Positive reactions to placebo in children undergoing double-blind, placebo-controlled food challenge

The gold standard in the diagnosis of food allergy is the double-blind, placebo-controlled oral food challenge (DBPCFC). During this challenge, patients receive the allergenic food and placebo on separate randomized days, while being monitored for clinical reactions. Interestingly, some reactions are assessed as positive although the patients had received placebo. The aim of our study was to analyze incidence and characteristics of positive placebo reactions during DBPCFCs.

In food-allergic children, we retrospectively analyzed positive placebo reactions in DBPCFCs in 740 placebo challenges in our department. Individual characteristics were compared, such as age or IgE levels, as well as clinical symptoms.

Of all placebo challenges, 2.8% (21 of 740) were assessed as positive. Young children (age ≤ 1.5 years) had more (P = 0.047) positive placebo challenges (4.0%) compared to older children (age > 1.5 years; 1.5%). Children with positive placebo challenges had higher levels of total IgE (median 201 kU/L) compared to negatively classified children (median 110 kU/L). In children with positive placebo reactions, skin symptoms were observed significantly more often, with a worsening of atopic eczema (AE) as the most reported symptom.

Placebo reactions in DBPCFC are not common. Worsening of AE is the most frequent clinical reaction associated with positive placebo challenges, and young children (age ≤ 1.5 years) seem to be affected more often. Therefore - contrary to current recommendations - DBPCFC tests should be considered in infants and young children, especially those with a history of AE.