Journals RSS : Gourt

Panniculitis With Arthralgia in Patients With Melanoma Treated With Selective BRAF Inhibitors and Its Management [Observation]

Background Painful lobular panniculitis appears to be a novel cutaneous adverse effect of selective BRAF inhibitors. Observation We report the clinical course and management in 2 women with metastatic melanomas harboring the BRAFV600E mutation, who developed panniculitis with arthralgia during therapy with selective oral BRAF inhibitors. Panniculitis with arthralgia was the acute presenting adverse effect in both patients. Painful, red, nodular lesions were located on the upper and lower extremities. Biopsy specimens of the nodules showed a mild, predominantly lobular neutrophilic panniculitis. Analgesic and anti-inflammatory treatment improved panniculitis and arthralgia in both cases. It was also necessary to reduce the BRAF inhibitor dose in 1 patient. Conclusions During therapy with selective BRAF inhibitors, panniculitis with arthralgia represents a new adverse effect that can require dose reduction. In case of this adverse effect, treatment with nonsteroidal anti-inflammatory drugs, such as etoricoxib, should be initiated early to keep patients on treatment and to avoid drug discontinuation and tumor progression.

Phase I Clinical Trial of O6-Benzylguanine and Topical Carmustine in the Treatment of Cutaneous T-Cell Lymphoma, Mycosis Fungoides Type [Study]

Objectives To evaluate the toxic effects and maximum tolerated dose of topical carmustine [1,3-bis (2-chloroethyl)-1-nitrosourea] following intravenous O6-benzylguanine in the treatment of cutaneous T-cell lymphoma (CTCL), and to determine pharmacodynamics of O6-alkylguanine DNA alkyltransferase activity in treated CTCL lesions. Design Open-label, dose-escalation, phase I trial. Setting Dermatology outpatient clinic and clinical research unit at a university teaching hospital. Patients A total of 21 adult patients (11 male, 10 female) with early-stage (IA-IIA) refractory CTCL, mycosis fungoides type, treated with topical carmustine following intravenous O6-benzylguanine. Intervention Treatment once every 2 weeks with 120 mg/m2 intravenous O6-benzylguanine followed 1 hour later by whole-body, low-dose topical carmustine starting at 10 mg, with 10-mg incremental dose-escalation in 3 patient cohorts. Cutaneous T-cell lymphoma lesional skin biopsy specimens were taken at baseline and 6 hours, 24 hours, and 1 week after the first O6-benzylguanine infusion for analysis of O6-alkylguanine-DNA alkyltransferase activity. Main Outcome Measures Clinical response measured by physical examination and severity-weighted assessment tool measurements, safety data acquired by review of adverse events at study visits, and O6-alkylguanine-DNA alkyltransferase activity in treated lesion skin biopsy specimens. Results A minimal toxic effect was observed through the 40-mg carmustine dose level with 76% of adverse events being grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Mean baseline O6-alkylguanine-DNA alkyltransferase activity in CTCL lesions was 3 times greater than in normal controls and was diminished by a median of 100% at 6 and 24 hours following O6-benzylguanine with recovery at 1 week. Clinical disease reduction correlated positively with O6-alkylguanine-DNA alkyltransferase activity at 168 hours (P = .02) and inversely with area under the curve of O6-alkylguanine-DNA alkyltransferase over 1 week (P = .01). Twelve partial responses and 4 complete responses were observed (overall response, 76% [95% CI, 0.55-0.89]). Five patients discontinued therapy owing to adverse events with a possible, probable, or definite relationship to the study drug. Conclusion O6-benzylguanine significantly depletes O6-alkylguanine-DNA alkyltransferase in CTCL lesions and in combination with topical carmustine is well tolerated and shows meaningful clinical responses in CTCL at markedly reduced total carmustine treatment doses. Trial Registration clinicaltrials.gov Identifier: NCT00003613

Trends in Melanoma Mortality Among Non-Hispanic Whites by Educational Attainment, 1993-2007 [Study]

Objective To evaluate overall trends in melanoma mortality rates among non-Hispanic whites by educational level. Design Descriptive study. Setting Death certificate records from 26 states, representing approximately 45% of the US population as reported by the National Center for Health Statistics, with recorded educational level information and population data from the US Bureau of Census Current Population Survey. Patients Recorded deaths from malignant melanoma in non-Hispanic whites reported from 1993 through 2007. Main Outcome Measures Age-standardized mortality rates for melanoma were evaluated by educational attainment (a marker of socioeconomic status) among non-Hispanic whites (aged 25-64 years) from 1993 through 2007. Rate ratios assessed the time trend in age-adjusted death rates by sex and educational level. Mortality differentials in educational level were measured using the regression-based Relative Index of Inequality. All statistical tests were 2-sided. Results Melanoma mortality declined significantly between 1993-1997 and 2003-2007 in men (RR [rate ratio], 0.916; 95% CI, 0.878-0.954; P < .001) and women (RR, 0.907; 95% CI, 0.857-0.957; P < .001). However, these declines occurred only among the most educated persons (≥13 years of education irrespective of sex), and nonsignificant increases were found among the least-educated individuals, specifically men (P = .17). As a result, the Relative Index of Inequality by education in melanoma mortality in 2003-2007 relative to 1993-1997 (baseline) widened by 51.7% in men and by 35.7% in women. Conclusions Recent declines in melanoma mortality rates among non-Hispanic whites in the United States mainly reflect declines among the most-educated individuals. The widening disparities in melanoma mortality rates by education calls for early detection strategies to effectively target high-risk, less-educated, non-Hispanic white individuals.

The Children and Sunscreen Study: A Crossover Trial Investigating Children's Sunscreen Application Thickness and the Influence of Age and Dispenser Type [Study]

Objectives To measure the thickness at which primary schoolchildren apply sunscreen on school day mornings and to compare it with the thickness (2.00 mg/cm2) at which sunscreen is tested during product development, as well as to investigate how application thickness was influenced by age of the child (school grades 1-7) and by dispenser type (500-mL pump, 125-mL squeeze bottle, or 50-mL roll-on). Design A crossover quasiexperimental study design comparing 3 sunscreen dispenser types. Setting Children aged 5 to 12 years from public primary schools (grades 1-7) in Queensland, Australia. Participants Children (n = 87) and their parents randomly recruited from the enrollment lists of 7 primary schools. Each child provided up to 3 observations (n = 258). Intervention Children applied sunscreen during 3 consecutive school weeks (Monday through Friday) for the first application of the day using a different dispenser each week. Main Outcome Measure Thickness of sunscreen application (in milligrams per square centimeter). The dispensers were weighed before and after use to calculate the weight of sunscreen applied. This was divided by the coverage area of application (in square centimeters), which was calculated by multiplying the children's body surface area by the percentage of the body covered with sunscreen. Results Children applied their sunscreen at a median thickness of 0.48 mg/cm2. Children applied significantly more sunscreen when using the pump (0.75 mg/cm2) and the squeeze bottle (0.57 mg/cm2) compared with the roll-on (0.22 mg/cm2) (P < .001 for both). Conclusions Regardless of age, primary schoolchildren apply sunscreen at substantially less than 1.00 mg/cm2, similar to what has been observed among adults. Some sunscreen dispensers seem to facilitate thicker application than others.

Prediction of Sentinel Lymph Node Positivity by Growth Rate of Cutaneous Melanoma [Study]

Objective To determine whether growth rate (GR) of cutaneous melanoma predicts the histological sentinel lymph node (SLN) positivity. Design Retrospective cohort study. Setting Two tertiary melanoma referral centers. Patients A total of 698 patients with invasive primary cutaneous melanoma in whom the SLN was identified between January 1, 2000, and June 30, 2010. Main Outcome Measure Based on previous studies, a surrogate measure for GR in primary invasive melanoma was calculated as the ratio of Breslow thickness to time to melanoma development. Results The SLN was positive in 20.2% of patients. Multivariate logistic regression analysis revealed that GR, Breslow thickness, and the presence of microscopic satellitosis were independently associated with SLN positivity. The probability of SLN positivity was 8.2% for slow-growth melanomas (<0.10 mm/mo) compared with 19.8% for intermediate-growth melanomas (0.10-0.50 mm/mo) and 37.7% for fast-growth melanomas (>0.50 mm/mo). Growth rate was not an independent predictive factor for survival. Conclusion Growth rate of primary cutaneous melanoma, together with Breslow thickness and the presence of microscopic satellitosis, predicts the histological SLN positivity.

Communication About Family Members' Risk of Melanoma: Self-reported Practices of Dermatologists in the United States [Study]

Objectives To assess current self-reported communication and screening practices of dermatologists to their patients with melanoma about family members' risk of melanoma at the time of diagnosis and to understand the barriers that dermatologists encounter in communicating risk to patients. Design Descriptive survey study. Setting Office-based practicing physicians in the United States. Participants One thousand dermatologists. Main Outcome Measure Melanoma risk communication practices. Results Of 974 eligible dermatologists, 406 completed the survey (response rate, 41.7%). Almost 85% of dermatologists reported that they often or always communicate risk to patients with melanoma about their first-degree relatives, and almost 80% reported that they often or always advise their patients with melanoma that their older children (≥18 years) may be at greater risk of skin cancer. However, less than 50% of dermatologists routinely offered to screen first-degree relatives who live nearby, while only 19.7% used medical record reminders to note communication of melanoma risk to family members. Most dermatologists reported no major barriers to melanoma risk communication. However, the presence of "any risk communication barrier" (time constraints, absence of guidelines, or lack of written material) was associated with reduced melanoma risk communication practices by dermatologists. Conclusions The observed high rates of self-reported risk communication by dermatologists to patients with melanoma about their first-degree family members are encouraging. However, the reported low rates of actual screening of first-degree relatives warrant easy-to-administer office-based medical record reminders to facilitate and optimize screening of at-risk relatives.

A Cross-sectional Study Examining the Correlation Between Sunless Tanning Product Use and Tanning Beliefs and Behaviors [Study]

Objectives To establish the effect of sunless tanning products on tanning behaviors and to determine characteristics of sunless tanning product users. Design A cross-sectional survey study conducted between May 30, 2007, and December 4, 2007. Setting The Emory University campus and surrounding locations in Atlanta, Georgia. Participants Four hundred fifteen community and university-affiliated women. Main Outcome Measures Self-reported use of sunless tanning products and UV radiation tanning methods. Results Forty-eight percent of participants had used sunless tanning products, 70.6% had tanned in the sun, and 26.0% had used tanning beds at least once in the past year. Most participants (92.7%) believed that tanned skin is more attractive than untanned skin, and 79.2% reported feeling better about themselves when tan. Many sunless tanning product users reported decreased frequency of tanning in the sun (36.8%) or in tanning beds (38%) because of product use. Frequent users were more likely to have decreased their UV radiation exposure. Lighter complexion, frequent use of UV radiation tanning methods, feeling better about oneself when tan, and having a history of skin cancer were independently associated with sunless tanning product use. Conclusions The desire for tanned skin remains strong despite growing awareness of the dangers of UV radiation exposure. In some women, sunless tanning product use is associated with decreased UV radiation tanning frequency, especially in women who use them repeatedly. Improvements in the appearance of sunless tanning product tans may allow wider acceptance by the public and further decreases in UV radiation tanning practices.

Calcinosis Cutis Occurring in Association With Autoimmune Connective Tissue Disease: The Mayo Clinic Experience With 78 Patients, 1996-2009 [Study]

Objective To describe characteristics and treatment of patients with calcinosis cutis in the clinical setting of autoimmune connective tissue disease (ACTD). Design Retrospective study. Setting Tertiary referral center. Patients Seventy-eight patients with calcinosis cutis and ACTD between 1996 and 2009. Main Outcome Measures Clinical features, treatments, and outcomes of patients with calcinosis cutis in the clinical setting of ACTD. Results Of 78 patients (mean age at onset of calcinosis cutis, 40.1 years), 64 (82%) were female. The following diseases were associated with calcinosis cutis: dermatomyositis (n = 30) with classic (n = 15), juvenile (n = 14), and amyopathic (n = 1) subtypes; systemic sclerosis with limited cutaneous scleroderma (n = 24); lupus panniculitis (n = 4); systemic lupus erythematosus (n = 2); mixed connective tissue disease (n = 4); overlap connective tissue disease (n = 6); undifferentiated connective tissue disease (n = 6); polymyositis (n = 1); and rheumatoid arthritis (n = 1). Therapy for calcinosis cutis consisted of medical treatment alone (n = 19), surgical therapy alone (n = 11), combined medical and surgical treatment (n = 17), no treatment (n = 30), and unknown (n = 1). Diltiazem hydrochloride was the most commonly used medical therapy, with 9 of 17 patients having a partial response. Twenty-eight patients had surgical excision of 1 or more lesions of calcinosis cutis: 22 had a complete response, 5 had a partial response, and 1 had no response. Conclusions Dermatomyositis and systemic sclerosis were the most common ACTDs associated with calcinosis cutis. Although no treatment was uniformly effective, surgical excision of symptomatic lesions and medical treatment with diltiazem provided benefit for some patients.

A Systematic Review of Treatments for Hidradenitis Suppurativa [Study]

Objectives To conduct a systematic review of the effectiveness of various modalities to treat hidradenitis suppurativa (HS) and to establish recommendations on its appropriate management. Data Sources MEDLINE, Cochrane, and PubMed databases. Study Selection English-language prospective, retrospective, and case studies describing at least 4 patients with HS. Data Extraction Data quality and validity were addressed by multiple reviewers using independent extraction. Data Synthesis Studies were categorized as treatments using antibiotics, biological agents, laser surgery, excisional surgery, or miscellaneous modalities. Of 62 publications included in the review, 4 studies met criteria to be assigned the highest grade for quality of evidence. Conclusions Shown to be effective treatments for HS were a clindamycin-rifampin combination regimen, a course of infliximab, monthly Nd:YAG laser sessions, and surgical excision and primary closure with a gentamicin sulfate–collagen sponge. Most therapies used to treat HS were supported by limited or weak scientific evidence. A treatment approach is presented based on the evidence and on clinical experience at the Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. This review emphasizes the need for large randomized controlled trials to evaluate treatment options for HS.

Poor Benefit/Risk Balance of Intravenous Immunoglobulins in DRESS [Research Letter]

Combination Treatments for Psoriasis: A Systematic Review and Meta-analysis [Evidence-Based Dermatology: Review]

Objective To summarize the current state of evidence for combination topical and systemic therapies for mild to severe psoriasis. Data Sources We performed a systematic search for all entries in PubMed, CINAHL, Cochrane Review, and EMBASE related to combination treatments for psoriasis through July 2010. Study Selection We included randomized controlled trials that reported proportion of disease clearance or mean change in clinical severity score (or provided these data through communication with study authors) for efficacy of a combination treatment for psoriasis compared with 1 or more corresponding monotherapies. Data Extraction Study data were extracted by 3 independent investigators, with disagreement resolved by consensus. The proportion of patients who achieved clearance, definition of clearance, means and standard deviations for baseline disease symptom score and final disease symptom score, and major design characteristics were extracted for each study. Data Synthesis Combination treatments consisting of vitamin D derivative and corticosteroid, vitamin D derivative and UV-B, vitamin A derivative and psoralen–UV-A, vitamin A derivative and corticosteroid, vitamin A derivative and UV-B, corticosteroid and hydrocolloid occlusion dressings, UV-B and alefacept, and vitamins A and D derivatives were more effective than 1 or more monotherapies using the likelihood of clearance as the outcome. Blinding status and potency of the corticosteroid treatment used were significant sources of heterogeneity between studies. Conclusions The results demonstrate the need for additional long-term trials with standardized outcome measures to evaluate the efficacy and adverse effects of combination therapies for psoriasis and highlight the possible effects of trial design characteristics on results.

Maggot Therapy for Wound Debridement: A Randomized Multicenter Trial [Study]

Objective To study the efficacy of bagged larvae on wound debridement compared with conventional treatment. Design Randomized, multicenter, controlled, prospective phase 3 trial with blinded assessment of outcome measures by a single observer. Setting Two hospital referral centers in Caen and Lyon, France. Patients Random sampling of 119 patients with a nonhealing, sloughy wound 40 cm2 or smaller, less than 2 cm deep, and an ankle brachial index of 0.8 or higher. Intervention During a 2-week hospital stay, patients received either maggot debridement therapy (MDT) or conventional treatment. At discharge, conventional dressings were applied and a follow-up visit occurred at day 30. Main Outcome Measure Percentage of slough in wounds at day 15. Results There was a significant difference between groups at day 8 (54.5% in the MDT group and 66.5% in the control group) (P = .04). The mean percentage of slough at day 15 was 55.4% in the MDT group and 53.8% in the control group (P = .78). Conclusions Although MDT shows no significant benefit at day 15 compared with conventional treatment, debridement by MDT is significantly faster and occurs during the first week of treatment. Because there is no benefit in continuing the treatment after 1 week, another type of dressing should be used after 2 or 3 applications of MDT. Trial Registration clinicaltrials.gov Identifier: NCT01211236

Melanoma Mimic: A Case of Multiple Pagetoid Spitz Nevi [Observation]

Background Differentiating Spitz nevi from melanoma can be difficult. Pagetoid spread of melanocytes is among the features making diagnosis difficult. Rare reports of isolated pagetoid Spitz nevi exist. Observations We present a unique case of multiple pagetoid Spitz nevi initially diagnosed as multiple in situ melanomas. Germline karyotyping, CDK4 and CDKN2A sequencing, and comparative genomic hybridization of HRAS, BRAF, KRAS, RAF1, CDKN2A, Rb1, MAP2K1, MAP2K2, PTEN, and PTPN11 genes did not identify mutations in this case. Germline and somatic sequencing of BRAF exon 15 revealed no mutations at V600D/E/K. In addition, single-nucleotide polymorphism microarray analysis (330K) on lesional and normal skin revealed no genome-wide copy number changes or loss of heterozygosity. Conclusions Clinicians should be aware of the occurrence of multiple pagetoid Spitz nevi to avoid morbidity associated with the misdiagnosis of multiple melanomas. The genetic mechanisms of pagetoid spread of melanocytes are not fully understood.

Association of Pharyngitis With Oral Antibiotic Use for the Treatment of Acne: A Cross-sectional and Prospective Cohort Study [Study]

Objective To prospectively evaluate the association between antibiotics used to treat acne and pharyngitis. Design Cross-sectional and 9-month prospective cohort. Setting Urban university setting. Participants University students. Intervention Participants were asked to fill out a survey form, were swabbed for culture, and had a visual examination for acne. Main Outcome Measure Report of pharyngitis. Results In the cross-sectional study, 10 of the 15 students receiving oral antibiotics for acne reported an episode of pharyngitis in the previous 30 days, whereas 47 of the 130 students not receiving oral antibiotics, but who had acne, reported an episode of pharyngitis in the prior month. The unadjusted odds ratio (OR) (95% CI) associating current oral antibiotic use in acne patients with a self-reported episode of pharyngitis was 3.53 (95% CI, 1.14-10.95). In the cohort study, there were 358 female and 218 male participants; 36 (6.2%) received oral antibiotics for acne during the study, and 96 (16.6%) received topical antibiotics for acne. Using mixed model logistic regression, the OR was 4.34 (95% CI, 1.51-12.47) associating oral antibiotic use with pharyngitis. Less than 1% of participants were colonized by group A streptococcus, which was not associated with pharyngitis. Conclusions Our studies show that that the odds of reporting pharyngitis is more than 3 times baseline in patients receiving oral antibiotics for acne vs those who are not receiving oral antibiotics. The true clinical importance of these findings needs to be evaluated further by prospective studies, but this finding is not associated with group A streptococcus.

Prevention of Glucocorticoid-Induced Osteoporosis in Immunobullous Diseases With Alendronate: A Randomized, Double-blind, Placebo-Controlled Study [Study]

Objective To evaluate the efficacy and safety of oral alendronate sodium therapy once daily in preventing glucocorticoid-induced bone loss in patients with immunobullous skin diseases treated with long-term glucocorticoid therapy. Design A 12-month randomized, double-blind, placebo-controlled trial. Setting A tertiary referral dermatology center in Singapore. Participants Patients newly diagnosed as having an immunobullous disease and deemed to require at least 6 months of systemic glucocorticoid therapy. Interventions The patients were randomized to receive either oral alendronate sodium (10 mg/d) or a matching placebo for 12 months. All patients also received concurrent calcium with vitamin D, 2 tablets daily. Main Outcome Measures Percent change in bone mineral density (BMD) at the lumbar spine and the femoral neck at 12 months. Results A total of 29 patients (alendronate [n = 15], placebo [n = 14]) were evaluated. The percent change in BMD in the alendronate group was +3.7% and +3.5% at the lumbar spine and the femoral neck, respectively, whereas in the placebo group, it was –1.4% and –0.7% at the lumbar spine and the femoral neck, respectively. The increase in BMD observed in the alendronate group compared with the placebo group was statistically significant at both the lumbar spine (P = .01) and the femoral neck (P = .01). There was also a statistically significant decrease in serum heat-labile alkaline phosphatase levels after 12 months (–32.6%, P < .01) in the alendronate group but not in the placebo group. Adverse events were generally minor, and the frequency of occurrence did not differ significantly between both treatment groups (P = .59). Conclusions There were statistically significant increases in BMD at both the lumbar spine (P = .01) and the femoral neck (P = .01) with alendronate therapy. It is imperative to use bisphophonate therapy in patients with immunobullous disorders who are receiving oral corticosteroids because it largely prevents the morbidity associated with low BMD.

Impact of Smoking in Cutaneous Lupus Erythematosus [Study]

Objective To investigate cigarette smoking in cutaneous lupus erythematosus (CLE). Design Prospective longitudinal cohort study. Setting Urban cutaneous autoimmune disease clinic. Participants A total of 218 individuals with CLE or systemic lupus erythematosus and lupus nonspecific skin disease seen between January 5, 2007, and July 30, 2010. Main Outcome Measures Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores to assess disease severity and response to treatment and Skindex 29+3 scores to assess patient quality of life. Results Current smokers with lupus erythematosus had higher median CLASI scores (9.5) than did never (7.0) and past (6.0) smokers with CLE (P = .02). Current smokers had higher median scores on all the Skindex 29+3 subsets. Current smokers taking hydroxychloroquine sulfate had higher quinacrine hydrochloride use than did nonsmokers (P = .04). Two to 7 months after enrollment, current smokers (median CLASI change, –3) treated with only antimalarial agents improved more than never (1) and past (0) smokers (P = .02). Eight months or more after enrollment, current smokers (CLASI change, 3.5) treated with antimalarial drugs plus at least 1 additional immunomodulator improved less than never (–1.5) and past (0) smokers (P = .04). Conclusions Current smokers with lupus erythematosus had worse disease, had worse quality of life, and were more often treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. Never and past smokers showed greater improvement when treated with antimalarial agents plus at least 1 additional immunomodulator. Current smokers had greater improvement when treated with antimalarial drugs only.

Soluble Adenylyl Cyclase Antibody Profile as a Diagnostic Adjunct in the Assessment of Pigmented Lesions [Study]

Objective To investigate the usefulness of a novel marker for melanocytic proliferations. Design Using a novel monoclonal antibody against soluble adenylyl cyclase (sAC), various benign and malignant melanocytic proliferations were immunostained. Setting Weill Medical College of Cornell University dermatopathology laboratory. Main Outcome Measures The results were qualitative, not quantifiable. Results The sAC immunostaining produced distinctive patterns that paralleled melanomagenesis. At one pole of the spectrum were benign nevi, including atypical nevi of special sites and recurrent nevi showing a distinct pattern of dotlike Golgi staining, while at the opposite pole was melanoma, in which many cells demonstrated an intense pannuclear expression pattern, often accompanied by loss of the Golgi expression pattern. Melanomas of lentigo maligna and acral lentiginous subtypes exhibited the most striking pannuclear expression, while nodular melanomas showed the least, although with supervening enhanced diffuse cytoplasmic expression. Loss of the Golgi expression pattern was a feature of malignant melanoma. Conclusion The sAC expression pattern is complex but seems discriminatory, with distinctive and variable staining patterns according to the nature of the lesion biopsied.

Hidradenitis Suppurativa: The Role of Deficient Cutaneous Innate Immunity [Study]

Objective To evaluate the expression of innate immunity markers at the site of nodules caused by hidradenitis suppurativa (HS). Design Prospective analysis of 12 patients with HS. Setting Unité de Cancéro-Dermatologie, Nantes Hospital, Nantes; Service de Dermatologie, Poitiers Hospital, Poitiers; and Service de Dermatologie, Clinique de Courlancy, Reims, France Patients Twelve patients (Hurley stage I or II) in whom the disease had progressed for at least 6 months and who had a minimum of 2 closed nodules in typical sites. Main Outcome Measures Two biopsies were performed at baseline: one in a closed inflammatory nodule and one in healthy adjoining skin. Patients were treated for 3 months with zinc gluconate at a dosage of 90 mg/d. A new biopsy was then performed in the same nodule. Innate immunity markers (toll-like receptors 2, 3, 4, 7, and 9; intercellular adhesion molecule 1; interleukin [IL] 6 and 10; tumor necrosis factor; α melanocyte stimulating hormone; transforming growth factor β; β-defensin 2 and 4; and insulinlike growth factor 1) were studied by immunohistochemical analysis. Results We observed significantly decreased expression (P < .001) of all the innate immunity markers studied except IL-10 in nonlesional and lesional HS skin. The downregulation of innate markers was significantly stronger in lesional HS skin compared with normal skin except for tumor necrosis factor. Three months of zinc treatment induced a significant increase in the expression of all the markers involved in innate immunity. Conclusion Our study demonstrates for the first time, to our knowledge, that a deficiency of the main innate immunity markers in typical HS sites may explain the development of chronic inflammatory nodules in this disease.

Efficacy and Safety of Apremilast in Chronic Cutaneous Sarcoidosis [Research Letters]

Natural Gene Therapy in Dystrophic Epidermolysis Bullosa [Observation]

Background Dystrophic epidermolysis bullosa is a genetic blistering disorder caused by mutations in the type VII collagen gene, COL7A1. In revertant mosaicism, germline mutations are corrected by somatic events resulting in a mosaic disease distribution. This "natural gene therapy" phenomenon long has been recognized in other forms of epidermolysis bullosa but only recently in dystrophic epidermolysis bullosa. Observations We describe a 21-year-old man with recessive dystrophic epidermolysis bullosa carrying the homozygous c.6508C>T (p.Gln2170X) nonsense mutation who reported an unaffected skin patch on his neck where blisters never had occurred. Immunofluorescent type VII collagen staining was normal in 80% of the unaffected skin biopsy; however, it was strongly reduced in the affected skin. In the unaffected skin, the somatic nucleotide substitution c.6510G>T reverted the germline nonsense codon to tyrosine (p.Gln2170Tyr), thereby restoring functional protein production. Conclusions Revertant mosaicism is considered rare in recessive dystrophic epidermolysis bullosa. However, it might be more common than previously anticipated because our patient is the third in whom revertant mosaicism was identified in a short period of time. The correction mechanism is different than that previously reported. Systematic examination of patients with recessive dystrophic epidermolysis bullosa, therefore, will likely reveal more patients with revertant patches. This is important because the natural gene therapy phenomenon may provide opportunities for revertant cell therapy.

Risk Factors for Lentigo Maligna Melanoma Compared With Superficial Spreading Melanoma: A Case-Control Study in Australia [Study]

Objective To investigate risk factors for lentigo maligna melanoma (LMM) compared with superficial spreading melanoma (SSM). Design Population-based case-control study in Queensland, Australia. Setting General community. Participants Population-based sample of 49 patients with LMM and 141 with SSM (in situ or invasive) aged 14 to 86 years at diagnosis in 1979 and 1980 and 232 control subjects. Response rates were 97.1% in cases and 91.8% in controls. Main Outcome Measures Risks of both subtypes in relation to phenotypic and environmental factors, estimated by multinomial logistic regression. Results The number of solar lentigines was the strongest determinant for LMM (odds ratio [OR], 15.93; P < .001 for trend) and significantly weaker for SSM (4.61; P < .001 for trend; P = .04 for homogeneity). Skin cancer history was significantly associated with LMM (OR, 2.84) but not with SSM (1.33; P = .07 for homogeneity). In contrast, the number of nevi was the strongest determinant for SSM (OR, 23.22; P < .001 for trend) while significantly weaker for LMM (3.60; P = .02 for trend; P < .001 for homogeneity). Multiple lifetime sunburns almost tripled the risk for SSM, whereas no association was detected with LMM (P = .04 for homogeneity). Shared risk factors for both subtypes were the number of solar keratoses (P < .001 for trend for both) and sun-sensitive complexion (ie, light eye/hair colors, sunburn propensity, and freckling) (2-fold to 5-fold increased risks). Conclusions A propensity to lentigines is a stronger predictor of LMM, whereas high nevus propensity is a stronger predictor of SSM. Skin cancer history appears to determine LMM risk only, whereas the number of lifetime sunburns determines SSM only. Prevention strategies could be tailored differently given these distinctive points of difference.

Tissue Eosinophilia: Not an Indicator of Drug-Induced Subacute Cutaneous Lupus Erythematosus [Study]

Objective To investigate whether tissue eosinophilia is a differentiating histopathologic feature of drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) compared with non-DI–SCLE. Design Retrospective medical record review with prospective blinded histopathologic analysis. Setting University-affiliated dermatology and dermatopathology practice. Patients Fifty-nine patients with SCLE were divided into DI (n = 15) and non-DI (n = 44) groups. Main Outcome Measures A dermatopathologist masked to the etiologic associations reviewed corresponding histopathologic specimens. For each patient, an eosinophil ratio was calculated as the mean eosinophil score (averaging eosinophil counts from 10 high-power histologic fields) divided by the intensity of inflammation. Eosinophil ratios for both groups were compared using the Mann-Whitney test. Results No significant difference was found in mean eosinophil ratios in the DI vs non-DI groups (0.11 vs 0.004; P = .34). Mucin deposition was present in both populations and was not significantly different (P = .18). The inflammatory infiltrate was superficial and deep in 10 patients (67%) in the DI group vs 24 (55%) in the non-DI group. Periadnexal inflammation was observed in 12 patients (80%) in the DI group vs 37 (84%) in the non-DI group, and basal layer liquefaction with dyskeratosis was seen in 15 patients (100%) in the DI group and in 37 (84%) in the non-DI group. Conclusions Tissue eosinophilia is not a differentiating histopathologic feature of DI-SCLE. Careful review of a patient's drug history in correlation with clinical findings remains the standard for identifying a drug as an etiologic or exacerbating factor in patients with SCLE.

About This Journal [About This Journal]

This Month in Archives of Dermatology [This Month in Archives of Dermatology]

Blue Atrophy of the Skin From Cocaine Injections. [Archives a Century Ago]

Interstitial Granulomatous Dermatitis With Arthritis Responding to Tocilizumab [The Cutting Edge: Challenges in Medical and Surgical Therapies]

Error in Byline in: Erythematous Patches and Plaques on the Chest With Induration of the Breasts [Correction]

High Frequency of Genital Lichen Sclerosus in a Prospective Series of 76 Patients With Morphea: Toward a Better Understanding of the Spectrum of Morphea [Study]

Objective To compare the frequency of genital lichen sclerosus (LS) in patients with morphea with that of control patients. Design A prospective multicenter study. Setting Four French academic dermatology departments: Strasbourg, Montpellier, Tenon Hospital Paris, and Henri Mondor Hospital Créteil. Patients Patients were recruited from November 1, 2008, through June 30, 2010. Seventy-six patients with morphea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled. Interventions A complete clinical examination and, if deemed necessary, a cutaneous biopsy. Main Outcome Measure The frequency of genital LS. Results There were 58 women and 18 men (a 3:1 ratio) with a median age of 59 years. Mean (range) age at diagnosis was 54 (13-87) years. Forty-nine patients had plaque morphea, 9 had generalized morphea, and 18 had linear morphea. Three patients (3%) in the control group and 29 patients (38%) with morphea had LS (odds ratio, 19.8; 95% CI, 5.7-106.9; P < .001). Twenty-two patients with plaque morphea (45%) and only 1 patient with linear morphea (6%) had associated genital LS. Conclusions Genital LS is significantly more frequent in patients with morphea than in unaffected individuals. Forty-five percent of patients with plaque morphea have associated LS. Complete clinical examination, including careful inspection of genital mucosa, should therefore be mandatory in patients with morphea because genital LS bears a risk of evolution into squamous cell carcinoma and thus needs treatment with topical corticosteroids.

Missing Genital Lichen Sclerosus in Patients With Morphea: Don't Ask? Don't Tell?: Comment on "High Frequency of Genital Lichen Sclerosus in a Prospective Series of 76 Patients With Morphea" [Practice Gaps]

The Contribution of Nodular Subtype to Melanoma Mortality in the United States, 1978 to 2007 [Study]

Objective To gain insight into reducing melanoma mortality by examining epidemiologic trends by subtype with emphasis on the contribution of each subtype to melanoma-related death. Design Retrospective population-based cohort study. Setting Original 9 registries of the Surveillance, Epidemiology, and End Results Program from 1978 to 2007. Participants A total of 111 478 patients with histologically confirmed invasive melanoma. Main Outcome Measure Proportion of ultimately fatal melanomas by subtype. Results Among melanomas of known subtype, superficial spreading melanoma comprised 66% of incident melanomas and 46% of ultimately fatal melanomas; nodular melanoma comprised 14% of incident melanomas and 37% of ultimately fatal melanomas. For superficial spreading melanoma, overall incidence per 100 000 per year increased (from 4.28 to 6.63), ultimately fatal incidence remained stable (at 0.56 to 0.51), and 10-year relative survival increased (from 90.6% to 96.5%) when comparing successive 5-year intervals. In contrast, for nodular melanoma, the overall incidence (1.30-1.32), ultimately fatal incidence (0.46-0.44), and 10-year relative survival rate (61.8%-61.5%) remained stable. Epidemiologic trends of melanoma, not otherwise specified, were similar to superficial spreading melanoma. There was a strong negative correlation between the proportion of melanoma, not otherwise specified, among all melanomas, and the proportion of superficial spreading melanoma, among melanomas of known subtype (r = –0.80; P = .01), across the registries. Conclusions Superficial spreading and nodular melanoma constitute similar proportions of ultimately fatal melanomas. Although incidence of and survival from superficial spreading melanoma have increased from 1978 to 2007, neither the incidence of nor survival from nodular melanoma has changed. Public health efforts should include a focus on nodular melanoma for maximum reduction of melanoma mortality.

October 2011 Archives Web Quiz Winner [Archives Web Quiz Winner]

Relationship Between the Depth of Facial Wrinkles and the Density of the Retinacula Cutis [Study]

Objective To identify whether there is a relationship between the depth of facial wrinkles and the density of the retinacula cutis in the subcutaneous tissue of the skin. Design Wrinkle depth was assessed with image analysis on the forehead and the lateral canthus of human cadavers. The density of the retinacula cutis was measured in Azan-Mallory–stained skin sections obtained around the wrinkles. Setting Gross Anatomy Section, Kagoshima University Graduate School of Medical and Dental Sciences. Participants Fifty-five male and female cadavers (35-93 years old). Main Outcome Measures The maximum depth of each wrinkle was used to represent the wrinkle's degree. In the skin sections, the density of the retinacula cutis was measured around the deepest point of each wrinkle in a 1-mm-wide area (the wrinkle-specific area) and a 10-mm-wide area that included the wrinkle (the wrinkle-inclusive area). Results In both the wrinkle-specific and wrinkle-inclusive areas, the retinacula cutis densities became lower in the forehead and in the lateral canthus areas. When a wrinkle was shallow, the density was lower in the wrinkle-specific area than in the wrinkle-inclusive area. With wrinkle progression, the density difference between the wrinkle-specific and the wrinkle-inclusive areas gradually decreased until there was no apparent difference. Conclusions Facial wrinkles seem to develop above sites of reduced lower retinacula cutis density. As a wrinkle develops, the density decreases in both the wrinkle-specific and the wrinkle-inclusive areas, whereas the density difference between those areas vanishes.

Top-Accessed Article: On Beauty [The Best of the Best]

Comparable Effectiveness of Endovenous Laser Ablation and High Ligation With Stripping of the Great Saphenous Vein: Two-Year Results of a Randomized Clinical Trial (RELACS Study) [Study]

Objective To compare the clinical efficacy and safety of endovenous laser treatment (EVLT) with high ligation and stripping (HLS) as standard treatment for great saphenous vein (GSV) insufficiency. Design Two-center randomized controlled trial with 2-year follow-up. Setting Interventions were performed on ambulatory and hospitalized patients at 2 vein centers, a university dermatology department (EVLT-treated group), and a specialized vein clinic (HLS-treated group). Patients Random sample of 400 patients with GSV insufficiency. Interventions Patients were assigned (1:1) to EVLT or HLS of the GSV from September 2004 through March 2007; 185 and 161 patients (limbs), respectively, were treated per protocol. Main Outcome Measures Clinically recurrent varicose veins after surgery (REVAS classification, primary study objective), duplex-detected saphenofemoral recurrence, clinical venous severity scoring (Homburg Varicose Vein Severity Score), hemodynamics (venous refilling time), quality of life (Chronic Venous Insufficiency Questionnaire 2), adverse effects, and visual analog scale–based evaluations of patients' satisfaction. Results Clinically recurrent varicose veins after surgery were similarly observed in both groups: 16.2% (EVLT-treated group) vs 23.1% (HLS-treated group); P = .15. Duplex-detected saphenofemoral refluxes occurred significantly more frequently after EVLT (17.8% vs 1.3%; P < .001). Both treatments equally improved medical condition (Homburg Varicose Vein Severity Score) and disease-related quality of life. Endovenous laser treatment caused more adverse effects (phlebitic reaction, tightness, dyspigmentation) but revealed advantages concerning hemodynamics, recovery, and cosmetic outcome. Conclusions Both EVLT and HLS are comparably safe and effective procedures to treat GSV incompetence. The significantly higher rate and the course of duplex-detected saphenofemoral recurrences after EVLT remain a matter of further investigations. Trial Registration isrctn.org Identifier: ISRCTN18322872

Impact of Live Interactive Teledermatology on Diagnosis, Disease Management, and Clinical Outcomes [Study]

Objective To assess the impact of live interactive teledermatology consultations on changes in diagnosis, disease management, and clinical outcomes. Design We conducted a retrospective analysis of 1500 patients evaluated via live interactive teledermatology between 2003 and 2005 at the University of California, Davis. We compared diagnoses and treatment plans between the referring physicians and the teledermatologists. Patients with 2 or more teledermatology visits within a 1-year period were assessed for changes in clinical outcomes. Setting Academic medical center with an established teledermatology program since 1996. Participants Medical records were evaluated for 1500 patients who underwent live interactive teledermatology consultation. Patients seen for more than 1 teledermatology visit were included in the clinical outcome assessment. Intervention Live interactive teledermatology consultation. Main Outcome Measures Changes in diagnosis, disease management, and clinical outcome. Results Compared with diagnoses and treatment plans from referring physicians, the 1500 live interactive teledermatology consultations resulted in changes in diagnosis in 69.9% of patients and changes in disease management in 97.7% of patients. Among 313 patients with at least 2 teledermatology visits within 1 year, clinical improvement was observed in 68.7% of patients. Multivariate analysis showed that changes in diagnosis (P = .01), changes in disease management (P < .001), and the number of teledermatology visits (P < .001) were significantly associated with improved clinical outcomes. Conclusions Live interactive teledermatology consultations result in changes in diagnosis and disease management in most consultations. The numbers of live interactive teledermatology visits and changes in diagnosis and disease management are significantly associated with improved clinical outcomes.

Trends in Pediatric Psoriasis Outpatient Health Care Delivery in the United States [Study]

Objective To characterize patterns of childhood psoriasis health care delivery from 1979-2007. Design Retrospective, cross-sectional investigation using National Ambulatory Medical Care Survey data. Setting US ambulatory physician offices from 1979 through 2007. Patients Children with psoriasis ages 0 (birth) to 18 years. Main Outcome Measures Demographics, physician specialty, and medications prescribed. Results There were an estimated 3.8 million visits for psoriasis over the study interval with a median of 123 420 visits per year. Dermatologists saw 63% of patients, pediatricians saw 17%, and internists, 14%. The numbers of visits were equal between sexes but ranged by age group: patients ages 13 to 18 years accounted for 47% of visits, those ages 8 to 12 years for 35%, and those ages 0 to 7 for 18%. Ninety-three percent of patients were white. Topical corticosteroids were the most commonly prescribed medications. Children 0 to 9 years old received equally potent corticosteroids as children 10 to 18 years old. Among all patients, the most prescribed medication was topical betamethasone; among those ages 0 to 9 years, tacrolimus; and among those ages 10 to 18 years, betamethasone. By physician specialty, the most prescribed medications were high-potency steroids for dermatologists and internists, and topical tacrolimus for pediatricians. Topical calcineurin inhibitors were not among the top 20 most prescribed medications by dermatologists, and systemic antipsoriatic agents were not among the top 20 most prescribed medications in any age group. Conclusions Over the 28-year interval, outpatient visits for pediatric psoriasis were attended primarily by white children older than 8 years in equal number by sex. Dermatologists and pediatricians saw the majority, and treatment approach differed by physician specialty and patient age. Treatment guidelines for childhood psoriasis may help reduce treatment variability.

Prescribing Patterns by Dermatologists and Primary Care Providers for Pediatric Psoriasis: Comment on "Trends in Pediatric Psoriasis Outpatient Health Care Delivery in the United States" [Practice Gaps]

Banding Pattern on Polarized Hair Microscopic Examination and Unilateral Polymicrogyria in a Patient With Steroid Sulfatase Deficiency [Observation]

Background Several forms of ichthyosis are associated with neurologic manifestations, including Sjögren-Larsson syndrome, Refsum disease, and mental retardation–enteropathy-deafness-neuropathy-ichthyosis-keratoderma (MEDNIK) syndrome. We report a case of X-linked steroid sulfatase deficiency, ichthyosis, seizures, abnormal hair banding pattern, and unilateral polymicrogyria. Observations A 3-year-old Caucasian male with a history of ichthyosis since birth presented with generalized tonic seizures. Findings from a physical examination were remarkable for thin hair, retinitis pigmentosa, and poor dentition. Polarized light microscopic examination of all the hair samples demonstrated a banding pattern. Magnetic resonance imaging of the brain revealed left hemispheric polymicrogyria with decreased sulcal pattern and stable asymmetric dilation of the left lateral ventricle. Constitutional microarray revealed the typical approximately 1.5-Mb deletion of the steroid sulfatase gene. Conclusions Steroid sulfatase deficiency is a cause of X-linked ichthyosis; however, our patient also had retinitis pigmentosa, seizures, and abnormal hair findings. The presence of abnormal hair with a banding pattern on polarized microscopy may be helpful for diagnosis; however, this pattern is not specific to this disease. In addition, to our knowledge, the presence of a malformation of cortical development has not been previously reported in patients with steroid sulfatase deficiency.

Mikhail Bulgakov: The Master and Syphilis [Notable Notes]

Cutaneous Manifestations of DOCK8 Deficiency Syndrome [Observation]

Background Mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia. Many patients with DOCK8 deficiency were previously thought to have a variant of Job's syndrome. Distinguishing between DOCK8 deficiency and Job's syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging. The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes. Observations Twenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCK8 were evaluated. Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections. Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in 5 patients during adolescence and young adulthood. Conclusions DOCK8 deficiency and Job's syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses. However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job's syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia.

A Novel Mutation in the PORCN Gene Underlying a Case of Almost Unilateral Focal Dermal Hypoplasia [Observation]

Background Focal dermal hypoplasia (also known as Goltz syndrome) is an X-linked dominant syndrome characterized by patchy hypoplastic skin with soft-tissue, skeletal, dental, and ocular defects that are secondary to mutations in the PORCN gene. To our knowledge, only 5 cases of focal dermal hypoplasia with unilateral presentation have been reported, and molecular studies were not performed in any of the cases. Observations A 17-year-old girl was seen with features of almost unilateral focal dermal hypoplasia. These included left cleft hand, dental dysplasia, left mammary hypoplasia, deviation of the sacral line, raspberrylike papillomas in the perianal region, syndactyly of the second and third digits of the left foot, and linear streaks of dermal hypoplasia and pigmented lesions on her left hemibody. Conclusions Mutation analysis of PORCN revealed a novel heterozygous mutation in exon 10, c.854-855insACCTGAC; [p.T285fsX316], resulting in a premature stop signal. Analysis of the X-chromosome inactivation status was performed on blood and skin DNA samples, showing random inactivation in blood and unaffected skin and skewed inactivation in affected skin, highlighting the role of X-chromosome inactivation in X-linked disease expression.

Tonsuring and the Western Wig and Hair Extension Market [Notable Notes]

Polarized Microscopy as a Helpful Tool to Distinguish Chronic Nonscarring Alopecia From Scarring Alopecia [Observation]

Background Nonscarring alopecia differs from scarring alopecia on pathologic examination by the preservation of follicular units and lack of follicular dropout. However, long-standing cases of active nonscarring hair loss can show follicular dropout on pathologic examination and can be difficult to interpret. Observations We describe a patient with nonscarring alopecia that was misdiagnosed as scarring alopecia due to difficulty in distinguishing between scarred tracts (follicular dropout) and long-persisting fibrovascular streamers. Polarized light microscopy permits us to distinguish follicular scars from fibrous streamers because the fibrous streamers are birefringent negative for collagen. The main advantages of polarized microscopy are that it is fast and cost free and can screen all sections within minutes; it is also easy to interpret for beginners because there is a built-in control of birefringent-positive dermal collagen. Conclusion Polarized light can be used in the pathological evaluation of hair loss to distinguish between the follicular scars in scarring alopecia and the fibrovascular streamers in long-standing nonscarring alopecia.

Consensus Guidelines for the Management of Plaque Psoriasis [Consensus Statement]

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus–infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

Cancer Risk in Patients With Chronic Urticaria: A Population-Based Cohort Study [Evidence-Based Dermatology: Study]

Objective To investigate the relative risk of cancer among patients with chronic urticaria in the Taiwanese population. Design Retrospective population-based cohort study. Setting The National Health Insurance Research Database of Taiwan from January 1, 1996, through December 31, 2008. Participants A total of 12 720 patients with chronic urticaria, with long-term antihistamine use and no history of malignant tumors, autoimmune diseases, atopy, or allergic diseases. Main Outcome Measure Relative cancer risk calculated by standardized incidence ratios. Results There were 704 cancers among chronic urticaria patients. An increased risk of cancer (standardized incidence ratio, 2.2; 95% CI, 2.0-2.3), especially hematologic malignant tumor (4.1; 3.1-5.4), was observed. The relative risk of cancer varied by age and was highest among those aged 20 to 39 years in comparison with the general population. Most cancer cases were detected within the first year of diagnosis. The risk of non-Hodgkin lymphoma was greatest (standardized incidence ratio, 4.4; 95% CI, 3.0-6.1) among the hematologic cancers. Conclusions Patients with chronic urticaria are at increased risk of cancer, especially hematologic malignant tumors. Further studies are needed to delineate the associations.

Charles Bukowski and Sylvia Plath on Moles and Melanoma [Notable Notes]

Imiquimod vs Cryotherapy for Molluscum Contagiosum: A Randomized Controlled Trial [Evidence-Based Dermatology: Research Commentary]

Maturation of an Idea: A Historical Perspective on the Association of Psoriasis With the Metabolic Syndrome and Cardiovascular Disease [Notable Notes]

Blistering Mucosal Eruption in a Young Woman With Systemic Lupus Erythematosus--Quiz Case [Off-Center Fold]

Blistering Mucosal Eruption in a Young Woman With Systemic Lupus Erythematosus--Diagnosis [Off-Center Fold]

Erythematous Patches on the Chest--Quiz Case [Off-Center Fold]

Erythematous Patches on the Chest--Diagnosis [Off-Center Fold]

Firm Nodule on the Shoulder--Quiz Case [Off-Center Fold]

Firm Nodule on the Shoulder--Diagnosis [Off-Center Fold]

Reticulate Hyperpigmentation of the Vulva--Quiz Case [Off-Center Fold]

Reticulate Hyperpigmentation of the Vulva--Diagnosis [Off-Center Fold]

A Small Study of the Relationship Between Abobotulinum Toxin A Concentration and Forehead Wrinkle Reduction [Research Letters]

Dilution, Reconstitution, and Complexity: Comment on "A Small Study of the Relationship Between Abobotulinum Toxin A Concentration and Forehead Wrinkle Reduction" [Practice Gaps]

Implementation of the Federal Excise Tax on Indoor Tanning Services in Illinois [Research Letters]

Attitudes Toward Indoor Tanning Among Users of Sunless Tanning Products [Research Letters]

Photodynamic Therapy With 5-Aminolevulinic Acid Intralesional Injection for Pyogenic Granuloma [Research Letters]

Acquired Epidermodysplasia Verruciformis Syndrome in HIV-Infected Pediatric Patients: Prospective Treatment Trial With Topical Glycolic Acid and Human Papillomavirus Genotype Characterization [Research Letters]

A Population-Based Study of Acne and Body Mass Index in Adolescents [Research Letters]

Narrowband UV-B Phototherapy During Pregnancy and Folic Acid Depletion [Correspondence]

Interferon-{gamma} Release Assay [Correspondence]

Resolution of Skin Maladies of the Trapped Chilean Miners: The Unplanned Underground Copper-Impregnated Antifungal Socks "Trial" [Correspondence]

An Acrochordon-Like Melanoma Metastasis [Correspondence]

A Novel Application of Topical Rapamycin Formulation, an Inhibitor of mTOR, for Patients With Hypomelanotic Macules in Tuberous Sclerosis Complex [Correspondence]

Atypical Gingivitis Heralding a Case of Orofacial Granulomatosis [Correspondence]

Congenital Mucinous Eccrine Nevi in an Infant With Chronic Granulomatous Disease [Correspondence]

White Shiny Structures in Melanoma and BCC [skINsight]

Monitoring Peripheral Blood CD4+ Intracellular Adenosine Triphosphate Concentration in Patients with Psoriasis Treated with Fumaric Acid Esters.

Monitoring Peripheral Blood CD4+ Intracellular Adenosine Triphosphate Concentration in Patients with Psoriasis Treated with Fumaric Acid Esters. Acta Derm Venereol. 2012 Feb 1; Authors: Gambichler T, Scola N, Rotterdam S, Höxtermann S, Haghikia A, Faissner S, Kreuter A, Bechara FG, Altmeyer P, Chan A PMID: 22294455 [PubMed - as supplied by publisher]

Phylloid Hypermelanosis in a Child with Psychomotor Delay, Cicatricial Alopecia, Hearing Loss and Polythelia.

Phylloid Hypermelanosis in a Child with Psychomotor Delay, Cicatricial Alopecia, Hearing Loss and Polythelia. Acta Derm Venereol. 2012 Feb 1; Authors: Bygum A, Petkov Y, Graakjaer J, Jensen UB, Fagerberg C PMID: 22294434 [PubMed - as supplied by publisher]

Impaired Expression of Tim-3 on Th17 and Th1 Cells in Psoriasis.

Impaired Expression of Tim-3 on Th17 and Th1 Cells in Psoriasis. Acta Derm Venereol. 2012 Feb 1; Authors: Kanai Y, Satoh T, Igawa K, Yokozeki H Abstract Psoriasis is a chronic skin disease mediated by Th17 and/or Th1 cells. Tim-3 is a cell surface molecule preferentially expressed on Th17 and Th1 cells. The interaction of Tim-3 with Tim-3 ligand inhibits cytokine production. To assess whether T cells in psoriasis have functional abnormalities, expression of cell surface Tim-3 on blood T cells producing interleukin-17 (Th17/Tc17 cells) or interferon-γ (Th1/Tc1 cells) was examined by flow cytometry. Psoriasis patients had higher numbers of Th17 and Tc17 cells, as well as Th1 and Tc1 cells, than healthy donors. However, Th17, Th1 and Tc1 cells in psoriasis did not efficiently express Tim-3 upon activation, compared with those from atopic dermatitis and healthy donors. Tim-3- cells showed more potent cytokine production than Tim-3+ cells. Impaired Tim-3 expression allows Th17, Th1 and Tc1 cells to escape from Tim-3-mediated negative regulatory systems and may contribute to the pathogenesis of psoriasis. PMID: 22294262 [PubMed - as supplied by publisher]

Beyond Zoster: Sensory and Immune Changes in Zoster-affected Dermatomes.

Beyond Zoster: Sensory and Immune Changes in Zoster-affected Dermatomes. Acta Derm Venereol. 2012 Feb 1; Authors: Ruocco V, Sangiuliano S, Brunetti G, Ruocco E Abstract Neuroepidermal tropism of varicella-zoster virus accounts for cutaneous and nerve lesions following herpes zoster. Skin lesions heal in a few weeks and may or may not leave visible scars. Nerve lesions involve peripheral sensory fibres, sometimes causing permanent damage that results in partial denervation of the affected dermatome. The effects of the nerve injury involve the sensibility function, thus causing neuralgia, itch, allodynia, hypo- or anaesthesia, as well as the immune function that is related to neuropeptide release, thus altering immune control in the affected dermatome. The neuro-immune destabilization in the zoster-infected site paves the way for the onset of many and various immunity-related disorders along the affected dermatome. PMID: 22294236 [PubMed - as supplied by publisher]

Methotrexate Reduces the Occurrences of Cerebrovascular Events among Taiwanese Psoriatic Patients: A Nationwide Population-Based Study.

Methotrexate Reduces the Occurrences of Cerebrovascular Events among Taiwanese Psoriatic Patients: A Nationwide Population-Based Study. Acta Derm Venereol. 2012 Feb 1; Authors: Lan CC, Ko YC, Yu HS, Wu CS, Li WC, Lu YW, Chen YC, Chin YY, Yang YH, Chen GS Abstract Psoriasis is a chronic inflammatory disease. The aim of this study was to evaluate the effects of methotrexate and retinoid on risks for developing cerebrovascular disease among psoriatic patients. A population-based nested case-control study was conducted using the Taiwanese National Health Insurance database. Cox proportional hazards models were adopted. The hazard ratio (HR) of newly developed cerebrovascular disease was 1.28 (95% confidence interval (CI) = 1.162-1.413; p < 0.0001) for psoriatic vs. non-psoriatic subjects. In terms of the effects of methotrexate or retinoid on the occurrence of cerebrovascular disease, a significant protection effect (HR = 0.50; 95% CI = 0.27-0.92; p = 0.0264) was found for patients with methotrexate prescription. Retinoid prescription showed no protective effect. Further analyses revealed that a low cumulative methotrexate dose is associated with significant protective effect (HR = 0.53; 95% CI = 0.28-1.00; p = 0.0486) while a high cumulative dose was not (HR 0.80; 95% CI = 0.11-5.68; p = 0.8214). These results suggest that psoriatic patients receiving low-dose methotrexate treatment may have reduced risk for developing cerebrovascular disease. Further prospective study should be performed to validate the vasculoprotective effect of this treatment strategy. PMID: 22294195 [PubMed - as supplied by publisher]

Acquired Dermal Melanocytosis Induced by Psoralen Plus Ultraviolet A Therapy.

Acquired Dermal Melanocytosis Induced by Psoralen Plus Ultraviolet A Therapy. Acta Derm Venereol. 2012 Feb 1; Authors: Nagase K, Hirashima N, Koba S, Inoue T, Misago N, Narisawa Y PMID: 22294134 [PubMed - as supplied by publisher]

Disseminated Cutaneous Glomangiomas in an Adolescent Boy.

Disseminated Cutaneous Glomangiomas in an Adolescent Boy. Acta Derm Venereol. 2012 Feb 1; Authors: Borovaya A, Kunte C, Flaig MJ, Albrecht K, Goldscheider I, Korting HC, Ruzicka T, Sárdy M PMID: 22294072 [PubMed - as supplied by publisher]

Eccrine Poromatosis Associated with Polychemotherapy.

Eccrine Poromatosis Associated with Polychemotherapy. Acta Derm Venereol. 2012 Feb 1; Authors: Fujii K, Aochi S, Takeshima C, Ohtsuka M, Hamada T, Asagoe K, Aoyama Y, Morizane S, Iwatsuki K Abstract Eccrine poroma frequently occurs as a solitary tumour, and only a few reports have described the occurrence of multiple lesions. Multiple eccrine poromas, or eccrine poromatosis, may occur in patients who have undergone radiotherapy and/or polychemotherapy. We report here four cases of multiple eccrine poromas in patients who were either undergoing, or had undergone, intensive chemotherapy (from 6 months to 16 years prior to onset). Three patients had non-Hodgkin's lymphoma and one had malignant fibrous histiocytosis. The number of lesions varied from 3 to > 20 in each patient, and all the lesions occurred on non-irradiated skin. The histopatho-logical features were consistent with those of eccrine poroma, Pinkus type. In addition to radiation therapy, intensive chemotherapy may play a role in the pathogenesis of multiple eccrine poromas even many years after treatment. PMID: 22294042 [PubMed - as supplied by publisher]

Acute Streptococcal Infection of the Vulva.

Acute Streptococcal Infection of the Vulva. Acta Derm Venereol. 2012 Feb 1; Authors: Veraldi S, Francia C, Marzano AV PMID: 22293992 [PubMed - as supplied by publisher]

Multiple Blisters Along the Lip Vermilion are a Clue to Bullous Lupus Erythematosus.

Multiple Blisters Along the Lip Vermilion are a Clue to Bullous Lupus Erythematosus. Acta Derm Venereol. 2012 Feb 1; Authors: Nico MM, Lourenço SV PMID: 22293956 [PubMed - as supplied by publisher]

Topical Tacrolimus and 50% Zinc Oxide Paste for Hailey-Hailey Disease: Less is More.

Topical Tacrolimus and 50% Zinc Oxide Paste for Hailey-Hailey Disease: Less is More. Acta Derm Venereol. 2012 Feb 1; Authors: Pagliarello C, Paradisi A, Dianzani C, Paradisi M, Persichetti P PMID: 22293917 [PubMed - as supplied by publisher]

Epstein-Barr Virus-positive Mucocutaneous Ulcers as a Manifestation of Methotrexate-associated B-cell Lymphoproliferative Disorders.

Epstein-Barr Virus-positive Mucocutaneous Ulcers as a Manifestation of Methotrexate-associated B-cell Lymphoproliferative Disorders. Acta Derm Venereol. 2012 Feb 1; Authors: Hashizume H, Uchiyama I, Kawamura T, Suda T, Takigawa M, Tokura Y PMID: 22293895 [PubMed - as supplied by publisher]

Incidental Gastric Signet-ring Cell Carcinoma Metastasis to the Skin in Basal Cell Carcinoma.

Incidental Gastric Signet-ring Cell Carcinoma Metastasis to the Skin in Basal Cell Carcinoma. Acta Derm Venereol. 2012 Feb 1; Authors: Nakamura Y, Satomi K, Noguchi M, Shibata-Ito M, Fujisawa Y, Kawachi Y, Otsuka F PMID: 22293867 [PubMed - as supplied by publisher]

Elastoderma: An Uncommon Cause of Acquired Hyperextensible Skin.

Elastoderma: An Uncommon Cause of Acquired Hyperextensible Skin. Acta Derm Venereol. 2012 Feb 1; Authors: de Waal AC, Blokx WA, Seyger MM, van Rossum MM PMID: 22293849 [PubMed - as supplied by publisher]

Mid-dermal Elastolysis: Another Dermatological Clue to Autoimmunity?

Mid-dermal Elastolysis: Another Dermatological Clue to Autoimmunity? Acta Derm Venereol. 2012 Feb 1; Authors: Martínez-Escala ME, Rozas E, Pujol RM, Herrero-González JE PMID: 22293825 [PubMed - as supplied by publisher]

No Association between Infections, HLA Type and Other Transplant-related Factors and Risk of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients.

No Association between Infections, HLA Type and Other Transplant-related Factors and Risk of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients. Acta Derm Venereol. 2012 Feb 1; Authors: Ingvar A, Smedby KE, Lindelöf B, Fernberg P, Bellocco R, Tufveson G, Höglund P, Adami J Abstract Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types. PMID: 22293782 [PubMed - as supplied by publisher]

Isotopic Response of Graft Versus Host Disease Following Herpes Zoster Infection: Case Report and Review of the Literature.

Isotopic Response of Graft Versus Host Disease Following Herpes Zoster Infection: Case Report and Review of the Literature. Acta Derm Venereol. 2012 Feb 1; Authors: Mehra T, Metzler G, Bauer J, Köberle M, Garbe C PMID: 22293729 [PubMed - as supplied by publisher]

Serum Levels of CC Chemokine Receptor 4 and CXC Chemokine Receptor 3 Ligands in CD8+ Sézary Syndrome.

Serum Levels of CC Chemokine Receptor 4 and CXC Chemokine Receptor 3 Ligands in CD8+ Sézary Syndrome. Acta Derm Venereol. 2012 Feb 1; Authors: Uchi H, Hayashida S, Takahara M, Moroi Y, Furue M PMID: 22293715 [PubMed - as supplied by publisher]

Henoch-Schönlein Purpura Associated With Solid-organ Malignancies: Three Case Reports and a Literature Review.

Henoch-Schönlein Purpura Associated With Solid-organ Malignancies: Three Case Reports and a Literature Review. Acta Derm Venereol. 2012 Feb 1; Authors: Podjasek JO, Wetter DA, Pittelkow MR, A D Abstract Adult Henoch-Schönlein purpura (HSP) is rarely associated with solid-organ malignancies. We describe here three adult patients with HSP diagnosed within 3 months of the diagnosis of associated solid-organ malignancies, including pulmonary, prostate, and renal carcinomas. Two patients had complete remission with a combination of immunosuppressive therapies and treatment of the associated malignancy. The third patient had partial remission with immunosuppressive therapies, but never received treatment for the associated malignancy and did not achieve complete remission before his death 10 months after diagnosis of HSP. These cases suggest that HSP associated with solid-organ malignancies may be resistant to immunosuppressive therapies without treatment of the associated malignancy. Therefore, evaluation for solid-organ malignancies should be considered in adult patients without an identifiable cause of HSP, especially if the disease is not self-limited or does not respond appropriately to treatment. PMID: 22293661 [PubMed - as supplied by publisher]

First Reported Case of the Swedish New Variant of Chlamydia trachomatis (nvCT) in Eastern Europe (Russia), and Evaluation of Russian Nucleic Acid Amplification Tests Regarding Their Ability to Detect nvCT.

First Reported Case of the Swedish New Variant of Chlamydia trachomatis (nvCT) in Eastern Europe (Russia), and Evaluation of Russian Nucleic Acid Amplification Tests Regarding Their Ability to Detect nvCT. Acta Derm Venereol. 2012 Feb 1; Authors: Shipitsyna E, Hadad R, Ryzhkova O, Savicheva A, Domeika M, Unemo M PMID: 22293657 [PubMed - as supplied by publisher]

Treatment of Cutaneous Warts: An Evidence-Based Review

A Psychodermatology Clinic: The Concept, the Format, and Our Observations from Israel

Clinical Manifestations of Cutaneous Metastases: A Review with Special Emphasis on Cutaneous Metastases Mimicking Keratoacanthoma

Comparative Effectiveness of Topical Calcineurin Inhibitors in Adult Patients with Atopic Dermatitis

Trigeminal Trophic Syndrome from Stroke: An Under-Recognized Central Neuropathic Itch Syndrome

Plasma Cell Balanitis Presenting in a Patient with a History of Syphilis

Spotlight on Ustekinumab in Moderate To Severe Plaque Psoriasis

Treatment Options for Primary Hyperhidrosis

The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation

Abstract Anti-inflammatory therapeutic options for the topical treatment of skin diseases with inflammatory or allergic contribution are mostly limited to topical glucocorticoids and calcineurin inhibitors. Both compound classes induce adverse effects. Elevation of intracellular cyclic adenosine monophosphate (cAMP) by inhibition of phosphodiesterase 4 was shown to induce potent anti-inflammatory effects, but the safety profile of currently available compounds is not sufficient. A different approach to increase intracellular cAMP is the substitution of chemically stabilized cAMP analogues. Bucladesine is a stabilized cAMP analogue with an excellent safety profile which had been marketed as topical treatment of impaired wound healing. In the current study, a novel water free emulsion containing bucladesine was evaluated for anti-inflammatory effects. In the arachidonic acid induced ear oedema model in mice, single or multiple administration of an emulsion containing 1.5% was capable of significantly reducing the inflammatory oedema. The data indicate that bucladesine represents an interesting treatment option for skin diseases where an anti-inflammatory activity is indicated. Due to the established clinical safety, this agent may bridge the gap between potent agents such as glucocorticoids or calcineurin inhibitors and emollients without active compounds. Content Type Journal ArticleCategory Short CommunicationPages 1-5DOI 10.1007/s00403-012-1216-6Authors Chris Rundfeldt, Drug-Consult.Net, Toepfferspark 2a, 39108 Magdeburg, GermanyHartwig Steckel, Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, GermanyTorben Sörensen, Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, GermanyPiotr Wlaź, Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Akademicka 19, PL-20033 Lublin, Poland Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Erratum to: Oral doxycycline for the treatment of chronic leg ulceration

Erratum to: Oral doxycycline for the treatment of chronic leg ulceration Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s00403-012-1211-yAuthors Genevieve M. Sadler, Department of Dermatology, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA 6009, AustraliaHilary J. Wallace, Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley, AustraliaMichael C. Stacey, School of Surgery, Fremantle Hospital, University of Western Australia, Fremantle, Australia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Studies of cell signaling in a reconstructed human epidermis exposed to sensitizers: IL-8 synthesis and release depend on EGFR activation

Abstract Models of reconstructed human epidermis (RHE) holding proliferating and fully differentiated cultured keratinocytes allow in vitro investigation of early molecular and cellular epidermal events during the complex response of keratinocytes at the onset of allergic contact dermatitis (ACD) or sensitization. In this study, data collected on RHE exposed to well-characterized sensitizing chemicals, such as dinitrofluorobenzene, oxazolone, cinnamaldehyde and isoeugenol, revealed a transient expression of IL-8 mRNA in association with abundant IL-8 cell release. Investigations of keratinocyte signaling illustrate transient activation by tissue exposure to sensitizing chemicals of the epidermal growth factor receptor (EGFR). This activation of EGFR tyrosine kinase is involved in the expression and release of IL-8. The IL-8 release appears also to be partially dependent on p38 and ERK 1/2 MAPK activation. Moreover, data suggest that heparin-binding EGF-like growth factor (HB-EGF) expression and release induced after exposure of RHE to sensitizing chemicals are also under the control of EGFR tyrosine kinase activity, independently of the IL-8 expression and release. Mechanistic approach of keratinocyte responses in the context of RHE underlying regulation of expression and release of epidermal cytokines and growth factors after topical application of sensitizing chemicals is proposed to identify biomarkers which could then be analysed for in vitro toxicological screening of new or undefined compounds. Content Type Journal ArticleCategory Original PaperPages 1-15DOI 10.1007/s00403-012-1209-5Authors Aurélie Frankart, Cell and Tissue Laboratory, URPHYM (Research Unit for Molecular Physiology), NARILIS, University of Namur (FUNDP), 61 Rue de Bruxelles, 5000, Namur, BelgiumAlain Coquette, Department of Biology, SGS Life Science, Wavre, BelgiumKlaus-Rudolf Schroeder, Henkel AG & Co., Düsseldorf, GermanyYves Poumay, Cell and Tissue Laboratory, URPHYM (Research Unit for Molecular Physiology), NARILIS, University of Namur (FUNDP), 61 Rue de Bruxelles, 5000, Namur, Belgium Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

DNA damage after acute exposure of mice skin to physiological doses of UVB and UVA light

Abstract Solar ultraviolet (UV) radiation is an important risk factor in skin carcinogenesis. This has been attributed mainly to the UVB waveband because the high-energetic photons are capable of interacting with DNA and inducing DNA damage. Recently, UVA light has also gained increasing interest in relation to DNA alteration. Although UVA photons are less energetic than UVB, they comprise a major fraction of sunlight UV radiation and penetrate deep into the skin. The study was carried out to compare the acute effects of UVA and UVB light on SKH-1 mice in relation to DNA damage and associated parameters. Mice were exposed to UVA (10 and 20 J/cm2) or UVB (200 and 800 mJ/cm2) radiation. The number of DNA single-strand breaks (SSB) in lymphocytes, amount of phosphorylated histone H2AX (gamma-H2AX) and apoptosis or DNA fragmentation (TUNEL-positive cells) in skin sections and level of gamma-H2AX, activated caspase-3 and phosphorylated p53 in skin were evaluated after 4 and 24 h. SSB analyzed by alkaline comet assay were found to be 4 and 24 h following UVB and UVA treatment, respectively. TUNEL and gamma-H2AX-positive cell were observed only in UVB exposed animals at both time intervals. The level of activated caspase-3 and phospho-p53 was increased 24 h after UVA and UVB radiation and was more apparent in UVB treated mice. The results indicate that the mechanism of DNA damage caused by acute UVA exposure includes formation of SSB (oxidative damage), but not double-strand breaks. Content Type Journal ArticleCategory Short CommunicationPages 1-6DOI 10.1007/s00403-012-1212-xAuthors Alena Rajnochová Svobodová, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicAdéla Galandáková, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicJarmila Šianská, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicDalibor Doležal, Center for Laboratory Animals, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicRadka Lichnovská, Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicJitka Ulrichová, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech RepublicJitka Vostálová, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Ichthyin/NIPAL4 localizes to keratins and desmosomes in epidermis and Ichthyin mutations affect epidermal lipid metabolism

Abstract Autosomal recessive congenital ichthyosis (ARCI) is a group of disorders characterized by abnormal desquamation of the skin and a disrupted epidermal water barrier. Ichthyin/NIPAL4 gene mutations have been identified in a subgroup of ARCI patients, but the role of ichthyin in epidermis remains elusive. In order to obtain new insights concerning the characteristics of ichthyin and the ARCI pathogenesis, we studied the expression and localization of ichthyin and related epidermal components in cultured keratinocytes and skin sections from patients with Ichthyin mutations and healthy controls. We observed an up-regulation of Ichthyin mRNA levels after in vitro differentiation of keratinocytes from both a patient with Ichthyin mutations and controls. Confocal and electron microscopy analyses of immunolabeled skin sections revealed that ichthyin localizes to desmosomes and keratins in both patients with mutant Ichthyin and controls, with an increased immunolabeling in patients. Nile red lipid analysis of skin sections exposed intra-cellular lipid accumulations in cells of the granular and cornified layers in patients but not in controls, consistent with the pathognomonic lipid membrane structures previously identified in epidermis from patients. Our combined findings indicate that ichthyin is associated with keratins and desmosomes in epidermis and is involved in lipid metabolism, possibly through processing of lamellar bodies. These results provide new clues to the understanding of the epidermal water barrier and the pathogenesis in ARCI. Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s00403-012-1207-7Authors Johanna Dahlqvist, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75185 Uppsala, SwedenGunilla T. Westermark, Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, SwedenAnders Vahlquist, Department of Medical Sciences, Uppsala University Hospital, 75185 Uppsala, SwedenNiklas Dahl, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75185 Uppsala, Sweden Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Exploring the role of prolactin in psoriasis

Abstract Prolactin (PRL) is well recognised for its role(s) in mammary gland development and function. Moreover, its role in skin biology, including the potent regulation of human hair growth, is becoming clearer. Less widely appreciated, however, is the potential role of PRL in the pathobiology of psoriasis. While the relationship between PRL and psoriasis remains enigmatic, several recent publications on the PRL–psoriasis connection have demonstrated a reawakening of interest in this conundrum. We take the occasion of these reports to underscore the importance of dissecting the role(s) of PRL in the aetiopathology of psoriasis, not least since this may help to identify novel hormonal treatment strategies in its management. Content Type Journal ArticleCategory News & ViewsPages 1-4DOI 10.1007/s00403-012-1208-6Authors Ewan A. Langan, Dermatology Centre, Salford Royal NHS Foundation Trust, School of Translational Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UKChristopher E. M. Griffiths, Dermatology Centre, Salford Royal NHS Foundation Trust, School of Translational Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UKRalf Paus, Dermatology Centre, Salford Royal NHS Foundation Trust, School of Translational Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Ani s 1 and Ani s 7 recombinant allergens are able to differentiate distinct Anisakissimplex-associated allergic clinical disorders

Abstract Diagnosis in gastro-allergic anisakiasis (GAA) is straightforward, when clinical history is combined with further allergological evaluation of specific IgE by means of skin prick test and serum specific IgE. In Anisakis simplex sensitisation associated chronic urticaria (CU+), clinical evaluation of possible previous parasitism is difficult, and positive serum specific IgE could be due to cross-reactivity or other unknown factors. In this study, we evaluated the association between IgE seropositivity to the recombinant allergens Ani s 1 and Ani s 7 and several A. simplex-associated allergic disorders. Twenty-eight patients with GAA and 40 patients with CU+ were studied and their IgE responses were compared with a control group composed of patients with chronic urticaria not sensitized to A. simplex (CU−) according to the skin prick test, as well as a group of 15 healthy subjects not referring urticaria or currently A. simplex associated symptoms. 82.1% of GAA patients and 42.5% of CU+ patients were positive for Ani s 1 (P < 0.001), while the Ani s 7 allergen was recognized by 92.9 and 92.5% of sera from patients with GAA and CU+, respectively. The combined positivity obtained for both allergens reached 100% in GAA, and 95% in CU+. IgE determinations to Ani s 1 and Ani s 7 allergens are useful to diagnose the Anisakis infections and to differentiate among several A. simplex-associated allergic disorders. The IgE responses to Ani s 1 are mainly associated with GAA, while this molecule cannot be considered a major allergen in CU+ patients. Content Type Journal ArticleCategory Original PaperPages 1-6DOI 10.1007/s00403-012-1206-8Authors C. Cuéllar, Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, SpainA. Daschner, Servicio de Alergia, Instituto de Investigación Sanitaria, Hospital Universitario de La Princesa, C/Diego de León, 62, 28006 Madrid, SpainA. Valls, Servicio de Alergia, Instituto de Investigación Sanitaria, Hospital Universitario de La Princesa, C/Diego de León, 62, 28006 Madrid, SpainC. De Frutos, Servicio de Alergia, Instituto de Investigación Sanitaria, Hospital Universitario de La Princesa, C/Diego de León, 62, 28006 Madrid, SpainV. Fernández-Fígares, Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, SpainA. M. Anadón, Laboratorio de Parasitología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, SpainE. Rodríguez, Servicio de Parasitología, Centro Nacional de Microbiología, Majadahonda, SpainT. Gárate, Servicio de Parasitología, Centro Nacional de Microbiología, Majadahonda, SpainM. Rodero, Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, SpainF. M. Ubeira, Laboratorio de Parasitología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Reduced expression of microtubule-associated protein 1 light chain 3 in hypertrophic scars

Abstract Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development, and homeostasis. Aberration of this process associates with the pathogeneses of several diseases in mammals. Hypertrophic scar (HS) is characterized by an abundance of collagenous tissue with hypercellularity. However, the molecular mechanism in HS formation is poorly understood. We compared the autophagic capacity in HS and its normal skin (NS) counterparts and explored the molecular mechanism of autophagy during the formation of HS. Microtubule-associated protein 1 light chain 3 (LC3) proteins in HS and NS were detected by immunohistochemistry, Western blot and quantitative real-time PCR (qPCR). The data showed that LC3 positive staining in HS was less intensive relative to NS group (p < 0.05). Three forms of LC3, with molecular weights of about 19 kDa (proLC3), 18 kDa (LC3-I) and 16 kDa (LC3-II), respectively, expressed in NS by Western blot. In contrast, only proLC3 expressed while both LC3-I and LC3-II were significantly downregulated in HS. The protein level of beclin 1 in HS was significantly lower compared with NS (p < 0.05). LC3 and beclin 1 mRNA levels in HS were significantly lower than that in NS (p < 0.05). These results suggest that the generation of LC3-I and LC3-II are interrupted in HS, and that the resultant decrease of autophagic capacity may associate with the pathogenesis of HS. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00403-012-1204-xAuthors Ji-Hong Shi, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaDa-Hai Hu, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaZhan-Feng Zhang, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaXiao-Zhi Bai, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaHong-Tao Wang, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaXiong-Xiang Zhu, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaYing-Jun Su, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, ChinaChao-Wu Tang, Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi’an, Shaanxi 710032, China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Protective effects of β-glucan against oxidative injury induced by 2.45-GHz electromagnetic radiation in the skin tissue of rats

Abstract In recent times, there is widespread use of 2.45-GHz irradiation-emitting devices in industrial, medical, military and domestic application. The aim of the present study was to investigate the effect of 2.45-GHz electromagnetic radiation (EMR) on the oxidant and antioxidant status of skin and to examine the possible protective effects of β-glucans against the oxidative injury. Thirty-two male Wistar albino rats were randomly divided into four equal groups: control; sham exposed; EMR; and EMR + β-glucan. A 2.45-GHz EMR emitted device from the experimental exposure was applied to the EMR group and EMR + β-glucan group for 60 min daily, respectively, for 4 weeks. β-glucan was administered via gavage at a dose of 50 mg/kg/day before each exposure to radiation in the treatment group. The activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the concentration of malondialdehyde (MDA) were measured in tissue homogenates of the skin. Exposure to 2.45-GHz EMR caused a significant increase in MDA levels and CAT activity, while the activities of SOD and GSH-Px decreased in skin tissues. Systemic β-glucan significantly reversed the elevation of MDA levels and the reduction of SOD activities. β-glucan treatment also slightly enhanced the activity of CAT and prevented the depletion of GSH-Px activity caused by EMR, but not statistically significantly. The present study demonstrated the role of oxidative mechanisms in EMR-induced skin tissue damages and that β-glucan could ameliorate oxidative skin injury via its antioxidant properties. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00403-012-1205-9Authors Ali Murat Ceyhan, Department of Dermatology, Medical Faculty, Suleyman Demirel University, 32200 Cunur, Isparta, TurkeyVahide Baysal Akkaya, Department of Dermatology, Medical Faculty, Suleyman Demirel University, 32200 Cunur, Isparta, TurkeyŞeyma Celik Güleçol, Department of Dermatology, Medical Faculty, Suleyman Demirel University, 32200 Cunur, Isparta, TurkeyBetül Mermi Ceyhan, Department of Medical Biochemistry, Medical Faculty, Suleyman Demirel University, Isparta, TurkeyFehmi Özgüner, Department of Physiology, Medical Faculty, Suleyman Demirel University, Isparta, TurkeyWenChieh Chen, Department of Dermatology and Allergy, Technische Universität München, Munich, Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Psoriasis increased the risk of diabetes: a meta-analysis

Abstract To evaluate the association between psoriasis and risk of diabetes, pertinent studies were identified by searching electronic databases and by reviewing the reference lists of retrieved articles. We included observational studies that examined the association between psoriasis and risk of diabetes. Two reviewers independently assessed eligibility and used a standardized form to collect data from published studies. The study quality was assessed by the Newcastle–Ottawa Scale. A total of 22 eligible studies that included 3,307,516 participants fulfilled the inclusion criteria. Compared to individuals without psoriasis, subjects with psoriasis had a 1.42-fold increased risk of diabetes (95% CI, 1.40–1.45). Findings from this meta-analysis suggest that individuals with psoriasis may have a modestly increased risk of diabetes. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00403-011-1200-6Authors Juan Cheng, Department of Dermatology, Beijing 302 Hospital, Beijing, ChinaDayu Kuai, Department of Digestion, Lu He Hospital, Beijing, ChinaLi Zhang, Department of Dermatology, Beijing 307 Hospital, Beijing, ChinaXueqin Yang, Department of Dermatology, Air Force General Hospital, Beijing, ChinaBing Qiu, Civil Aviation Medicine Center of Civil Aviation Administration of China, Beijing, China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effects of low pseudoallergen diet on urticarial activity and leukotriene levels in chronic urticaria

Abstract Pseudoallergens and leukotrienes (LTs) may have a role in chronic urticaria (CU). The aim of our study is to evaluate the response to the low pseudoallergen diet therapy in patients with CU and the change in LT levels in diet responsive and non-responsive patients. 34 patients with CU were put on diet for 4 weeks. All patients kept a daily score sheet of pruritus and whealing symptoms. The urticarial activity score (UAS) of each patient was calculated with the sum of pruritus and wheal score. The sum score of the first 7 consecutive days (UAS7-first week) and last 7 days (UAS7-fourth week) were used to compare the clinical outcome of the diet. A reduction of ≥50% in UAS7-fourth week compared to UAS7-first week was considered as “response”. Urinary LTE4 (uLTE4) level of each patient was measured at baseline and after the 4 week of diet therapy. 14 of the patients (41.2%) were responsive to diet therapy. Baseline uLTE4 levels were similar between responsive and non-responsive patients (P = 0.540). Second uLTE4 levels (after the 4 week of diet therapy) were significantly lower in responsives than in non-responsive patients (P < 0.001). Second uLTE4 levels of responsives were significantly lower than the baseline values (P = 0.019), whereas this was not significant for non-responsives (P = 0.070). There was a significant correlation between the change in uLTE4 levels and the change in mean urticarial activity scores (r = 0.554, P = 0.001) in the whole study population. In conclusion, low pseudoallergen diet helps to reduce the urticarial activity in CU. The change in urticarial activity correlates with the change in LT levels. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s00403-011-1203-3Authors Gulsen Akoglu, Department of Dermatology, Faculty of Medicine, Hacettepe University, P. O. 06100, Sihhiye, Ankara, TurkeyNilgun Atakan, Department of Dermatology, Faculty of Medicine, Hacettepe University, P. O. 06100, Sihhiye, Ankara, TurkeyBanu Çakır, Department of Public Health, Faculty of Medicine, Hacettepe University, Ankara, TurkeyOmer Kalayci, Pediatric Allergy and Asthma Unit, Faculty of Medicine, Hacettepe University, Ankara, TurkeyMutlu Hayran, Research Unit, Faculty of Medicine, Hacettepe University, Ankara, Turkey Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Kinetics of neuronal contribution during the development of a contact allergic reaction

Abstract The nervous system contributes to allergic contact dermatitis (ACD). Elucidation of the implication of the nervous system during different stages of ACD could be of therapeutic value. Our aim was to study the kinetics and contribution of the nervous system to ACD by investigating innervation and expression of neuropeptides in skin biopsies obtained at 0, 6, 24, 48 and 72 h post-challenge. Biopsies were stained using antisera against protein gene product (PGP) 9.5, growth associated protein (GAP)-43, substance P and its receptor (R) neurokinin (NK)-1, NKA and NK-2R, and calcitonin gene-related peptide (CGRP). GAP-43-immunoreactive (ir) nerves revealed a time-dependent increase that was more pronounced at 48 and 72 h, while PGP 9.5-ir nerves remained unaltered. Substance P-, NKA- and CGRP-ir nerves at 0 and 6 h were significantly higher compared to later time points, whereas NKA-, NK-1R- and NK-2R-ir cells were lower. A dramatic rise in cell numbers was noted at 24 h. Our findings demonstrate the implication of nerves and sensory neuropeptides during the kinetics of ACD and suggest a possibility to target this system at an early time point for therapy. Content Type Journal ArticleCategory Original PaperPages 1-9DOI 10.1007/s00403-011-1202-4Authors Reem Altawil, Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenJonathan Lyström, Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, SwedenHusameldin El-Nour, Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Oral doxycycline for the treatment of chronic leg ulceration

Abstract This pilot study investigated oral doxycycline as an adjunct to compression therapy for non-healing venous leg ulcers. Ten patients received doxycycline 20 mg twice daily (low-dose doxycycline) and ten patients received doxycycline 100 mg twice daily (high-dose doxycycline). Utilising a pre-test post-test study design, ulcer area was measured and wound fluid was collected before and after 4 weeks of treatment. In the high-dose doxycycline group, the reduction in median ulcer area was 48% (p = 0.1) and there was a significant reduction in wound fluid total matrix metalloprotease-1 (p = 0.02). These effects were not observed with low-dose doxycycline. There were no significant changes in wound fluid tumour necrosis factor-α or quantitative bacteriology following treatment with low-dose or high-dose doxycycline. There was no significant relationship between change in ulcer area and matrix metalloprotease-1, -8 or -9 activities in wound fluid at the end of treatment. Median wound fluid doxycycline concentrations after 4 weeks of treatment were 0.2 (0.45 μM) and 2.3 (5.18 μM) in the low-dose and high-dose groups, respectively, which are lower than that previously shown to inhibit matrix metalloproteases and tumour necrosis factor-α. Our study suggests that doxycycline 100 mg twice daily may improve the healing rate of recalcitrant leg ulcers, however the mechanism remains unclear. Content Type Journal ArticleCategory Short CommunicationPages 1-7DOI 10.1007/s00403-011-1201-5Authors Genevieve M. Sadler, Department of Dermatology, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, WA 6009, AustraliaHilary J. Wallace, Burn Injury Research Unit, School of Surgery, University of Western Australia, Crawley, AustraliaMichael C. Stacey, School of Surgery, Fremantle Hospital, University of Western Australia, Fremantle, Australia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Development and characterization of phyto-vesicles of β-sitosterol for the treatment of androgenetic alopecia

Abstract Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of alopecia, which affects millions of men and women worldwide, and is an androgen driven disorder. To study the effect of β-sitosterol phyto-vesicles on AGA, the testosterone-induced alopecia model was used. For the study, the albino rats were used and the period of study was 21 days. β-Sitosterol is a phytosterol which is chemically similar to cholesterol. This compound was found suitable for the preparation of phyto-vesicles by the process involving its complexation with phosphatidyl choline. Pharmacokinetic studies of β-sitosterol reveal its poor absorption through the intestine. The objective of the present study is to enhance the bioavailability of β-sitosterol by its complexation with phosphatidyl choline and then to formulate it as phyto-vesicles for the treatment of alopecia. The complex of β-sitosterol was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, TLC, UV, IR and NMR spectroscopy. This complex was then formulated as phyto-vesicles and then characterized. The results revealed that effect on alopecia is better in case of phyto-vesicles as compared to the complex, physical mixture and the β-sitosterol itself. Enhanced bioavailability of the β-sitosterol complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and β-sitosterol, in terms of better absorption and improved activity for the treatment of alopecia. Content Type Journal ArticleCategory Original PaperPages 1-9DOI 10.1007/s00403-011-1199-8Authors Kirti Upadhyay, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar, 470003 Madhya Pradesh, IndiaNishant Kumar Gupta, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar, 470003 Madhya Pradesh, IndiaVinod Kumar Dixit, Department of Pharmaceutical Sciences, Dr. H. S. Gour Vishwavidyalaya, Sagar, 470003 Madhya Pradesh, India Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. −765G>C PTGS2 polymorphism and NMSC risk

Abstract Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 −765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 −765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR–RFLP technique to explore −765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 −765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In BCC and SCC patients with GG genotype, CRP level is significantly increased compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group comparison of CRP levels showed significantly lower CRP levels in patients carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients (p < 0.0001). PTGS2 −765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 −765G>C polymorphism and COX-2 activity or CRP levels. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00403-011-1194-0Authors Relu Cocoş, “Carol Davila” University of Medicine and Pharmacy, Bucharest, RomaniaSorina Schipor, “C. I. Parhon” National Institute of Endocrinology, Bucharest, RomaniaIlinca Nicolae, Dermatovenereological Center/Clinical Hospital of Dermato-venereology “Prof. Dr. Scarlat Longhin”, Bucharest, RomaniaCecilia Thomescu, Dermatovenereological Center/Clinical Hospital of Dermato-venereology “Prof. Dr. Scarlat Longhin”, Bucharest, RomaniaFlorina Raicu, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis

Abstract Atopic dermatitis (AD) is a chronic inflammatory disease of the skin for which there are no reliable biomarkers to assess clinical severity. Serum interleukin-18 (IL-18) levels may be associated with AD severity. To identify putative biomarkers associated with clinical severity in adult AD patients, we enrolled 121 adult AD patients (mean age 35.7 years) and 50 healthy controls (mean age 31.7 years). We compared these groups for blood eosinophils and serum levels of IL-18, thymus and activation-regulated chemokine (TARC), total IgE, and lactate dehydrogenase (LDH). We also determined S. aureus enterotoxin B (SEB) specific IgE levels and the SCORingAD (SCORAD) scores for AD patients. For AD patients, stepwise logistic regression was used to estimate odds ratios (OR) for each biomarker for the likelihood of having AD, and multiple linear regression was used to identify biomarkers associated with SCORAD scores. Compared with healthy controls, adult AD patients had higher levels of IL-18, TARC, total IgE, eosinophils, and LDH. TARC levels had the highest OR for AD occurrence, while the OR for IL-18 was insignificant. Also, IL-18 was not related to the presence of SEB-IgE. Notably, IL-18 levels were significantly associated with SCORAD scores, as were TARC, total IgE, and LDH levels. A panel of biomarkers (IL-18, TARC, total IgE, and LDH) may be more useful to accurately assess clinical severity in adult AD patients. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00403-011-1198-9Authors Kenzen Kou, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanMichiko Aihara, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanTomoko Matsunaga, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanHuichin Chen, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanMasataka Taguri, Departments of Biostatistics and Epidemiology, Yokohama City University Medical Centre, 4-57 Urafunecho, Minami-ku, Yokohama City, 232-0024 JapanSatoshi Morita, Departments of Biostatistics and Epidemiology, Yokohama City University Medical Centre, 4-57 Urafunecho, Minami-ku, Yokohama City, 232-0024 JapanHiroyuki Fujita, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanYukie Yamaguchi, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 JapanTakeshi Kambara, Department of Dermatology, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama City, 232-0024 JapanZenro Ikezawa, Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, 236-0004 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Inflammatory peeling skin syndrome caused a novel mutation in CDSN

Abstract Generalized peeling skin syndrome (PSS) is a rare autosomal recessive dermatosis manifesting with continuous exfoliation of the stratum corneum. The inflammatory (type B) subtype of PSS was recently found to be caused by deleterious mutations in the CDSN gene encoding corneodesmosin, a major component of desmosomal junctions in the uppermost layers of the epidermis. In the present study, we assessed a 10-month-old baby, who presented with generalized superficial peeling of the skin. Using PCR amplification and direct sequencing, we identified the third PSS-associated mutation in CDSN, a homozygous 4 bp duplication in the second exon of the gene (c.164_167dup GCCT; p.Thr57ProfsX6). These data further support the notion that corneodesmosin deficiency impairs cell–cell adhesion in the upper epidermis, paving the way for an abnormal inflammatory response due to epidermal barrier disruption. Content Type Journal ArticleCategory Short CommunicationPages 1-5DOI 10.1007/s00403-011-1195-zAuthors Dana Fuchs Telem, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, 64239 Tel Aviv, IsraelShirli Israeli, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, 64239 Tel Aviv, IsraelOfer Sarig, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, 64239 Tel Aviv, IsraelEli Sprecher, Department of Dermatology, Tel Aviv Sourasky Medical Center, 6, Weizmann Street, 64239 Tel Aviv, Israel Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Increased miRNA-146a and miRNA-155 expressions in oral lichen planus

Abstract Oral lichen planus (OLP) is a chronic inflammatory disease T helper 1 lymphocytes (Th1)-mediated. Interferon-gamma (IFN-γ) plays a central role in local immune response in this disease. MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs that have important biological and pathological functions due to their potential mechanism regulating gene expression. Recently, some studies have demonstrated that miRNA-146a and miRNA-155 participate in immune response regulation, and are important in several chronic inflammatory and autoimmune diseases. The purpose of the present study was to investigate the expression of the miRNA-146a and miRNA-155 in 31 OLP lesions compared to normal oral mucosa and blood samples. Quantitative real-time polymerase chain reaction was used to analyze miRNA expressions. Our results showed increased expression of miRNA-146a and miRNA-155 in OLP lesions. In conclusion, these data highlight the possibility of miRNA-146a and miRNA-155 involvement in the regulation of the immune response in OLP. Content Type Journal ArticleCategory Original PaperPages 1-5DOI 10.1007/s00403-011-1197-xAuthors Telma Cristina Arão, Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BrazilAndré Luiz Sena Guimarães, School of Dentistry, Universidade Estadual de Montes Claros, Belo Horizonte, MG, BrazilAlfredo Maurício Batista de Paula, School of Dentistry, Universidade Estadual de Montes Claros, Belo Horizonte, MG, BrazilCarolina Cavaliéri Gomes, Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BrazilRicardo Santiago Gomez, Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Clinical significance of circulating platelet-activating factor acetylhydrolase levels in systemic sclerosis

Abstract Platelet-activating factor acetylhydrolase (PAF-AH) has been demonstrated to be one of anti-inflammatory and anti-apoptotic factors, suggesting the potential to be involved in the development of systemic sclerosis (SSc). The aim of this study is to determine serum PAF-AH levels and their clinical associations in patients with SSc. Serum PAF-AH levels were examined by enzyme-linked immunosorbent assay in 57 patients with SSc and 24 healthy individuals. Serum PAF-AH levels were significantly elevated in SSc patients (130.4 ± 69.5 ng/ml) compared with healthy individuals (81.6 ± 34.8 ng/ml; P < 0.001). Among SSc patients, there were no differences in serum PAF-AH levels between those with diffuse cutaneous SSc (135.5 ± 79.3 ng/ml; n = 29) and those with limited cutaneous SSc (125.1 ± 58.6 ng/ml; n = 28). Patients with SSc who had raised PAF-AH levels less often had digital ulcers and arthritis/arthralgias than those with normal PAF-AH levels. The results show that serum PAF-AH levels were increased in patients with SSc and associated with a lower frequency of pitting scars/digital ulcers and arthritis/arthralgias. PAF-AH could be a protective factor against the development of digital ulcers and arthritis/arthralgia in this disease and as such would be a useful serological marker for disease severity. Content Type Journal ArticleCategory Original PaperPages 1-6DOI 10.1007/s00403-011-1196-yAuthors Koichi Yanaba, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanYoshihide Asano, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanYayoi Tada, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanMakoto Sugaya, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanTakafumi Kadono, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanShinichi Sato, Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers

Abstract Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment. Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s00403-011-1192-2Authors Hiroyuki Kamei, Department of Clinical Pharmacy Practice and Health Care Management, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503 JapanAmi Isaji, Department of Clinical Pharmacy Practice and Health Care Management, Faculty of Pharmacy, Meijo University, Nagoya, 468-8503 JapanYukihiro Noda, Division of Clinical Sciences and Neuropsychopharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, 468-8503 JapanKazuhiro Ishikawa, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 466-8550 JapanKoji Senzaki, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 466-8550 JapanKiyofumi Yamada, Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 466-8550 JapanKazumitsu Sugiura, Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8560 JapanYasushi Tomita, Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 466-8560 JapanToshitaka Nabeshima, Department of Chemical Pharmacology, Graduate School of Pharmaceutical Science, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Detection and comparison of two types of ATP2C1 gene mutations in Chinese patients with Hailey–Hailey disease

Abstract The gene ATP2C1 is identified as the defective gene in Hailey–Hailey disease (HHD). The nonsense and missense are two common types of mutations and have ,respectively, been detected in many HHD patients. The aims of our study were to identify the pathogenic ATP2C1 abnormality in Chinese HHD patients, and to compare nonsense and missense mutations in vivo to provide further understanding of the molecular and the physiological basis of HHD. The nucleotide sequencing of the ATP2C1 gene was performed in HHD patients, unaffected family members and 100 unrelated individuals. Meanwhile, we detected and analyzed the clinical manifestations, the expression of ATP2C1 mRNA and hSPCA1 protein in the two types of mutations. Three heterozygous mutations were identified, including a previously reported nonsense mutation (R799X), two novel missense mutations (D644G) and (R417K). The results of comparisons between two types of mutations showed that the common clinical features, the similarly low-level expressions of ATP2C1 mRNA and hSPCA1 protein, but the ATP2C1 mRNA expression of nonsense mutation was lower than missense mutation and even less than half the level of normal people. Our findings expand the known spectrum of ATP2C1 mutations in HHD. We supported the haploinsufficiency theory as prevalent mechanism in both types of mutations, and believed that the differences of ATP2C1 mRNA expressions in peripheral blood may relate with the type of mutation and reflect the state of illness of patients. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00403-011-1185-1Authors Dingwei Zhang, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of ChinaXiaoli Li, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of ChinaShengxiang Xiao, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of ChinaJia Huo, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of ChinaShuang Wang, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of ChinaPengjun Zhou, Department of Dermatology, The Second Hospital, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, 710004 Shaanxi, People’s Republic of China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease)

Abstract The neurofibromatosis type 1 (NF1) is characterized by specific cutaneous features (neurofibromas, “café-au-lait” spots of the skin) and alterations of several tissue (nervous, vascular) and bone deformities, such as scoliosis, congenital pseudoarthrosis and bone dysplasia of tibia. Moreover, several studies have shown systemic involvement of bone tissue in NF1 patients, leading to reduced bone mass. The aim of our study was to evaluate some bone mineral metabolism parameters before and after calcium and vitamin D supplementation in NF1 patients. We evaluated in 70 NF1 consecutive patients the mineral metabolism and bone mineral density compared with 40 normal subjects. We showed bone alterations in 35% of patients and the increase of bone formation markers, such as bone isoenzyme of alkaline phosphatase (41.2 ± 15.5 vs. 25.6 ± 8.7 UI; P < 0.05, respectively) and osteocalcin (18.1 ± 5.6 vs. 7.6 ± 1.9 ng/ml; P < 0.05) and reduction of circulating levels of (25OH)-vitamin D (21.8 ± 12.3 ng/ml) with an high percentage of hypovitaminosys D (>60%). Moreover, we revealed a significant reduction of bone mass density at spine (L1–L4) (0.935 ± 0.13 vs. 1.110 ± 0.17 g/cm2; P < 0.001) and femoral neck side (0.765 ± 0.09 vs. 0.839 ± 0.12 g/cm2; P < 0.02), with high prevalence of osteopenia (44%) and osteoporosis (18%). After 12 months of calcium (1,200 mg/die) and cholecalciferol (800 UI/die) supplementation, we found a significant increase of (25) OH-vitamin D level (21.8 ± 12.3 vs. 35 ± 13 ng/ml; P < 0.01), without changes in bone mass density. In conclusion, NF1 patients may present a mineral bone involvement, with vitamin D deficiency; calcium and vitamin D supplementation is necessary to restore these bone mineral metabolic alterations. Content Type Journal ArticleCategory Short CommunicationPages 1-7DOI 10.1007/s00403-011-1191-3Authors Luigi Petramala, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalySandra Giustini, Department of Dermatology, University ‘‘Sapienza’’, Rome, ItalyLaura Zinnamosca, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyCristiano Marinelli, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyLuciano Colangelo, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyGiuseppina Cilenti, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyMaria Chiara Formicuccia, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyEmilio D’Erasmo, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, ItalyStefano Calvieri, Department of Dermatology, University ‘‘Sapienza’’, Rome, ItalyClaudio Letizia, Department of Internal Medicine and Medical Specialties, Secondary Hypertension Unit, University ‘‘Sapienza’’, Viale del Policlinico 155, 00161 Rome, Italy Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Severe phenotypes in two Tunisian families with novel XPA mutations: evidence for a correlation between mutation location and disease severity

Abstract Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity. Content Type Journal ArticleCategory Original PaperPages 1-6DOI 10.1007/s00403-011-1190-4Authors O. Messaoud, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaM. Ben Rekaya, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaH. Ouragini, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaS. Benfadhel, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaH. Azaiez, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaR. Kefi, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaN. Gouider-Khouja, Neurology Institute of Tunis, Tunis, TunisiaI. Mokhtar, Dermatology Department, Habib Thameur Hospital, Tunis, TunisiaA. Amouri, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, TunisiaM. S. Boubaker, Anatomo-Pathology Department, Pasteur Institute of Tunis, Tunis, TunisiaM. Zghal, Dermatology Department, Habib Thameur Hospital, Tunis, TunisiaS. Abdelhak, “Molecular Investigation of Genetic Orphan Diseases” Research Unit, Pasteur Institute of Tunis, Tunis, Tunisia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Osteopontin, a protein with cytokine-like properties: a possible involvement in pemphigus vulgaris

Abstract Pemphigus is an autoimmune blistering disease characterized by severe and chronic course, histopathologically characterized by infiltration of a large quantity of eosinophils, neutrophils, and activated Th1 and Th2 cells around the blister. Polarization of Th cells to Th1 or Th2 phenotypes, a critical aspect of cell-mediated immunity, is influenced by production of early cytokines, including osteopontin. To determine the involvement of osteopontin in pemphigus vulgaris patients in active stage of the disease, auto-antibodies to desmoglein-1 and desmoglein-3 and plasmatic osteopontin levels were examined by ELISA tests. In this work, significant plasmatic level of osteopontin in PV patients with active stage of disease were found particularly in those patients with both skin and oral pemphigus. OPN might drive the immune responses playing an important role in pemphigus onset. Content Type Journal ArticleCategory Short CommunicationPages 1-4DOI 10.1007/s00403-011-1186-0Authors A. Baroni, Department of Dermatology, Second University of Naples, Naples, ItalyA. De Filippis, Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples (SUN), Via Luigi de Crecchio no. 7, 80138 Naples, ItalyE. Buommino, Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples (SUN), Via Luigi de Crecchio no. 7, 80138 Naples, ItalyR. A. Satriano, Department of Dermatology, Second University of Naples, Naples, ItalyV. Cozza, Department of Mathematics and Statistics, University Study of Naples “Federico II”, Naples, Italy Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A putative in vitro organotypic model of molting with human skin explants

Abstract We report finding a simple method to partially reproduce the characteristic process of molting that takes place in invertebrates using human skin explants in vitro. In this method, human skin explants discarded from regular plastic surgery procedures were kept, submersed, in regular growth medium for 10 days at 4°C. After that period, the skin explants were cultured at the air–liquid interface for another 10 days. Histological analysis of the skin revealed the formation of one full epidermal structure and an additional intermediate epidermal structure containing a putative stratum corneum, superimposed one of top of the other, in which we consider an equivalent model of “molting” or “ecdysis”. Basic analysis of cell proliferation and differentiation of the explants at different stages of the process are briefly presented. We believe this model can be used in the study of certain human skin diseases as well as in comparative animal physiology. Content Type Journal ArticleCategory Original PaperPages 1-9DOI 10.1007/s00403-011-1187-zAuthors A. Peramo, Department of Oral and Maxillofacial Surgery, University of Michigan, 1150W. Medical Drive, MSRBII A560, Ann Arbor, MI 48109, USAS. E. Feinberg, Department of Oral and Maxillofacial Surgery, University of Michigan, 1150W. Medical Drive, MSRBII A560, Ann Arbor, MI 48109, USAC. L. Marcelo, Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Comparative genomic hybridisation analysis of keloid tissue in Caucasians suggests possible involvement of HLA-DRB5 in disease pathogenesis

Abstract Keloid disease (KD) is a common fibroproliferative disorder that can occur following cutaneous injury in genetically susceptible individuals. Familial predisposition, high prevalence in certain populations and occurrence in twins suggest a strong genetic component to KD. However, to date no single causative gene has been identified. Copy number variations (CNVs) in genes have been associated with several human diseases including common skin disorders. The objective of this study was, therefore to determine if CNVs in the human genome may contribute to the development of KD. Agilent SurePrint G3 one Million microarrays were used to detect DNA copy number differences in keloid scars of four Caucasian females and compared to commercial reference DNA samples. Subsequent validation was performed with quantitative polymerase chain reactions (qPCR) using 15 KD cases and 27 Caucasian controls. Further validation using a second cohort was carried out with an additional 11 Caucasian controls and 10 KD cases developed from minor skin puncture wounds (caused by acne, vaccination or chickenpox). HLA-DRB1*15 was typed using allele-specific primers in PCR. Five CNV regions located at chromosome (chr) 6p21.32, chr11q11, chr17q12, chr8p23.1, chr22q13.1, chr19p13.1 and chr2q14.3 were selected for validation with qPCR. When comparing controls to subgroups of KD, according to their cause of scarring, chr6p21.32 (primer design targetting HLA-DRB5) was significantly (P < 0.005) associated with KD developed from minor skin puncture wounds, which is further validated using a larger sample size (P < 0.001). The presence of HLA-DRB5 was associated with HLA-DRB1*15 status; 18 out of 19 individuals were positive for both HLA-DRB5 and HLA-DRB1*15 allele. In conclusion, these preliminary findings further support the possible contribution of the HLA genes in KD pathogenesis. Content Type Journal ArticleCategory Short CommunicationPages 1-9DOI 10.1007/s00403-011-1182-4Authors Barbara Shih, Plastic and Reconstructive Surgery Research, School of Translational Medicine, The Manchester Interdisciplinary Biocentre (MIB), University of Manchester, 131 Princess Street, Manchester, M17ND UKArdeshir Bayat, Plastic and Reconstructive Surgery Research, School of Translational Medicine, The Manchester Interdisciplinary Biocentre (MIB), University of Manchester, 131 Princess Street, Manchester, M17ND UK Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Pirfenidone suppresses keloid fibroblast-embedded collagen gel contraction

Abstract Keloid is a clinically intractable disease that causes disfigurement, itching, and pain due to abnormal proliferation of fibroblasts and production of collagen. Pirfenidone is a novel anti-fibrotic agent that inhibits the progression of fibrosis occurring in the keloid lesions of the lung and kidney. In order to examine whether pirfenidone has a therapeutic effect on keloid lesions, we prepared an in vitro wound contraction model with keloid fibroblasts. The gel contractility of a mixture of keloid fibroblasts and an acid-soluble collagen solution was examined with/without transforming growth factor (TGF)-β1 in the presence or absence of pirfenidone. Real time RT-PCR was performed to detect mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 quantitatively in keloid fibroblasts incubated with/without TGF-β1 in the presence or absence of pirfenidone. The contractility of keloid fibroblast-embedded collagen gel was increased after the addition of TGF-β1. Pirfenidone suppressed gel contraction with TGF-β1 dose dependently. TGF-β1 stimulated mRNA expression of TGFB1, CTGF, aSMA, and Col1A1 in keloid fibroblasts, while pirfenidone significantly inhibited mRNA expression of CTGF and aSMA in the identical cells. These findings suggest that pirfenidone suppresses the contraction of keloid-derived fibroblasts by inhibiting the down-stream pathway of TGF-β1, thus demonstrating its therapeutic utility for the treatment of keloid lesions. Content Type Journal ArticleCategory Short CommunicationPages 1-6DOI 10.1007/s00403-011-1184-2Authors Masuyoshi Saito, Department of Dermatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023 JapanMasashi Yamazaki, Department of Dermatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023 JapanTatsuo Maeda, Department of Dermatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023 JapanHajime Matsumura, Department of Plastic Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, JapanYasuhiro Setoguchi, Department of Respiratory Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, JapanRyoji Tsuboi, Department of Dermatology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A simple, noninvasive and efficient method for transdermal delivery of siRNA

Abstract Effective delivery of therapeutic agents is the most challenging hurdle in the use of RNA interference for research and in the clinic. Here, we assessed whether a short synthetic peptide, ACSSSPSKHCG (TD-1), could be transported through rat footpad (follicle-free) skin and efficiently deliver small interfering RNA (siRNA) to knock down a target gene. Fluorescence microscopy revealed that topical co-administration of FITC-labeled TD-1 and FAM-labeled siRNA distributed uniformly from the epidermis to the subcutaneous tissue of rat footpad skin. Transmission electron microscopy revealed the absence of cell–cell junctions and enlarged spaces between epithelial cells in the TD-1-treated footpad skin. TD-1 delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. TD-1 can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of TD-1 and siRNA into the epidermis for gene knockdown. The system might have potential for siRNA delivery in skin for drug therapy. Content Type Journal ArticleCategory Original PaperPages 1-6DOI 10.1007/s00403-011-1181-5Authors Chang-Min Lin, Department of Plastic and Reconstructive Surgery, Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, No. 57, ChangPing Road, ShanTou City, Guangdong Province, ChinaKeng Huang, Emergency Department, Second Affiliated Hospital, Shantou University Medical College, ShanTou City, ChinaYang Zeng, Department of Histology and Embryology, Shantou University Medical College, ShanTou City, ChinaXian-Cai Chen, Department of Histology and Embryology, Shantou University Medical College, ShanTou City, ChinaSen Wang, Department of Plastic and Reconstructive Surgery, Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, No. 57, ChangPing Road, ShanTou City, Guangdong Province, ChinaYu Li, Department of Plastic and Reconstructive Surgery, Tissue Engineering Laboratory, First Affiliated Hospital, Shantou University Medical College, No. 57, ChangPing Road, ShanTou City, Guangdong Province, China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Comparison of the spread of three botulinum toxin type A preparations

Abstract Botulinum toxins are frequently used in esthetics to improve the appearance of facial wrinkles. In this setting, precise localization of the neurotoxin is required to produce the desired clinical effects. Unwanted effects can occur if the neurotoxin diffuses into untargeted muscle. Therefore, a neurotoxin with low and predictable spread would be preferable for esthetic applications. The aim of this study was to investigate the spread of three approved botulinum toxin type A preparations, with and without complexing proteins, by measuring and comparing the size of the anhidrotic halos they produced following injection of equivalent doses in an identical volume into the forehead of patients. The results showed that incobotulinumtoxinA and onabotulinumtoxinA displayed comparable spread at 6 weeks (maximal area of anhidrosis within 6 weeks) and area under the effect curve (AUEC) over 6 months. However, abobotulinumtoxinA, when assuming a 1:2.5 injection volume ratio, produced a statistically significantly greater maximal area of anhidrosis within 6 weeks and AUEC over 6 months compared with incobotulinumtoxinA. All preparations were well tolerated. The results of this study demonstrate that incobotulinumtoxinA and onabotulinumtoxinA have comparable spread, while abobotulinumtoxinA has significantly greater spread than incobotulinumtoxinA. Content Type Journal ArticleCategory Original PaperPages 1-7DOI 10.1007/s00403-011-1179-zAuthors Martina Kerscher, Division of Biochemistry and Molecular Biology, Cosmetic Science, University of Hamburg, Martin Luther King Platz 6, 20146 Hamburg, GermanySusanna Roll, Merz Pharmaceuticals GmbH, Frankfurt, GermanyAndreas Becker, Merz Pharmaceuticals GmbH, Frankfurt, GermanyWalter Wigger-Alberti, Bioskin GmbH, Hamburg, Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Endothelial and axon reflex vasodilatation to acetylcholine in rosacea-affected skin

Abstract Rosacea is a chronic skin disorder, characterized by persistent painful facial flushing and often accompanied by papules and pustules. To investigate the mechanism of facial flushing in rosacea, acetylcholine was administered by iontophoresis to a 10-mm diameter site in the forehead of 31 patients with rosacea and in 29 controls of similar age and sex distribution. During the iontophoresis, current strengths doubled in eight steps from 2.5 to 320 μA. For each step, skin blood flow was monitored during 60 s of iontophoresis and for 2 min afterwards with laser Doppler flow probes at the site of iontophoresis and 5–8 mm away in the region of axon reflex vasodilatation. Vascular responses to acetylcholine were similar in patients and controls, but stinging sensations were greater in patients than in controls at the most intense current strength. In addition, axon reflex vasodilatation was greater in patients with severe than mild rosacea. These findings suggest that activation of nociceptive nerve fibres contributes to skin sensitivity in patients with rosacea, and that axon reflexes augment flushing in patients with the most severe symptoms. Content Type Journal ArticleCategory Original PaperPages 1-5DOI 10.1007/s00403-011-1177-1Authors Peter D. Drummond, School of Psychology, Murdoch University, Perth, WA 6150, AustraliaDaphne Su, School of Psychology, Murdoch University, Perth, WA 6150, Australia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4

Abstract During wound healing and tissue repair the dermal fibroblast-to-myofibroblast transdifferentiation plays an important role, transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor of transdifferentiation. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression. The involvement of miRNAs and their roles in TGF-β1-induced myofibroblast transdifferentiation remains to be determined in detail. The current study found that the expression of miR-146a was upregulated in human dermal fibroblasts cells in response to TGF-β1 stimulation in dose-dependent manner by quantitative RT-PCR. Bioinformatic analyses predict that signaling effectors mothers against decapentaplegic protein 4 (SMAD4) is a miR-146a target gene. Luciferase assay demonstrated that miR-146a mimics suppressed SMAD4 3′-UTR reporter construct activity. Furthermore, miR-146a overexpression in dermal fibroblast did not decrease target mRNA levels, but significantly reduced target protein expression. In addition, dermal fibroblasts transfected with miR-146a mimics exhibited attenuated TGF-β1 -induced α-smooth muscle actin (α-SMA) expression compared with the control. This study demonstrated that miR-146a may function as a novel negative regulator to modulate myofibroblast transdifferentiation during TGF-β1 induction by targeting SMAD4. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s00403-011-1178-0Authors Zhen Liu, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaCui-Ling Lu, Department of Critical Care Medicine, The 309th Hospital of PLA, Beijing, 100091 ChinaLi-Ping Cui, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaYong-Liang Hu, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaQi Yu, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaYing Jiang, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaTian Ma, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaDa-Kai Jiao, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaDi Wang, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 ChinaChi-Yu Jia, Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091 China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Measuring Melasma Patients' Quality of Life using Willingness to Pay and Time Trade-off Methods in Thai Population

Background: Melasma is a common hyperpigmentation disorder that has a significant effect on an individual's quality of life. However, there is no preference-based measurement that reflects quality of life in patients with melasma. The objective of this study was to assess the impact of melasma on quality of life by using a health status measurement - the Dermatology Life Quality Index (DLQI) - and a preference-based measurement - Willingness to Pay (WTP) and Time Trade-Off (TTO). Methods: A cross-sectional descriptive study was conducted. Seventy-eight patients with melasma who attended the melasma clinic at Siriraj Hospital from February to March 2009 were recruited in this study. The Thai version of the DLQI, questionnaires about WTP, standard TTO, and daily TTO were used to assess patients' quality of life. Results: Seventy-seven (98.7%) patients were female with a mean age of 47.8 7.9 years. The mean health utility based on standard TTO was 0.96. The utility obtained by the daily TTO method was 0.92 and was significantly correlated with an economically inactive occupation (p<0.05). The mean monthly WTP for the most effective treatment was 1,157 baht (7.2% of monthly income), ranging from 100 to 5,000 baht (1 USD 35.1 baht). The WTP was significantly correlated with monthly personal income and the total DLQI score. Conclusion: The WTP method could be a useful tool with which to measure the quality of life of patients with melasma.

Classic Kaposi's Sarcoma In Morocco: Clinico -epidemiological study at the National Institute Of Oncology

Background: Classic Kaposi's sarcoma (CKS) is a rare disease likely associated with human herpes virus 8 (HHV-8) infection, and occurs predominantly in Jewish, Mediterranean and middle eastern men .There is a dearth of data in Moroccan patients with CKS regarding epidemiology, clinical characteristics and outcomes. This report examines a cohort of patients with CKS evaluated at the national institute of oncology over 11-year period. Methods: A retrospective analysis of patients referred to the national institute of oncology with classical Kaposi sarcoma, between January 1998 and February 2008, was performed. Reviewed information included demographics, clinical and pathological staging, death or last follow-up. Results: During the study period, 56 patients with a diagnosis of CKS have been referred to our hospital. There were 11(19,7%) females and 45 (80,3%) males (male-to-female ratio: 4:1). Mean age at diagnosis was 61,7 ± 15 (range: 15- 86 years). Nodules and/or plaques were the most frequent type of lesion. The most common location was the lower limbs, particularly the distal lower extremity (90%). In addition to skin involvement, visceral spread was evident in 9 cases. The most common visceral involvement sites were lymph nodes (44%), lung (22%), and gastrointestinal tract (22%). Associated lymphoedema was seen in 24 (42%) of the patients. There were 18 stage I patients (32,14%), 8: stage II (14,28%), 21 stage III(37,5%) and 9 stage IV (16,07%). A second primary malignancy was diagnosed in 6 cases (10,7%), none of the reticuloendothelial system.With a median follow-up of 45 months, 38 (67,8) patients are alive, of whom 25 (65,78%) patients with stable disease, five with progressive disease currently under systemic chemotherapy and 8(21,05%) are alive and free of disease, over a mean interval of 5 years. Conclusion: This is the largest reported series in our context. In Morocco, CKS exhibits some special characteristics including a disseminated skin disease at diagnosis especially in men, a more common visceral or lymph node involvement and a less frequent association with second malignancies.

An ex vivo, assessor blind, randomised, parallel group, comparative efficacy trial of the ovicidal activity of three pediculicides after a single application - melaleuca oil and lavender oil, eucalyptus oil and lemon tea tree oil, and a "suffocation" pediculicide

Background: There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length.MethodSubjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). Treatment : The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. Results: 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the group treated with melaleuca oil and lavender oil had an ovicidal efficacy of 44.4% (SD 23%) and the group treated with the "suffocation" pediculicide had an ovicidal efficacy of 68.3% (SD 38%). Conclusion: Ovicidal efficacy varied substantially among treatments, from 3.3% to 68.3%. The "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%) pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The "suffocation" pediculicide and TTO/LO are also highly efficacious against the crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be recommended as first line treatments.Trial RegistrationThe study was listed at the Australian/New Zealand Clinical Trial Registry (ANZCTR): reg. no. 12609000884202.

Effectiveness of Photodynamic Therapy for Mammary and Extra-mammary Paget's Disease: A state of the science review

Background: Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease. Methods: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale. Results: 21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses. Conclusions: Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.

Opportunistic screening for skin cancer using a mobile unit in Brazil

Background: Skin cancer is the most common malignancy in the white population worldwide. In Brazil, the National Cancer Institute (INCA) estimates that in 2010 there will be 119,780 and 5,930 new cases of non-melanoma skin cancer and melanoma, respectively. The aim of this study was to evaluate the use of a mobile unit in the diagnosis and treatment of skin cancer in several poor regions of Brazil. Methods: The diagnosis of skin cancer was accomplished through active medical screening in the prevention Mobile Unit (MU) of Barretos Cancer Hospital (BCH). The study population consisted of patients examined in the MU between 2004 and 2007, and their suspicious lesions were subjected to histopathological evaluation. Data were collected prospectively from standardized forms and analyzed. Results: During the screening, 17,857 consultations were carried out. A total of 2012 (11.2%) cases of skin cancer were diagnosed. The predominant histological type reported was basal cell carcinoma (n = 1,642 or 81.6%), followed by squamous cell carcinoma (n = 303 or 15.1%), Bowen's disease (n = 25 or 1.2%), malignant melanoma (n = 23 or 1.1%), basosquamous cell carcinoma (n = 3 or 0.1%), miscellaneous lesions (12 or 0.6%), and metatypical carcinoma (n = 4 or 0.2%). Only 0.6% of lesions were stage III. There were no stage IV non-melanoma skin lesions, as well as no melanomas stages III and IV, found. Conclusions: It was observed that the MU can be a useful tool for early skin cancer diagnosis and treatment. This program probably is important, especially in developing countries with inadequate public health systems and social inequality.

Family eczema-history in 2-year olds with eczema; a prospective, population-based study. The PACT-study, Norway.

Background: A maternal line of inheritance regarding eczema has been described in several studies, whereas others find associations to both a maternal as well as a paternal line of inheritance. When studying family history of eczema symptoms, cohort studies including siblings are rare. Time point for assessing family eczema-history could be of importance when studying the associations between family eczema-history and children with eczema, as parents with unaffected children may not recall mild symptoms in other siblings or their own disease history. We therefore aimed to study the associations between reported eczema in mother, father and siblings and reported eczema in index child where information on family history was collected at two different ages of index child. Methods: Parents/children participating in The Prevention of Allergy among Children in Trondheim (PACT) study were given questionnaires on reported eczema symptoms in mother, father and siblings at 6 weeks and 1 year. When index child was 2 years of age, a detailed questionnaire on different health issues with emphasize on different allergy related disorders were filled in. Results: Both maternal and paternal reports on eczema were significantly associated with eczema in index child. Reporting family eczema-history at 1 year (N = 3087), "eczema sibling only" [adjusted odds ratio (aOR) = 3.13 (2.27-4.33)] as well as all other family-groups containing siblings with eczema were strongly associated with eczema 2 years. When family eczema-history was reported at 6 weeks (N = 2657), reporting of "eczema sibling only" was not associated to reported eczema at 2 years in index child [aOR = 1.31 (0.77-2.23)]. Conclusions: Having sibling(s) with eczema strengthened the associations between maternal and paternal reports on eczema with eczema in index child only when exposure was reported at 1 year. These findings indicate that results from questionnaires-based studies of family eczema-history depend on whether or not index child has yet developed eczema.Trial registrationISRCTN: ISRCTN28090297

Mapping randomized controlled trials of treatments for eczema - The GREAT database (The Global Resource of Eczema Trials: a collection of key data on randomized controlled trials of treatments for eczema from 2000 to 2010)

Background: Massive duplication of effort occurs when researchers all over the world undertake extensive searches for randomized controlled trials when preparing systematic reviews, when developing evidence-based guidelines and when applying for research funding for eczema treatments. Such duplication wastes valuable resources.Searching for randomized controlled trials of eczema is a laborious task involving scrutiny of thousands of individual references from diverse electronic databases in order to obtain a few papers of interest. Clinicians and patients who wish to find out more about a particular treatment are at risk of missing the relevant evidence if they are not trained in electronic bibliographic searching. Systematic reviews cannot be relied upon to comprehensively inform current optimal eczema treatments due to incomplete coverage and because many may be out of date.An international, publically available and comprehensive resource which brings together all randomized controlled trials on eczema treatment using a highly sensitive search has the potential to release more filtered knowledge about patient care to those who need it most and to significantly shorten the duration and costs of many clinical eczema research and guideline projects.DescriptionThe Global Resource of EczemA Trials brings together information on all randomized controlled trials of eczema treatments published from the beginning of 2000 up to the end of 2010 and will be updated every month.We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library and the Cochrane Skin Group Specialised Register, MEDLINE, EMBASE, LILACS, AMED and CINHAL databases. We included 268 RCTs (24th March 2011) covering over 70 different treatment interventions.The structure of the Global Resource of Eczema Trials allows the user as much, or as little, specificity when retrieving information on trials as they wish, in an easy to use format. For each trial, the database gives the citation for the published report and also provides enough information to enable a user to decide whether the trial is worth further scrutiny. Conclusions: The Global Resource of Eczema Trials has been created to facilitate knowledge mobilization into healthcare and to reduce wastage of research time through unnecessary duplication. The collective time saved by research groups around the world can now be used to make strides in optimising the treatment of eczema, in order to further benefit people with eczema. The database can be accessed free of charge at http://www.greatdatabase.org.uk

Establishment of a murine epidermal cell line suitable for in vitro and in vivo skin modelling

Background: Skin diseases are a major health problem. Some of the most severe conditions involve genetic disorders, including cancer. Several of these human diseases have been modelled in genetically modified mice, thus becoming a highly valuable preclinical tool for the treatment of these pathologies. However, development of three-dimensional models of skin using keratinocytes from normal and/or genetically modified mice has been hindered by the difficulty to subculture murine epidermal keratinocytes. Methods: We have generated a murine epidermal cell line by serially passaging keratinocytes isolated from the back skin of adult mice. We have termed this cell line COCA. Cell culture is done in fully defined media and does not require feeder cells or any other coating methods. Results: COCA retained its capacity to differentiate and stratify in response to increased calcium concentration in the cell culture medium for more than 75 passages. These cells, including late passage, can form epidermis-like structures in three-dimensional in vitro models with a well-preserved pattern of proliferation and differentiation. Furthermore, these cells form epidermis in grafting assays in vivo, and do not develop tumorigenic ability. Conclusions: We propose that COCA constitutes a good experimental system for in vitro and in vivo skin modelling. Also, cell lines from genetically modified mice of interest in skin biology could be established using the method we have developed. COCA keratinocytes would be a suitable control, within a similar background, when studying the biological implications of these alterations.

The burden of co-existing dermatological disorders and their tendency of being overlooked among patients admitted to Muhimbili National hospital in Dar es Salaam, Tanzania

Background: Skin diseases are underestimated and overlooked by most clinicians despite being common in clinical practice. Many patients are hospitalized with co-existing dermatological conditions which may not be detected and managed by the attending physicians. The objective of this study was to determine the burden of co-existing and overlooked dermatological disorders among patients admitted to medical wards of Muhimbili National hospital in Dar es Salaam.Study design and settingsA hospital-based descriptive cross-sectional study conducted at Muhimbili National hospital in Dar es Salaam, Tanzania. Methods: Patients were consecutively recruited from the medical wards. Detailed interview to obtain clinico-demographic characteristics was followed by a complete physical examination. Dermatological diagnoses were made mainly clinically. Appropriate confirmatory laboratory investigations were performed where necessary. Data was analyzed using the 'Statistical Package for Social Sciences' (SPSS) program version 10.0. A p-value of < 0.5 was statistically significant. Results: Three hundred and ninety patients admitted to medical wards were enrolled into the study of whom, 221(56.7%) were females. The mean age was 36.7 ± 17.9 (range 7-84 years). Overall, 232/390 patients (59.5%) had co-existing dermatological disorders with 49% (191/390) having one, 9% (36/390) two and 5 patients (1%) three. A wide range of co-existing skin diseases was encountered, the most diverse being non-infectious conditions which together accounted for 36.4% (142/390) while infectious dermatoses accounted for 31.5% (123/390). The leading infectious skin diseases were superficial fungal infections accounting for 18%. Pruritic papular eruption of HIV/AIDS (PPE) and seborrheic eczema were the most common non-infectious conditions, each accounting for 4.3%. Of the 232/390 patients with dermatological disorders, 191/232 (82.3%) and 154/232 (66.3%) had been overlooked by their referring and admitting doctors respectively. Conclusion: Dermatological disorders are common among patients admitted to medical wards and many are not detected by their referring or admitting physicians. Basic dermatological education should be emphasized to improve knowledge and awareness among clinicians.

Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a randomized clinical trial

Background: Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo. Methods: This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid. Results: The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively. Conclusion: Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo.Trial RegistrationchiCTRTRC10000930

Oculocerebral Hypopigmentation Syndrome Maps to Chromosome 3q27.1q29

Dermatology (DOI:10.1159/000335609)

Copy Number Variations on Chromosome 4q26–27 Are Associated with Cantu Syndrome

Dermatology (DOI:10.1159/000333800)

Evaluation of the German Guideline for Chronic Pruritus: Results of a Retrospective Study on 385 Patients

Dermatology (DOI:10.1159/000335782)

Linear Pitting and Splinter Haemorrhages Are More Commonly Seen in the Nails of Patients with Established Psoriasis in Comparison to Psoriatic Arthritis

Dermatology (DOI:10.1159/000335571)

Eosinophilia during Psoriasis Treatment with TNF Antagonists

Dermatology (DOI:10.1159/000334805)

ADAM33 as a Psoriasis Susceptibility Gene in the Han Population of Northeastern China

Dermatology (DOI:10.1159/000335417)

High-Risk Human Papillomavirus Infection in Bowen’s Disease of the Nail Unit: Report of Three Cases and Review of the Literature

Dermatology (DOI:10.1159/000335371)

Intrapatient Comparison of 308-nm Monochromatic Excimer Light and Localized Narrow-Band UVB Phototherapy in the Treatment of Vitiligo: A Randomized Controlled Trial

Dermatology (DOI:10.1159/000335272)

Morphology of Pilonidal Sinus Disease: Some Evidence of Its Being a Unilocalized Type of Hidradenitis Suppurativa

Dermatology (DOI:10.1159/000335373)

IgG4-Related Skin Disease, a Mimic of Angiolymphoid Hyperplasia with Eosinophilia

Dermatology (DOI:10.1159/000335372)

Primary Focal Hyperhidrosis in a New Family Not Linked to Known Loci

Dermatology (DOI:10.1159/000334936)

Efficacious Treatment of Non-Dermatophyte Mould Onychomycosis with Topical Amphotericin B

Dermatology (DOI:10.1159/000335093)

Dermatological Signs and Symptoms of Measles: A Prospective Case Series and Comparison with the Literature

Dermatology (DOI:10.1159/000335091)

ILDS Newsletter No. 22

Dermatology 2011;223:285–288 (DOI:10.1159/000335276)

Treatment of Small Superficial Haemangioma with Timolol 0.5% Ophthalmic Solution: A Series of 20 Cases

Dermatology (DOI:10.1159/000334778)

Efficacy of Ustekinumab in Nail Psoriasis and Improvement in Nail-Associated Quality of Life in a Population Treated with Ustekinumab for Cutaneous Psoriasis: An Open Prospective Unblinded Study

Dermatology (DOI:10.1159/000334482)

Pressure Ulcers: Description of a New Model and Use of Mesenchymal Stem Cells for Repair

Dermatology 2011;223:266–284 (DOI:10.1159/000334628)

The Transposition Advancement Flap for Repair of Postsurgical Defects on the Upper Lip

Dermatology 2011;223:203–206 (DOI:10.1159/000334337)

Fractional Transepidermal Delivery: A Histological Analysis

Dermatology (DOI:10.1159/000334165)

ILDS Newsletter No. 21

Dermatology 2011;223:189–192 (DOI:10.1159/000334638)

Port-wine stains are more than skin-deep! Expanding the spectrum of extracutaneous manifestations of nevi flammei of the head and neck.

Port-wine stains are more than skin-deep! Expanding the spectrum of extracutaneous manifestations of nevi flammei of the head and neck. Eur J Dermatol. 2012 Jan 27; Authors: Eivazi B, Roessler M, Pfützner W, Teymoortash A, Werner JA, Happle R Abstract It is well known that port-wine stains of the upper part of the face may herald abnormalities of the brain or eye in the form of Sturge-Weber syndrome. This study focuses on other extracutaneous anomalies in patients with nevi flammei of the head and neck, giving rise to functional complications. Patients and methods. A retrospective study was performed on patients with port-wine stains involving the head and neck area. Records were reviewed for demographic parameters, extent of the lesion, clinical complications, diagnostic measures, previous treatments, ultimate therapeutic approach, and outcome. Results. Nine patients, mean age 50.4 years, with port-wine stains and clinical symptoms due to extracutaneous involvement, were admitted and treated from 2006 to 2009. Major clinical features included macrocheilia in three cases, gingival bleeding in two, dysphonia with globus sensation, painful parotideal swelling with recurrent otitis, painful lingual swelling, recurrent epistaxis, and nasal obstruction in one case each. Cases with lower lip hypertrophy were treated by conventional surgical approaches. Recurrent epistaxis and nasal obstruction due to affected inferior turbinate were treated by Nd:YAG laser therapy, and globus sensation and dysphonia by speech therapy. Patients with gingival affection and recurrent otitis were treated by local ear care. Conclusion. Port-wine stains in the head and neck may develop extracutaneous manifestations causing severe problems. A multimodal and interdisciplinary approach is mandatory for an appropriate treatment. PMID: 22285557 [PubMed - as supplied by publisher]

Author Index Vol. 3, No. 4, 2004

Exog Dermatol 2004;3:201-202 (DOI:10.1159/000091311)

Title Page / Table of Contents

Exog Dermatol 2004;3:161-167 (DOI:10.1159/000091310)

Posters

Exog Dermatol 2004;3:191-200 (DOI:10.1159/000090061)

Oral Presentations

Exog Dermatol 2004;3:169-190 (DOI:10.1159/000090060)

Contents Vol. 3, 2004

Exog Dermatol 2004;3:353–354 (DOI:10.1159/000094132)

Subject Index Vol. 3, 2004

Exog Dermatol 2004;3:352 (DOI:10.1159/000094131)

Author Index Vol. 3, 2004

Exog Dermatol 2004;3:351 (DOI:10.1159/000094130)

Acknowledgement to Referees for Exogenous Dermatology 2004

Exog Dermatol 2004;3:350 (DOI:10.1159/000094129)

Stratum Corneum: An Ideal Osmometer?

Exog Dermatol 2004;3:339–349 (DOI:10.1159/000093798)

Mosquito Bite Therapy: Evidenced-Based

Exog Dermatol 2004;3:332–338 (DOI:10.1159/000093650)

Author and Subject Index Vol. 3, No. 5, 2004

Exog Dermatol 2004;3:262 (DOI:10.1159/000093147)

Title Page / Table of Contents

Exog Dermatol 2004;3:203–205 (DOI:10.1159/000093146)

Is There Evidence that Geraniol Causes Allergic Contact Dermatitis?

Exog Dermatol 2004;3:318–331 (DOI:10.1159/000092824)

Propylene Glycol Today

Exog Dermatol 2004;3:313–317 (DOI:10.1159/000092606)

Sensitization Potential of Citronellol

Exog Dermatol 2004;3:307–312 (DOI:10.1159/000092445)

Quantitative Follow-Up of the Cutaneous Barrier Function in Wound Healing

Exog Dermatol 2004;3:303–306 (DOI:10.1159/000092010)

Reevaluation of the Importance of Barrier Dysfunction in the Nonlesional Dry Skin of Atopic Dermatitis Patients through the Use of Two Barrier Creams

Exog Dermatol 2004;3:293–302 (DOI:10.1159/000091910)

Recharacterization of the Nonlesional Dry Skin in Atopic Dermatitis through Disrupted Barrier Function

Exog Dermatol 2004;3:282–292 (DOI:10.1159/000091909)

Damage to Human Hair Caused by Repeated Bleaching Combined with Daily Weathering during Daily Life Activities

Exog Dermatol 2004;3:273–281 (DOI:10.1159/000091908)

The Conundrum of Inducible Nitric Oxide Synthase in Chronic Leg Ulcers

Exog Dermatol 2004;3:270–272 (DOI:10.1159/000091907)

Teledermatology: state-of-the-art and future perspectives

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 1-3.

Why is there poor adherence to topical corticosteroid therapy in atopic dermatitis?

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 5-7.

Is self-reporting a form fruste of medical experimentation? Personal insights from the ‘family’ literature of a dermatologist and his children

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 9-12.

News in brief

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 13-15.

Calcipotriene foam, 0.005% in mild-to-moderate plaque psoriasis

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 17-26.

A new era for the management of metastatic melanoma

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 27-35.

Skin cancer in organ transplant recipients

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 37-45.

The role of immunopathologic assessment of skin biopsies in mild rejection of hand composite tissue allotransplantation

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 47-50.

Immunotherapy for melanoma

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 51-68.

New emerging diseases or syndromes in dermatopathology with impact on clinical management

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 69-80.

Netherton syndrome: new advances in the clinic, disease mechanism and treatment

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 81-92.

Current topics in infectious diseases of the skin

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 93-106.

Acknowledgements

Expert Review of Dermatology , February 2012, Vol. 7, No. 1, Pages 107-107.

Hydroa Vacciniforme Is Associated with Increased Numbers of Epstein-Barr Virus-Infected γδT Cells.

Hydroa Vacciniforme Is Associated with Increased Numbers of Epstein-Barr Virus-Infected γδT Cells. J Invest Dermatol. 2012 Feb 2; Authors: Hirai Y, Yamamoto T, Kimura H, Ito Y, Tsuji K, Miyake T, Morizane S, Suzuki D, Fujii K, Iwatsuki K Abstract Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)(+) T-cell infiltration. We have summarized clinical manifestations of HV, and analyzed EBV(+) T-cell subsets as well as EBV DNA load in lymphocyte fractions, in comparison with hypersensitivity to mosquito bites (HMB), an EBV-associated T/natural killer (NK) lymphoproliferative disorder. We found that 31 of 33 (93.9%) HV lesions were composed of EBV(+) T cells and reactive EBV(-) cytotoxic T cells, without significant CD56(+) cell infiltration, whereas many CD56(+) cells were present in 8 of 9 (88.9%) HMB lesions. Of 13 (20.6%) HMB patients with or without HV, 12 (92.3%) showed increased percentages (>32%) of NK cells in the peripheral blood, whereas in the 16 patients with HV alone, 14 (87.5%) showed no increase. Of the 11 HV patients, 10 (90.9%) had increased percentages (>5%) of circulating γδT cells, with a mean value of 15.7 ± 2.9%, and the γδT-cell fractions contained larger amounts of EBV DNA than non-γδT-cell fractions. A triple-labeling method revealed that all three HV patients examined had increased percentages of EBER(+), T-cell receptor (TCR)γδ(+), and TCRαβ(-) cells. Our observations indicate that HV is associated with increased numbers of EBV(+) γδT cells, whereas HMB is associated with EBV(+) NK cells.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.461. PMID: 22297643 [PubMed - as supplied by publisher]

Application of an Indoleamine 2,3-Dioxygenase-Expressing Skin Substitute Improves Scar Formation in a Fibrotic Animal Model.

Application of an Indoleamine 2,3-Dioxygenase-Expressing Skin Substitute Improves Scar Formation in a Fibrotic Animal Model. J Invest Dermatol. 2012 Feb 2; Authors: Chavez-Munoz C, Hartwell R, Jalili RB, Carr M, Kilani RT, Jafarnejad SM, Rahmani-Neishabour E, Forouzandeh F, Boyce ST, Ghahary A PMID: 22297642 [PubMed - as supplied by publisher]

Oral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials.

Oral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials. J Invest Dermatol. 2012 Feb 2; Authors: Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL PMID: 22297641 [PubMed - as supplied by publisher]

Low Herpesvirus Entry Mediator (HVEM) Expression on Dermal Fibroblasts Contributes to a Th2-Dominant Microenvironment in Advanced Cutaneous T-Cell Lymphoma.

Low Herpesvirus Entry Mediator (HVEM) Expression on Dermal Fibroblasts Contributes to a Th2-Dominant Microenvironment in Advanced Cutaneous T-Cell Lymphoma. J Invest Dermatol. 2012 Feb 2; Authors: Miyagaki T, Sugaya M, Suga H, Morimura S, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S Abstract LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes) is a ligand for HVEM. LIGHT-HVEM interactions are important in T helper type 1 (Th1) immune responses. In some cases with early stages of cutaneous T cell lymphoma (CTCL), IL-2, IFN-γ, and Th1 chemokines are expressed in lesional skin, while IL-4, IL-5, and Th2 chemokines are dominant in advanced CTCL. In this study, we investigated roles of LIGHT and HVEM in the microenvironment of CTCL. LIGHT enhanced production of Th1 chemokines, such as CXC chemokine ligand (CXCL) 9, CXCL10, and CXCL11, from IFN-γ-treated dermal fibroblasts via phosphorylation of inhibitor κBα. Messenger RNA levels of these chemokines were increased in lesional skin of early CTCL. Interestingly, while LIGHT expression in CTCL skin correlated with disease progression, HVEM expression was significantly decreased in advanced CTCL skin. HVEM was detected in dermal fibroblasts in early CTCL skin, but not in advanced CTCL skin in situ. These results suggest that low HVEM expression on dermal fibroblasts in advanced CTCL skin attenuates expression of Th1 chemokines, which may contribute to a shift to a Th2-dominant microenvironment as disease progresses.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.470. PMID: 22297640 [PubMed - as supplied by publisher]

Identification of Quantitative Trait Loci in Experimental Epidermolysis Bullosa Acquisita.

Identification of Quantitative Trait Loci in Experimental Epidermolysis Bullosa Acquisita. J Invest Dermatol. 2012 Feb 2; Authors: Ludwig RJ, Müller S, Marques AD, Recke A, Schmidt E, Zillikens D, Möller S, Ibrahim SM Abstract Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. Several lines of evidence underscore the contribution of autoantibodies against type VII collagen (COL7) to the pathogenesis of EBA. Furthermore, EBA susceptibility is associated with the MHC haplotype in patients (HLA-DR2) and in immunization-induced EBA in mice (H2s). The latter study indicated an additional contribution of non-MHC genes to disease susceptibility. To identify non-MHC genes controlling EBA susceptibility, we intercrossed EBA-susceptible MRL/MpJ with EBA-resistant NZM2410/J and BXD2/TyJ as well as Cast mice. Mice of the fourth generation of this four-way autoimmune-prone advanced intercross line were immunized with a fragment of murine COL7 to induce EBA. Anti-COL7 autoantibodies were detected in 84% of mice, whereas deposition of complement at the dermal-epidermal junction (DEJ) was observed in 50% of the animals; 33% of immunized mice presented with overt clinical EBA. Onset of clinical disease was associated with several quantitative trait loci (QTLs) located on chromosomes 9, 12, 14, and 19, whereas maximum disease severity was linked to QTLs on chromosomes 1, 15, and 19. This more detailed insight into the pathogenesis of EBA may eventually lead to new treatment strategies for EBA and other autoantibody-mediated diseases.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.466. PMID: 22297639 [PubMed - as supplied by publisher]

Prognostic Importance of the Mitotic Marker Phosphohistone H3 in Cutaneous Nodular Melanoma.

Prognostic Importance of the Mitotic Marker Phosphohistone H3 in Cutaneous Nodular Melanoma. J Invest Dermatol. 2012 Feb 2; Authors: Ladstein RG, Bachmann IM, Straume O, Akslen LA Abstract Mitotic count is a known prognostic predictor in cutaneous melanoma, and is included in the current American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. The mitotic marker phosphohistone H3 (PHH3) is considered to facilitate counting of mitosis, and the purpose of this study was to evaluate the prognostic significance and strength of PHH3 in comparison with standard mitotic counting in cutaneous malignant melanoma. A total of 457 consecutive cases of nodular cutaneous melanoma were initially included in this series. The mitotic count was assessed on hematoxylin and eosin sections, and PHH3 was then examined by immunohistochemistry on standard sections of paraffin-embedded tumor tissue. Both the mitotic count and the number of PHH3-stained mitotic figures were recorded in a minimum area of 1 mm(2). Increased mitotic count and PHH3 value were both associated with unfavorable features like tumor thickness and presence of ulceration. Univariate survival analysis showed a highly significant prognostic impact of mitotic count and PHH3, whereas multivariate analysis indicated PHH3 to be a stronger prognostic indicator than mitotic count. Assessment of mitotic activity by PHH3 immunostaining might have important practical advantages, and should be further studied to consider a place in routine examination of all cutaneous melanomas.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.464. PMID: 22297638 [PubMed - as supplied by publisher]

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells.

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells. J Invest Dermatol. 2012 Feb 2; Authors: Kovacs D, Flori E, Maresca V, Ottaviani M, Aspite N, Dell'anna ML, Panzella L, Napolitano A, Picardo M, d'Ischia M Abstract Interest in colorless intermediates of melanocyte metabolism has traditionally been related to their role as melanin precursors, though several lines of evidence scattered in the literature suggested that these compounds may exert an antioxidant and protective function per se unrelated to pigment synthesis. Herein, we disclose the remarkable protective and differentiating effects of 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a diffusible dopachrome tautomerase (DCT)-dependent eumelanin intermediate, on primary cultures of human keratinocytes. At micromolar concentrations, DHICA induced: (a) time- and dose-dependent reduction of cell proliferation without concomitant toxicity; (b) enhanced expression of early (spinous keratins K1 and K10 and envelope protein involucrin) and late (loricrin and filaggrin) differentiation markers; (c) increased activities and expression of antioxidant enzymes; and (d) decreased cell damage and apoptosis following UVA exposure. The hitherto unrecognized role of DHICA as an antiproliferative, protective, and antiapoptotic endogenous cell messenger points to a reappraisal of the biological functions of melanocytes and DCT in skin homeostasis and photoprotection beyond the mere provision of melanin pigments, and provides, to our knowledge, a previously unreported possible explanation to the higher resistance of the dark-skinned eumelanic phenotypes to sunburn and skin cancer.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.457. PMID: 22297637 [PubMed - as supplied by publisher]

A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive CD8(+) T-Cell Accumulation in the Skin.

A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive CD8(+) T-Cell Accumulation in the Skin. J Invest Dermatol. 2012 Feb 2; Authors: Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA Abstract Vitiligo is an autoimmune disease of the skin causing disfiguring patchy depigmentation of the epidermis and, less commonly, hair. Therapeutic options for vitiligo are limited, reflecting in part limited knowledge of disease pathogenesis. Existing mouse models of vitiligo consist of hair depigmentation but lack prominent epidermal involvement, which is the hallmark of human disease. They are thus unable to provide a platform to fully investigate disease mechanisms and treatment. CD8(+) T cells have been implicated in the pathogenesis of vitiligo, and expression of IFN-γ is increased in the lesional skin of patients, however, it is currently unknown what role IFN-γ has in disease. Here, we have developed an adoptive transfer mouse model of vitiligo using melanocyte-specific CD8(+) T cells, which recapitulates the human condition by inducing epidermal depigmentation while sparing the hair. Like active lesions in human vitiligo, histology of depigmenting skin reveals a patchy mononuclear infiltrate and single-cell infiltration of the epidermis. Depigmentation is accompanied by accumulation of autoreactive CD8(+) T cells in the skin, quantifiable loss of tyrosinase transcript, and local IFN-γ production. Neutralization of IFN-γ with antibody prevents CD8(+) T-cell accumulation and depigmentation, suggesting a therapeutic potential for this approach.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.463. PMID: 22297636 [PubMed - as supplied by publisher]

Hair Cycle Resting Phase Is Regulated by Cyclic Epithelial FGF18 Signaling.

Hair Cycle Resting Phase Is Regulated by Cyclic Epithelial FGF18 Signaling. J Invest Dermatol. 2012 Feb 2; Authors: Kimura-Ueki M, Oda Y, Oki J, Komi-Kuramochi A, Honda E, Asada M, Suzuki M, Imamura T Abstract Hair follicles repeatedly cycle through growth (anagen), regression (catagen), and resting (telogen) phases. Although the signaling molecules involved in the anagen and anagen-catagen transition have been studied extensively, the signaling that controls telogen is only partly understood. Here we show that fibroblast growth factor (Fgf)18 is expressed in a hair stem cell niche throughout telogen, and that it regulates the hair cycle through the non-growth phases. When the Fgf18 gene is conditionally knocked out in keratin 5-positive epithelial cells in mice, telogen becomes very short, giving rise to a strikingly rapid succession of hair cycles. In wild-type mice, hair follicle growth during anagen is strongly suppressed by local delivery of FGF18 protein. Our results demonstrate that epithelial FGF18 signaling and its reduction in the milieu of hair stem cells are crucial for the maintenance of resting and growth phase, respectively.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.490. PMID: 22297635 [PubMed - as supplied by publisher]

IL-12 and IL-23 Affect Photocarcinogenesis Differently.

IL-12 and IL-23 Affect Photocarcinogenesis Differently. J Invest Dermatol. 2012 Feb 2; Authors: Jantschitsch C, Weichenthal M, Proksch E, Schwarz T, Schwarz A Abstract Induction of DNA damage by UVR is the key event in photocarcinogenesis. IL-12 and IL-23 are related heterodimeric cytokines consisting of a common p40 unit and a p35/IL-12 and a p19/IL-23 chain, respectively. Both exert immunomodulatory activities but are also found to reduce UVR-induced DNA damage presumably via induction of DNA repair. As both cytokines are also produced in the skin, they may mitigate the risk to develop UVR-induced skin cancer. This appears to be the case as mice lacking p40 were previously shown to be at higher risk for skin tumors upon chronic UVR exposure. As these mice express neither IL-12 nor IL-23, the individual effects of IL-12 or IL-23 could not be evaluated. Thus, mice lacking p35 (IL-12p35-/-) or p19 (IL-23p19-/-) were subjected to chronic UVR exposure. The Kaplan-Meier analysis indicated a significantly increased probability of tumor development in IL-23p19-/- but not in IL-12p35-/- mice. Taken together, in our model, loss of IL-23, but not of IL-12, enhances development of UVR-induced skin tumors, indicating that IL-23 but not IL-12 may counteract photocarcinogenesis. This may have impact on the development of future strategies utilizing antibodies against IL-12 and IL-23, respectively, for the treatment of inflammatory dermatoses.Journal of Investigative Dermatology advance online publication, 2 February 2012; doi:10.1038/jid.2011.469. PMID: 22297634 [PubMed - as supplied by publisher]

IFN-α Enhances IL-22 Receptor Expression in Keratinocytes: A Possible Role in the Development of Psoriasis.

IFN-α Enhances IL-22 Receptor Expression in Keratinocytes: A Possible Role in the Development of Psoriasis. J Invest Dermatol. 2012 Feb 2; Authors: Tohyama M, Yang L, Hanakawa Y, Dai X, Shirakata Y, Sayama K PMID: 22297633 [PubMed - as supplied by publisher]

Critical Role of Paxillin in Aging of Human Skin.

Critical Role of Paxillin in Aging of Human Skin. J Invest Dermatol. 2012 Feb 2; Authors: Zheng Q, Chen S, Chen Y, Lyga J, Santhanam U PMID: 22297632 [PubMed - as supplied by publisher]