Search

Pemphigus represents a spectrum of potentially life-threatening autoimmune-mediated skin blistering conditions caused by antibody production against desmoglein 1 and 3 (anti-DSG 1 and 3) in keratinocytes. Greater than 50% of pemphigus patients experience relapse, which complicates long-term medical management, including risks associated with re-treatment and complications such as infection and dehydration. This review aims to elucidate mechanisms, risk factors, and medications associated with pemphigus relapse. Mechanisms of relapse include the persistence of auto-reactive B-cell populations post-treatment and CD20- B-cell populations that reactivate after B-cell depletion therapy. Risk factors for relapse include high body surface area (BSA) of pemphigus involvement, high body mass index, high severity according to the Pemphigus Disease Area Index (PDAI) at onset, treatment delay, and high anti-DSG1 and DSG3 titers post-treatment. Targeted B-cell localization is associated with better clinical outcomes, including less frequent relapses. Rituximab is currently the gold standard of treatment for moderate-severe pemphigus and has relapse rates of 11%-44% in selected studies, with a mean time to relapse of 5.8 months to 36 months following treatment. Relapse rates across lymphoma dosing (375 mg/m 2 ) versus rheumatoid arthritis dosing (1 g dosing weekly) was inconsistent; however, more frequent dosing, earlier treatment, and higher cumulative dosing were associated with lower relapse rates. Alternative agents that have clinical efficacy include corticosteroid monotherapy, mycophenolate mofetil, azathioprine, and intravenous immunoglobulin. Future studies should include head-to-head comparators over long follow-up periods to identify the best treatment agents associated with the least relapse risk., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Competing Interests: Dr Rao is a speaker for Incyte. The other authors have no conflicts of interest to declare.

Pemphigus represents a spectrum of autoimmune-mediated blistering diseases associated with high morbidity, mortality and reduced quality of life (QoL). Despite an increase in pemphigus clinical trials, the varied instrument measurements of disease severity and QoL outcomes make comparisons between studies challenging. This study aimed to evaluate trends in the use of disease severity and QoL outcome measurements in pemphigus clinical trials. A review of pemphigus clinical trials was conducted using the PubMed, Embase, Cochrane Reviews and ClinicalTrials.gov databases up until September 2023. Only pemphigus randomized clinical trials that assessed at least one disease severity and/or QoL outcome were included. Overall, 53 clinical trials were eligible for this review. All clinical trials evaluated a disease severity outcome, with the Pemphigus Disease Area Index being the most used validated questionnaire (28.3% of trials) and more popular after 2015 (47.8% of trials since). The autoimmune bullous skin disorder intensity score (7.6%) and visual analogue measurements (7.6%) have fallen out of favour. Most studies now include lab parameters (56.5% of trials after 2015), with anti-desmoglein 1 and 3 antibody levels (30.2%), immunoglobulins (IgG and/or IgM and IgA) (11.3%), and anti-drug antibody levels (7.6%) being frequently evaluated. A small portion of trials evaluated QoL (26.5% of studies), with the autoimmune bullous quality of life being the most common (15.1%), however QoL utilization as an outcome measure has been increasing since 2015 (61.1% of trials since). Standardising the use of validated outcome measurements allows for better data interpretation, comparability and clinical application of results., Competing Interests: Dr. Rao is a speaker for Incyte and Amgen. The authors declare no conflicts of interest., (© 2024 The Author(s). Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH., Materials and Methods: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality., Results: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort., Conclusions: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort., Competing Interests: Conflicts of interest None., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP)., Data Sources: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023., Study Selection and Data Extraction: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included., Data Synthesis: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 ( P = 0.0005), 0.35 ( P = 0.0057), and 0.47 ( P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab., Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents., Conclusion: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SRF has received research, speaking and/or consulting support from AbbVie, Accordant, Almirall, Alvotech, Amgen, Arcutis, Arena, Argenx, Biocon, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Eurofins, Forte, Galderma, Helsinn, Janssen, Leo Pharma, Micreos, Mylan, Novartis, Ono, Ortho Dermatology, Pfizer, Regeneron, Samsung, Sanofi, Sun Pharma, UCB, Verrica, Voluntis, and vTv Therapeutics. He is founder and part owner of Causa Research and holds stock in Sensal Health. BKR is a speaker for Incyte. All other authors have no conflicts of interest to declare.

Background: Fairness products are an essential component of daily beauty routines for many individuals in subcontinental Asia. However, it is important to be aware that these products often contain ingredients that can be detrimental to the skin and are banned in several developed countries., Objective: Our study aims to analyze the content of fairness cream commercials in order to gain a deeper understanding of the information used to persuade and influence consumers to use these products., Methods: Fairness cream commercials originating from countries in subcontinental Asia, including India, Pakistan, Bangladesh, Sri Lanka, and Nepal, were specifically searched and analyzed on the YouTube platform., Results: An analysis of 152 fairness cream commercials on YouTube identified 84.21% of commercials targeted female consumers, while only 15.79% targeted male consumers. 77.63% of commercials used celebrities in their commercials and 47.37% of commercials mentioned specific ingredients., Conclusions: Based on our findings, it is crucial for dermatologists to take an active role in educating patients and consumers about the potential risks associated with certain ingredients found in fairness creams. Dermatologists should emphasize the importance of prioritizing overall skin health rather than solely focusing on skin lightening., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: The objective of this study was to review the safety and efficacy of deucravacitinib, a tyrosine kinase 2 (TYK2) inhibitor for moderate to severe plaque psoriasis., Data Sources: Literature was reviewed from MEDLINE and Clinicaltrials.gov up to December 2022 using the terms "deucravacitinib" and "BMS-986165.", Study Selection: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of deucravacitinib were included. A total of 6 trial results were included., Study Selection and Data Extraction: Deucravacitinib showed clinical efficacy across all the phase II and III clinical trials. Excluding the long-term extension study, there were 2248 subjects across all studies, with 63.2% of patients receiving deucravacitinib 6 mg daily. Of these subjects, the average proportion achieving a PASI 75 (a reduction of greater than 75% in the Psoriasis Area and Severity Index) at week 16 was 65.1%. Patients receiving deucravacitinib 6 mg once daily had a higher rate of achieving both PASI 75 response and a Static Physician's Global Assessment (sPGA) score of 0 or 1, compared with oral apremilast 30 mg twice daily. The safety profile of deucravacitinib includes mild adverse events (AEs), most commonly nasopharyngitis, with serious AEs reported ranging from 1.35% to 9.5%., Relevance to Patient Care and Clinical Practice in Comparison With Existing Medications: While many available therapies for moderate to severe plaque psoriasis rely on an injectable dosage form or extensive monitoring, deucravacitinib can potentially reduce patient medication-related burden. This review summarizes the efficacy and safety of oral deucravacitinib for the treatment of severe plaque psoriasis., Conclusion: Deucravacitinib shows a consistent efficacy and safety profile as the first oral TYK2 inhibitor approved for adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy or phototherapy treatment., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Approximately 0.7% of patients taking angiotensin-converting enzyme inhibitors (ACEIs) develop ACEI-induced angioedema (ACEI-IA). With no approved treatments for ACEI-IA, the risk of complications is concerning. Tranexamic acid (TXA) has the potential to prevent intubations and resolve ACEI-IA by inhibiting the downstream production of bradykinin. In this review, we aim to evaluate the safety and efficacy of TXA use in ACEI-IA. We queried the PubMed database for studies involving TXA for ACEI-IA from January 2003 to January 2023. Seven studies met the study inclusion criteria. Our results demonstrate that TXA may improve angioedema symptoms and prevent intubation. In addition, its availability, low cost, and safety profile support its use for improving the symptoms and complications of ACEI-IA in an emergency setting.

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making., Competing Interests: Dr. Rao is a speaker for Incyte. All other authors have no disclosures., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)