Ocular mucous membrane pemphigoid: a review.

Ocular mucous membrane pemphigoid (MMP) is a rare, immuno-mediated chronic progressive condition of the conjunctiva characterized by blisters developing from sub-epithelial tissue through disruption of the adhesions between the conjunctival epithelium and the sub-epithelium. Patients with ocular MMP, in many cases, develop profound conjunctival scarring and visual impairment. Furthermore, ocular MMP may lead to a progressive secondary corneal vascularization and to corneal opacification. Ocular MMP is difficult to diagnose during the initial stages because of false negatives during biopsy and variability in the clinical presentation. Most of the current pharmacological treatments aim to control the inflammatory response to reduce the progressive tissue remodeling which leads to the formation of a fibrotic scar. The course and prognosis of ocular MMP depend on the severity and progression of the disease after systemic immunomodulatory therapy. The aim of this review is to provide a comprehensive analysis of the current literature on established and emerging concepts in ocular MMP, with special attention to its clinical presentation, diagnosis, treatment, and pathogenic mechanisms, including the role of some cytokines and growth factors in the development of the disease.

Ocular Cicatricial Pemphigoid: Camouflaged as Persistent Conjunctivitis.

Ocular cicatricial pemphigoid (OCP) is a rare autoimmune disease with heterogenous clinical manifestations. The classical lesion involves ocular conjunctiva that leads to progressive scarring and fibrosis which ultimately results in visual loss. We report a case of a young male, who had chronic conjunctivitis which remained un-responsive to conventional treatment and results in significant morbidity. Later, it was diagnosed as ocular cicatricial pemphigoid involving eyes, nasal cavity, larynx as well as skin. Patient received immuo-suppressive therapy, which helped in arresting the disease process.

Applications of biomaterials in corneal wound healing.

Disease affecting the cornea is a common cause of blindness worldwide. To date, the amniotic membrane (AM) is the most widely used clinical method for cornea regeneration. However, donor-dependent differences in the AM may result in variable clinical outcomes. To overcome this issue, biomaterials are currently under investigation for corneal regeneration in vitro and in vivo. In this article, we highlight the recent advances in hydrogels, bioengineered prosthetic devices, contact lenses, and drug delivery systems for corneal regeneration. In clinical studies, the therapeutic effects of biomaterials, including fibrin and collagen-based hydrogels and silicone contact lenses, have been demonstrated in damaged cornea. The combination of cells and biomaterials may provide potential treatment in corneal wound healing in the future.

Mucous membrane pemphigoid affecting the oral cavity: short review on etiopathogenesis, diagnosis and treatment.

Oral mucous membrane pemphigoid (OMMP) is a rare inflammatory autoimmune mucocutaneous disorder. Oral mucosa is affected in 90% of cases. Its development is chronic, with a possible involvement of ocular, laryngeal and genital mucosa. Spontaneous remission is rare. Although the etiology of OMMP is still unclear, there is evidence that it is a complex autoimmune disease mediated by autoantibodies directed against different components of the basement membrane zone. Cellular immunity is also involved in the pathogenesis. Atrophic and erosive lesions are the sequelae of the rupture of the subepithelial blisters. The treatment is usually aimed at relieving pain and may include corticosteroids and immunosuppressive agents. However, the use of these drugs may be inefficacious. Oral hygiene and follow-up are mandatory for patients affected by OMMP. It is important to increase awareness of oral lesions in autoimmune blistering/erosive dermatologic conditions.

Ocular mucous membrane pemphigoid after Lyell syndrome: occasional finding or predisposing event?

PURPOSE: Ocular mucous membrane pemphigoid (OMMP) is an autoimmune disease involving the eye and characterized by subepithelial detachment resulting from an immunologic reaction against conjunctival basal membrane zone (BMZ) antigens. Lyell syndrome (LS) is a drug-induced, T cell-mediated, cytotoxic reaction involving the mucocutaneous areas. Two patients with LS are presented in whom OMMP developed. DESIGN: Report of 2 cases. PARTICIPANTS: Two male patients, 80 and 60 years old, with persistent corneal ulcerations, corneal melting, and inflammation some months after an LS episode. METHODS: Conjunctival biopsy samples were obtained to perform direct immunofluorescence (DIF) and histologic analyses. Indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) also were performed. MAIN OUTCOME MEASURES: Immunodeposit findings on the conjunctival BMZ obtained by DIF and IIF, inflammatory infiltration of the corneoconjunctival samples studied by histologic analysis, and autoantibodies of patient sera directed against BMZ antigens tested by ELISA. RESULTS: Direct immunofluorescence analyses showed immunoglobulin G and complement 3 component deposits along the BMZ in a linear pattern. Histologic analysis revealed the presence of eosinophils, neutrophils, and mast cells with fibrin deposition in the substantia propria of both patients; the data confirmed the clinical suspicion of OMMP. The IIF and ELISA results were negative. CONCLUSIONS: Chronic eye surface injury associated with LS may promote autoimmunization against ocular epithelial BMZ antigens, playing a strategic role in the subsequent onset of OMMP. The occurrence of OMMP after LS could be an occasional finding, or conversely, LS could be an underestimated predisposing factor in the development of OMMP.

Pathogenesis of mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) is the clinical phenotype of a group of autoimmune blistering diseases characterized by autoantibodies directed against different structural proteins in epidermal basement membranes. The clinical course and prognosis of MMP are affected by the specific autoantigen targeted, the titer and bioactivity profile of corresponding autoantibodies, and the specific mucosal sites of disease activity. Irreversible scarring and loss of function must be prevented by early diagnosis and appropriate interventions.

[Cicatricial pemphigoid, mucous membrane pemphigoid]. / Pemphigoïde cicatricielle, pemphigoïde des muqueuses.

Mucous membrane pemphigoid belongs to the family of sub-epidermal bullous diseases and is clinically characterized by mucosal involvement leading to fibrosis and scarring. Cutaneous involvement is unfrequent and oral mucosa and conjunctivas are the most frequently involves mucosa. Treatment relies on anti-inflammatory and immunosuppressive drugs. The main goal is the limitation of the fibrosing potential of the autoimmune deposits within various mucous membranes.

Penfigoide benigno de las mucosas: reporte de caso clínico / Benign pemphigoid of the oral mucosa: report of a clinical case

El penfigoide benigno de las mucosas es una enfermedad autoinmune ampollar. En un 80 por ciento de los casos está afectada la mucosa oral, de ahí la importancia que dicha enfermedad la conozca el odontólogo general y el especialista. El siguiente caso muestra el compromiso de la mucosa gingival en una paciente de 12 años de edad.

Exacerbation of undiagnosed ocular cicatricial pemphigoid after repair of involutional entropion.

We report a case of exacerbation of undiagnosed ocular cicatricial pemphigoid after repair of involutional entropion. A lateral tarsal strip was performed to address entropion in the setting of eyelid laxity. No evidence of ocular cicatricial pemphigoid was observed before surgery. Postoperatively the patient developed intense conjunctival inflammation and diffuse symblepharon formation. Conjunctival biopsy demonstrated immunoglobulin and complement deposition at the basement membrane consistent with ocular cicatricial pemphigoid. Clinicians should be aware of the possibility of underlying ocular cicatricial pemphigoid in all patients with entropion, including those without a cicatricial component.

[Mucous membrane pemphigoid with ocular involvement. Part I: Clinical manifestations, pathogenesis and diagnosis]. / Schleimhautpemphigoid mit okulärer beteiligung. Teil I: Klinik, pathogenese und diagnostik.

Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder characterized by predominant involvement of mucous membranes and the presence of autoantibodies against proteins of the dermal-epidermal junction. Lesions most frequently develop in the oral cavity followed, in descending order of frequency, by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus. When the lesions are restricted to the conjunctiva, the term ocular pemphigoid may be applied. Cicatrization of the plica is considered a pathognomonic sign in early disease. Recurrent conjunctival inflammation results in subepithelial fibrosis, which leads to fornix shortening, symblepharon formation and subsequent trichiasis and entropion. Even in the absence of conjunctival inflammation, ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency, tear deficiency, and lid malpositions may occur and result in a total keratinization of the ocular surface. The diagnosis is based on clinical findings and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal-epidermal junction by direct immunofluorescence microscopy of a perilesional biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6, alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of ocular involvement, preferential reactivity against beta4 integrin has been described.

Mucous membrane pemphigoid: clinical aspects, immunopathological features and therapy.

More than 50 years have passed since Civatte, Lever, and others described the clinical and histopathological characteristics of mucous membrane pemphigoid (synonym: cicatricial pemphigoid). This enigmatic, relapsing, and often eventually progressive subepithelial blistering disorder of the mucous membranes and skin continues to challenge investigators trying to understand the pathogenesis of the disease and prevent its progression. Mucous membrane pemphigoid typically begins in late adulthood and has a variable prognosis. Fifty percent of patients will develop esophageal and ocular lesions that heal with secondary atrophy leading to stenosis of the upper aerodigestive tract and blindness in uncontrolled disease. Recent progress has been made in understanding the cause, the immunological components, and the pathologic process of mucous membrane pemphigoid. The short-term clinical and pathological manifestations of disease activity have been reduced by new therapies, although the degree of long-term benefit from these treatments awaits further study.

Ocular cicatricial pemphigoid.

PURPOSE OF REVIEW: To review the content and importance of articles on ocular cicatricial pemphigoid (OCP), or mucous membrane pemphigoid (MMP) with relevance to ocular involvement, published from 2005 to 2006. RECENT FINDINGS: There is wide antigenic heterogeneity in MMP and OCP and attempts are being made to link this with clinical variations with varying degrees of success. A larger study demonstrates a link between multiple autoantibody reactivity and disease severity. Details of epitope specificity are emerging. A highly sensitive ELISA for laminin 5 has been developed which may provide prognostic information.Clinically, younger OCP patients show more severe ocular disease and are less well controlled by medication. A systematic review shows good evidence only for steroids and cyclophosphamide in OCP. Continued small trials suggest some role for the expensive intravenous immunoglobulin therapy in OCP where conventional treatment fails. Ocular reconstruction surgery has made some progression, and is enhanced by adjunctive medical therapy; osteo-odonto-keratoprosthesis offers some hope of prolonged retention of limited vision in end-stage disease. SUMMARY: OCP remains a difficult disease to manage well and the progress being made in understanding disease mechanisms is whence true disease-modifying, safe therapy is likely to emerge in the future.

Benign mucous membrane pemphigoid of the upper aero-digestive tract: rare paraneoplastic syndrome presentation in renal cell carcinoma.

Benign mucous membrane pemphigoid is a rare autoimmune disorder affecting the upper aero-digestive tract and conjunctivae. This is a case presentation of benign mucous membrane pemphigoid affecting the oral mucosa, pharynx, oesophagus and larynx, leading to cicatricial lesions in the pharynx and larynx, causing dysphagia, hoarseness and stridor. The alternative forms of management for laryngeal scarring due to this disease are explained. The patient was later diagnosed with advanced renal cell carcinoma, raising the possibility of cicatricial pemphigoid manifesting as a paraneoplastic syndrome of underlying renal cell carcinoma.

Cicatricial pemphigoid of the oropharynx after allogeneic stem cell transplantation for relapsed follicular lymphoma.

A 44-year-old woman with refractory follicular lymphoma underwent allogeneic stem cell transplantation (SCT) and achieved complete remission. Grade III acute graft-versus-host disease (GVHD) developed on day 23, but no chronic GVHD occurred. The patient developed severe erosion with bullous lesions in the oral cavity 18 months after SCT. At that time, the lymphoma remained in complete remission, and she had no clinical or laboratory findings suggesting chronic GVHD. A biopsy of the oral mucosa showed moderate lymphoplasmacytic infiltration and subepidermal bullae, and direct immunofluorescence staining demonstrated linear deposition of C3 at the dermo-epidermal junction. An immunoblotting assay using human epidermal extracts confirmed the presence in her serum of an antibody against the 230-kd bullous pemphigoid antigen 1 (BPAG1). A diagnosis of cicatricial pemphigoid (CP) was made, and complete resolution of the CP was achieved with prednisolone therapy. The occurrence of autoimmune blistering diseases is rare after allogeneic SCT.