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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]

Although relatively uncommon, autoimmune bullous diseases carry the risk of increased mortality and can significantly impact quality of life. This group of diseases is broad and encompasses subepidermal conditions such as bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis, and linear IgA bullous dermatosis, as well as intraepidermal conditions such as pemphigus and its variants. The pathophysiology of each condition is incompletely understood but broadly involves the formation of autoantibodies targeting skin adhesion proteins, a process that relies on a complex interplay between a dysregulated immune system, genetic predisposition, and environmental factors. We review the impact of nutrition on pathogenesis, clinical course, and treatment of various autoimmune bullous diseases. [ABSTRACT FROM AUTHOR]

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. [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]

Cicatricial Pemphigoid is a subepithelial bullous dermatosis which essentially involves the mucous membranes with cicatricial evolution We report the case of a 66-year old patient hospitalized with erosive gingivitis associated with dysphagia, dyspnea and blurred vision. Dermatologic examination showed erosive lesions involving the palate and the pharynx. Ophthalmologic examination showed symblepharons, ectropion and bilateral cataract. Gingival biopsy revealed a necrotic detachment of the buccal epithelium. Direct immunofluorescence showed linear IgA deposit at the dermo-epidermal junction. Indirect immunofluorescence test was negative. The diagnosis of cicatricial pemphigoid was confirmed. Esophagogastroduodenoscopy objectified double stenosis of the esophagus. Nasopharyngeal and bronchial endoscopy showed ulceration of the epiglottis, hypopharynx, pharynx and bronchial tree. The patient was treated with Solumedrol bolus corresponding to 0.5mg/kg/day prednisone associated with 100mg/day disulone. The patient showed a favorable early clinical outcome complicated because of the aggravation of dysphagia and esophageal stenosis after 2 months. Our case study is singular due to the occurrence of a cicatricial pemphigoid in a male patient with a serious clinical picture due to lesions extending to conjunctival, oral, nasal, esophageal and bronchial mucous membranes associated with direct immunofluorescence only showing IgA deposit. [ABSTRACT FROM AUTHOR]

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]

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]

Introduction. Mucous membrane pemphigoid (MMP) is a rare autoimmune disease, characterized by subepithelial bullae healing with scar, usually occurring in elderly patients. The clinical picture may be variable and blisters or erosions may be present in the oral cavity, conjunctiva, pharynx, larynx, oesophagus, the genitourinary tract and occasionally on the skin. Objective. Presentation of two patients with MMP due to the rare involvement of mucous membranes of the oral cavity and oesophagus, and additionally the scalp. Case reports. The first case is an 86-year old patient with long-term ocular MMP, in whom in spite of remission of ocular lesions, extensive ulceration in the fronto-parietal area of the scalp without a tendency to heal appeared after several years of MMP duration. The second case concerns a 75-year old patient treated for many years due to ocular cicatricial pemphigoid with good response. However, later in the disease course blisters occurred on the skin, mucous membranes of the oral cavity and oesophagus, resulting in swallowing difficulties. Conclusions. These cases were presented due to the rare involvement of mucous membranes of the oral cavity and oesophagus, and additionally the scalp. [ABSTRACT FROM AUTHOR]

Cicatricial pemphigoid (CP) (new name: mucous membrane pemphigoid, MMP) is a rare bullous autoimmune-related disorder which affects mainly people over 60 years old. Antibodies IgG against a basement membrane of an epidermis are detected in the serum, and deposits of IgG and complement C3 are visible in the direct immunofluorescnece test. Damage results in bullae at the dermo-epidermal junction, which are cicatrized. Blisters are found usually on mucous membrane, but they may also appear on dermis. Ophthalmic lesions that may sometimes result in blindness belong to the most characteristic features of the disorder. A difficult-to-diagnose case of a 70 year old woman who developed cicatricial pemphigoid has been reported. [ABSTRACT FROM AUTHOR]

Cicatricial pemhigoid (CP) also named mucous membrane pemphigoid (MMP) is a rare bullosus disease, which usually affecting elderly patients. Subepithelial blisters especially localized on the mucous membrane of the mouth and the eyes. The esophagus and the genitals are involved occasionally. The diagnosis is made on the basis of clinical and immunological features. In the article we present two cases of cicatricial pemphigoid with esophageal strictures. Because of this the patients required immunosupresive and chirurgical treatment. The male patient presented lesions in the rare for cicatrical pemphigoid localizations such as the skin and the genitals. Both patients had typical ocular scars. [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]

Abstract: Autoimmune mucocutaneous blistering diseases (AMBD) are an interesting group of rare diseases that affect the mucous membranes and the skin and are frequently or potentially fatal. The clinical presentation is significantly variable, as is the course and prognosis. The immunopathology is well characterized and the target antigens to which the autoantibodies are directed have been studied by various investigators. A significant majority of the patients respond to conventional therapy, which consists of high-dose long-term systemic corticosteroids and immunosuppressive agents. This treatment program has significantly improved the prognosis in many patients. In such patients, significant side effects of the drugs may appear and produce a very poor quality of life. In patients with progressive diseases, especially those with mucous membrane pemphigoid, the significant sequela; such as blindness, aphonia, and stenosis of the anal and vaginal canals can occur. In several patients treated with conventional immunosuppressive therapy, death occurs as a consequence of prolonged immune suppression leading to opportunistic infections. In this manuscript, the published data on the use of immunoglobulins intravenous (IGIV) in patients with AMBD is presented. The most important features of IGIV in patients with AMBD are: 1) the ability to clinically control the disease; 2) the ability to induce and maintain a long-term clinical remission; 3) a lower incidence of side effects; and 4) a higher quality of life. The important characteristic of the IGIV therapy in the AMBD is two-fold. First, the therapy, when given according to a published protocol, produces a lasting and long-term clinical remission, rather than a temporary arrest of the disease. Second, the therapy, as described in the protocol, has a very definitive endpoint. Consequently, once the patients are treated and go into long-term remission, the therapy is no longer required. The significant positive results obtained with IGIV are to a large extent also due to the associated aggressive topical therapy that was used and the frequent use of sublesional injections with triamcinolone. The rapid and early detection of cutaneous and mucosal infections and their treatment with systemic antibiotics is also a very important feature of IGIV therapy. When patients are under long-term conventional therapy, the infections are often not detected because they lack the ability to mount signs of inflammation. It is also becoming increasingly clear for patients to have a successful outcome, in treatment with IGIV therapy, it is critical that the physician spends a significant amount of time with each patient, monitor the therapy closely, and be familiar with the overall health of the patient. It is also best if the therapies are instituted by a physician who has significant interest and experience in blistering diseases and IGIV therapy. [Copyright &y& Elsevier]

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]

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]

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1) presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2) entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3) presence of conventional immunosuppressive therapy at the time of ocular involvement; (4) a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16–30) in group A and 45 months (range 21–90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0–4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0–1.5, P < 0.05). Both groups of patients were studied during the same time period.The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed. [Copyright &y& Elsevier]

Background: Anti-laminin 5 cicatricial pemphigoid (CP) is a mucosal-dominant subepithelial blistering disease characterized by IgG anti-basement membrane zone autoantibodies, that bind to dermal side of 1 M NaCl split skin and immunoprecipitate laminin 5. Laminin 5 is an epidermis-specific extracellular matrix consisting of α3, β3 and γ2 subunits. Recent studies have suggested that autoantibodies of anti-laminin 5 CP recognize the G domains of α3 subunit. Objective: We examined the reactivity of anti-laminin 5 CP by immunoblotting using purified laminin 5 and recombinant proteins of α3 subunit. Method: We first examined the reactivity of anti-laminin 5 CP by immunoblotting using purified laminin 5. To further investigate the epitopes in the G domains of α3 subunit, we produced recombinant proteins of G1–2, G1–3, G2–3, G3–5 domains, that covered entire G domain, and examined the reactivity of anti-laminin 5 CP sera with these recombinant proteins by immunoblotting. Results: By immunoblotting using purified laminin 5, 7 of 21 anti-laminin 5 CP sera reacted with α3 subunit, while 8 sera reacted with β3 subunit and one serum reacted with γ2 subunit. Two sera reacted with both α3 and β3 subunits, while seven sera did not show positive reactivity. This result indicates that the reactivity of anti-laminin 5 CP sera is much more heterogeneous, although the previous studies suggested that most sera reacted with α3 subunit. However, in the studies using recombinant proteins of G domains of α3 subunit, none of the CP sera, including the sera reactive with α3 subunit in purified laminin 5, reacted with any recombinant proteins. The reason for this negative reactivity with the recombinant proteins is not clear. Conclusion: The immunoblotting using purified laminin 5 should be useful technique for the diagnosis of anti-laminin 5 CP, although the sensitivity was less than conventional immunoprecipitation analysis. [Copyright &y& Elsevier]

Background: cicatricial pemphigoid and bullous pemphigoid are characterized by circulating autoantibodies to the hemidesmosomal protein, BP180. Different clinical features between cicatricial pemphigoid and bullous pemphigoid appear to correlate with distinct target epitopes on BP180. Previous studies demonstrated that the majority of bullous pemphigoid sera react with immunodominant membrane-proximal non-collagenous domain (NC16a) on the extracellular portion of BP180, whereas cicatricial pemphigoid antibodies are directed to the C-terminal domains of BP180. However, the fine sites within the C-terminal domain of BP180 recognized by autoantibodies in patients with cicatricial pemphigoid and bullous pemphigoid have not yet been clearly elucidated. Objectives: the aim of the present study was to analyze the fine specificity of the reactivity within the C-terminal domain of BP180 for the autoantibodies in sera from patients with cicatricial pemphigoid, and to compare the reactivity with that of bullous pemphigoid sera. Methods and results: we generated three recombinant proteins with 101 amino acids, which together cover the C-terminal domain of BP180. We confirmed that cicatricial pemphigoid sera mainly react with most C-terminal portion, whereas bullous pemphigoid sera react with more N-terminal domains. Conclusion: this study implicated that autoantibodies of sera from patients with cicatricial pemphigoid and bullous pemphigoid reacted differently within C-terminal domain of BP180. [Copyright &y& Elsevier]

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]

In human and canine patients with mucous membrane (cicatricial) pemphigoid (MMP), circulating autoantibodies have been shown to target multiple epidermal basement membrane antigenic epitopes. These autoantigens include collagen XVII in humans and dogs, as well as laminin-5, laminin-6 or integrin alpha-6/beta-4 in human beings. The purpose of this study was to determine if autoantibodies targeted laminin-5 in a cat exhibiting clinical and microscopic lesions resembling those of MMP in humans. In this patient, an indirect immunofluorescence (IF) assay revealed circulating IgG and IgA autoantibodies that bound to the basement membrane zone on the dermal side of salt-split gingiva (titer 1:1000 for IgG and 1:50 for IgA). Immunoblotting, performed with affinity-purified human laminin-5, demonstrated that the autoantibodies bound the alpha-3 chain of this heterotrimer. These observations identify laminin-5 as one of the antigens recognized by circulating autoantibodies in this feline homologue of MMP in humans and dogs. [Copyright &y& Elsevier]

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is an autoimmune mucocutaneous, blistering disease which can lead to blindness and/or death from sudden asphyxiation, secondary to a scarring process. Conventional therapy for the treatment of MMP consists of high-dose systemic corticosteroids and/or immunosuppressive agents. Some patients do not respond to these treatments and develop multiple serious side effects, which can be potentially fatal. In such patients, alternative treatment modalities are needed. This study presents the use of intravenous immunoglobulin (IVIg) therapy in 15 patients with severe MMP whose disease was nonresponsive to the prolonged use of high-dose systemic corticosteroids and immunosuppressive agents and who developed multiple side effects to them. All 15 patients received an IVIg dose of 1–2 g/kg/cycle. The following objective parameters were used to assess the clinical outcome pre- and post-IVIg therapy: number of side effects, frequencies of recurrences and relapses, duration and total dosage of prednisone therapy, and the quality of life. The differences in these variables between the pre- and post-IVIg data were statistically analyzed using the SAS UNIVARIATE software running the two-sided Wilcoxon signed-rank and sign tests. A statistically significant difference was observed between pre- and post-IVIg therapy data when comparing the aforementioned variables. All 15 patients had an effective clinical response, were able to discontinue previous systemic therapies, and eventually achieved a prolonged clinical remission. IVIg improved the quality of life in all 15 patients and demonstrated a steroid-sparing effect. No serious side effects were observed. IVIg therapy is a safe and effective alternative modality in the treatment of patients with nonresponsive and progressive MMP and can induce a sustained clinical remission. [Copyright &y& Elsevier]

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 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]

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]

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]

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]

Vulvar cicatricial pemphigoid is a rare variant of bullous pemphigoid, which is characterized by isolated and localized vulvar involvement, observed in childhood. The typical clinical finding is erosive lesions of the vulva healing with scar formation. Ocular involvement may be associated with vulvar disease or may develop during the follow-up. On histopathologic examination of the lesions, subepidermal blister and on direct immunofluorescence study, linear deposition of Ig G and C3 are observed. The differential diagnosis includes lichen sclerosus and, sexual abuse should be considered at first. Topical and systemic steroids and dapsone are the main treatment options. Ophthalmological examination and follow-up should be repeated on every six months for ocular involvement. Here, we report development of vulvar cicatricial pemphigoid in an 11-year-old girl with clinical and histopathological findings. [ABSTRACT FROM AUTHOR]

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]

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.