{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T20:53:37Z","timestamp":1789073617432,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology\/European League Against Rheumatism (ACR\/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.<\/jats:p>","DOI":"10.3390\/jcm13133780","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T13:26:43Z","timestamp":1719494803000},"page":"3780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Doah","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SangYoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-3000","authenticated-orcid":false,"given":"Helen","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1080\/14397595.2020.1859710","article-title":"The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD","volume":"31","author":"Umehara","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.semarthrit.2013.11.008","article-title":"Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review","volume":"43","author":"Wallace","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41584-020-0500-7","article-title":"IgG4-related disease: An update on pathophysiology and implications for clinical care","volume":"16","author":"Perugino","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s00296-014-3153-5","article-title":"Tubulointerstitial fibrosis in patients with IgG4-related kidney disease: Pathological findings on repeat renal biopsy","volume":"35","author":"Arai","year":"2015","journal-title":"Rheumatol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/jgh.16136","article-title":"Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study","volume":"38","author":"Cho","year":"2023","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1136\/bjo-2021-320936","article-title":"Treatment outcomes and their determinants of IgG4-related ophthalmic disease: A territory-wide cohort study","volume":"107","author":"Lai","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cai, S., Hu, Z., Chen, Y., Zhong, J., and Dong, L. (2022). Potential roles of non-lymphocytic cells in the pathogenesis of IgG4-related disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.940581"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/annrheumdis-2018-214603","article-title":"Clinical phenotypes of IgG4-related disease: An analysis of two international cross-sectional cohorts","volume":"78","author":"Wallace","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1136\/annrheumdis-2019-216561","article-title":"The 2019 American College of Rheumatology\/European League Against Rheumatism classification criteria for IgG4-related disease","volume":"79","author":"Wallace","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/s41433-020-1083-x","article-title":"Clinical features and outcomes of IgG4-related idiopathic orbital inflammatory disease: From a large southern China-based cohort","volume":"35","author":"Chen","year":"2021","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/aos.14048","article-title":"The treatment outcomes in IgG4-related orbital disease: A systematic review of the literature","volume":"97","author":"Detiger","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/1756-185X.13088","article-title":"Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: A preliminary randomized controlled trial","volume":"20","author":"Wu","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1080\/14397595.2016.1259602","article-title":"A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease","volume":"27","author":"Masaki","year":"2017","journal-title":"Mod. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/IOP.0000000000001975","article-title":"Clinical Outcomes of IgG4-Related Ophthalmic Disease and Idiopathic Sclerosing Orbital Inflammation","volume":"38","author":"Son","year":"2022","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/rheumatology\/keu228","article-title":"Identification of relapse predictors in IgG4-related disease using multivariate analysis of clinical data at the first visit and initial treatment","volume":"54","author":"Yamamoto","year":"2015","journal-title":"Rheumatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e6205","DOI":"10.1097\/MD.0000000000006205","article-title":"Ophthalmic manifestations in IgG4-related disease: Clinical presentation and response to treatment in a French case-series","volume":"96","author":"Ebbo","year":"2017","journal-title":"Medicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/ceo.12316","article-title":"Sequential biopsies from immunoglobulin G4-related orbital disease demonstrate progressive fibrosis","volume":"42","author":"Andrew","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev-med-050219-034449","article-title":"Clinical Perspectives on IgG4-Related Disease and Its Classification","volume":"73","author":"Katz","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"ref_19","first-page":"638","article-title":"Review of IgG4-related disease","volume":"42","year":"2019","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"iii123","DOI":"10.1093\/rheumatology\/kez667","article-title":"IgG4-related disease: A clinical perspective","volume":"59","author":"Maritati","year":"2020","journal-title":"Rheumatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.36290\/vnl.2022.070","article-title":"IgG4-related disease. Clinical manifestation differential diagnosis and recent International Diagnostic Criteria for IgG4-related disease","volume":"68","author":"Adam","year":"2022","journal-title":"Vnitr. Lek."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s10067-023-06501-2","article-title":"Tear levels of IL-7, IL-1\u03b1, and IL-1\u03b2 may differentiate between IgG4-related disease and Sj\u00f6gren\u2019s syndrome","volume":"42","author":"Lima","year":"2023","journal-title":"Clin. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1440-1827.2008.02257.x","article-title":"Ocular adnexal IgG4-related disease has uniform clinicopathology","volume":"58","author":"Sato","year":"2008","journal-title":"Pathol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00417-013-2548-4","article-title":"Location and frequency of lesions in patients with IgG4-related ophthalmic diseases","volume":"252","author":"Sogabe","year":"2014","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"568","DOI":"10.3341\/kjo.2022.0076","article-title":"Immunoglobulin G4-related Ophthalmic Disease of the Caruncle: A Case Report","volume":"36","author":"Lee","year":"2022","journal-title":"Korean J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.18240\/ijo.2020.08.08","article-title":"CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: Multi-institutional case series","volume":"13","author":"Yoo","year":"2020","journal-title":"Int. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13075-022-02757-2","article-title":"Pathological count of IgG4-positive plasmacytes suggests extraophthalmic involvement and relapse in patients with IgG4-related ophthalmic disease: A retrospective study","volume":"24","author":"Yuan","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Choi, S.J., Ahn, S.M., Oh, J.S., Hong, S., Lee, C.K., Yoo, B., and Kim, Y.G. (2023). Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0282852"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1007\/s00535-014-0945-z","article-title":"Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis","volume":"49","author":"Kamisawa","year":"2014","journal-title":"J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1001\/archophthalmol.2010.45","article-title":"Ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder","volume":"128","author":"Kubota","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/joim.12942","article-title":"Clinical outcomes and predictive relapse factors of IgG4-related disease following treatment: A long-term cohort study","volume":"286","author":"Peng","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13075-021-02489-9","article-title":"Clinical features and relapse risks of IgG4-related ophthalmic disease: A single-center experience in China","volume":"23","author":"Zhao","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00296-017-3730-5","article-title":"Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): A series from a tertiary care teaching hospital in South India","volume":"38","author":"Gupta","year":"2018","journal-title":"Rheumatol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e000295","DOI":"10.1136\/bmjophth-2019-000295","article-title":"The natural course of IgG4-related ophthalmic disease after debulking surgery: A single-centre retrospective study","volume":"4","author":"Ominato","year":"2019","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1136\/annrheumdis-2014-206605","article-title":"Rituximab for IgG4-related disease: A prospective, open-label trial","volume":"74","author":"Carruthers","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ebbo, M., Grados, A., Samson, M., Groh, M., Loundou, A., Rigolet, A., Terrier, B., Guillaud, C., Carra-Dalliere, C., and Renou, F. (2017). Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183844"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/MD.0b013e3182431ef6","article-title":"Rituximab for the treatment of IgG4-related disease: Lessons from 10 consecutive patients","volume":"91","author":"Khosroshahi","year":"2012","journal-title":"Medicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejim.2019.12.029","article-title":"Long-term efficacy of maintenance therapy with Rituximab for IgG4-related disease","volume":"74","author":"Campochiaro","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_39","first-page":"275","article-title":"The treatment outcomes in IgG4-related disease","volume":"76","author":"Karim","year":"2018","journal-title":"Neth. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/annrheumdis-2016-210012","article-title":"Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase","volume":"76","author":"Manukyan","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0002-9394(02)01392-2","article-title":"Hydroxychloroquine and chloroquine retinopathy: Screening for drug toxicity","volume":"133","author":"Browning","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gan, L., Luo, X., Fei, Y., Peng, L., Zhou, J., Li, J., Lu, H., Liu, Z., Zhang, P., and Liu, X. (2021). Long-Term Outcomes of IgG4-Related Ophthalmic Disease in a Chinese IgG4-Related Disease Cohort. Front. Med., 8.","DOI":"10.3389\/fmed.2021.784520"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/13\/3780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:06:37Z","timestamp":1760108797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/13\/3780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,27]]},"references-count":42,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["jcm13133780"],"URL":"https:\/\/doi.org\/10.3390\/jcm13133780","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,27]]}}}