Ocular Cicatricial Pemphigoid: Diagnosis and Treatment
Diagnosis
Conjunctival biopsy with direct immunofluorescence is the gold standard for confirming ocular cicatricial pemphigoid (OMMP), though up to 40% of patients may have negative biopsy results that do not exclude the diagnosis. 1
Clinical Presentation to Recognize
- Bilateral, often asymmetric bulbar conjunctival injection with papillary conjunctivitis 2
- Progressive conjunctival subepithelial fibrosis and keratinization beginning in the fornices 2
- Conjunctival scarring with forniceal foreshortening, symblepharon formation 2
- Punctal stenosis and keratinization 2
- Keratitis, eyelid thickening, and meibomian gland dysfunction 2
- Onset typically over age 60, more common in women 2
- Chronic course with remissions and exacerbations 2
Critical Diagnostic Pitfall
Topical glaucoma medications (particularly pilocarpine and timolol) can produce OMMP-like disease ranging from self-limited to progressive disease indistinguishable from true OMMP 2, 3. Review all current and past topical medications, as drug-induced cicatrizing conjunctivitis may show identical histopathological changes to autoimmune OMMP 3.
Differential Diagnosis to Exclude
- Stevens-Johnson syndrome/toxic epidermal necrolysis (acute onset with systemic mucocutaneous involvement, medication or infection trigger) 2
- Graft-versus-host disease (history of allogeneic stem cell transplantation) 2
- Atopic disease and underlying neoplasms (paraneoplastic pemphigus, paraneoplastic lichen planus) 2
Staging Systems
- Foster staging system (based on clinical signs) 1
- Mondino and Brown system (based on inferior fornix depth loss) 1
Extraocular Involvement Assessment
Examine for involvement of other mucous membranes: oral cavity, nasopharynx, larynx, esophagus, trachea, genitourinary tract, anus, and skin 2, 1. Extraocular involvement occurs in 50% of patients 4.
Treatment Approach
The primary goal is to halt disease progression with systemic immunosuppression, as 75% of untreated cases develop visual loss and 90% can be controlled with long-term systemic therapy. 1, 4
First-Line Therapy for Mild-to-Moderate Disease
Dapsone is the first-line treatment in patients without G6PD deficiency 1. However, dapsone causes the highest number of treatment-related side effects, particularly hematologic complications (anemia, leukopenia) 4.
Escalation for Severe or Refractory Disease
When dapsone is insufficient or contraindicated, use immunosuppressants:
- Methotrexate (causes the least side effects among immunosuppressants) 4
- Azathioprine 1, 4
- Mycophenolate mofetil 1
- Cyclosporine 1
32% of patients require two agents simultaneously to control disease activity 4.
Refractory Disease Management
For cases unresponsive to conventional therapy:
Adjunctive Corticosteroid Use
Prednisone should be used only as adjunctive treatment, not monotherapy 4. Corticosteroid-related complications (cardiovascular, endocrinologic) are common in this elderly population 4.
Long-Term Management Reality
46% of patients achieving disease control require continuation of systemic treatment indefinitely to prevent recurrences, and 10% progress despite multiple drug trials 4. This necessitates lifelong monitoring for drug toxicity in elderly patients 4.
Ocular Surface Management
Dry Eye Treatment
- Constant lubricating medication 1
- Topical corticosteroids 1
- Topical cyclosporine-A 1
- Topical tacrolimus 1
Surgical Considerations
Surgery (for entropion, trichiasis, symblepharon, or cataract) should only be performed during quiescent disease phase, as minor conjunctival trauma can significantly worsen disease activity 1, 5.
Monitoring for Complications
Vision-Threatening Sequelae
- Severe dry eye syndrome with goblet cell loss and mucin deficiency 2, 1
- Corneal erosions, ulceration, perforation 2, 1, 5
- Corneal neovascularization and scarring 2, 1
- Corneal keratinization 2, 1, 5
- Limbal stem cell deficiency 2
- Entropion and trichiasis 2, 1, 5
- Secondary bacterial conjunctivitis 2
7% of eyes are legally blind at presentation, increasing to 21% at end of follow-up despite treatment 4.
Treatment-Related Toxicity Monitoring
Most common side effects requiring surveillance: