Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

In response to recent advancements in inflammatory bowel disease (IBD) management, the British Society of Gastroenterology (BSG) Clinical Services and Standards Committee (CSSC) has commissioned the BSG IBD section to update its guidelines, last revised in 2019. These updated guidelines aim to complement the IBD standards and promote the use of the national primary care diagnostic pathway for lower gastrointestinal symptoms to enhance diagnostic accuracy and timeliness. Formulated through a systematic and transparent process, this document reflects a consensus of best practices based on current evidence. The guideline, while developed primarily for the UK, is structured to support IBD management internationally. It is endorsed by the BSG executive board and CSSC without external commercial funding, with involvement primarily supported through professional roles in public institutions and the National Health Service (NHS). Methodological revisions since the prior guidelines have enhanced rigor in technical review and development, with methodology details published independently following peer review. In developing the recommendations, 89 clinical experts and stakeholders participated in an online survey, identifying primary outcomes, such as clinical and endoscopic remission, as well as adverse event metrics, all stratified by clinically relevant effect sizes. These guidelines are intended to support clinical decision-making but are not prescriptive, recognizing that individual clinical scenarios may warrant tailored approaches. Further research may inform future revisions as new evidence emerges.

Objective.: To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM).Methods.: Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions.Results.: Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM.Conclusion.: The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.

The recognition of the primacy of enthesitis in animal models of spondyloarthritis and the prevalence of clinically occult enthesopathy in psoriatic subjects and of persistent joint pain in PsA subjects who have ostensibly good reduction of joint swelling under biological therapy has highlighted the potential impact of polyenthesitis in psoriatic disease. In daily practice, the formal demonstration of enthesitis is challenging for the following reasons: the relatively avascular nature of enthesis, often leading to the absence of overt clinical inflammatory signs; the frequent lack of elevation of inflammatory markers; and finally, the limitations of current imaging techniques to provide supportive evidence for inflammation in these areas. Consequently, enthesitis may present as widespread pain indistinguishable from FM or may emerge as the dominant feature after successful biological therapy for suppression of synovitis. The unmet needs in the differentiation between FM and enthesitis in psoriatic disease patients are highlighted and critically evaluated in this article.

Objective . The aim of the study was to evaluate the pattern of the lymphoid organization in the synovial tissue of patients affected with juvenile idiopathic arthritis (JIA). Methods . A total of 40 JIA patients who underwent synoviectomy or synovial biopsies were enrolled. The mean age at surgery was 15.1 yrs (range 6–30 yrs) and the mean disease duration was 6.7 yrs (range 3 months to 22.2 yrs). Tissue specimens were grouped according to the following criteria: (i) diffuse perivascular infiltrate without lymphoid organization, (ii) T cell–B cell aggregates with or without germinal centre reaction. Results . Synovial tissues from 12 JIA patients did not show any sign of lymphoid organization, whereas 28 patients displayed a variable number of T–B cell aggregates. Typical features consistent with a germinal centre reaction were present in two JIA patients only. Lymphoid organization in JIA patients did not correlate with the duration and severity of the disease or with the degree of synovial inflammation, but did positively correlate with the presence of anti-nuclear antibodies. Moreover, a diffuse lymphocyte infiltration was significantly related to the presence of an acute phase of inflammation and the presence of lymphoid aggregates correlated with the degree of plasma cells infiltration. Conclusions . Lymphoid neogenesis in JIA represents a phase in the immunopathological process that characterize the development of inflammatory synovitis. It is not related to disease activity or severity, but appears to be more frequent in patients with circulating anti-nuclear antibodies.

Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5⁺-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 is an RNA sensor and a key pattern recognition receptor for the SARS-CoV-2 virus. This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using a 15 muscle-specific autoantibodies (MSAs) panel, between Janurary 2018 and December 2022 in Yorkshire, UK. MDA5-positivity was correlated with clinical features and outcome, and regional SARS-CoV-2 positivity and vaccination rates. Gene expression patterns in COVID-19 were compared with autoimmune lung disease and idiopathic pulmonary fibrosis (IPF) to gain clues into the genesis of the observed MDA5⁺-DM outbreak. Sixty new anti-MDA5+, but not other MSAs surged between 2020 and 2022, increasing from 0.4% in 2019 to 2.1% (2020), 4.8% (2021) and 1.7% (2022). Few (8/60) had a prior history of confirmed COVID-19, peak rates overlapped with regional SARS-COV-2 community positivity rates in 2021, and 58% (35/60) had received anti-SARS-CoV-2 vaccines. 25/60 cases developed ILD which rapidly progression with death in 8 cases. Among the 35/60 non-ILD cases, 14 had myositis, 17 Raynaud phenomena and 10 had dermatomyositis spectrum rashes. Transcriptomic studies showed strong IFIH1 (gene encoding for MDA5) induction in COVID-19 and autoimmune-ILD, but not IPF, and IFIH1 strongly correlated with an IL-15-centric type-1 interferon response and an activated CD8+ T cell signature that is an immunologic hallmark of progressive ILD in the setting of systemic autoimmune rheumatic diseases. The IFIH1 rs1990760TT variant blunted such response. A distinct pattern of MDA5-autoimmunity cases surged contemporaneously with circulation of the SARS-COV-2 virus during COVID-19. Bioinformatic insights suggest a shared immunopathology with known autoimmune lung disease mechanisms. This work was supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC), and in part by the National Institutes of Health (NIH) grant R01-AI155696 and pilot awards from the UC Office of the President (UCOP)-RGPO (R00RG2628, R00RG2642 and R01RG3780) to P.G. S.S was supported in part by R01-AI141630 (to P.G) and in part through funds from the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.