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Diabetes mellitus (DM) is an important cause of chronic wounds and non-traumatic amputation. The prevalence and number of cases of diabetic mellitus are increasing worldwide. Keratinocytes, the outermost layer of the epidermis, play an important role in wound healing. A high glucose environment may disrupt the physiologic functions of keratinocytes, resulting in prolonged inflammation, impaired proliferation, and the migration of keratinocytes and impaired angiogenesis. This review provides an overview of keratinocyte dysfunctions in a high glucose environment. Effective and safe therapeutic approaches for promoting diabetic wound healing can be developed if molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments are elucidated.

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/Objective: The prevalence of selected psychiatric disorders, such as depression and anxiety, is higher in patients with psoriasis. However, the association between psoriasis and schizophrenia is less clear. Here, we investigated whether the prevalence of schizophrenia is higher in patients with psoriasis. Methods: In this cross-sectional study, we analyzed the 1-million-person cohort enrolled from Taiwan's National Health Insurance Research Database. Psoriasis, schizophrenia, and comorbidities were ascertained by the International Classification of Diseases, 9th revision, Clinical Modification coding. For schizophrenia, the concomitant catastrophic illness certificate was used to verify the diagnosis. The prevalence of schizophrenia in patients with psoriasis was compared with the prevalence of schizophrenia in a comparable population using a generalized linear mixed model. Results: The prevalence of schizophrenia was significantly higher in patients with psoriasis than in the comparison population [prevalence ratio = 1.77, 95% confidence interval (CI) = 1.48–2.12, p

Background: Previous studies have shown that topical corticosteroid (TCS) use induces structural abnormalities of the stratum corneum (SC), resulting in permeability barrier disruption. It is well-known that epidermal barrier perturbation induces a cytokine cascade, leading to cutaneous inflammation. Accordingly, we hypothesize that barrier disruption caused by long-term TCS therapy may trigger a cutaneous cytokine cascade, which plays an important role in withdrawal dermatitis (WD) following discontinuation of TCS. The objective of this study was to elucidate the possible mechanism of WD. Methods: Hairless mice were treated once daily with 0.064% betamethasone dipropionate ointment for 6 weeks. After discontinuation of TCS, we examined the transepidermal water loss (TEWL), SC lipids and expression of the cytokines interleukin 1-alpha (IL1-α) and tumor necrosis factor-alpha (TNF-α) and their downstream signaling pathway in the following 2 weeks. Results: We observed upregulation of IL1-α, TNF-α, inhibitor of nuclear factor kappa-B kinase subunits alpha and beta (IKK1, IKK2) and nuclear factor kappa-B (NF-κB) in the epidermis, accompanied by a significantly higher TEWL after TCS cessation. These cytokines gradually disappeared with concomitant normalization of TEWL after 1 week. Only negligible amounts of the aforementioned cytokines were observed in the dermis. Furthermore, concurrent application of petrolatum during TCS treatment decreased barrier impairment and production of cytokines. Conclusion: An epidermis-derived cytokine cascade was observed following TCS-induced barrier disruption, which is similar to that from permeability barrier insults by acetone or tape stripping. The study suggests that concurrent application of skin care products during TCS treatment improves barrier homeostasis, and should become a standard practice to alleviate TCS-induced WD.

Background: Nail changes, including onychomadesis (nail shedding) and Beau’s line, following hand-foot-mouth disease (HFMD) are a common emergence at the stage of late complications of HFMD. However, the exact mechanism is still unknown. Therefore, we conducted this study to elucidate the mechanism of nail changes following HFMD. Methods: We collected 11 patients suffering from onychomadesis following HFMD. Nail samples from all of them were collected. Real time reverse transcription polymerase chain reaction (RT-PCR) and sequencing for human enteroviruses (HEV) were performed. Throat swabs for RT-PCR and sequencing for HEV were performed for three cases. Results: RT-PCR demonstrated the presence of Coxackievirus A6 (CVA6) in nail samples from three patients and one with Echovirus. Conclusion: In conclusion, we believe that the major cause of onychomadesis following HFMD is that certain novel viruses, mostly CVA6, are virulent and may damage nail matrix. Direct injury caused by cutaneous lesions of HFMD around nail matrix is a minor cause. There are still other virulent HEV which may result in onychomadesis. In addition, the novel strain of CVA6 also causes atypical clinical presentations, such as adult involvement and delayed-onset palmar and plantar desquamation. Physicians should be familiar with atypical presentations caused by novel viruses to avoid misdiagnosis and even inform patients of the possibility of onychomadesis that may take place weeks later to reassure patients.

Modulation of nuclear factor-kappa B (NF-κB) expression has important clinical implications including anti-inflammation. Recently, we have shown that direct regulation of NF-κB/p65 subunit may account for tacrolimus ointment’s remarkable clinical efficacy on treating inflammatory dermatoses. However, NF-κB is a dimeric transcription factor formed by hetero- or homodimeration of the five Rel family proteins. The complete operational scheme of different NF-κB subunits remains obscure. It has been shown that homodimers consist of NF-κB/p50 may serve an inhibitory role in suppressing inflammation while dimers consisting of NF-κB/p65 activate inflammatory pathway. Our current study aimed to explore the effects of ultraviolet B (UVB) on epidermal keratinocytes in terms of specific NF-κB subunits NF-κB/p50 and NF-κB/p65. Additionally, the effects of tacrolimus on differential regulation of NF-κB subunits of UVB irradiated keratinocytes were also investigated. Our result showed that UVB sequentially regulated the activities of different subunits of NF-κB: the activity of NF-κB/p50 was downregulated in the early stage (6 hours), followed by upregulation of NF-κB/p65 in the later stage (12 hours). The results from immunofluorescence, immunocytochemical, and immunohistochemical analyses indicated that the nuclear expression of NF-κB/p50 could be seen constitutively while the nuclear expression of NF-κB/p65 could only be seen after UVB irradiation. Furthermore, treatment with tacrolimus didn’t affect the nuclear activation and translocation of NF-κB/p50, while the UVB induced NF-κB/p65 nuclear expression was suppressed by tacrolimus. In summary, we have shown that UVB irradiation sequentially regulated different NF-κB subunits. The clinical efficacy of tacrolimus may be attributed to its specific regulatory effect on NF-κB/p65 but not NF-κB/p50 of the NF-κB pathway.

Dyschromatosis universalis hereditaria (DUH) is a rare disease that is inherited both in autosomal dominant and autosomal recessive patterns. It is characterized by appearance of pinpoint to pea-sized hypo- and hyper-pigmented macules distributed in a reticulated pattern over the trunk and limbs within the first few years of life. Although the pathogenesis is still not clear, some authors proposed that decreased melanosome synthesis rate may underlie this disorder. We describe a 56-year-old female and her 24-year-old son with generalized symmetrically distributed hypo- and hyper-pigmented macules. After clinical, histological and ultrastructural examination, we proposed defect in melanosome transfer from melanocytes to keratinocytes may underlie the pathogenesis of DUH.

Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More recently, studies have shown that psoriasis is a systemic inflammatory disorder which can be associated with various comorbidities. In particular, psoriasis is associated with an increased risk of developing severe vascular events such as myocardial infarction and stroke. In addition, the prevalence rates of cardiovascular risk factors are increased, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. Consequently, mortality rates have been found to be increased and life expectancy decreased in patients with psoriasis, as compared to the general population. Various studies have also shown that systemic treatments for psoriasis, including methotrexate and tumor necrosis factor-α inhibitors, may significantly decrease cardiovascular risk. Mechanistically, the presence of common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability may explain the association between psoriasis and cardiometabolic disorders. In this article, we review the evidence regarding the association between psoriasis and cardiovascular comorbidities, focusing on severe vascular events, cardiovascular risk factors and implications for treatment.

Segmental vitiligo (SV) is a special form of vitiligo occurring in a dermatomal distribution, and an abnormality involving the sympathetic nerves supplying the affected dermatome is known to underlie this disorder. Previously, we have shown that SV is associated with an abnormal increase in cutaneous blood flow and adrenoceptor responses in the affected areas. Since SV is resistant to conventional forms of therapy, its management represents a challenge for dermatologists. Low energy helium-neon lasers (He-Ne laser, wavelength 632.8nm) have been employed as a therapeutic instrument in many clinical situations, including vitiligo management and repair of nerve injury. The purpose of this study was to evaluate the effectiveness and safety of He-Ne lasers in treating SV, and determine their effects on the repair of sympathetic nerve dysfunction. Forty patients with stable-stage SV on the head and/or neck were enrolled in this study. He-Ne laser irradiation was administered locally at 3.0J/cm2 with point stimulation once or twice weekly. Cutaneous microcirculatory assessments in six SV patients were performed using a laser Doppler flowmeter. The sympathetic adrenoceptor response of cutaneous microcirculation was determined by measuring cutaneous blood flow before, during and after iontophoresis with sympathomimetic drugs (phenylephrine, clonidine and propranolol). All measurements of microcirculation obtained at SV lesions were simultaneously compared with contralateral normal skin, both before and after He-Ne laser treatment. After an average of 17 treatment sessions, initial repigmentation was noticed in the majority of patients. Marked repigmentation (> 50%) was observed in 60% of patients with successive treatments. Cutaneous blood flow was significantly higher at SV lesions compared with contralateral skin, but this was normalized after He-Ne laser treatment. In addition, the abnormal decrease in cutaneous blood flow in response to clonidine was improved by He-Ne laser therapy. Our study showed that He-Ne laser therapy is an effective treatment for SV by normalizing dysfunctions of cutaneous blood flow and adrenoceptor responses in SV patients. Thus, the beneficial effects of He-Ne laser therapy may be mediated in part by a reparative effect on sympathetic nerve dysfunction.

Atopic dermatitis (AD) is a pruritic recurring inflammatory skin disease. Recently, topical tacrolimus has been developed to treat AD. This report presents the first clinical experience with topical tacrolimus in Taiwan. This open-label, single-arm study was conducted at three centers from February to May 2002. The duration of each individual treatment was 4 weeks. Two groups were defined: pediatric and adult. Efficacy was evaluated on the basis of the physician's global evaluation at the end of treatment. Success was defined as at least 50% improvement. Other evaluations included the Eczema Area and Severity Index (EASI), the percentage of body surface area (BSA) involved, the patient's assessment of pruritus, and the patient's assessment of overall response. Safety profile was established by monitoring changes in hematology and biochemistry profiles and tacrolimus concentration in blood. All adverse events were recorded. Twenty-six pediatric patients and 42 adult patients were enrolled. Overall success rates were 80.8% and 82.1% in the pediatric and adult groups, respectively. The declines in EASI, percentage of BSA affected, and patient's assessment of pruritus were significant (p < 0.001); 88% and 100% of pediatric and adult patients, respectively, reported a favorable response to treatment. Changes in blood samples were unremarkable. Of pediatric and adult patients, 61.5% and 76.2%, respectively, reported adverse events. The most common adverse event reported was skin burning, which did not result in discontinuation of therapy. This report reveals that tacrolimus ointment is effective and safe for the treatment of AD in Taiwanese patients.

Infantile generalized pustular psoriasis (von Zumbusch) is a rare form of psoriasis. Here, we report a 3-month-old Taiwanese girl who was treated with Chinese herbal medicine for abdominal fullness starting at 1 month of age. Around 1 month into the treatment, sudden onset of generalized erythematous plaques with scales and pustules was noted which lasted for 1 month. Histopathology of the skin lesion revealed accumulation of polymorphs within the parakeratotic stratum corneum and subcorneal neutrophilic pustules. Based on clinical presentation, histopathology, and negative bacterial cultures, our final diagnosis was infantile generalized pustular psoriasis. Both drug use and physical stress (abdominal fullness for 1 month) may play a role in inducing generalized pustular psoriasis in this patient. The patient responded well to topical treatment, and the disease is under control with only occasional flares. In summary, because infants are at a stage of rapid growth, timely diagnosis and tailored therapy according to response are essential to ensure that the disease process does not interfere with normal development.

Wu C-S, Yu C-L, Wu C-S, Lan C-CE, Yu H-S. Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes.Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation of vitiligo lesions are not thoroughly clarified. The purpose of our study was to investigate the effects of narrow-band UVB irradiation on melanocyte proliferation and migrationin vitro. Our results showed that the cell counts as well as[3H]thymidine uptake of melanocytes were significantly enhanced by narrow-band UVB-irradiated keratinocyte supernatants. In these supernatants, a significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1 (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated keratinocytes was significantly reduced by a selective endothelin-B (ET-B) receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte proliferation. Our results of time-lapse microphotography revealed a stimulatory effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK (p125FAK) expression on melanocyte was enhanced by narrow-band UVB irradiation. In this study, narrow-band UVB irradiation stimulated a significant increase in matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow-band UVB-irradiation-induced migration of melanocytes was significantly annihilated by the addition of p125FAK inhibitor (herbimycin-A) or MMP-2 inhibitor (GM6001). These results suggest that p125FAK and MMP-2 activity play important roles in narrow-band UVB-induced migration of melanocytes. Our results provide a theoretical basis for the effectiveness of narrow-band UVB irradiation in treating vitiligo. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the potential differences between atopic dermatitis (AD) and non-atopic hand eczema in terms of quality of life (QoL) scores in a university hospital nursing population in Taiwan. It found that both AD and non-atopic hand eczema showed negative impacts on QoL of those affected. It concluded that more attention should be given on this condition in order to provide more effective preventive strategies.

A letter to the editor is presented in response to the article "Effect of a preceding laser dermabrasion on the outcome of combined therapy with narrowband ultraviolet B and potent topical steroids for treating nonsegmental vitiligo in resistant localizations," by E. Fontas and colleagues that was published in the 2012 issue.

Bowens disease (BD), a carcinoma in situ of the skin, has been identified as an early lesion in arsenic carcinogenesis. Patients with arsenic-induced Bowens disease (As-BD) showed both cutaneous and systemic immune dysfunctions. We set out to evaluate the interactions between keratinocytes and lymphocytes in the context of As-BD carcinogenesis. Our results showed that As-BD lesions demonstrated a significant dermal CD4+ cell, an essential regulator of proper tumor immunity, undergoing apoptosis. In addition, it was found that the As-BD patients have lower percentage of peripheral CD4+ cells as compared with control subjects. However, the CD4+ cells from As-BD patients were less susceptible to arsenic-induced apoptosis, due to reduced tumor necrosis factor receptor 1 expression. Interestingly, arsenic was found to induce Fas expression on CD4+ cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasL-containing keratinocyte supernatant was able to induce comparable CD4+ cell apoptosis for both patients and controls. Using immunofluorescent staining, increased FasL was observed in keratinocytes of As-BD lesions and Fas was expressed among infiltrating CD4+ cells. Our findings suggested that systemically, the percentage of CD4+ cells was decreased in the peripheral blood of As-BD patients. These residual CD4+ cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD4+ cell apoptosis might be mediated by FasL from keratinocytes. This additional tumor-anti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory disease involving the skin and/or joints. Till 2016, there were five biologic agents for psoriatic arthritis treatment in Taiwan: etanercept, adalimumab, golimumab, ustekinumab, and secukinumab. Although European guidelines recommend tumor necrosis factor-α (TNF-α) inhibitors as the first-line biologic agents for axial disease of psoriatic arthritis, the drug survival of biologic agents in Asian populations remains unclear. Objectives: We investigated 5-year drug survival of biologic agents in patients with psoriatic arthritis. Methods: We used Kaohsiung Medical University Hospital Research Database to evaluate real-world 5-year drug survival of biologic agents for psoriatic arthritis in a medical center from southern Taiwan. Results: The 5-year drug survival rates of ustekinumab, etanercept, and adalimumab were significantly different. Ustekinumab and etanercept showed higher 5-year survival rates for psoriatic disease than adalimumab. Golimumab and secukinumab had a short follow-up time to obtain a conclusive 5-year survival rate. Conclusion: Considering that TNF-α inhibitors are often the first-line biologic agents for psoriatic arthritis in guidelines in western countries, the finding that ustekinumab is superior to TNF-α inhibitor adalimumab in terms of 5-year survival for psoriatic disease may imply that the therapeutic response of biologic agents may differ between different ethnic groups.

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.