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Abstract Background Psoriatic arthritis (PsA) is a chronic, potentially debilitating inflammatory arthritis often associated with psoriasis. Understanding the epidemiology of PsA across diverse populations can provide valuable insights into its global burden and the role of genetic and environmental factors. This study aimed to estimate PsA’s temporal trends, prevalence, and incidence, while assessing variations in age, gender, and ethnicity in Israel from 2016 to 2022. Methods Data were sourced from the Clalit Health Services (CHS) database, covering over half of the Israeli population. Algorithm-based definitions for PsA and psoriasis cases were used. Demographic factors, including age, gender, socioeconomic status (SES), ethnicity, urban/rural residence, BMI, and smoking status, were analyzed. Standardized prevalence and incidence rates were calculated. Logistic regression analyses examined associations of sociodemographic variables with PsA. Results In 2022, the prevalence of PsA was 0.221%, with an incidence rate of 13.54 per 100,000 population. This prevalence has tripled since 2006, reflecting a rising trend in PsA over time. Females exhibited a higher prevalence (1.15; 95%CI 1.09–1.21), and PsA was more common in Jewish individuals (1.58; 95%CI 1.45–1.71) those with higher SES (1.4; 95% CI 1.31, 1.5), and those with obesity (2.17; 95%CI 2.04–2.31). Conclusions This comprehensive population-based study pointed to an increase prevalence of PsA, emphasizing the rising healthcare demands and economic burden faced by this patient population. Further research is essential to delve into the factors driving these trends.

A 65-year-old woman was admitted to the neurology department with a suspected demyelinating disease due to complaints of progressive pain and weakness in both upper and lower limbs, as well as urinary incontinence. MRI of the spine revealed complex disc osteophyte with compression of the spinal cord in the cervical and lumbar spine at several vertebral levels, and localized enhancement in the cervical spine at the site of maximal spinal canal stenosis. During her hospitalization, the patient underwent extensive evaluation to rule out any systematic inflammatory diseases, infections, and malignancy. Chest CT revealed bilateral mediastinal lymphadenopathy. Transbronchial mediastinal lymph node biopsy showed numerous non-necrotizing granulomas without evidence of malignancy. After a thorough and careful exclusion of a demyelinating, infectious, and paraneoplastic myelopathies, and based on clinical, radiographic, and pathological findings, the patient was diagnosed with both neurosarcoidosis and spondylotic myelopathy. She was then treated for neurosarcoidosis, including glucocorticosteroids, azathioprine, and a biosimilar of the anti-TNF alpha agent infliximab, resulting in both clinical and radiographic improvement. Intramedullary spinal neurosarcoidosis is very rare and may present with clinical features of spondylotic myelopathy, with typical imaging findings occurring only in areas of spinal canal stenosis.

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin’ s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.

During progression of rheumatoid arthritis (RA), angiogenesis provides oxygen and nutrients for the cells’ increased metabolic demands and number. To turn on angiogenesis, pro-angiogenic factors must outweigh anti-angiogenic factors. We have previously shown that CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) can induce the expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) in a co-culture of the human HT1080 fibrosarcoma and U937 monocytic-like cell lines. However, whether CD147 influences anti-angiogenic factors was not known. We now show that relative to single cultures, the co-culture of these cells not only enhanced pro-angiogenic factors but also decreased the anti-angiogenic factors endostatin and thrombospondin-1 (Tsp-1), generally increasing the angiogenic potential as measured by a wound assay. Using anti-CD147 antibody, CD147 small interfering RNA (siRNA), and recombinant CD147, we demonstrate that CD147 hormetically regulates the generation of endostatin but has no effect on Tsp-1. Since endostatin is cleaved from collagen XVIII (Col18A), we applied different protease inhibitors and established that MMP-9 and proteasome 20S, but not cathepsins, are responsible for endostatin generation. MMP-9 and proteasome 20S collaborate to synergistically enhance endostatin generation, and in a non-cellular system, CD147 enhanced MMP-9 activity and hormetically regulated proteasome 20S activity. Serum samples obtained from RA patients and healthy controls mostly corroborated these findings, indicating clinical relevance. Cumulatively, these findings suggest that secreted CD147 mediates a possibly allosteric effect on MMP-9 and proteasome 20S activities and can serve as a switch that turns angiogenesis on or off, depending on its ambient concentrations in the microenvironment.

Limited information is available on the effectiveness of COVID-19 vaccination in patients with psoriasis and psoriatic arthritis (psoriatic disease (PsD)). The objective of our research was to assess the effectiveness of mRNA COVID-19 vaccination in preventing SARS-CoV-2 positivity and severe infection in a cohort of patients with PsD and the association of immunosuppressants on SARS-CoV-2 infection-related outcomes from December 2020 to December 2021. Vaccine effectiveness was assessed in a matched nested case control study using conditional logistic regression adjusted for demographics, comorbidities and immunosuppressant use. Study outcomes included SARS-CoV-2 positivity and severe COVID-19 (moderate-to-severe COVID-19-related hospitalizations or death). At least one dose of mRNA COVID-19 vaccine was associated with reduced risk of SARS-CoV-2 positivity and severe COVID-19 (OR = 0.41 (95% CI, 0.38–0.43) and OR = 0.15 (95% CI, 0.11–0.20), respectively). A more significant effect was found among patients who received three vaccines doses compared with those who did not receive any (OR (for positive SARS-CoV-2) = 0.13 (95% CI, 0.12–0.15) and OR (for severe disease) = 0.02 (0.01–0.05)). Etanercept and methotrexate were associated with higher risk of SARS-CoV-2 positivity (1.58 (1.19–2.10), p = 0.001 and 1.25 (1.03–1.51), p = 0.03, respectively). In conclusion, our results show that mRNA COVID-19 vaccines are effective in reducing both infection and severe COVID-19-related outcomes.

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case–control studies, identifying all new HZ cases diagnosed from 1 January–31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19–2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15–12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68–3.14).