Risk of major adverse cardiovascular events and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor-α and interleukin-12/23 inhibitors: a nationwide population-based cohort study in Korea.

PURPOSE: Few studies have investigated the impact of biologics on the risk of major adverse cardiovascular events (MACEs) among Korean patients with psoriatic diseases. We compared the risk of MACEs and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor (TNF)-α and interleukin (IL)-12/23 inhibitors in Korea. METHODS: Patients with psoriatic disease prescribed with TNF-α and IL-12/23 inhibitors since 2016 were selected from the Korean National Health Insurance Service (NHIS) Database. Follow-up data for MACEs and all-cause mortality between 2016 and 2020 were collected. A total of 2886 individuals were included, including 1987 IL-12/23 inhibitor users and 899 TNF-α inhibitor users. RESULTS: Compared with IL-12/23 inhibitor users, TNF-α inhibitor users had a higher prevalence of dyslipidemia and a significantly higher risk of all-cause mortality but not MACE. After controlling for age, female TNF-α inhibitor users had a significantly increased risk of all-cause mortality. Meanwhile, after controlling for sex, TNF-α inhibitor users aged 60 years or older demonstrated a significantly elevated risk of all-cause mortality. In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.

Comparison of metabolic and neurological comorbidities in Asian patients with psoriasis and atopic dermatitis.

Although various comorbidities have been noted to be associated with atopic dermatitis (AD) and psoriasis, few studies have compared comorbidities between the two diseases, and little is known about whether these comorbidities vary by the subtypes of psoriasis. In this study of 1:1 age- and sex-matched pair analysis between patients diagnosed with either psoriasis or AD at Asan Medical Center between 1991 and 2020, comorbidities, as determined by the International Classification of Diseases-10 codes, and likelihood ratios of metabolic and neurologic comorbidities in psoriasis compared with AD were studied using a logistic regression model. Among a total of 14,128 patients, the psoriasis group had higher odds of obesity (odds ratio [95% confidence interval]: 1.49 [1.34-1.66]), hypertension (1.14 [1.03-1.26]), diabetes mellitus (1.46 [1.29-1.66]), chronic kidney disease (1.59 [1.22-2.08]), and Parkinson's disease (2.1 [1.15-3.83]) than the AD group. Subgroup analysis revealed that patients with plaque psoriasis had higher odds of obesity (1.18 [1.05-1.33]), hypertension (1.18 [1.06-1.32]), diabetes mellitus (1.53 [1.34-1.75]), chronic kidney disease (1.66 [1.26-2.17]), and Parkinson's disease (2.12 [1.16-3.88]) compared with AD. Meanwhile, guttate psoriasis was associated with higher odds of dementia (3.63 [1.06-12.40]) and patients with generalized pustular psoriasis showed higher odds of diabetes mellitus (5.42 [1.56-18.83]) compared with AD. In conclusion, Asian patients with all types of psoriasis should be closely monitored for the development of metabolic and neurologic diseases, especially men and those aged ≥ 40 years.

A randomized, double-blinded, vehicle-controlled clinical trial of topical cryosim-1, a synthetic TRPM8 agonist, in prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is an intensively pruritic skin disease that negatively influences quality of life. Cryosim-1 (Intrinsic IB Spot) is a synthetic, selective transient receptor potential melastatin 8 agonist. AIMS: To investigate the efficacy and safety of cryosim-1 in PN patients. PATIENTS/METHODS: A randomized, double-blinded, placebo-controlled clinical trial including 30 patients was conducted. The numerical rating scale (NRS) of pruritus was evaluated before and 2 h after cryosim-1 application at every visit. RESULTS: At week 8, the mean pruritus NRS before serum application (4.7 ± 0.4 treatment, 6.1 ± 0.5 placebo; p = 0.045) and 2 h after serum application (2.8 ± 0.4 treatment, 4.3 ± 0.5 placebo; p = 0.031) were significantly lower in the treatment group, and the mean NRS for sleep disorder was significantly lower in the treatment group (2.2 ± 0.5 treatment, 4.2 ± 0.8 placebo; p = 0.031). The mean satisfaction scales for pruritus improvement were significantly higher in the treatment group (7.2 ± 0.6) than in the placebo group (4.0 ± 0.9; p = 0.005). There was no difference in TEWL between the two groups, and no adverse reactions were reported. CONCLUSIONS: Cryosim-1 is a safe and effective topical treatment for PN patients.

Baseline Serum neutrophil-to-lymphocyte ratio in acral melanoma compared with nonacral melanoma and its prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM), a cutaneous melanoma subtype, exhibits a poorer prognosis than nonacral cutaneous melanoma (NACM). The neutrophil-to-lymphocyte ratio (NLR) is emerging as a prognostic indicator across diverse cancers. OBJECTIVE: We explored the baseline NLR disparities between ALM and NACM, and the NLR's prognostic significance in patients with ALM. METHODS: We reviewed records of patients with ALM and NACM diagnosed between 1997 and 2022, analyzing medical data. RESULTS: Among 327 and 159 patients with ALM and NACM, respectively, baseline NLR varied based on distinct clinicopathologic factors between ALM and NACM. In stage 3 to 4 melanomas, the median NLR for ALM (2.18; IQR, 1.70-3.08) significantly surpassed NACM (1.74; IQR, 1.33-2.53) (P = .029). In patients with ALM, high NLR (hazard ratio, 1.64; 95% CI, 1.02-2.66; P = .043) was independently correlated with poor progression-free survival when adjusting for ulceration, Breslow thickness of ≥2 mm, and nodal invasion. LIMITATIONS: Single-center, retrospective design. CONCLUSION: Advanced-stage ALM exhibited a significantly higher baseline NLR compared with that of NACM. Evaluating baseline NLR could provide valuable prognostic insights for patients with ALM.

Morphological characteristics of facial scars: A retrospective analysis according to scar location, onset, age, and cause.

The morphology of facial scars shows a wide variation in terms of texture and colour. To date, there are no reliable predictors of aberrant scarring. We conducted a retrospective analysis to identify factors associated with specific scar features and types. Photographs and medical records of 428 patients with facial scars were retrospectively reviewed. Patients with keloids were excluded. The mean age of the patients was 45.43 ± 23.13 years with a male-to-female ratio of 1:1.36. Atrophic scars were the most common (42.8%), followed by flat scars (38.7%) and hypertrophic scars (18.5%). Scars on the forehead were more likely to be atrophic, whereas scars on the chin/jaw and around the mouth were more likely to be hypertrophic. Hypopigmentation was significantly more common in scars located on the forehead. Redness (erythema) was significantly more common in scars located on the chin/jaw. Old scars were less likely to be erythematous, and hypertrophic. Atrophic scars were more common in younger patients. Scars caused by dermatologic conditions, such as acne, were more likely to be atrophic, whereas surgical scars had the lowest risk of being atrophic or hypertrophic. In conclusion, the location, onset, and cause of facial scars were associated with specific features of scars.

Spatially Resolved Transcriptomes of CD30+-Transformed Mycosis Fungoides and Cutaneous Anaplastic Large-Cell Lymphoma.

Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.

A rare case of secondary cutaneous lymphoplasmacytic lymphoma clinically presenting as acquired cutis laxa.

Lymphoplasmacytic lymphoma (LPL) is a rare variant of non-Hodgkin lymphoma, accounting for <1% of cases. Skin involvement in LPL is quite rare-accounting for approximately 5% of extramedullary disease-and includes a variety of clinical morphologies, such as erythematous-to-violaceous plaques, violaceous nodules or tumors, and ulceration at various anatomical sites. Herein, we report the case of a 45-year-old Korean woman who presented with generalized erythematous indurated plaques and pendulous skin growths, which were asymptomatic, with marked diffuse infiltration of lymphocytes and plasma cells in the dermis. Immunohistochemical studies revealed that the lymphoid cells expressed CD3, CD79a, and cytoplasmic IgG, but lacked CD10 and IgM. Moreover, kappa light chain restriction and monoclonal immunoglobulin heavy chain gene rearrangement were observed. Upon further workup, lymphoma involvement was reported in multiple lymph nodes, including those in the cervical and axillary regions. This case shows a unique form of cutaneous LPL clinically presenting as acquired cutis laxa, emphasizing the dermatologists' need to be vigilant for variant forms of this disease.

Generation of a Melanoma and Nevus Data Set From Unstandardized Clinical Photographs on the Internet.

Importance: Artificial intelligence (AI) training for diagnosing dermatologic images requires large amounts of clean data. Dermatologic images have different compositions, and many are inaccessible due to privacy concerns, which hinder the development of AI. Objective: To build a training data set for discriminative and generative AI from unstandardized internet images of melanoma and nevus. Design, Setting, and Participants: In this diagnostic study, a total of 5619 (CAN5600 data set) and 2006 (CAN2000 data set; a manually revised subset of CAN5600) cropped lesion images of either melanoma or nevus were semiautomatically annotated from approximately 500 000 photographs on the internet using convolutional neural networks (CNNs), region-based CNNs, and large mask inpainting. For unsupervised pretraining, 132 673 possible lesions (LESION130k data set) were also created with diversity by collecting images from 18 482 websites in approximately 80 countries. A total of 5000 synthetic images (GAN5000 data set) were generated using the generative adversarial network (StyleGAN2-ADA; training, CAN2000 data set; pretraining, LESION130k data set). Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) for determining malignant neoplasms was analyzed. In each test, 1 of the 7 preexisting public data sets (total of 2312 images; including Edinburgh, an SNU subset, Asan test, Waterloo, 7-point criteria evaluation, PAD-UFES-20, and MED-NODE) was used as the test data set. Subsequently, a comparative study was conducted between the performance of the EfficientNet Lite0 CNN on the proposed data set and that trained on the remaining 6 preexisting data sets. Results: The EfficientNet Lite0 CNN trained on the annotated or synthetic images achieved higher or equivalent mean (SD) AUROCs to the EfficientNet Lite0 trained using the pathologically confirmed public data sets, including CAN5600 (0.874 [0.042]; P = .02), CAN2000 (0.848 [0.027]; P = .08), and GAN5000 (0.838 [0.040]; P = .31 [Wilcoxon signed rank test]) and the preexisting data sets combined (0.809 [0.063]) by the benefits of increased size of the training data set. Conclusions and Relevance: The synthetic data set in this diagnostic study was created using various AI technologies from internet images. A neural network trained on the created data set (CAN5600) performed better than the same network trained on preexisting data sets combined. Both the annotated (CAN5600 and LESION130k) and synthetic (GAN5000) data sets could be shared for AI training and consensus between physicians.

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.

Risk of incident autoimmune diseases in patients with newly diagnosed psoriatic disease: a nationwide population-based study.

There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective of this study was to assess the risk of autoimmune diseases in patients with newly diagnosed psoriatic disease. Using the Korean National Health Insurance Service database, patients with newly diagnosed psoriatic disease between 2007 and 2019 were included. Comparators were randomly selected and matched according to age and sex. A total of 321,354 patients with psoriatic disease and 321,354 matched comparators were included in this study. Patients with psoriatic disease had a significantly higher risk of Crohn's disease [adjusted hazard ratio (aHR), 1.95; 95% confidence interval (CI) 1.42-2.67], ulcerative colitis (aHR, 1.65; 95% CI 1.39-1.96), systemic lupus erythematosus (aHR, 1.86; 95% CI 1.34-2.57), rheumatoid arthritis (aHR, 1.63; 95% CI 1.52-1.76), ankylosing spondylitis (aHR, 2.32; 95% CI 1.95-2.77), alopecia areata (aHR, 1.41; 95% CI 1.35-1.46), and type 1 diabetes (aHR, 1.23; 95% CI 1.11-1.37). However, the risk of Graves' disease, Hashimoto's disease, Sjögren's syndrome, and systemic sclerosis was not significantly different between the groups. In conclusion, patients with newly diagnosed psoriatic disease may have a significantly increased risk of incident autoimmune diseases.

Cancer risks in patients with psoriasis administered biologics therapy: a nationwide population-based study.

PURPOSE: To assess cancer risks in patients with psoriasis and the effect of TNF-α inhibitor and interleukin (IL)-12/23 inhibitor therapy on those cancer risks. METHODS: Using the Korean Health Insurance Review and Assessment Service database, patients with newly diagnosed psoriasis between 2008 to 2019 were included. Standardized incidence ratios (SIRs) of overall and specific cancers were calculated in patients with psoriasis. The effect of TNF-α inhibitor and IL-12/23 inhibitor exposure on the risk of cancers was assessed by multivariable Cox regression models. RESULTS: In total, 191,678 patients with psoriasis were included in this study. The overall risk of cancer was significantly higher in patients with psoriasis than in the general population (SIR, 1.12; 95% confidence interval (CI), 1.09-1.14). TNF-α inhibitor users had a significantly higher risk for overall cancer (adjusted hazard ratio (aHR), 1.41; 95% CI 1.01-1.97). In contrast, IL-12/23 inhibitor exposure had a significantly lower risk for overall cancer (aHR, 0.57; 95% CI 0.37-0.87). Among specific cancers, the risks of non-Hodgkin lymphoma (aHR, 2.98; 95% CI 1.02-8.69) were increased by TNF-α inhibitor therapy, while the risk of other cancers, including nonmelanoma skin cancer (aHR, 2.31; 95% CI 0.51-10.46), was not significantly altered by TNF-α inhibitor therapy. CONCLUSION: TNF-α inhibitor therapy in psoriasis is associated with a significantly increased risk of overall cancer and lymphoma, while the risk of solid organ cancer was not affected by this therapy. The IL-12/23 inhibitor is not associated with an increased risk of any cancer.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Clinicopathological characteristics and prognosis of Merkel cell carcinoma: a single-center retrospective study in Korea.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with high mortality. However, its clinical characteristics in Asian patients remain uncertain owing to its low incidence. OBJECTIVE: To analyze the clinicopathological features of MCC and identify factors associated with its prognosis. METHODS: The medical records of 62 patients with MCC were retrospectively reviewed. Data on clinical features, survival outcomes, prognostic factors, histopathology and immunohistochemical profile of the patients were collected and analyzed. Merkel cell polyomavirus status was evaluated using immunohistochemistry. RESULTS: The incidence of MCC significantly increased over time. The mean duration of follow-up was 51.2 months, with an overall 5-year survival of 80.6%. More female patients with MCC were identified than male patients (1.3:1). Approximately half of the patients had stage I disease at the time of initial presentation. The primary tumor was frequently located in the lower extremities (40.3%), followed by the head and neck (32.3%), upper extremities (22.6%), and the trunk (4.8%). Male sex was associated with poorer overall survival (p = 0.003). Post-resection adjuvant radiotherapy significantly improved the overall survival (p = 0.023). Sentinel lymph node biopsy during surgery ameliorated the progression-free survival (p = 0.036) in patients with stage I or II cancer. Lymphovascular and perineural invasion were associated with a poor prognosis. Old age, immunohistochemical profiles, and Merkel cell polyomavirus-positivity were not associated with prognosis. CONCLUSION: Post-surgical adjuvant radiotherapy and sentinel lymph node biopsy significantly improve the course of MCC.

Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer.

Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.