What's New in Topicals for Atopic Dermatitis?

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.

Pediatric drug reaction with eosinophilia and systemic symptoms: A systematic review of the literature.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction including integumentary and internal organs. An extensive literature review of DRESS in the pediatric population has not been performed. METHODS: A literature search was performed to find reports of pediatric DRESS published between 1997 and March 2019. If not already included, each case was scored based on RegiSCAR criteria. Only "probable" or "definite" cases of DRESS were included in the analysis, totaling 130 cases. RESULTS: In the pediatric population, the average age of diagnosis for DRESS was 8.7 years old. The most common causative drugs include antiepileptics (50%) and antibiotics (30.8%). Time from drug exposure to DRESS presentation averaged 23.8 days. Common clinical symptoms include rash (99.2%) (typically morbilliform (89.2%)), fever (96.2%), eosinophilia (90%), and lymphadenopathy (74.6%). Human herpesvirus-6 reactivation was observed in 16.1% of cases. The most commonly affected internal organ was the liver (80%), followed by the spleen (21.5%) and kidney (15.4%). Management strategies involved, either alone or in combination, included corticosteroids (intravenous 60.8% and oral 41.5%), intravenous immunoglobulins (12.3%), plasmapheresis (2.3%), and ganciclovir (1.5%). Long-term sequelae occurred in 10.8% of patients, most commonly hypothyroidism (3.8%), liver failure (3.1%), and diabetes (2.3%). The mortality rate was 5.4%. CONCLUSION: This literature review highlights the presentation and course of pediatric DRESS. Morbilliform eruption, fever, and eosinophilia appear to be clinical hallmarks of pediatric DRESS. Common causative agents, specifically carbamazepine, are comparable to the adult population. Furthermore, the mortality rate from DRESS is significant and is similar between pediatric and adult patients.

Intralesional 5-fluorouracil (FU) as a treatment for nonmelanoma skin cancer (NMSC): A review.

The treatment paradigm for nonmelanoma skin cancer remains surgical. This fact combined with its remarkably high incidence positions it as the fifth most costly cancer to treat in the Medicare population. To address this, consideration of alternative medical therapeutics is warranted. Intralesional 5-fluorouracil is a potentially affordable option that may demand further investigation. This literature review examines current data on its efficacy and adverse effects.

An overview of the medical management of nonmelanoma skin cancer.

Importantly, NMSCs are increasing in prevalence, and full recognition of these diseases as life-threatening entities is paramount. Overall, data supporting adjuvant or systemic therapy in NMSCs are limited, but there are enough reports in the literature to suggest some benefit with systemic agents. Where available, we recommend patients investigate clinical trial options, including phase I studies. Newer targeted therapies and activation of the immune system may provide for a dramatic step forward in the management of these diseases; however, formal clinical trials are necessary to establish these new treatments as a standard of care.