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.

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.

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.

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.

Performance of PRAME immunohistochemistry compared with that of c-Kit, c-Myc, or cyclin D1 for the diagnosis of acral melanocytic tumors.

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.

Association between psoriasis and alopecia areata: A systematic review and meta-analysis.

The association between psoriasis and alopecia areata has not been thoroughly investigated. The objective of this study is to investigate the association of psoriasis with alopecia areata. An electronic search was conducted in August 2021. The analysis included studies that reported sufficient data on the prevalence, odds, or hazard of alopecia areata in patients with psoriasis or that of psoriasis in patients with alopecia areata. Meta-analysis using an inverse variance method was performed with a random-effects model, assuming inherent heterogeneity between the included studies. The subgroup analyses were performed according to the age group and study quality. A total of 27 studies were included. The pooled prevalence of alopecia areata among patients with psoriasis was 0.5% (95% confidence interval [CI], 0.3-0.7%). The pooled odds ratio of alopecia areata among patients with psoriasis was 2.71 (95% CI, 2.29-3.21), whereas the pooled prevalence of psoriasis among patients with alopecia areata was 2.5% (95% CI, 2.0-3.0%). Moreover, the pooled odds ratio of psoriasis among patients with alopecia areata was 3.52 (95% CI, 1.27-9.74). The association of psoriasis and alopecia areata remained in the subgroup analyses according to the age group and study quality. In conclusion, this study suggests a bidirectional association between psoriasis and alopecia areata. Clinical examinations may be necessary to determine the presence of comorbid alopecia areata in patients with psoriasis and vice versa.

Clinicopathological Factors Associated with the Prognosis and Chronicity of Lymphomatoid Papulosis: A Retrospective Cohort Study.

BACKGROUND: The clinical and pathological features of lymphomatoid papulosis (LYP) are diverse. The objective of this study is to evaluate the clinical and pathological features associated with the prognosis and clinical course of LYP. PATIENTS AND METHODS: The clinical and pathological features of LYP in a medical center database were retrospectively retrieved. RESULTS: Overall, 58 LYP patients were included in the study. The mean age at diagnosis was 39.1 years and the female-to-male ratio was 1:1.2. More than two-thirds (40/58, 69.0%) of the patients showed a chronic and recurrent disease course. A longer pre-diagnosis duration (odds ratio (OR), 1.01; 95% confidence interval (CI), 1.00-1.03) was significantly associated with secondary lymphoma development. Lower extremity involvement (OR, 10.40; 95% CI, 1.17-92.28) and the absence of eosinophils in the lesions (OR, 11.28; 95% CI, 1.01-126.24) were found to be significantly associated with the chronic and recurrent course of LYP. CONCLUSION: A longer pre-diagnosis duration is associated with secondary lymphoma, while a lower extremity involvement and the absence of lesional eosinophil infiltration are associated with the chronicity of LYP.

Clinical implications of facial psoriasis in children and adolescents.

BACKGROUND/OBJECTIVES: The clinical implications of facial involvement in pediatric patients with psoriasis have not been adequately studied. The objectives of this study are to evaluate the association between facial involvement and clinical features including disease severity of psoriasis in children and adolescents. METHODS: The clinical features of patients aged below 20 years diagnosed with psoriasis were retrospectively evaluated and grouped based on the presence or absence of facial involvement at presentation. Demographic and clinical data were compared between groups. RESULTS: Of the 175 patients, 110 patients (62.9%) had facial involvement of psoriasis at presentation. The group with facial involvement was significantly younger at disease onset (p = .032) and had a higher body mass index (BMI) (p = .043) and psoriasis area and severity index (PASI) score (p <.001). The severity of pruritus was significantly higher in the facial than in the non-facial group (p = .020). Involvement of the nose was associated with the highest disease severity as assessed by the PASI score and affected body surface area. A significantly higher number of treatment modalities were used in the facial group than in the non-facial group (p = .013). The BMI (odds ratio (OR), 1.39; 95% CI (confidence interval), 1.07-1.80) and PASI score (OR, 1.45; 95% CI, 1.03-2.03) were independent factors associated with facial involvement of psoriasis. CONCLUSIONS: Facial involvement in psoriasis was associated with higher disease severity and more treatment modalities in children and adolescents.

A randomized, double-blind, multi-center, placebo-controlled, Phase 2 clinical trial to evaluate the efficacy and safety of DWJ211 in the treatment of moderate to severe submental fat.

Excessive accumulation of submental fat (SMF) causes a lower face cosmetic problem. A lipolytic injectable has recently been developed as a solution. The objective of this study is to investigate the effects and safety of DWJ211 (a newly developed lipolytic injectable) in the reduction of SMF and to identify the optimum dose. In this multi-center, double-blind, placebo-controlled study, subjects with moderate to severe SMF were randomized to injections of DWJ211 0.5%, DWJ211 1%, DWJ211 2% or placebo in the submental area, every 4 weeks, up to Week 12. Efficacy was determined by improvements in physician-assisted SMF rating scales (PA-SMFRS) and subject-assisted SMF rating scales (SA-SMFRS) 4 weeks after the last treatment (Week 16). Safety was assessed by inquiries, subject diary entries of adverse events, laboratory tests, and vital sign checks. Of 140 enrolled subjects, 136 were included in the analysis. The proportions of subjects, who achieved ≥1-grade improvement on the PA-SMFRS were 41.7%, 65.7%, 84.4%, and 72.7%, and the proportions of subjects, who achieved ≥1-grade improvement on the SA-SMFRS were 50.0%, 71.4%, 93.8%, and 81.8% for the placebo, DWJ211 0.5%, DWJ211 1%, and DWJ211 2% group, respectively. Adverse drug reactions (ADRs) were more common in each of the treatment groups compared with placebo, with the most common ADR being injection site pain. No subjects experienced any serious adverse events. In conclusion, the 1% DWJ211 dose was beneficial for SMF reduction and had a tolerable safety profile. Thus, we selected 1% as the dose to be tested in a Phase 3 clinical trial.

Evaluation of Artificial Intelligence-Assisted Diagnosis of Skin Neoplasms: A Single-Center, Paralleled, Unmasked, Randomized Controlled Trial.

TRIAL DESIGN: This was a single-center, unmasked, paralleled, randomized controlled trial. METHODS: A randomized trial was conducted in a tertiary care institute in South Korea to validate whether artificial intelligence (AI) could augment the accuracy of nonexpert physicians in the real-world settings, which included diverse out-of-distribution conditions. Consecutive patients aged >19 years, having one or more skin lesions suspicious for skin cancer detected by either the patient or physician, were randomly allocated to four nondermatology trainees and four dermatology residents. The attending dermatologists examined the randomly allocated patients with (AI-assisted group) or without (unaided group) the real-time assistance of AI algorithm (https://b2020.modelderm.com#world; convolutional neural networks; unmasked design) after simple randomization of the patients. RESULTS: Using 576 consecutive cases (Fitzpatrick skin phototypes III or IV) with suspicious lesions out of the initial 603 recruitments, the accuracy of the AI-assisted group (n = 295, 53.9%) was found to be significantly higher than those of the unaided group (n = 281, 43.8%; P = 0.019). Whereas the augmentation was more significant from 54.7% (n = 150) to 30.7% (n = 138; P < 0.0001) in the nondermatology trainees who had the least experience in dermatology, it was not significant in the dermatology residents. The algorithm could help trainees in the AI-assisted group include more differential diagnoses than the unaided group (2.09 vs. 1.95 diagnoses; P = 0.0005). However, a 12.2% drop in Top-1 accuracy of the trainees was observed in cases in which all Top-3 predictions given by the algorithm were incorrect. CONCLUSIONS: The multiclass AI algorithm augmented the diagnostic accuracy of nonexpert physicians in dermatology.

Hyperpigmented mycosis fungoides: a retrospective and comparative analysis with other subtypes of mycosis fungoides.

In this study, the clinicopathologic features and survival outcomes of patients with hyperpigmented MF from a single tertiary referral center database were retrospectively evaluated. Hyperpigmented MF accounted for 10.9% (14/128) of all MF cases. The mean age at diagnosis was 46.9 years, and the female-to-male ratio was 1:1.3. Concurrent hypopigmented, ichthyosiform, and poikilodermatous lesions were detected in 21.4%, 14.3%, and 14.3% of the patients, respectively. Histopathologically, most patients (85.7%) showed interface change with pigment incontinence. Double negative (CD4- and CD8-) immunophenotypes were more frequent in patients with hyperpigmented MF (25%) than in those with other MF subtypes (9.8%). Most patients (85.7%) had early-stage disease at diagnosis. The survival outcomes did not differ significantly between hyperpigmented and other MF subtypes. In conclusion, hyperpigmented MF often accompanies other atypical MF variants and is frequently associated with atypical immunophenotypes. The outcomes of hyperpigmented MF are comparable to those of other MF subtypes.