Profile of local interleukin expression in a cohort of ocular cicatricial pemphigoid patients.

PURPOSE: We investigated the expression of IL-1, IL-6, IL-12, IL-13, and IL-17 in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP), also labeled as ocular mucous membrane pemphigoid (MMP). METHODS: A retrospective case-control study was done on 5 biopsy-proven OCP subjects and 6 healthy volunteers. Conjunctival specimens were obtained, and the local expression of IL-1, IL-6, IL-12, IL-13, and IL-17 was studied by immunohistochemistry. Clinical and therapeutic features were collected during follow-up. RESULTS: No remarkable IL-1, IL-6, IL-12, IL-13, or IL-17 expression was observed in normal conjunctival specimens. All OCP samples had remarkable amounts of IL-12 and IL-17 expression especially in the epithelium and stroma; there also was stromal overexpression of IL-6. The mean follow-up after the biopsy was 13 months (range 9-15 months). CONCLUSIONS: Our results demonstrated, for the first time to our knowledge, a local overexpression of IL-6, IL-12, and IL-17 in conjunctiva of OCP compared to controls.

Ocular and oral grading of mucous membrane pemphigoid.

BACKGROUND: A variety of methods have been described for grading ocular mucous membrane pemphigoid (MMP), each with their own limitations. In contrast, there are no reported grading systems for involvement of the oral mucosa. We wished to evaluate two ocular (one established and one proposed) and an oral mucosal grading system for MMP. METHODS: Patients with MMP were assessed by three ophthalmologists and two oral medicine physicians. Ocular disease was graded using the system described by Rowsey and a proposed system based on measurement of vertical depth and horizontal width measured from the bulbar conjunctival aspect. Oral assessment used a 'mucosal disease severity score' originally described for lichen planus, in which 17 areas of the mouth are scored for involvement, together with a pain score. Levels of agreement were evaluated using Fleiss' Kappa Statistic (k). RESULTS: Forty-four patients with MMP encompassing mild to severe disease were included. Good levels of agreement were observed between observers for both vertical (k:0.86) (upper 95% CI: 1.03 mm) and horizontal (k:0.80) (upper 95% CI: 3.01 mm) involvement for the proposed ocular system and the Rowsey system (k: 0.83) (upper 95% confidence interval: 3.19 mm). There was a high coefficient of determination (R(2)) between the ocular grading systems (0.81, p < 0.01). Oral grading showed excellent levels of agreement (k: 0.71) between observers. There was no significant association between the severity of oral and ocular disease using described grading systems. CONCLUSIONS: The proposed grading systems for both oral and ocular involvement in MMP are easy to use, and show good agreement between observers. The proposed ocular system correlates well with a currently used system, and overcomes some of the difficulties encountered with existing systems. For the individual patient, changes greater than 1.5 mm (vertical) and 3 mm (horizontal) are significant. This may increase our ability to detect change or disease progression. Although the risk of ocular involvement in patients with only oral involvement has been demonstrated, the severity of oral and ocular disease are not well-correlated, due in part to an absence of an ocular disease activity score.

Combination of rituximab and intravenous immunoglobulin for recalcitrant ocular cicatricial pemphigoid: a preliminary report.

PURPOSE: To compare the effectiveness and safety of the combination therapy of rituximab (RTX) and intravenous immunoglobulin (IVIg) to other immunosuppressive regimens in the treatment of ocular cicatricial pemphigoid (OCP). DESIGN: Retrospective, comparative, interventional case series. PARTICIPANTS: Twelve patients with OCP. METHODS: We reviewed medical records of 12 patients with OCP. Ten of the 12 patients were blind in 1 eye after initial systemic immunosuppressive therapies (phase 1 treatment). The patients were then divided into 2 groups based on treatments received during phase 2. The study group consisted of 6 patients who received the combination of RTX and IVIg during phase 2 of their treatment. For comparison purposes, the control group consisted of 6 patients who during phase 2 of their treatment received more aggressive immunosuppressive therapies, but not RTX and IVIg, because the insurance carriers refused to pay for the combination therapy. MAIN OUTCOME MEASURES: Blindness (best-corrected visual acuity [BCVA] < or =20/200) and OCP staging (Foster). RESULTS: The median total follow-up periods were 57.5 and 55.5 months in the control group and the study group, respectively. After phase 1 treatment, all 6 patients in the control group were blind in 1 eye. Similarly, 4 of the patients in the study group were blind in 1 eye, whereas 2 had good BCVA bilaterally but experienced persistent conjunctival inflammation despite phase 1 treatment. After phase 2 treatment, all 6 patients in the control group had OCP progression and became blind in both eyes. In contrast, BCVA was stable and no further progression of OCP staging was observed in all 6 patients in the study group. In the study group, the median follow-up from completion of the RTX and IVIg treatment protocol was 11 months. No adverse events, immediate or delayed, were reported in any of the patients who received the combination therapy of RTX and IVIg. CONCLUSIONS: In this preliminary study, the combination therapy of RTX and IVIg arrested disease progression and prevented total blindness in patients with recalcitrant OCP.

Differentiation of mucous membrane pemphigoid subgroups with confocal imaging.

OBJECTIVE: Mucous membrane pemphigoid is an immune-mediated subepithelial blistering disease consisting of immunologically heterogeneous subgroups. Differentiation between these subgroups is important because they differ in prognosis. This study uses oral mucosal pemphigoid specimens to investigate the utility of computer-aided fluorescence overlay antigen mapping and laser scanning confocal microscopy to differentiate subgroups of mucous membrane pemphigoid. STUDY DESIGN: Thirty oral mucosal biopsy specimens were cryosectioned and immunostained, although only 13 could be analyzed due to technical difficulties. In vivo bound antibodies and molecular markers of the basement membrane zone were differentially labeled with fluorescent antibodies. Fluorescent signals were imaged, and the spatial localization of in vivo bound antibodies was compared with the markers and analyzed. RESULTS: In vivo bound IgG antibodies colocalized with beta4-integrin in 3 cases, with laminin-5 in 8 cases, and with collagen VII in 2 cases. CONCLUSION: Fluorescence overlay antigen mapping and laser scanning confocal microscopy are useful techniques to differentiate pemphigoid subgroups in oral biopsy specimens.

Mucosal disease series. Number III. Mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory-especially immunosuppressive-therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice.

Penfigoide ampollar infantil: comunicación de un caso y revisión de la literatura / Infantile bullous pemphigoid: case report and literature review

Se presenta un caso de penfigoide ampollar en un niño de 8 años de edad, que presentaba ampollas localizadas en miembros inferiores. El diagnóstico fue confirmado por histopatología e inmunofluorescencia directa. Las lesiones involucionaron en 4 semanas con tratamiento local. Realizamos una revisión bibliográfica de esta entidad de rara aparición en la infancia

Penfigoide ampollar infantil: comunicación de un caso y revisión de la literatura / Infantile bullous pemphigoid: case report and literature review

Se presenta un caso de penfigoide ampollar en un niño de 8 años de edad, que presentaba ampollas localizadas en miembros inferiores. El diagnóstico fue confirmado por histopatología e inmunofluorescencia directa. Las lesiones involucionaron en 4 semanas con tratamiento local. Realizamos una revisión bibliográfica de esta entidad de rara aparición en la infancia (AU)

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. chi 2 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 root 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).

Vegetating cicatricial pemphigoid. A new subset of the cicatricial pemphigoid spectrum.

A case with widespread vegetating-pustular skin lesions, oral erosions, ulcerations and scarring, and conjunctival synechiae is reported. Clinically, histopathologically, and by immunofluorescence and electron microscopy this patient combined the features of pemphigoid vegetans, as described by Winkelmann and Su, and the mucocutaneous type of cicatricial pemphigoid. This observation suggests that a third subset of cicatricial pemphigoid can now be added to the two existing ones, the mucocutaneous and Brunsting-Perry types, and the designation vegetating cicatricial pemphigoid is proposed for this heretofore undescribed condition.