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Peripheral ulcerative keratitis may be associated with a variety of autoimmune diseases. In some diseases, corneal involvement occurs after the systemic disease has been present for many years, whereas in others, it may be the first manifestation. Regardless of the time of presentation, the development of corneal ulceration in the setting of systemic autoimmune disease may represent progression of a potentially life threatening disease. The relatively rare incidence of these diseases has limited publications over the past year to a few case series that have further characterized the natural history of the diseases associated with peripheral ulcerative keratitis. Current laboratory research has been directed at describing the antigenic targets within the cornea of the abnormal immune response in these patients and also the mechanism of keratolysis that results in ulceration.