Ulcerative keratitis is frequently associated with collagen vascular diseases and presents a predilection for peripheral corneal localization, due to the distinct morphologic and immunologic features of the limbal conjunctiva, which provides access for the circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates an immune-mediated vasculitis process, with inflammatory cells and mediators involvement by alteration of the vascular permeability. Peripheral ulcerative keratitis generally correlates with exacerbations of the background autoimmune systemic disease. Associated sceritis, specially the necrotizing form, is usually observed in severe cases, which may evolve in corneal perforation and loss of vision. Although the first-line of treatment in acute phases is represented by systemic administration of corticosteroids, immunosuppressive and cytotoxic agents are necessary for the treatment of peripheral ulcerative keratitis associated with systemic diseases.