An overview of psoriatic arthritis – epidemiology, clinical features, pathophysiology and novel treatment targets

Psoriatic arthritis is a chronic inflammatory joint disease occurring in a subgroup of patients suffering from psoriasis. This article gives an overview of the complexity of psoriatic arthritis, looking at several aspects of this heterogeneous disease, such as epidemiology, important clinical features and comorbidities as well as current concepts of the pathophysiology and subsequent insights in novel treatment targets.(VLID)348921

Impaired human hematopoiesis due to a cryptic intronic splicing mutation

Studies of allelic variation underlying genetic blood disorders have provided important insights into human hematopoiesis. Most often, the identified pathogenic mutations result in loss-of-function or missense changes. However, assessing the pathogenicity of noncoding variants can be challenging. Here, we characterize two unrelated patients with a distinct presentation of dyserythropoietic anemia and other impairments in hematopoiesis associated with an intronic mutation in GATA1 that is 24 nucleotides upstream of the canonical splice acceptor site. Functional studies demonstrate that this single-nucleotide alteration leads to reduced canonical splicing and increased use of an alternative splice acceptor site that causes a partial intron retention event. The resultant altered GATA1 contains a five-amino acid insertion at the C-terminus of the C-terminal zinc finger and has no observable activity. Collectively, our results demonstrate how altered splicing of GATA1, which reduces levels of the normal form of this master transcription factor, can result in distinct changes in human hematopoiesis

Sleep Quality in Patients with Rheumatoid Arthritis and Associations with Pain, Disability, Disease Duration, and Activity

We aimed to assess the subjective sleep quality in patients with rheumatoid arthritis (RA) and its correlation with disease activity, pain, inflammatory parameters, and functional disability. In a cross-sectional study, patients with confirmed RA diagnosis responded to a questionnaire (consisting of socio-demographic data, the Health Assessment Questionnaire Disability Index, and the Medical Outcome Study Sleep Scale). Disease activity was assessed with the Clinical Disease Activity Index, and pain levels using the visual analogue scale. In addition, inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor alpha) were analyzed. Ninety-five patients were analyzed, predominantly female, with an average age of 50.59 (9.61) years. Fifty-seven percent reported non-optimal sleep duration, where functional disability (92.7% vs. 69.8%; p = 0.006) and higher median pain levels (3.75 (2.36.0) vs. 2.5 (2.03.5); p = 0.003) were also more prevalent. No differences in sociodemographic variables, disease duration or activity, inflammatory parameters, or use of biological and corticosteroid therapy were observed. The multivariate regression analysis showed that more intense pain was associated with a lower likelihood of optimal sleep (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.470.98, p = 0.038). Patients with RA report a high prevalence of non-optimal sleep, which is linked to pain level. Clinicians need to be aware of this issue and the potential effects on health and functional status.(VLID)471776

Sexual health in patients with rheumatoid arthritis and the association between physical fitness and sexual function : a cross-sectional study

The aim of this study was to examine sexual health in patients with rheumatoid arthritis (RA), and to analyse factors associated with sexual health with a focus on physical fitness. One hundred RA patients aged between 18 and 65 years were included in a cross-sectional study. Handgrip strength and knee extensor strength were measured with a dynamometer, and physical performance with the Short Physical Performance Battery (SPPB). Fifty-four patients, mean age 47.8 (SD 10.6) years, 61% female, answered a questionnaire about sexual health. Fifty-seven percent reported, at least, sometimes having difficulty with sexual intercourse (27.8% due to joint stiffness, 24.1% due to fatigue, 18.5% due to pain). Handgrip strength and knee extensor strength significantly correlated with the desire to engage in sexual intercourse, frequency of sexual contact and satisfaction with overall sex life. The SPPB total score correlated with satisfaction with overall sex life, and the SPPB repeated chair stands test with the desire to have sexual intercourse and satisfaction with overall sex life. After adjusting for age, gender, disease activity, comorbidity, co-medication and pain intensity, the repeated chair stands test remained significantly associated with the frequency of sexual contact (0.53; 0.011.05) and with satisfaction with overall sex life (1.39; 0.282.51). The results of this study show that problems with sexual health are highly prevalent in patients with RA. The ability to rise from a chair is associated with sexual function, independent of disease activity and pain intensity.(VLID)358220

Factors Associated with Objectively Measured Physical Activity in Patients with Seropositive Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is associated with low levels of physical activity (PA). However, the factors related to low physical activity levels have rarely been studied. Methods: In this cross-sectional study, 70 seropositive RA patients were included. Physical activity was objectively assessed with an ActiGraph GT3X+ accelerometer. In addition, body mass index, smoking status, work ability, and clinical parameters (functional disabilities, disease activity, disease duration, pain, and inflammation parameters) were measured. Results: RA patients performed a mean of 215.2 (SD: 136.6) min a week of moderate physical activity and 9.1 (SD: 26.3) min of vigorous physical activity. The total amount of moderate and vigorous physical activity (MVPA) was associated with BMI, and functional disabilities. In addition, non-smokers and patients with better work ability did more MVPA. No association could be seen with disease activity, disease duration, pain, and inflammatory markers. After mutual adjusting of all the variables, only BMI showed a significant relationship with MVPA. Conclusions: RA patients perform de facto no physical activity with vigorous intensity. Factors related to low physical activity are BMI, functional disabilities, workability and smoking status, whereas due to the study design no causal and temporal link could be made

Impaired human hematopoiesis due to a cryptic intronic GATA1 splicing mutation

Studies of allelic variation underlying genetic blood disorders have provided important insights into human hematopoiesis. Most often, the identified pathogenic mutations result in loss-of-function or missense changes. However, assessing the pathogenicity of noncoding variants can be challenging. Here, we characterize two unrelated patients with a distinct presentation of dyserythropoietic anemia and other impairments in hematopoiesis associated with an intronic mutation in GATA1 that is 24 nucleotides upstream of the canonical splice acceptor site. Functional studies demonstrate that this single-nucleotide alteration leads to reduced canonical splicing and increased use of an alternative splice acceptor site that causes a partial intron retention event. The resultant altered GATA1 contains a five–amino acid insertion at the C-terminus of the C-terminal zinc finger and has no observable activity. Collectively, our results demonstrate how altered splicing of GATA1, which reduces levels of the normal form of this master transcription factor, can result in distinct changes in human hematopoiesis

JAK-Inhibitors - A Story of Success and Adverse Events

Rheumatoid arthritis (RA) is a systemic, chronic, immune-mediated inflammatory condition. Treatments options encompass conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) like tumor necrosis factor (TNF) inhibitors (TNFis) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) including Janus Kinase inhibitors (JAKinibs). Orally administered JAKinibs have demonstrated comparable or, in specific cases, superior efficacy compared to bDMARDs in inflammatory conditions. However, the escalating clinical utilization has been accompanied by the emergence of serious adverse effects, including major adverse cardiac events (MACE), malignancies and venous thrombotic episodes (VTE), leading to regulatory restrictions imposed by health authorities in both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)