Rationale: Mucous membrane pemphigoid (MMP) is a rare, autoimmune bullous disease that affects mucosal surfaces and skin. Early and aggressive treatment initiation may be warranted due to the risks of serious complications. However, it can be challenging to make an initial diagnosis. Viral infection such as hepatitis B virus (HBV) infection has been found to be associated with the formation of autoimmune bullous diseases. Patient concerns: The patient was a 43-year-old male with gingivitis and recurrent swelling over the neck, cheeks, lips, and eyelids. The patient presented at oral medicine, otolaryngology, plastic surgery, and ophthalmology sequentially, and was later referred to the rheumatology, dermatology, and family medicine departments. Recurrent hemorrhagic bullae on oral mucosa and skin scarring occurred 2 years after the onset of the initial symptoms. Diagnosis: Skin biopsy with direct immunofluorescence was performed under the suspicion of MMP. Lesional hematoxylin and eosin stain and perilesional direct immunofluorescence were consistent with MMP. Interventions: Systemic Prednisolone and topical corticosteroid were used to control the disease. Outcomes: A flare-up of hepatitis B developed as a result of systemic prednisolone use. The disease went through relapses and remissions. The patient is on low-dose prednisolone (5 mg/day) with a monthly outpatient visit in the family medicine department. Lessons: It would be useful for medical practitioners in different specialties to be alert of the heterogeneous presentations of MMP. Chronic HBV infection might be a risk factor for MMP. In patients with chronic HBV infection, treatment of MMP must be closely monitored for the risk of reactivation of HBV.

Eosinophilic pustular folliculitis (EPF) is classified into Ofuji disease, immunosuppression-associated EPF, and infancy-associated EPF. The association of EPF with Demodex infestation is rarely reported. We report five cases of EPF with Demodex overgrowth. All patients were young females presenting with recurrent, itchy papulopustules on the face for 2 months to 2 years. Laboratory tests revealed eosinophilia ( n = 2) and iron deficiency anemia ( n = 1). Skin biopsy of papulopustular lesions was performed in each patient, and all revealed folliculocentric infiltration with eosinophils. Infundibular pustules containing Demodex mites were found in two patients. All patients had high Demodex densities examined by superficial needle-scraping method (7–18 mites/5 pustules) and/or thumbnail-squeezing method (37–255 mites/cm 2 ). Based on the clinical and laboratory findings, the patients were either first treated as having demodicosis or as having EPF. According to the treatment responses, the cases might represent Demodex -induced EPF or EPF-like reaction (Cases 1–3) or demodicosis superimposed on EPF (Cases 4 and 5). In sum, we report five cases of EPF with Demodex overgrowth (demodicosis). These cases illustrate that the possibility of Demodex overgrowth should be considered in cases of EPF with incomplete treatment response to indomethacin and/or oral corticosteroids. Conversely, EPF should be considered in cases of demodicosis with incomplete responses to antiparasitic treatment.

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The epidemiology of depression in patients with psoriasis has not been well defined in the Asian population. This study evaluated the epidemiological features of, and risk factors for, depression among patients with psoriasis in Taiwan. A nationwide population-based cross-sectional study was undertaken using the National Health Insurance Research Database. This study included 17,086 patients with psoriasis and 1,607,242 patients from the general population. The prevalence of depression in patients with psoriasis was 11.52%, while the prevalence of depression in the general population was 7.73% (prevalence ratio 1.49, 95% confidence interval 1.43-1.55). Multivariable analysis showed that, in patients with psoriasis, risk factors associated with depression were: age 20-50 years, female sex, low income, and major comorbid diseases, including liver cirrhosis, renal disease, cardiovascular disease and cerebrovascular disease. Therefore, the prevalence of depression is higher in patients with psoriasis, particularly in young and middle-aged women with low income and major comorbidities.

BACKGROUND:Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center.METHODS:Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed.RESULTS:There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy.CONCLUSIONS:The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan.

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.

Livedoid vasculopathy (atrophie blanche) is a form of thrombotic vasculopathy. It is characterized by small ulcers that become crusted, and heal after several months to produce white atrophic scars. The most commonly affected sites are the lower legs, in particular the dorsum of the feet and ankles. To date, the dermoscopic features of livedoid vasculopathy have not been clearly described in the literature. In this observational study, we sought to evaluate the dermoscopic patterns of livedoid vasculopathy and determine whether the dermoscopic features are associated with certain histopathological characteristics. We evaluated 9 patients with livedoid vasculopathy by dermoscopy. Skin biopsy specimens were stained with hematoxylin and eosin for histopathologic examination, and dermoscopic features were correlated with histopathological characteristics. In the majority of patients with livedoid vasculopathy, examination with dermoscopy revealed central crusted ulcers or ivory white areas associated with peripheral pigmentation in a reticular pattern. In addition, increased vascular structures including linear and glomerular vessels were found. On histopathological examination, the central ivory white areas correlated with dermal fibrosis, the reticular pigmentation corresponded to epidermal basal layer hyperpigmentation or melanin within melanophages in the dermal papillae, and the vascular structures correlated with dilatation and proliferation of capillaries in the upper dermis. In summary, the most common dermoscopic features of livedoid vasculopathy identified in this study were central crusted ulcers or ivory white scar-like areas associated with peripheral reticular pigmentation and increased vascular structures. The characterization of dermoscopic criteria for livedoid vasculopathy may improve the accuracy in the clinical diagnosis and follow-up of this disease.

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.

Diabetes is an important health issue because of its increasing prevalence and association with impaired wound healing. Epidermal keratinocytes with overexpressed antiangiogenic molecule thrombospondin-1 (TSP1) have been shown to impair proper wound healing. This study examined the potential involvement of keratinocyte-derived TSP1 on diabetic wound healing. Cultured human keratinocytes and diabetic rat model were used to evaluate the effect of high-glucose environment on TSP1 expression in epidermal keratinocytes, and the molecular mechanisms involved in the process were also studied. We demonstrated that high-glucose environment increased TSP1 expression in keratinocytes. In addition, increased oxidative stress induced DNA hypomethylation at the TSP1 promoter region in keratinocytes exposed to high-glucose environment. Similar findings were found in our diabetic rat model. Early antioxidant administration normalized TSP1 expression and global DNA methylation status in diabetic rat skin and improved wound healing in vivo. Because oxidative stress contributed to TSP1 DNA hypomethylation, early recognition of diabetic condition and timely administration of antioxidant are logical approaches to reduce complications associated with diabetes as alterations in epigenome may not be reversible by controlling glucose levels during the later stages of disease course.

Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human β-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections.

E20 CUTIS WWW.CUTIS.COM To the Editor: Onychomadesis is characterized by separation of the nail plate from the matrix due to a temporary arrest in nail matrix activity. Hand-foot-and-mouth disease (HFMD) is a relatively common viral infection, especially in children. Although the relationship between onychomadesis and HFMD has been noted, there are few reports in the literature.1-9 We present 2 cases of onychomadesis following HFMD in Taiwanese siblings. A 3-year-old girl presented with proximal nail plate detachment from the proximal nail fold on the bilateral great toenails (Figure 1) and a transverse whole-thickness sulcus on the bilateral thumbnails (Figure 2) of several weeks’ duration. Her 6-year-old sister had similar nail changes. Hand-foot-and-mouth disease was diagnosed about 4 weeks prior to nail changes. The mother reported that only the younger Onychomadesis Following Hand-foot-and-mouth Disease

Background: Tranexamic acid and vitamin C derivatives are important reagent used in cosmetic skin-whitening products. Recently, self-perceptions regarding improvement in facial skin status have been increasingly recognized as an important outcome of whitening cosmetic products intervention. Aims: The purpose of the study was to determine the receptiveness of objective and self-perceived facial skin status using whitening cosmetic products. Methods: A total of 40 volunteers were photographed using the Visia? machine and completed questionnaires at pre- and post-operation (8 weeks after receiving whitening cosmetic products). Visia? digital image analysis and questionnaires were used for assessment of facial skin status. The receptiveness of objective and self-perceived measures was assessed by paired t test and Effect Size (ES). Results: There were progresses with regard to the surface spot (ES = 0.22), wrinkles (ES = 0.24), texture (ES = 0.31) and pores (ES = 0.21) after using cosmetic products with tranexamic acid. For self-perceived measures, there were significant progresses in pigmented spots (ES = 0.75), rough complexion (ES = 0.76), red complexion (ES = 0.41), wrinkle (ES = 0.58) and obvious pores (ES = 0.75). Conclusions: This study suggests that the whitening cosmetic products are associated with improvement of objective and self-perceived facial skin status. The results could be provided as available information for cosmetic investigation.

Ultraviolet B (UVB) radiation from the sun may lead to photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance, but sunscreen use did not reduce sunburn episodes. It was shown that UVB-induced erythema depends on surface exposure but not irradiance of UVB. We previously showed that irradiance plays a critical role in UVB-induced cell differentiation. This study investigated the impact of irradiance on UVB-induced photocarcinogenesis. For hairless mice receiving equivalent exposure of UVB radiation, the low irradiance (LI) UVB treated mice showed more rapid tumor development, larger tumor burden, and more keratinocytes harboring mutant p53 in the epidermis as compared to their high irradiance (HI) UVB treated counterpart. Mechanistically, using cell models, we demonstrated that LI UVB radiation allowed more keratinocytes harboring DNA damages to enter cell cycle via ERK-related signaling as compared to its HI UVB counterpart. These results indicated that at equivalent exposure, UVB radiation at LI has higher photocarcinogenic potential as compared to its HI counterpart. Since erythema is the observed sunburn at moderate doses and use of sunscreen was not found to associate with reduced sunburn episodes, the biological significance of sunburn with or without sunscreen use warrants further investigation.

BACKGROUND:The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined.OBJECTIVE:We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants.METHODS:A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development.RESULTS:Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose.LIMITATIONS:This study is retrospective in nature.CONCLUSION:Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy.

Artocarpin, a natural prenylated flavonoid, has been shown to have various biological properties. However, its effects on human cutaneous squamous cell carcinoma (SCC) have not been previously investigated. We set out to determine whether artocarpin has cytotoxic effects on SCC cells and whether its pharmacological activity is dependent on protein-nutrient concentration. Our results showed that treatment of HSC-1 cells (a human cutaneous SCC cell line) with artocarpin decreased cell viability and induced cell apoptosis by increasing caspase 3/7 activity. These effects were more pronounced at low fetal bovine serum (FBS) concentrations. Artocarpin induced an increase in the level of phospho-p38 and a decrease in the levels of phospho-ERK, phospho-JNK, phospho-Akt, phospho-mTOR, and phospho-S6K. High FBS concentrations in the culture media inhibited and delayed the uptake of artocarpin from the extracellular compartment (culture media) into the intracellular compartment, as determined by high performance liquid chromatography (HPLC) analysis. In conclusion, artocarpin induces apoptosis in HSC-1 cells through modulation of MAPK and Akt/mTOR pathways. Binding of artocarpin to proteins in the FBS may inhibit cellular uptake and reduce the cytotoxic activity of artocarpin on HSC-1 cells. Therefore, artocarpin may have potential use in the future as a form of treatment for cutaneous SCC.

BACKGROUND:Various clinician-assessed scoring criteria have been used to grade acute radiation dermatitis. However, it is not known whether these scoring criteria correlate with changes in objective skin biophysical parameters and patient-reported symptoms following radiotherapy. We seek to correlate three different clinician-assessed scoring criteria with skin biophysical changes and patient-reported symptoms in breast cancer patients undergoing radiotherapy. METHODS:A prospective cohort study was performed in a university hospital medical center. The severity of acute radiation dermatitis in 101 breast cancer patients was graded using the RTOG, CTCAE and WHO clinical scoring criteria. We also measured various skin biophysical parameters (skin blood flow, pigmentation, hydration, and pH) by non-invasive techniques before and after radiotherapy. Patient-reported breast symptoms (pain, itching, local heat, and tightness) were evaluated using a questionnaire. RESULTS:The three different clinician-assessed scoring criteria correlated most strongly with changes in cutaneous blood flow following radiotherapy for breast cancer (correlation coefficient 0.70 for RTOG, 0.68 for CTCAE, and 0.50 for WHO). All three scoring criteria also showed moderate correlation with changes in skin pigmentation (correlation coefficients 0.4-0.5), but showed no significant correlation with skin hydration or pH (correlation coefficients <0.2). The scoring criteria correlated poorly with patient-reported breast symptoms (correlation coefficients <0.3). CONCLUSIONS:The three clinician-assessed scoring criteria (especially the RTOG and CTCAE criteria) show strong correlation with cutaneous blood flow measurements, but correlate less well with other skin biophysical parameters and patient-reported symptoms.

Objectives To investigate the feasibility of manual segmentation by users of different backgrounds in a previously developed multifeature computer-aided diagnosis (CADx) system to classify melanocytic and non-melanocytic skin lesions based on conventional digital photographic images. Methods In total, 347 conventional photographs of melanocytic and non-melanocytic skin lesions were retrospectively reviewed, and manually segmented by two groups of physicians, dermatologists and general practitioners, as well as by an automated segmentation software program, JSEG. The performance of CADx based on inputs from these two groups of physicians and that of the JSEG program was compared using feature agreement analysis. Results The estimated area under the receiver operating characteristic curve for classification of benign or malignant skin lesions based were comparable on individual segmentation by the gold standard (0.893, 95% CI 0.856 to 0.930), dermatologists (0.886, 95% CI 0.863 to 0.908), general practitioners (0.883, 95% CI 0.864 to 0.903) and JSEG (0.856, 95% CI 0.812 to 0.899). The agreement in the malignancy probability scores among the physicians was excellent (intraclass correlation coefficient: 0.91). By selecting an optimal cut-off value of malignancy probability score, the sensitivity and specificity were 80.07% and 81.47% for dermatologists and 79.90% and 80.20% for general practitioners. Conclusions This study suggests that manual segmentation by general practitioners is feasible in the described CADx system for classifying benign and malignant skin lesions.

The Journal of DermatologyVolume 42, Issue 12 p. 1201-1202 Letter to the Editor Dermoscopy as a diagnostic aid in a case of systemic amyloidosis with initial presentation in skin Stephen Chu-Sung Hu, Stephen Chu-Sung Hu Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanSearch for more papers by this authorGwo-Shing Chen, Gwo-Shing Chen Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanSearch for more papers by this authorSheau-Fang Yang, Sheau-Fang Yang Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanSearch for more papers by this authorChing-Ying Wu, Corresponding Author Ching-Ying Wu Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Ching-Ying Wu, M.D., Department of Dermatology, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan. Email: [email protected]Search for more papers by this author Stephen Chu-Sung Hu, Stephen Chu-Sung Hu Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanSearch for more papers by this authorGwo-Shing Chen, Gwo-Shing Chen Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanSearch for more papers by this authorSheau-Fang Yang, Sheau-Fang Yang Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanSearch for more papers by this authorChing-Ying Wu, Corresponding Author Ching-Ying Wu Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Ching-Ying Wu, M.D., Department of Dermatology, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan. Email: [email protected]Search for more papers by this author First published: 05 October 2015 https://doi.org/10.1111/1346-8138.13103Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Fernandez-Flores A. Cutaneous amyloidosis: a concept review. Am J Dermatopathol 2012; 34: 1–14. 2Gertz MA. Immunoglobulin light chain amyloidosis: 2014 update on diagnosis, prognosis, and treatment. Am J Hematol 2014; 89: 1132–1140. 3Steciuk A, Dompmartin A, Troussard X et al. Cutaneous amyloidosis and possible association with systemic amyloidosis. Int J Dermatol 2002; 41: 127–132. 4Silverstein SR. Primary, systemic amyloidosis and the dermatologist: where classic skin lesions may provide the clue for early diagnosis. Dermatol Online J 2005; 11: 5. 5Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol 1988; 18(1 Pt 1): 1–16. Citing Literature Volume42, Issue12December 2015Pages 1201-1202 ReferencesRelatedInformation

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