Ocular cicatricial pemphigoid (OCP) involves the conjunctiva in the majority of cases and causes progressive cicatrization. It is a rare condition and the diagnosis may be overlooked in the early stages, hence the true incidence may be underestimated. Incidence rates vary between one in 12,000 to one in 60,000.1
The pathogenesis of the condition is not completely understood. OCP has been described as a type II immune reaction characterized by the deposition of immunoreactants (immunoglobulin G, immunoglobulin A, immunoglobulin M, and/or complement) along the epithelial basement membrane zone. One particular antigen, the β4 subunit of α6β4 integrin, has been identified as the target in the basement membrane zone of the conjunctiva and epidermis for the immune reaction in OCP.2
Autoantibodies are produced against a variety of adhesion molecules in the hemidesmosome–epithelial membrane complex. Production of proinflammatory cytokines stimulates migration of lymphocytes, eosinophils, neutrophils, and mast cells to the basement membrane. Fibroblast activation interferes with collagen production, eventually resulting in cicatricial changes in the conjunctiva. The resulting fibrotic changes cause dry eye, meibomian gland dysfunction, trichiasis, persistent corneal epithelial defects, and corneal scarring.
Management, prognosis, and treatment depend on the extent of the condition. Sequential photographs are useful to monitor the disease progression. The Foster classification system relies on the clinical progression of disease ().3
Foster classification of ocular cicatricial pemphigoid
In advanced cases, corneal involvement manifest by keratopathy with persistent epithelial defects, stromal ulceration, and neovascularization may lead to secondary microbial keratitis with perforation and endophthalmitis.
The definitive diagnosis requires demonstration of immunoglobulin or complement deposition at the epithelial basement membrane of biopsied conjunctiva. A negative biopsy does not exclude OCP. Repeat biopsy should include more sensitive immunoperoxidase staining with supplemental avidin–biotin complex methodology.4
The differential diagnosis includes infective conjunctivitis such as that caused by adenovirus, systemic disorders such as systemic lupus erythematosus, and Wegener’s granulomatosis, side effects from topical ocular medications such as pilocarpine, trauma caused to the ocular surface from chemical or thermal burns, or multiple surgical procedures.5
Mucocutaneous disorders such as acne rosacea, Stevens–Johnson syndrome, and atopy may simulate the clinical signs of OCP.6
The treatment of the condition should address both the systemic immune response and local ocular sequelae of the condition.
Topical treatment includes preservative-free artificial tear replacements, topical antibiotics, and steroids. The surgical management of lid conditions such as trichiasis and entropion is best considered when the disease is quiescent as surgical manipulation of the conjunctival surface may promote progression of cicatrization. Systemic treatment is best managed by a physician as immunomodulatory treatment necessitating frequent blood test monitoring is often necessary. Dapsone is a synthetic sulfone first used in the treatment of leprosy in the 1940s. Its antiinflammatory action is thought to be mediated by stabilizing lysosomal membranes, decreasing the release of proteolytic enzymes, and by the inhibition of the myeloperoxidase-mediated cytotoxic system in neutrophils.8
Dapsone has been shown to halt the progression of fibrosis in OCP,9
and is of use in patients confirmed not to be glucose-6-phosphate dehydrogenase deficient. Azathioprine has been shown to be effective as an adjunctive agent in OCP.10
The use of immunosuppressive therapy is of use as steroid sparing agents avoid the well-recognized long-term side effects of oral steroids.