Albert S. Chiou

Advanced aging skin and itch: addressing an unmet need.

Itch is the most common skin disorder in the elderly and frequently diminishes quality of life in this population. The high prevalence of pruritus in elderly patients is attributed in part to the decline in the normal physiology of the advanced aging skin, and reflects poor hydration, impaired skin barrier, and altered neural function, all ultimately contributing to inflammation and pruritus. As the elderly population continues to grow, practitioners need to be aware of how to evaluate and manage pruritus, recognizing the common conditions contributing to itch in elderly patients as well as the challenges of treatment in this group. Ultimately, management of pruritus will require an individually tailored approach that is guided by a patients general health, severity of symptoms, and the potential adverse effects of itch therapies.

Tazarotene: Randomized, Double-Blind, Vehicle-Controlled, and Open-Label Concurrent Trials for Basal Cell Carcinoma Prevention and Therapy in Patients with Basal Cell Nevus Syndrome

Sporadic human basal cell carcinomas (BCC) are generally well managed with current surgical modalities. However, in the subset of high-risk patients predisposed to developing large numbers of BCCs, there is an unmet need for effective, low-morbidity chemoprevention. This population includes fair-skinned patients with extensive sun exposure and those with genodermatoses such as the basal cell nevus (Gorlin) syndrome (BCNS). Tazarotene (Tazorac, Allergan) is a topical retinoid with relative specificity for RAR-β and RAR-γ receptors. We previously demonstrated tazarotenes robust anti-BCC efficacy in Ptch1+/− mice, a murine equivalent of BCNS, and others have found it to have some efficacy against sporadic human BCCs. We report here results of a randomized, double-blind, vehicle-controlled study in patients with BCNS evaluating the efficacy of topically applied tazarotene for BCC chemoprevention (N = 34 subjects), along with an open-label trial evaluating tazarotenes efficacy for chemotherapy of BCC lesions (N = 36 subjects) for a maximum follow-up period of 3 years. We found that only 6% of patients had a chemopreventive response and that only 6% of treated BCC target lesions were clinically cured. Our studies provide no evidence for either chemopreventive or chemotherapeutic effect of tazarotene against BCCs in patients with BCNS. Cancer Prev Res; 7(3); 292–9. ©2014 AACR.

Reaction of Cl with CD4 excited to the second C-D stretching overtone

The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C-D oscillator, as in the case of |2100>, wherein a small population of ground-state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction.

Localized bullous pemphigoid in a melanoma patient with dual exposure to PD-1 checkpoint inhibition and radiation therapy

BP: bullous pemphigoid PD-1: programmed cell-death receptor

Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging

Significance Timely detection of microscopic tumors is of utmost importance in cancer diagnostics. We show that desorption electrospray ionization mass spectrometry imaging (DESI-MSI) can successfully locate microscopic aggregates of a common skin cancer, basal cell carcinoma (BCC), and distinguish them from adjacent normal skin. DESI-MSI unveils an altered chemical profile in BCC region, including lipids and metabolites, and does not rely on visual identification of histopathologic features. We processed specimens from 86 Mohs micrographic surgeries, with nearly 60% of tumors sized less than 1 mm in diameter. By applying the statistical method of least absolute shrinkage and selection operator (Lasso) on collected DESI-MSI data, we were able to achieve up to 94.1% diagnostic accuracy compared with pathological evaluation of BCC. Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-µm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200–1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.

Histiocytoses and Malignancy

Histiocytes are tissue macrophages or dendritic cells derived from the bone marrow. An abnormal proliferation of histiocytes is the defining features of the histiocytoses. Of these, the most well known is likely Langerhans cell histiocytosis, as it often presents in infancy and can mimic other more common infantile conditions such as diaper dermatitis and seborrheic dermatitis. Juvenile xanthogranuloma is the most common non-Langerhan cell histiocytosis, presenting typically as an erythematous, yellow or orange papule. The other histiocytoses are quite rare. Some, such as benign cephalic histiocytosis, are predominantly seen in children, whereas others, such as xanthoma disseminatum and multicentric reticulohistiocytosis, are predominantly seen in adults.