Matrix Metalloproteinases and Autoimmune Bulbous Diseases: Expression of MMP-2, -3, and -9 in Bullous Pemphigoid, Pemphigus Vulgaris, and Pemphigus Foliaceus / 대한피부과학회지

BACKGROUND: Matrix metalloproteinases (MMPs) participate in extracellular matrix degradation and may play an important role in basal membrane damage in many dermatologic diseases. Recent studies implicated the importance of MMP-9 in the pathogenesis of bulla formation of bullous pemphigoid (BP). Various autoimmune bullous diseases are strongly associated with desmosome or hemidesmosome pathologies, and show an increased level of lesional MMP and exposed autoantigens from these structures. OBJECTIVE: This study evaluated the level of MMP-2, -3, and -9 in three types of autoimmune bullous disease [BP, pemphigus vulgaris (PV), pemphigus foliaceus (PF)] with the aim of investigating the role of MMPs in the pathogenesis of autoimmune bullous diseases. METHODS: Sample specimens were obtained from skin lesions of patients with BP (n=12), PV (n=10), and PF (n=12), and from normal controls (n=8). The immunohistochemical expression of MMP-2, -3, and -9 was analyzed and serum levels of MMP-2, -3, and -9 were measured by enzyme-linked immunosorbant assay (ELISA). The results were analyzed with reference to graded levels of clinical severity. RESULTS: Expression of dermal MMP-2, -3, and -9 were increased in BP, PV, and PF (p=0.036, 0.022, and 0.015, respectively). However, decreased expression of the three MMPs in the epidermis of skin lesions may have resulted from epidermal destruction. ELISA-determined serum levels of MMP-2, -3, and -9 increased in BP, PV and PF. Interestingly, MMP-2 was significantly increased in the sera of BP patients (p=0.015), consistent with the previous studies concerning the role of gelatinase (MMP-2 and -9) in the pathogenesis of BP. In BP patients, clinical severity was proportional to increased levels of MMP-2 in both skin lesions and and sera. CONCLUSION: The increased expression of MMP-2, -3, and -9 in skin lesions and sera may reflect the involvement of these enzymes in the mechanism of bulla formation in autoimmune bullous diseases including BP. In addition, expression of MMP and clinical severity may be closely connected.

A Statistical Observation on 1,430 Cases of Cutaneous Malignant Tumors over 20 Years (1987~2006) in Gwangju City and Chonnam Province / 대한피부과학회지

BACKGROUND: The incidence of cutaneous malignant tumors has recently markedly increased due to the increased longevity of life, along with the changes of social and environmental factors. However, few articles have reported on these changes, from a statistical aspect, of malignant skin tumors in Gwangju City and Chonnam Province. OBJECTIVE: Our purpose was to clarify the recent trends and changes in the incidence and clinical patterns of cutaneous malignant tumors observed in Gwangju City and Chonnam Province and to compare them with the previously reported data. METHODS: A total of 1,430 cases were pathologically diagnosed as cutaneous malignant tumor during a 20 year period between January 1987 and December 2006 at the Department of Dermatology in Chonnam National University Hospital. The tumor incidence and its changes, the age and gender distribution and the anatomical sites were investigated. RESULTS: The average annual incidence of cutaneous malignant tumors among the total number of outpatients was 1.4+/-0.5%. The incidence of cutaneous malignant tumors increased with time in 10-year intervals, from 1+/-0.25% (1987~1996) to 1.83+/-0.38% (1997~2006). Among the malignant tumors, the incidence of basal cell carcinoma (BCC) was increased up to 1.14% (1997~2006) as compared to 0.05% (1987~1996). The most common tumor among the 1,430 patients with cutaneous malignant tumor was BCC (58.96%), followed by squamous cell carcinoma (SCC) (17.58%), malignant melanoma (MM) (10.01%), metastatic carcinoma (3.57%) and malignant lymphoma (3.01%). The mean age of onset of the patients who were diagnosed with cutaneous malignant tumors was 63.64 years old (males: 62.23, females: 63.61) in this study. There was a similar incidence of malignant skin tumors between the males and females (1:1.04). The most common site for the development of malignant skin tumors were the head and neck where 94.54% of the BCCs and 63.3% of SCCs developed. The nose (33.02%) was the most preferential site for BCC, followed by the cheek (20.72%). SCC most frequently developed in the cheek (20.72%), followed by the lower lip (10.76%). The most frequent site for the development of MM was the sole and heel (36.37%) rather than the head and neck (14.7%). CONCLUSION: The total number of patients and the incidence of malignant skin tumors have gradually increased in the area of Gwangju City and Chonnam Province. Especially, BCC has markedly increased and this is mainly due to the increment of aged people in this area, along withsocial and environmental factors.

Toxic Epidermal Necrolysis Induced by the Topical Carbonic Anhydrase Inhibitors Brinzolamide and Dorzolamide

Brinzolamide and dorzolamide are highly specific topical carbonic anhydrase inhibitors (CAIs). They lower intraocular pressure (IOP) by reducing the rate of aqueous humour formation without serious side effects. Although systemic CAIs are the most potent medications for lowering intraocular pressure for conditions with ocular hypertension, many cases with adverse systemic reactions have been reported, including Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN). Here, we report 2 cases of TEN that were associated with topical CAIs rather than systemic CAIs.

Expression of Peroxiredoxin I in the Epidermis of Vitiligo / 대한피부과학회지

BACKGROUND: Although the pathogenesis of vitiligo isn't fully understood, a recent study demonstrates that oxidative stress plays an important role to induce vitiligo. Peroxiredoxin (Prx) is a novel peroxidase family to remove hydrogen peroxide using thioredoxin system, which is consisted of thioredoxin, thioredoxin reductase, and NADPH. OBJECTIVE: This study aimed to investigate the change of expression of Prx I to elucidate the role of oxidative stress in the pathogenesis of vitiligo. METHODS: Sample specimens were obtained from the lesional skin of vitiligo patients, and non-depigmented skin was obtained from the perilesional area as control samples. The skin samples were immediately frozen using liquid nitrogen, and then section samples were prepared to perform immunohistochemical staining with antibodies for Prx I. Some of the skin biopsy samples were used for primary culture of keratinocytes. Protein extracts from the expanded keratinocytes were prepared for Western blot analysis of Prx I. RESULTS: In vitiligo, the ubiquitous expression of Prx I in all layers of epidermis, which was also observed in the normal perilesional skin, was reduced in the depigmented lesion of vitiligo patients. The reduction of Prx I was remarkable from the lesions which were exposed to sunlight. Consistently, Prx I expression from the lesional keratinocytes were noticeably reduced in comparison with that from perilesional keratinocytes. CONCLUSION: Our results showing that Prx I is impaired in the epidermis of depigmented lesions of vitiligo patients suggest that oxidative stress is an important factor to induce vitiligo.