Blistering Diseases (blistering + disease)

Distribution by Scientific Domains

Kinds of Blistering Diseases

  • autoimmune blistering disease
  • subepidermal blistering disease

  • Selected Abstracts

    Genetic variation in COL17A1 and the development of bullous pemphigoid

    Samantha Winsey
    Background: Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin characterized by autoantibody attack on collagen XVII. Objectives: To characterize the genetic complexity of COL17A1, the gene which encodes for the autoantigen collagen XVII. The data will be used to determine whether there is an association between polymorphisms and haplotypes of COL17A1 and genetic susceptibility to development of BP. Methods: The genetic complexity in COL17A1 was deduced by screening and then sequencing the gene. Haplotypes were constructed from the resulting polymorphisms using the statistical programme PHASE. The linkage disequilibrium (D,) between the polymorphisms was deduced from haplotypic data using the statistical programme GOLD. Association of the polymorphisms and haplotypes was tested for, in a cohort of BP patients and controls. Results: Screening of COL17A1 for genetic variation was carried out in 29 individuals of North European caucasoid origin, and it revealed 19 single-nucleotide polymorphisms in approximately 14.7 kb of sequence. These variants resulted in 60 different haplotypes in 191 individuals, of which 13 occurred above 1% in the population. D, between the variants was found to be extensive, have a low correlation with physical distance and to extend over 33.8 kb. No association was found with any of the polymorphisms or haplotypes and development of BP, when tested for, in a cohort of patients and controls. Conclusion: This study provides an extensive description of the genetic variation in COL17A1 and shows no association of the genetic variants with susceptibility to BP. [source]

    What's new in bullous pemphigoid

    Hideyuki UJIIE
    Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP patients have autoantibodies against type XVII collagen (COL17, also called BP180 or BPAG2), a type II transmembrane protein that spans the lamina lucida and projects into the lamina densa of the epidermal basement membrane. The non-collagenous 16A domain of COL17 is considered to contain pathogenic epitopes of BP. The transfer of immunoglobulin (Ig)G from BP patients fails to cause blisters on mouse skin probably due to differences between humans and mice in the amino acid sequence of NC16A pathogenic epitope of COL17. Passive transfer of rabbit IgG antibodies against the murine homolog of human COL17 NC16A triggers immune reactions to COL17 in mice, including complement activation, mast cell degranulation and neutrophilic infiltration, resulting in dermal,epidermal separation. Recent studies using COL17-humanized mice that express human COL17 but lack murine COL17 were the first to demonstrate the pathogenicity of anti-COL17 human BP IgG autoantibodies in vivo. These new findings provide a greater understanding of BP pathomechanisms and facilitate the development of novel specific and efficient therapeutic strategies for BP. [source]

    Immunoglobulin A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in a patient with atypical bullous pemphigoid

    Fumi YAMAKI
    Abstract Bullous pemphigoid is an autoimmune subepidermal blistering disease associated with autoantibodies against BP180 and BP230. We report herein a rare case of bullous pemphigoid with newly formed annular erythematous lesions when bullous skin lesions were in remission. Various immunological studies revealed immunoglobulin (Ig)A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in addition to IgG antibodies against BP180 and BP230. These clinical and immunological changes in a patient are a rare event, suggesting an epitope-spreading phenomenon. [source]

    Anti-p200 pemphigoid: A novel autoimmune subepidermal blistering disease

    Amrei DILLING
    ABSTRACT Anti-p200 pemphigoid is a recently defined autoimmune subepidermal blistering disease characterized by circulating and tissue-bound autoantibodies to a 200-kDa protein (p200) of the dermal,epidermal junction (DEJ). This DEJ constituent is thought to be important for adhesion of basal keratinocytes to the underlying dermis. While the exact identity of p200 remains unknown, it has been demonstrated to be immunologically and biochemically distinct from all major autoantigens of the DEJ, including bullous pemphigoid antigens 180 and 230, laminin 1, 5 and 6, ,6,4 integrin, and type VII collagen. Clinically, most reported cases present with tense blisters as well as urticarial papules and plaques, closely resembling bullous pemphigoid. Histopathological examination of lesional skin biopsies shows subepidermal split formation and superficial inflammatory infiltrate typically dominated by neutrophils. Immunopathologically, linear deposits of immunoglobulin (Ig)G and C3 are detected along the DEJ by direct immunofluorescence microscopy of perilesional skin. Indirect immunofluorescence microscopy of patients' sera on NaCl-split human skin demonstrates circulating IgG autoantibodies labeling the dermal side of the split. By immunoblotting, these autoantibodies recognize a 200-kDa protein of human dermis. Biochemical characterization of the p200 molecule revealed a noncollagenous N-glycosylated acidic protein with an isoelectric point of approximately 5.5. We present an overview of the pathogenesis, clinical features, diagnosis and treatment of this new disease entity. [source]

    Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

    N. Oyama
    Summary 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%), ,4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) ,4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to ,4 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. [source]

    Increased activity of plasma and tissue kallikreins, plasma kininase II and salivary kallikrein in pemphigus foliaceus (fogo selvagem)

    T.B. Rosatelli
    Summary Background, Pemphigus foliaceus (PF) is an autoimmune blistering disease of unknown aetiology, which is endemic in Brazil. Although the pathogenesis of PF is still unknown, proteins of the contact system have been implicated. Objectives, As the components of the kinin system may interact with those of the contact system, in this study we evaluated the plasma levels of high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK), and the activity of plasma kallikrein, tissue kallikrein and kininase II in plasma of patients with PF presenting with Nikolsky's sign. As kidneys and salivary glands are relevant sources of tissue kallikrein for plasma, we also evaluated urinary/salivary kallikrein and urinary kininase II activities. Methods, Fifteen patients and 15 age- and sex-matched controls were studied. Kininogen levels were determined by enzyme-linked immunosorbent assay, and the activities of kallikreins and kininase II were determined using selective chromogenic substrates. Results, Compared with controls, plasma HK levels were decreased (P = 0031), whereas the activities of plasma kallikrein, tissue kallikrein and kininase II in plasma, and the activity of salivary kallikrein, were increased in patients (P < 0001 for each comparison). Plasma levels of LK and the activities of urinary kallikrein and urinary kininase II were not significantly different from controls. Conclusions, Diminished levels of HK associated with increased activities of plasma kallikrein and kininase II indicate that the kinin system is activated at the systemic level in PF. As active plasma kallikreins may act on some proteins of the contact system, it is possible that the enzyme may contribute to blister formation. The further observation of an increased tissue kallikrein activity at the systemic and saliva levels may be interpreted as a systemic reflex of skin inflammation. Whether the activation of the kinin system is a cause or a consequence of blister formation needs further clarification. [source]

    A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice

    M. Aoki-Ota
    Summary Background, Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3,/, mice to Rag2,/, immunodeficient mice that expressed Dsg3. Objectives, We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3,/, mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. Methods, We adoptively transferred naive Dsg3,/, splenocytes into Rag2,/, mice and compared their PV phenoytpe with those mice receiving immunized Dsg3,/, splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. Results, Mice that received naive Dsg3,/, splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3,/, mice were essential for the production of anti-Dsg3 IgG antibodies. Conclusions, Dsg3-specific naive lymphocytes in Dsg3,/, mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets. [source]

    Plectin, an unusual target antigen in bullous pemphigoid

    E. Laffitte
    Background Bullous pemphigoid (BP) is a blistering disease associated with autoantibodies directed against two components of hemidesmosomes, BP180 and BP230. Objectives To assess whether BP patients have autoantibodies targeting plectin, another hemidesmosomal component showing extensive homology to BP230. Methods Examination of sera from 16 patients with BP, using immunoprecipitation studies followed by immunoblotting. Results Serum of one of the 16 (6%) patients with BP contain autoantibodies binding to plectin, while no reactivity was found with sera from three control subjects. Sera from all 16 BP patients immunoprecipitated BP230 from extracts of biosynthetically radiolabelled human keratinocytes. Conclusions Our results indicate that sera from BP patients might contain autoantibodies binding to plectin. Although this protein and BP230 are closely sequence-related, the occurrence of autoantibodies binding to plectin is a rare phenomenon in BP. [source]

    A review of high-dose intravenous immunoglobulin (hdIVIg) in the treatment of the autoimmune blistering disorders

    S. Jolles
    High-dose intravenous immunoglobulin (hdIVIg) is being used increasingly for dermatological indications. Its mode of action is via a number of proposed mechanisms and it is not associated with the many side-effects of steroids and other immunosuppressive agents. The evidence for using hdIVIg in the treatment of autoimmune bullous disorders is based on uncontrolled trials and case reports. However, there are now 62 reported patients and this review aims to make a critical assessment of the current data. This has been obtained from a Medline search of the English literature from 1966 to 2000 for pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, pemphigoid gestationis, cicatricial pemphigoid, epidermolysis bullosa acquisita and linear IgA disease. Taken together hdIVIg was effective in 81% of the patients with blistering disease. Patients appear to be more likely to respond when hdIVIg is used as adjunctive therapy (91% response rate) than as monotherapy (56% response rate). hdIVIg may offer a safe potential therapeutic avenue for resistant cases of the autoimmune bullous disorders but should be further assessed using double-blind placebo-controlled trials. [source]

    Long-term efficacy of biologics in dermatology

    Leslie Castelo-Soccio
    ABSTRACT Chronic dermatologic diseases affect millions of people. The long-term nature of these diseases creates psychological and financial burden as well as substantially impacts patients' quality of life. Biologics, including adalimumab, etanercept, alefacept, efalizumab, and infliximab, are the newest therapeutic agents in the treatment of moderate-to-severe psoriasis and psoriatic arthritis and have been used in a variety of other dermatologic diseases. These agents act relatively quickly and effectively in 12-week clinical trials. Because these agents are used to treat patients for longer than 12 weeks, there is a need to review the safety and efficacy of these agents over longer periods of time. Many levels of evidence are available for biologics including high level of evidence from large, randomized, double-blind, placebo-controlled clinical studies. This review focuses on the available data for efficacy and safety for greater than 24 weeks of therapy. The studies supporting the use of rituximab and intravenous immunoglobulin in autoimmune blistering diseases are also presented in this review. [source]

    Glucocorticoids in the treatment of bullous diseases

    Danielle M. DeHoratius
    This article reviews recent advances in the treatment and management of bullous diseases with glucocorticoids. Since the 1950s, when oral cortisone acetate was introduced for the treatment of dermatologic disease, glucocorticoids have remained an important treatment modality. In particular, glucocorticoids are very effective for patients with autoimmune diseases because of their anti-inflammatory and immunosuppressive properties. However, patients with these diseases are often treated with prolonged courses of glucocorticoids, and consequently are at risk for steroid-induced side effects. In this article we present an in-depth discussion of the indications for glucocorticoid treatment in autoimmune blistering diseases. In addition, we discuss how to recognize, treat, and prevent side effects that result from the use of glucocorticoids. [source]

    Inhibitors of purine and pyrimidine synthesis: mycophenolate, azathioprine, and leflunomide

    Daniel Mimouni
    The major goal in the treatment of autoimmune blistering diseases has changed from simply keeping the patient alive to suppressing disease while maintaining quality of life and minimizing drug side effects. Researchers and clinicians are constantly seeking steroid-sparing agents that would allow a dose reduction in corticosteroids with no loss of benefit. Purine and pyrimidine base inhibitors are commonly used for this purpose. These drugs act by inhibiting cell division and inducing cell death. The pharmacologic and clinical aspects of azathioprine, mycophenolate mofetil, and leflunomide are discussed in this review. [source]

    Animal models for autoimmune bullous dermatoses

    Katja Bieber
    Abstract:, Autoimmune bullous dermatoses are a group of severe diseases, which are clinically characterized by blisters and erosions of skin and/or mucous membranes. In order to investigate the pathogenesis of these potentially life-threatening diseases and to develop more specific therapeutic approaches, animal models have been developed that aim to reproduce the clinical, histological and immunopathological findings. We here review established and novel animal models of autoimmune skin blistering diseases and discuss their applications and limitations. [source]

    Mechanisms of blister induction by autoantibodies

    Cassian Sitaru
    Abstract:, Autoimmune diseases are characterized by defined self-antigens, organ specificity, autoreactive T cells and/or autoantibodies that can transfer disease. Autoimmune blistering diseases are organ-specific autoimmune diseases associated with an immune response directed to structural proteins mediating cell,cell and cell,matrix adhesion in the skin. While both autoreactive T and B cells have been detected and characterized in patients with autoimmune blistering diseases, current evidence generally supports a pathogenic role of autoantibodies for blister formation. The immunopathology associated with blisters induced by autoantibodies relies on several mechanisms of action. Autoantibodies from patients with pemphigus diseases can exert a direct effect just by binding to their target mediated by steric hindrance and/or by triggering the transduction of a signal to the cell. In most subepidermal autoimmune blistering conditions, in addition to the binding to their target antigen, autoantibodies need to interact with factors of the innate immune system, including the complement system and inflammatory cells, in order to induce blisters. Generally, decisive progress has been made in the characterization of the mechanisms of blister formation in autoimmune skin diseases. However, various aspects, including the exact contribution of steric hindrance and signal transduction for pemphigus IgG-induced acantholysis or the fine tuning of the inflammatory cascade triggered by autoantibodies in some subepidermal blistering diseases, still need to be addressed. Understanding the mechanisms by which autoantibodies induce blisters should facilitate the development of more specific therapeutic strategies of autoimmune blistering diseases. [source]

    Upregulation of P-cadherin expression in the lesional skin of pemphigus, Hailey-Hailey disease and Darier's disease

    Megumi Hakuno
    Background: Autoimmune blistering diseases, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are known to be caused by binding of autoantibodies to the desmosomal cadherins, desmoglein 3 and desmoglein 1, respectively. Recently, mutations in the genes coding Ca2+ pumps leads to inherited blistering diseases, Hailey-Hailey disease (HHD) and Darier's disease (DD). Cadherins are a family of Ca2+ -dependent cell adhesion molecules and P-cadherin is one of the major cadherins expressed in the epidermis. Although detailed mechanisms of acantholysis of these blistering diseases have not been fully clarified, abnormal expression of cadherins caused by altered Ca2+ concentration due to the binding of autoantibodies to cell surface or by mutations in Ca2+ pumps is suggested to be involved in mechanisms of acantholysis of these atuoimmune and inherited blistering diseases. The purpose of the present study was to determine whether altered P-cadherin expression is present in these diseases. Method: Distribution patterns of P-cadherin in skin specimens from patients with PV (n=2), PF (n=2), HHD (n=4) and DD (n=3), were examined with confocal laser scanning microscopy using two anti-P-cadherin antibodies, 6A9 and NCC-CAD-299. Results: In normal control skin, P-cadherin expression was restricted to the basal layer. In contrast, positive immunostaining of P-cadherin was observed not only in the basal cells, but also in the suprabasal cells in lesional skin of all the acantholytic diseases. Conclusions: The present results clearly demonstrated that upregulation of P-cadherin expression occurs in the acantholysis in all the four blistering diseases PV, PF, HHD and DD. Upregulation of P-cadherin may be involved in the pathomechanism of both the autoimmune blistering diseases and the inherited blistering diseases. [source]

    Catenin dislocation in oral pemphigus vulgaris

    Michele Davide Mignogna
    Abstract: Cell-to-cell adhesion is mediated by cadherins (integral membrane proteins), which form a complex with catenins (cytoplasmatic proteins). While E-cadherin expression has been extensively studied in many human skin diseases, less is known about the expression levels of catenins in oral blistering diseases. The purpose of this study was to evaluate the role of these proteins in the pathogenesis of acantholysis in oral pemphigus vulgaris. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 7 cases of oral pemphigus vulgaris (PV) at various stages of the disease and, as controls, in 18 healthy patients. Healthy cases showed, as reported in the literature, a strong reactivity with both beta- and gamma-catenins, with the intensity of staining progressively decreasing from the spinous to the keratinised layers of epithelium, which had a prevalent cellular membrane expression. In PV patients, we detected a loss of membrane expression of these molecules with a progressive displacement of the signal toward the cytosol and, for gamma-catenin, nuclear dislocation, particularly in areas with intense acantholysis. [source]

    PL1 Subepithelial bullous diseases , topic overview

    ORAL DISEASES, Issue 2006
    M Mravak-Stipeti
    Subepithelial bullous diseases comprise the group of mucocutaneous autoimmune blistering diseases characterized by subepithelial separation and the deposition of immunoglobulin and complement against several antigens along the basement membrane zone (BMZ). This result in spectrum of diseases that affect skin, oral mucosa, and other mucosal membranes and include bullous pemphigoid (BP), mucous membrane (cicatricial) pemphigoid (MMP), linear IgA disease (LAD), and chronic bullous dermatosis of childhood (CBDC). The most common clinical features are oral erosions, desquamative gingivitis and conjunctival fibrosis, as well as skin lesions, predominantly in older female population. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. In addition to the clinical presentation and a subepithelial vesicle or bullae on routine histologic analysis, the diagnosis is based on direct and indirect immunofluorescence studies. The nature of the disease is determined by the target antigens in the epithelium and BMZ such as antigen 180 (BP180), antigen 230 (BP230), laminin 5, and beta 4 integrin. Circulating IgG and IgA antibodies bind to different epitopes of BP180. The use of salt-split skin substrate enables differentiation between epidermal and dermal 'binders'. Since the antigen and the antibody titer appear to have direct relationships with the disease severity, and a combination of clinical finding and antibody titer provides valuable prognostic data, these investigations should be carried out routinely. Clinicians should recognize clinical spectrum of SBD, the histopathologic and immunopathologic characteristics, the differential diagnosis, the treatment, and the natural history of the disease. Involvement of oral medicine specialists, dermatologists, ophthalmologists, otolaryngologists and gastroenterologists contribute to early diagnosis and will aid in providing SBD patients with the highest quality of care. [source]

    Number III Mucous membrane pemphigoid

    ORAL DISEASES, Issue 4 2005
    J Bagan
    Mucous membrane pemphigoid (MMP) is a sub-epithelial vesiculobullous disorder. It is now quite evident that a number of sub-epithelial vesiculobullous disorders may produce similar clinical pictures, and also that a range of variants of MMP exist, with antibodies directed against various hemidesmosomal components or components of the epithelial basement membrane. The term immune-mediated sub-epithelial blistering diseases (IMSEBD) has therefore been used. Immunological differences may account for the significant differences in their clinical presentation and responses to therapy, but unfortunately data on this are few. The diagnosis and management of IMSEBD on clinical grounds alone is impossible and a full history, general, and oral examination, and biopsy with immunostaining are now invariably required, sometimes supplemented with other investigations. No single treatment regimen reliably controls all these disorders, and it is not known if the specific subsets of MMP will respond to different drugs. Currently, apart from improving oral hygiene, immunomodulatory,especially immunosuppressive,therapy is typically used to control oral lesions. The present paper reviews pemphigoid, describing the present understanding of this fascinating clinical phenotype, summarising the increasing number of subsets with sometimes-different natural histories and immunological features, and outlining current clinical practice. [source]

    Angina bullosa haemorrhagica: presentation of eight new cases and a review of the literature

    ORAL DISEASES, Issue 1 2002
    M Giuliani
    Angina bullosa haemorrhagica (ABH) describes the acute and sometimes painful onset of oral blood-filled vesicles and bullae not attributable to blood dyscrasia, vesiculo-bullous disorders, systemic diseases or other known causes. The haemorrhagic bullae spontaneously burst after a short time resulting in ragged, often painless, superficial erosions that heal spontaneously within 1 week without scarring. Although the pathogenesis is still unclear, ABH seems to be a multifactorial phenomenon: dental or functional trauma seems to be the major provoking factor. The lesions of ABH can be easily confused with other mucosal diseases. It is important that the presentation of this benign disorder is distinguished from other more serious disorders with similar presenting features. The aim of this paper is to report the clinical features of eight cases of ABH, in an attempt to distinguish ABH from other blistering diseases of oral mucosa and to describe their management. [source]

    Antiplectin autoantibodies in subepidermal blistering diseases

    J.J.A. Buijsrogge
    Summary Background, Hemidesmosomal proteins may become targets of autoimmunity in subepidermal blistering diseases. Well-known recognized autoantigens are the intracellular plaque protein BP230, the transmembrane BP180 and its shed ectodomain LAD-1. Objectives, To establish the prevalence of autoimmunity against plectin, another intracellular plaque protein, and to investigate its antigenic sites. Methods, Two hundred and eighty-two patients with subepidermal blistering diseases, investigated by routine immunoblot analysis for possible antiplectin antibodies, were included in the study. Epitope mapping was performed using recombinantly produced overlapping plectin domains from the actin-binding domain to the rod domain. The COOH-terminal region of plectin was not included in the study. Results, In 11 of 282 (39%) patients an immunoblot staining pattern identical to that of antiplectin monoclonal antibody HD121 was found. Affinity-purified antibodies bound back to normal human skin in a pattern typical for plectin, i.e. to the epidermal basement membrane zone as well as to keratinocytes in the epidermis, and to myocytes. No binding was seen to plectin-deficient skin of a patient with epidermolysis bullosa simplex with muscular dystrophy. Epitope mapping of the plectin molecule showed that the central coiled-coil rod domain is an immunodominant hotspot as 92% of the sera with antiplectin antibodies reacted with it. Most patients with antiplectin antibodies also had antibodies to other pemphigoid antigens. Conclusions, Plectin is a minor pemphigoid antigen with an immunodominant epitope located on the central rod domain. [source]

    An evaluation of the usefulness of mycophenolate mofetil in pemphigus

    A.M. Powell
    SummaryBackground Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. Objectives The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. Methods Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. Results Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. Conclusions We found that MMF permitted a reduction in prednisolone dosage without disease relapse. [source]

    Rituximab in refractory autoimmune bullous diseases

    E. Schmidt
    Summary Treatment of autoimmune blistering diseases consists of systemic glucocorticosteroids usually in combination with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators such as dapsone, antibiotics, intravenous immunoglobulins, and immunoadsorption. In some patients, these treatment regimens are not sufficient to control disease activity and/or lead to intolerable adverse events. Rituximab, originally developed for the treatment of non-Hodgkin's lymphoma, is an anti-CD20 humanized monoclonal antibody leading to transitory B-cell depletion. For this indication, rituximab is widely employed, and severe side-effects rarely observed. Subsequently, the B-cell-depleting effect of rituximab has been exploited successfully in various autoimmune disorders, including autoimmune blistering diseases. Here, we review the effect of rituximab in such diseases. To date, application of rituximab has been reported in 26 treatment-resistant patients with the vulgaris, foliaceus, and paraneoplastic variants of pemphigus as well as in bullous pemphigoid and epidermolysis bullosa acquisita. All but a single patient showed clinical improvement with reduction of lesion formation. In about a third, a clinical remission requiring further immunsuppressive medication was achieved, and in about a quarter, complete remission was induced. In addition, the mode of action and adverse events of rituximab as well as adjuvant immunosuppressive treatments, and the effect on levels of circulating autoantibodies in these patients are discussed. [source]