Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.

The Physiology of Postharvest Tea (Camellia sinensis) Leaves, According to Metabolic Phenotypes and Gene Expression Analysis.

Proper postharvest storage preserves horticultural products, including tea, until they can be processed. However, few studies have focused on the physiology of ripening and senescence during postharvest storage, which affects the flavor and quality of tea. In this study, physiological and biochemical indexes of the leaves of tea cultivar 'Yinghong 9' preserved at a low temperature and high relative humidity (15-18 °C and 85-95%, PTL) were compared to those of leaves stored at ambient conditions (24 ± 2 °C and relative humidity of 65% ± 5%, UTL). Water content, chromatism, chlorophyll fluorescence, and key metabolites (caffeine, theanine, and catechins) were analyzed over a period of 24 h, and volatilized compounds were determined after 24 h. In addition, the expression of key biosynthesis genes for catechin, caffeine, theanine, and terpene were quantified. The results showed that water content, chromatism, and chlorophyll fluorescence of preserved leaves were more similar to fresh tea leaves than unpreserved tea leaves. After 24 h, the content of aroma volatiles and caffeine significantly increased, while theanine decreased in both groups. Multiple catechin monomers showed distinct changes within 24 h, and EGCG was significantly higher in preserved tea. The expression levels of CsFAS and CsTSI were consistent with the content of farnesene and theanine, respectively, but TCS1 and TCS2 expression did not correlate with caffeine content. Principal component analysis considered results from multiple indexes and suggested that the freshness of PTL was superior to that of UTL. Taken together, preservation conditions in postharvest storage caused a series of physiological and metabolic variations of tea leaves, which were different from those of unpreserved tea leaves. Comprehensive evaluation showed that the preservation conditions used in this study were effective at maintaining the freshness of tea leaves for 2-6 h. This study illustrates the metabolic changes that occur in postharvest tea leaves, which will provide a foundation for improvements to postharvest practices for tea leaves.

Supporting Underrepresented in Medicine (UIM) and non-UIM Trainees Applying into Dermatology: A Qualitative Analysis.

BACKGROUND: Recently, there have been calls to improve diversity among the dermatology workforce, with emphasis placed on the resident selection process and trainee pipeline. However, there is limited data on the perspectives of dermatology applicants, especially among UIM trainees, and the support that they need and want to successfully apply in dermatology. METHODS: To assess trainee perspectives, we disseminated a survey to medical students, interns (matched into dermatology), and dermatology residents asking how dermatology residency programs can best support trainees through the dermatology application process. We developed a codebook drawing upon grounded theory methodology, and consensus coded all qualitative responses. RESULTS: We received 224 qualitative responses from underrepresented in medicine (UIM) (65, 29.0%) and non-UIM trainees (159, 70.9%). UIM trainees were more likely to mention diversity and inclusion initiatives (46.2% vs 3.8%, P<0.001), transparency in program information (40.0% vs 24.5%, P=0.021), holistic review (30.8% vs 6.3%, P<0.001), UIM student outreach/pipeline programs (23.1% vs 0.6%, P<0.001), and mentorship (21.5% vs 8.2%, P=0.009). CONCLUSION: Improving programmatic efforts to address unique challenges UIM trainees face when applying into dermatology is instrumental to mitigating barriers. We highlight opportunities for dermatology residency programs to create a more fair and equitable dermatology application process and support a more diverse pipeline of future dermatologists. J Drugs Dermatol. 2021;20(7):795-797. doi:10.36849/JDD.6043.

Pediatric Pseudo-pseudoxanthoma Elasticum Resulting From D-Penicillamine Treatment for Wilson Disease.

We describe a 14-year-old boy with Wilson disease (WD) who first developed pseudo-pseudoxanthoma elasticum (PPXE) after 4.5 years of treatment with D-penicillamine. Although previously reported cases have occurred in adults following at least a decade of high-dose D-penicillamine use, this case demonstrates that D-penicillamine-induced PPXE can present in children with shorter treatment courses. Upon this diagnosis, the patient was switched from D-penicillamine to trientine, with adequate cupriuresis and stabilization of the skin lesion. Prompt diagnosis and management of PPXE in children can limit systemic progression and prevent long-term complications.

Evaluation of a Comprehensive Skin Toxicity Program for Patients Treated With Epidermal Growth Factor Receptor Inhibitors at a Cancer Treatment Center.

Importance: Up to 90% of patients treated with an epidermal growth factor receptor inhibitor (EGFRi) experience cutaneous toxic effects that are negatively associated with quality of life and lead to treatment interruptions. The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity. Objective: To evaluate the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of EGFRi-associated cutaneous toxic effects. Design, Setting, and Participants: A retrospective cohort study was conducted of all adult patients receiving at least 1 dose of cetuximab at the Dana-Farber Cancer Institute in the calendar year 2012 (2 years after publication of the Skin Toxicity Evaluation Protocol With Panitumumab) or the calendar year 2017 (2 years after full implementation of the Skin Toxicities from Anticancer Therapies program). Main Outcomes and Measures: Primary outcomes were rate of preemptive rash treatment and selection of preemptive agents. Secondary outcomes were incidence of rash, rates of rescue treatments, rates of cetuximab dose changes or interruptions, and overall survival at 2 years. Results: There were 118 patients (85 men; median age, 62.4 years [range, 23.5-91.7 years]) treated with cetuximab in 2012 and 90 patients (70 men; median age, 62.5 years [range, 30.7-90.5 years]) treated with cetuximab in 2017; 11 patients (9%) in 2012 and 31 patients (34%) in 2017 were treated at Dana-Farber Cancer Institute affiliate sites. At cetuximab treatment initiation, 29 patients (25%) in 2012 and 42 patients (47%) in 2017 were prophylactically treated for skin toxicity (P < .001). From 2012 to 2017, preemptive tetracycline use (13 of 29 [45%] to 30 of 42 [71%]; P = .02) and topical corticosteroid use (2 of 29 [7%] to 24 of 42 [57%]; P < .001) increased and topical antibiotic use (23 of 29 [79%] to 18 of 42 [43%]; P = .002) decreased. There was no significant difference in incidence of rash by prophylaxis status. Patients prescribed prophylactic treatment were 94% less likely to require a first rescue treatment for rash (adjusted odds ratio, 0.06; 95% CI, 0.02-0.16; P < .001), 74% less likely to require a second rescue treatment for rash (adjusted odds ratio, 0.26; 95% CI, 0.08-0.83; P = .02), and 79% less likely to experience a cetuximab dose change or interruption (adjusted odds ratio, 0.21; 95% CI, 0.06-0.81; P = .02) than patients not prescribed prophylactic treatment, adjusting for treatment site and year. Conclusions and Relevance: Dermatologists can add value to oncology care by raising awareness of appropriate treatment options and increasing adherence to evidence-based prophylaxis protocols for EGFRi-associated rash, which is associated with decreased interventions and toxicity-associated chemotherapy interruptions.

Creating and Managing a Phototherapy Center.

Phototherapy is a safe and effective treatment for many benign and malignant inflammatory cutaneous diseases. Treatment courses require consistent visits over the course of weeks to months, and one barrier for patients in accessing this treatment is the lack of a geographically convenient phototherapy center. To expand access, new phototherapy centers can be created, and this can be done in a series of steps. These include considering the physical space, anticipating the finances, laying the operational groundwork, and establishing a consent and education process.

How It Works: The Immunology Underlying Phototherapy.

Phototherapeutic modalities induce apoptosis of keratinocytes and immune cells, impact cytokine production, downregulate the IL-23/Th17 axis, and induce regulatory T cells. As in anti-IL-17 or anti-IL-23 antibody treatment, the dual action of phototherapy on skin and the immune system is likely responsible for sustained resolution of lesions in diseases such as psoriasis. In cutaneous T cell lymphoma, phototherapy may function by causing tumor cell apoptosis and eliminating the neoplastic and inflammatory infiltrate. Further research on phototherapeutic mechanisms will help advance, optimize, and refine dermatologic treatments and may open up novel avenues for treatment strategies in dermatology and beyond.