A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation.

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives-methylparaben and phenoxyethanol-but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.

Effects of 308 nm excimer light treatment on the skin microbiome of atopic dermatitis patients.

BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.

A case of post-mogamulizumab relapse of acute-type adult T-cell leukemia/lymphoma successfully treated with mogamulizumab and etoposide.

A 70-year-old man presented to us with the chief complaints of a generalized rash and a mass in the right clavicular region that he first noticed in the year 2012. Biopsy of the mass led to the diagnosis of cutaneous nodular mass-type adult T-cell leukemia/lymphoma (ATLL) in March 2013. Phototherapy was started, and the symptoms improved temporarily. However, in late June 2013, the serum lactate dehydrogenase (LDH) level increased to 358 IU/L, which was 1.6 times higher than the upper limit of the reference range; based on the findings, transformation of the disease to the acute type was diagnosed. The patient was treated with 6 courses of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone), which resulted in complete remission (CR). However, the rash recurred in late October 2013, and treatment with mogamulizumab was initiated. A total of 8 courses of mogamulizumab were administered, which resulted in CR. The rash and cutaneous nodular masses recurred again in January 2014, and a total of 8 courses of mogamulizumab were administered again starting in February 2014. However, the patient's symptoms began to worsen gradually. Phototherapy was also initiated, but had to be discontinued due to the development of photosensitivity. Treatment with the combination of mogamulizumab and etoposide (25 mg/day for 21 days) was started in May 2014. The nodular mass rapidly decreased in size. The rash or cutaneous nodular mass had not recurred as of August 2014. Thus, combined therapy with mogamulizumab plus etoposide is considered to be effective for resolution of the cutaneous nodular masses in patients with ATLL.

Can persistent toenail fungus be successfully treated with a laser?

Onychomycosis is a common disease seen in dermatology practice. Most patients with onychomycosis opt for treatment due to the social stigma attached to the unsightly appearance, as well as the pain that can at times make walking difficult. However, in many cases, onychomycosis is resistant to oral antifungal medication, which is the first-line therapy for this disease. In recent years, we have attempted a new treatment method using a long-pulsed 1,064nm Nd :YAG laser (Cutera Inc., Brisbane, CA, USA) in refractory cases with onychomycosis. Using 1) a laser beam with a spot size of 5.0 mm and 2) sequential irradiation at low fluence, we 3) applied the laser to the infected lesions in a motion similar to showering, while maintaining a distance of several centimeters from the skin (Laser Genesis(TM)). Treatment efficacy was assessed using nail turbidity scores on a five-point scale. Improvement in onychomycosis was noted in more than 68.8% of all cases, thus demonstrating the high efficacy of this method. No major adverse reactions were observed during the treatment period. Since its mechanism of action clearly differs from that of antifungal agents, it can be considered a useful treatment option for cases with onychomycosis resistant to antifungal therapy. Future studies should examine "combined therapy" with oral / topical antifungal agents and this laser treatment, which may provide a significant improvement in the level of satisfaction among patients with onychomycosis.

Clinical trial of a laser device called fractional photothermolysis system for acne scars.

Ablative laser resurfacing is an effective treatment for acne scars. However, edema and prolonged erythema are common. Additionally, scarring and hyperpigmentation are often induced. A new concept of laser called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation without significant side-effects. We treated 10 patients with acne scars using this laser system (Reliant Fraxel SR Laser). All the patients were successfully treated with minimal adverse effects. The fractional photothermolysis system represents an optional method for the treatment of acne scars.