Background: Understanding the age-related morphological changes of facial soft tissue is fundamental in achieving improved outcomes of rejuvenating procedures. Three-dimensional (3D) photogrammetry is a reliable and convenient anthropometric tool to assess facial soft tissue. Objective: The aim of this study was to establish age-related facial soft tissue morphology in Korean adult females using non-invasive 3D photogrammetry. Methods: One hundred and ninety-two female participants were divided into three groups based on age: the younger group (aged 20∼39 years), middle group (40∼59 years), and older group (60∼79 years). Thirty-six landmarks were identified via 3D photogrammetric scanning (Morpheus 3D, Morpheus Co., Ltd., Seongnam, Korea). Fortyone facial dimensions were analyzed using the imaging software to find significance between the age groups. Results: Smaller upper-facial volume (p=0.019) and shorter upperfacial height (p=0.034) were observed in the older group than in the younger group. In the mid-face, narrowed palpebral fissure (p<0.001) with elongated upper eyelid height (p<0.001) and widened nose (p<0.001) were observed in the older group compared with the younger group. Longer lower-facial height (p<0.001) with longer and wider philtrum (p<0.001, p=0.004, respectively), shorter lower vermilion height (p<0.001), wider mouth width (p<0.001), and smaller lower vermilion angle (p<0.001) were seen in the older group when compared with the younger group. Moreover, greater angles of nasofrontal, nasomental, and labiomental angle (p=0.015, p=0.015, p=0.080, respectively), and smaller nasofacial angle (p=0.034) were observed in the older group than in the younger group. Conclusion: Our results provide clues of aging-related facial morphological characteristics in Korean female population. (Ann Dermatol 33(1) 52∼60, 2021)

Background: Oral alitretinoin is effective in the treatment of chronic hand eczema (CHE), and ≥12 weeks of alitretinoin treatment has been shown to be effective in Korean patients. However, in the real world, a considerable number of patients discontinue alitretinoin, which leads to treatment failure. Objective: To evaluate the compliance rate of alitretinoin treatment and explore common reasons for poor compliance in patients with CHE in the real world. Methods: We retrospectively reviewed the electronic medical records of CHE patients treated with alitretinoin. We defined 'poor-compliance' as subjects who were treated with alitretinoin for <12 weeks and 'good-compliance' as subjects who were treated with alitretinoin for ≥12 weeks. We reviewed the demographics, dose, and duration of alitretinoin usage, efficacy, and reasons for poor compliance. Results: A total of 137 subjects were enrolled, and 77 (56.2%) did not complete the 12-week treatment with alitretinoin. Among them, the non-improvement rate was significantly higher in the poor-compliance group than in the good-compliance group (p<0.01). The main reasons for the alitretinoin cessation in the poor-compliance group were insufficient response (40.8%), followed by high cost (34.7%), and adverse events (24.5%). Conclusion: Alitretinoin appears the preferred longterm treatment option for CHE. Although there are complaints about late efficacy, cost, and side effects, following proper explanation, these should not justify discontinuation. Physicians need to recognize the reasons for poor compliance with alitretinoin for each patient and suggest continuing alitretinoin for the successful treatment of CHE. (Ann Dermatol 33(1) 46 ∼51, 2021)

Background: Local hyperthermia is recommended for the treatment of patients with fixed cutaneous sporotrichosis, though the effectiveness and mechanisms of action remain elusive. While neutrophils represent the main inflammatory cells associated with sporotrichosis lesions, the issue of whether hyperthermia is involved with interactions between neutrophils and Sporothrix globosa remains unclear. Objective: To evaluate the effect of local hyperthermia on sporotrichosis and determine whether local hyperthermia involves effects of neutrophils against Sporothrix. Methods: For the in vivo study, mice were infected with yeast cells of S. globosa followed by treatment with local hyperthermia. In vitro, an isolated Sporothrix strain was co-cultured with or without neutrophils and subjected under different temperatures. Immunofluorescence was used to assess the formation of neutrophil extracellular trap (NETs) were formed under these different culture conditions and the number of fungi colony forming units were compared. Results: Hyperthermia was significantly more effective in clearing the lesions in the mouse model, as compared to sham treatment. Neutrophils failed to exert any fungicidal effects against S. globosa in response to hyperthermia. Moreover, NETs were formed after interaction with S. globosa, and the percentage of NETs formed was not significantly different at 41℃ or 37℃. Conclusion: While hyperthermia could serve as an effective therapy for fixed cutaneous sporotrichosis, this ability does not involve the formation of NETs. (Ann Dermatol 33(1) 37∼45, 2021)

Background: Atopic dermatitis (AD) is characterized by chronic, relapsing skin inflammation (eczema) with itchy sensation. Keratinocytes, which are located at the outermost part of our body, are supposed to play important roles at the early phase of type 2 inflammation including AD pathogenesis. Objective: The purpose of this study was to evaluate whether keratinocytes-derived reactive oxygen species (ROS) could be produced by the allergens or non-allergens, and the keratinocytes- derived ROS could modulate a set of biomarkers for type 2 inflammation of the skin. Methods: Normal human epidermal keratinocytes (NHEKs) were treated with an allergen of house dust mites (HDM) or a non-allergen of compound 48/80 (C48/80). Then, biomarkers for type 2 inflammation of the skin including those for neurogenic inflammation were checked by reverse transcriptase-polymerase chain reaction and western immunoblot experiments. Results: HDM or C48/80 was found to upregulate expression levels of our tested biomarkers, including type 2 T helper-driving pathway (KLK5, PAR2, and NFκB), epithelial-cell-derived cytokines (thymic stromal lymphopoietin, interleukin [IL]-25, IL-33), and neurogenic inflammation (NGF, CGRP). The HDMor C-48/80-induced expression levels of the biomarkers could be blocked by an antioxidant treatment with 5 mM N-acetyl- cysteine. In contrast, pro-oxidant treatment with 1 mM H2O2 could upregulate expression levels of the tested biomarkers in NHEKs. Conclusion: Our results reveal that keratinocytes- derived ROS, irrespective to their origins from allergens or non-allergens, have a potential to induce type 2 inflammation of AD skin. (Ann Dermatol 33(1) 26∼36, 2021)

Background: Acral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear. Objective: To investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma. Methods: A retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors. Results: The heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were observed in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p= 0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p>0.05). Conclusion: PTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients. (Ann Dermatol 33(1) 18∼25, 2021)

Background: Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP; <40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C*06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective: To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods: We first calculated the MHC-based heritability of EOP and LOP respectively. Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previous study. Results: We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%). Further association analysis identified three independent loci (HLA-C*01:02, p=6.70×10-8; HLA-A amino acid position 9, p=3.27×10-17; and HLA-A amino acid position 161, p=5.75×10-10) that confer specific susceptibility to EOP. Our data also confirmed HLA-C*06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C*06:02-positive psoriasis patients have earlier onset. Conclusion: Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision. (Ann Dermatol 33(1) 61∼67, 2021)

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory condition presenting with painful, deep-seated abscesses and sinus tracts in multifocal locations. Rarely, longstanding inflammation in HS may lead to serious complications, such as cutaneous squamous cell carcinoma (SCC) (also termed Marjolin ulcer). Herein, we report a case of invasive cutaneous SCC arising from chronic ulcers of a HS patient. A 40-year old Korean male, a current smoker with 20 pack-year history, presented with a history of painful, recurrent, deep-seated abscesses and ulcers on the buttocks since his late teens, thus classified as Hurley stage III. A large purulent ulcer developed on the right buttock several months ago. Initial treatment was focused on controlling infection and facilitating wound healing. The lesion showed 50% reduction of size in 6 weeks, but also developed foul odor and showed fungating margins. Multiple skin biopsies were consistent with invasive SCC. Magnetic resonance imaging revealed a few enlarged lymph nodes on the right inguinal area, which was confirmed as metastasis on frozen biopsy. Slow Mohs micrographic surgery and radical right inguinal lymph node dissection was done. Incidence rates of SCC arising from HS have been reported up to 4.6%. To our knowledge, this is the first report of cutaneous SCC arising from HS in Korea. Our case emphasizes that the diagnosis of cutaneous SCC in HS should not be delayed, and early surgical intervention is crucial for better outcomes. (Ann Dermatol 33(1) 68∼72, 2021)

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an uncommon skin eruption and characterized histopatho-logically by the presence of granulomatous inflammation with or without leukocytoclastic vasculitis. PNGD is known to be associated with various immune-mediated connective tissue diseases such as rheumatoid arthritis and lupus erythematosus. However, to our knowledge, a case of PNGD in a patient with Behçet's disease is extremely rare and only one case has been reported in foreign literature to date. Herein, we report an unusual case of a 60-year-old female with Behçet's disease who presented multiple erythematous to flesh-colored papules on the extremities, buttocks, and ear lobes and was diagnosed with PNGD. After the treatment of systemic corticosteroids, colchicine and azathioprine, the skin lesions and oral ulcers improved. The patient is under observation without recurrence of skin lesions for 6 months. (Ann Dermatol 33(1) 73∼76, 2021)

Recently, biologic therapy has become a major advance in the management of moderate-to-severe psoriasis. Although the overall safety profile of biologics is favorable, primary infection or reactivation of latent tuberculosis (TB) is the major concern in the setting of tumor necrosis factor-alpha inhibitor therapy. Therefore, the treatment of latent tuberculosis infection (LTBI) before starting biologics is mandatory to prevent the reactivation of LTBI. A 27-year-old female was treated with adalimumab due to psoriasis. As latent TB was detected by the interferon-γ release assay, we started isoniazid treatment (300 mg/day) 3 weeks before starting adalimumab and maintained this for 6 months. Although the patient's psoriatic skin lesions improved, after 45 weeks of adalimumab therapy, she visited the emergency department because of fever and back pain for 2 weeks. Abdominopelvic computed tomography (CT) and chest CT revealed multiple nodular lesions on both lungs, peritoneal wall, mesentery, and spleen, along with ascites. In the ascitic fluid, adenosine deaminase was increased to 96.4 U/L, and Mycobacterium tuberculosis grew in an acid-fast bacilli culture. The patient was diagnosed with disseminated TB and treated with conventional TB medication with discontinuation of adalimumab. Five months after the completion of TB treatment, the ustekinumab, an interleukin (IL)-12/IL-23 inhibitor, was administered. Until now, her skin lesions are under excellent control without reactivation of TB for 9 months after starting ustekinumab. (Ann Dermatol 33(1) 77∼81, 2021)