Anatomic distribution of IgG4-related disease in chronic orbital inflammatory lesions

Abstract

Purpose : IgG4-related disease is a newly-recognized systemic auto-inflammatory condition characterized by tumefactive lesions, storiform fibrosis, lymphoplasmacytic infiltrates enriched with IgG4+ plasma cells, and elevated serum IgG4 levels. It can involve virtually every organ but has a particular affinity for the orbits. Currently, the epidemiology of this disease remains poorly described. Thus, in this study, we report the prevalence and anatomic distribution of IgG4-related disease in 50 chronic orbital inflammatory lesions biopsied between 2011 and 2016 in a large academic center.

Methods : Biopsies of orbital structures with chronic inflammatory lesions without lymphoproliferative diseases or infectious microorganisms from 2011 to 2016 were retrospectively included in the study. Immunohistochemistry was performed with antibodies against IgG and IgG4. Those with mean IgG4+/IgG+ plasma cell ratios >30% were classified as IgG4-related disease. Histopathologic analysis and serum IgG4 levels, when available, were also documented.

Results : The study included 55 patients: 22 male (40%) and 33 female (60%); 23 Caucasians, 3 African-Americans, 7 Hispanics, 10 Asians, and 11 of other ethnicities. The mean age was 57±19 years. The specimens included 29 lacrimal sac (53%), 6 lacrimal gland (11%), 19 orbital masses (35%), and 1 eyelid skin lesion. Five biopsies — 2 orbital masses, 1 lacrimal sac, and 2 lacrimal glands — had mean IgG4+/IgG+ plasma cell ratios >30%, and 4 had mean IgG4+/IgG+ plasma cell ratios >60%. The 5 patients (3 males and 2 females) had a mean age of 65.6±13 years, and included 2 Caucasians, 1 Hispanic, 1 Asian, and 1 of other ethnicity. Three of the 5 patients had IgG4 serum levels available: 2 had elevated serum IgG4 and 1 was normal. All 3 patients responded to steroid therapy. Of note, 2 other orbital mass biopsies showed IgG4/IgG plasma cell ratios of around 20% and were later diagnosed as IgG4-related disease and granulomatosis with polyangiitis.

Conclusions : IgG4-related disease accounted for a minority of chronic inflammatory orbital lesions biopsied in this study, generally affecting older patients, and presenting as an orbital mass or with lacrimal sac or lacrimal gland involvement. IgG4+/IgG+ plasma cell ratios may not be >30% in all cases of IgG4-related disease and can be elevated in other inflammatory diseases; thus, histopathological correlation is critical for accurate diagnosis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.