Thyroid-Associated Ophthalmopathy and Dermopathy

Abstract

Graves' ophthalmopathy [thyroid-associated ophthalmopathy (TAO)] and dermopathy [thyroid-associated dermopathy (TAD)] are extrathyroidal manifestations of Graves' disease, which should be viewed as a multisystem autoimmune disease involving thyrocytes but also orbital and pretibial fibroblasts. Smoking is a risk factor for TAO, and cessation of smoking is useful in the primary, secondary and tertiary prevention of TAO. The immunopathogenesis of TAO and TAD looks very similar. Fibroblasts expressing functional thyroid-stimulating hormone (TSH) receptors have been identified as the target cells of the autoimmune attack. T cells sensitized to thyroid antigens (or TSH receptor stimulating antibodies, TSAb, in later stages) may recognize shared antigens on fibroblasts, inducing release of cytokines. This results in the production of hydrophylic glycosaminoglycans, causing tissue swelling. Recent findings point to the insulin-like growth factor (IGF)-1 receptor on fibroblasts as another likely autoantigen. TAO appears to be primarily a Th1-cell-mediated disease. Intravenous methylprednisolone pulses are now recommended as the treatment of choice in severe active TAO and topical corticosteroids under occlusive dressings for TAD. Rehabilitative surgery for TAO should wait until the disease has become inactive. Promising new but still experimental treatment modalities involve monoclonal antibodies against particular cytokines or T-cell surface molecules.