Acta Ophthalmologica 2017
Letter to the Editor IgG4-related disease as an emerging cause of scleritis Faiz Karim,1 Joeri de Hoog,2 Dion Paridaens,3 Rob Verdijk,4 Marco Schreurs,5 Aniki Rothova,2 Martin van Hagen1 and Jan van Laar1 1 Department of Internal Medicine, Section Clinical Immunology, Erasmus MC, Rotterdam, The Netherlands 2 Department of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands 3 Department of Orbital Surgery, The Rotterdam Eye Hospital, Rotterdam, The Netherlands 4 Department of Pathology, Section Ophthalmic Pathology, Erasmus MC, Rotterdam, The Netherlands 5 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
doi: 10.1111/aos.13376
Editor,
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everal orbital manifestations of IgG4related disease (IgG4-RD) have been published in different cohort studies (Wallace et al. 2014); however, the relationship between IgG4-RD and scleritis has only been described in some case reports (Paulus et al. 2012; Caso et al. 2014; Heidari et al. 2014; Ohno et al. 2014; Philippakis et al. 2015). Here, we report the results of our study evaluating the occurrence of IgG4RD in a well-defined cohort of idiopathic scleritis patients. Medical records of patients with idiopathic scleritis diagnosed between April 1992 and July 2016 were reviewed for demographic and clinical characteristics. Patients with secondary scleritis due to an associated systemic or infectious disease were excluded. Histologically proven cases were classified as definite IgG4-RD (Deshpande et al. 2012), while idiopathic scleritis with elevated serum IgG4 was classified as probable IgG4-RD (Xu et al. 2016). In 15 cases, out of total 38 cases, sufficient data could be retrieved to adequately study the given classifications showing two definite cases of IgG4-RD and three cases of probable IgG4-RD (Table S1).
IgG4-RD has only recently been recognized as a systemic clinical entity (Karim et al. 2016). Several conditions such as Mikulicz’s disease are now reclassified under the umbrella of IgG4-RD. Since the first report on scleritis due to IgG4-RD in 2012, only sporadic cases have been published (Paulus et al. 2012; Caso et al. 2014; Ohno et al. 2014; Lee et al. 2015; Philippakis et al. 2015; Table S1 provides an overview of previously published reports on scleritis and IgG4-RD). In this study, we emphasize IgG4-RD as a cause of scleritis in a larger cohort. There are some limitations in this study. Primarily the retrospective nature limited the access to potential additional histological or serological data. Additionally, in the past the inability to screen patients systemically with sensitive and novel radiographic studies such as FDG-PET/CT scanning might cause underdiagnoses, as most patients were swiftly treated with immunosuppressive agents masking systemic symptoms of IgG4-RD and thus hamper recognition by FDG-PET/CT scanning. Scleritis is not often histologically evaluated because of potential complications; however, elevated serum IgG4 levels could be supportive and indicative for further additional imaging with, for example, PET-scanning to establish tissue diagnosis. FDG-PET/ CT scan is useful for diagnosis, staging and the degree of organ involvement as well as for monitoring of disease activity (Karim et al. 2016). We recommend additional survey of serum IgG4 in cases of idiopathic scleritis, and when elevated, additional PET imaging should be considered. Possible abnormalities on FDG-PET/CT scan could be potential sources for histological examination. Adequate diagnostics can prevent delay in obtaining the diagnosis and subsequently treatment of the disease and can prevent systemic manifestation of IgG4-RD. To diagnose, IgG4-RD is relevant because potential irreversible organ damage due to fibrosis may occur when not treated appropriately. When indicated, glucocorticoids are mostly the first choice of treatment and may follow by conventional immunosuppressive agents such as methotrexate. Improving evidence for rituximab in the treatment of IgG4-RD is emerging leading to clinical remissions in patients with IgG4-RD with different organ manifestations (Karim et al. 2016). In conclusion, this study and previously published case reports emphasize IgG4-RD as an emerging cause of idiopathic scleritis. In addition to the well-known causes, IgG4RD can be added as a novel cause of scleritis. Improved awareness will lead to more effective and swift diagnosis and
therapy and may prevent irreversible organ damage.
References Caso F, Fiocco U, Costa L, Sfriso P, Punzi L & Doria A (2014): Successful use of rituximab in a young patient with immunoglobulin G4-related disease and refractory scleritis. Joint Bone Spine 81: 190–192. Deshpande V, Zen Y, Chan JK et al. (2012): Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25: 1181–1192. Heidari P, Verdijk RM, Van Den Bosch WA & Paridaens D (2014): Biopsy-proven recurrence of unilateral IgG4-related orbital inflammation after 20 years. Orbit 33: 388–391. KarimF,LoeffenJ,BramerW,WestenbergL,VerdijkR,van Hagen M & van Laar J (2016): IgG4-related disease: a systematic review of this unrecognized disease in pediatrics. Pediatr Rheumatol OnlineJ 14: 18. Lee CS, Harocopos GJ, Kraus CL, Lee AY, Van Stavern GP, Couch SM & Rao PK (2015): IgG4-associated orbital and ocular inflammation. J Ophthalmic Inflamm Infect 5: 15. Ohno K, Sato Y, Ohshima K et al. (2014): IgG4-related disease involving the sclera. Mod Rheumatol 24: 195–198. Paulus YM, Cockerham KP, Cockerham GC & Gratzinger D (2012): IgG4-positive sclerosing orbital inflammation involving the conjunctiva: a case report. Ocul Immunol Inflamm 20: 375–377. Philippakis E, Cassoux N, Charlotte F, LeHoang P, Bodaghi B, Bloch-Queyrat C & Touitou V (2015): IgG4-related disease masquerading as recurrent scleritis and chronic conjunctivitis. Ocul Immunol Inflamm 23: 168–172. Wallace ZS, Deshpande V & Stone JH (2014): Ophthalmic manifestations of IgG4-related disease: singlecenter experience and literature review. Semin Arthritis Rheum 43: 806–817. Xu WL, Ling YC, Wang ZK & Deng F (2016): Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis. Sci Rep 6: 32035.
Correspondence: A. Faiz Karim Department of Internal Medicine Section Clinical Immunology Erasmus MC University Medical Centre Rotterdam ‘s-Gravendijkwal 230 3015 CE Rotterdam The Netherlands Tel: +31628433278 Fax: +31107033146 Email:
[email protected]
Dr Rob Verdijk and Dr Dion Paridaens were supported by grant 3.3.0 from the Combined Ocular Research Rotterdam.
Supporting Information Additional Supporting Information may be found in the online version of this article: Table S1. Characteristics of patients with idiopathic scleritis and (suspected) IgG4RD in our study compared with previously published case reports.
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