Subepidermal Bullous Disorder Research Articles

Patterns of Periodic Acid–Schiff Staining in Subepidermal Bullous Disorders with Emphasis on Bullous Pemphigoid

Abstract Background: Direct immunofluorescence (DIF) including salt split skin technique is quintessential in the diagnosis of subepidermal bullous disorders. These techniques are expensive and require technical expertise, limiting their diagnostic utility. The property of periodic-acid–Schiff to stain the basement membrane and the patterns produced by it was observed in a cohort of subepidermal bullous disorders, to see if it offers an alternative cost-effective testing method. Materials and Methods: This was a retrospective, observational study conducted in the department of general pathology, in a tertiary care medical center, over a period of 4 years. Only those cases for which paraffin sections, DIF and direct salt split skin immunofluorescence technique were available were included. The levels of anti-bullous pemphigoid (BP) antibodies were collected where available. Results: Of the 21 cases analyzed, 15 were BP, two each of epidermolysis bullosa acquisita (EBA) and lichen planus pemphigoides (LPP), one each of porphyria cutanea tarda (PCT), and bullous systemic lupus erythematosus (SLE). All the cases of BP, LPP and EBA showed a floor pattern of staining with periodic acid–Schiff (PAS) stain. Roof pattern of staining was observed in bullous SLE and PCT. PAS was found to be useful in diagnosing BP, especially in conjunction with an eosinophil rich bulla and anti-BP antibodies. Conclusion: We found that PAS stain could be an adjunct to hematoxylin and eosin stain when the diagnosis of BP is in doubt. However, larger sample size is needed to study its utility in other subepidermal bullous disorders.

Anti-interleukin 4 receptor α antibody for the treatment of Chinese bullous pemphigoid patients with diverse comorbidities and a 1-year follow-up: a monocentric real-world study.

Bullous pemphigoid (BP) is a common subepidermal bullous disorder that lacks adequate treatment alternatives. Dupilumab, an anti-interleukin (IL) 4 receptor α antibody blocking Th2 molecules IL-4 and 13, has been used off-label and shown to be effective in refractory BP cases. BP patients with various disease severities and comorbidities were included in this case series. All patients received dupilumab alone or in combination with immunosuppressants in a real-world setting. Complete remission (CR) was defined as the absence of pruritus symptoms and previous BP eruptions, with only hyperpigmentation patches and without newly occurring lesions for at least 4 weeks. Disease relapse was classified as the appearance of three or more new lesions within 1 month or at least one large urticarial or eczematous lesion that did not resolve within a week. Ten individuals were enrolled in this case series. Pruritus symptoms and BP eruptions improved significantly in nine patients (90%). Seven patients (70%) attained CR, including all mild-to-moderate (100%) cases and three of six (50%) severe BP cases. At the dupilumab monotherapy stage, eosinophilia was observed in two severe cases. One patient out of seven (14.3%) relapsed after 1 year of follow-up after CR. Treatment of BP with diverse comorbidities with anti-IL-4 receptor α antibody provides further credentials to a prospective randomized study. More impressive efficacy and safety profiles were observed in patients with mild-to-moderate disease after 1 year of follow-up. Eosinophilia may occur in patients receiving dupilumab monotherapy.

Immunobullous Disorder: A Diagnostic Dilemma Faced at a Tertiary Care Centre in Kanyakumari, Tamil Nadu, India

Introduction: Immunobullous disorders are morphologically heterogenous and hence the differentiation between various subtypes is essential for proper treatment and prognosis. Prompt diagnosis needs clinicopathological concordance added with Immunofluorescence (IF) in particular Direct Immunofluorescence (DIF) study to avoid discrepancies. Aim: To study the clinicopathological profile along with immunological features and to analyse the utility of IF in particular DIF of immunobullous disorders. Materials and Methods: The present study was a single institution based cross-sectional observational hospital study done in the department of pathology in SreeMookambika Institute of Medical Sciences, Tamil Nadu over a period of one year (July 2019-August 2020) involving 70 outpatients in the department of dermatology with clinical evidence of bullous disorders. Two biopsies were taken from the patient, one from a newly formed bulla or vesicle for Haematoxylin and Eosin (H&E) stain and the other from a perilesional normal looking skin for DIF study. Statistical analysis was done by using SPSS software. Chi-square test was used for statistical analysis. A p-value of less than 0.05 was considered as statistically significant. However, the final diagnosis was arrived after considering clinical, bedside investigations, histopathology and DIF study. Results: Out of seventy (70) patients included in this study, the most common age group of distribution was between 51-60 years in a frequency of 22 (31.4%). Out of 70 patients, 39 patients were diagnosed with intraepidermal bullous disorders and 31 patients were diagnosed with subepidermal bullous disorders. The most common disorder diagnosed was based on clinical findings was Pemphigus Vulgaris (PV) 31 (44.3%) followed by Bullous Pemphigoid (BP) 23 (32.9%). The common disorder diagnosed based on histopathology was PV 33 (47.1%). Clinical and histopathological concordance was conclusive in 31 cases of PV. The percentage of diagnosis of DIF was positive in 67 (95.71%). Patients which reached to inconclusive (DIF was not definite) diagnosis was in only three patients. Conclusion: Since, in most of the cases there occurs an overlap in clinical and histopathological features, IF in particular, DIF plays a sensitive tool in confirming diagnosis as well as distinguishing immunobullous disorders from other disorders.

Utility of the pattern-based approach using BIOCHIP-indirect immunofluorescence in the evaluation of subepidermal bullous disorders.

Subepidermal bullous disorders (SEBD) are a heterogeneous group of vesiculobullous diseases because of antibody-mediated destruction of proteins of the dermo-epidermal junction. Direct immunofluorescence (DIF) is the gold standard for diagnosis. BIOCHIP-indirect immunofluorescence (IIF) is a novel serological test that combines multiple target antigens in a single field. The present study aimed to evaluate the utility of the pattern-based approach in BIOCHIP-IIF for the diagnosis of SEBD. Seventy cases of BIOCHIP-IIF that showed clinical, histopathological, and/or DIF features favoring SEBD were included in the study. The interpretation in the BIOCHIP was categorized into one of the following patterns. Pattern I: basement membrane zone (BMZ) staining in monkey esophagus (ME), primate salt-split skin (SSS)-roof staining, BP180+ and/or BP230+; Pattern II: roof staining in SSS, BP180- and BP230- with or without BMZ staining in ME; Pattern III: floor staining in SSS, BP180- and BP230-; and pattern IV: negative in SSS and other substrates. The findings were correlated with histopathology and/or DIF. Fifty (71.5%) cases showed pattern I or the typical bullous pemphigoid (BP) pattern. Eight (11.4%) cases showed pattern II. Patterns III and IV were observed in seven (10%) and five (7.1%) cases, respectively. BP was the most common diagnosis in patterns I and II, while anti-p200 pemphigoid was most common in pattern III, as confirmed by immunoblotting. The sensitivity of pattern I in the diagnosis of BP was 96%. BIOCHIP-IIF showed a good correlation with DIF and histopathology in the diagnosis of SEBD. This can be used as a first-line investigation in case of bullous disorders.

Vesiculo-Bullous Eruption Following COVID Vaccination

Bullous pemphigoid (BP) is an autoimmune sub-epidermal bullous disorder with a complex etiopathogenesis, predominately affecting the elderly. We report a case of COVID vaccination- induced BP, in a 30-year-old previously healthy Indian male who presented with a 1month history of itchy generalized vesiculo-bullous eruption that developed 3 days after receiving the first dose of the COVID vaccination. Histological examination and direct immunofluorescence study showed a sub-epidermal blister with a dermal inflammatory infiltrate and linear epidermal staining of IgG and C3 along the basement membrane zone in an n-serrated pattern. Treatment with oral prednisolone and oral doxycycline resulted in significant improvement in his condition. To our knowledge, there are limited case reports to date particularly in the Middle-East, which describe BP triggered by COVID vaccination.

A retrospective study on clinical and demographic features of autoimmune vesiculobullous disorders from a rural tertiary care institute in Tamil Nadu

<p class="abstract"><strong>Background:</strong> Autoimmune vesiculobullous disorders are a heterogenous group of skin diseases in which autoantibodies are directed against cell adhesion molecules which are essential for the integrity of skin and oral mucosa. They are clinically characterized by the presence of vesicles, bullae or erosions over the skin and/ or mucosa depending on the antibodies involved. They are divided into intraepidermal and subepidermal based on the location of the bulla. Among intraepidermal bullous disorders, pemphigus vulgaris (PV) is most common. Bullous pemphigoid (BP) is the most common among the subepidermal bullous disorders. Although they occur worldwide, the incidence shows geographical variation. A retrospective study was carried out with the objective to analyse the clinical and demographic profile of patients with autoimmune vesiculobullous disorders among patients attending a tertiary care teaching hospital in a rural setup.</p><p class="abstract"><strong>Methods:</strong> A total of 137 case sheets were audited from the Medical Records Department of our institute. Details were collected and tabulated, compiled and analysed.<strong></strong></p><p class="abstract"><strong>Results:</strong> Out of the 137 cases studied, intraepidermal autoimmune vesiculobullous disorders accounted for 63.4% of cases, and subepidermal autoimmune vesiculobullous disorders accounted for 36.6% of cases. Out of the 137 cases, 74 patients (54%) were females, and 63 patients (46%) were males. Majority of the patients were in the age group of 51-60 years (29.9%), followed by 41-50 years (24.1%) and 61-70 years (17.5%).</p><p class="abstract"><strong>Conclusions:</strong> Pemphigus vulgaris was the most common among the intraepidermal autoimmune vesiculobullous disorders, and bullous pemphigoid was the most common among the subepidermal autoimmune vesiculobullous disorders.</p>

A role for auto-immunity in chronic rhinosinusitis? Lessons learned from sub-epidermal bullous disorders of the skin.

Chronic rhinosinusitis (CRS) is a frequent chronic condition, which has origins in complex interactions between genetic, immunological and microbial factors. The role of auto-immunity in CRS remains unclear, although recent studies have started to emerge in CRS patient refractory to maximal medical management. We discuss the possible auto-immunity link between CRS and other skin diseases, in particular acquired bullous dermatoses, and review the current evidence. We raise additional considerations for auto-immunity from both research and clinical standpoints.

Utility of Direct Immunofluorescence Studies in Subclassification of Autoimmune Sub-Epidermal Bullous Diseases: A 2-Year Study in a Tertiary Care Hospital.

Sub-epidermal bullous disorders belong to immunobullous diseases which develop as a result of autoantibody action against epidermal basement membrane proteins. Clinically, they are tense bullae and do not rupture easily. They are classified into various forms based on histopathology and direct immunofluorescence patterns. This study was undertaken to assess the incidence of various sub-epidermal bullous disorders and the utility of direct immunofluorescence in accurately classifying them, and to study the intensity and pattern of immunofluorescence in various sub-epidermal bullous disorders Material and Method: A 2-year study of 38 cases of sub-epidermal bullous disorders sent for direct immunofluorescence studies formed the study group. The specimens were processed as per standard protocols. The clinical details were obtained from case files and requisition sent for histopathological and direct immunofluorescence studies. Thirty-eight patients were diagnosed to have sub-epidermal bullous disorders over the period of 2 years. Twenty five cases of Bullous Pemphigoid, 5 cases of Dermatitis Herpetiformis, 3 cases of Linear IgA Bullous disorder, 2 cases of Bullous Systemic Lupus Erythematoses and 1 case each of Epidermolysis Bullosa Acquisita, Cicatricial Pemphigoid and Pemphigus Gestationis was diagnosed. Positive direct immunofluorescence was seen in 91.3% of the cases. Histopathology alone cannot classify sub-epidermal bullous disorders and direct immunofluorescence studies are mandatory in all of them. Bullous Pemphigoid needs to be distinguished from Epidermolysis Bullosa Acquisita which requires Salt split direct immunofluorescence studies. Dermatitis Herpetiformis, Bullous Systemic Lupus Erythematosus and Linear IgA Bullous disorder show more or less similar histological picture with neutrophilic microabscess. Direct immunofluorescence studies help in the majority of cases but further testing such as immunoblotting, immunoelectron microscopy or indirect immunofluorescence becomes essential in cases with overlapping features.

Childhood Epidermolysis Bullosa Acquisita: Confirmation of Diagnosis by Skin Deficient in Type VII Collagen, Enzyme-linked Immunosorbent Assay, and Immunoblotting.

Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disorder characterized by autoantibodies against Type VII collagen. It usually affects adults; childhood EBA is rare. We describe a 10-year-old girl presenting with recurrent tense blisters predominantly on legs, dorsa of hands and feet accompanied by oral erosions since the age of 5 years. Direct immunofluorescence (IF) microscopy showed linear deposition of IgG and C3 along the basement membrane zone (BMZ); indirect IF microscopy on salt-split skin revealed staining of IgG to the dermal side of the split. The patient's serum did not show BMZ staining in recessive dystrophic epidermolysis bullosa skin deficient for Type VII collagen, thus confirming autoantibody reactivity against Type VII collagen. Circulating antibodies against the immunodominant noncollagenous 1 domain of Type VII collagen were detected by ELISA and immunoblotting studies. The patient was treated with oral corticosteroids and dapsone with good improvement.

Heat shock protein 90 inhibition: A potential double- or triple-edged sword in the treatment of mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is a subtype of autoimmune subepidermal blistering diseases characterized by autoantibodies to structural components of the hemidesmosome primarily affecting mucous membranes. Inflammation-related progressive scarring can lead to serious complications, including blindness, and the disease may be associated with malignancy. Conventional immunosuppressive treatment is often insufficiently effective and limited due to side effects, warranting new therapeutic options ideally targeting both inflammation and extensively recalcitrant cicatrization. Heat shock protein 90 (Hsp90) is a cell stress-inducible chaperone required for the function of a large number of client proteins, and its pharmacological inhibition has proven to be effective and relatively safe in patients with cancer. Recent observations also suggest a promising role of Hsp90 as drug target in preclinical in vivo murine models of autoimmune diseases such as subepidermal bullous and fibrotic autoimmune disorders comprising epidermolysis bullosa acquisita and systemic sclerosis, respectively, which exhibit some pathophysiological features reminiscent of MMP. This article thus hypothesizes that Hsp90 blockade could represent a double-edged sword in MMP treatment by targeting pathogenic factors of inflammatory blister and fibrosis formation. Moreover, Hsp90 inhibitors could even be proclaimed as a triple-edged sword in case of an underlying malignancy. Future studies investigating the role of Hsp90 in MMP are needed to clarify whether Hsp90 inhibition could become a novel treatment approach for patients with this potentially devastating disease.

Unusual histological infiltrate in two cases of bullous mastocytosis

Aim To illustrate the unusual histology of bullous mastocytosis and to emphasise the importance of suspecting the diagnosis in infantile bullous disorders. The histopathology of bullous mastocytosis is known to show a monomorphic CD117 positive and metachromatic infiltrate under the blister. Method We observed two cases where H&E stains were misleading and only the clinical suspicion prompted a Giemsa stain. Result In the first case mast cells were not identified and their presence was not suspected by us on H&E stained sections. Further mast were not identified by us on H&E stained sections on review, even after we had identified them easily and in abundance on Giemsa stain. The predominant infiltrate mimicked lymphoid cells with few neutrophils and occasional eosinophils. The second case remarkably showed subepidermal oedema with abundance of neutrophils. Similar to the first case the mast cells were not identified on H&E stain and even on review. The histopathology in the second case had a differential of neutrophilic subepidermal bullous disorder. Conclusion Histo or immunohistochemical stains for mast cells should be done in all infantile blisters with lymphocyte-like or even with a predominantly neutrophilic infiltrate even if mast cells are not identified on H&E initially.

Bullous pemphigoid

Bullous pemphigoid (BP) is a relatively common autoimmune vesicobullous disease encountered in India. It is a subepidermal bullous disorder most commonly seen in the elderly and manifests as tense blisters on urticarial base, predominantly over flexures, and is associated with pruritus. The diagnosis can be confirmed by histology, direct and indirect immunofluorescence. Several new diagnostic techniques have also been developed. Treatment of BP is based on the extent and rate of progression of the disease. Several topical and systemic anti-inflammatory and immunosuppressive agents have been used with variable results.

Current Treatment of Autoimmune Blistering Diseases

Autoimmune bullous diseases are a heterogeneous group of disorders that can be subdivided according to the level of split formation in the intraepidermal blistering pemphigus diseases and subepidermal bullous disorders, latter including pemphigoid diseases, epidermolysis bullosa acquisita, and dermatitis herpetiformis. In the majority of autoimmune bullous disorders, disease activity can be sufficiently controlled by systemic corticosteroids in combination with further immunosuppressants/immunomodulants such as dapsone, doxycycline, methotrexate, azathioprine, or mycophenolate mofetil. In contrast, in pemphigus, mucous membrane pemphigoid, and epidermolysis bullosa acquisita, treatment is challenging and only in a minority of patients, conventional immunosuppressive therapy induces clinical remission. Since only a few years ago, only cyclophosphamide and high-dose intravenous immunoglobulin were available as potent second-line therapies. Meanwhile, immunoadsorption and the monoclonal anti-CD20 antibody rituximab have been established as further therapeutic options. Here, both conventional therapies and novel treatment regimens for autoimmune blistering diseases are discussed.

Mixed immunobullous disorder most consistent with the IgA-form of epidermolysis bullosa acquisita

We describe a case of non-scarring, generalized, cutaneous and mucosal subepidermal bullous dermatosis that is characterized histopathologically by a neutrophilic infiltrate and strong linear staining with both IgA and IgG along the basement-membrane zone. Autoantibodies to collagen VII of both the IgA and IgG4 subtypes were detected by indirect immunofluorescence test, which led led to a diagnosis of epidermolysis bullosa aquisita (EBA). EBA is a subepidermal bullous disorder that is mediated by autoantibodies, which are directed against type VII collagen. The distinct clinical presentations of EBA are reviewed and discussed in the context of the unique autoantibody profile of this case.

Therapieoptimierung bei schweren bullösen Autoimmundermatosen

Autoimmune bullous diseases are a heterogeneous group of disorders that can be subdivided according to the level of split formation in the intraepidermal blistering pemphigus diseases and subepidermal bullous disorders, latter including pemphigoid diseases, epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis. In the majority of autoimmune bullous disorders, disease activity can be sufficiently controlled by systemic corticosteroids in combination with further immunsuppressants/-modulants such as dapsone, doxycycline, azathioprine, mycophenolate mofetil, or methotrexate. In contrast, in pemphigus, mucous membrane pemphigoid, and EBA, treatment is challenging and conventional immunosuppressive therapy induces clinical remission only in a minority of patients. Until recently, only cyclosphosphamide and high-dose intravenous immunoglobulin (IVIG) were available as potent second-line therapies. Meanwhile, immunoadsorption and the monoclonal anti-CD20 antibody rituximab have been established as further therapeutic options. The present review focuses on efficacy, adverse events, treatment protocols, and mechanisms of action of IVIG, immunoadsorption, and rituximab in the treatment of severe and/or refractory patients with bullous autoimmune diseases.

Research in practice: diagnosis of subepidermal autoimmune bullous disorders

Subepidermal autoimmune bullous disorders are a heterogeneous group of diseases that are associated with autoantibodies to hemidesmosomal proteins (pemphigoid group, epidermolysis bullosa acquisita) or epidermal/tissue transglutaminase (dermatitis herpetiformis). Characterization of the target antigens has led to the description of novel entities such as anti-p200 pemphigoid and has greatly facilitated the diagnosis of these diseases. Precise identification of target antigens is of therapeutic relevance since treatment options may greatly differ between these disorders. By the use of various in vitro and in vivo systems, the pathogenic relevance of autoantibodies to different hemidesmosomal constituents, including BP180 (type XVII collagen), laminin 332 (laminin 5), alpha6beta4 integrin, and type VII collagen has been demonstrated. The translation of this basic scientific work has subsequently led to the development of specific autoantibody detection systems that are not only of diagnostic use but also allow the monitoring of circulating autoantibody levels during the course of the disease and thus are helpful in guiding treatment decisions in these patients.

Dermatose por IgA linear induzida pela gestação

A dermatose por IgA linear é doença bolhosa auto-imune subepidérmica rara, caracterizada pelo depósito linear de IgA na zona da membrana basal da epiderme. Nos relatos de gestação em pacientes com essa dermatose, nota-se sempre melhora do quadro clínico. Contrariando essas observações,é apresentado caso de dermatose por IgA linear induzida pela gestação, que demonstrou boa resposta terapêutica à dapsona e prednisona , sem complicações materno-fetais.

Severity and Phenotype of Bullous Pemphigoid Relate to Autoantibody Profile Against the NH2- and COOH-Terminal Regions of the BP180 Ectodomain

Bullous pemphigoid, the most common autoimmune subepidermal bullous disorder, is associated with autoantibodies targeting antigenic sites clustered within the extracellular domain of BP180. To investigate epitope and subclass specificity of autoantibodies in bullous pemphigoid, we developed an enzyme-linked immunosorbent assay utilizing baculovirus-expressed recombinant forms of the NH2- and COOH-terminal regions of the extracellular domain of BP180 and examined sera obtained from patients with active bullous pemphigoid (n=116) and controls (n=100). Ninety-three (80%) and 54 (47%) of the 116 bullous pemphigoid sera recognized the NH2- and COOH-terminal regions, respectively, of the extracellular domain of BP180. Detailed analysis demonstrates that (i) this novel enzyme-linked immunosorbent assay is highly specific (98%) and sensitive (93%) as 108 of 116 bullous pemphigoid sera reacted with at least one of the baculovirus-derived recombinants, (ii) in active bullous pemphigoid, autoantibodies against the NH2-terminus of the extracellular domain of BP180 were predominantly of the IgG1 class, whereas a dual IgG1 and IgG4 response to this region was related to a more severe skin involvement, (iii) autoreactivity against both the NH2- and COOH-terminal regions was more frequently detected in patients with mucosal lesions, and (iv) levels of IgG (and IgG1) against the NH2-terminal, but not against the COOH-terminal portion of the extracellular domain of BP180, reflected disease severity indicating that autoantibodies against the NH2-terminus are critical in the pathogenesis of bullous pemphigoid. In conclusion, this novel enzyme-linked immunosorbent assay represents a highly sensitive and specific assay for rapid diagnosis of bullous pemphigoid and related disorders and may provide predictive parameters for the management of bullous pemphigoid patients.

Clinical, histopathologic, and therapeutic aspects of subepidermal autoimmune bullous diseases with IgG on the floor of salt-split skin.

About 12% of patients with subepidermal autoimmune bullous disease and immunoglobulin G (IgG) at the dermal-epidermal junction present diseases other than bullous pemphigoid. We report the clinical, histopathologic, and therapeutic aspects of eight cases of subepidermal bullous disorder with IgG on the floor of salt-split skin. A predominant neutrophilic infiltrate was detected in six of the eight patients. In one patient, the inflammatory infiltrate was neutrophilic and eosinophilic in the same proportion. A good response to dapsone alone or combined with prednisone was observed in six patients. The salt-split skin direct immunofluorescence test is useful for its diagnostic and therapeutic implications.

IgG Autoantibodies from Bullous Pemphigoid Patients Recognize Multiple Antigenic Reactive Sites Located Predominantly Within the B and C Subdomains of the COOH-Terminus of BP230

Bullous pemphigoid is a subepidermal bullous disorder characterized by an autoantibody response against the bullous pemphigoid antigen 230 (BP230) and the bullous pemphigoid antigen 180 (BP180), a cytoplasmic component and a transmembrane component, respectively, of hemidesmosomes. Although immunodominant sequences within the extracellular domain of BP180 have been identified, characterization of the antigenic sites on BP230 is still incomplete. To identify autoantibody-reactive sites on BP230 and to examine whether the targeted regions are contained within functionally important domains, recombinant fragments encompassing almost the entire BP230 were used to assess the reactivity of 25 bullous pemphigoid sera by immunoblotting. Our results demonstrate that (i) the region bearing the B and C subdomains of the COOH-terminus of BP230 contains immunodominant sequences recognized by the majority of bullous pemphigoid sera; (ii) additional autoantibody- reactive sites are present over extended regions of the NH2-terminal half of BP230 without evidence for antigenic cross-reactivity between the NH2- and COOH-termini of BP230; and, finally, (iii) autoantibodies reacting with the BP230 tail predominantly belong to the IgG4 and IgG1 subclasses, suggesting that both autoreactive TH2 and autoreactive TH1 cells regulate the autoantibody response to immunodominant sequences of BP230. As the COOH- terminus of BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque, whereas its NH2-terminus contains sequences important for its interaction with other constituents of hemidesmosomes, autoantibodies to BP230 might precipitate subepidermal blister formation and perpetuate the disease not only by eliciting an inflammatory reaction but also by interfering with the function of BP230 and thus the stability of hemidesmosomes.