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Background and Aims: In the case of mucous membrane pemphigoid with gingival expression (gMMP), the complete healing of the gingiva is generally not achieved despite medical treatment. Therefore, patients' oral comfort is impaired. The dysbiotic periodontal microbiota, generated by a lack of oral hygiene associated with persistent gingival pain, could the immunopathological mechanism to persist. The main objective of this study was to characterize the subgingival microbiota of the gMMP patients, and to highlight a potential link between this microbiological data and the clinical data. Methods: Subgingival biofilm was collected from 15 gMMP patients, medically treated or not, but not receiving periodontal treatment. The usual clinical periodontal parameters were recorded. The biofilm was analyzed by polymerase chain reaction quantitative. The risk factors of severe erosive gingivitis and severe periodontitis were assessed using Chi‐square or Fischer's exact test were used. Results: Whatever the medical and periodontal conditions of the patients, the results showed the existence of three main communities of periodontopathic, dysbiotic bacteria. The first including Tannnerella forsythia, Peptostreptococcus micros, Fusobacterium nucleatum, and Campylobacter rectus, was found in 100% of the patients, the second enriched with Treponema denticola in 60% and the third enriched with Porphyromonas gingivalis and Prevotella intermedia in 26%. Furthermore, there was a significant positive link between the duration of gMMP and the severity of erosive gingivitis (p = 0.009), and the loss of deep periodontal tissue (p = 0.04). Conclusion: This pilot study suggests a high periodontal risk in gMMP patients. The pathological processes, autoimmune on the one hand and plaque‐induced on the other, may amplify each other. The application of periodontal therapy is therefore necessary in parallel with medical treatment. Nevertheless, further controlled studies are required to validate and complement these preliminary results. [ABSTRACT FROM AUTHOR]

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is a heterogeneous group of subepidermal blistering diseases that affect the mucous membranes, most frequently in the eye and oral cavity. MMP is often unrecognized or misdiagnosed in its early stages due to its rarity and nonspecific presentation. We present the case of a 69-year-old female in which MMP of the vulva was not initially suspected. The first biopsy, from lesional tissue for routine histology, revealed fibrosis, late-stage granulation tissue, and nonspecific findings. A second biopsy, from perilesional tissue for direct immunofluorescence (DIF), revealed DIF findings typical of MMP. Scrutiny of both the first and second biopsies revealed a subtle but telling histologic feature: subepithelial clefts along adnexae in the context of a scarring process with neutrophils and eosinophils, which can be an important clue to MMP. This histologic clue has been previously described; reinforcing its importance may prove useful for future cases, especially those for which DIF is not feasible. Our case demonstrates the protean presentations of MMP, the need for persistence in sampling unusual cases, and the relevance of inconspicuous histologic features. The report highlights this underrecognized yet potentially decisive histologic clue to MMP, reviews current biopsy guidelines when MMP is suspected, and delineates the clinical and morphological features of vulvar MMP. [ABSTRACT FROM AUTHOR]

Anti-laminin (LM) 332-type mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease and was originally discovered as anti-epiligrin cicatricial pemphigoid. Anti-LM332-type MMP has clinical manifestations similar to those of other types of MMP and can only be distinguished through the detection of circulating autoantibodies against LM332. Our group and others have established a number of immunological methods with varying sensitivity and specificity for detection of anti-LM332 autoantibodies; however, none of the established methods has been widely used for clinical diagnosis. There is currently no unified standard treatment, and it is very difficult to completely cure anti-LM332-type MMP. In addition, an increasing body of evidence suggests that there may be a strong correlation between anti-LM332-type MMP and tumors. In this article, we review the current progression of diagnosis and treatment of anti-LM332-type MMP, as well as the possible correlation between anti-LM332-type MMP and tumors. [ABSTRACT FROM AUTHOR]

Desquamative gingivitis (DG) is a clinical term that describes erythema, desquamation and erosions of the gingiva, of various etiologies. Although the clinical aspect is not specific for a certain disease, an accurate diagnosis of the underlying disorder is necessary because the disease course, prognosis and treatment vary according to the cause. DG may inflict significant oral discomfort, which is why patients typically present to the dentist for a first consultation, rendering it important for these specialists to be informed about this condition. Our paper aims to review the ethiopatogenesis and diagnostic approach of DG, focusing on the most common underlying disorders (autoimmune bullous dermatoses and lichen planus) and on the management of these patients. Potential etiological agents leading to an inflammatory immune response in the oral mucosa and DG appearance include genetic predisposition, metabolic, neuropsychiatric, infectious factors, medication, dental materials, graft-versus-host reaction and autoimmunity. A thorough anamnesis, a careful clinical examination, paraclinical explorations including histopathological exam and direct immunofluorescence are necessary to formulate an appropriate diagnosis. Proper and prompt management of these patients lead to a better prognosis and improved quality of life, and must include management in the dental office with sanitizing the oral cavity, instructing the patient for rigorous oral hygiene, periodic follow-up for bacterial plaque detection and removal, as well as topical and systemic therapy depending on the underlying disorder, based on treatment algorithms. A multidisciplinary approach for the diagnosis and follow-up of DG in the context of pemphigus vulgaris, bullous pemphigoid, cicatricial pemhigoid or lichen planus is necessary, including consultations with dermatologists, oral medicine specialists and dentists. [ABSTRACT FROM AUTHOR]

Dental management of patients with autoimmune vesiculobullous disorders is complicated because of prominent involvement of oral mucosa, increased risk of oral disease, and difficulty in rendering dental care. Although these diseases are relatively uncommon, dental practitioners should be familiar with the oral sequelae of these conditions and their management. Pemphigus vulgaris, cicatricial pemphigoid, and epidermolysis bullosa represent the most common autoimmune oral vesiculobullous diseases. This case-illustrated review summarizes the pathogenesis, diagnostic features, and natural history of oral vesiculobullous disorders, placing an emphasis on the treatment and prevention of associated oral disease aimed at maintaining a healthy, functional dentition. [ABSTRACT FROM AUTHOR]

Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital Würzburg. Twentyone patients (70%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid. [ABSTRACT FROM AUTHOR]

Copyright of Pan African Medical Journal is the property of Pan African Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mucous membrane pemphigoid has been documented previously in only 19 patients under the age of 20 years. We report a 14-year-old female who had erosions of the oral, ocular, anal and genital mucosa, congestion, hoarseness of voice, dysphagia, and recurrent cough. Symblepharon formation in both eyes necessitated surgical correction. Biopsy of tissue from a solitary cutaneous lesion demonstrated a subepidermal bulla. Direct immunofluorescence showed the deposition of IgG in linear pattern along the dermoepidermal junction. Therapy was begun, consisting of prednisolone at 1 mg/kg/day, in combination with dapsone at 2 mg/kg/day. Azathioprine was added later for control of the disease. The patient showed good clinical response. [ABSTRACT FROM AUTHOR]

Background: Mucous membrane pemphigoid (MMP) is considered an autoimmune blistering disease that predominantly affects mucous membranes. Various treatments are available for controlling the diseases, but not all of them may respond. Materials and Methods: PubMed and Google Scholar were searched for all the associated studies until 2015, using the keywords such as "cicatricial pemphigoid" or "ocular pemphigoid" or "mucous membrane pemphigoid" or "MMP" and "intravenous immunoglobulin" or "IVIg" to find all the relevant studies. The last search update was for September 2, 2015. Among the searched items, only English studies were included in the review. Results: After excluding nonrelevant studies, 13 studies with a total number of seventy patients with MMP who were under treatment with IVIg were analyzed. The 65 patients responded completely, one did not respond, two had partially responded, and the remaining two patients stopped IVIg therapy, which resulted in ocular cicatricial pemphigoid progression. Majority of the studies reported mild adverse effects while two of them did not report any unwanted side effect. The most common side effect was headache, followed by nausea. Most of the patients who had a cessation of IVIg therapy before achieving clinical remission experienced the disease progression. Conclusion: Overall, it can be concluded that IVIg therapy was very helpful in treatment of MMP patients who did not respond to conventional therapy or stopped using them for various side effects. Adverse effects associated with IVIg therapy were considerably lower than conventional therapy that can lead toward treatment with this agent in patients who suffer from severe side effects. [ABSTRACT FROM AUTHOR]

Uncommon bullous skin disorders including mucous membrane pemphigoid can sometimes involve the esophageal mucosa, but are not thought to be associated with esophageal neoplasia. A 57-year-old Caucasian woman with a history of refractory painful oral ulceration due to mucous membrane pemphigoid was found to have esophageal mucous membrane pemphigoid when her dysphagia and acid reflux symptoms were investigated. Repeated endoscopies with esophageal dilatation were performed for her recurrent stricturing esophageal mucous membrane pemphigoid. Five years after esophageal involvement was diagnosed, she developed squamous cell carcinoma of the oesophagus. Chronic inflammation of the squamous esophageal mucosal lining may explain the development of esophageal squamous cell carcinoma in esophageal mucous membrane pemphigoid. Gastroenterologists, endoscopists and dermatologists should be mindful of esophageal involvement in mucous membrane pemphigoid and a possible link with esophageal cancer. [ABSTRACT FROM AUTHOR]

Linear immunoglobulin A (IgA) dermatosis (LAD) is a rare autoimmune disorder that presents as a vesiculo-bullous lesion with cutaneous manifestations, but rare oral mucosal involvement. Here we discuss a case of a vesiculobullous lesion with severe oral and ocular mucosal involvement mimicking pemphigoid with histopathological evidence of subepithelial blisters. Direct immunofluorescence (DIF) confirmed the lesion as LAD of adult variant, although with atypical clinical features. [ABSTRACT FROM AUTHOR]

To analyze the control of intraocular pressure (IOP) with an Ahmed glaucoma drainage device (AGDD) in two groups of glaucoma patients-one with cicatricial ocular surface disease (COSD) and one with aniridia. This is a retrospective comparative case series of nine patients (11 eyes) with COSD and six patients (8 eyes) with aniridia who underwent AGDD surgery to control IOP. The main outcome measure in both groups was stability of IOP between 6 and 21 mmHg. Mean IOP decreased significantly in both groups after AGDD surgery (29.6 ± 8.7 vs 14.7 ± 2.5, p = 0.008 in the COSD group; 26.3 ± 8.2 vs 15.3 ± 5.8, p = 0.008 in the aniridia group). Over a mean post-surgery follow-up of 37.1 months in the COSD group, we managed to control IOP in nine eyes; IOP control was successful in 87 % of eyes at 12 months and 58 % of eyes at 26 months. Over a mean post-surgery follow-up of 37.4 months in the aniridia group, we managed to control the IOP in seven eyes; IOP control was successful in 87 % of eyes at 12 months. AGDD surgery had no significant deleterious effect on visual acuity in either group. A severe complication occurred in one eye (1/8) in the aniridia group (lost vision due to retinal detachment) and in one eye (1/11) in the COSD group (tube exposure). AGDD surgery is effective in controlling IOP and has a low complication rate in COSD and aniridia patients; however, some of the complications are severe and prompt management is needed to prevent deleterious results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mucous Membrane Pemphigoid, a new denomination of cicatricial pemphigoid, encompasses a group of chronic subepithelial autoimmune blistering diseases that predominantly affect the oral cavity and the eyes (conjunctivitis and symblepharon). CASE DETAILS: A rare case of Mucous Membrane Pemphigoid (MMP) in a human immunodeficiency virus (HIV) positive patient is discussed with clinicohistopathologicalpresentation. CONCLUSION: Since our patient was HIV-positive and had lesions restricted to the oral mucosa with ocular involvement, only topical and intralesional steroids were preferred as the first line of treatment. Systemic corticosteroid therapy raises a concern regarding immunosuppression. [ABSTRACT FROM AUTHOR]

Copyright of Dermatology Review / Przeglad Dermatologiczny is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mucous membrane pemphigoid (MMP) is an immune-mediated systemic disease affecting the mucosa of the mouth, eyes, nasopharynx, GI tract, genitalia and skin. Chronic inflammation and subepithelial blisters of the mucosa result in progressive scarring. Ocular MMP is characterized by a chronic cicatrizing conjunctivitis, which leads to symblepharon, entropion, trichiasis, severe dry eye, cornea ulceration and potential blindness when untreated. One of the most effective treatments for ocular MMP is the combination therapy of cyclophosphamide (administered for 12-18 months) and oral corticosteroids (tapered over 3-4 months). This regimen has proven effective in controlling conjunctival inflammation, halting mucosal scarring and preventing potential vision loss, and is typically used for severe disease. Long-term drug-free remission is achievable in patients with this regimen. For all immunosuppressive medications, careful monitoring for drug-related side effects is crucial. [ABSTRACT FROM AUTHOR]

Intravenous immunoglobulin has been used in the treatment of various dermatological conditions, including toxic epidermal necrolysis, bullous pemphigoid and pemphigus vulgaris. From March 2008, the National Blood Authority has implemented the 'Criteria for the clinical use of intravenous immunoglobulins in Australia'. The new criteria have formalized the eligibility requirements for several dermatological conditions. This may increase access to intravenous immunoglobulin for treatment for these conditions. However, there remain stringent eligibility criteria with which dermatologists need to be acquainted. In some conditions, dermatology review is mandated by these criteria while in other conditions with skin manifestations, referral to other specialists is required. The following article provides a summary of the salient points in relation to the clinical use of intravenous immunoglobulin in dermatology, as well as its production and supply in Australia. [ABSTRACT FROM AUTHOR]

Mucous membrane pemphigoid and pemphigus vulgaris are autoimmune blistering disorders in which many similar drugs and therapeutic strategies are utilized. In general, localized disease can be treated with topical agents. In contrast, patients with more severe and progressive disease usually require a combination of systemic corticosteroids and immunosuppressive medications. Oral corticosteroids, adjuvant immunosuppressive agents, antibiotics such as dapsone and immunomodulatory procedures like intravenous immunoglobulin are the main therapeutic agents used in treating these two disorders. Much of the morbidity and mortality associated with these disorders are related to the sites involved and to the drugs used for therapy. Treatment should be individualized based on severity, extent, and rate of progression of disease, comorbidities, and age of the patient. Serum levels of specific autoantibodies and indirect immunofluorescence titers, in certain cases, can be used to monitor response to therapy. [ABSTRACT FROM AUTHOR]

Background Antilaminin-332 mucous membrane pemphigoid (MMP) is a chronic autoimmune bullous disease that is often associated with internal malignancy. IgG autoantibodies against laminin-332 in patients with MMP are well documented; however, IgA and IgE autoantibodies against laminin-332 have not yet been described. Objectives To characterize IgA and IgE autoantibodies binding to laminin-332 in sera from patients with antilaminin-332 MMP. Methods Sera and skin samples from four patients who met the following criteria were used: (i) subepidermal blistering lesions present on the mucous membranes; (ii) in vivo deposition of IgG along the epidermal basement membrane zone of sampled skin; (iii) circulating IgG antibasement membrane zone antibodies that react with the dermal side of salt-split normal human skin; and (iv) circulating IgG autoantibodies that do not show positivity against type VII collagen or 200-kDa protein (p200 antigen) in immunoblot analysis using dermal extracts. Circulating IgG/IgA/IgE class autoantibodies against laminin-332 were determined by immunoblotting. Results Circulating IgG autoantibodies against the γ2, α3/γ2, α3 and α3/β3/γ2 subunits of laminin-332 were demonstrated in sera from four patients, respectively. Serum from one of the four patients showed IgA reactivity with the α3/β3/γ2 subunits of laminin-332. Serum from one of the four patients showed IgE reactivity with the γ2 subunit of laminin-332. The control sera failed to display IgG/IgA/IgE reactivity to laminin-332. Conclusions In addition to IgG autoantibodies, circulating IgA and IgE autoantibodies against laminin-332 are detectable in a subset of patients with antilaminin-332 MMP. [ABSTRACT FROM AUTHOR]

Background Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. Objectives To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Methods Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Results Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), β4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) β4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to β4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Conclusions Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cicatricial pemphigoid is the most common of the immunobullous disorders causing conjunctival cicatrization and is an autoimmune disease in which the ocular component of the immunopathology is directed at the conjunctival basement membrane. The disease is usually bilateral and more common in females, with most cases occurring between 30–90 years, and most often in the seventh decade. The disease occasionally occurs in children. Tear deficiency is a major cause of symptoms, although loss of vision is usually due to surface failure before the onset of aqueous tear deficiency, which occurs late in the progression of the disease. Management of the dry eye must be integrated with the management of the other components of both the ocular surface disease and inflammation. Management requires plastic surgery for the lid and lash malposition, tetracyclines and lid hygiene for the accompanying blepharitis. For the dry eye, the use of lubricants without preservatives is important, to avoid toxicity, and lubricant ointment is helpful for the relief of symptoms in terminally dry eyes without the capacity for surface wetting. Contact lenses, either large limbal diameter rigid gas permeable or gas permeable scleral lenses, are useful for treating dry eye and improving vision in some patients. Control of the conjunctival inflammation is mandatory to prevent disease progression and usually requires systemic immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Background: The progressive scarring observed in cicatricial pemphigoid (CP) is still partially unexplained but recently the release of soluble fibrogenic factors by inflammatory infiltrating cells has been considered as pathogenically relevant. In the present study we evaluated the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in CP in comparison to bullous pemphigoid (BP) patients, investigating the role of cytokine profile as possible cause of the different disease evolution.Methods: Biopsies from patients with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied by in situ hybridisation performing a new amplification system based on biotinyl-tyramide. As control, four patients affected by BP were also examined, together with healthy tissue from two CP and two BP patients, respectively.Results: In CP IL-4 mRNA expression was present in 4 out of 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, IL-4 hybridisation signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all BP cases. Healthy specimens did not show any expression for IL-4, IL-5 and IFN-gamma, while a poor staining for TGF-beta was found in epithelium and subjunctional areas.Conclusions: Our results highlight the presence of a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP suggest that the involvement of additional factors is responsible for the scarring course typical of CP. [ABSTRACT FROM AUTHOR]

Abstract: The process that induces chronic progressive scarring in cicatricial pemphigoid (CP), a rare group of autoimmune mucocutaneous blistering diseases, is still under investigation. The tendency to heal with scar formation observed in CP could be due to the specific localization of the antigen in the basement membrane zone or could depend on the frequent recurrence of the disease in a localized area. The release of soluble fibrogenic factors by inflammatory infiltrating cells has also been considered as pathogenetically relevant. The aim of this study is to evaluate the expression of mRNA for IL-4, IL-5, TGF-β1 , IFN-γ in patients with CP, and investigate the role of the cytokine profile as a possible cause of the clinical features and course of the disease. Fourteen patients (3 male, 11 female; age range 40–72 years) with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied. The formalin-fixed and paraffin-embedded biopsies were examined by in situ hybridization performing a new amplification system based on biotinyl-tyramide. As a control, 4 patients (2 male, 2 female; age range 58–73 years) affected by bullous pemphigoid (BP), the most common autoimmune subepidermal blistering disease, were also examined. In CP, IL-4 mRNA expression was present in 4 out of the 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-β1 and IFN-γ mRNAs were identified in 9 and 11 CP cases, respectively. In BP, an IL-4 hybridization signal could not be observed in any of the cases. By contrast IL-5, TGF-β1 and IFN-γ mRNA analyses were positive in all four BP cases. Our results suggest the presence of a T-cell population with a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, on the basis of the constant... [ABSTRACT FROM AUTHOR]

Background Different subepidermal autoimmune blistering skin disorders are characterized by linear deposition of IgA, sometimes accompanied by linear IgG, along the epidermal basement membrane zone. Identification of the targeted autoantigen is usually attempted by immunoblotting. Although immunoblotting works well for human IgG, the method is less successful for IgA and often no or only faint signals are obtained. Objectives To improve the method of immunoblotting for diagnosis of IgA-mediated bullous dermatoses. Methods Eleven sera, selected from patients with linear deposition of IgA along the epidermal basement membrane zone in vivo, were tested by immunoblotting for antigen specificity using different primary incubation temperatures. Results No reliable information regarding IgA antigen specificity was obtained when the primary incubation was undertaken at room temperature. In 10 of 11 sera, IgA bound to the 180-kDa bullous pemphigoid antigen (BP180) when the primary incubation temperature was increased to 37 °C. Conclusions Primary incubation at room temperature may result in false-negative results in the IgA–BP180 immunoblot assay. [ABSTRACT FROM AUTHOR]

Cicatricial pemphigoid is a heterogeneous group of autoimmune subepidermal blistering diseases associated most commonly with autoantibodies to bullous pemphigoid (BP)180 and less frequently with those to laminin 5 or type VII collagen. In addition, a few cases have been described with autoantibodies to the β4 subunit of α6β4 integrin. We describe a patient with extensive disease of ocular, oral, pharyngeal, laryngeal and genital mucous membranes that healed with scarring of conjunctivae. IgG autoantibodies bound to the dermal–epidermal junction on direct immunofluorescence (IF) microscopy and to the epidermal side of 1 mol L-1 NaCl-split skin on indirect IF microscopy. Our patient's circulating IgG recognized a 205-kDa protein in extracts of 293T cells transfected with the β4 subunit of α6β4 integrin and in the cell extract of DJM-1 cells. Our patient's IgG and IgA autoantibodies also reacted with full-length BP180 derived from epidermal extracts and the ectodomain of BP180 (LAD-1) derived from culture supernatant of keratinocytes. In addition, a weak IgG reaction with BP230 was noted. The disease rapidly responded to dexamethasone-cyclophosphamide pulse therapy, and immunoblot reactivity to both β4 integrin and BP180 decreased according to disease activity. [ABSTRACT FROM AUTHOR]

Background Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA-DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous membrane pemphigoid (MMP) using serological and DNA-based methods. Objectives To analyse the class I and II alleles expressed in well-defined clinical and immunopathological subgroups of MMP, in order to establish whether specific alleles or haplotypes might in part explain disease susceptibility, clinical sites of involvement or disease severity. Methods Subgroups of patients were analysed according to the following clinical criteria: age of onset, sex, sites of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal, oesophageal, laryngeal, perianal), disease severity and history of autoimmune disease. Subgroups were also analysed according to the following immunopathological criteria: autoantibody profile, the presence of circulating antibasement membrane IgG or IgA antibodies and the detection of target basement membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. Results Class I HLA typing showed no significant disease or subgroup associations. Class II DRB1 typing showed a significantly increased allelic frequency in MMP vs. controls for DRB1*11 (RR = 2·08, Pc < 0·0000056). For DQB1, MMP vs. controls, there was a significantly increased allelic frequency for DQB1*0301 (Pc < 0·00000028) in both males and females; all clinical sites of involvement, with the exception of laryngeal, oesophageal and perianal sites and in patients with detectable circulating anti-BMZ IgG compared with those negative for IgG (P < 0·0096, Pc < 0·019). A positive trend was noted in patients with ocular involvement compared with no ocular involvement and in patients with a clinical score >= 10 compared with < 10. We found no difference in DQB1*0301 allele frequency between subgroups with or without BP180 or BP230 target antigens. Haplotype frequencies... [ABSTRACT FROM AUTHOR]

Mucous membrane pemphigoid or cicatricial pemphigoid is a mucocutaneous blistering disease characterized by autoantibodies to different molecules in the basement membrane zone. Our objectives were to identify the target antigen recognized by sera from 20 untreated patients with pemphigoid disease limited to the oral cavity, and to determine the pathogenicity of autoantibodies in oral pemphigoid, with an organ culture model. We conducted indirect immunofluorescence, immunoblot, and immunoprecipitation assays, with accompanying absorption experiments, using normal human skin, conjunctiva and gingiva, bovine gingiva and a tumor cell line, which were reacted with sera from patients with oral pemphigoid, anti-α6 antibody, and control sera. Sera of oral pemphigoid patients selectively and specifically bound to human α6 integrin, a 120-kDa protein present in gingiva and the tumor cell line. Oral pemphigoid sera and anti-α6 antibody produced separation of epithelium from basement membrane (blister formation) of normal human buccal mucosa, after 48 hours, in organ culture. [ABSTRACT FROM AUTHOR]

Linear IgA disease (LAD) is an autoimmune subepidermal blistering skin disease characterized by the linear deposition of IgA at the dermoepidermal junction. Serum from patients with LAD most commonly contains autoantibodies that are directed against the hemidesmosomal transmembrane glycoprotein BP180 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoantibodies in different autoimmune bullous skin diseases, including bullous pemphigoid and cicatricial pemphigoid (CP). However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we used three recombinant GST fusion proteins, together roughly covering the entire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain. The strongest reactivity was observed with the C-terminal portion of BP180. This is also the major region recognized by autoantibodies in patients with CP. This finding correlates with the observation that there may be significant overlap of the clinical and immunopathological findings in LAD and CP. [ABSTRACT FROM AUTHOR]

Background Bullous pemphigoid (BP), linear IgA bullous dermatosis (LABD) and cicatricial pemphigoid (CP) are clinically distinct autoimmune bullous skin diseases characterized by autoantibodies against components of the epidermal basement membrane. Like most patients with BP, a significant subgroup of patients with CP has circulating IgG specific for BP180, a transmembraneous protein of hemidesmosomes. Moreover, sera of patients with LABD contain IgA autoantibodies reactive with a 97/120-kDa protein, LABD antigen 1, which is highly homologous to the extracellular portion of BP180. Objectives We aimed to determine whether, in these diseases, autoantibody reactivity to BP180 is restricted to distinct immunoglobulin subtypes. Methods Utilizing a baculovirus-encoded form of the ectodomain of BP180, sera from patients with BP (n = 10), CP (n = 9), LABD (n = 10) and normal human control sera (n = 10) were analysed by immunoblot for IgG, IgA and IgE reactivity against BP180. Results All of 10 BP sera displayed IgG, IgA and IgE reactivity with BP180. Six and seven of nine CP sera, respectively, contained IgG and IgA autoantibodies reactive with BP180, but none of nine sera contained BP180-specific IgE. Nine of 10 LABD sera contained IgA, and six of 10 IgG, which was reactive with BP180, but none of 10 sera showed IgE reactivity to BP180. Conclusions The presence of IgG and IgA autoantibody responses to BP180 in patients with three clinically distinct autoimmune bullous diseases indicates that an autoimmune response to the same distinct adhesion protein may lead to different clinical manifestations. It is therefore conceivable that variable epitopes of BP180 are targeted by the different autoantibody isotypes, resulting in the distinct clinical pictures. [ABSTRACT FROM AUTHOR]

Background Type XVII collagen promotes adhesion of basal keratinocytes to epidermal basement membrane, and is the target of disease in patients with certain inherited or acquired blistering diseases. Two forms of type XVII collagen are produced by cultured human keratinocytes: a 180-kDa full-length, transmembrane protein, and a recently identified 120-kDa soluble fragment that corresponds to its collagenous ectodomain. Objectives We aimed to determine the incidence and pattern of reactivity of autoantibodies against the 180- and 120-kDa forms of type XVII collagen in sera from 40 patients with bullous pemphigoid (BP), pemphigoid gestationis or cicatricial pemphigoid (CP), as well as six patients with linear IgA dermatosis (LAD). Methods Various immunochemical techniques were used. Results These studies found that the 120-kDa fragment of type XVII collagen was bound by circulating autoantibodies in 13 of 38 patients with BP or CP and all six patients with LAD. While many pemphigoid sera had specific reactivity against one but not both forms of this protein, autoantibodies from patients with LAD bound only the soluble ectodomain. Conclusions These findings are consistent with the presence of both neoepitopes and cross-reactive epitopes on the ectodomain of type XVII collagen. The finding that sera from patients with LAD showed specific reactivity to epidermal basement membrane suggests that such neoepitopes are present in human skin and that their targeting by autoantibodies may contribute to disease pathogenesis. [ABSTRACT FROM AUTHOR]

We describe two patients with severe oral cicatricial pemphigoid, one of whom also had severe pharyngeal involvement. Both patients were resistant to treatment with corticosteroids and other standard immunosuppressive therapies. Plasma exchange alone proved to be only temporarily effective, but the combination of plasma exchange with subsequent cyclophosphamide resulted in a remission in both patients. Both patients experienced mild side-effects during the plasma exchange treatment (urticaria and mild hypotension). At present, at follow-up of 6 and 9 years, respectively, the patients have no symptoms of active disease and have not required any further immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Localized vulval pemphigoid of childhood (LVPC) has previously been reported in six girls. Clinical features and immunopathological data have suggested it to be a morphological variant of bullous pemphigoid. Epitope targets of the autoantibodies of these patients have not been defined in detail. We describe a 9-year-old girl with possible cicatricial LVPC and circulating IgG antibodies directed against native collagen XVII/BP180, its 120-kDa soluble ectodomain and against the C-terminus of collagen XVII/BP180. No reactivity was detected towards the NC16A domain of collagen XVII/BP180. Linear IgG and C3 deposits were found along the cutaneous basement membrane zone. On 1 mol/L salt-split skin, IgG autoantibodies were shown to bind to the epidermis, and the HLA type II allele DQB1*0301, a marker with significantly increased occurrence in patients with ocular and oral cicatricial pemphigoid, was identified in this patient. Our data suggest that LVPC is a variant of bullous pemphigoid in which direct immunofluorescence microscopy combined with immunoblot analysis can deliver valuable diagnostic information for differential diagnosis. However, differentiation between the scarring and non-scarring course of the disease cannot be made with the present diagnostic markers and therefore careful follow-up of patients with LVPC is required. [ABSTRACT FROM AUTHOR]

We have recently shown in a cohort of patients (n = 67) with mucous membrane pemphigoid, 63 of whom had cicatricial pemphigoid (CP), that the presence of both IgG and IgA circulating antibasement membrane zone antibodies was associated with a more severe and persistent disease. In this study we sought to ascertain whether in CP, serial titres of IgG and IgA might provide a reliable marker of disease activity. Serum titres for IgG and IgA antibodies were assayed at 6- to 12-monthly intervals in 56 patients over 32.2 ± 20.3 (mean ± SD) months. Antibody titres were correlated with the clinical score recorded at each follow-up visit. Sequential titres for both IgG (P < 0.001) and IgA (P = 0.015) were significantly associated with variations in disease activity. Greatest improvement was seen in patients with the greatest change in either IgG or IgA antibody titre. We suggest that serial antibody titres may therefore be useful in the assessment and management of CP. [ABSTRACT FROM AUTHOR]

We describe five girls with vulval pemphigoid: two had bullous pemphigoid confined to the vulva and three had cicatricial pemphigoid. They demonstrate a spectrum of severity from localized disease to extensive vulval scarring necessitating long-term immunosuppressive therapy and surgical correction. The age at onset of their disease ranged between 6 and 13 years. All presented with vulval discomfort and erosions. Three had oral lesions, two perianal and one eye and cutaneous involvement. Two girls with only vulval lesions and one with vulval and oral lesions responded well to topical steroids. In two, systemic treatment with prednisolone and dapsone or azathioprine was required. The diagnosis was made on the basis of histology and immunofluorescence (IF). All had positive direct IF with IgG and C3. Indirect IF demonstrated circulating IgG binding to the basement membrane zone in four, with dermal or epidermal binding on salt-split skin substrate. Immunoblotting revealed antibodies to the BP230 and BP180 antigens. Immunoelectron microscopy in the child with dermal binding IgG and BP180 and BP230 on immunoblotting showed labelling at the lamina densa–lamina lucida interface adjacent to hemidesmosomes. [ABSTRACT FROM AUTHOR]

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease. [ABSTRACT FROM AUTHOR]

Bullous diseases of the oral mucosa and skin were originally classified on the basis of clinical and histological criteria. The discovery of auto antibodies in some of these patients and the introduction of molecular biology have resulted in a new understanding of the pathological mechanisms of many of the bullous lesions. In this article, updated topics of the immune-mediated bullous lesions which involve oral mucosa and skin are reviewed. Pemphigus antigens, which are desmosomal-associated proteins and belong to the cadherin superfamily of cell adhesion proteins, have been isolated, and their genes have been cloned. The antigens which react with auto antibodies from patients with bullous pemphigoid, cicatricial pemphigoid, acquired epidermolysis bullosa, and linear IgA disease are all proteins of the hemidesmosome basement membrane complex. Interestingly, most of the antigens also appear to be the target for mutations seen in patients with the inherited type of epidermolysis bullosa in which bullous lesions are a prominent clinical feature. [ABSTRACT FROM AUTHOR]

We present herein the exceedingly uncommon case of a patient with cicatricial pemphigoid (CP) who gradually developed conjunctival, oral, and esophageal involvement. Despite long-term medical management with dapsone and disulone, the ocular lesions progressed to produce further scarring, which led to ankyloblepharon, symblepharon, and ultimately, blindness of the right eye. After a period of 5 years the patient developed a total esophageal stricture, intractable by dilation, necessitating esophageal reconstruction. The details of an original procedure using a continuous colic loop are described, highlighting the better tolerance of this technique by a high-risk patient. A discussion on the recent advances in diagnosing bullous dermatoses is presented following this case report. [ABSTRACT FROM AUTHOR]

Background: Cicatricial pemphigoid (CP) (benign mucous membrane pemphigoid) is a rare, blistering disease of skin and mucous membrane. The disease rarely extends to involve the esophagus, and there are only a few cases reported in the radiological literature. The aims of this study were to document the frequency of esophageal involvement and to describe the findings on upper GI barium studies.Methods: A total of 197 patients with CP were seen at our institution from 1981 to 1991. The clinical and radiological findings of these patients were reviewed and compared with findings reported in the literature.Results: Esophageal involvement was documented in seven patients. Cervical esophageal webs were found in five of the seven patients. Two patients had single esophageal webs while three had multiple webs. Frank strictures of the esophagus were also seen in five patients. These were most common in the cervical esophagus, but strictures were also found in the mid and lower esophagus. Two of the strictures resulted in significant dysphagia and required multiple endoscopic dilatations. One of the dilatations was complicated by mucosal injury, and follow-up barium examination showed dissection of the esophageal mucosa from the cervical esophagus to the esophagogastric junction. One patient demonstrated intramural pseudodiverticulosis in the cervical esophagus. Functional disturbances demonstrated on barium studies included tracheal aspiration in two patients and nasopharyngeal reflux in three.Conclusions: CP involves the esophagus in approximately 5% of cases. The hypopharynx and cervical esophagus are most commonly involved, but any portion of the esophagus may be involved, and multiple levels of involvement may be seen. Cervical esophageal webs, often multiple or complex, are the most common appearance on barium studies, but frank strictures are also found. Secondary manifestations of esophageal involvement include nasopharyngeal reflux, tracheal aspiration, and intramural pseudodiverticulosis. [ABSTRACT FROM AUTHOR]

Two patients with clinical and laboratory evidence of co-existing lichen sclerosus and cicatricial pemphigoid are reported. Autoimmune bullous diseases affecting the vulva may mimic lichen sclerosus but in these two patients both diseases were present. These two diseases have not previously been reported simultaneously to date. [ABSTRACT FROM AUTHOR]

Mucous membrane pemphigoid describes a rare heterogeneous group of chronic, inflammatory, mucous membrane-dominated, subepithelial blistering diseases that manifest a varying constellation of oral, ocular, skin, genital, nasopharyngeal, esophageal, and laryngeal lesions. Life-threatening airway obstruction and sight-threatening ocular scarring can occur in this condition, which is rarely reported in Indian literature. Vitiligo is another acquired autoimmune disorder characterized by loss of melanocytes. Vitiligo is associated with a number of disorders also considered to be autoimmune. Here we report a very rare coexistence of MMP and vitiligo, the first such report from India. [ABSTRACT FROM AUTHOR]

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Objective:Cicatricial pemphigoid can affect all mucosa of the upper aerodigestive tract; however, hypopharyngeal involvement is less frequent.Case report:This paper presents a 69-year-old male diagnosed as having cicatricial pemphigoid who was experiencing difficulty swallowing. Videofluorography with barium swallow demonstrated narrow flow through the medial hypopharynx, but not through the lateral hypopharynx. Direct laryngoscopy revealed that the postcricoid hypopharyngeal lumen had become narrow due to circumferential scar formation. Interestingly, detached thin membranous webs were observed beyond the circumferential scar.Conclusion:This report describes important videofluorographic and direct laryngoscopic findings showing rare hypopharyngeal involvement in a case of cicatricial pemphigoid. [ABSTRACT FROM PUBLISHER]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cicatricial pemphigoid is a rare disease primarily affecting the elderly. Only a few cases of childhood cicatricial pemphigoid have been reported in the literature. We present a case of cicatricial pemphigoid involving the vulvar region in a child. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to anti-epiligrin cicatricial pemphigoid in the previous issue.

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. [ABSTRACT FROM AUTHOR]