Photodynamic Therapy for Benign Cutaneous Neurofibromas Using Aminolevulinic Acid Topical Application and 633 nm Red Light Illumination.

Background: Neurofibromatosis type 1 (NF1) has no current effective treatments beyond surgery. Topical photodynamic therapy (PDT) has the potential to provide a less invasive treatment modality. Objective: Based on murine data, we hypothesized PDT could be used for the treatment of cutaneous neurofibromas (cNF). Methods and results: We conducted a phase I trial to examine absorption and conversion of topical aminolevulinic acid (ALA) in cNF and determine safety in a dose escalation study. ALA or control vehicle was applied to neurofibromas through microneedle-assisted delivery (n = 4) and excised specimens were examined 24 h later for protoporphyrin IX fluorescence. Fluorescence was detected in the tumors at 304 ± 94 U/µm2, while adjacent paralesional normal skin and vehicle-treated tumors showed no fluorescence (p < 0.0001). Subsequently, neurofibromas (n = 27) were treated with ALA and irradiated with 633 nm red light 18 h later, at escalating dosages of 50 and 100 mJ/cm2. Maximum tolerable dose was established at 100 mJ/cm2. Light microscopy study of tumors biopsied 48 h after PDT (ALA n = 14 and vehicle n = 4) showed mixed inflammatory infiltrate in the ALA, but not in the vehicle-treated tumors or perilesional normal skin. TUNEL evaluation showed 42.5 ± 19.9 apoptotic cells per visual field for ALA-treated and 1.1 ± 1.4 for vehicle-treated tumors (p = 0.002). Conclusions: In the first reported clinical trial of PDT for NF1, PDT targeted neurofibromas specifically, and may offer a normal tissue-sparing treatment modality in the future. This study is registered at Clintrials.gov (NCT01682811).

The microRNA landscape of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1000000 cases per year, of which roughly 20-30% are squamous cell carcinoma. To better understand and treat this challenging cancer, current research focuses on development of novel strategies to improve the understanding of tumor biogenesis on an individual basis. microRNAs are becoming important biomarkers in the diagnosis, prognosis and treatment of cSCC. This review describes the current knowledge on miRNA expression in cSCC and its role as a biomarker for personalized medicine.

Chemical Tattoo Treatment Leading to Systemic Cobalt Hypersensitivity.

An otherwise healthy 36-year-old Caucasian woman, without prior history of atopic dermatitis or eczema, presented to an outside dermatologist with a generalized, severely pruritic eruption involving the entire body except the face. One month previously, she had used a 50% trichloroacetic acid tattoo removal solution on a blue-colored tattoo on the medial aspect of the left ankle. The patient's eruption persisted for 7 months, and after several attempts to slowly taper her prednisone dose, she presented to our institution. On physical examination, there was a 3-cm erythematous, lichenified plaque surrounding the tattoo (Figure). On the trunk and upper regions of the arms, there were scattered, 1- to 2-cm, nummular patches and plaques. Biopsy of a truncal lesion revealed spongiotic pustules with a mixed dermal infiltrate and scattered eosinophils, consistent with subacute spongiotic dermatitis.

A Rare Case of Vancomycin-Induced Linear Immunoglobulin A Bullous Dermatosis.

Linear IgA bullous dermatosis (LABD) is an autoimmune vesiculobullous disease, which is typically idiopathic but can also rarely be caused by medications or infections. Vancomycin is the most common drug associated with LABD. Lesions typically appear 24 hours to 15 days after the first dose of vancomycin. It is best characterized pathologically by subepidermal bulla (blister) formation with linear IgA deposition at the dermoepidermal junction. Here we report an 86-year-old male with a history of left knee osteoarthritis who underwent a left knee arthroplasty and subsequently developed a prosthetic joint infection. This infection was treated with intravenous vancomycin as well as placement of a vancomycin impregnated joint spacer. Five days following initiation of antibiotic therapy, he presented with a vesiculobullous eruption on an erythematous base over his trunk, extremities, and oral mucosa. The eruption resolved completely when intravenous vancomycin was discontinued and colchicine treatment was begun. Curiously, complete resolution occurred despite the presence of the vancomycin containing joint spacer. The diagnosis of vancomycin-induced linear IgA bullous dermatosis was made based on characteristic clinical and histopathologic presentations.

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants: This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results: Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

Building a global teledermatology collaboration.

Skin disease is common in low-resource countries and is associated with significant morbidity. The disease burden is often heightened by lack of access to adequate diagnosis and treatment. Teledermatology is a growing healthcare delivery modality that allows access to subspecialty care at a distance. This article describes how a low-cost teledermatology program was launched through collaboration between the Medical College of Wisconsin and Hillside Healthcare International. Several factors are required for a teledermatology program to be successful, beginning with a partnership between two entities that targets a locally identified need and is mutually beneficial to invested partners. The program should utilize the expertise of each partner, be based on an agreed upon process with clearly defined objectives, and protect patient privacy. After a program is implemented, adaptation to address challenges and best meet the needs of all parties involved will allow for continued success and sustainability. This process can serve as a model for other programs desiring to establish similar teledermatology partnerships in an academic setting.

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness.

Disseminated Nocardia infection presenting as hemorrhagic pustules and ecthyma in a woman with systemic lupus erythematosus and antiphospholipid antibody syndrome.

BACKGROUND: Nocardia is an opportunistic pathogen that can cause disseminated infection in immunocompromised hosts. The most common type of skin lesion reported with disseminated Nocardia is a subcutaneous nodule; however, there are reports with unusual cutaneous presentations. Long term corticosteroid treatment is one of the largest risk factors for developing disseminated Nocardia. Initial treatment is empiric as each strain has unique susceptibilities and it takes weeks to speciate and test sensitivities. MAIN OBSERVATIONS: A 66-year-old female on long term corticosteroids for systemic lupus erythematosus (SLE) and antiphospholipid syndrome presented with a polymorphous skin eruption and systemic symptoms concerning for infection. Especially concerning were areas of hemorrhagic pustules on the lower legs, and two ecthymatous lesions on the thigh. Tissue culture Gram stain revealed Gram positive branching filamentous rods concerning for Nocardia. The patient improved with empiric treatment. CONCLUSIONS: This case of Nocardiosis had unusual cutaneous findings that could have misguided the clinician, but the tissue culture and Gram stain proved to be useful for rapid diagnosis and proper treatment.

A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin.

In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 hours after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress has a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 hours after exposure.