Vesicular Darier's disease: a case report and review of the English literature of a rare disease variant.

Darier's disease is an autosomal dominant inherited skin disorder resulting from mutations in the ATP2A2 gene, which encodes SERCA2, an endoplasmic reticulum calcium ATPase. Darier's disease classically manifests as confluent hyperkeratotic brown-to-red papules that manifest and follow a seborrheic distribution, which include the chest, neck, trunk, and face. Vesicular Darier's disease is a rare variant of the disorder where patients develop numerous vesicles and bullae concurrently or independent of the more typical lesions found in Darier's disease.

Arginine Catabolic Mobile Element in Evolution and Pathogenicity of the Community-Associated Methicillin-Resistant Staphylococcus aureus Strain USA300.

USA300 is a predominant community-associated methicillin-resistant Staphylococcus aureus strain which carries an arginine catabolic mobile element (ACME). ACME contains potential virulence factors including an arginine deiminase (arc) pathway and an oligopeptide permease (opp-3) system, which are proposed to play a role in bacterial virulence and transmission. However, the role of ACME in evolution and pathogenicity of USA300 remains to be elucidated. ACME and arcA deletion mutants were created by allelic replacement from a USA300 clinical isolate. By comparing wild type and isogenic ACME deletion USA300 strains, ACME was shown not to contribute to bacterial survival on plastic surfaces, and mouse skin surfaces. ACME did not contribute to bacterial virulence in cell invasion and cytotoxicity assays, invertebrate killing assays and a mouse skin infection model. Wild-type ACME negative USA300 clinical isolates showed similar associations with invasive anatomic sites as ACME positive isolates. Our experiments also demonstrated that ACME can spontaneously excise from the bacterial chromosome to generate an ACME deletion strain at a low frequency. Our results do not support that the ACME element alone is a significant factor in the transmission and virulence of USA300 strain, and ACME may have been coincidently incorporated into the genome of USA300.

Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor-κB inflammatory signaling pathway in human skin cells.

INTRODUCTION: Corynebacterium tuberculostearicum (C. t.) is a ubiquitous bacterium that colonizes human skin. In contrast to other members of the genus Corynebacterium, such as toxigenic Corynebacterium diphtheriae or the opportunistic pathogen Corynebacterium jeikeium, several studies suggest that C. t. may play a role in skin health and disease. However, the mechanisms underlying these effects remain poorly understood. METHODS: To investigate whether C. t. induces inflammatory pathways in primary human epidermal keratinocytes (HEKs) and human cutaneous squamous carcinoma cells (SCCs), cell culture, reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay, immunofluorescence microscopy, Western blot, chromatin immunoprecipitation-PCR, small interfering RNA knockdown and luciferase reporter expression system were used. RESULTS: Herein, we demonstrate that C. t. upregulates the messenger RNA (mRNA) and protein levels of inflammatory mediators in two human skin cell lines, HEKs and SCCs. We further show activation of the canonical nuclear factor-κB (NF-κB) pathway in response to C. t. infection, including phosphorylation of the inhibitor of κB (IκB), the nuclear translocation of NF-κB subunit (NF-κB-P65 ) and the recruitment of NF-κB-P65 and RNA polymerase to the NF-κB response elements at the promoter region of the inflammatory genes. Lastly, the data confirm that C. t.-induced tumor necrosis factor mRNA expression in HEKs is toll-like receptor 2 (TLR2 ) dependent. CONCLUSION: Our results offer a mechanistic model for C. t.-induced inflammation in human keratinocytes via TLR2 and activation of IκB kinase and downstream signaling through the canonical NF-κB pathway. Relevance to chronic inflammatory diseases of the skin and cutaneous oncology is discussed.

Epidermal Carcinoma of the Conchal Bowl: Creation of a Multidisciplinary Pathway Approach.

BACKGROUND: Malignant neoplasms of the auricle make up 6% of all skin cancers. Management of cutaneous neoplasms of the conchal bowl presents a unique challenge in visualizing and defining margins that may extend into the external auditory canal (EAC). OBJECTIVES: The objective of this study was to create a multidisciplinary pathway for cutaneous carcinoma of the conchal bowl extending into the EAC. METHODS: We present a series of patients that were referred to dermatology or otolaryngology, with cutaneous neoplasms arising in the conchal bowl. A consensus approach from otolaryngology and dermatology, for evaluation and treatment, was created based on evaluation of these cases, and review of the otolaryngology and dermatology literature, in collaboration between the two specialties. RESULTS: Initial evaluation should be done by both dermatology and otolaryngology, with otomicroscopic evaluation of the canal. Imaging is recommended for lesions that approach the EAC, for bony and soft tissue spread. Excision of the tumor with Mohs micrographic surgery to achieve clearance in the conchal bowl should be performed initially. If extension into the external auditory meatus is present, otolaryngology would proceed with en bloc resection. Repair is dictated by the defect, with both specialties involved in follow-up. CONCLUSIONS: In collaboration between dermatology and otolaryngology, and following review of the literature, a pathway was created to manage skin cancer of the conchal bowl. This resulted in a stepwise approach for evaluation and management, ensuring that patients have a streamlined pathway for the treatment of these lesions.

Mohs Micrographic Surgery Dermatopathology Concordance in Canada: A Single-Institution Experience.

BACKGROUND:: Mohs micrographic surgery (MMS) is a surgical modality that achieves high cure rates of nonmelanoma skin cancers but is dependent on accurate histologic examination of surgical margins. Therefore, quality assurance is essential to ongoing assessment of histological margins. OBJECTIVES:: To prospectively determine the concordance rate between a Mohs surgeon (MS) and dermatopathologist (DP) with respect to tumour status (ie, present or absent) and tumour type. Secondary end points were to determine the relationship between discordant interpretations and slide quality and to assess the feasibility of using an electronic webform for data collection. METHODS:: Ten percent (10%) of the planned MMS cases between January 2015 and March 2016 were randomly selected by a histotechnologist at the start of each month. The MS and DP were blinded to the chosen cases, and slides were reviewed independently at the beginning of the following month. Data were collected using an online webform. A blinded third party determined if there were discrepancies in interpretation, and any discordant slides were reviewed together and a consensus was reached. RESULTS:: A total of 270 slides from 54 total cases were reviewed. The overall tumour status concordance rate was 93.6%. Cohen's κ was 0.86. Tumour type concordance was 98.9%. No discrepancy required a change in patient care. All discrepant slides were from cases that required multiple stages. CONCLUSIONS:: This is the first study looking at MS-DP concordance in Canada, and our findings support the MS acting as his or her own pathologist.

Photodynamic Therapy Followed by Mohs Micrographic Surgery Compared to Mohs Micrographic Surgery Alone for the Treatment of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised Controlled Trial.

INTRODUCTION: Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the "gold standard" treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate. Other treatment modalities used include photodynamic therapy (PDT). BACKGROUND: We aimed to study the efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size when compared with MMS alone. MATERIALS AND METHODS: Our study was a single-centre, single-blinded, randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. RESULTS: In the PDT arm, five out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. CONCLUSION: Our pilot study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this combination therapy.

Treatment of port wine stains with photodynamic therapy, using pulsed dye laser as a light source, compared with pulsed dye laser alone: a pilot study.

BACKGROUND AND OBJECTIVES: Laser-induced photo thermal damage has been combined with photodynamic therapy (PDT) using a systemic photosensitiser to treat vascular lesions. The efficacy of PDT using systemic 5-aminolaevulinic acid (5-ALA) as the photosensitiser and pulsed dye laser (PDL) as the light source in port wine stains (PWS) is unknown. STUDY DESIGNS/MATERIALS AND METHODS: We conducted an internally controlled pilot study comparing the efficacy of PDT using PDL as a light source, to PDL alone in the treatment of PWS. RESULTS: The PWS improved slightly in all patients but no significant difference was found between the three treatment arms in terms of lesional lightening or incidence and severity of side effects. CONCLUSIONS: There was no evidence of increased efficacy of PDT using PDL as a light source compared to PDL alone. There was also no significant difference in adverse events. Further studies using different treatment regimens over longer periods of time may be warranted.

Photodynamic therapy: is it a valuable treatment option for actinic keratoses?

Photodynamic therapy (PDT) is proposed as an effective therapy with a good safety profile for patients with actinic keratoses. PDT involves the application of a photosensitizer to dysplastic or neoplastic tissue such that when exposed to light of an appropriate wavelength, the target tissue undergoes a cytotoxic reaction. Studies to date have demonstrated that PDT for the treatment of patients with actinic keratoses achieves clearance of lesions with minimal morbidity, maintenance of functional integrity of underlying tissues, and excellent cosmetic results. We present a review of the treatment of patients with actinic keratoses and the role of PDT in this context.