Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved ...disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (
p
< 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (
p
< 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (
p
= 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.
Many rheumatic diseases may present with an inflammatory joint syndrome, affecting the small joints of the hands, of which rheumatoid (RA) and psoriatic arthritis (PsA) being one of the most common. ...The aim of this systematic review was to focus on the literature evidence regarding the added value of ultrasound (US) of the hand in the differential diagnosis between RA and PsA. Pubmed and Scopus were searched to identify original manuscripts, published in the last 20 years utilising ultrasonography to reveal specific hand US patterns. Studies were eligible if they: (1) included adults (over 18 years) with a diagnosis of RA/PsA; (2) were published in the English language; (3) were published in peer-reviewed journals; (4) included description of the US machine; (5) used US for assessment of hand joints, periarticular tissues and nails. The search yielded 322 published studies, of which 16 were deemed relevant and were included in the present study. Overall, there was heterogeneity with regard to the pathology examined. Based on the included studies analysis, hand US patterns have several basic features to be considered—location of gray scale (GS) inflammatory findings, involvement of periarticular soft tissue, distribution and extent of Doppler signal (intra- and peri-articular), bone reaction, shape and location of erosions, involvement of tendons without synovial sheath, involvement of enthesis and nail abnormalities. Future research could focus on determining the sensitivity and specificity of the different US detected hand patterns in patients with early arthritis.
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.
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 (
= 0.04) and miR-30a-5p (
= 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) (
= 0.044) and the Nuclear enriched abundant transcript 1 (NEAT1) (
= 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.
To investigate the impact of body mass index (BMI) on clinical disease activity indices and clinical and sonographic remission rates in patients with rheumatoid arthritis (RA).
Sixty-three patients ...with RA were categorized according to BMI score into three groups: normal (BMI<25), overweight (BMI 25-30) and obese (BMI≥30). Thirty-three of them were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and 30 with biologic DMARDs (bDMARDs). Patients underwent clinical and laboratory assessment and musculoskeletal ultrasound examination (MSUS) at baseline and at 6 months after initiation of therapy. We evaluated the rate of clinical and sonographic remission (defined as Power Doppler score (PD) = 0) and its correlation with BMI score.
In the csDMARDs group, 60% of the normal weight patients reached DAS28 remission; 33.3% of the overweight; and 0% of the obese patients. In the bDMARDs group, the percentage of remission was as follows: 60% in the normal weight subgroup, 33.3% in the overweight; and 15.8% in the obese. Within the csDMARDs treatment group, two significant correlations were found: BMI score-DAS 28 at 6th month, rs = .372, p = .033; BMI score-DAS 28 categories, rs = .447, p = .014. Within the bDMARDs group, three significant correlations were identified: BMI score-PDUS at sixth month, rs = .506, p =.004; BMI score-DAS 28, rs = .511, p = .004; BMI score-DAS 28 categories, rs = .592, p = .001. Sonographic remission rates at 6 months were significantly higher in the normal BMI category in both treatment groups.
BMI influences the treatment response, clinical disease activity indices and the rates of clinical and sonographic remission in patients with RA. Obesity and overweight are associated with lower remission rates regardless of the type of treatment.
Background: One of the most common complications in psoriasis is the development of secondary gout that often remains undiagnosed for many years. In some cases, the clinical symptoms of gout precede ...the manifestation of cutaneous psoriasis, leading to progression of the disease and early onset of complications. According to the world data, there is a strong correlation between psoriasis vulgaris and psoriatic arthritis on the one hand and gout on the other ranging from 3 to 40%. In Bulgaria, there are no studies observing the frequency of secondary gout in psoriatic patients. Purpose: We present 3 patients with psoriatic arthritis first misdiagnosed like gout. Results: Due to the diagnostic mistake, the disease is active despite the optimal urate-lowering therapy. When initiating the underlying antirheumatic therapy for psoriatic arthritis, patient’s attacks and the number of tophi starts to decrease and uric acid levels remain stable in reference values. Conclusion: These three case reports reveal the difficult differentiation of the types of arthritis and the importance of correct diagnosis in order to optimize the therapy and reduce the risk of developing complications that leads to increased mortality of the patients.
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 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.
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