Types of skin intervention
One of the possible reasons for the variable findings in the above clinical trials is the type of skin intervention used. Most commercially available moisturizers are either oil-based (emollients), water-based (humectants) or occlusives and each have different effects on the skin barrier, TEWL, skin pH and stratum corneum hydration status. A head-to-head study comparing different types of emollients in adults with AD found that both glycerol-only and urea-glycerol combination emollients were able to improve TEWL and natural moisturizing factor (NMF) levels, and protected against skin irritation caused by sodium lauryl sulphate (SLS) exposure.39 However, paraffin-based emollients had no effect on the skin barrier and even reduced NMF levels in the skin. Paraffin- or petrolatum- based emollients were, however, one of the most common types of emollients used in the moisturizer trials.30-32, 40 The Effective Prevention of Atopic dermatitis by applying Fams baby (PAF) study found that a commercial emollient (Fams baby) applied once daily in high-risk infants from birth to age 32 weeks reduced both AD and food allergy risk compared to twice daily application and also in comparison to another commercial emollient (2e). (Table 1) 41 Both emollients contained a combination of various ingredients, thus while it is difficult to identify the active ingredient which may exert a greater effect in allergy prevention, these findings suggest a role for further research into this area.
Earlier murine studies demonstrated that the optimal concentration of lipid mixtures that was able to accelerate skin barrier recovery was a combination of cholesterol, ceramides, essential and non-essential free fatty acids in a 3:1:1:1 ratio, with cholesterol as the dominant lipid.42 A test cream containing this tri-lipid combination was shown in a subsequent clinical trial to be able to improve skin integrity and hydration, reduce TEWL and SLS-induced irritation to a greater extent than a basic emollient.43 Newer generation moisturizers now incorporate a 3:1:1 ratio of cholesterol, ceramides, and free fatty acids to maintain a skin composition and pH which is most similar to the human skin’s natural composition.
A small pilot study compared the effects of 12 weeks of total body application of daily tri-lipid cream (EpiCeram™, provided by Primus Pharmaceuticals) vs a paraffin/petrolatum-based cream (Aveeno™) in infants between 4 and 9 months with and without dry skin/AD.44 They found that infants using the tri-lipid cream had lower total IgE, higher total IgG4, lower peanut-specific IgG4/IgE ratios, as well as lower levels of pro-inflammatory IL-4+ expressing CD4+ T cells and higher levels of IL-10+ expressing and LAP+ - expressing CD4+ T cells than infants using the paraffin/petrolatum-based cream. This suggests that the tri-lipid emollient was superior to the paraffin/petrolatum-based cream in reducing Th-2 proinflammatory responses and promoting tolerogenic T cell pathways. The ongoing PEBBLES study also used a similar tri-lipid, ceramide dominant emollient as its primary intervention.33 Its promising pilot findings of reduced AD and food sensitization in the treatment arm suggests that tri-lipid emollients may also be superior to basic paraffin/petrolatum-based moisturizers in AD and FA prevention.
Bathing frequency and type of bath oils could also impact the skin barrier. The Enquiring About Tolerance (EAT) study enrolled normal-risk infants at birth to examine the effect of early allergenic food introduction on food allergy outcomes.45 A post-hoc analysis in this study found that increased bathing frequency was associated with increased TEWL, even after excluding infants with existing AD in a sensitivity analysis. Bath oils and emollients were also used more frequently in infants who had raised TEWL levels, suggesting the possibility that early bathing practices with skin interventions causing skin barrier disruption could account for increased rates of food sensitization or food allergy. However, a subsequent publication did not find significant associations between bathing frequency and food allergy overall in this cohort.46 In this follow-up study, however, increased use of moisturizer at 3 months of age was associated with increased food sensitization and food allergy, assessed at 1 and 3 years of age, even in those with no visible eczema at baseline.46 Each additional moisturization per week was associated with an 18% increase in the odds of developing food allergy in infants without visible eczema; and 20% in infants with eczema. Parental reports suggested that the most common type of moisturizers used in EAT was olive oil. There was, however, insufficient power to analyze the type of moisturizer formulation against FA risk in this study. It could thus be postulated that topical moisturizer applications could either increase skin exposure to food allergens on the hands of caregivers; facilitate passage of food allergens across the skin barrier or may have a direct deleterious effect on the skin barrier which allows passage of the food allergen through to the dermis.