Epigenetic Modulation of Gene Expression during Keratinocyte Differentiation

BACKGROUND: Epigenetic modulation of gene expression occurs by various methods, including DNA methylation and histone modification. DNA methylation of specific genes may affect the chromatin structure, preventing access by the transcriptional machinery. Although gene expression is dramatically changed during keratinocyte differentiation, there is no evidence of epigenetic modulation during the process of epidermal stratification. OBJECTIVE: We investigated whether epigenetic modulation is involved in keratinocyte differentiation-specific gene regulation. METHODS: We used trypsin to produce epidermal fragmentation (named T1-T4) and performed a morphological analysis using hematoxylin-eosin stain and cytokeratin expression based on reverse transcription polymerase chain reaction. We then constructed a DNA methylation microarray. RESULTS: Each epidermal fragment showed morphological features of the epithelial layer. T1 represented the basal layer, T2 was the spinous layer, T3 was the granular layer, and T4 was the cornified layer. The level of the K14 proliferation marker was increased in the T1 fraction, and the level of K10 differentiation marker was increased in the T2-T4 fractions. Using a methylation microarray with the T1 and T4 fractions, we obtained many hypermethylated and hypomethylated genes from differentiated keratinocytes. CONCLUSION: The importance of epigenetic modulation in target gene expression during keratinocyte differentiation is identified.

Identification of Cutaneous Mycobacterium massiliense Infections Associated with Repeated Surgical Procedures

Mycobacterium massiliense, an emerging pathogen that is increasingly reported as a causative agent in infections occurring during medical procedures, is difficult to be identified using conventional methods. Here we report the case of a cutaneous M. massiliense infection that was associated with repeated surgical procedures and that was identified via a comparative sequence analysis of rpoB and hsp65. The patient showed a substantial response to treatment with a combination of antimicrobial therapies consisting of clarithromycin, amikacin, and cefoxitin for 6 months.

A Case of Isolated Plexiform Neurofibroma in a Patient with Myasthenia Gravis

We report a case of an isolated plexiform neurofibroma occurring in a patient with myasthenia gravis. A 48-year-old man presented with asymptomatic skin-colored nodules on the tip of his 4th finger. Microscopically, a plexiform neurofibroma was identified located in the dermis that appeared to originate from small superficial nerves. He had a 20-year history of treated myasthenia gravis; otherwise, his personal and family histories were unremarkable. Given that myasthenia gravis is a disorder of the peripheral nerves, plexiform neurofibromas could be associated with myasthenia gravis. However, the development of an isolated plexiform neurofibroma in a case of myasthenia gravis has not yet been reported. The occurrence of a neurofibromas in a patient with myasthenia gravis suggests a link in the pathogenesis of these two diseases.

Expression of N-terminal truncated desmoglein 3 (Delta NDg3) in epidermis and its role in keratinocyte differentiation

During a search for keratinocyte differentiation-related genes, we obtained a cDNA fragment from the 5'-untranslated region of a previously identified splicing variant of desmoglein 3 (Dg3). This transcript encodes a protein of 282 amino acids, which corresponds to the N-terminal truncated intracellular domain of Dg3 (Delta NDg3). Northern blot analysis detected a 4.6-kb transcript matching the predicted size of Delta NDg3 mRNA, and Western blot analysis with an antibody raised against the Dg3 C-terminus (H-145) detected a 31-kDa protein. Increased Delta NDg3 expression was observed in differentiating keratinocytes by RT-PCR and Western blot analysis, suggesting that Delta NDg3 is indeed a differentiation-related gene product. In immunohistochemical studies of normal and pathologic tissues, H-145 antibody detected the protein in the cytoplasm of suprabasal layer cells, whereas an antibody directed against the N-terminal region of Dg3 (AF1720) reacted with a membrane protein in the basal layer. In addition, Delta NDg3 transcript and protein were upregulated in psoriatic epidermis, and protein expression appeared to increase in epidermal tumors including Bowen's disease and squamous cell carcinoma. Moreover, overexpression of Delta NDg3 led to increased migration and weakening of cell adhesion. These results suggest that Delta NDg3 have a role in keratinocyte differentiation, and that may be related with tumorigenesis of epithelial origin.

A Case of Trichobalstic Carcinoma / 대한피부과학회지

Trichoblastoma is a benign cutaneous neoplasm that consists of follicular germinative cells. There have only been a few case reports describing the malignant counterpart of trichoblastoma. We report trichoblastic neoplasms that show histological features of malignancy. The histological sections revealed locally aggressive neoplasms showing prominent differentiation towards hair germ and follicular sheath with formation of papillary mesenchymal bodies and follicular bulb-like structures. The tumor was widely excised with a clear margin. No sign of recurrence has been noted 1 year later.

A Case of Amniotic Band Syndrome / 대한피부과학회지

The amniotic band syndrome is a collection of fetal malformations associated with fibrous band that appears to entangle or entrap various fetal part, in utero, leading to deformation, malformation or disruption. Its pathogenesis has been debated in the literature for many years. The associated anomalies vary from minor limb anomalies to major craniofacial defects and visceral defects. We experienced a case of limb anomalies due to amniotic band and present the findings with a brief review of literature.

A Case of the Generalized Type of Acquired Dermal Melanocytosis with ABNOM and Acquired Bilateral Nevus of Ito-like Macules / 대한피부과학회지

Dermal melanocytosis is histologically characterized by the presence of ectopic melanocytes in the dermis. Mongolian spots, nevus of Ota, nevus of Ito and blue nevus are the most common types and these are usually present at birth or in early childhood. However, it has been reported that several types of dermal melanocytosis could appear in adult life. We report here on an unusual case of acquired dermal melanocytosis occurring in a 51 year-old female. She had bilaterall brownish or slate-bluish pigmented patches on the face and the posterior auricular, supraclavicular, scapular and back areas. The skin biopsy specimen taken from the upper back revealed scattered, darkly pigmented, spindle-shaped cells and dendritic cells containing abundant golden brown pigment in the dermis.

Quality of Life of Alopecia Areata Patients / 대한피부과학회지

BACKGROUND: Hair constitutes an integral part of our self and our self-identity, which is why hair loss may cause a broad range of psychological problems related to our identity. However, the association between quality of life (QOL) in alopecia areata (AA) patients and their clinical characteristics has not yet been investigated in Korea. OBJECTIVE: The purpose of this study is to compare the QOL in patients with AA and healthy controls by using Hairdex scale. The relationship between their QOL and their clinical characteristics will be investigated. METHODS: 102 AA patients and 82 healthy controls were recruited in this study and compared by use of Hairdex. Correlation analysis was performed to examine the relationship between the QOL and the clinical characteristics of patients with AA. RESULTS: The total Hairdex scores and all domain scores, except those of the symptomatic domain, of the Hairdex scales in AA were higher than those of the healthy controls. Clinical characteristics, including the age, disease duration, AA type, AA area, treatment satisfaction, treatment history, anxiety and depression, showed significant correlation with QOL. Of these characteristics, the depression and treatment satisfaction showed strong association with QOL. CONCLUSION: AA can a impair patient's quality of life and has a significant psychological impact.

Cutaneous Metastasis from Hepatocellular Carcinoma Mimicking Pyogenic Granuloma / 대한피부과학회지

Skin lesions can sometimes be the presenting sign of metastatic cancers. We report a case of skin metastasis resembling pyogenic granuloma from hepatocellular carcinoma, which is a common malignancy in Korea. A 79-year-old male presented with a 1 month history of a dark-reddish nodule on his left cheek, which was thought to be pyogenic granuloma. On histopathologic examination, it was composed of tumor cells and intervening sinusoids and therefore showed characteristics of hepatocellular carcinoma. We confirmed hepatocellular carcinoma upon abdomen computer tomography. We present this case along with a review of previous reports of cutaneous metastasis from hepatocellular carcinoma.

14 Cases with Acute Diffuse Alopecia Areata / 대한피부과학회지

BACKGROUND: Acute diffuse alopecia areata (AA) was described as a unique AA which mimics anagen effluvium, or in which the initial hair loss is diffuse and followed by total denudation of scalp within several weeks or months. In spite of its peculiar clinical feature, there was neither further characterization nor known effective treatment for this form of AA. OBJECTIVE: To evaluate the characteristic clinical findings of acute diffuse AA and confirm the effect of high dose methyl prednisolone therapy. METHODS: The medical records of 13 patients with acute diffuse AA between January 2002 and April 2006 at the Department of Dermatology, Chungnam National University Hospital were reviewed. All patients were treated with high dose methylprednisolone therapy. RESULTS: Of the 13 patients who completed the study, 8 patients (61.5%) were male and 5 patients (38.5%) were female. The mean age was 29.6 years old. The progress of hair loss stopped 2.4 weeks on average after initial treatment and newly emerging hairs were recognized 4.1 weeks on average after initial treatment. 84.6% (11/13) of patients showed terminal hair growth, and 46.2% (6/13) of patients completely responded to this therapy. CONCLUSION: Acute diffuse alopecia areata can occur in male as well as in female patients. High dose methylprednisolone therapy appears to be effective in patients with rapidly progressing acute diffuse alopecia areata to prevent the progression of the disease.

A Case of Thermal Keratosis along with Erythema Ab Igne / 대한피부과학회지

We report a case of thermal keratosis with erythema ab igne which occurred on the dorsal side of a patient's left hand due to chronic exposure to infrared rays. A 62-year-old male presented with reticular hyperpigmentation on the dorsal side of his left hand and left knee along with multiple hyperkeratotic nodules on the dorsal side of his left hand without any symptoms. He had a hobby of playing internet games with a heater on his left side. A skin biopsy of the hyperkeratotic lesion showed hyperkeratosis and acanthosis in the epidermis. The dermis revealed many elastic fibers and superficial perivascular monocytic infiltration. The patient was diagnosed with thermal keratosis and erythema ab igne due to his history of chronic infrared exposure, distinctive clinical characteristics and the biopsy results. The application of topical steroid with the recommendation to cease exposure to heaters resulted in the almost disappearance of the papules and a little restoration of the skin color.

13 Cases of Leukoderma Punctata after Narrowband UVB Therapy in Vitiligo Patients / 대한피부과학회지

BACKGROUND: Leukoderma punctata is a peculiar disorder with punctiform, hypopigmented and achromic spots. Histopathologically, a focal reduction of melanocytes and melanin granules are found in the depigmented macule. The phototoxic effect of phototherapy on melanocytes has been suggested as the most likely cause. This occurs mostly after application of systemic or topical psolaren on photochemotherapy. However, a case following narrowband UVB therapy is very rare. OBJECTIVE: The purpose of our study was to investigate the characteristics of leukoderma punctata patients and find the cause of leukoderma punctata. METHODS: We reviewed the medical records of leukoderma punctata patients, and a skin biopsy was taken from punctiform hypopigmented macules. The tissues were stained with hematoxyline and eosin, Fontana-Masson, and dopa-oxidase. RESULTS: The average age of patients was 51 years old. There was no difference between results of male and female patients. Involvement sites of patients were mostly the arms and legs. 76% of patients did not have preceding subjective symptoms. In eight of nine patients, a marked reduction of melanin and melanocytes was noted with both Fontana-Masson staining and dopa-oxidase staining. The average total period of PUVA therapy was 26 months and average total dose of PUVA irradiation was 351.2 J/cm2 in leukoderma punctata patients. Before leukoderma punctata developed, the average total period of narrowband UVB therapy was 6.9 months and average total dose of narrowband UVB was 22.45 J/cm2. The results suggest that leukoderma punctata developed in very small dose of narrowband UVB, although it did not develop with large doses of PUVA. CONCLUSION: Narrowband UVB (311 nm) is the most likely spectrum for development of leukoderma punctata.

A Case of Verrucous Hyperplasia with Lymphedema of Leg Amputation Stump / 대한피부과학회지

Verrucous hyperplasia appears as multiple, warty, coalescent papules arising on the distal portion of amputation stump skin, yet it displays no histological evidence of viral warts. It occurs when the chronic pressure of a poor prosthetic fit disrupts vascular and lymphatic channels, subsequently causing chronic tissue edema. We report a case of 30 year old male, with 15 year history of wearing below-the-knee prosthesis, who presented with a verrucous papule that arose at his amputation site. Histopathological findings showed hyperkeratosis, acanthosis, superficial dermal edema and dilated thick vessles oriented vertical to the skin surface. Verrucous hyperplasia with lymphedema was diagnosed on the basis of clinical and histological findings.