Sex-Based Medicine Meets Psoriatic Arthritis: Lessons Learned and to Learn

Humorally associated autoimmune diseases generally show a female predominance whereas ankylosing spondylitis, a disease that overlaps with psoriatic arthritis (PsA), shows a male predominance. The present review ascertains the current knowledge of sex-specific differences related to psoriatic arthritis (PsA), a chronic, inflammatory condition associated with psoriasis. Sex differences may have important implications for clinical research in PsA and in terms of epidemiology (incidence, prevalence, lifetime risk, survival, and mortality), clinical, radiological, and laboratory features, and response to treatment. While nationwide surveys and large-scale databases and registries show no sex-specific differences, varying male/female ratios have been reported, ranging from 0.42 to 2.75 (comparable with those reported for psoriasis vulgaris: ranging from 0.28 to 2.38). This may reflect subtle, complex, nonlinear interactions between the biological make-up of the individual (genetic and epigenetic differences), hormonal components including menopausal status, environmental exposures including skeletal physical stressing, and psychological variables. There exists methodological heterogeneity and paucity of data concerning sex-specific differences, in terms of the specific population studied, study design, and the diagnostic criteria utilized. Harmonizing and reconciling these discrepancies would be of crucial importance in achieving the ambitious goals of personalized/individualized medicine and further standardized meta-data and Big Data could help disentangle and elucidate the precise mechanisms of underlying potential PsA sex-specific differences

Mechanistic immunological based classification of rheumatoid arthritis

The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological disease continuum model of inflammation against self with “pure” adaptive and innate immune disease at opposite boundaries, we propose a novel immune mechanistic classification describing the heterogeneity within RA. Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to seronegative RA phenotypes including some so called palindromic RA cases. However, just as innate and adaptive immunity are closely functionally integrated, some ACPA+ RA cases have superimposed “autoinflammatory” features including abrupt onset attacks, severe attacks, self-limiting attacks, relevant autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory pathway therapies including colchicine and IL-1 pathway blockade. An emergent feature from this classification that non-destructive RA phenotypes, both innate and adaptive, have disease epicentres situated in the extracapsular tissues. This mixed innate and adaptive immunopathogenesis may be the key to understanding severe disease flares, resistant disease subsets that are unresponsive to standard therapy and for therapies that target the autoinflammatory component of disease that are not currently considered by expert therapeutic recommendations

Harnessing Big Data, Smart and Digital Technologies and Artificial Intelligence for Preventing, Early Intercepting, Managing, and Treating Psoriatic Arthritis: Insights From a Systematic Review of the Literature

Background: Rheumatological and dermatological disorders contribute to a significant portion of the global burden of disease. Big Data are increasingly having a more and more relevant role, being highly ubiquitous and pervasive in contemporary society and paving the way for new, unprecedented perspectives in biomedicine, including dermatology and rheumatology. Rheumatology and dermatology can potentially benefit from Big Data. Methods: A systematic review of the literature was conducted according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines, mining “Uno per tutti”, a highly integrated and automated tool/meta-database developed at the University of Genoa, Genoa, Italy, and consisting of 20 major scholarly electronic databases, including PubMed/MEDLINE. Big Data- or artificial intelligence-based studies were judged based on the modified Qiao’s critical appraisal tool for critical methodological quality assessment of Big Data/machine learning-based studies. Other studies designed as cross-sectional, longitudinal, or randomized investigations, reviews/overviews or expert opinions/commentaries were evaluated by means of the relevant “Joanna Briggs Institute” (JBI)’s critical appraisal tool for the critical methodological quality assessment. Results: Fourteen papers were included in the present systematic review of the literature. Most of the studies included concerned molecular applications of Big Data, especially in the fields of genomics and post-genomics. Other studies concerned epidemiological applications, with a practical dearth of studies assessing smart and digital applications for psoriatic arthritis patients. Conclusions: Big Data can be a real paradigm shift that revolutionizes rheumatological and dermatological practice and clinical research, helping to early intercept psoriatic arthritis patients. However, there are some methodological issues that should be properly addressed (like recording and association biases) and some ethical issues that should be considered (such as privacy). Therefore, further research in the field is warranted. Systematic Review Registration: Registration code 10.17605/OSF.IO/4KCU2

Enthesitis: Much More Than Focal Insertion Point Inflammation

Purpose of Review Recognition of the importance of enthesitis as the pivotal pathological process underpinning spondyloarthropathies (SpA) has increased in recent years. Thus, we summarized the current knowledge on the pathogenic role of enthesitis on SpA shown by both animal models and human studies in vivo. Recent Findings Experimental models have shown several SpA-like diseases that commence at entheses and are linked to nail disease as well as dactylitis, two important entheseal-associated conditions in humans. Frequently, enthesitis is not the primary outcome measure in studies of peripheral PsA and SpA although arguably it is the key parameter being indirectly assessed in spinal disease in ankylosing spondylitis. The use of different agents including JAK, IL-17, and IL-23 inhibitors contributes significantly to our understanding of enthesitis in terms of involved immune pathways. Summary Enthesitis and enthesis organ inflammation may be the primary pathological process underlying SpA associated skeletal inflammation. Emergent studies are beginning to elucidate the molecular basis for this type of joint inflammatory response

The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study

Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)—a disease that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (p < 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (p = 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (p < 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (p < 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (p < 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (p = 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings

Correction to: The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man.

The original article can be found online

Discrepancies Between Classic and Digital Epidemiology in Searching for the Mayaro Virus: Preliminary Qualitative and Quantitative Analysis of Google Trends

Background: Mayaro virus (MAYV), first discovered in Trinidad in 1954, is spread by the Haemagogus mosquito. Small outbreaks have been described in the past in the Amazon jungles of Brazil and other parts of South America. Recently, a case was reported in rural Haiti. Objective: Given the emerging importance of MAYV, we aimed to explore the feasibility of exploiting a Web-based tool for monitoring and tracking MAYV cases. Methods: Google Trends is an online tracking system. A Google-based approach is particularly useful to monitor especially infectious diseases epidemics. We searched Google Trends from its inception (from January 2004 through to May 2017) for MAYV-related Web searches worldwide. Results: We noted a burst in search volumes in the period from July 2016 (relative search volume [RSV]=13%) to December 2016 (RSV=18%), with a peak in September 2016 (RSV=100%). Before this burst, the average search activity related to MAYV was very low (median 1%). MAYV-related queries were concentrated in the Caribbean. Scientific interest from the research community and media coverage affected digital seeking behavior. Conclusions: MAYV has always circulated in South America. Its recent appearance in the Caribbean has been a source of concern, which resulted in a burst of Internet queries. While Google Trends cannot be used to perform real-time epidemiological surveillance of MAYV, it can be exploited to capture the public’s reaction to outbreaks. Public health workers should be aware of this, in that information and communication technologies could be used to communicate with users, reassure them about their concerns, and to empower them in making decisions affecting their health

Computer vision syndrome among Al-Rayan Medical Colleges students, Madinah, Saudi Arabia

Background: Digital devices now become a part of university student’s life, and with prolonged use, they may experience some ocular problems like dryness, headache, eye strain, and pain. These symptoms and others constitute computer vision syndrome (CVS). Our study aimed to assess CVS among Al-Rayan medical college students and to evaluate students’ behaviors related to preventing CVS. Methods: A cross-sectional, questionnaire-based study was performed among the students of Alrayan Medical College from the period from November to December 2022, with a sample size of 270 cases. Data were collected using (CVS-Q) questionnaire. Results: Near half of the participants (53.7%) were suffering from CVS. The most reported symptoms included headache (43.3%), tearing (42.9%), burning (39.3%), and blurred vision (35.1%). The most significant measures applied to minimize the impact of electronic devices were putting the digital device at enough distance (p value=0.001) and adjusting the screen brightness of the digital device (p value=0.004). Conclusions: This study disclosed that CVS is a common problem among medical students. The manifestation of CVS was affected by the frequency and duration of electronic device use

T Helper 2 IL-4/IL-13 dual blockade with dupilumab is linked to some emergent T helper 17‒type diseases, including seronegative arthritis and enthesitis/enthesopathy, but not to humoral autoimmune diseases

Dupilumab, an IL-4/IL-13 receptor blocker, has been linked to emergent seronegative inflammatory arthritis and psoriasis that form part of the spondyloarthropathy spectrum. We systematically investigated patterns of immune disorders, including predominantly T helper 17‒(spondyloarthropathy pattern) and T helper 2‒mediated disorders and humoral autoimmune pattern diseases, using VigiBase, the World Health Organization's global pharmacovigilance of adverse drug reactions. Several bioinformatics databases and repositories were mined to couple dupilumab-related immunopharmacovigilance with molecular cascades relevant to reported findings. A total of 37,848 dupilumab adverse drug reaction cases were reported, with skin, eye, and musculoskeletal systems most affected. Seronegative arthritis (OR = 9.61), psoriasis (OR = 1.48), enthesitis/enthesopathy (OR = 12.65), and iridocyclitis (OR = 3.77) were highly associated. However, ankylosing spondylitis and inflammatory bowel disease were not conclusively associated. Overall, classic polygenic humoral‒mediated autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus were not associated with dupilumab use. Pathway analysis identified several biological pathways potentially involved in dupilumab‒associated adverse drug reactions, including the fibroblast GF receptor (in particular, FGFR2) pathway. MicroRNAs analysis revealed the potential involvement of hsa-miR-21-5p and hsa-miR-335-5p. In conclusion, IL-4/IL-13 blockers are not unexpectedly protective against humoral autoimmune diseases but dynamically skew immune responses toward some IL-23/IL-17 cytokine pathway‒related diseases. IL-4/13 axis also plays a role in homeostatic tissue repair and we noted evidence for a link with ocular and arterial pathology