IgG4‐related disease as an emerging cause of scleritis

Several orbital manifestations of IgG4-related 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 IgG4-RD 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, IgG4-RD 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. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.