Treatment Of Pediatric Atopic Dermatitis Research Articles

Network Pharmacology, Molecular Docking and Experimental Verification Revealing the Mechanism of Fule Cream against Childhood Atopic Dermatitis.

The Fule Cream (FLC) is an herbal formula widely used for the treatment of pediatric atopic dermatitis (AD), however, the main active components and functional mechanisms of FLC remain unclear. This study performed an initial exploration of the potential acting mechanisms of FLC in childhood AD treatment through analyses of an AD mouse model using network pharmacology, molecular docking technology, and RNA-seq analysis. The main bioactive ingredients and potential targets of FLC were collected from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and SwissTargetPrediction databases. An herb-compound-target network was built using Cytoscape 3.7.2. The disease targets of pediatric AD were searched in the DisGeNET, Therapeutic Target Database (TTD), OMIM, DrugBank and GeneCards databases. The overlapping targets between the active compounds and the disease were imported into the STRING database for the construction of the protein-protein interaction (PPI) network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersection targets were performed, and molecular docking verification of the core compounds and targets was then performed using AutoDock Vina 1.1.2. The AD mouse model for experimental verification was induced by MC903. The herb-compound-target network included 415 nodes and 1990 edges. Quercetin, luteolin, beta-sitosterol, wogonin, ursolic acid, apigenin, stigmasterol, kaempferol, sitogluside and myricetin were key nodes. The targets with higher degree values were IL-4, IL-10, IL-1α, IL-1β, TNFα, CXCL8, CCL2, CXCL10, CSF2, and IL-6. GO enrichment and KEGG analyses illustrated that important biological functions involved response to extracellular stimulus, regulation of cell adhesion and migration, inflammatory response, cellular response to cytokine stimulus, and cytokine receptor binding. The signaling pathways in the FLC treatment of pediatric AD mainly involve the PI3K-Akt signaling pathway, cytokine‒cytokine receptor interaction, chemokine signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. The binding energy scores of the compounds and targets indicate a good binding activity. Luteolin, quercetin, and kaempferol showed a strong binding activity with TNFα and IL-4. This study illustrates the main bioactive components and potential mechanisms of FLC in the treatment of childhood AD, and provides a basis and reference for subsequent exploration.

Biologics and oral small-molecule inhibitors for treatment of pediatric atopic dermatitis: Opportunities and challenges.

Atopic dermatitis (AD) is a complex disease characterized by recurrent eczematous lesions and refractory pruritus that drastically impairs quality of life. Due to the chronic and relapsing course, patients are easily trapped in the debilitating condition. Classical therapies show limitations, especially for patients with moderate-to-severe phenotypes. Advanced new insights in targeted therapies exhibit great application prospects which were reinforced by the more profound understanding of the disease pathogenesis. However, the sustained efficiency, biosafety, and long-term benefits still remain in further exploration. This review summarizes recent clinical studies on oral small-molecule inhibitors and biological agents for pediatric AD patients, which provides the latest frontiers to clinicians.

Next-Gen biotherapeutics: A systematic review and network meta-analysis on postbiotics as treatment for pediatric atopic dermatitis.

Due to the recency of the postbiotic field, no head-to-head postbiotic studies have investigated its biotherapeutic potential for atopic dermatitis (AD). No network meta-analysis (NMA) has been conducted to synthesize relevant studies comparing postbiotic interventions for AD. To assess the comparative efficacy and safety of postbiotic strains in the treatment of pediatric AD. This was an NMA of randomized controlled studies that evaluated postbiotics in treating pediatric AD. Systematic search of databases and registers from inception to November 30, 2022. Three authors independently performed the search, screening, and appraisal using the Cochrane risk-of-bias tool version 2 and data extraction. Data analysis was performed using STATA14 software. Nine studies evaluated eight postbiotic preparations. Lactobacillus rhamnosus IDCC 3201 (LR) ranked highest in the efficacy outcome. Compared to placebo, LR may be effective in reducing symptoms of atopic dermatitis in the main analysis (SMD -0.53, 95%CI -1.02 to -0.04) and sensitivity analysis involving studies that used SCORAD (MD -5.52, 95% CI -10.46 to -0.58), based on low-certainty evidence. Based on moderate-certainty evidence, LR probably did not increase the risk of adverse events (RR 0.97, 95% CI 0.79, 1.21). Although Lactobacillus paracasei GM080 (LP2) ranked highest in the safety outcome, it may not reduce AD symptoms compared to placebo (SMD -0.03, 95% CI -0.37, 0.32) based on low-certainty evidence. LR showed significant benefits in children with AD based on low-certainty evidence. Further investigation of LR is recommended.

Biologics for pediatric atopic dermatitis: A protocol of a systematic review and meta-analysis.

Atopic dermatitis is a chronic pruritic inflammatory skin disease commonly occurring in children. The objective of this study is to evaluate the treatment of pediatric atopic dermatitis with biologics, as they have displayed immense promising results in several recent clinical trials on atopic dermatitis (AD). We will conduct an extensive search for RCTs in several databases, including Embase, Cochrane Library, Web of Science, and PubMed, from the inception of the study till 15th May 2022. The primary outcomes will be the proportion of patients with EASI 75/90/100 after 12-16 weeks of treatment. The secondary outcomes will include the Numerical Rating Scale (NRS), Investigator Global Assessment (IGA)0-1, body surface area (BSA), Dermatology Life Quality Index (DLQI) scores, and incidence of adverse reactions. All studies will be screened by two independent researchers. They will assess the risk of bias in the included studies according to the RCTs bias risk evaluation tool in Cochrane System Review Manual 5.1.0. Meta-analysis will be performed using RevMan V.5.3.0 software. The research results will provide a reference for the clinical application of biological agents in pediatric atopic dermatitis. We aim to evaluate the efficacy and safety of biologics in pediatric atopic dermatitis cases and provide evidence-based data for easy clinical application. CRD42022319052 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).

Dupilumab in daily practice for the treatment of pediatric atopic dermatitis: 28-week clinical and biomarker results from the BioDay registry.

Dupilumab has proven to be an effective and safe treatment for atopic dermatitis (AD) in pediatric patients in clinical trials. However, few daily practice studies are available. The aim of this study is to evaluate the effect of 28 weeks dupilumab treatment on effectiveness, safety, and serum biomarkers in pediatric patients with moderate-to-severe AD in daily practice. Patients visited the outpatient clinic at baseline, 4, 16, and 28 weeks of treatment. Disease severity was assessed by the Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), Numeric Rating Scale (NRS)-pruritus and -pain, and the Patient-Oriented Eczema Measure (POEM). Side effects were evaluated. Nineteen severity-associated serum biomarkers were measured. Predicted-EASI (p-EASI) was calculated. Sixty-one patients were included. Respectively 75.4%, 49.2%, and 24.6% reached EASI-50, EASI-75, and EASI-90 and 36.1% achieved an IGA-score (almost) clear. Improvement of ≥4 points on POEM, NRS-pruritus, and NRS-pain was reached by 84.7%, 45.3%, and 77.4%, respectively. Most reported side effects were conjunctivitis (n= 10) and headache (n= 4). Biomarkers TARC, PARC, periostin, sIL-2Ra, and eotaxin-3 significantly decreased during treatment. The p-EASI showed a significant correlation with disease severity. Dupilumab treatment significantly improved disease severity and disease-associated symptoms and decreased severity-associated serum biomarkers in pediatric AD patients in daily practice.

Efficacy of Probiotic Supplementation for the Treatment of Pediatric Atopic Dermatitis. A Systematic Review and Meta-analysis: Assessment of SCORAD Index, Serum Immunoglobulin-E, and Interleukin-4 Parameters

Efficacy of Probiotic Supplementation for the Treatment of Pediatric Atopic Dermatitis. A Systematic Review and Meta-analysis: Assessment of SCORAD Index, Serum Immunoglobulin-E, and Interleukin-4 Parameters

Cyclosporine shows benefit as compared to methotrexate for treatment of pediatric atopic dermatitis refractory to topical medications when rapidity of clinical response is of key importance to the patient

A clinical decision report appraising El-Khalawany MA, Hassan H, Shaaban D, Ghonaim N, Eassa B. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. European Journal of Pediatrics. 2012;172(3):351-356. https://doi.org10.1007/s00431-012-1893-3 for a pediatric patient with severe atopic dermatitis.

Comparative effectiveness of probiotic strains for the treatment of pediatric atopic dermatitis: A systematic review and network meta-analysis.

The current evidence on the use of probiotics in treating atopic dermatitis is inconclusive. This study determined the comparative effectiveness of the different types of probiotic strains in treating pediatric atopic dermatitis. Systematic and manual search for all randomized controlled trials available from inception until January 31, 2020, was done. Two independent authors conducted the search, screening, appraisal, and data abstraction. Network meta-analysis was conducted using STATA 14 software. Twenty-two studies involving 28 different probiotic strains were included. The top three ranked probiotic strains in terms of efficacy are Mix1 (Bifidobacterium animalis subsp lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lactobacillus casei CECT 9104); Lactobacillus casei DN-114001; and Mix6 (Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus salivarius). Compared with placebo, Mix1 reduces atopic dermatitis symptoms with high certainty evidence (SMD -1.94, 95% CI -2.65 to -1.24; 47 participants). Mix6 compared with placebo probably reduces atopic dermatitis symptoms based on moderate certainty evidence (SMD -0.85, 95% CI -1.50 to -0.20; 40 participants). Lactobacillus casei DN-114001 compared with placebo may reduce atopic dermatitis symptoms based on low certainty evidence (SMD -1.35, 95% CI -2.04 to -0.65). In terms of safety, the highest ranked strain is Lactobacillus fermentum VRI-003, while the lowest ranked strain is Lactobacillus rhamnosus GG. Certain probiotic preparations show benefit in reducing allergic symptoms in pediatric atopic dermatitis.

A Review of Probiotic Supplementation and Feasibility of Topical Application for the Treatment of Pediatric Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease that commonly occurs in early childhood. To date, the pharmacological treatment of atopic dermatitis is far from ideal, poses several limitations, and constantly requires novel approaches. The theory that appropriate colonization of gut bacteria during infancy influences the development of the immune system has prompted numerous clinical trials that have evaluated the effectiveness of probiotic supplementation for the prevention and treatment of atopic eczema in children. In addition, topical application of probiotics has been demonstrated to improve the skin's barrier function, which might contribute to reduce the severity of atopic dermatitis. In this article, we review the literature and data regarding the use of probiotics, both by oral administration and topical application, for the treatment of atopic dermatitis. We also summarize the knowledge on the potential mechanisms by which probiotics influence the gut and exert their skin effects. Probiotic supplementation seems to be an attractive strategy to prevent and treat pediatric atopic dermatitis. However, to enable the treatment to be fully effective, the period of supplementation should be considered. Moreover, in future studies, a combination of probiotic supplementation and simultaneous topical application of creams containing probiotics might also be considered.

Efficacy and patient opinion of wet wrap dressings using 0.1% triamcinolone ointment versus cream in the treatment of pediatric atopic dermatitis: A randomized split-body control study

Efficacy and patient opinion of wet wrap dressings using 0.1% triamcinolone ointment versus cream in the treatment of pediatric atopic dermatitis: A randomized split-body control study

Bathing Frequency Recommendations for Children with Atopic Dermatitis: Results of Three Observational Pilot Surveys.

The results from three online surveys of dermatologists, allergists and immunologists, and primary care physicians (PCPs) regarding routine bathing frequency recommendations for children with atopic dermatitis (AD) are presented. The results suggest that PCPs approach bathing frequency differently than specialists, with PCPs recommending daily bathing less than 50% of the time and specialists recommending daily bathing more than 50% of the time. Because there is lack of consensus, studies are needed to evaluate whether bathing frequency makes a clinical difference in the treatment of pediatric AD.

Maternal Adherence Factors in the Treatment of Pediatric Atopic Dermatitis

Maternal Adherence Factors in the Treatment of Pediatric Atopic Dermatitis

A randomized trial of Lactobacillus plantarum CJLP133 for the treatment of atopic dermatitis

There have been considerable disagreements regarding the therapeutic effects of probiotics in atopic dermatitis (AD). We performed this study to examine whether the oral administration of Lactobacillus plantarum CJLP133 improves pediatric AD. In a randomized, double-blind, placebo-controlled study, either L. plantarum CJLP133 at a dosage of 0.5 × 10(10) colony-forming units or placebo in children aged 12 months to 13 yr was given twice a day for 12 wk. SCOring of Atopic Dermatitis (SCORAD) scores, eosinophil counts, serum total IgE, and cytokines were evaluated. Forty-four of 58 patients in the probiotic group and 39 of 60 patients in the placebo group completed the study. The SCORAD score at week 14 was lower in the probiotic group than in the placebo group (p = 0.044). The mean change in the SCORAD score from weeks 2 to 14 was 9.1 in the probiotic group, which was greater than the mean change of 1.8 in the placebo group (p = 0.004). No statistical differences in the total use of topical corticosteroids were found between two groups (p = 0.815). In the probiotic group, the total eosinophil count was significantly lower at the end of the intervention compared to the baseline measurements (p = 0.023). Logarithmic IFN-γ and IL-4 were significantly decreased by the end of the intervention compared to baseline measurements in the probiotic group (p < 0.001 and 0.049). Our results suggest that supplementation with probiotic L. plantarum CJLP133 is beneficial in the treatment of pediatric AD.

Systemic Treatment of Pediatric Atopic Dermatitis with Azathioprine and Mycophenolate Mofetil

Severe forms of atopic dermatitis (AD) cause significant morbidity in vulnerable pediatric populations and necessitate treatment with systemic therapy. The existing literature concerning the treatment of severe pediatric AD with azathioprine (AZ) and mycophenolate mofetil (MM) is sparse. The purpose of this case series is to examine the use of these two drugs in the treatment of severe pediatric AD. Medical records of 28 pediatric patients with AD from the University of North Carolina at Chapel Hill pediatric dermatology clinic treated using these two drugs were analyzed for laboratory values, thiopurine methyltransferase (TPMT) levels, symptoms, infections, and other relevant data. Patients were also contacted via the telephone to ascertain outcomes and any missing data. Treatment outcomes were scored into three categories: significant improvement, some improvement, and no improvement. AZ dosing was correlated to TPMT levels successfully, with comparable levels of improvement in the heterozygous and homozygous wild-type groups. Absolute eosinophil count corresponded to AD activity and treatment response across both treatment modalities in 18 of 26 (69%) patients. Seventeen of 28 (61%) patients treated with AZ and eight of 12 (66%) treated with MM reported significant improvement. We had lower rates of laboratory abnormalities and side effects with MM than with AZ but similar rates of cutaneous infections. Treatment outcomes did not appear to differ with race, sex, or TPMT level. We experienced success with AZ and MM in the treatment of severe pediatric AD. Coordinating treatment to each patient's unique morbidities is the best way to choose systemic treatments.

Spotlight on Topical Pimecrolimus in Pediatric Atopic Dermatitis†

Topical pimecrolimus 1% cream (Elidel) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1-2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.

Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis: An open-label pilot study

Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis: An open-label pilot study

Topical Pimecrolimus

Topical pimecrolimus 1% cream (Elidel) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life (HR-QOL) of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment (hereafter topical tacrolimus) in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1-2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.

Effect of sequential applications of topical tacrolimus and topical corticosteroids in the treatment of pediatric atopic dermatitis: An open-label pilot study

The efficacy of combination therapy with topical corticosteroids and tacrolimus in the treatment of atopic dermatitis remains to be established. Our aim was to determine whether a regimen of sequential application of topical corticosteroids and topical tacrolimus is effective in the treatment of pediatric atopic dermatitis. A second goal was to assess the impact of this treatment regimen on quality of life (QOL) and the response shift on QOL changes. The study regimen consisted of 3 phases. In the induction phase, patients were treated for a 2-week period with application of 0.03% tacrolimus ointment in the morning and application of a strong- or weak-potency corticosteroid ointment in the evening. In the transitional phase, they were treated for an additional 2 weeks with 0.03% tacrolimus ointment twice daily on weekdays and concurrent application of tacrolimus and a topical corticosteroid ointment on weekend days. In the maintenance phase, the corticosteroid ointment was discontinued and 0.03% tacrolimus ointment was applied twice daily for an additional 2 weeks. Daily application of tacrolimus ointment was then discontinued and replaced by an emollient with application of 0.03% tacrolimus ointment only when necessary for an additional 6 weeks. The Eczema Area and Severity Index score, Investigators' Global Assessment, severity of pruritus and sleep disturbance scores, and QOL evaluation were measured. After 12 weeks, the patients completed a retrospective version of the pretreatment QOL evaluation for analysis of response shift bias. Eczema Area and Severity Index scores decreased by the sixth week, and continued improvement was observed during an additional 6-week period. Both the pruritus and sleep disturbance scores decreased throughout the study. Of patients, 90% showed marked clinical improvement at week 6 and 96% at week 12. On the Children's Dermatology Life Quality Index and the Infant's Dermatology QOL Index survey, mean QOL scores improved after completion of therapy at week 12. The mean difference between the pretest and the retrospective pretest scores indicated the presence of a response shift bias. This was an uncontrolled, open-label study. Conclusions are limited by the small sample size. A fixed sequential regimen of application of tacrolimus ointment with tapering of topical corticosteroids may limit the long-term use and adverse effects of topical corticosteroids, while maintaining clinical control of pediatric atopic dermatitis and improving the QOL. The finding of a response shift bias suggests that parents/guardians underestimate the seriousness of skin disease and its impact on QOL.

Efficacy of probiotics in the treatment of pediatric atopic dermatitis: a meta-analysis of randomized controlled trials

Several articles describing the efficacy of probiotics in atopic dermatitis (AD) have been published. However, not all studies support a similar outcome. To determine whether probiotics are efficacious in treating AD and to explore whether type of probiotic used, duration of therapy, patient age, severity of disease, and IgE sensitization are factors in determining efficacy. For this meta-analysis of randomized controlled trials describing the efficacy of probiotics in AD, a comprehensive search was performed of databases through January 2008. Three reviewers independently evaluated the studies for methodological qualities. All the data were analyzed, and forest plots were evaluated for the overall efficacy of probiotics in AD and the therapeutic benefit to subgroups of selected patient populations. Eleven studies were identified, and data from 10 studies (n = 678) were available to analyze. There was an overall statistically significant difference favoring probiotics compared with placebo in reducing the Scoring of Atopic Dermatitis Severity Index score (mean change from baseline, -3.01; 95% confidence interval, -5.36 to -0.66; P = .01). Children with moderately severe disease were more likely to benefit. Duration of probiotic administration, age, and type of probiotic used did not affect outcome. Data from this meta-analysis suggest a modestrole for probiotics in pediatric AD. The effect is seen in moderately severe rather than mild disease.

W1387 Efficacy of Probiotics in Treatment of Pediatric Atopic Dermatitis: A Meta-Analysis of Randomized, Controlled Trials

W1387 Efficacy of Probiotics in Treatment of Pediatric Atopic Dermatitis: A Meta-Analysis of Randomized, Controlled Trials