Introduction: Pemphigus vulgaris is a life-threatening, autoimmune bullous disease caused by desmogleins (Dsg) 1 and 3 au- toantibodies. It is a rare disease with an incidence rate of 0.5 to 3.2 per 100,000 per year. It typically presents as painful, flaccid blisters and erosions on both the skin and mucous membranes. Case report: We present a 43-year-old male with painless penile erosions of 1-month duration. He was evaluated for sexually transmitted infections, but laboratory tests yielded negative results. Subsequently, vesicles and bullae on the back and hyper- keratotic lesions on the malar area appeared, leading to the differential diagnoses of bullous diseases. Skin biopsy was done revealing intraepidermal suprabasal blisters with acantholytic cells. Direct Immunofluorescence demonstrated positive inter- cellular deposits of IgG and C3. ELISA Dsg 1 and Dsg 3 were positive (ratio of 1.857 and 4.580, respectively). A final diagnosis of pem- phigus vulgaris (PV) was made. The patient has remained in remission after a 3-month course of prednisone and azathioprine. Conclusion This is a unique case of PV presenting with an unusual manifestation of painless penile erosions. There have been limited reports of PV with penile skin involvement and all cases presented with painful lesions. Because painless penile lesions as presenting feature is rare, the diagnosis may be easily missed. This case demonstrates that thorough dermatologic examination and early diagnosis despite atypical findings are crucial to provide timely and appropriate treatment as this determines the clinical outcome of the disease.
Pemphigus ; Desmogleins ; Azathioprine

No abstract available.
Antibodies ; Desmoglein 1 ; Desmogleins ; Pemphigus

BACKGROUND: Pemphigus foliaceus(PF) and pemphigus vulgaris(PV) have different target antigens which belong to the desmoglein(DG) subfamily of the desmosomal cadherins; DG in the case of PF and PV antigen(PVA) in the case of PV. OBJECTIVE: Because DG is also a normal major component of the intercellular adhesive core, we investigated the immunohistochemical distribution of DG in PF to compare and contrast the findings with those of PV. METHODS: Immunohistochemical analysis using streptavidin-biotin complex method with anti-DG monoclonal antibody was done in six cases of PF and six cases of PV, as well as two samples of normal skin as control. RESULTS: Both disorders showed abnormal intense diffuse cytoplasmic staining patterns in the lesional skin. Contrary to PF, showing complete loss of normal, rim-like, membranous staining, two of six cases of PV showed the relatively well preserved normal staining pat-terns in the upper epidermis. CONCLUSION: The differences in the expression of DG in the lesional skins between PF and PV suggest that PVA is distinct from DG, although an overlapping of antigens between PF and PV could exist.
Adhesives ; Cytoplasm ; Desmogleins* ; Desmosomal Cadherins ; Epidermis ; Methods ; Pemphigus* ; Skin

BACKGROUND: Measuring the quality of life (QOL) is important in the evaluation of nonclinical aspects of diseases, for the discovery of functional and psychological limitations, and in choosing treatment in the initial phase of the disease. Pemphigus is a potentially fatal autoimmune bullous disease caused by autoantibodies against desmogleins (cadherin family proteins in desmosomes). Thus far, there has been no published study on QOL in Korean patients with pemphigus. OBJECTIVE: To study the impact of pemphigus on the QOL in a large number of Korean patients. METHODS: Sixty-six patients enrolled at the Gangnam Severance Hospital from March 2012 to March 2013 were assessed for QOL by using the Dermatology Life Quality Index (DLQI), and for anxiety and depression by using the General Health Questionnaire (GHQ). Spearman's rank-order correlation, t-test, and ANOVA were used to identify the relations between the DLQI score and other clinical variables. RESULTS: Pemphigus vulgaris and pemphigus foliaceus significantly reduced the QOL of patients. The average DLQI score for all patients was 10.18. The mean DLQI score was 13.45 in patients in the active state and 5.15 in the patients in the remission state. The DLQI score highly correlated with disease severity, titer of anti-desmoglein 1 in enzyme-linked immunosorbent assay, and the corticosteroid dose. However, the QOL was not affected by sex, age, subtype of pemphigus, duration of disease, or comorbidities. Forty-two percent of the patients showed a positive result in the GHQ, reflecting probable minor psychiatric nonpsychotic conditions, and the GHQ score positively correlated to the DLQI score. CONCLUSION: Pemphigus significantly impairs the QOL of patients. The QOL of Korean pemphigus patients significantly correlates with clinical severity. Therefore, considerable attention should be paid to the patients' QOL and psychological states as well as clinical status.
Anxiety ; Autoantibodies ; Comorbidity ; Depression ; Dermatology ; Desmogleins ; Enzyme-Linked Immunosorbent Assay ; Humans ; Pemphigus* ; Quality of Life*

BACKGROUND: Desmogleins are calcium-dependent transmembrane glycoproteins of the desmosome that form an import component of the junction complexes of epithelial cells. Desmogleins are involved in maintaining the structural integrity of tissues. So far, four different desmogleins (Dsg1, Dsg2, Dsg3 and Dsg4) have been identified. OBJECTIVE: The purpose of this study was to observe the distribution pattern of desmoglein-3 in the fetal skin during development. METHODS: Skin was obtained from the sole, scalp and lip of 34 fetuses that ranged in age from 10 to 39 weeks of gestational age. Immunohistochemical staining was performed on the paraffin embedded tissue using anti-human monoclonal antibody against the desmoglein-3. RESULTS: The expression of desmoglein-3 in the epidermis appeared in the basal layer of the sole at the 10th week of gestation age. Thereafter, a stronger expression was noted in the middle layer of the sole and scalp epidermis. The basal layer had a stronger expression than did the other layers of the epidermis, followed by the middle and superficial layers. A stronger expression of desmoglein-3 in hair was noted in the outer root sheath, the bulge cells and the eccrine duct cells. The expression of desmoglein-3 in the lip mucosa was strong in both the basal and middle layers, while the skin side of the mucosa showed a stronger expression in basal layer. CONCLUSION: These results suggested that desmoglein-3 plays an important role in the development and differentiation of the epidermis and skin adnexa in the fetal stage, and especially in basal and suprabasal layers.
Desmogleins ; Desmosomes ; Epidermis ; Epithelial Cells ; Fetus ; Gestational Age ; Glycoproteins ; Hair ; Lip ; Mucous Membrane ; Paraffin ; Pregnancy ; Scalp ; Skin

BACKGROUND: Desmosomes are cell-cell adhesion complexes that provide mechanical integrity to keratinocytes by linking them to keratin intermediate filaments. Desmosomes are composed of two major transmembrane proteins, desmoglein and desmocollin. In humans, four desmoglein isoforms have been identified: Dsg1, Dsg2, Dsg3, and Dsg4. Desmogleins are Ca2+-dependent adhesion molecules and play important parts in the formation and maintenance of desmosomes. Desmoglein-1 is the main skin-associated desmosomal cadherin. It is expressed throughout the epidermis, but most prominently in the differentiated layers. OBJECTIVE: The purpose of this study was to observe the distribution pattern of desmoglein-1 in the skin and oral mucosa during fetal development. METHODS: Skin was obtained from the sole and scalp of 35 fetuses, ranging from 10 to 37 weeks of gestational age. Immunohistochemical staining was performed on paraffin embedded tissue using anti-human monoclonal antibody against desmoglein-1. RESULTS: Expression of desmoglein-1 in the epidermis appeared in the upper layer of the sole, but the basal layer was negative at the 10th gestational age. Thereafter, stratification began with stronger expression in the middle layer than in the basal layer of the sole and scalp epidermis. Expression in the middle spinous layer is stronger in the fetal period than in other layers of the epidermis. Expression in the superficial layer seemed to increase in later stages. Expression of desmoglein-1 in hair was strong in the infundibulum, inner root sheath, sebaceous glandular epithelium, and eccrine duct epithelium. Expression of desmoglein-1 in oral lip mucosa was very weak or negative in the upper half of the mucosal epithelium, though the lower half was strongly positive, while the skin side of the mucosa was similar with the sole skin. CONCLUSION: Desmoglein-1 may play a complementary role in the maintenance of epithelial integrity along with other desmogleins, because desmoglein-1 distribution is slightly different from that of desmoglein-3 in epidermis, hair and mucosa in fetal skin development.
Desmogleins ; Desmosomes ; Epidermis ; Epithelium ; Fetus ; Gestational Age ; Hair ; Humans ; Intermediate Filaments ; Keratinocytes ; Keratins ; Lip ; Mouth Mucosa ; Mucous Membrane ; Paraffin ; Protein Isoforms ; Proteins ; Scalp ; Skin

BACKGROUND: Desmosomes are adhesive intercellular junctions that form an important component of the junction complexes of epithelial cells. They provide intercellular links between the intermediate filament cytoskeletons of adjacent cells and are thus involved in maintaining the structural integrity of tissues. OBJECTIVE: Calcium and retinoids are major regulators of epidermal differentiation and their role on keratin proteins are well known. However, their effects on desmosome moleucles are unknown. To address this question we initiated a study of the effects of these epidermal differentiation regulators on desmosomal components, i.e., desmoplakin, desmoglein, and pemphigus antigens. METHODS: We used monoclonal antibodies against desmoplakin(DP) and desmoglein(DG), and sera from patients with pemphigus vulgaris(PV), pemphigus foliaceus(PF) and paraneoplastic pemphigus (PNP) to study the effects of calcium and retinoic acids, which are major regulators of epidermal differentation, on desmosomal protein formation in human cultured deratinocytes. We performed immunofluorescence, immunoblotting and immunoprecipitation study using human keratinocytes cultured in high calcium media with or without retinoic acid and in low calcium media with or without retinoic acid. RESULTS: 1. In low calcium (0.15mM) media, PV antigen and DG were produced in a small amount and it appeared that these desmosomal proteins were located in cytosol. Whereas in high calcium (1.8mM) media, production of these desmosomal proteins was increased not they were assembled at the desmosomal structures located in cell-cell contact margins. 2. PF antigen, which was identical to the DG, were not produced or expressed in cultured keratinocytes even when cultured in high calcium media. 3. PNP antigen and DP were produced in cultured keratinocytes grown in both high low calcium media but their production was increased in high calcium media and only in high calcium media they were assembled at the desmosomal structures. 4. Retinoic acids induced loosening of cell-cell contacts of cultured keratinocytes and decreased the production of desmosomal proteins. CONCLUSION: Our results suggests calcium is a major regulator of the production and assembly of desmosomal proteins including pemphigus antigens, but PF sera and monoclonal antibodies against DG show different antigen binding characteristics. It appears that retinoic acids inhibit production of desmosomal proteins.
Adhesives ; Antibodies, Monoclonal ; Calcium* ; Cytoskeleton ; Cytosol ; Desmogleins ; Desmoplakins ; Desmosomes* ; Epithelial Cells ; Fluorescent Antibody Technique ; Humans ; Immunoblotting ; Immunoprecipitation ; Intercellular Junctions ; Intermediate Filaments ; Keratinocytes ; Pemphigus ; Retinoids ; Tretinoin*

BACKGROUND: Pemphigus is a severe blistering disorder caused by autoantibodies to desmogleins 1 and 3. Because some patients with pemphigus never enter into remission, new immunosuppressants are warranted. Rituximab is a chimeric monoclonal antibody binding to the CD20 antigen on B cells, which proved to be effective in recalcitrant pemphigus. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of Rituximab in the treatment of refractory pemphigus vulgaris. METHODS: A retrospective analysis was conducted of six patients with recalcitrant pemphigus vulgaris in Yongdong Severance Hospital. Rituximab was administered intravenously at a dosage of 375 mg/m(2) body surface area. Five patient received 2 cycles of Rituximab treatment with an interval of 7 days. One patient received 5 cycles of treatment. The mean follow-up after treatment was 9.3 months (range, 2 months to 16 months). RESULTS: All the patients presented clinical improvements. The average pemphigus vulgaris severity score decreased from 12.2 to 2.5 after treatment. No adverse effects were observed. CONCLUSION: Rituximab has been proved as an effective and safe treatment for refractory pemphigus vulgaris.
Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; Autoantibodies ; B-Lymphocytes ; Blister ; Body Surface Area ; Desmogleins ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; Pemphigus ; Retrospective Studies ; Rituximab

BACKGROUND: Topical retinoids induce skin fragility. As corneodesmosomes are important adhesion structures in the epidermal cohesion, an effect of retinoids on corneodesmosomes has been suspected. OBJECTIVE: The aim of this study was to investigate the effect of retinoid on the expression of corneodesmosomal components including desmoglein (DSG) 1, desmocollin (DSC) 1, corneodesmosin (CDSN) and kallikrein (KLK)s. METHODS: 2% all-trans-retinol or ethanol was applied to the back of hairless mice for five days, and the structure of the stratum corneum was examined by transmission electron microscopy. The cultured human keratinocytes were treated with all-trans-retinoic acid (RA) in low or high calcium media for 24 hours. RESULTS: Topical retinol increased corneocyte detachment and degradation of corneodesmosomes. RA significantly decreased DSG1 and DSC1 expression at the mRNA and protein levels in keratinocytes that were cultured in both low- and high-calcium media. On the other hand, CDSN mRNA levels did not decrease in low-calcium media or increase in high-calcium media after RA treatment. KLK5 and KLK7 expression did not increase after RA treatment. CONCLUSION: Our results indicate that DSG1 and DSC1 downregulation by RA could be related to the increased degradation of corneodesmosomes and consequent desquamation induced by retinoids.
Animals ; Calcium ; Desmoglein 1 ; Desmogleins ; Down-Regulation ; Ethanol ; Hand ; Humans ; Kallikreins ; Keratinocytes ; Mice ; Mice, Hairless ; Microscopy, Electron, Transmission ; Retinoids ; RNA, Messenger ; Skin ; Tretinoin ; Vitamin A

Pemphigus is a group of blistering autoimmune diseases that affect the skin and mucous membranes with autoantibodies against desmoglein. Among the pemphigus subtypes, pemphigus erythematosus is one of the rare lupus-like variant subtypes of pemphigus that shares common clinical and histopathological manifestations with systemic lupus erythematosus. The lesions appear clinically as erythematous erosive patches on the face in a butterfly distribution, and they manifest subcorneal acantholysis histopathologically. There is concomitant basement membrane zone deposition of immunoglobulin and complement in lesional skin in addition to intercellular space staining in the epidermis. Two cases of pemphigus erythematosus have been reported domestically. Here, we report a case of pemphigus erythematosus in an 18-year old woman.
Acantholysis ; Autoantibodies ; Autoimmune Diseases ; Basement Membrane ; Blister ; Butterflies ; Complement System Proteins ; Desmogleins ; Epidermis ; Extracellular Space ; Female ; Humans ; Immunoglobulins ; Lupus Erythematosus, Systemic ; Mucous Membrane ; Pemphigus ; Skin