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