Area of Focus
Year (Reference)
Study Name or Publication Title
Author
Key findings or recommendations
Notable Limitations
Population Studied
Type of Study
Level of Evidence173
Cutaneous Sensitization 1994190 Increased airways responsiveness in mice depends on local challenge with antigen Saloga J, et al. First evidence to support that sensitization could occur through skin Murine skin differs from human skin Murine model Mechanistic Level 5
Cutaneous Sensitization 2003191 Avon Longitudinal Study of Parents and Children (ALSPAC) Lack G, et al. Peanut allergy associated with topical use of peanut oil infants, but not with maternal consumption UK, general population Population-based, longitudinal birth cohort Level 2
The Role of Filaggrin in AD
200693
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Palmer CNA, et al.
AD was more common in homozygous or compound heterozygous for FLG null alleles, and nearly absent in those without
Only 2 mutations had been identified and analyzed, both common in those of European ancestry, but rare in other ethnicities
9 Irish families with icthyosis vulgaris and/or AD; 2 cohorts of Scottish children with and without asthma; Danish children from the COPSAC study
Multiple cohorts
Level 2
The Role of Filaggrin in FA 201166 Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy Brown SJ, et al. FLG loss-of-function mutations significantly increase the risk of peanut allergy, suggesting a role for epithelial barrier dysfunction Different definitions of AD and criteria for diagnosing peanut allergy were used in the different populations; difficult to distinguish the role of AD from FLG status, and other variables affecting the development of peanut allergy; the effect varied in different populations despite all being predominantly white and of European ancestry English, Dutch, and Irish subjects with peanut allergy and controls; replicated in a white, Canadian case-control population Case-control study Level 3
Skin barrier Dysfunction and Transcutaneous Sensitization in FA 201427 Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations Brough HA, et al. Exposure to peanut protein in household dust demonstrated a dose-response relationship with measures of peanut sensitization and allergy at 8 and 11y in children with FLG mutations, when controlling for other factors; no effect of exposure was seen in children with WT-FLG Peanut allergy not challenge-proven in all subjects; overall small number of subjects with peanut allergy, FLG gene status, and exposure history; excluded non-Caucasians as the 6 FLG mutations studied were only defined in Caucasians UK, high risk infants (family history of atopy) Observational study within randomized controlled study Level 3
Topical intervention for AD
2014192
Application of moisturizer to neonates prevents development of atopic dermatitis
Horimoku K, et al.
Daily application of an emulsion-based moisturizer starting at 1week of life prevented AD in 1/3 of infants at 8m
Control group could use petroleum jelly if desired, which may be beneficial for SB, limiting the impact of the intervention
Japan, high risk
RCT
Level 2
Oral Tolerance Induction
2015193 & 2016194
LEAP & LEAP-On
du Toit, et al.
Early introduction and regular consumption of peanut in infants at high risk for FA prevents peanut allergy, and likely induces durable, and long-lasting tolerance
Excluded infants with peanut SPT>4mm at entry
UK, high risk cohort
Randomized, open-label, controlled trial
Level 2
Preventative Emollient Therapy for AD and FA
2018195
A randomised trial of a barrier lipid replacement strategy for the prevention of atopic dermatitis and allergic sensitisation: The PEBBLES Pilot Study
Lowe AJ, et al.
Twice daily application of emollient rich in ceramides to infants in the first 3weeks of life through 6m demonstrated a trend towards less AD and food sensitization at 12month; infants who had emollient applier BID for at least 5/7 day per week did have a significant reduction in food sensitization
Food sensitization only assessed at 1y, not later in life and not challenge-proven; Small n=80), pilot study.
Australia, high risk infants (parental history of atopy)
Pilot randomized, parallel, single-blind, controlled trial
Level 3
Assessing Skin Barrier Dysfunction 2019196 The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype Leung DYM, et al. Using a non-invasive, well-tolerated skin tape stripping method, identifies unique immature skin barrier characteristics in the stratum corneum that distinguish between children with AD and FA (AD+FA+) from those with AD but without FA (AD+FA-) Results require validation in larger, diverse populations with challenge-proven allergy to a variety of foods, not just peanut 62 US children classified as AD+FA+, AD+FA- or controls Blinded, prospective mechanistic study Level 3
Proactive Early AD Treatment and the Prevention of FA 2019197 Prevention of Allergy via Cutaneous Intervention (PACI) pilot Miyaji Y, et al. Earlier aggressive treatment of AD shortened its duration in infants, and resulted in fewer food allergies at 2 years of life Smaller, retrospective pilot study; cohorts had significant differences in baseline characteristics Japan Retrospective cohort Level 4
Preventative Emollient Therapy for AD and FA 2020198 Barrier Enhancement for Eczema Prevention (BEEP) Chalmers JR, et al. No evidence for prevention of AD at 2y with daily emollient use, but possible slight increase in infection risk, and nonsignificant increase in FA (largely to egg) in the intervention group Choice of emollient; limited FA assessment; median time to initiation of skin care at 11 days of life UK, high risk Pragmatic, parallel group RCT Level 2
Oral Tolerance Induction 2020199 Preventing food allergy in infancy and childhood de Silva D, et al. Early introduction of cooked egg (not raw or pasteurized egg) likely helps prevent egg allergy; avoiding supplementation with cow’s milk-based formula in the first week of life may slightly reduce milk allergy; nearly every other dietary intervention reviewed has little to no effect Many are small studies of lower certainty of evidence, findings need to be validated in large, heterogeneous populations n/a Systematic review with meta-analysis Level 2
Preventative Emollient Therapy for AD and FA 2020200 Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) Skjerven HO, et al. Found no decrease in AD or FA at 12m with skin emollient use, early complementary feeding or both Skin intervention started at 2 weeks of life using a bath oil and cream; early food introduction began with peanut butter at 3m; overall poor adherence in the intervention groups; low statistical power to assess FA (results for FA at 3y forthcoming) Scandinavian standard risk birth cohort Prospective interventional, cluster-randomized controlled trial Level 2
Link between Emollient use and Food Allergy
2021171
Association of frequent moisturizer use in early infancy with the development of food allergy
Perkin M, et al.
Observed an increased risk of food allergy with the application of moisturizer more frequent than once daily
All but 1 case of FA developed in children with at least 1 atopic parent; AD assessed at 3m enrolment visit only; the cohort frequently used oils for baby massage, which may prevent formation of an intact skin barrier; unable to control for some potential confounding factors
UK, exclusively breastfed standard risk cohort enrolled in the EAT study and randomized to standard vs early introduction of 6 foods with poor protocol adherence
Retrospective analysis of questionnaire data
Level 3/4