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ABOUT THIS JOURNAL: About This Journal

THIS MONTH IN ARCHIVES OF DERMATOLOGY: This Month in Archives of Dermatology

ARCHIVES A CENTURY AGO: Multiple Dactylitis Syphilitica (Phalangitis Heredo-Syphilitica, Hochsinger) in an Infant.

THE CUTTING EDGE: Treatment of Refractory Chronic Urticaria With Sirolimus

STUDY: Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases: Optimal Levels as Adjunctive Tools for Azathioprine Monitoring

Objective To prospectively determine optimal levels of 6-thioguanine nucleotide for disease remission in patients with immunobullous disease treated with azathioprine. Design Prospective, longitudinal study. Laboratory tests and clinical evaluations were performed monthly for 6 months and then every 2 to 3 months (median follow-up, 13.4 months). Setting Tertiary care medical center. Patients Twenty-seven patients with immunobullous disease treated with azathioprine were enrolled during a 2-year period. Twelve met the criteria for evaluation of optimal levels of 6-thioguanine nucleotide. Main Outcome Measures Blood levels of 6-thioguanine nucleotide, 6-methylmercaptopurine, and thiopurine methyltransferase by polymerase chain reaction and enzyme activity were measured longitudinally during treatment. Results The range of 6-thioguanine nucleotide was 48 to 457 pmol/8 x 108 red blood cells (RBCs), with an average optimal level of 190.7 pmol/8 x 108 RBCs for all patients. The mean optimal levels were 179.4 and 205.6 pmol/8 x 108 RBCs for pemphigus and pemphigoid, respectively. Limited disease required less 6-thioguanine, with a mean of 145.3 pmol/8 x 108 RBCs. Longitudinal induction of thiopurine methyltransferase activity was observed during treatment. Patients with recalcitrant disease showed higher induction of enzyme activity (with an increase of 9.1 to 23.6 U/mL of RBCs above baseline) than did those with responsive disease. Conclusions Optimal levels of 6-thioguanine nucleotide metabolites for disease remission in dermatology patients are 150 to 300 pmol/8 x 108 RBCs. High levels of the inactive metabolite 6-methylmercaptopurine and induction of thiopurine methyltransferase are associated with recalcitrant disease.

ANNOUCEMENT: Archives Feature

STUDY: Clinical and Mutational Heterogeneity of Darier Disease in Tunisian Families

Objective To study the mutation spectrum and phenotype-genotype correlation of Darier disease (DD) in Tunisian patients. Design Case series. Setting Referral center: Department of Dermatology (La Rabta Hospital), Tunis, Tunisia. Patients Eight large Tunisian families with DD, with a total of 23 patients and 9 unaffected family members. Main Outcome Measure Patients were investigated at the clinical, histological, and genetic levels. Families were genotyped with 5 microsatellite markers spanning the ATP2A2 gene. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Results Typical clinical features of DD were constantly present. Phenotypic variation within and between the studied families was observed. Different neuropsychiatric disorders were seen in 5 families, and various cutaneous and extracutaneous original clinical associations were observed. The haplotype analysis led to the identification of different haplotypes cosegregating with the disease in the studied families. Mutation screening of the ATP2A2 gene revealed 3 recurrent mutations (119-120delAG, R677X, and D702N) and 4 novel variations: 2 missense mutations (G217A and L900R), one microinsertion (2772-2779 ins C), and one microdeletion (1747-1749 del 2T). Conclusions Our findings provide evidence for clinical and mutational heterogeneity of Tunisian families with DD. No obvious phenotype-genotype correlation was established. To our knowledge, this is the first molecular investigation of DD in the North African population.

NOTABLE NOTES: Marie Antoinette Syndrome

STUDY: Topical Fluorouracil for Actinic Keratoses and Photoaging: A Clinical and Molecular Analysis

Objective To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses. Design Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation. Setting Academic referral center. Patients Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment. Main Outcome Measures Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires. Results One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1β), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again. Conclusions Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.

CALL FOR PAPERS: Notable Notes

STUDY: Prognostic Factors in Primary Cutaneous Anaplastic Large Cell Lymphoma: Characterization of Clinical Subset With Worse Outcome

Objectives To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL. Design Retrospective cohort study. Setting The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics. Patients A total of 48 patients with pcALCL evaluated from 1990 through 2005. Main Outcome Measures Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays. Results Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters. Conclusions Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

OBSERVATION: Primary Cutaneous T-Cell Lymphoma Localized to the Lower Leg: A Distinct, Locally Aggressive Cutaneous T-Cell Lymphoma

Background Distinct categories of skin lymphoma with preferential site localization and unique clinical behavior, including leg-type primary cutaneous diffuse large B-cell lymphoma, have recently been described. Although these entities are rare, they exhibit reproducible clinicopathologic features, and their recognition may allow more appropriate treatment protocols. Observations We describe the distinctive clinicopathologic features that were observed in 3 patients with an unusual variant of primary cutaneous T-cell lymphoma. All cases originated on the legs of elderly patients and exhibited a locally aggressive clinical behavior with relatively rapid relapses after radiotherapy and resistance to other therapies. Histologically, dense dermal-centered infiltrates of atypical, variably sized mature helper T cells were identified. One patient died of progressive disease. Conclusions Rare cases of primary cutaneous lymphomas do not necessarily fit current criteria for a standard diagnostic category but may represent unique clinicopathologic entities, such as primary cutaneous T-cell lymphoma localized to the lower leg. It is important to be able to identify these unusual lymphoma variants for prognosis and adequate treatment. The aggressive nature of lymphomas preferentially localized on the lower extremities may not be restricted to B-cell or cytotoxic neoplasms.

OBSERVATION: Ioversol-Induced Acute Generalized Exanthematous Pustulosis: A Case Report

Background Acute generalized exanthematous pustulosis (AGEP) is a relatively rare exfoliative dermatosis consisting of a generalized eruption of sterile, nonfollicular pustules arising on widespread erythematous and edematous skin that is usually caused by drugs. It has an acute onset, and patients often have systemic manifestations, including leukocytosis, fever, and hemodynamic instability. Rarely has AGEP been associated with radiocontrast dyes. Observations We describe an 84-year-old man who developed AGEP on 2 separate occasions after receiving an infusion of an ioversol-containing radiocontrast dye. Conclusion Acute generalized exanthematous pustulosis may occur after the use of intravenous radiocontrast dye.

OBSERVATION: Pregnancy and Estrogen Receptor {beta} Expression in a Large Congenital Nevus

Background Large congenital nevi carry a slightly increased risk of melanoma. Pregnancy poses an additional challenge in the monitoring of these patients because little is known regarding the effects of increased estrogen levels on congenital nevi. Observations A young woman was observed to have clinical lightening of her garment nevus and satellite nevi during 2 sequential pregnancies. Postpartum, the patient experienced darkening and repigmentation in her large garment nevus, with continued lightening of nearby satellite lesions. In addition to photographic documentation of these changes, biopsy samples taken during pregnant and nonpregnant periods underwent immunohistochemical evaluation for estrogen receptor β (ERβ), the predominant estrogen receptor in nevi and melanomas. Biopsy samples collected during pregnancy showed a decrease in nuclear staining for ERβ compared with samples collected after pregnancy. These changes in ERβ expression were not associated with histologic atypia during pregnancy or after delivery. Conclusions Congenital nevi may be unique in their response to altered estrogen levels. Given the slightly increased risk of melanoma in giant congenital nevi and the dearth of information available regarding the effects of pregnancy on congenital nevi, this case illustrates the need for further study of these pigmented lesions.

OBSERVATION: Familial Primary Localized Cutaneous Amyloidosis in Brazil

Background Macular and lichen amyloidosis are clinical variants of primary localized cutaneous amyloidosis (PLCA). Most cases are sporadic, but approximately 10% of cases may be familial. To our knowledge, the clinicopathologic and molecular features of such pedigrees, however, have not been studied in detail. Observations We assessed 2 Brazilian families with either lichen-type (family 1 had 14 affected subjects) or macular-type (family 2 had 7 affected subjects) PLCA. Typically, in both pedigrees, the onset of symptoms was around puberty, and pruritus usually began on the lower legs. Findings from lesional skin biopsy samples from both families showed thioflavin T–positive material in the papillary dermis, which was more prominent in the lichen phenotype in family 1. Spontaneous improvement occurred in 3 subjects (from both families) after age 25 years. All affected individuals in family 1 had a heterozygous missense mutation in the OSMR gene (p.I691T), but no pathogenic mutation in OSMR was found in family 2. Conclusions Familial PLCA shows autosomal dominant inheritance, but there is clinical and genetic heterogeneity and variable clinical penetrance. Demonstration of mutations in the OSMR gene provides new insight into mechanisms of itch and apoptosis in human skin.

ARCHIVES WEB QUIZ WINNER: March 2009 Archives Web Quiz Winner

EVIDENCE-BASED DERMATOLOGY: STUDY: Association of Psoriasis With Coronary Artery, Cerebrovascular, and Peripheral Vascular Diseases and Mortality

Objective To examine the cardiovascular risk factors in patients with psoriasis and the association between psoriasis and coronary artery, cerebrovascular, and peripheral vascular diseases. Design Observational study. Setting Large Department of Veterans Affairs hospital. Patients The study included 3236 patients with psoriasis and 2500 patients without psoriasis (controls). Main Outcome Measures Using International Classification of Diseases, Ninth Revision, Clinical Modification, codes, we compared the prevalence of traditional cardiovascular risk factors and other vascular diseases as well as mortality between patients with psoriasis and controls. Results Similar to previous studies, we found a higher prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking in patients with psoriasis. After controlling for these variables, we found a higher prevalence not only of ischemic heart disease (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.51-2.11) but also of cerebrovascular (OR, 1.70; 95% CI, 1.33-2.17) and peripheral vascular (OR, 1.98; 95% CI, 1.32-2.82) diseases in patients with psoriasis compared with controls. Psoriasis was also found to be an independent risk factor for mortality (OR, 1.86; 95% CI, 1.56-2.21). Conclusions Psoriasis is associated with atherosclerosis. This association applies to coronary artery, cerebrovascular, and peripheral vascular diseases and results in increased mortality.

EVIDENCE-BASED DERMATOLOGY: RESEARCH COMMENTARY: Adalimumab vs Methotrexate for the Treatment of Chronic Plaque Psoriasis

EVIDENCE-BASED DERMATOLOGY: RESEARCH COMMENTARY: Adalimumab vs Methotrexate for the Treatment of Chronic Plaque Psoriasis--Reply

EDITORIAL: Optimizing Clinical Use of Azathioprine With Newer Pharmacogenetic Data

EDITORIAL: Cutaneous Lymphomas: What Can We Learn From Location?

ON THE HORIZON: Potential New Insight Into the Pathogenesis of Psoriasis

OFF-CENTER FOLD: An Unusual Pruritic Eruption of the Feet--Quiz Case

OFF-CENTER FOLD: An Unusual Pruritic Eruption of the Feet--Diagnosis

OFF-CENTER FOLD: Exophytic Plaques, Blisters, and Mouth Ulcers--Quiz Case

OFF-CENTER FOLD: Exophytic Plaques, Blisters, and Mouth Ulcers--Diagnosis

OFF-CENTER FOLD: Annular Patches and Plaques on the Scrotum and Buttocks--Quiz Case

OFF-CENTER FOLD: Annular Patches and Plaques on the Scrotum and Buttocks--Diagnosis

OFF-CENTER FOLD: A Violaceous Nodule on the Knee--Quiz Case

OFF-CENTER FOLD: A Violaceous Nodule on the Knee--Diagnosis

RESEARCH LETTERS: Patients' Fears and Expectations: Exploring the Hidden Agenda in Our Consultation

CORRESPONDENCE: Calciphylaxis Associated With Chronic Inflammatory Conditions, Immunosuppression Therapy, and Normal Renal Function: A Report of 2 Cases

CORRESPONDENCE: Lentigo Maligna Melanoma With Folliculotropism: Dermoscopic Features During Rapid Progression

SKINSIGHT: New Dermoscopic Pattern in Actinic Keratosis and Related Conditions

Keloid occurring in a tattoo after laser hair removal.

Related Articles Keloid occurring in a tattoo after laser hair removal. Acta Derm Venereol. 2009;89(3):334-5 Authors: Kluger N, Hakimi S, Del Giudice P PMID: 19479149 [PubMed - in process]

Efficiency and safety of etanercept after acute hepatitis induced by infliximab for psoriasis.

Related Articles Efficiency and safety of etanercept after acute hepatitis induced by infliximab for psoriasis. Acta Derm Venereol. 2009;89(3):332-4 Authors: Kluger N, Girard C, Guillot B, Bessis D PMID: 19479148 [PubMed - in process]

Subcutaneous Metastasis due to Primary Central Nervous System Malignant Lymphoma.

Related Articles Subcutaneous Metastasis due to Primary Central Nervous System Malignant Lymphoma. Acta Derm Venereol. 2009;89(3):331-2 Authors: Koga M, Yoshida Y, Koga K, Nakayama J PMID: 19479147 [PubMed - in process]

Coexistence of recurrent generalized morphea and systemic sclerosis.

Related Articles Coexistence of recurrent generalized morphea and systemic sclerosis. Acta Derm Venereol. 2009;89(3):329-30 Authors: Hayashi M, Ichiki Y, Kitajima Y PMID: 19479146 [PubMed - in process]

Tattoo-associated Pseudolymphomatous Reaction and its Successful Treatment with Hydroxychloroquine.

Related Articles Tattoo-associated Pseudolymphomatous Reaction and its Successful Treatment with Hydroxychloroquine. Acta Derm Venereol. 2009;89(3):327-8 Authors: Patrizi A, Raone B, Savoia F, Bacci F, Pileri A, Gurioli C, Neri I PMID: 19479145 [PubMed - in process]

Cutaneous lichenoid eruption caused by imatinib mesylate in a Japanese patient with chronic myeloid leukaemia.

Related Articles Cutaneous lichenoid eruption caused by imatinib mesylate in a Japanese patient with chronic myeloid leukaemia. Acta Derm Venereol. 2009;89(3):325-6 Authors: Kawakami T, Kawanabe T, Soma Y PMID: 19479144 [PubMed - in process]

Cutaneous ciliated cyst on the leg in a woman of menopausal age.

Related Articles Cutaneous ciliated cyst on the leg in a woman of menopausal age. Acta Derm Venereol. 2009;89(3):323-4 Authors: Torisu-Itakura H, Itakura E, Horiuchi R, Matsumura M, Kiryu H, Takeshita T, Ohjimi Y, Furue M PMID: 19479143 [PubMed - in process]

Erythematous macules on the feet in a case of cardiac myxoma.

Related Articles Erythematous macules on the feet in a case of cardiac myxoma. Acta Derm Venereol. 2009;89(3):321-2 Authors: Bursztejn AC, Bellut A, Weber-Muller F, Champigneulle J, Beurey P, Cuny JF, Barbaud A, Schmutz JL PMID: 19479142 [PubMed - in process]

Erythema Annulare Centrifugum Associated with Mantle B-cell Non-Hodgkin's Lymphoma.

Related Articles Erythema Annulare Centrifugum Associated with Mantle B-cell Non-Hodgkin's Lymphoma. Acta Derm Venereol. 2009;89(3):319-20 Authors: Carlesimo M, Fidanza L, Mari E, Pranteda G, Cacchi C, Veggia B, Cox MC, Camplone G PMID: 19479141 [PubMed - in process]

Fatal lymphangiosarcoma revealed by lymphoedema of the neck.

Related Articles Fatal lymphangiosarcoma revealed by lymphoedema of the neck. Acta Derm Venereol. 2009;89(3):318-9 Authors: Lalanne N, Ezzedine K, Vergier B, Liferman F, Taïeb A, Jouary T PMID: 19479140 [PubMed - in process]

Multiple Accessory Tragi without Cartilage: Relationship with Hair Follicle Naevi?

Related Articles Multiple Accessory Tragi without Cartilage: Relationship with Hair Follicle Naevi? Acta Derm Venereol. 2009;89(3):316-7 Authors: Asahina A, Mitomi H, Sakurai N, Fujita H PMID: 19479139 [PubMed - in process]

Prolonged Course of Acute Generalized Exanthematous Pustulosis with Liver Involvement due to Sensitization to Amoxicillin and Paracetamol.

Related Articles Prolonged Course of Acute Generalized Exanthematous Pustulosis with Liver Involvement due to Sensitization to Amoxicillin and Paracetamol. Acta Derm Venereol. 2009;89(3):314-5 Authors: Treudler R, Grunewald S, Gebhardt C, Simon JC PMID: 19479138 [PubMed - in process]

Acne keloidalis of the scalp in a renal transplant patient treated with cyclosporine.

Related Articles Acne keloidalis of the scalp in a renal transplant patient treated with cyclosporine. Acta Derm Venereol. 2009;89(3):312-3 Authors: Piaserico S, Fortina AB, Cavallini F, Alaibac M PMID: 19479137 [PubMed - in process]

Lichen spinulosus in an alcoholic patient.

Related Articles Lichen spinulosus in an alcoholic patient. Acta Derm Venereol. 2009;89(3):311-2 Authors: Kabashima R, Sugita K, Kabashima K, Nakamura M, Tokura Y PMID: 19479136 [PubMed - in process]

Phacomatosis cesioflammea associated with pectus excavatum.

Related Articles Phacomatosis cesioflammea associated with pectus excavatum. Acta Derm Venereol. 2009;89(3):309-10 Authors: Wu CY, Chen PH, Chen GS PMID: 19479135 [PubMed - in process]

Is There a Connection Between Mannan-binding Lectin Deficiency and Chronic Leg Ulcers?

Related Articles Is There a Connection Between Mannan-binding Lectin Deficiency and Chronic Leg Ulcers? Acta Derm Venereol. 2009;89(3):307-8 Authors: Bitsch M, Christiansen M, Laursen I, Engel AM, Holstein PE, Karlsmark T PMID: 19479134 [PubMed - in process]

A Randomized, Single-blind Comparison of the Efficacy, Tolerability and Cosmetic Acceptance of Propyless(R) or Fenuril(R) Treatment of Patients with Dry Skin.

Related Articles A Randomized, Single-blind Comparison of the Efficacy, Tolerability and Cosmetic Acceptance of Propyless(R) or Fenuril(R) Treatment of Patients with Dry Skin. Acta Derm Venereol. 2009;89(3):305-7 Authors: Faergemann J, Olsson P, Svensson A PMID: 19479133 [PubMed - in process]

Ex Vivo Analyses of Ano-genital Wart Lymphocytes to Study the Human Papillomavirus Immune Response.

Related Articles Ex Vivo Analyses of Ano-genital Wart Lymphocytes to Study the Human Papillomavirus Immune Response. Acta Derm Venereol. 2009;89(3):303-4 Authors: Heaps A, Hanna N, Stanley M, Goon P PMID: 19479132 [PubMed - in process]

Purely cutaneous langerhans' cell histiocytosis in an adult woman.

Related Articles Purely cutaneous langerhans' cell histiocytosis in an adult woman. Acta Derm Venereol. 2009;89(3):299-301 Authors: Campanati A, Simonetti O, Marconi B, Giuliodori K, Ganzetti G, Brandozzi G, Bernardini ML, Ranaldi R, Offidani A PMID: 19479131 [PubMed - in process]

Treatment of Disseminated Granuloma Annulare with Low-dose Fumaric Acid.

Related Articles Treatment of Disseminated Granuloma Annulare with Low-dose Fumaric Acid. Acta Derm Venereol. 2009;89(3):295-8 Authors: Weber HO, Borelli C, Röcken M, Schaller M While localized variants of granuloma annulare are typically self-limited, disseminated granuloma annulare tends to be chronic and often therapy-resistant. Treatment with fumaric acid esters is effective for severe forms of psoriasis. Disseminated granuloma annulare has also been reported to respond to fumaric acid esters. We treated 8 patients (mean age 64.2 years; 4 men, 4 women) with low-dose fumaric acid esters for 1-18 months. One patient showed complete clearance, 4 marked improvement, one slight to moderate improvement and one no response. One patient discontinued treatment due to nausea after one month and another stopped it after 18 months. Five out of 8 patients tolerated the treatment well. Six patients developed transient, mild leucopaenia and one eosinophilia. None of these blood abnormalities necessitated discontinuation of therapy. Low-dose fumaric acid esters significantly improve disseminated granuloma annulare in approximately 63% of patients. Larger, controlled, prospective studies are needed to evaluate its efficacy and safety in this setting. PMID: 19479130 [PubMed - in process]

Assessment of cryotherapy for the treatment of verrucous epidermal naevi.

Related Articles Assessment of cryotherapy for the treatment of verrucous epidermal naevi. Acta Derm Venereol. 2009;89(3):292-4 Authors: Panagiotopoulos A, Chasapi V, Nikolaou V, Stavropoulos PG, Kafouros K, Petridis A, Katsambas A Epidermal naevi are hamartomas that are characterized by hyperplasia of the epidermis and adnexal structures and may be associated with serious disfiguration. Management of epidermal naevi is challenging. We present here our experience with cryosurgery in the treatment of verrucous epidermal naevi. The aim of this study was to determine the efficacy and safety of cryosurgery for the treatment of epidermal naevi. Nine patients with verrucous epidermal naevi and two with extensive unilateral epidermal naevus were treated with cryosurgery. Two cycles of open spray technique were used, 10-15 sec each, depending on the size and extent of the naevus. Ten patients had their naevi treated successfully in 2-5 sessions with two cycles of therapy, and the cosmetic result was excellent with no scarring. One patient showed a relapse within 8 months after the treatment. One patient with phototype IV developed hypochromic scarring, but repigmentation occurred after 6 months. Postoperative healing time was 10-20 days. Cryosurgery is an extremely effective therapeutic modality for the treatment of epidermal naevi. The low cost, the simplicity of the technique and the good cosmetic result makes cryosurgery an excellent therapeutic modality for the treatment of epidermal naevus. PMID: 19479129 [PubMed - in process]

Effect of calcipotriol on etanercept partial responder psoriasis vulgaris and psoriatic arthritis patients.

Related Articles Effect of calcipotriol on etanercept partial responder psoriasis vulgaris and psoriatic arthritis patients. Acta Derm Venereol. 2009;89(3):288-91 Authors: Campione E, Mazzotta A, Paternò EJ, Diluvio L, Prinz JC, Chimenti S Patients who respond only partially to etanercept may require additional treatments that act synergistically to improve their therapeutic response while at the same time reducing the dose required and the risk of side-effects. The aim of this study was to evaluate the effecti veness of topical calcipotriol in etanercept partial responder patients. We enrolled 120 patients affected by psoriasis vulgaris and psoriatic arthritis. A 50 mg dose of etanercept was administered twice weekly for the first 12 weeks, followed by a 25 mg dose twice weekly for an additional 12 weeks. At week 12, for 45 patients who had not achieved PASI 50, calcipotriol cream was also prescribed twice daily for 4 weeks and then once daily for a further 8 weeks. At week 24, of the 45 patients in the group treated with etanercept plus calcipotriol, 14 (31.1%) had achieved PASI 75, and 23 PASI 50, while 8 (17.7%) had dropped out of therapy; of the 75 patients who continued etanercept in monotherapy with a 25 mg dose twice weekly for another 12 weeks, 71 (94.6%) had achieved PASI 50 and 57 (76.0%) PASI 75. The application of calcipotriol in etanercept partial responder patients had therefore helped 37 out of 120 patients (31%) achieve at least PASI 50. This is the first report about the controlled combination of topical calcipotriol and etanercept in a large group of psoriatic patients. The efficacy and cost-effectiveness of the combined treatment is evidenced by the good response shown at week 24 by a group of etanercept low-responder patients using drugs sparingly and limiting likely toxicity. PMID: 19479128 [PubMed - in process]

Neopterin and C-reactive protein in the course of stevens-johnson syndrome: report of a case.

Related Articles Neopterin and C-reactive protein in the course of stevens-johnson syndrome: report of a case. Acta Derm Venereol. 2009;89(3):285-7 Authors: Bertram L, Liss Y, Grözinger M We describe a patient originally suffering from a depressive syndrome who developed Stevens-Johnson syndrome after 12 days of treatment with lamotrigine. The clinical symptoms and the inflammation parameters neopterin and C-reactive protein were documented. Neopterin values showed a good correlation with the course of the disease, which, to the best of our knowledge, has not been reported previously. C-reactive protein followed the neopterin curve with a delay of 4 days. Since neopterin is a widely available parameter it should be considered as a routine measurement in this type of hyperergic reaction. It might help to identify the beginning, the maximum and the regression of the disease in order to support therapeutic decisions. PMID: 19479127 [PubMed - in process]

Body Dysmorphic Disorder in University Students with Skin Diseases Compared with Healthy Controls.

Related Articles Body Dysmorphic Disorder in University Students with Skin Diseases Compared with Healthy Controls. Acta Derm Venereol. 2009 May;89(3):281-284 Authors: Kaymak Y, Taner E, Simşek I Body dysmorphic disorder appears relatively frequently in dermatological and cosmetic surgery settings; in fact, dermatologists may be the type of practitioner most often consulted by patients with body dysmorphic disorder. The aim of this study was to evaluate body dysmorphic disorder symptoms in Turkish university students with skin diseases. A total of 107 outpatients diagnosed with any skin disease and 109 age- and sex-matched healthy subjects recruited from the students of the same university were enrolled in the study. Subjects in both the patient and the control groups completed the Beck Depression Inventory and the Body Dysmorphic Symptoms Scale (BDSS). Groups differed on the basis of BDSS scores (t = 3.74, p = 0.001), with higher scores in the group with skin diseases compared with those for healthy controls. Subjects with skin diseases and higher BDSS scores had higher Beck Depression Inventory scores compared with those with lower BDSS scores (z = 4.13, p = 0.001). This study suggests that patients with skin disease have higher body dysmorphic disorder scores compared with healthy controls. PMID: 19479126 [PubMed - as supplied by publisher]

Onychophagia as a Spectrum of Obsessive-compulsive Disorder.

Related Articles Onychophagia as a Spectrum of Obsessive-compulsive Disorder. Acta Derm Venereol. 2009;89(3):278-80 Authors: Pacan P, Grzesiak M, Reich A, Szepietowski JC Onychophagia can be explained as a kind of a compulsion that may cause destruction of the nails. Habitual nail biting is a common behaviour among children and young adults. By the age of 18 years the frequency of this behaviour decreases, but it may persist in some adults. Nail biting is an under-recognized problem, which may occur on a continuum ranging from mild to severe. Nail biting has received little attention in the psychiatric and dermatological literature. Its position in widely accepted classifications of psychiatric disorders (ICD-10 and DSM-IV) remains unclear. This disorder seems to be related to obsessive-compulsive spectrum disorder. Here, we present three case reports of onychophagia and co-occurring psychopathological symptoms and discuss the close relationship of onychophagia to obsessive- compulsive spectrum disorder and possible treatment modalities. Psychiatric evaluation of co-occurring psycho pathological symptoms in patients with onychophagia, especially those with chronic, severe or complicated nail biting, may be helpful in making a choice of individual therapy. Serotonin re-uptake inhibitors seem to be the treatment of choice in severe onychophagia. PMID: 19479125 [PubMed - in process]

Impact of Scratching on Itch and Sympathetic Reflexes Induced by Cowhage (Mucuna pruriens) and Histamine.

Related Articles Impact of Scratching on Itch and Sympathetic Reflexes Induced by Cowhage (Mucuna pruriens) and Histamine. Acta Derm Venereol. 2009;89(3):271-7 Authors: Kosteletzky F, Namer B, Forster C, Handwerker HO Cowhage and histamine, both applied via spicules, were used to induce itch. The quality and intensity of the sensations, axon reflex flare, sympathetic skin vasoconstrictions and the interference of scratching with itch processing were studied. Axon reflex flare reactions were measured by laser Doppler imaging and reflex vasoconstrictions in the finger were recorded by laser Doppler flowmetry. Magnitude of itch sensations was assessed on an electronic visual analogue scale while the skin was intermittently scratched proximal to the application site. The quality of itch was assessed with a questionnaire. Only histamine produced an axon reflex flare. Histamine itch increased faster, but recovered more slowly after scratching, by which it was more effectively suppressed. Cowhage induced a sharper itch sensation and stronger vasoconstrictor reflexes. These findings support the notion that both agents activate different pathways. The differences in sympathetic reflex induction and in the modulation by scratching indicate differential central nervous processing. PMID: 19479124 [PubMed - in process]

Frequency and treatment of trichotillomania in poland.

Related Articles Frequency and treatment of trichotillomania in poland. Acta Derm Venereol. 2009;89(3):267-70 Authors: Szepietowski JC, Salomon J, Pacan P, Hrehorów E, Zalewska A Although trichotillomania is a relatively common disorder no large epidemiological studies are available. The aims of this study were to determine the frequency of trichotillomania as identified by Polish dermatologists, and to evaluate the treatment modalities used. A questionnaire was sent to 172 dermatologists; 118 (68.6%) responded. The questions covered demographic data, frequency of trichotillomania and treatments used. During the course of their working lives 68% of respondents had observed at least one patient with trichotillomania and 11% were currently treating such a patient. More than 30% of respondents had observed one or two cases of trichotillomania during the past 5 years, 11% had seen 3-5 cases, 3% had seen 6-10 cases, and 5% had seen more than 10 patients. Of the respondents, 40.7% always and 28.8% often asked for a psychiatric opinion. Dermatologists with more experience more frequently (p < 0.05) obtained a psychiatric opinion. Some dermatologists (15.3%) used their own pharmacological treatment (anxiety-relieving drugs and sedatives). Trichotillomania is a relatively common disorder; however, not all dermatologists are sufficiently prepared to treat it. PMID: 19479123 [PubMed - in process]

Epidemiological study of psoriasis in the national health insurance database in taiwan.

Related Articles Epidemiological study of psoriasis in the national health insurance database in taiwan. Acta Derm Venereol. 2009;89(3):262-6 Authors: Chang YT, Chen TJ, Liu PC, Chen YC, Chen YJ, Huang YL, Jih JS, Chen CC, Lee DD, Wang WJ, Lin MW, Liu HN The aim of this study was to determine the prevalence, treatment modalities and comorbidity of psoriasis in Taiwan. A nationally representative cohort of 1,000,000 individuals from the National Health Insurance database was followed up for the years 2000 to 2006. Their claims data was used for an epidemiological study. The mean one-year prevalence of psoriasis was 0.23% for men and 0.16% for women, respectively. The prevalence of psoriasis increased more rapidly in male patients aged 30 years and over and reached its peak in patients aged 70 years and over, regardless of sex. Overall, 98.4% of patients received treatment with topical corticosteroids, while 13.1% used Chinese herbal medicines and 13.6% received systemic treatment. Patients with psoriasis had a higher comorbidity of diabetes, hyperlipidaemia, and hypertension. In conclusion, in contrast to Caucasians, the prevalence of psoriasis in Taiwanese people is high er in men than in women and the prevalence increases significantly in patients over 70 years of age. PMID: 19479122 [PubMed - in process]

Total Serum IgE as a Parameter to Differentiate Between Intrinsic and Extrinsic Atopic Dermatitis in Children.

Related Articles Total Serum IgE as a Parameter to Differentiate Between Intrinsic and Extrinsic Atopic Dermatitis in Children. Acta Derm Venereol. 2009;89(3):257-61 Authors: Ott H, Stanzel S, Ocklenburg C, Merk HF, Baron JM, Lehmann S Atopic dermatitis (AD) has been sub-classified into extrinsic and intrinsic types according to the presence or not of allergen-specific IgE antibodies. Although total serum IgE levels are frequently elevated in AD, their potential to predict allergen-specific IgE (asIgE) has rare ly been studied. We investigated 103 children with AD and suspected allergen-specific sensitization. A thorough clinical examination, a structured medical history and total serum IgE and asIgE measurements were performed. Fifty-three male and 50 female patients, median age 35 months (range 3 months to 17 years), were recruited. Sixty-three percent of patients were asIgE positive, while 37% did not reveal such IgE antibodies; median total serum IgE levels were 224.0 kU/l (14-12,013 kU/l) and 25.2 kU/l (0-4352 kU/l), respectively. Associations of asIgE status with atopic co-morbidity and total serum IgE levels were statistically significant. At a cut-off total serum IgE level of 106 kU/l (sensitivity 68.7%; specificity 92.3%), positive and negative predicted values (93.6% and 64.3%, respectively) were determined. Clinical decision points predictive of positive asIgE results were identified in 90%, 95% and 99% of patients, respectively. Total serum IgE values were significantly associated with the asIgE status of investigated patients. However, these preliminary data warrant further large-scale investigations before total serum IgE levels can be regarded as a clinically useful parameter between patients with extrinsic atopic dermatitis and intrinsic atopic dermatitis. PMID: 19479121 [PubMed - in process]

Measuring the Prevalence of Chronic Itch in the General Population: Development and Validation of a Questionnaire for Use in Large-scale Studies.

Related Articles Measuring the Prevalence of Chronic Itch in the General Population: Development and Validation of a Questionnaire for Use in Large-scale Studies. Acta Derm Venereol. 2009;89(3):250-6 Authors: Matterne U, Strassner T, Apfelbacher CJ, Diepgen TL, Weisshaar E Itching is the most frequent symptom in dermatology. Little is known about its occurrence and its characteristics in the general population. Instruments specifically designed to measure itch are scarce. The aim of this pilot study was to develop and validate an instrument measuring prevalence and characteristics of chronic itch in the general population. A questionnaire was developed and administered to a sample from the general population (n = 200) and a sample (n = 100) of itch-clinic patients. Life time prevalence of itch was 22.6% in non-patients and 100% in patients. Principal component, internal consist ency and correlational analyses revealed the instrument to be able to reliably and validly measure itch. Strength of itch was higher in patients and was associated with itch- related quality of life and affect in both groups. Preliminary results indicate that itch is prevalent in the general population. We intend to utilize this parsimonious and easy-to-administer questionnaire in a forthcoming population-based study. PMID: 19479120 [PubMed - in process]

Prostacyclin Analogue Iloprost Influences Endothelial Cell-associated Soluble Adhesion Molecules and Growth Factors in Patients with Systemic Sclerosis: A Time Course Study of Serum Concentrations.

Related Articles Prostacyclin Analogue Iloprost Influences Endothelial Cell-associated Soluble Adhesion Molecules and Growth Factors in Patients with Systemic Sclerosis: A Time Course Study of Serum Concentrations. Acta Derm Venereol. 2009;89(3):245-9 Authors: Rehberger P, Beckheinrich-Mrowka P, Haustein UF, Sticherling M Systemic sclerosis is a connective tissue disorder with unclear aetiology and pathogenesis. However, there is evidence that microvascular changes belong to the early symptoms of the disease. These are associated with increased serum levels of markers of endothelium activation, such as adhesion molecules and growth factors. The stable prostacyclin analogue iloprost is licensed for vascular symptoms (Raynaud's phenomenon) and was recently shown to exert short-term effects on these markers. In this study, serum samples (n = 13) from patients with systemic sclerosis were examined for serum levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1, E-selectin, endothelin-1 and vascular endothelial growth factor over 6 months after iloprost infusions in order to detect possible long-term effects. Iloprost significantly reduced initially elevated levels of these markers, partly until the end of the observation period (E-selectin, VCAM-1, endothelin-1). These effects provide serological evidence for the benefits of iloprost infusions that are seen clinically in patients with systemic sclerosis. PMID: 19479119 [PubMed - in process]

Drug-induced Pruritus: A Review.

Related Articles Drug-induced Pruritus: A Review. Acta Derm Venereol. 2009;89(3):236-44 Authors: Reich A, Ständer S, Szepietowski JC Pruritus is an unpleasant sensation that leads to scratching. In addition to several diseases, the administration of drugs may induce pruritus. It is estimated that pruritus accounts for approximately 5% of all skin adverse reactions after drug intake. However, to date there has been no systematic review of the natural course and possible underlying mechanisms of drug-induced pruritus. For example, no clear distinction has been made between acute or chronic (lasting more than 6 weeks) forms of pruritus. This review presents a systematic categorization of the different forms of drug-induced pruritus, with special emphasis on a therapeutic approach to this side-effect. PMID: 19479118 [PubMed - in process]

Progress in heritable skin diseases: translational implications of mutation analysis and prospects of molecular therapies*.

Related Articles Progress in heritable skin diseases: translational implications of mutation analysis and prospects of molecular therapies*. Acta Derm Venereol. 2009;89(3):228-35 Authors: Uitto J Epidermolysis bullosa, a group of blistering disorders, serves as the paradigm of the tremendous progress made in understanding the molecular genetics of heritable skin diseases. Mutations in 10 distinct genes have been disclosed in the classic forms of epidermolysis bullosa, and the level of expression of the mutated genes within the cutaneous basement membrane zone, the types and combinations of mutations and their consequences at the mRNA and protein levels, when placed in the context of the individual's genetic background and exposure to environmental trauma, all determine the subtype and the phenotypic severity in each case. The translational implications of mutation analysis include improved diagnosis and subclassification, refined genetic counseling of families at risk, and development of DNA-based pre natal and preimplantation genetic diagnosis. The prospects of molecular therapies for epidermolysis bullosa include further development of strategies for gene therapy, protein replacement therapy and cell-based therapies, including stem cell therapy and bone marrow transfer. Collectively, advances in the molecular genetics of heritable skin diseases clearly emphasize the value of basic research for improved diagnostics and patient care for genetic skin diseases. PMID: 19479117 [PubMed - in process]

Toenail Onychomycosis in Diabetic Patients: Issues and Management

Dapsone 5 Gel: A Review of its Efficacy and Safety in the Treatment of Acne Vulgaris

Impact of Topical Calcineurin Inhibitors on Quality of Life in Patients with Atopic Dermatitis

Acute Urticaria and Angioedema: Diagnostic and Treatment Considerations

The Role of Topical Retinoids in the Treatment of Pigmentary Disorders: An Evidence-Based Review

Focal Acral Hyperpigmentation in a Patient Undergoing Chemotherapy with Capecitabine

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Overlap due to Oral Temozolomide and Cranial Radiotherapy

Vitiligo Koebnerized by Behcet Disease Genital Ulceration

Basal Cell Carcinoma Presenting Late in a Shotgun Scar

Book Reviews

Recurrent mutations in functionally-related EDA and EDAR genes underlie X-linked isolated hypodontia and autosomal recessive hypohidrotic ectodermal dysplasia

Abstract Mutations in three functionally related genes EDA, EDAR and EDARDD have been reported to cause hypohidrotic ectodermal dysplasia (HED), which is characterized by sparse hair, reduced ability to sweat, and hypodontia. In few cases mutations in the EDA gene have been found to result in X-linked recessive isolated hypodontia. In the study, presented here, we have ascertained two large Pakistani families (A and B) with autosomal recessive form of hypohidrotic ectodermal dysplasia and X-linked recessive isolated hypodontia. Genetic mapping showed linkage of family A to EDAR gene on chromosome 2q11-q13 and family B to EDA gene on chromosome Xq12-q13.1. Subsequently, DNA sequencing of the coding regions of EDAR and EDA genes revealed previously described mutations. Sequence analysis identified a four base-pair splice-junction deletion mutation (c.718_721delAAAG) in EDAR gene in family A and a missense mutation (c.T1091C; p.M364T) in EDA gene in family B. Recurrence of mutations in EDAR and EDA genes in unrelated families is evocative of the dispersion of ancestral chromosome in different locality groups through common ancestors. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0975-1Authors Zahid Azeem, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanSyed Kamran-Ul-Hassan Naqvi, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanMuhammad Ansar, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanAbdul Wali, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanAbdul Khaliq Naveed, National University of Sciences and Technology (NUST) Department of Biochemistry and Molecular Biology Rawalpindi Cantt PakistanGhazanfar Ali, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanMuhammad Jawad Hassan, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanMuhammad Tariq, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanSulman Basit, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad PakistanWasim Ahmad, Quaid-i-Azam University Department of Biochemistry, Faculty of Biological Sciences Islamabad Pakistan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Time-kinetic study of repigmentation in vitiligo patients by tacrolimus or pimecrolimus

Abstract New topical immunomodulators have been reported to cause repigmentation of vitiligo lesions. However, time-kinetics of such repigmentation in different anatomic locations is not well known. We performed a randomized double-blind placebo control study with tacrolimus versus the vehicle and a nonrandomized control study with pimecrolimus to evaluate the time to reach significant pigmentation, its duration and extent in treated areas. Antioxidant status of serum was also assessed. Twenty patients, in the tacrolimus study, had one pair of lesions on different localizations, and 20 on face and/or upper limbs for pimecrolimus. The extent of repigmentation was evaluated by slides and mapmakings at baseline and every 4 weeks during 7 months. Adverse events were recorded. The derivatives of oxygen metabolites, the ferric reducing ability of serum and vitamin E were assessed. Three groups of patients were identified with the tacrolimus study. Eight had no significant change in response characterized by a parallel increase of repigmentation or none in treated and control areas. Nine had a better repigmentation to tacrolimus at fifth month of treatment. Three had a marked repigmentation in control areas at the end of treatment. Repigmentation was significant on the face compared to upper-limbs with pimecrolimus from fourth to seventh month. A significant reduction of oxidative stress and an increase in antioxidant capacity in serum of patients treated with topical tacrolimus was observed, while those treated with pimecrolimus did not show any significant changes but an increase in vitamin E. Our work defines three periods in repigmentation, triggering during the first 4 months, increase in pigmentation with tacrolimus and a plateau or a sustained repigmentation. The continuity of the treatment seems necessary to ensure a prolonged repigmenting effect and even an enhanced one, such as the one we observed on the face with pimecrolimus. The extent of repigmentation was more significant on the face compared to other locations probably due to differences in melanocyte density. Furthermore, we did not find any relationship between repigmentation and the duration of vitiligo. Tacrolimus was able to reduce the systemic oxidative stress independently from its repigmenting capacity. Both drugs were well tolerated. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0973-3Authors L. J. Lubaki, Hôpital Erasme, Université Libre de Bruxelles Department of Dermatology 808 Route de Lennik 1070 Brussels BelgiumG. Ghanem, Université Libre de Bruxelles LOCE, Institut J. Bordet Brussels BelgiumP. Vereecken, Hôpital Erasme, Université Libre de Bruxelles Department of Dermatology 808 Route de Lennik 1070 Brussels BelgiumE. Fouty, Public Health School, Université Libre de Bruxelles Brussels BelgiumL. Benammar, Hôpital Erasme, Université Libre de Bruxelles Department of Pharmacy Brussels BelgiumJ. Vadoud-Seyedi, Hôpital Erasme, Université Libre de Bruxelles Department of Dermatology 808 Route de Lennik 1070 Brussels BelgiumM. L. Dell’Anna, Instituto Dermatologico San Gallicano Rome ItalyS. Briganti, Instituto Dermatologico San Gallicano Rome ItalyM. Picardo, Instituto Dermatologico San Gallicano Rome ItalyM. Heenen, Hôpital Erasme, Université Libre de Bruxelles Department of Dermatology 808 Route de Lennik 1070 Brussels Belgium Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Autoantibodies to sweat glands detected by different methods in serum and in tissue from patients affected by a new variant of endemic pemphigus foliaceus

Abstract Examining the patients with a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia, (El Bagre-EPF), we noted several polymorphic clinical lesions around their axillary areas. Based on our clinical findings and on previous histopathological studies on the skin of these patients that showed abnormalities in their sweat glands, and the presence of mercuric selenides and iodines by autometallography assay, we decided to investigate immunoreactivity to the sweat glands in these patients. We tested for autoreactivity utilizing direct and indirect immunofluorescence (DIF, IIF). To be able to distinguish between non-specific immune deposits and real autoimmune response, and knowing that sweat glands have some intrinsic autofluorescence for the presence of lipofuscin granules (that naturally fluoresce under the UV light microscope), as well as by the presence of secretory IgA, we used simultaneously immunohistochemistry (IHC). We tested ten El Bagre-EPF patients, ten healthy controls from the endemic area and ten healthy controls from the United States. We were able to visualize a specific autoreactivity to sweat glands in 8/10 cases of El Bagre-EPF by DIF, IIF and by IHC. In addition when using anti-human monoclonal antibodies to CD3, CD68, and CD20, we confirmed the presence of several specific immune responses in situ, an around the sweat glands. No healthy control cases yielded positive findings. In some chronic cases, decrease and sometimes a complete absence of sweat glands and other skin appendices was found. In addition to this, sclerodermoid changes or early sclerodermatous changes sometimes extending into the adipose tissue as a membranous lipodystrophy were observed. Autoreactivity to the neurovascular components around the sweat glands were also observed. Our data demonstrate for the first time that there is immunoreactivity toward sweat glands in El Bagre-EPF patients that seems to destroy some of these structures. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0972-4Authors Ana Maria Abreu-Velez, Georgia Dermatopathology Associates 1534 North Decatur Rd. NE; Suite 206 Atlanta GA 30307-1000 USAMichael S. Howard, Georgia Dermatopathology Associates 1534 North Decatur Rd. NE; Suite 206 Atlanta GA 30307-1000 USAKen Hashimoto, University of Michigan Medical Center Ann Arbor MI USATakashi Hashimoto, Kurume University Department of Dermatology, School of Medicine Kurume Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Are cosmetic products which include an SPF appropriate for daily use?

Abstract The goal of this study is to investigate commercially available cosmetics (foundations, skin care creams) which also claim to include a sun protection factor (SPF). Are these products, which are not considered sunscreen products, helpful or could they be harmful? Using an in vitro method, we tested the effectiveness of 35 commercially available products against UVB and UVA radiation. For each product, our testing focused on determining the following four values in terms of current legal recommendations: SPF, UVA protection factor (PF-UVA), UVB/UVA ratio and critical wavelength (λc). We also tested each product’s level of photostability. Effectively, when considering instructions for use (skincare products are applied once, in the morning) any product displaying an SPF must be particularly photostable, since its labeling does not indicate reapplication. In contrast, the packaging on sunscreen products clearly indicates the necessity of frequent reapplication. Out of the 35 products we tested, seven do not comply with legislation regarding sunscreen products. This non-compliance translates into insufficient protection against UVA radiation. The products sold in pharmacies did comply. In terms of photostability, only eight products out of the original 35 proved to be sufficiently photostable. It would seem inappropriate to use filters in the formulas of non-sunscreen cosmetics. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0974-2Authors Delphine Séhédic, Université de Nantes, Nantes Atlantique Universités, LPiC, MMS, EA2160 Faculty of Pharmacy 1 rue G. Veil, BP 53508 44000 Nantes FranceArmelle Hardy-Boismartel, Université de Nantes, Nantes Atlantique Universités, LPiC, MMS, EA2160 Faculty of Pharmacy 1 rue G. Veil, BP 53508 44000 Nantes FranceCéline Couteau, Université de Nantes, Nantes Atlantique Universités, LPiC, MMS, EA2160 Faculty of Pharmacy 1 rue G. Veil, BP 53508 44000 Nantes FranceLaurence J. M. Coiffard, Université de Nantes, Nantes Atlantique Universités, LPiC, MMS, EA2160 Faculty of Pharmacy 1 rue G. Veil, BP 53508 44000 Nantes France Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A novel point mutation at donor splice-site in intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of Ehlers–Danlos syndrome

Abstract Vascular type of Ehlers–Danlos syndrome (EDS) is the most severe type of EDS. It is an autosomal dominantly inherited disorder that results from mutations within the α1 type III collagen gene (COL3A1). We report a novel point mutation at donor splice-site in intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of EDS. Since the age of approximately 8 months, the patient had had repeated episodes of purpura and gradually developed thin, translucent skin. She had a past history of pneumothorax. At the initial examination, she was found to have the characteristic facies, i.e., bird-like face, of the vascular type of EDS, thinning of skin over the limbs and trunk, and scattered purpura. The blood vessels under the skin could be clearly visualized. She showed hypermobility of the small joints of all the four limbs and acrogeric changes of the hands and feet. Analysis of the amount of collagen synthesized from cultured dermal fibroblasts by SDS-polyacrylamide gel electrophoresis and fluorography was conducted based on the clinical suspicion of the vascular type of EDS, and a marked reduction in the synthesis of type III collagen was observed. Genetic analysis of the COL3A1 revealed a novel point mutation at the donor splice-site of intron 42, which resulted in the inclusion of 30 nucleotides into the mature mRNA of one allele. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0970-6Authors Hiroshi Okita, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 JapanYasunori Ikeda, Utsunomiya Kinen Hospital Department of Surgery Utsunomiya Tochigi JapanYoshihiko Mitsuhashi, Tokyo Medical University Department of Dermatology Tokyo JapanHiromi Namikawa, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 JapanYohei Kitamura, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 JapanYoichiro Hamasaki, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 JapanSoji Yamazaki, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 JapanAtsushi Hatamochi, Dokkyo Medical University Department of Dermatology 880 Kitakobayashi Mibu Tochigi 321-0293 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Impaired cutaneous wound healing with excess granulation tissue formation in TNFα-null mice

Abstract We examined the effects of lacking tumor necrosis factor α (TNFα) on the healing process of a cutaneous wound in mice using TNFα-deficient mice. A full-thickness circular cutaneous wound 5.0 mm in diameter was produced in the dorsal skin of wild-type (WT) or TNFα-null (KO) mice. After specific intervals of healing, the healing pattern was evaluated by macroscopic observation, histology, immunohistochemistry, or real-time reverse transcription-polymerase chain reaction. Effect of Smad7 gene transfer on the healing phenotype of KO mice was also examined. The results showed that loss of TNFα promotes granulation tissue formation and retards reepithelialization in a circular wound in mouse dorsal skin. Immunohistochemistry showed that distribution of macrophages and myofibroblasts in newly generated granulation tissue seemed similar between WT and KO mice. However, lacking TNFα enhanced mRNA expression of TGFβ1 and collagen Iα2 in such tissue. Smad7 gene transfer counteracted excess granulation tissue formation in KO mice. In conclusion, lacking TNFα potentiates Smad-mediated fibrogenic reaction in healing dermis and retards reepithelialization in a healing mouse cutaneous wound. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0969-zAuthors Maki Shinozaki, Wakayama Medical University School of Medicine Department of Critical Care Medicine 811-1 Kimiidera Wakayama 641-0012 JapanYuka Okada, Wakayama Medical University School of Medicine Department of Ophthalmology 811-1 Kimiidera Wakayama 641-0012 JapanAi Kitano, Wakayama Medical University School of Medicine Department of Ophthalmology 811-1 Kimiidera Wakayama 641-0012 JapanKazuo Ikeda, Nagoya City University Department of Functional Anatomy 1, Sumikawa, Mizuho Nagoya 467-8601 JapanShizuya Saika, Wakayama Medical University School of Medicine Department of Ophthalmology 811-1 Kimiidera Wakayama 641-0012 JapanMasahiro Shinozaki, Wakayama Medical University School of Medicine Department of Critical Care Medicine 811-1 Kimiidera Wakayama 641-0012 Japan Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Novel mutations in the P2RY5 gene in one Turkish and two Indian patients presenting with hypotrichosis and woolly hair

Abstract Hypotrichosis simplex comprises a group of non-syndromic human alopecias. Diffuse loss of hair typically starts in early childhood and progresses throughout adolescence. We and others have previously reported mutations in the P2RY5 gene and the LIPH gene as being causal factors of autosomal recessive hypotrichosis simplex with or without woolly hair. In the present study, we analyzed one Turkish family and two non-related girls of Indian ethnicity affected with hypotrichosis and woolly hair for mutations in these genes. We identified as yet unreported mutations in the P2RY5 gene: a 1-base pair deletion (c.472delC) and a 4-base pair duplication (c.64_67dupTGCA), both of which lead to frameshifts resulting in truncated proteins. Our study increases the spectrum of known P2RY5 mutations and highlights the importance of this receptor in human hair growth and texture. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0971-5Authors Sandra M. Pasternack, University of Bonn Institute of Human Genetics Wilhelmstrasse 31 53111 Bonn GermanySundaram Murugusundram, Skin, Hair and Nail Clinic Chennai IndiaSibylle Eigelshoven, University of Düsseldorf Department of Dermatology Düsseldorf GermanyMelanie Müller, University of Bonn Institute of Human Genetics Wilhelmstrasse 31 53111 Bonn GermanyRoland Kruse, University of Düsseldorf Department of Dermatology Düsseldorf GermanyPercy Lehmann, HELIOS Clinic Wuppertal, University of Witten/Herdecke Center for Dermatology, Allergology and Environmental Medicine Wuppertal GermanyRegina C. Betz, University of Bonn Institute of Human Genetics Wilhelmstrasse 31 53111 Bonn Germany Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions

Abstract In psoriasis, leukocytes that infiltrate skin lesions have been shown to be involved in the pathogenesis of this disease. Previous investigations reporting the presence of CXCR3+ T lymphocytes in psoriatic lesional skin have suggested a role of this receptor in the recruitment of T cells into the lesion. The purpose of this study was to quantify the mRNA levels of CXCR3 and to perform a systematic analysis of the cell populations that express CXCR3 in human lesional and non-lesional psoriatic biopsies. We showed by real-time reverse transcriptase-polymerase chain reaction that the mRNA levels of CXCR3 and its ligands, CXCL9-11, were significantly elevated in psoriatic lesions, as compared to non-lesional samples. Serial cryostat sections of psoriasis skin biopsies were evaluated by immunohistochemistry. The number of CXCR3+ cells was low in non-lesional tissues. Quantitative image analysis demonstrated significant increases in the number of both epidermal and dermal CXCR3+ cells in lesional compared with non-lesional biopsies. The majority of CXCR3+ cells were located in the dermis of the lesional skin and 74% were demonstrated to be CD3+ T lymphocytes. A small number of CXCR3+ cells were CD68+ myeloid cells. In addition, we found that nearly all BDCA-2+ plasmacytoid dendritic cells in the psoriatic biopsies were CXCR3+. These findings support and extend prior reports suggesting the potential role for CXCR3 in the pathophysiology of plaque psoriasis, by mediating the recruitment of plasmacytoid dendritic cells and T cells into the developing lesions. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0966-2Authors Shu-Cheng Chen, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Inflammation/Neurobiology Department K15-2700, 2015 Galloping Hill Road Kenilworth NJ 07033 USAMarjan de Groot, University of Amsterdam Department of Dermatology, Academic Medical Center Amsterdam The NetherlandsDavid Kinsley, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Inflammation/Neurobiology Department K15-2700, 2015 Galloping Hill Road Kenilworth NJ 07033 USAMaureen Laverty, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Kenilworth USATerrill McClanahan, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Kenilworth USAMaria Arreaza, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Kenilworth USAEric L. Gustafson, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Kenilworth USAMarcel B. M. Teunissen, University of Amsterdam Department of Dermatology, Academic Medical Center Amsterdam The NetherlandsMenno A. de Rie, University of Amsterdam Department of Dermatology, Academic Medical Center Amsterdam The NetherlandsJay S. Fine, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Inflammation/Neurobiology Department K15-2700, 2015 Galloping Hill Road Kenilworth NJ 07033 USAMaarten Kraan, Schering-Plough Research Institute, Schering-Plough Pharmaceutical Inc Kenilworth USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Localization and quantification of intact, undamaged right-handed double-stranded B-DNA, and denatured single-stranded DNA in normal human epidermis and its effects on apoptosis and terminal differentiation (denucleation)

Abstract Quantification of two types of nucleic acids [double-stranded (ds-) and single-stranded (ss-) DNA] was performed to understand the distribution of DNA within the epidermal strata and to examine the effects of DNA structure on gene expression, viz., apoptosis and terminal differentiation. In addition, we examined the precise starting point of cell death within the epidermis (suprabasal layer); examined how DNA structure affects gene expression of melanocytes; and characterized the “transitional cells” located between the stratum granulosum and stratum corneum, viz., epidermal phase transition zone (EPTZ). Ultrasensitive anti-DNA antibody probes (ds-DNA, ss-DNA), the Feulgen reaction, histological stains (morphological characterization) and the terminal deoxyribonucleotidyl transferase (TUNEL) assay (apoptosis) were used to characterize cell death in normal human epidermis. This study characterized, for the first time, the deterioration of right-handed ds-B-DNA and the increase in denatured ss-DNA during epidermal maturation. For the first time, this approach also allowed for the quantitative and qualitative characterization of DNA content and structure in all epidermal strata, using anti-ds-B-DNA and anti-ss-DNA antibodies. In order to improve the retention and quality of DNA, a novel histotechnological processing procedure was used. The results indicate that the largest decline in DNA occurred within the stratum granulosum, followed by the EPTZ, and the stratum spinosum. Not all epidermal nuclei lost DNA, indicating two differentiating keratinocyte pathways, viz., apoptotic and non-apoptotic. Both pathways united in the stratum granulosum. These results suggest that keratinocyte terminal differentiation and apoptosis are distinct cellular events, cell death begins earlier than expected, and molecular epidermal events take place in a gradual and orderly manner within keratinocytes. During maturation, ds-B-DNA decreases as ss-DNA increases. Therefore, during differentiation of keratinocytes, both DNA content and DNA structure are altered. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0965-3Authors Claude E. Gagna, The University of Medicine and Dentistry of New Jersey-Medical School Department of Pathology and Laboratory Medicine Newark NJ 07103 USANorman J. Chan, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAPatricia N. Farnsworth, The University of Medicine and Dentistry of New Jersey-Medical School Department of Physiology and Pharmacology Newark NJ 07103 USAHon-Reen Kuo, The University of Medicine and Dentistry of New Jersey-Medical School Department of Pathology and Laboratory Medicine Newark NJ 07103 USATrishla R. Kanthala, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAAnup H. Patel, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USANeel H. Patel, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAAmy Law, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAPriti P. Patel, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAScott A. Richards, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USATony Yam, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAAnthony Nici, New York Institute of Technology College of Arts and Sciences, New York College of Osteopathic Medicine NYCOM, Bldg. #2, Room #362 Old Westbury NY 11568-8000 USAW. Clark Lambert, The University of Medicine and Dentistry of New Jersey-Medical School Department of Pathology and Laboratory Medicine Newark NJ 07103 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Apolipoprotein E gene polymorphism in psoriasis

Abstract Polymorphism in the apolipoprotein E gene has been associated with several neurological, cardiological and ophthalmological diseases. Apolipoprotein E is involved in psoriasis by modifying mitogen-activated T lymphocyte proliferation and by assuring protection against some infections. We evaluated the apolipoprotein E gene polymorphism in patients suffering from psoriasis (compared to matched controls) in Thrace, Northern Greece. One hundred and forty patients suffering from psoriasis vulgaris and 155 matched controls were included in this study and genotyped by semi-nested polymerase chain reaction RFLPs; the results were evaluated by conditional logistic regression. In psoriasis vulgaris patients, the e2 allele showed higher frequency (6.1%, P = 0.021) versus matched controls (2.3%). The above data were ascertained particularly enforced in psoriasis vulgaris male patients (P = 0.031) as well as in late onset psoriasis vulgaris (P = 0.029). Implication of apolipoprotein E in the pathogenesis of psoriasis has been indicated. Allele e2 is more frequent in psoriatic patients and its presence is more evident in late onset psoriasis vulgaris. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0968-0Authors Anthony Karpouzis, University Clinic of Dermatology, Democritus University of Thrace Faculty of Medicine 68100 Alexandroupolis GreeceRozina Caridha, University Laboratory of Medical Biology, Democritus University of Thrace Faculty of Medicine 681 00 Alexandroupolis GreeceGregory Tripsianis, Democritus University of Thrace Faculty of Medicine, Department of Medical Statistics 68100 Alexandroupolis GreeceCharalambos Michailidis, University Laboratory of Medical Biology, Democritus University of Thrace Faculty of Medicine 681 00 Alexandroupolis GreeceGeorge Martinis, University Hospital of Alexandroupolis Department of Blood Donation 68100 Alexandroupolis GreeceStavroula Vouliana Veletza, University Laboratory of Medical Biology, Democritus University of Thrace Faculty of Medicine 681 00 Alexandroupolis Greece Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 6 / July, 2009

Immunochemotherapy for Bcl-2 and MUM-negative aggressive primary cutaneous B-cell non-Hodgkin’s lymphoma

Abstract The case of a 44-year-old man with a primary cutaneous large B-cell non-Hodgkin’s lymphoma of the scalp is reported. His mother died of gastric lymphoma and his sib brother is in a 20-year remission of T-cell lymphoma. The patient presented with a 16-year history of occipital and parietal alopecia and a recently worsening scalp rash. The histopathology and immunohistochemistry performed in April 2006 indicated a bcl-6+, MUM− and bcl-2−, primary cutaneous follicle center B-cell non-Hodgkin’s lymphoma, with an aggressive transformation to a diffuse large B-cell lymphoma. Bone marrow biopsy and CT chest, abdomen, and pelvis were negative for systemic lymphoma. The patient had an excellent clinical and histological resolution following 8 cycles of rituximab and CHOP protocol immunochemotherapy, and remains in complete remission until now. The protracted indolent phase of the disease, the familial history of lymphoma, the histological aggressive features and the patient’s excellent response to immunochemotherapy all contribute to a very unusual manifestation of this disease. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0967-1Authors Natasa Colovic, Institute of Hematology Clinical Center Serbia Koste Todorovica 2 11000 Belgrade SerbiaVladimir Jurisic, Institute of Hematology Clinical Center Serbia Koste Todorovica 2 11000 Belgrade SerbiaTatjana Terzic, Institute for Pathology Belgrade SerbiaHenry Dushan Atkinson, St Mary’s Hospital Imperial College School of Medicine London UKMilica Colovic, Institute of Hematology Clinical Center Serbia Koste Todorovica 2 11000 Belgrade Serbia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

New mutations of Darier disease in Tunisian patients

Abstract Darier’s disease (DD, MIM 124200) also known as Darier-White disease and keratosis follicularis, is a rare autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead). Pathogenic mutations in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) 2 gene underlie the disease. In the present study, we performed genetic investigation of three unrelated Tunisian families affected by DD. Mutation screening was performed by direct sequencing of the coding region and exon/intron boundaries of the ATP2A2 gene. Patients in the 3 studied families exhibited classical DD phenotype. DD was associated with neurological and cardiac disorders in one family. Two novel mutations were identified: a missense mutation (R559Q) and a frameshift mutation (1713-1714 del 2A). Both pathogenic mutations are located in exon 13 of the ATP2A2 gene and affected the ATP-binding site of the SERCA2 protein. In one family, no mutation was found within the coding region and exon/intron boundaries of the ATP2A2 gene. Our findings provide further evidence for the genetic heterogeneity of DD in Tunisia and that most mutations involved in this disease are family specific. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0963-5Authors Mbarka Bchetnia, Institut Pasteur de Tunis “Molecular Investigation of Genetic Orphan Diseases” Research Unit BP 74, 13 Place, Pasteur 1002 Tunis Belvédère TunisiaRym Benmously, Habib Thameur Hospital Dermatology Department Tunis TunisiaAhlem Sabrine Ben Brick, Institut Pasteur de Tunis “Molecular Investigation of Genetic Orphan Diseases” Research Unit BP 74, 13 Place, Pasteur 1002 Tunis Belvédère TunisiaCherine Charfeddine, Institut Pasteur de Tunis “Molecular Investigation of Genetic Orphan Diseases” Research Unit BP 74, 13 Place, Pasteur 1002 Tunis Belvédère TunisiaYoussef Ben Ameur, Habib Thameur Hospital Cardiology Department Tunis TunisiaMohamed Fajraoui, Cardiology Clinic Zarzis TunisiaAchraf Debbiche, Habib Thameur Hospital Histopathology Department Tunis TunisiaMohamed Ben Ayed, Habib Thameur Hospital Histopathology Department Tunis TunisiaMourad Mokni, La Rabta Hospital “Hereditary Keratinization Disorders” Research Unit Tunis TunisiaSamy Fenniche, Habib Thameur Hospital Dermatology Department Tunis TunisiaInçaf Mokhtar, Habib Thameur Hospital Dermatology Department Tunis TunisiaSonia Abdelhak, Institut Pasteur de Tunis “Molecular Investigation of Genetic Orphan Diseases” Research Unit BP 74, 13 Place, Pasteur 1002 Tunis Belvédère Tunisia Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo

Abstract Vitiligo is an acquired skin disease, characterized by white areas on the skin due to loss of functional melanocytes. The pathogenesis of the disease is still unclear. Published data show the involvement of oxidative stress in the pathophysiology of vitiligo. A total of 30 vitiligo patients and 30 healthy controls were included in this study. We estimated serum levels of malondialdehyde (MDA), vitamins E and C, total antioxidant activity and whole blood levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in vitiligo patients and controls. We found significantly higher levels of MDA and significantly lower levels of SOD, GPx, vitamins C and E and total antioxidant activity in vitiligo patients compared with controls. This study is a maiden attempt to report on antioxidant parameters of both generalized/localized-type Indian vitiligo patients. Our results confirmed that oxidative stress may play an important role in the pathogenesis of vitiligo and cause melanocyte damage in vitiligo. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0964-4Authors Rehan Khan, All India Institute of Medical Sciences Department of Biochemistry New Delhi 110029 IndiaAbhigyan Satyam, All India Institute of Medical Sciences Department of Biochemistry New Delhi 110029 IndiaSomesh Gupta, All India Institute of Medical Sciences Department of Dermatology and Venereology New Delhi 110029 IndiaVinod K. Sharma, All India Institute of Medical Sciences Department of Dermatology and Venereology New Delhi 110029 IndiaAlpana Sharma, All India Institute of Medical Sciences Department of Biochemistry New Delhi 110029 India Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

PGP 9.5 expression in cutaneous keratoacanthomas and squamous cell carcinomas

Abstract The aim of the study was to investigate the expression of PGP 9.5 in cutaneous keratoacanthomas (KAs) and squamous cell carcinomas (SCCs). Thirty-one cases of KA (10 in the growth stage, 9 in the mature phase and 12 in the involution stage) and 36 SCCs including 13 well differentiated cases, 12 moderately differentiated tumors, 7 poorly differentiated lesions and 4 pseudoadenoid entities were investigated. PGP 9.5 expression was positively correlated with tumor stage (P < 0.001) and potential perineural invasion (P < 0.001). There was no significant difference in the distribution of patients presenting variable levels of PGP 9.5 staining with regard to maximal tumor size and the extent and degree of stromal invasion. PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0962-6Authors Aikaterini Mastoraki, Attikon University Hospital, Medical School, Athens University 4th Department of Surgery 1 Rimini str, 12462, Chaidari Athens GreeceEleftherios Ioannidis, Attikon University Hospital, Medical School, Athens University 4th Department of Surgery 1 Rimini str, 12462, Chaidari Athens GreeceEfstratios Patsouris, University of Athens Department of Dermatopathology 75 Mikras Asias str 11527 Athens GreeceMichael Safioleas, Attikon University Hospital, Medical School, Athens University 4th Department of Surgery 1 Rimini str, 12462, Chaidari Athens GreeceKiriaki Aroni, University of Athens Department of Dermatopathology 75 Mikras Asias str 11527 Athens Greece Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Humanized anti-CD2 monoclonal antibody treatment of plaque psoriasis: efficacy and pharmacodynamic results of two randomized, double-blind, placebo-controlled studies of intravenous and subcutaneous siplizumab

Abstract New biologic therapies focused primarily on cytokine pathways, some targeting T cell-mediated immune responses, are being developed for the treatment of psoriasis. Siplizumab is a humanized anti-CD2 monoclonal antibody that interferes with costimulation necessary for T cell activation and proliferation. We assessed the biological activity, serum concentrations, and pharmacodynamic effects of siplizumab in patients with plaque psoriasis. Two multicenter, phase II randomized, double-blind, placebo-controlled studies were conducted: one study randomized 124 patients to one of two intravenous (IV) doses (0.012 and 0.04 mg/kg) of siplizumab, given every 2 weeks × 8 doses; the other study randomized 420 patients to one of three subcutaneous (SC) dose regimens of siplizumab given weekly (5 mg for 12 weeks, 5 mg for 6 weeks, and 7 mg for 4 weeks) or placebo for 12 weeks. Adults with plaque psoriasis involving ≥10% of the body surface area and who were not receiving psoriasis therapy were eligible. Treatment with siplizumab resulted in reductions in psoriasis severity, but most of the effects were not statistically significant compared with placebo. Statistically significant differences among IV siplizumab-treated and placebo groups were observed at study day 28, with greater psoriasis area and severity index (PASI) score reductions from baseline in the siplizumab groups. The difference in PASI50 response rates between the 0.04 mg/kg siplizumab and placebo groups was also statistically significant at day 28. A trend toward clinical improvement was observed in SC siplizumab-treated groups. Significant reductions in circulating absolute lymphocyte counts and CD2+ (CD3+, CD8+, and CD16+/56+), but not CD2− (CD19+ and CD14+), lymphocyte populations were observed. These changes were not accompanied by concomitant reductions in infiltrating CD3+ lymphocytes in psoriatic lesions, epidermal thickness, or keratin 16 (K16) and intercellular adhesion molecule (ICAM) expression. The effect of siplizumab did not differentially affect CD45RO+ and CD45RA+ lymphocytes. Low or undetectable mean trough serum concentrations of siplizumab following IV or SC treatment were observed. Pharmacokinetic data coupled with higher-than-expected placebo clinical response rates may partly explain siplizumab’s marginal clinical activity. Higher doses of siplizumab may be required to detect significant improvements in psoriasis; however, further development of this agent was not planned. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0961-7Authors Robert Bissonnette, Innovaderm Research Inc. 1851 Sherbrooke Street East, Suite 502 Montreal QC H2K 4L5 CanadaRichard G. Langley, Dalhousie University Department of Medicine Halifax NS B3H 4R2 CanadaKim Papp, Probity Medical Research 135 Union Street East Waterloo ON N2J 1C4 CanadaRobert Matheson, Oregon Medical Research Center P.C., 9495 South West Locust Street, Suite G Portland OR 97223 USADarryl Toth, 2425 Tecumseh Road East Suite 210 Windsor ON N8W 1E6 CanadaMicki Hultquist, MedImmune, LLC One MedImmune Way Gaithersburg MD 20878 USAGregory P. Geba, MedImmune, LLC One MedImmune Way Gaithersburg MD 20878 USABarbara White, MedImmune, LLC One MedImmune Way Gaithersburg MD 20878 USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 6 / July, 2009

Activation of peroxisome proliferator-activated receptor-γ inhibits transforming growth factor-β1 induction of connective tissue growth factor and extracellular matrix in hypertrophic scar fibroblasts in vitro

Abstract Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-γ ligands in the presence of transforming growth factor-β1 (TGF-β1). In growth-arrested HSFs, a PPAR-γ natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFβ1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-γ (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-β1/Smad pathway. These results suggest that in TGFβ1-stimulated HSFs, PPAR-γ ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-γ and Smad may be involved in the inhibitory effects of PPAR-γ ligands. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0959-1Authors Guo-You Zhang, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaTao Cheng, Shanghai Jiaotong University Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, School of Medicine Shanghai ChinaMing-Hua Zheng, The First Affiliated Hospital of Wenzhou Medical College Department of Infection and Liver Diseases Wenzhou ChinaCheng-Gang Yi, Fourth Military Medical University Institute of Plastic Surgery, Xijing Hospital Xi’an Shanxi ChinaHua Pan, Fourth Military Medical University Institute of Plastic Surgery, Xijing Hospital Xi’an Shanxi ChinaZhi-Jie Li, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaXing-Long Chen, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaQing Yu, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaLiang-Fu Jiang, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaFei-Ya Zhou, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaXiao-Yang Li, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaJing-Quan Yang, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaTing-Gang Chu, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang ChinaWei-Yang Gao, The 2nd Affiliated Hospital of Wenzhou Medical College Department of Hand and Plastic Surgery Xueyuan West Road 109# 325027 Wenzhou Zhejiang China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Moisturizers change the mRNA expression of enzymes synthesizing skin barrier lipids

Abstract In a previous study, 7-week treatment of normal human skin with two test moisturizers, Complex cream and Hydrocarbon cream, was shown to affect mRNA expression of certain genes involved in keratinocyte differentiation. Moreover, the treatment altered transepidermal water loss (TEWL) in opposite directions. In the present study, the mRNA expression of genes important for formation of barrier lipids, i.e., cholesterol, free fatty acids and ceramides, was examined. Treatment with Hydrocarbon cream, which increased TEWL, also elevated the gene expression of GBA, SPTLC2, SMPD1, ALOX12B, ALOXE3, and HMGCS1. In addition, the expression of PPARG was decreased. On the other hand, Complex cream, which decreased TEWL, induced only the expression of PPARG, although not confirmed at the protein level. Furthermore, in the untreated skin, a correlation between the mRNA expression of PPARG and ACACB, and TEWL was found, suggesting that these genes are important for the skin barrier homeostasis. The observed changes further demonstrate that long-term treatment with certain moisturizers may induce dysfunctional skin barrier, and as a consequence several signaling pathways are altered. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0958-2Authors Izabela Buraczewska, University Hospital Department of Medical Sciences, Dermatology and Venereology 751 85 Uppsala SwedenBerit Berne, University Hospital Department of Medical Sciences, Dermatology and Venereology 751 85 Uppsala SwedenMagnus Lindberg, University Hospital Örebro Department of Dermatology 701 85 Örebro SwedenMarie Lodén, ACO HUD NORDIC AB Box 622 194 26 Upplands Väsby SwedenHans Törmä, University Hospital Department of Medical Sciences, Dermatology and Venereology 751 85 Uppsala Sweden Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

Changes in S100A8 expression in UV-irradiated and aged human skin in vivo

Abstract S100A8, a calcium-binding protein, is associated with keratinocyte differentiation, inflammation and wound healing. S100A8 is induced by various skin stresses and diseases, which suggests that S100A8 plays a role in those processes. However, it has not been reported how the expression of S100A8 is affected during skin aging or whether S100A8 plays a role in the skin aging process. In this study, we investigated the changes in S100A8 mRNA and protein following acute UV irradiation to human buttock skin and by intrinsic aging and photoaging in human sun-protected (upper-inner arm) and sun-exposed (forearm) skin of elderly subjects. Real-time PCR, western blot and immunohistochemical staining analyses of UV-irradiated young buttock skin revealed that S100A8 protein expression was increased at 24 h (3.0-fold) and 48 h (4.4-fold) after UV irradiation. S100A8 mRNA and protein were more highly expressed by 2.3- and 4.0-fold, respectively, in the sun-protected skin of elderly people than in that of young people. In addition, the sun-exposed skin of elderly expressed more S100A8 mRNA and protein than the sun-protected skin of the same individuals. In immunohistochemical staining, facial (photoaged) skin ≥72 years showed higher epidermal expression of S100A8 than that of the other age groups. Based on the above results, our data suggest that the expression of S100A8 is affected by acute UV irradiation, intrinsic aging and photoaging processes. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0960-8Authors Young Mee Lee, Seoul National University Hospital Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute 28, Yeongeon-Dong, Chongno-Gu Seoul 110-744 KoreaYeon Kyung Kim, Seoul National University Hospital Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute 28, Yeongeon-Dong, Chongno-Gu Seoul 110-744 KoreaHee Chul Eun, Seoul National University Hospital Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute 28, Yeongeon-Dong, Chongno-Gu Seoul 110-744 KoreaJin Ho Chung, Seoul National University Hospital Department of Dermatology, Seoul National University College of Medicine and Laboratory of Cutaneous Aging Research, Clinical Research Institute 28, Yeongeon-Dong, Chongno-Gu Seoul 110-744 Korea Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

A novel KIT missense mutation in one Chinese family with piebaldism

Abstract Piebaldism is an autosomal dominant disorder characterized by congenital leukoderma, mostly affecting forehead, abdomen and knee. Previous studies have revealed that piebaldism is caused by mutations of the KIT gene, which encodes the cell surface transmembrane tyrosine kinase receptor for KIT ligand. We reported here a Chinese Han family with piebaldism, and performed mutation detection of KIT gene by direct sequencing. A novel missense mutation C58G was identified in the patients, but not in the healthy individuals from the family and 100 unrelated controls. This study contributes to the database on KIT in piebaldism and enriches the knowledge about the genotype/phenotype correlation. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00403-009-0955-5Authors Xian-Yong Yin, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaYun-Qing Ren, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaSen Yang, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaSheng-Xin Xu, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaFu-Sheng Zhou, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaWen-Hui Du, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaDa Lin, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaPei-Guang Wang, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaShu-Mei Zhang, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of ChinaXue-Jun Zhang, Anhui Medical University Institute of Dermatology 81 Meishan Road 230032 Hefei Anhui People’s Republic of China Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696 Journal Volume Volume 301 Journal Issue Volume 301, Number 5 / June, 2009

The effect of the moisture content of a local heat source on the blood flow response of the skin

Abstract Numerous studies have examined the effect of local and global heating of the body on skin blood flow. However, the effect of the moisture content of the heat source on the skin blood flow response has not been examined. Thirty-three subjects, without diabetes or cardiovascular disease, between the ages of 22 and 32 were examined to determine the relationship between the effects of dry vs. moist heat applied for the same length of time and with the skin clamped at the same skin temperature on the blood flow response of the skin. The skin, heated with an infrared heat lamp (skin temperature monitored with a thermocouple) to 40°C for 15 min, was either kept moist with wet towels or, in a separate experiment, kept dry with Drierite (a desiccant) between the towels to remove any moisture. Before and after heat exposure of the forearm, blood pressure, heart rate, skin moisture content, skin temperature, and skin blood flow were recorded. The results of the experiment showed that there was no change in skin moisture after 15 min exposure to dry heat at 40°C. However, with moist heat, skin moisture increased by 43.7%, a significant increase (P < 0.05). With dry heat, blood flow increased from the resting value by 282.3% whereas with moist heat, blood flow increased by 386% over rest, a significant increase over dry heat (P < 0.05). Thus, with a set increase in skin temperature, moist heat was a better heating modality than dry heat. The reason may be linked to moisture sensitivity in calcium channels in the vascular endothelial cell. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00403-009-0957-3Authors Jerrold Scott Petrofsky, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAGurinder Bains, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAChinna Raju, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAEverett Lohman, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USALee Berk, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAMichelle Prowse, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAShashi Gunda, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAPiyush Madani, Loma Linda University Department of Physical Therapy Loma Linda CA 92350 USAJennifer Batt, Azusa Pacific University Department of Physical Therapy Azusa CA USA Journal Archives of Dermatological ResearchOnline ISSN 1432-069XPrint ISSN 0340-3696

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.

Nonlinear modeling of venous leg ulcer healing rates

Background: The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics. Methods: We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments. Results: A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model. Conclusion: We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.

Mutation analysis of the Gadd45 gene at exon 4 in atypical fibroxanthoma

Background: Atypical fibroxanthoma (AFX) histologically mimics high-grade sarcoma in the skin, although it follows a benign clinical course. AFX occurs in the sun-exposed skin and for this reason, an association with ultraviolet light has long been suspected. Bax and Gadd45 are p53 effector proteins. Bax is a programmed cell death protein and belongs to the Bcl-2 family. Gadd45 is a multifunctional DNA damage-inducible gene associated with the process of DNA damage. Methods: Immunohistochemical expression of Bax was analyzed in 7 cases of AFX, and in 7 cases of benign fibrous histiocytoma (BFH) used as a comparison. The expression pattern of Bax was compared to previously reported p53 and Gadd45 expressions in a correspondent series. Mutation of the Gadd45 gene at exon 4 was also analyzed in AFX. Results: AFX and BFH showed immunoreactivities respectively for Bax (3/7, 0/7), Gadd45 (4/7, 1/7) and p53 (2/7, 0/7). There was no exact correlation between p53 expression and Bax or Gadd45 expression. However, the pattern of expression between Bax and Gadd45 was also the same, with the exception of one case. No mutation of the Gadd45 gene at exon 4 was observed in a series of 6 AFX cases where DNA was available (0/6). Conclusion: These results suggest a possible association between Bax and Gadd45 in AFX, and may refute any possibility of dysfunction of Gadd45 in terms of gene mutation, at least at exon 4 of the Gadd45 gene.

Dermatitis associated with exposure to a marine cyanobacterium during recreational water exposure

Background: Anecdotal evidence reported an outbreak of symptoms on Fraser Island during the late 1990s similar to those expected from exposure to dermotoxins found in the cyanobacterium L. majuscula. This coincided with the presence of a bloom of L. majuscula. Methods: Records from the Fraser Island National Parks First aid station were examined. Information on cyanobacterial blooms at Fraser Island were obtained from Queensland National Parks rangers. Results: Examination of first aid records from Fraser Island revealed an outbreak of symptoms predominantly in January and February 1998. Conclusion: During a bloom of L. majuscula there were numerous reports of symptoms that could be attributed to dermotoxins found in L. majuscula. The other four years examined had no L. majuscula blooms and the number of L. majuscula symptoms was much reduced. These cases comprised a high percentage of the cases treated at the first aid station.

Assessment of a new questionnaire for self-reported sun sensitivity in an occupational skin cancer screening program

Background: Sun sensitivity of the skin is a risk factor for the development of cutaneous melanoma and other skin cancers. Epidemiological studies on causal factors for the development of melanoma must control for sun sensitivity as a confounder. A standardized instrument for measuring sun sensitivity has not been established yet. It is assumed that many studies show a high potential of residual confounding for sun sensitivity. In the present study, a new questionnaire for the assessment of self-reported sun sensitivity is administered and examined. Methods: Prior to an occupational skin cancer screening program, the 745 participating employees were asked to fill in a questionnaire for self-assessment of sun sensitivity. The questionnaire was developed by experts of the working group "Round Table Sunbeds" (RTS) to limit the health hazards of sunbed use in Germany. A sun sensitivity score (RTS-score) was calculated using 10 indicators. The internal consistency of the questionnaire and the agreement with other methods (convergent validity) were examined. Results: The RTS-score was calculated for 655 study participants who were 18 to 65 years of age. The correlation of the items among each other was between 0.12 and 0.62. The items and the RTS-score correlated between 0.46 and 0.77. The internal consistency showed a reliability coefficient with 0.82 (Cronbach's alpha). The comparison with the Fitzpatrick classification, the prevailing standard, was possible in 617 cases with a rank correlation of rs = 0.65. The categorization of the RTS-score in four risk groups showed correct classification to the four skin types of Fitzpatrick in 75% of the cases. Other methods for the assessment of sun sensitivity displayed varying agreements with the RTS-score. Conclusion: The RTS questionnaire showed a sufficient internal consistency. There is a good convergent validity between the RTS-score and the Fritzpatrick classification avoiding shortcomings of the prevailing standard. The questionnaire represents a simple, reliable and valid instrument for the assessment of sun sensitivity. The questionnaire can be useful for epidemiological studies as well as for skin cancer prevention. Further development and standardization of sun sensitivity assessments is necessary to strengthen the evidence of epidemiological studies on causal factors of melanoma and other skin cancers.

Melasma and its association with different types of nevi in women: A case control study

Background: Very little is known about possible association of nevi and melasma. The study objective was to determine if there is an association between melasma and existence of different kinds of nevi. Methods: In a case-control study, 120 female melasma patients referred to dermatology clinic of Ardabil and 120 patients referred to other specialty clinics who lacked melasma were enrolled after matching for age. Number of different types of nevi including lentigines and melanocytic nevi were compared between case and control group patients. Data were entered into the computer and analyzed by SPSS 13 statistical software. Results: Mean number of lentigines was 25.5 in melasma group compared to 8 in control group(P < 0.01). Mean number of melanocytic nevi was 13.2 in cases compared to 2.8 in control group(P < 0.001). Multivariate analysis showed that existence of freckles, lentigines and more than three melanocytic nevi were positively related to developing melasma. The chance of melasma increased up to 23 times for patients having more than three melanocytic nevi. Congenital nevi were observed among 10% both in case and control groups. Campbell de morgan angiomas were seen among 26 patients(21.8%) in case group compared to 6 patients(5%) in control group. Conclusion: Existence of lentigines and melanocytic nevi increases chance of having melasma

A systematic review of natural health product treatment for vitiligo

Background: Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods: Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results: Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion: Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral Ginkgo biloba as monotherapy show promise and warrant further investigation.

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

Background: Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors. Methods: 0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts. Results: Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin. Conclusion: Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.