COVID-19 in patients with rheumatological diseases in the Eastern Province of Saudi Arabia.

The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Morphologic, dynamic and high-resolution microscopy MRI in early-onset spondyloarthritis finger dactylitis.

OBJECTIVE: Up to now, the pathophysiology of SpA dactylitis has not been entirely clarified. It is not clear which are the involved tissues and which is the primary lesion of the "sausage-like" digit. The aim of our study was to examine the finger structures in early-onset finger dactylitis using high-resolution microscopy MRI together with morphologic and dynamic MRI. SUBJECTS AND METHODS: In a 6-month period, 13 SpA patients (7 females and 6 males), mean age 54.07 years (range 37-73 years) and mean disease duration 7.07 years (range 1-44 years) with early-onset finger dactylitis (less than 3 months) were recruited. Nine patients had PsA, 3 HLA-B27-positive uSpA and 1 HLA-B27-negative uSpA. One patient had 2 dactylitis fingers. Ten healthy volunteers matched for age and sex with no personal and family history of SpA were enrolled. All dactylitis fingers and randomly selected fingers of the normal control subjects were imaged by morphologic, dynamic and high-resolution microscopy MRI. RESULTS: We have found flexor tenosynovitis in all the 14 dactylitis fingers, joint synovitis in 5 and oedema in the finger soft tissue in 10. In 2 dactylitis fingers, there was oedema at the insertion of the joint capsule suggesting enthesitis. In 5 dactylitis fingers, there was only mild enhancement at the enthesis organ (collateral ligament, flexor and extensor tendons). CONCLUSIONS: Our MRI study on early-onset dactylitis demonstrates that flexor tenosynovitis, joint synovitis and oedema of the digit soft tissue are the predominant alterations visible in the early phase of evolution of dactylitis and that, therefore, enthesitis may not be considered the primary lesion of dactylitis.

Psoriasis and adverse pregnancy outcomes: A nationwide case-control study in 491,274 women in Denmark.

Background: The chronic systemic inflammation associated with psoriasis supposedly creates an undesirable milieu for a pregnancy, resulting in an increased risk of adverse pregnancy outcomes (APOs). Objective: To investigate the association between psoriasis and APOs as well as how the association differs according to psoriasis severity (mild and moderate-to-severe). Methods: This nationwide register-based case-control study collected data from 1973 to 2017. Cases were APOs (spontaneous abortion, ectopic pregnancy [EP], intrauterine fetal death, and stillbirth). Singleton live births were controls. Adjusted logistic regression models were used for statistical analyses. Results: In total, 42,041 (8.56%) APOs and 449,233 (91.44%) controls were included. EP was the only APO that was found to be statistically associated with psoriasis (odds ratio, 1.34; 95% CI, 1.06-1.68). Odds ratio for EP was the highest for women with moderate-to-severe psoriasis (odds ratio, 2.77; 95% CI, 1.13-6.76). The absolute risk of EP was 2.48% higher for women with moderate-to-severe psoriasis compared with women without psoriasis (3.98% vs 1.50%). Limitations: No access to clinical data confirming psoriasis severity. Conclusion: The present study found a significant association between EP and psoriasis (absolute risk of 3.98%). As EP is the leading cause of maternal morbidity and mortality in the first trimester of pregnancy, our findings call for particular care for women of reproductive age with psoriasis.

Factors influencing clinician prescribing of disease-modifying anti-rheumatic drugs for inflammatory arthritis: A systematic review and thematic synthesis of qualitative studies.

Understanding factors that influence prescribing of disease-modifying anti-rheumatic drugs (DMARDs) will inform strategies to optimise care of people with inflammatory arthritis. We performed a systematic review and thematic synthesis of qualitative studies to explore these factors. Inclusion criteria were: use of qualitative or mixed methods; rheumatologist, nurse or pharmacist perspectives; prescription of any DMARD (conventional [cs], targeted synthetic [ts], biologic [b], biosimilars) and/or glucocorticoids; in any healthcare setting in any country. MEDLINE, Embase and EBSCOhost CINAHL Plus were searched from inception to 15 June 2021. Pairs of review authors independently identified studies for inclusion, assessed methodological quality using the Critical Appraisal Skills Programme checklist, and extracted and thematically synthesised data. Confidence in synthesis themes was evaluated using the GRADE Confidence in Evidence from Reviews of Qualitative research (CERQual) approach. We included 15 studies involving 716 clinicians (683 rheumatologists, 27 nurses, 6 pharmacists) across 10 countries, all focusing on management of patients with rheumatoid arthritis (RA). Six themes were identified: Rheumatologist prescribing is influenced by patients' characteristics, preferences, symptoms and negative responses to medication; Rheumatologist knowledge, experience, habits and subjective judgements are strong drivers of prescribing behaviour; High demands on consultation time impede shared decision-making; Costs and complexity of medication funding arrangements limit prescribing options; Clinicians recognise the importance of providing patient education about medication options; and Clinicians value colleagues' opinions and support to inform prescribing decisions. The majority of themes were graded as moderate confidence (n  =  4), reflecting they are likely to reasonably represent the factors influencing prescribing of DMARDs to people with RA. Quality improvement strategies that address these factors are likely to support best practice pharmacologic management of RA and may be potentially applicable to other types of inflammatory arthritis. High demand on consultation time and complexity of medication funding arrangements are system factors that may or may not be amenable to change. Easily accessible living national guidelines which include lay summaries and treatment algorithms to support prescribing decisions may address some of the themes.

Exploring the translational potential of clusterin as a biomarker of early osteoarthritis.

BACKGROUND: Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer's disease due to its ability to bind amyloid-ß peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation. METHODS: In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). RESULTS: Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA. CONCLUSION: There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.

Circulating Mir-140 and leptin improve the accuracy of the differential diagnosis between psoriatic arthritis and rheumatoid arthritis: a case-control study.

The differential diagnosis of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) is difficult because of the lack of diagnostic clinical signs and reliable biomarkers. This study investigated microRNAs (miRNA) and adipokines as potential additional markers to discriminate PsA from RA. The expression profile of miRNA (miR-21, miR-140, miR-146a, miR-155, miR-181b, miR-223, miR-let-7e) and inflammatory cytokines (IL-1ß, IL-6, IL-17a, IL-23a, TNF-α) from peripheral blood mononuclear cells of PsA and RA patients compared to healthy controls (HC) were evaluated by real-time PCR, and serum adipokines (adiponectin, chemerin, leptin, resistin, visfatin) and cytokines by ELISA assay. Univariable binary logistic regression was used to find the association between PsA and potential predictors. The gene expression of miRNA and cytokines and the serum levels of adipokines were found significantly different in PsA and RA patients compared to HC, as well as in PsA versus RA. MiR-140 gene expression resulted up-regulated in PsA patients and reduced in RA in comparison to HC, and, for the first time, significantly higher in PsA compared with RA. Serum levels of IL-23a and leptin were significantly increased in PsA and RA populations than in HC, as well as in PsA versus RA. Furthermore, circulating TNF-α was up-regulated in PsA and RA in comparison to controls, while resulted higher in RA than in PsA. Univariable binary logistic regression analysis found the above-mentioned markers associated to PsA versus RA. Our results first demonstrated an increased expression of circulating miR-140 and serum leptin in PsA patients compared to RA, which were identified as potential additional biomarkers to discriminate PsA from RA. Since the differential diagnosis of PsA and RA poses challenges in clinical practice, our data may help to enhance the diagnostic performance of PsA in daily practice.

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis.

Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs, i.e., TD-MN, which aims to specifically deliver TAC and DIC to skin and articular cavity, achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA. In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of ∼100 µm, while the tip-layer delivered DIC up to ∼300 µm into the articular cavity. TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling, muscle atrophy, and cartilage destruction. Importantly, TD-MN significantly inhibited the serum TNF-α and IL-17A in psoriatic and arthritic rats. The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity, providing a convenient and effective strategy for meeting the requirements of PsA treatment.

Non-adherence and discontinuation rate for oral and parenteral methotrexate: A retrospective-cohort study in 8,952 patients with psoriatic arthritis.

BACKGROUND AND AIMS: Treatment options for PsA, following non-steroidal anti-inflammatory drugs (NSAIDs), include conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), particularly methotrexate (MTX). The present study was performed to determine the non-adherence and discontinuation rates of different methotrexate (MTX) formulations in psoriatic arthritis (PsA). APPROACH AND RESULTS: We performed a retrospective-cohort study on patients with PsA identified by disease-specific code in the administrative-health-databases of a Northern Italian region (Lombardy) between 2004 and 2015. Subjects were defined as non-adherent if less than 80% of the prescribed MTX dose was taken based on the time between each prescription. Discontinuation rates were calculated using the time between the first and the last MTX prescription over an observation period of 120 months. Among 8952 patients with PsA, 33% were treated with MTX (mean dosage 10 mg/week ± 2.5 mg standard deviation), more frequently (59%) in its parenteral formulation at a 10 mg weekly dosage (35%). Oral glucocorticoids were prescribed to 21% of patients, while non-steroidal anti-inflammatory drugs to 45%. Approximately 37% of patients with PsA were defined as non-adherent to MTX, with the oral formulation associated with an increased risk of non-adherence (hazard ratio 2.08, 95% confidence interval 1.84-2.35, p < 0.001) compared with parenteral 10-15 mg weekly doses. Oral MTX was discontinued in 52% of cases without a significantly increased risk of discontinuation compared to parenteral formulations which, at higher dosages, had a more favorable retention rate. CONCLUSION: Oral MTX formulation is associated with a 2-fold risk of non-adherence compared to MTX parenteral route in PsA.