각질형성세포에서 레티노인산(All-trans Retinoic Acid)에 의한 IL-8 발현의 기전

Background: Retinoic acid (RA) has been reported to induce the up-regulation of inflammatory cytokines such as IL-1, TNF-α and IL-8 in dermal fibroblasts and keratinocytes. There is no evidence to support a direct interaction between the RA-mediated transcriptional machinery and IL-8 gene transcription. Objective: The aim of this study is to clarify the mechanism of the up-regulation of IL-8 in keratinocytes by RA. Methods: The IL-1, IL-8, TNF-α and MCP-1 mRNA expressions in HaCaT cells stimulated by RA were measured by quantitative RT-PCR. The effects of a NF-κB inhibitor and IL-1 receptor antagonist (ra) on the IL-8 mRNA expression were measured by quantitative RT-PCR. Electrophoretic motility shift assay (EMSA) was conducted on the RA-stimulated HaCaT cells that were or were not treated with NF-κB inhibitor to measure the NF-κB binding activity in each group. The phospho-IκB activity in the HaCaT cells after stimulation with RA was also measured by Western blotting. Results: An up-regulation of the IL-8 gene expression by RA was demonstrated in the HaCaT cells. The inhibition assay revealed the involvement of the NF-κB binding site of the IL-8 gene in the RA-enhanced promoter activity. EMSA demonstrated that RA enhanced the formation of the DNA-NF-κB complex. There was no evidence to support IL-1 as an intermediate stimulus between the RA-mediated transcriptional machinery and IL-8 gene transcription. Western blot analysis revealed increased phospho-IκB activity in the HaCaT cells after stimulation with RA. Conclusion: Our result suggested that the IL-8 gene expression of HaCaT cells after RA stimulation is caused by the activation of IKK and the dissociation of IκB from NF-κB and the transcription of NF-κB in the nucleusope

Circulating Eosinophil and Neutrophil Counts Correlate with Disease Severity in Bullous Pemphigoid

Background: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by tissue- bound and circulating autoantibodies directed against BP180 and/or BP230 antigens. Various inflammatory cells are involved in the development of blister in BP. Objective: The aim of this study was to evaluate the correlation between peripheral leukocyte counts and BP severity. Methods: We retrospectively included 60 patients with BP, who had not been treated with systemic steroid at the time of blood sampling. The patients were classified into two groups, those with admission history (admission group) and those without admission history (non-admission group). Disease severity was evaluated using three parameters: admission history, initial steroid dosage, and modified version of a pemphigus scoring system. We evaluated the correlation between peripheral leukocyte counts and disease severity measured by the three parameters. Results: The admission group showed a significant increase in disease severity measured by initial steroid dosage and severity score compared with the non-admission group. Additionally, the admission group had increased total leukocyte, eosinophil, and neutrophil counts. In the correlation study, the peripheral eosinophil and neutrophil counts showed positive correlation with BP severity evaluated by both initial steroid dosage and the pemphigus scoring system. Conclusion: Peripheral eosinophil and neutrophil counts can be used as a marker in predicting disease severity in patients with BP. (Ann Dermatol 30(5) 544∼549, 2018)ope

A Case of Pseudo-Kaposi's Sarcoma Associated with Klippel-Trenaunay Syndrome

Pseudo-Kaposi’s sarcoma is an unusual cutaneous sequelae of chronic venous insufficiency and congenital vascular malformation of the lower extremities. It is a benign vascular process encountered on the lower extremities, which resembles a superficial form of stasis dermatitis, however, is clinically characterized by circumscribed violaceous, brown or dusky papules and plaques. We, herein, report a case of unilateral pseudo-Kaposi’s sarcoma associated with Klippel-Trenaunay syndrome.ope

A Usual Frameshift and Delayed Termination Codon Mutation in Keratin 5 Causes a Novel Type of Epidermolysis Bullosa Simplex with Migratory Circinate Erythema

We report here two unrelated families in Japan and Korea having patients with a unique type of epidermolysis bullosa simplex and a novel mutation in the keratin gene KRT5, i.e., a frameshift and delayed stop codon inconsistent with any subtype described before. The patients showed migratory circinate erythema and multiple vesicles on the circular belt-like areas affected by erythema. Electron microscopy of skin biopsies showed a reduction in the number of keratin intermediate filaments in the basal cells without tonofilament clumping. We identified a novel heterozygous deletion mutation (1649delG of KRT5) in both cases. This deletion is predicted to produce a mutant keratin 5 protein with a frameshift of its terminal 41 amino acids and 35 amino acids longer than the wild-type keratin 5 protein due to a delayed termination codon. As the same abnormal elongated mutant KRT5 gene was found in the independent families, the predicted abnormal elongated keratin protein is likely to lead to an atypical clinical phenotype that has never been reported, possibly by interfering with the functional interaction between keratin and its associated proteins.ope

Clinical Study of Korean Patients with Linear IgA Bullous Dermatosis

Background: Linear IgA bullous dermatosis (LABD) is an autoimmune, chronic bullous disease characterized by sub-epithelial bullae with linear IgA deposits along the basement membrane. LABD primarily affects young children and adults. There has been no study on LABD in Korea to date. Objective: The purpose of this study was to evaluate the clinical features, laboratory examinations, treatments, and outcomes of Korean LABD patients. Patient characteristics including age at disease onset, gender, medical associations, medications, immunofluorescence findings, disease duration, treatment, and outcome were analyzed. Methods: A retrospective analysis was conducted on 16 LABD patients diagnosed at Gangnam Severance Hospital between 1999 and 2014. Results: A total of 16 LABD patients were included in the study, 5 children and 11 adults. The mean ages at disease onset in children and adults were 3.2 and 41 years, respectively. Eighty percent of children with LABD showed complete remission. In adults, partial remission was achieved in 36.4%, and complete remission in 54.5% of patients. Two patients were diagnosed with drug-induced LABD, and 2 with ulcerative colitis-associated LABD. Conclusion: Our report differed from previous reports in that all 5 children with LABD were male, and the incidence in adults was higher in females than males. Most patients responded well to dapsone and oral prednisolone. Since LABD is rare and can be misdiagnosed as impetigo or bullous pemphigoid, diagnosis by immunofluorescence microscopy is necessary for proper treatment to attain disease remission.ope

eDNA Cloning of the 210-kDa Paraneoplastic Pemphigus Antigen Reveals that Envoplakin Is a Component of the Antigen Complex

Although the 210 and 190-kDa proteins are the most frequently detected antigens reacting with sera of patients with paraneoplastic pemphigus (PNP) in immunoblot analysis, there is still uncertainty as to the nature of these PNP antigens. To isolate and characterize a cDNA clone encoding the 210-kDa PNP antigen, we screened a human keratinocyte lambda gt 11 cDNA expression library by the immunoperoxidase method with serum IgG from a PNP patient. The IgG used for the immunoscreening of a keratinocyte cDNA expression library recognized 210- and 190-kDa antigens by immunoblotting. A single clone, called here the PNP clone, producing a fusion protein that reacted strongly with the patient's IgG, was further characterized. Only the PNP patient's IgG, but not IgG from a normal control, pemphigus foliaceus, or pemphigus vulgaris patients, bound the plaques of this positive clone. Furthermore, PNP IgG affinity purified on plaques of this clone, but not unrelated clones, bound to keratinocyte cell surfaces by immunofluorescence and reacted with the 210-kDa PNP antigen by immunoblotting. EcoRI digestion of the clone's cDNA insert demonstrated a 1.4-kbp fragment. This cDNA insert was placed into a M13 mp 18 vector and sequenced. Sequence analysis revealed that the cDNA insert of the PNP clone encodes a part of the central rod domain and the COOH-terminal C domain of envoplakin, a newly defined precursor of the cornified envelope that is homologous to desmoplakin. This result demonstrates that the 210-kDa PNP antigen is envoplakin and PNP is an autoimmune disease that produces autoantibodies against intermediate filament-associated proteins in desmosomes and hemidesmosomes, desmoplakin, bullous pemphigoid antigen 1 (BPAG 1), and envoplakin.ope

Paraneoplastic pemphigus developed shortly after resection of follicular dendritic cell sarcoma

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Eruptive pseudoangiomatosis: three cases in Korean middle-aged women

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Genotype–Phenotype Correlation in Recessive Dystrophic Epidermolysis Bullosa: When Missense Doesn't Make Sense

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A Case of Xanthoma Disseminatum Presenting as Pedunculating Nodules and Plaques

Xanthoma disseminatum is a rare mucocutaneous xanthomatosis classified as a benign form of non-Langerhans cell histiocytosis. We describe an illustrative case with extensive mucocutaneous involvement which was unresponsive to treatment. The patient presented with numerous variable-sized, yellow-brown papules and confluent plaques on the perorbital, perioral, neck, axilla, upper chest, groin, perianal, antecubital fossae and popliteal fossae including the upper respiratory tract. She was treated with oral cyclophosphamide but showed no clinical improvement. She then developed dyspnea, dysphagia and experience defecation difficulties, so was treated with palliative surgery to help relieve the symptoms.ope