Best emollients for eczema (BEE) - comparing four types of emollients in children with eczema: protocol for randomised trial and nested qualitative study.

INTRODUCTION: Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend 'leave-on' emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease 'flares'. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first. METHODS AND ANALYSIS: Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments). SETTING: general practitioner surgeries in England. PARTICIPANTS: children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients. INTERVENTIONS: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care. FOLLOW-UP: 52 weeks. PRIMARY OUTCOME: validated patient-orientated eczema measure measured weekly for 16 weeks. SECONDARY OUTCOMES: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact). SAMPLE SIZE: 520 participants (130 per group). ANALYSIS: intention-to-treat using linear mixed models for repeated measures.Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically. ETHICS AND DISSEMINATION: Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN84540529.

A Global Review on the Risk Factors and Management of Early Atopic Dermatitis in Children Ages 0 to 2 Years Old

Introduction: Atopic dermatitis (AD) is a chronic, relapsing skin disease starting typically in atopic-prone children between 3­6 months of age, with most children having developed AD by the age of 5 years. Intense itching leads to sleep disturbance, especially in younger children and toddlers. This review explores early intervention in infants and young children with AD by controlling skin barrier function and inflammation at the earliest time point using a moisturizer and a proactive treatment. Methods: A working group of experienced clinicians managing pediatric populations with AD convened for a meeting. The panel reviewed the literature surrounding early intervention in infants and young children with AD and developed and discussed clinical questions aimed at optimizing clinical outcomes. Results: Complex gene/immune system/environment interactions are involved in AD development. Epidermal barrier defects play a central role in the condition, with various studies showing impairment of skin barrier function at birth may precede clinical AD. Dynamic changes take place in the amounts of skin lipids during infancy. Studies confirm that daily use of a moisturizer from birth onwards may offer benefits in improving skin barrier function and possibly prevention of AD, especially in high-risk, atopic prone newborns. Plant-based moisturizers were shown to be safe and effective when applied in pediatric patients with AD and may provide a TCS-sparing effect while improving skin condition. Conclusion: Dry skin conditions during infancy may predict the subsequent development of AD. Consequently, emollient therapy from birth represents a feasible, safe, and effective approach for AD prevention. Therefore, parental education and the application of moisturizers are recommended as an integral part of AD prevention, treatment, and maintenance. J Drugs Dermatol. 2019;18(10):1020-1027.

Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCT.

BACKGROUND: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema. DESIGN: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups. SETTING: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically. PARTICIPANTS: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation. INTERVENTIONS: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required. MAIN OUTCOME MEASURES: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding. RESULTS: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years (n = 264 in the intervention group, n = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping. LIMITATIONS: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups. CONCLUSION: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema. FUTURE WORK: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84102309. FUNDING: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 22, No. 57. See the NIHR Journals Library website for further project information.

Effectiveness and cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children (The BEEP trial): protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis). METHODS: This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires. DISCUSSION: This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases. TRIAL REGISTRATION: ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014.

Choice of Moisturiser for Eczema Treatment (COMET): study protocol for a randomized controlled trial.

BACKGROUND: Eczema is common in children and in the UK most cases are managed in primary care. The foundation of all treatment is the regular use of leave-on emollients to preserve and restore moisture to the skin. This not only improves comfort but may also reduce the need for rescue treatment for 'flares', such as topical corticosteroids. However, clinicians can prescribe many different types of emollient and there is a paucity of evidence to guide this choice. One reason for this may be the challenges of conducting a clinical trial: are parents or carers of young children willing to be randomly allocated an emollient and followed up for a meaningful amount of time? DESIGN: This is a single-centre feasibility study of a pragmatic, four-arm, single-masked, randomized trial. Children with eczema who are eligible (from 1 month to less than 5 years of age, not known to be sensitive or allergic to any of study emollients or their constituents) are recruited via their general practices. Participants are allocated Aveeno® lotion, Diprobase® cream, Doublebase® gel or Hydromol® ointment via a web-based system, using a simple randomization process in a 1:1:1:1 fashion. Researchers are masked to the study emollient. Participants are assessed at baseline and followed up for 3 months. Data are collected by daily diaries, monthly researcher visits and review of electronic medical records. Because this is a feasibility study, a formal sample size calculation for the estimation of treatment effectiveness has not be made but we aim to recruit 160 participants. DISCUSSION: Recruitment is on-going. At the end of the study, as well as being able to answer the question, 'Is it is possible to recruit and retain children with eczema from primary care into a four-arm randomized trial of emollients?', we will also have collected important data on the acceptability and effectiveness of four commonly used emollients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21828118 and Clinical Trials Register EudraCT2013-003001-26.

Efficacy and tolerance assessment of a new type of dermocosmetic in infants and children with moderate atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory and pruritic skin disorder. OBJECTIVES: To assess the efficacy and tolerance of a new emollient (SBT complex) in subjects with moderate AD. METHODS: Subjects received twice daily for 168 days (6 months) either SBT complex or emollient base adjunctively or alternately with topical corticosteroids or calcineurin inhibitors. Evolution of AD was assessed throughout the study using usual AD assessment criteria including SCORAD and PO-SCORAD. Quality of life was assessed at Day 0 and Day 168. RESULTS: At Day 168, a significant decrease with SBT complex was observed for the SCORAD and the PO-SCORAD scores (P < 0.05), the primary efficacy criteria. A total of 76% of SBT complex subjects did not relapse and time-to-relapse increased compared to the emollient base subjects. Intensity, dryness, and quality of life (P < 0.05) had improved in subjects using SBT complex. The product was well tolerated with less physical and functional signs in the SBT than in the emollient base group. CONCLUSION: The new emollient dermocosmetic SBT complex applied adjunctively or alternately with topical AD treatments significantly improved AD without any safety concerns. SBT complex may play an important role in the restoration of the natural skin barrier.

Atopic dermatitis - all you can do from the outside.

Atopic dermatitis (AD) affects both the epidermal barrier and the immune system and, as such, therapy needs to address both. Skin cleansing supported by emollients and moisturizers is the primary topical therapy when treating patients with AD. However, it should be remembered that the direct use of emollients on inflamed skin is poorly tolerated and that the flares need to be treated effectively, usually by topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI). This contribution outlines a number of strategies for effectively managing AD, from reactive therapy using TCS and TCI to proactive therapy. Proactive therapy is an alternative, evidence-based, immunologically founded treatment approach, based on the fact that normal-looking, nonlesional skin of patients with AD is not normal. The advantage of the proactive approach is that the patients are in control of their disease and are actively involved in its management. The avoidance of external irritants is recommended wherever possible.

Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study).

BACKGROUND: For long-term management of atopic eczema, the use of skin care creams is recommended, but effectiveness of this treatment is not well established. OBJECTIVE: The objective of this study was to yield data on the skin care properties of a cream with a unique lamellar matrix containing N-palmitoylethanolamine (PEA) and to assess quality-of-life variables in patients with mild to moderate atopic eczema. SETTING: In this multinational, multicentre, observational, non-controlled, prospective cohort study, patients between 2 and 70 years of age were enrolled. All patients were supplied with the study product sufficient for treatment over the entire study period. Outcome was followed in periods between 3 and 7 days and 4 and 6 weeks after study start. Data were gathered from doctor reports and patient self-assessments via patient questionnaires. RESULTS: Data from 2456 patients entered the database. The mean examination intervals were 6 days for the 3- to 7-day period and 38 days for the 4- to 6-week period. At study end, intensities of erythema, pruritus, excoriation, scaling, lichenification and dryness were significantly reduced with a combined score reduction of 58.6% in the entire population (57.7% in adults > 12 years and 60.5% in children

Bath emollients for atopic eczema: why use them?

Emollient preparations play a central role in the treatment of people with dry skin associated with conditions such as atopic eczema.1,2 As well as being advised to apply emollient creams or ointments directly to the skin, people with atopic eczema are commonly prescribed bath emollients.3 Each year, the NHS spends over pound16million on bath emollients (at an average cost of pound6.29 per item).4 This represents 38% of the total cost of treatments prescribed for preschool children with eczema, matching the proportion spent on emollients for application directly to the skin.5 What clinical contribution do bath emollients make in the treatment of people with atopic eczema?

Functional assessment of a washing emulsion for sensitive skin: mild impairment of stratum corneum hydration, pH, barrier function, lipid content, integrity and cohesion in a controlled washing test.

BACKGROUND/PURPOSE: Sensitive skin has been described as a skin type with higher reactivity than normal skin and exaggerated reactions to external irritants. Washing with soaps is harmful for barrier-related parameters. Cutaneous irritation induced by cleansing products under exaggerated test conditions, e.g. patch testing, is not necessarily predictive of the irritation occurring under standardized daily use conditions. The purpose of the study was to assess the effect of an improved washing solution for sensitive skin in a half-site comparison on barrier-related parameters. METHODS: Thirty healthy volunteers with self-reported sensitive and so-called problematic skin performed standardized washings with a soap-free washing emulsion with mild acidity (pH 5.5) for 3 weeks. Test areas were both forearms and the cheek. Non-invasive biophysical measurements of the following skin parameters, epidermal permeability barrier function measured as transepidermal water loss (TEWL), stratum corneum (SC) hydration, pH value, skin surface lipids, skin temperature and SC integrity/cohesion, were assessed prior to the first washing, on days 7, 14 and 21 after beginning the washing procedure. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. SC integrity was quantified by measuring TEWL after sequential stripping with D-Squame tapes. RESULTS: The use of the washing emulsion led to a mild damage of the epidermal permeability barrier function with no marked difference to water application. Furthermore, a mild but significant dehydration was assessed after 21 days vs. baseline without any differences between the water-treated and the washing emulsion-treated forearm. On the cheek no dehydration was detectable but the lipid content was reduced under the washing emulsion. The pH value increased in all three test areas after 21 days, again without significant differences between water and the washing solution. SC cohesion was quantified using two independent methods on D-Squame tapes: optical spectroscopy measuring the absorbance and a protein assay assessing the total protein (Bradford). Both methods showed a good correlation. The SC cohesion decreased after 21 days on the water-treated as well as on the washing emulsion-treated arm. The decrease over time was significant when used the optical spectroscopy measuring. A standardized questionnaire revealed positive characteristics of the washing emulsion and good acceptance. CONCLUSION: The investigated standardized washing model with the endpoints epidermal barrier function, SC hydration, surface pH, skin surface lipids, skin temperature and SC integrity/cohesion showed only mild damage comparable to washing with water.

Assessment of diaper-clogging potential of petrolatum moisture barriers.

Petrolatum-based ointments often are used to treat and prevent incontinence dermatitis. However, anecdotal reports indicate that petrolatum ointments may affect the absorbency of disposable briefs also commonly used in incontinence management. To examine whether petrolatum ointments clog a commonly used absorbent brief, a randomized, balanced-block design study was conducted in a controlled laboratory setting to compare the brief-clogging potential of three petrolatum ointments to a non-alcohol barrier film. Test products were applied to 6-cm x 6-cm test sites on the volar forearms of 16 volunteers. Pre-weighed mini briefs were applied to the test sites in a manner that simulates normal brief wear. After 5 minutes of wear, the mini briefs were weighed to determine percent of product transfer from skin to mini brief. The mini briefs then were reapplied to the same test sites and a synthetic urine solution was introduced between the skin and the mini brief. Mini briefs subsequently were removed to determine fluid uptake by weight. Results indicate significant differences between the four test products (P < 0.01) both in percent transfer and in mini brief fluid absorption. From 59% to 69% of the petrolatum-based products transferred from the skin to the mini briefs and a 54% to 90% reduction in fluid uptake was noted, as determined by weight. The non-alcohol barrier film did not transfer to the mini brief and fluid uptake was minimally affected. Further study in the clinical and practice settings to determine the effect and consequences of barrier product transfer on absorbent garments is warranted.

Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate.

Acetyl Triethyl Citrate, Acetyl Tributyl Citrate, Acetyl Trihexyl Citrate, and Acetyl Trioctyl Citrate all function as plasticizers in cosmetics. Additionally, the Trihexyl and Trioctyl forms are described as skin-conditioning agents-emollients, although there are currently no reported uses of Acetyl Trihexyl Citrate or Acetyl Trioctyl Citrate. Acetyl Triethyl Citrate and Acetyl Tributyl Citrate are used in nail products at concentrations up to 7%. Recognizing that there are no reported uses of Acetyl Trihexyl or Trioctyl Citrate, if they were to be used in the future, their concentration of use is expected to be no higher than that reported for Acetyl Triethyl and Tributyl Citrate. These ingredients were sufficiently similar in structure that safety test data on one were considered applicable to all. Approximately 99% of orally administered Acetyl Tributyl Citrate is excreted-intermediate metabolites include acetyl citrate, monobutyl citrate, acetyl monobutyl citrate, dibutyl citrate, and acetyl dibutyl citrate. In acute, short-term, subchronic, and chronic feeding studies, these ingredients were relatively nontoxic. Differences from controls were either not statistically significant or not related to any organ toxicity. Ocular exposures produced moderate reactions that cleared by 48 hours after instillation. Dermal application was not toxic in rabbits. In a guinea pig maximization test, Acetyl Triethyl Citrate was a sensitizer whereas Acetyl Tributyl Citrate was not. Limited clinical testing of Acetyl Triethyl Citrate and Acetyl Tributyl Citrate was negative for both skin irritation and sensitization. These clinical data were considered more relevant than the guinea pig maximization data, suggesting to the Cosmetic Ingredient Review Expert Panel that none of these ingredients would be a sensitizer. Physiologic effects noted with intravenous delivery of Acetyl Triethyl Citrate or Acetyl Tributyl Citrate include dose-related decreases in blood pressure and intestinal muscular spasms. These ingredients were not genotoxic in bacterial or mammalian test systems. No significant differences in tumor induction (lymphomas) were noted in rats fed Acetyl Tributyl Citrate for 2 year. Acetyl Tributyl Citrate was not a developmental or reproductive toxicant in studies in mice and rats. Based on all the available data, these ingredients were considered safe as used in cosmetics.

Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema.

OBJECTIVE: To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. DESIGN: Randomised, double blind, parallel group study of 18 weeks' duration. SETTING: 13 general practices and a teaching hospital in the Nottingham area. PARTICIPANTS: 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. INTERVENTIONS: 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. MAIN OUTCOME MEASURES: Primary outcomes were total number of scratch-free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. RESULTS: No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval -2.0 to 4.0, P=0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. CONCLUSION: A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.