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Pemphigus disease and mucous membrane pemphigoid are autoimmune blistering diseases (AIBDs) which may involve both oral and extra-oral tissues. The Bristol Joint Oral Medicine and Dermatology Combined Clinic was set up in 2014, with the primary aim of improving the standard of care for patients with AIBDs. This interdisciplinary approach aimed to address the medical management challenges due to the multisite nature of these AIBDs.We present a narrative report of the clinical work undertaken within this clinic, focused on the management of this patient cohort within a five-year span (2017-2022). This report outlines the multisite nature of AIBDs and the range of topical and systemic treatments that were employed to achieve adequate disease control and optimise outcomes for patients. We reflect on the experiential benefits of this multidisciplinary clinic extended beyond immediate patient benefits to areas such as specialist training, both from a dermatologist's and oral physician's perspective., (© 2024. The Author(s).)

Purpose: Ocular mucous membrane pemphigoid (OcMMP) is a rare eye disease characterized by relapsing-remitting or persisting long-lasting inflammatory events associated with progressive scarring. Despite long-term immunomodulating therapy, abnormal fibrosis keeps worsening in patients with OcMMP. This study investigates the fibrotic process in patients with OcMMP, as well as the critical role of the epithelium in modulating the local fibrosis., Methods: In this prospective, observational pilot study, patients affected by long-lasting OcMMP were compared with age- and gender-matched healthy controls. Clinical grading was assessed, and conjunctival biopsy and impression cytology were performed. Conjunctival samples were used for quantifying the expression of transcripts regulating the inflammatory and fibrogenic processes., Results: Ocular surface clinical and functional markers worsened in patients with OcMMP with fibrotic disease progression. In more advanced disease stages, both impression cytologies and conjunctival biopsies revealed increased tissue remodeling and profibrotic markers (α-SMA and TGF-β), and decreased levels of inflammatory markers (I-CAM1, IL-10, and IL-17). Increased epithelial expression of profibrotic markers and histological changes were detected., Conclusions: Chronic OcMMP is characterized by a progressive, aberrant self-sustaining fibrotic process that worsens clinical signs and symptoms. Conjunctival epithelial cells may transdifferentiate into myofibroblast-like phenotypes when chronically exposed to high levels of inflammation, as in the case of OcMMP. Tissue remodeling markers in OcMMP could be used as early diagnostic, prognostic, and therapeutic biomarkers, harvested in a non-invasive and painless procedure such as impression cytologies.

Mucous membrane pemphigoid (MMP) is a pemphigoid disease with predominant mucous membrane involvement. It mainly affects the mucous membranes of the mouth, eyes, nose and pharynx, but also the larynx, trachea, esophagus, genital and perianal regions. The manifestation of the disease covers a wide spectrum from gingival erythema and single oral lesions to severe tracheal strictures that obstruct breathing and conjunctival scarring with marked visual impairment and, not infrequently, blindness. In addition to a clinical picture of predominant mucosal involvement, diagnosis is based on direct immunofluorescence of a peri-lesional biopsy and serology. The main target antigen is BP180 (collagen XVII), and reactivity with laminin 332 is associated with malignancy in approximately 25 % of MMP patients. The treatment of MMP is challenging. On the one hand, due to the involvement of different mucous membranes, good interdisciplinary cooperation is required; on the other hand, due to the rarity of the disease, no randomized controlled clinical trials are available. The aim of this guideline is to present the clinical picture, including severity and scoring systems, and to give guidance for diagnosing and treating this complex disease. In MMP, interdisciplinary cooperation plays an essential role as well as the prompt diagnosis and initiation of adequate therapy in order to avoid irreversible damage to the mucous membranes with serious complications., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Drug induced cicatrizing conjunctivitis (DICC) is defined as a disease in which conjunctival cicatrization develops as a response to the chronic use of inciting topical and, rarely, systemic medications. DICC accounts for up to one third of cases of pseudopemphigoid, a large group of cicatrizing conjunctival diseases sharing similar clinical features to those of mucous membrane pemphigoid (MMP) but generally without the morbidity of progressive scarring or the need for systemic immunosuppression. The preservatives in topical anti-glaucoma medications (AGM) are the most frequently implicated inciting causes of DICC although topical antivirals, vasoconstrictors and mydriatics and some systemic drugs have been implicated. The literature review summarizes the classification, epidemiology, etiopathogenesis, histopathology, clinical presentation, diagnosis, management, and treatment outcomes of DICC in the context of a case series of 23 patients (42 eyes) with AGM induced DICC, from India and the UK. In this series all subjects reacted to preserved AGM with one exception, who also reacted to non-preserved AGM. At diagnosis >70% of eyes showed punctal scarring, inflammation, and forniceal shortening. Pemphigoid studies were negative in the 19/23 patients in whom they were carried out. DICC can be classified as non-progressive, progressive with positive pemphigoid immunopathology or progressive with negative pemphigoid immunopathology. It is unclear whether progressive DICC is a stand-alone disease, or concurrent (or drug induced) ocular MMP. Progressive cases should currently be treated as ocular MMP. The diagnosis can be made clinically when there is rapid resolution of symptoms and inflammation, usually within 1-16 weeks, after withdrawal of suspected inciting medications, ideally by temporary substitution of oral carbonic anhydrase inhibitors. If the response to withdrawal is uncertain, or the progression of inflammation and scarring continues then patients must be evaluated to exclude concurrent (or drug induced) MMP, and other potential causes of CC, for which the treatment and prognosis is different. Management, in addition to withdrawing inciting medications, may require short-term treatment of conjunctival inflammation with steroids, treatment of associated corneal disease with contact lenses or surface reconstructive surgery, control of intra-ocular pressure with non-preserved AGM and, in some, surgery for glaucoma or for trichiasis and entropion., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal or chemical injury are considered severe ocular surface disorders (OSDs) because they affect the entire ocular surface, including corneal and conjunctival epithelial stem cells. In patients with severe OSDs, the long-term prognosis for limbal transplantation is poor, and the related corneal opacity and cicatrization lead to devastating visual impairment. To date, there is no standardized treatment to improve vision in cases with severe OSD. Investigating novel treatment methods for severe OSDs, our group began cultivated oral mucosal epithelial transplantation in 2002 and developed a limbal-supported rigid-type contact lens that can be applied as a nonsurgical treatment. When used in combination, these treatment methods make it possible to successfully restore vision in cases with severe OSDs.

This is a report of a case with mucous membrane pemphigoid (MMP) with severe eye involvement and concurrent COVID-19 treated successfully using simultaneous high dose intravenous immunoglobulin (IVIg) and anti-viral treatment as hydroxychloroquine, lopinavir/ritonavir, and ribavirin. He had finished a 2-g cycle of rituximab (RTX) in late January. He was receiving mycophenolate mofetil (MMF) for one month and 30 mg prednisolone for three months until his hospitalization. Prednisolone was tapered to 15 mg when current COVID-19 was suspected, considering his recent cough, dyspnea, and fever.

Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear diagnosis or experience recurrent symptoms despite treatment. The 3 most common etiologies of vaginitis are trichomonas, bacterial vaginosis, and vulvovaginal candidiasis, which account for an estimated 70% of cases. The remaining 30% may be related to other causes of vaginitis, including atrophic vaginitis, desquamative inflammatory vaginitis, and vaginal erosive disease. The purpose of this review is to describe the noncandidal causes of acute and recurrent vaginitis, with the goal of improving the likelihood of accurate diagnosis as well as efficient and effective therapy. We excluded candidal vaginitis from our review because there was a recently published review on this topic in the Journal. The clinical presentation and evaluation of patients with symptoms of vaginitis can be triaged into 1 of 2 diagnostic pathways: noninflammatory and inflammatory vaginitis. The most common noninflammatory cause is bacterial vaginosis. Features such as irritation, purulent discharge, and the presence of polymorphonuclear neutrophils are more suggestive of an inflammatory process. Trichomoniasis is the most common cause of inflammatory vaginitis. Other well-described forms of inflammatory vaginitis include atrophic vaginitis, desquamative inflammatory vaginitis, and erosive disease. We present a review of the pathogenesis, symptoms, examination findings, diagnostic testing, and treatment for each of these causes of noncandidal vaginitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Pemphigus diseases (PDs) and mucous membrane pemphigoid (MMP) are a group of immune-mediated mucocutaneous disorders clinically characterized by the formation of blisters, erosions and ulcers. The skin and mucous membranes are predominantly affected, with the oropharyngeal mucosa as the initially involved site. Ocular involvement is also a frequent feature of these diseases. Because of the considerable overlap in their clinical presentations, the diagnosis of PDs vs. MMP can be challenging. A recognition of their specific immunological and histopathologic features is crucial in the differential diagnosis. Treatment modalities include systemically administered corticosteroids, steroid-sparing immunosuppressive agents, and biologic therapies (rituximab, intravenous immunoglobulins, and anti-tumor necrosis factor agents). Topical, oral, conjunctival, or intralesional corticosteroids as well as anti-inflammatory drugs and antibiotics are prescribed as needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The treatment of refractory autoimmune blistering diseases (AIBDs) has always been a challenge. Because randomized controlled trials are lacking, treatment has been based on analysis of anecdotal data. The last 2 decades has seen the use of rituximab become a conventional treatment in the therapeutic armamentarium of AIBDs, leading to its Food and Drug Administration indication for pemphigus vulgaris in 2018. We review the current updated data on the use of rituximab including dosing, protocols, and its role in the algorithm of AIBDs. In addition, we discuss several promising novel emerging therapeutic agents for AIBDs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Painful oral vesiculoerosive diseases (OVD) include lichen planus, pemphigus vulgaris, mucous membrane pemphigoid, erythema multiforme, and recurrent aphthous stomatitis. OVD lesions have an immunopathic cause. Treatment is aimed at reducing the immunologic and the following inflammatory response. The mainstay of OVD management is topical or systemic corticosteroids to include topical triamcinolone, fluocinonide, and clobetasol, whereas systemic medications used in practice can include dexamethasone, prednisone, and prednisolone. Oral herpetic lesions can be primary or recurrent. If management is desired, they can be treated by topical or systemic antiviral drugs. Topical antiviral creams include prescription acyclovir, penciclovir and over-the-counter docosanol., (Published by Elsevier Inc.)

Mucous membrane pemphigoid (MMP) encompasses a group of autoantibody-mediated, subepithelial blistering diseases, which primarily affect mucosal surfaces including oral, ocular, skin, genital, nasopharyngeal and oesophageal sites. We present a first description of laryngoceles as a manifestation of mucous membrane pemphigoid resulting in dynamic airway closure. Mucosal injury at other sites had previously resulted in pathergy and localised cicatrisation. We discuss successful combined medical and transcutaneous surgical intervention designed to avoid tracheostomy and minimise iatrogenic laryngeal cicatrisation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepidermal blistering disease with predominant mucosal involvement. In this article, we report a young patient with mucosal and extensive cutaneous involvement in the form of large erosions mimicking those of pemphigus vulgaris thus leading to diagnostic dilemma. We were unable to find any other previous reports with such extensive cutaneous erosions mimicking those of pemphigus vulgaris. Laminin 5 was the antigen found on knockout substrate testing. Antiepiligrin CP is a distinct subtype of CP with antibodies against laminin 5. This subtype is mostly associated with malignancy but no underlying malignancy was found in our case. Present report also highlights the importance of knockout substrate testing when immunoblot is not available., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Oral signs are frequently the first manifestation of autoimmune diseases. For this reason, dentists play an important role in the detection of emerging autoimmune pathologies. Indeed, an early diagnosis can play a decisive role in improving the quality of treatment strategies as well as quality of life. This can be obtained thanks to specific knowledge of oral manifestations of autoimmune diseases. This review is aimed at describing oral presentations, diagnosis, and treatment strategies for systemic lupus erythematosus, Sjögren syndrome, pemphigus vulgaris, mucous membrane pemphigoid, and Behcet disease.

Purpose: To evaluate whether conjunctival biopsy findings in patients with ocular mucous membrane pemphigoid (MMP) persist as positive or revert to negative following treatment with immunomodulatory therapy (IMT)., Methods: Patients with biopsy-proven MMP were treated with IMT for at least 2 years before undergoing repeat conjunctival biopsy for immunofluorescence microscopy. Their records were reviewed and findings evaluated to ascertain which patients' biopsies showed antibody deposition on the conjunctival basement membrane., Results: Following 2 years of IMT, conjunctival biopsies showed persistent antibody deposition in two patients, and were negative in four patients., Conclusions: Conjunctival biopsies in patients with ocular MMP may show reversion to inactive disease following IMT. Post-treatment biopsy might be clinically useful as a means of evaluating the efficacy of therapy in this chronic disease.

A 73-year-old woman was treated 8 years previously for synchronous breast and uterine neoplasms. She presented with a severe sore throat, odynophagia, dysphonia, dyspnoea, ocular irritation and weight loss over the last 3 months. Physical examination revealed ulcerations in the oral cavity, posterior pharyngeal wall and supraglottic larynx, nasal crusting, bilateral conjunctivitis and three cutaneous blisters. A diagnosis of anti-laminin 5 mucous membrane pemphigoid was retained, based on skin biopsy, direct immunofluorescence and immunoprecipitation. A positron emission tomography (PET)-CT detected multiple adenopathies. Cytology revealed adenocarcinoma with an immunocytology compatible with a breast origin and this was considered as a late metastatic recurrence of her previous breast cancer. A treatment of prednisone, dapsone and hormonotherapy was introduced, but intravenous immunoglobulin and rituximab were added due to new mucosal lesions. Despite treatment, a posterior laryngeal scar and bilateral symblepharon were developed. After 3 years, the patient is still alive and reports a satisfactory quality of life., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring., Competing Interests: JK Dart is involved with the development of ALDH inhibition for scarring under the Patent PCT/GB2015/051292 held by UCL Business plc.

Objective: The purpose of the study was to evaluate the relationship between mucous membrane pemphigoid and a state of hypothyroidism. The study included analysis of the dental charts of 40 subjects with clinically and histologically confirmed diagnosis of mucous membrane pemphigoid and 35 age- and gender-matched subjects, from the same clinic, with no diagnosis of vesiculo-ulcerative lesions., Results: Thirteen subjects from the pemphigoid group (32%) had a hypothyroid condition, compared to four subjects (11%) from the control group (P = .030). Within the mucous membrane pemphigoid subjects who had a history of hypothyroidism, 83% were females. Although cases of hypothyroidism and autoimmune blistering oral disorders such as lichen planus were described in the past, this is the first report of an association between mucous membrane pemphigoid and hypothyroidism. A case report describes a patient who presented with desquamative gingivitis and vesicular lesions, and was diagnosed with mucous membrane pemphigoid and Hashimoto's thyroiditis., Conclusion: The general dental provider should be familiar with mucous membrane pemphigoid and the potential association with hypothyroidism. Early diagnosis of hypothyroidism is significant because replacement may prevent a significant morbidity associated with this condition. Therefore, the general dental provider should be aware of oral conditions presented as desquamative gingivitis and their potential association with hypothyroidism.

Purpose: Despite the availability of systemic immunosuppressants, cicatricial conjunctivitis (CC) remains a potentially blinding ocular surface disease. We aim to describe the combined use of rituximab (RTX) and intravenous immunoglobulin (IVIg) for severe recalcitrant autoimmune CC., Methods: In this single-center retrospective interventional case series with follow-up between 32 and 65 months, 3 cases with mucous membrane pemphigoid (patients 1-3) and 1 case with linear IgA disease (patient 4) were included. Initial conventional immunosuppressive therapy regimens included systemic steroids, dapsone, and mycophenolate. At the time of initiation of RTX and IVIg, all patients had only one eye with good visual acuity or good visual potential. Treatment included 1 to 2 cycles of RTX (1000 mg twice at an interval of 2 weeks apart), and 2 to 9 monthly courses of IVIg (2 g/kg over 3 days). Outcome measures were blindness, as defined by best spectacle-corrected visual acuity <0.05 on a decimal scale, and clinical staging of cicatricial disease (Rowsey and Foster staging)., Results: In 4 presented cases, progression of cicatricial disease was stopped as assessed by the Foster grading scale and visual acuity was stabilized in all patients. Conjunctival scarring was stabilized in 2 cases and continued to progress in 2 cases. One patient developed septicemia 6 weeks after RTX infusion, which was successfully treated., Conclusions: Combination therapy of RTX and IVIg is a potent treatment regimen for recalcitrant autoimmune CC. Further prospective controlled studies on efficacy and safety are warranted before widespread clinical application.

Mucocutaneous diseases affect the oral cavity and can present a diagnostic challenge. They can have systemic involvement, necessitating multidisciplinary management. Frequently, patients will see their general dentists initially for evaluation. A better understanding of mucocutaneous diseases can prevent delay in appropriate diagnosis and treatment. Oral lichen planus, mucous membrane pemphigoid and pemphigus vulgaris are three mucocutaneous diseases that affect the oral mucosa. This review describes the clinical features, epidemiology, etiology, pathogenesis and management for each condition.

We describe two patients with anti-BP180-type mucous membrane pemphigoid (MMP), who were correctly diagnosed and treated in early stages through the cooperation of dentists and dermatologists. Patient 1 was a 74-year-old woman who visited our dental department due to blisters over the oral mucosa and eruptions on the skin. She had also experienced bleeding of the gingiva and palate mucosa. Biopsy specimens from the oral mucosa revealed detachment of epithelial basement membrane and subepithelial lamina propria with slight chronic inflammation. Direct immunofluorescence (DIF) revealed linear IgG and IgA deposits along the basement membrane zone (BMZ). Indirect immunofluorescence (IIF) using 1 M-NaCl split normal human skin showed binding of IgG and IgA on the epidermal side. On immunoblot analysis, IgG and IgA autoantibodies reacted with the C-terminal protein of BP180. These findings indicated a diagnosis of anti-BP180-type MMP. Patient 2 was a 59-year-old woman who was referred to our dental department with a history of blisters and large erosions on the gingiva. Biopsy specimens from the oral mucosa revealed partial junctional separation at the level of the basement membrane. DIF showed linear depositions of IgG and C3 along the BMZ. IIF, using 1 M-NaCl split normal human skin, revealed circulating anti-BMZ-IgG antibodies bound to the epidermal side. These findings indicated a diagnosis of anti-BP180-type MMP. Both patients were treated successfully with systemic or topical steroids and oral health care. In conclusion, appropriate clinical examination and cooperation among medical specialists are important for the early diagnosis and treatment of patients with recurrent and chronic stomatitis and for their good prognosis.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Oral mucosal diseases encompass several common conditions that affect the general population. Some of these disorders present with signs and symptoms that are pathognomonic for the condition, whereas others present with similar features that can make clinical diagnosis difficult to achieve. It is important for physicians to have a clear understanding of these disorders to provide appropriate care to patients. This article reviews clinical aspects of common oral mucosal disorders, including candidiasis, herpes simplex viral infections, aphthous stomatitis, lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To report a rare case of microsporidial and polymicrobial keratitis in a patient with Sjogren's syndrome and ocular cicatricial pemphigoid., Method: This is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with microbial keratitis after using a Boston sclera contact lens for a painful epithelial defect. After 9 days of medical treatment, she underwent therapeutic penetrating keratoplasty., Results: 10% potassium hydroxide and calcofluor white wet mount revealed microsporidial spores. Gram positive cocci and Gram variable bacilli on Gram stain were identified as Staphylococcus epidermidis and Corynebacterium accolens in culture. Histopathological examination of the corneal tissue confirmed the presence of microsporidial spores., Conclusion: Microsporidal keratitis can occur in patients with severe ocular surface disease due to SS and OCP. Predisposing factors include dry eye, local and systemic immunosuppression and Boston scleral contact lens. Early surgical intervention may be needed to eradicate the infection., (Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: This review article summarizes the recent literature in regards to advancements in the diagnosis and management of mucous membrane pemphigoid (MMP) published in the English literature since May 2011., Recent Findings: MMP is an uncommon, subepithelial blistering conjunctivitis that is commonly associated with vision loss. Distinct subgroups of MMP have recently been identified using advanced immunohistochemical techniques. Antiepiligrin MMP has been described as a distinct entity with a relationship to certain solid organ malignancies. There is evidence that conventional immunomodulators such as mycophenolate mofetil and biologics such as rituximab are effective in halting disease progression. Unfortunately, the majority of patients at presentation to tertiary centers already have advanced disease. Novel regenerative techniques such as stem cell therapy as well as traditional surgical approaches such as keratoprosthesis might be required for the restoration of vision in patients with significant corneal scarring., Summary: Despite advances in available immunosuppressive treatment regimens, significant ocular morbidity persists possibly secondary to difficulty in diagnosis. Additionally, absence of clinically detectable inflammation in a significant proportion of patients causes delay in the treatment and leads to progressive scarring. Surgical management of the complications of MMP remains challenging, with high failure rates over long-term follow-up.

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.

Mucous membrane pemphigoid (MMP) is clinically characterized by predominant involvement of mucous membranes which in case of conjunctival lesions can lead to blindness. In MMP, autoantibodies are directed against different proteins of the dermal-epidermal junction; in 25% of cases, laminin 332 is the target. Anti-laminin 332 MMP with ocular involvement is particularly difficult to treat. A 46-year-old Caucasian man with anti-laminin 332 pemphigoid and extensive oral and nasal erosions as well as severe conjunctival involvement did not respond to intravenous dexamethasone-cyclophosphamide pulses combined with oral cyclophosphamide. After initiation of a therapeutic regimen originally established for the treatment of pemphigus, including immunoapheresis and rituximab in combination with intravenous dexamethasone-cyclophosphamide pulses and oral mycophenolate mofetil, lesions cleared within 4 months and circulating autoantibody levels became undetectable 3 months later. This is the first report of the successful use of adjuvant immunoapheresis and rituximab in previously treatment-refractory anti-laminin 332 MMP.

Purpose: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom., Patients and Methods: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed., Results: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation., Conclusions: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.

Ocular cicatricial pemphigoid is a devastating autoimmune blistering disorder mainly affecting the conjunctiva but frequently associated with systemic mucosal findings. This article is an update of the pathogenesis, ocular findings, differential diagnosis, and approaches to treatment.

Objective: To explore the experience of daily life of persons with chronic oral mucosal conditions., Methods:   Purposive sampling was used to recruit patients from the Oral Medicine Unit of Cork University Dental School and Hospital. An experienced independent facilitator convened the focus groups and conducted individual interviews in a non clinical setting. Focus groups were mixed with regard to gender, age, chronic oral mucosal condition, time since diagnosis and severity. A total of 24 patients took part, including patients with oral lichen planus, mucous membrane pemphigoid, pemphigus vulgaris, recurrent aphthous stomatitis and orofacial granulomatosis., Results:   Analysis of the interviews revealed that patient views could be divided into the following themes - biopsychosocial issues, treatment limitations and side effects, unpredictability of the conditions and the potential for malignant transformation and issues for the healthcare professionals., Conclusion: Chronic oral mucosal conditions impact upon the experience of daily life of patients in a variety of areas from physical health and functioning, to concerns about their future. The role of the oral medicine practitioner in treating patients with chronic oral mucosal diseases extends beyond active management and symptomatic relief to the management of all aspects of these conditions that impact upon their daily lives., (© 2010 John Wiley & Sons A/S.)

Background: Mucous membrane pemphigoid is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature., Objective: To assess the efficacy and tolerance of treatment regimens proposed in mucous membrane pemphigoid (MMP), from a systematic review of the literature., Methods: Randomized control trials have been identified using the PubMed and Embase databases up to April 2009. Uncontrolled prospective and retrospective studies have also been analyzed., Results: Literature analysis confirms that clinical and therapeutic trials are very uncommon in MMP; only retrospective series or case reports are available and have been analyzed. Therefore, the level of evidence is usually weak. Twenty-four series have been analyzed in this review. Dapsone remains the first line treatment in non-ocular forms of MMP. Sulfasalazine or cyclins can be used when dapsone is not tolerated or effective. Corticosteroids can be used to control inflammatory flares of the disease. Immunosuppressants are not used as the first line of treatment and can be added to anti-inflammatory drugs for a better control of MMP. Cyclophophamide or mycophenolate mofetil can be used, especially in the elderly. In ocular forms of the disease, the severity and chronicity of ocular involvement is the main therapeutical target. Non-scarring conjunctivitis can be treated by dapsone monotherapy. Ocular flares of the disease can be treated with systemic corticosteroids or cyclophosphamide. Many immunomodulating drugs are under evaluation. Intravenous immunoglobulins, etanercept or rituximab can be proposed when cyclophosphamide is not able to control the disease., Conclusion: Data from the literature did not allow identifying the best therapeutic regimen, mainly because of the lack of prospective comparative studies. Dapsone remains the first line treatment in MMP. Immunosuppressive or immunomodulating drugs should be discussed patient by patient., (Copyright © 2011. Published by Elsevier Masson SAS.)

This article discusses the classic autoimmune diseases: pemphigus vulgaris, mucosal pemphigoid, and oral lichen planus. These are generally considered of autoimmune origin or, at a minimum, immune system mediated. Cause, diagnosis, and treatment are discussed. As management of these diseases progresses, continued advances in molecular pathogenesis will allow insight into which strategies can be employed in interfering with the complex cascade of events leading to mucosal impairment and clinical morbidity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To analyze the clinical characterization of ocular cicatricial pemphigoid (OCP)., Methods: It was a retrospective series case study. Five consecutive patients referred for the evaluation of possible OCP from January 2005 to October 2008 in Departments of Ophthalmology and Dermatology of Peking University First Hospital. History and clinical characterization of 5 cases (10 eyes) OCP having been misdiagnosed were analyzed to find the causes of misdiagnosis., Results: All of cases were diagnosed as chronic conjunctivitis during the early stages of the diseases, one case was diagnosed as Stevens-Johnson syndrome and one as Sjögren syndrome during the later stage. It was two to five years from the first time to see a doctor to definite diagnosis. All of cases have been prescribed antibiotic eye drops for a long times, one case has been undergone three times trichiasis operation and made the disease progression. Among the five patients with OCP, 3 eyes were diagnosed Stage II, 5 eyes Stage III, 2 eyes Stage IV. Three cases were positive of bacterial culture. Only in 1 case, there was slight increase of iron protein as tumor mark. Inflammation was controlled by the end of the study, but cicatrization of 2 cases still progressed., Conclusion: Manifestation of OCP can mimic chronic conjunctivitis during the early stages, it is important to pay high attention to OCP, misdiagnosis may be stopped.

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., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Childhood oral pemphigoid is extremely rare and usually takes the form of desquamative gingivitis., Case Report: We describe a 6-year-old boy who presented with gingival bleeding, pain, eating difficulty, and peeling of the gums. Clinical examination revealed desquamative gingivitis with no extra-oral involvement. The diagnosis was established as oral pemphigoid based on the clinical, histological, and immunofluorescence findings. Symptoms resolved on treatment with occlusive topical corticosteroids. The patient was a carrier of the HLA-DQB(1)*0301 allele., Conclusion: Mucous membrane pemphigoid should be considered in the differential diagnosis of chronic desquamative gingivitis in childhood. Occlusive therapy with topical fluocinonide may alleviate the symptoms.

Purpose: The purpose of this study is to report a case of fluid-ventilated scleral rigid gas permeable lens use in the management of ocular cicatricial pemphigoid., Methods: A 74-year-old woman was referred to our clinic in May 2007 with a 4-year history of ocular pain and declining visual acuity. She had been diagnosed with ocular cicatricial pemphigoid by her previous eye care provider. Despite aggressive systemic and topical therapy, she developed persistent corneal epithelial defects in both eyes (3 mm in diameter OD, 4 mm x 8 mm OS). Her best spectacle-corrected visual acuity was significantly reduced (20/150 OD, hand motion OS). She was fit with Jupiter scleral lenses for continuous wear to help preserve corneal integrity and visual function., Results: Within 6 weeks of initiation of scleral lens wear, her corneal epithelial defects had healed and progression of stromal thinning was arrested. Her visual acuity with the scleral lenses was 20/50 OD and hand motion in the left eye. Her ocular surface and visual function have been maintained for 17 months after the initiation of scleral lens wear., Conclusions: If severe ocular cicatricial pemphigoid threatens corneal integrity despite traditional management, scleral contact lenses may play a role in the visual rehabilitation and ocular surface protection in select patients with this disease.

Purpose: Cicatricial pemphigoid is a rare chronic autoimmune disease, characterized by progressive alterations on the skin and mucous membranes. Ocular lesions consists of chronic conjunctivitis, progressive subepithelial fibrosis on the conjunctival fornix together with symblepharon formation, obstruction of the Meibomian ducts, sicca syndrome, and occasionally, entropion associated with consequent trichiasis and corneal ulcers., Methods: A 9-year-old patient with cicatricial pemphigoid with severe eye involvement came to our observation. A complete anamnesis, ophthalmologic examination, and systemic evaluation, including serum antibody levels evaluation and biopsies of mouth, vulva, parotid, and intestine mucosa, were performed., Results: Ocular examination showed blepharospasm, conjunctival hyperemia, symblepharon, total cicatricial corneal leucoma, severe dryness, trichiasis, and eyelid edema. The results of medical and surgical treatment are reported., Conclusions: Given the serious clinical picture, possibly due to a late diagnosis, it was not possible to avoid relapse and appearance of new cicatricial adherences for which we considered wait and see the most appropriate approach, protecting the anterior segment of both eyes, sacrificing their function. Further follow-up was not possible as the patient died. An early diagnosis would have had a significant influence on the clinical course and on the response to therapy.

Ocular mucous membrane pemphigoid presents some of the most challenging dilemmas in anterior segment management. Diagnosis is made difficult by the insensitivity of immunopathological investigations and the differential diagnosis of other scarring conjunctival disorders. The management of the associated ocular surface disease involves control of blepharitis, dry eye, filamentary keratitis, keratinization, lid malposition, and persistent epithelial defect, as well as the identification and avoidance of toxicity. Inflammation associated with the underlying disorder demands the use of systemic immunosuppressive therapy in many patients. New biological immunotherapies have been used when conventional immunosuppressive therapies fail. Ophthalmic plastic surgery is essential for the management of lid malposition and corneal exposure. Improving vision may require the use of specialized contact lenses, cataract surgery, and corneal and ocular surface reconstructive surgery. All surgery must be integrated with ocular surface treatment and immunosuppressive treatment to avoid disease exacerbations.

Treatment of mucous membrane pemphigoid (MMP) aims at reduction of conjunctival inflammation by means of systemic immunosuppression. In addition, cicatricial progression and management of the resulting ocular surface disease requires topical conservative or surgical measures. The former includes systemic immunosuppression with steroids and other immunosuppressive agents: dapsone in mild to moderate disease and cyclophosphamide in severe cases have been established in two randomized trials. Other agents such as methotrexate, azathioprine, mycophenolate mofetil or monoclonal antibodies including daclizumab or rituximab were found to be effective in uncontrolled small studies. Surgery is primarily focused on eyelid problems such as entropium and trichiasis. Ocular surface disease and secondary complications, e.g. cataract formation and glaucoma, may need surgical treatment. Any surgery is associated with the risk of a relapse of inflammation and should be postponed until inflammation is controlled by systemic therapy. Management of MMP patients requires close collaboration of a specialized ophthalmologist with specialists from dermatology and internal medicine.

Background: The mainstay of therapy of autoimmune mucocutaneous blistering diseases has been prolonged high-dose systemic corticosteroids and immunosuppressive agents. Recently, high-dose intravenous immunoglobulin (IVIg) has been employed in selected cases, with excellent results in most of them., Objective: We sought to evaluate the outcome of the use of IVIg in patients with autoimmune mucocutaneous blistering diseases refractory to conventional therapy or with contraindications for it., Methods: We performed a retrospective analysis of clinical response to monthly cycles of IVIg in 19 patients affected with autoimmune mucocutaneous blistering diseases: 10 patients with pemphigus vulgaris (PV), 2 with pemphigus foliaceus (PF), 4 with mucous membrane pemphigoid (MMP), 2 with epidermolysis bullosa acquisita, and one with linear IgA bullous dermatosis., Results: Four (21%) of 19 cases presented a complete response (2 PV, 1 MMP and 1 epidermolysis bullosa acquisita). Five (26%) patients did not respond to the treatment (3 PV, 1 PF, 1 MMP). Ten patients (53%) had a partial response., Limitations: This was a retrospective noncontrolled study with a heterogeneous group of patients., Conclusion: The effectiveness of IVIg was inferior to that previously reported. This difference could be attributed to the preparations employed, the different severity of the disease, or individual responses in each patient dependent on Fc receptor gamma polymorphisms.