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A 10-year-old boy presented with a 1-day history of multiple painful erythematous skin lesions on his upper and lower extremities. He was admitted to the Department of Pediatrics with persistent right lower abdominal pain and diarrhea. Punch biopsy of a skin lesion on his lower leg showed necrotizing granulomatous vasculitis with septal panniculitis consistent with polyarteritis nodosa, and our differential diagnosis included cutaneous manifestations of Croh's disease. Abdominal ultrasonography revealed distended colonic loops suggestive of inflammatory bowel disease. Upper and lower gastrointestinal endoscopy revealed lesions involving the duodenum, cecum, colon, and rectum. He developed multiple perianal fistulas during hospitalization. Additional laboratory tests revealed positive results for anti-saccharomyces cerevisiae and antinuclear antibodies. Based on his clinical presentation and laboratory findings, he was diagnosed with Crohn's disease associated with cutaneous polyarteritis nodosa. We report a rare case of a child who presented with cutaneous polyarteritis nodosa as an extraintestinal manifestation of Crohn's disease.

Wolf's isotopic response refers to the occurrence of a novel skin disease at the site of a preceding treated or untreated skin disease. Although the most common preceding skin disease was found to be herpes zoster (HZ), HZ-related dermatological phenomena are not well known in the literature. We report a case of HZ granulomatous dermatitis in a 77-year-old female with a previous history of hypertension, diabetes mellitus, chronic kidney disease, and HZ. She presented with a 3-month history of a pruritic skin lesion on her right thigh. The location of the lesion was consistent with a previous HZ site. Histopathological examination revealed lympho- histiocytic infiltration in the superficial dermis, forming a granulomatous structure. Based on clinical and histopathological findings, we made a diagnosis of granulomatous dermatitis at a previous HZ site. We assumed that the lesion arose from an isotopic response of Wolf. The patient was treated with topical steroids for 3 months and showed clearance of the lesion and symptom. We suggest that treatment should be based on the individual disease, which in our case was topical steroid.

Background Vitiligo is a skin depigmentation disorder, for which, repigmentation treatment with combined follicular unit extraction (FUE) graft and narrowband ultraviolet B (NBUVB) is considered superior to micro-punch graft therapy. BMP4 can induce MITF expression in Neural crest stem cells (NCSCs), and α-MSH subsequently promotes the differentiation of MITF-expressing cells along the melanocyte lineage. Objective To investigate why FUE grafting is superior to epidermal mini grafting in promoting hair follicles (HF) melanocyte cell survival and longevity, we planned the in vitro experiments HF bulge NCSCs differentiate into melanocyte precursors under the co-treatment of BMP4 and α-MSH. Methods Cells that migrated from the HF bulge of scalp were cultured and assessed using immunofluorescence. Transcriptome analysis was performed on RNA sequencing results. Results Basic fibroblast growth factor promotes the proliferation and survival of NCSCs, with spontaneous differentiation into SOX10+/SOX2+ glial progenitors, but not into SOX10+/MITF+ precursor melanocytes. Both BMP4 and α-MSH promoted the differentiation into MITF-expressing cells. RNA sequencing revealed a downregulation in neuregulin-1 (NRG1) and sermaphorin 3C (SEMA3C), and upregulation in WNT10A. Furthermore, FUE grafting had a source of reservoir melanocytes superior to mini- grafting in treatment for vitiligo. Conclusion We obtained SOX10+/MITF+ precursor melanocytes through an induction of differentiation along the melanocyte lineage by BMP4 and α-MSH. According to the RNA sequencing results that NRG1 and SEMA3C were downregulated and WNT10A was upregulated, we postulated that HF NCSCs differentiated into melanocyte by co-treatment of BMP4 and α-MSH. Overall, FUE grafting is a more robust and substitutive treatment option for vitiligo.

A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow- band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient. (Ann Dermatol 32(4) 327∼330, 2020)

Patients with atopic dermatitis have high rates of skin surface colonization of Staphylococcus aureus. At the same time, S. aureus is the major causative organism in infective endocarditis, approximately accounting for 30%~50% cases of infective endocarditis. A 22-year-old male with severe atopic dermatitis presented with fever and myalgia. He was diagnosed with active infective endocarditis causing multiple cerebral infarction, splenic infarction, and septic shoulder requiring synovectomy. Blood culture proved methicillinsensitive Staphylococcus aureus bacteremia, and the culture from the skin revealed same bacteria. After treated with intravenous antibiotics for 6 weeks, patient was improved. Another 42-year-old female with severe atopic dermatitis who presented with fever and chilling was hospitalized due to acute infective endocarditis. She also had left flank pain and visual disturbance, due to splenic infarction and acute cerebral infarction, respectively. As blood culture revealed methicillin-sensitive Staphylococcus aureus bacteremia, she treated with intravenous antibiotics for 6 weeks. The route of entry of two patients was attributed to the patient eczematous scratching lesion of poorly controlled atopic dermatitis. Infective endocarditis can result in the context of acute deterioration of atopic dermatitis. Dermatologists need to pay attention to this risk and actively manage such conditions in order to decrease the risk of infective endocarditis arising from skin lesions in atopic patients. For these reasons, we herein report two cases of infective endocarditis in patients with atopic dermatitis.

Pediatric alopecia areata (AA) can affect the quality of life (QoL) of patients and their family members. Research on the QoL and burden on family members in pediatric AA is limited.This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA.This nationwide multicenter questionnaire study enrolled AA patients between the ages of 5 and 18 years from March 1, 2017 to February 28, 2018. Enrolled patients and their parents completed the modified Children's Dermatology Life Quality Index (CDLQI) and the modified Dermatitis Family Impact (mDFI). The disease severity was measured using the Severity of Alopecia Tool (SALT) survey scores.A total of 268 patients with AA from 22 hospitals participated in this study. Our study found that the efficacy and satisfaction of previous treatments of AA decreased as the severity of the disease increased. The use of home-based therapies and traditional medicines increased with the increasing severity of the disease, but the efficacy felt by patients was limited. CDLQI and mDFI scores were higher in patients with extensive AA than those with mild to moderate AA. The economic and time burden of the family members also increased as the severity of the disease increased.The severity of the AA is indirectly proportional to the QoL of patients and their family members and directly proportional to the burden. Physicians need to understand these characteristics of pediatric AA and provide appropriate intervention to patients and their family members.

Background Rosacea is a chronic inflammatory disease characterized by centrofacial erythema. Excess cathelicidin is suggested to be important to the pathophysiology of the disease. Recently, presence of a vitamin D response element was revealed in the cathelicidin gene promoter. Objective The aim of this study was to determine whether vitamin D and cathelicidin are associated with rosacea, both serologically and histopathologically. Methods Subjects with rosacea and without chronic skin disorders were enrolled in the patient and control groups, respectively. Serum 25-hydroxy-vitamin D and cathelicidin levels were measured. Tissue expression of cathelicidin and vitamin D receptor were measured with immunostaining-intensity-distribution index. Results The mean serum 25-hydroxyvitamin D level of patients with rosacea was 12.18±5.65 ng/ml, which is lower than that of the controls (17.41±6.75 ng/ml). Mean serum cathelicidin levels in patients with rosacea and the controls were 85.0±26.1 ng/ml and 55.0±23.3 ng/ml, respectively. Cathelicidin expression in rosacea tissue was significantly higher than that in control tissue (5.21 vs. 4.03). No significant difference was observed in vitamin D receptor expression. Conclusion Higher cathelicidin expression in rosacea supports the hypothesis that an abnormal inflammatory response of the innate immune system is important in pathogenesis of rosacea, but the role of high cathelicidin serum levels is complicated. Serum vitamin D was lower in patients with rosacea, although serum cathelicidin was higher than that of the controls. This suggests that the role of vitamin D level in the pathogenesis of rosacea merits further investigation.

BACKGROUND Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (

A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL.

Friction melanosis (FM) is an acquired pigmented disease that is caused by recurrent mechanical stress. There is no previous report explaining the presence of tiny brown-colored particles confined to the corneal layer. We describe a case of a rare form of FM of the finger that showed a relatively transient clinical course. A 17-year-old Korean female presented with a 5-month history of an asymptomatic localized hyperpigmented patch on the tip of the right index finger. The dermoscopic examination revealed homogenous globular pattern, which favored pigmentation over hemorrhage. Histopathologically, hyperkeratosis and acanthosis with lymphohistiocytic infiltration of the superficial dermis were noted on hematoxylin and eosin staining; however, there was neither a definite increase in melanophages in the upper dermis nor melanocytic proliferation in the basal layer. Per high-power field, multiple brown-colored tiny particles were scattered in the corneal layer. The particles were not dyed by Fontana-Masson stain, iron stain, and S-100. We questioned the patient about the presence of irritation and found that she had bought new shoes at the time of the onset. She was habituated to placing her fingers in her shoes while wearing them because they were slightly tight. The lesion disappeared spontaneously a week after the cause of friction was eliminated. Altogether, we encountered a rare form of FM that occurred in a rare location with a transient clinical course. Further cases on pigmentation restricted to finger tips might reveal the origin of the particles.

BACKGROUND Psoriasis is associated with increased risk of cardiovascular morbidities, especially in severe cases. Severity of the disease has been known to be associated with higher prevalence of these risk factors. However, in the absence of robust measurements, studies to date relied mostly on treatment spectrum as a proxy for the severity. OBJECTIVE To evaluate the relationship between psoriasis area and severity index (PASI) and cardiovascular risk factors in Korean patients. METHODS Presence of diabetes mellitus (DM), hypertension, smoking history was surveyed through questionnaires and serum lipid profile analysis were done after fasting overnight. The severity of psoriasis was assessed using PASI scores: mild

Background Vitiligo is a skin depigmentation disorder, for which, repigmentation treatment with combined follicular unit extraction (FUE) graft and narrowband ultraviolet B (NBUVB) is considered superior to micro-punch graft therapy. BMP4 can induce MITF expression in Neural crest stem cells (NCSCs), and α-MSH subsequently promotes the differentiation of MITF-expressing cells along the melanocyte lineage. Objective To investigate why FUE grafting is superior to epidermal mini grafting in promoting hair follicles (HF) melanocyte cell survival and longevity, we planned the in vitro experiments HF bulge NCSCs differentiate into melanocyte precursors under the co-treatment of BMP4 and α-MSH. Methods Cells that migrated from the HF bulge of scalp were cultured and assessed using immunofluorescence. Transcriptome analysis was performed on RNA sequencing results. Results Basic fibroblast growth factor promotes the proliferation and survival of NCSCs, with spontaneous differentiation into SOX10+/SOX2+ glial progenitors, but not into SOX10+/MITF+ precursor melanocytes. Both BMP4 and α-MSH promoted the differentiation into MITF-expressing cells. RNA sequencing revealed a downregulation in neuregulin-1 (NRG1) and sermaphorin 3C (SEMA3C), and upregulation in WNT10A. Furthermore, FUE grafting had a source of reservoir melanocytes superior to mini- grafting in treatment for vitiligo. Conclusion We obtained SOX10+/MITF+ precursor melanocytes through an induction of differentiation along the melanocyte lineage by BMP4 and α-MSH. According to the RNA sequencing results that NRG1 and SEMA3C were downregulated and WNT10A was upregulated, we postulated that HF NCSCs differentiated into melanocyte by co-treatment of BMP4 and α-MSH. Overall, FUE grafting is a more robust and substitutive treatment option for vitiligo.

Solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal neoplasm that usually arises in the pleura, but also has been reported in numerous extrapleural locations, including cutaneous site. The skin lesion presents as a circumscribed nodule or tumor, mainly on the head and neck. A 41-year-old male presented with 6 months history of nail lesion without symptom on the left third finger. The lesion is slightly yellowish discoloration with subungual erythematous nodule and distal onycholysis. Biopsy specimen from the nail lesion showed the spindle cells form patternless pattern with hypercellular and hypocellular area. And small blood vessels and dilated vascular spaces were present. The result of special stain for specimen showed that positive for CD34, Bcl-2, and CD99 but negative for S-100, FactorXIIIa, and smooth muscle action. Recognition of this uncommon location of SFT is important because of possible confusion with other subungual tumors, including glomus tumor, fibroma and other fibrohistiocytic tumors like dermatofibrosarcoma protuberans, superficial acral fibromyxoma and cellular digital fibroma. Here in, we report a case of SFT of subungual region. We think this case is interesting because of uncommon location and may be helpful to more understand the character of this disease.

Spitzoid melanoma is a subtype of melanoma that, clinically and histologically, resembles a Spitz nevus. Clinically, spitzoid melanomas usually evolve from amelanotic nodular lesions, growing to 1 cm or more in diameter. They often remain clinically undiagnosed because of their wide variety of clinical appearances and a lack of pigmentation. Distinguishing a Spitz nevus from a spitzoid melanoma can be extremely difficult. Features that favor the diagnosis of a spitzoid melanoma are asymmetrical shape, diameter greater than 1 cm, a lesion with a deep invasive component, and a high degree of cytologic atypia. There have been only rare reports in the literature of the presence of giant cells in malignant melanoma, and the presence of these cells may result in its misdiagnosis as a histiocytic tumor. We present a case of spitzoid melanoma on the right ankle of a 22-year-old-woman.

Background A number of studies have suggested an increased frequency of cardiovascular (CV) diseases in patients with psoriasis. Objective In this study, we assessed the awareness among psoriasis patients and dermatologists in private primary clinics about the increased CV risk linked to psoriasis, and examined the screening behaviors of dermatologists for CV risk factors in psoriasis patients. Methods We distributed questionnaires to dermatologists in primary clinics and to psoriasis patients about their awareness of the increased CV risk factors related with psoriasis. Results One hundred four patients and 50 dermatologists were included. 64.4% of patients and 92% of dermatologists answered that they know about the increased risk of CV diseases in psoriasis patients. However, far fewer dermatologists than expected followed the screening guidelines for CV risk factors. We found that the duration (p

Background: Few studies have compared the efficacy, cosmetic outcomes, and adverse events between 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and methyl aminolevulinate-PDT (MAL-PDT) for actinic keratoses (AKs) in Asian ethnic populations with dark-skin. Objective: We retrospectively compared the long-term efficacy, recurrence rates, cosmetic outcomes, and safety of ALA-PDT versus MAL-PDT for facial AKs in Koreans. Methods: A total of 222 facial AKs in 58 patients were included in this study. A total of 153 lesions (29 patients) were treated with 5-ALA, and 69 lesions (29 patients) with MAL. ALA and MAL creams were applied for 6 hours and 3 hours, respectively; the lesions were then illuminated with a halogen lamp at 150 J/cm 2 for ALA-PDT and a diode lamp at 37 J/cm 2 for MAL-PDT. Results: The complete response rates of ALA-PDT and MAL-PDT were 56.9% and 50.7%, respectively, with no significant difference at 12 months after treatment. No significant difference in recurrence rates was observed between the 2 PDT modalities at either 6 or 12 months after treatment. There was no significant difference in the cosmetic outcomes between the 2 treatment modalities at 12 months after PDT. However, ALA-PDT caused significantly more painful than MAL-PDT (p=0.005). The adverse events were mild to moderate, transient, and self-limiting for both modalities. Conclusion: MAL-PDT was similar to ALA-PDT in terms of long-term efficacy, recurrence rates, cosmetic outcomes, and adverse events; however, it was a significantly less painful procedure than ALA-PDT in our study. (Ann Dermatol 26(3) 321∼331, 2014)

Background: In the majority of melanomas, the RAS/RAF/ MEK/ERK signaling pathway is constitutively activated, due to oncogenic mutations in the BRAF and NRAS genes. The BRAF mutation has been mainly described in Caucasian melanomas. However, there is a lack of study evaluating the status, and the clinical significance, of BRAF mutation in the Asian population. Objective: This study was aimed to determine the frequency of BRAF mutation, and to evaluate the correlation of BRAF status with clinicopathologic features and outcomes, in Korean primary acral lentiginous melanoma (ALM) patients. Methods: ALM samples (n=36) were analyzed for the BRAF V600E mutation, by dual-priming oligonucleotide (DPO) based real-time polymerase chain reaction. The clinicopathologic features and prognosis of the patients were analyzed with BRAF mutation status. Results: The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated with clinicopathologic features, except for the age factor. All of the BRAF-mutant patients survived without recurrence or metastasis, and have a better clinical outcome than BRAF wild-type patients. Conclusion: In Korean primary ALM, a low frequency of BRAF mutation was shown; and BRAF mutation presented with a favorable prognosis. These results indicate that other distinctive genetic mechanisms may have more important roles in the development and progression of disease. Further multicenter study with large sample size is firmly needed, to confirm the results of our preliminary study.

Background: Psoriasis and psoriatic arthritis (PsA) are included in the group of immune-mediated inflammatory diseases (IMIDs) caused by systemic inflammation; however, indicators for monitoring inflammatory activity in patients with psoriasis, such as the Psoriasis Area and Severity Index (PASI), are limited. Objective: To determine whether the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire can be used to monitor disease activity in patients with psoriasis. Methods: This was a multicenter, noninterventional, cross-sectional study. Demographic factors and PASI and PASE scores were collected to investigate associations between each. Results: PASE data were available for 1,255 patients, of whom 498 (39.7%) had a score of ≥37. Compared with the group with PASE score ＜37, the group with score ≥37 had a higher proportion of women (34.9% vs. 48.8%, p＜0.0001), older mean age at diagnosis (36.4 vs. 41.7 years, p＜0.0001), more severe disease activity using PASI and body surface area measures (p=0.0021 and p=0.0008, respectively), and higher mean body mass index (23.7 vs. 24.1, p=0.0411). In a multiple linear regression model, PASE score was positively associated with cutaneous disease activity (p＜0.0001). Conclusion: After risk-adjustment, PASE was positively associated with PASI, which suggests that PASE can be sensitive to disease activity. Since psoriasis is regarded as one of the IMIDs, PASE may be utilized as a tool not only to screen PsA but also to monitor disease activity. (Ann Dermatol 31(1) 29∼36, 2019)

Background Plasma cell cheilitis is an unusual benign plasma cell proliferative disease of an unknown etiology that typically presents on the lip. Objective The aim of this study was to investigate the clinicopathological characteristics of 13 cases of plasma cell cheilitis. Methods The present study investigated the clinical manifestations, treatment modalities, and outcome of 13 patients diagnosed with plasma cell cheilitis from 2011 to 2016 at Kangdong Sacred Heart Hospital and Hallym University Sacred Heart Hospital. Biopsy specimens of the all cases were evaluated using conventional hematoxylin and eosin staining with kappa and lambda immunoglobulin light chain immunohistochemistry. Results The age of the patients ranged from 39 to 86 years (mean, 64.7 years), with male predominance. Histopathologically, 61.5% and 38.5% of patients showed band-like and pan dermal plasmacytic infiltrates, respectively. Eosinophilic infiltration was noted in 69.2% of patients. All cases showed both kappa and lambda immunoglobulin light chain reactivities, and kappa predominance was confirmed in 9 patients (69.2%). A majority of the patients was treated with local therapy, such as intralesional steroid injection with topical tacrolimus. Among the 13 patients, plasma cell cheilitis completely resolved, partially resolved, and recurred in 3 (23.1%), 5 (38.5%), and 5 patients (38.5%), respectively. Conclusion Plasma cell cheilitis presented as erosive edematous circumscribed patches or plaques affecting mainly the lower lip of elderly male patients. The majority of histopathology cases showed characteristic plasma cell aggregation on the upper dermis that was immunopositive for immunoglobulin light chain, with kappa predominance.

Giant vascular eccrine spiradenomas (GVESs) are a rare variant of the eccrine spiradenoma that develops from the sweat gland. It is different from the eccrine spiradenoma in its larger size and greater degree of vascularity. Bleeding and/or ulceration are common clinical features of this tumor, and are the reason why it is often clinically confused with a vascular or malignant tumor. Here, a rare case of GVES without bleeding or ulceration is reported.

A cutaneous metaplastic synovial cyst (CMSC) is a cyst lined with metaplastic synovial tissue, which includes the formation of an intracystic villous structure resembling hyperplastic synovial villi. Clinically, the lesion is a tender, subcutaneous nodule that usually occurs at the site of previous surgical trauma and is frequently misdiagnosed as a suture granuloma. The actual cause remains unclear; however, trauma is presumed to be a precipitating factor, as most reported cases have demonstrated a history of antecedent cutaneous injury. Here, we present a case of CMSC in a 51-year-old woman who presented with a cystic mass localized in the left sole. She had no history of previous trauma or surgical procedures performed in the area. Although the case explained in this report is a spontaneous case of CMSC that occurred without a history of trauma, it is believed to have been caused by constant and chronic pressure since CMSC occurred in the first metatarsal head area, a part of the sole where heavy pressure is consistently applied.

Sinusoidal hemangioma is a distinctive subset of a group of lesions known collectively as cavernous hemangiomas. Clinically, it develops in adults, predominantly females, and presents as a solitary, painless, bluish, deep dermal or subcutaneous nodule. Lipoma is the most common benign soft tissue tumor. Lipoma is distinguished from sinusoidal hemangioma on both clinical and histological grounds. Several studies have suggested that adipocytes originate from perivascular cells during adipogenesis. Angiogenic cytokines released by adipocytes play a role in the vasoproliferative response. The rearrangement or loss of chromosome 13 can also be associated with hemangioma. However, no previous cases of sinusoidal hemangioma have been associated with benign tumors like lipoma. Here, we describe an unusual case of sinusoidal hemangioma that occurred together with a lipoma on the right upper arm of a 43-year-old male.

Background: Empirical evidences for efficacy of hot spring (HS) water in inflammatory skin disorders have not been substantiated with sufficient, immunological “hard evidence”. Mageumsan HS water, characterized by its weakly-alkaline properties and low total dissolved solids content, has been known to alleviate various immune-inflammatory skin diseases, including atopic dermatitis (AD). Objective: The trial attempted to quantitatively analyze in vitro expression levels of chemical mediators in cutaneous inflammation from HaCaT cell line treated with Mageumsan HS, and suggest the likely mode of action through which it exerts the apparent anti-inflammatory effects in AD. Methods: Using membranebased human antibody array kit, customized to include 30 different, keratinocyte-derived mediator proteins, their expression levels (including interleukin [IL]-1, IL-6, IL-8, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, and granulocyte macrophage colony-stimulating factor) were assessed in vitro. Selected key proteins were further quantified with enzyme-linked immunosorbent assay. Results: There was a clear pattern of overall suppression of the mediators, especially those noted for their pro-inflammatory role in AD (monocyte chemoattractant protein [MCP]-1, regulated on activation, normal T cell expressed and secreted, cutaneous T-cell-attracting chemokine, Eotaxin, and macrophage inflammatory protein-1α, etc.). Also, reduced expression of involucrin and cytokeratin 1 was also reduced in the HS-treated group. Conclusion: The present study has shown that Mageumsan HS water may exert its effects on inflammatory skin disorders through regulation of proinflammatory cytokines. These evidences are to be supported with further future investigations to elucidate immunological mechanism behind these beneficial effects of HS water in the chronically inflamed skin of AD. (Ann Dermatol 30(3) 322∼330, 2018)

Background Recently, the number of domestic pets has increased. As a consequence, sensitization to animal allergens, such as cat or dog allergens, has become a problem. Objective We studied the annual trends of sensitization to cats or dogs, and the characteristics of the patients. Methods We retrospectively analyzed the medical records of 7,469 patients who visited a dermatology clinic and underwent an allergic profile test, from January 2011 to December 2015. Specific immunoglobulin E (IgE) levels to cat or dog antibody greater than 3.50 IU/ml were regarded as positive results. Results In all, 274 patients showed significant increase in levels of specific IgE antibody to dog, and 307 revealed increase in levels of of specific IgE antibody to cat. The prevalence of these specific IgEs increased from 2011 to 2015. Independent risks for sensitization to cat allergens were sensitization to dog, but not to house dust, Dermatophagoides pteronyssinus, and D. farinae. Independent risks for sensitization to dog allergens were sensitization to cat, but not to house dust, D. pteronyssinus, and D. farinae. Total IgE level was not related to specific IgE level against either cats or dogs. Conclusion In conclusion, the prevalence of sensitization to cat or dog has increased. Sensitization to cat or dog is related to each other, but is irrelevant to the total IgE level.

Background: Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. Objective: To investigate the expression of periostin and other molecules in localized scleroderma. Methods: A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. Results: Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p=0.013), diffuse periostin positivity (42.9% vs. 0%, p=0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p=0.001) in patients than in the controls. Conclusion: Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma. (Ann Dermatol 29(3) 268∼275, 2017)

Dear Editor: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma that accounts for 18% of peripheral T-cell lymphoma, and cutaneous AITL has not been well characterized in terms of clinical and histopathologic features1. Because AITL is usually diagnosed based on lymph node biopsy, it is difficult for physicians to diagnose cutaneous AITL without lymphadenopathy. Eighty-four years old female visited our hospital with nodules on both calves. The patient claimed that she had first noticed tender nodules several months prior to the visit and that they have gradually increased in size (Fig. 1A). Examination results indicated skin-colored palpable hard nodules with tenderness, about 3.0×3.0 cm in size. The nodule histologically revealed prominent vascular proliferation surrounded by abundant epitheloid histiocytes and lymphocytes without prominent nuclear atypia in the dermis (Fig. 2A, B). There were many positive cells in CD3 and CD68 (Fig. 2C, D), foci of small aggregates of positive cells in CD31, and negative cells in S100 protein, CD1a and Epstein-Barr virus (EBV). T-cell receptor-γ gene rearrangement was found to be monoclonal. In suspicion of cutaneous T-cell lymphoma, she underwent further evaluation, such as laboratory test, whole-body computed tomography (CT), and positron emission tomography-CT in hemato-oncology. On a follow-up visit, the nodule on her left calf became a progressive ulcer with a granulation-like base (Fig. 1B). However, we could not find any evidence of infection. Inguinal lymphadenopathy was identified from imaging study, and lymph node biopsy was performed (Fig. 2F, G). Many cells in the lymph node showed positive reactions for CD3, CD4, CD5, CD21 and programmed death-1 (PD-1) (Fig. 2H~L), but negative reactions for CD8, CD20 and EBV. An additional stain for PD-1 of the skin was also positive (Fig. 2E). Based on these immunohistological findings, we were able to diagnose the skin lesion as AITL. After 6 months, she developed aggressive malignant lymphadenopathy in multiple regions of the body. Fig. 1 (A) Localized hard subcutaneous nodules about 3.0×3.0 cm in size with no epidermal changes were palpable on both calves. (B) After several weeks, the nodule on the left calf developed into a progressive ulcer covered with granulation-like tissues, ... Fig. 2 (A~E) Histopathological findings of skin biopsy. (A) Dense inflammatory cell infiltration into the deep dermis (H&E, ×40). (B) Numerous small to medium-sized vascular channels surrounded by densely mixed inflammatory cells, especially ... Skin involvement occurs in up to 50% of AITL patients and presents with nonspecific maculopapular eruption in most cases, but less commonly in patients with nodules1. Our patient first presented with cutaneous nodules, and histologically showed vascular proliferation with abundant histiocytic infiltration. Progressive ulceration made AITL diagnose more difficult until the lymph node biopsy result was obtained. However, PD-1 staining for the lymph node and the skin was useful in making the diagnosis2. Until now, predominant histiocytic infiltrate in cutaneous AITL such as our case has not been described. Only a few AITL cases have been reported with nodular lesion histologically showing presence of histiocytes. Although histiocytes' role in cutaneous lymphoma has been described in prominent granulomatous reaction, most cases were of mycosis fungoides3 and rare cases of AITL. CD68 has been known as negative prognostic marker for lymphoma-associated macrophage in follicular lymphoma4 and classic Hodgkin's lymphoma5. In our opinion, abundant histiocytic infiltration in cutaneous AITL may be associated with the cutaneous nodules and also with the progressive ulcer, and histiocytes might play a more aggressive role in the clinical features of AITL, which will be evaluated in the future.

Dear Editor: Benign lichenoid keratosis (BLK) usually presents as a solitary lesion that occurs predominantly on the trunk and upper extremities in middle-aged women. The pathogenesis of BLK is unclear; however, it has been suggested that BLK may be associated with the inflammatory stage of regressing solar lentigo (SL)1. Here, we report an interesting case of porokeratosis presenting with a BLK-like appearance. A 56-year-old female patient visited our clinic with a skin lesion on the right elbow that had appeared 3 years ago. The skin lesion was found by accident and gave no trouble to the patient except for a sense of a slowly spreading lesion. The skin lesion consisted of two relatively well-defined erythematous to dark brownish, about 20×10 mm, flat patches with a slightly elevated border on her right elbow (Fig. 1). The skin lesion histologically revealed hyperkeratosis, parakeratosis, and acanthosis with vacuolar alteration of the basal cell layer, and a dense band-like lymphocytic infiltration (Fig. 2). In addition, on another side, the epidermis also showed dermal lichenoid infiltration together with a parakeratotic column (Fig. 2). On the basis of these clinical and histological features, we diagnosed the lesions as porokeratosis presenting with a BLK-like appearance. Fig. 1 Well-demarcated erythematous, brownish and focal pigmented patches surrounded by a thread-like elevated border on the right elbow. Black arrowhead: Fig. 2A and B. White arrowhead: Fig. 2C and D. Fig. 2 (A) Hyperkeratosis, parakeratosis, acanthosis and wedged hypergranulation were observed with a dense lichenoid lymphocytic infiltration at the superficial dermis (H&E, ×40). (B) Parakeratosis with vacuolar alteration of the basal cell ... In 2005, Morgan et al.1 defined five different clinical and pathologic subtypes of BLK, and three-fourth of classic-type cases showed at least focal changes of lentigo especially at the periphery of the lesion, providing evidence that BLK represents a lymphocyte-mediated regression of a pre-existing lentigo. In our case, the clinicopathologic findings were close to a classic type; however, the preexisting lentigo was not remarkable and an unusual finding of cornoid lamella was found. Disseminated superficial actinic porokeratosis (DSAP) is the most common type of porokeratosis, with multiple lesions localized predominantly on the sun-exposed surface of the limbs. Berger et al.2 suggested that actinic porokeratosis should be considered as a potential primary lesion giving rise to BLK. In addition, 61 cases of DSAP showed lichenoid infiltrate in 23 (38%) cases3. Recently, Aydingoz et al.4 reported a case of a rare presentation of BLK as a lichenoid interphase tissue response to porokeratosis. The exact pathogenesis and causes of BLK is unclear. To date, it has been proposed that BLK represents a regressive form of preexisting epidermal tumors such as SL and seborrheic keratosis. Moreover, BLK is referred to as "sunlight-induced clonal growths of abnormal epidermal cells." together with SL, large cell acanthoma, and actinic keratosis5. As a result, we thought that BLK might be triggered by ultraviolet light and considered as a spectrum of sequential sun-exposed reactions in previous skin lesions such as porokeratosis. Regression is a phenomenon present in a variety of cutaneous lesions, and BLK has been generally considered a regressive pattern. Our case suggests that a regressive pattern of porokeratosis should be reconsidered and be included in the pathogenesis of BLK. However, it still needs to be considered that BLK might be a phenomenon resulting from dermo-epidermal changes induced by sun-exposure rather than a regressing stage of specific skin diseases.

A 4-month-old infant presented with asymptomatic soft nodules on his right forearm, which had developed since birth. On the suspicion of nevus lipomatosus superficialis (NLS), biopsy was performed. Histopathologic findings showed monomorphic polygonal cells with abundant granular cytoplasm. Immunohistochemical stains for CD68 and vimentin were strongly positive, but were negative for S-100 protein. Based on the pathologic findings, the patient was diagnosed as non-neural granular cell tumor (NN-GCT). GCT can be divided into conventional and non-neural GCT by immunoreactivity for S-100 protein. NN-GCT is typically manifested as a well-circumscribed, papulo-nodular dermal mass, and is known to occur in a younger group than does in conventional GCT, but is rare among children. To our knowledge, there have been no case reports of NN-GCT which appeared at birth and presented as grouped nodules. Therefore, we report this interesting case of congenital NN-GCT clinically mimicking NLS.

Dear Editor: Imatinib mesylate (Gleevec; Novartis AG, Basel, Switzerland), a selective tyrosine receptor kinase inhibitor, is increasingly used for treating chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, and high-grade gastrointestinal stromal tumors (GISTs)1. Several cases of cutaneous reactions after imatinib use have been reported1. We report a case of EM after imatinib administration for the treatment of a GIST. A 66-year-old woman was referred for pruritus from the department of oncology. She received a diagnosis of a GIST, for which she received adjuvant imatinib therapy after gastric wedge resection. She noticed a pruritic rash on her trunk after 5 weeks of 400 mg/day imatinib therapy. Physical examination revealed generalized variable-sized erythematous wheal-like patches with some targetoid lesions on the trunk, face, and extremities (Fig. 1). Immunoglobulin (Ig) G and IgM antibodies to the herpes simplex virus were not detected. A skin biopsy from the trunk revealed vacuolar degeneration, tagging of lymphocytes along the dermal-epidermal junction, and perivascular lymphocytic and some eosinophilic infiltrations in the upper dermis (Fig. 2A). Some dyskeratotic and necrotic keratinocytes were obvious in the epidermis (Fig. 2B); therefore, EM was diagnosed. As imatinib was the only medication administered to the patient, it was considered the most probable cause. Imatinib was discontinued, and oral steroid and antihistamine were prescribed. For 2 weeks, 30 mg/day steroid, tapered to 5 mg/day, was administered. One month after the discontinuation of imatinib therapy, the rash was fully cured. Imatinib treatment was restarted at a lower dose of 100 mg/day without steroids; no skin lesion developed for 2 months. However, when the dose was increased to 200 mg/day without oral steroids, a similar rash developed. The patient could continue imatinib therapy with a gradual dose escalation from 100 to 200 mg/day with concomitant 5 mg/day oral steroids. No additional skin lesions were detected during 5 months of follow-up. Fig. 1 Clinical manifestations of the patient. (A) Generalized erythematous variable-sized wheal-like patches on the trunk. (B) Several lesions showing the typical targetoid appearance. Fig. 2 Histopathological findings of the lesion. (A) Vacuolar degeneration, tagging of lymphocytes along the dermal-epidermal junction, and perivascular lymphocytic and a few eosinophilic infiltrations in the upper dermis (H&E, ×200). (B) Spongiosis ... It is estimated that approximately 7%~21% of patients treated with imatinib experience variable degrees of skin eruptions2. There are a few reports of imatinib-induced EM. Park et al.3 reviewed patients with cutaneous eruptions after imatinib therapy, and 2 of 10 patients (20%) had EM-like drug eruptions. The cutaneous adverse effects of imatinib are dose dependent and seemingly related to a pharmacological effect of the drug1,2. The most common skin reactions are maculopapular rashes1,2, and these are spontaneously relieved with a minimal dose of antihistamine or topical steroids. Several uncommon or severe reactions such as Stevens-Johnson syndrome have also been reported; however, they seem to be an idiosyncratic adverse reaction of hypersensitivity4. These reactions require the concomitant use of oral steroids, and immediate discontinuation of imatinib therapy is imperative4,5. Here, we observed a case of imatinib-induced EM. We noted a dose-dependent relation; thus, we consider that imatinib-induced EM is related to a pharmacological effect of imatinib. The skin lesion subsided and did not recur only with the concomitant use of low-dose oral steroids. As imatinib is a very effective therapeutic agent and alternative treatment options are limited, recognition of adverse cutaneous reactions after imatinib therapy and the appropriate management required is helpful.

Background: Certain epidermal appendage tumors, incl-uding hyperplasias (hamartomas), adenomas, benign epithe-liomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-β1, TGF-β2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood. Objective: The aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-β1/β2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation. Methods: Immunohistochemistry was performed in follicular and sebaceous tumors using anti-bodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF- β1, and TGF-β2. Results: Gli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differen-tiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-β1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation. Conclusion: We propose that p63 and/or TGF-β1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma. (Ann Dermatol 26(6) 713∼721, 2014)

Dear Editor: Multiple eruptive dermatofibromas (MEDF) are very rare and usually have been associated with autoimmune diseases, immunosuppressant therapy, hematologic malignancy, and other conditions. Zaccaria et al.1 noted that the incidence of MEDF is higher in patients with underlying diseases than in healthy persons. A 64-year-old man visited our department because of multiple lesions of the skin that had developed rapidly during the previous 3 months. Physical examination revealed firm, brownish, dome-shaped papules (>30) that were 5~10 mm in diameter, with lateral dimpled signs, on the trunk and legs (Fig. 1). He did not have any specific medical or family history. Excision biopsy of a papule on the right thigh showed a relatively well-demarcated dermal nodule composed of tightly interdigitating fascicles of spindle-shaped fibrohistiocytic cells (Fig. 2A, B). Immunohistochemical analysis revealed that many of the tumor cells were positive for factor XIIIa (Fig. 2C) and negative for CD34. Laboratory tests were conducted to rule out connective tissue disease and immunosuppressive state. Complete blood cell count, metabolic and hepatitis panels, erythrocyte sedimentation rate, analysis of T-cell subset, C3/C4, immunoglobulins, and thyroid-stimulating hormone showed normal results. Anti-human immunodeficiency virus antibody, antinuclear antibody, and double-stranded DNA antibody were all negative. Fig. 1 (A) Multiple brownish, dome-shaped nodules that were 5~10 mm in diameter on the trunk and legs. (B) A bean-sized, brownish, firm nodule on the right thigh. Fig. 2 (A) Excision biopsy of 1 papule on the right thigh showed a relatively well- demarcated dermal nodule overlaid by hyperplastic epidermis with basal hyperpigmentation (H&E, ×20). (B) Proliferation of spindle-shaped fibrohistiocytic cells ... One or several dermatofibromas (DF; 15) are extremely rare. In 1970, Baraf and Shapiro2 first described multiple DF. Ammirati et al.3 proposed that MEDF should be defined as the presence of 5~8 DF appearing within a period of 4 months. However, this criterion is arbitrarily chosen, and therefore, it might not be entirely valid for all cases. It is important to note the dynamic changes in some lesions within a short period, in contrast to the static state usually observed in DF4. Indeed, some cases reported as MEDF did not meet the criteria or did not indicate the period of development. In our review of the literature published between 1973 and 2012, 21 of 72 subjects were otherwise healthy, whereas 51 (70%) had an underlying disease. Forty-one cases (80%) among the patients with underlying disease were related to various immunodeficiency states. The etiology of DF is unclear. It was proposed that DF represents an abortive immunoreactive process mediated by dermal dendritic cells, developing as a response to a putative pathogen that the suppressed immune system cannot clear5. Accordingly, the development of MEDF could be considered a manifestation of immunosuppression; however, in our case, no abnormal specific immune defect or a medical history of using immunosuppressive agents could be found. Herein, we report a rare case of MEDF in a healthy adult, along with a literature review.

Ticks are parasites that usually suck the blood of wild or domestic animals; rarely, they ingest human blood and spread various febrile infectious diseases along with skin problems. Out of 40 cases of tick bite reported in Korea, only 3 were caused by nymphal ticks, and tick bites by nymphal Amblyomma testudinarium have not been reported previously. Herein, we report a rare case of tick bite by nymphal A. testudinarium. A 57-year-old woman presented with an asymptomatic solitary erythematous nodule on the left thigh that had been present for 6 days. The tick, which the patient removed from the lesion and brought to the hospital, was identified as a nymphal A. testudinarium. Doxycycline (200 mg) was used as treatment, and after seven days of use, the patient improved and no other lesions were detected.

Background: Facial involvement of psoriasis is known to be one of the clinical manifestations that indicate the severity of the psoriasis and thought to be more closely associated with certain distribution. Centrofacial (CF) psoriasis has been suggested to be related with severity of systemic disease while peripherofacial (PF) psoriasis has been thought to have connection with scalp psoriasis. Objective: To analyze the epidemiologic characteristics, clinical features and subjective feelings of patients with facial psoriasis and to find out relationship between scalp psoriasis and facial involvement according to the facial types. Methods: One hundred nineteen facial psoriasis patients were categorized into 3 types according to the distribution: PF type, CF type and mixed facial (MF) type. Onset and duration of facial and scalp psoriasis, and their relationship were questioned. Severity and extent of psoriasis on whole body, face, and scalp were rated by clinicians. Results: There was no significant difference of whole body psoriasis area and severity index (PASI) and body surface area (BSA) score but scalp PASI and BSA was much higher in PF psoriasis compared to CF psoriasis (scalp PASI, 17.9 vs. 10.1; p=0.005) (scalp BSA, 40.9 vs. 22.2; p=0.002). According to the questionnaire, patient’s objective feeling about the spreading of scalp lesion to facial area was markedly more prominent in the patients with peripheral involvement (PF+MF, 90.1%; CF, 54.2%; p＜0.0001). Conclusion: Among subtypes of facial psoriasis, PF psoriasis is closely associated with spreading of scalp lesion into the face rather than reflecting the disease severity. (Ann Dermatol 28(4) 422∼426, 2016)

Background: Ecklonia cava is a brown alga that contains various compounds, including carotenoids, fucoidans, and phlorotannins. E. cava polyphenols (ECPs) are known to increase fibroblast survival. The human dermal papilla cell (hDPC) has the properties of mesenchymal-origin fibroblasts. Objective: This study aims to investigate the effect of ECPs on human hair growth promotion in vitro and ex vivo. Methods: MTT assays were conducted to examine the effect of ECPs on hDPC proliferation. Hair growth was measured using ex-vivo hair follicle cultures. Real-time polymerase chain reaction was performed to evaluate the mRNA expression of various growth factors in ECP-treated hDPCs. Results: Treatment with 10 μg/ml purified polyphenols from E. cava (PPE) enhanced the proliferation of hDPCs 30.3% more than in the negative control (p＜0.001). Furthermore, 0.1 μg/ml PPE extended the human hair shaft 30.8% longer than the negative control over 9 days (p＜0.05). Insulin-like growth factor-1 (IGF-1) mRNA expression increased 3.2-fold in hDPCs following treatment with 6 μg/ml PPE (p＜0.05). Vascular endothelial growth factor (VEGF) mRNA expression was also increased 2.0-fold by 3 μg/ml PPE (p＜0.05). Treatment with 10 μg/ml PPE reduced oxidative stress in hDPCs (p＜0.05). Conclusion: These results suggest that PPE could enhance human hair growth. This can be explained by hDPC proliferation coupled with increases in growth factors such as IGF-1 and VEGF. Reducing oxidative stress is also thought to help increase hDPCs. These favorable results suggest that PPE is a promising therapeutic candidate for hair loss. (Ann Dermatol 28(1) 15∼21, 2016)