BACKGROUND: Apoptosis, or programmed cell death, may participate with pathogenesis of intercellular detachment and loss of cell-matrix interaction. Autoimmune bullous dermatoses is an entity charaterized by bullous lesions of the skin and mucosa, and autoantibodies to the specific tissue components. OBJECTIVE: The purpose of this study was to investigate the induction of apoptosis in the lesional skin of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). METHODS: Hoechst 33342 (bisbenzimide) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was performed to determine the induction of apoptosis in the lesional skin of each disease. RESULTS: In PV and PF, typical findings of apoptosis were observed in the lesional epidermis showing acantholysis. However, in BP and EBA, no apoptosis of the epidermis was observed. CONCLUSION: These results suggest that apoptosis is only associated with acantholysis of the epidermal keratinocytes, one of many components of pathogenesis in bullous disease, in patients with pemphigus.
Acantholysis ; Apoptosis ; Autoantibodies ; Blister ; Cell Death ; Epidermis ; Epidermolysis Bullosa Acquisita* ; Epidermolysis Bullosa* ; Humans ; Keratinocytes ; Mucous Membrane ; Pemphigoid, Bullous* ; Pemphigus* ; Skin ; Skin Diseases, Vesiculobullous

BACKGROUND: Autoimmune blistering skin diseases such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid and epidermolysis bullosa acquisita substantially affect patients' daily life and psychosocial well-being. OBJECTIVE: The aim of this study was to evaluate the quality of life (QOL) in patients with autoimmune blistering diseases and to identify the factors that can influence their QOL by comparing them to healthy controls. METHODS: Forty patients with autoimmune blistering skin diseases and 40 healthy controls were interviewed using the Korean version of Skindex-29. The study assessed the clinical severity of the disease. RESULTS: The total, symptom, function, and emotion scores of Skindex-29 were significantly higher in patients with autoimmune blistering skin diseases (35.28, 40.78, 30.57, and 36.67, respectively) than in the healthy controls (6.90, 9.38, 5.47, and 6.60, respectively) (p<0.001). Higher disease severity had a negative correlation with QOL in patients with blistering skin diseases, and QOL was lower when patients had low levels of satisfaction with treatment. CONCLUSION: The results show that autoimmune blistering skin diseases can affect patients' QOL. In addition, disease severity and low satisfaction with treatment are important factors that reduce QOL. Development of new treatments should improve treatment efficacy and the QOL of patients with autoimmune blistering diseases.
Blister* ; Epidermolysis Bullosa Acquisita ; Humans ; Pemphigoid, Bullous ; Pemphigus ; Quality of Life* ; Skin Diseases* ; Skin Diseases, Vesiculobullous ; Treatment Outcome

BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare significant group of dermatoses that pose great challenges to the dermatologist. So far, few epidemiological surveys for the whole spectrum of ABDs have been completed in Korea, though many epidemiological survey have focused on single ABDs. OBJECTIVE: The aim of this study was to evaluate the incidence and clinical findings of patients in the Chonnam Province of Korea with ABDs over a 5 year period. METHODS: A retrospective analysis was conducted on 52 ABDs patients from 2002 to 2006. ABDs were diagnosed chiefly by histopathologic findings, immunofluoresence (IF), and immunoblotting with epidermal and dermal human foreskin extract. For the exact diagnosis of ABDs, several additional diagnostic methods such as indirect IF with salt-split normal skin, immunoblotting (IB) with normal keratinocyte cells, enzyme-linked immunosorbent assay (ELISA) with recombinant proteins, immunoprecipitaion (IP) were also performed. RESULTS: Out of 52 patients diagnosed with ABDs during the study period, pemphigus vulgaris was observed to be the commonest ABD (38.5%) followed by bullous pemphigoid (29.8%), pemphigus foliaceus (17.8%), epidermolysis bullosa acquisita (5.8%), paraneoplastic pemphigus, pemphigoid gestationis (3.8%), and linear IgA bullous dermatoses (1.9%). CONCLUSION: This study showed the incidence of the ABDs in Chonnam-Gwangju province area were very low (52 cases over 5 years) and was stationary over this period. Pemphigus vulgaris and bullous pemphigoid were common diseases among many ABDs. The incidence of ABDs in Korea as a whole needs to be investigated.
Enzyme-Linked Immunosorbent Assay ; Epidemiologic Studies ; Epidermolysis Bullosa Acquisita ; Female ; Foreskin ; Humans ; Immunoblotting ; Immunoglobulin A ; Incidence ; Keratinocytes ; Korea ; Pemphigoid Gestationis ; Pemphigoid, Bullous ; Pemphigus ; Recombinant Proteins ; Retrospective Studies ; Skin ; Skin Diseases ; Skin Diseases, Vesiculobullous

The clinical spectruni of epidermolysis bullosa acquisita(EBA) is much broader than originally thought. Although the full extent of the clinical presenation is still being defined, it is now known that EBA include the followings: a non-inflammatory mechanobullous condition equating wit,h classical EBA; an inflammatory vesiculosullous eruption mimicking bullous pernphigoid; and a mucosal-centered disease with sarring similar to cicatricial pemphigoid. Among the nine cases of EBA, aged between 34 to 70 year-old, seen in recent years, three patients had mechanobullous lesions with skin fragilities and scarrings; three patients had inflammatory bullous eruptions, and three other patient had combined features of mechanobullous/inflammatory bullous lesions. Mucous membrane lesions were recognized in sex cases, and the rnos! frequent site of involvement was the oral mucosae. According to observations of these patients episodes of inflammatory bullous eruptions appeared to be present in seven cases and have been considered as early sympoms of the disease. It has been noted, however, that in two cases lesions develop d as an non-inflammatory mechanobullous from thonset. Based on the ability of EBA to mimick bullous pemphigoid or cicatricial pernphogoid and the fact that such cases have perhaps been missed, we feel EBA is more common than past literature has suggested.
Aged ; Blister ; Cicatrix ; Epidermolysis Bullosa Acquisita* ; Epidermolysis Bullosa* ; Humans ; Mouth Mucosa ; Mucous Membrane ; Pemphigoid, Benign Mucous Membrane ; Pemphigoid, Bullous ; Skin

BACKGROUND: Pemphigus (P; pemphigus vulgaris, PV; pemphigus foliaceus, PF), bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are autoimmune blistering skin diseases induced by IgG autoantibodies. In some cases of these diseases IgA autoantibodies can be detected at the lesional skin as well as in the sera. OBJECTIVE: The aims of this study were to examine the frequencies of circulating disease-specific IgA autoantibodies in addition to IgG, in P, BP and EBA; possible clinical relevancies in connection with the presence of IgA autoantibodies in the sera were also reviewed with the patients in each disease. PATIENTS/METHODS: Twenty new patients of the individual diseases who showed positive indirect immunofluorescence findings of IgG were selected. Immunoblotting and multi-step immunostaining were performed ('amplified alkaline phosphatase immunoblot' preparations [Bio-Rad BRL]) with patients' sera using tissue antigens of A431 cell culture-extracts. RESULTS: Among the above 20-patient groups in P, 7 cases (PV 3, PF 4) were positive for serum IgA autoantibodies. In BP and EBA, 4 cases and 16 cases were positive for circulating IgA autoantibodies, respectively. Between the positivity-rate found in each category, patients with EBA showed a significant high positive frequency of 80% as compared with others having P or BP (p>0.045). There were no statistically significant clinical correlations between the serologic findings of IgA-positivities and the clinical expressions of the diseases including mucous membrane involvements in each disease (p>0.3). CONCLUSIONS: The frequency-rates of dual expressions of autoantibodies, IgG and IgA, were relatively lower in patients with P (35%) and BP (20%) than those patients with EBA showing a significant high rate (80%). Clinical relevancies with the presence of serum IgA autoantibodies were not seen in this study, perhaps indicating further immunopathological and clinical evaluations might be necessary to define the role of IgA autoantibodies in each disease.
Alkaline Phosphatase ; Autoantibodies* ; Blister ; Epidermolysis Bullosa Acquisita* ; Epidermolysis Bullosa* ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoblotting ; Immunoglobulin A* ; Immunoglobulin G ; Mucous Membrane ; Pemphigoid, Bullous* ; Pemphigus* ; Skin ; Skin Diseases ; Skin Diseases, Vesiculobullous

BACKGROUND: In autoimmune bullous dermatoses, such as pemphigus and bullous pemphigoid, variations in the expression of the antigen in different body locations are recognized. OBJECTIVE: The degree of expession of epidermolysis bullosa acquisita (EBA) antigen in different sites on the body surface was estimated from the highest dilution factor of EBA sera that gave a positive reaction at a site by indirect immunofluorescence (IF). METHODS: Two sera, obtained from EBA patients with inflammatory and mechanobullous skin lesions, having antihody titers of 160 against the dermal component of the NaCl split skin, were used by indirect IF techniques with 20 specimens (2 from each of 10 locations) of normal human skin from different sites. These 20 skin samples were obtained from 10 healthy adults (1-3 from each individual). RESULTS: The greatest expression of the antigen was in the skin taken from the upper back with the titer of 160. EBA antigen was least recognized in skin specimens from the inner thigh and calf. Skin from the scalp, abdomen, and anterior chest and others demonstrated intermediate degrees of expression. CONCLUSION: There was some moderate degree of variation in the expression of EBA antigens in skin samples obtained from different locations on the body. It seems however that there is not any positive correlation between the degree of expression of EBA antigen in each location and predilection sites (possibly the trunk) of clinical lesions in EBA.
Abdomen ; Adult ; Epidermolysis Bullosa Acquisita* ; Epidermolysis Bullosa* ; Fluorescent Antibody Technique, Indirect ; Humans ; Pemphigoid, Bullous ; Pemphigus ; Scalp ; Skin ; Skin Diseases, Vesiculobullous ; Thigh ; Thorax

Pemphgus vulgaris (PV), Bullus pemphigoid (BP), and Epidermolysis bullous acqusita (EBA) are autoimmune bullous dermatoses, characterized by circulating IgG autoantibodies. These antibodies react with antigens located at the intercellular substance (ICS) of epidermis, basement membrane zone (BMZ), and subepidermal anchoring fibril zone (AFZ), respectively. The subclass distribution of IgG autoantibodies, and the properties and degrees of complement fixing activities of these autoantibodies in each of the above diseases have not been well understood. Indirect immunofluorescence and in vitro complement stainings were performed for the titration of subclasses of IgG antibodies and for the immunofluorescence staining reactivities of complement components C3, C4, C5b-9, H, C4bp, and S. Each serum specimen from five cases of PV, five cases of BP. and three cases of EBA was tested. The findings of multistep technique with monoclonal and polyclonal antibodies are as follows : All four subclasses of IgG antibodies were identified at the antigenic sites in these group, however there were some differences in the antibodies titers. In PV and BP the dominant subclass of highest antibody titer was IgG1 and/or IgG4. In EBA only IgG4 was dominant in all three cases. The results of complement component stainings, in most of the cases of PV, showed positive for C3 and C4 but were negative for the other components or inhibitor proteins at the ICS of epidermis. In BP most of the cases revealed positive staining reactivities at the BMZ for C3, C4, C5b-9, H, and C4bp-9 with no staining reactivities for the inhibitor proteins No significant relevancy was found between the titers of complement fixing IgG subclasses and the numbers of positive complement staining reactivities for complement components. The results suggest that the complement system may contribute more strongly to the formation of bullous lesions in BP and EBA than in PV.
Antibodies ; Autoantibodies ; Basement Membrane ; Blister ; Complement Membrane Attack Complex ; Complement System Proteins ; Epidermis ; Epidermolysis Bullosa Acquisita* ; Epidermolysis Bullosa* ; Fluorescent Antibody Technique ; Fluorescent Antibody Technique, Indirect ; Immunoglobulin G ; Pemphigoid, Bullous* ; Pemphigus* ; Skin Diseases, Vesiculobullous

Immunologic or immunopathologic assays are neccesary for the diagnosis of autoimmune bullous dermatoses including pemphigus vulgaris (PV), bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). The objectives of this study is to compare the sensitivity and usefulness of indirect immunofluorescence 0F) with that of immunoblot assay using amplified alkaline phosphatase staining system in the diagnosis of the above diseases; detection of disease-specific IgG autoantibodies. We selected 4 patients in each bullous dermatosis of PV, BP, and EBA, who had serum levels of IgG autoantibodies at a titer of 1:80 or higher. In each three disease, 2 patients with negative serum antibodies or serum titer lower than 1:20, were also enrolled. Among the former 4-patient groups the titers of IgG antibodies found on indirect IF were in the range of 1:80 to 1:160, whereas the titers recognized by immunoblot assay were 1 or 2 dilutions higher in most of these patients. In the latter 2-patient groups, 4 out of the 6 cases revealed antibody-positive on immunoblot-staining membrane. The indirect IF can be performed easily and seems favorable in the aspect of cost-effectiveness. However, immunoblot assay with sensitive staining method would be warranted in cases of antibody-negative or atypical clinical variants of autoimmunebullous dermatoses to confirm the diagnosis.
Alkaline Phosphatase ; Antibodies ; Autoantibodies ; Diagnosis ; Epidermolysis Bullosa Acquisita ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoglobulin G ; Membranes ; Pemphigoid, Bullous ; Pemphigus ; Skin Diseases ; Skin Diseases, Vesiculobullous*

This study was done to observe the statistical difference on bullous skin disease patients (pemphigus, bullous pemphigoid, dermatitis herpetiformis, epidermolysis bullosa) who visited the department of dermatology, Kyungpook National University Hospital,from January 1966 to Deceniber 1985, For those 24 cases which tested positive under direct immunofluorescent (DIF) testing, agreement percentage of histopathologic diagnosis was compared. The results were summarized as follows : 1) 51 of 45,091 new outpatients (0.113%) were bullous skin disease patients. 2) By sex, age and monthly distribution, there was no significant difference, though epidermolysis bullosa was seen for the most part in those under 10 years of age. 3) By individual disease distribution, the pemphigus cases numbered 8, of which most cases were within the 30~60 year age group. Bullous pemphigoid cases numbered 14, of which most cases were over 50 years of age. Female patients were 2.5 times more common than male patients. Dermatitis herpetiformis cases numbered 20, and were relatively diminished in recent years. The peak age group was the 3rd decade. Epidermolysis bullosa numbered 9 cases. 4) The compatibility of the histopathologic diagnosis to the DIF diagnosis in 24 DIF positive cases indicated that of DIF positive pemphigus the histopathologic diagnrsis agreed with the DIF diagnosis in 75%, of bullous pemphigoid, 58% and of dermatitis herpetiformis, 50%.
Dermatitis Herpetiformis ; Dermatology ; Diagnosis ; Epidermolysis Bullosa ; Female ; Gyeongsangbuk-do ; Humans ; Male ; Outpatients ; Pemphigoid, Bullous ; Pemphigus ; Skin Diseases, Vesiculobullous* ; Statistics as Topic*

A 21 year-old lady had erythemas and bullae on the trunk for 20 days. Biopsy specimens showed subepidermal blister and deposits of IgG and IgA along the basement membrane zone (BMZ). Her serum antibodies of IgG and IgA were observed to recognize 290/145 kD antigens derived from A431-cell line. The other patient of 62 year-old woman had recurrent oral erosions and erosio-ulcerative plaques on her anterior chest for the past 2 years. Tissue specimens showed subepidermal blister and deposits of IgG and IgA at the BMZ. The patients serum had IgG and IgA antibodies which had binding specificities to the 230 kD pemphigoid antigen. The above two cases of epidermolysis billosa acquisita and cicatricial pemphigoid with IgG and IgA antibodies of comparable titers in each may be rarely encountered ones.
Antibodies* ; Basement Membrane ; Biopsy ; Blister* ; Epidermolysis Bullosa Acquisita ; Erythema ; Female ; Humans ; Immunoglobulin A* ; Immunoglobulin G* ; Middle Aged ; Pemphigoid, Benign Mucous Membrane* ; Pemphigoid, Bullous ; Thorax ; Young Adult