesis. In the course of this disease a dysfunction of the immune system occurs, which involves the production of autoantibodies and the deposition of immune complexes, which contributes to the damage of various organs. The most commonly involved organs include: kidneys, skin, joints, the eye, respiratory system, and the cardiovascular and nervous systems, both central and peripheral. In recent years there have been reports regarding the role of cytokines in the pathogenesis of various organs’ involvement. However, until now it has not been entirely clear which cytokines are responsible for either the stimulation or inhibition of the inflammatory response, which could be helpful in establishing a relationship with the clinical picture. In this article reports are summarized regarding Interleukins 4, 7, 10, 18 (IL-4, IL-7, IL-10, IL-18) and their relationship with organ involvement in SLE. Interleukin 4 is indicated as a protective cytokine by its role in preventing the development of an autoimmune response. In the case of IL-7, it has a role in increasing the proliferation of autoreactive T-cell clones and the development of the disease. The IL-10, despite its protective effect, is found in patients with SLE at significantly higher concentrations than in the general population and correlates with the SLEDAI disease activity level scale. Interleukin 18 has a pro-inflammatory effect, contributing to damage to tissues and organs. In the serum of patients with SLE significantly higher levels of IL-18 were found than in the control group; there was also a statistically significant positive correlation between serum IL-18 levels and SLEDAI disease activity level scale and anti-dsDNA antibody titers. Increasing levels of serum IL-18 in SLE patients is associated with an increased risk of cardiovascular disease. In addition, IL-18 has an important role in the involvement of the kidneys and skin in SLE patients.

Introduction : Multiple myeloma is a cancer of the lymphatic system characterized by the proliferation and accumulation of monoclonal plasma cells which in most cases produce monoclonal immunoglobulin. It occurs most often in the elderly. The first symptoms of myeloma are nonspecific. There are, among others, bone pain and weakness associated with anaemia. In advanced myeloma the symptoms mostly arise from the co-existence of osteolytic lesions and pathological fractures. The clinical presentation of multiple myeloma may resemble many other diseases, including rheumatic diseases. Case report : In this publication, we present a case of a patient reporting symptoms of connective tissue disease in the course of multiple myeloma. Conclusion : Symptoms of connective tissue disease may precede or mask the symptoms of cancer. In cases of uncharacteristic course diagnostics should always be expanded to consider proliferative diseases.

Introduction. The aim of our study was to determine the electrocardiography (ECG) and holter abnormalities among patients with dermatomyositis (DM) or polymyositis (PM). Material and methods. We examined 19 patients with PM and 11 patients with DM (23 females) and 30 healthy subjects (22 females). Mean disease duration was 6.5 ± 4.7 years. ECG parameters (QRS, PQ, P wave, conduction disturbances) and heart rate variability data, QT/QTc, ventricular extra beats, creatine kinase, aldolase and lactate dehydrogenase activities were assessed. Results. We did not observe any statistically significant differences in parameters assessing the autonomic system function, the QT/QTc, ventricular rhythm disorders. Intraventricular conduction disturbances were observed in 16.6% of patients with PM/DM. Finally, there were significant differences when comparing enzyme activities. Higher enzyme activities in DM/PM did not correlate with the diurnal variability of cardiac rhythm. Conclusions. This suggests no tendency of DM and PM to involve the autonomic nervous system. Conduction disturbances in DM and PM affect mainly the His-Purkinje system.

Wstęp: Zespół aktywacji makrofagów (MAS) jest rzadkim powikłaniem chorób autoimmunologicznych. U jego podstawy leżą zaburzenia funkcjonowania układu immunologicznego. Sympto­matologia może być różna, z różną dynamiką narastania objawów.Opis przypadku: Kobieta z ustalonym rozpoznaniem choroby Stilla u dorosłych została przyjęta do kliniki z powodu gorączki trwającej od 7 dni, osłabienia, wysypki obejmującej skórę całego ciała oraz objawów dyspeptycznych. W trakcie diagnostyki stwierdzono pancytopenię, hipertrójglicerydemię, hiperferrytynemię, hipofibrynogenemię, podwyższoną aktywność wszystkich enzymów wątrobowych, podwyższone stężenie białka C-reaktywnego, a także obecność przeciwciał przeciwjądrowych. W leczeniu początkowo zastosowano empiryczną antybiotykoterapię oraz pulsy metyloprednizolonu, co jednak nie przyniosło poprawy. Po otrzymaniu wyniku badania cytologicznego szpiku, w którym opisano pobudzoną fagocytozę mogącą odpowiadać zespołowi MAS, doleczenia włączono deksametazon oraz cyklosporynę A i wówczas stwierdzono poprawę. Chora zostawała pod stałą opieką przyklinicznej poradni reumatologicznej i od 20 miesięcy nie nastąpił nawrót MAS.Wnioski: Zespół aktywacji makrofagów jest rzadkim, groźnym powikłaniem chorób autoimmunologicznych wymagającym szybkiego rozpoznania i agresywnego leczenia.

Background Color duplex ultrasonography (CDU) is most promising tool for the assessment of large vessel giant cell arteritis (LV-GCA). There is a need to define ultrasound findings consistent with the diagnosis of GCA. Objectives We aimed to score intima-media thickness (IMT) reference ranges for LV-GCA in polish patients. Methods 214 patients suspected for GCA and evaluated with CDU were included in the study and followed up for min 9 months. Large vessel CDU, together with arteritis/non-arteritis categorization, were performed before or within 1 week after treatment initiation by a single physician. Vasculitis was defined as hypoechoic, homogenous, increase of IMT with distorted wall structure resulting in no clear intima-media structure, over long distance (not limited only to the place of arterial bifurcations). ROC curves were calculated. Results GCA was diagnosed in 81 patients, polymyalgia rheumatica (PMR) in 131 (characteristics – Table 1). Extracranial LV-GCA was diagnosed in 43 patients: axillary vasculitis in 23 patients, common carotid artery (CCA) – 24, subclavian – 18, superficial femoral – 11, brachial (all spreading per continuum from axillary arteritis) – 8. In 83 remaining patients other diagnosis was confirmed, and they served as non-GCA/PMR controls. Mean IMT in LV-GCA was significantly higher versus controls and isolated PMR (Fig. 1). IMT in GCA was not significantly influenced by gender, hypertension and smoking in contrast with IMT in controls. Proposed cut off values for IMT depicting vasculitis in GCA patients are presented in Table 2. 100% specificity for vasculitis (vs GCA without large vessel vasculitis) was reached with axillary IMT of 1.06 mm (62% sens.), subclavian – 1.35 mm (38% sens.), superficial femoral – 1.55 mm (60% sens.), CCA – 1.27 mm (22% sens.). Conclusions We demonstrated that cut off values may discriminate between GCA and its mimics as well as between presence and lack of vasculitis in different arteries in GCA. References Milchert M, Diamantopoulos A, Brzosko M. Atlas of ultrasound application in large vessel arteritis: giant cell arteritis and Takayasu arteritis. Wydawnictwo Pomorskiej Akademii Medycznej, Szczecin, 2016. Disclosure of Interest None declared

Dotychczas opisano wiele przypadków pojawienia się autoprzeciwciał i objawów chorobowych po ekspozycji na adiuwanty, nie tylko w kontekście wszczepienia silikonowych implantów piersi, ale również jako bardzo rzadko występujące odczyny poszczepienne, zespół wojny w Zatoce Perskiej (Gulf war syndrome) czy zespół makrofagowego zapalenia mięśniowo-powięziowego. Grupę chorób, których objawy wystąpiły po tego typu ekspozycji, nazwano autoimmunologicznym zespołem indukowanym przez adiuwanty (autoimmune/inflammatory syndrome induced by adjuvants – ASIA). Do adiuwantów, oprócz silikonowych implantów, zalicza się krzem, skwalen i glin, a także składniki pigmentów stosowanych do wykonywania tatuaży itp. Analizując piśmiennictwo odnoszące się do wpływu adiuwantów na rozwój chorób autoimmunologicznych, nasuwa się wniosek, że oprócz długotrwałej ekspozycji na silikon konieczne jest również współistnienie innych czynników, takich jak predyspozycja genetyczna czy wpływ czynników środowiskowych. Metaanalizy jednoznacznie nie potwierdzają zwiększenia ryzyka wystąpienia choroby autoimmunologicznej po wszczepieniu silikonowych implantów piersi lub wykonaniu tatuażu, ale możliwe jest zwiększenie predyspozycji do ich wystąpienia w pewnej grupie badanych pacjentów. W populacji ogólnej pozytywny wpływ stosowanych szczepień jest znaczący, a ryzyko wystąpienia poważnych odczynów poszczepiennych jest nieporównywalnie mniejsze niż ryzyko zachorowania na daną jednostkę chorobową i wystąpienia jej powikłań, również u chorych z rozpoznanymi chorobami reumatycznymi. Ze względu na niejednorodność wyników dotychczasowych badań oraz trudności w diagnostyce i rozpoznawaniu ASIA, konieczne będzie prowadzenie dalszych badań na temat wpływu adiuwantów na rozwój chorób autoimmunologicznych oraz dopracowanie kryteriów ASIA, które pozwalają obecnie na zbyt łatwe rozpoznawanie tego zespołu.

Background Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). The aim of this study was to evaluate association between serum levels of IL-23 and vascular involvement in SLE patients. Materials and methods Study was performed in 94 SLE patients (82 women and 12 men) aged 19–73 years and in 27 age and gender matched controls. Serum IL-23 was measured with ELISA method using R and D Systems tests. Carotid intima-media thickness and the presence of atherosclerotic plaques in carotid and lower extremities arteries were analysed with B-mode ultrasound. Ankle-brachial and high resistance indexes were measured with Doppler ultrasonography. We took into account classical cardiovascular risk factors (hypertension, dyslipidemia, hyperglycemia, overweight/obesity, smoking, oral contraceptives, positive family history of cardiovascular disease), selected clinical manifestations (cardiovascular, cerebrovascular, lupus nephritis, Raynaud’s phenomenon, livedo reticularis, vasculitis, other thromboembolic complications), profile of autoantibodies (antinuclear, antiphospholipid, anti-neutrophil cytoplasmic, anti-endothelial cell). Statistical analysis was performed with: chi 2 Yates, chi 2 Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0.0005). Patients with high levels of IL-23 more frequently developed atherosclerosis showed as the presence of plaques in right common femoral artery (OR=10.1; 95% CI:1.2–85.1) and lupus nephritis (OR=3.2; 95% CI:1.1–9.6). Among classical atherosclerotic risk factors only obesity was significantly associated with IL-23 (OR=3.8; 95% CI:1.2–12.3). Immunological characteristics significantly related to IL-23 were anti-phosphatidylethanolamine antibodies (OR=12.7; 95% CI:1.5–108.1) and anti-SS-B antibodies (OR=11.8; 95% CI:1.5–94.8). Association with anti-cardiolipin and anti-prothrombin antibodies was on the border of statistical significance (OR=2.3; 95% CI:0.9–5.7 and OR=8.4; 95% CI:1.0–71.1 respectively). Conclusions IL-23 may be involved in lupus nephritis pathogenesis. 2. IL-23 through its significant association with obesity and antiphospholipid antibodies may promote hypercoagulable state contributing to atherothrombosis development in SLE patients.

Objectives. To analyze the correlation between the serum concentration of interleukin- (IL-) 23 and atherosclerotic changes, traditional atherosclerotic risk factors, the autoantibody profile, and involvement of selected organs in systemic lupus erythematosus (SLE) patients.Patients and Methods. We studied 94 SLE patients and 27 controls. We analyzed the IL-23 serum concentration, autoantibodies, carotid intima-media thickness and atherosclerotic plaque, the ankle-brachial index, atherosclerotic risk factors, and organ manifestations.Results. Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0.0015). On the basis of multivariate stepwise analysis, we revealed that high levels of IL-23 were associated with atherosclerotic plaque in common femoral arteries (OR = 12.67; 95% CI: 1.41–113.84), lupus nephritis (OR = 3.69; 95% CI: 1.16–12.22), and obesity (OR = 4.21; 95% CI: 1.40–12.67). Autoantibodies related to IL-23 were anti-phosphatidylethanolamine antibodies (OR = 11.06; 95% CI: 1.24–98.65) and anti-SS-B/La antibodies (OR = 15.43; 95% CI: 1.73–137.25).Conclusions. IL-23 may be involved in lupus nephritis pathogenesis. Through its association with obesity and selected antiphospholipid antibodies, IL-23 might promote a hypercoagulable state contributing to atherothrombosis development in SLE patients.

To assess the association between PTPN22 1858C>T gene polymorphism and susceptibility to, and clinical presentation of, systemic lupus erythematosus (SLE). Our study included 135 SLE patients (120 women and 15 men; mean age 45.1 years; mean course of disease from 0.5 to 31 years) and 201 healthy subjects. The PTPN22 1858C>T gene polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism. A significantly higher incidence of genotype CT in patients with SLE (36.3 %) was found, compared with the control group (24.9 %). The frequencies of C1858 and T1858 alleles were 78.1 and 21.9 % in SLE patients and 86.1 and 13.9 % in controls, respectively. Significantly higher SLE susceptibility was observed in patients carrying at least one T allele (p = 0.009; OR 1.86; 95 % CI 0.14–3.05). Significant association of the PTPN22 T1858 allele (CT + TT vs.CC) and secondary antiphospholipid syndrome was observed (p = 0.049). In SLE patients carrying the T1858 allele, higher levels of antiphospholipid antibodies (anticardiolipin antibodies and/or lupus anticoagulant) were found (p = 0.030; OR 2.17; 95 % CI 1.07–4.44).

Biosimilars are follow-up versions of innovative medicines with proved high similarity to the reference product. There may be some minor differences in clinically inactive components of a molecule which can be clinically significant, but they do not substantially affect the high resemblance to the original drug in their safety and potency. Introduction of the biosimilars brings hope to reduce the cost of treatment, so their availability will increase further as the expiration of patents on biotechnologically produced drugs will follow, which is currently taking place. There are new biosimilar drugs being introduced recently; these are monoclonal antibodies. They are much more structurally complicated compared to the first biotech drugs such as insulin, and their production processes are much more complex. Biosimilars as the end products of such sophisticated technology are affected by many variables. It is not possible to create "biogenerics," but only biosimilar drugs. Therefore, despite their similarities to the reference molecules, biosimilars are too different to forego clinical trials. Clinical trials of biosimilars need to be much broader than for generics, but they are limited compared to the reference biologicals' testing. Placebo controlled clinical trials are not required before registering a new biosimilar. Immunogenicity is a major source of concern related to biosimilars, although there may be the same problem with the original drugs.

Biological drugs revolutionized the treatment of inflammatory rheumatic diseases. Access to treatment presents substantial variability across Europe. The economic level of a particular country as well as administrative restrictions have been proved as determining factors of biological drug uptake. The objective of this paper was to provide an overview of biological treatment in six selected Central and Eastern European (CEE) countries, namely in the Bulgaria, Czech Republic, Hungary, Poland, Romania and Slovakia. The literature is summarized with regard to the epidemiology, disease burden and use of biological agents in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Moreover, an estimate is provided on the prevalence and number of patients with biological treatment based on international and local sources. In view of the limited availability of information and uncertainty in data, there is an urgent need for development of systematic and comprehensive data collection in inflammatory rheumatic diseases in CEE countries.

We have read with great interest the observation of Dasgupta et al. 1 We would like to propose an extended definition of slope sign in giant cell arteritis (GCA) formerly named slide sign,2,3 and present our method of assessing it by using the anteromedial ultrasound examination method of the large supraaortic vessels.4 Slope sign is a pathologically increased intima-media thickness (IMT)5 that spreads over a long arterial segment and slides down to a normal brachial artery where a normal intima-media structure (double line) is observed. This definition contains a description of pathological findings in the axillary artery—a typical location for vasculitis in GCA, contrasting with normal findings in brachial artery—which is usually not involved by vasculitis.6 Slope sign may not be limited to the place of arterial bifurcation of the subscapular artery, which is a typical location of atherosclerotic plaque. A transition zone …

Objective.To assess radiographic progression, physical function, clinical disease activity, and safety in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX) and who were treated with tocilizumab-MTX or MTX during Year 2 of a 2-year study.Methods.During Year 1, patients were randomized to placebo-MTX, 4 mg/kg tocilizumab-MTX, or 8 mg/kg tocilizumab-MTX. During Year 2, patients continued the initial double-blind treatment or switched to open-label 8 mg/kg tocilizumab-MTX. Co-primary endpoints at Week 104 were mean change from baseline in Genant-modified Total Sharp Score (GmTSS) and adjusted mean area under the curve (AUC) for change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI). Signs and symptoms of RA and safety were also evaluated.Results.At Week 104, mean change from baseline in GmTSS was significantly lower for patients initially randomized to tocilizumab-MTX 4 mg/kg (0.58; p = 0.0025) or 8 mg/kg (0.37; p < 0.0001) than for patients initially randomized to placebo-MTX (1.96). Adjusted mean AUC of change from baseline in HAQ-DI was also significantly lower in patients initially randomized to tocilizumab-MTX 4 mg/kg (–287.5; p < 0.0001) or 8 mg/kg (–320.8; p < 0.0001) than in patients initially randomized to placebo-MTX (–139.4). Signs and symptoms of RA were maintained or showed improvement. No new safety signals were noted.Conclusion.Compared with placebo-MTX, tocilizumab-MTX significantly inhibited structural joint damage and improved physical function in patients with RA who previously had inadequate response to MTX. An extension of this study is continuing and will provide additional longterm efficacy and safety data. National Clinical Trials registry NCT00106535.

To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC.

Aortitis is one of the manifestations of giant cell arteritis (GCA) and is included in its definition. There is a significantly increased risk of aortic aneurysm formation in GCA patients. In some GCA patients aortic aneurysm dissection is diagnosed only in autopsy. Monitoring of these patients, especially in long lasting disease, requires a doctor’s awareness of the possibility of aneurysm formation and aortic aneurysm dissection. Based on the available reports it cannot be confirmed whether intensification of aortitis treatment in GCA prevents the development of aneurysms. This article presents an overview of the available literature and our own experience on a rational diagnosis of inflammation and aneurysms of the aorta in GCA, as well as the prospects for its prevention.

Objectives. In this study, we assessed the extra-articular symptoms in constellation with selected serum cytokines and disease activity in spondyloarthritis (SpA). Patients and Methods. We studied 287 SpA patients: 131 had AS, 110 had PsA, and 46 had SAPHO. We assessed extra-articular symptoms in all cases. In 191 SpA patients, we measured serum interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-23 (IL-23), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). Results. Patients with acute anterior uveitis (AAU) had higher VAS (P=0.0008), BADSDAI (P=0.0001), ASDAS-ESR (P=0.04), CRP (P=0.006), IL-6 (P=0.02), and IL-18 (P=0.03) levels. Patients with inflammatory bowel disease (IBD) had higher VAS (P=0.03), CRP (P=0.0009), and IL-6 (P=0.0003) levels. Patients with skin psoriasis had lower VAS (P=0.001) and BASDAI (P=0.00007) levels. Patients with psoriatic onycholysis had lower VAS (P=0.006), BASDAI (P=0.00001), and CRP (P=0.02) and higher IL-23 (P=0.04) levels. Patients with PPP had lower BASDAI (P=0.04) and higher ET-1 (P=0.001) levels. Conclusions. SpA patients with increased serum IL-18 and decreased serum ET-1 had an increased risk of extra-articular symptoms. In SpA patients, increased disease activity was associated with an increased risk of AAU and IBD and a decreased risk of skin psoriasis, psoriatic onycholysis, and PPP.

Antiphospholipid syndrome (APS) is one of the most common reasons of thromboembolic complications in the course of connective tissue diseases. There is a strong relationship between presence of antiphospholipid antibodies and the risk of thrombosis. APS related thromboembolic complications range from superficial vein thrombosis up to rapidly developing, life threatening, multi-organ embolism. We present a case of a 21-year old female who presented with myocardial infarction as the first symptom of systemic lupus erythematosus and APS. Afterwards she was consequently treated with antithrombotic and anti-aggregation agents but it did not prevent her from reoccurrence of middle retinal vein. During the 10-year follow up she presented with reoccurring neurological symptoms i.e.: headache, memory deficits, concentration loss and impairment of the cognitive functions. She was found many times to be positive for IgG and IgM anticardiolipin antibodies, anti-beta2glicoprotein-I antibodies and lupus anticoagulant.

Aim: To test the hypothesis that a therapeutic dose of ocrelizumab (200 mg × 2), can be administered as a single-infusion (400 mg × 1) to achieve clinical efficacy and safety in patients with active rheumatoid arthritis. Patients & methods: Three hundred and fourteen patients were randomized to double-blind placebo, ocrelizumab single-infusion or dual-infusion. The primary end point is American College of Rheumatology (ACR)20 response at week 24 for single-infusion ocrelizumab versus placebo. Results: At 24 weeks, ACR20 responses for patients treated with single-infusion ocrelizumab were not statistically significantly superior to placebo (37.6% [95% CI: 28.8–46.4%] vs 28.1% [95% CI: 17.1–39.1%]; p = 0.2253). ACR20 for dual-infusion ocrelizumab was 52.7% (95% CI: 44.1–61.2%). Initial depletion of peripheral B cells appeared comparable after single and dual-infusions. However, subsequent B-cell repletion occurred earlier after single-infusion. Adverse events were comparable across groups. Conclusion: Ocrel...

Objective To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX. Methods A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented. Results Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (−144.1 and −128.4 units, respectively) than with placebo (−58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events. Conclusion The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile.