Emollients for prevention of atopic dermatitis in infancy

Abstract

Atopic dermatitis (also known as eczema and atopic eczema) is the most common chronic inflammatory disorder of the skin and affects around a quarter of children.1Odhiambo JA Williams HC Clayton TO Robertson CF Asher MI Global variations in prevalence of eczema symptoms in children from ISAAC phase three.J Allergy Clin Immunol. 2009; 124 (58.e23): 1251Summary Full Text Full Text PDF PubMed Scopus (492) Google Scholar Worldwide, its prevalence is increasing2Asher MI Montefort S Bjorksten B et al.Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys.Lancet. 2006; 368: 733-743Summary Full Text Full Text PDF PubMed Scopus (2804) Google Scholar and persistence into adulthood is common.3Abuabara K Yu AM Okhovat JP Allen IE Langan SM The prevalence of atopic dermatitis beyond childhood: a systematic review and meta-analysis of longitudinal studies.Allergy. 2018; 73: 696-704Crossref PubMed Scopus (63) Google Scholar The first manifestations usually appear in early life with dry, cracked, scaly, and erythematous skin, and at all ages intractable pruritus. Atopic dermatitis can result in impaired quality of life for individuals and their families, alongside considerable social and financial burden.4Drucker AM Wang AR Li WQ Sevetson E Block JK Qureshi AA The burden of atopic dermatitis: summary of a report for the National Eczema Association.J Invest Dermatol. 2017; 137: 26-30Summary Full Text Full Text PDF PubMed Scopus (197) Google Scholar Moreover, there is no known cure or established strategies for prevention. Early onset atopic dermatitis is often the hallmark of an atopic diathesis. Mutations in the filaggrin gene (FLG)—which encodes a protein crucial to epidermal function and skin barrier integrity—is associated with atopic dermatitis, food sensitisation, and allergy.5Irvine AD McLean WH Leung DY Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (710) Google Scholar Therefore, the skin barrier might play a key role in the development of atopic dermatitis and subsequently, via epicutaneous sensitisation through damaged skin, in food allergies. However, skin barrier dysfunction can be apparent in the first weeks of life, before the development of atopic dermatitis,6Kelleher M Dunn-Galvin A Hourihane JO et al.Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year.J Allergy Clin Immunol. 2015; 135 (35.e1): 930Summary Full Text Full Text PDF PubMed Scopus (174) Google Scholar and FLG mutations are associated with food allergy even in the absence of atopic dermatitis,7Brown SJ Asai Y Cordell HJ et al.Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.J Allergy Clin Immunol. 2011; 127: 661-667Summary Full Text Full Text PDF PubMed Scopus (291) Google Scholar suggesting that interventions to improve skin barrier function from infancy have the potential to prevent the skin condition and development of food allergy independently. Emollients are the primary management strategy of atopic dermatitis and include leave-on creams or ointments and bath additives. Regular, liberal use of emollients aims to maintain skin moisture, repair or enhance the skin barrier, and reduce the need for anti-inflammatory measures. Small proof of concept pilot studies provided strong efficacy signals for the hypothesis that daily emollient use could prevent atopic dermatitis,8Kvenshagen BK Carlsen KH Mowinckel P Berents TL Carlsen KC Can early skin care normalise dry skin and possibly prevent atopic eczema? A pilot study in young infants.Allergol Immunopathol (Madr). 2014; 42: 539-543Crossref PubMed Scopus (17) Google Scholar, 9Horimukai K Morita K Narita M et al.Application of moisturizer to neonates prevents development of atopic dermatitis.J Allergy Clin Immunol. 2014; 134 (30.e6): 824Summary Full Text Full Text PDF PubMed Scopus (359) Google Scholar, 10Simpson EL Chalmers JR Hanifin JM et al.Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention.J Allergy Clin Immunol. 2014; 134: 818-823Summary Full Text Full Text PDF PubMed Scopus (437) Google Scholar and prompted two large pragmatic prevention trials.11Skjerven HO Rehbinder EM Vettukattil R et al.Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32983-6Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 12Chalmers JR Haines RH Bradshaw LE Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32984-8Summary Full Text Full Text PDF Scopus (43) Google Scholar The null findings of Håvard Ove Skjerven and colleagues11Skjerven HO Rehbinder EM Vettukattil R et al.Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32983-6Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar and Joanne Chalmers and colleagues12Chalmers JR Haines RH Bradshaw LE Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32984-8Summary Full Text Full Text PDF Scopus (43) Google Scholar in The Lancet were unexpected. They found no evidence that daily emollient use in either a population-based11Skjerven HO Rehbinder EM Vettukattil R et al.Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32983-6Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar or high-risk cohort12Chalmers JR Haines RH Bradshaw LE Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32984-8Summary Full Text Full Text PDF Scopus (43) Google Scholar of infants during the first year of life could delay, suppress, or prevent atopic dermatitis. Skjerven and colleagues report the primary outcome of atopic dermatitis at 12 months of age in the Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) study,11Skjerven HO Rehbinder EM Vettukattil R et al.Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32983-6Summary Full Text Full Text PDF PubMed Scopus (42) Google Scholar a large pragmatic population-based randomised trial done in Norway and Sweden. 2397 newborn infants (53% boys, 47% girls) were cluster-randomly assigned in a 2 × 2 factorial design to either: controls with no specific advice on skin care and advice to follow national infant feeding guidelines; regular skin emollients (bath oil and facial cream) from 2 weeks of age; early complementary feeding of common food allergens (peanut, milk, wheat, and egg) introduced between 12 weeks and 16 weeks of age; or both interventions. Atopic dermatitis occurred in 8% of infants in the no intervention group, 11% in the skin intervention group, 9% in the food intervention group, and 5% in the combined intervention group. The primary hypothesis that either skin or food intervention reduced atopic dermatitis was not confirmed, but an unexpected significant interaction was shown between the interventions, which could represent a chance finding or suggests that multiple prevention strategies work synergistically. Notably, the combined intervention was included for the food allergy outcomes and the possible additive effects will be explored further when the infants reach age 36 months. No safety concerns were identified. Compliance to the interventions was suboptimal, with full protocol adherence in only 27% of participants in the skin intervention group and 32% in the food intervention group. As a pragmatic, population-based intervention, these adherence results provide important information on the feasibility of implementing primary prevention strategies at the population level, in which additional bathing regimens and feeding protocols appear challenging to maintain in regular infant care. Chalmers and colleagues report the primary outcome of eczema at 2 years of age in the Barrier Enhancement for Eczema Prevention (BEEP) study,12Chalmers JR Haines RH Bradshaw LE Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trial.Lancet. 2020; (online Feb 19.)https://doi.org/10.1016/S0140-6736(19)32984-8Summary Full Text Full Text PDF Scopus (43) Google Scholar a multicentre, pragmatic, two-arm, parallel group, randomised controlled trial done in the UK. 1394 newborn infants (53% boys, 47% girls) at high risk of allergy (family history of atopic disease) were randomly assigned to receive daily application of emollient for the first year plus standard skin care advice, or standard skin care advice only. The intervention, commenced at a median age of 11 days, did not prevent the development of eczema at age 2 years, which occurred in 23% of the emollient group and 25% of the control group. Unexpectedly, the secondary outcome of food allergy occurred more frequently in the intervention group (7%) than in the control group (5%), (adjusted relative risk 1·47, 95% CI 0·93–2·33), largely attributable to egg allergy; however, less than a third of food allergy diagnoses were based on the gold standard oral food challenge. Contrary to the hypothesis that emollients would enhance the skin barrier, preventing epicutaneous sensitisation and food allergy, emollient use might enhance transfer and uptake of food allergens. Additionally, skin infections occurred more frequently in the emollient group than in the control group (adjusted incidence rate ratio 1·55, 95% CI 1·15–2·09), suggesting that application of emollient can also assist inoculation of pathogens on the infant skin or disturb the natural protective skin microbiome. The absence of a preventive effect on atopic dermatitis might be associated with the type, frequency of application, and timing of commencement of emollient. Following promising results of a trend to reduced atopic dermatitis and food sensitisation at age 12 months from a pilot study using a ceramide-dominant emollient with a slightly acidic pH, twice daily from birth, a large randomised controlled trial in high-risk infants, Prevention of Eczema by a Barrier Lipid Equilibrium Strategy (PEBBLES), is underway to confirm these findings including food allergy endpoints.13Lowe A Su J Tang M et al.PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy.BMJ Open. 2019; 9e024594Crossref PubMed Scopus (19) Google Scholar Although, even if the results show a reduction in these atopic outcomes, lessons from PreventADALL suggest this intensive twice daily emollient regimen, not to mention the high cost of this complex formulation, could affect its potential viability as a population-based preventive strategy. An ongoing prospective individual patient data meta-analysis will provide additional evidence on any association between use of emollients during the first year of life and reduction in atopic dermatitis, food allergy, and associated health outcomes.14Kelleher M Cro S Cornelius V et al.Skin care interventions in infants for preventing eczema and food allergy (protocol).Cochrane Database Syst Rev. 2020; 2CD013534Google Scholar However, at this stage, emollients should not be recommended for the primary prevention of atopic dermatitis in infants. We declare no competing interests. Daily emollient during infancy for prevention of eczema: the BEEP randomised controlled trialWe found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. Full-Text PDF Open AccessSkin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trialNeither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Full-Text PDF

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