• Elvis Hysa, Carlo Alberto Cutolo, Emanuele Gotelli, Greta Pacini, Carlotta Schenone, Elke O Kreps, Vanessa Smith, and Maurizio Cutolo.
• Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, Italy - IRCCS Rheumatology Unit, San Martino Polyclinic, University of Genoa, Genoa, Italy.
• Eur. J. Clin. Invest. 2021 Aug 1; 51 (8): e13572e13572.

BackgroundUveitis is one of the most frequent ophthalmologic manifestations in rheumatology. 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.MethodsIn 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, Behçet's disease and sarcoidosis get the major impact.ResultsIn Behçet's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and γδ 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-related uveitis derives from a complex interaction between genetic background and extra-ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro-inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro-inflammatory cytokines, TNF-α 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.ConclusionsAwareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.© 2021 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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