Recent Insights into the Role of DNA Methylation and Histone Modifications in Systemic Sclerosis: A Scoping Review.

Systemic sclerosis is a complex idiopathic disease originating from an intricate interplay between genetic susceptibility, environmental factors, and epigenetic modifications. This scoping review aims to map the advancements made regarding DNA methylation abnormalities and histone modifications in systemic sclerosis in the past decade. A literature search was conducted using three electronic databases (Scopus, Web of Science and PubMed) to identify relevant articles. A total of 44 studies were selected for this review, demonstrating the critical contribution of epigenetic perturbations in multiple cell types to disease pathogenesis. In conclusion, this scoping review has elucidated the significant discoveries made in the past decade regarding the role of DNA methylation and histone modifications in systemic sclerosis. Further progress in the field could lead to the development of novel treatment possibilities targeting epigenetic marks.

Severe Acro-osteolysis Mimicking Arthritis Mutilans in a Patient with Primary Hyperparathyroidism: A Case Report.

BACKGROUND: Primary hyperparathyroidism (PHPT) should be considered in the differential diagnosis of a patient with suspected secondary osteoporosis, and severe osteoporosis with multiple fractures is frequently the first clinical manifestation of the disease. CASE PRESENTATION: Mutilating arthritis (arthritis mutilans) can be part of the clinical presentation of a number of rheumatic diseases, most commonly seen in psoriatic arthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, but also in systemic lupus, systemic sclerosis, and multicentric reticulohistiocytosis. Evidence exists that subperiosteal and subchondral bone resorption, seen in PHPT, could induce the so-called 'osteogenic synovitis', which could eventually lead to the development of a secondary osteoarthritis with bone deformities. CONCLUSION: Here, we present a case report of a patient initially diagnosed with PHPT who presented with mutilating arthritis of the finger joints and discuss whether the severe acro-osteolysis is a manifestation of the endocrinopathy or whether there is a co-existing undiagnosed inflammatory joint disease.

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

The COVID-19 pandemic's impact on rheumatic disease patients' satisfaction with access to medical services.

The COVID-19 hurt various lifestyle aspects, especially the treatment and follow-up of patients with chronic diseases such as autoimmune inflammatory rheumatic diseases (RD). The new circumstances changed the frequency of medical examinations and the way patients with rheumatic diseases are followed up. The objective is to study the impact of COVID-19 on RD patients' satisfaction with access to medical services. A national multicenter observational cross-sectional anonymous online survey was conducted on patients with RD using a specially developed web-based platform and structured questionnaire https://rheumatologycovid19.bg/ . The study was carried out with the support of intra-university project №6/2022 MU-Plovdiv. 1288 patients participated, with an average age of 47.03 (SD ± 12.80 years), of whom 992 (81.6%) were women. The questionnaire contained 41 questions grouped into 5 panels. Descriptive statistics were used-mean, alternative analysis, logistic regression and Decision Tree using the CRT (classification and regression trees) method. The study found that RD patients' satisfaction with access to medical services was influenced by communication type and the frequency of visits to the rheumatologist, difficulties in prescribing and finding medicines and the presence of comorbidities. The likelihood of patients' satisfaction with their rheumatologist was 5.5 and 3 times higher for in-person and other means of communication, respectively, compared to those without any communication. The relative share of patients who communicated by phone was larger (59%) compared to pre-pandemic (41%), where direct contact with the physician prevailed (80%). The results of the study confirmed the need to optimize remote access to medical care for patients with RD during the pandemic.

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

OBJECTIVES: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases. METHODS: The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis. Patients had discontinued one prior TNFαi (due to loss of efficacy, tolerability, or inconvenience) and were followed for 12 months after GLM initiation. Primary endpoints included the proportion of patients achieving low disease activity (LDA, DAS28-CRP<3.2) in RA, minimal disease activity (MDA, fulfilment of 5 of 7 outcome measures) in PsA, or low disease activity (ASDAS<2.1) in axSpA at 6 months. Disease activity at 3 and 12 months and quality of life (QoL; EQ-5D-3L) were also assessed. Adverse events were monitored. Protocol-specified analyses were based on observed data. RESULTS: In 712 patients, (n=325, RA; 186, PsA; 201, axSpA), mean age was 54 years, 64% were female, and median disease duration was 5 years. Primary endpoints were achieved in 58.3% (RA), 45.5% (PsA), and 45.4% (axSpA) of patients; disease activity improvements were observed at 3 and 12 months and EQ-5D-3L results showed improved QoL over time. The treatment persistence rate at 12 months was 67.8% of patients. No new safety signals were observed. CONCLUSIONS: This pooled analysis of the GO-BEYOND studies showed that treatment with GLM was effective and represented a valid second-line option for RA, PsA, and axSpA patients.

Effect of the body mass index, basal metabolic rate, and body fat on the radiofrequency echographic multi-spectrometry (REMS)-based bone mineral density and fracture risk: a cross-sectional study.

Radiofrequency echographic multi-spectrometry (REMS) is a method to assess bone mineral density (BMD) of the axial skeleton, fragility score (FS), body mass index (BMI), basal metabolic rate (BMR), and body fat (BF) in %. The aim of the study was to investigate the influence of the BMI, BMR, and BF on the BMD and fracture risk with REMS. We conducted a cross-sectional study among 313 women, aged 20-90 years who underwent a screening for osteoporosis with REMS. Kruskal-Wallis was used to analyze the differences in BMI, BMR, and BF between the groups according to the BMD: normal BMD, osteopenia and osteoporosis and differences in the FS, fracture risk assessment (FRAX) for major osteoporotic fractures and for hip fractures (HF) according to the BMI groups: underweight, normal weight, overweight, obese, and extreme obese. Linear regression was used to assess the correlations BMI-BMD, BMR-BMD, and BF-BMD. BMI, BMR, and BF differed significantly between the groups according to the BMD (p < 0.001, p = 0.028, and p < 0.001, respectively). BMR showed high positive correlation to BMD (R = 0.765) with 95% confidence interval (CI) [0.715, 0.807] and significance of p < 0.001. BMI correlated significantly to BMD (p < 0.001), the correlation was low positive (R = 0.362) with 95% CI [0.262, 0.455]. In the BMI groups, there was significant difference in FRAX for HF and FS with p value 0.014 and < 0.001, respectively. Subjects with low BMI, BMR, and BF are at high risk for osteoporosis. Underweight women show significantly high fracture risk, assessed with FRAX and FS.

High-resolution musculoskeletal ultrasonography and elastography for eosinophilic fasciitis diagnosis and follow-up: a case-based review.

Eosinophilic fasciitis (EF) remains a rare condition without precise diagnostic criteria due to common symptoms with other autoimmune diseases requiring broad differential diagnosis. This paper describes the use of high-resolution musculoskeletal ultrasonography and elastography in the diagnosis and follow-up of eosinophilic fasciitis through the case of a 56-year-old male patient. In addition to laboratory data, instrumental data, and biopsy, musculoskeletal ultrasonography (US) was used both in the diagnostic process and in the follow-up period for an objective assessment of the changes in the patient's condition and response to treatment. The US showed disorganization of the myofibrils adjacent to the superficial fascia, edema, and thickening of the fascia and subcutaneous edema. In addition, the use of shear-wave elastography (SWE) demonstrated significantly reduced skin elasticity. High-frequency musculoskeletal ultrasound in combination with SWE is an effective method both for the diagnosis of EF and for the follow-up of the changes occurring after therapy. Based on the fact that it can easily differentiate the substrate of involvement, such as skin, subcutaneous tissue, or muscle fascia, ultrasound can be used to distinguish EF from other skin and muscle diseases.

First multi-center retrospective study assessed the compliance with and persistence of biological therapies in Bulgarian population with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9 months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.

An observational study of the radiofrequency echographic multi-spectrometry (REMS)-based fragility score of the lumbar spine and total fracture risk at 5 years in women.

A novel fragility score (FS) parameter, obtained during radiofrequency echographic multi-spectrometry (REMS), was developed to estimate the ultrasound-based skeletal fragility. The aim of our study is to assess the REMS-based FS of the lumbar spine (LS) among the Bulgarian women and to compare their characteristics acquired with REMS between fracture risk classes corresponding to a total fracture risk at 5 years for major osteoporotic fractures (MOF). A total of 100 Bulgarian women, who underwent a screening for osteoporotic fracture risk using the REMS technology, were included in a prospective observational study. The mean age was 60 years (years) ± 13.9 standard deviations. We assessed the FS of the LS and for each subject. The fracture risk class (R1-R7) was identified using a table combining measured REMS T score and FS values. The mean FS was 36.9 ± 17.4 SD (range: 18.5-84.3). Twelve subjects (12%) were classified into the R6 group, twenty-three (23%) into the R5, sixty-one (61%) into R4, and four (4%) into R3. Statistical analysis showed significant difference in age, height, BMD, T score, Z score, age of menopause, FRAX for MOF, and FRAX for hip fractures between the risk class groups. This is the first study which showed the REMS-based FS of the lumbar spine among the Bulgarian women. T score alone is not a good predictor of fractures. Our study showed that its use in combination with the fragility score obtained during REMS offers a robust assessment of the fracture risk at 5 years for MOF.

Ultrasound description and follow up of painful cervical interspinous bursitis in a Polymyalgia Rheumatica patient - a case report.

We present a Polymyalgia Rheumatica (PMR) case with active Cervical Interspinous Bursitis (CIB) causing debilitat-ing neck pain as the most intensive symptom of the disease as reported by the patient. CIB was diagnosed and followed by Musculoskeletal Ultrasound (MSUS). MSUS examination of patient's posterior cervical region reviled well demarcated an-/ hypoechoic lesions around and cranially of the spinous processes of the sixth and seventh cervical vertebra. The initial detailed sonographic characteristics of the CIB are described, as well as the evolution of lesions size and extent with the treatment and patient's clinical improvement. To our knowledge this is the rst detailed sonographic description of CIB in PMR.

Adherence to biological therapies in patients with rheumatoid arthritis: a retrospective cohort study.

The advent of biologic disease-modifying antirheumatic drugs has dramatically changed the comprehensions of treatment and long-term prognosis in patients with rheumatoid arthritis. The potent therapeutic results can only be achieved if the patients adhere to prescribed medications. The objective of this study was to estimate the impact of age, gender, duration of the disease, concomitant Methotrexate therapy, prior exposure to biologic agents, disease activity, functional capacity, and health-related quality of life on adherence to biologic treatment among Bulgarian population with rheumatoid arthritis. This was a retrospective observational cohort study that included 179 patients. At the baseline visit and subsequent follow-up assessments at 6, 12, 24 and 36 months, patients were interviewed by a physician and underwent physical examinations. We monitored the changes in disease activity, functional capacity and health-related quality of life on each time point. Univariate and multivariate binary logistic regression was used to determine the prognostic value of possible predictors of treatment adherence. Our findings showed that only DAS28 score [odd ratio (OR) = 1.174; 95% CI 1.74-2.362] and HAQ score (OR 2.803; 95% CI 1.428-5.503) remained significant for the treatment adherence throughout the study period. The adherence to the biologic disease-modifying anti-rheumatic drugs among Bulgarian patients with rheumatoid arthritis is suboptimal. A multifaceted and comprehensive knowledge of the influencing factors can be useful for the development of different strategies that can improve treatment adherence.

Rheumatoid arthritis and the proinflammatory cytokine IL-17.

INTRODUCTION: Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients. AIM: To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA. MATERIALS AND METHODS: Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients. RESULTS: The mean serum level of IL-17 in RA patients was higher (12.8 pg/ml) than that in healthy controls (7.9 pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/-) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/-) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/-) and IL-17 (rs=0.388, p=0.015). CONCLUSIONS: The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients' group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients.

Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria-Results from a 7-Year Study.

Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including a control group on standard-of-care therapy (SC) with simple analgesics and physical exercises, and a study group (SG) on standard-of-care therapy supplemented by vitamin D3 and intravenous administration of zoledronic acid (5 mg) yearly for 3 consecutive years. Patient groups were homogenized regarding the following: (1) radiographic grade (RG), including 75 patients with hip OA RG II according to the Kellgren-Lawrence grading system (K/L), and 75 with RG III on K/L; (2) radiographic model (RM), as each of the K/L grades was subdivided into three subgroups consisting of 25 patients of different RMs: atrophic ('A'), intermediate ('I'), and hypertrophic ('H'); (3) gender-equal ratio of men and women in each subgroup (Female/Male = 15/10). The following parameters were assessed: (1) clinical parameters (CP), pain at walking (WP-VAS 100 mm), functional ability (WOMAC-C), and time to total hip replacement (tTHR); (2) radiographic indicators(RI)-joint space width (JSW) and speed of joint space narrowing (JSN), changes in BMD (DXA), including proximal femur (PF-BMD), lumbar spine (LS-BMD), and total body (TB-BMD); (3) laboratory parameters (LP)-vitamin D3 levels and levels of BT/CT markers. RV were assessed every 12 months, whereas CV/LV were assessed every 6 months. Results: Cross-sectional analysis (CsA) at baseline showed statistically significant differences (SSD) at p < 0.05 in CP (WP, WOMAC-C); BMD of all sites and levels of CT/BT markers between the 'A' and 'H' RM groups in all patients. Longitudinal analysis (LtA) showed SSD (p < 0.05) between CG and SG in all CP (WP, WOMAC-C, tTHR) parameters of RP (mJSW, JSN), BMD of all sites, and levels of CT/BT markers for all 'A' models and in 30% of 'I'-RMs (those with elevated markers for BT/CT at baseline and during the observation period). Conclusion: The presence of SSD at baseline ('A' vs. 'H') supported the thesis that at least two different subgroups of HOA exist: one associated with 'A' and the other with 'H' models. D3 supplementation and the intravenous administration of bisphosphonate were the treatment strategies that slowed down RP and postponed tTHR by over 12 months in the 'A' and 'I' RM with elevated BT/CT markers.

Ochronotic arthropathy in the context of spondyloarthritis differential diagnosis: a case-based review.

Alkaptonuria is a disease often forgotten because of its rarity. Its pathogenic mechanism is the deficiency of one of the enzymes of the tyrosine degradation pathway-homogentisate-1, 2-dioxygenase, which sequelae is accumulation and deposition of its metabolite homogentisic acid in connective tissues and urine. Alkaptonuria presents as a clinical triad-darkening urine upon prolonged exposure to air, pigmentation of connective tissues and debilitating arthropathy. We present a case report of a 67-year old patient with alkaptonuria who presented with the clinical triad, but was mistakenly diagnosed as having ankylosing spondylitis in the past. Currently there is no treatment for the disease hence the management strategy was focused on symptoms control with analgesics, physical therapy, dietary modification, vitamin C supplementation, and joint arthroplasty. Alkaptonuria's clinical features are extensively described in the literature and despite the fact that it is a rare disease, due to the similar radiographic changes with spondyloarthropathies, it should be included in the differential diagnosis in young patients presenting with severe joint involvement. Early recognition of the disease is necessary since its natural evolution is joint destruction leading to significant reduction in the quality of life. Alkaptonuria's articular features in the spine and peripheral tissues are well described using the classical imaging techniques. Musculoskeletal ultrasonography shows a characteristic set of findings in the soft tissues, including synovium, cartilage, tendons and entheses.

Assessment of serum and synovial fluid MMP-3 and MPO as biomarkers for psoriatic arthritis and their relation to disease activity indices.

Research on biomarkers for the diagnosis and monitoring of psoriatic arthritis (PsA) is ongoing. The purpose of this study was to assess the potential of serum and synovial fluid matrix metalloproteinase-3 (MMP-3) and myeloperoxidase (MPO) as biomarkers for PsA and their relation to disease activity indices. This case-control study involved 156 psoriatic arthritis patients, 50 gonarthrosis patients, and 30 healthy controls. The target parameters were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Serum MMP-3 and MPO levels were elevated in the PsA patients in comparison to the two control groups (p < 0.001) and distinguished PsA from GoA patients and healthy controls with 100% accuracy. Synovial MMP-3 discriminated PsA from GoA patients irrespective of the presence of crystals (AUC = 1.00). PsA patients with crystals in the synovial fluid had elevated synovial MPO (p < 0.001) and were distinguished from PsA patients without crystals with accuracy of 88.50% and from GoA patients with accuracy of 88.30%. Synovial fluid MPO was positively associated with the following indicators of disease activity: VAS (rs = 0.396); DAPSA (rs = 0.365); mCPDAI (rs = 0.323). Synovial MMP-3 showed a weaker positive association with DAPSA (rs = 0.202) and mCPDAI (rs = 0.223). Our results suggest that serum MMP-3 and MPO could serve as biomarkers for PsA. Synovial fluid MMP-3 showed a potential as a biomarker for PsA versus GoA. Synovial MPO could be utilized as a marker for the presence of crystals in PsA patients.

Assessment of TNF-α expression in unstable atherosclerotic plaques, serum IL-6 and TNF-α levels in patients with acute coronary syndrome and rheumatoid arthritis.

The role of inflammatory cytokines is well researched in acute coronary syndrome (ACS) and rheumatoid arthritis (RA), but not in the presence of both conditions. This study aimed to compare TNF-α expression, serum TNF-α, IL-6, and hs-CRP in ACS patients with RA (n = 46) with ACS patients without RA (n = 49) and healthy controls (n = 50). TNF-α expression was assessed from coronary artery samples, taken during coronary artery bypass surgery. Serum levels TNF-α, IL-6, and hs-CRP were measured 24 and 48 h after cardiac surgery. Stronger TNF-α expression was observed in the ACS patients with RA versus the ACS patients without RA, p = 0.001. Serum TNF-α, IL-6, and hs-CRP at the 24th h were significantly elevated in both patient groups and distinguished them from the healthy controls with accuracy ranging from 80 to 99%. At the 48th h, serum TNF-α and IL-6 in the ACS group without RA decreased to those of the healthy controls but remained high in the group with RA. ACS cases with RA could be correctly identified from the levels of IL-6 (AUC = 0.885, 95% CI 0.791 to 0.938) and TNF-α (AUC = 0.852, 95%CI 0.720 to 0.922). Our results suggest that the presence of RA in ACS cases is likely to provoke stronger TNF-α expression on atherosclerotic plaques, aggravate the pro-inflammatory response, and sustain it even after the cardiac stress is lowered. In ACS cases with RA, long-term monitoring and control of TNF-α and IL-6 levels can be a useful preventive strategy.

A Seven-Joint Ultrasound Score for Differentiating Between Rheumatoid and Psoriatic Arthritis.

BACKGROUND: Differentiating between seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA) presenting only with the involvement of the small joints of the hands can be challenging. Implementing musculoskeletal ultrasound (US) to reveal specific patterns of joint and tendon involvement may have an added value in the management of early arthritis. OBJECTIVE: The aim was to investigate whether a seven-joint US score was able to distinguish between patients with RA and PsA. MATERIALS AND METHODS: One hundred and forty-one patients with RA, 65 patients with PsA, and 45 healthy controls (HC) were included in the current study. US assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint was performed, and the following scores were calculated: synovitis and tenosynovitis/ paratenonitis scores on grayscale ultrasound (GSUS) and on power Doppler (PD) US, erosion score, US7 score. RESULTS: RA patients had significantly higher median scores of GS synovitis, PD synovitis, erosions, and US7 than PsA patients (p < 0.001). PsA patients had significantly higher median scores of GS tenosynovitis/paratenonitis and PD tenosynovitis/paratenonitis (p < 0.001). All US scores were significantly higher for both patient groups as compared to the HC group (p < 0.001). CONCLUSION: Sonographic evaluation by a seven-joint score can be helpful in the differentiation between rheumatoid and psoriatic arthritis.

The lncRNAs/miR-30e/CHI3L1 Axis Is Dysregulated in Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease with completely undefined etiology and treatment difficulties. The expression of both protein coding and non-coding RNAs is dysregulated during disease development. We aimed to examine a possible regulatory axis implemented in the control of chitinase-3 like protein 1 (CHI3L1) or YKL-40, an inflammation-associated glycoprotein, shown to be elevated in SSc. A panel of seven miRNAs and three lncRNAs potentially involved in the control of CHI3L1 were selected on the basis of in silico analysis. TagMan assay was used to evaluate the expression levels of miRNAs and RT-qPCR for lncRNAs in white blood cells (WBCs) and plasma from SSc patients and healthy controls. Among the eight screened miRNAs, miR-30e-5p (p = 0.04) and miR-30a-5p (p = 0.01) were significantly downregulated in WBCs and plasma of SSc patients, respectively. On the contrary, the expression of the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) (p = 0.044) and the Nuclear enriched abundant transcript 1 (NEAT1) (p = 0.008) in WBCs was upregulated compared to the controls. Increased levels of MALAT1 and NEAT1 could be associated with the downregulation of miR-30e-5p and miR-30a-5p expression in WBCs and plasma. We present novel data on the involvement of a possible regulatory axis lncRNAs/miR-30e/CHI3L1 in SSc and hypothesize that MALAT1 and NEAT1 could act as miR-30e-5p and miR-30a-5p decoys. This may be a reason for the increased serum levels of CHI3L1 in SSc patients.

Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population.

Background: Osteoporosis is a common chronic disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of the bone, which are associated with increased risk of fragility fractures. Currently the most popular tool is the fracture risk assessment model FRAX to calculate the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF). Objective: To investigate the prevalence of low BMD at axial sites and fracture risk in Bulgarian population. Methods: We retrospectively analyzed dual energy X-ray absorptiometry (DXA) scan results of 12 478 subjects. Scan results included BMD and T-score assessments of lumbar spine and femoral neck. FRAX major osteoprotic fracture (MOF) and FRAX hip fracture (HF) were assessed in subjects between 40 and 90 years using BMD values. Results: Of total 12478 subjects, 12119 were women and 359 were men. The mean age of the subjects was 61 years (yrs.) ± 10 yrs. The overall prevalence of low BMD at the lumbar spine was 6084/9336 subjects (65.2%). 3502/9336 subjects (37.5%) were considered as osteopenic and 2582/9336 subjects (27.7%) were considered as osteoporotic. The overall prevalence of low BMD at the femoral neck was 2036/3140 (64.8%). 1641/3140 subjects (52.3%) were classified as osteopenic and 395/3 140 subjects (12.6%) were classified as osteoporotic. The mean values of FRAX MOF and FRAX HF increased significantly with increasing the age interval. Conclusion: This study is the largest epidemiological research in Bulgaria up to date about the prevalence of low BMD at axial sites.

Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial.

OBJECTIVE: ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients. METHODS: Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab. RESULTS: At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes. CONCLUSION: A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT02771210.