Chronic Rheumatic Disease Research Articles

AKAP12 and RNF11 as Diagnostic Markers of Fibromyalgia and Their Correlation with Immune Infiltration.

Fibromyalgia (FM) is a chronic nonarticular rheumatic disease mainly characterized by diffuse disseminated skeletal muscle pain, with varied symptoms including anxiety, sleep disturbance, and fatigue. Due to its unknown etiology and pathogenesis, FM is easily ignored in clinical practice, resulting in unclear diagnosis and difficult treatment. This study is aimed at investigating whether AKAP12 and RNF11 can be used as biomarkers for the diagnosis of FM and at determining their correlation with immune infiltration. The FM dataset in Gene Expression Omnibus (GEO) database was downloaded and was randomly divided into the training and test sets. Differentially expressed genes (DEGs) were screened, and functional correlation analysis was performed. Diagnostic markers of FM were screened and validated by random forest (RF). The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was then used to evaluate immune cell infiltration in the FM patients' peripheral blood. Finally, Spearman's rank correlation analysis was used to identify correlation between the diagnostic indexes and immune cell infiltration. A total of 69 DEGs were selected. Results indicated that AKAP12 and RNF11 can be used as diagnostic markers of FM, and CD8 + T cells might contribute in the pathogenesis of FM. In addition, AKAP12 was positively correlated with CD8 + T cells, while RNF11 was negatively correlated with CD8 + T cells. In conclusion, AKAP12 and RNF11 can be used as diagnostic indicators of FM, and CD8 + T cells may be involved in the occurrence and development of FM.

Metallothionein-1 is Positively Correlated with Inflammation and Ankylosing Spondylitis Activity.

IntroductionAnkylosing spondylitis (AS) is a common form of chronic inflammatory rheumatic disease. Metallothionein-1 (MT-1) has been known to play an immunosuppressive role in various noninfectious inflammatory diseases, especially osteoarthritis and rheumatoid arthritis, thus inhibiting inflammation and pathogenesis in various diseases. However, whether MT-1 is related to AS is unclear. Here, we examined the levels of MT-1 in patients with AS and its correlation with the disease activity, complication, clinical indexes, and inflammatory cytokines and attempted to explain the effect of MT-1 on inflammation in AS.MethodsThe messenger RNA (mRNA) and protein expression of MT-1 in patients with AS were detected through real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The associations between serum MT-1 protein level and clinical indexes or proinflammatory cytokines in AS were analyzed using the Spearman correlation test.ResultsThe mRNAs and serum protein levels of MT-1 were significantly higher in patients with AS, especially in patients with active AS and patients with osteoporosis (OP) than in healthy controls (HCs), and no difference was observed between patients with inactive AS and HCs. Serum MT-1 levels positively correlated with disease activity, proinflammatory cytokines, and clinical indexes Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein, C-reactive protein level, and erythrocyte sedimentation rate in patients with AS.ConclusionMT-1 expression was upregulated in patients with active AS but not in those with inactive AS and positively correlated with clinical indexes, especially in OP, as well as with proinflammatory cytokines tumor necrosis factor–alpha, interleukin (IL)-1β, and IL-6 in patients with AS.

17 Anemia in juvenile idiopathic arthritis: analysis of associated factors

Abstract Background Anaemia is the most frequent hematological disorder in chronic inflammatory rheumatic disease. Few studies have focused on this impairment in juvenile idiopathic arthritis (JIA). Objectives To identify the factors associated with anaemia in JIA. Methods We conducted a retrospective study including adults with long-standing JIA according to the International League of Associations for Rheumatology (ILAR) criteria over a period of 28 years (1994–2022). Demographic, clinical, biological, and radiographic data were collected. These parameters were compared according to the presence or absence of anaemia. Results Seventeen women and 12 men were enrolled. The mean age was 35.69 ± 11.72 [18–61] years. The mean age of disease onset was 11.10 ± 4.25 [2–16] years. The average diagnostic delay was 52.96 ± 95.97 [0–336] months. The average disease duration was 24.48 ± 12.76 [1–47] years. The polyarticular form was the most frequent (n = 16). Rheumatoid factor, ACPA and antinuclear antibodies were present in 41.4%, 24.1% and 17.2% of cases respectively. Mean CRP values were 42.74 ± 63.37 [2–218] mg/l, a biological inflammatory syndrome was present in 19 cases. NSAIDs, corticosteroids and methotrexate were used in 62.1% (n = 18), 69% (n = 20) and 79.3% (n = 23) respectively. Anaemia was noted in 69% (n = 20) of cases, it was hypochromic in 8 cases and microcytic in 11 cases. The mean haemoglobin value was 11.31 2.10 [6.5–15] g/dl. Anaemia was associated with the following parameters in our study: female sex (88.2% vs 41.7%; p = 0.008), absence of anti-nuclear antibodies (76.9% vs 20%; p = 0.026) and corticosteroid therapy (85% vs 33.3%; p = 0.005). However, the comparison of patients according to the presence of anaemia did not show any significant difference for these parameters: age, age at onset, diagnostic delay, duration of symptoms, extra-articular manifestations, CRP value, presence of biological inflammatory syndrome, rheumatoid factor, ACPA, erosive nature and treatment (NSAIDs and methotrexate). Conclusion Anaemia is common in JIA. Its treatment is part of the overall management of the disease.

Evaluation of the impact of successful percutaneous balloon mitral valvuloplasty on the left ventricular twist and untwist mechanics by the two dimensional speckle tracking imaging

Background: MS is one of the most prevalent valve abnormalities in people with chronic rheumatic heart disease (RHD). The effect of Inoue and multi-track successful percutaneous balloon mitral valvuloplasty (PBMV) on the twist and untwist mechanisms of the left ventricle was evaluated using non-invasive two-dimensional speckle tracking imaging (STI). Methods: This study was conducted on patients with mitral stenosis of rheumatic origin fulfilling the criteria for PBMV. Cases were categorized into two equal groups; group 1: 30 Patients underwent PBMV using Inoue technique and group 2: 30 Patients underwent PBMV using multi-track technique. All patients were subjected to full history and clinical examination, twelve leads surface electrocardiogram (ECG) before and after the procedure, two-dimensional and Doppler echocardiography, LV twist and untwist measured by the 2D the two-dimensional speckle tracking imaging (STI) before and after the procedure and PBMV. Results: In both techniques; the mitral valve area (MVA) was highly significantly increased after balloon mitral valvuloplasty (BMV), while mean pressure gradient (MPG) and the estimated systolic pulmonary artery pressure (PAP) were highly significantly decreased. The apical rotation, basal rotation, twist and untwist were highly significantly decreased after the procedure in each technique.

Management of chronic rheumatic diseases in women 18–45 years of age in Asia Pacific: insights from patient and clinician surveys

ObjectivePerspectives of women aged 18–45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported.MethodsOnline surveys were completed by women, pregnant in the past 2–5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs.ResultsAmong 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy.Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were ‘very comfortable’ with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18–45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort.ConclusionsPatients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC.

Association of short-term exposure to ambient PM1 with total and cause-specific cardiovascular disease mortality

BackgroundThe acute effects of exposure to ambient particulate matter with an aerodynamic diameter ≤1 μm (PM1) on cardiovascular disease (CVD) mortality remain unclear. ObjectivesTo investigate whether short-term exposure to ambient PM1 was associated with mortality from total and/or cause-specific CVDs, and estimate the excess mortality. MethodsA time-stratified case-crossover study was conducted among 1,081,507 CVD deaths in Jiangsu province, China from 2015 to 2020. We assessed daily residential ambient PM1 exposures using a validated grid dataset for each subject. Conditional logistic regression models and distributed lag linear or nonlinear models were employed to quantify the association of PM1 exposure with mortality during the same day of CVD death and 1 day prior. ResultsEach 10 μg/m3 increase of PM1 exposure was significantly associated with a 1.46 % (95 % confidence interval: 1.28 %, 1.65 %), 1.95 % (1.28 %, 2.63 %), 1.16 % (0.86 %, 1.47 %), 1.41 % (1.13 %, 1.69 %), and 1.83 % (1.37 %, 2.30 %) increased odds of mortality from total CVDs, hypertensive diseases (HDs), ischemic heart diseases (IHDs), stroke, and sequelae of stroke, respectively (all p <0.05). No significant association was identified with mortality from pulmonary heart disease or chronic rheumatic heart diseases. The excess fraction of total CVD mortality attributable to PM1 exposure was 5.71 %, while the cause-specific excess fractions ranged from 4.98 % for IHDs to 7.46 % for HDs. Significantly higher excess fractions were observed for total and certain cause-specific CVD mortality in adults 80 years or older. ConclusionsWe found that short-term exposure to ambient PM1 was significantly associated with an increased odds of mortality from total and specific CVDs and may lead to considerable excess mortality especially among older adults. Our findings highlight a potential approach to prevent premature CVD deaths by reducing PM1 exposures and provide essential quantitative data for the development of future air quality standards for ambient PM1.

Increased rates of fragrance allergy in fibromyalgia individuals tested with the Swedish baseline patch test series.

Contact allergy can manifest in a variety of ways clinically. Systemic contact allergy may occasionally present with pain in muscles and joints. Fibromyalgia is a chronic rheumatic disease characterized by pain and with virtually unknown aetiology. The aim of this study was to investigate the contact allergy rates to the sensitizers in a baseline series and compare with corresponding rates in dermatitis patients and the general population. Patch testing with the Swedish baseline series was performed in 120 individuals with fibromyalgia. Fisher's exact test was used for pair-wise comparisons of contact allergy rates between the fibromyalgia group and two control groups, dermatitis patients and individuals in the general population. Contact allergy was significantly more common in the fibromyalgia group compared to the general population concerning nickel and the fragrance markers Myroxolon pereirae and fragrance mix I. There were fewer allergic reactions to preservatives in the fibromyalgia group compared with the dermatitis group. Myroxolon pereirae and fragrance mix I represent besides fragrance allergy also allergy to flavouring substances which indicate that oral exposure to flavouring substances and hygiene products might be important for sensitization and possibly elicitation of systemic contact allergy symptoms in fibromyalgia individuals.

Promising approaches to early diagnosis of chronic rheumatic heart disease

Aim to determine the prevalence of acute rheumatic fever (ARF) in children and chronic rheumatic heart disease (HRHD) in adults on the example of the Samara region and to propose measures for the early detection and prevention of valvular heart lesions.&#x0D; Material and methods. The authors cite the material of their own research, indicating a significant prevalence of rheumatic etiology of valvular lesions that required surgical treatment in 20162020 in the Samara region. We retrospectively analyzed the prevalence of acute rheumatic fever and chronic rheumatic heart disease in out-patients of a large polyclinic of Samara city.&#x0D; Results. The study demonstrates the low frequency of acute rheumatic fever in the Russian Federation along with the disproportionately high prevalence of chronic rheumatic heart disease.&#x0D; Conclusion. It is advisable to supplement the procedure for preventive medical examinations of the underage, has being in force in the territory of the Russian Federation since 2017, by ultrasound examination of the heart for the timely diagnosis of chronic rheumatic heart disease and long-term treatment with benzathine penicillin. In this case, it is also possible to identify previously undiagnosed congenital heart defects and heart diseases that manifest in adolescence.

Intravenous treatment adherence of patients with chronic inflammatory rheumatic diseases during the COVID-19 pandemic: experience of a single center.

Introduction: Patients with chronic inflammatory rheumatic diseases (CIRD) who receive intravenous therapy requiring hospitalization are likely to be more affected than those with receiving oral therapy during COVID-19 pandemic. We aimed to investigate the effect of the COVID-19 pandemic on adherence to treatment in patients with CIRD receiving intravenous treatments. Methods: We evaluated patients with CIRD who were treated with intravenous immunosuppressive therapy such as rituximab (RTX), cyclophosphamide (CTX), infliximab (IFX), tocilizumab (TCZ) and abatacept (ABA) in our inpatient rheumatology clinic. The patients' medical treatment compliance and clinical follow-up were evaluated. Treatment discontinuation was decided according to postponement of at least one dose and discontinuation of CIRD treatments. Demographics and clinical characteristics were compared between treatment-incompliant (TI) and treatment-compliant (TC) groups. Results: A total of 181 CIRD patients were enrolled. Rheumatoid arthritis was the most common disease requiring intravenous immunosuppressive treatment followed by axial spondyloarthritis and Behçet's disease. Joint involvement was the most common followed by lung and kidney involvements. Rituximab was the most widely used intravenous immunosuppressive treatment for the CIRD. 34% patients have postponed at least one dose of their intravenous CIRD treatment and 25% discontinued. Fear of COVID-19 and SARS-CoV-2 positivity were the most common reasons. The TI group had a longer disease duration and a higher frequency of inflammatory arthritis than the TC group (p=0.013 and p=0.044, respectively). Conclusions: Fear of COVID-19 and SARS-CoV-2 positivity seemed to be the major reasons for discontinuing/postponing intravenous treatments in CIRD patients. Patients with long disease duration and less systemic involvement may be more prone to discontinuing their treatments.

Fungal endocarditis

Endocarditis is inflammation of the innermost lining of the heart including the valves. It can be of infective or noninfective etiology. It is a relatively rare disease with high morbidity and mortality. There are a very few cases reported from India. Infective endocarditis due to fungal organisms accounts for 2%–4% of endocarditis. We report a case of Aspergillus endocarditis in a patient with chronic rheumatic heart disease, which was incidentally diagnosed during surgery. The patient was treated with mitral valve replacement and antifungal agents. One year after surgery, the patient has a good prosthetic valve function with no evidence of vegetations.

Evaluation of Metabolic Syndrome in Egyptian Patients with Radiographic and Non-Radiographic Axial Spondyloarthritis (Cross Sectional Study)

Background: Axial spondyloarthritis is a chronic inflammatory rheumatic disease that has a great risk for metabolic syndrome. Our aim was to study metabolic syndrome (MetS) in radiographic and non- radiographic axial spondyloarthritis patients in Egyptian population. Methods: The cross-sectional study included 60 consecutive Ax-SpA patients aged 25-55 years fulfilling the Assessment of Spondyloarthritis International Society criteria; they were divided into 40 patients with radiographic and 20 patients with non- radiographic axial spodyloarthritis. MetS was assessed using new international diabetes federation definition. Results: The prevalence of MetS was higher in radiographic patients (37.50%) than non-radiographic axial spondyloarthritis (20%) (X2 = 0.170, P = 0.242) with significant differences between the two groups as regard triglycerides (p = 0.012*) and HDL cholesterol (p &lt; 0.001*). Decreased HDL-cholesterol was the most frequent metabolic syndrome component with a prevalence of 66.66% (40 patients) in both groups. Conclusion: Metabolic syndrome was more prevalent in radiographic axial spodyloarthritis. Therefore, follow up of these patients is important for early detection of any cardiovascular events.

Artritis idiopática juvenil

Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of chronic arthritis of unknown origin that appear before 16 years of age and persist for more than six weeks, once other causes are excluded. They are characterized by the presence of joint inflammation and are accompanied to a greater or lesser extent by systematic manifestations. It is the most frequent chronic inflammatory rheumatic disease in childhood. The currently accepted classification groups are those described by the International League of Associations for Rheumatology (ILAR). However, new modifications to these criteria have recently been proposed. JIA has a multifactorial etiopathogenesis, immunological mechanisms, and environmental mechanisms that act on a genetically predisposed individual. Except for the systemic JIA subtype, which has an autoinflammatory basis, the remaining JIA forms have a clear autoimmune component. Early diagnosis and adequate treatment are crucial for avoiding complications. This treatment must be individualized based on clinical manifestations and the degree of organ involvement. In addition to glucocorticoids and synthetic disease-modifying drugs (DMDs), the prognosis of JIA has notably improved since the introduction of biological DMDs.

A Controlled Community Study of Distress and Resilience in Women Diagnosed with Fibromyalgia and Systemic Lupus Erythematosus.

This study examines psychological and physical influences on the distress and well-being of patients with chronic rheumatic diseases. The study aims were to (1) evaluate the relative contribution of objective disease activity and psychological factors on the wellbeing of patients with systemic lupus erythematosus (SLE); (2) to compare the psychological distress of SLE patients to fibromyalgia (FM) patients and healthy controls, and to (3) characterize subgroups of patients by performing cluster analysis using psychological variables. Participants were ascertained from closed forums and social media channels resulting in 41 women with a diagnosis of SLE, 47 with a diagnosis of FM, and 77 healthy controls (HC). Hierarchical linear regression for well-being of SLE patients found that most of the variance was accounted for by social support. Cluster analysis performed on the entire sample identified two clusters, a distressed group tending to Type D personality, anxiety and depression, low in well-being and social support, and a resilient group; the proportion of resilient individuals was highest in the HC intermediate in the SLE group and lowest in the FM group. The importance of psychological variables vs disease severity in these two rheumatic diseases for wellbeing is demonstrated by these results. The results suggest that psychological interventions that enhance the experience of social support in medical settings, might benefit patients with both diseases, and be of particular importance to the well-being of patients who are more distressed.

Role of Ultrasound Evaluation of Temporomandibular Joint in Juvenile Idiopathic Arthritis: A Systematic Review.

Background: Juvenile idiopathic arthritis (JIA) is childhood’s most frequent chronic rheumatic disease. JIA is a broad term that includes all arthritides starting before 16 years, lasting at least six weeks, and of unknown cause. The temporomandibular joint (TMJ) could be involved in JIA both at onset and during the disease course. The presence of TMJ synovitis might severely impair dentofacial maturation in pediatric patients. The ultrasound (US) application to detect early signs of TMJ synovitis in children with JIA has provided contradictory results. We sought to assess the current role of TMJ US in JIA through a systematic literature review. Methods: The systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: The literature search found 345 records. After duplicates removal, 253 records were screened, 20 full-text articles were reviewed to assess their eligibility, and 7 of them were included in the qualitative analysis. Joint effusion was the most recorded parameter, followed by bony condylar abnormalities. Compared to contrast enhancement MRI, the capability to detect signs of active synovitis of TMJ by US is low, especially at the early stages. Conclusion: Understanding how US may help diagnose and manage children with JIA is advisable for several reasons. MRI cannot be frequently repeated, may need sedation, and is expensive. The constant technical improvement of US will undoubtedly allow for better evaluation of what, in the past, was not clear or not even captured by sonography. So far, the role of US in the assessment of TMJ involvement in JIA is indubitably secondary to the MRI. Even so, we think that a baseline MRI of TMJ and the repetition of the sonography over time might both help the interpretation of US images and intercept significative changes.

State of child health: acute rheumatic fever in Aotearoa New Zealand

ABSTRACT Rheumatic fever is a well-recognised public health problem in Aotearoa New Zealand that is potentially preventable by addressing the social and environmental determinants of health and ensuring equitable access to primary healthcare services. We present data on the hospitalisations of children aged 0–14 years for acute rheumatic fever (ARF) during the period 2000–2020, and the early stages of the COVID-19 pandemic to May 2021. Persistent inequity by ethnicity and by socioeconomic deprivation was observed, particularly for Pacific children, for Māori children, and for children living in the most deprived areas (NZDep quintile 5). The government implemented a programme to prevent rheumatic fever between July 2012 and June 2017. Hospitalisation data suggest that the programme was reducing the incidence of ARF in children, but this trend was not sustained. There was minimal change to the number of hospitalisations for ARF during early period of the COVID-19 pandemic. If untreated, ARF can cause chronic rheumatic heart disease. The persistently high rates of hospitalisations and the unequal burden of disease for vulnerable groups should no longer be tolerated, since they can be effectively addressed by implementation of evidence-based strategies to prevent, treat, and control this disease.

Role of cellular senescence in the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic rheumatic disease that is characterized by immune activation, vasculopathy and fibrosis of the skin and internal organs. It has been proposed that premature onset of ageing pathways and associated senescent changes in cells contribute to the clinical and pathological features of SSc. The aim of this review is to critically review recent insights into the involvement of cellular senescence in SSc. Cellular senescence plays a critical role in SSc pathogenesis, particularly involving endothelial cells and fibroblasts. Immunosenescence could also contribute to SSc pathogenesis by direct alteration of cellular functions or indirect promotion of defective immune surveillance. Molecular studies have shed some light on how cellular senescence contributes to fibrosis. Recent and planned proof-of-concept trials using senotherapeutics showed promising results in fibrotic diseases, including SSc. There is increasing evidence implicating cellular senescence in SSc. The mechanisms underlying premature cellular senescence in SSc, and its potential role in pathogenesis, merit further investigation. Emerging drugs targeting senescence-related pathways might be potential therapeutic options for SSc.

Development of robust finite element models to investigate the stability of osteochondral grafts within porcine femoral condyles

Osteoarthritis (OA) is the most prevalent chronic rheumatic disease worldwide with knee OA having an estimated lifetime risk of approximately 14%. Autologous osteochondral grafting has demonstrated positive outcomes in some patients, however, understanding of the biomechanical function and how treatments can be optimised remains limited. Increased short-term stability of the grafts allows cartilage surfaces to remain congruent prior to graft integration. In this study methods for generating specimen specific finite element (FE) models of osteochondral grafts were developed, using parallel experimental data for calibration and validation. Experimental testing of the force required to displace osteochondral grafts by 2 mm was conducted on three porcine knees, each with four grafts. Specimen specific FE models of the hosts and grafts were created from registered μCT scans captured from each knee (pre- and post-test). Material properties were based on the μCT background with a conversion between μCT voxel brightness and Young's modulus. This conversion was based on the results of the separate testing of eight porcine condyles and optimization of specimen specific FE models. The comparison between the experimental and computational push-in forces gave a strong agreement with a concordance correlation coefficient (CCC) = 0.75, validating the modelling approach. The modelling process showed that homogenous material properties based on whole bone BV/TV calculations are insufficient for accurate modelling and that an intricate description of the density distribution is required. The robust methodology can provide a method of testing different treatment options and can be used to investigate graft stability in full tibiofemoral joints.

Isolation, Behavioral Changes, and Low Seroprevalence of SARS-CoV-2 Antibodies in Patients With Systemic Lupus Erythematosus or Rheumatoid Arthritis.

ObjectivePatients with chronic rheumatic diseases (CRDs), such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), require special attention during the COVID‐19 pandemic as they are considered at risk of severe infections. Our objective was to assess the seroprevalence of SARS–CoV‐2 in patients with SLE and RA and to assess patient behavior, disease‐related symptoms, and mental health.MethodsMore than 900 participants were included: 405 patients with RA or SLE (CRD patients) and 513 blood donors. All participants had blood SARS–CoV‐2 total antibodies measured (sensitivity 96.7%, specificity 99.5%) and answered a questionnaire concerning behavior, anxiety, and symptoms of depression (Patient Health Questionnaire 9). The CRD patients were further asked about physical activity, adherence to medication, and disease‐related symptoms.ResultsCRD patients had a significantly lower seroprevalence of SARS–CoV‐2 antibodies (n = 1 of 365, 0.3%) compared to blood donors (n = 10 of 513, 1.9%; P = 0.03). Almost 60% of patients were unable to exercise as usual, and increased pain and disease activity was experienced by 34% and 24% of patients, respectively. Almost 10% of patients reduced or discontinued their immunosuppressive treatments at their own initiative. Symptoms of moderate depression were present in 19% of patients compared to 6.8% of blood donors (P < 0.001).ConclusionLow seroprevalence in patients with CRDs indicates successful mitigation of exposure to SARS–CoV‐2. However, this mitigation appears to occur at the expense of physical activity, experience of increased pain, disease activity, and symptoms of depression. There is a need for care providers to be aware of these negative side effects and for further studies to investigate the possible long‐term consequences.

IL-33/ST2 axis contributes to the dermal fibrosis of systemic sclerosis via promoting fibroblasts activation

BackgroundSystemic sclerosis (SSc) is a chronic immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs. Interleukin-33 (IL-33) has been recently implicated in several autoimmune diseases through its receptor ST2. ObjectiveThe aim of this study was to investigate the role and underlying mechanism of IL-33/ST2 axis in the fibrotic disorder of SSc. MethodsThe bleomycin (BLM)-induced fibrotic skin and skin biopsies of SSc patients were used to detect the expression of IL-33 and ST2. Human dermal fibroblasts were stimulated with recombinant IL-33(rIL-33) protein and their activation, proliferation and migration were assessed. The role of IL-33/ST2 axis was investigated in mouse fibrosis model via histologically assessing skin fibrosis after IL-33 gene knockout. ST2 neutralizing antibody treatment was also obtained to estimate the possible effect. ResultsThe number IL-33+ cells and ST2+ cells were increased in the lesion skin of SSc patients and BLM-induced mouse. Human skin fibroblasts highly expressed ST2 protein, and the proliferation, migration, and collagen expression were significantly elevated after rIL-33 stimulation, accompanied by the activation of MAPKs and NF-kB pathways. The severity of skin fibrosis was significantly reduced in il33-/- mice compared with WT mice. Blockade of IL-33 receptor using an anti-ST2 neutralizing antibody effectively ameliorated the skin fibrosis. ConclusionThese data indicate that IL-33/ST2 axis contributes to the fibrotic skin injury of SSc via promoting fibroblasts activation, and IL-33/ST2 blockade might serve as a novel strategy to inhibit the fibrosis progression in patients of SSc.

Association of fear assessment in inflammatory rheumatic diseases (FAIR) questionnaire with ankylosing spondylitis quality of life and disease activity in patients with ankylosing spondylitis

Background/Aim: Fear against disease course, treatment, and limitations in family, work, and social life are commonly seen but mostly overlooked by physicians of patients with chronic inflammatory rheumatic diseases. Ankylosing spondylitis (AS) is a chronic inflammatory disease in young adults characterized by limitations in spinal mobility. The Fear Assessment (FAIR) Questionnaire was designed especially for patients with rheumatoid arthritis and spondyloarthritis to assess the level of fear from the patient’s perspective. Here we evaluate the FAIR score in AS patients and its association with disease activity, AS quality of life (ASQoL), depression, anxiety, and fatigue levels.&#x0D; Methods: This cross-sectional study included 79 patients with AS, and disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), AS-Disease Activity Score-C reactive protein, and functional status was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Patient global assessment of disease and pain were scored on 0–10 cm visual analog scores. All patients completed FAIR and ASQoL questionnaires. The depression and anxiety were evaluated by Hospital Anxiety and Depression Scale (HADS), and fatigue was assessed by Fatigue Severity Scale (FSS).&#x0D; Results: The mean age of AS patients (62% male) was 41.7 (11.3) years. Most of the patients were on biological disease-modifying anti-rheumatic drugs (bDMARDs). The patients’ median BASDAI, ASDAS-CRP, and BASFI were 5.4 (range, 3.8–7.4), 3.83 (1.4), and 4.0 (range, 2.3–6.2), respectively. The overall FAIR, ASQoL, FSS, HADS-depression, and HADS-anxiety scores were 75 (range, 52–91), 9.6 (5.2), 5.4 (range, 4.1–7), 7.7 (4.4) and 9.6 (5.2), respectively. There were statistically significant correlations between disease activity indices and FAIR, ASQoL, FSS, and HADS scores. The FAIR scores significantly correlated with ASQoL, FSS, and HADS scores. The patients with active disease (BASDAI ≥ 4) had significantly higher levels of FAIR, ASQoL, FSS, and HADS. The best cut-off value for the FAIR score of AS patients with moderate to severe disease activity was 50 (AUC: 0.734, 95% CI [0.599–0.870], P = 0.002), with a sensitivity of 89.8%, specificity of 55%, positive likelihood ratio of 1.99, and Youden index of 0.45.&#x0D; Conclusion: This study shows that AS patients face a high level of fear which is associated with higher disease activity, higher risk of mood disorders, and lower quality of life. Physicians should not only focus on the physical improvement of the patient but also handle the fear of patients against their diseases and their treatment. This holistic approach will improve the dialogue between the physician and the patient, which will result in increased compliance with treatment and will raise the quality of care.