<Emphasis Type="Italic">Trichophyton mentagrophytes </Emphasis>– vom Schneeleoparden zum Menschen

Sources of infection for Trichophyton (T.) mentagrophytes—a zoophilic dermatophyte—comprise pet rodents (guinea pigs, mice, rabbits) and sometimes cats. Human infections due to dermatophytes after contact with zoo animals, however, are extreme rare. Four zoo keepers from Basel Zoo were diagnosed to suffer from tinea manus and tinea corporis due to T. mentagrophytes. The 22-year-old daughter of one zoo keeper was also infected with tinea corporis after having worked in the snow leopard section for one day. The strain of the index patient was confirmed by a direct uniplex-PCR-EIA and sequence analysis of the ribosomal internal transcribed spacer (ITS) region (18S rRNA, ITS1, 5.8S rRNA, ITS2, 28S rRNA) as T. mentagrophytes. Three young snow leopards from Basel Zoo were identified as the origin of the fungal skin infection. The transmission occurred due to direct contact of the zoo keepers with the young snow leopards when removing hedgehog ticks (Ixodes hexagonus). Two adult snow leopards had developed focal alopecia of the facial region which was diagnosed as dermatomycoses due to T. mentagrophytes by the zoo veterinarians. By sequence analysis, both the strains from the animals and a single strain of the index patient showed 100% accordance proving transmission of T. mentagrophytes from animals to the zoo keepers. Molecular biological identification revealed a strong relationship to a strain of T. mentagrophytes from European mink (Mustela lutreola) from Finland. Treatment of patients was started using topical ointment with azole antifungals, and oral terbinafine 250?mg once daily for 4 weeks. Both adult snow leopards and the asymptomatic young animals were treated with oral itraconazole.     

Aging decreases collagen IV expression <Emphasis Type="Italic">in vivo</Emphasis> in the dermo-epidermal junction and <Emphasis Type="Italic">in vitro</Emphasis> in dermal fibroblasts: possible involvement of TGF-β1

Background

Collagen IV is a major component of the dermo-epidermal junction (DEJ).

Objectives

To study expression of collagen IV upon aging in the DEJ and dermal fibroblasts isolated from the same patients. A model of senescent fibroblasts was developed in order to identify biological compounds that might restore the level of collagen IV.

Materials & methods

Skin fragments of women (30 to 70 years old) were collected. Localisation of collagen IV expression in the DEJ was studied by immunofluorescence. Fibroblast collagen IV expression was studied by real-time PCR, ELISA, and western blotting. Premature senescence was simulated by exposing fibroblasts to subcytotoxic H₂O₂ concentrations.

Results

Collagen IV decreased in the DEJ and fibroblasts relative to age. TGF-β1 treatment significantly increased collagen IV gene and protein expression in fibroblasts and restored expression in the model of senescence. Addition of TGF-β1-neutralizing antibody to fibroblast cultures decreased collagen IV expression.

Conclusion

Taken together, the results suggest that the decrease in collagen IV in the DEJ, relative to age, could be due to a decrease in collagen IV expression by senescent dermal fibroblasts and may involve TGF-β1 signalling.

     

RETRACTED ARTICLE: <Emphasis Type="Italic">Gln50Ter</Emphasis> Polymorphism of <Emphasis Type="Italic">Fcγ</Emphasis> receptor IIB gene associated with genetic susceptibility to human systemic lupus erythematosus in Chinese populations

The aim of this study was to investigate the role of FcγRIIB gene in susceptibility to systemic lupus erythematosus (SLE) using family-based association methods. In total, 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, who met the American College of Rheumatology (ACR) 1997 criteria, were recruited, as were 316 family members of these patients. A family-based association analysis was used to explore the relationship between gene polymorphism and SLE. We studied three single-nucleotide polymorphisms (SNPs, rs10917661, rs5017567, and rs1050499) encoding non-synonymous substitution in the FcγRIIB gene with respect to genetic susceptibility to SLE in collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR-restriction fragment length polymorphism method. Among 119 SLE patients, the frequencies of FcγRIIB Gln/Gln,Gln/Ter and Ter/Ter genotypes were 12.7, 60.7 and 26.6%. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at a SNP, rs10917661, in exon 2 of FcγRIIB gene were significantly associated with genetic susceptibility to SLE in additive model (exon 2, Z = 3.444, P = 0.00057). transmission/disequilibrium test (TDT) and sibship disequilibuium test (SDT) analysis showed an excess of the alleles of 50Ter from heterozygous parents to affected offspring (χ² = 10.88, P = 0.0013). However, the rs5017567 and rs1050499 SNPs were not found in Chinese population. Our findings provide strong evidence suggesting that a FcγRIIB–Gln50Ter loci might be the susceptible factor of SLE in Chinese population.     

<Emphasis Type="Italic">In vivo</Emphasis> assessment of the effect of a cream containing <Emphasis Type="Italic">Avena Rhealba</Emphasis><Superscript>®</Superscript> extract and hyaluronic acid on the restoration of the skin barrier in de-epidermised skin produced with an erbium-YAG laser

Background

Wound healing studies require standardised methods for evaluating wounding and skin repair.

Objectives

Our study aimed to demonstrate the suitability of the erbium-YAG (Er-YAG) laser method to produce reliable epidermal lesions for evaluation of different skin repair creams.

Materials and methods

Skin de-epidermised by Er-YAG laser (four uniform epidermal ablations, area 8 × 8mm, in 21 healthy subjects) was treated with a product (A) containing Avena Rhealba ^® extract and hyaluronic acid and assessed for epidermal regeneration and barrier restoration. This treatment was compared to two reference products (B) and (C) and an untreated control. Over 22 days of treatment, doubleblind measurements ofwound characteristics were made for instrumental (wound surface area, barrier restoration, 3D skin topography) and clinical evaluation (lesion quality and tolerance).

Results

Tested product (A) resulted in a shorter time (9 days) and faster rate of wound closure than product C (12 days) and the untreated zone (16 days). Results for products (A) and (B) were similar. Clinical evaluation of lesion quality showed the same trends as the wound area/closure parameter. Barrier recovery assessments revealed that all three products showed a similar rate of decreasing Transepidermal Water Loss (TEWL), which was significantly faster than the rate for the control.

Conclusion

In conclusion, the laser-induced epidermal wound model provided standardised lesions, enabling discrimination between different topical skin repair products.

     

Postmarketing Experience of Intralesional Collagenase <Emphasis Type="Italic">Clostridium histolyticum</Emphasis> (Xiaflex®) Injection in Men with Peyronie’s Disease

Purpose of Review

There are limited data on postmarketing patient outcomes, as well as safety and management of complications, with use of intralesional collagenase Clostridium histolyticum (Xiaflex®). This review aims to highlight recent postmarketing experiences and management concepts of intralesional collagenase C. histolyticum (Xiaflex®) use.

Recent Findings

Postmarketing data may help determine whether the frequency of collagenase C. histolyticum-related corporal ruptures is similar to real-world clinical experience compared to phase III clinical trials. Additionally, corporal ruptures have been observed outside the recommended abstinence period outlined by the Risk Evaluation and Mitigation Strategy protocol. These findings, coupled with compromised tissue quality observed at time of surgical repair, have led to controversies in the management of collagenase C. histolyticum-related corporal ruptures.

Summary

Corporal ruptures remain a concern as reported in the Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Study trials. With evidence of advanced local tissue degradation leading to delayed corporal ruptures, an evolving management of these injuries is developing. Close observation, rather than surgical intervention, may be an appropriate treatment option for selected patients. Lengthening the recommended abstinence period from the time of the last injection may be prudent with the administration of intralesional collagenase C. histolyticum. Postmarketing efficacy data have been consistent with phase III trials.

     

Novel mutations of the <Emphasis Type="Italic">ATP2A2</Emphasis> gene in two families with Darier’s disease

Darier’s disease (DD) is an autosomal dominant genodermatology. Mutations in the ATP2A2 gene encoding sarco-endoplasmic reticulum calcium pumping ATPase type 2 (SERCA2) have been identified as the molecular basis of DD. The aim of this study was to report two Chinese pedigree of DD and to explore the genetic mutations. Polymerase chain reaction was carried out to amplify the exons and flanking intron boundaries of the ATP2A2 gene followed by direct sequencing. Two novel missense mutations were identified, a change of C203 to A (A68E) in exon 3 was found in one family and a change of C2759 to T (S920F) in exon 19 in the other, which were located within the transmembrane domain of SERCA2, highly conserved during evolution. The A68E and S920F mutations might be regarded as the causes of the disease in two Chinese families, but these were not tested functionally. Additional functional experiments are necessary to verify the relevance and suitability of these findings for future use in genetic counseling and prenatal diagnosis.     

Fermentable metabolite of <Emphasis Type="Italic">Zymomonas mobilis</Emphasis> controls collagen reduction in photoaging skin by improving TGF-β/Smad signaling suppression

Solar ultraviolet (UV) irradiation causes damages on human skin and premature skin aging (photoaging). UV-induced reduction of type I collagen in dermis is widely considered primarily induction of wrinkled appearance of photoaging skin. Type I procollagen synthesis is reduced under UV irradiation by blocking transforming growth factor-β (TGF-β)/Smad signaling; more specifically, it is down-regulation of TGF-β type II receptor (TβRII). Therefore, preventing UV-induced loss of TβRII results decreased type I collagen reduction in photoaging skin. Zymomonas mobilis is an alcohol fermentable, gram-negative facultative anaerobic bacterium whose effect on skin tissue is scarcely studied. We investigated the protective effects of fermentable metabolite of Z. mobilis (FM of Z. mobilis) against reduction of type I procollagen synthesis of UV-induced down-regulation of TβRII in human dermal fibroblasts FM of Z. mobilis was obtained from lyophilization of bacterium culture supernatant. The levels of TβRII and type I procollagen mRNA in human dermal fibroblasts were measured by quantitative real-time RT-PCR, and TβRII protein levels were assayed by western blotting. TβRII, type I procollagen, and type I collagen proteins in human dermal fibroblasts or hairless mouse skin were detected by immunostaining. FM of Z. mobilis inhibited down regulation of TβRII mRNA, and protein levels in UVB irradiated human dermal fibroblasts consequently recover reduced type I procollagen synthesis. These results indicate UVB irradiation inhibits type I procollagen synthesis by suppression of TGF-β/Smad signaling pathway, and FM of Z. mobilis has inhibitory effect on UVB-induced reduction of type I procollagen synthesis. While short period UVB irradiation decreased both TβRII and type I procollagen protein levels in hairless mouse skin, topical application of FM of Z. mobilis prevented this decrease. Wrinkle formation in hairless mouse skin surface was accelerated by continuous 5 month UVB irradiation along with a reduction of type I collagen in the dermis, but this change was prevented by topical application of FM of Z. mobilis. From this experimental data, it is suggested that FM of Z. mobilis is effective for suppression of wrinkle formation in photoaging skin by inhibition of type I procollagen synthesis reduction.     

Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser <Emphasis Type="Italic">versus</Emphasis> ablative CO<Subscript>2</Subscript> fractional laser–a randomized controlled trial

Background

Lentigines solares (LS) on the dorsum of hands are often esthetically disturbing. Q-switched ruby laser treatment is highly effective in the treatment of these lesions. Ablative fractional photothermolysis may be a suitable alternative.We compared the Q-switched ruby laser with ablative CO₂ fractional photothermolysis for the treatment of solar lentigines.

Objective

To evaluate the efficacy and side-effects of 694nm Q-switched ruby laser (Sinon) with the ablative 10,600nm CO₂ fractional laser (Quantel Excel O2) in an intra-individual side-to-side comparison in the treatment of LS on the dorsum of hands.

Material and methods

Eleven patients were included in the study. The hands of each patient were randomized for treatment with the two laser systems. Three treatment sessions were scheduled at weeks 0, 4 and 8. Evaluations by patients, treating physician and blinded experts were scheduled at weeks 0, 4, 8, 16 and 24.

Results

The Q-switched ruby laser was significantly more efficacious than the ablative CO₂ fractional laser for removing LS on the dorsum of hands (p = 0.01).

Conclusion

In this first study on this topic, the Q-switched ruby laser was superior to the ablative CO₂ fractional laser in the treatment of lentigines solares on the dorsum of hands.

     

The Canadian Dermatology Workforce Survey: Implications for the Future of Canadian Dermatology—Who will be <Emphasis Type="Italic">your</Emphasis> skin expert?

Objective To survey Canadian dermatologists for specialty-specific physician resource information including demographics, workload and future career plans.Background and Methods In 2001, the Canadian Dermatology Association (CDA) surveyed 555 dermatologists in Canada to gain specialty-specific physician resource information. Three hundred and seventy-one dermatologists (69%) provided information about themselves, their workloads and their future career goals.Results The average Canadian dermatologist is 52 years old and 35% of practicing dermatologists are over the age of 55. Eighty-nine percent of dermatologists practice in an urban setting, 19% include practice in a rural setting while less than 0.5% practice in remote areas. Canadian dermatologists spend 61% of their clinical time providing services in Medical Dermatology. Within 5 years, 50% of dermatologists reported that they plan to reduce their practices or retire.Conclusion The Canadian Dermatology Workforce Survey provides a snapshot of the current practice of dermatology in Canada. It also serves to highlight the critical shortage of dermatologists, which will continue to worsen without immediate, innovative planning for the future.

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SommaireObjectif Mener une enquête auprès des dermatologues canadiens en vue de recueillir des données sur les spécialtiés, y compris les données démographiques, la charge de travail et le plan de carrière.Antécédents et methodes En 2001, lAssociation canadienne de dermatologie (ACD) a mené une enquête auprès de 555 dermatologues au Canada en vue dobtenir des données propres aux spécialités. Parmi les dermatologues sondés, 371 (69%) ont fourni de linformation sur eux-mêmes, leur charge de travail et leurs objectifs de carrière.Résultats Le dermatologue canadien moyen est âgé de 52 ans, et 35% des dermatologues actifs ont plus de 55 ans. Parmi les dermatologues actifs, 89% travaillent dans des villes, 19% exercent dans des régions rurales alors que 0.5% se trouvent dans des régions éloignées. Au Canada, les dermatologues passent 61% de leur temps en clinique à offrir des services en dermatologie médicale. Au cours des 5 prochaines années, 50% des répondants comptent réduire leur temps de travail ou aller en retraite.Conclusion Lenquête sur les ressources dermatologiques trace le profil actuel de la profession au Canada. Également, lenquête souligne le manque de dermatologues qui saggrave sans quil ny ait en place une stratégic immédiate et novatrice pour lavenir.

     

Alemtuzumab is an effective third-line treatment <Emphasis Type="Italic">versus</Emphasis> single-agent gemcitabine or pralatrexate for refractory Sézary syndrome: a systematic review

The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly characterized. To elucidate the effectiveness of alemtuzumab versus other third-line options for the treatment of refractory SS, we conducted a meta-analysis of existing data. A systematic review was performed in March 2017 based on a search using Ovid-MEDLINE® and OVID-EMBASE® for articles evaluating single-agent alemtuzumab, gemcitabine, or pralatrexate for the treatment of SS and mycosis fungoides (MF). Twenty-two publications were identified that fulfilled all search criteria (total n = 323 patients), with six publications of lower quality being excluded from our analysis in order to decrease the risk of bias (final: n = 308 patients; 93 with SS and 147 with MF). Across all studies, alemtuzumab was significantly more effective in patients with SS (overall response rate [ORR]: 81%; complete response rate [CRR]: 38%) than patients with MF (ORR: 29%; CRR: 8%). However, gemc-itabine was more effective than alemtuzumab or pralatrexate in treating MF. Alemtuzumab-treated patients had more frequent side effects, which were influenced by route of administration and dose. There was a lower incidence of lymphopenia and other serious adverse events in patients treated with subcutaneous (38%) compared to intravenous regimens (68%), and lower-dose (5%) compared to high-dose alemtuzumab regimens (54%). No significant differences were found in the effectiveness of different routes of administration or dosing regimens. Our review supports the use of low-dose subcutaneous alemtuzumab as a third-line treatment for SS.     

A novel <Emphasis Type="Italic">PLEC</Emphasis> nonsense homozygous mutation (c.7159G &gt; T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report

Background

Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disease, characterized mainly by skin blistering at birth or shortly thereafter, progressive muscle weakness, and rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM *601282), which encodes plectin, a structural protein expressed in several tissues, including epithelia and muscle. We describe a patient affected with EBS-MD and diffuse alopecia in which we identified a novel pathogenic mutation by PCR amplification of all coding exons and exon–intron boundaries of PLEC gene, followed by bidirectional Sanger sequencing.

Case presentation

The patient, a 28-year-old female and only child of consanguineous healthy parents, was born after uneventful pregnancy. At 2 days of age, she developed skin and oral mucosal blistering, accompanied by voice hoarseness. On physical examination as an adult, we observed diffuse non-scarring alopecia on the scalp, onychodystrophy (pachyonychia) in all 20 nails, dental decay, mild dysphonia, and severe muscle atrophy mainly affecting the extremities. Neurological examination showed profoundly diminished reflexes. Mutation analysis revealed the patient to be homozygous for the novel PLEC nonsense mutation ? c.7159G?>?T (p.Glu2387*) ? located in exon 31. Thismutation predicts the lack of expression of the full-length plectin isoform.

Conclusion

The present case appears to be the second association of EBS-MD with diffuse alopecia, both cases having different mutations involving PLEC exon 31. It remains to be elucidated whether diffuse alopecia results from PLEC mutations and/or from environmental factors.

     

Why care about Linear Hair Growth Rates (LHGR)? A study using <Emphasis Type="Italic">in vivo</Emphasis> imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL)

Background

The words “hair growth” frequently encompass many aspects other than just growth.

Objectives

Report on a validation method for precise non-invasive measurement of thickness together with linear hair growth rates of individual hair fibres. To verify the possible correlation between thickness and linear growth rate of scalp hair in male pattern hair loss as compared with healthy male controls.

Materials and methods

To document the process of validation of hair growth measurement from in vivo image capturing and manual processing, followed by computer assisted image analysis. We analysed 179 paired images obtained with the contrast-enhanced-phototrichogram method with exogen collection (CE-PTG-EC) in 13 healthy male controls and in 87 men with male pattern hair loss (MPHL).

Results

There was a global positive correlation between thickness and growth rate (ANOVA; p<0.0001) and a statistically significantly (ANOVA; p<0.0005) slower growth rate in MPHL as compared with equally thick hairs from controls. Finally, the growth rate recorded in the more severe patterns was significantly (ANOVA; P≤0.001) reduced compared with equally thick hair from less severely affected MPHL or controls subjects.

Conclusion

Reduced growth rate, together with thinning and shortening of the anagen phase duration in MPHL might contribute together to the global impression of decreased hair volume on the top of the head. Amongst other structural and functional parameters characterizing hair follicle regression, linear hair growth rate warrants further investigation, as it may be relevant in terms of self-perception of hair coverage, quantitative diagnosis and prognostic factor of the therapeutic response.

     

Levels of TGF-β<Subscript>1</Subscript> in serum and culture supernatants of CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> T cells from patients with non-segmental vitiligo

Compelling evidences support an autoimmune basis of non-segmental vitiligo, and dysregulation of CD4⁺CD25⁺ regulatory T cell (Treg) is assumed to contribute to the pathogenesis of vitiligo. Serum levels of transforming growth factor-β (TGF-β), an important immunoregulatory cytokine produced by Treg cells, has been reported significantly decreased in patients with vitiligo. However, relation between the decrease in TGF-β and the dysfunction of Treg cells in pathogenesis of vitiligo was still undemonstrated. To further reveal the role of TGF-β in vitiligo, 46 patients with non-segmental vitiligo and 25 age- and sex-matched healthy control subjects were enrolled in the study. CD4⁺CD25⁺ T cells isolated from peripheral venous blood with a CD4⁺CD25⁺ regulatory T cell isolation kit were cultured with or without anti-CD3 mAbs and anti-CD28 mAbs for 4 days. The TGF-β1 levels in serum and culture supernatants were detected by enzyme-linked immunosorbent assay in both groups. We have found that the TGF-β1 levels both in serum and culture supernatants in the presence of anti-CD3 mAbs and anti-CD28 mAbs were decreased in the active vitiligo group when compared with the control group or stable vitiligo group, and were negatively correlated with the percentage of involved body area. These results suggested that TGF-β may play a role in the pathogenesis of non-segmental vitiligo related to the suppressive function of Tregs.     

Prednicarbate (Dermatop<Superscript>®</Superscript>): Profile of a Corticosteroid

Background Topical steroids have been a popular choice for treating various cutaneous disorders; however, the potential for significant local and systemic adverse events, like skin atrophy and hypothalamic–pituitary–adrenal (HPA) axis suppression, has limited their use.Objective This article reviews the topical steroid prednicarbate through its mechanism of action, clinical efficacy, and adverse events profile.Methods Published literature containing the word “prednicarbate” was examined and summarized.Results Prednicarbate is a nonhalogenated, double-ester derivative of prednisolone that has been used in the treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses such as atopic dermatitis. It has a favorable benefit–risk ratio, low skin atrophy potential, and high anti-inflammatory action.Conclusion These characteristics make prednicarbate an ideal alternative agent for children, elderly patients, and those who require long-term intermittent treatment.

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SommaireAntécédents Les stéroïdes topiques représentent un choix populaire dans le traitement de divers troubles cutanés. Toutefois, la possibilité d’événements indésirables locaux et systémiques, tels que 1’atrophie cutanée et la suppression de 1’axe hypothalamo-hypophyso-surrénalien, ont limité leur usage.Objectif Cette étude souligne le mécanisme d’action, 1’efficacité clinique et le profil des événements indésirables du prednicarbate, un stéroïde topique.Méthode Les articles spécialisés publiés contenant le terme ‹prednicarbate› ont été revus et résumés.Résultats Le prednicarbate est un dérivé du prednisone, non halogéné et double ester, utilisé dans le traitement des manifestations inflammatoires et pruritiques des dermatoses qui réagissent aux corticostéroïdes, telles que les dermatites atopiques. Le prednicarbate présente un rapport avantage-risque favorable, avec un faible potentiel d’atrophie cutanée et une action anti-inflammatoire puissante.Conclusion Grâce à ces caractéristiques, le prednicarbate est un agent alternatif idéal pour les enfants, les personnes âgées et les patients nécessitant un traitement intermittent de longue durée.

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The work was supported in part by Dermik Laboratories.