Immunoglobulin G4–Related Disease
Immunoglobulin G4–related disease (IgG4-RD) is a fibroinflammatory disorder that may affect 1 or more organs (Fig 4-16). Orbital disease may occur alone or with systemic disease, either synchronously or metachronously. Within the orbit, the disease most commonly affects the lacrimal gland, and orbital involvement occurs in common patterns, including the following:
enlargement of the orbital nerves (typically the infraorbital), extraocular muscles, and lacrimal gland, often with sinusitis, peripheral eosinophilia, and systemic involvement
sclerosing dacryoadenitis (unilateral or bilateral)
sclerosing orbital inflammation without dacryoadenitis
Figure 4-16 Immunoglobulin G4–related disease (IgG4-RD) of the lacrimal gland. A, Photograph of a patient with left-sided proptosis. B and C, Axial and coronal CT imaging studies, respectively, show enlargement of the left lacrimal gland region. D, Photograph shows patient improvement after immunosuppressive treatment.
(Courtesy of Julian D. Perry, MD, and Alexander D. Blandford, MD.)
Histologic examination shows lymphoplasmacytic infiltrates with large numbers of immunoglobulin G4 (IgG4)-positive plasma cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration. A consensus statement set the minimum number of IgG4-positive plasma cells for the lacrimal gland at greater than 100 per high-power field; however, many published series report smaller numbers of cells. In most cases, the ratio of IgG4-to-IgG plasma cells is greater than 40%. Given the spectrum of histologic findings, the diagnosis requires integrating clinical, imaging, and histopathologic criteria.
About half of patients with the orbital disease will also have disease in other organs. Rheumatological evaluation often includes examination for salivary gland, lymph node, lung, liver, and retroperitoneal involvement using various imaging studies, including CT, MRI, and CT-PET (positron emission tomography) scanning. Serologic testing may show peripheral eosinophilia and elevated IgG4 levels.
Treatment includes the use of corticosteroids and other immunosuppressants and biologic agents, including rituximab. Another monoclonal antibody that targets CD19 shows promise to treat this condition as well.
Immunoglobulin G4–related disease comprises a significant proportion of what was previously labeled nonspecific orbital inflammation; thus, biopsy of orbital inflammatory lesions should routinely include an examination for features of IgG4-RD. With greater understanding of inflammatory disease, other conditions previously labeled nonspecific orbital inflammation may be elucidated.
McNab AA, McKelvie P. IgG4-related ophthalmic disease. Part I: background and pathology. Ophthalmic Plast Reconstr Surg. 2015;31(2):83–88.
McNab AA, McKelvie P. IgG4-related ophthalmic disease. Part II: clinical aspects. Ophthalmic Plast Reconstr Surg. 2015;31(3):167–178.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.