Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2.

Background: Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). Methods: To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Results: Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Discussion: Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.

Clinicopathological and immunohistochemical characteristics of bullous pilomatricoma: a retrospective, single-center study, and comparison with ordinary pilomatricoma.

BACKGROUND: Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. OBJECTIVES: This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. METHODS: The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. RESULTS: Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. STUDY LIMITATIONS: The study was retrospective, and the sample size was small. CONCLUSION: The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.

Risk of Alopecia Areata After COVID-19.

This cohort study examines the incidence, prevalence, and risk of alopecia areata after COVID-19.

Three Cases of Recalcitrant Pediatric Tinea Capitis Successfully Treated with Griseofulvin.

Tinea capitis is an infection of the scalp hair follicles and surrounding skin that primarily occurs in prepubertal children. Microsporum canis remains the most common pathogen causing tinea capitis in Asian countries, including South Korea, although the causative organism of this condition varies across geographical regions and time periods. Systemic antifungal agents are the mainstay treatments for tinea capitis; however, the therapeutic responses to antifungal drugs may vary depending on the causative species, and treatment failure may occur owing to drug resistance. Although dermatophytosis resistant to clinical treatment have been increasingly encountered, recalcitrant tinea capitis cases have rarely been reported. Herein, we report three cases of tinea capitis caused by M. canis in children. All three patients showed unsatisfactory clinical responses to prolonged courses of oral terbinafine or itraconazole without achieving mycological cure; however, they were successfully treated with oral griseofulvin. Although griseofulvin is not currently available or licensed for use in many countries, including South Korea, it is one of the most effective agents against Microsporum species and remains the most widely used first-line treatment for tinea capitis in children, based on dermatology textbooks and reliable treatment guidelines.

Facial tinea incognito: a clinical, dermoscopic and mycological study of 38 cases.

BACKGROUND: Tinea incognito (TI) is a dermatophytic infection of the skin that is modified by steroid use. As a result, it shows atypical clinical presentations that can lead to misdiagnosis. TI occurring on the face is most frequently misdiagnosed as cutaneous fungal infection, however, very limited information is available on facial TI. OBJECTIVES: This study aimed to characterize the clinical, dermoscopic and mycological features of facial TI. MATERIALS & METHODS: We retrospectively evaluated 38 patients with mycologically proven facial TI at a single institution in Korea between July, 2014 and July, 2021. RESULTS: The patients had a mean age of 59.6 ± 20.4 years and showed a slight female predominance (male-to-female ratio of 1:1.38). The most common clinical presentation was an eczema-like pattern (47.4%), followed by rosacea-like (15.8%), psoriasis-like (10.5%), lupus erythematosus-like (10.5%), cellulitis-like (7.9%), and folliculitis-like (7.9%) patterns. The mean duration from disease onset to diagnostic confirmation was 3.4 months. Overall, 78.9% of the patients had accompanying chronic systemic diseases, and 57.9% had concurrent tinea infections at other skin sites, mainly the feet and toenails. On dermoscopy, scales and dilated vascular patterns (arborizing vessels and telangiectasia) were commonly observed on glabrous skin, with follicular patterns, such as black dots, broken hairs, and empty follicles. The characteristic trichoscopic features were comma, corkscrew, Morse code-like, and translucent hairs. CONCLUSION: The clinical characteristics and distinct dermoscopic features described in this article may aid in the differential diagnosis of facial TI while reducing diagnostic delays and unnecessary treatments.

SIRT1 downregulation provokes immune-inflammatory responses in hair follicle outer root sheath cells and may contribute to development of alopecia areata.

BACKGROUND: Silent information regulator 1 (SIRT1), a type III histone deacetylase, is involved in various cutaneous and systemic autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and psoriasis. However, little is known about the role of SIRT1 in the development of alopecia areata (AA). OBJECTIVES: This study investigated whether SIRT1 regulates the hair follicle immune system and is involved in AA pathogenesis. METHODS: SIRT1 expression in human scalp tissue was analyzed using immunohistochemical staining, qPCR, and western blotting. The regulatory effect of SIRT1 was evaluated after stimulation with the double-stranded RNA mimic polyinosinic:polycytidylic acid (poly I:C) in hair follicle outer root sheath (ORS) cells and C3H/HeJ mice. RESULTS: SIRT1 expression was significantly reduced in the AA scalp compared to the normal scalp. SIRT1 inhibition upregulated MHC class I polypeptide-related sequence A and UL16 binding protein 3 in hair follicle ORS cells. SIRT1 inhibition also promoted the production of Th1 cytokines (IFN-γ and TNF-α), IFN-inducible chemokines (CXCL9 and CXCL10), and T cell migration in ORS cells. Conversely, SIRT1 activation suppressed the autoreactive inflammatory responses. The counteractive effect of the immune response by SIRT1 was mediated through the deacetylation of NF-κB and phosphorylation of STAT3. CONCLUSION: SIRT1 downregulation induces immune-inflammatory responses in hair follicle ORS cells and may contribute to AA development.

Intravascular Papillary Endothelial Hyperplasia in Association with Eccrine Angiokeratomatous Hamartoma.

Eccrine angiokeratomatous hamartoma is a variant of eccrine angiomatous hamartoma. Histopathologically, it shows both features of eccrine angiomatous hamartoma with components of angiokeratoma. Eccrine angiokeratomatous hamartoma is extremely rare. Eccrine angiokeratomatous hamartoma in our case co-existed with intravascular papillary endothelial hyperplasia. This is the first reported case.

Association of adenotonsillar disease and adenotonsillectomy with the development of vitiligo: A nationwide population-based cohort study.

Background: Vitiligo is a common acquired skin depigmentation disorder and is associated with various other autoimmune diseases which include thyroid disease and rheumatoid arthritis. Similarly, adenotonsillar disease (ATD) may induce inflammatory or autoimmune diseases in other organs which include the skin. However, the influence of ATD on the development of vitiligo has not been studied. Objectives: To determine the association between ATD and adenotonsillectomy, and the development of vitiligo. Design and methods: Using data from the National Health Insurance Service database, patients diagnosed with ATD between 2008 and 2010 were included in the study. We performed two rounds of 1:1 propensity score matching in the ATD and adenotonsillectomy groups. The ATD and non-ATD groups both included 206,514 individuals. Among the ATD group, the adenotonsillectomy and non-adenotonsillectomy groups both included 23,354 individuals. Each individual was monitored until 2019. The primary end point was the risk of vitiligo. Using the Cox Proportional Hazards model, the incidence of vitiligo and the hazard ratio (HR) were calculated. Results: The incidence of vitiligo was 1.16-fold higher in the ATD group than in the non-ATD group [adjusted HR (aHR), 1.16; 95% confidence interval (CI), 1.09-1.24] and 0.82-fold lower in the adenotonsillectomy group than in the non-adenotonsillectomy group (aHR, 0.82; 95% CI, 0.68-0.99). Additionally, the other risk factors for developing vitiligo included thyroid disease (aHR, 1.48; 95% CI, 1.11-1.98), age younger than 30 years (aHR, 1.18; 95% CI, 1.09-1.27), and age over 60 years (aHR, 1.22; 95% CI, 1.06-1.41), whereas factors including rural residency (aHR, 0.91; 95% CI, 0.85-0.98) and low economic status (aHR 0.87; 95% CI, 0.82-0.93) were associated with decreased incidence of vitiligo. Conclusion: In this study, ATD increases the risk of vitiligo and adenotonsillectomy attenuates its development. Clinicians should consider ATD as a pathogenic factor for vitiligo and the potential effect of adenotonsillectomy in its management.

First report of Tulip Virus X infecting tulip (Tulipa gesneriana) in Korea.

Tulip virus X (tulip virus X, TVX) is a member of the genus Potexvirus (family Alphaflexiviridae) and is a positive single-stranded RNA virus. TVX was described first in Scotland (Mowat 1982), followed by several countries (Yamaji et al. 2001; Tzanetakis et al. 2005; Ward et al. 2008; Dees et al. 2011; Sochacki and Komorowska 2012; Wylie et al. 2019). In April 2021, 86 whole tulip plants showing viral symptoms in leaves (mosaic, yellowing, and malformation) and flowers (color breaking) were collected in Chilgok, Chuncheon, Goseong, Yecheon and Yesan, Korea. Furthermore, high-throughput sequencing was performed to identify viruses that infect tulips in Korea. Total RNA was extracted from pooled the leaves and petals using a Maxwell® 16 LEV Plant RNA Kit (Promega, Madison, USA). We constructed a single library using the TruSeq Stranded Total RNA LT Sample Prep Kit for Plant (Illumina, San Diego, USA). The library was 100 bp paired-end sequenced using Illumina's NovaSeq 6000 (Macrogen, Seoul, Korea) and was assembled de novo using Trinity software version trinityrnaseq_r20140717, with default parameters. The contigs were annotated as in previous study (Lee et al. 2020), revealing a single contig each related to TVX, lily symptomless virus (LSV), and tulip breaking virus (TBV) was generated from 648 million total reads. The TVX-related contig (GenBank ON205948) consisting of 6,076 bp showed 99.52% nucleotide identity (6027/6056 bp) with TVX-J (GenBank AB066288). We conducted an RT-PCR assay to validate the presence of viruses with specific primers as TVX-F5093/R5624 (5'-CTATCCGGACTCATTCTACTTC/GTGCGTTCCAGATAAGCTTG-3'), LSV-F7013/R7338 (5'-CTTGGTCGACAGGGACATAAC/GATTGGAATTGTGCTTTTCAGC-3'), and TBV-F7515/R8116 (5'-GTGTGTCATGGATGATTGTTG/CAACTGATTTGCTACCGCTAG-3'). Consequently, TVX were detected in 13 of 86 samples. Moreover, LSV and TBV were detected in 15 and 26 samples, respectively. However, the yellowing and mosaic observed in the TVX infected samples were not observed in the LSV and TBV infected samples. Subsequently, two TVX amplicons were selected, cloned and sequenced. The obtained sequences were 532 bp and were named YS24 and YS38 (GenBank LC664027 and LC664028), respectively. The Korean isolates showed 98.68% (525/532 bp) and 99.62% (530/532 bp) identity with Australian isolate (GenBank MH886522) in BLASTn analysis. To bioassay for TVX, the infected tulip leaf tissue from which YS24 was obtained was used to sap-inoculate, in triplicates, 15 species of indicator plants (Nicotiana benthamiana, N. clevelandii, N. debneyi, N. glutinosa, N. rustica, N. tabacum, Datura stramonium, Glycine max, Phaseolus vulgaris, Chenopodium amaranticolor, C. quinoa, Cucumis sativus, Cu. melo, Gomphrena globosa, and Tetragonia tetragonioides). After 14 days of inoculation, we observed distinct chlorotic spots on inoculated and upper leaves of C. quinoa, but no symptoms were observed in other indicator plants. In RT-PCR assay using TVX-specific primers, only C. quinoa showed a positive reaction. In previous studies, C. amaranticolor, C. quinoa, G. globosa, and N. benthamiana were known as the experimental host of TVX (Dees et al. 2011; Tzanetakis et al. 2005), but only C. quinoa was confirmed to be susceptible to the Korean isolate. Furthermore, transmission electron microscopy revealed typical flexuous rod-shaped viral particles in the inoculated C. quinoa. To our knowledge, this is the first report of TVX infecting tulips in Korea.

A Clinicohistopathological Analysis of Cutaneous Fibrous Histiocytomas of the Finger.

BACKGROUND: Cutaneous fibrous histiocytoma (CFH) is a common, benign skin tumor predominantly occurring on the extremities or trunk. However, CFH on the finger is rare. OBJECTIVE: This study was undertaken to examine the clinicohistopathological features of CFH of the finger. MATERIALS AND METHODS: This is a retrospective study of 12 CFHs located on fingers in a tertiary hospital in Korea. All case slides were retrieved from saved files. RESULTS: Ages of the CHF of the finger affected individuals ranged from 9 to 48 years with a male-to-female ratio of 1.4:1. Picker's nodule or wart was the most common clinical diagnosis. In only 2 out of the 12 cases was the pre-biopsy diagnosis of CFH ventured. Fibrocollagenous type was the most common histological type. Majority of the cases were mitotically inactive, exhibiting only 0-1 mitoses per high-power field and there was no recurrence. Tumor cells were uniformly CD34 negative. CONCLUSION: Because CFH can resemble malignancies including dermatofibrosarcoma protuberans, a lack of familiarity with the occurrence of CFH of the finger may lead to more aggressive treatment. Dermatologists should include CFH in their differential diagnosis of circumscribed nodules on the fingers to ensure proper management.