Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition that has been recognized relatively recently. It can affect various organs throughout the body, leading to swelling, inflammation, and scar tissue formation. This article will focus specifically on how IgG4-RD impacts the eyes and surrounding structures, known as IgG4-related ophthalmic disease (IgG4-ROD).
Overview of IgG4-Related Disease
IgG4-RD is characterized by inflammation, often accompanied by fibrosis, or scarring. It is an immune-mediated condition involving an abnormally regulated immune system. While it can affect almost any organ, commonly involved areas include the pancreas, kidneys, salivary glands, and orbital structures.
The disease often presents as mass-like lesions that can mimic tumors, making accurate diagnosis challenging. Although elevated serum IgG4 levels are frequently observed in patients, this alone is not sufficient for a definitive diagnosis.
How IgG4-RD Affects the Eyes and Its Symptoms
IgG4-RD can significantly affect the eyes and surrounding tissues, known as IgG4-related ophthalmic disease (IgG4-ROD). The lacrimal glands, responsible for tear production, are the most frequently involved ocular structure, with approximately 62-69% of patients experiencing involvement. This often leads to painless swelling of the upper eyelid, which may be unilateral or bilateral.
The disease can also affect orbital tissues, which are the soft tissues behind the eyeball, as well as the extraocular muscles that control eye movement. Inflammation and fibrosis in these areas can cause proptosis, or bulging of the eyes, and can restrict eye movements, potentially leading to double vision (diplopia). Other symptoms may include pain or discomfort, numbness in nerves, such as the infraorbital or supraorbital nerves, and in some cases, vision loss if the optic nerve is compressed.
Less common ocular manifestations include conjunctivitis, scleritis (inflammation of the white outer layer of the eyeball), and uveitis (inflammation of the middle layer of the eye). Involvement of the nasolacrimal duct system can result in excessive tearing (epiphora). The chronic inflammation and subsequent scarring from IgG4-ROD can lead to significant functional impairment and, if left untreated, irreversible tissue damage.
Diagnosing IgG4-RD in the Eye
The diagnostic process for IgG4-ROD involves a combination of clinical evaluation, imaging studies, and laboratory tests, with a tissue biopsy often being necessary for a definitive diagnosis. Clinical examination may reveal characteristic swelling or masses in the affected ocular structures.
Imaging studies, such as computed tomography (CT) scans or magnetic resonance imaging (MRI) of the orbits, are used to visualize the extent of inflammation and identify affected tissues. These scans can show enlargement of the lacrimal glands, extraocular muscles, or nerves. Enlargement of the infraorbital nerve, where its diameter is greater than that of the optic nerve in the coronal plane, is considered a suspicious sign.
Blood tests may reveal elevated serum levels of IgG4. However, elevated IgG4 levels are not specific to IgG4-RD and can be seen in other conditions, and some patients with confirmed IgG4-RD may have normal serum IgG4 levels. Therefore, a definitive diagnosis typically relies on a biopsy of the affected tissue, which shows characteristic histopathological features, including a dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and sometimes obliterative phlebitis. For diagnosis, the ratio of IgG4-positive cells to IgG-positive cells should be 40% or above, or there should be more than 50 IgG4-positive cells per high-power field.
Treatment Approaches
Treatment for IgG4-ROD aims to reduce inflammation, prevent further tissue damage, and manage symptoms. Systemic corticosteroids, such as prednisone, are typically the first-line treatment due to their effectiveness in reducing inflammation. Nearly all patients respond to glucocorticoids, and this dramatic response has even been suggested as a diagnostic criterion.
Despite the initial positive response, a high rate of relapse is common during steroid tapering or after cessation, with approximately 40-68% of patients experiencing recurrence. For patients who are intolerant to corticosteroids, have steroid-resistant disease, or experience frequent relapses, second-line or steroid-sparing agents are considered. Rituximab, a monoclonal antibody that targets CD20-positive B cells, has shown promise as an effective treatment, leading to swift clinical and radiological improvement and prolonged remission.
Surgical interventions may be considered in specific circumstances, such as for debulking large masses that cause compression or for managing complications. However, medical therapy remains the mainstay of treatment. Long-term management and monitoring are important due to the relapsing-remitting nature of the disease and the potential for involvement of other organs.