Peripheral Ulcerative Keratitis Associated with Autoimmune Diseases

*Marta Świerczyńska, Agnieszka Tronina and Ewa Mrukwa-Kominek*

### **Abstract**

Peripheral ulcerative keratitis (PUK) is a destructive inflammatory disease of the juxtalimbal cornea associated with crescent-shaped corneal stromal thinning, epithelial defect, and inflammatory corneal infiltrate. Inflammation of other adjacent tissues, particularly the sclera, is seen quite frequently. Predilection of the peripheral cornea for PUK is explained by its anatomical and physiological characteristics. Both cell-mediated and humoral immunity, in conjunction with the corneal tissue-destroying action of metalloproteinases (MMPs), are implicated in the pathogenesis of PUK. Nearly half of all cases of noninfectious PUK are associated with connective tissue diseases (rheumatoid arthritis (RA) is the most frequent underlying disease) and vasculitis (mostly granulomatous with polyangiitis (GPA)). It is important to determine the etiology and exclude conditions that could mimic PUK e.g., marginal keratitis or Terrien's marginal degeneration (TMD). Therapy should comprise the attenuation of ophthalmic inflammation, but the underlying disease should be treated as a priority. For autoimmune diseases, it is crucial to work closely with internist/rheumatologist to determine an effective immunomodulatory therapeutic approach. PUK is also known to be a potentially devastating and vision-threatening condition that may lead to corneal melting and perforation, requiring surgical intervention. This chapter provides a comprehensive update of current knowledge and therapeutic methods.

**Keywords:** peripheral ulcerative keratitis, PUK, autoimmune disease, collagen disease, vasculitis, rheumatoid arthritis, granulomatosis with polyangiitis, immunomodulatory therapy

### **1. Introduction**

Peripheral ulcerative keratitis (PUK) is a destructive inflammatory disease, defined as a clinical triad of a rapidly progressive, crescent-shaped area of peripheral corneal thinning, an epithelial defect, and an inflammatory corneal infiltrate. The inflammation often extends to adjacent tissues: conjunctiva, iris, episclera, and sclera [1]. Over time, progressive ulceration can lead to corneal perforation, which in the case of underlying autoimmune etiology has serious ocular morbidity [2]. Although the pathogenesis of

PUK is still not fully understood, it is assumed that peculiar anatomical and physiological features of the peripheral cornea, environmental factors, and cell-mediated and auto-antibody-mediated responses are involved [1, 3–6]. The postulated mechanisms causing PUK are autoimmune reactions to the corneal antigens, circulating immune complex depositions as well as hypersensitivity reaction to exogenous antigens [3].

PUK, after anterior uveitis, is the second most common ocular complication of autoimmune diseases [7]. However, its incidence varies by only 0.2–3 people per million annually [8, 9]. The prevalence is assumed to be higher in the female gender [9], although some studies indicate equal incidence in both sexes [10]. PUK may be caused by a variety of pathological processes, including both ocular and systemic infectious and noninfectious conditions. It is reported that approximately 50% of PUK cases are associated with collagen diseases and various types of vasculitis [11]. PUK can appear at any stage of an already diagnosed underlying systemic disorder and might suggest its exacerbation; however, it may also be the first symptom of a systemic condition. PUK-associated ocular complications and systemic morbidity and mortality can be decreased with timely diagnosis and prompt treatment [4–6].
