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James T Rosenbaum, Amanda Wong, David J Wilson, Megan Troxell, Donald Houghton, Hans E Grossniklaus, Dongseok Choi, Stephen R Planck, Orbital Inflammatory Disease Consortium; Prevalence and Histological Correlations in Patients with IgG4-Related Orbital Disease (ROD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):4602.
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The detection of IgG4+ cells in lacrimal or orbital biopsies has been associated with a distinct syndrome designated IgG4-ROD. Nevertheless, controversy surrounds the prevalence and histological implication of IgG4 staining.
116 biopsies of either anterior orbit or lacrimal gland from 106 subjects were collected from 9 centers representing the US, Canada, Australia, and Saudi Arabia. Two ophthalmic pathologists scored the tissue for inflammation and fibrosis, while two other pathologists graded IgG4 and total IgG staining by immunohistology.
Based on a low stringency threshold of ≥10 cells per high power field, IgG4+ staining was not found in normal tissue (n=22) or the anterior orbit from patients with thyroid ophthalmopathy (n=27). By this criterion, IgG4 staining was detected in 17 of biopsies (36%) from 47 patients with nonspecific orbital inflammation (NSOI), 5 of 6 with granulomatosis associated with polyangiitis (GPA) (83%), and 5 of 11 with sarcoidosis (45%). However, if a diagnosis of IgG4-ROD also required a ratio of IgG4 to IgG of ≥ 0.4, only 4% of NSOI, 67% of GPA, and none of the tissues from patients with sarcoidosis was positive. Likewise, a higher stringency threshold of >30 cells per high power field, which is proposed by some authors, would markedly reduce the number of cases considered positive. The presence of IgG4+ cells correlated with inflammation and fibrosis in the lacrimal gland but not in the orbit of patients with NSOI. No tissues showed obliterative phlebitis or storiform fibrosis. Analysis of immunosuppression prior to biopsy did not suggest a uniquely aggressive clinical course for patients with IgG4 staining.
The prevalence of IgG4 staining varied considerably among patients with NSOI, GPA, or sarcoid involving the orbit or lacrimal gland depending on the disease and histological criteria used to identify IgG4-ROD. Although IgG4 staining reportedly identifies a unique orbital disease, IgG4 staining was often found in patients with GPA and sometimes in patients with sarcoid. Even at IgG4+ cell counts lower than some authors consider positive for IgG4-ROD, IgG4 staining is correlated with fibrosis in lacrimal tissue.
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