IgG4-related ophthalmic disease. Part I: background and pathology.

PURPOSE: To review the current state of knowledge of IgG4-related ophthalmic disease (IgG4-ROD). METHODS: A review of the literature and personal experience of the authors. RESULTS: IgG4-related disease is a recently recognized fibroinflammatory disorder that may affect 1 or more organs. It is characterized by lymphoplasmacytic infiltrates with large numbers of IgG4 positive plasma cells, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration as well as peripheral eosinophilia, and in some cases, elevated serum levels of IgG4. These features are not always seen, and the diagnosis should be made by integrating clinical, imaging, and histopathological data, with reference to recently defined diagnostic criteria. IgG4-ROD forms a significant proportion of what has previously been labeled "idiopathic orbital inflammation" or reactive lymphoid hyperplasia. Orbital disease may occur alone, at the same time as disease elsewhere, or metachronously with systemic disease. Although almost any ocular adnexal tissue may be affected, there are several more common recognizable patterns of IgG4-ROD: 1) sclerosing dacryoadenitis; 2) enlargement of orbital nerves (most commonly the infraorbital nerve) associated with orbital myositis and lacrimal gland disease, often in combination with paranasal sinus disease, eosinophilia, and systemic involvement; and 3) sclerosing orbital inflammation. CONCLUSIONS: Patients presenting with orbital inflammatory lesions should have biopsies obtained whenever possible. The examining pathologist should routinely look for features of IgG4-ROD, and if found, the patient should be investigated for other organ involvement. Early treatment may prevent destructive changes in affected tissues.