Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy: a multicenter, investigator-blinded, randomized, parallel group controlled trial (PACI Study)—protocol for a randomized controlled trial

Abstract

BackgroundAtopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis.MethodsThis study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N = 650) 7–13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen’s egg allergy at the age of 28 weeks.DiscussionThis is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis.Trial registration UMIN-CTR: UMIN000028043Electronic supplementary materialThe online version of this article (10.1186/s13601-018-0233-8) contains supplementary material, which is available to authorized users.

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

“…However, results from two large RCTs using preventative emollient therapy have had initial negative results for the prevention of AD (BEEP 113 and PreventADALL 114 ) and FA (BEEP) 113 and other RCTs are ongoing (CASCADE—A Community‐based Assessment of Skin Care, Allergies, and Eczema, and PEBBLES) (Tables 1 and 2). There are also secondary prevention studies (Table 3) using both emollients and proactive topical steroid treatments ongoing or planned (PACI study: Prevention of Allergy via Cutaneous Intervention Study) 170 . Regardless as to whether these studies are positive or negative in their findings, they will help inform this important area of research.…”

“…There are also secondary prevention studies (Table 3) using both emollients and proactive topical steroid treatments ongoing or planned (PACI study: Prevention of Allergy via Cutaneous Intervention Study). 170 Regardless as to whether these studies are positive or negative in their findings, they will help inform this important area of research. A summary of the major milestones in this field are presented in BOX 1 and future research perspectives are presented in BOX 2.…”

Reference values for salivary cortisol in healthy young infants by liquid chromatography–tandem mass spectrometry

“…Salivary cortisol evaluation might be more useful in future studies. Our study group is conducting a randomized, controlled trial for young atopic dermatitis infants . We plan to use the reference values of salivary cortisol from this study.…”

Atopic Dermatitis and Food Allergy: A Complex Interplay What We Know and What We Would Like to Learn

“…Regarding preventive strategies for food allergy and AD, studies have focused on early restoration of skin barrier impairment and/or early introduction of food allergens in high-risk children to promote food tolerance [ 86 , 87 , 88 , 89 , 90 ].…”

“…Inconsistently, preliminary findings from PEBBLES (Prevention of Eczema By a Barrier Lipid Equilibrium Strategy), a pilot randomized, parallel, single-blind controlled study that used a ceramide-containing cream in high-risk infants from birth up to 6 months, showed a reduction in AD incidence at 12 months and as well as in food sensitization at 6 and 12 months in the treatment group compared to controls [ 87 ]. A RCT is ongoing (PACI trial) to determine whether early aggressive treatment of AD with a combination of emollients and topical corticosteroids in infants may prevent the development of subsequent allergen sensitization and associated allergic disorders such as food allergy, asthma, and allergic rhinitis [ 88 ].…”