Ocular Cicatricial Pemphigoid

Educational Objectives

The goal of this program is to improve management of ocular cicatricial pemphigoid. After hearing and assimilating this program, the clinician will be better able to:

1. Diagnose ocular cicatricial pemphigoid.

Summary

Chronic cicatrizing conjunctivitis (CCC): in addition to pemphigoid, CCC can be caused by other conditions; history may be suggestive of Stevens–Johnson Syndrome and Loiasis (with skin involvement); however, history may not be helpful in conditions like rosacea, eczema, and lichen planus; the speaker recalls a patient presenting with bilateral conjunctivitis, symblepharon formation, and early keratopathy (suspected pemphigoid) who was found to be allergic to mite feces; consider other causes; conjunctival biopsy is advisable

Mucous membrane pemphigoid (MMP): can involve skin but usually does not; oral involvement is most common, followed by ocular involvement; MMP can be lethal, and esophageal involvement can lead to asymptomatic stricture (slow and progressive) and death; patients may be positive for immunoglobulin (Ig) G, IgA, or complement deposition at the epithelial basement membrane zone (BMZ) and circulating autoantibodies; autoantibodies in patients with bullous pemphigoid include bullous pemphigoid antigen (BPAg) 1, BPAg2, laminin-5, and laminin-6; antibodies against β4 peptide of the α6β4 integrin are present in patients with ocular cicatricial pemphigoid (OCP)

Pathophysiology of OCP: pemphigoid antibodies bind at the lamina lucida of the BM; α6β4 integrin molecule attaches the epithelium and the BMZ; Bhol et al (2000) identified the β4 subunit of the α6β4 integrin as the (most common) target integrin antigen in patients with OCP; autoantibodies to the conjunctival BMZ can be detected in all patients with active pemphigoid disease and are pathogenic; the binding of the autoantigen in the BM sets in motion a complex cascade of events leading to inflammation that progresses slowly; many patients with OCP in the early stages do not develop symptoms for several years; medications that can act as a trigger for OCP include practolol (antihypertensive drug), topical medications, and some glaucoma drugs; the microbe that triggers OCP has not yet been identified; the cascade of events triggered by the binding of the autoantibody affects signal transduction and attachment molecule relationship; cytokines, including transforming growth factor-β and interferon-γ, play a vital role, resulting in fibrosis

Classification system for OCP: Foster staging system — stage 1 is characterized by chronic conjunctivitis with subepithelial fibrosis; the most commonly associated gene is HLA-DQB1*0301; stage 2 is frank foreshortening of the inferior fornix; stage 3 is the presence of symblepharon; stage 4 is end-stage disease; early treatment is recommended (especially, stage 1 or 2); if the disease is more advanced at the time of initial observation, the likelihood of progression in the next 2 yr is higher

Management of OCP: end-stage pemphigoid is difficult to treat; keratoprosthesis can be helpful in some patients; immunomodulatory therapy in the early stages can halt the autoimmune process; the most effective treatments include intravenous Ig (IVIg) and rituximab (expensive and tedious) and are indicated for rapidly progressive disease; initiate treatment with dapsone or methotrexate and follow with mycophenolate mofetil (eg, CellCept) or azathioprine (eg, Azasan, Imuran); cyclophosphamide (eg, Cytoxan) can be used if the disease is uncontrolled; high-dose IVIg and rituximab can be used as a last resort

Readings

Bhol KC, Dans MJ, Simmons RK, et al. The autoantibodies to alpha 6 beta 4 integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human beta 4. J Immunol. 2000;165(5):2824-2829. doi:10.4049/jimmunol.165.5.2824.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Foster was recorded at the 2024 Ocular Inflammatory Disease Crash Course, held on September 21, 2024, in Louisville, KY, and presented by The Ocular Immunology and Uveitis Foundation, Weston, MA. For more information about upcoming CME activities from this presenter, please visit https://uveitis.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

OP631001

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.