Tal Gazitt

Background/Objective: The emergence of the COVID-19 pandemic has raised significant concerns regarding its impact on immune-mediated diseases, particularly with respect to disease induction and exacerbation. We aimed to investigate the potential association between SARS-CoV-2 infection and COVID-19 vaccination and the development of Psoriatic Arthritis (PsA). Methods: A retrospective nested case-control study in a cohort of 3,122,602 adults without a diagnosis of PsA was conducted using a database of a large health care provider. Newly diagnosed patients with PsA aged 18 years and older were identified from the database between 1 January 2021 and 30 June 2022 and were matched by age and sex to 10 non-PsA controls. Patients were tracked to assess their exposure to SARS-CoV-2 within six months prior to diagnosis (inception date). The primary outcome of exposure to SARS-CoV-2 was compared in the cases and controls. Univariate and multivariate conditional logistic regression analyses were performed, adjusting for Body Mass Index (BMI), smoking, socioeconomic status (SES), the Charlson comorbidity index, ethnicity, psoriasis and COVID-19 vaccination status within six months. Results: Overall, 718 patients had a new diagnosis of PsA and were matched with 7180 controls. SARS-CoV-2 exposure among PsA cases was (N = 88/718, 12.3%) compared to controls (N = 755/7180, 10.5%), the difference was not statistically significant (p = 0.115). No statistically significant association was found between SARS-CoV-2 infection and PsA development after adjusting for all confounders (OR = 1.08, 95% CI [0.76–1.54], p = 0.652). COVID-19 vaccination was also not associated with PsA development (OR = 1.10, 95% CI [0.86–1.41], p = 0.45). Conclusions: This study found no statistically significant association between SARS-CoV-2 exposure or COVID-19 vaccination and PsA development within six months post-exposure; however, small differences cannot be excluded.

Introduction/objective: Giant Cell Arteritis (GCA) is relatively rare in the Middle East compared to Western countries. We aimed to retrospectively investigate the demographic, clinical, and imaging characteristics and the definitive diagnoses of patients referred to a GCA fast-track clinic (FTC) in the northwest of Israel with a mixed population of Arabs and Jews. Methods: Demographic, clinical and laboratory data of patients referred to GCA-FTC between 2022 and 2024 were retrospectively collected. The Southend Pre-Test Probability Score for GCA (GCAPS) was calculated. Patients underwent color-Doppler ultrasound (CDUS) for the temporal and axillary arteries. The definitive diagnosis was determined by the treating rheumatologist based on clinical features, CDUS, additional imaging tests, and/or biopsy results. Results: Seventy-two consecutive outpatients with a suspected diagnosis of GCA were included. The mean age was 74.6 ± 8.8years, 63% were females. Of these individuals, 19/72 had a low GCAPS, of whom 2 were diagnosed with GCA; 40/72 had an intermediate GCAPS, of whom 14 had a positive CDUS but only 9 had GCA diagnosis; and of 13 patients with high GCAPS, 10 were confirmed as having GCA by CDUS and one patient was diagnosed by computed tomography angiography (CTA). Large-vessel involvement was documented in only 2/22 GCA patients. Among non-GCA patients, the most common diagnoses were pure polymyalgia rheumatica (PMR), migraine headache, infection, calcium-pyrophosphate deposition disease (CPPD), and temporomandibular joint (TMJ) dysfunction. Conclusions: The GCAPS is a reliable tool for risk-stratifying patients referred to the GCA-FTC in this study population. The sensitivity and specificity of CDUS was 90.9% and 88%, respectively. A relatively low prevalence of large vessel involvement was documented. Our results suggest that rheumatologists should remain vigilant regarding the differential diagnoses in patients with suspected GCA. Key Points • Our study is the first study in the Middle East to utilize color-Doppler ultrasonography (CDUS) in Giant Cell Arteritis Fast Track Clinic (GCA-FTC) setting, and it was found to have very high sensitivity (90.9) and specificity (88.0%). • In our study population, the Southend Pre-Test Probability Score for GCA (GCAPS) was found to be a reliable tool for risk- stratifying patients referred to the GCA-FTC. • Based on our findings, rheumatologists should remain vigilant regarding the differential diagnoses of patients with suspected GCA, including pure PMR, migraine headache, infection, CPPD and TMJ dysfunction.

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.

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).

Objective To assess the frequency of uveitis in patients with psoriatic arthritis (PsA) in the era of biologics and to identify risk factors associated with uveitis. Methods A retrospective matched cohort study was conducted within the database of a large healthcare provider. Newly diagnosed 6147 adult PsA patients between 2005 and 2020 were matched by the index date of PsA diagnosis, age, sex, and ethnicity to 23,999 randomly selected controls. This cohort was used to examine the association between PsA and uveitis. An additional analysis was conducted within the PsA group to identify uveitis risk factors, using two analytic approaches: a retrospective cohort study and a nested case-control study. Results Uveitis was diagnosed in 107 patients in the PsA group (1.7%) vs 187 (0.8%) patients in the control group (adjusted HR, 2.38, 95% CI 1.80–3.15, pppp=0.001] were independently associated with uveitis. Only one PsA patient with uveitis (out of 107) required systemic oral treatment with prednisone, while the rest of the patients were treated with topical glucocorticosteroids only. Conclusion PsA is associated with increased risk of uveitis. Past uveitis and treatment with etanercept were associated with higher risk of uveitis. Key Points • Psoriatic arthritis (PsA) is a major risk factor for uveitis with hazard ratio of 2.38 compared to healthy individuals without PsA. • Among PsA patients, the past event of uveitis and treatment with etanercept are risk factors for uveitis. • Uveitis in patients treated with biologics for their PsA requires topical therapy only in most of the cases.

Despite the increasing recognition of cardiac involvement in systemic sarcoidosis, the diagnosis of cardiac sarcoidosis (CS) remains challenging. Our aim is to present a comprehensive, retrospective case series of CS patients, focusing on the current diagnostic guidelines and management of this life-threatening condition. In our case series, patient data were collected retrospectively, including hospital admission records and rheumatology and cardiology clinic visit notes, detailing demographic, clinical, laboratory, pathology, and imaging studies, as well as cardiac devices and prescribed medications. Cases were divided into definite and probable CS based on the 2014 Heart Rhythm Society guidelines as well as presumed CS based on imaging criteria and clinical findings. Overall, 19 CS patients were included, 17 of whom were diagnosed with probable or presumed CS based on cardiac magnetic resonance imaging (CMR) and/or cardiac positron emission tomography using ¹⁸F-Fluorodeoxyglucose (PET-FDG) without supporting endomyocardial biopsy (EMB). The majority of CS patients were male (53%), with a mean age of 52.9 ± 11.8, with CS being the initial manifestation of sarcoidosis in 63% of cases. Most patients presented with high-grade AVB (63%), followed by heart failure (42%) and ventricular tachyarrhythmia (VT) (26%). This case series highlights the significance of utilizing updated diagnostic criteria relying on CMR and PET-FDG given that cardiac involvement can be the initial manifestation of systemic sarcoidosis, requiring prompt diagnosis and treatment to prevent morbidity and mortality.

Glucocorticosteroid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis but is underdiagnosed and undertreated. Our aim in this communication is to review the literature on the implementation of current GIO prevention practices such as calcium and vitamin D supplementation with emphasis on the rheumatologists’ perspective relating to the need for development of novel GIO educational prevention measures.