eMedicine Specialties > Ophthalmology > Cornea

Peripheral Ulcerative Keratitis

Author: Ellen N Yu, MD, Consulting Staff, Department of Ophthalmology, St Luke's Medical Center, Quezon City, Philippines
Coauthor(s): C Stephen Foster, MD, FACS, FACR, FAAO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution
Contributor Information and Disclosures

Updated: Dec 8, 2008

Introduction

Background

Peripheral corneal ulceration is a potentially devastating disorder consisting of a crescent-shaped destructive inflammation at the margin of corneal stroma that is associated with an epithelial defect, presence of stromal inflammatory cells, and progressive stromal degradation and thinning. Commonly referred to as peripheral ulcerative keratitis (PUK), it can quickly produce progressive necrosis of the corneal stroma, leading to perforation and blindness.¹

See related CME at Cornea and External Disease.

Pathophysiology

The peripheral cornea has distinct morphologic and immunologic characteristics that predispose it to inflammatory reactions. Unlike the avascular central cornea, the peripheral cornea is closer to limbal conjunctiva and derives part of its nutrient supply from the limbal capillary arcade, a source of immunocompetent cells, for example, macrophages, Langerhans cells, lymphocytes, and plasma cells.^2,3 Any inflammatory stimulus in the peripheral cornea that is caused by invasion of microbial organisms (bacteria, virus, fungi, and parasites), immune complex deposition (in systemic immune diseases), trauma, malignancy, or dermatologic conditions may produce local and systemic immune responses, resulting in neutrophil recruitment and complement activation (both classic and alternative pathways) in both tissue and vessels.²

Activated complement components can increase vascular permeability and further generate chemotactic factors for neutrophils (eg, C3a, C5a). Neutrophils, in turn, infiltrate the peripheral cornea and release proteolytic and collagenolytic enzymes, reactive oxygen metabolites, and proinflammatory substances (eg, platelet-activating factor, leukotrienes, prostaglandins), causing dissolution and degradation of the corneal stroma.^4,5 In addition, the inflamed limbal conjunctiva itself is capable of producing collagenase, which contributes to stromal degradation.⁶

Systemic diseases that may cause immune complex deposition at the peripheral cornea and PUK include such collagen vascular diseases as rheumatoid arthritis (RA), Wegener granulomatosis (WG), polyarteritis nodosa (PAN), relapsing polychondritis (RP), and systemic lupus erythematosus (SLE). Infectious conditions, whether systemic (eg, hepatitis, syphilis) or local (eg, herpes simplex keratitis, fungal keratitis), and noninfectious local disorders (eg, Mooren ulcer, marginal keratitis) also may cause PUK.

In summary, the major pathophysiologic mechanism of PUK is a result of degradation and tissue necrosis of corneal stroma produced by degradative enzymes, which are released primarily by neutrophils attracted into the area by diverse stimuli.

Frequency

United States

PUK is uncommon. RA has been reported as the most common collagen vascular disorder that causes PUK, accounting for 34% of noninfectious PUK.^6,7,8 PUK may be the initial manifestation of WG and PAN. PUK is rare in patients with RP; only 2 of 112 patients with RP were reported to develop PUK in a clinical review study.⁹ PUK has also been reported to be associated with SLE, although this is uncommon.^3,10 Mooren ulcer is a rare local autoimmune disease associated with PUK, with only 287 cases reported in the world literature, although some of these cases may have been the presenting manifestation of an occult systemic disease rather than true Mooren ulcer.¹¹

Mortality/Morbidity

PUK produces great morbidity from the pain and resultant visual disability. It can be a harbinger of death if the underlying disease is not diagnosed and successfully treated.

Race

No good data are available on racial predilection for PUK.

Sex

Since PUK is more common in people with collagen vascular disorders (especially RA), it is more common in females than in males. However, PUK caused by Mooren ulcer is more common in males than in females.^11,12

Age

Age varies and is dependent on the associated systemic or local disorder.

Clinical

History

PUK is frequently a manifestation of an occult systemic disease. Thus, a thorough systemic history is very important and should include chief complaint, characteristics of present illness, past medical history, family history, and a meticulous review of systems.⁴

• Ocular symptoms vary, but nonspecific foreign body sensation with or without eye pain, tearing, photophobia, and reduced visual acuity are the most common symptoms for patients with PUK.
• Loss of vision can occur quickly when PUK progresses.
• PUK associated with RA, WG, PAN, and RP is often linked with scleritis, and eye pain may be pronounced in these individuals.⁴ PUK in patients with Mooren ulcer may also produce pain, although there is no scleral involvement.
• Past medical history and review of systems helps to determine the possible underlying systemic diseases. RA, SLE, PAN, WG, or RP may present with the following symptoms, which should be emphasized in the review of systems¹² :
  • General - Constitutional symptoms, such as chills, fever, poor appetite, recent weight loss, and fatigue
  • Skin - Rashes, nodules, vesicles, ulcer, nail changes, and periungual infarcts
  • Respiratory - Coughing, wheezing, pneumonia, and shortness of breath
  • Cardiac - Chest pain or discomfort and dyspnea
  • Gastrointestinal - Abdominal pain, nausea, vomiting, difficulty swallowing, and diarrhea
  • Musculoskeletal - Muscle or joint pain, arthritis, back pain, and limitation of motion
  • Neurologic - Headaches, seizures, psychiatric, paralysis, and numbness/tingling
  • Other systemic symptoms - Deafness, swollen ear lobes, ear infections, vertigo, and noises in ears (suggestive of RP)

Physical

• Examination should be complete and include an overview of the head (including the nose, mouth, and external ear), trunk, joints, and extremities.⁴ Skin lesions should also be noted.
• A complete ophthalmic examination should be performed with special emphasis on the conjunctiva, sclera, and cornea. Anterior chamber, vitreous, and fundus examinations are also important.
• Patients with PUK typically present with decreased visual acuity (secondary to induced irregular astigmatism), tearing, and eye irritation with or without pain of variable duration.⁵
• Slit lamp examination reveals a crescent-shaped destructive lesion of the juxtalimbal corneal stroma associated with an epithelial defect, stromal yellow-white infiltrates composed of inflammatory cells, and varying degrees of corneal stromal thinning (minimal to full thickness) adjacent to the limbus.⁶
• In severe cases, the peripheral cornea is progressively destroyed circumferentially and centrally.
• PUK accompanied by necrotizing scleritis almost always indicates the presence of a potentially lethal systemic disease.⁴
• The anterior chamber should be evaluated for depth and inflammation.
• A posterior segment examination is typically indicated to help determine the underlying etiology.

Causes

The etiologies for developing PUK are multiple and extensive. Connective tissue and vasculitic diseases are the major risk factors. Other disorders that can cause PUK include systemic and local infectious conditions, as well as local degenerative disorders.

The differential diagnosis of PUK is outlined below (Feldman, 2000).⁴

• Noninfectious conditions
  • Systemic - RA, SLE, RP, sarcoidosis, progressive systemic sclerosis, rosacea, WG, PAN, giant cell arteritis, inflammatory bowel disease, metabolic conditions, and nutritional deficiencies
  • Local - Mooren ulcer, marginal keratitis, blepharitis (eg, staphylococcal infection, rosacea), contact lens use, chemical injury to the eyes, trauma, surgery, neurotrophic and neuroparalytic causes,  keratoconjunctivitis sicca, Terrien marginal degeneration, pellucid marginal degeneration, and furrow degeneration⁵
• Infectious conditions
  • Systemic -Shigella species, tuberculosis, syphilis, hepatitis, HIV, gonococcus, Salmonella species, and bacillary dysentery
  • Local - Herpes simplex keratitis, varicella-zoster keratitis, bacterial keratitis, fungal keratitis, and Acanthamoeba species
• Masquerade - Malignancy - Leukemia¹³

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