Atopic Dermatitis In Infants Research Articles

Maternal supplementation with Limosilactobacillus reuteri FN041 for preventing infants with atopic dermatitis: study protocol for a randomized controlled trial.

Atopic dermatitis (AD) has increased rapidly with rapid urbanization; however, the treatment options for AD are lacking because the commonly used therapies can only alleviate symptoms. Limosilactobacillus reuteri (L. reuteri), FN041 is a specific strain isolated from human breast milk, and its protective potential against AD has been confirmed. This study aims to assess the efficacy of maternal consumption of L. reuteri FN041 during late pregnancy and lactation in preventing infantile AD. First, a randomized, double-blind, placebo-controlled intervention study will be conducted on 340 pregnant females with babies at high risk for AD. These subjects will be randomly divided into four groups of different doses of L. reuteri FN041 (1 × 109, 5 × 109, and 1 × 1010 CFU/d) along with a placebo. The safety and efficacy of maternal use of L. reuteri FN041 for preventing infantile AD will be analyzed, and the most efficient dosage of L. reuteri FN041 will be determined. Subsequently, a multicenter cohort study of 500 pregnant females with babies at high risk for AD will be conducted to promote the maternal application of L. reuteri FN041. These subjects will be administered L. reuteri FN041 at the optimal dose determined during the first stage of late pregnancy and lactation, and their babies will be analyzed for AD development. Recruitment was initiated in October 2022. The primary outcome is the cumulative incidence of AD at 24 months after maternal consumption of L. reuteri FN041 during late pregnancy and lactation, whereas the secondary outcome is the efficiency of L. reuteri FN041 transfer from the mother's gut to breast milk and then the infant's gut after oral supplementation. This study will demonstrate the efficacy of edible probiotics isolated from breast milk in preventing or treating AD in infants. Accordingly, we provide population-based advice for administering specific probiotics for the primary prevention of AD in pregnant females. Understanding the underlying mechanisms of probiotic strains derived from breast milk can promote their application in preventing infant diseases associated with intestinal microbiota imbalance and immune disorders. https://www.chictr.org.cn/, identifier [ChiCTR2300075611].

Beyond the Skin: Reduced Lung Function Associated With Atopic Dermatitis in Infants.

Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma. To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD. Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n= 150) and an HC group (n= 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA. The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%. TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.

Birth mode is associated with development of atopic dermatitis in infancy and early childhood.

Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing. Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life. We included 2129 mother-child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age. AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD. CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.

PA30 The modifying effect of maternal body mass index on the influence of maternal vitamin D supplementation on offspring risk of atopic eczema

Abstract We recently published evidence from a randomized controlled trial of the protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema in infants that were breastfed for &amp;gt; 1 month. Reports that cholecalciferol supplementation has a smaller effect on circulating 25-hydroxyvitamin D levels in individuals with a higher body mass index (BMI) led us to examine whether maternal BMI modifies the effect of vitamin D supplementation on offspring atopic eczema in the first 4 years of life. In the Maternal Vitamin D Osteoporosis Study, which was a double-blind, randomized, placebo-controlled trial, mothers were supplemented (from 14 weeks’ gestation until delivery) with cholecalciferol 1000 IU daily or matched placebo. Maternal characteristics, including BMI, were recorded from pre-pregnancy, and offspring atopic eczema was ascertained based on the UK Working Party Criteria for the Definition of Atopic Dermatitis at the age of 12 (n = 636), 24 (n = 611) and 48 (n = 450) months. Mothers and offspring characteristics did not differ between the intervention and placebo groups except for longer breastfeeding duration in the intervention group. Maternal pre-pregnancy BMI was found to modify the effect of intervention on offspring eczema, so associations between maternal cholecalciferol supplementation and offspring eczema were stratified by categories of BMI (&amp;lt; 25, 25–30 and &amp;gt; 30 kg m−2), with findings expressed as odds ratios (ORs). Models were adjusted for breastfeeding duration, and infant sex as sensitivity analysis showed that the intervention had an impact on male infants that were breastfed. As reported previously, the offspring of mothers who received 1000 IU cholecalciferol had lower ORs of atopic eczema at 12 months of age [OR 0.57, 95% confidence interval (CI) 0.33–0.98]; the intervention did not affect the risk of atopic eczema in offspring at 24 and 48 months. Stratified analysis demonstrated reduced odds of atopic eczema at 12 months of age in the intervention group in infants whose mothers had a BMI &amp;lt; 25 kg m−2 (OR 0.28, 95% CI 0.09–0.92) and 25–30 kg m−2 (OR 0.20, 95% CI 0.04–1.06) but not for those with a maternal BMI &amp;gt; 30 kg m−2. The risk of atopic eczema at 24 and 48 months of age in offspring in the intervention group was not modified by maternal baseline BMI, and interaction terms between intervention and BMI were not statistically significant (P &amp;gt; 0.2). These RCT findings support evidence of an attenuated effect of cholecalciferol supplementation in mothers with a higher BMI and point toward potential preventative strategies for offspring eczema where maternal cholecalciferol supplementation can be considered and doses adjusted for BMI.

Meta-analysis on preventive and therapeutic effects of probiotic supplementation in infant atopic dermatitis.

Despite a large body of research, the effect of probiotic administration on the incidence and severity of atopic dermatitis (AD) shows conflicting results. We aimed to investigate whether probiotic supplementation reduces the incidence and severity of AD. Three databases were systematically searched. A 22% lower incidence of AD was found in the probiotic group. The reduction in incidence was 49% when probiotics were given to pregnant and lactating mothers, and 27% when they were given to pregnant mothers and infants. A 39% reduction of AD incidence was achieved when administered to pregnant-breastfeeding mothers and infants. Significant differences in SCORAD (SCORing Atopic Dermatitis) favoring probiotics were observed, but the IDLQI remained unchanged. Lactobacillus (L.) rhamnosus was the most documented strain, but it turned out to be ineffective in reducing SCORAD. Conversely, L. paracasei and L. sakei showed a significant decrease in SCORAD. Probiotics are effective in the prevention of AD, but the effect is less conclusive for the treatment of AD, especially in infants <1year. The intake of probiotics by breastfeeding mothers is an important measure and may become a novel preventive strategy. The preventive effect of probiotics against AD is not associated with family background or AD risk. L. paracasei and L. sakei show the greatest reduction in SCORAD.

426 Association of stratum corneum and breast milk factors with the development of atopic dermatitis in infancy: A prospective birth cohort study

426 Association of stratum corneum and breast milk factors with the development of atopic dermatitis in infancy: A prospective birth cohort study

Facial atopic dermatitis is associated with sensitization to cow's milk, egg whites, and peanuts in children under 36 months

Atopic dermatitis (AD) in early childhood often precedes the development of food sensitization and allergy, but the role of treating AD to prevent food allergy remains poorly understood. Our objective was to assess the relationship between facial dermatitis and food sensitization to cow's milk, egg whites, and peanuts in early childhood, as aggressive treatment of facial dermatitis could serve as a potential opportunity for food sensitization prevention. By 3 years of age, food sensitization levels to cow's milk, egg whites, and peanuts were 48% greater in children with facial AD than in children with no facial involvement of their AD. Additional research is needed to determine if facial involvement of AD in infants and young children is associated with increased food allergy.

Enhanced early skin treatment for atopic dermatitis in infants reduces food allergy

Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. This study enrolled 650 infants and analyzed 640 infants (enhanced [n= 318] or conventional [n= 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P= .0028; risk difference: -10.5%, upper bound of a 1-sided CI: -3.0%), while it lowered body weight (mean difference: -422 g, 95% CI: -553 to -292 g) and height (mean difference: -0.8 cm, 95% CI: -1.22 to -0.33 cm) at 28 weeks of age. This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs.

MRNAs in skin surface lipids unveiled atopic dermatitis at one month.

The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1-2 months is unreported. We aimed to examine the molecular pathogenesis of very early-onset AD by skin surface lipid-RNA (SSL-RNA) using a non-invasive technology in infants aged 1 and 2 months from a prospective cohort. We collected sebum by oil-blotting film of infants aged 1 and 2 months and analyzed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. Infants with AD aged one month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes, and keratinization. They also had higher expression of several genes involved in Th2-, Th17-, and Th22-type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged one month with neonatal acne and diagnosed with AD aged two months already had gene expression patterns similar to AD aged one month in terms of redox, lipid synthesis, metabolism, and barrier-related gene expression. We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged one month. We also revealed that neonatal acne at one month could predict the subsequent development of AD by sebum transcriptome data.

Skin care interventions and early complementary food introduction for the prevention of atopic dermatitis in infants

аtopic dermatitis and food allergy are common diseases that usually begin in early childhood and can occur together in the same individuals. The aim of this study was to assess the significance of interventions such as skin care products for the skin barrier improvement, breastfeeding and early complementary foods introduction for the primary prevention of atopic dermatitis and food allergy in infants by building logistic regression models. We performed a survey of 97 parents of children. The survey was conducted with the help of Google forms and distributed on the Internet. Method of building and analysing logistic regression models was used to analyse the association of the risk of atopic dermatitis in children with the factor characteristics. Characteristics were as follows: "Skin care 1: application moisturizers to the infant's skin", "Skin care 2: bathing infants with water containing moisturizing substances or moisturizing oils", "Skin care 3: usage of less soap, bathing the child less often", "paternal history of atopy", "duration of breastfeeding less than 1 year", "early introduction of supplementary food (up to the 6th month of life)". We obtained the following results: 42.2% of respondents reported about the application of moisturizing cream, parents of 16.5% of children were using moisturizing oil for bathing the child, 12.4% of parents used less soap and bathed the child less often, 28.9% reported that they were not using any interventions. It was established that when applying care method 1, namely applying moisturizing agents to the infant’s skin, the risk of developing atopic dermatitis increases, OR=12.8 (95% CI 3.89 - 42.3) (p&lt;0.0001). When constructing a three-factor logistic regression model for predicting the risk of food allergy, no dependence was found between the development of food allergy and the presence of allergic diseases in parents, the period of introduction of complementary foods, and the duration of breastfeeding. Thus, this study did not reveal the protective role of skin care products, breastfeeding, and early introduction of complementary foods for the development of atopic dermatitis and food allergies in children. Multivariate analysis showed that atopic dermatitis is associated with emollients application to the infant’s skin. The use of moisturizing creams for the treatment of already existing atopic dermatitis or the path of percutaneous sensitization to allergens could have influenced the data.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Pimecrolimus for the Treatment of Atopic Dermatitis in Infants: An Asian Perspective.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3months and 2years of age in the Asian population.

Low Levels of Carotenoids in Maternal Serum and Breast Milk Associate with the Development of Atopic Dermatitis in Infancy

Although it has been shown that maternal intake of vegetables during pregnancy was associated with a decrease in the odds of eczema, the association between maternal and infant carotenoid levels and the development of Atopic dermatitis (AD) in infancy is not clear.

Early Skin Inflammatory Biomarker is Predictive of Development and Persistence of Atopic Dermatitis in Infants up to 12m of age

The STOP AD trial, a randomized, open-label, trial evaluating the effect of short-term (first four postnatal days to 8 weeks) skin barrier protection using AVEENO® Dermexa Fast & Long-Lasting Balm in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of AD at 12 months of age (Allergy 2022.doi: 10.1111/all.15491). Biomarkers that may predict at an early age risk of AD were measured.

Prenatal maternal anxiety promotes atopic dermatitis in offspring via placental DNA methylation changes.

Maternal anxiety during pregnancy has been previously reported to be associated with atopic dermatitis (AD) in offspring. The potential mechanism is not yet proven but epigenetic change may be suggested. We examined whether maternal anxiety during pregnancy may alter placental DNA methylation, then develop AD in the offspring. We evaluated maternal anxiety at 36 weeks of gestation by self-reported questionnaires, the State-Trait Anxiety Inventory-Trait subscale (STAI-T), in the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) study. AD was diagnosed at 6 months of age by pediatric allergists. We stratified the subjects into four groups according to the STAI score of mothers and diagnosis of AD in children. Placental genome-wide methylation microarray was analyzed using Infinium 450K BeadChip and selected genes were validated by pyrosequencing. From microarray, several differential methylation sites were identified in AD and healthy subjects and in total subjects, regarding to the STAI scores. Among differential methylation sites in microarray, six sites were selected for pyrosequencing. And site of matrix metalloproteinases 27 (MMP27) among 6 sites showed decreased methylation in AD infants with high STAI mothers compared to healthy infants with low STAI mothers. Epigenetic change in placenta can be a suggesting mechanism for the development of AD in offspring at 6 months of age associated with maternal anxiety during pregnancy and MMP27 may be a candidate gene.

Systematic review and network meta-analysis of different types of emollient for the prevention of atopic dermatitis in infants.

Prophylactic application of emollients has been an effective strategy against infant atopic dermatitis (AD); however, the difference of different emollients is unknown. We performed this network meta-analysis to compare different emollients in preventing infant AD. A systematic search was performed in PubMed, EMBASE and Cochrane library to identify relevant studies from their inception through 28 February, 2022. We evaluated the quality of eligible studies using the Cochrane risk of bias assessment tool. Data analysis was performed using STATA 14.0. Eleven studies were included for data analysis. Direct meta-analysis suggested that early application of emollients effectively prevented AD development in high-risk infants (risk ratio [RR], 0.64; 95% confidence interval [CI], 0.47 to 0.88). Network meta-analysis suggested that emollient emulsion might the better option for preventing infant AD development, with a surface under the cumulative ranking curve (SUCRA) of 82.6% for all populations, 78.0% for high-risk populations and 79.2% for populations with food sensitization. Moreover, subjects receiving emollients more frequently experienced adverse events. Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants and emollient emulsion may be the optimal type. Future study with well-designed and large scale are warranted to validate our findings.

The associations of maternal and children's gut microbiota with the development of atopic dermatitis for children aged 2 years.

It is critical to investigate the underlying pathophysiological mechanisms in the development of atopic dermatitis. The microbiota hypothesis suggested that the development of allergic diseases may be attributed to the gut microbiota of mother-offspring pairs. The purpose of this study was to investigate the relationship among maternal-offspring gut microbiota and the subsequent development of atopic dermatitis in infants and toddlers at 2 years old. A total of 36 maternal-offspring pairs were enrolled and followed up to 2 years postpartum in central China. Demographic information and stool samples were collected perinatally from pregnant mothers and again postpartum from their respective offspring at the following time intervals: time of birth, 6 months, 1 year and 2 years. Stool samples were sequenced with the 16S Illumina MiSeq platform. Logistic regression analysis was used to explore the differences in gut microbiota between the atopic dermatitis group and control group. Our results showed that mothers of infants and toddlers with atopic dermatitis had higher abundance of Candidatus_Stoquefichus and Pseudomonas in pregnancy and that infants and toddlers with atopic dermatitis had higher abundance of Eubacterium_xylanophilum_group at birth, Ruminococcus_gauvreauii_group at 1 year and UCG-002 at 2 years, and lower abundance of Gemella and Veillonella at 2 years. Additionally, the results demonstrated a lower abundance of Prevotella in mothers of infants and toddlers with atopic dermatitis compared to mothers of the control group, although no statistical difference was found in the subsequent analysis. The results of this study support that gut microbiota status among mother-offspring pairs appears to be associated with the pathophysiological development of pediatric atopic dermatitis.

Association between early life antibiotic exposure and development of early childhood atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease commonly onset during infancy. We examine the association between pre-and postnatal antibiotic exposure and the development of AD. A retrospective, observational study analyzed 4106 infants at the University of Florida from June 2011 to April 2017. Antibiotic exposure during the first year of life was associated with a lower risk of AD. The association was strongest for exposure during the first month of life. There were no significant differences in the rates of AD in infants with or without exposure to antibiotics in months 2 through 12, when examined by month. Antibiotic exposure during week 2 of life was associated with lower risk of AD, with weeks 1, 3, and 4 demonstrating a similar trend. Retrospective data collection from a single center, use of electronic medical record, patient compliance with prescribed medication, and variable follow-up. Early life exposures, such as antibiotics, may lead to long-term changes in immunity. Murine models of atopic dermatitis demonstrate a "critical window" for the development of immune tolerance to cutaneous microbes. Our findings suggest that there may also be a "critical window" for immune tolerance in human infants, influenced by antibiotic exposure.

Effectiveness of a standardized skin care regimen to prevent atopic dermatitis in infants at risk for atopy: a randomized, pragmatic, parallel-group study.

It has been proposed that regular emollient application in early life could enhance skin barrier function and prevent atopic dermatitis (AD) especially in predisposed infants. This hypothesis was supported by evidence from exploratory and pilot trials showing protective effects in terms of reduced cumulative atopic dermatitis incidence with the use of daily emollient therapy starting immediately after birth. To investigate the effectiveness of a standardized skin care regimen for infants on the development of AD compared to not structured skin care regimen in infants with atopic predisposition. Prospective, parallel group, randomized, pragmatic, investigator-blinded intervention trial including 160 infants with 52 weeks intervention and 52 weeks follow up phase up to the age of two years. Infants were randomly assigned to receive a standardized skin care regimen including once daily leave-on product application (lipid content 21%) or skin care as preferred by the parents. Using the intention to treat approach, the cumulative AD incidence was 10.6% after one year, and 19.5% after two years in the total sample. There were no statistical significant differences between intervention and control groups. Skin barrier parameters between the intervention and control groups were comparable. AD severity was higher and quality of life was more affected in the control group. Regular emollient application during the first year of life does not prevent the development of atopic dermatitis. A standardized skin care regimen does not delay skin barrier development or causes side effects.

Managing atopic dermatitis in infants.

Classical flexural involvement may not develop until later in childhood. Other transient forms of dermatitis, including irritant dermatitis and seborrheic dermatitis, should be differentiated from atopic dermatitis.[1][1] New evidence has shown that, applied twice daily and as required, any class