Peripheral Ulcerative Keratitis: Definition and Differential Diagnosis
Peripheral ulcerative keratitis (PUK) is a sight-threatening inflammatory condition characterized by progressive peripheral corneal stromal thinning with an overlying epithelial defect, often reflecting underlying systemic autoimmune disease and requiring urgent evaluation to prevent corneal perforation and vision loss 1, 2.
What is Peripheral Ulcerative Keratitis?
PUK represents a destructive inflammatory process affecting the peripheral cornea through both cell-mediated and antibody-mediated immune mechanisms. The pathophysiology involves immune complex deposition in terminal limbal vessels, triggering vasculitis with subsequent release of matrix metalloproteinases that destroy corneal stroma 2, 3. The peripheral cornea's unique anatomy—with its rich vascular supply from the limbal conjunctiva—makes it particularly vulnerable to circulating immune complexes and inflammatory mediators 3.
Clinical presentation typically includes:
- Painful vision loss with photophobia
- Crescent-shaped peripheral corneal ulceration with stromal thinning
- Adjacent inflammation (scleritis, episcleritis, iritis, or conjunctivitis)
- Progressive nature that can lead to perforation if untreated 2
Differential Diagnosis
The differential diagnosis must distinguish between infectious and noninfectious causes, as management differs fundamentally 4.
Infectious Causes
Bacterial keratitis:
- Typically more suppurative appearance
- May present with peripheral location, especially staphylococcus-associated marginal keratitis
- Contact lens wear is the leading risk factor in developed countries 4
Fungal keratitis:
- Dry rather than suppurative appearance
- Feathered edge with satellite lesions
- Posterior plaque formation
- Ring infiltrate pattern 4
Acanthamoeba keratitis:
- Severe pain disproportionate to clinical findings
- Radial keratoneuritis (inflammation along corneal nerves)
- Ring infiltrate pattern
- Associated with contact lens wear 4
Viral keratitis:
- HSV, VZV, or Epstein-Barr virus
- Immunologically mediated infiltrates
- May have necrotizing stromal disease
- Prone to bacterial superinfection in severe cases 4
Noninfectious Causes
Systemic autoimmune diseases (most critical to identify):
- Rheumatoid arthritis (most common association)
- Systemic lupus erythematosus
- Granulomatosis with polyangiitis (Wegener's)
- Polyarteritis nodosa
- Juvenile idiopathic arthritis (in pediatric cases) 4, 2, 5
Important clinical pearl: PUK often correlates with exacerbations of the underlying systemic disease and may herald life-threatening systemic complications 6, 3.
Mooren's ulcer:
- Idiopathic form of PUK
- Diagnosis of exclusion after ruling out systemic and infectious causes
- Progressive peripheral corneal ulceration without systemic disease 1, 2
Other noninfectious causes:
- Phlyctenular keratitis (hypersensitivity reaction to bacterial antigens)
- Staphylococcus-associated marginal keratitis (immune-mediated, not infectious)
- Contact lens-related sterile infiltrates (particularly extended-wear lenses)
- Inflammatory disorders: sarcoidosis
- Dermatologic conditions: severe ocular rosacea
- Allergic conditions: vernal or atopic keratoconjunctivitis 4
Key Distinguishing Features
Terrien marginal degeneration (critical to differentiate):
- Noninflammatory peripheral corneal thinning
- Painless, slowly progressive
- No epithelial defect or acute inflammation
- Does not require immunosuppression 2
Marginal keratitis:
- Typically less severe stromal involvement
- Clear zone between infiltrate and limbus
- Often bilateral and self-limited
- Associated with blepharitis or staphylococcal colonization 4
Diagnostic Approach
When evaluating suspected PUK, immediately determine if this is infectious or autoimmune-related, as this fundamentally changes management 6, 7.
For infectious workup:
- Obtain corneal scrapings for smears and cultures when clinical uncertainty exists
- Consider confocal microscopy for Acanthamoeba if ring infiltrate present
- Start empiric antibiotics if bacterial superinfection suspected 4
For systemic disease workup:
- Complete blood count, comprehensive metabolic panel
- Inflammatory markers: ESR, CRP (elevated in most autoimmune-associated PUK) 5, 8
- Autoimmune serologies: ANA, RF, ANCA, anti-CCP
- Chest imaging for granulomatosis with polyangiitis or sarcoidosis
- Rheumatology consultation for joint examination and systemic evaluation 6, 7
Critical pitfall: Necrotizing scleritis frequently accompanies severe PUK and indicates high risk for perforation—this requires aggressive systemic immunosuppression 3.
Management Implications
The presence of PUK demands urgent action because corneal perforation can occur rapidly. Treatment requires addressing both local corneal disease and underlying systemic pathology through a stepladder approach from topical therapy to systemic immunosuppression and biologics, with surgical intervention reserved for impending or actual perforation 1, 6, 2.
Interdisciplinary management with rheumatology or internal medicine is essential, as PUK may be the presenting sign of life-threatening systemic disease 6, 7.