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Background Acral melanomas are known to have a low frequency of BRAF mutation, in contrary to higher KIT mutation. Recently, VE1 immunostaining was reported to have a good correlation with BRAF mutation status. Objective We aimed to evaluate the clinicopathological features of BRAF-mutated acral melanomas and validate the correlation of the VE1 immunohistochemical stains in those cases. Methods The clinical features (age, sex, anatomical site), and histopathological characteristics of 41 patients with acral melanoma were evaluated. We performed a next-generation sequencing to detect BRAF mutation status. We also determined the correlation of VE1 immunohistochemical staining with BRAF mutation status. Results Among 19 acral melanomas with BRAF mutation, common histopathological subtype was acral lentiginous melanoma (8/19, 42%) and nodular melanoma (8/19, 42%) and superficial spreading melanoma (3/19, 16%) followed. VE1 immunostaining results were positive in all 15 cases with BRAF V600E mutation (sensitivity 100%), and negative in 4 cases of BRAF non-V600E mutation. However, VE1 immunostaining was negative in all 22 patients with BRAF wild-type. Conclusion VE1 immunostaining had a good correlation with BRAF V600E mutation status.

Background Ingenol mebutate gel is a novel, field-directed topical treatment for actinic keratosis (AK). Most pivotal studies have targeted Western populations. No clinical study has been conducted to investigate its efficacy and safety in Asian populations. Objectives To evaluate the efficacy and safety of ingenol mebutate gel for treating AK of face/scalp and trunk/extremities in a large Asian (Korean) population. Patients and methods In this multicentre, open-label, interventional, parallel-group, prospective phase IV study (PERFECT, trial registration no.: NCT02716714), the eligible patients were allocated into either the face/scalp or the trunk/extremities group, according to their selected treatment area location. After application of ingenol mebutate gel, the participants were followed up for 6 months. The primary efficacy endpoint was complete clearance (CC) of AK lesions in the selected treatment area at day 57. Quality of life was evaluated using Skindex-29. Safety endpoints included local skin responses, scar, pigmentation, pain and adverse events. Results In total, 78·1% [95% confidence interval (CI) 66·86-86·92%] of subjects had CC at day 57, with 76·6% (95% CI 64·31-86·25%) in the face/scalp group and 88·9% (95% CI 51·75-99·72%) in the trunk/extremities group. Among them, CC was sustained in 88·9% (48 of 54, 95% CI 77·37-95·81%) at month 6. The local skin responses significantly increased 1 day after the treatment compared with baseline, and decreased afterwards. Among the total subjects, 7·8% (6 of 77) had hyperpigmentation on the application area. Scars were not reported. Conclusions Ingenol mebutate is effective for the treatment of AK in Asians, with tolerable safety profiles.

Pyoderma gangrenosum (PG) is a rare chronic neutrophilic dermatosis characterized by painful necrotic ulceration. The most common diseases associated with PG are inflammatory bowel disease, certain rheumatologic and hematologic diseases, and malignancy. Here, we describe the case of a 60-year-old man who presented with pruritic and painful erythematous ulcerative macules and patches on both lower extremities, and was diagnosed with PG based on his clinical and histologic features. His PG became exacerbated despite standard therapy with a high-dose systemic steroid in combination with dapsone and cyclosporine. Systemic evaluation of underlying conditions revealed rectal adenocarcinoma at the rectosigmoid junction (T3N0M0), which was completely removed via Hartmann's procedure followed by adjuvant chemotherapy. Two months after anticancer therapy, his PG was completely healed with hypertrophic scarring. Herein, we present the first case of paraneoplastic PG caused by rectal adenocarcinoma in Korea.

BACKGROUND Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (

Background Orthonyxia is an effective, noninvasive treatment for transverse nail curvature deformity. Objective To discover the factors influencing treatment results of superelastic wire orthonyxia (SEWO). Material and methods A retrospective study was conducted using clinical records of patients treated with SEWO. A multiple linear regression model was used to explain the correlation between correction pace (% per week) and the other collected variables (patient age, sex, position of treated toe, wire diameter [WD, mm], wire residence time [WRT, weeks], nail plate thickness [PT, mm], baseline nail curvature index [NCI], number of previous treatments, and the correction pace of previous treatments [CPT, % per week]). A logistic regression model was used to identify risk factors for adverse effects. Results A total of 475 cases were collected from 197 patients. The correction pace was positively related to baseline NCI, WD, and correction pace in previous treatment. Also, it was negatively related to WRT and nail PT. No clinical factor was correlated with the occurrence of side effects. Conclusion The correction pace of SEWO is affected by the baseline NCI, the diameter of the wire, nail PT, the CPT, and the WRT.

Background Psychological aspect and quality of life should be considered in treating patients with psoriasis. Objective We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. Methods The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). Results Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). Conclusion The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Background: Bullous pemphigoid (BP) is a common autoimmune- mediated blistering skin disease that is significantly associated with mortality and morbidity. However, few studies regarding the mortality and comorbidity profiles of BP have been reported in Korea. Objective: To evaluate and compare the mortality, comorbidity profiles, and risk factors between patients with BP who visited our clinic and an age-matched general population of Korea. Methods: We retrospectively evaluated 103 patients diagnosed with BP between 2006 and 2013 at Chonnam National University Hospital in Gwangju, Korea. Results: The 1-year, 2-year, and 5-year mortality rates of the patients were 18.44%, 28.16%, and 42.00%, respectively. The median age was 76 years (range, 41∼96 years). The standardized mortality ratio of patients with BP was 1.83 times that of the age- and sex-matched general population of Korea. Old age at the time of diagnosis, cardiac disease and renal disease were associated with increased 5-year mortality. In addition, the prevalence of diabetes, stroke, dementia, and Parkinson’s disease was higher among BP patients than in the general population. Conclusion: The mortality rate of patients with BP is higher than that of the general Korean population. Korean patients with BP are more likely to have dementia, Parkinson’s disease, diabetes, and stroke. Risk factors for increased 5-year mortality include old age at the time of diagnosis and medical comorbidities, especially cardiac disease and renal disease. (Ann Dermatol 30(1) 13∼19, 2018)

Background: Rosacea is a chronic cutaneous disease. Therapeutic modalities should be chosen based on the identified sub-types and clinical features in each patient. Vascular lasers, including intense pulsed light (IPL), are reportedly safe and effective in treating erythematotelan-giectatic rosacea (ETR). Objective: In this study, we assess the comparative efficacy of IPL related to several factors including clinical severity and the age of patients with ETR. Methods: Patients with ETR were classified into two groups according to the National Rosacea Society Severity Guideline. Severity score and erythema index (EI) were measured using a clinical scorecard and mexameter. For additional evaluation of therapeutic efficacy, investigator and patient global assessments (IGA, PGA) were checked. Efficacy of IPL was analyzed according to severity score, EI, IGA, and PGA related to sex, age, lactic acid stinging test, and severity. Results: Analyses of the efficacy of IPL according to severity score, EI, IGA, and PGA based on sex, age, lactic acid stinging test, and severity revealed significant differences with age and severity only. Conclusion: This study supports the efficacy of IPL treatment for patients with ETR. IPL may be more effective in patients with more severe ETR and in younger patients with ETR. (Ann Dermatol 26(4) 491~495, 2014)

The cutaneous manifestations of chronic active Epstein-Barr virus (EBV) infection can be diverse. Among them, hydroa vacciniforme-like eruption is one of the best-known features. Although rare, mucosal ulcers have been reported to be associated with EBV as a result of primary infection or immune suppression. We describe a 65-year-old female with recurrent necrotic papulovesicles on the face and both arms for 2 years. She also complained of recurrent oral and genital mucosal ulcers developing simultaneously with skin eruptions. They appeared periodically during the spring and summer and were triggered or aggravated by sun exposure. Skin biopsies from the face and genitalia showed identical findings with dense lymphocytic infiltrations. In addition, in situ hybridization revealed EBV-positive lymphoid cells in both specimens. To our knowledge, this is the first case of serologically and pathologically proven chronic active EBV infection presenting hydroa vacciniforme-like eruption and orogenital ulcers at the same time in one patient.

Cutaneous metastatic carcinoma of the nose is a rare presentation associated with lung cancer. We report here 3 cases of cutaneous metastatic carcinoma of the nose that originated from lung cancer. Two men, age 61 and 76 years, with lung cancers were referred for evaluation of a tumour on the tip of the nose. The third patient, a 57-year-old man, had developed a rosacea-like tumour on the tip of the nose; although he had no history of internal cancer, whole-body positron-emission tomography-computed tomography revealed a primary lung cancer. Skin biopsies of all 3 cases showed metastatic squamous cell carcinoma, and all primary lung cancers were squamous cell carcinomas. Only 3 patients are described here, and further reports are needed to substantiate this interesting phenomenon. When an elderly patient presents to dermatology with a tumour on the nose with or without known internal cancer, it is necessary to approach the diagnosis with caution.

Precise clinicopathological correlations of the clinical features of metastatic breast carcinoma with lymphatic-specific markers are rare. We classified 28 patients with metastatic breast carcinoma according to their clinical features. Immunohistochemical staining was performed using D2-40, CD31 and CD34. Of the 28 patients, 8 (28.6%) had inflammatory metastatic carcinoma, 6 (21.4%) had the telangiectatic type, 5 had the nodular type, 3 had the en cuirasse type, 3 had alopecia neoplastica, and 3 had a combination of features. D2-40 staining revealed dilated lymphatic channels (lymphangiectasia) in the upper dermis of all patients; in addition, 13 patients (46.4%) had intralymphatic tumour-cell emboli, which were common in those with the inflammatory and telangiectatic types. Intratumoral lymphatic invasion in the main tumour nodule was seen in 12 patients (42.9%). Our results suggest that cutaneous metastatic breast carcinomas have various clinical presentations, and that lymphatic vessels play an important role in all types of cutaneous metastasis.

Castleman's disease (CD) is an uncommon B-cell lymphoproliferative disorder characterized by lymph node hyperplasia with vascular proliferation. Cutaneous involvement in CD is rare. A 65-year-old man presented with a 7-year history of gradually developing multiple reddish to violaceous indurated plaques on the scalp, trunk, and legs. On physical examination, there were palpable enlarged cervical, axillary, and inguinal lymph nodes. Laboratory examination revealed anemia, thrombocytosis, hyperproteinemia, hypoalbuminemia, and polyclonal hypergammaglobulinemia. An inguinal lymph node biopsy and a skin biopsy were performed and the patient was diagnosed with the plasma cell type of CD. Chemotherapy was started and the lesions have responded to treatment.

Background There has been little research on extramammary Paget’s disease (EMPD) conducted in Asia. Methods The aim of this multicenter study was to investigate the clinicopathological features, biological behavior, and treatment of EMPD in 194 Korean patients over a five-year period. Results As expected, this disease exhibited a male dominance (3.9:1) pattern. To distinguish the true association of malignancy with EMPD from coincidental occurrence of malignancy, we modified Chanda’s guidelines. This analysis determined that there was an accompanying malignancy in 26 patients (14.4%), which included stomach (six cases), rectum (three cases), and colon (three cases) malignancies. With regard to treatment, 112 patients (58%) underwent conventional excisions, and 22 (11.4%) had Mohs surgery. Follow-up data for periods of 3–180 months were available for 147 patients; these data indicated that 42 patients (28.6%) experienced local recurrences. Patients who underwent Mohs micrographic surgery experienced a lower rate of recurrence (12.5%) than patients who underwent conventional excision (33.3%). Conclusions In summary, this Korean population-based study demonstrated that the clinical features of EMPD, such as gender predominance, are consistent with reports from other Asian population-based studies. However, this study additionally demonstrated that the rate of association with malignancy in the Korean population (14.4%) was higher than that observed in other Asian studies.

We describe a 74-year-old man presenting with a 10-year history of an asymptomatic, skin-colored hard plaque on his left cheek. Microscopy revealed well-demarcated tumor with peripheral palisading and peritumoral clefting in the dermis. The tumor included many plasmacytoid cells with cytoplasmic hyaline inclusions and eccentric nuclei. Electron microscopic examination showed that hyaline inclusions consisted of aggregates of filaments. Immunoperoxidase staining showed diffuse cytoplasmic expression of 34bE12, smooth muscle actin, calponin and p63. We diagnosed the patient with basal cell carcinoma (BCC) with myoepithelial differentiation and treated him with excision. Eight months postoperatively, the patient remained well with no recurrence. This distinct variant of BCC with myoepithelial differentiation, showing cytoplasmic hyaline inclusions and eccentric nuclei, has previously been confusingly termed ‘signet-ring cell BCC’. However, these plasmacytoid cells differ from signet-ring cells with vacuolated cytoplasm. To avoid confusion, we suggest the designation ‘BCC with myoepithelial differentiation’. Na SY, Choi Y-D, Choi C, Kim S-J, Won YH, Yun SJ. Basal cell carcinoma with myoepithelial differentiation: a distinct plasmacytoid cell variant with hyaline inclusions.

Background: Psoriasis and psoriatic arthritis (PsA) are included in the group of immune-mediated inflammatory diseases (IMIDs) caused by systemic inflammation; however, indicators for monitoring inflammatory activity in patients with psoriasis, such as the Psoriasis Area and Severity Index (PASI), are limited. Objective: To determine whether the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire can be used to monitor disease activity in patients with psoriasis. Methods: This was a multicenter, noninterventional, cross-sectional study. Demographic factors and PASI and PASE scores were collected to investigate associations between each. Results: PASE data were available for 1,255 patients, of whom 498 (39.7%) had a score of ≥37. Compared with the group with PASE score ＜37, the group with score ≥37 had a higher proportion of women (34.9% vs. 48.8%, p＜0.0001), older mean age at diagnosis (36.4 vs. 41.7 years, p＜0.0001), more severe disease activity using PASI and body surface area measures (p=0.0021 and p=0.0008, respectively), and higher mean body mass index (23.7 vs. 24.1, p=0.0411). In a multiple linear regression model, PASE score was positively associated with cutaneous disease activity (p＜0.0001). Conclusion: After risk-adjustment, PASE was positively associated with PASI, which suggests that PASE can be sensitive to disease activity. Since psoriasis is regarded as one of the IMIDs, PASE may be utilized as a tool not only to screen PsA but also to monitor disease activity. (Ann Dermatol 31(1) 29∼36, 2019)

We report a 68-year-old Korean man presenting with asymptomatic erythematous polycyclic annular firm plaques on his back that spread to the right shoulder. Histopathologic examination showed dense, diffuse infiltrates involving the entire dermis, consisting of atypical lymphocytes with many centrocytes and a few centroblasts. Spindle-shaped cells with elongated, twisted nuclei containing dispersed chromatin were also seen. Immunohistochemical analysis showed that all of the cells were strongly positive for CD20, CD21, CD79a and CD45, while they were negative for CD3, CD5, CD10, CD23, CD35, CD43, CD45RO and CD68. The spindle cells were also negative for smooth-muscle actin, desmin, S-100 and CD34. They consistently expressed nuclear bcl-6, but did not express bcl-2, multiple myeloma-1 and p16. We diagnosed him with primary cutaneous spindle cell B-cell lymphoma (PCSBCL) and treated him with six cycles of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab (R-CHOP) chemotherapy; his skin lesions disappeared completely. Immunohistochemical profiles suggest that PCSBCL is a variant of primary cutaneous follicle center lymphoma.

Although non-scarring diffuse hair loss has been frequently observed in systemic lupus erythematosus (SLE) patients, the pattern of hair loss with regard to its frequency in SLE has been rarely studied. The aim of this cross-sectional study was to evaluate the hair loss patterns in SLE during the course of disease. We evaluated 122 SLE patients (age range, 13-71 years; mean age, 32.7 +/- 10.6; female : male ratio, 12.6:1), by conducting interviews about hair loss patterns before and after a diagnosis of SLE using a questionnaire format. History taking and physical examinations were done at the time of interview, and photographs were taken to discriminate the active LE-specific scarring hair loss from the LE-nonspecific diffuse hair loss. Frequency and correlation analysis were performed on the data from the interviews and photographs for determining their relation with the SLE Disease Activity Index (SLEDAI). We found that 104 patients experienced at least one hair loss event before or during the course of SLE. Eighteen patients experienced patch alopecia, including eight who experienced this malady both before and after the diagnosis; thus, the overall prevalence of patch alopecia was 14.8% (18/122). Eighty-six patients experienced hair loss after diagnosis, of which non-scarring diffuse hair loss was the most common pattern (65.1%, 56/86) followed by non-scarring patch alopecia (15.1%, 13/86). The interview survey failed to identify a statistically significant relationship between the hair loss pattern and the SLEDAI. Our results suggest that non-scarring patch alopecia is also an important pattern in SLE that should be included in the differential diagnosis of alopecia areata and confirmed by histopathological examination.

The epidemiological and clinicopathological features of cutaneous lymphoma may vary by geographical area. However, only a few large-scale epidemiological studies of cutaneous lymphoma have been performed, mainly in the USA and Europe. This aim of this study was to determine the recent characteristics of cutaneous lymphoma in Korea according to the WHO/EORTC classification. A total of 422 patients with newly diagnosed cutaneous lymphoma from January 2009 to December 2013 comprising 293 cases of mature T-cell and natural killer (NK)-cell lymphoma and 39 cases of mature B-cell lymphoma were retrospectively reviewed. The incidence of mature B-cell lymphoma was lower in Korea than in Europe and the USA. Diffuse large B-cell lymphoma was more prevalent in Korea than in Western countries. The incidence of extranodal NK/T-cell lymphoma, nasal-type was higher in Korea than in Western countries and Japan.

This study sought to develop a therapeutic algorithm for selecting the optimal systemic drugs to treat moderate to severe psoriasis, based on the patient's Psoriasis Area Severity Index (PASI) score. Data from 191 patients undergoing treatment for plaque psoriasis were retrospectively analyzed. Pre- and post-treatment PASI scores were compared across patients treated with acitretin of retinoic acid (RA; n = 95), methotrexate (MTX; n = 41) or cyclosporin A (CsA; n = 55). The PASI score improvement was examined at weeks 4 (primary end-point) and 12 (secondary end-point). MTX and CsA had a higher global therapeutic efficacy, with more patients exhibiting a marked improvement (≥75% improvement in PASI [PASI 75]) at week 12 with MTX (56.1%, P = 0.028) and CsA (54.5%, P = 0.025) than RA (35.8%). Multivariate analysis adjusting for confounders produced consistent results (P = 0.026). For patients with severe psoriasis (PASI >12), the PASI 75 response was higher with CsA (55.6%) than RA (31.5%) (P = 0.023) at week 4 and higher with MTX (57.1%, P = 0.029) and CsA (61.5%, P = 0.017) than RA (21.7%) at week 12. Because RA is a standard systemic drug, the RA group was divided into two subgroups based on the PASI 50 response at week 12. Marked or moderate improvement (PASI ≥50) with RA was observed in patients with a pretreatment PASI score less than 14. Thus, oral RA is recommended as a first-line drug for patients with PASI of less than 14, and MTX or CsA are recommended for patients with PASI of 14 or more.

Drug rash with eosinophilia and systemic symptoms (DRESS) is characterized by fever, rash and internal organ involvement after exposure to certain drugs. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Cross-sensitivity between not only the aromatic anticonvulsants, but also the aromatic and non-aromatic anticonvulsants, is possible. We report here a case of a Korean woman who had previously tolerated valproate, but developed DRESS due to valproate after carbamazepine intake, which indicates cross-sensitivity. Her skin lesions displayed diffuse oedematous patches on the entire body associated with tense bullae on her arms and legs. Circulating auto-antibody to 190-kDa antigen was detected in the patient's serum by indirect immunofluorescence and immunoblotting, which might contribute to a pathogenic role in DRESS.

The purpose of this study is to determine the frequency of responses to selected fragrances in patients with suspected fragrance allergy and to evaluate the risk factors. 9 dermatology departments of university hospitals have participated in this study for the past 1 year. To determine allergic response to fragrances, 18 additional fragrances in addition to the Korean standard and a commercial fragrance series were patch-tested in patients with suspecting cosmetic contact dermatitis. Over 80% of the patients were women, and the most common site was the face. Cinnamic alcohol and sandalwood oil (Santalum album L.) showed high frequencies of positive responses. Of the specific fragrances, ebanol, alpha-isomethyl-ionone (methyl ionone-gamma) and Lyral (hydroxyisohexyl 3-cyclohexane carboxdaldehyde) showed high positive responses. We compared the results obtained during this study with those of other studies and concluded that including additional fragrance allergens may be useful for the detection of fragrance allergy.

Atopic dermatitis is a chronically relapsing, common inflammatory skin disease, which significantly affects quality of life negatively in many respects. Topical steroids are the mainstay of atopic dermatitis treatment but they carry the risk of local side effects. A topical formulation of tacrolimus, a macrolide calcineurin inhibitor, has recently been developed.To evaluate the efficacy and safety of 0.03% tacrolimus ointment for the treatment of moderate to severe atopic dermatitis in Korea.An open, non-comparative, multi-center study with 4 weeks' follow-up was performed. A total of 180 patients (aged 2-57 years old) were enrolled. Tacrolimus ointment (0.03%) was applied to all involved areas twice daily. Efficacy was evaluated by an investigator's global assessment, the eczema area and severity index score, and by the patient's assessment of pruritus and clinical response at baseline, and after weeks 1, 2 and 4. Dermatology life quality index (DLQI), children's DLQI (CDLQI) and toddler's DLQI were assessed at baseline and at week 4. The safety assessment included monitoring all adverse events and clinical laboratory values.All efficacy parameters were improved. The mean EASI (eczema area and severity index) score was 19.7 at baseline and reduced to 8.0 at the end of the study. Moderate improvement was observed by the investigator's global assessment after 4 weeks' treatment. A marked decrease of pruritus was observed, and mild or moderate improvement was observed by patients' global assessments after the treatment period. Significant benefits in terms of quality of life in adults and children with atopic dermatitis were obtained. The most common adverse events associated with tacrolimus treatment were transient skin burning sensation (45.3%) and pruritus (41.6%) at the site of application.0.03% tacrolimus ointment should be considered effective and safe in both Korean children and adults with moderate to severe atopic dermatitis.

Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratinocytes, melanocytes and endothelial cells in response to proinflammatory cytokines and UV radiation, has been reported to prevent UV-induced apoptosis in the skin. We have examined the effects of NO on UVB-induced lipid peroxidation in murine skin in vivo. UVB induced a dose-dependent increase in lipid peroxidation of skin extracts in vitro; however, lipid peroxidation in the skin in vivo remained unaffected at irradiation doses of less than 1.0 J cm-2 and decreased significantly at doses over 1.5 J cm-2 (P < 0.01). Time-delayed inhibition of lipid peroxidation in the skin in vivo was observed after irradiation at 1.5 J cm-2. Administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxidation (P < 0.05), while it suppressed the ear-swelling response (ESR), a biological marker of inflammation. By contrast, administration of sodium nitroprusside, an NO enhancer, suppressed lipid peroxidation (P < 0. 01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) was observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm-2. The UVB-induced iNOS expression was markedly inhibited by L-NAME, suggesting that iNOS is a major enzyme in the production of NO. These results suggest that NO acts as a mediator of the inflammatory response in UVB-irradiated skin, and that lipid peroxidation is inversely regulated with the NO-mediated inflammatory response in vivo.

BACKGROUND. Glycolic acid treatment is believed to reverse the photoaging process by increasing collagen synthesis in the skin. However, this effect has not been clearly defined even though alpha hydroxy acid products are used extensively. OBJECTIVE. This study aimed to define the primary effect of glycolic acid on collagen synthesis that may be achieved by functional activation or proliferation of fibroblasts. METHODS. Glycolic acid treatment was compared in vivo with lactic acid (hairless mice) and in vitro to malic acid (normal human skin fibroblast culture) with controls. To find the functional activation of fibroblasts, Northern blot assay for type I collagen synthesis with histometric analysis (in vivo) was performed. Cell proliferation assay (MTT) with procollagen type I C-peptide (PICP) enzyme immunoassay and radioisotope ([ 3 H]proline) incorporated collagen production from cultured fibroblasts were determined. RESULTS. The in vivo collagen mRNA expression with histometric analysis revealed greater collagen synthesis by glycolic acid compared with lactic acid and control. In vitro cell proliferative effect of glycolic and greater amount of collagen production showed a steady increase in a dose-dependent manner. CONCLUSION. Both in vivo and in vitro, glycolic acid treatment increased the production of collagen and fibroblast proliferation. These effects may be the mechanism by which glycolic acid reverses the process of photoaging. © 1998 by the American Society for Dermatologic Surgery, Inc. Dermatol Surg 1998;24: 1054-1058.

A 46-year-old man visited our department with masses on the face and a skin problem. Approximately 15 years ago, he had noticed marked thickening of the skin on the face and scalp, which had exaggerated progressively to produce deep wrinklings with seborrhea ( Fig. 1). He had profuse perspiration of the face, hands, feet, and the upper aspects of the trunk. Figure 1. Clinical features of pachydermoperiostosis, consisting of thickened skin folds and deep wrinkles on the forehead and scalp. A large ulcerative tumor on the nasal dorsum and a nodular one on the glabellar area (arrow) can be seen. Three years earlier, he developed a single nodule on the nose, which progressed to an ulcerated mass. In addition, another tender nodule was noticed on the glabella 3 months prior to his visit. He had chronic epigastralgia and diffuse arthralgia. His brother, 52 years old, had similar lesions of pachydermia and cutis verticis gyrata with digital clubbings. His two sisters had no skin lesions, but suffered from congenital cyanotic heart disease and spinal deformity, respectively. Human leukocyte antigen (HLA) typings between the two affected brothers revealed almost identical HLA-A, HLA-B, and HLA-C class I antigens. On physical examination, the patient was a short, underdeveloped man with a height of 153 cm and weight of 44 kg. The larger tumor on the nose was 3.0 × 3.5 cm in diameter, producing a perforated tunnel connecting to the nasal cavity. Facial follicular papules, blepharoptosis, palmoplantar blanching, plantar thickening with fissures, and swelling of the knees and ankles were also observed. Histopathologic findings of the main tumor revealed pleomorphic, atypical squamous cells with mixed inflammatory cells, and numerous horn pearls with abnormal keratinization in the epidermis and dermis ( Fig. 2). The second tumor was a 1.0-cm-sized, deep-seated, firm nodule. The skin biopsy from this nodule showed the same findings as those of the larger tumor. In the thickened skin of the forehead, diffuse mucinous thickening of the dermis was remarkable, which exhibited a positive reaction to alcian blue stain at pH 2.5, and hypertrophied sebaceous glands were found in the dermis. Figure 2. Photomicrograph of biopsy specimen from the ulcerative tumor on the nasal dorsum shows typical features of well-differentiated squamous cell carcinoma Laboratory examinations showed findings of severe iron deficiency anemia. In serum electrophoresis, there was albumin/globulin inversion. 1Bone studies showed thoracic scoliosis and cortical thickening of the long bones. There were peptic ulcers on the gastric pylorus and bulb of duodenum from gastroduodenoscopy. The chromosomal analysis, which is constitutional or stressed by UVB (3.2–19.2 J/m2 ), diepoxybutane (DEB, 0.1 μg/mL), 2and mitomycin (MMC, 0.1 μg/mL), showed neither numerical nor structural aberrations; however, karyotyping in synchronized lymphocyte culture with methotrexate treatment (final concentration, 10–7 m) showed 10 breakage points at five cells from 20 lymphocytes ( Fig. 3). Electron microscopic study and tissue cultures searching for morphologic abnormality of the fibroblasts near the nodules showed no significant specific findings. Figure 3. Karyotyping of the lymphocytes from the patient shows multiple chromatid breaks in chromosome 4 at band 4p15, chromosome 7 at band 7p15 (left), chromosome 9 at band 9p22, and chromosome 14 at band 14q24 (right) For the reduction of the ulcerative tumor before surgical intervention, the patient was irradiated with an electron beam over 7 weeks (total dose, 7000 cGy). Also, the glabellar nodule was removed and facial rhytidectomy was performed. With a recommendation to avoid sunlight, no lesions had developed during follow-up for 1 year.

Ginkgo bilobα studies have focused on the anti-inflammatory effects of the major components, ginkgolide and bilobalide, whereas little is known about their effect on fibroblasts. This study demonstrated the enhancing effects of Ginkgo L. extracts, especially the fiavonoid fractions: quercetin, kaempfe-rol, sciadopitysin, ginkgetin, isoginkgetin, on the proliferation of normal human skin fibroblast in vitro measured by MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and direct hemocytometer cell count. Furthermore, increased production of collagen and extracellular fi-bronectin were documented by radioisotope (2,3-3H-proline) incorporated collagen assay, procollagen type I C-peptide assay and by immunoturbidimetric assay. These proliferative effects suggest another useful pharmacologic application of Ginkgo L. extracts in addition to their well-known anti-inflammatory effect.

Autoimmune progesterone dermatitis is a rare cyclic premenstrual reaction to progesterone produced during the luteal phase of the menstrual cycle. The clinical symptoms of autoimmune progesterone dermatitis overlap with other forms of dermatosis such as erythema multiforme, eczema, fixed drug eruption, urticaria, and angioedema. We experienced 3 cases of autoimmune progesterone dermatitis. All patients had a recurrent history of monthly skin eruptions. Skin lesions normally began a few days before menstruation and resolved a few days later. Patients were confirmed to have autoimmune progesterone dermatitis by the results of the progesterone intradermal test. All three patients had different clinical findings such as erythema annulare centrifugum, urticaria, contact dermatitis, and rosacea. Because patients presented with variable clinical manifestations, they could have been easily misdiagnosed. The patients were treated with oral contraceptive, antihistamine and steroids for symptom control. We propose that dermatologists should consider autoimmune progesterone dermatitis in cases of recurrent cyclic skin eruptions in female patients. Further, if this condition is suspected, thorough history taking including that on menstrual cycle and intradermal progesterone test should be performed.

Summary The immunosuppressive peptide cyclosporin A (CyA) is an extremely effective therapy for severe recalcitrant psoriasis, although its mechanism of action is unknown. In this study, we examined the effect of CyA on keratinocyte growth and cytokine expression, and showed that CyA inhibits the growth of murine and human keratinocytes (KC) and KC cell lines. In addition, CyA inhibits the expression of cytokine genes in a dose-dependent fashion. After 2 days' incubation with 20 μM CyA, interleukin-lα (IL- α), interleukin-1β (IL-l β), and interleukin 8 (IL-8) mRNA were decreased by 4-fold, 3·3-fold and 3·3-fold, respectively, in COLO-16, a keratinocyte cell line. IL-1 biological activity recovered from COLO-16 culture supernatants decreased to one-fifth of that of controls. In the murine KC cell line PAM 212, 10 μ CyA treatment for 2 days downregulated IL-1α, tumour necrosis factor-α (TNF-α) and IL-1 receptor by 60%, but had no effect on the message for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), ornithine decarboxylase and β-actin. Cells cultured for 5 days in the presence of CyA required much lower concentrations (2 μM) to achieve the same degree of inhibition of IL-1α. Similar tissue concentrations of CyA have been reported in psoriatics undergoing CyA therapy. The inhibition of KC growth caused by CyA treatment could be partially overcome by the addition of 0·l–1·0 ng/ml of recombinant IL-1α simultaneously with CyA, suggesting that the growth inhibitory effect of CyA on KC cultures is due in part to loss of autocrine cytokine stimulation. Collectively, these data suggest that CyA may exert some of its therapeutic effects in psoriasis by inhibiting the release of KC cytokines, so terminating epidermal hyperproliferation. As some of these cytokines (IL-1, IL-8 and TNF-α) are chemotactic for leucocytes, or induce endothelial adhesion molecules, infiltration and inflammation may also be reduced by their inhibition.

Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and this is characterized by acute, nonfollicular sterile pustules on a background of edematous erythema. Hydroxychloroquine (HCQ) has been widely used to treat rheumatic and dermatologic diseases and HCQ has been reported to be an uncommon cause of AGEP. A 38-year-old woman with a 1-year history of dermatomyositis and polyarthralgia was treated with HCQ due to a lack of response to a previous medication. Three weeks after starting HCQ therapy, the pustular skin lesion developed and then this resolved after the HCQ was withdrawn and steroid treatment was started. A similar pustular eruption developed after HCQ was accidentally readministered.

Dermatological examination is critical for the evaluation of lupus erythematosus. However, little is known about the epidemiology and clinical characteristics of the lupus erythematosus patients that visit dermatology clinics with the chief complaint of skin lesions, especially among Asian populations. We performed this study to determine the epidemiology of cutaneous lupus erythematosus for three subtypes: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus, and for lupus erythematosus non-specific skin disease. Also, we sought to determine the relationship between each type of lupus erythematosus, by the skin manifestations and systemic lupus erythematosus. The medical records of lupus erythematosus patients that were diagnosed by their clinical manifestations, skin biopsy results, and laboratory findings from January 1998 through December 2007 were reviewed. A total of 117 patients were diagnosed with lupus erythematosus; 62 cases had chronic cutaneous lupus erythematosus, 11 had subacute cutaneous lupus erythematosus, and 41 had acute cutaneous lupus erythematosus. The remaining three had systemic lupus erythematosus features with lupus erythematosus non-specific skin lesions such as Raynaud phenomenon, livedo reticularis/vasculitis, non-scarring alopecia, and periungual telangiectasia. The acute cutaneous lupus erythematosus subgroup showed extreme female predominance (9.2:1) whereas subacute and chronic cutaneous lupus erythematosus subgroups did not. Patients with chronic cutaneous lupus erythematosus tended to be older than other groups (peak incidence in the fifth decade). Incidence of laboratory abnormalities, including positive connective tissue markers such as antinuclear, double-strand DNA, and Ro/SS-A antibodies, were present in the order acute, subacute, and chronic cutaneous lupus erythematosus. Acute cutaneous lupus erythematosus almost always indicated systemic involvement of lupus erythematosus, whereas chronic cutaneous lupus erythematosus did not predict the development or existence of systemic lupus erythematosus and had a benign clinical course. Careful consideration of lupus erythematosus non-specific skin lesions may help detect systemic lupus erythematosus regardless of the diagnosis of cutaneous lupus erythematosus. Lupus (2009) 18, 1320—1326.

Dapsone has potent anti-inflammatory effects, and is used in the treatment of leprosy, cutaneous vasculitis, neutrophilic dermatoses, and dermatitis herpetiformis and other blistering disorders. However, it may cause severe adverse reactions such as hypersensitivity syndrome, which is characterized by fever, skin rash, hepatitis and lymphadenopathy. We report a 44-year-old female Korean patient with dapsone hypersensitivity syndrome (DHS) that presented as a bullous skin eruption. The patient had a 1-year history of urticarial vasculitis, treated with antihistamines, prednisolone and dapsone. Although the skin lesions improved, she reported fever, nausea, abdominal pain, jaundice, fatigue and skin rashes. On physical examination, there were generalized erythematous macules and purpura with facial oedema that developed into vesicles on the upper limbs. Histological examination of a skin biopsy of a vesicular lesion found subepidermal oedema with a mixed inflammatory cell infiltrate, including eosinophils in the dermis. Indirect immunofluorescence testing using normal foreskin as substrate revealed IgG deposits in the basement membrane zone. Circulating autoantibodies against antigens of 190 and 230 kDa were found by immunoblotting analysis using epidermal extracts. This case illustrates DHS with the formation of circulating autoantibodies.

Background: Although rosacea is a chronic cutaneous inflammatory disorder that’s commonly seen in adults, the etiology and pathogenesis of the illness remain unclear. A well established diagnostic classification and grading system may play a critical role in performing research and it would serve as a diagnostic reference in the clinical field. Objective: We sought to classify the patients with the new standard classification and grading system and we wanted determine the peculiar features and relationships of each subtype. We also analyzed the relationships between the degree of sun exposure and each subtype. Methods: We reviewed the medical records and clinical photos of 168 patients who were diagnosed with rosacea from 2002 to 2007 at our hospital. The standard classification and grading system suggested by the National Rosacea Society (NRS) Expert Committee was adopted to evaluate each patient’s subtype and the severity. Results: The male：female ratio was 1： 2.29. The mean age at the time of diagnosis was 47.8 years. The mean duration of disease was 3.5 years. Sun exposure and hot baths/exercise were the two most common precipitating factors, while the majority of patients did not have any specific factor that relieved their symptoms. According to the NRS classification and grading system, the patients were classified into four subtypes. One hundred sixty two (96.4%) patients were diagnosed with the erythematotelangiectatic subtype irrespective of severity. Eighty five (50.6%) patients had the papulopustular subtype and 24 (14.3%) patients had ocular rosacea. Eight (4.8%) patients displayed mild phymatous change. The degree of sun exposure had significant correlation with the development and severity of the erythematotelangiectatic subtype (p