{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:58:46Z","timestamp":1789675126918,"version":"4.0.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203918\/Z\/16\/Z"],"award-info":[{"award-number":["203918\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/5"],"award-info":[{"award-number":["MC_UU_00011\/5"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Ophthal Inflamm Infect"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable risk to vision. The aim of this systematic review was to synthesise evidence of environmental risk factors for JIA-U and identify risk factors which may be modifiable or used to stratify JIA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This systematic review was carried out in accordance with PRISMA guidelines. Four online databases - Cumulative Index of Nursing and Allied Health Literature, Web of Science, MEDLINE and Embase - were searched from database inception to 12th August 2020. Identified studies were screened by two independent reviewers against pre-defined inclusion and exclusion criteria. Data was extracted from all primary studies meeting inclusion criteria and independently checked.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three studies from 895 unique records which met the inclusion criteria, each examining a different environmental risk factor. This systematic review includes 973, predominantly female, participants with JIA across these three studies. The use of allergy medication or documentation of \u201callergy\u201d\/\u201callergic\u201d in the medical records was associated with an increased risk of JIA-U in all models presented. Vitamin D sufficiency was associated with reduced risk of JIA-U. There was insufficient evidence to support an association between seasonality and JIA-U.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This review identifies a potential role for allergy and vitamin D in JIA-U. It also illustrates the paucity of data regarding environmental risk factors for JIA-U and highlights the need for further research to both identify additional risk factors and replicate existing findings.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12348-021-00247-1","type":"journal-article","created":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T23:05:46Z","timestamp":1621811146000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["\u201cEnvironmental risk factors associated with juvenile idiopathic arthritis associated uveitis: a systematic review of the literature\u201d"],"prefix":"10.1186","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7385-6307","authenticated-orcid":false,"given":"Sarah L. N.","family":"Clarke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie S.","family":"Mageean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Carlton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Simonini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma C.","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline L.","family":"Relton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athimalaipet V.","family":"Ramanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"issue":"12","key":"247_CR1","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.3899\/jrheum.130302","volume":"40","author":"ST Angeles-Han","year":"2013","unstructured":"Angeles-Han ST, Pelajo CF, Vogler LB, Rouster-Stevens K, Kennedy C, Ponder L, McCracken C, Lopez-Benitez J, Drews-Botsch C, Prahalad S, The CARRA Registry Investigators (2013) Risk markers of juvenile idiopathic arthritis-associated uveitis in the childhood arthritis and rheumatology research Alliance (CARRA) registry. J Rheumatol 40(12):2088\u20132096. https:\/\/doi.org\/10.3899\/jrheum.130302","journal-title":"J Rheumatol"},{"key":"247_CR2","doi-asserted-by":"publisher","first-page":"461078","DOI":"10.1155\/2014\/461078","volume":"2014","author":"A Moradi","year":"2014","unstructured":"Moradi A, Amin RM, Thorne JE (2014) The role of gender in juvenile idiopathic arthritis-associated uveitis. J Ophthalmol 2014:461078","journal-title":"J Ophthalmol"},{"issue":"12","key":"247_CR3","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1093\/rheumatology\/41.12.1440","volume":"41","author":"JC Packham","year":"2002","unstructured":"Packham JC, Hall MA (2002) Long-term follow-up of 246 adults with juvenile idiopathic arthritis: social function, relationships and sexual activity. Rheumatology. 41(12):1440\u20131443. https:\/\/doi.org\/10.1093\/rheumatology\/41.12.1440","journal-title":"Rheumatology."},{"key":"247_CR4","volume-title":"Guidelines for Screening for Uveitis in Juvenile Idiopathic Arthritis","author":"British Society for Paediatric and Adolescent Rheumatology, Royal College of Ophthalmology","year":"2006","unstructured":"British Society for Paediatric and Adolescent Rheumatology, Royal College of Ophthalmology. Guidelines for Screening for Uveitis in Juvenile Idiopathic Arthritis. 2006"},{"issue":"1","key":"247_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12969-016-0088-2","volume":"14","author":"SL Clarke","year":"2016","unstructured":"Clarke SL, Sen ES, Ramanan AV (2016) Juvenile idiopathic arthritis-associated uveitis. Pediatr Rheumatol Online J 14(1):27. https:\/\/doi.org\/10.1186\/s12969-016-0088-2","journal-title":"Pediatr Rheumatol Online J"},{"key":"247_CR6","doi-asserted-by":"publisher","first-page":"108322","DOI":"10.1016\/j.clim.2019.108322","volume":"211","author":"ES Sen","year":"2019","unstructured":"Sen ES, Ramanan AV (2019) Juvenile idiopathic arthritis-associated uveitis. Clin Immunol 211:108322","journal-title":"Clin Immunol"},{"issue":"7","key":"247_CR7","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/art.40484","volume":"70","author":"AJW Haasnoot","year":"2018","unstructured":"Haasnoot AJW, Schilham MW, Kamphuis S, Hissink Muller PCE, Heiligenhaus A, Foell D et al (2018) Identification of an amino acid motif in HLA-DRbeta1 that distinguishes uveitis in patients with juvenile idiopathic arthritis. Arthritis Rheumatol 70(7):1155\u20131165. https:\/\/doi.org\/10.1002\/art.40484","journal-title":"Arthritis Rheumatol"},{"issue":"5","key":"247_CR8","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.survophthal.2014.03.002","volume":"59","author":"V Kalinina Ayuso","year":"2014","unstructured":"Kalinina Ayuso V, Makhotkina N, van Tent-Hoeve M, de Groot-Mijnes JD, Wulffraat NM, Rothova A et al (2014) Pathogenesis of juvenile idiopathic arthritis associated uveitis: the known and unknown. Surv Ophthalmol 59(5):517\u2013531. https:\/\/doi.org\/10.1016\/j.survophthal.2014.03.002","journal-title":"Surv Ophthalmol"},{"issue":"10","key":"247_CR9","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.jclinepi.2009.06.005","volume":"62","author":"D Moher","year":"2009","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006\u20131012. https:\/\/doi.org\/10.1016\/j.jclinepi.2009.06.005","journal-title":"J Clin Epidemiol"},{"key":"247_CR10","unstructured":"Clarke S, Mageean K, Ramanan AV, Simonini G (2017) Environmental risk factors associated with juvenile idiopathic arthritis and juvenile idiopathic arthritis associated uveitis [Available from: https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php? RecordID=78306]"},{"issue":"1","key":"247_CR11","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","volume":"5","author":"M Ouzzani","year":"2016","unstructured":"Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A (2016) Rayyan-a web and mobile app for systematic reviews. Syst Rev 5(1):210. https:\/\/doi.org\/10.1186\/s13643-016-0384-4","journal-title":"Syst Rev"},{"key":"247_CR12","unstructured":"Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al., The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http:\/\/www.ohrica\/programs\/clinical_epidemiology\/oxfordasp. Accessed 2021"},{"issue":"11","key":"247_CR13","first-page":"2446","volume":"29","author":"F Zulian","year":"2002","unstructured":"Zulian F, Martini G, Falcini F, Gerloni V, Zannin ME, Pinello L, Fantini F, Facchin P (2002) Early predictors of severe course of uveitis in oligoarticular juvenile idiopathic arthritis. J Rheumatol 29(11):2446\u20132453","journal-title":"J Rheumatol"},{"key":"247_CR14","doi-asserted-by":"crossref","unstructured":"Cole TS, Frankovich J, Iyer S, LePendu P, Bauer-Mehren A, Shah NH (2013) Profiling risk factors for chronic uveitis in juvenile idiopathic arthritis: A new model for EHR-based research. Pediatr Rheumatol 11(1) (no pagination)(45)","DOI":"10.1186\/1546-0096-11-45"},{"key":"247_CR15","doi-asserted-by":"crossref","unstructured":"Sengler C, Zink J, Klotsche J, Niewerth M, Liedmann I, Horneff G et al (2018) Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis - Data from a German inception cohort. Arthritis Res Ther 20(1)","DOI":"10.1186\/s13075-018-1765-y"},{"issue":"6","key":"247_CR16","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1093\/rheumatology\/kem053","volume":"46","author":"A Heiligenhaus","year":"2007","unstructured":"Heiligenhaus A, Niewerth M, Ganser G, Heinz C, Minden K, German Uveitis in Childhood Study Group (2007) Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines. Rheumatology (Oxford) 46(6):1015\u20131019","journal-title":"Rheumatology (Oxford)"},{"issue":"11","key":"247_CR17","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1016\/S0161-6420(01)00773-4","volume":"108","author":"K Kotaniemi","year":"2001","unstructured":"Kotaniemi K, Kautiainen H, Karma A, Aho K (2001) Occurrence of uveitis in recently diagnosed juvenile chronic arthritis: a prospective study. Ophthalmology 108(11):2071\u20132075. https:\/\/doi.org\/10.1016\/S0161-6420(01)00773-4","journal-title":"Ophthalmology"},{"issue":"2","key":"247_CR18","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/art.20815","volume":"52","author":"CM Duffy","year":"2005","unstructured":"Duffy CM, Colbert RA, Laxer RM, Schanberg LE, Bowyer SL (2005) Nomenclature and classification in chronic childhood arthritis: time for a change? Arthritis Rheum 52(2):382\u2013385. https:\/\/doi.org\/10.1002\/art.20815","journal-title":"Arthritis Rheum"},{"key":"247_CR19","unstructured":"Zierhut M, Deuter C, Murray PI (2011) Classification of Uveitis \u2013 Current Guidelines. Eur Ophthalmol Rev 77(8)"},{"key":"247_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jaut.2017.06.001","volume":"82","author":"A Watad","year":"2017","unstructured":"Watad A, Azrielant S, Bragazzi NL, Sharif K, David P, Katz I, Aljadeff G, Quaresma M, Tanay G, Adawi M, Amital H, Shoenfeld Y (2017) Seasonality and autoimmune diseases: the contribution of the four seasons to the mosaic of autoimmunity. J Autoimmun 82:13\u201330. https:\/\/doi.org\/10.1016\/j.jaut.2017.06.001","journal-title":"J Autoimmun"},{"issue":"12","key":"247_CR21","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1183\/09031936.96.09122630","volume":"9","author":"D Lieberman","year":"1996","unstructured":"Lieberman D, Lieberman D, Porath A (1996) Seasonal variation in community-acquired pneumonia. Eur Respir J 9(12):2630\u20132634. https:\/\/doi.org\/10.1183\/09031936.96.09122630","journal-title":"Eur Respir J"},{"issue":"1","key":"247_CR22","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/infdis\/146.1.103","volume":"146","author":"M Moore","year":"1982","unstructured":"Moore M (1982) Centers for disease control. Enteroviral disease in the United States, 1970-1979. J Infect Dis 146(1):103\u2013108. https:\/\/doi.org\/10.1093\/infdis\/146.1.103","journal-title":"J Infect Dis"},{"key":"247_CR23","doi-asserted-by":"crossref","unstructured":"Smatti MK, Cyprian FS, Nasrallah GK, Al Thani AA, Almishal RO, Yassine HM (2019) Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms. Viruses 11(8):762","DOI":"10.3390\/v11080762"},{"issue":"7","key":"247_CR24","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1093\/aje\/kwt446","volume":"179","author":"MG Kimlin","year":"2014","unstructured":"Kimlin MG, Lucas RM, Harrison SL, van der Mei I, Armstrong BK, Whiteman DC, Kricker A, Nowak M, Brodie AM, Sun J (2014) The contributions of solar ultraviolet radiation exposure and other determinants to serum 25-hydroxyvitamin D concentrations in Australian adults: the AusD study. Am J Epidemiol 179(7):864\u2013874. https:\/\/doi.org\/10.1093\/aje\/kwt446","journal-title":"Am J Epidemiol"},{"issue":"9","key":"247_CR25","doi-asserted-by":"publisher","first-page":"102350","DOI":"10.1016\/j.autrev.2019.102350","volume":"18","author":"G Murdaca","year":"2019","unstructured":"Murdaca G, Tonacci A, Negrini S, Greco M, Borro M, Puppo F, Gangemi S (2019) Emerging role of vitamin D in autoimmune diseases: an update on evidence and therapeutic implications. Autoimmun Rev 18(9):102350. https:\/\/doi.org\/10.1016\/j.autrev.2019.102350","journal-title":"Autoimmun Rev"},{"issue":"5","key":"247_CR26","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1001\/jamaophthalmol.2018.0642","volume":"136","author":"L Sobrin","year":"2018","unstructured":"Sobrin L, Stanwyck LK, Pan W, Hubbard RA, Kempen JH, VanderBeek BL (2018) Association of Hypovitaminosis D with Increased Risk of uveitis in a large health care claims database. JAMA Ophthalmol 136(5):548\u2013552. https:\/\/doi.org\/10.1001\/jamaophthalmol.2018.0642","journal-title":"JAMA Ophthalmol"},{"issue":"7","key":"247_CR27","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","volume":"136","author":"TR Mosmann","year":"1986","unstructured":"Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136(7):2348\u20132357","journal-title":"J Immunol"},{"issue":"2","key":"247_CR28","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/BF02786470","volume":"20","author":"VK Singh","year":"1999","unstructured":"Singh VK, Mehrotra S, Agarwal SS (1999) The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. Immunol Res 20(2):147\u2013161. https:\/\/doi.org\/10.1007\/BF02786470","journal-title":"Immunol Res"},{"issue":"2","key":"247_CR29","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nm1551","volume":"13","author":"L Steinman","year":"2007","unstructured":"Steinman L (2007) A brief history of TH17, the first major revision in the TH1\/TH2 hypothesis of T cell\u2013mediated tissue damage. Nat Med 13(2):139\u2013145. https:\/\/doi.org\/10.1038\/nm1551","journal-title":"Nat Med"},{"key":"247_CR30","doi-asserted-by":"crossref","unstructured":"Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K (2019) Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis. Eur Respir J 54(5)","DOI":"10.1183\/13993003.00476-2019"},{"key":"247_CR31","doi-asserted-by":"publisher","first-page":"253","DOI":"10.2147\/OARRR.S165916","volume":"11","author":"DB Horton","year":"2019","unstructured":"Horton DB, Shenoi S (2019) Review of environmental factors and juvenile idiopathic arthritis. Open Access Rheumatol 11:253\u2013267. https:\/\/doi.org\/10.2147\/OARRR.S165916","journal-title":"Open Access Rheumatol"},{"issue":"6","key":"247_CR32","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.jbspin.2019.06.001","volume":"86","author":"JL Hayworth","year":"2019","unstructured":"Hayworth JL, Turk MA, Nevskaya T, Pope JE (2019) The frequency of uveitis in patients with juvenile inflammatory rheumatic diseases. Joint Bone Spine 86(6):685\u2013690. https:\/\/doi.org\/10.1016\/j.jbspin.2019.06.001","journal-title":"Joint Bone Spine"}],"container-title":["Journal of Ophthalmic Inflammation and Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12348-021-00247-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12348-021-00247-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12348-021-00247-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T02:06:29Z","timestamp":1699063589000},"score":1,"resource":{"primary":{"URL":"https:\/\/joii-journal.springeropen.com\/articles\/10.1186\/s12348-021-00247-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["247"],"URL":"https:\/\/doi.org\/10.1186\/s12348-021-00247-1","relation":{},"ISSN":["1869-5760"],"issn-type":[{"value":"1869-5760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,24]]},"assertion":[{"value":"4 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval and consent to participate.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SLNC \u2013 none declared.KSM \u2013 none declared.HC \u2013 none declared.GS \u2013 has received speaker fees\/Honoraria from Abbvie, and Novartis.GCS \u2013 none declared.CLR \u2013 none declared.AVR \u2013 has received speaker fees\/honoraria\/consultancy from Abbvie, Eli Lilly, Pfizer, Roche, SOBI, Novartis and UCB.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15"}}