Dose-response in double-blind, placebo-controlled oral food challenges in children with atopic dermatitis

Background: Double-blind, placebo-controlled oral food challenges (DBPCFCs) are considered the "gold standard" for diagnosing food hypersensitivity, b ut the dose that elicits positive challenges, or determinants that may pred ict dose-response relationships, have not been reported. Objective: Our purpose was to determine the quantity of food that elicits r eactions during DBPCFCs and to evaluate parameters that may predict the pro vocative dose and severity of reaction. Methods: We reviewed challenge data for all positive challenges to 6 common allergenic foods in children with atopic dermatitis evaluated for food all ergy over a 13-year period. Challenge food was generally administered in 6 doses at 10- to 15-minute intervals beginning with 400 to 500 mg and comple ting with a total of 8 to 10 g of food, An open feeding of a larger portion followed negative challenges. At the physician's discretion, a lower start ing dose was occasionally used (100 mg, 250 mg), Food-specific IgE antibody concentrations (radioallergosorbent test [RAST]) were determined on stored sera of 20 % of the challenges selected randomly and 99.6 % had prick skin tests (PSTs) performed to the challenged food. Results: A total of 196 children (45% male; median age 5 y 9 mo; atopic der matitis 98%, asthma 62%) had 513 positive challenges distributed as follows : egg 267, milk 117, soy 53, wheat 40, peanut 24, fish 12. The percentage o f children reacting at the first dose (500 mg or less) was as follows: egg 49%, milk 55%, soy 28%, wheat 25%, peanut 26%, and fish 17%. Twenty-six mil k challenges and 22 egg challenges were positive at a first dose of 250 mg; 3 milk challenges and 7 egg challenges were positive at a first dose of 10 0 mg, Eleven pel cent of the reactions that occurred on the first dose were severe. The percentage reacting after the final dose of the DBPCFC (or dur ing open challenge) a ere egg 11%, milk 12%, soy 19%, wheat 12.5%, peanut 8 .7%, and fish 25%. There was not a strong correlation between PST absolute wheal size or score (adjusted for histamine controls) and dose at reaction or severity of reaction (R-s range -0.22 to 0.39 for particular foods), Ser um concentration of food-specific IgE did not correlate well with the dose causing a reaction or with severity (R-s range -0.40 to 0.55 for particular foods). Conclusions: This food-allergic population may react to as little as 100 mg of food, possibly less, and the dose causing a reaction and the severity o f reaction is not predicted by PST or PAST Lower doses (100 mg or less) sho uld he investigated for their appropriateness in initiating DBPCFCs.