Alopecia areata is a representative inflammatory skin disease that is associated with various environmental stimuli. While psychological stress is believed to be a major pathogenetic trigger in alopecia areata, infants and newborns also suffer from the disease, suggesting the possible presence of other environmental factors. Daily lifestyle is well known to be involved in various inflammatory diseases and influences the severity of inflammatory skin diseases. However, only a limited number of studies have summarized these influences on alopecia areata. In this review article, we summarize lifestyle factor-related influences on the pathogenesis of alopecia areata and focus on environmental factors, such as smoking, alcohol consumption, sleep, obesity, fatty acids, and gluten consumption.

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Dietary nutrition intake is essential for human beings and influences various physiological and pathological actions in the human body. Among various nutritional factors, dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been shown to have various beneficial effects against inflammatory diseases. In addition to their therapeutic potency against inflammation, omega-3 PUFAs have also been shown to have anti-tumor effects via various mechanisms, such as cell arrest and apoptosis. To date, limited information is available on these effects in cutaneous malignancies. In this review, we focused on the effect of omega-3 PUFAs on skin cancers, especially malignant melanoma, basal cell carcinoma, lymphoma, and squamous cell carcinoma and discussed the detailed molecular mechanism of the omega-3 PUFA-mediated anti-tumor response. We also explored the molecular mechanisms mediated by epigenetic modifications, cell adhesion molecules, and anti-tumor immune responses.

Mycosis fungoides is recognized as an indolent cutaneous malignant T-cell lymphoma. In contrast, there are few therapeutic options for advanced forms of mycosis fungoides. Since immunotherapy is desirable as an alternative therapeutic option, identifying candidate molecules is an important goal for clinicians. Although tumor-derived negative immunomodulatory molecules, such as PD-1/PD-L1, have been identified in various malignancies, the useful positive immunological drivers of mycosis fungoides are largely unknown. We found that the stimulator of interferon (IFN) genes (STING) was highly upregulated in early-stage mycosis fungoides. Immunohistochemical examination revealed different STING staining patterns in patients with mycosis fungoides. Although there were no significant differences in clinical factors’ characteristics, STING expression was associated with the survival of patients with mycosis fungoides. The survival rate was significantly poor in patients with low STING-expressing mycosis fungoides. Univariate and multivariate analyses revealed that low STING expression was associated with an increased hazard ratio. Our results indicate that STING expression independently influences the prognosis of mycosis fungoides.

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.