ABSTRACT
Uric acid produced by guanine deaminase (GDA) is involved in photoaging and hyperpigmentation. Reactive oxygen species (ROS) generated by uric acid plays a role in photoaging. However, the mechanism by which uric acid stimulates melanogenesis in GDA-overexpressing keratinocytes is unclear. Keratinocyte-derived paracrine factors have been identified as important mechanisms of ultraviolet-induced melanogenesis. Therefore, the role of paracrine melanogenic growth factors in GDA-induced hypermelanosis mediated by uric acid was examined. The relationships between ROS and these growth factors were examined.Primary cultured normal keratinocytes overexpressed with wild type or mutant GDA and those treated with xanthine or uric acid in the presence or absence of allopurinol, H2O2, or N-acetylcysteine (NAC) were used in this study. Intracellular and extracellular bFGF and SCF levels were increased in keratinocytes by wild type, but not by loss-of-function mutants of GDA overexpression. Culture supernatants from GDA-overexpressing keratinocytes stimulated melanogenesis, which was restored by anti-bFGF and anti-SCF antibodies. Allopurinol treatment reduced the expression levels of bFGF and SCF in both GDA-overexpressing and normal keratinocytes exposed to exogenous xanthine; the exogenous uric acid increased their expression levels. H2O2-stimulated tyrosinase expression and melanogenesis were restored by NAC pretreatment. However, H2O2 or NAC did not upregulate or downregulate bFGF or SCF, respectively. Overall, uric acid could be involved in melanogenesis induced by GDA overexpression in keratinocytes via bFGF and SCF upregulation not via ROS generation.
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Background@#Dapsone has been used for a long time to treat skin diseases. Although various drug-related side effects and adverse reactions to dapsone have been reported, most studies have addressed only one or two specific reactions to dapsone. @*Objective@#This study aimed to investigate the overall adverse reactions to dapsone in Koreans and their relationship with patient demographics. @*Methods@#A retrospective analysis was conducted by reviewing the electronic medical records from 2005 to 2020. The association between adverse drug reactions and dapsone use was assessed using the Naranjo scale. Correlations between variables and adverse reactions were analyzed using univariate and logistic regression analyses. @*Results@#The overall incidence of adverse drug reactions to dapsone was 7.7% (41 of 533 patients). The incidence was significantly higher in female than in male, and predictable adverse reactions were significantly higher (6.8%, 36 of 533 patients) than in unpredictable cases (0.9%, 5 of 533 patients). The most common adverse event was methemoglobinemia/anemia (3.0%, 16 of 533 patients), and the least common was hypersensitivity syndrome, which occurred in only one case (0.2%, 1 of 533 patients). With the exception of hypersensitivity syndrome, which is a severe drug-related side effects and adverse reactions, most patients recovered after drug discontinuation. @*Conclusion@#Dapsone can be used relatively safely for various chronic diseases if medical personnel are aware of its adverse reactions.
ABSTRACT
Oxidative stress-induced melanocyte apoptosis is linked to the immune system and plays a critical role in the pathogenesis of vitiligo. Aquaporin-3 (AQP3), which is downregulated in vitiligo keratinocytes, regulates intracellular H2O2 accumulation. However, the role of AQP3 in oxidative stress is uncertain in vitiligo. This study investigated the effect of downregulated AQP3 on oxidative stress in vitiligo using lesional and non-lesional skin specimen sets from vitiligo patients and primary cultured adult normal human epidermal keratinocytes, with or without downregulation and overexpression of AQP3 in the presence or absence of H2O2 treatment. The levels of nuclear factor E2-related factor 2 (NRF2) and/or its main target, NAD(P)H quinone dehydrogenase 1 (NQO-1), were lower in the lesional keratinocytes and cultured keratinocytes with AQP3 knockdown, but were increased in keratinocytes upon AQP3 overexpression. Ratios of NRF2 nuclear translocation and NQO-1 expression levels were further reduced in AQP3-knockdown keratinocytes following H2O2 treatment. The conditioned media from AQP3-knockdown keratinocytes treated with H2O2 contained higher concentrations of reactive oxygen species (ROS). Moreover, the number of viable melanocytes was reduced when the conditioned media were added to the culture media. Overall, AQP3 downregulation in the keratinocytes of patients with vitiligo can induce oxidative stress in neighboring melanocytes, leading to melanocyte death.
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Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.
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Background@#Differentiating between verruca plana (VP) and VP-like seborrheic keratosis (SK) is difficult and little research has been performed on the topic. @*Objective@#The aim of this study was to elucidate clinical differences between these two diseases. @*Methods@#We conducted a retrospective review of cases of VP and VP-like SK identified by biopsy. Demographics (age and gender) and clinical information (location, color, distribution, and shape) were collected. @*Results@#A total of 224 cases were identified. Thirty-nine cases were finally diagnosed with VP (17.4%) and 159 cases with VP-like SK (71.0%). The rest of the diagnoses accounted for 26 cases. On multivariate analysis, extremities (odds ratio [OR] 7.91, confidence interval [CI] 2.61∼23.93), flesh color (OR 3.69, CI 1.43∼9.49), erythematous color (OR 36.83, CI 7.50∼180.84), and clustered distribution (OR 4.73, CI 1.66∼13.46) were significantly associated with VP. Shape is not predictive in VP occurence. @*Conclusion@#We provide clinical information regarding the differentiation of VP and VP-like SK, which should prove useful in clinical dermatological practice.
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Background@#Causative antigens in allergic contact dermatitis (ACD) can be changed by several variables, including time and place. Change in antigens over a period of time in the same institution is one way to reduce the variables; however, these investigations have rarely been performed in Korea. @*Objective@#To investigate the change in patch test results by comparing with the results obtained 10 years ago at the same hospital. @*Methods@#Patch test results were analyzed retrospectively through the medical records of patients with suspected ACD who underwent the patch test using Korean standard series between September 2015 and September 2018. The institutional Review Board of the Dongguk University Ilsan Hospital approved this study. The results of the patch test were compared with those obtained 10 years ago. @*Results@#A total of 360 patients (males: 142, females: 218) were included. Compared with the results obtained 10 years ago, the positivity rates of metal-related allergens (nickel sulfate, cobalt chloride, and potassium dichromate), fragrance allergens, and 4-phenylenediamine base were increased, whereas the positivity rates of mercury ammonium chloride, thimerosal, and formaldehyde were decreased. @*Conclusion@#The patch test results obtained at the same hospital over a 10-year interval suggest that causative allergens in ACD could change with time lapse. In the future, collaborative studies including a number of participating hospitals are needed for obtaining more reliable results.
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Background@#Despite the numerous treatment options for cutaneous warts, choosing the appropriate method for optimum results can be challenging. Treatment strategies should be individualized according to the patient and lesion characteristics. However, there is a paucity of research on the clinical factors predicting treatment response. @*Objective@#To investigate the efficacy of diphenylcyclopropenone immunotherapy for warts, based on anatomical location @*Methods@#This retrospective study included 262 wart lesions from 99 patients treated with diphenylcyclopropenone immunotherapy for warts between 2007 and 2018. The lesions were divided into three groups−periungual wart, palmoplantar wart, or hair-bearing skin wart−according to anatomical location. Periungual warts were divided into hyponychium, proximal nail fold, and lateral nail fold-type subgroups. Treatment success rates were compared between the groups. @*Results@#The treatment success rate of periungual warts (75.3%) was significantly higher than those of palmoplantar (60.4%) and hair-bearing skin (60.3%) warts. No significant differences were observed between the treatment success rates of the periungual wart subgroups. @*Conclusion@#Diphenylcyclopropenone immunotherapy is an effective treatment modality for periungual warts.
ABSTRACT
No abstract available.
Subject(s)
Diagnosis , Emergencies , Emergency Service, Hospital , KoreaABSTRACT
Rhus is a common cause of allergic contact dermatitis (ACD), particularly in East Asia. Rhus can cause localized contact dermatitis following direct contact with the skin, and systemic contact dermatitis following its ingestion, causing pruritus, erythema, and occasionally blistering. Bullous pemphigoid (BP) is an acquired subepidermal autoimmune bullous disease that typically occurs in the elderly. Although BP usually occurs sporadically, some precipitating factors of BP have been suggested, such as other autoimmune diseases, drugs, and malignancies. We report a rare case of BP induced by ingestion of Rhus in a 54-year-old man who presented with itchy erythematous rash and blisters on the whole body, initially misdiagnosed as ACD, and treated with systemic steroids.
ABSTRACT
Rhus is a common cause of allergic contact dermatitis (ACD), particularly in East Asia. Rhus can cause localized contact dermatitis following direct contact with the skin, and systemic contact dermatitis following its ingestion, causing pruritus, erythema, and occasionally blistering. Bullous pemphigoid (BP) is an acquired subepidermal autoimmune bullous disease that typically occurs in the elderly. Although BP usually occurs sporadically, some precipitating factors of BP have been suggested, such as other autoimmune diseases, drugs, and malignancies. We report a rare case of BP induced by ingestion of Rhus in a 54-year-old man who presented with itchy erythematous rash and blisters on the whole body, initially misdiagnosed as ACD, and treated with systemic steroids.
ABSTRACT
Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance outcomes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested. However, role of cocultured ADSCs in proliferation and migration of melanocytes remains unclear. This study determined the effect of ADSCs on production of growth factors and expression levels of intergrins in primary culture of adult human melanocytes with or without ADSCs and in nude mice grafted with such melanocytes. Higher amounts of growth factors for melanocytes, such as bFGF and SCF were produced and released from ADSCs by coculturing with melanocytes. Relative levels of integrins β1, α5, and α6 as well as adhesion to fibronectin and laminin were increased in melanocytes cocultured with ADSCs. Such increases were inhibited by neutralization of bFGF or SCF. Relative levels of bFGF, SCF and integrins were increased in nude mice skin after grafting with melanocyte+ADSC cocultures. Collectively, these results indicate that ADSCs can stimulate proliferation and migration of melanocytes by increasing expression of integrins in melanocytes through upregulation of production/release of melanocyte growth factors such as bFGF and SCF.
Subject(s)
Adult , Animals , Humans , Mice , Coculture Techniques , Extracellular Matrix , Fibronectins , Integrins , Intercellular Signaling Peptides and Proteins , Laminin , Melanocytes , Mice, Nude , Skin , Stem Cells , Transplants , Up-RegulationABSTRACT
Orofacial granulomatosis is a rare granulomatous inflammatory disease, characterized by recurrent orofacial swelling. Infectious, genetic, and immunologic etiologies are suggested, but not fully understood. Herein, we report a case of synchronous orofacial granulomatosis with brain cavernous hemangioma in a 44-year-old female patient, which may be considered paraneoplastic syndrome.
Subject(s)
Adult , Female , Humans , Brain , Granulomatosis, Orofacial , Hemangioma, Cavernous , Hemangioma, Cavernous, Central Nervous System , Paraneoplastic SyndromesABSTRACT
PURPOSE: Human leukocyte antigen (HLA) has been recognized as the most important genetic risk factor for severe cutaneous adverse drug reactions (SCARs) caused by certain drugs. However, cumulated observations suggest the presence of genetic risk factors for SCARs other than drug-specific HLA. We aimed to identify a common genetic risk factor of SCARs across multiple drugs. METHODS: We performed 2 independent genome-wide association studies (GWASs). A total of 68 and 38 subjects with a diagnosis of SCAR were enrolled in each GWAS. Their allele frequencies were compared to those of healthy subjects in Korea. RESULTS: No single nucleotide polymorphism (SNP) with genome-wide significance was found in either GWAS. We next selected and annotated the 200 top-ranked SNPs from each GWAS. These 2 sets of annotated genes were then entered into the web interface of ConsensusPathDB for a pathway-level analysis. The Fas signaling pathway was significantly over-represented in each gene set from the 2 GWASs. CONCLUSIONS: Our observations suggest that the Fas signaling pathway may be a common genetic risk factor for SCARs across multiple drugs.
Subject(s)
Humans , Cicatrix , Diagnosis , Drug-Related Side Effects and Adverse Reactions , Gene Frequency , Genome-Wide Association Study , Healthy Volunteers , Korea , Leukocytes , Polymorphism, Single Nucleotide , Risk Factors , Stevens-Johnson SyndromeABSTRACT
Extracellular interleukin 1 alpha (IL-1α) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-1α is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-1α and IL-1β mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-1α and IL-1β in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-1α and IL-1β, suggesting potential applications to predict skin irritation.
Subject(s)
Adult , Animals , Humans , Mice , Apoptosis , Epidermis , Hand , In Vitro Techniques , Interleukin 1 Receptor Antagonist Protein , Interleukin-1 , Interleukin-1alpha , Keratinocytes , Microarray Analysis , Necrosis , RNA, Messenger , Skin , Sodium Dodecyl Sulfate , TretinoinABSTRACT
No abstract available.
Subject(s)
Atherosclerosis , Bacterial Infections , Foot Ulcer , Foot , Tinea Pedis , TineaABSTRACT
BACKGROUND: Hydroquinone (HQ) is frequently combined with retinoic acid (RA) to enhance lightening efficacy, which may also affect skin irritancy. Although skin irritation leads to postinflammatory hyperpigmentation, little research has been performed to compare skin irritancy between each component and the combination. OBJECTIVE: This study was done to examine whether HQ-RA combination increased skin irritation induced by HQ or RA alone. METHODS: Patch testing was performed using maximum therapeutic and higher concentrations of HQ and RA in 10 volunteers, and then, it was performed using their popular therapeutic concentrations and combination in the other 20 volunteers. In vitro irritation was also assessed in primary cultured normal human keratinocytes treated with 80% and 50% cell survival doses of HQ, 80% cell survival dose of RA, and their combination. RESULTS: The combination in patch testing induced stronger erythema than the corresponding concentrations of HQ and RA, which was remarkable with use of combination of higher concentrations. In cultured keratinocytes, the RA combination significantly decreased cell viability, but increased cytotoxicity and extracellular interleukin 1 alpha release with corresponding doses of HQ. CONCLUSION: The results of patch tests and in vitro irritation assessment tests suggested that HQ and RA increased skin irritation when used in combination.
Subject(s)
Humans , Cell Survival , Erythema , Hyperpigmentation , In Vitro Techniques , Interleukin-1alpha , Keratinocytes , Patch Tests , Skin , Tretinoin , VolunteersABSTRACT
BACKGROUND: Palmar hyperhidrosis is a common disorder of excessive sweating. A number of studies have demonstrated the effectiveness of iontophoresis in the treatment of palmar hyperhidrosis. However, controlled clinical studies on iontophoresis for palmar hyperhidrosis have been limited. OBJECTIVE: To determine the efficacy and safety of iontophoresis in the treatment of palmar hyperhidrosis with a randomized, sham-controlled, single-blind, and parallel-designed study. METHODS: Twenty nine patients with significant palmar hyperhidrosis were enrolled in this study. They received active iontophoresis treatment (group A) or sham treatment (group B). Iontophoresis was performed 20 minutes each time, five times per week, for 2 weeks. Its efficacy was assessed with starch-iodine test, mean sweat secretion rate, and hyperhidrosis disease severity scale. RESULTS: Twenty-seven of the 29 patients completed the 2-week treatment. After completion of 10 times of treatment, results of the starch-iodine test showed clinical improvement in 92.9% of patients in group A and 38.5% of patients in group B (p=0.001). The mean sweat secretion rate was reduced by 91.8% of patients in group A and by 39.1% of patients in group B (p<0.001). Improvement in quality of life was reported by 78.6% of patients in group A and by 30.8% of patients in group B (p=0.028). In group A, one case of localized adverse event was noted, although no adverse event was encountered in group B. CONCLUSION: Tap water iontophoresis could be used as an effective and safe treatment modality for palmar hyperhidrosis.
Subject(s)
Humans , Hyperhidrosis , Iontophoresis , Placebos , Quality of Life , Sweat , Sweating , WaterABSTRACT
Diagnostic methods for drug allergy include the patient's history, in vivo skin test, in vitro laboratory test, and provocation test. However, the history is often not reliable, procedures for in vivo and in vitro tests are not standardized, and provocation tests are sometimes harmful to patients. Generally, skin prick and intradermal tests are useful for immediate reactions; in contrast, patch test and delayed reading of both skin prick and intradermal tests are helpful for delayed reactions. A drug provocation test is the gold standard for both responses, and it is necessary to be aware of exact indications and contraindications with appropriate drugs, doses, and intervals. To date, several methods have been developed to detect culprit agents for drug hypersensitivity reactions, but they are neither completely well validated nor standardized. Based on this awareness and necessity, the Korean Academy of Asthma, Allergy and Clinical Immunology launched the Standardization Committee to review the international guidelines and the literature, and then developed the consensus report on the procedures and applications of diagnostic tests for drug allergy.