Correlations Between Serum Cytokine Levels and the Use of a Moisturizer in Elderly Women in Accordance with the Improvement of Objective and Subjective Skin Condition.

Purpose: In the skin of elderly people with dryness, the production of inflammatory cytokines tends to be induced under the influence of external stimuli. Therefore, there has been a hypothesis that the deterioration of skin conditions due to aging is linked to systemic inflammation. This study aimed to verify the possibility that the use of moisturizer improves skin condition and suppresses systemic inflammation. Methods: As an open study, the participants (n=75) were randomly assigned to either control group or moisturizer group. Participants in the moisturizer group used a moisturizer called Grafa Moisture Keep Milk MC at least twice a day for four weeks on the entire body below the neck. Objective skin conditions (overall dry skin score, water content of the stratum corneum, and transepidermal water loss) and serum cytokine levels (IL-1α, IL-1ß, IL-4, IL-5, IL-6, IL-8, and TNF-α) were evaluated before and after the study in both groups. Subjective skin condition (questionnaire evaluation) was also assessed in the moisturizer group after the study. Results: Serum IL-6 level was significantly reduced in the moisturizer group (n=16) compared with the control group (n=36). In addition, there was an inverse correlation between serum IL-5 and the subjective moisturizing effect in the questionnaire evaluation, suggesting that the moisturizer improved subjective symptoms of dryness by reducing IL-5 levels. Furthermore, there was a positive correlation between IL-5 and IL-6, indicating that they are regulated by common upstream factors. A significant positive correlation of transepidermal water loss with serum IL-4 levels was also detected. Conclusion: The application of the moisturizer to the entire body not only improved subjective and objective skin condition, it may also reduce the levels of circulating inflammatory cytokines. Umin Clinical Trials Registry: Registration number: UMIN 000052024.

Analysis of skin aging patterns using a facial imaging system in patients with atopic dermatitis.

BACKGROUND: There are few studies on skin aging in patients with atopic dermatitis (AD). OBJECTIVES: To clarify the characteristics of facial skin aging in AD patients. MATERIALS & METHODS: Using facial images obtained by a digital imaging system (VISIA evolution), we compared the severity scores for 10 aging signs in 53 women in the AD group and 29 women in the healthy control group, all 35-49 years old. RESULTS: The severity scores for fine lines on the forehead, periorbital wrinkles, nasolabial folds, and texture of the mouth contour were significantly higher in the AD group than in the controls. However, in order to exclude a direct effect of dermatitis at the time of measurement, cases with signs of AD at the evaluation site were excluded from the AD group (defined as the AD [non-lesion] group), revealing no statistical significance between the AD (non-lesion) group and the healthy control group for any of the 10 facial signs. Age subset analysis showed that for individuals in their late 40s, the AD (non-lesion) group exhibited significantly higher scores for crow's feet wrinkle and nasolabial fold compared to the healthy control group. Furthermore, these two scores correlated with one other, suggesting that they may be induced by the same factors. CONCLUSION: The results of this study show that skin aging associated with AD is prominent in areas prone to transient wrinkling by frequent blinking and speaking or facial expressions. Understanding of the need for appropriate AD treatment from a cosmetic perspective may increase patient adherence.

Glycoprotein M6A upregulation detected by transcriptome analysis controls the proliferation of keloidal fibroblasts.

Hypertrophic scars and keloids are fibroproliferative disorders caused by abnormal wound healing. Their exact cause has not been found, but abnormalities during the wound healing process including inflammatory, immune, genetic, and other factors are thought to predispose an individual to excessive scarring. In the present study, we performed transcriptome analysis of established keloid cell lines (KEL FIB), focusing on gene expression analysis and fusion gene detection for the first time. For gene expression analysis, fragments per kilobase per million map read values were calculated, which were validated by real-time PCR and immunohistochemistry. Fusion genes were predicted by transcriptome sequence, and validated by Sanger sequence and G-banding. As a result, GPM6A was shown in the expression analysis to be upregulated in KEL FIB compared with normal fibroblasts. The GPM6A upregulation in KEL FIB was confirmed by real-time PCR, and GPM6A messenger ribonucleic acid expression was consistently significantly elevated in the tissues of hypertrophic scar and keloid compared to normal skin. Immunohistochemistry also revealed that the number of fibroblast-like spindle-shaped cells positive for GPM6A was significantly increased in keloidal tissues. GPM6A inhibition by small interfering ribonucleic acid significantly reduced the number of KEL FIB. On the other hand, although we hypothesized that fusion genes are involved in the pathogenesis of keloids, the transcriptome analysis could not prove the presence of fusion genes in KEL FIB. Taken together, GPM6A upregulation may have an inducible effect on cell proliferation in keloidal fibroblasts. GPM6A can be a novel therapeutic target in hypertrophic scars and keloids. The inflammatory nature may be more prominent in the pathogenesis of keloids, rather than being skin tumors, as proposed by Ogawa et al. Future studies using several cell lines will be required.

The clinical significance of dupilumab-induced blood eosinophil elevation in Japanese patients with atopic dermatitis.

This study aims to clarify the clinical significance of dupilumab-induced elevation of blood eosinophil in Japanese patients with atopic dermatitis (AD). Eosinophil elevation was defined as ≥ 5% increase of eosinophil percentage within one year after dupilumab initiation. Seven patients (15.7%) were shown to have eosinophil elevation, six of whom developed dupilumab-associated conjunctivitis (DAC) and were accompanied with DAC more frequently than those without eosinophil elevation, with statistically significant difference. Eosinophil percentage resolved spontaneously in all seven patients, including the one without DAC, despite the continuation of dupilumab treatment. None of the patients with eosinophil elevation had cardiac or pulmonary complications attributable to the hypereosinophilia. The patients with eosinophil elevation were all male. Furthermore, none of four patients in whom efficacy of dupilumab was < 25% showed eosinophil elevation. Childhood onset tended to be more common in patients with the elevation of eosinophil. This study suggests that most eosinophil elevation is associated with DAC, and that the eosinophil ratio is a biomarker for DAC.

Dupilumab Improves Pruritus in Netherton Syndrome: A Case Study.

The patient was a 26-year-old male. He had red and scaling skin of the entire body since birth, as well as an elevated level of serum IgE. Genetic testing revealed a mutation in the SPINK5 gene, which had confirmed the diagnosis with Netherton syndrome. He has had significant pruritis since birth, and subsequently had symptoms of sleeping disorders and concentration difficulty throughout the day. Since treatment with various antihistamines were not effective, we administered dupilumab and found that it was effective in immediate elimination of pruritus and gradual reduction of the rash. Dupilumab has been administered for one year without any adverse events or recurrence of symptoms. Although studies have previously described cases who used dupilumab for Netherton syndrome, reported effects have been limited or transient. Additional studies are needed to confirm the effect of dupilumab for Netherton syndrome, which currently lack any effective treatment strategies.

Primary cutaneous peripheral T-cell lymphoma, not otherwise specified, associated with lymphomatoid papulosis after a 9-year follow up: A case report.

Lymphomatoid papulosis (LyP) is a self-limiting cutaneous T-cell lymphoproliferative disorder that may progress into malignant lymphoma. Most of the previously reported associated lymphomas are primary cutaneous anaplastic large-cell lymphoma and mycosis fungoides with a low mortality rate. We report a case of primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), associated with LyP after long-term follow up. The patient was a 79-year old Japanese man followed up for 9 years. He suddenly developed a 3-cm ulcerated lesion on his forehead, which was diagnosed as an exacerbation of LyP. The lesion regressed after conservative treatment, but the patient soon developed multifocal pcPTCL-NOS. Thereafter, the patient developed pneumonia and cerebral infarction and died within a few months of the onset of malignant lymphoma. Aggressive cutaneous lymphoma may develop in LyP patients. The present case re-emphasizes the need for careful follow up of patients with persistent LyP.