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We report a case of concomitant periocular yellowish papules and plaques with symmetric weakness and paresthesia of the distal limbs in a 63-year-old man.

Supplementary Table S1. Comparing characteristics of the study subjects from two medical centers Supplementary Table S2. Association of selected SNPs within 13 betel related candidate genes in all OSCC cases and controls. Supplementary Table S3. Interaction between GRSs and consuming quantities of betel nut. Supplementary Table S4. Associations between tumor stage, GRS and BQ chewing. Supplementary Figure S1. Comparison of areas under the ROC curves of early and advanced stage oral cancer sensitivity and specificity. GRS has higher AUC for early stage oral cancer than advanced stage oral cancer. However, BQ chewing has higher AUC for advanced stage oral cancer than early stage oral cancer.

We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case–control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34–14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70–575.73). The synergy index was 16.58 (95% CI, 2.27–70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355–62. ©2017 AACR.

Phototherapy is the most commonly used modality for repigmenting vitiligo. Currently, UVB emitting devices, including narrow-band UVB (NBUVB) and excimer laser/light, are considered as the treatment of choice. While emitting wavelengths at close proximity, excimer lights emit higher irradiance (HI; W/m2 ) compared to NBUVB. Clinical reports have shown that excimer light is more efficacious in treating vitiligo compared to NBUVB, and we demonstrated that irradiance plays a critical role in promoting melanoblasts differentiation. UVB radiation from the sun is closely associated with photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance (low irradiance (LI) UVB). Sunscreen use was associated with skin cancer reduction in clinical trials. Paradoxically, sunscreen use was associated with increased sunburn episodes in the real-world settings. It was shown that UVB-induced sunburn depends on fluence (J/m2 ) but not irradiance of UVB radiation. We investigated the significance of irradiance in the context of UVB-induced carcinogenesis of the skin. For mice receiving equivalent fluence of UVB exposure, the LIUVB-treated mice showed earlier tumor development, larger tumor burden, and more epidermal keratinocytes harboring mutant p53 as compared to their HIUVB-treated counterparts. These results suggested that at equivalent fluence, LIUVB radiation has more photocarcinogenic potential on the skin compared to its HI counterpart. Since development of sunburn with or without sunscreen use indicates that certain threshold of UVB fluence has been received by the skin at LI and HI, respectively, sunburn episodes with sunscreen use (LIUVB) are more damaging to the skin compared to that without sunscreen (HIUVB) application. In summary, since irradiance plays an important role determining the biological effects of UVB radiation on the skin, future related studies should take this critical parameter into consideration.

Psoriasis is an inflammatory skin disease with a well-established link to obesity. Excess body weight is associated with higher psoriasis severity. Besides, obesity reduces the effectiveness of systemic therapy. Herein, we reported a morbidly obese patient with severe psoriasis who had only partial response to adalimumab, achieved satisfactory clearance of psoriatic lesions after bariatric surgery in combination with adalimumab therapy. Since bariatric surgery is effective for reducing weight as well as improving psoriasis severity, morbidly obese psoriasis patients who failed noninvasive weight reduction strategies may consider bariatric surgery as a potential adjuvant treatment.

Background How diseases associated with skin discoloration affect the quality of life (QoL) has rarely been examined. In this study, we directly compared the QoL and willingness to pay (WTP) among patients with skin disorders associated with facial discoloration. Methods A single-center, cross-sectional study consisting of patients seeking treatment for facial discoloration was performed. All patients completed the dermatology life quality index (DLQI) and the short form 36 (SF-36) health survey questionnaires. Additionally, information regarding monthly income and the WTP for a complete cure of the affected condition was obtained. Results Patients with melasma (58), lentigo (56), postinflammatory hyperpigmentation (5), vitiligo (51), acne-induced erythema (10), and rosacea (31) were enrolled. Vitiligo, acne-induced erythema, and rosacea patients reported significantly worse QoL compared to lentigines or melasma patients as evaluated by DLQI. Using SF-36, rosacea patients were affected mentally the most as they reported the worst mental component scores, and the scores were significantly worse than that of melasma patients (rosacea vs. melisma = 46.5 vs. 52.7, p = 0.007). Vitiligo patients had the worst general health scores. Although there were no differences in the WTP among different diseases, the vitiligo group had the highest percentage of patients willing to pay more than 40% of their monthly income for a complete cure. Conclusions The impact on QoL is different among skin diseases associated with facial discoloration. Only vitiligo patients reported worse general health as compared to the general population, explaining the discordance between life quality scores and WTP in these patients.

An easy and objective way to evaluate mid-face sagging is marking straight lines between the nasal alar and the mandibular angle, one in the supine and the other in an upright position. The maximal distance between the two lines drawn is measured. Statistic analyses shows that this maximum distance demonstrates positive correlation with age and body mass index that reflects the level of mid-face sagging. This simple method may be utilised to evaluate the effect of anti-ageing treatment on the face in the context of mid-face sagging.

Nipple adenoma is a rare benign tumor of the nipple due to mammary proliferation of the lactiferous ducts. Common presentation of the tumor includes nipple erosion, erythema, scaling, and eczematous change of the overlying skin. Delayed diagnosis is common since its clinical presentation resembles that of other benign or malignant condition of the nipple, such as nipple eczema or Paget's disease. Timely identification with histopathological correlation is essential for appropriate management. We herein describe the clinical and histopathological characteristics of two cases of nipple adenoma.

Aims Sunscreen use, which prolonged the time required to develop sunburn by reducing the irradiance (mW/cm2) of the UVB radiation, is thought to protect the skin from developing cancers. Recently, in addition to fluence (mJ/cm2), irradiance of the UVB radiation was demonstrated to play an important role leading to photocarcinogenesis of the skin. After equivalent fluence of UVB exposure, enhanced aberrant keratinocyte proliferation contributes significantly to the photocarcinogenic capacity of low irradiance (LI) UVB as compared to its high irradiance (HI) UVB counterpart. However, the mechanism involved remains unclear. Main methods Relevant cell and animal models were employed to investigate the effects of equivalent UVB fluence administered at HI or LI on keratinocyte proliferation. Additionally, the mechanisms involved were also explored. Key findings We found that at equivalent fluence, LIUVB induces significantly higher reactive oxidative species (ROS) production, cell proliferation, as well as phosphorylated AKT (pAKT) expression in both cell and animal models as compare to its HIUVB counterpart. Pretreating cultured keratinocytes with antioxidant or AKT inhibitor significantly reduced the UVB-induced ROS, cell proliferation, and pAKT expression. Additionally, these pretreatments abrogate the difference between the LI and HIUVB treated keratinocytes. Similar findings were noted using animal model treated with AKT inhibitor. Significance In summary, at equivalent fluence, LIUVB induces significantly more aberrant epidermal proliferation via enhanced ROS and pAKT signaling. Reducing UVB-induced AKT phosphorylation presents a novel strategy to improve the protective capacity of the currently available sunscreens.

Since localized treatment for vitiligo is as essential as systemic treatment, a reliable instrument for target evaluation is needed besides those for whole body evaluation. We developed the Vitiligo Extent Score for a Target Area (VESTA) using reference images of both marginal and perifollicular repigmentation to measure the repigmentation rate (%) in a target lesion. In the validation study, a total of 65 dermatologists in 10 institutes evaluated 17 pairs of vitiligo images (pre- and post-treatment) using both a rough estimate and the VESTA. The VESTA (concordance correlation coefficient: 0.949, 95% confidence interval [CI] 0.942-0.955) was significantly more accurate than the rough estimate (0.896, 95% CI: 0.883-0.908). It was also associated with better inter-rater reliability over the rough estimate, albeit not significant. The VESTA can afford intuitive, convenient, and reliable assessment of the treatment response in a target area, and would be useful in clinical practice as well as retrospective studies.

Background Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. Objectives To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. Methods A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. Results 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p Conclusion The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.

Pemphigus foliaceus (PF) is a chronic autoimmune blistering dermatosis (ABD) that often involves the face, scalp and trunk. Kaposi's varicelliform eruption (KVE) is a viral vesicular dermatosis that rarely complicates ABD. In addition, KVE infrequently causes ocular involvement including herpes simplex keratitis (HSK). Timely diagnosis of KVE may be difficult in patients with PF due to their overlapping clinical features. In this report, we described a 79-year-old female with PF complicated by KVE and bilateral HSK. This report reminds physicians that KVE should be considered in patients with refractory PF and other ABD.

Background Skin cancer is an important environmentally-related health issue. Although sun exposure is closely associated with increasing environmental heat, the effects of environmental heat on the skin, especially in the context of photocarcinogenesis, has not been carefully examined. Objectives This study aimed to explore the effects and interactions of UVB radiation and environmental heat on photocarcinogenesis of the skin using cell and animal models. Methods Cultured keratinocytes and hairless mice were exposed to different treatment conditions including UVB radiation and environmental heat. The effects of treatment on keratinocyte and mice skin were evaluated at indicated time points. Results UVB induced DNA damage was significantly lower in keratinocytes that were pretreated in an environment with slightly elevated temperature followed by UVB treatment (Heat-UVB) as compared to UVB and UVB radiation followed by exposure to equivalent increase in environmental heat (UVB-Heat) groups. Similar phenomenon was observed in terms of keratinocyte viability. In the animal model, it was found that Heat-UVB treated mice showed delayed and reduced tumor formation as compared to the UVB and UVB-Heat treated groups. Quantum simulation analyses demonstrated that the energy required for CPD formation at environment with higher temperature required considerable higher energy as compared to CPD formation at lower temperature. Conclusion Taken together, our results demonstrated that with equivalent UVB exposure, higher temperature environment may protect cells against subsequent UVB-induced DNA damages.

Background Diabetes is an important global health issue due to its increasing prevalence and association with various complications. Impaired wound healing is a serious complication associated with diabetes that frequently results in infection and amputation. Galectin-7 (Gal-7) has been reported to play an important role during skin wound healing. Previously, we had demonstrated that high glucose environment alters physiologic functions of keratinocytes and contributes to impaired wound healing in diabetic condition. Objective In this study, we hypothesized that Gal-7 expression of keratinocytes may be involved in delayed wound healing of diabetics. Methods Using cultured human keratinocytes and diabetic mice model, the Gal-7 expression was evaluated under high glucose environment. Results Our results demonstrated that high-glucose environment reduced Gal-7 expression, a molecule that plays an important role in keratinocyte migration. Additionally, we found that increased O-linked N-Acetyl-glucosamine (O-GlcNAc) is responsible for reduced Gal-7 expression in keratinocytes exposed to high glucose environment. Conclusion Taken together, restoring the levels of Gal-7 and O-GlcNAc glycosylation may present novel therapeutic approach to promote wound healing in diabetic patients.

We integrated genetic risk scores (GRS) and environmental factors for identifying high-risk subjects for oral squamous cell carcinoma (OSCC) occurrence by using case–control study. A total of 447 patients diagnosed with OSCC and 580 unrelated subjects were recruited from two medical centers in Taiwan. A multinomial logistic regression model was conducted to access interaction between GRS and betel quid (BQ) chewing. We employed ROC curve to compare the accuracy of OSCC occurrence. Four tag SNPs were found in NOTCH1, BRCA1, COL9A1, and HSPA13 genes that were significantly associated with OSCC occurrence. GRS was calculated by the four tag SNP risk alleles. The higher GRS (scores = 4) remained independently associated with risk of OSCC after adjustment for age, the use of alcohol, BQ, and cigarette: adjusted OR = 4.42 [95% confidence interval (95% CI), 1.34–14.55]. The GRS and BQ chewing interaction showed an increased risk for OSCC occurrence with adjusting for other substance use and age (OR = 70.77; 95% CI, 8.70–575.73). The synergy index was 16.58 (95% CI, 2.27–70.56), suggesting a positive additive interaction between GRS and BQ chewing. The areas under the ROC curves (AUROC) were 0.91 for combined GRS and BQ chewing with sensitivity of 88.6% and specificity of 86.7%. The AUROC of GRS and BQ chewing is above 90%, which may be valuable in identifying high-risk subjects. Early screening can allow the clinician to provide the appropriate intervention and to reduce the OSCC occurrence. Cancer Prev Res; 10(6); 355–62. ©2017 AACR.

Background Macrophages play important roles during wound healing, and delayed healing in diabetics is associated with sustained inflammation. M1 type macrophage is recognized to secrete excessive amount of tumor necrosis factor-alpha (TNF-α) as compared to its M2 counterpart. Objectives We hypothesized that macrophage polarization is different between diabetic and normal rats during skin wounding and has direct impact on keratinocyte function in the context of re-epithelialization. Methods Skin wounds were created in diabetic and control rats. The phenotypes of infiltrating macrophages, the levels of TNF-α, and the rate of wound closure were determined. Using cell model, the effects of M1 type macrophage on keratinocyte migration were evaluated, and the potential regulatory pathways were determined. Results The percentage of M1 macrophages and the levels of TNF-α expression were significantly higher in the perilesional area of diabetic rats as compared to control. The condition media (CM) from M1 type macrophage upregulated tissue inhibitor metalloproteinases (TIMP)-1 expression in keratinocytes and significantly reduced keratinocyte migratory capacity. Addition of neutralizing TNF-α antibody to the CM or gene-silencing of TIMP1 in keratinocytes restored the keratinocyte migratory capacity. Treating wounds of diabetic rats with TNF-α antagonist improved the wound healing process. Conclusions In summary, high glucose wound environment harbored more M1 macrophages infiltration, an event that created excess TNF-α micro-environment. TNF-α upregulated TIMP1 expression in keratinocytes and resulted in impaired keratinocyte migration. Taken together, these events contributed to impaired wound healing during diabetic condition, and targeting TNF-α is a potential therapeutic option to improve diabetic wound healing.

Psoriasis is associated with certain psychiatric disorders such as anxiety and depression. Although a growing body of literature has indicated high prevalence of anxiety in patients with psoriasis, it is unclear if the incidence of anxiety is correlated with severity of psoriasis. In this article, we hypothesize that anxiety is not correlated with severity of psoriasis, and therefore the issue of anxiety should not be neglected in patients with mild psoriasis. To testify this hypothesis, we performed a pilot study to investigate the correlation between anxiety questionnaires and severity of psoriasis. Thirty-two patients with psoriasis were recruited. The patients were further classified into mild or moderate to severe psoriasis according to their body surface area or Psoriasis Area Severity Index (PASI). Zung's self-rating anxiety scale (SAS) and SF-36 were adopted to evaluate anxiety and quality of life, respectively. Spearman's rank correlation coefficients were calculated between SAS and each scale of SF-36 among these 32 patients. SAS is negatively correlated with role limitation due to emotional problems, vitality, emotional well-being of SF-36. Although SAS is not significantly different between mild and moderate to severe psoriasis, the detected levels of anxiety were higher than normative standards. Physicians should not neglect potential anxiety in patients who have mild psoriasis. Inter-discipline collaboration between psychiatry and dermatology is required to provide comprehensive patient care.