Topical Treatment Of Atopic Dermatitis Research Articles

Oral and topical administration of a geranyl acetophenone attenuates DNCB-induced atopic dermatitis-like skin lesions in BALB/c mice

Atopic dermatitis (AD) is a chronic, allergic inflammatory skin disorder that lacks a definite cure. Using a mouse DNCB-induced AD-like skin lesions model, this study evaluated the potential therapeutic utility of tHGA as an oral and topical treatment for AD. Male BALB/c mice were sensitised and challenged with 1% and 0.5% DNCB on their shaved dorsal skin. Mice in the treatment group were administered tHGA (20, 40, and 80 mg/kg) orally three times per week for 2 weeks, or tHGA (0.2%, 1%, and 5%) topically once daily for 12 days. On day 34, the mice were euthanized, and blood and dorsal skin samples were obtained for analysis. All doses of orally and topically administered tHGA significantly improved scratching, epidermal thickness, blood eosinophilia and mast cell infiltration. There was a minor discrepancy between the two routes of administration, with orally treated tHGA showing significant reductions in Scoring of Atopic Dermatitis (SCORAD), tissue eosinophil infiltration, serum IgE and skin IL-4 levels with treatment of 40 and 80 mg/kg tHGA, whereas topically applied tHGA showed significant reductions in all dosages. These findings suggest that tHGA exhibited therapeutic potential for AD as both oral and topical treatment ameliorates AD-like symptoms in the murine model.

Activated zinc pyrithione in topical treatment of atopic dermatitis: a case report

Atopic dermatitis is a systemic multifactorial genetically determined inflammatory skin condition characterized by an impairment of the epidermal barrier and Type 2 inflammation. Atopic dermatitis is highly prevalent, especially among children. Many authors consider atopic dermatitis as the initial stage of the atopic march, which typically manifests in the first year of life. Topical agents such as topical glucocorticosteroids and topical calcineurin inhibitors are the first-line treatments for atopic dermatitis. In recent years, there has been an increasing use of modern systemic anti-inflammatory agents, such as monoclonal antibodies and Janus kinase inhibitors. Therapy of patients with atopic dermatitis is aimed at relieving itching, improving skin barrier function, reducing inflammation, preventing skin infection and exacerbations. The effectiveness of treatment lies not only in improving the symptoms and quality of life of patients with atopic dermatitis, but also in preventing them from developing chronic or severe symptoms. Modern topical glucocorticosteroids and their combinations, have a proven high safety profile. However, available data on adverse events associated with their use often lead patients and their parents to develop a negative, phobic attitude towards treatment with these drugs. Zinc pyrithione, an activated form of zinc, is a safe and highly effective medication with anti-inflammatory, antifungal, and antibacterial properties. This article presents two clinical cases of moderate to severe atopic dermatitis in children, demonstrating the effectiveness of using activated zinc pyrithione in comprehensive therapy for this condition.

Adolescent with severe atopic dermatitis and comorbid joit disease: remission achievement by selective JAK1-inhibitor treatment

Atopic dermatitis is a heterogenous in terms of inflammatory pathways and severity prognosis skin disease. The typical clinical manifestations of the disease are intense itching and eczematisation of the skin. The prevalence of atopic dermatitis is markedly higher in children than in adult patients. Persistence of clinical manifestations and recurrent exacerbations of the disease in adolescents can determine the prognosis for decades of working age, leading to a decrease in the quality of life, socialisation and educational success. Some patients demonstrate severe recurrent course of the disease which do not respond on standard topical anti-inflammatory preparations. Comorbid diseases (not only atopic ones) could serve additional factors complicating atopic dermatitis control achievement. The adolescent patient (well-known for low adherence to topical treatment) could become a special difficulty in clinical management. A clinical case of successful systemic therapy (upadacitinib 15 mg once daily) of severe atopic dermatitis patient comorbid with immunologically-driven joint disease presented. Previous topical treatment of atopic dermatitis was inefficient. Effectiveness (indexes SCORAD and DLQI, digital itch scale) and safety (laboratory data and complains) were evaluated for more than 1 year (15 months) of therapy. Rapid and sustain positive changes in course control of atopic dermatitis with possible T2-associated and other inflammatory mediators were demonstrated.

New Topical Treatment for Atopic Dermatitis

The primary approach for managing atopic dermatitis (AD) involves the use of topical corticosteroids as the first-line treatment.While high-potency topical corticosteroids have shown to be effective, they come with an increased risk of local and, rarely, systemic adverse effects. Additionally, patients often experience a relapsing and remitting course. A revolutionary topical treatment for psoriasis and AD has recently received patent approval from the Spanish Ministry of Industry, Trade, and Tourism. This innovative treatment, presented in the form of a lotion, includes a combination of clobetasol, papaverine hydrochloride, spironolactone, a milk-peptide complex, and propylene glycol. An 18-year-old female presented with AD on the back of her neck and scalp. The patient had no significant past medical history and primarily complained of intense pruritus in the AD lesions. The patient received guidance to apply our recently patented lotion, Psorisbye, once a day for 5 days. In total, 50 ml of Psorisbye was utilized over 4 days. On the fifth day, the patient underwent an examination at the outpatient clinic. The patient reported a significant improvement in pruritus sensations and observed a reduction in scaled lesions. Upon evaluating our patient, a comparison of the lesions before and after applying the topical treatment for 4 days revealed a notable improvement in the SCORAD index, decreasing from 49.95 to 0. While the results of Psorisbye in this case show promise, it is crucial to conduct further studies with larger sample sizes and extended follow-up periods to validate the findings presented in our case report.

Commentary: A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Commentary: A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Exploration of costunolide derivatives as potential anti-inflammatory agents for topical treatment of atopic dermatitis by inhibiting MAPK/NF-κB pathways

Atopic dermatitis (AD) is a common inflammatory disease and it is very difficult to treat. In the present work, a series of costunolide derivatives have been prepared, and in vitro and in vivo anti-inflammatory activities have evaluated. The results showed that most derivatives displayed good inhibition of NO generation with low cytotoxicity, and 7d could inhibit the phosphorylation of P38, P65 NF-κB and IκB-α in LPS-induced RAW264.7 model. The in vivo researches showed that 7d could improve skin injury symptoms, decrease Th2-type cytokine levels, inhibit HIS levels, alleviate scratching and repaire the damaged skin barrier through the inhibition of phosphorylation of MAPK and NF-κB signaling pathways on MC903-induced AD model. Therefore, costunolide derivatives may be new potent anti-AD agents for further study.

Integrative Approaches to Sleep Management in Skin Disease: Systematic Review.

Dermatological conditions, especially when severe, can lead to sleep disturbances that affect a patient's quality of life. However, limited research exists on the efficacy of treatments for improving sleep parameters in skin conditions. The objective was to perform a systematic review of the literature on dermatological conditions and the treatments available for improving sleep parameters. A literature review was performed using the PubMed, Ovid MEDLINE, Embase, Cochrane, and ClinicalTrials.gov databases from 1945 to 2021. After filtering based on our exclusion criteria, studies were graded using the SORT (Strength of Recommendation Taxonomy) algorithm, and only those receiving a grade of "2" or better were included. In total, 25 treatment studies (n=11,025) assessing sleep parameters related to dermatological conditions were found. Dupilumab appeared to be the best-supported and most effective treatment for improving sleep in atopic dermatitis (AD) but had frequent adverse effects. Topical treatments for AD were mostly ineffective, but procedural treatments showed some promise. Treatments for other conditions appeared efficacious. The evaluation of sleep parameter changes in dermatological treatments is predominantly restricted to AD. Systemic interventions such as dupilumab and procedural interventions were the most efficacious. Sleep changes in other dermatoses were limited by a paucity of available studies. The inclusion of a sleep assessment component to a broader range of dermatological treatment studies is warranted.

A comparative randomized clinical trial evaluating the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment of atopic dermatitis in children.

Background: Atopic dermatitis (AD) aetiology is not exactly identified, but it is characterized by pruritic skin reactions with elevation in the levels of inflammatory markers. Despite the fact that Corticosteroids are the mainstay therapy in the management of AD, they have many local and systemic adverse effects. Objective: The aim of this study is to evaluate the efficacy and safety of topical tacrolimus ointment in comparison to topical hydrocortisone cream in the management of the AD of children diagnosed with AD. Patients and Methods: This study was conducted on 200 children with AD. They were simply randomized into two groups, the tacrolimus group treated with 0.03% topical tacrolimus ointment and the hydrocortisone group treated with 1% hydrocortisone cream twice daily during the 3weeks study period. Results: At the end of the study, both the tacrolimus and hydrocortisone groups showed a significant decline in the mean serum level of IL-10, IL-17, and IL-23 (p < 0.05) when compared to their baseline levels. However, the tacrolimus group showed a more significant decrease (p < 0.05) in the mean serum level of IL-10, IL-17, and IL-23 as compared to the hydrocortisone group [Mean differences = 1.600, 95% CI: 0.9858-2.214; 1.300, 95% CI: 1.086-1.514 and 4.200, 95% CI: 3.321-5.079]. Moreover, the median mEASI decreased similarly from 32 to 21 in the tacrolimus group and from 30 to 22 in the hydrocortisone group (p > 0.05) [Median difference = -2.000, 95% CI: -2.651 to -1.349; Median difference = 1.000, 95% CI: 0.3489-1.651]. Mild to moderate transient stinging and erythema were the main adverse effects that showed higher incidence in the tacrolimus group than in the hydrocortisone group (p < 0.05). In most cases, they resolved within 3-4days. Besides, tacrolimus ointment did not cause skin atrophy as compared to the hydrocortisone group (p < 0.05). Conclusion: Tacrolimus ointment is more beneficial than hydrocortisone cream in managing AD in children in terms of lowering the inflammatory markers, however, there is no difference on the dermatitis severity scale. Moreover, tacrolimus is safer with a better side effect profile compared to hydrocortisone. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05324618).

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials

BackgroundAtopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. ObjectivesWe systematically synthesized the benefits and harms of AD prescription topical treatments. MethodsFor the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to September 5, 2022 for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using seven classes—group 1 being most potent. OSF: https://osf.io/q5m6s. Results219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty, pimecrolimus improved six of seven outcomes—among the best for two; high-dose tacrolimus (0.1%) improved five—among the best for two; low-dose tacrolimus (0.03%) improved five—among the best for one. With moderate-to-high certainty, group 5 TCS improved six—among the best for three; group 4 TCS and delgocitinib improved four—among the best for two; ruxolitinib improved four—among the best for one; group 1 TCS improved three—among the best for two. These interventions did not increase harms. Crisaborole and difamilast were intermediately effective, but uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. ConclusionsFor individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

A case series evaluating the efficacy of herbal oil-based Bambusa vulgaris (Bamboo) leaf extracts as a topical treatment for atopic dermatitis

BackgroundAtopic dermatitis (AD) is a chronic, immune-mediated inflammatory skin disease and incurable that affects both children and adults. Up-to-now, there is no established animal model for AD that can be used in treatment experiments hence it challenges. This case series study aimed to describe the primary clinical treatment outcomes in volunteers with AD when using herbal oil-based bamboo leaf extracts. MethodsDerma gel's ingredients includes: (a) Total Bamboo leaf extracts (50%); (b) Mixed herbal oils (olive, curcumin, coconut, sweet gourd in equal volume, 10%); (c) Vaseline (40%) (d) Skin penetration enhancement additives. It was tested for safety and fast antimicrobial activity before using as a supportive AD treatment. From January to December 2022, 9 cases of AD (ranging from mild to severe) were recruited, including children and adult. The patients applied Derma gel with total bamboo leaf extracts three times a day for three months. The Three Item Severity (TIS) score was used to assess the severity of AD, which included evaluating erythema, edema, papulation, and excoriation at baseline and after 3 months of follow-up. ResultsAmong the 9 AD participants (2 mild, 3 moderate, and 4 severe), 8 out of 9 regardless of the severity of their condition or age, experience with corticosteroids became asymptomatic AD after 3 months of using Dermal gel. ConclusionThese primary results suggested that Bambusa vulgaris leaf extracts could potentially be effective in alleviating AD symptoms and promoting asymptomatic periods. To further validate these findings, additional investigation through randomized clinical trials is necessary. If confirmed, these results could contribute to the development of a novel topical herbal medicine for AD treatment.

H10 An Oscar for Lassar

Abstract Oscar Lassar (1849–1907) was born in Hamburg to a wealthy merchant family and received a top-class education. After enrolling in the school of medicine at Heidelberg, he volunteered for military service at the outbreak of the Franco–Prussian war in 1870. He served on the front line, was promoted to officer in reserves and decorated with the Iron Cross for his bravery. He returned to complete his medical training and would eventually open a dermatology hospital in Berlin, which unified patient care, research and teaching. In only a few years this hospital would become world renowned. Catering for both inpatient and outpatient care, he was able to offer a wide range of treatments, including complex topical therapy, electrotherapy and surgical procedures. His pasta salicylica (Lassar’s paste) remains to this day a great topical treatment for atopic dermatitis. Lassar recognized the importance of an experienced nursing team to support these activities. Furthermore, he understood the importance of a well-equipped dermatology department and was quick to acquire innovative technology to expand therapeutic options, including X-ray equipment for the treatment of tumours and a Finsen carbon arc lamp for treating lupus vulgaris, thus augmenting his reputation as a Wunderarzt. Lassar made great contributions towards solidifying dermatology as a highly regarded speciality through the establishment of journals and speciality societies. He involved himself in public health measures by campaigning for the establishment of public baths, which would allow even the poorest in society to enjoy clean water facilities at a low cost, thereby reducing the spread of infectious diseases. As a man, he was described as a larger-than-life character with a personal style that meant newspapers gladly reported on his activities, making him an excellent public relations master. Lassar’s recreation was chiefly riding and driving. He was an excellent linguist, an admirable host and fond of children, for whom he wrote Geschichten und Gedichten fiir kleine Kinder (Stories and Poems for Little Children). He died in an automobile accident and his burial on Christmas Eve was marked nationally by the German newspapers, and internationally by his patients and colleagues. In Lassar, we have a great historical example of effective visionary leadership that enabled the expansion of dermatological practice and the promotion of patient care at the time.

430 Comparison of effectiveness of topical treatments for atopic dermatitis

Abstract Atopic dermatitis (AD) is a chronic inflammatory condition that affects 15% of children and 7.3% of adults in the USA. While topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs) are considered the mainstay of topical treatments for AD management, long-term use is cautioned due to possible adverse effects (AEs). We present and review the efficacy and safety of new FDA-approved topical agents, topical agents currently in clinical trials, and TCs and TCIs that are currently available for AD management. We also present and compare the safety and efficacy of new and old FDA-approved topical agents, along with other topical treatments that are currently in clinical trials for AD management. An extensive review of the literature was performed using the PubMed, Cochrane, Scopus and ClinicalKey databases with year parameters set between 2014 and 2022. Search keywords included ‘atopic dermatitis’, ‘topical treatments’, ‘comparison’, ‘effectiveness’, ‘new topical treatments for AD’, ‘JAK inhibitors’, ‘PDE-4 inhibitors’, ‘delgocitinib’, ‘crisaborole’ and ‘tapinarof’. We identified four topical drug classes that are efficacious in treating AD: corticosteroids, calcineurin inhibitors, phosphodiesterase-4 (PDE-4) inhibitors and aryl hydrocarbon receptor agonists. Criteria for treatment success were an IGA score of 0 or 1 and improvement ≥2 grades from baseline. Treatment varied among studies from 2 to 24 weeks. Topical corticosteroids were the most effective after adjusting for vehicle (0.05% clobetasol propionate emulsion foam, 38%; 0.1% clocortolone pivalate, 31.6% IGA reduction), followed by tapinarof 1% cream with 29% of patients achieving treatment success, TCIs (0.03% tacrolimus ointment, 24.8%; 1% pimecrolimus cream, 32.1% vehicle-adjusted achieving IGA of ≤2) and PDE-4 inhibitors (2% crisaborole ointment, 10.4%). Tapinarof was the most efficacious in treating AD. There is a lack of head-to-head trials for topical treatments for AD. Due to the tremendous burden of AD on patients’ physical and mental health, there is a need for additional therapies.

Once-Daily Crisaborole Ointment, 2%, as a Long-Term Maintenance Treatment in Patients Aged ≥ 3 Months with Mild-to-Moderate Atopic Dermatitis: A 52-Week Clinical Study.

Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥3 months with mild-to-moderate AD involving ≥5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. ClinicalTrials.gov, NCT04040192, 31 July 2019.

Pharmacological Profile of Difamilast, a Novel Selective Phosphodiesterase 4 Inhibitor, for Topical Treatment of Atopic Dermatitis.

PDE4 inhibitors are expected to be anti-inflammatory agents based on their mechanism of action, but the application of this drug class is limited by a narrow therapeutic window due to adverse effects associated with gastrointestinal function. Difamilast, a novel selective phosphodiesterase 4 (PDE4) inhibitor, demonstrated significant efficacy without adverse reactions such as nausea and diarrhea in patients with atopic dermatitis (AD) and was recently approved in Japan. In this study, we investigated the pharmacological and pharmacokinetic properties of difamilast to provide nonclinical data to help understand the clinical effects. Difamilast selectively inhibited recombinant human PDE4 activity in assays. The IC50 of difamilast against PDE4B, a PDE4 subtype that plays an important role in the inflammatory response, was 0.0112 μM, representing a 6.6-fold decrease compared with the IC50 against PDE4D (0.0738 μM), a subtype that can trigger emesis. Difamilast inhibited TNF-α production in human (IC50 = 0.0109 μM) and mouse (IC50 = 0.0035 μM) peripheral blood mononuclear cells and improved skin inflammation in a mouse model of chronic allergic contact dermatitis. These effects of difamilast on TNF-α production and dermatitis were superior to those of other topical PDE4 inhibitors: CP-80633, cipamfylline, and crisaborole. In pharmacokinetic studies using miniature pigs and rats, the concentrations of difamilast in the blood and brain after topical application were not sufficient to support pharmacological activity. This nonclinical study contributes to explain the efficacy and safety of difamilast with a sufficient therapeutic window in the clinical trials. SIGNIFICANCE STATEMENT: This is the first report on the nonclinical pharmacological profile of difamilast ointment, a novel topical PDE4 inhibitor that demonstrated utility in clinical trials in patients with atopic dermatitis. Difamilast, which has high PDE4 selectivity (especially for the PDE4B subtype), ameliorated chronic allergic contact dermatitis in mice after topical application, with a pharmacokinetic profile in animals that suggests few systemic side effects; thus, difamilast is a promising new therapeutic treatment for atopic dermatitis.

Crisaborole reverses dysregulation of the mild to moderate atopic dermatitis proteome toward nonlesional and normal skin

Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited. In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects. Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14days. Punch biopsy specimens were collected for biomarker analysis at baseline from all participants, then from AD patients only at day 8 (optional) and day 15. Compared to the vehicle, crisaborole significantly reversed dysregulation of the overall lesional proteome and of key markers and pathways (eg, Th2, Th17/Th22, and T-cell activation) associated with AD pathogenesis toward both nonlesional and normal skin. Significant clinical correlations were observed with markers associated with nociception and Th2, Th17, and neutrophilic activation. Study limitations include predominance of white patients in the cohort, relatively short treatment time, and regimented administration of crisaborole. Our results demonstrate crisaborole-induced normalization of the AD proteome toward a nonlesional molecular phenotype and further support topical PDE4 inhibition in the treatment of mild to moderate AD.

Iatrogenic Contact Dermatitis in a Patient with Atopic Dermatitis

: The relationship between atopic and allergic contact dermatitis is often discussed, especially in children. The damaged skin barrier in atopic patients can make the skin more permeable to exogenous agents and increase the risk of triggering contact dermatitis. Topical treatment of atopic dermatitis is associated with skin sensitization to several drugs, including antiseptics, emollients, and topical corticosteroids. The early onset of atopic dermatitis, as in the case reported here, the severity of the disease, and IgE-mediated sensitization are identified as the main risk factors associated with sensitization to topical treatments for atopic dermatitis. We report a two-year-old child with a previous diagnosis of atopic dermatitis, whose condition was aggravated by inadequate medical treatment.

Topical Administration of Crisaborole in Mild to Moderate Atopic Dermatitis: A Systematic Review and Meta‐Analysis

Background. Crisaborole has been considered a promising alternative for topical treatment of atopic dermatitis (AD), mainly supported by AD‐301 and AD‐302. However, critical insights into these two studies have previously been proposed. Objective. To make a comprehensive assessment of the application of crisaborole in mild to moderate AD. Methods. A systematic review and meta‐analysis were conducted, in which only randomized controlled trials comparing the application of crisaborole twice daily to vehicle or other active treatment in patients with mild to moderate AD were included. The selection of outcomes was based on the recommendation of the HOME initiative. Patient‐reported symptoms, clinician‐reported signs, health‐related quality of life, and the safety of crisaborole were all assessed using appropriate measurement instruments. Results. Eight RCTs with 2266 patients were included in the pooled analysis. Compared to those treated with vehicle, patients on crisaborole experienced a greater improvement in NRS (MD −0.70; 95% CI −0.94 to −0.47), POEM (MD −3.50; 95% CI −4.34 to −2.66), EASI (MD −14.49%; 95% CI −18.24% to −10.73%), ISGA (RR 1.45; 95% CI 1.28 to 1.63), DLQI (MD −1.54; 95% CI −2.17 to −0.92), and DFI (MD −1.16; 95% CI −1.72 to −0.59) during the 4‐week treatment. More patients achieved EASI 75 (RR 1.71; 95% CI 1.43 to 2.04) with crisaborole administration. There was no significant difference between two interventions in the incidence of AEs (RR 1.12; 95% CI 0.98 to 1.29), SAEs (RR 1.89; 95% CI 0.47 to 7.60), or AE‐related withdrawal (RR 0.87; 95% CI 0.47 to 1.60). One RCT also made comparison between crisaborole and pimecrolimus, suggesting that no significant difference was detected in the improvement of EASI or NRS at most time points. Conclusion. High‐quality evidence was provided to demonstrate that the short‐term application of crisaborole is safe and efficacious for the treatment of mild to moderate AD. The practical efficacy of crisaborole is similar to that of pimecrolimus.

Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild-moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used compounds include topical corticosteroids and calcineurin inhibitors, although their use might be burdened by side effects, poor response, and low patient compliance. Consequently, new innovative drugs with higher efficacy and safety both in the short and long term need to be integrated into clinical practice. A deeper understanding of the complex pathogenesis of the disease has led to identifying new therapeutic targets and to the development of innovative therapeutics. This narrative review aims to collect data on selected promising topical drugs that are in an advanced stage of development.

Genomic control of inflammation in experimental atopic dermatitis

Atopic Dermatitis (AD) or eczema, a recurrent allergic inflammation of the skin, afflicts 10–20% of children and 5% adults of all racial and ethnic groups globally. We report a new topical treatment of AD by a Nuclear Transport Checkpoint Inhibitor (NTCI), which targets two nuclear transport shuttles, importin α5 and importin β1. In the preclinical model of AD, induced by the active vitamin D3 analog MC903 (calcipotriol), NTCI suppressed the expression of keratinocyte-derived cytokine, Thymic Stromal Lymphopoietin (TSLP), the key gene in AD development. Moreover, the genes encoding mediators of TH2 response, IL-4 and its receptor IL-4Rα were also silenced together with the genes encoding cytokines IL-1β, IL-6, IL-13, IL-23α, IL-33, IFN-γ, GM-CSF, VEGF A, the chemokines RANTES and IL-8, and intracellular signal transducers COX-2 and iNOS. Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial (AMTX-100 CF, NCT04313400).

Novel Pullulan/Gellan Gum Bilayer Film as a Vehicle for Silibinin-Loaded Nanocapsules in the Topical Treatment of Atopic Dermatitis.

In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameters in a similar or more pronounced way than silibinin solution and vehicle film, as well as than hydrocortisone, a classical treatment of AD. In conclusion, these data suggest that itself gellan gum/pullulan bilayer film might attenuate the effects induced by DNCB, acting together with silibinin-loaded nanocapsules, which protected the skin from oxidative damage, improving the therapeutic effect in this AD-model.