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Melanoma Associated With Long-term Voriconazole Therapy: A New Manifestation of Chronic Photosensitivity [Observation]

Background Voriconazole is a triazole antifungal agent approved by the US Food and Drug Administration for serious fungal infections, including with Aspergillus, Fusarium, Pseudallescheria, and Scedosporium species. In initial clinical trials, approximately 2% of patients developed cutaneous reactions, including photosensitivity, cheilitis, and xerosis. Subsequent reports have implicated voriconazole as a cause of severe photosensitivity and accelerated photoaging, pseudoporphyria cutanea tarda, and aggressive squamous cell carcinoma.Observation We report 5 melanoma in situ lesions in the setting of extreme photosensitivity associated with long-term voriconazole therapy.Conclusions We recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage. Further study of the mechanism underlying voriconazole photosensitivity and oncogenesis is warranted.Published online January 18, 2010 (doi:10.1001 /archdermatol.2009.362).

Publishing Online Ahead of Print [Announcement]

About This Journal [About This Journal]

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

Memorial to Dr. Ernest Besnier from the New York Dermatological Society [Archives a Century Ago]

Basal Cell Nevus Syndrome: A Brave New World [The Cutting Edge]

Anti-Bullous Pemphigoid 180 and 230 Antibodies in a Sample of Unaffected Subjects [Study]

Objective To evaluate the prevalence of autoantibodies against 2 hemidesmosomal proteins typically found in patients with bullous pemphigoid (BP), BP antigen II (BP180) and BP antigen I (BP230), in persons without BP. Design Cross-sectional study. Setting Academic medical center. Patients An age- and sex-stratified, random, population-based sample of local county patients seen during 2007: 20 men and 20 women per decade of age (from age 20 to 89 years) and 57 patients (33 women and 24 men) aged 90 to 99 years. Intervention Stored serum samples were retrieved for analysis by enzyme-linked immunosorbent assay and indirect immunofluorescence. Main Outcome Measure Presence of circulating autoantibodies to BP180 and BP230. Results Of the 337 study patients, 25 (7.4%) were positive for 1 or both autoantibodies; these 25 samples all tested negative with indirect immunofluorescence. Autoantibody levels did not vary by age or sex. Conclusions Bullous pemphigoid has a higher incidence in the elderly population, but the prevalence of antibodies to BP180 and BP230 did not increase significantly with age or vary by sex in this population-based sample. Other exogenous factors may affect the development of these autoantibodies in a population without clinically evident immunobullous disease, including limitations inherent to the test (false-positive rate).

Incidence of Dermatomyositis and Clinically Amyopathic Dermatomyositis: A Population-Based Study in Olmsted County, Minnesota [Study]

Objectives To identify new and existing cases of dermatomyositis and its subtypes in Olmsted County, Minnesota, from 1976 through 2007, and to establish a population-based estimate of the incidence and prevalence of dermatomyositis and amyopathic dermatomyositis. Design Retrospective population-based study. Setting Community-based epidemiology project. Patients Patients with a diagnosis of dermatomyositis were identified from the Rochester Epidemiology Project. Main Outcome Measures Incidence of dermatomyositis and clinically amyopathic dermatomyositis and risk of malignancy in clinically amyopathic dermatomyositis. Results Of the 29 patients identified, 6 (21%) had the clinically amyopathic subtype of dermatomyositis and 22 (76%) were female. Overall age- and sex-adjusted incidence of dermatomyositis including all subtypes was 9.63 (95% confidence interval [CI], 6.09-13.17) per 1 million persons and 2.08 (95% CI, 0.39-3.77) per 1 million persons for clinically amyopathic dermatomyositis. Age- and sex-adjusted prevalence for all subtypes of dermatomyositis was 21.42 (95% CI, 13.07-29.77) per 100 000 persons. Eight patients (28%) had a malignant condition during the study period; the risk of malignancy (odds ratio) for classic dermatomyositis compared with clinically amyopathic dermatomyositis was 4.61 but was not statistically significant (95% CI, 0.22-96.09) (P = .44). Conclusions Dermatomyositis is a rare disease, and clinically amyopathic dermatomyositis represents an estimated 20% of all dermatomyositis cases. Larger population-based studies are needed to estimate the risk of malignancy associated with subtypes of dermatomyositis, particularly clinically amyopathic dermatomyositis.

Comparison of Treatment of Cherry Angiomata With Pulsed-Dye Laser, Potassium Titanyl Phosphate Laser, and Electrodesiccation: A Randomized Controlled Trial [Study]

Objective To assess the comparative efficacy of energy treatments in resolving cherry angiomata. Design Rater-blinded randomized controlled trial. Setting Outpatient dermatology clinic in an urban referral academic medical center. Participants Fifteen healthy adults aged 21 to 65 years were enrolled. Two eligible individuals who were approached declined to participate, and no one enrolled was withdrawn for adverse effects. Interventions For each participant, 3 areas on the torso were demarcated such that each area contained 4 cherry angiomata. Each area was then randomly assigned to receive 1 of the 3 treatments: pulsed-dye laser (PDL) (595 nm), potassium titanyl phosphate (KTP) laser (532 nm), or electrodesiccation. Two treatments spaced 2 weeks apart were delivered to each area. Main Outcome Measures Standardized photographs from before treatment and 3 months after the last treatment were evaluated for color and texture on visual analog scales. Results Mean change in color was a significant improvement of 7.77 (P < .001), but there was no significant difference across treatment arms (P = .19). Mean change in texture was a significant improvement of 6.23 (P < .001), and the degree of textural change also differed across treatments (P < .001). In pairwise comparisons, cherry angiomata treated with electrodesiccation were significantly less improved than were those receiving KTP laser (P = .003) and those treated with PDL (P = .001). The effects of KTP laser and PDL on texture were not different (P = .50). Conclusions Cherry angiomata can be effectively treated with electrodesiccation and with laser. Laser, especially PDL, may minimize the likelihood of treatment-associated textural change. Trial Registration clinicaltrials.gov Identifier: NCT00509977

October 2009 Archives Web Quiz Winner [Archives Web Quiz Winner]

In Vitro and In Vivo Laser Treatments of Tattoos: High Efficiency and Low Fluences [Study]

Objective To analyze the absorption of tattoo inks related to their in vivo and in vitro behavior under laser irradiation to improve laser-assisted tattoo removal. Design The absorption of 21 tattoo inks in a wavelength range from 300 to 800 nm was characterized by reflection spectroscopy from samples consisting of inks mixed in gelatin. Tattoo inks were removed in vitro using pulsed laser radiation with different variables, and morphologic analysis of the irradiated areas was performed. Setting An interdisciplinary laser laboratory with a common industrial project with the Spanish company Milesman S.A. Participant One person was voluntarily tattooed with 2 of the studied inks. Main Outcome Measures (1) First approach to the optimum dose for pigment removal in in vitro models. (2) Correlation between the in vitro and in vivo situations at the optimum dose. Results Reflection spectroscopy facilitated selection of the most adequate laser wavelengths for tattoo removal. Red, orange, and rose inks were successfully lightened at 532 nm with 0.6 J/cm2; brown at 1064 nm with 0.3 J/cm2; yellow and green at 448 nm with 2.6 J/cm2; and blue at 600 nm with 0.9 J/cm2. Similar colors in in vitro and in vivo tattoos responded with the same efficiency to the laser variables. Conclusions High efficiency is reached in the removal of in vivo tattoos by using an irradiation wavelength at which the percentage of reflection from the pigment is minimal. Under this condition, laser pulses can be used with a low fluence, minimizing adverse effects and clinical time.

Volunteering With Health Volunteers Overseas [Announcement]

Recent Trends in Systemic Psoriasis Treatment Costs [Study]

Objectives To analyze the current total cost of systemic therapy for psoriasis and to compare annual trends in the cost of both generic and brand-name therapies with trends in the Consumer Price Index–Urban since 2000. Design A cost model was developed that includes costs for prescription drugs, office visits, and suggested laboratory tests and monitoring procedures. Annual trends in psoriasis drug costs from 2000 through 2008 were analyzed by calculating the percentage change in the average wholesale price from the previous year; these values were compared with changes in the yearly Consumer Price Index–Urban values. Setting The United States. Main Outcome Measures Total annual costs for systemic psoriasis therapies and trends in cost compared with the trends in Consumer Price Index–Urban values (equivalent to inflation). Results Current total annual costs for systemic psoriasis therapies ranged from $1197 (methotrexate) to $27 577 (alefacept, two 12-week courses). Trends in the average wholesale price of brand-name psoriasis therapies from 2000 through 2008 demonstrate an average increase of 66% (range, –24% to +316%); thus, costs of several brand-name psoriasis drugs greatly outpaced the rates of inflation for all items and all prescription drugs. Conclusions Despite the higher monitoring costs associated with traditional systemic therapies, annual costs of biologics exceed those of other available therapies. Current trends demonstrate that systemic psoriasis therapy costs are increasing at a much higher rate compared with general inflation.

The Safety and Efficacy of Pimecrolimus, 1%, Cream for the Treatment of Netherton Syndrome: Results From an Exploratory Study [Observation]

Background Impaired skin integrity in patients with Netherton syndrome (NS) results in significant systemic absorption of topically applied medications. Some have advocated the administration of pimecrolimus, 1%, topical cream for the treatment of patients with NS. Insufficient data exist with regard to its safety, systemic absorption, and efficacy. Observations An exploratory study was conducted involving 3 children with NS who received twice-daily application of pimecrolimus, 1%, cream over 18 months. There were no notable abnormalities in hematologic or chemistry profiles. Blood levels of pimecrolimus ranged from 0.625 to 7.08 ng/mL, with peak levels reached during the first month in all 3 patients. Dramatic reductions were observed in the Netherton Area and Severity Assessment, Eczema Area and Severity Index, Investigator Global Evaluation of Disease, and pruritus scores compared with baseline levels. Conclusions Use of pimecrolimus, 1%, cream was well tolerated and demonstrated marked improvements in nearly all of the parameters evaluated. Patients treated with pimecrolimus responded rapidly, within the first month of treatment, and improvement persisted throughout the study period. In adult patients receiving oral pimecrolimus, blood levels as high as 54 ng/mL for 3 months have not shown clinically significant immunosuppression. Absorption of pimecrolimus, 1%, cream was detectable, but levels were much lower than expected even when applied to 50% of total body surface area. Larger studies are warranted to determine the safety and efficacy of pimecrolimus, 1%, cream in the treatment of NS. Trial Registration clinicaltrials.gov Identifier: NCT00208026

Buschke-Ollendorff Syndrome: Absence of LEMD3 Mutation in an Affected Family [Observation]

Background Buschke-Ollendorff syndrome (BOS), an autosomal dominant disorder, features small, acquired, asymptomatic, symmetrical foci of osteosclerosis detected radiographically in epimetaphyseal bone (osteopoikilosis) (OPK) together with connective tissue nevi or juvenile elastomas. Heterozygous, loss-of-function, germline mutation in the LEMD3 gene (which encodes an inner nuclear membrane protein called LEMD3, or MAN1) has been repeatedly documented in patients with BOS or OPK. Observations We describe a father and son with multiple yellowish papules and nodules coalescing into cobblestone nevoid plaques consistent with nevus elasticus. Radiographs of the father show multiple, small, bone islands within the hands, wrists, distal femurs, proximal tibias, and left distal fibula consistent with OPK. Although the clinical findings are diagnostic of Buschke-Ollendorf syndrome, analysis of the LEMD3 gene showed no exonic mutations. Conclusion Absence of LEMD3 mutation in the exons and splice sites of a family with BOS suggests that there is genetic heterogeneity for this disorder.

Cock's Peculiar Tumor [Notable Notes]

Disfiguring Generalized Verrucosis in an Indonesian Man With Idiopathic CD4 Lymphopenia [Observation]

Background Human papillomavirus (HPV) infections cause a spectrum of clinical disease states, depending on the causative HPV and the characteristics of the infected host, especially the status of cell-mediated immunity. Generalized verrucosis is an unusual clinical presentation of a disseminated HPV infection associated with severe immunodeficiency status. Observations We present a case of extreme disfigurement associated with an HPV-2 (common wart virus) infection. Virologic studies, immune status of the patient, and treatment(s) are summarized. Conclusions The severe disfigurement of this patient was a result of an underlying severe immunodeficiency, permissive for a disseminated HPV-2 infection that was allowed to progress for many years before the initiation of therapy. Such a rare case illustrates the natural history of generalized verrucosis in the setting of severe immunodeficiency in the absence of sustained medical interventions. Medical and surgical treatments resulted in marked improvement in the general health of this patient, as well as improvement of the disfigurement that resulted from the generalized verrucosis.

Prevalence of Autoantibodies to Bullous Pemphigoid Antigens Within the Normal Population [Editorial]

Clinically Amyopathic Dermatomyositis: What Can We Now Tell Our Patients? [Editorial]

Ulcerated Facial Nodules in a Renal Transplant Recipient--Quiz Case [Off-Center Fold]

Ulcerated Facial Nodules in a Renal Transplant Recipient--Diagnosis [Off-Center Fold]

Pruritic Reticular Eruption on the Chest of a 24-Year-Old Woman--Quiz Case [Off-Center Fold]

Pruritic Reticular Eruption on the Chest of a 24-Year-Old Woman--Diagnosis [Off-Center Fold]

Erythematous Erosive Patch on the Left Nipple--Quiz Case [Off-Center Fold]

Erythematous Erosive Patch on the Left Nipple--Diagnosis [Off-Center Fold]

Hemochromatosis and Bilateral Yellow Papules of the Neck--Quiz Case [Off-Center Fold]

Hemochromatosis and Bilateral Yellow Papules of the Neck--Diagnosis [Off-Center Fold]

Lack of Wnt5A Expression in Merkel Cell Carcinoma [Research Letters]

Combined Treatment With Rituximab and Anthracycline-Containing Chemotherapy for Primary Cutaneous Large B-Cell Lymphomas, Leg Type, in Elderly Patients [Research Letters]

Comparing the Efficacy of an In-Person Intervention With a Skin Self-examination Workbook [Research Letters]

A Simple Solution to the Common Problem of Ecchymosis [Research Letters]

Pretibial Lymphoplasmacytic Plaque in Children [Correspondence]

A Novel Mutation in the TAP2 Gene in Bare Lymphocyte Syndrome: Association With Metastatic Cutaneous Squamous Cell Carcinoma [Correspondence]

Hereditary Benign Telangiectasia: Two Families With Punctate Telangiectasias Surrounded by Anemic Halos [Correspondence]

Therapeutic Effect of Clopidogrel on Cutaneous Polyarteritis Nodosa [Correspondence]

The Dermatologic Manifestation of Novel Influenza A(H1N1) [Correspondence]

Complete and Durable Clinical Response of Malignant Pyoderma to Tacrolimus in Combination With Dapsone and Prednisone [Correspondence]

Reversal of Canities [Correspondence]

Dermoscopic Subpatterns of Ashy Dermatosis Related to Lichen Planus [skINsight]

Hypopigmented Patches in a Caucasian Male: A Quiz.

Hypopigmented Patches in a Caucasian Male: A Quiz. Acta Derm Venereol. 2010 Jan;90(1):109-111 Authors: Costa IM, Queiroz Zancanaro PC Abstract is missing (Quiz). PMID: 20107748 [PubMed - as supplied by publisher]

Butterfly Rash in a Young Boy: A Quiz.

Butterfly Rash in a Young Boy: A Quiz. Acta Derm Venereol. 2010 Jan;90(1):109-111 Authors: Benedix F, Geyer A, Röcken M, Biedermann T Abstract is missing (Quiz). PMID: 20107747 [PubMed - as supplied by publisher]

Cutaneous cryptococcosis in a patient with cirrhosis and hepatitis C virus infection.

Cutaneous cryptococcosis in a patient with cirrhosis and hepatitis C virus infection. Acta Derm Venereol. 2010;90(1):106-7 Authors: Miura T, Kawakami Y, Otsuka M, Hachiya M, Yamanoi T, Ohashi K, Suzutani T, Yamamoto T PMID: 20107746 [PubMed - in process]

Fumaric Acid esters in severe ulcerative necrobiosis lipoidica: a case report and evaluation of current therapies.

Fumaric Acid esters in severe ulcerative necrobiosis lipoidica: a case report and evaluation of current therapies. Acta Derm Venereol. 2010;90(1):104-6 Authors: Eberle FC, Ghoreschi K, Hertl M PMID: 20107745 [PubMed - in process]

Extranodal NK/T-cell Lymphoma, Nasal Type, Possibly Arising from Chronic Epstein-Barr Virus Infection.

Extranodal NK/T-cell Lymphoma, Nasal Type, Possibly Arising from Chronic Epstein-Barr Virus Infection. Acta Derm Venereol. 2010;90(1):102-3 Authors: Seishima M, Yuge M, Kosugi H, Nagasaka T PMID: 20107744 [PubMed - in process]

Perigastrostomy Infection Caused by Mycobacterium abscessus in an Immunocompetent Patient.

Perigastrostomy Infection Caused by Mycobacterium abscessus in an Immunocompetent Patient. Acta Derm Venereol. 2010;90(1):100-1 Authors: Chiu HY, Liu KL, Liao YH PMID: 20107743 [PubMed - in process]

Citrobacter koseri Cellulitis During Anti-CD20 Monoclonal Antibody (Ofatumumab) Treatment for B-cell Chronic Lymphocytic Leukaemia.

Citrobacter koseri Cellulitis During Anti-CD20 Monoclonal Antibody (Ofatumumab) Treatment for B-cell Chronic Lymphocytic Leukaemia. Acta Derm Venereol. 2010;90(1):99-100 Authors: Kluger N, Cartron G, Bessis D, Guillot B, Girard C PMID: 20107742 [PubMed - in process]

Body Dysmorphic Disorder in a Hairdresser: Contact Dermatitis due to Voluntary Exposure to Occupationally Relevant Allergens.

Body Dysmorphic Disorder in a Hairdresser: Contact Dermatitis due to Voluntary Exposure to Occupationally Relevant Allergens. Acta Derm Venereol. 2010;90(1):97-8 Authors: Matterne U, Shab A, Weisshaar E PMID: 20107741 [PubMed - in process]

A New SPINK5 Donor Splice Site Mutation in Siblings with Netherton Syndrome.

A New SPINK5 Donor Splice Site Mutation in Siblings with Netherton Syndrome. Acta Derm Venereol. 2010;90(1):95-6 Authors: Tüysüz B, Ojalvo D, Mat C, Zambruno G, Covaciu C, Castiglia D, D'Alessio M PMID: 20107740 [PubMed - in process]

Mutations in lipase h gene underlie autosomal recessive hypotrichosis in five pakistani families.

Mutations in lipase h gene underlie autosomal recessive hypotrichosis in five pakistani families. Acta Derm Venereol. 2010;90(1):93-4 Authors: Kalsoom UE, Habib R, Khan B, Ali G, Ali N, Ansar M, Ahmad W PMID: 20107739 [PubMed - in process]

Livedoid Vasculopathy Associated with Plasminogen Activator Inhibitor-1 Promoter Homozygosity (4G/4G) and Prothrombin G20210A Heterozygosity: Response to t-PA Therapy.

Livedoid Vasculopathy Associated with Plasminogen Activator Inhibitor-1 Promoter Homozygosity (4G/4G) and Prothrombin G20210A Heterozygosity: Response to t-PA Therapy. Acta Derm Venereol. 2010;90(1):91-2 Authors: Antunes J, Filipe P, André M, Fraga A, Miltenyi G, Marques Gomes M PMID: 20107738 [PubMed - in process]

Paraneoplastic pemphigus associated with malignant gastrointestinal stromal tumour.

Paraneoplastic pemphigus associated with malignant gastrointestinal stromal tumour. Acta Derm Venereol. 2010;90(1):89-90 Authors: Masu T, Okuyama R, Tsunoda T, Hashimoto T PMID: 20107737 [PubMed - in process]

Melanoma of the penis: a clinical dermoscopic case study.

Melanoma of the penis: a clinical dermoscopic case study. Acta Derm Venereol. 2010;90(1):87-8 Authors: de Giorgi V, Grazzini M, Massi D, Rossari S, Gori A, Janowska A, Bruscino N, Lotti T PMID: 20107736 [PubMed - in process]

Photoleukomelanoderma possibly caused by etretinate in a patient with psoriasis.

Photoleukomelanoderma possibly caused by etretinate in a patient with psoriasis. Acta Derm Venereol. 2010;90(1):85-6 Authors: Seishima M, Shibuya Y, Kato G, Watanabe K PMID: 20107735 [PubMed - in process]

Dermoscopic evolution of vascular pattern in two cases of amelanotic melanoma.

Dermoscopic evolution of vascular pattern in two cases of amelanotic melanoma. Acta Derm Venereol. 2010;90(1):83-5 Authors: Piccolo D PMID: 20107734 [PubMed - in process]

Penile swelling and ulceration.

Penile swelling and ulceration. Acta Derm Venereol. 2010;90(1):81-2 Authors: Imbert E, Milpied B, Jouary T, Versapuech J, Goussot JF, Taieb A, Ezzedine K PMID: 20107733 [PubMed - in process]

Dyshidrosiform palmoplantar pemphigoid in a young man: response to dapsone.

Dyshidrosiform palmoplantar pemphigoid in a young man: response to dapsone. Acta Derm Venereol. 2010;90(1):80-1 Authors: Lupi F, Masini C, Ruffelli M, Puddu P, Cianchini G PMID: 20107732 [PubMed - in process]

Hypertrophic Lichenoid Eruption due to Furosemide.

Hypertrophic Lichenoid Eruption due to Furosemide. Acta Derm Venereol. 2010;90(1):78-9 Authors: Arias-Santiago S, Aneiros-Fernandez J, Aceituno-Madera P, Burkhardt-Perez P, Naranjo Sintes R PMID: 20107731 [PubMed - in process]

Lichenoid Drug Eruption with Palmoplantar Hyperkeratosis due to Imatinib Mesylate: A Case Report and a Review of the Literature.

Lichenoid Drug Eruption with Palmoplantar Hyperkeratosis due to Imatinib Mesylate: A Case Report and a Review of the Literature. Acta Derm Venereol. 2010;90(1):73-6 Authors: Kuraishi N, Nagai Y, Hasegawa M, Ishikawa O Cutaneous adverse effects of imatinib mesylate (Glivec) are common and various types of skin eruptions have been reported. We report here a 57-year-old man who presented with lichen planus-like lesions on his extremities and palmoplantar hyperkeratosis due to the use of imatinib mesylate for chronic myeloid leukaemia. The skin lesions improved after discontinuation of imatinib mesylate but re-administration of the drug at a lower dose provoked a mild recurrence. He could, however, continue to take the drug at the lower dose and his skin lesions were well-controlled by topical corticosteroid treatment. The literature on lichenoid drug eruption due to imatinib mesylate is reviewed. PMID: 20107730 [PubMed - in process]

Leukaemic Cutaneous T-cell Lymphoma-Manifesting Papuloerythroderma with CD3- CD4+ Phenotype.

Leukaemic Cutaneous T-cell Lymphoma-Manifesting Papuloerythroderma with CD3- CD4+ Phenotype. Acta Derm Venereol. 2010;90(1):68-72 Authors: Shimauchi T, Sugita K, Nakamura M, Tokura Y The leukaemic form of cutaneous T-cell lymphoma, as represented by Sézary syndrome, exhibits erythroderma. We describe here an indolent leukaemic patient with cutaneous T-cell lymphoma, who initially had a nodulo-tumourous eruption with a crop of solid papules, but finally presented with papuloerythroderma. Histologically, the skin lesions showed non-epidermotropic dermal infiltration of atypical lymphocytes with lymphoid follicles and a granulomatous change. The circulating malignant CD4+CCR4+ T cells lacked the expression of T-cell receptor and did not respond to concanavalin A. The unresponsiveness of T cells to the T-cell mitogen may be associated with the non-epidermotropic behaviour of the tumour cells and the initially non-erythrodermic eruption. PMID: 20107729 [PubMed - in process]

Hereditary progressive mucinous histiocytosis: first report in a male patient.

Hereditary progressive mucinous histiocytosis: first report in a male patient. Acta Derm Venereol. 2010;90(1):65-7 Authors: Schlegel C, Metzler G, Burgdorf W, Schaller M Progressive mucinous histiocytosis is a very rare, benign, non-Langerhans' cell histiocytosis limited to the skin. In total ten patients (all women) in four families and three sporadic cases have been reported. We report here the first published case of a male patient with progressive mucinous histiocytosis. The multiple red papules on the scalp and forearms were asymptomatic and had slowly increased over approximately the past 20 years. The patient's mother had similar lesions. Histological examination revealed nodules in the dermis with histiocytes and mucin deposition. The histiocytes stained positively with CD31 and negative with CD34, CAM 5.2, PGM-1 and factor XIIIa. Ultrastructurally, the histiocytes showed numerous circular myelin bodies and zebra bodies reminiscent of those seen in lysosomal storage diseases. The genetic transmission of hereditary progressive mucinous histiocytosis remains unclear; we assume an autosomal dominant transmission with some hormonal factor that makes hereditary progressive mucinous histiocytosis more likely in women. PMID: 20107728 [PubMed - in process]

Safety and efficacy of tacrolimus ointment versus pimecrolimus cream in the treatment of patients with atopic dermatitis previously treated with corticosteroids.

Safety and efficacy of tacrolimus ointment versus pimecrolimus cream in the treatment of patients with atopic dermatitis previously treated with corticosteroids. Acta Derm Venereol. 2010;90(1):58-64 Authors: Kirsner RS, Heffernan MP, Antaya R Adult and pediatric patients (n = 347) with atopic dermatitis enrolled in three multicenter, randomized, 6-week studies who had previously used steroids were analyzed to examine the null hypothesis that improvement in atopic dermatitis initiated after prior treatment with steroids eliminates any subsequent treatment differences between tacrolimus ointment and pimecrolimus cream. Of these patients, 171 were randomized to tacrolimus ointment and 176 to pimecrolimus cream. Based on improvement in the Eczema Area and Severity Index at the end of study, tacrolimus ointment was significantly more effective than pimecrolimus cream (p = 0.0002). Tacrolimus ointment was also significantly more effective than pimecrolimus cream at the end of study in all secondary end-points. Overall, the frequency of adverse events was comparable between treatment groups (24.0% for tacrolimus ointment vs. 25.6% for pimecrolimus cream). Tacrolimus ointment is more effective, with a similar safety profile, compared with pimecrolimus cream in patients with atopic dermatitis previously treated with topical corticosteroids. PMID: 20107727 [PubMed - in process]

Fusidic Acid-resistant Staphylococcus aureus in Impetigo Contagiosa and Secondarily Infected Atopic Dermatitis.

Fusidic Acid-resistant Staphylococcus aureus in Impetigo Contagiosa and Secondarily Infected Atopic Dermatitis. Acta Derm Venereol. 2010;90(1):52-7 Authors: Alsterholm M, Flytström I, Bergbrant IM, N J Fusidic acid-resistant Staphylococcus aureus (FRSA) has been identified as a causative agent in outbreaks of impetigo and its emergence has been associated with increased use of topical fusidic acid. The frequency of FRSA in atopic dermatitis (AD) has been less extensively investigated. The aim of this study was to investigate the bacterial spectrum and frequency of FRSA in patients with impetigo or secondarily infected AD. A prospective study in our clinic in 2004 to 2008 included 38 patients with impetigo and 37 with secondarily infected AD. S. aureus was the predominant finding in all groups (bullous impetigo 92% (12/13), impetigo 76% (19/25) and secondarily infected AD 89% (33/37)). Seventy-five percent of S. aureus were fusidic acid resistant in bullous impetigo, 32% in impetigo and 6.1% in secondarily infected AD (bullous impetigo vs. AD p < 0.0001, impetigo vs. AD p < 0.05). We then performed a retrospective patient record review including all patients with impetigo or secondarily infected AD seen at the clinic during the first and last year of the prospective study. In the first year 33% (19/58) of the S. aureus isolates were fusidic acid-resistant in impetigo and 12% (5/43) in secondarily infected AD (p < 0.05). In the last year corresponding values were 24% (6/25) for impetigo and 2.2% (1/45) for AD (p < 0.01). In summary, the prospective study and the patient record review both showed higher FRSA levels in impetigo than in AD. FRSA levels were persistently low in AD. Continued restrictive use of topical fusidic acid is advised to limit an increase in FRSA levels in dermatology patients. PMID: 20107726 [PubMed - in process]

Role of attentional focus on bodily sensations in sensitivity to itch and pain.

Role of attentional focus on bodily sensations in sensitivity to itch and pain. Acta Derm Venereol. 2010;90(1):46-51 Authors: van Laarhoven AI, Kraaimaat FW, Wilder-Smith OH, Evers AW Patients frequently report high levels of physical symptoms, such as itch and pain, which do not completely correspond to pathophysiological findings, possibly indication heightened sensitivity to physical symptoms. Sensitivity to itch and pain is thought to be affected by processes such as attentional focus on bodily sensations. We investigated the role of attentional focus in sensitivity to various somatosensory stimuli evoking both itch and pain sensations in healthy female subjects. Different mechanical, chemical and electrical stimuli of quantitative sensory testing were applied. Attentional focus on bodily sensations was measured using validated questionnaires. The results indicated that focusing on bodily sensations is associated with higher levels of experienced itch and pain but not with tolerance to stimuli. This suggests that attentional focusing on bodily sensations is a mechanism responsible for sensitivity to different physical sensations, such as itch and pain. PMID: 20107725 [PubMed - in process]

Skin pain and discomfort in psoriasis: an exploratory study of symptom prevalence and characteristics.

Skin pain and discomfort in psoriasis: an exploratory study of symptom prevalence and characteristics. Acta Derm Venereol. 2010;90(1):39-45 Authors: Ljosaa TM, Rustoen T, Mörk C, Stubhaug A, Miaskowski C, Paul SM, Wahl AK Few studies have investigated subjective sensory skin symptoms in patients with psoriasis. The aim of this study was to investigate prevalence and characteristics of psoriasis-related skin pain and discomfort, and evaluate differences in demographic/clinical characteristics among patients with or without skin symptoms. A total of 139 patients was recruited for this exploratory, descriptive, cross-sectional study. Data were obtained through interviews and questionnaires. While 42.6% reported skin pain, 36.7% reported skin discomfort. Mean average symptom intensity score (0-10 numeric rating scale) was 4.4 for pain and 3.5 for discomfort. Unpleasant, surface, sensitive, itchy, and hot/burning were the most common symptom qualities. Sleep was the most severely affected function. No differences were found in demographic characteristics. However, larger proportions of patients with skin symptoms had more severe psoriasis (p < 0.05). In conclusion, pain and discomfort are more common and more severe in patients with psoriasis than previously estimated. PMID: 20107724 [PubMed - in process]

How Robust are the Dermatology Life Quality Index and Other Self-reported Subjective Symptom Scores when Exposed to a Range of Experimental Biases?

How Robust are the Dermatology Life Quality Index and Other Self-reported Subjective Symptom Scores when Exposed to a Range of Experimental Biases? Acta Derm Venereol. 2010;90(1):34-8 Authors: Murray CS, Rees JL Subjective-symptom tools used in dermatology have rarely been experimentally tested for cognitive "focus" and "framing" biases. We investigated the effects of affective biases on the Dermatology Life Quality Index (DLQI), the Global Health Question and visual analogue scores. Two experiments tested the response to affect-eliciting words and film. We demonstrated no significant difference in median DLQI scores for subjects exposed to negative vs. neutral words (medians 8.5 and 9.5, respectively), or negative vs. positive words (medians 6.0 and 9.0, respectively, overall p = 0.41.) Median DLQI scores were similar for groups who had (8.0), or had not (9.0), seen a video clip about a severe skin condition (p = 0.34). Finally, we compared an Amended DLQI (ADLQI), the DLQI re-worded into neutral "frames\", with the standard DLQI. ADLQI median scores were higher (ADLQI 8.25, DLQI 6.75), but not significantly so (p = 0.47). We have been unable to demonstrate any effects of the biases studied, but the statistical power of our study is modest. PMID: 20107723 [PubMed - in process]

Effect of tobacco smoking and alcohol consumption on the prevalence of nickel sensitization and contact sensitization.

Effect of tobacco smoking and alcohol consumption on the prevalence of nickel sensitization and contact sensitization. Acta Derm Venereol. 2010;90(1):27-33 Authors: Thyssen JP, Johansen JD, Menné T, Nielsen NH, Linneberg A There is evidence that stimulants such as alcohol and tobacco have an effect on the immune system, but little is known about how these lifestyle factors affect the prevalence of contact sensitization. This study investigated whether smoking and alcohol consumption were associated with contact sensitization and nickel sensitization. A random sample of adults (n=3460) from the general population of Copenhagen was invited to participate in a general health examination including patch-testing. Alcohol consumption was not associated with nickel sensitization, whereas a significant trend (p<0.05) was identified between smoking status and nickel sensitization in an adjusted model; i.e. nickel sensitization was higher among both previous smokers (odds ratio (OR) = 1.19; confidence interval (CI) = 0.81-1.76), current light smokers (OR=1.50; CI=0.94-2.37) and current heavy smokers (OR=1.56; CI = 0.87-2.80) compared with never smokers. This study confirmed that smoking is associated with nickel sensitization, but rejected an association with alcohol consumption. PMID: 20107722 [PubMed - in process]

Psoriasis and hypertension: a case-control study.

Psoriasis and hypertension: a case-control study. Acta Derm Venereol. 2010;90(1):23-6 Authors: Cohen AD, Weitzman D, Dreiher J In recent years, numerous reports have demonstrated an association between psoriasis and metabolic syndrome. However, some studies failed to demonstrate an association between psoriasis and hypertension. The aim of the present study was to examine the association between psoriasis and hypertension. Psoriasis patients of a health-maintenance organization were compared with enrollees without psoriasis regarding the prevalence of hypertension in a case-control study. The study included 12,502 psoriasis patients over the age of 20 years and 24,285 age- and sex-frequency-matched controls. The prevalence of hypertension was significantly higher in psoriasis patients than controls (38.8%, 29.1%, respectively, p<0.001). In a multivariate analysis, hypertension was associated with psoriasis after controlling for age, sex, smoking status, obesity, diabetes, non-steroidal anti-inflammatory drugs (NSAIDs) and use of Cox-2 inhibitors (odds ratio: 1.37, 95% confidence interval: 1.29-1.46). The results of this study support the previously noted association between psoriasis and hypertension. We suggest that patients with psoriasis should be routinely screened for the presence of hypertension. PMID: 20107721 [PubMed - in process]

Indomethacin-induced Reduction in CRTH2 in Eosinophilic Pustular Folliculitis (Ofuji's Disease): A Proposed Mechanism of Action.

Indomethacin-induced Reduction in CRTH2 in Eosinophilic Pustular Folliculitis (Ofuji's Disease): A Proposed Mechanism of Action. Acta Derm Venereol. 2010;90(1):18-22 Authors: Satoh T, Shimura C, Miyagishi C, Yokozeki H Eosinophilic pustular folliculitis is an inflammatory skin disease characterized by pruritic follicular papulopustules. It is usually resistant to topical and/or systemic corticosteroids, but it responds well to systemic indomethacin. We report here two patients with classical-type disease who were treated with systemic indomethacin. As indomethacin is an inhibitor of cyclo-oxygenases and a potent agonist of the prostaglandin D2 (PGD2) receptor, CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells), we investigated the effects of indomethacin on CRTH2 expression by leukocytes. CRTH2 was expressed on blood eosinophils and lymphocytes. In vitro treatment with indomethacin suppressed the expression of CRTH2 on these cells. In addition, systemic treatment with indomethacin reduced eosinophil CRTH2 expression in another patient in association with improvement of skin lesions and blood eosinophilia. A number of inflammatory cells expressed haematopoietic PGD synthase, an essential enzyme for generating PGD2 in skin lesions of eosinophilic pustular folliculitis. A PGD2-CRTH2 interaction may be involved in the pathogenesis. Moreover, indomethacin may exert its therapeutic effect via reducing CRTH2 expression, as well as by inhibiting PGD2 synthesis. PMID: 20107720 [PubMed - in process]

Pruritus in cutaneous T-cell lymphomas: frequent, often severe and difficult to treat.

Pruritus in cutaneous T-cell lymphomas: frequent, often severe and difficult to treat. Acta Derm Venereol. 2010;90(1):12-7 Authors: Meyer N, Paul C, Misery L Pruritus has a well-known association with Hodgkin's disease and other nodal lymphomas; indeed it often reveals the disease. Pruritus is also an important symptom of cutaneous T-cell lymphomas. Lymphoma-associated itch is thus both frequent and severe, but its pathophysiology remains unclear. Few studies have evaluated the efficacy of therapeutic agents in the management of cutaneous T-cell lymphoma-related pruritus. The main objective of treatment remains disease control. Pruritus management is generally based on the physician's experience. Treatment is very difficult, especially in Sézary syndrome. We present here management strategies for cutaneous lymphoma-associated pruritus. PMID: 20107719 [PubMed - in process]

A practical classification of childhood hypopigmentation disorders.

A practical classification of childhood hypopigmentation disorders. Acta Derm Venereol. 2010;90(1):6-11 Authors: Tey HL Hypopigmentation disorders in children can be due to a wide variety of congenital and acquired diseases. A clinical approach to hypopigmentation disorders based on the typical age of onset and the extent of lesions is proposed. The disorders are categorized into onset in early and later childhood, and in each category they are subdivided into localized and generalized pigmentary disorders. Clinical findings, comprising the sites of involvement, degree of pigment loss, and associated morphological findings, are used to distinguish the disorders further. This classification provides a systematic approach to a clinical condition in which the causes are heterogeneous and histological examination of the skin is rarely diagnostic. PMID: 20107718 [PubMed - in process]

Bullous pemphigoid masquerading as recurrent vesicular hand eczema.

Bullous pemphigoid masquerading as recurrent vesicular hand eczema. Acta Derm Venereol. 2010;90(1):4-5 Authors: Veien NK Lupi et al. present, on p. 80-81, an interesting case report of dyshidrosiform palmo-plantar pemphigoid. They describe a 20-year-old man who had had itchy vesicles on his palms and soles for 1 year. Histologically, a subepidermal vesicle was seen, and direct immunofluorescence showed continuous linear deposition of IgG and C3 at the dermal-epidermal junction. An enzyme-linked immunosorbent assay (ELISA) for circulating antibodies against bullous pemphigoid antigen BP 180 was positive. Based on the figures in their report, the current case was, morphologically, classical recurrent vesicular hand eczema. However, the features that distinguish the current case from recurrent vesicular hand eczema (dyshidrotic eczema or pompholyx) are: (i) that histopathology showed a subepidermal vesicle, while recurrent vesicular hand eczema shows spongiosis and intraepidermal vesicles; (ii) that direct immunofluorescence showed linear deposition of IgG and C3 along the dermal-epidermal junction; and (iii) no improvement was seen after 16 weeks of therapy with 25 mg prednisone daily. Recurrent vesicular hand eczema usually responds well to this treatment. The terms dyshidrosis, pompholyx and acute and recurrent vesicular hand eczema have been used interchangeably to describe eruptions of tiny vesicles with sparse or no inflammation on the palms and sometimes also on the soles. If vesicles coalesce they may form bullae. The term dyshidrosis or dyshidrosiform is best avoided. It has been shown repeatedly that there is no connection between the vesicles and the acrosyringium in vesicular hand dermatitis. The term pompholyx is best reserved for the rare, sudden, severe, self-healing vesicular and/or bullous eruptions on the palms and, occasionally also, on the soles with no or sparse inflammation (1, 2). Indeed, the term "pompholyx" could be replaced by "acute vesicular hand eczema". The aetiology of this condition is unknown. Recurrent vesicular hand dermatitis is probably the best term to describe the more common, milder vesicular eruptions on the palms with sharp delineation to palmar skin and with no or moderate inflammation. A multitude of aetiologies have been linked to this eczematous eruption, including allergic and irritant contact dermatitis, systemic contact dermatitis and dermatophytid. It is probably useful to consider recurrent vesicular hand dermatitis to be a characteristic but non-specific reaction pattern of palmar and plantar skin with many possible causes (3). Thus the title of the current case report could have been "Bullous pemphigoid masquerading as recurrent vesicular hand dermatitis". PMID: 20107717 [PubMed - in process]

Fusidic Acid Resistant Staphylococcus aureus and Skin Disease.

Fusidic Acid Resistant Staphylococcus aureus and Skin Disease. Acta Derm Venereol. 2010;90(1):4 Authors: Lomholt HB In this issue Alsterholm et al. (p. 52-57) present data from Sweden on fusidic acid resistant Staphylococcus aureus (FRSA) isolated from cases of impetigo and atopic dermatitis, respectively. They found high numbers of FRSA in impetigo, ranging from 75% in bullous impetigo to 32% in non-bullous impetigo. By contrast, significantly lower numbers of FRSA (6.1%) were detected in secondarily infected atopic dermatitis. Unfortunately, the FRSA strains were not genotyped. The high numbers, especially in bullous impetigo, could be due to infection by the well-described clone that has caused widespread outbreaks of impetigo in several European countries, including Norway, Sweden and Denmark, during the last 10 years. The low number of FRSA in secondarily infected atopic dermatitis may indicate that the impetigo clone is not a frequent colonizer of atopic dermatitis. The small number of other studies, published from other geographical areas, have shown FRSA levels in atopic dermatitis ranging from 6% to 50%. All cases were seen at a single dermatological department after referral from general practitioners, and only a minority of patients seen in the study period 2004 to 2008 were included. There may therefore be an important selection bias and the results are not necessarily true for impetigo and atopic dermatitis patients in primary care. However, it is important continuously to follow the development of fusidic acid resistance among S. aureus and to remind the medical community that restricted use of this antibiotic seems necessary to keep resistance rates as low as possible. For atopic dermatitis it is a clinical impression that secondary infection with S. aureus promotes inflammation in flares, and that the addition of antiseptics or antibiotics leads to improved efficiency of treatment in the most severely infected cases. Interestingly, a recent Cochrane Review did not find any evidence that the addition of oral or local antibiotics was of benefit in atopic dermatitis. However, the available data are insufficient for firm conclusions to be drawn. PMID: 20107716 [PubMed - in process]

Subjective dermatology outcomes: how you frame the question may not be that important after all.

Subjective dermatology outcomes: how you frame the question may not be that important after all. Acta Derm Venereol. 2010;90(1):3-4 Authors: William H PMID: 20107715 [PubMed - in process]

Moving towards open access: high-quality research and publication is essential, but visibility of the work is critical.

Moving towards open access: high-quality research and publication is essential, but visibility of the work is critical. Acta Derm Venereol. 2010;90(1):3 Authors: Vahlquist A, Egelrud T, Andersson A PMID: 20107714 [PubMed - in process]

The Role of Toll-Like Receptors in Host Defenses and Their Relevance to Dermatologic Diseases

Complementary and Alternative Medicine in Alopecia Areata

A Current Review of Juvenile Pemphigus Vulgaris: Analysis of Data on Clinical Outcomes

Antibacterial Prophylaxis in Dermatologic Surgery: An Evidence-Based Review

Topical Treatment of Actinic Keratoses with Piroxicam 1 Gel: A Preliminary Open-Label Study Utilizing a New Clinical Score

Topical Pimecrolimus 1 Cream for Resistant Seborrheic Dermatitis of the Face: An Open-Label Study

Trends in Dermatology Publications over the Past 15 Years

Coexistence of Basal Cell Carcinomas and Multiple Sebaceous Gland Hyperplasias in a Cyclosporine (Ciclosporin)-Treated Renal Transplant Recipient

Cutaneous Collagenous Vasculopathy: Ultrastructural and Immunohistochemical Study of a New Case

Cutaneous Xanthogranulomas, Hepatosplenomegaly, Anemia, and Thrombocytopenia as Presenting Signs of Juvenile Myelomonocytic Leukemia

Recurrent Episodes of Painful and Pruritic Red Skin Lesions

Clearance of experimental cutaneous Staphylococcus aureus infections in mice

Abstract Staphylococcal skin infections are quite common in human patients. These infections often clear spontaneously, but may also progress locally and/or disseminate to cause serious and sometimes fatal deep infections. The present studies were undertaken to examine the clearance phase of experimental cutaneous Staphylococcus aureus infections in a mouse model system. Previous work in this system has shown that staphylococci applied to the skin rapidly disseminate to the spleen and kidney. In the present experiments the bacteria were found to persist at the skin infection site at a time (8 days after inoculation) when they had disappeared from the spleen and kidney. Examination of the infected skin at earlier times revealed rapid (within 6 h) invasion into the stratum corneum, stratum Malpighii, and dermis, but subsequent redistribution of bacteria (at 1–2 days) to more superficial sites, particularly crusts located just above the skin surface. The crusts seen in these infections were of two distinct types, which were termed type 1 and type 2. Type 1 crusts appeared first, consisted of bacteria, inflammatory cells, and debris, and developed over an intact epidermis. Type 2 crusts arose from the process of dermal necrosis previously reported to take place at 2 days in this model system. In the latter situation the bacteria were not really cleared from the epidermis and dermis; rather those layers were transformed into a superficial crust that contained the bacteria. Deep hair follicle infections in the dermis were found in these infections, but they did not persist and did not seem to be a reservoir for organisms in the dermis. Resolution of these experimental infections appeared to involve redistribution of invading bacteria to more superficial locations in crusts above the skin surface, marked proliferation of the epidermis, loss of the bacteria-laden crusts from the skin, and eventual healing of the cutaneous damage. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-010-1030-yAuthors Charles C. Onunkwo, Medical College of Wisconsin Division of Infectious Diseases, Department of Medicine Milwaukee WI 53226 USABeth L. Hahn, Medical College of Wisconsin Division of Infectious Diseases, Department of Medicine Milwaukee WI 53226 USAPeter G. Sohnle, Medical College of Wisconsin Division of Infectious Diseases, Department of Medicine Milwaukee WI 53226 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

The association of the BLK gene with SLE was replicated in Chinese Han

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease influenced by genetic and environmental factors. Recently, single nucleotide polymorphisms (SNPs) in the region of B lymphoid tyrosine kinase (BLK) have been shown to be associated with SLE in Caucasian population. In this paper, we genotyped SNP rs2248932 in 1,396 SLE patients of Chinese Han and 4,362 ethnically matched control subjects by using the Sequenom MassArray system. We confirmed that SNP rs2248932 in BLK gene was significantly associated with SLE (P = 1.41 × 10−8 for the allele frequency, Odds ratio [OR] = 0.74, 95% confidence interval (CI): 0.66–0.82).The association of BLK in Chinese SLE patients was consistent with a dominant model (P = 8.88 × 10−9, OR = 0.69, 95% CI: 0.61–0.79). In contrast to the Caucasian, this risk allele was the major allele in the Chinese Han; the risk allele frequency was higher in Chinese Han than in Caucasian. We did not find the association between this SNP and any subphenotype of SLE. The SNP rs2248932 was correlated to the expression of BLK mRNA. We conclude that the association of the BLK region with SLE was replicated in Chinese Han population living in mainland. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-010-1029-4Authors Zheng Zhang, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaKun-Ju Zhu, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaQiang Xu, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaXue-Jun Zhang, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaLiang-Dan Sun, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaHou-Feng Zheng, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaJan-Wen Han, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaCheng Quan, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaSheng-Quan Zhang, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaLi-Qiong Cai, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaSheng-Xin Xu, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaXian-Bo Zuo, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaHui Cheng, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaSen Yang, Anhui Medical University Department of Dermatology, Institute of Dermatology, The First Affiliated Hospital 81 Meishan Road 230032 Hefei Anhui People’s Republic of China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Genetics of keloid scarring

Abstract Keloid scarring, also known as keloid disease (KD), is a common, abnormally raised fibroproliferative cutaneous lesion that can occur following even minor skin trauma. The aetiopathogenesis of KD has remained an enigma todate compounded by an ill-defined clinical management. There is strong evidence suggesting a genetic susceptibility in individuals affected by KD, including familial heritability, common occurrence in twins and high prevalence in certain ethnic populations. This review aims to address the genetic aspects of KD that have been described in present literature that include inheritance patterns, linkage studies, case–control association studies, whole genome gene expression microarray studies and gene pathways that were significant in KD. In addition to our clinical and scientific background in KD, we used search engines, Scopus, Scirus and PubMed, which searched for key terms covering various genetic aspects of KD. Additionally, genes reported in seven whole genome gene expression microarray studies were separately compared in detail. Our findings indicate a varied inheritance pattern in KD (predominantly autosomal dominant), linkage loci (chromosomes 2q23 and 7p11), several human leukocyte antigen (HLA) alleles (HLA-DRB1*15, HLA-DQA1*0104, DQ-B1*0501 and DQB1*0503), negative candidate gene case–control association studies and at least 25 dysregulated genes reported in multiple microarray studies. The major pathways reportedly proposed to be involved in KD include apoptosis, mitogen-activated protein kinase, transforming growth factor-β, interleukin-6 and plasminogen activator inhibitor-1. In summary, involvement of more than one gene is likely to be responsible for susceptibility to KD. A better understanding of the genes involved in KD may potentially lead to the development of more effective diagnostic, therapeutic and prognostic measures. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-1014-yAuthors Barbara Shih, University of Manchester Plastic and Reconstructive Surgery Research, Epithelial Sciences, School of Translational Medicine, The Manchester Interdisciplinary Biocentre (MIB) 131 Princess Street Manchester M17ND UKArdeshir Bayat, University of Manchester Plastic and Reconstructive Surgery Research, Epithelial Sciences, School of Translational Medicine, The Manchester Interdisciplinary Biocentre (MIB) 131 Princess Street Manchester M17ND UK Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Restoration of peripheral blood T cell repertoire complexity during remission in advanced cutaneous T cell lymphoma

Abstract In advanced stages, cutaneous T cell lymphomas (CTCL) are associated with increased mortality from infections and also increased susceptibility to skin malignancies. In this study, we analyzed the complexity of the peripheral blood T cell repertoire with a sensitive b-variable (BV) complementarity-determining region 3 (CDR3) spectratyping analysis and flow cytometry in three-stage IV CTCL/Sezary syndrome patients who achieved complete clinical remission after therapy. The T cell repertoire of peripheral blood T cells before treatment was profoundly abnormal across multiple BV subfamilies. Following treatment, CDR3 spectratype patterns showed dramatic restoration of normal diversity and complexity. However, absolute CD4 counts across multiple BV families remained low for many months, even after identifiable circulating malignant T cell populations were eliminated. These data suggest that the diversity of the T cell repertoire can be recovered after successful treatment of even advanced CTCL. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1023-xAuthors Kei-ichi Yamanaka, Harvard Institutes of Medicine Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital 77 Avenue Louis Pasteur Boston MA 02115 USARobert C. Fuhlbrigge, Harvard Institutes of Medicine Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital 77 Avenue Louis Pasteur Boston MA 02115 USAHitoshi Mizutani, Graduate School of Medicine, Mie University Department of Dermatology 2-174, Edobashi Tsu Mie 514-8507 JapanThomas S. Kupper, Harvard Institutes of Medicine Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women’s Hospital 77 Avenue Louis Pasteur Boston MA 02115 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Cutaneous PGP 9.5 distribution patterns in hidradenitis suppurativa

Abstract The aim of this study was to investigate the presence and density of the nerve fibre-marker protein gene product 9.5 (PGP 9.5), with immunohistochemistry, in skin from patients with hidradenitis suppurativa (HS). Punch biopsies were obtained from 16 patients; 10 with involvement of the groin and six with axillary disease. Specimens were taken from HS lesions in the groin or axilla, clinically non-involved skin and from 12 healthy control subjects. Coded slides were observed in the microscope and PGP 9.5 positive nerve fibre profiles (profiles) as well as PGP 9.5 positive cells (cells) were counted. The overall impression was that the median number of profiles was decreased in lesional epidermis, yet statistically significant only in the groin (p = 0.0014). The median number of profiles in dermis was significantly decreased in lesional skin of the axilla, whereas in the groin there were contradictory findings with significantly increased number of profiles in upper dermis and non-significant in mid and lower dermis. The number of cells with strong immunofluorescence was few or absent in epidermis, but increased in dermis in the lesional skin. This difference was statistically significant throughout the dermis in specimens from the groin (p < 0.01) and showed the same trend, although not significant, in the axilla. The PGP 9.5 immunofluorescent cells were not yet further investigated, so it is not exactly known what cell type they represent. In conclusion, despite several study limitations, the findings indicate that PGP 9.5 positive nerve fibres could be involved in the pathogenesis of HS. Both regarding the profiles and the cells, further studies remain to show if these differences are primary events, or secondary to e g chronic inflammation, which is considered a major issue of HS. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-010-1028-5Authors Karin Sartorius, Karolinska Institutet, Karolinska University Hospital Huddinge Section of Dermatology, Department of Medicine Stockholm SwedenLennart Emtestam, Karolinska Institutet, Karolinska University Hospital Huddinge Section of Dermatology, Department of Medicine Stockholm SwedenJan Lapins, Karolinska Institutet, Karolinska University Hospital Huddinge Section of Dermatology, Department of Medicine Stockholm SwedenOlle Johansson, Karolinska Institutet The Experimental Dermatology Unit, Department of Neuroscience Stockholm Sweden Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Identification of two novel DSRAD mutations in two Chinese families with dyschromatosis symmetrica hereditaria

Identification of two novel DSRAD mutations in two Chinese families with dyschromatosis symmetrica hereditaria Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00403-009-1027-6Authors Qingqiang Xu, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaShengxiang Xiao, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaJia Huo, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaYingying Dong, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaJianwen Ren, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaXiaopeng Wang, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaJunhong Ma, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaJingang An, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of ChinaYan Liu, Xi’an Jiaotong University Department of Dermatology, Second Hospital 157 Xiwu Road 710004 Xi’an Shaanxi People’s Republic of China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Clinical comparison of psoriasis in Korean adults and children: correlation with serum anti-streptolysin O titers

Abstract Psoriasis is a relatively common disorder in children and can be triggered by an upper respiratory tract infection. The aim of this study was to compare the clinical features of psoriasis in children and adult. In addition, we evaluated the relationship between anti-streptolysin O (ASO) titers and the clinical features of psoriasis. A total of 30 childhood psoriasis patients and 30 adult psoriasis patients were evaluated. Childhood psoriasis had a facial predominance when compared with the adult psoriasis. The childhood psoriasis patients with high ASO titers had guttate psoriasis more frequently than patients with normal ASO titers. In children with plaque-type psoriasis, psoriasis area and severity index score was increased in the high ASO titer group than normal ASO titer group. In conclusion, if the children with psoriasis show increased ASO titer, the physician should pay attention to the worsening of the psoriasis. Furthermore, early treatment of streptococcal infections might be beneficial in childhood psoriasis. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1025-8Authors Sue Kyung Kim, Ajou University School of Medicine Department of Dermatology 5 Wonchon-Dong, Yeongtong-Gu Suwon 443-721 South KoreaHee Young Kang, Ajou University School of Medicine Department of Dermatology 5 Wonchon-Dong, Yeongtong-Gu Suwon 443-721 South KoreaYou Chan Kim, Ajou University School of Medicine Department of Dermatology 5 Wonchon-Dong, Yeongtong-Gu Suwon 443-721 South KoreaEun-So Lee, Ajou University School of Medicine Department of Dermatology 5 Wonchon-Dong, Yeongtong-Gu Suwon 443-721 South Korea Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Purified proteins from leishmania amastigotes-induced delayed type hypersensitivity reactions and remission of collagen-induced arthritis in animal models

Abstract A treatment preparation composed of purified Leishmania (L) antigenic fractions (AS210) induced linear delayed type hypersensitivity (DTH) reactions over a 1–40 μg dose range, in guinea pigs. When a DBA-1 mouse collagen induced arthritis (CIA) model was used to compare AS210 treatment against: a polyvalent vaccine (AS110-1), a monovalent vaccine (AS110-2) and placebo, the AS210 treated mice had the least amount of forepaw inflammation and the lowest mean arthritis scores (MAS). When MAS for day(s) 1–40 were analyzed using one way ANOVA, statistically significant (P < 0.05) differences were seen for the following study groups: PBS versus Dexamethasone and PBS versus AS210. Subsequently, the ANOVA analysis results were corroborated by the Mann–Whitney test: analysis of the first group (P < 0.001) and analysis of the second group (P < 0.001). Comparison between dexamethasone and AS210 at different time intervals by Mann–Whitney test were as follows: day 0–day 5 both treatments had equal values (P = 1.00), from day-7 to 20 AS210 treatment had lower MAS values than dexamethasone (P = 0.037), and from day-21 to 30, AS210 MAS were similar to dexamethasone values (P = 0.319). No statistical difference was observed between AS110-1, AS110-2, and placebo groups. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1026-7Authors Jose Antonio O’Daly, Astralis LTD. 75 Passaic Ave. Fairfield NJ 07004 USAJ. P. Gleason, Astralis LTD. 75 Passaic Ave. Fairfield NJ 07004 USAG. Peña, Astralis LTD. 75 Passaic Ave. Fairfield NJ 07004 USAI. Colorado, Astralis LTD. 75 Passaic Ave. Fairfield NJ 07004 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Immunoadsorption in dermatology

Abstract Immunoadsorption (IA), also termed immunoapheresis, has been established as effective and specific tool advantageous to plasmapheresis to remove immunoglobulin and immune complexes and in cytapheresis, immune cells from the circulation. IA was successfully used in various autoantibody-mediated diseases, e.g. acquired hemophilia, myasthenia gravis, dilated cardiomyopathy, and Guillain–Barré syndrome. In dermatology, IA has been applied as an effective adjuvant treatment for autoimmune bullous diseases. Autoimmune blistering disorders are a heterogeneous group of diseases that are associated with autoantibodies to desmosomal (pemphigus group) and basal membrane zone proteins (pemphigoid group, epidermolysis bullosa acquisita). Because the pathogenic relevance of autoantibodies was clearly demonstrated in the majority of these disorders, removal of autoantibodies, therefore, appears to be a rational therapeutic approach for these patients. IA has been shown to effectively lower the autoantibody levels and leads to rapid clinical responses in patients with immunobullous disorders. Here, clinical effects and adverse events of IA in more than 50 reported patients with autoimmune blistering disorders are reviewed. In addition, an overview of the available IA systems and treatment protocols is provided and guidelines of a recent consensus of German, Austrian, and Swiss experts for the use of IA in autoimmune bullous diseases are summarized. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-1024-9Authors Enno Schmidt, University of Lübeck Department of Dermatology Ratzeburger Allee 160 23560 Lübeck GermanyDetlef Zillikens, University of Lübeck Department of Dermatology Ratzeburger Allee 160 23560 Lübeck Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Ichthyosis in Sjögren–Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion

Abstract Sjögren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum–stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1022-yAuthors William B. Rizzo, University of Nebraska Medical Center Department of Pediatrics 985456 Nebraska Medical Center Omaha NE 68198-5456 USADana S’Aulis, University of Nebraska Medical Center Department of Pediatrics 985456 Nebraska Medical Center Omaha NE 68198-5456 USAM. Anitia Jennings, University of Nebraska Medical Center Department of Pediatrics 985456 Nebraska Medical Center Omaha NE 68198-5456 USADebra A. Crumrine, University of California Department of Dermatology San Francisco CA USAMary L. Williams, University of California Department of Dermatology San Francisco CA USAPeter M. Elias, University of California Department of Dermatology San Francisco CA USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes

Abstract Acne is a complex, chronic and common skin disorder of pilosebaceous units. Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes via androgen stimulation and inflammatory cytokines are the major factors involved in the pathophysiology of acne. In addition, it is known that keratinocytes play an important role in acne synthesizing a number of inflammatory cytokines. However, the nature of the association between inflammatory cytokines and sebocytes in acne remains unclear. Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne. To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α). Upregulation of IL-6 and TNF-α in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-α were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1019-6Authors Weon Ju Lee, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaHong Dae Jung, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaSeong Geun Chi, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaByung Soo Kim, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaSeok-Jong Lee, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaDo Won Kim, Kyungpook National University School of Medicine Department of Dermatology 200, Dongduk-ro, Jung-gu Daegu Republic of KoreaMoon Kyu Kim, Kyungpook National University School of Medicine Department of Immunology Jung-gu Daegu Republic of KoreaJung Chul Kim, Kyungpook National University School of Medicine Department of Immunology Jung-gu Daegu Republic of Korea Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment

Abstract Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1021-zAuthors Nicolas Atrux-Tallau, Université Lyon 1 Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée”, Faculté de Pharmacie 8 avenue Rockefeller 69373 Lyon Cedex 08 FranceCéline Romagny, Université Lyon 1 Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée”, Faculté de Pharmacie 8 avenue Rockefeller 69373 Lyon Cedex 08 FranceKarine Padois, Université Lyon 1 Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée”, Faculté de Pharmacie 8 avenue Rockefeller 69373 Lyon Cedex 08 FranceAlain Denis, Bioderma Laboratoire Dermatologique 75 Cours Albert Thomas 69003 Lyon FranceMarek Haftek, Hôpital Edouard Herriot Laboratoire de Recherche Dermatologique, Pavillon R, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée” 5 Place d’Arsonval 69437 Lyon Cedex 03 FranceFrançoise Falson, Université Lyon 1 Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée”, Faculté de Pharmacie 8 avenue Rockefeller 69373 Lyon Cedex 08 FranceFabrice Pirot, Université Lyon 1 Laboratoire de Recherche et Développement de Pharmacie Galénique Industrielle, EA 4169, “Fonctions normales et pathologiques de la barrière cutanée”, Faculté de Pharmacie 8 avenue Rockefeller 69373 Lyon Cedex 08 FranceHoward I. Maibach, University of California, San Francisco Department of Dermatology San Francisco CA 94143-0989 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Platelet activating factor stimulates arachidonic acid release in differentiated keratinocytes via arachidonyl non-selective phospholipase A2

Abstract Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is known to be present in excess in psoriatic skin, but its exact role is uncertain. In the present study we demonstrate for the first time the role of group VI PLA2 in PAF-induced arachidonic acid release in highly differentiated human keratinocytes. The group IVα PLA2 also participates in the release, while secretory PLA2s play a minor role. Two anti-inflammatory synthetic fatty acids, tetradecylthioacetic acid and tetradecylselenoacetic acid, are shown to interfere with signalling events upstream of group IVα PLA2 activation. In summary, our major novel finding is the involvement of the arachidonyl non-selective group VI PLA2 in PAF-induced inflammatory responses. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1017-8Authors Katarina Mariann Jørgensen, Norwegian University of Science and Technology, NTNU Department of Biology Trondheim NorwayHanne Solvang Felberg, Norwegian University of Science and Technology, NTNU Department of Biology Trondheim NorwayRolf K. Berge, Haukeland Hospital Division of Clinical Biochemistry Bergen NorwayAstrid Lægreid, Norwegian University of Science and Technology, NTNU Department of Cancer Research and Molecular Medicine Trondheim NorwayBerit Johansen, Norwegian University of Science and Technology, NTNU Department of Biology Trondheim Norway Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

p38 MAPK-regulated EGFR internalization takes place in keratinocyte monolayer during stress conditions

Abstract The epidermis is the outermost protection of the organism. As so, defence program has to be initiated in stress situation in order to protect keratinocytes. The EGF receptor (EGFR) controls cell proliferation and migration in keratinocytes, being a major regulator of keratinocyte homeostasis within the epidermis. The EGFR is known to be internalized without addition of ligand under the control of p38 MAPK during stress conditions in HeLa cells, but also following lipid rafts disruption in keratinocytes. This could represent an alternative internalization process that removes the EGFR from cell surface. Here, we investigated whether other stress conditions such as scratch wounding keratinocyte monolayer or incubation with a sensitizer chemical (i.e. DNFB), could also induce this peculiar mechanism of EGFR internalization. Our results show that both stressing conditions induce p38 MAPK activation concomitantly with EGFR internalization, independently of ligand binding to the EGFR. Inhibition of p38 MAPK activity during scratch wound blocks EGFR internalization at the margin of the wound while cell migration is impeded. Our results show thus that the p38 MAPK-dependent EGFR internalization is a process shared by keratinocytes when submitted to challenging conditions. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1020-0Authors Sylviane Lambert, University of Namur (FUNDP) Cell and Tissue Laboratory, URPHYM 61, rue de Bruxelles 5000 Namur BelgiumAurélie Frankart, University of Namur (FUNDP) Cell and Tissue Laboratory, URPHYM 61, rue de Bruxelles 5000 Namur BelgiumYves Poumay, University of Namur (FUNDP) Cell and Tissue Laboratory, URPHYM 61, rue de Bruxelles 5000 Namur Belgium Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide

Abstract Researches on stem cells bring promise to functional skin repair. In particular, it has been recently suggested that mesenchymal stem cells (MSCs) could positively affect cutaneous wound healing through differentiation and paracrine action. The molecular mechanisms are not clear, even if there is increasing evidence for an important action of nitric oxide (NO), probably mediated by the regulation of the gene encoding for vascular endothelial growth factor (VEGF). The aim of our study was to investigate the immunohistochemical expression of VEGF and nitric oxide synthase (NOS) isoforms in human skin-derived MSCs, as well as the production of VEGF and NO, because these cells are less well characterized than bone marrow MSCs. MSCs were obtained from skin biopsies of healthy adult patients undergoing cosmetic plastic surgery, expanded and characterized for specific surface antigens. The cells were then evaluated for the immunohistochemical expression of VEGF, and NOS isoforms, as well as for VEGF and NO secretion in cell culture medium. Our immunohistochemical analysis showed that proliferating MSCs derived from human skin exhibit VEGF expression at cytoplasmic level as well as cytosolic and nuclear localization of all the three isoforms of NOS, even if with different patterns. In addition, our data evidenced the release of both VEGF and NO in cell culture supernatants. In conclusion, our results suggest that a therapeutic approach based on the human skin-derived MSCs may have a positive effect in wound healing conditions, through their ability to provide VEGF and NO to the damaged area. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1018-7Authors Eleonora Salvolini, Polytechnic University of Marche Department of Molecular Pathology and Innovative Therapies, Histology Section Via Tronto 10/A 60020 Ancona ItalyGuendalina Lucarini, Polytechnic University of Marche Department of Molecular Pathology and Innovative Therapies, Histology Section Via Tronto 10/A 60020 Ancona ItalyAntonio Zizzi, Polytechnic University of Marche Department of Molecular Pathology and Innovative Therapies, Histology Section Via Tronto 10/A 60020 Ancona ItalyMonia Orciani, Polytechnic University of Marche Department of Molecular Pathology and Innovative Therapies, Histology Section Via Tronto 10/A 60020 Ancona ItalyGiovanni Di Benedetto, Polytechnic University of Marche Department of Plastic and Reconstructive Surgery Ancona ItalyRoberto Di Primio, Polytechnic University of Marche Department of Molecular Pathology and Innovative Therapies, Histology Section Via Tronto 10/A 60020 Ancona Italy Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Apolipoprotein epsilon4 allele and psoriasis severity

Apolipoprotein epsilon4 allele and psoriasis severity Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00403-009-1016-9Authors Viroj Wiwanitkit, Wiwanitkit House, Bangkhae Bangkok 10160 Thailand Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

A compound heterozygous mutation in the EDAR gene in a Spanish family with autosomal recessive hypohidrotic ectodermal dysplasia

Abstract Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterised by sparse hair, lack of sweat glands and malformation of teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal forms result from mutations in either the EDAR or the EDARADD gene. The X-linked and autosomal forms are phenotypically indistinguishable. For the purpose of genetic counselling, it is, therefore, important to know which gene is involved. In this study, we ascertained a Spanish family demonstrating the autosomal recessive form of HED. Affected individuals in the family showed the characteristic features of HED, including fine and sparse scalp hair, sparse eyebrows and eyelashes, periorbital hyperpigmentation, prominent lips, hypodontia and conical teeth, reduced sweating, and dry and thin skin. Sequence analysis of the EDAR gene revealed a novel compound heterozygous mutation [c.52-2A>G; c.212G>A (p.Cys71Tyr)]. Our finding extends the body of evidence that supports the significance of the EDAR signalling pathway in the ectodermal morphogenesis. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1013-zAuthors M. R. Moya-Quiles, Virgen de la Arrixaca University Hospital Biochemistry and Clinical Genetic Centre 30120 El Palmar Murcia SpainM. J. Ballesta-Martínez, Virgen de la Arrixaca University Hospital Unit of Medical Genetics, Department of Pediatrics 30120 El Palmar Murcia SpainV. López-González, Virgen de la Arrixaca University Hospital Unit of Medical Genetics, Department of Pediatrics 30120 El Palmar Murcia SpainG. Glover, Virgen de la Arrixaca University Hospital Biochemistry and Clinical Genetic Centre 30120 El Palmar Murcia SpainE. Guillén-Navarro, Virgen de la Arrixaca University Hospital Unit of Medical Genetics, Department of Pediatrics 30120 El Palmar Murcia Spain Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Apolipoprotein E4 and psoriasis

Apolipoprotein E4 and psoriasis Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00403-009-1015-xAuthors Hong-Liang Zhang, The First Hospital of Jilin University Department of Neurology Changchun ChinaJiang Wu, The First Hospital of Jilin University Department of Neurology Changchun China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Protease and pro-inflammatory cytokine concentrations are elevated in chronic compared to acute wounds and can be modulated by collagen type I in vitro

Abstract Physiological wound repair is a highly regulated, complex process, which leads to formation of new tissue after injury. However, the healing process is not perfect and healing impairments can occur. Delayed healing and formation of chronic wounds has been linked to the excessive production of proteolytic enzymes leading to reduced amounts of growth factors and successive destruction of the extracellular matrix. It has been implied that there is an alteration in the normal control mechanisms regulating the levels of these enzymes. The study presented provides data on the concentration of proteases and cytokines in wound fluid from chronic when compared with acute wounds. Levels of proteases such as PMN elastase, matrix metalloproteinases-2 (MMP-2), and MMP-13 were found to be profoundly elevated in chronic when compared with acute wound fluids. In addition, concentrations of IL-1β, IL-6, and IL-8 were shown to be significantly higher in chronic than in acute wounds. Furthermore, the ability of a wound dressing, consisting of bovine collagen type I, to bind pro-inflammatory cytokines was investigated. Collagen type I was able to bind significant amounts of the pro-inflammatory cytokines in vitro. Thus, it should be able to establish a more physiological wound milieu in vivo and promote healing. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1011-1Authors Cornelia Wiegand, University Hospital Jena Department of Dermatology and Dermatological Allergy Erfurter Str. 35 07740 Jena GermanyUte Schönfelder, University Hospital Jena Department of Dermatology and Dermatological Allergy Erfurter Str. 35 07740 Jena GermanyMartin Abel, Lohmann & Rauscher GmbH & Co. KG 56579 Rengsdorf GermanyPeter Ruth, Lohmann & Rauscher GmbH & Co. KG 56564 Neuwied GermanyMartin Kaatz, University Hospital Jena Department of Dermatology and Dermatological Allergy Erfurter Str. 35 07740 Jena GermanyUta-Christina Hipler, University Hospital Jena Department of Dermatology and Dermatological Allergy Erfurter Str. 35 07740 Jena Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Imiquimod induces apoptosis of human melanocytes

Abstract Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogen-activated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These findings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1012-0Authors Chul-Ho Kim, Ajou University School of Medicine Department of Otolaryngology Suwon KoreaJoo Hee Ahn, Ajou University School of Medicine Department of Dermatology Suwon 443-721 KoreaSung Un Kang, Ajou University School of Medicine Department of Otolaryngology Suwon KoreaHye Sook Hwang, Ajou University School of Medicine Department of Otolaryngology Suwon KoreaMi Hye Lee, Ajou University School of Medicine Department of Otolaryngology Suwon KoreaJung Hee Pyun, Ajou University School of Medicine Department of Otolaryngology Suwon KoreaHee Young Kang, Ajou University School of Medicine Department of Dermatology Suwon 443-721 Korea Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Relationship between urokinase plasminogen activator receptor (uPAR) and the invasion of human prenatal hair follicle

Abstract During the morphogenesis of hair follicles, the invasive migration of basal keratinocytes resembles cell’s dissemination of tissue remodeling. The urokinase-type plasminogen activator receptor (uPAR) appears to be a key molecule in the metastasis. In order to elucidate the relationship between uPAR and the invasion of the human hair follicle, immunohistochemistry, RT-PCR, plasmids transfection, and western blot were used. The results showed that uPAR was expressed in the outermost epithelial cells of the hair follicle and the basal keratinocytes of epidermis, and that the expression decreased with the development of the hair follicle. The cells of the outer root sheath (ORS) and interfollicle epidermis, which overexpressed uPAR, acquired increased invasiveness; however, they showed decreased invasion with overexpression of the urokinase-type plasminogen activator amino terminal fragment (uPA ATF), which inhibited the combination of uPAR and uPA competitively, and the cell invasive migration with overexpressed uPAR was required activated extracellular signal-regulated kinases (ERK). These results implied that overexpression of uPAR promote the invasive migration of hair follicle into the dermis in uPA-dependent and independent manner during human prenatal development. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1010-2Authors Qiangguo Gao, Third Military Medical University Department of Cell Biology, College of Basic Medicine 400038 Chongqing People’s Republic of ChinaGang Fu, Third Military Medical University Department of Haematology of Southwest Hospital 400038 Chongqing People’s Republic of ChinaGang Huang, Third Military Medical University Department of Medical Genetics, College of Basic Medicine 400038 Chongqing People’s Republic of ChinaXiaohua Lian, Third Military Medical University Department of Cell Biology, College of Basic Medicine 400038 Chongqing People’s Republic of ChinaJin Yu, Third Military Medical University Department of Cell Biology, College of Basic Medicine 400038 Chongqing People’s Republic of ChinaTian Yang, Third Military Medical University Department of Cell Biology, College of Basic Medicine 400038 Chongqing People’s Republic of China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

The skin pathergy test: innately useful?

Abstract Pathergy is the term used to describe hyper-reactivity of the skin that occurs in response to minimal trauma. A positive skin pathergy test (SPT), characterised by erythematous induration at the site of the needle stick with a small pustule containing sterile pus at its centre, is among the criteria required for a diagnosis of Behçet’s disease (BD) and in certain population has been shown to be highly specific for this condition. Problems with standardising the induction manoeuvre for the SPT as well as the method of assessment of the response have limited the usefulness of the SPT in the clinical setting. Extensive investigation into histopathological and immunological aspects of pathergy has led to a number of hypotheses relating to the aetiology of the skin pathergy reaction and the disease itself, but the cause is considered to be unknown. Pathergy lesions, the development of new skin lesions or the aggravation of existing ones following trivial trauma, are also reported in pyoderma gangrenosum and has been noted in other neutrophilic dermatoses such as Sweet’s syndrome. The response of such patient groups to the systematic application of the SPT has not been described. We propose that a new way of considering the pathergy reaction is to see it as an aberration of the skin’s innate reactivity from a homeostatic reactive mode closely coupled to tissue healing to an abnormal destructive/inflammatory mode. Our understanding of BD and other similar conditions would profit by more detailed mechanistic knowledge of skin homeostasis to minimal trauma in both health and disease through a more structured and systematic use of the SPT. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-1008-9Authors Alexandra Varol, Liverpool Hospital Department of Dermatology Sydney AustraliaOliver Seifert, Ryhov Hospital Division of Dermatology Jönköping SwedenChris D. Anderson, Linköping University Hospital Division of Dermatology, Department of Clinical and Experimental Medicine Linköping Sweden Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Treatment of Laugier–Hunziker syndrome with the Q-switched alexandrite laser in 22 Chinese patients

Abstract Laugier–Hunziker syndrome (LHS), a rare, acquired pigmentary disorder of the lips, oral mucosa, and fingers, is known to be an entirely benign disease with no systemic manifestations. In the past, the pigmentation has been treated efficiently in a few patients with the Q-switched neodymium: yttrium–aluminum–garnet (Nd:YAG) laser and the Q-switched alexandrite laser (QSAL). In order to evaluate the efficacy and safety of QSAL on Chinese patients of LHS, we treated 22 patients with QSAL in the past 5 years. Treatments were delivered on a bimonthly or trimonthly basis until the abnormal pigmentation totally disappeared. Patients were evaluated at each visit for evidence of dyspigmentation, scarring, or other untoward effects from the laser treatment. Our 22 subjects consisted of 18 females and 4 males with a mean age of 42.4 years. After only one session of laser treatment, the clearing on the lips was as follow: 18 (81.8%) excellent, 2 (9.1%) good, 1 (4.5%) fair and 1 (4.5%) poor. Eighteen patients (81.8%) with LHS, who had achieved excellent clearing after only one session of laser treatment, did not receive further treatment. Among the left four patients, three patients (13.6%) achieved complete results after three laser treatments. Only one patient required six sessions to achieve complete clearance. No scarring was noted after any of the treatments. The appearance of pigmentation on mucous membranes in a middle-aged patient without a significant family history for skin disorders should prompt consideration for the possible diagnosis of LHS. Our study has also demonstrated QSAL to be highly effective and safe in the treatment of LHS. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0930-1Authors Ya-Gang Zuo, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing ChinaDong-lai Ma, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing ChinaHong-zhong Jin, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing ChinaYue-hua Liu, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing ChinaHong-wei Wang, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing ChinaQiu-ning Sun, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Department of Dermatology Beijing China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

A novel human skin chamber model to study wound infection ex vivo

Abstract Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum® and cultivated for 7 days in an air–liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (105 CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this timepoint, 1.8 × 108 CFU/g tissue of P. aeruginosa and 2 × 107 CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum® is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum® presents a convenient model and may help to standardize wound research. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1009-8Authors Lars Steinstraesser, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyM. Sorkin, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyA. D. Niederbichler, Medizinische Hochschule Hannover Department of Plastic, Hand and Reconstructive Surgery, Burn Center Hannover GermanyM. Becerikli, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyJ. Stupka, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyA. Daigeler, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyM. R. Kesting, Technische Universität München Department of Oral and Maxillofacial Surgery, Klinikum Rechts der Isar Munich GermanyI. Stricker, Ruhr University School of Medicine Department of Pathology Bochum GermanyF. Jacobsen, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum GermanyM. Schulte, Ruhr University Bochum Department of Plastic Surgery, BG University Hospital Bergmannsheil Bochum Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A single UVB exposure increases the expression of functional KIT in human melanocytes by up-regulating MITF expression through the phosphorylation of p38/CREB

Abstract KIT is an essential receptor that modulates melanocyte function and whose function is disrupted in several pigmentary disorders. However, little is known about the effects of a single UVB exposure on the expression of KIT and two important regulatory transcription factors, MITF and AP-2α, in human melanocytes. We found that a single UVB exposure of human melanocytes induces an early decrease and a subsequent increase in functional KIT expression in concert with up-regulated MITF expression. The increased MITF expression was accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB. The UVB-stimulated expression of KIT could be completely abolished by a p38 inhibitor, concomitant with a reduced phosphorylation of CREB and a down-regulation of MITF expression. Interestingly, in non-UVB exposed human melanocytes, a MEK inhibitor stimulated the phosphorylation of p38/CREB which was associated with an increased production of MITF and KIT in a pattern similar to that induced by UVB. These findings indicate that UVB stimulates functional KIT expression in human melanocytes via the up-regulation of MITF which is, in turn, due to the activation of p38 and CREB. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1007-xAuthors Yuki Mizutani, Tokyo Women’s Medical University Department of Dermatology 8-1 Kawadacho, Shinjyuku Tokyo 162-8666 JapanNobukazu Hayashi, Tokyo Women’s Medical University Department of Dermatology 8-1 Kawadacho, Shinjyuku Tokyo 162-8666 JapanMakoto Kawashima, Tokyo Women’s Medical University Department of Dermatology 8-1 Kawadacho, Shinjyuku Tokyo 162-8666 JapanGenji Imokawa, Tokyo Women’s Medical University Department of Dermatology 8-1 Kawadacho, Shinjyuku Tokyo 162-8666 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effect of epinastine hydrochloride on murine self-scratching behavior after skin-scratching stimulation

Abstract The itch–scratch cycle aggravates chronic inflammatory skin diseases. We have previously reported that mice begin to scratch themselves within several minutes after skin-scratching stimulation. This is associated with an increase in release of substance P (SP) from sensory nerve fibers in the skin, and the self-scratching behavior is suppressed by neurokinin-1 receptor (NK-1R) antagonist. Thus, SP may play a pivotal role in self-scratching behavior. The purpose of this study was to investigate the effect of second-generation histamine H1-receptor antagonists on self-scratching behavior in mice. After oral administration of epinastine hydrochloride (epinastine) (total dose 50 ± 5 mg/kg for 7 days) or the vehicle only to ICR mice for 7 days, skin-scratching stimulation was administered to the dorsal skin for 10 min. Self-scratching behavior was recorded by video camera for 10 min. Twenty-four hours later, skin tissue was harvested and stained with toluidine blue. Immunohistochemical staining for SP was performed, and SP and nerve growth factor (NGF) concentrations were measured by enzyme-linked immunosorbent assay. Self-scratching behavior, mast cell degranulation, and NGF concentration decreased, and the length of SP-positive nerve fibers and SP concentrations increased significantly in the epinastine-treated group, when compared with the vehicle control group. We conclude that epinastine inhibits mast cell degranulation by attenuating SP release from sensory nerve fibers, which results in inhibition of self-scratching behavior. These results suggest that second-generation histamine H1-receptor antagonists might efficaciously control itch–scratch cycle-related skin diseases. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1006-yAuthors Halifu Yilinuer, Nippon Medical School Department of Dermatology Sendagi 1-1-5, Bunkyo-ku Tokyo 113-8603 JapanJunichi Yamaoka, Nippon Medical School Department of Dermatology Sendagi 1-1-5, Bunkyo-ku Tokyo 113-8603 JapanSeiji Kawana, Nippon Medical School Department of Dermatology Sendagi 1-1-5, Bunkyo-ku Tokyo 113-8603 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Mid-dermal elastolysis revisited

Abstract The clinical as well as histological data of 79 mid-dermal elastolysis (MDE) patients reported in the literature were evaluated. MDE is an acquired skin condition of the elastic tissue predominantly manifesting on the trunk and proximal extremities of young women. Most commonly observed skin changes include patches of well-circumscribed fine wrinkles (type I) and perifollicular papular protrusions (type II). Rarely, MDE may also occur with persistent reticular erythema and wrinkling (type III). The critical diagnostic histopathological feature of MDE is the selective loss of elastic fibres in the mid-dermis. Mild lymphohistiocytic infiltrates, elastophagocytosis of elastic fibres by macrophages, and even multinucleate giant cells are occasionally observed in MDE lesions. Immunohistological studies and cell culture experiments indicate that dysbalances in elastin turnover are associated with pathological degradative processes including increased elastolytic activity that finally lead to loss of elastic fibres in the mid-dermis. First-line differential diagnoses may include closely related conditions such as anetoderma, annular elastolytic giant cell granuloma, cutis laxa acquisita and pseudoxanthoma elasticum-like papillary dermal elastolysis. Future therapeutic approaches in MDE patients should focus on agents that are able to block increased elastase activity and induce elastin synthesis. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-1004-0Authors Thilo Gambichler, Ruhr-University Bochum Department of Dermatology Gudrunstr. 56 44791 Bochum Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Apolipoprotein ε4 allele is associated with psoriasis severity

Abstract Many reports provided strong evidence of the influence of genetic factors in the pathogenesis of psoriasis (Ps). A higher prevalence of lipid disorders in psoriatic patients has been reported. Because apolipoprotein E (apoE) is involved in lipid metabolism, APOE gene variants could be candidates to influence Ps-risk. However, data about the potential influence of the APOE genotypes in Ps are inconclusive. Our objective was to investigate the relationship between the common APOE-ε2/ε3/ε4 variation and Ps in a Caucasian population. Our study involved 331 unrelated Ps-patients and 400 healthy controls. Patients and controls were genotyped for the APOE-ε2/ε3/ε4 polymorphism, and allele and genotype frequencies were statistically compared between the two groups and between patients according to disease severity. Mean lipid values were also compared between the APOE genotypes. Allele and genotype frequencies did not differ between patients and controls. APOE-ε4 carriers were significantly more frequent in patients with severe Ps compared to controls (P = 0.003) and to non-severe Ps (P = 0.017). No significant difference in mean lipid values was found between the APOE genotypes. The APOE-ε4 allele could be a risk factor for developing a severe form of psoriasis. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1002-2Authors Pablo Coto-Segura, Hospital Universitario Central de Asturias (HUCA) Dermatology II Department Celestino Villamil s/n 33006 Oviedo SpainEliecer Coto, HUCA Molecular Genetics Department Oviedo SpainVictoria Alvarez, HUCA Molecular Genetics Department Oviedo SpainBlanca Morales, HUCA Molecular Genetics Department Oviedo SpainJavier Soto-Sánchez, Hospital Universitario Central de Asturias (HUCA) Dermatology II Department Celestino Villamil s/n 33006 Oviedo SpainA. I. Corao, HUCA Molecular Genetics Department Oviedo SpainJorge Santos-Juanes, Hospital Universitario Central de Asturias (HUCA) Dermatology II Department Celestino Villamil s/n 33006 Oviedo Spain Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

A novel missense mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma

Abstract Multiple familial trichoepithelioma (MFT, OMIM 601606) is an autosomal dominantly inherited disease. It is characterized by numerous skin-colored papules on the central face. Pathogenic mutations in the CYLD gene have been identified. In this report, we identified a novel mutation of CYLD gene in a Chinese family with MFT. It is a novel heterozygous nucleotide G→A transition at position 2,317 in exon 17 of the CYLD gene. Our study expands the database on the CYLD gene mutations in MFT. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-1003-1Authors Fu-Xi Wang, Shenzhen Second People’s Hospital Department of Dermatology 3002 Sungang West Road 518039 Shenzhen Guangdong ChinaLi-Jia Yang, Nanjing Medical University Department of Dermatology, Affiliated Wuxi No.2 Hospital 214002 Wuxi Jiangsu ChinaMing Li, Nanjing Medical University Department of Dermatology, Affiliated Wuxi No.2 Hospital 214002 Wuxi Jiangsu ChinaShu-Lin Zhang, Shenzhen Second People’s Hospital Department of Dermatology 3002 Sungang West Road 518039 Shenzhen Guangdong ChinaXiao-Hong Zhu, Nanjing Medical University Department of Dermatology, Affiliated Wuxi No.2 Hospital 214002 Wuxi Jiangsu China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Association between basal, squamous cell carcinomas, dysplastic nevi and myotonic muscular dystrophy indicates an important role of RNA-binding proteins in development of human skin cancer

Abstract Myotonic muscular dystrophy (MMD) is caused by an abnormal function of RNA-binding proteins (RBP) resulting in DNA spliceopathy. A case of a patient, with MMD multiple basal and squamous cell carcinomas and dysplastic nevi, is described. The association between MMD and non-melanoma skin cancer has been reported before; however, this association was described before the genetic defect of myotonic dystrophy has been fully elucidated. The author proposes a genetic mechanism on how abnormal function of RBP can result or contribute to the development of human skin cancer and propose an explanation for this association between MMD and cutaneous carcinogenesis. Content Type Journal ArticleCategory News & ViewsDOI 10.1007/s00403-009-0997-8Authors Alexander Zemtsov, Indiana University School of Medicine Department of Clinical Dermatology 2525 University Avenue, Suite 402 Muncie IN 47303 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms

Abstract Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-1001-3Authors Joi A. Nichols, University of Alabama at Birmingham Department of Dermatology 1670 University Boulevard, Volker Hall 557 P.O. Box 202 Birmingham AL 35294 USASantosh K. Katiyar, University of Alabama at Birmingham Department of Dermatology 1670 University Boulevard, Volker Hall 557 P.O. Box 202 Birmingham AL 35294 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Optical coherence tomography imaging of psoriasis vulgaris: correlation with histology and disease severity

Abstract Epidermal thickness (ET) has been suggested as a surrogate measure of psoriasis severity. Optical coherence tomography (OCT) is a recent imaging technology that provides real-time skin images to a depth of 1.8 mm with a micrometre resolution. OCT may provide an accurate in vivo measure of ET. It is, therefore, speculated that OCT may be used in the assessment of psoriasis vulgaris. A total of 23 patients with psoriasis vulgaris were systematically evaluated by OCT imaging and skin biopsy during treatment. Biopsies were graded for disease severity, and additional evaluation was done by the physician via psoriasis area and severity index (PASI) score, and by the patient through measures such as self-administered PASI, psoriasis life stress inventory index and dermatology life quality index. ET was calculated from OCT images. In comparison to normal skin, psoriasis appeared with a more irregular surface with a stronger entrance signal, a serrated dermo-epidermal junction was found and a less signal intensity in the dermis as shown in OCT images. ET measured in untreated plaques was thicker reflecting epidermal hyperproliferation and inflammation. The changes were significantly correlated with the biopsy grading (r 2 = 0.41, p = 0.001) and ET significantly decreased with treatment (p = 0.0001). ET correlated significantly with self-reported measures of disease severity, but not with physician-assessed global PASI. The data suggest that OCT may be used to measure ET in psoriasis and the measurements correlate with several other parameters of disease severity. This implies that OCT assessment of psoriatic plaques may provide a useful method for non-invasive in vivo method to follow the evolution of psoriasis lesions. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-1000-4Authors Hanan Morsy, Roskilde Hospital, University of Copenhagen Department of Dermatology, Health Sciences Faculty 4000 Roskilde DenmarkSoren Kamp, Roskilde Hospital, University of Copenhagen Department of Dermatology, Health Sciences Faculty 4000 Roskilde DenmarkLars Thrane, Risoe National Laboratory Department of Optics and Plasma Research Roskilde DenmarkNille Behrendt, Roskilde Hospital Department of Histopathology 4000 Roskilde DenmarkBirgit Saunder, Glostrup Hospital, Copenhagen University Department of Ophthalmology Glostrup DenmarkHisham Zayan, Assuit University Department of Dermatology Cairo EgyptEnsaf Abd Elmagid, Assuit University Department of Dermatology Cairo EgyptGregor B. E. Jemec, Roskilde Hospital, University of Copenhagen Department of Dermatology, Health Sciences Faculty 4000 Roskilde Denmark Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Prunella vulgaris extract and rosmarinic acid prevent UVB-induced DNA damage and oxidative stress in HaCaT keratinocytes

Abstract Solar radiation is a very important exogenous factor in skin pathogenesis and can lead to the development of a number of skin disorders. UVB irradiation is known to induce oxidative stress, inflammation and especially DNA lesions in exposed cells. It is important, therefore, to identify agents that can offer protection against UVB-caused skin damage. Natural compounds have been studied for their possible ability to control/modulate various lifestyle-related diseases. The application of plant compounds/extracts with screening, antioxidant and anti-inflammatory activities may also successfully protect the skin against UV-caused injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295–315 nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and post-treatment of HaCaT cells with PVE (5–50 mg/l) and RA (0.18–1.8 mg/l) reduced breakage together with the apoptotic process. PVE and RA also significantly eliminated ROS production and diminished IL-6 release. Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs to be demonstrated in vivo. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0999-6Authors Jitka Vostálová, Palacký University Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry Hněvotínská 3 77515 Olomouc Czech RepublicAdéla Zdařilová, Palacký University Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry Hněvotínská 3 77515 Olomouc Czech RepublicAlena Svobodová, Palacký University Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry Hněvotínská 3 77515 Olomouc Czech Republic Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Capparis spinosa protects against oxidative stress in systemic sclerosis dermal fibroblasts

Abstract High reactive oxygen species (ROS), Ha-Ras, and active ERK1/2 in fibroblasts play an essential role in the pathogenesis of systemic sclerosis (SSc). The present study was carried out to evaluate the effects of the ethanol extract from fruits of Capparis Spinosa L. (ECS) on oxidative stress and ROS-ERK1/2-Ha-Ras signal loop in SSc dermal fibroblasts in vitro. Cultured dermal fibroblasts from three SSc patients and three normal controls were treated with ECS by different concentration (10, 50, 100 μg/ml). ECS significantly reduced the production of O2 –, H2O2, and ROS in SSc fibroblasts in a dose-dependent manner. ECS effectively minimized the loss of cell viability and apoptosis induced by H2O2 in normal and SSc fibroblasts. Furthermore, the protective effect of ECS on SSc fibroblasts was more significant than on normal ones. ECS decreased the expression of P-ERK1/2 and Ha-Ras in a dose-dependent manner. In conclusion, ECS exhibits a notable activity in protecting against oxidative stress and interrupting of ROS-ERK1/2-Ha-Ras signal loop in SSc, suggesting its potential protective effects against skin sclerosis. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0998-7Authors Yue-lan Cao, Zhejiang University Department of Dermatology, Second Affiliated Hospital, School of Medicine 88 Jiefang Road 310009 Hangzhou ChinaXin Li, Hangzhou Center for Disease Control and Prevention Department of STD and AIDS Prevention 310006 Hangzhou ChinaMin Zheng, Zhejiang University Department of Dermatology, Second Affiliated Hospital, School of Medicine 88 Jiefang Road 310009 Hangzhou China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Autoantibody against one of the antioxidant repair enzymes, methionine sulfoxide reductase A, in systemic sclerosis: association with pulmonary fibrosis and vascular damage

Abstract Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis and vascular changes in the skin and internal organs with autoimmune background. It has been suggested that oxidative stress plays an important role in the development of SSc. To determine the prevalence and clinical correlation of autoantibody to methionine sulfoxide reductase A (MSRA), one of the antioxidant repair enzymes, in SSc, serum anti-MSRA autoantibody levels were examined in patients with SSc by enzyme-linked immunosorbent assay using recombinant MSRA. The presence of anti-MSRA antibody was evaluated by immunoblotting. To determine the functional relevance of anti-MSRA antibody in vivo, we assessed whether anti-MSRA antibody was able to inhibit MSRA enzymatic activity. Serum anti-MSRA antibody levels in SSc patients were significantly higher compared to controls and this autoantibody was detected in 33% of SSc patients. Serum anti-MSRA levels were significantly elevated in SSc patients with pulmonary fibrosis, cardiac involvement, or decreased total antioxidant power compared with those without them. Anti-MSRA antibodies also correlated positively with renal vascular damage determined as pulsatility index by color-flow Doppler ultrasonography of the renal interlobar arteries and negatively with pulmonary function tests. Furthermore, anti-MSRA antibody levels correlated positively with serum levels of 8-isoprostane and heat shock protein 70 that are markers of oxidative and cellular stresses. Remarkably, MSRA activity was inhibited by IgG isolated from SSc sera containing IgG anti-MSRA antibody. These results suggest that elevated anti-MSRA autoantibody is associated with the disease severity of SSc and may enhance the oxidative stress by inhibiting MSRA enzymatic activity. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0996-9Authors Fumihide Ogawa, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanKazuhiro Shimizu, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanToshihide Hara, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanEiji Muroi, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanKazuhiro Komura, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanMotoi Takenaka, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 JapanMinoru Hasegawa, Kanazawa University Graduate School of Medical Science Department of Dermatology Kanazawa JapanManabu Fujimoto, Kanazawa University Graduate School of Medical Science Department of Dermatology Kanazawa JapanKazuhiko Takehara, Kanazawa University Graduate School of Medical Science Department of Dermatology Kanazawa JapanShinichi Sato, Nagasaki University Graduate School of Biomedical Sciences Department of Dermatology 1-7-1 Sakamoto Nagasaki 852-8501 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Upregulation of chemokine (C–C motif) ligand 20 in adult epidermal keratinocytes in direct current electric fields

Abstract Electric fields (EFs) of around 100 mV/mm are present in normal healing wounds and induce the directional migration of epithelial cells. Reepithelialization during wound healing thus may be controlled in part by this electrical signal. In this study, the early transcriptional response of human epidermal keratinocytes to EFs is examined using microarrays. Increased expression of various chemokines, interleukins, and other inflammatory response genes indicates that EFs stimulate keratinocyte activation and immune stimulatory activity. Gene expression activity further suggests that interleukin 1 is either released or activated in EFs. Expression of the chemokine CCL20 steadily increases at 100 mV/mm over time until around 8 h after exposure. This chemokine is also expressed at field strengths of 300 mV/mm—above the level of endogenous wound fields. The early effects of EFs on epithelial gene expression activity identified in these studies suggest the importance of naturally occurring EFs both in repair mechanisms and for the possibility of controlling these responses therapeutically. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0995-xAuthors Jessica Amber Jennings, University of Alabama at Birmingham Department of Biomedical Engineering 1075 13th St. South Birmingham AL 35294 USADongquan Chen, Universtiy of Alabma at Birmingham Biostatistics and Bioinformatics Unit, Comprehensive Cancer Center 1530 3rd Avenue South Birmingham AL 35294 USADale S. Feldman, University of Alabama at Birmingham Department of Biomedical Engineering 1075 13th St. South Birmingham AL 35294 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effects of a three-session skin rejuvenation treatment using stabilized hyaluronic acid-based gel of non-animal origin on skin elasticity: a pilot study

Abstract The purpose of this study was to evaluate in vivo the effects of micropuncture injections of stabilized hyaluronic acid-based gel of non-animal origin (NASHA™, Restylane Vital™) on skin elasticity, a major aspect of skin ageing. Patients (n = 19) underwent a series of three treatment sessions, spaced 4 weeks apart, with NASHA injected into the lower facial cheeks. Using the suction principle, 12 parameters describing the viscoelastic properties of the skin were assessed, before each treatment session and at follow-up visits 4 and 16 weeks after the last treatment. Treatment with NASHA significantly increased skin firmness and improved its viscoelastic recovery capacities. The most significant differences from baseline were noted at the end of the study. The changes observed in this study may underlie some of the cosmetic improvements noted after treatment with NASHA. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0988-9Authors Tilmann Reuther, University of Hamburg Division of Cosmetic Sciences, Department of Chemistry Martin-Luther-King-Platz 6 20146 Hamburg GermanyJulia Bayrhammer, University of Hamburg Division of Cosmetic Sciences, Department of Chemistry Martin-Luther-King-Platz 6 20146 Hamburg GermanyMartina Kerscher, University of Hamburg Division of Cosmetic Sciences, Department of Chemistry Martin-Luther-King-Platz 6 20146 Hamburg Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Patented natural avocado sugars modulate the HBD-2 expression in human keratinocytes through the involvement of protein kinase C and protein tyrosine kinases

Abstract Skin keratinocytes constitute a protective mechanical barrier against invading microorganisms. Stimulated keratinocytes produce endogenous peptides such as the β-defensins that have direct antimicrobial activity against a broad spectrum of pathogens, including most bacteria, certain fungi and enveloped viruses. In particular, human β-defensin 2 (HBD-2) is virtually absent in normal skin and its expression in human keratinocytes requires stimulation by cytokines or bacteria. AV119, a patented avocado sugar, triggers the up-regulation of HBD-2, but the signalling mechanisms involved in this up-regulation in stimulated keratinocytes are not fully understood. In the present study, we examined the intracellular signalling pathways and nuclear responses in skin keratinocytes that contribute to HBD-2 gene expression upon stimulation with AV119. Our data provide information on signalling pathways in which the activation of protein tyrosine kinases (PTKs) and protein kinase C (PKC) takes place and leads to AP-1 and HBD-2 gene activation. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0991-1Authors Iole Paoletti, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyElisabetta Buommino, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyLaura Tudisco, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyCaroline Baudouin, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyPhilippe Msika, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyMaria Antonietta Tufano, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyAdone Baroni, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples ItalyGiovanna Donnarumma, Second University of Naples Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology Via Costantinopoli, 16 80100 Naples Italy Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

Abstract Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional changes in dendritic cells (DC). We investigated the effect of lipopolysaccharide (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and immunofluorescence and on mRNA by real-time PCR. As DC models, we used a skin DC line and DC derived from human blood monocytes. We observed that all tested chemicals increased thioredoxin-1 expression, which is only transient for irritants, being the strongest effect observed for LPS (63 ± 15%). To address the involvement of thioredoxin-1 in DC maturation, we analysed the effect of an activator of thioredoxin-1 expression, hydrogen peroxide, on CD86 expression, a marker of DC maturation. We found that hydrogen peroxide increases thioredoxin-1 and CD86 expression reinforcing thioredoxin-1 involvement in DC maturation. Because mitogen-activated protein kinases and PI3K are activated upon DC maturation, we also analysed their involvement in thioredoxin-1 modulation. We verified that LPS-induced upregulation of thioredoxin-1 expression was dependent on PI3K pathway. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0993-zAuthors Vera Francisco, University of Coimbra Center for Neuroscience and Cell Biology 3004-517 Coimbra PortugalBruno Miguel Neves, University of Coimbra Center for Neuroscience and Cell Biology 3004-517 Coimbra PortugalMaria Teresa Cruz, University of Coimbra Center for Neuroscience and Cell Biology 3004-517 Coimbra PortugalMargarida Gonçalo, Coimbra’s University Hospitals Department of Dermatology, Faculty of Medicine Praceta Dr. Mota Pinto 3004-561 Coimbra PortugalAmérico Figueiredo, Coimbra’s University Hospitals Department of Dermatology, Faculty of Medicine Praceta Dr. Mota Pinto 3004-561 Coimbra PortugalCarlos B. Duarte, University of Coimbra Center for Neuroscience and Cell Biology 3004-517 Coimbra PortugalMaria Celeste Lopes, University of Coimbra Center for Neuroscience and Cell Biology 3004-517 Coimbra Portugal Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

The UV response of the skin: a review of the MAPK, NFκB and TNFα signal transduction pathways

Abstract The sun emits different types of ultraviolet (UV) light. Our skin is a natural target of UV radiation which is involved in vitamin D3 production in our body. UV radiation at high doses is an environmental carcinogen which can elicit skin damage as well as inducing skin cancer. It can mediate inflammatory and immunological reactions through activation of receptors, DNA/RNA damage and production of reactive oxygen species. It is also involved in the release of pro-inflammatory cytokines, of which TNFα has been implicated in tumorigenic activities. In order to mediate its effects, UV radiation is known to activate multiple signalling cascades such as the p38 MAPK, Jun N-terminal kinase, extracellular signal-regulated kinase 1/2 and NFκB pathways in skin cells. The role each of these pathways plays in mediating the release of cytokines such as TNFα remains to be fully characterized. Once the function of these pathways is known, this information may provide for the formulation of therapy which will prevent the release of immunosuppressive cytokines resulting in a reduction in skin cancer formation. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-0994-yAuthors Visalini Muthusamy, RMIT University School of Medical Sciences PO Box 71 Bundoora VIC 3083 AustraliaTerrence J. Piva, RMIT University School of Medical Sciences PO Box 71 Bundoora VIC 3083 Australia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Lymphocyte subsets in peripheral blood of patients with psoriasis before and after treatment with leishmania antigens

Abstract Peripheral blood mononuclear cells (PBMC) collected from subjects prior to treatment and post-treatment with a vaccine composed of leishmania antigens were analyzed by flow cytometry. Upon analysis, it was noticed that lymphocyte subsets (LS) varied with psoriasis area and severity index (PASI) range (1–10, 11–20 and 21–72). Pre-treatment absolute values of gated LS were as follows. CD4+CD8−, CD3+CD8−, CD8+CD3+, CD8+CD4− and CD8+HLA− decreased in PBMC as PASI increased, suggesting migration from the blood to the skin. Contrary to the previous finding, the following LS, CD8+HLA+ and HLA+CD8−, and membrane surface immunoglobulin IgA+, IgD+ and IgM+ increased in PBMC as PASI increased, suggesting activation and proliferation by unknown antigens. After treatment with seven doses of AS100, the following LS, CD3+CD8−, CD8+CD3−, HLA+CD8−, CD8+HLA+ and CD4+CD8−, increased, while CD8+CD3+, CD8+HLA−, CD19 and CD8+CD4+ decreased in PBMC. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0992-0Authors Jose Antonio O’Daly, Astralis LTD. 75 Passaic Ave. Fairfield NJ 07004 USABeatriz Rodriguez, Instituto Venezolano de Investigaciones Científicas Altos de Pipe Km. 10 Carretera Panamericana Caracas 1010A VenezuelaTania Ovalles, Instituto Venezolano de Investigaciones Científicas Altos de Pipe Km. 10 Carretera Panamericana Caracas 1010A VenezuelaCivel Pelaez, Center for Psoriasis Research and Treatment Ave. Las Ciencias, Calle Codazzi, Los Chaguaramos Caracas Venezuela Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Rhodiola rosea ability to enrich cellular antioxidant defences of cultured human keratinocytes

Abstract Keratinocytes are cells strongly exposed to oxidative stress, but normally good equipped for antioxidant responses. However, it has long been suggested that exogenous antioxidants could play a useful role in minimizing the adverse skin responses associated with such oxidant species. In this work it was paid attention to the extract of Rhodiola rosea L. roots by using the phytocomplex as a whole because of the important activity of its composition and mutual distribution of its components. We have measured the protection afforded by the extract to reduced glutathione levels, glyceraldehyde-3-phosphate dehydrogenase activity, and thiobarbituric acid reactive substances levels in cultured human keratinocytes (NCTC 2544) exposed to different oxidative insults: Fe(II)/ascorbate, Fe(II)/H2O2, and tert-butyl-hydroperoxide. We also have investigated the influence of the R. rosea extract on the production of intracellular reactive oxygen species and on the activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). Furthermore, we have demonstrated that R. rosea extract was able to increase in a time- and dose-dependent manner the activity of the trans plasma membrane oxido reductase activity as an indirect evaluation of the intracellular redox status and this effect was already evident with small concentration of the extract and in a long time. As a result, NCTC 2544 are able to better counteract to several oxidative insults if incubated with R. rosea extract demonstrating a very good antioxidant activity of this phytocomplex. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0985-zAuthors Cinzia Calcabrini, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyRoberta De Bellis, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyUmberto Mancini, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyLuigi Cucchiarini, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyLucia Potenza, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyRoberta De Sanctis, Università degli Studi di Urbino “Carlo Bo” Istituto di Chimica Biologica “Giorgio Fornaini” Via A. Saffi, 2 61029 Urbino PU ItalyVania Patrone, Università degli Studi di Urbino “Carlo Bo” Istituto di Igiene Urbino PU ItalyCarla Scesa, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia Rome ItalyMarina Dachà, Università Campus Bio-Medico Rome Italy Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Genetic evidence for involvement of the IL23 pathway in Thai psoriatics

Abstract A recent genome-wide association analysis of psoriasis identified IL12B and IL23R as significantly associated with psoriasis. Here we report association test results of a Thai cohort consisting of 206 psoriasis cases and 114 controls. The IL23R SNPs rs7530511 and rs11209026, and IL12B SNPs rs3212227 and rs6887695 were genotyped using Taqman assays. Data were analyzed using a logistic regression model for linear trend of association. One of the IL23R markers, rs7530511, was marginally significant (P = 0.017). The other IL23R marker, rs11209026, was not polymorphic. One of the IL12B markers, rs3212227, showed significant association with psoriasis (OR = 1.64, P = 0.0058) while the other, rs6887695, did not (OR = 1.29, P = 0.12). Haplotype analysis of the two IL12B SNPs yielded highly significant association (P = 0.00081, OR = 1.73). These results showed that IL12B is an important genetic factor in psoriasis pathogenesis in the Thai population, with an association strong enough to yield significant confirmatory evidence using a modest sample size. Together with previously reported evidence for IL12B association in Caucasian, Japanese, and Chinese psoriatics, our results support the hypothesis that genes encoding components of the IL23-mediated inflammatory pathway are important determinants of psoriasis pathogenesis across multiple racial groups. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0986-yAuthors Rajan P. Nair, University of Michigan Department of Dermatology 3430 CCGC, Box 5932 1500 East Medical Center Dr. Ann Arbor MI 48109-5932 USAPhilip E. Stuart, University of Michigan Department of Dermatology 3430 CCGC, Box 5932 1500 East Medical Center Dr. Ann Arbor MI 48109-5932 USAPreya Kullavanijaya, Institute of Dermatology Bangkok ThailandPrisana Kullavanijaya, Institute of Dermatology Bangkok ThailandTrilokraj Tejasvi, University of Michigan Department of Dermatology 3430 CCGC, Box 5932 1500 East Medical Center Dr. Ann Arbor MI 48109-5932 USAJohn J. Voorhees, University of Michigan Department of Dermatology 1910 TC, Box 5314 1500 East Medical Center Dr. Ann Arbor MI 48109-5314 USAJames T. Elder, University of Michigan Department of Dermatology 3312 CCGC, Box 5932 1500 East Medical Center Dr. Ann Arbor MI 48109-5932 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 2 / March, 2010

Expression and function of glycogen synthase kinase-3 in human hair follicles

Abstract β-Catenin is involved in the hair follicle morphogenesis and stem cell differentiation, and inhibition of glycogen synthase kinase-3 (GSK-3) increases β-catenin concentration in the cytoplasm. To examine the effects of GSK-3 inhibition on the hair follicle epithelium, we first examined the expression of GSK-3 in plucked human hair follicles by RT-PCR and found GSK-3 expression in hair follicles. Western blotting with a GSK-3β-specific antibody, Y174, also demonstrated GSK-3β expression in the follicles. Moreover, GSK-3β immunostaining with Y174 showed that GSK-3β colocalized with hair follicle bulge markers. Contrary to GSK-3β, GSK-3α was widely expressed throughout the follicles when immunostained with a specific antibody, EP793Y. We then investigated the influence of GSK-3 inhibition. A GSK-3 inhibitor, BIO, promoted the growth of human outer root sheath cells, which could be cultured for up to four passages. The BIO-treated cells exhibited smaller and more undifferentiated morphology than control cells. Moreover, in organ culture of plucked human hair, outer root sheath cells in the middle of a hair follicle proliferated when cultured with BIO. These results indicate that GSK-3β is expressed in hair bulge stem cells and BIO promotes the growth of ORS cells, possibly by regulating the GSK-3 signaling pathway. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0987-xAuthors Koichi Yamauchi, Hair Clinic Reve-21 Corporation 2-1-61 Shiromi, Chuo-ku Osaka 540-6122 JapanAkira Kurosaka, Kyoto Sangyo University Department of Biotechnology, Faculty of Engineering Kamigamo-motoyama, Kita-ku Kyoto 603-8555 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Comparison between human fetal and adult skin

Abstract Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22 weeks’ gestation) and adult skin biopsies, the expression patterns of several epidermal proteins (K10, K14, K16, K17, SKALP, involucrin), basement membrane proteins, Ki-67, blood vessels and extracellular matrix proteins (fibronectin, chondroitin sulfate, elastin) were determined using immunohistochemistry. The expression profiles of K17, involucrin, dermal Ki-67, fibronectin and chondroitin sulfate were higher in the fetal skin than in adult skin. In the fetal skin, elastin was not present in the dermis, but it was found in the adult skin. The expression patterns of basement membrane proteins, blood vessels, K10, K14, K16 and epidermal Ki-67 were similar in human fetal skin and adult skin. In this systematic overview, most of the differences between fetal and adult skin were found at the level of dermal extracellular matrix molecules expression. This study suggests that, especially, dermal components are important in fetal scarless healing. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0989-8Authors Neeltje A. Coolen, Association of Dutch Burn Centres P.O. Box 1015 1940 EA Beverwijk The NetherlandsKelly C. W. M. Schouten, Association of Dutch Burn Centres P.O. Box 1015 1940 EA Beverwijk The NetherlandsEsther Middelkoop, Association of Dutch Burn Centres P.O. Box 1015 1940 EA Beverwijk The NetherlandsMagda M. W. Ulrich, Association of Dutch Burn Centres P.O. Box 1015 1940 EA Beverwijk The Netherlands Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Behçet’s disease: an algorithmic approach to its treatment

Abstract Behçet’s disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology with the clinical features of mucocutaneous lesions, ocular, vascular, articular, gastrointestinal, urogenital, pulmonary, and neurologic involvement. Mucocutaneous lesions figure prominently in the presentation and diagnosis, and may be considered the hallmarks of BD. Therefore, their recognition may permit earlier diagnosis and treatment. Although, the treatment has become much more effective in recent years, BD is still associated with severe morbidity and considerable mortality. The main aim of the treatment should be the prevention of irreversible organ damage. Therefore, close monitoring, early and appropriate treatment is mandatory to reduce morbidity and mortality. We reviewed the current state of knowledge regarding the therapeutic approaches for BD and designed a stepwise, symptom-based, algorithmic approach, mainly based on controlled studies and our clinical experience in this field to provide a rational framework for selecting the appropriate therapy along the various treatment choices. Content Type Journal ArticleCategory Mini ReviewDOI 10.1007/s00403-009-0990-2Authors Erkan Alpsoy, Akdeniz University School of Medicine Department of Dermatology and Venerology Antalya 07070 TurkeyAyse Akman, Akdeniz University School of Medicine Department of Dermatology and Venerology Antalya 07070 Turkey Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 10 / October, 2009

PCR analysis for Wolbachia in human and canine Demodex mites

Abstract In many skin diseases such as Demodex folliculitis, rosacea- or steroid-induced rosacea Demodex mites are present in abundance and are at least partially held responsible for causing these disorders. Although it is known that these diseases respond well to tetracyclines, it is unclear if this is due to the antiinflammatory effects of the antibiotics or to an antibacterial effect on so far unknown bacteria within the Demodex mites. As in filariasis, where the response to doxycycline can be explained by the presence of Wolbachia within the filarial nematodes, this study was performed to see whether Wolbachia also use Demodex mites as their hosts. Human and canine Demodex mite samples were taken by skin scrapings and tested by PCR for the presence of Wolbachia DNA. Wolbachia pipientis DNA was used as positive control. In none of the DNA extracts, Wolbachia were detected showing no evidence for the presence of these bacteria in Demodex mites. The response of Demodex aggravated or Demodex caused diseases to tetracyclines seems not to be due to the presence of Wolbachia in Demodex mites in contrast to the results seen in filariasis. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0984-0Authors Sibylle N. Borgo, Ludwig-Maximilian-University Department of Dermatology and Allergology Frauenlobstrasse 9-11 80337 Munich GermanyElke C. Sattler, Ludwig-Maximilian-University Department of Dermatology and Allergology Frauenlobstrasse 9-11 80337 Munich GermanyMichael Hogardt, Ludwig-Maximilian-University Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Munich GermanyKristin Adler, Ludwig-Maximilian-University Max von Pettenkofer-Institute for Hygiene and Medical Microbiology Munich GermanyGerd Plewig, Ludwig-Maximilian-University Department of Dermatology and Allergology Frauenlobstrasse 9-11 80337 Munich Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 10 / October, 2009

Topical tamoxifen therapy in hypertrophic scars or keloids in burns

Abstract As acute burn patients have experienced increasing survival rates, the number of patients who need specific care due to aberrant scarring is also increasing. The burned skin often responds with fibrotic tissue proliferation, which can lead to a hypertrophic scar or a keloid. Non-physiologic scars are mostly not acceptable for the burn patient. Intradermal and topical therapy in burns comprise the treatment of the skin injury and its possible texture, elasticity and color alterations with the aid of active substances that result in fibroblastic modulation. An alteration of cytokine levels may mediate these effects, and evidences suggest that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF)-β1. The addition of tamoxifen, a non-steroidal anti-estrogen, usually used in breast cancer, to standard treatment may lead to improved wound healing in keloids by decreasing the expression of TGF-β1, with the consequent inhibitions of both fibroblast proliferation and collagen production. Topical tamoxifen citrate chemical treatment has been shown to improve scarring. However, prospective studies must be undertaken to validate the inclusion of tamoxifen into standard clinical practice. Content Type Journal ArticleCategory News and ViewsDOI 10.1007/s00403-009-0983-1Authors Alfredo Gragnani, Federal University of Sao Paulo Division of Plastic Surgery, Department of Surgery Napoleão de Barros St 715, 4th Floor Sao Paulo 04024-002 SP BrazilMario Warde, Federal University of Sao Paulo Division of Plastic Surgery, Department of Surgery Napoleão de Barros St 715, 4th Floor Sao Paulo 04024-002 SP BrazilFabianne Furtado, Federal University of Sao Paulo Division of Plastic Surgery, Department of Surgery Napoleão de Barros St 715, 4th Floor Sao Paulo 04024-002 SP BrazilLydia Masako Ferreira, Federal University of Sao Paulo Division of Plastic Surgery, Department of Surgery Napoleão de Barros St 715, 4th Floor Sao Paulo 04024-002 SP Brazil Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 302 Journal Issue Volume 302, Number 1 / January, 2010

Validity, reliability, and sensitivity-to-change properties of the psoriatic arthritis screening and evaluation questionnaire

Abstract Psoriatic arthritis (PsA) is an inflammatory arthritis associated with irreversible joint damage in a subset of individuals. There is a need to screen early for this condition to prevent damage. To meet this need, we have developed the psoriatic arthritis screening and evaluation (PASE) questionnaire. The 15-item PASE questionnaire was administered to 190 individuals with either psoriasis or PsA. The PASE questionnaire was readministered to a subset of individuals with PsA in order to assess test–retest reliability and sensitivity-to-change. Receiver operator curves were constructed to optimize sensitivity and specificity for the diagnosis of PsA. Of the 190 participating in the study, 19.5% (37/191) participants were diagnosed with PsA. PASE total scores ranged from 15 to 74 (possible range, 15–75). The PsA group had a median Total score of 51 (25th and 75th percentile 44 and 57), and non-PsA group had a median total score of 34 (25th and 75th percentile 21 and 49) (p < 0.001). A PASE total score of 44 was able to distinguish PsA from non-PsA participants with 76% sensitivity and 76% specificity. Furthermore, 13 of the 15 items demonstrated significant test–retest reliability as assessed by Pearson correlation coefficient (r ≥ 0.5). PASE was sensitive-to-change with therapy; PASE scores were significantly lower for PsA individuals after systemic therapy (p < 0.034). The PASE questionnaire is a valid and reliable tool to screen for active PsA among individuals with psoriasis. PASE scores may be used as a marker of therapeutic response. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0981-3Authors Patrick Lee Dominguez, Harvard Medical School Department of Dermatology, Center for Skin and Related Musculoskeletal Diseases, Brigham and Women’s Hospital (BWH) 45 Francis St, 221L Boston MA 02115 USAM. Elaine Husni, Cleveland Clinic Foundation Department of Rheumatologic and Immunologic Diseases Cleveland OH USAElizabeth W. Holt, Tulane School of Public Health and Tropical Medicine Department of Epidemiology New Orleans LA USAStephanie Tyler, Harvard Medical School Department of Dermatology, Center for Skin and Related Musculoskeletal Diseases, Brigham and Women’s Hospital (BWH) 45 Francis St, 221L Boston MA 02115 USAAbrar A. Qureshi, Harvard Medical School Department of Dermatology, Center for Skin and Related Musculoskeletal Diseases, Brigham and Women’s Hospital (BWH) 45 Francis St, 221L Boston MA 02115 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 8 / September, 2009

Decrease in Mycobacterium tuberculosis specific immune responses in patients with untreated psoriasis living in a tuberculosis endemic area

Abstract Tuberculosis has emerged as a major concern in patients with immuno-mediated diseases, including psoriasis, undergoing treatment with biologicals. However, it is not known whether the chronically activated immune system of psoriasis patients interferes with their Mycobacterium tuberculosis (Mtb)-specific immunity, especially in tuberculosis-endemic areas like Brazil. We evaluated T-cell responses to a Mtb lysate and to the recombinant Mtb proteins ESAT-6 and Ag85B of tuberculin skin test (TST) positive and TST negative patients with severe or mild/moderate, untreated psoriasis in three different assays: lymphocyte proliferation, enzyme immunoassay for interferon (IFN)-γ and interleukin (IL)-10 production by peripheral blood mononuclear cells and overnight enzyme immunospot (ELISpot) for enumerating IFN-γ-secreting cells. In our cohort, a low proportion (29%) of the severe psoriasis patients tested were TST-positive. IFN-γ and IL-10 secretion and T-cell proliferation to Mtb antigens were reduced in TST-negative but not in TST-positive patients with severe psoriasis when compared to healthy controls with the same TST status. Similarly, severe psoriasis patients had decreased cytokine secretion and proliferative response to phytohemagglutinin. However, most psoriasis patients and healthy controls showed detectable numbers of IFN-γ-secreting effector-memory T-cells in response to Mtb antigens by ELISpot. TST-negative, mild/moderate psoriasis patients had responses that were mostly intermediary between TST-negative controls and severe psoriasis patients. Thus, patients with severe psoriasis possess decreased anti-Mtb central memory T-cell responses, which may lead to false-negative results in the diagnosis of TB infection, but retain T-cell memory-effector activity against Mtb antigens. We hypothesize that the latter may confer some protection against tuberculosis reactivation. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0982-2Authors Léia C. R. Silva, Medical School of the University of São Paulo Laboratory of Dermatology and Immunodeficiencies Av. Dr. Enéas de Carvalho Aguiar 500 3º. Floor Sao Paulo BrazilGuilherme G. Silveira, Medical School of the University of São Paulo Laboratory of Dermatology and Immunodeficiencies Av. Dr. Enéas de Carvalho Aguiar 500 3º. Floor Sao Paulo BrazilMarcelo Arnone, Medical School of the University of São Paulo Division of Clinical Dermatology, Hospital das Clínicas Av. Dr. Enéas de Carvalho Aguiar 255 Sao Paulo BrazilRicardo Romiti, Medical School of the University of São Paulo Division of Clinical Dermatology, Hospital das Clínicas Av. Dr. Enéas de Carvalho Aguiar 255 Sao Paulo BrazilAnnemiek Geluk, Leiden University Medical Center Department of Infectious Diseases Leiden The NetherlandsKees C. L. M. Franken, Leiden University Medical Center Department of Infectious Diseases Leiden The NetherlandsAlberto José da Silva Duarte, Medical School of the University of São Paulo Laboratory of Dermatology and Immunodeficiencies Av. Dr. Enéas de Carvalho Aguiar 500 3º. Floor Sao Paulo BrazilMaria Denise Fonseca Takahashi, Medical School of the University of São Paulo Division of Clinical Dermatology, Hospital das Clínicas Av. Dr. Enéas de Carvalho Aguiar 255 Sao Paulo BrazilGil Benard, Medical School of the University of São Paulo Laboratory of Dermatology and Immunodeficiencies Av. Dr. Enéas de Carvalho Aguiar 500 3º. Floor Sao Paulo Brazil Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A new two-phase dimeticone pediculicide shows high efficacy in a comparative bioassay

Background: Dimeticones kill head lice by physical means. Here we assessed in a comparative bioassay the ex vivo efficacy of "NYDA® sensitiv", a new two-phase dimeticone-based pediculicide similar to a product established on the market, but without fragrances. Methods: We compared efficacy of the new product to a positive dimeticone control group, a sample of four other insecticidal and natural head lice products marketed in Germany, and an untreated control. In a bioassay, lice were exposed ex vivo to products and examined for activity for up to 24 hours, following a standard protocol. Results: After 6 and 24 hours, 13.7 and 88.5% of untreated control lice did not show major vital signs. In contrast, no lice showed major vital signs 5 minutes after treatment with the new product or the control dimeticone group (NYDA®). This effect persisted at all observation points (100% efficacy). Efficacy of 0.5% permethrin (Infectopedicul®) ranged between 76 and 96% in evaluations between 5 min and 6 hours. All lice treated with a coconut-based compound (mosquito® Läuseshampoo) did not show major vital signs after 5 min, but mortality was only 58% after one hour. Pyrethrum extract (Goldgeist® forte) showed an efficacy of 22 - 52% between 5 min and 3 hours after treatment; after 6 hours, 76% of lice were judged dead. An oxyphthirine®-based compound (Liberalice DUO LP-PRO®) killed 22 - 54% of lice in the first 6 hours. Conclusions: The two-phase dimeticone compound NYDA® sensitiv is highly efficacious. The removal of fragrances as compared to an established dimeticone product did not affect in vitro efficacy.

Attitudes of dermatologists in the southeastern United States regarding treatment of alopecia areata: a cross-sectional survey study.

Background: Little evidence exists to guide treatment of alopecia areata (AA). The current practices in treatment of children compared to adults and of progressive stages of hair loss are unknown. The objective of this study was to examine the current practices of southeastern United States dermatologists for the treatment of AA. Methods: Dermatologists were sent anonymous questionnaires regarding their treatment practices by mail. Respondents' frequencies of treatment in children compared to adults and in patchy hair loss compared to widespread hair loss were compared with Wilcoxon signed-ranks tests and Friedman tests. As a secondary source, the National Alopecia Areata Registry (NAAR) database was analyzed for patients' treatment histories. Results: Survey results suggested that dermatologists recommend treatment less frequently for children than adults and for more advanced hair loss. NAAR data confirmed that offering no treatment for AA is relatively common. Conclusion: Dermatologists' treatment of AA is inconsistent. A stronger evidence base will provide more consistent treatment options.

Professional use of the internet among Saudi Arabian dermatologists: a cross-sectional survey

Background: The internet is an increasingly important tool for physicians, but the extent to which it is used by dermatologists is unknown. We aimed to investigate the utilization of the internet by dermatologists in Saudi Arabia for medical purposes during their daily practice and to clarify the reasons for its use and non-use. Methods: A self-administered questionnaire was distributed to all 160 dermatologists attending the National Dermatology conference in 2007. Results: A total of 107 questionnaires were completed. Sixty-two percent of respondents had access to the internet in the workplace. The use of the internet to update medical knowledge was reported by 91%.Only 27% had internet access in consultation rooms. The majority of information retrieval occurred outside patient consultation hours (91%).Only 13% reported using the internet during patient consultation. Possible reasons included: lack of access (54%), time pressure (37%), possible interference with the physician-patient relationship (30%), and that use of the internet was too time-consuming (10%). The mean searching time used to solve a clinical problem was 34 ± 3 minutes. Fifty-eight percent used Pubmed; however, 77% of the dermatologists had no training at all in how to use this tool. Conclusion: Professional medical use of the internet is widespread among dermatologists in Saudi Arabia. Providing access to the internet in the workplace and training of dermatologists to perform effective electronic searches are badly needed to improve the professional medical use of internet, which is expected to lead to better delivery of patient care.

Volumizing effects of a smooth, highly cohesive, viscous 20-mg/mL hyaluronic acid volumizing filler: prospective European study

Background: Facial volume loss contributes significantly to facial aging. The 20-mg/mL hyaluronic acid (HA) formulation used in this study is a smooth, highly cohesive, viscous, fully reversible, volumizing filler indicated to restore facial volume. This first prospective study evaluated use in current aesthetic clinical practice. Methods: A pan-European evaluation conducted under guidelines of the World Association of Opinion and Marketing Research, the trial comprised a baseline visit (visit 1) and a follow-up (visit 2) at 14 ± 7 days posttreatment. Physicians photographed patients at each visit. Each patient was treated with the 20-mg/mL HA volumizing filler as supplied in standard packaging. Procedural details, aesthetic outcomes, safety, and physician and patient ratings of their experience were recorded. Results: Fifteen physicians and 70 patients (91% female; mean age: 50 years) participated. Mean volume loss at baseline was 3.7 (moderate) on the Facial Volume Loss Scale. Local anesthesia was used in 64.3% of cases. Most injections (85%) were administered with needles rather than cannulas. Of the 208 injections, 59% were in the malar region, primarily above the periosteum. Subcutaneous injections were most common for other sites. The mean total injection volume per patient was 4.6 mL. The mean volume loss score declined significantly (P < .001) to 2.1 at visit 2. On the Global Aesthetic Improvement Scale, 88% and 76% of the treatments were rated very much improved or much improved by physicians and patients, respectively. Of the physicians, 95.6% rated this HA filler as very or fairly easy to use. Similarly, 92% of patients were very likely or quite likely to return for treatment; nearly all (98%) would recommend this treatment to friends. Transient (mean duration: 5.5 days) injection-site adverse events (AEs) occurred in 24 patients. Bruising was the most common AE. Conclusion: The 20-mg/mL smooth, highly cohesive, viscous, volumizing HA filler was effective, well tolerated, and easy to use in current clinical practice. Participants were very likely to recommend this product to colleagues and friends, and patients would be very or quite likely to request this product for future treatments.

Familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity

Background: Familial keloids have been reported, having either autosomal dominant or autosomal recessive inheritance. We wished to determine the inheritance pattern and phenotype of keloids among multigenerational families, as a prelude to a positional mapping strategy to identify candidate genes. Methods: We studied three African American families, one Afro-Caribbean family and one Asian-American family. Phenotyping including assessing all patients for the presence, distribution, and appearance of keloids, together with the timing of keloid onset and provocative factors. The clinical trial was registered at clinicaltrials.gov (NCT 00005802). Results: Age of keloid onset varied considerably within families, but commonly occurred by the second decade. The fraction of affected individuals was 38%, 45%, 62%, 67% and 73% among the five families respectively. Keloid severity and morphology differed within and between families. A novel finding is that certain families manifest keloids in distinct locations, with one family showing an excess of extremity keloids and two families showing an excess of axilla-groin keloids. Conclusion: Familial keloids appear to most commonly manifest autosomal dominant or semidominant inheritance, and there may be familial patterns of keloid distribution.

Role of the EGF +61A>G polymorphism in melanoma pathogenesis: an experience on a large series of Italian cases and controls.

Background: A single nucleotide polymorphism (61A>G) in the epidermal growth factor (EGF) gene has been implicated in both melanoma pathogenesis and increased melanoma risk. To further evaluate this association, we conducted a case-control study in a clinic-based Italian population. Methods: Individuals with less than 10 (N = 127) or more than 100 (N = 128) benign nevi, and patients with cutaneous melanoma (N = 418) were investigated for the EGF +61A>G polymorphism, using an automated sequencing approach. Results: Overall, no difference in EGF genotype frequencies was observed among subjects with different number of nevi as well as when non-melanoma healthy controls were compared with the melanoma patients. However, a heterogeneous distribution of the frequencies of the G/G genotype was detected among cases and controls originating from North Italy (21.1 and 18.3%, respectively) vs. those from South Italy (12.6 and 17.1%, respectively). Conclusion: Our findings further suggest that EGF +61A>G polymorphism may have a limited impact on predisposition and/or pathogenesis of melanoma and its prevalence may vary in different populations.

A population-based survey on tanning bed use in Germany

Background: The suntanning industry has grown up over the last decade in Europe, mainly because tanned skin is considered socially desirable and attractive. Because of the potential negative impact of artificial tanning on public health, this study was to investigate tanning bed use behaviour, UV related risk perception and beliefs about tanning in the German population. Methods: In 2007, a representative telephone survey was carried out among 1501 German residents aged 14 years and older. Results: More than one fourth (28%) of the German population have used tanning beds at least once before in their lifetime. High-frequency tanning behaviour, i.e. using tanning beds more than 10 times per year, were recorded for 11%. Men and women aged 18 to 44 years and young women under the age of 18 used tanning beds more frequently (>10 times per year). Tanning bed use was positively related to appearance and lifestyle related beliefs as well as to the perception that tanned skin is healthy. Conclusion: This analysis indicates that tanning bed use is common in Germany. The positive relationships of appearance and health related beliefs with tanning bed use are of great concern. The results indicate underlying misconceptions about the positive effect of artificial UV radiation compared to natural UV radiation particular for high-frequency tanners. The data shows the importance as well as the limitations for risk communication in its current effort to inform effectively about the dangers of artificial UV radiation.

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

Background: The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. In vitro data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients. Methods: We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping.The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test. Results: Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls.The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively. Conclusion: These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.

Prevalence and characteristics of aquagenic pruritus in a young African population

Background: Aquagenic pruritus (AP) occurs during or after contact of the skin with water such as occurs in bathing. Methods: This study aims to describe the prevalence of aquagenic pruritus in a young adult population and describe the circumstances of bathing.A Population-based cross sectional study involving administration of Questionnaires to young adult Nigerians on the occurrence of pruritus associated with bathing. Results: The prevalence of bathing pruritus among respondents in this study was 23.8%. The commonest type of water respondents itch to was rain water (23%) followed by cold water (19%). 8.33% of respondents feels like avoiding bathing because of these. Conclusion: Bathing pruritus is a common finding among young adult Nigerians in the general population.

Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection

Background: Herpes simplex virus infection (HSV) is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis) or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores), using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm2 of acyclovir 5% cream or penciclovir 1% cream. Methods: After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physico-chemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results: Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion: Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of penciclovir through the epidermis into the deeper basal cells.