Periocular Manifestations and Management of Immunoglobulin G4-Related Disease

Abstract

Immunoglobulin G4-related disease (IgG4-RD) comprises a spectrum of inflammatory conditions characterized by lymphoplasmacytic infiltration by IgG4+ plasma cells, resultant tumefactive lesions at various locations in the body, storiform fibrosis, and elevated serum IgG4 levels. IgG4-related ophthalmic disease (IgG4-ROD) can occur in isolation or in conjunction with systemic findings. The most common manifestations of IgG4-ROD are dacryoadenitis and eyelid edema, though patients may also have trigeminal nerve enlargement, extraocular muscle involvement, and other orbital soft tissue lesions and inflammation. Workup is multifactorial and should include full body imaging, serum IgG4 levels, and biopsy, which must include staining for IgG4+ plasma cells and may show hallmark storiform fibrosis and/or obliterative phlebitis. IgG4-ROD can be misdiagnosed due to potential clinical, radiographic, and histopathologic overlap with other orbital inflammatory conditions; however, the presence of infraorbital or supraorbital nerve enlargement on imaging, as well as biopsy with strong levels of IgG4 histochemical staining, can be helpful in distinguishing IgG4-ROD from other orbital inflammatory pathology. Steroids are typically first-line treatment, although given high rates of recurrence, patients may require concurrent or subsequent treatment with steroid-sparing agents, most commonly rituximab.

Keywords: IgG4; dacryoadenitis; immunoglobulin G4-related ophthalmic disease; immunoglobulin-related disease; infraorbital nerve; obliterative phlebitis; orbit; orbital inflammatory syndrome; rituximab; storiform fibrosis.