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.