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Rituximab for relapsing IgG4-related ophthalmic disease resistant to corticosteroids: Literature review and a case report

Articles in Press

Document Type : Case Report

Authors

1 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Neurology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD) is a newly recognized term for patients with IgG4-related disease (IgG4-RD) with ocular adnexal involvement. It primarily affects the orbit, lacrimal glands, extraocular muscles, and other periocular structures, leading to orbital masses, proptosis, and potential vision impairment. This study aims to present a case of bilateral IgG4-ROD to highlight its diagnostic approaches and therapeutic options.
Case Report: We report a case of 34-year-old woman presenting with bilateral proptosis. Imaging revealed involvement of lacrimal glands as well as a right retrobulbar mass encasing ocular muscles. Despite having a normal serum IgG4 level (28 mg/dl), the diagnosis of IgG4-ROD was made based on presence of ophthalmic tissue mass and IgG4-positive plasma cells in histopathology (> 40%). Recurrence of periorbital symptoms occurred five months after initial remission while being on glucocorticoids (GCs) and azathioprine (AZA).
Conclusion: Symptoms improved after being switched to rituximab (RTX), and the patient remained symptom-free during a one-year follow-up. IgG4-ROD can manifest as a pseudotumor with involvement of adjacent tissues and should be considered in approaching ocular lesions. Appropriate workup to detect multi-organ involvement is essential.  Refractory or recurrent IgG4-ROD is not unusual, and therefore maintenance or intensifying treatment can prevent irreversible organ damage. RTX is a promising treatment option for corticosteroid-resistant cases.

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References
  1. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet 2015; 385(9976): 1460-71.
  2. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012; 25(9): 1181-92.
  3. Goto H, Takahira M, Azumi A. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol 2015; 59(1): 1-7.
  4. Phaopraphat K, Ngamjanyaporn P, Narongroeknawin P, Kasitanon N, Katchamart W. Clinical manifestations, clinical course, and outcomes of immunoglobulin G4-related disease. Int J Rheum Dis 2020; 23(11): 1468-73.
  5. Ebbo M, Patient M, Grados A, Groh M, Desblaches J, Hachulla E, et al. Ophthalmic manifestations in IgG4-related disease: Clinical presentation and response to treatment in a French case-series. Medicine (Baltimore) 2017; 96(10): e6205.
  6. Japanese study group of IgG4-related ophthalmic disease. A prevalence study of IgG4-related ophthalmic disease in Japan. Jpn J Ophthalmol 2013; 57(6): 573-9.
  7. Wallace ZS, Deshpande V, Stone JH. Ophthalmic manifestations of IgG4-related disease: single-center experience and literature review. Semin Arthritis Rheum 2014; 43(6): 806-17.
  8. Sogabe Y, Ohshima K, Azumi A, Takahira M, Kase S, Tsuji H, et al. Location and frequency of lesions in patients with IgG4-related ophthalmic diseases. Graefes Arch Clin Exp Ophthalmol 2014; 252(3): 531-8.
  9. Zhao Z, Mou D, Wang Z, Zeng Q, Wang Z, Xue J, et al. Clinical features and relapse risks of IgG4-related ophthalmic disease: a single-center experience in China. Arthritis Res Ther 2021; 23(1): 98.
  10. Gan L, Luo X, Fei Y, Peng L, Zhou J, Li J, et al. Ophthalmic involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 573 patients. BMC Ophthalmol 2021; 21(1): 447.
  11. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol 2015; 67(7): 1688-99.
  12. Orozco-Gálvez O, Fernández-Codina A, Lanzillotta M, Ebbo M, Schleinitz N, Culver EL, et al. Development of an algorithm for IgG4-related disease management. Autoimmun Rev 2023; 22(3): 103273.
  13. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366(6): 539-51.
  14. Wallace ZS, Khosroshahi A, Jakobiec FA, Deshpande V, Hatton MP, Ritter J, et al. IgG4-related systemic disease as a cause of "idiopathic" orbital inflammation, including orbital myositis, and trigeminal nerve involvement. Surv Ophthalmol 2012; 57(1): 26-33.
  15. Cheuk W, Yuen HK, Chan JK. Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol 2007; 31(4): 643-5.
  16. Suzuki D, Shimizu K, Shiratori K. Effect of steroid therapy on the serum igg4 levels and the clinical manifestations of autoimmune pancreatitis. Pancreas 2008; 37(4): 497.
  17. Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis 2015; 74(1): 14-8.
  18. Kwon OC, Park MC, Kim YG. Correlation between serologic parameters and disease activity of IgG4-related disease: Differences between patients with normal and elevated serum IgG4 concentrations. Front Immunol 2022; 13: 1020459.
  19. Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis Rheumatol 2015; 67(9): 2466-75.
  20. Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. Apmis 2018; 126(6): 459-76.
  21. Gan L, Luo X, Fei Y, Peng L, Zhou J, Li J, et al. Long-Term Outcomes of IgG4-Related Ophthalmic Disease in a Chinese IgG4-Related Disease Cohort. Front Med (Lausanne) 2021; 8: 784520.
  22. Detiger SE, Karim AF, Verdijk RM, van Hagen PM, van Laar JAM, Paridaens D. The treatment outcomes in IgG4-related orbital disease: a systematic review of the literature. Acta Ophthalmol 2019; 97(5): 451-9.
  23. Wu A, Andrew NH, McNab AA, Selva D. IgG4-Related Ophthalmic Disease: Pooling of Published Cases and Literature Review. Curr Allergy Asthma Rep 2015; 15(6): 27.
  24. Baptista B, Casian A, Gunawardena H, D'Cruz D, Rice CM. Neurological Manifestations of IgG4-Related Disease. Curr Treat Options Neurol 2017; 19(4): 14.
  25. Liu C, Zhang P, Zhang W. Immunological mechanism of IgG4-related disease. J Transl Autoimmun 2020; 3: 100047.
  26. Lin W, Jin L, Chen H, Wu Q, Fei Y, Zheng W, et al. B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren's syndrome: the similarities and differences. Arthritis Res Ther 2014; 16(3): R118.
  27. Khosroshahi A, Bloch DB, Deshpande V, Stone JH. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum 2010; 62(6): 1755-62.
  28. Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis 2015; 74(6): 1171-7.
  29. Omar D, Chen Y, Cong Y, Dong L. Glucocorticoids and steroid sparing medications monotherapies or in combination for IgG4-RD: a systematic review and network meta-analysis. Rheumatology (Oxford) 2020; 59(4): 718-26.
Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 28 May 2026
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