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Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery., Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction., Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4 th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients,14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery., Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4 th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kharouf, Eviatar, Braun, Pokroy-Shapira, Brodavka, Zloof, Agmon-Levin, Toledano, Oren, Lidar, Zisman, Tavor, Amit-Vazina, Sabbah, Breuer, Dagan, Beshara-Garzuzi, Markovits, Elias, Feld, Tayer-Shifman, Gazitt, Reitblatt, Rubin, Haddad, Giryes, Paran, Peleg, Molad, Elkayam, Mevorach, Balbir-Gurman and Braun-Moscovici.) more...

Objectives: To evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls., Methods: A prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2-6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2-6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample., Results: The two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, p<0.0001, and 96.55% versus 74.26%, p<0.0001 at 2-6 weeks and at 6 months, respectively. The third vaccine dose restored the seropositive response in all controls and 80.47% of patients with AIIRD, p=0.0028. All patients treated with methotrexate monotherapy, anticytokine biologics, abatacept and janus kinase (JAK) inhibitors regained the humoral response after the third vaccine, compared with only a third of patients treated with rituximab, entailing a 16.1-fold risk for a negative humoral response, p≤0.0001. Cellular immune response in rituximab-treated patients was preserved before and after the third vaccine and was similar to controls. Breakthrough COVID-19 rate during the Delta surge was similar in patients and controls, 1.83% versus 1.43%, p=1., Conclusions: The two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Objectives: As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness of reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD., Methods: The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two rheumatology departments in Israel., Results: The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: RA (n = 4), Sjogren's syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in five cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in an RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects., Conclusion: Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...

Introduction: Vaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited., Methods: A multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2-6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose., Results: Following vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients., Conclusion: mRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Objective: To assess the attitudes and common practices of adult rheumatologists in the US regarding health care transition (HCT) for young adults with rheumatic diseases., Methods: An anonymous online survey was sent to US adult rheumatologist members of the American College of Rheumatology to collect demographic data and information on attitudes and common practices regarding the transition process., Results: Of 4,064 contacted rheumatologists, 203 (5%) completed the survey. Almost half of respondents (45.1%) were never trained in transition practices, and 74.7% were not familiar with the American Academy of Pediatrics/American Academy of Family Physicians/American College of Physicians Consensus Statement About Transitions for Youth with Special Healthcare Needs. Only 56.2% felt comfortable caring for former pediatric patients. The vast majority of respondents (90.7%) did not have a multidisciplinary transition team, and 37% did not have a plan for transitioning pediatric patients into their practice. Most adult rheumatologists were unsatisfied with the current transition process (92.9%), due to insufficient resources, personnel (91.1%), and time in clinic (86.9%). They also were unsatisfied with referral data received concerning previous treatments (48.9%), hospitalization history (48%), disease activity index (45.1%), medical history summary (43.9%), comorbidities (36.4%), medication list (34.1%), and disease classification (32.6%). Three major barriers to HCT were lack of insurance reimbursement (33.7%), knowledge about community resources (30.8%), and lapses in care between primary provider and specialist (27.8%)., Conclusion: This survey identified substantial gaps in knowledge and resources regarding HCT for young adults with rheumatic diseases. These may be best addressed by further training, research, dedicated resources, adequate payment, and practice guidelines., (© 2019, American College of Rheumatology.) more...

Background: The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients., Methods: A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0-6, 6-12, 12-18, and 18-24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results., Results: The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0-6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18-24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from -0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18-24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18-24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study., Conclusions: TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels. more...

Seronegative spondyloarthritis (SpA) represents a group of diseases that share certain genetic, clinical, and radiographic features. Enthesitis, inflammation at the site of tendon insertion into the bone, involving both the axial and the peripheral joints, is an important sign of SpA. Clinical diagnosis of enthesitis, however, is neither sensitive nor specific; thus, the diagnosis of enthesitis often relies on typical abnormalities in imaging studies. Due to its low costs and availability, ultrasound is emerging as the preferred technique for detection of enthesitis for both clinical and research purposes. Ultrasonographic features of enthesitis include tendon hypoechogenicity and thickening, calcifications, bone erosions, and Doppler signal. Several semi-quantitative scoring systems have been developed to quantify ultrasonographic abnormalities of the entheses. These methods have been used for early diagnosis and classification of SpA as well as for monitoring response to treatment., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.) more...

Objective: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases., Methods: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review., Results: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene., Conclusion: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient. more...