Clinical Implications of Expression of Endoglin and Survivin in Patients with Primary Cutaneous Angiosarcoma in an Asian Population / 대한피부과학회지

Background@#Targeted therapy and immunotherapy such as programmed death-1 (PD-1) targeting have been introduced for treating many types of cancers, including primary cutaneous angiosarcoma (CA). However, studies that examined other targeted molecules in CA are scarce. @*Objective@#We aim to declare the expression of endoglin and survivin in addition to PD-1 and assess the clinical correlation between the expression of these molecules and clinical variables, overall survival (OS), and progressionfree survival (PFS) in CA. @*Methods@#We identified 51 patients diagnosed with CA at Asan Medical Center over the last 14 years, based on the staining results of paraffin sections of tissue samples for endoglin, survivin, and PD-1 that were reviewed by two dermatologists. @*Results@#Statistical analysis for the correlation between results and clinical data of CA revealed that whereas 35 (63.6%) and 30 samples (54.5%) were positive for endoglin and survivin respectively, only nine samples were positive for PD-1 (16.4%). Co-expression of endoglin and survivin was detected in 24 lesions (p=0.013) and was significantly correlated to head, neck, face, and scalp (HNFS) lesions in CA (p=0.005, p=0.038, respectively). However, the expression of these target molecules did not correlate with the OS or PFS of CA. @*Conclusion@#Considering that HNFS type CA is associated with unfavorable clinical outcomes in similar populations, our findings can be helpful in matching patients with CA with effective targeted therapy.

Real-World Experience of the Efficacy and Safety of Upadacitinib 15 mg in Patients with Atopic Dermatitis in Korea / 대한피부과학회지

Background@#Upadacitinib is an oral Janus kinase1 (JAK1)-selective inhibitor, which showed a quick and significant effect on patients with atopic dermatitis in several phase 3 clinical studies. Although, an increasing number of studies have reported data on the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis, no studies have yet been published in Korea. @*Objective@#We assessed the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis in Korean patients. @*Methods@#A total of 17 patients with atopic dermatitis who received 15 mg of oral upadacitinib everyday for 16 weeks, were included in this retrospective single-center study. Based on electronic medical records, the clinical characteristics, Eczema Area and Severity Index (EASI) score, and adverse events were investigated. @*Results@#The mean EASI score was significantly reduced at 4 weeks of upadacitinib treatment (8.81±9.00) and gradually reduced at week 8 (5.70±7.38), week 12 (4.55±6.23), and week 16 (4.58±6.74) (p＜0.001). At week 16, 61.54%, 30.77%, and 15.38% of patients achieved EASI 75, EASI 90, and EASI 100 responses, respectively. There was no statistically significant difference between EASI 75 and EASI 90 by age or gender at week 16 (p＞0.05). A total of 13 people (76.5%) had adverse events, of which acne was the most common. In all patients, the symptoms were mild and self-limited, and no patient discontinued treatment. @*Conclusion@#Upadacitinib was effective and safe for Korean patients with atopic dermatitis in real-world clinical practice.

Excited Skin Syndrome after Patch Testing in a Patient with Atopic Dermatitis Treated with Dupilumab / 대한피부과학회지

The effect of dupilumab on allergic contact dermatitis or patch testing is unknown. Here, we present a case of excited skin syndrome that appeared after patch testing during dupilumab treatment. A 21-year-old woman presented with atopic dermatitis that showed only a partial response to cyclosporine and dupilumab. A patch test was performed to check for underlying allergic contact dermatitis. The result was consistent with excited skin syndrome.Some studies argue that dupilumab suppresses allergic reactions triggered by allergens that activate the Th2 pathway. Others suggest that it does not affect the result of patch testing, regardless of the type of allergen tested. Even if dupilumab suppresses a certain allergic or immunologic pathway, this case shows that it cannot mask excited skin syndrome on patch testing.

Two Cases of Linear Lichen Planus Pigmentosus of the Chin in Korean Women Treated by Fractional Lasers and Polydeoxyribonucleotide Injection

Linear lichen planus pigmentosus is a rare subtype of lichen planus pigmentosus that follows Blaschko’s lines, leaving long-standing residual atrophy and pigmentation, especially in dark-skinned populations. Conventional treatments have several limitations regarding the alleviation of pigmentation and atrophy. We report two cases of Korean women with linear lichen planus pigmentosus on their faces who were successfully treated with fractional lasers and intralesional injection of polydeoxyribonucleotide.

Clinicopathologic Characteristics of Nipple Adenoma: Comparison with Malignant Proliferative Diseases / 대한피부과학회지

Background@#Nipple adenoma (NA) is a rare benign tumor arising in the lactiferous ducts of the nipple. It typically presents as a palpable nodule, erosion, or discharge with erythema of the nipple. NA is different from other mammary proliferative diseases of the nipple; however, its clinicopathologic characteristics have been scarcely elucidated. @*Objective@#In this study, we aimed to assess the clinical and histopathological characteristics of NA and compare them with mammary Paget’s diseases and breast carcinomas of the nipple. @*Methods@#We retrospectively reviewed fifteen patients with NA. Furthermore, we reviewed fifteen patients with nipple Paget’s diseases and five patients with breast carcinomas (ductal carcinoma in situ and invasive ductal carcinoma). Skin lesions’ clinical characteristics and general histopathological findings were investigated. @*Results@#NA showed significantly early onset (p=0.014), delayed time for onset to diagnosis (p=0.026), and smaller lesion than other nipple malignant diseases (p＜0.001). NA was predominantly localized on the right side and exhibited as more palpable mass and less nipple discharge as initial symptoms. Estimated prevalence of Korean cases (0.026%) was twice higher than Western countries (0.012%). p16 immunostaining in NA and other malignant diseases did not differ. @*Conclusion@#NA is a benign neoplasm arising on the nipple. NA showed earlier onset with smaller size at initial presentation than other malignant diseases which presented more crusts. Unnecessary surgical procedures for NA should be avoided with preceding clinical differential diagnosis.

Impact of Pediatric Alopecia Areata on Quality of Life of Patients and Their Family Members: A Nationwide Multicenter Questionnaire Study

Background@#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. @*Objective@#This nationwide multicenter questionnaire study described the QoL and burden of the family members of patients with pediatric AA. @*Methods@#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. @*Results@#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. @*Conclusion@#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.

Revisiting Riehl’s Melanosis in Korean Patients: Clinicopathological Features, Blood Chemistry, and Immunohistochemistry / 대한피부과학회지

Background@#Riehl’s melanosis of the face and neck has been reported in middle-aged women who have darker skin types. Recently, cases of Riehl’s melanosis have been on the rise in Korea, which might reflect the increased use of various cosmetic products and procedures. @*Objective@#This study was designed to analyze the clinicopathological characteristics and treatment outcomes of Riehl’s melanosis in Korean patients. @*Methods@#We closely observed 80 patients with Riehl’s melanosis diagnosed in Asan Medical Center and Hanyang University Medical Center between 2005 and 2015. A skin biopsy was analyzed in 51 patients, and a patch test was carried out in 16 patients. @*Results@#Patients with chronic Riehl’s melanosis (＞12 months) had an increased frequency of previous laser treatments. Patients with acute Riehl’s melanosis (＜3 months) reported a previous history of dry skin, itching, or irritation as a result of the use of hair dye. Patients older than 50 years, with darker skin type, and with a longer disease duration (＞12 months) had poor response rates. Chronic Riehl’s melanosis may be preceded by repeated irritation of barrier-compromised skin, and acute Riehl’s melanosis seems to be an allergic form of Riehl’s melanosis. @*Conclusion@#Riehl’s melanosis has different clinical manifestations according to disease duration and different treatment responses based on disease duration.

A case of cribriform carcinoma of the skin: a newly described rare condition

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a followup period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

Longevity of Cross-linked Hyaluronic Acid Filler Depending on Injection Depth: In Vivo Study Using a Small Animal Model / 대한피부과학회지

Background@#Hyaluronic acid (HA) is the material used most often for soft tissue augmentation. Both agent factors, such as type of fillers and host factors, including technical manipulation, are known to affect the longevity of HA fillers. Although the relationship between longevity and filler composition has been widely studied, quantitative analysis to evaluate the difference in longevity of HA filler depending on injection depth has not yet been reported.Objective This study estimates injection depth-dependent degradation of HA filler in vivo using a rat model to evaluate its longevity. @*Methods@#Three Sprague–Dawley rats were assigned to each group based on sampling timepoints. Four injections were administered intradermally on one side of the back of rats and four more injections were administered subcutaneously on the other side. Histological specimens from the injected site were obtained at 2 (Group 1), 5 (Group 2), 9 (Group 3), 13 (Group 4), 20 (Group 5), and 33 (Group 6) weeks after initial implantation. External size of the implant site was calculated using caliper measurement at sampling timepoints. @*Results@#Although caliper-based analysis did not reveal a significant difference between intradermal and subdermal sites in all groups (p＞0.05), volumetric analysis of histological specimens demonstrated a difference in injection depth-dependent degradation rate. The volume ratio decreased over time in the subdermal injection sites, but it maintained a greater volume ratio than intradermal injection sites during the experiment (Groups 1∼6, p＜0.007).At 20 weeks after implantation, approximately half of the HA filler remained in the subdermal injection sites, whereas ＞80% of the filler was lost from intradermal injection sites. After the initial injection, time taken for the implant volume to reduce to half of its original value at intradermal and subdermal sites was 13 and 20 weeks, respectively. @*Conclusion@#This study demonstrates histological changes occurring in implanted HA filler materials over time and compares the injection depth-dependent longevity of materials. Caliper-based analysis did not show a significant difference between the intradermal and subdermal sites. However, quantitative analysis based on histological volumetric analysis revealed that subdermal injection lasts longer than intradermal injection.

Characterization and Prognostic Significance of Cutaneous Adverse Events to Anti-Programmed Cell Death-1 Therapy

BACKGROUND: Anti-programmed cell death-1 (PD-1) immunotherapy using antibodies such as nivolumab or pembrolizumab has shown promise for treating various types of cancer. In this study, we reviewed the frequency and spectrum of cutaneous adverse events (AEs) caused by PD-1 antibodies and their possible correlation with treatment response. METHODS: We reviewed records of all patients from a single institution treated with either nivolumab or pembrolizumab from August 1, 2014 to April 1, 2017. RESULTS: Of 211 patients included in the study, 134 (63.5%) were treated with nivolumab and 77 (36.5%) with pembrolizumab. Thirty-five patients (16.4%) developed cutaneous AEs. Cutaneous AEs were significantly associated with longer treatment cycles (P = 0.001). The prevalence of cutaneous AEs did not differ between nivolumab (17.2%) and pembrolizumab (15.6%). Patient age, gender, baseline Eastern Cooperative Oncology Group scale and underlying malignancy were not associated with development of cutaneous AEs. Median time until onset of cutaneous AEs was 50.0 days (range, 1–378 days). Anti-PD-1 therapy was tolerable in most of patients with grade 1 (65.2%) and grade 2 (23.9%) cutaneous AEs. Pruritus (32.6%) and eczema (21.7%) were the most commonly reported cutaneous AEs. In lung cancer patients, cutaneous AEs were not associated with better treatment outcomes after adjusting for the number of treatment cycles. CONCLUSION: Both pembrolizumab and nivolumab exhibited tolerable cutaneous safety profiles in a variety of cancer patients undergoing anti-PD-1 therapy. Cutaneous AEs of anti-PD-1 therapy were not associated with antibody type, underlying malignancy, patient characteristics, or improved response.

Metformin, an Activator of AMPK, Promotes the Growth of Hair Follicles via the AMPK/β-catenin Signaling Pathway / 대한피부과학회지

BACKGROUND: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. OBJECTIVE: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. METHODS: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. RESULTS: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. CONCLUSION: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future.

A Case of Microcystic Adnexal Carcinoma with Secondary Cicatricial Alopecia / 대한피부과학회지

Microcystic adnexal carcinoma (MAC) was first described in 1982 by Goldstein. Considered a rare malignant skin appendageal tumor, it is often underdiagnosed due to its clinical and histopathological resemblance to other cutaneous neoplasms. MAC is locally aggressive with infiltration of perineural spaces, subcutaneous tissue, skeletal muscles, and so on. Aggressive treatment including wide local excision, Mohs micrographic surgery, or radiation therapy is necessary owing to the high recurrence rate. Herein, we report a case of a 47-year-old Korean woman with a skin-colored hardened plaque on the scalp with a clinical diagnosis of cicatricial alopecia and histopathological diagnosis of MAC. After treatment by Mohs micrographic surgery, the patient is being followed up regularly without any sign of recurrence. This case demonstrates an uncommon topography of MAC on the scalp with secondary cicatricial alopecia and highlights the need for awareness of the potential for MAC in the diagnosis of alopecia with a slow-growing tumor.

Two Cases of Postoperative Pyoderma Gangrenosum / 대한피부과학회지

Pyoderma gangrenosum (PG) is an uncommon ulcerating inflammatory neutrophilic dermatosis. Multifactorial pathogenesis has been reported because the underlying mechanism needs to be clearly elucidated. A pathergic reaction is a pathogenic aggravating factor of PG. The occurrence of postoperative PG (PPG) within and involving the borders of a surgical incision site suggests the role of a pathergic reaction in PG. Massive debridement should be avoided in PPG, and it should be immediately managed with oral prednisolone. We present 2 cases of PPG with different clinical courses according to the primary management.

The Incidence of Other Primary Cancers in Patients with Cutaneous Lymphoma

BACKGROUND: Skin cancer is the most common other primary cancer in patients with lymphoma. However, an intriguing association between cutaneous lymphoma and other primary cancers has been suggested in a few studies. OBJECTIVE: This study investigated other primary cancers in patients with cutaneous lymphoma to evaluate the risk for occurrence of each type of cancer. METHODS: We screened for other primary cancers in 428 patients with cutaneous lymphoma. Clinical features were analyzed according to the lineage and origin of the lymphomas. We calculated the standardized incidence ratio with statistical analysis for each group according to age. RESULTS: Among 330 patients with cutaneous T cell lymphoma and 98 with cutaneous B cell lymphoma, a total of 43 cancers in 38 patients were finally included. Other primary cancers were prevalent in patients with cutaneous B cell lymphoma and patients with secondary cutaneous lymphoma. However, those differences were not significant when the age was calibrated by multiple logistic regression. Metachronously higher standardized incidence ratios were observed for primary lung (standardized incidence ratio [SIR], 14.81; 95% confidence interval [CI], 3.05~39.54), skin (SIR, 68.05; 95% CI, 14.03~181.62), and breast (SIR, 12.91; 95% CI, 1.56~41.41) cancers with statistical significance. CONCLUSION: Other primary cancers more preferentially occurred in patients with cutaneous lymphoma. Clinicians should carefully examine patients with cutaneous lymphoma for other cancers, especially lung, skin, and breast cancers.

Metastatic Cutaneous Duodenal Gastrointestinal Stromal Tumor: A Possible Clue to Multiple Metastases

We report a case of a 69-year-old man with metastatic cutaneous duodenal gastrointestinal stromal tumor, which led to find multiple metastases on orbital muscle and scalp. The patient presented with a rapidly growing chest nodule with mild tenderness. He underwent surgical resection for duodenal gastrointestinal stromal tumor and had been treated with imatinib for three years. Histopathological examination of the chest nodule was consistent with gastrointestinal stromal tumor. A brain magnetic resonance imaging of follow work-up revealed multiple metastases at the left superior rectus muscle and occipital scalp. Under the diagnosis with imatinib-resistant duodenal gastrointestinal stromal tumors, a second-line therapy with sunitinib was tried. After six weeks, his skin lesion was completely improved and other metastatic cancers showed a response of stable disease. This is the first reported case of a cutaneous metastasis from duodenal GIST. This report emphasizes the importance of a full-skin examination in patients with a medical history of gastrointestinal stromal tumor which leads to find multiple metastases.

Pancreatic Extraskeletal Osteosarcoma Metastasizing to the Scalp

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

A Case of Plexiform Fibrohistiocytic Tumor on Finger

No abstract available.

A Case of Acral Pseudolymphomatous Angiokeratoma of Children (APACHE) / 대한피부과학회지

No abstract available.

Scrotal Ulcer Probably Induced by All-trans Retinoic Acid Therapy in a Patient with Acute Promyelocytic Leukemia / 대한피부과학회지

No abstract available.

Topical Tacrolimus for the Treatment of Atopic Dermatitis with Truncal Lesion

BACKGROUND: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions. METHODS: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28. RESULTS: Two hundred and ninety-one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p < 0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period. CONCLUSION: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients.