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Background Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is important for xenobiotic metabolism and binds to various endogenous and exogenous ligands in the skin. However, the functional role of AhR in patients with psoriasis (PS) and atopic dermatitis (AD) remains unclear. Objective We aimed to determine whether AhR-regulated factors (AhR, CYP1A1, interleukin [IL]-17, IL-22) were affected by AhR ligands (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) in chronic inflammatory skin diseases such as PS and AD. Methods The expression levels of AhR-related factors were determined by quantitative PCR, western blotting, and immunocytochemistry. Specific siRNA targeting AhR was used to inhibit gene expression in human peripheral blood mononuclear cells (PBMC). Cytokine assays were performed to determine the protein production of CD4+ T cells. Results In comparison with healthy controls, TCDD-treated PBMCs and CD4+ T cells from patients with PS and AD showed an increase in AhR gene levels as well as significantly increased expression of AhR-related factors (such as AhR, CYP1A1, IL-17, and IL-22). In contrast, 6-formyl indolo [3,2-b] carbazole (FICZ) inversely affected the differentiation of CD4+ T cells and their cytokine expression levels as compared with TCDD. CD4+ T cells from patients with AD and PS showed higher expression levels of AhR, CYP1A1, IL-17, and IL-22. Conclusion Our results suggest that TCDD-induced AhR-related factor upregulation in AD and PS patients may increase the expression of AhR-regulatory genes, thereby contributing to the development of AD and PS.

Psoriasis is a chronic inflammatory systemic disease primarily affecting the skin, but which often involves considerable comorbidities as well. One-third of psoriasis cases start during childhood. In pediatric psoriasis, an association with several medical comorbidities is also indicated. Furthermore, because of its chronic nature and frequent relapses, psoriatic patients tend to require long-term treatment and experience negative impacts on their quality of life. Considering the different clinical characteristics of pediatric psoriasis, it has recently been presented that the pathogenesis of pediatric psoriasis is distinct from adult psoriasis. Treatment for pediatric psoriasis usually involves the same methods as for adults. However, most treatments in pediatric psoriasis are used off-label and research in this regard is still lacking. Targeted therapies involving newly developed biologics are also increasingly being applied to psoriasis in children. This review summarizes the clinical characteristics of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and treatments in pediatric psoriasis. This was undertaken to widen the understanding of these relevant aspects and to provide better management of pediatric psoriasis by clinicians.

Chlorpheniramine maleate is commonly used antihistamine. Since antihistamines are the main therapeutic agents for symptomatic treatment of urticaria, anaphylaxis to antihistamines may lead to errors in diagnosis and treatment. We report a case of anaphylaxis induced by chlorpheniramine maleate confirmed by intradermal test. A 35-year-old female experienced history of anaphylaxis after intramuscular injection of chlorpheniramine maleate. Skin prick test was negative, but intradermal test was positive. Patient also experienced mild dizziness after intradermal test and refused to perform any further evaluation such as oral challenge test. Anaphylaxis for chlorpheniramine maleate is very rare but should be considered.

Lymphangiomas are rare benign congenital lymphatic malformations. They can be divided into three groups: cutaneous lymphangioma circumscriptum (CLC), cavernous, and cystic. CLC is the most common type, and rarely occurs with cavernous or cystic lymphangioma under the lesion. Here, we describe the case of a 9-year-old girl who presented with an asymptomatic vesicular lesion on her back. She was finally diagnosed with CLC by clinical manifestations, dermoscopic findings, and histologic findings. Seven years ago, there was a history of surgical operation in the department of general surgery, and the surgery was soft tissue cystic lymphangioma removal surgery. There was no skin lesion for seven years after surgery, but one occurred a month ago. Herein, we present a case of CLC that occurred after a long interval after surgery for soft tissue cystic lymphangioma.

Background: Anaphylaxis is an allergic disease that requires special handling due to its potential fatality. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. However, actual data on the prevalence or causes of anaphylaxis in Korea are limited. Methods: The emergency room attendees diagnosed with anaphylaxis between 2011 and 2015 in five university hospitals were included. Medical records were reviewed retrospectively. Results: During the 5 years, a total of 505 subjects were diagnosed with anaphylaxis. Respiratory presentations were more common in children than in adults, while adults presented more frequently with cardiovascular symptoms. Intraoral angioedema was more often observed in the countryside than in the city. Insect stings/bites were more common in the countryside than in the city. Drugs were much more common in adults than in children. In the countryside, the frequency of anaphylaxis was higher in summer and autumn than in spring and winter. The use of corticosteroids was less common in children than in adults, while children more frequently got treatment with inhaled beta 2 agonist. Conclusions: The principal causes of anaphylaxis in Korean patients were food, drugs, and stings/bites. The cause, clinical features and management of anaphylaxis were significantly different depending on age and region. These real-world data on anaphylaxis could be helpful to deepen that understanding of this condition for physicians and patients.

Pruritus is a relatively common symptom that anyone can experience at any point in their life and is more common in the elderly. Pruritus in elderly can be defined as chronic pruritus in a person over 65 years old. The pathophysiology of pruritus in elderly is still unclear, and the quality of life is reduced. Generally, itch can be clinically classified into six types: Itch caused by systemic diseases, itch caused by skin diseases, neuropathic pruritus, psychogenic pruritus, pruritus with multiple factors, and from unknown causes. Senile pruritus can be defined as a chronic pruritus of unknown origin in elderly people. Various neuronal mediators, signaling mechanisms at neuronal terminals, central and peripheral neurotransmission pathways, and neuronal sensitizations are included in the processes causing itch. A variety of therapies are used and several novel drugs are being developed to relieve itch, including systemic and topical treatments.

Asivatrep is a potent and selective antagonist of transient receptor potential vanilloid subfamily V member 1 (TRPV1), which plays an important role in itch and inflammation in atopic dermatitis (AD).This current study aimed to evaluate the efficacy and safety of asivatrep cream in patients with AD.For this phase 3 double-blind, vehicle-controlled study, patients aged ≥12 years with mild to moderate AD were enrolled and randomly assigned 2:1 to the 1.0% asivatrep or vehicle group for 8 weeks of twice-daily application (n = 240). The primary end point was the proportion of patients with an Investigator's Global Assessment score (IGA) of 0 or 1 at week 8. Standard safety assessments were conducted.At week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1 (P .001); significantly more had ≥2 points of improvement on the IGA from baseline score (20.3% vs 7.7%; P = .01). The mean percentage reduction in the Eczema Area and Severity Index (EASI) score was 44.3% for the asivatrep group and 21.4% for the vehicle group at week 8 (P .001). Significantly more asivatrep-treated patients experienced an improvement of at least 50%, 75%, and 90% on the EASI than the vehicle group. The mean ± SD change in the pruritus visual analog scale score at week 8 was -2.3 ± 2.4 for the asivatrep group and -1.5 ± 2.4 for the vehicle group (P = .02). No significant safety issues were reported.Asivatrep improved clinical signs and symptoms of AD and was well tolerated.

A 46-year-old woman presented with slightly itching, painless erythematous nodules on the face, neck, and genital area. Initial differential diagnoses included cutaneous lymphoma. We performed punch biopsy on her neck. In histopathology, interface dermatitis with some nodular infiltration of numerous neutrophils and plasma cells was observed, therefore, serologic tests for syphilis were performed. Owing to positive serologic test results and dramatically improved skin lesions after treatment with benzathine penicillin, nodular secondary syphilis was diagnosed. Nodular skin lesions in secondary syphilis are uncommon and often misleading. Our case suggests secondary syphilis should be considered in the differential diagnosis of nodular lesions.

Background: Histamine in food is known to cause food poisoning and allergic reactions. We usually ingest histamine in cooked food, but there are few studies about the influence of cooking method on the histamine level. Objective: The purpose of this study was to determine the influence of cooking methods on the concentration of histamine in foods. Methods: The foods chosen were those kinds consumed frequently and cooked by grilling, boiling, and frying. The histamine level of the food was measured using enzyme-linked immunosorbent assay. Results: Grilled seafood had higher histamine levels than raw or boiled seafood. For meat, grilling increased the histamine level, whereas boiling decreased it. For eggs, there was not much difference in histamine level according to cooking method. Fried vegetables had higher histamine levels than raw vegetables. And fermented foods didn’t show much difference in histamine level after being boiled. Conclusion: The histamine level in food has changed according to the cooking method used to prepare it. Frying and grilling increased histamine level in foods, whereas boiling had little influence or even decreased it. The boiling method might be helpful to control the effect of histamine in histamine-sensitive or susceptible patients, compared with frying and grilling. (Ann Dermatol 29(6) 706∼714, 2017)

Background Excessive wound healing can lead to hypertrophic scars, which are not only a cosmetic issue but could also be itchy or painful. Previously, we reported that, in comparison with normal tissue, thymic stromal lymphopoietin (TSLP) expression was increased in skin burn scars when the activation of transient receptor potential vanilloid-3 (TRPV3) of keratinocytes was increased. However, the functional role of TRPV3 in dermal fibrosis remains unclear. Objective We aimed to determine whether TRPV3 affects the collagen production of human primary dermal fibroblasts (HPDFs) and to investigate the mechanism involved. Method Human primary dermal fibroblasts were cultured and transformed into myofibroblasts using TSLP and carvacrol. Expression levels of α-SMA, fibronectin, and COL1A1 were determined using qPCR, western blotting, and immunofluorescence staining. Ca2+ influx was measured using a calcium-sensitive fluorescent dye, Fura3-AM. Nuclear factor of activated T-cells (NFAT) and phosphorylated-Smad2/3 were determined by western blotting. Silencing of TRPV3 with TRPV3-specific small interference RNA was evaluated using qPCR and western blotting. Results The expression levels of α-SMA, fibronectin, COL1A1, and TSLP were significantly increased in carvacrol-treated HPDFs. The expression levels of α-SMA, fibronectin, and COL1A1 were significantly increased by TSLP. The expression levels of TSLP and COL1A1 were significantly blocked by TRPV3 silencing in HPDFs. Regulation of Ca2+ influx and the expression levels of NFAT and p-Smad2/3 were significantly increased in carvacrol-treated HPDFs. ECM productions induced via the TRPV3/TSLP/Smad2/3 pathways. Conclusions The activation of the TRPV3 channels regulates dermal fibrosis by reducing extracellular matrix production via the TRPV3/TSLP/Smad2/3 pathways in dermal fibroblasts.

Recently, the mTOR signaling has emerged as an important player in the pathogenesis of psoriasis. We previously found that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced psoriatic skin inflammation was related to the inhibition of autophagy in keratinocytes. However, the effects and detailed molecular mechanisms of the mTOR inhibitor rapamycin and TCDD on psoriasis in vivo remain to be elucidated. In this study, we aimed to evaluate the effects of rapamycin and TCDD on skin lesions in imiquimod (IMQ)-induced psoriasis using a mouse model. TCDD aggravated skin inflammation in an IMQ-induced psoriatic mouse model. Furthermore, TCDD increased the expression of aryl hydrocarbon receptor (AHR), CYP1A1, proinflammatory cytokines, oxidative stress markers (NADPH oxidase (Nox) 2, Nox4), and phosphorylated P65NF-ĸB, whereas the expression of autophagy-related factors and the antioxidant marker nuclear factor-erythroid 2-related factor 2 (NRF2) decreased. Rapamycin reduced the aggravated skin inflammation induced by TCDD and restored TCDD-induced autophagy suppression and the increase of AHR expression, oxidative stress, and inflammatory response in the skin lesions of a psoriatic mouse model. In conclusion, we demonstrated that rapamycin alleviates TCDD-induced aggravated dermatitis in mice with imiquimod-induced psoriasis-like dermatitis through AHR and autophagy modulation.

Post burn pruritus is a common distressing sequela of burn wounds. Empirical antipruritic treatment often fails to have a satisfactory outcome, as the mechanism of it has not been fully elucidated. The aim of this study was to evaluate the manifestation of transient receptor potential vanilloid 3 (TRPV3), transient receptor potential ankyrin 1 (TRPA1) and other related receptors in post burn pruritus. Sixty-five burn patients with (n = 40) or without (n = 25) pruritus were investigated, including skin biopsies. Keratinocytes and fibroblasts from skin biopsy samples were separated. Real time-PCR showed that mRNA of TRPV3 was significantly increased in keratinocytes from pruritic burn scars than in keratinocytes from non-pruritic burn scars. With TRPV3 activation, intracellular Ca2+ concentrations were more significantly increased in keratinocytes from pruritic burn scars than in those from non-pruritic ones. Additionally, mRNA and protein levels of protease-activated receptor 2 (PAR2) and neurokinin-1 receptor (NK1R) were also significantly increased in pruritic burn scars. In conclusion, we confirmed that TRPV3, PAR2, and NK1R were highly expressed in pruritic burn scars. These results may help determine a novel mechanism for post burn pruritus. This article is protected by copyright. All rights reserved.

BACKGROUND The etiology of chronic urticaria (CU) remains unknown in most patients. Possible causes in some cases include food, but the role of allergy to food antigens in patients with CU remains controversial. OBJECTIVE The aim of this study was to evaluate the association between food allergy and CU. METHODS Korean patients with CU were assessed for a previous history of food allergy that caused symptoms of CU. Blood samples were taken from 350 patients to measure food allergen-specific IgE. Based on history and laboratory results, open oral food challenge (OFC) tests were performed. RESULTS Of 350 participants, 46 (13.1%) claimed to have experienced previous food hypersensitivity. Pork (n=16) was the main food mentioned, followed by beef (n=7), shrimp (n=6), and mackerel (n=6). We found that 73 participants (20.9%) had elevated levels of food-specific IgE, with pork (n=30), wheat (n=25), and beef (n=23) being the most common. However, when the open OFC tests were conducted in 102 participants with self-reported food hypersensitivity or raised levels of food-specific IgE, only four participants showed a positive reaction to pork (n=3) or crab (n=1). CONCLUSION Although some participants claimed to have a history of CU related to food intake, when an open OFC test was conducted, few of them had positive results. We therefore conclude that food allergy is an uncommon cause of chronic CU.

Background: The aryl hydrocarbon receptor (AHR) and autophagy are both important to maintain skin homeostasis. However, they are also involved in skin disorders. So far, their roles in psoriasis pathogenesis are unknown. Objective: We studied the immunohistochemical and gene expression of AHR, CYP1A1, and microtubule-associated protein light chain 3 (LC3) in lesional skin of psoriasis patients to determine correlations among them. Methods: We included 24 psoriasis patients and ten healthy volunteers. Skin biopsies were collected. AHR, CYP1A1, and LC3 protein expression was examined by immunohistochemistry, immunofluorescence, and western blotting. AHR, CYP1A1, LC3, ATG5, BECN1 and Nrf2 mRNA levels were measured by quantitative polymerase chain reaction. Results: AHR and CYP1A1 protein expression were higher in psoriasis lesional skin than in normal skin. LC3 protein expression was lower in psoriasis lesions than in normal controls. AHR and CYP1A1 protein expression in psoriasis lesions showed significant positive correlations with mean epidermal thickness and inflammatory cell density. Significant negative correlations were noted between LC3 protein expression in psoriasis lesions and the mean epidermal thickness or inflammatory cell density. A significant negative correlation was found between AHR and LC3 expression in psoriatic skin. AHR, CYP1A1 and Nrf2 mRNA expression were upregulated while LC3, ATG5, and BECN1 mRNA were down-regulated, in psoriatic lesional skin compared with normal controls. Conclusion: AHR and autophagy could play a role in psoriasis pathogenesis by modifying epidermal hyperproliferation and inflammation. AHR and autophagy regulation are potential therapeutic targets in chronic inflammatory skin diseases. (Ann Dermatol 33(2) 138∼146, 2021)

Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus that can cause permanent scarring. Treatment of DLE includes protection from sunlight and artificial sources of ultraviolet light, as well as systemic and topical medications. The first-line standard therapies are antimalarials and topical steroids. Other systemic therapies include systemic steroid, azathioprine, dapsone, and immunosuppressive agents. Topical tacrolimus and pimecrolimus have also been evaluated. Recent studies reported that several treatments, including pulsed dye laser, CO2 laser, intense pulsed light (IPL), and 1,064-nm long-pulse neodymium-doped yttrium aluminum (Nd:YAG) have been used for the cosmetic treatment of DLE. Here, we report a case of a DLE scar that was successfully treated with a combination therapy of IPL and Q-switched 1,064-nm Nd:YAG laser.

Background: prurigo is a chronic skin disorder associated with a history of chronic pruritus. The pathogenesis of prurigo is largely unknown and the treatment of prurigo is unsatisfactory and challenging. Conventional systemic treatments may be beneficial, however, their possible side effects and possible transient efficacy is still a problem. We aimed to present the clinical course and effect of treatment with alitretinoin on patients with prurigo nodularis initially treated with conventional treatments like oral antihistamine, cyclosporine, and phototherapy. Methods: all the patients had prurigo nodularis refractory to conventional treatment. Their medical records included demographic features, past medical history, duration of disease, and treatment modalities, and the clinical courses of the patients were reviewed for this retrospective study. We evaluated patient pruritus and skin lesions for the duration. Results: we present reports involving 10 patients with refractory prurigo. All the patients in our cases were treated with oral alitretinoin after previous treatments and reported the improvement of skin lesions and pruritus within 2 weeks to 3 months. Conclusions: we suggest that oral alitretinoin may be an effective and well tolerated treatment option for patients with intractable prurigo. Further clinical studies are warranted to confirm the long-lasting efficacy and safety of alitretinoin for treating patients with prurigo.

Background Malignant melanoma is a cutaneous malignancy with a high mortality rate and high potential for metastases. Detailed information on the clinicopathologic characteristics and prognostic factors of cutaneous melanoma is currently limited in Korea. This study aimed to identify the epidemiological and clinicopathologic characteristics of primary cutaneous melanoma in Korean patients, and to assess which prognostic variables could influence both the development of metastases in primary cutaneous melanoma and overall survival (OS). Methods A total of 261 patients diagnosed with primary cutaneous melanoma in seven medical centers between 1997 and 2017 were retrospectively investigated with regard to clinical presentation, localization of the tumor, histopathologic subtype, and survival time. Results The nodular histologic subtype, ulceration, and Breslow thickness were significantly associated with the development of metastasis; and overweight and obesity (body mass index > 23) were significantly associated with increased Breslow thickness. The location of the metastases appeared to influence OS: brain metastases were associated with the highest risk of death, followed by gastrointestinal, lung, and extra-regional lymph node metastases. Conclusion In this study, tumor thickness, nodular histologic subtype, and ulceration predicted metastatic spread of primary cutaneous melanoma. In addition, OS was associated with the location of metastases. Obesity was related to the prognosis of primary cutaneous melanoma. Clinicians should bear these findings in mind when forming a diagnosis because of the risk of a poor prognosis., Graphical Abstract

Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy stimulation suppressed AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD- and chloroquine-induced p65NF-&kappa, B and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-&kappa, B/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis.

Corticosteroids are potent anti-inflammatory and anti-allergic agents used in the treatment of various inflammatory diseases, including allergic disease. They are frequently considered the therapy-of-choice for many skin diseases. However, allergic reactions caused by corticosteroids have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 32-year-old woman with triamcinolone-induced immediate hypersensitivity reaction, in which the patient had a positive prick test result with triamcinolone. She has had atopic dermatitis (AD) for three years. She had used systemic steroid, cyclosporine, and antihistamine with topical steroids for AD. In clinic, approximately 10 minutes after intralesional injection of triamcinolone, she complained of erythematous patches with slight elevation and itching on the face, trunk, and both hands. After intravenous injection of dexamethasone, her symptoms got worse. After treatment with epinephrine, all symptoms resolved within two hours. We performed an open test and skin prick test. She had a positive result only from the prick test with triamcinolone; all other steroids showed negative results from the open tests. Dermatologists should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids., Graphical Abstract

Background Rosacea is associated with chronic systemic disease. However, research is lacking in Asian countries. Objective To evaluate the association between rosacea and cardiovascular diseases (CVDs) related systemic comorbidities, and the use of antihypertensive and antihyperlipidemic drugs in Korea. Methods A five-year retrospective study, using hospital database, was conducted in five medical centers for five years. Totally 1,399,528 patients were evaluated. Results The overall frequency for diagnosed rosacea was 0.18% over five years (2,536 rosacea patients). Patients with diabetes and patients with dyslipidemia were more likely to have rosacea (odd ratio [OR] 2.724, 95% confidence interval [CI] 1.295~5.730, p=0.016; OR 1.788, 95% CI 1.445~2.212, p

Few studies of atopic dermatitis (AD) in adult patients have evaluated differences in clinical features of AD according to onset age. We aimed to characterize the clinical features of AD in adult patients according to age of onset. Subjects with AD outpatient visiting the Department of Dermatology at Kangnam Sacred Heart Hospital were recruited for this study. A dermatologist conducted clinical evaluation, a survey of demographics, and onset of AD-associated signs and symptoms for each participant. Total immunoglobulin E (IgE) was also tested. A total of 280 adult AD patients were enrolled, among which 232 patients (82.86%) showed pre-adult-onset (age < 18 years) and 48 patients (17.14%) had adult-onset (age ≥ 18 years) of AD. There were significant differences between the 2 groups in the area of initial involvement (P = 0.017) and in treatment history (P = 0.010). Interestingly, patients with body mass index (BMI) ≥ 25 showed significantly higher Eczema Area and Severity Index (EASI) scores than did patients with BMI < 25 in the pre-adult-onset adult AD group (P = 0.048). On the other hand, there were no significant differences in sex, family history, BMI, EASI, and total IgE between patients with pre-adult-onset AD and patients with adult-onset AD. Our findings suggest that, even though many common features exist, there are significant differences between the clinical characteristics of pre-adult-onset and adult-onset AD subgroups, in adult patients with AD., Graphical Abstract

Background: Skin diseases characterized by epithelial barrier dysfunction show altered sphingolipid metabolism, which results in changes in the stratum corneum intercellular lipid components and structure. Under pathological conditions, 1-deoxysphingolipids form as atypical sphingolipids from de novo sphingolipid biosynthesis. Objective: This study investigated the potential role of 1-deoxysphingolipids in skin barrier dysfunction secondary to X-ray and ultraviolet B (UVB) irradiation in vitro and in vivo. It was also evaluated changes in the expression of 1-deoxysphingolipids in lesional human skin of atopic dermatitis. Methods: In this study, the changes in these 1-deoxysphingolipids levels of skin and serum samples were investigated in skin barrier dysfunction associated with X-ray and UVB irradiation in vitro and in vivo. Results: Increased 1-deoxysphingolipids were observed in cultured normal human epidermal keratinocytes after X-ray irradiation. X-ray or UVB irradiation increased the production of 1-deoxysphingosine in a reconstituted 3-dimensional (3D) skin model. Interestingly, treatment with a physiological lipid mixture (multi-lamellar emulsion contained pseudoceramide), which can strengthen the epidermal permeability barrier function, resulted in decreased 1-deoxysphingosine formation in a reconstituted 3D skin model. Further investigation using a hairless mouse model showed similar preventive effects of physiological lipid mixture against 1-deoxysphingosine formation after X-ray irradiation. An increased level of 1-dexoysphingosine in the stratum corneum was also observed in lesional skin of atopic dermatitis. Conclusion: 1-deoxysphingosine might be a novel biomarker of skin barrier dysfunction and a physiological lipid mixture treatment could prevent 1-deoxysphingosine production and consequent skin barrier dysfunction. (Ann Dermatol 32(4) 306∼318, 2020)

Background: Several epidemiological studies have shown that the atopic tendency increases in the obese population. Objective: The aim of this study was to confirm the effect of weight reduction on improvement of atopic dermatitis (AD) symptoms and to investigate the relationship between AD severity and the level of serum adipokines. Methods: Forty subjects who were AD outpatients were recruited for this study. Obese patients were divided into a weight maintenance group and weight reduction group. During the study period, patient information was collected that included measured body mass index (BMI), Eczema Area and Severity Index (EASI), and visual analogue scale for pruritus. Adiponectin, leptin, eosinophil count, and total immunoglobulin E were also tested. Results: In the weight reduction group, there was a significant improvement in the EASI score, however, no significant improvement was determined in the weight maintenance group. BMI and EASI showed positive correlation. The adiponectin level was lower in AD patients compared to healthy controls, and it was significantly lower in obese patients compared with normal weight patients. Serum levels of leptin were significantly different among control, obese patient group, and normal weight patient group. There was no statistically significant relationship between serum adipokine level and EASI. Conclusion: In our study, weight reduction was associated with significant improvement of AD symptoms. Related adipokine levels were significantly different among the control, normal weight AD patient group, and obese AD patient group. (Ann Dermatol 32(4) 319∼326, 2020)

Background: There has been a paucity of data about the difference in gene expression between melasma lesional skin and normal adjacent one. Objective: Our aim was to identify novel genes involved in the pathogenesis of melasma. Methods: We performed a microarray analysis and confirmed the results on quantitative real-time polymerase chain reaction (qRT-PCR) in Korean women with melasma. Results: There were 334 genes whose degree of expression showed a significant difference between melasma lesional skin and normal adjacent one. Of these, five were confirmed on qRT-PCR. In melasma lesional skin, there were down-regulation of genes involved in the PPAR signaling pathway and up-regulation of genes involved in neuronal component and the functions of stratum corneum barrier. Conclusion: This result suggests that the pathogenesis of melasma might be associated with novel genes involved in the above signaling pathway in Korean women.

A eutectic mixture of lidocaine and prilocaine (EMLA) is used topically to provide local anesthesia for a variety of painful superficial procedures. Although the side effects of EMLA are usually mild and transient local reactions, potentially life-threatening complications can occur. We report a case of generalized seizures and methemoglobinemia after topical application of EMLA for curettage of molluscum contagiosum lesions in a 3.5-year-old girl with atopic dermatitis.

Cowden’s disease is a rare autosomal dominant, multiple hamartoma syndrome with characteristic mucocutaneous lesions. It is associated with abnormalities of the breast, thyroid, and gastrointestinal tract; and is characterized by multiple hamartomas in the gastrointestinal tract and mucocutaneous lesions such as trichilemmomas, oral papillomatosis, facial papules, and acral keratosis. A 21-year-old male patient presented with erythematous facial papules, oral mucosal papillomatosis, and punctate palmoplantar hyperkeratosis indicating a definite case of Cowden’s disease. This disease derives from variable expression resulting from a mutation in the PTEN gene. Gastrointestinal endoscopy and colonoscopy revealed multiple hamartomas in the stomach and colon. On thyroid ultrasonography, several probable benign nodules were noted in the right thyroid gland. He had no pertinent family history and no other systemic findings. Further regular laboratory and image studies will be planned for our patient, as well as his family members. Sporadic Cowden’s disease is rarely observed. Herein, we report a case of Cowden’s disease without known family history. Dermatologists should be aware of the possibility of Cowden syndrome based on its several dermatologic findings. (Ann Dermatol 31(3) 325∼330, 2019)

The treatment of Riehl's melanosis is difficult and challenging. Recently, a low-fluence 1064-nm quality (Q)-switched neodymium: yttrium-aluminum-garnet (Nd: YAG) laser method, referred to as ‘laser toning’, has been used in the treatment of melasma in Asian countries. We present here a series of cases of Riehl's melanosis that were treated effectively with a novel Q-switched Nd: YAG laser that was operated as a dual-pulse at half-fluence and 140-μs intervals.

Background: In adult patients with chronic urticaria (CU), the prevalence of food allergy is low compared to childhood patients. However, there are many patients who report food-related aggravation of CU, and some of them may have histamine intolerance. Objective: The aim of this study was to evaluate the role of ingested histamine and to investigate the effect of a histamine-free diet in adult patients with CU. Methods: Twenty-two adult patients with CU were enrolled. Foods with high amounts of histamine were prohibited to all patients for four weeks. The degree of severity of the urticaria was evaluated using the urticaria severity score (USS) and urticaria activity score (UAS). Plasma histamine levels and diamine oxidase (DAO) activity were determined and compared before (baseline) and after the histamine-free diet. Results: Twenty-two adult patients were recruited and completed four weeks of histamine-free diet. The USS and UAS scores each showed significant differences before and after the histamine-free diet (p=0.010, p=0.006). There was a significant reduction in plasma histamine level after the histamine free-diet, compared with baseline (p=0.010). However, DAO activity did not change after the histamine-free diet (p=0.165). Conclusion: Our study suggested that ingested histamine might be related to CU severity and that a histamine-free diet is helpful for treatment of adult patients with CU. (Ann Dermatol 30(2) 164∼172, 2018)

Background: Atopic dermatitis (AD) is related to a deficiency of delta-6-desaturase, an enzyme responsible for converting linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) as a source of GLA has been of interest in the management of AD. Objective: The aim of this randomized, double-blinded, placebo-controlled clinical study is to evaluate the efficacy and safety of EPO in Korean patients with AD. Methods: Fifty mild AD patients with an Eczema Area Severity Index (EASI) score of 10 or less were enrolled and randomly divided into two groups. The first group received an oval unmarked capsule containing 450 mg of EPO (40 mg of GLA) per capsule, while placebo capsules identical in appearance and containing 450 mg of soybean oil were given to the other group. Treatment continued for a period of four months. EASI scores, transepidermal water loss (TEWL), and skin hydration were evaluated in all the AD patients at the baseline, and in months 1, 2, 3, and 4 of the study. Results: At the end of month 4, the patients of the EPO group showed a significant improvement in the EASI score (p=0.040), whereas the patients of the placebo group did not. There was a significant difference in the EASI score between the EPO and placebo groups (p=0.010). Although not statistically significant, the TEWL and skin hydration also slightly improved in the EPO patients group. Conclusion: We suggest that EPO is a safe and effective medicine for Korean patients with mild AD. (Ann Dermatol 30(4) 409∼416, 2018)

Tacrolimus, a calcineurin inhibitor, formerly also known as FK506, is a macrolactam drug isolated from Streptomyces tsukubaensis. Its mode of action closely parallels the action of cyclosprorin A (CsA) and can be used for the treatment of inflammatory and autoimmune skin diseases in which systemic CsA has proved effective against psoriasis, pyoderma gangrenosum, atopic dermatitis, lupus erythematosus and graft versus host disease (GVHD). Although several cases of epidermal cysts have been reported in patients using cyclosporine and other immunosuppressants after organ transplantation; such types of cases have yet not been reported after administration of tacrolimus. However, we report herein a case of presence of multiple, various sized epidermal cysts in a renal transplant recipient receiving tacrolimus.

Subepidermal calcified nodule is an uncommon form of calcinosis cutis, which most commonly occurs in children. It usually presents as an asymptomatic, solitary verrucous nodule on the head and neck region, but occasionally as multiple lesions. Serum calcium and phosphorus levels are usually normal. Histopathology shows well-formed homogeneous eosinophilic material and granules in the upper dermis. Material in the dermis stained with von Kossa was positive. We report on an unusual case of a subepidermal calcified nodule occurring on the sole. A 21-month-old male presented with an oval-shaped, whitish, hard nodule measuring 5×5 mm on the left sole, without any previous history of trauma.

Cutaneous squamous cell carcinoma (SCC) is a very common resectable cancer; however, cutaneous SCC is highly resistant to chemotherapy if metastasis develops. Activating transcription factor 3 (ATF3) has been suggested as a marker of advanced or metastatic cutaneous SCC. Autophagy is one of the most important mechanisms in cancer biology and commonly induced by in vitro serum starvation. To investigate the role of autophagy activation in cutaneous SCC, we activated autophagic pathways by serum starvation in SCC13 and ATF3-overexpressing SCC13 (ATF3-SCC13) cell lines. ATF3-SCC13 cells demonstrated high proliferative capacity and low p53 and autophagy levels in comparison with control SCC13 cells under basal conditions. Intriguingly, autophagic stimulation via serum starvation resulted in growth inhibition and senescence in both cells, while ATF3-SCC13 cells further demonstrated growth inhibition and senescence. Apoptosis was not significantly induced by autophagy activation. Taken together, autophagy activation may be a promising antitumor approach for advanced cutaneous SCC.

Polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are major environmental pollutants, and their effects on the human body critically depend on the aryl hydrocarbon receptor (AhR). The aim of this study was to evaluate the significance of the AhR and its ligands in chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Expression of AhR-related mRNA was increased in lesional skin from patients with AD and psoriasis compared to those of normal skin from healthy controls. The AhR and aryl hydrocarbon receptor nuclear translocator were colocalized in the nuclei of keratinocytes at the lower epidermis of psoriatic lesions, which suggested activation of the AhR pathway. After treatment of normal human epidermal keratinocytes with TCDD or PCBs, IL-6 and IL-8 production were increased. The results of this study suggest that AhR is highly expressed in the acute lesional skin of patients with AD and psoriasis, and the AhR pathway is activated especially in psoriasis.

Background The Atopic Dermatitis Antecubital Severity (ADAS) score is a new objective scale for the assessment of the severity of atopic dermatitis (AD). It is calculated by multiplying the intensity of inflammatory signs by the size of an antecubital eczema lesion. Aim To test the validity, reliability, and sensitivity to changes of the ADAS score compared with those of the Eczema Area and Severity Index (EASI) score. Methods Forty patients with AD were enrolled and treated with a moisturizer. At baseline, and in weeks 1 and 2, two independent evaluators measured the ADAS score, the EASI score, and the investigator's global assessment score rated on a six-point scale. Results The ADAS score showed a higher validity than the EASI score. The superiority of the ADAS to the EASI was prominent in mild AD. Inter-evaluator reliability was excellent in both the ADAS score and the EASI. The sensitivity to changes was higher in the ADAS score than in the EASI score. Conclusions The ADAS score may be used as a simple scoring system with good validity, reliability, and sensitivity to changes, especially in patients with mild-to-moderate AD.

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into "non-inflammatory" and "inflammatory" groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri-lesional skin of ten cases in the non-inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68(+) melanophages, CD117(+) mast cells, and LCA(+) leukocytes in the inflammatory group than in the non-inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.

Background Atopic dermatitis (AD) is characterized by itching and eczema-like skin lesions, and its symptoms alleviate with age. Recently, the prevalence of AD has increased among adolescents and adults. The increasing prevalence of AD seems to be related to westernized lifestyles and dietary patterns. Objective The aim of this study was to evaluate the dietary patterns and nutrient intake of patients with AD. Methods The study population consisted of 50 children with AD who visited the Department of Dermatology at Kangnam Sacred Heart Hospital, Seoul, Korea from May 2008 to May 2009. Physical condition and calorie intake were evaluated using the Eczema Area and Severity Index score and Food Record Questionnaire completed by the subjects, and the data were analyzed using the Nutritional Assessment Program Can-pro 3.0 (The Korean Nutrition Society, 2005) program to determine the gap between the actual ingestion and average requirements of 3 major nutrients (i.e. carbohydrates, proteins, and lipids), vitamins (i.e. A, B, C, and E), niacin, folic acid, calcium, iron, phosphorus, and zinc in all subjects. Results The intake rate of proteins was 18.02% (recommended dietary allowance [RDA], 7%~20%), of carbohydrates was 67.7% (RDA, 55%~70%), and of lipids was 14.24% (RDA, 15%~30%). Thirty-one subjects (62%) showed deficiency of folic acid, and 21 subjects (42%), of iron supplements. Conclusion Essential nutrient intake tends to be lower in AD patients than in healthy subjects, and this low intake is closely related to the severity of AD.

Background: It is well known that atopic dermatitis (AD) is related to food hypersensitivity, although its prevalence varies among several studies according to age group, severity, country, survey time, and test method. Objective: To examine the prevalence and status of food hypersensitivity among childhood AD patients in Korea. Methods: A total of 95 patients were enrolled in the study. The history of food hypersensitivity was collected by interviews. The severity of AD was evaluated by eczema area and severity index (EASI). We took blood samples to measure serum total and food-specific immunoglobulin E (IgE) levels. Based on the histories and serum IgE levels, open oral food challenge (OFC) testing was performed to confirm food hypersensitivity. Results: Forty- two (44.2%) of the 95 AD patients had histories of food hypersensitivity. They reported that the most common suspicious foods were egg (n=13, 13.7%), pork (n=9, 9.5%) and cow milk (n=8, 8.4%). The mean EASI score was 16.05±9.76. Thirty-nine (41.1%) of the 95 patients showed elevated serum food-specific IgE levels. The specific IgE levels were elevated for egg (n=17, 17.9%), milk (n=12, 12.6%), peanut (n=10, 10.5%) and wheat (n=8, 8.4%). Fifty-one (53.8%) of 95 patients underwent open OFC, and only 7 (13.7%) of these patients showed positive reactions. Conclusion: The overall prevalence of food hypersensitivity in patients with childhood AD in Korea was 8.3% (7/84). The most common foods causing food hypersensitivity were egg and milk. Among the foods causing hypersensitivity, AD patients in Korea often underestimated peanut, while they overestimated pork. (Ann Dermatol 25(2) 196∼202, 2013)

Background: Recent epidemiologic studies have shown that environmental contaminants such as air pollution and tobacco smoke play an important role in the pathophysiology of atopic dermatitis (AD). Objective: The aim of this study was to evaluate the relationship between the severity of AD and indoor air pollution. Methods: The study population consisted of 425 children from 9 kindergartens, Korea. The authors surveyed the prevalence of AD and evaluated disease severity by the eczema area and severity index (EASI) score and investigator’s global assessment (IGA). After measuring indoor air pollution, a program to improve indoor air quality was conducted in 9 kindergartens. Seven months later, the prevalence and disease severity were evaluated. Results: The initial prevalence of AD was 8% and the mean EASI score was 2.37. The levels of particulate material 10 (PM10) and carbon dioxide (CO2) were higher in some kindergartens compared to the normal values. Subsequent to the completion of the indoor air quality improvement program, the mean PM10 level was significantly decreased from 182.7 to 73.4 μg/m 3 . After the completion of the program, the prevalence of AD and the mean EASI were decreased, and the changes were both statistically significant. The mean number of hospital visits decreased from 1.3 per month during the first survey to 0.7 per month during the second survey, which was statistically significant. Conclusion: Indoor air pollution could be related to AD. The reduction of PM10 through improving indoor air quality should be considered in kindergartens and schools in order to prevent and relieve AD in children. (Ann Dermatol 25(3) 292∼297, 2013)

Dear Editor: Congenital melanocytic nevus (CMN) is a melanocytic nevus that is either present at birth or appears during the latter stages of infancy1. Nevus sebaceous has been described as the hamartomatous locus of an embryologically defective pilosebaceous unit2. Here, we describe how we used the pinhole technique with an erbium-doped yttrium aluminium garnet (erbium : YAG) laser to treat nevi lesions in different patients. A 25-year-old male was diagnosed with CMN on his nose at birth (Fig. 1A). Emla cream (AstraZeneca AB, Sodertalje, Sweden) was applied to the treatment area prior to starting the procedure. The erbium : YAG laser (Action Er : YAG; Lutronic Corporation, Goyang, Korea) was used in continuous-wave mode, with 1-mm spot size and output power of 0.2 mJ/cm2. Multiple small holes measuring 1 mm in diameter were made on the periphery of the CMN lesion. A hydrocolloid dressing (DuoDERM Extra Thin CGF dressing; ConvaTec, ER Squibb & Sons, Princeton, NJ, USA) was applied to the lesions for ≥2 weeks after treatment. After performing 5 laser sessions at 4-week intervals, the cutaneous lesions resolved. There was no evidence of recurrence at the 1-year follow-up examination (Fig. 1B). Fig. 1 Congenital melanocytic nevus (CMN) in a 25-year-old man. (A) Before treatment: a solitary, 1-cm brown patch is visible on the right alar area of the nose. (B) One year after the final treatment session, the skin lesions resolved with minimal scarring. ... A 5-month-old infant was referred to our outpatient unit for CMN on the forearm (Fig. 1C). We performed the pinhole method of treatment using the erbium : YAG laser (Lutronic) in continuous-wave mode, with 1-mm spot size and output power of 0.2 mJ/cm2 (Fig. 1D). After receiving 6 treatment sessions at 2-month intervals, slight superficial pigmentation persisted (Fig. 1E). A 40-year-old woman presented with nevus sebaceous lesions on the right side of her forehead (Fig. 2A). We performed the pinhole method of treatment using the erbium : YAG laser (Lutronic) in continuous-wave mode, with 1-mm spot size and output power of 0.2 mJ/cm2. After receiving 5 treatment sessions at 4-week intervals, the patient showed marked improvement with only mild hypopigmentation (Fig. 2B). No recurrence was noted at the 6-month follow-up examination (Fig. 2C). Fig. 2 Nevus sebaceous lesions in a 40-year-old woman. (A) Before treatment, two 2.5-cm, well-demarcated, yellow, verrucous plaques were visible on the right side of the forehead. (B) Deep line- and doughnut-shaped holes were created to remove the nevus sebaceus ... Herein, we described how nevi lesions were effectively treated using the pinhole method. This simple method involves making multiple small holes at 2~5-mm intervals using a CO2 laser that penetrates the epidermis and deeper dermis3. The holes produced using the pinhole method are surrounded by untreated areas that promote rapid epidermal repair, thereby reducing the downtime and likelihood of side effects4. The other advantages of performing the pinhole method with ablative lasers are that this laser is easy to use and inexpensive, as ablative lasers are usually available in most dermatology clinics. To the best of our knowledge, this is the first report on the application of the pinhole method for the treatment of CMN and nevus sebaceous, so it is difficult to compare the advantages and disadvantages of the pinhole method with those of conventional treatment methods. Therefore, it is necessary to conduct further studies with a large sample to confirm the effectiveness and safety of the pinhole method. In conclusion, we suggest using the pinhole method with erbium : YAG laser as an alternative therapy for treating nevi lesions.

Background: Previous clinical trials with evening primrose oil in atopic dermatitis (AD) treatment have shown different results. In addition, the optimal dose and duration of treatment with evening primrose oil have not yet been determined. Objective: The aim of this study is to investigate the dose-response treatment effects of evening primrose oil on clinical symptoms of AD and serum concentrations of polyunsaturated fatty acids. Methods: Forty AD patients were enrolled for the study and randomly divided into 2 groups: those who received evening primrose oil 160 mg daily for 8 weeks and those who received 320 mg of evening primrose oil twice daily for 8 weeks. We evaluated the Eczema Area Severity Index (EASI) scores of all AD patients at weeks 0, 2, 4 and 8. In addition, we measured the levels of serum fatty acids, including C16 : 0 (palmitic), C18 : 2n (linoleic), C18 : 3n (linolenic) and C20 : 4 (arachidonic acid) using gas chromatography. Results: The serum fatty acid levels C18 : 3n and C20 : 4 were higher in the 320 mg group than in the 160 mg group, with statistical significance. After evening primrose oil treatment, EASI scores were reduced in the 2 groups. The improvement in EASI scores was greater in the 320 mg group than in the 160 mg group. There were no side effects seen in either group during the study in the 2 groups. Conclusion: The results of this study suggest that the 320 mg and 160 mg groups may be equally effective in treating AD patients and show dose-dependent effects on serum fatty acid levels and EASI scores. (Ann Dermatol 25(3) 285∼291, 2013)

Melanoma with rhabdoid features is an uncommon variant of malignant melanoma. Here, we describe a rare case of primary rhabdoid malignant melanoma. A 54-year-old man presented with a black tumor measuring 3×4 cm on the right forearm. Histologic sections showed a tumor mass with rhabdoid features composed entirely of polygonal neoplastic cells with eccentric nuclei, prominent nucleoli, and large hyaline cytoplasmic inclusions. The tumor cells were immunoreactive with HMB-45, S100, Fontana-Masson silver and vimentin, and negative for smooth muscle actin, CD68, CD34, CD99, synaptophysin, desmin, and PAS. The differential diagnosis for this tumor included malignant peripheral nerve sheath tumor, malignant peripheral neuroectodermal tumor and rhabdomyosarcoma. The patient was treated with a wide excision and a local skin graft. The excised tumor was entirely composed of rhabdoid tumor cells. No recurrence or metastasis was evident 4 months after removal. This article is relevant to rare cases of primary malignant melanomas showing rhabdoid tumor cells over the entire excised lesion.

Atopic dermatitis (AD) has numerous trigger factors. The question of whether foods can aggravate AD remains open to debate. Although a number of published papers have detailed the relationship between food allergies and AD, little research has examined the question of how food intolerance affects AD. For the purposes of this study, a six-year-old Korean boy with AD was admitted to the hospital for evaluation of the possibility of food, particularly pork, as a triggering factor in his skin disease. He had a history of worsening of symptoms when eating pork. Total serum IgE concentration was 157 IU/ml. House dust was class 2.2 (1.5 IU/ml) in MAST. All other MAST items were negative. In an oral food challenge test, he showed a positive result after eating 200 g of pork, but did not show a positive result after eating 60 g of pork. After discharge, we attempted to keep him on a balanced diet that included various types of food and prohibited him from eating food that contains a high level of histamine. After keeping the patient on a balanced and low-histamine dietary regimen, his AD symptoms showed improvement and have not worsened for more than seven months. A low-histamine, balanced diet could be helpful for AD patients having symptoms that resemble histamine intolerance in which their AD symptoms worsened after intake of histamine-rich foods, but in which food allergy tests are negative.

Background: Atopic dermatitis (AD) is frequently associated with food allergies. In addition to the skin prick test (SPT) and serum-specific IgE, the atopy patch test (APT) has been introduced as a diagnostic procedure for food allergies. Objective: Our aim was to evaluate the diagnostic value of the APT, the SPT and the serum-specific IgE levels compared with that of oral food challenge test against milk and egg in AD patients. Methods: We conducted the SPT and APT, and determined the serum-specific IgE levels against milk and egg antigens for 101 patients. Oral food challenge tests were conducted for 86 out of 101 AD patients. The sensitivity, specificity and positive and negative predictable values were calculated for all the tests. Results: Twenty-five patients were positive to oral food challenges. The sensitivity of the APT for milk was 66.7%, while the figures for the SPT and the serum-specific IgE were 35.5% and 14.2%. The sensitivity of the APT for egg was 50%, while that for the SPT and serum-specific IgE were 21.4% and 6.7%. Conclusion: We were able to conclude that the APT test seems to be a valuable additional tool for the diagnostic method of food