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Background In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Particulate matter (PM2.5) is an environmental pollutant causing skin inflammatory diseases via epidermal barrier damage. However, the mechanism and related gene expression induced by PM2.5 remains unclear. Our aim was to determine the effect of PM2.5 on human skin tissue ex vivo, and elucidate the mechanism of T helper 17 cell-related inflammatory cytokine and skin barrier function. We verified the expression levels of gene in PM2.5-treated human skin tissue using Quantseq (3' mRNA-Seq), and Gene Ontology (GO) terms and protein-protein interaction (PPI) networks were performed. The PM2.5 treatment significantly enhanced the expression of Th 1, 2, 17 and 22 cell-related genes (cut-off value: │1.2 │ fold change and p 0.05). Most of all, Th17 cell-related genes are upregulated and those genes are associated with skin epidermal barrier function and Aryl hydrocarbon receptor (AhR), a xenobiotic receptor, pathway. In human keratinocyte cell lines, AhR-regulated genes (e.g. AhRR, CYP1A1, IL6 and IL36G), Th17 cell-related genes (e.g. IL17C) and epidermal barrier-related genes (e.g. SPRR2A and KRT71) are significantly increased after PM2.5. In the protein level, the secretion of IL-6 and IL-36G was increased in human skin tissue following PM2.5 treatment, and the expression of SPRR2A and KRT71 was significantly increased. PM2.5 exposure could ruin the skin epidermal barrier function via AhR- and Th17 cell-related inflammatory pathway.

Lysophosphatidylcholine (LPC) is a bioactive lysolipid known to contribute to the development of lung allergic diseases. However, it remains unknown whether LPC possesses proinflammatory properties in the skin as well. Here, we investigated this issue by injection of LPC into the murine contact hypersensitivity (CHS) model induced by 2,4-dinitrofluorobenzene (DNFB). LPC increased the expression of IL17, recruited more neutrophils, and eventually aggravated the CHS in the skins. Moreover, the effects of LPC diminished after neutralizing IL17 or depleting neutrophils. Mechanistically, LPC upregulated not only IL17 but also CXCL1 and CXCL2 in a G2A-dependent manner. Taken together, our study demonstrated that the upregulation of LPC could contribute to allergic skin inflammation by increasing IL17 expression and neutrophil recruitment via G2A receptor. [BMB Reports 2021; 54(4): 203-208].

Hye Ran Kim, Hye One Kim, Jin Cheol Kim, Chun Wook Park, Bo Young Chung Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, Republic of KoreaCorrespondence: Bo Young Chung, Department of Dermatology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, Republic of Korea, Tel +82-2-829-9092, Fax +82-2-832-3237, Email victoryby777@gmail.comObjective: Psoriasis is a chronic inflammatory skin disorder associated with impairment of epidermal differentiation. Many signaling pathways, including those involved in aryl hydrocarbon receptor (AHR) and autophagy dysfunction, are reportedly associated with the pathogenesis of psoriasis. However, the discrete effects of dioxin via AHR activation or autophagy on the epidermal barrier remain unclear. In the current study, we evaluated the effects of autophagy modulators (chloroquine [CQ] and rapamycin) and the AHR agonist TCDD on the expression of epidermal barrier proteins in psoriasis-like keratinocytes and psoriasis lesional skin tissue culture.Methods: Polycytokine-stimulated human keratinocytes and psoriasis skin biopsies were treated with TCDD, CQ, or rapamycin, and the expression of keratinocyte differentiation-related factors, such as S100A7, S100A8, HRNR, IVL, FLG, and KRT10, was examined by Western blotting or quantitative-polymerase chain reaction.Results: TCDD upregulated S100A7 and S100A8 expression in polycytokine-stimulated HaCaT cells compared to that in unstimulated cells. CQ decreased HRNR, IVL, and KRT10 mRNA levels, while rapamycin increased HRNR, IVL, and KRT10 mRNA levels in HaCaT cells relative to that in unstimulated cells. Co-treatment with CQ reversed TCDD-induced elevation in FLG, HRNR, and IVL mRNA expression. In psoriasis skin tissue, TCDD induced the upregulation of HRNR, IVL, S100A7, and S100A8 compared with that in normal skin. In ex vivo cultures treated with CQ, IVL expression in psoriasis skin tissue was repressed compared to that in normal skin tissue.Conclusion: Our data suggest that autophagy modulation or AHR activation affects processes involved in epidermal differentiation and relates to the pathogenesis of chronic inflammatory skin diseases with skin barrier abnormalities such as psoriasis.Keywords: aryl hydrocarbon receptor, autophagy, keratinocyte differentiation, 2,3,7,8-tetrachlorodibenzo-p-dioxin, chloroquine

Background: Atopic dermatitis (AD) is an inflammatory skin disease of multiple phenotypes and endotypes, and is highly prevalent in children. Many people of all ages, including active adolescents, pregnant women, and the elderly, suffer from AD, experiencing chronicity, flares, and unexpected relapse. Dexpanthenol has multiple pharmacological effects and has been employed to treat various skin disorders such as AD. We aimed to summarize the up-to-date evidence relating to dexpanthenol and to provide a consensus on how to use dexpanthenol effectively for the treatment of AD. Methods: The evidence to date on the application and efficacy of dexpanthenol in AD was reviewed. The literature search focused on dexpanthenol use and the improvement of skin barrier function, the prevention of acute flares, and its topical corticosteroid (TCS) sparing effects. Evidence and recommendations for special groups such as pregnant women, and the effects of dexpanthenol and emollient plus in maintenance therapy, were also summarized. Results: Dexpanthenol is effective and well-tolerated for the treatment of AD. Dexpanthenol improves skin barrier function, reduces acute and frequent flares, has a significant TCS sparing effect, and enhances wound healing for skin lesions. Conclusion: This review article provides helpful advice for clinicians and patients on the proper maintenance treatment of AD. Dexpanthenol, as an active ingredient in ointments or emollients, is suitable for the treatment and maintenance of AD. This paper will guide dermatologists and clinicians to consider dexpanthenol as a treatment option for mild to moderate AD.

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.

Background Several tools can provide a reliable and accurate evaluation of pruritus, including the visual analog scale (VAS), numeric rating scale (NRS), verbal rating scale (VRS), and multidimensional questionnaires such as the Itch Severity Scale (ISS). However, no single method is considered a gold standard. Objective We evaluated the validity and reliability of VAS, NRS, VRS, and ISS and their correlation with a pruritus-specific quality of life instrument, ItchyQoL. Methods A total of 419 patients (215 men and 204 women) with chronic pruritus (mean age, 46.58 years) recorded their pruritus intensity on VAS, NRS, VRS, and ISS. Retest reliability was analyzed in a second assessment 3 hours after the initial assessment. All participants answered ItchyQoL. Results A strong correlation between VAS, NRS, and VRS was found. ISS showed a low intercorrelation validity with these tools. However, ISS was more strongly correlated with ItchyQoL. The retest reliability scores were similar for VAS, NRS, and VRS but lower than the scores obtained for ISS. Limitations Limitations include patient heterogeneity and recall bias. Conclusion The assessment of pruritus is challenging because of the subjective symptoms and the multifactorial nature. Therefore, more studies are needed to determine the best strategy to assess itch intensity.

Rosacea is a chronic inflammatory skin disease with a multifactorial etiology. Recently, associations between serum homocysteine (Hcy) levels and inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa, have been reported. However, no study has explored the levels of serum Hcy, folic acid, and vitamin BTo investigate serum Hcy, vitamin BThis case-control study included 138 PPR patients and 58 healthy controls. The serum levels of Hcy, vitamin BSerum vitamin BOur results suggest a possible association between hyperhomocysteinemia and vitamin B

Itching is an unpleasant sensation that provokes the desire to scratch. In general, itching is caused by dermatologic diseases, but it can also be caused by systemic diseases. Since itching hampers patients’ quality of life, it is important to understand the appropriate treatment and pathophysiology of pruritus caused by systemic diseases to improve the quality of life. Mechanisms are being studied through animal or human studies, and various treatments are being tested through clinical trials. We report current trends of two major systemic diseases: chronic kidney disease and cholestatic liver disease. This review summarizes the causes and pathophysiology of systemic diseases with pruritus and appropriate treatments. This article will contribute to patients’ quality of life. Further research will help understand the mechanisms and develop new strategies in the future.

With the expansion of the COVID‐19 vaccination drive, an increasing number of adverse effects are surfacing. A 74‐year‐old woman presented with multiple erythematous and itchy patches on several sites. She had no relevant medical history, apart from the first AZD1222 vaccination 1 month previously. Microscopically, epidermal changes, including mild spongiosis and parakeratosis, were observed. Tight perivascular lymphocytic infiltration (coat‐sleeve pattern) was also observed in the dermis. The final diagnosis was erythema annulare centrifugum (EAC) induced by SARS‐CoV‐2 vaccination. Based on this report, dermatologists should be aware of the possibility of EAC from the AZD1222 vaccination.

Various methods have been used for scar prevention; however, the optimal method remains unclear. We investigated the efficacy of combinational intense pulsed light (IPL)/fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment in early wound healing. This was a prospective, randomized, controlled split wound trial. Scars were divided into three sites: the combined IPL/fractional Er:YAG treatment, fractional Er:YAG laser treatment, and untreated control sites. Treatment was conducted in three sessions: at removal of stitches and after 4 and 8 weeks. Treatment efficacy was evaluated using the Patient Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS) scores. The erythema index (EI) and melanin index (MI) were measured. In the total POSAS score, the IPL/fractional Er:YAG site showed steady and significant improvement, in contrast to the other sites. At week 8, the combined treatment sites had better POSAS scores than the fractional Er:YAG laser alone sites (p = 0.001) and the control sites (p = 0.000). The effect of combinational treatment was maintained until the follow-up period by comparing the Er:YAG (p = 0.015) and control sites (p = 0.007). In terms of VSS scores, the IPL/fractional Er:YAG combined treatment sites had consistent improvement at week 8 (p = 0.005) and week 20 (p = 0.02) compared to that at week 4, while the other sites showed no such improvement. In conclusion, the combination of IPL and Er:YAG showed more favorable effects on scar prevention than Er:YAG or no treatment. IPL/Er:YAG therapy could be an effective and safe strategy in the early wound healing process for reducing scar formation.

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.

Darier disease is an autosomal dominant disorder with dark crusty patches and is classified as hereditary acantholytic dermatosis. Keratotic papules and crust are often present on the scalp, forehead, chest, back, upper arms, elbows, groin, and behind the ears, predominantly in seborrheic areas. A 48-year-old male patient presented skin lesions with pruritus on the trunk and both upper and lower extremities. He first noticed the lesion 15 years before. On physical examination, there were multiple erythematous papules with crust on the trunk and red-brown colored keratotic plaque on both extremities. The suspected histopathological diagnosis was psoriasis vulgaris. The patient’s skin lesions and pruritus were significantly improved after the psoriasis treatment. While continuing psoriasis treatment, the patient showed sudden worsening of the skin lesions on the scalp, abdomen, and fingernails (V-shaped nicks) with pruritus. Punch biopsy was performed on the abdominal lesion again and the final diagnosis was Darier disease. The patient was then treated using alitretinoin while maintaining the use of guselkumab for psoriasis. There are only a few cases that we found in which patients with Darier disease also had psoriasis. We report this rare case of Darier disease with psoriasis and propose that an additional biopsy might be necessary for accurate diagnosis and proper treatment.

As interest in skin increases, the cosmetic market is also growing. It is difficult to choose between the numerous types of basic cosmetics on the market. This article aims to provide advice and guidance on which products to recommend according to a patient’s skin condition. Appropriate application of a moisturizer attempts not only to improve the dryness, but also improve the skin’s natural barrier function to protect the skin from internal and external irritants to keep the skin healthy. Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants, lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to provide readers with the background they need to choose the right moisturizer for themselves. As moisturizers play an important role as adjuvant in the treatment of common skin diseases, such as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be recommended in consideration of the ingredients, effectiveness and safety of each product, and the skin condition of each patient.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported. AIM: To assess the clinical features of mask-induced dermatoses and to recommend prevention and treatment options. METHODS: From April to August 2020, questionnaires including topics such as demographic information, pre-existing skin disorders, reported mask-related symptoms, daily mask-wearing duration and frequency, types of masks used and whether the participant was a healthcare worker, were distributed to patients in 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis and recorded treatments. RESULTS: Itchiness was the most frequent symptom, mostly affecting the cheeks. The most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and worsening of pre-existing acne (16.97%). Daily wearing of masks was significantly (P = 0.02) associated with new-onset contact dermatitis. More than half of patients with pre-existing skin problems experienced disease worsening while wearing masks. Longer duration of wearing (> 6 h/day, P = 0.04) and use of cotton masks (P

The aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, is important for xenobiotic metabolism and binds to various endogenous and exogenous ligands present in the skin. AhR is known to be associated with diseases in various organs; however, its functions in chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis (PS), have recently been elucidated. Here, we discuss the molecular mechanisms of AhR related to chronic inflammatory skin diseases, such as AD and PS, and the mechanisms of action of AhR on the skin immune system. The importance of AhR molecular biological pathways, clinical features in animal models, and AhR ligands in skin diseases need to be investigated. In conclusion, the therapeutic effects of AhR ligands are demonstrated based on the relationship between AhR and skin diseases. Nevertheless, further studies are required to elucidate the detailed roles of AhR in chronic inflammatory skin diseases.

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.

Background: Hand eczema refers to eczema located on the hands, regardless of its etiology or morphology. Despite its high prevalence and significant impact on patients’ quality of life, treatment is frequently challenging because of its heterogeneity, chronic and recurrent course, and lack of well-organized randomized controlled trials of the various treatment options. Objective: These consensus guidelines aim to provide evidence-based recommendations on the diagnosis and management of hand eczema to improve patient care by helping physicians make more efficient and transparent decisions. Methods: A modified Delphi method, comprising two rounds of email questionnaires with face-to-face meetings in between, was adopted for the consensus process that took place between February and September 2020. Forty experts in the field of skin allergy and contact dermatitis were invited to participate in the expert panel. Results: Consensus was reached for the domains of classification, diagnostic evaluation, and treatment; and a therapeutic ladder to manage chronic hand eczema was developed. Conclusion: These are the first consensus guidelines for chronic hand eczema in the Asian population, which will help standardize care and assist clinical decision-making in the diagnosis and treatment of chronic hand eczema. (Ann Dermatol 33(4) 351∼ 360, 2021)

Background and objectives: Postburn pruritus is a common complication of scars in burn patients. In our previous study, we discovered increased expression of TRPV3, TRPV4, and TRPA1. Among them, TRPV3, in particular, is predominantly expressed in the epidermis of the tissue of pruritic burn scars. We sought to evaluate the correlation between the expression of TRPV3 activators and itching after application of TRPV3 activator carvacrol over burn scars. Materials and Methods: Design: This was a double-blind clinical trial with non-randomized distribution. Setting: This study was performed in a hospital setting. Patients or participants: Patients with itching of burn scars (numerical rating scale (NRS), &lt, 3, n = 8, Group 1 and NRS, &ge, n = 16, Group 2) and healthy volunteers (n = 18, Group 3) were included. Interventions: The investigational drug carvacrol (100%, 75%, and 50%) and control drug (10% ethanol) were applied over the scars using IQ Ultimate&trade, 1 &times, 1 cm chamber sheets. Main variables of interest: The presence of pruritus, erythema, edema, and other skin lesions was evaluated. The verbal NRS scores were also compared. Results: Carvacrol induced more itching in Group 2 than in Groups 1 and 3. In Group 2, 100%, 75%, and 50% carvacrol caused significantly more itching (NRS score, 5.18 &plusmn, 3.04, 5.18 &plusmn, 3.04, and 4.93 &plusmn, 2.96, respectively) than that in Group 1 (NRS score, 1.00 &plusmn, 1.80, 1.00 &plusmn, 1.80, and 1.00 &plusmn, 1.80, respectively) and Group 3 (NRS score, 2.38 &plusmn, 1.94, 1.27 &plusmn, 1.32, respectively). Conclusions: The TRPV3 activator carvacrol can cause itching if applied over burn scars. This study can help understand the mechanism and prognosis of post-burn itching and contribute to the development of its treatment.

Rosacea with severe neurological symptoms such as burning and stinging is often not treated effectively by conventional therapies. The aim of this study was to investigate the clinical characteristics of Korean rosacea patients with prominent neurological symptoms. The demographic features, medical history, clinical manifestations and treatment modalities of 17 neurogenic rosacea patients who had prominent neurological symptoms and 106 erythematotelangiectatic rosacea (ETR) patients as a control group were investigated. All 17 neurogenic rosacea patients had severe persistent erythema with burning/stinging sensation limited to both cheeks. Among these patients, 94.1% were female (16/17). Heat stimuli (58.8%, 10/17) and stress (52.9%, 9/17) were major aggravating factors. Fourteen of 17 patients (82.3%) improved after receiving anticonvulsants and antidepressants. In conclusion, rosacea patients with severe neurological symptoms show distinct clinical manifestations and should be classified separately, and a different therapeutic approach is necessary for them.

Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited.To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea.Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured.Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt.A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD.

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.

It is known that DNA hypomethylation of aryl hydrocarbon receptor repressor (AhRR), one of the epigenetic markers of environmental pollutants, causes skin diseases. However, the function and mechanisms are still unknown. We aimed to determine whether AhRR is hypomethylated in PBMC of psoriasis patients, as well as to examine the expression of psoriasis-related inflammatory cytokines and antimicrobial peptides after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in HaCaT cells overexpressing or silencing AhRR. AhRR was determined by qPCR, Western blot, immunohistochemistry, and immunocytochemistry in skin tissue and HaCaT cells. DNA methylation of AhRR was performed by Infinium Human Methylation450 BeadChip in PBMC of psoriasis patients and methylation-specific PCR (MSP) in HaCaT cells. NF-κB pp50 translocation and activity were performed by immunocytochemistry and luciferase reporter assay, respectively. We verified AhRR gene expression in the epidermis from psoriasis patients and healthy controls. AhRR hypomethylation in PBMC of psoriasis patients and pAhRR-HaCaT cells was confirmed. The expression level of AhRR was increased in both TCDD-treated HaCaT cells and pAhRR-HaCaT cells. NF-κB pp50 translocation and activity increased with TCDD. Our results showed that AhRR was hypomethylated and overexpressed in the lesional skin of patients with psoriasis, thereby increasing AhRR gene expression and regulating pro-inflammatory cytokines through the NF-κB signaling pathway in TCDD-treated HaCaT cells.

Itching is prevalent in children with skin disorders and associated with effects on their mood, quality of life, and social functioning. Surprisingly, there are no data on childhood prevalence of pruritus in the general population. The aim of this article is to explore the epidemiology, clinical manifestation, and treatment for itch (pruritus) in the pediatric population (from infancy to adolescence), and to be helpful to primary care physicians who assess and diagnose pediatric patients with itching. In this study, we searched for specific keywords using PubMed and MEDLINE (Ovid) and, then, refined the retrieved searches for each cause and treatment. As a result of reviewing the literature, atopic dermatitis was shown to be the most common cause of itching, especially during infancy and through preschool. Not only skin disorders but also systemic diseases, drugs, and postburn states can predispose an individual to itching in childhood. There are traditional and newly developed treatment modalities for itching in pediatric patients. However, because the pharmacokinetics and pharmacodynamics of childhood are different from those of adults, the medications for itching have to be applied carefully for these age groups. There are many areas to be elucidated regarding the prevalence and objective assessment of pruritus in pediatric patients. Moreover, the safety profiles of medications in the pediatric population need to be better understood. Further studies to investigate itching in childhood are warranted.

A comparison between responses to allergens based on the TRUE Test®(TT) and IQ® Chamber (IQC) in Europeans has been previously reported, however, no such study has been performed in Asians. To compare allergen responses using the TT and IQC (using the Korean standard series) in order to gather more information regarding the positive response rates for each allergen and the clinical value of IQC. Suspected contact dermatitis patients were enrolled and tested with 18 allergens using the TT and IQC. The test was performed in 214 patients. Simultaneous positive results for both tests were recorded in 242 cases (positive concordance rate: 66.7%). IQC yielded more positive results. Allergens with a high positive concordance rate were nickel sulphate (82.1%), thimerosal (78.6%), and p-phenylenediamine (73.3%). IQC mostly showed similar or higher positive rates than TT, with high concordance. We recommend the IQC method as a screening test in patients with suspected contact dermatitis. To compensate for possible false positive results, careful history taking and a different patch test should be performed when appropriate.

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.

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

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.