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Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) in approximately 30% of cases with a significant burden on the quality of life since it represents a cause of blindness in up to 20% of cases in Western countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this review, we provide a comprehensive overview of the pathophysiology of uveitis associated with SIRDs. According to our literature survey on the epidemiology of uveitis among SIRDs, spondyloarthritides, Beh\u00e7et's disease and sarcoidosis get the major impact.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In Beh\u00e7et's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and \u03b3\u03b4 T cells. All contribute to a great destructive inflammatory environment with the most serious visual damage resulting from the involvement of the posterior segment of the eye. In contrast, spondyloarthritides\u2010related uveitis derives from a complex interaction between genetic background and extra\u2010ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro\u2010inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro\u2010inflammatory cytokines, TNF\u2010\u03b1 among all, leads to intraocular inflammation. Lastly, granuloma formation represents the primary hallmark lesion in sarcoid uveitis. This suggests a profound link between the innate system that mainly recruits activated macrophages and adaptive system involving by Th1, Th17 and Th17.1 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Awareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13572","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T10:02:55Z","timestamp":1618394575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-0983","authenticated-orcid":false,"given":"Elvis","family":"Hysa","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology Department of Internal Medicine Italy \u2013 IRCCS Rheumatology Unit San Martino Polyclinic University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Alberto","family":"Cutolo","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic DiNOGMI IRCCS Ophthalmology Unit San Martino Polyclinic University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Gotelli","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology Department of Internal Medicine Italy \u2013 IRCCS Rheumatology Unit San Martino Polyclinic University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Pacini","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology Department of Internal Medicine Italy \u2013 IRCCS Rheumatology Unit San Martino Polyclinic University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Schenone","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology Department of Internal Medicine Italy \u2013 IRCCS Rheumatology Unit San Martino Polyclinic University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke O","family":"Kreps","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ghent University Hospital Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6271-7945","authenticated-orcid":false,"given":"Vanessa","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Department of Rheumatology Ghent. 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