Immune-Mediated Subepithelial Blistering Diseases of Mucous Membranes: Pure Ocular Cicatricial Pemphigoid Is a Unique Clinical and Immunopathological Entity Distinct From Bullous Pemphigoid and Other Subsets Identified by Antigenic Specificity of Autoantibodies

Background and Design.—There is much confusion in the clinical classification of immune-mediated subepithelial blistering diseases of mucous membranes. We conducted a 6-year comprehensive study to better classify this heterogeneous disease group. Indirect immunofluorescence was performed on a salt-split-skin substrate to detect circulating antibasement membrane antibodies (n=47). Serologic reactivity against cultured keratinocyte antigens was examined by immunoblots (n=38) and immunoprecipitation (n=15). The results were correlated with the clinical features and direct immunofluorescence data of the entire patient group (n=87) without preassignment of clinical diagnoses. χ² Statistical analyses compared these results with those of the classic bullous pemphigoid group (n=36). Results.—When compared with the bullous pemphigoid patients, a subset of patients with combined oral mucosal and skin lesions demonstrated marked similarity in direct and indirect immunofluorescence findings and in serologic reactivity to bullous pemphigoid antigens. By contrast, a subset of patients with only ocular lesions exhibited significantly lower in vivo deposits of IgG and C3, higher deposits of fibrin, virtual absence of circulating antibodies, and negative serologic reactivity to bullous pemphigoid antigens. Conclusions.—Ocular patients without skin or mouth lesions, in particular those with negative indirect immunofluorescence, should be distinctively classified as ocular cicatricial pemphigoid, a unique clinical and immunopathologic entity. Patients with mucous membrane involvement who also demonstrate skin lesions and antibodies to the roof of salt-split-skin substrate should be classified as anti-BP Ag mucosal pemphigoid, even though they may exhibit severe oral and/or ocular diseases. The remaining mucous membrane patients are heterogeneous. Some can be classified on the basis of autoantibodies to other basement membrane determinants, or if serum autoantibody negative, on the basis of clinical features (ie, pure oral mucosal pemphigoid or overlapping mucosal involvement).