Risk of Cutaneous T Cell Lymphoma with Psoriasis Biologic Therapies.

BACKGROUND: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.

Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

The Role of Skin Substitutes in Dermatologic Surgery: A Practical Review.

BACKGROUND: The number of skin substitutes (SS) available for wound care management has increased markedly in the last few decades. This presents a challenge as dermatologists attempt to determine the appropriate setting for a skin substitute use. OBJECTIVE: This is a practical review of SS used in dermatologic surgery to assist clinicians in their selection of SS by providing information about the efficacy, risk, availability, shelf-life, and relative cost of the available options. METHODS AND MATERIALS: Relevant data were identified through a search of PubMed, a manual search of relevant company websites, a manual search of the reference sections of relevant papers, and communicating with subject experts. RESULTS: SS can be divided into 7 categories based on composition: amnion, cultured epithelial autograft, acellular allograft, cellular allografts, xenografts, composites, and synthetics. These groups offer unique benefits and disadvantages that are outlined in the manuscript and tables. CONCLUSION: Considerations of the characteristics, settings of use, and efficacies of SS may allow more effective wound care and the potential for faster healing times. Additional studies are needed to evaluate and compare the healing benefits of these substitutes. Trials comparing the efficacy of each of the common SS vs each other and granulation are needed. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7132.

Mendelian Randomization Studies in Psoriasis and Psoriatic Arthritis: A Systematic Review.

Psoriasis (PSO) and psoriatic arthritis (PSA) are inflammatory diseases with complex genetic and environmental contributions. Although studies have identified environmental and clinical associations with PSO/PSA, causality is difficult to establish. Mendelian randomization (MR) employs the random assortment of genetic alleles at birth to evaluate the causal impact of exposures. We systematically reviewed 27 MR studies in PSO/PSA examining health behaviors, comorbidities, and biomarkers. Exposures, including smoking, obesity, cardiovascular disease, and Crohn's disease, were causal for PSO and PSA, whereas PSO was causally associated with several comorbidities. These findings provide insights that can guide preventive counseling and precision medicine.

Biologic insights from single-cell studies of psoriasis and psoriatic arthritis.

INTRODUCTION: Psoriasis (PSO) and psoriatic arthritis (PSA) represent a large burden of global inflammatory disease, but sustained treatment response and early diagnosis remain challenging. Both conditions arise from complex immune cell dysregulation. Single-cell techniques, including single-cell RNA sequencing (scRNA-seq), have revolutionized our understanding of pathogenesis by illuminating heterogeneous cell populations and their interactions. AREAS COVERED: We discuss the transcriptional profiles and cellular interactions unique to PSO/PSA affecting T cells, myeloid cells, keratinocytes, innate lymphoid cells, and stromal cells. We also review advances, limitations, and future challenges associated with single-cell studies. EXPERT OPINION: Following analyses of 22 single-cell studies, several themes emerged. A small subpopulation of cells can have a large impact on disease pathogenesis. Multiple cell types identified via scRNA-seq play supporting roles in PSO pathogenesis, contrary to the traditional paradigm focusing on IL-23/IL-17 signaling among dendritic cells and T cells. Immune cell states are dynamic, with psoriatic subpopulations aberrantly re-activating and differentiating into inflammatory phenotypes depending on surrounding signaling cues. Comparison of circulating immune cells with resident skin/joint cells has uncovered specific T cell clonotypes associated with the disease. Finally, machine learning models demonstrate great promise in identifying biomarkers to diagnose clinically ambiguous rashes and PSA at earlier stages.

Management of full-thickness skin grafts.

Full-thickness skin grafts are a commonly used reconstructive method following Mohs micrographic surgery. The literature varies on the most appropriate methods of suturing and securing grafts as well as best practices to dress the graft postoperatively. Our objective was to review various approaches to management of full-thickness skin grafts, including suturing the graft, securing the graft, and topical emollient use on the graft postoperatively. It was found that absorbable sutures, plain gut, provide preferable outcomes with full-thickness skin grafts. The tie-over bolster is the most-used method for securing skin grafts after placement, although several other methods have demonstrated efficacy, including the polyurethane foam, sandwich, and quilting suture methods. While various topical emollients are used in the immediate postoperative period, plain white petrolatum is the least likely to form allergic contact dermatitis.

The presence of idiopathic thrombocytopenic purpura correlates with lower rate of acute ST-elevation myocardial infarction.

Background: Platelets are important in the pathogenesis of myocardial infarction (MI). We hypothesize that patients with acquired thrombocytopenia such as idiopathic thrombocytopenic purpura (ITP) may have lower MI rate. Materials & method: The Nationwide Inpatient Sample was used for this study. We analyzed the correlation between ST-elevation MI (STEMI) and ITP utilizing ICD-9 codes. Results: STEMI rate was lower in patients with ITP. We found that, in 2002, STEMI occurred in 0.64% of patients with ITP versus 0.89 (p < 0.007) and for 2011 0.30 versus 0.48 (p < 0.005). After adjusting for tobacco use, diabetes, hypertension, hyperlipidemia, gender and age, STEMI rate remained lower in ITP patients. Conclusion: ITP appears to be associated with lower STEMI rate suggesting low platelet count may exert protective effect from STEMI.

Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection.

Sofosbuvir-velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

Does breastfeeding protect children from asthma? Analysis of NHANES III survey data.

We sought to determine whether breastfeeding (yes/no) or its duration protects against the development of childhood asthma, its severity or age of onset. We conducted a secondary analysis of youth files of the National Health and Nutrition Examination Survey III (1988-94), and reviewed data from 6,783 children age 2 months to 6 years (3,316 breastfed), excluding children with a history of low birth weight or treatment in a neonatal intensive care unit. Study participants were breastfed an average of 157 days. The average age at onset of asthma was 14.3 months. In the logistic regression model, "ever breast-fed" was not a significant protective factor for developing asthma. Significant predictive factors were the mother's age at child's birth (beta = -0.08, p < 0.01), and a parent having asthma or hayfever (beta = 0.46, p < 0.01). In the linear regression model, the duration of breastfeeding was not a predictor for age at onset of asthma (beta = 0.01, p = 0.53). Only maternal smoking during pregnancy was a significant predictor of age at onset of asthma (beta = -7.59, p < 0.01). Breastfeeding does not appear to prevent asthma, delay its onset, or reduce its severity. However, breastfeeding is still recommended for its many other benefits.