Orbital IgG4-Related Disease: Clinical Features and Diagnosis

Orbital IgG4-related disease, which can occur in adults of any age, is characterized by IgG4-positive lymphoplasmacytic infiltrations in ocular adnexal tissues. The signs and symptoms include chronic noninflammatory lid swelling and proptosis. Patients often have a history of allergic disease and elevated serum levels of IgG4 and IgE as well as hypergammaglobulinemia. Orbital IgG4-related disease must be differentiated from idiopathic orbital inflammation and ocular adnexal marginal zone B-cell lymphoma to ensure appropriate and effective treatment. Systemic steroid therapy decreases the size of the lesions, but relapse often occurs when systemic steroid therapy is discontinued. 1. Introduction IgG4-related diseases are systemic syndromes characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in the body. Orbital tissues are affected by IgG4-related conditions. It was first observed that Mikulicz’s disease correlated with IgG4-related disease [1] and later determined that IgG4-related disease can occur in any ocular adnexal tissues [2–5]. Here, we review the clinicopathological features, differential diagnosis, and treatments of orbital IgG4-related disease on the basis of a meta-analysis of 42 patients including 3 case series studies. 2. Clinical Presentation The median age of patients with orbital IgG4-related disease is 59 years (range: 30 to 86 years) with a 1？:？1 male-to-female ratio [3–5]. Notably, there is a 1？:？3 for bilateral lacrimal lesions similar to finding in Mikulicz’s disease [1]. Although orbital IgG4-related disease can occur in men and women of any age, many patients have a history of allergic diseases such as asthma and allergic rhinitis. The signs and symptoms of orbital IgG4-related disease are chronic lid swelling (Figure 1) and proptosis (Figure 2), but otherwise there are only mild signs, or no signs of inflammation or periocular pain. Ocular motility is restricted mildly if at all, despite the presence of one or more enlargements of the large extraocular muscles (Figure 1). There are generally no visual disturbances, although they may occur due to apical orbital lesions (Figure 2). Imaging studies show infiltrative lesions in ocular adnexal tissues such as the lacrimal glands (Figure 1) [2–5], extraocular muscles (Figure 1) [3, 4], infraorbital nerves (Figure 2) [4], optic nerve sheath [4], lacrimal sac [6], and even cavernous sinus (Figure 2) or the intracranial extension [4]. In cases of orbital IgG4-related disease, 62% have bilateral lesions, 69% have lacrimal gland