Topical Treatment Of Atopic Dermatitis Research Articles

New and Upcoming Topical Treatments for Atopic Dermatitis: A Review of the Literature.

Atopic dermatitis (AD) is a chronic inflammatory dermatosis with periods of exacerbation and remissions. AD is characterized by intense, persistent pruritus and heterogeneity in clinical symptomatology and severity. Therapeutic goals include the amelioration of cutaneous eruptions, diminishing relapses and eventually the disease burden. To date, topical corticosteroids (TCS) and calcineurin inhibitors (TCI) have yet been deemed the mainstay of topical treatments in AD management. Nevertheless, despite their indisputable efficiency, TCS and TCI are not indicated for continuous long-term use given their safety profile. While research in AD has concentrated predominantly on systemic therapies, more than 30 novel topical compounds are under development. The existing data appear encouraging, with some regimens that are already FDA-approved (ruxolitinib was the most recent in September 2021) and several pharmaceutical pipeline products for mild-to-moderate AD that are in an advanced stage of development, such as tapinarof, difamilast and roflumilast. Larger, long-term studies are still required to evaluate the efficacy and safety of these novel compounds in the long run and weigh their advantages over present treatments. In this review, we aim to provide an overview of the latest knowledge about AD topical treatments, echoing upcoming research trends.

Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: Phase 3, randomized, vehicle-controlled study (CAPTAIN-AD)

Asivatrep is a potent and selective antagonist of transient receptor potential vanilloid subfamily V member 1 (TRPV1), which plays an important role in itch and inflammation in atopic dermatitis (AD). This current study aimed to evaluate the efficacy and safety of asivatrep cream in patients with AD. For this phase 3 double-blind, vehicle-controlled study, patients aged ≥12 years with mild to moderate AD were enrolled and randomly assigned 2:1 to the 1.0% asivatrep or vehicle group for 8 weeks of twice-daily application (n= 240). The primary end point was the proportion of patients with an Investigator's Global Assessment score (IGA) of 0 or 1 at week 8. Standard safety assessments were conducted. At week 8, significantly more patients in the asivatrep group (36.0%) than in the vehicle group (12.8%) had IGA scores of 0 or 1 (P< .001); significantly more had ≥2 points of improvement on the IGA from baseline score (20.3% vs 7.7%; P= .01). The mean percentage reduction in the Eczema Area and Severity Index (EASI) score was 44.3% for the asivatrep group and 21.4% for the vehicle group at week 8 (P< .001). Significantly more asivatrep-treated patients experienced an improvement of at least 50%, 75%, and 90% on the EASI than the vehicle group. The mean± SD change in the pruritus visual analog scale score at week 8 was -2.3± 2.4 for the asivatrep group and -1.5± 2.4 for the vehicle group (P= .02). No significant safety issues were reported. Asivatrep improved clinical signs and symptoms of AD and was well tolerated.

Practical algorithm to inform clinical decision-making in the topical treatment of atopic dermatitis.

Atopic dermatitis is a chronic relapsing, inflammatory skin disorder associated with skin barrier dysfunction, the prevalence of which has increased dramatically in developing countries. In this article, we propose a treatment algorithm for patients with mild-to-moderate and severe atopic dermatitis flares in daily clinical practice. An international panel of 15 dermatology and allergy experts from eight countries was formed to develop a practical algorithm for the treatment of patients with atopic dermatitis, with a particular focus on topical therapies. In cases of mild-to-moderate atopic dermatitis involving sensitive skin areas, the topical calcineurin inhibitor pimecrolimus should be applied twice daily at the first signs of atopic dermatitis. For other body locations, patients should apply a topical calcineurin inhibitor, either pimecrolimus or tacrolimus, twice daily at the first signs of atopic dermatitis, such as pruritus, or twice weekly in previously affected skin areas. Emollients should be used regularly. Patients experiencing acute atopic dermatitis flares in sensitive skin areas should apply a topical corticosteroid twice daily or alternate once-daily topical corticosteroid/topical calcineurin inhibitor until symptoms improve. Following improvement, topical corticosteroid therapy should be discontinued and patients switched to a topical calcineurin inhibitor. Maintenance therapy should include the use of pimecrolimus once daily for sensitive areas and tacrolimus for other body locations. This treatment algorithm can help guide clinical decision-making in the treatment of atopic dermatitis.

Bacteriotherapy for the skin

Medicine Atopic dermatitis, a form of eczema, can be exacerbated by colonization of the affected skin with Staphylococcus aureus . Nakatsuji et al. report a phase 1 clinical trial of Staphylococcus hominis A9 ( Sh A9) as a topical treatment for atopic dermatitis. Sh A9 is found on the skin of healthy people and selectively inhibits strains of S. aureus that have been associated with atopic dermatitis. It also improves atopic dermatitis in mice. The authors report that Sh A9 treatment did not cause serious adverse events, and S. aureus abundance was reduced, even during a short 7-day trial. Additionally, application of Sh A9 altered the microbial composition on affected skin, suggesting that the treatment induces a more beneficial skin microbiota. Nat. Med. 10.1038/s41591-021-01256-2 (2021).

Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis.

In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC50=0.42nM) as compared to Crisaborole (IC50=57.20nM), along with favorable isoform specificity. In the phorbol ester (PMA)-induced mouse ear oedema model, 72 exerted remarkably greater efficacy than Crisaborole at the same dosage (P<0.05). Moreover, the ointment of 72 exerted dramatically enhanced therapeutic potency than the ointment of Crisaborole (P<0.05) in the calcipotriol-induced mouse AD model. In addition to the potent invitro and invivo activity, 72 displayed favorable safety in the repeated oral dose toxicity study and did not exhibit phototoxicity. With the above attractive biological performance, 72 is worthy of further functional investigation as a novel anti-AD therapeutic agent.

Practical Recommendations for the Topical Treatment of Atopic Dermatitis in South and East Asia

IntroductionThere is some evidence to suggest that the prevalence of atopic dermatitis (AD) in Asia is rising. We have therefore developed an algorithm for the topical treatment of AD throughout South and East Asia for use by primary care physicians, pediatricians and dermatologists.MethodsNine AD experts from South and East Asia and one from Europe developed the algorithm based upon treatment guidelines, relevant literature and local treatment practices. The algorithm outlines current best practice for the use of emollients, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with the intention of simplifying the treatment regimen of mild-to-moderate AD in South and East Asia.ResultsPatients with AD should bathe and cleanse affected skin to remove crusts and scales daily. Emollients should also be applied daily as a maintenance treatment. When selecting appropriate topical anti-inflammatory treatment for AD flares, several factors should be taken into consideration, including the patient’s age, attitude to treatment options and site of AD lesions. Given the concerns regarding the risk of skin atrophy with use of TCS, a TCI should be used to treat AD lesions in sensitive skin areas: pimecrolimus is recommended for mild-to-moderate AD in these locations, while tacrolimus should be considered for moderate and severe cases. Either pimecrolimus or tacrolimus is recommended for flares in other, non-sensitive body locations. A proactive or intermittent maintenance treatment strategy involving regular emollient use and twice-weekly application of a TCI to previously affected areas is encouraged to reduce the risk of flares.ConclusionsThe algorithm proposed here is intended to simplify the topical treatment of mild-to-moderate AD in daily practice in South and East Asian countries.

The Active Compounds and Therapeutic Mechanisms of Pentaherbs Formula for Oral and Topical Treatment of Atopic Dermatitis Based on Network Pharmacology.

To examine the molecular targets and therapeutic mechanism of a clinically proven Chinese medicinal pentaherbs formula (PHF) in atopic dermatitis (AD), we analyzed the active compounds and core targets, performed network and molecular docking analysis, and investigated interacting pathways. Information on compounds in PHF was obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using the Drugbank database. AD-related genes were gathered using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Network analysis was performed by Cytoscape software and protein-protein interaction was analyzed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources were applied for the enrichment analysis of the potential biological process and pathways associated with the intersection targets between PHF and AD. Autodock software was used to perform protein compound docking analysis. We identified 43 active compounds in PHF associated with 117 targets, and 57 active compounds associated with 107 targets that form the main pathways linked to oral and topical treatment of AD, respectively. Among them, quercetin, luteolin, and kaempferol are key chemicals targeting the core genes involved in the oral use of PHF against AD, while apigenin, ursolic acid, and rosmarinic acid could be used in topical treatment of PHF against AD. The compound–target–disease network constructed in the current study reveals close interactions between multiple components and multiple targets. Enrichment analysis further supports the biological processes and signaling pathways identified, indicating the involvement of IL-17 and tumor necrosis factor signaling pathways in the action of PHF on AD. Our data demonstrated the main compounds and potential pharmacological mechanisms of oral and topical application of PHF in AD.

The use of probiotics and bacteria-derived preparations in topical treatment of atopic dermatitis—A systematic review

Atopic dermatitis (AD) is a highly widespread inflammatory skin disease affecting 5% to 20% of the population, associated with reduced quality of life, increased health care expenditures, and increased risk of developing other allergic diseases. The pathologic chain of phenomena in AD starts with (1) impaired skin barrier function, through (2) decreased bacterial diversity of the skin, and (3) susceptibility to skin infections (including Staphylococcus aureus predomination and colonization), toward (4) immune dysregulation.

The use of probiotics in topical treatment of atopic dermatitis – a systematic review

The use of probiotics in topical treatment of atopic dermatitis – a systematic review

Comparing the Potential for Irritation of a Ceramide-Based Moisturizer with a Urea-Based Moisturizer for Pediatric Atopic Dermatitis.

IntroductionMoisturizers are one of the mainstays of the topical treatment of atopic dermatitis (AD). One of the adverse effects of moisturizers is skin irritation, especially on excoriated AD skin. We compared the potential for irritation of two commercially available moisturizer products for the treatment of AD: a ceramide-based moisturizer (Ceradan® Cream; Hyphens Pharma Pte Ltd, Singapore) and a urea 5% moisturizer (Aqurea Lite Cream; ICA Pharma Pte Ltd, Singapore).MethodsWe performed a prospective single-blind randomized controlled study recruiting AD patients aged between 8 and 16 years with symmetrical or near symmetrical scratch marks (excoriations) of at least grade 2 to 3 severity score, according to the Eczema Area and Severity Index (EASI), over bilateral antecubital fossae. Subjects were randomized to receive the ceramide-based moisturizer to either the left or right antecubital fossa or urea 5% cream to the other antecubital fossa. Subjects were asked to grade the immediate skin irritation of both creams on a standard visual analogue scale (VAS) and which cream they would prefer to use as a daily moisturizer. Primary outcome was the mean irritant score of each cream, and secondary outcome was the subjects’ preference of either cream as their daily moisturizer.ResultsA total of 42 participants were enrolled with a mean age of 11 years 5 months. The ceramide-based cream had a significantly lower mean VAS score (mean 0.69, SD = 1.63) for irritation compared with urea 5% cream (1.43, SD = 1.64) (p = 0.035). More participants also preferred the ceramide-based cream over urea 5% cream (62% versus 38%) as their daily moisturizer, but this did not reach statistical significance (p = 0.164).ConclusionsA ceramide-based moisturizer may be considered as a suitable choice for children to minimize irritation from moisturizer treatment for AD.

Topical Calcineurin Inhibitor Tacrolimus in Orabase: an Alternative Treatment for Erosive Oral Lichen Planus

Tacrolimus, a macrolide with immunosuppressive properties through the inhibition of T-lymphocyte activation, was approved as a second line topical treatment for atopic dermatitis, but has been largely used with beneficial effects in other dermatological conditions that involve a disregulation of the cellular immune response. Oral lichen planus is a T-cell�mediated autoimmune disease in which autocytotoxic CD8+ T cells trigger apoptosis of oral epithelial cells. Our study aimed to analyze the clinical efficacy of tacrolimus 0.03% and 0.1% in orabase as monotherapy on oral erosive lesions of lichen planus, in a group of 20 patients consulted in the Dermatology Clinic of the University C.F. Hospital Iasi during a period of five years. Our results show total or partial remission of oral erosive lesions in most patients at 3 months follow-up. However, after treatment discontinuation relapses are common, which is why intermittent use of topical tacrolimus is needed for longer periods to prevent recurrences. Further large scale studies are necessary to establish efficacy and safety profile of prolonged use of tacrolimus on mucosal membranes, as well as the most appropriate vehicle and concentration.

Sensitive UHPLC-MS/MS method for the determination of tacrolimus in minipig whole blood.

Background: Tacrolimus, a potent immunosuppressant drug widely used systemically to reduce the risk of organ rejection in transplants, has been repositioned for topical treatment of atopic dermatitis. Results & methodology: This work describes the optimization of a new method for the determination of tacrolimus in whole blood after topical administration. Sample treatment consisted of an automated procedure based on protein precipitation followed by solid-phase extraction. The present method showed good performance with quantitation limits of 10 pg ml-1 and intra- and interday precision and accuracy lower than 15 and 10%, respectively. Conclusion: A new highly sensitive UHPLC-MS/MS method has been developed enabling a better characterization of the minipig blood plasma pharmacokinetic behavior of tacrolimus after topical administration.

Наружная терапия атопического дерматита: клинический случай

Наружная терапия атопического дерматита: клинический случай

A Systematic Review of the Efficacy and Safety of Probiotics in Topical Treatment of Atopic Dermatitis

A Systematic Review of the Efficacy and Safety of Probiotics in Topical Treatment of Atopic Dermatitis

Novel Cytoplasmic Bacteriocin Compounds Derived from Staphylococcus epidermidis Selectively Kill Staphylococcus aureus, Including Methicillin-Resistant Staphylococcus aureus (MRSA).

Staphylococcus aureus (S. aureus) is one of the well-known agents causing atopic dermatitis (AD) in susceptible individuals, and Staphylococcus epidermidis (S. epidermidis) produces class I thermostable bacteriocins that can selectively kill S. aureus, suggesting protective roles against AD. There is a large need for developing precise therapies only to target S. aureus and not to harm the beneficial microbiome. On the agar well diffusion assay, live planktonic S. epidermidis showed clear zones of inhibition of S. aureus growth, but heat-killed cells and cell-free supernatants did not show this. These results would lead us to hypothesize that cytoplasmic bacteriocin from S. epidermidis will be a promising agent to inhibit S. aureus growth. Therefore, we have extracted a novel thermolabile cytoplasmic bacteriocin from S. epidermidis using trichloroactic acid (TCA)/acetone precipitation method after cell lysis with a SDS-containing buffer. These bacteriocin selectively exhibited antimicrobial activity against S. aureus and methicillin-resistance Staphylococcus aureus (MRSA), presenting no active actions against S. epidermidis, E. coli, and Salmonella Typhimurium. The extracted cytoplasmic bacteriocin compounds revealed several diffuse bands of approximately 40–70 kDa by SDS-PAGE. These findings suggest that these cytoplasmic bacteriocin compounds would be a great potential means for S. aureus growth inhibition and topical AD treatment.

Suppression of DNCB-Induced Atopic Skin Lesions in Mice by Wikstroemia indica Extract

Wikstroemia indica (L.) C.A. Mey. is used in traditional Chinese medicine to treat inflammatory diseases such as arthritis and bronchitis. In this study, we aimed to investigate the effects of an ethanolic extract of W. indica on cutaneous inflammation in mice with 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). Dermal administration of W. indica ethanolic extract to DNCB-sensitized hairless mice with dermatitis, for two weeks, reduced erythema, scaling, and edema. Skin hydration was improved and transepidermal water loss was reduced at a W. indica concentration of 1%. Furthermore, W. indica also significantly reduced serum IgE and IL-4 concentrations in our mouse model. These results suggest that W. indica has potential as a topical treatment for AD and as an adjunctive agent to control AD.

Efficacy and safety of indigo naturalis ointment in Treating Atopic Dermatitis: A randomized clinical trial.

Indigo naturalis, a herbal medicine with a history of use dating back to ancient times, may be a good alternative topical treatment for atopic dermatitis (AD). To provide empirical evidence of the efficacy and safety of Indigo naturalis ointment in treating AD. In this randomized double-blind clinical trial, participants aged 6 to 65 years with AD affecting less than 40% of their body surface area (BSA) and an Investigator's Global Assessment (IGA) score of 2 to 4 were randomized (2:1) to receive either Lindioil ointment or a vehicle ointment twice daily for 6 weeks. The primary endpoint was the percentage change in the Eczema Area Severity Index (EASI) from baseline to week 6. Secondary endpoints were as follows: EASI improvement ≥50%, 75%, and 90%; IGA score; BSA affected by AD; pruritus severity; and Dermatology Life Quality Index. The safety assessment included adverse events (AEs), laboratory tests, and physical examinations. The Lindioil group (32 participants) and vehicle group (16 participants) achieved mean percentage EASI reductions of 49.9%±36.5% (95% CI 36.8%-63.1%) and 19.6%±52.2% (95% CI -8.2%-47.4%), respectively (P=0.0235). The Lindioil group also showed greater improvement in every secondary assessment category. No significant AEs occurred. Indigo naturalis ointment is effective for treating mild to severe AD topically, and appears to be safe. This is the first clinical trial to provide evidence supporting topical indigo-based AD treatment. ClinicalTrials.gov identifier: NCT02669888.

Correlation of nipple eczema in pregnancy with atopic dermatitis in Northern India: a study of 100 cases

BackgroundNipple eczema is a less common presentation of atopic dermatitis. No studies in the literature have correlated nipple eczema in pregnancy as a manifestation of atopic dermatitis. ObjectiveTo evaluate whether nipple eczema presenting in pregnancy is a manifestation of atopic dermatitis. MethodsThis was a prospective observational study including 100 women who presented with nipple eczema for the first time during pregnancy. The exclusion criteria were any patient with previous history of nipple eczema, those already on oral or topical treatment for atopic dermatitis or nipple eczema, and other disorders mimicking eczema. Patients were divided into two groups ‒ nipple eczema with atopic dermatitis and without atopic dermatitis. Demographic data, clinical features, total leukocyte count, differential leukocyte count, absolute eosinophil counts, and serum IgE levels were compared between the two groups to detect association between nipple eczema in pregnancy and atopic dermatitis. ResultsOut of 100 patients, 39 were diagnosed with atopic dermatitis, whereas 61 were ruled out to have any features suggestive of atopic dermatitis. There were no statistically significant differences in mean age, mean duration of symptoms, and serum IgE levels. In patients with atopic dermatitis, bilateral symptoms were noted more commonly than in patients without the disease, but this was statistically insignificant. Study limitationsLack of long term follow-up and no large studies in literature to compare results. ConclusionNipple eczema in pregnancy follows a similar pattern as in other age groups. The clinical profile of patients is similar in cases with and without atopic dermatitis.

Pharmacological activity of difamilast, a novel PDE4 inhibitor for the topical treatment of atopic dermatitis: Comparison with other PDE4 inhibitors

Pharmacological activity of difamilast, a novel PDE4 inhibitor for the topical treatment of atopic dermatitis: Comparison with other PDE4 inhibitors

671 Discovery of LEO 39652 a novel PDE4 inhibitor for topical treatment of atopic dermatitis

Topical treatment of severe atopic dermatitis frequently requires application of drug to more than 30% of the body surface area of the patient. The atopic skin barrier is highly compromised and thus there is a risk that a large portion of the applied dose will reach the systemic circulation, leading to a significant systemic load of the applied compound. Previously we have described the discovery of LEO 29102, a “soft” PDE4 inhibitor designed to achieve high local skin concentrations but low systemic exposure upon topical application, due to a high systemic clearance driven by rapid liver metabolism.[1] In the end, the clinical development of this compound was however discontinued in part due to safety concerns related to the systemic exposure of the candidate drug. Here we wish to describe our effort to reduce even further the systemic compound exposure observed upon topical administration, an exercise with the aim of minimizing the risk of target-related, systemic side effects. The approach was to benefit from esterase-mediated compound degradation in compartments like the blood. Despite the fact that tissue distribution in humans is not fully characterized for all esterases, some differences in expression levels in for instance skin versus blood have been reported. Thus it was hypothesized that it should be possible to identify ester-containing compounds suitable for topical delivery. Compounds that should be sufficiently stable in skin to provide the desired pharmacological effect but at the same time they should be rapidly degraded both in blood and by the liver. Here we report the discovery of a novel series of PDE4 inhibitors and our efforts to optimize the in vitro pharmacokinetics of these using phenotypic screening models of skin and blood stability. Eventually LEO 39652 was selected as a clinical development candidate and a characterization of its metabolism, pharmacokinetic profile as well as the early clinical efficacy data obtained with this compound will be presented in this poster.[1] J. Med. Chem., 2014, 57 (14), 5893–5903