Anti-fibrotic Effect of Silibinin in Keloid Fibroblasts and a Bleomycin-induced, Scleroderma-like Animal Model / 대한피부과학회지

BACKGROUND: Silibinin reduces the expression of Type I collagen in normal skin fibroblasts through down-regulation of the TGF-beta/smad pathway. However, it is largely unknown whether silibinin can reduce the expression of Type I collagen in vivo sclerotic animal models, as well as in keloid fibroblasts. OBJECTIVE: The purpose of this study was to investigate the effect of silibinin on the expressions of type I collagen, matrix metalloproteinase-1 (MMP-1), MMP-2, smad2/3, and TGF-b1 receptor in keloid fibroblasts in vitro, and to evaluate the anti-fibrotic effect of silibinin in a bleomycin-induced, scleroderma-like animal model in vivo. METHODS: Keloid and normal skin fibroblasts were treated with silibinin (20~100 mM), and the expressions of type I collagen, MMP-1, MMP-2, and TGF-b1 receptor were analyzed with western blot. The animal model was established by bleomycin treatment (1.0 mg/mL) for 2 weeks in C57/BL9 mice. Then silibinin was injected on one side of the back and the same volume of normal saline was injected on the other side of the back. The specimen was evaluated with H&E, Masson-trichrome, and TGF-beta1 immunohistochemical staining. RESULTS: Expressions of Type I collagen, MMP-1, and MMP-2 decreased, but the expression of TGF-beta1 receptor increased in keloid fibroblasts after silibinin treatment. Thickened dermis with dense extracellular matrix and inflammatory cell infiltration of the bleomycin-induced, scleroderma-like animal model improved after silibinin treatment. Expression of TGF-beta1 decreased after silibinin treatment in the bleomycin-induced, scleroderma-like animal model. CONCLUSION: Silibinin treatment decreased the expression of Type I collagen in keloid fibroblasts in vitro. In addition, silibinin decreased the expression of Type I collagen by inhibiting TGF-beta1 expression in the bleomycin-induced, scleroderma-like animal model. These results indicate that silibinin has the potential to be an effective antifibrotic agent.

Weber-Cockayne Type Epidermolysis Bullosa Simplex Resulting from a Novel Mutation (c. 608T>C) in the Keratin 5 Gene

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).

Lupus Profundus with Segmental Distribution on Leg, Following the Lines of Blaschko in a Child / 대한피부과학회지

Lupus profundus is a rare subtype of chronic cutaneous lupus erythematosus, which shows a tender subcutaneous nodule or plaque. The face, arm, buttock, trunk and thighs are frequently involved. Lupus profundus can be associated with or without systemic lupus erythematosus. But due to its rarity, it is difficult to diagnosis and there are not many reports regarding its characteristics, including its distribution. In this case, a 13-year-old boy has visited with several violaceous non-tender nodules on Lt. upper thigh with segmental distribution, which follows the Blaschko's line. Through skin biopsy and its immunoflourescent study, we diagnosed lupus profundus. We here report a case of lupus profundus with segmental distribution following the lines of Blaschko's in a child.

Primary Cutaneous Nocardiosis with Sporotrichoid Pattern by N. brasiliensis in Lung Cancer Patient / 대한피부과학회지

Nocardia is aerobic gram positive bacteria, which is found in the soil. Cutaneous nocardiosis is divided into the primary skin infection and secondary infection due to systemic dissemination from the internal organ. Its clinical manifestations are mycetoma, lymphocutaneous infection and superficial infection, such as abscess or granuloma. In lymphocutaneous infection, it is important to make differential diagnosis with other diseases with sporotrichoid pattern, such as sporotrichosis, leishmaniasis and mycobacterial infection. In our case, 58 year old male who had history of chemotherapy due to lung cancer visited with granulomatous nodule on the left wrist, and following lymphangitis along the forearm for 2 months. Through a skin biopsy, culture, AFB stain and 16S rRNA gene sequencing, cutaneous nocardiosis by N. brasiliensis was diagnosed.

Pityriasis Versicolor on Penile Shaft in a Renal Transplant Recipient

Pityriasis versicolor is a superficial infection of the stratum corneum, which is caused by the Malassezia species. Tge Malassezia species consist of 12 subspecies, including M. furfur, M. pachydermatis, M. symphodialis and M. globasa. The Malassezia species are classified as a normal flora, particularly in the sebum rich areas of the skin, and they convert from saprophytic yeast to parasitic mycelial morpholgic form to cause clinical disease. But majorities of their distributions are in the upper back, the neck, the thighs, and the forearm, and not in the penis. It is well known that the renal transplant patients, who take immunosuppressive agents, have impairment in the protective cell mediated immunity. Thus, they are more susceptible to infectious diseases, such as a fungal infection. Therefore, clinical manifestations show higher incidence of disease, but they mostly occur in an expected distribution. We here report a case of pityriasis versicolor in a renal transplant recipient on penile shaft, which is an unusual area.

Curcumin Induced Decreased Expression of Type I Collagen in Human Skin Fibroblast Through Down-regulation of Smad2/3 Expressions / 대한피부과학회지

BACKGROUND: Imbalance among TGF-beta/Smad pathway, MMP-1, and TIMP-1 expressions results in sclerotic skin disease, such as scleroderma, hypertrophic scar, and keloids. Curcumin, a phytochemical extracted from the rhizomes of Curcuma longa, showed an anti-fibrotic effect in an animal study, such as a pulmonary and cholangioductal fibrosis animal model. However, the expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 in curcumin treated human skin fibroblasts is largely unknown. OBJECTIVE: The purpose of this study was to investigate the expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 proteins in curcumin-treated human skin fibroblasts. METHODS: Human skin fibroblasts were treated by various concentrations of curcumin (1~40 uM). The expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 proteins were analyzed by Western blot analysis. In addition, activities of type I collagen promoter were analyzed by the CAT assay. RESULTS: The expression of type I collagen decreased but the expression of MMP-1 and TIMP-1 increased by curcumin treatment in a dose and time dependent manner in Western blot analysis. Type I collagen promoter activities were decreased by curcumin treatment in the CAT assay. Smad2/3 expression decreased by curcumin treatment but TGF-beta1 induced Smad2/3 activation was not decreased by curcumin treatment following Western blot analysis. CONCLUSION: Decrease of type I collagen expression through the inhibition of Smad2/3 and increase of the expression of MMP-1, which is the degradating enzyme of type I collagen, in human skin fibroblasts by curcumin treatment offer expectation of curcumin as antifibrotic agent.

Deep Adiaspiromycosis Caused by Chrysosporium Associated with Long-Term Treatment with Immunosuppresants in a Patient with Pemphigus Vulgaris / 대한피부과학회지

Adiaspiromycosis is known as an infection that is due to Chrysosporium species which are filamentous soil saprophytes that cause pulmonary infection in rare cases but are classified mainly as a contaminant rather than a pathogen in dermatological areas. Deep fungal infections, commonly by Aspergillosis and Candida, are associated with patients who have an impaired skin barrier or immunosuppression and it takes a long time to identify the pathogen because it is hard to diagnosis it without clinical suspicion. In our case, a 56-year-old female living in a rural area who took immunosuppressants including cyclophosphamide, mycophenolate mefetil, and prednisolone due to pemphigus vulgaris presented at our clinic with an erythematous patch with pustular discharges on the left forearm for 2 months. She had been treated with antibiotics under the impression of cellulitis but was not responsive to it. A Chrysosporium species was identified by tissue culture and treatment was successful with an antifungal agent. We here report a case of deep fungal infection caused by Chrysosporium species without pulmonary infiltration which is a rare manifestation.

Stewart-Treves Syndrome Arising in a Chronic Lymphedematous Leg / 대한피부과학회지

Angiosarcoma is a rare malignancy of a vasculo-eptihelial origin. It is divided into three categories. The first category is primary anigosarcoma, which occurs in the face and scalp of elderly patients without any predisposing factors. The second is Stewart-Treves Syndrome, which is a subset of chronic lymphedema. The third is a post irradiation angiosarcoma that occurs at the site of prior irradiation. Generally in Stewart-Treves Syndrome, there is a pre-existing chronic lymphedema on the upper extremities due to the wide excision of breast cancer with or without radiation therapy. We here report on a case of a 60-year-old female with chronic lymphedema on the leg and who had a history of hysterectomy due to cervical cancer. The patient had purple-colored tender nodule and ulcer with exudate on the chronic lymphedematous leg and was diagnosed as angiosarcoma by a skin biopsy.