Eczema treatment for food allergy prevention
In established eczema, early intervention to prevent food sensitization
or clinical food allergy, the next stage in the pathogenesis of the
atopic march, is paramount. Several studies have examined various modes
of eczema treatment approaches for food allergy prevention. A systematic
review found that targeting only barrier repair through skin care did
not prevent food allergy.47 Schneider et
al.48 reported that pimecrolimus 1% cream applied in
a reactive treatment (i.e., application only on visible eczema lesions)
did not prevent food allergy in infants with atopic dermatitis. Weak
anti-inflammatory medications used in the reactive treatment for
clinical lesions alone might thus be insufficient to prevent food
allergy development. It was thus hypothesized that sufficient
anti-inflammatory treatment for both clinical and subclinical skin
lesions may be required, through a proactive approach.
Proactive treatment is a long-term maintenance approach using
anti-inflammatory agents for active and previously active flare-prone
skin to treat chronic subclinical skin inflammation and prevent
flares-up.49, 50 Proactive treatment that follows
initial induction of remission has been used for long-term control of
persistent atopic dermatitis.51, 52 Fukuie et al
conducted a randomized open-label trial comparing proactive topical
corticosteroid therapy (twice weekly application to all previous flare
areas after complete resolution of a flare) to reactive therapy (topical
corticosteroids only during a flare) in children aged 3 months to 7
years with moderate to severe AD.53 The proactive
group experienced significant reductions in AD severity, quality of life
scores and serum TARC levels compared to the reactive group. Another
observational study found that infants aged 1-4 months who received
active eczema treatment with topical glucocorticoids for 10 days
followed first by maintenance therapy with pimecrolimus 1% cream twice
daily for 3 months, and continued on pimecrolimus twice daily three
times a week until age 1 year had a lower risk of food allergen
sensitization compared with infants who received only reactive treatment
with topical steroids during eczema flares. 54 A
retrospective study by Miyaji at al.6 also suggested
that early enhanced proactive topical steroid therapy on both clinical
and subclinical skin lesions of infants with atopic dermatitis might
prevent the onset of food allergy. Yamamoto-Hanada et al.55, 56 subsequently conducted a randomized controlled
trial, the Prevention of Allergy via Cutaneous Intervention (PACI)
Study, to examine the efficacy of early aggressive, proactive treatment
of infant eczema for prevention of hen’s egg allergy. They found that
early enhanced proactive treatment of both visible and non-visible
eczema lesions in infants with a low potency topical steroid cream from
birth resulted in a 25% reduction in hen’s egg allergy onset at the age
of 28 weeks when compared with reactive therapy - conventional treatment
targeting only visible eczema lesions. The PACI study thus demonstrated
proof of principle that enhanced proactive treatment targeting both
clinical and subclinical lesions of early-onset eczema could reduce food
allergy risk, confirming the importance of adequate treatment of eczema
for food allergy prevention. However, there was a trend towards reduced
body weight and height in the enhanced treatment group compared to the
conventional group, suggesting that further refinement of this approach
is likely required. For example, the potency and duration of topical
steroid applications may require tailoring according to the severity of
skin inflammation. Non-steroid topical ointments such as topical PDE4
inhibitors and topical JAK inhibitors may also be safer alternatives but
have yet to be studied in this context.
The Stopping Eczema and Allergy (SEAL) study [NCT03742414] is an
ongoing randomized, controlled, parallel design, open-label phase 2
clinical trial which is recruiting infants from who have already
developed atopic dermatitis (AD or eczema) by 12 weeks of age. The study
aims to compare the efficacy of proactive treatment with a tri-lipid
skin barrier cream (Epiceram) versus a moisturizer, plus proactive use
of a topical corticosteroid: fluticasone propionate cream 0.05%,
against reactive AD therapy as standard care, in reducing the occurrence
and severity of AD in early infancy and for prevention of FA. The
primary outcome is challenge-proven food allergy at age 3 years, and
secondary outcomes include changes in baseline AD severity (Scoring
Atopic Dermatitis (SCORAD)) at ages 1, 2 and 3 years. The results of
this study will shed further insights into the utility of early
aggressive AD therapy for FA prevention.
Existing measures for food allergy prevention, such as early
introduction of allergenic foods, may be less efficacious in infants
with uncontrolled eczema. In the Prevention of Egg Allergy with Tiny
Amount Intake (PETIT) study, Natsume et al. showed that infants with
poorly controlled eczema developed hen’s egg allergy despite early
introduction of hen’s egg.57 In the Learning Early
About Peanut allergy (LEAP) study, the protective effect of early peanut
introduction was lower in infants with severe eczema (67% reduction)
compared with children with mild (85% reduction) and moderate (87%
reduction) eczema.58 This suggests that in infants
with moderate to severe eczema, it is essential for a combination of
skin (adequate eczema control) and oral (early allergenic food
introduction) interventions to be implemented in tandem for the greatest
protective effect against food allergy development prevention, in line
with the dual-allergen exposure hypothesis.59, 60