Peripheral Ulcerative Keratitis

Peripheral ulcerative keratitis (PUK) is a crescent-shaped, progressive thinning and ulceration of the peripheral cornea.

It is one of the ophthalmic findings that most reliably signals serious, sometimes life-threatening, systemic autoimmune disease.

Roughly half of cases are associated with an underlying systemic connective tissue or vasculitic disorder, which is why PUK deserves a fundamentally different level of urgency and workup than an ordinary peripheral corneal thinning process.

Pathogenesis

The peripheral cornea sits adjacent to the limbal vasculature and is uniquely exposed to circulating immune complexes and inflammatory mediators in a way the avascular central cornea is not, which is part of why autoimmune and vasculitic disease so often manifests here first.

Immune complex deposition activates complement and recruits inflammatory cells that release collagenases and other proteolytic enzymes, progressively destroying the peripheral corneal stroma and producing the characteristic crescentic ulceration with an overhanging, undermined leading edge.

This same mechanism explains why PUK so often coexists with scleritis, since the adjacent sclera shares the same limbal vascular supply and is exposed to the same circulating immune complexes driving the corneal process.

Systemic Associations

Rheumatoid arthritis — the most common systemic association overall, particularly in longstanding, seropositive, erosive disease
Granulomatosis with polyangiitis (formerly Wegener’s) — PUK can be a presenting feature, and its appearance should prompt urgent ANCA testing and systemic workup
Relapsing polychondritis — cartilage inflammation elsewhere (ears, nose, airway) alongside the ocular finding
Systemic lupus erythematosus
Polyarteritis nodosa and other systemic vasculitides
Mooren’s ulcer — an idiopathic form without systemic disease, a diagnosis of exclusion once the above have been ruled out

PUK associated with active systemic vasculitis carries a serious prognosis if untreated, with reported mortality driven by the underlying systemic disease (cardiac and renal involvement) rather than the eye finding itself, which is the central reason PUK triggers an urgent, thorough systemic workup rather than purely local ocular treatment.

Clinical Presentation

Patients present with pain, redness, photophobia, and tearing localized to the peripheral cornea, sometimes with visible thinning or a grayish infiltrate visible even without magnification in advanced cases.

Progression can be rapid: untreated PUK can lead to corneal perforation within days to weeks, when driven by an active systemic vasculitic process rather than the more indolent course sometimes seen in idiopathic Mooren’s ulcer.

Pain that seems disproportionate to the visible degree of corneal involvement, or that fails to improve with treatments aimed at more common causes of peripheral corneal irritation, should prompt reconsideration of the diagnosis and a more urgent, systemic-focused evaluation.

Exam Findings

Crescent-shaped peripheral corneal ulceration with stromal thinning
An undermined, overhanging central edge to the ulcer, a characteristic feature
Adjacent limbal and conjunctival injection
Absence of a clear infectious epithelial defect pattern (helping distinguish it from infectious keratitis)
Associated scleritis in a meaningful proportion of cases, particularly when systemic vasculitis is the driver

Differential Diagnosis

Terrien’s marginal degeneration — peripheral thinning but non-inflammatory, painless, slowly progressive, with an intact epithelium
Infectious peripheral keratitis — positive culture, typically a clearer infectious trigger (contact lens wear, trauma)
Marginal (staphylococcal hypersensitivity) keratitis — separated from the limbus by a clear zone, less destructive
Pellucid marginal degeneration — inferior thinning with characteristic topography, non-inflammatory
Neurotrophic keratopathy — reduced corneal sensation, different ulcer morphology

Diagnostic Evaluation

Any new case of PUK warrants a systemic workup, even in a patient without a known prior diagnosis of autoimmune disease, because PUK can be the presenting feature of a systemic vasculitis.

Complete blood count, inflammatory markers (ESR, CRP), rheumatoid factor, ANCA, antinuclear antibody, complement levels, and renal function testing are typically obtained, with the exact panel tailored to the clinical picture and guided by rheumatology input.

Mooren’s ulcer remains a diagnosis of exclusion, reached only once this systemic workup is negative.

Because a patient can present with PUK as their very first sign of an otherwise undiagnosed systemic vasculitis, urgent rheumatology involvement at the time of diagnosis — rather than after results return — allows the systemic workup and any necessary treatment to proceed in parallel rather than sequentially, which can matter when the underlying disease is progressing quickly.

Management

Systemic immunosuppression — often starting with corticosteroids and escalating to steroid-sparing agents (methotrexate, cyclophosphamide, or biologic agents depending on the underlying disease and severity) — is the cornerstone of treatment when PUK is associated with systemic vasculitis, coordinated closely with rheumatology, because controlling the systemic disease is what ultimately controls the ocular process.

Topical corticosteroids have a more limited and sometimes even counterproductive role, because they can worsen stromal melting in some cases without addressing the underlying immune complex-driven process.

Local measures — lubrication, bandage contact lenses, and tissue adhesive or patch grafting for impending or actual perforation — protect the ocular surface while systemic treatment takes effect.

Urgent surgical intervention (conjunctival resection, tectonic grafting) is reserved for eyes with perforation or severe, progressive thinning threatening globe integrity.

Because untreated systemic disease can also affect the fellow eye or recur even after an initial episode appears controlled, long-term rheumatologic follow-up continues well beyond resolution of the acute corneal findings, with any recurrence of ocular symptoms treated as a potential signal of renewed systemic disease activity.

References

Foster CS, Sainz de la Maza M. Peripheral ulcerative keratitis. In: The Sclera.
Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheumatic Disease Clinics of North America.
Tauber J, Sainz de la Maza M, Hoang-Xuan T, Foster CS. An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis. Cornea.
American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea.

Peripheral Ulcerative Keratitis: A Corneal Sign of Systemic Vasculitis