Early skin inflammatory biomarker is predictive of development and persistence of atopic dermatitis in infants.

BACKGROUND: The Short-Term Topical Application for Prevention of Atopic Dermatitis (STOP AD) study, a randomized, open-label trial evaluating the effect of short-term (from the first 4 postnatal days to age 8 weeks) skin barrier protection using Aveeno Dermexa Fast & Long-Lasting Balm (Johnson & Johnson, New Brunswick, NJ) in infants with a parent with allergic disease, demonstrated decreased cumulative incidence and decreased prevalence of atopic dermatitis (AD) at age 12 months. OBJECTIVE: In the STOP AD study, we aimed to identify skin biomarkers that are associated with risk of development of AD. METHODS: Skin swabs were collected from the cheek and antecubital fossa (AF) at baseline, age 8 weeks, and age 12 months from subsets of study participants from the intervention arm (n = 43 of 119) and control arm (n = 43 of 138) and were analyzed for specific cytokines (CCL27, CXCL2, human ß-defensin-1 [hBD-1], IL-18, IL-8, IL-1α, IL-1 receptor antagonist [IL-1RA], IL-1ß, S100A8/9, and IL-36γ) by ELISA. RESULTS: Higher titers of S100A8/9 at the AF at age 8 weeks in infants with the filaggrin wild-type genotype (FLGwt), but not in those with filaggrin loss-of-function mutation (FLGmut), predicted (1) development of AD in the first year of life (P = .033), (2) presence of AD at ages 6 or 12 months (P = .009 and .035, respectively), (3) persistence of AD between ages 6 and 12 months (P < .001), and (4) development of AD with the emollient intervention. CONCLUSION: Increased titers of S100A8/9 from skin swabs of the AF in high-risk infants at age 8 weeks with FLGwt were predictive of AD development in the first year of life and other AD features. These findings suggest that there are different molecular pathways leading to AD in individuals with FLGmut and in individuals with FLGwt. Early identification of infants who are likely to develop AD will allow more targeted interventions.

Skin-centered strategies in food allergy prevention.

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta-analyses have demonstrated either no effect or only a slight positive effect on FA prevention. However, a careful review of the clinical trials reveals that different emollients were used, which may have explained some of the discrepancies between study results. Emollient application protocols also varied widely between studies. While firm conclusions cannot be drawn with regard to their overall efficacy at preventing FA, the available data provide valuable insight into the characteristics that could be associated with a more effective intervention. Namely, successful trials tended to use emollients with an acidic pH of 5.5, applied over the entire body, and combined with topical corticosteroids in affected areas. Consensus on the optimal strategy to restore skin barrier function could help improve the homogeneity and clinical relevance of future trials on this topic. In the meantime, clinicians should avoid products associated with worse outcomes.

Comparing emollient use with topical luliconazole (azole) in the maintenance of remission of chronic and recurrent dermatophytosis. An open-label, randomized prospective active-controlled non-inferiority study.

BACKGROUND: Literature on emollient use in the management of chronic and recurrent dermatophytosis is limited. OBJECTIVE: To assess the efficacy of emollient in the remission maintenance of chronic and recurrent dermatophytosis. METHODS: In this randomized open-label study with the intention to treat, 80 patients with chronic recurrent dermatophytosis were randomized into two groups, where both groups were treated adequately for 6 weeks, followed by continuation of topical azole in group A and topical emollient in group B for 6 weeks. Clinical remission was determined by disappearance signs and symptoms of tinea lesions with or without hyperpigmentation. Physician and patient global assessment scores were evaluated every 2 weeks for 6 weeks to assess remission maintenance. RESULTS: A total of 80 patients of chronic and recurrent dermatophytosis were assessed for remission maintenance. The recurrence of disease occurred in 20 patients overall, wherein 7 patients (17.5%) in group A and 13 patients (32.5%) in group B at the end of the study (18 weeks); however, the difference between the two groups was not statistically significant (p = .121). The mean physician global assessment scores of group A and group B at 12 weeks were 4.45 ± 0.74 and 4.15 ± 0.92, 4.43 ± 0.90 and 4.10 ± 0.98 at 14 weeks, 4.0 ± 1.32 and 3.98 ± 1.23 at 16 weeks, 3.85 ± 1.44 and 3.90 ± 1.35 at 18 weeks, respectively. The mean patient global assessment scores of group A and group B were 4.65 ± 0.62 and 4.25 ± 0.87 at 12 weeks, 4.40 ± 0.87 and 4.17 ± 0.98 at 14 weeks, 4.18 ± 1.15 and 4.12 ± 1.30 at 16 weeks and 3.97 ± 1.33 and 3.90 ± 1.51 at 18 weeks. CONCLUSION: The present study concludes that the efficacy of emollient was not inferior to topical luliconazole for maintaining remission in chronic and recurrent dermatophytosis.

Postnatal care and acceptability of emollient therapy in very low birthweight infants in Harare, Zimbabwe: a qualitative analysis.

BACKGROUND: Preterm birth (birth before 37 completed weeks of pregnancy) is the leading cause of neonatal and child under-five mortality globally, both of which are highest regionally in sub-Saharan Africa. The skin barrier plays a critical role in neonatal health and increasing evidence supports the use of topical emollient therapy to promote postnatal growth and reduce hospital-acquired infections in preterm infants. The World Health Organization (WHO) currently recommends emollient therapy in preterm or low birthweight infants globally but calls for further research on impacts of emollient use, especially in Africa. Little is known about postnatal skincare practices and the tradition of oil massage across sub-Saharan Africa. Further documentation is necessary to understand the context for future emollient intervention trials. METHODS: 61 semi-structured interviews with mothers who just delivered preterm or term infants and 4 focus group discussions (32 participants) with physician and nurse providers of newborn care were conducted at Sally Mugabe Central Hospital (SMCH), in Harare, Zimbabwe. SMCH is the principal public-sector tertiary care hospital for newborn infants in the northern part of the country. Mothers and healthcare professionals were questioned about newborn care at the hospital, current neonatal skincare and bathing practices, and the community's receptivity to a future emollient therapy clinical trial. RESULTS: Postnatal skincare is centrally important to Zimbabwean communities and petroleum jelly application is nearly universal. The use of cooking oil and other natural oils on infants is also part of traditional customs. The primary needs and desires of mothers who have just given birth to preterm infants are having greater agency in their children's care and financial support in purchasing prescribed medications while at the hospital. Community receptivity to emollient therapy as a cost-effective treatment is high, particularly if mothers are trained to assist with the intervention. CONCLUSION: Emollient therapy will likely be well-received by communities in and around Harare because of its accordance with current skincare practices and perceptions; however, cultural norms and the experiences of new mothers who have given birth at a facility highlight challenges and considerations for future clinical trial execution. TRIAL REGISTRATION: Clinicaltrials.gov NCT05461404.

Introducing the model of repeated exposure of skin to antiseptics: Randomised pilot trial.

INTRODUCTION: Intensified hand hygiene measures were recommended for preventing the spread of SARS-CoV-2. However, these measures can lead to skin damage and the development of hand eczema, particularly among health professionals. OBJECTIVES: This pilot study aimed to evaluate the effects of repeated antiseptic use on healthy skin under controlled conditions and to assess the emollient use. METHODS: Twelve healthy volunteers (nine females, age = 22.3 ± 2.8 years (mean ± SD), Fitzpatrick phototypes II and III) with no skin diseases were recruited. Antiseptic was applied daily for 3 weeks on the volar sides of forearms. Emollient cream was also applied daily. Skin assessments were performed using non-invasive methods (transepidermal water loss-TEWL, skin hydration, erythema and melanin content). RESULTS: Prolonged antiseptic use increased TEWL, decreased hydration and elevated erythema and melanin levels. Emollient cream significantly reduced TEWL and improved hydration on antiseptic-treated sites, and also enhanced hydration on intact skin. CONCLUSIONS: Prolonged use of antiseptics can have adverse effects on the skin, including barrier disruption and inflammation. Emollient showed promise in improving skin hydration and reducing the damage caused by antiseptics. Further research with a larger sample is needed to confirm these findings and assess emollient efficacy during frequent antiseptic use.

Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions.

INTRODUCTION: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. METHODS: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. RESULTS: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. CONCLUSION: Synergistic effects of the test product's pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.

Impact of multilamellar formulations on stratum corneum lipid organization and epidermal lipid barrier enhancement (Part II).

INTRODUCTION: The integrity of the stratum corneum (SC) is crucial for the skin's barrier function, protecting against environmental stressors and minimizing transepidermal water loss. Advances in skincare formulations have introduced multilamellar systems designed to emulate the SC's lipid composition and organization. This study hypothesizes that the application of a multilamellar cream will significantly impact the SC's lipid content and lamellar structure, thereby enhancing the epidermal barrier. METHODS: A saturated phosphatidylcholine-based multilamellar cream was applied to a cohort of adult subjects with very dry skin. Electron microscopy was utilized to analyse the micro-morphology of the cream and its integration into the lipid-depleted SC. Lipid analysis was conducted to quantify changes in the intercellular lipid matrix. RESULTS: Transmission-electron microscopy (TEM) imaging demonstrated that the multilamellar cream possesses a structured arrangement comparable to the natural SC architecture. Short-term application revealed a time-dependent restoration of lipid bilayers, while a 14-day regimen showed a marked increase in lipid lamellae density and length within the SC. Lipid analysis indicated a significant increase in total lipid content, with notable enhancements in ceramide and free fatty acid levels, without altering cholesterol levels. Lipid ratio analysis further confirmed the rebalancing of the SC's lipid composition. DISCUSSION: The multilamellar cream selectively increased specific lipids critical for barrier function, suggesting an action mechanism that aligns with the skin's natural regulatory processes. This selective augmentation indicates the potential of the formulation to not only restore but also enhance the epidermal barrier, with the maintenance of physiological lipid ratios suggesting compatibility with intrinsic repair mechanisms. CONCLUSION: The study confirms that a multilamellar cream can significantly improve the SC's lipid composition and structural integrity, indicating enhanced barrier function. They are pivotal for skincare professionals, dermatologists, and product developers, enriching the understanding of multilamellar creams' benefits and applications in improving epidermal barrier function.

INTRODUCTION: l'intégrité de la couche cornée (SC, stratum corneum) est essentielle pour la fonction de barrière cutanée, protégeant contre les facteurs de stress environnementaux et réduisant au minimum la perte d'eau transépidermique. Les progrès en matière de formulations pour soins de la peau ont introduit des systèmes multilamellaires conçus pour simuler la composition et l'organisation lipidique du SC. Cette étude émet l'hypothèse que l'application d'une crème multilamellaire aura un impact significatif sur la teneur en lipides et la structure lamellaire du SC, améliorant ainsi la barrière épidermique. MÉTHODES: Une crème multilamellaire à base de phosphatidylcholine saturée a été appliquée à une cohorte de sujets adultes présentant une peau très sèche. La microscopie électronique a été utilisée pour analyser la micromorphologie de la crème et son intégration dans le SC délipidé. Une analyse lipidique a été réalisée pour quantifier les changements dans la matrice lipidique intercellulaire. RÉSULTATS: l'imagerie par TEM a démontré que la crème multilamellaire possède un agencement structuré comparable à l'architecture naturelle du SC. L'application à court terme a révélé une restauration dépendante du temps des bicouches lipidiques, tandis qu'un schéma posologique de 14 jours a montré une augmentation marquée de la densité et de la longueur des lamelles lipidiques au sein du SC. L'analyse lipidique a indiqué une augmentation significative de la teneur lipidique totale, avec des améliorations notables des taux de céramide et d'acides gras libres, sans altérer les taux de cholestérol. L'analyse du rapport lipidique a confirmé le rééquilibrage de la composition lipidique du SC. DISCUSSION: la crème multilamellaire a augmenté de manière sélective les lipides spécifiques essentiels à la fonction de barrière, suggérant un mécanisme d'action qui s'aligne sur les processus de régulation naturels de la peau. Cette augmentation sélective indique le potentiel de la formulation non seulement à restaurer, mais également à améliorer la barrière épidermique, avec le maintien des rapports lipidiques physiologiques suggérant une compatibilité avec les mécanismes de réparation intrinsèques. CONCLUSION: l'étude confirme qu'une crème multilamellaire peut améliorer de manière significative la composition lipidique et l'intégrité structurelle du SC, ce qui indique une meilleure fonction de barrière. Ils sont essentiels pour les professionnels de la peau, les dermatologues et les développeurs de produits, et enrichissent la compréhension des bénéfices et des applications des crèmes multilamellaires dans l'amélioration de la fonction de la barrière épidermique.

Clinical efficacy of a multilamellar cream on skin physiology and microbiome in an epidermal stress model: A controlled double-blinded study.

INTRODUCTION: Stratum corneum (SC) is essential for skin barrier function, mitigating water loss and shielding against potentially harmful substances and allergens. The SC's lipid matrix, arranged in a lamellar structure, is integral to its protective role. Our study explores the restoration effects of a multilamellar cream with an acidic pH compared to a basic placebo cream on skin physiology and its interaction with the skin microbiome after stress induction via tape stripping (TS). MATERIALS AND METHODS: In this double-blind study, 14 healthy participants aged 21-58 years were assessed pre- and post-tape stripping, followed by a 14 days application of a multilamellar test cream and a placebo cream with evaluations on days 7, 14 and 17 for sustained effects. Skin physiology was analysed in terms of epidermal barrier function, SC hydration and surface pH. The microbiome was analysed by 16S rRNA amplicon sequencing the 16S rRNA gene using Illumina MiSeq, with subsequent species identification. RESULTS: Our study showed significant improvements in skin barrier repair and SC hydration with verum, particularly after 14 days of application, while both creams initially enhanced stratum corneum hydration. No significant changes in surface-pH were detected. The skin microbiome analysis revealed that TS slightly decreased alpha diversity, a trend that verum significantly reversed, enhancing diversity beyond baseline levels after 14 days. Overall, while both creams contributed to a broader microbial phyla diversity over time, no significant changes in the abundance of specific genera or species were noted between treatments. DISCUSSION AND CONCLUSION: Our study delineates the efficacy of a pH-optimized multilamellar cream in enhancing epidermal barrier recovery and SC hydration post-sequential TS, in contrast to an unstructured basic placebo. Verum cream significantly improved skin barrier function and SC hydration at day 14, with sustained effects evident beyond the treatment period. Furthermore, the multilamellar formulation facilitated the restitution of cutaneous microbiome diversity, a key indicator of healthy skin ecology, underscoring the symbiotic relationship between barrier integrity and microbial composition. These findings underscore the importance of multilamellar emollient structures in dermatological therapeutics, with potential implications for the design of advanced skincare interventions that holistically support cutaneous resilience and homeostasis.

INTRODUCTION: La couche cornée (stratum corneum, SC) est essentielle pour la fonction de barrière cutanée, atténuant la perte d'eau et protégeant contre les substances et allergènes potentiellement nocifs. Disposée selon une structure lamellaire, la matrice lipidique de la SC est constitutive de son rôle protecteur. Notre étude explore les effets de restauration d'une crème multilamellaire à pH acide par rapport à une crème placebo de base sur la physiologie de la peau et son interaction avec le microbiome de la peau après induction de stress via un test tape stripping (TS). MATÉRIELS ET MÉTHODES: Dans cette étude en double aveugle, 14 participants en bonne santé âgés de 21 à 58 ans ont été évalués avant et après tape stipping, puis ont procédé à l'application pendant 14 jours d'une crème test multilamellaire et d'une crème placebo avec des évaluations aux jours 7, 14 et 17 pour les effets durables. La physiologie de la peau a été analysée en termes de fonction de la barrière épidermique, d'hydratation SC et de pH de surface. Le microbiome a été analysé par séquençage de l'amplicon de l'ARNr 16S sur le gène de l'ARNr 16S à l'aide d'Illumina MiSeq, avec identification ultérieure des espèces. RÉSULTATS: Notre étude a montré des améliorations significatives de la réparation de la barrière cutanée et de l'hydratation SC avec le traitement actif, en particulier après 14 jours d'application, tandis que les deux crèmes avaient initialement amélioré l'hydratation de la couche cornée. Aucun changement significatif du pH de surface n'a été détecté. L'analyse du microbiome cutané a révélé que le TS diminuait légèrement la diversité alpha, une tendance qui s'est significativement inversée avec le traitement actif : une amélioration de la diversité au­delà des taux initiaux était observée après 14 jours. Dans l'ensemble, bien que les deux crèmes aient contribué à une plus grande diversité des phyla microbiennes au fil du temps, aucune variation significative dans l'abondance de genres ou d'espèces spécifiques n'a été observée entre les traitements. DISCUSSION ET CONCLUSION: Notre étude délimite l'efficacité d'une crème multilamellaire à pH optimisé pour améliorer la réparation de la barrière épidermique et l'hydratation SC après un TS séquentiel, contrairement à un placebo basique non structuré. La crème contenant le traitement actif a significativement amélioré la fonction de barrière cutanée et l'hydratation SC au jour 14, avec des effets durables évidents au­delà de la période de traitement. En outre, la formulation multilamellaire a facilité la restitution de la diversité du microbiome cutané, un indicateur clé d'une écologie de peau en bonne santé, soulignant la relation symbiotique entre l'intégrité de la barrière et la composition microbienne. Ces résultats soulignent l'importance des structures émollientes multilamellaires dans les traitements dermatologiques, avec des implications potentielles pour la conception d'interventions cutanées avancées qui soutiennent de manière holistique la résilience cutanée et l'homéostasie.

Topical emollient prevents the development of atopic dermatitis and atopic march in mice.

To investigate the effect of emollient on atopic march in a murine model of atopic dermatitis (AD). Following induction of AD with topical calcipotriol (MC903) and ovalbumin (OVA), one group of mice was treated topically with a linoleic acid-ceramide-containing emollient, while mice without emollient treatment served as disease controls. After 28 days, clinical, histological and transcriptomic analyses were performed in the skin lesions and the lung as well as serum cytokine levels. Treatments of mice with MC903 and OVA induced a typical phenotype of AD, accompanied by increased expression levels of Th2 and basophil-related genes in the lung. Topical emollients markedly decreased the severity of skin lesions and inflammatory cell infiltration. Moreover, emollient treatments significantly downregulated expression levels of AD-related genes (286 of 1450 differentially expressed genes), including those related to innate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and epidermal permeability barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2), etc. Downregulated genes were enriched in mitochondrial OXPHOS-related pathways, while upregulated genes were mainly enriched in axon guidance and tight junctions. Moreover, topical emollient treatments decreased total serum levels of IL-4, along with substantial reductions in IgE and thymic stromal lymphopoietin (TSLP) levels. Furthermore, 187 of 275 upregulated genes in lung tissue were also significantly downregulated, including those involved in leucocyte chemotaxis (Ccl9, Ccr2, Retnlg, Ccl3, Cxcl10, Il1r2, etc.) and basophil activation (Mcpt8, Cd200r3, Fcer1a, Ms4a2). In conclusion, topical emollient not only reduces skin inflammation, but also mitigates systemic inflammation by decreasing TSLP and IgE levels. Moreover, topical emollient reduces chemokine production and basophil infiltration and activation in the lung.

Early initiation of short-term emollient use for the prevention of atopic dermatitis in high-risk infants-The STOP-AD randomised controlled trial.

BACKGROUND: Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high-risk infants at 12 months. METHODS: This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months. RESULTS: Three hundred twenty-one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p > 0.05). CONCLUSIONS: This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants.

Early emollient bathing is associated with subsequent atopic dermatitis in an unselected birth cohort study.

BACKGROUND: Skin barrier dysfunction is a key component of the pathogenesis of atopic dermatitis (AD). Recent research on barrier optimization to prevent AD has shown mixed results. The aim of this study was to assess the relationship between emollient bathing at 2 months and the trajectory of AD in the first 2 years of life in a large unselected observational birth cohort study. METHODS: The Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study enrolled 2183 infants. Variables extracted from the database related to early skincare, skin barrier function, parental history of atopy, and AD outcomes. Statistical analysis was performed to adjust for potential confounding variables. RESULTS: One thousand five hundred five children had data on AD status available at 6, 12, and 24 months. Prevalence of AD was 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months. Adjusted for potential confounding variables, the odds of AD at any point were higher among infants who had emollient baths at 2 months (OR (95% CI): 2.41 (1.56 to 3.72), p < .001). Following multivariable analysis, the odds of AD were higher among infants who had both emollient baths and frequent emollient application at 2 months, compared with infants who had neither (OR (95% CI) at 6 months 1.74 (1.18-2.58), p = .038), (OR (95% CI) at 12 months 2.59 (1.69-3.94), p < .001), (OR (95% CI) at 24 months 1.87 (1.21-2.90), p = .009). CONCLUSION: Early emollient bathing was associated with greater development of AD by 2 years of age in this population-based birth cohort study.

Perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda: a qualitative study.

BACKGROUND: The skin is a major route of infection in the neonatal period, especially in low birthweight (LBW) infants. Appropriate and safe neonatal skin care practices are required to reduce this risk. The perceptions and beliefs of mothers and other caregivers towards various neonatal skin care practices in our setting have been documented. Data from Asia suggests that the application of emollient to the skin of LBW infants can promote growth, reduce serious neonatal infections, and potentially reduce mortality. This is the first study to explore the acceptability of emollients and massage as part of neonatal skin care in a low-resource setting in sub-Saharan Africa (SSA) that is representative of the majority of government health facilities in Uganda and many in SSA. OBJECTIVE: To explore perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda. METHODS: We conducted a qualitative study consisting of three focus group discussions (30 participants), eight in-depth interviews with mothers/caregivers of preterm and term neonates and 12 key informant interviews with midwives, doctors and community health workers involved in neonatal care, to explore the perceptions and practices surrounding neonatal skin care and emollient use. Data collected were transcribed and analyzed using thematic content analysis. RESULTS: Mothers perceived that skin care began in utero. Skincare practices depended on the place of delivery; for deliveries in a health facility the skincare practices were mainly based on the health worker's advice. Vernix caseosa was often washed off due to its perceived undesirability and was attributed to sexual intercourse in the last trimester. Despite their deleterious attributes found in previous studies, petrolatum-based oils, petrolatum-based jellies and talcum baby powders were the most commonly reported items used in neonatal skin care. In our population, there was high acceptability of emollient therapy use; however, neonatal massage was treated with scepticism as mothers feared damaging the vulnerable neonate. Mothers suggested massage and emollient application be undertaken by health workers, if it becomes an intervention. CONCLUSIONS: In eastern Uganda, the perceptions and beliefs of mothers/caregivers toward neonatal skincare influenced their practices of which some could potentially be beneficial, and others harmful. Emollient use would be easily accepted if adequate sensitisation is conducted and using the gatekeepers such as health workers.

Emollients in infancy to prevent atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Several studies have evaluated prophylactic emollients as a preventive strategy against atopic dermatitis (AD) and food allergy (FA). We aimed to synthesize the evidence on efficacy and safety of prophylactic emollients started during the first 6 weeks of infancy for prevention of AD and FA. METHODS: MEDLINE, Embase, CINAHL, BIOSIS, and the Cochrane Library databases were searched systematically for randomized controlled trials published between January 2000 and July 2020, which assessed the effects of prophylactic emollients initiated within the first 6 weeks of life on the development of AD within 24 months of age, compared to no treatment. Risk of bias and certainty of evidence were assessed using the Cochrane Collaboration's tool and GRADE process, respectively. RESULTS: Of the 1486 articles identified, 10 studies fulfilled inclusion criteria. In infants given emollients, there was no significant reduction on the development of AD (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.64, 1.10) compared to the control group. However, there was significant benefit of prophylactic emollients (RR 0.75, 95% CI 0.62-1.11) in the high-risk population (n = 8 studies). There was also significant benefit (RR 0.59, 95% CI 0.43, 0.81) in studies (n = 6) where emollients were used continuously to the point of AD assessment; but not when treatment was ceased for an interval before AD assessment. There were no protective effects on FA found. CONCLUSION: The prophylactic application of emollients initiated in early infancy may prevent AD, especially in high-risk populations and when used continuously. We hypothesize that emollients may delay rather than prevent AD.

Enhanced phenotype of calcipotriol-induced atopic dermatitis in filaggrin-deficient mice.

Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG-deficient (Flg-/- ) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics on Flg-/- mice with calcipotriol (CPT)-induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generate Flg-/- mice and applied CPT to produce AD-like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin of Flg-/- mice to establish the AD-like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT-induced dermatitis in Flg-/- mice was more severer than that of wild-type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3+ T cells), and inflammatory cytokine expression (interleukin (IL)-4, IL-6, IL-13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation in Flg-/- mice with CPT-induced AD-like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT in Flg-/- mice could be utilized to search for drug targets in AD.

Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.

Comprehensive characterization of the structure and properties of human stratum corneum relating to barrier function and skin hydration: modulation by a moisturizer formulation.

The stratum corneum (SC) is key in the maintenance of the biomechanical barrier and hydration of skin. Our previous investigations showed beneficial effects of a combination of emollients on water capture and retention and protein and lipid organization, all of which are linked to dryness and dry skin damage. Here, we show how a formulation containing an emollient combination ("Trio") and its basal formulation (placebo) impacted the descriptors of SC hydration in SC layers. Only the Trio formulation-not its placebo formulation-modified SC biomechanical drying stress behaviour and imparted a high capacity to protect it from dehydration. This was in accordance with findings at the molecular level using Raman analyses and at the structural level using cryo-scanning electron microscopy (SEM). After topical application, only the Trio formulation profoundly increased lateral packing of lipids and their compactness. Cryo-SEM showed that, unlike the placebo formulation, the Trio formulation prevented the water loss when applied before the dehydration process. In conclusion, these studies demonstrate that stresses in the SC due to dehydration can be alleviated using a formulation containing emollients that interact with the SC lipid components.

Optimization, kinetic, and scaling-up of solvent-free lipase-catalyzed synthesis of ethylene glycol oleate emollient ester.

The use of enzymatic catalysts is an alternative to chemical catalysts as they can help to obtain products with less environmental impact, considered sustainable within the concept of green chemistry. The optimization, kinetic, lipase reuse, and scale-up of enzymatic production of ethylene glycol oleate in the batch mode were carried out using the NS 88011 lipase in a solvent-free system. For the optimization step, a 23 Central Composite Design was used and the optimized condition for the ethylene glycol oleate production, with conversions above 99%, was at 70 °C, 600 rpm, substrates molar ratio of 1:2, 1 wt% of NS 88011 in 32 H of reaction. Kinetic tests were also carried out with different amounts of enzyme, and it showed that by decreasing the amount of the enzyme, the conversion also decreases. The lipase reuse showed good conversions until the second cycle of use, after which it had a progressive reduction reaching 83% in the fourth cycle of use. The scale-up (ninefold increase) showed promising results, with conversion above 99%, achieving conversions similar to small-scale reactions. Therefore, this work proposed an environmentally safe route to produce an emollient ester using a low-cost biocatalyst in a solvent-free system.

Effect of topical applications of sunflower seed oil on systemic fatty acid levels in under-two children under rehabilitation for severe acute malnutrition in Bangladesh: a randomized controlled trial.

BACKGROUND: Children with severe acute malnutrition (SAM) have inadequate levels of fatty acids (FAs) and limited capacity for enteral nutritional rehabilitation. We hypothesized that topical high-linoleate sunflower seed oil (SSO) would be effective adjunctive treatment for children with SAM. METHODS: This study tested a prespecified secondary endpoint of a randomized, controlled, unblinded clinical trial with 212 children with SAM aged 2 to 24 months in two strata (2 to < 6 months, 6 to 24 months in a 1:2 ratio) at Dhaka Hospital of icddr,b, Bangladesh between January 2016 and December 2017. All children received standard-of-care management of SAM. Children randomized to the emollient group also received whole-body applications of 3 g/kg SSO three times daily for 10 days. We applied difference-in-difference analysis and unsupervised clustering analysis using t-distributed stochastic neighbor embedding (t-SNE) to visualize changes in FA levels in blood from day 0 to day 10 of children with SAM treated with emollient compared to no-emollient. RESULTS: Emollient therapy led to systematically higher increases in 26 of 29 FAs over time compared to the control. These effects were driven primarily by changes in younger subjects (27 of 29 FAs). Several FAs, especially those most abundant in SSO showed high-magnitude but non-significant incremental increases from day 0 to day 10 in the emollient group vs. the no-emollient group; for linoleic acid, a 237 µg/mL increase was attributable to enteral feeding and an incremental 98 µg/mL increase (41%) was due to emollient therapy. Behenic acid (22:0), gamma-linolenic acid (18:3n6), and eicosapentaenoic acid (20:5n3) were significantly increased in the younger age stratum; minimal changes were seen in the older children. CONCLUSIONS: SSO therapy for SAM augmented the impact of enteral feeding in increasing levels of several FAs in young children. Further research is warranted into optimizing this novel approach for nutritional rehabilitation of children with SAM, especially those < 6 months. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02616289 .

Developing a cosmetic series: Results from the ESSCA network, 2009-2018.

BACKGROUND: There is considerable variability across European patch test centres as to which allergens are included in local and national cosmetics series. OBJECTIVES: To propose a standardized, evidence-based cosmetic series for Europe based on up-to-date analysis of relevant contact allergens. METHODS: We collated data from the European Surveillance System on Contact Allergies (ESSCA) from 2009 to 2018 to determine which cosmetic allergens produce a high yield of contact allergy. Contact allergens with a prevalence of >0.3% that were considered relevant were included. Rare contact allergens were excluded if deemed no longer relevant or added to a supplemental cosmetic series for further analysis. RESULTS: Sensitization prevalences of 39 cosmetic contact allergens were tabulated. Thirty of these allergens yielded >0.3% positive reactions and are therefore included in our proposed European cosmetic series. Six were considered no longer relevant and therefore excluded. Three were included in a supplementary European cosmetic series. An additional nine allergens were included in either the core or supplemental European cosmetic series following literature review. CONCLUSION: We have derived a potential European cosmetic series based upon the above methods. This will require ongoing investigation based upon the changing exposure profiles of cosmetic allergens as well as new and evolving substances.

Clinical relevance of positive patch test reactions to lanolin: A ROAT study.

BACKGROUND: Lanolin is often included when patch testing for common contact allergens. The clinical relevance of a positive patch test reaction to lanolin markers is, however, still a subject for debate. OBJECTIVES: To evaluate Amerchol L101 as a marker of lanolin allergy and investigate the clinical impact of lanolin-containing moisturizers on healthy and damaged skin using the repeated open application test (ROAT). METHODS: Twelve test subjects and 14 controls were patch tested with Amerchol L 101 and additional lanolin markers. Subsequently, a blinded ROAT was performed on the arms of the study participants for 4 weeks. Each participant applied a lanolin-free cream base and two different lanolin-containing test creams twice daily on one arm with intact skin and on the other arm with irritant dermatitis, induced by sodium lauryl sulfate (SLS). RESULTS: Eleven test subjects (92%) had positive patch test reactions to Amerchol L 101 when retested and one test subject (8%) had a doubtful reaction. None of the study participants had any skin reactions to the ROAT on intact skin and all participants healed during the ROAT on damaged skin. CONCLUSIONS: Lanolin-containing emollients do not cause or worsen existing dermatitis when performing ROAT in volunteers patch test positive to Amerchol L101.