How Low Should We Go?

peanut protein without symptoms [5] . Blumchen et al. [6] targeted 500 mg of whole crushed peanuts, corresponding to 125 mg peanut protein, and found that some participants tolerated 4 g of crushed peanuts. Therefore, it is documented that participants could tolerate more than 10× the dose used for maintenance OIT. Other methodologies of immunotherapy which target lower maintenance doses than many OIT protocols include sublingual immunotherapy to milk and epicutaneous immunotherapy [reviewed in 2 ] ( fig. 1 ). If ingestion of a very low amount of food can elicit a clinical reaction, then perhaps very low doses can also be immune modifying. A review of published trials found that the minimum eliciting dose was 3.3 mg for milk [7] . This amount would correspond to about 0.009 ml or less than 1⁄4 of a drop of milk. In a recent edition of the International Archives of Allergy and Immunology , Yanagida et al. [8] explore the use of an LOIT protocol to milk in a severely milk-allergic population. The maintenance dose target was only 3 ml of milk or just over 100 mg of milk protein. This dose is less than 2% of what would traditionally be considered a serving of milk. They used an initial 5-day in-hospital dose escalation protocol with ongoing daily doses and any required dose escalation was at home. Of the 12 patients on treatment, 9/12 could drink 3 ml of milk daily without reactions and 4/12 could tolerate 25 ml, which Milk allergy is a common phenomenon with a prevalence of around 2% in 2-year-old children. Avoidance itself is not sufficient to prevent allergic reactions as suggested by one study reporting an incidence of 40% allergic reactions during a 12-month period. Thirty-seven percent of reactions were moderate to severe [1] . Therefore feasible treatment options for milk allergy are needed. Milk oral immunotherapy (OIT) has been investigated for treatment of milk allergy [2] . Many OIT trials targeted serving-size amounts of food such as approximately 5– 16 g in milk, 2 g in egg and 0.8–7 g in peanut OIT trials. Initial enthusiasm over OIT to milk was tempered by allergic reactions (19% with anaphylactic reaction at least once) and by limited long-term responders (31%) [3] . The OIT method of the recent long-term follow-up study of milk used 500 mg milk protein and had a median maximum tolerated dose after OIT of 1,400 mg [3] . Previous studies in peanut have shown that low-dose OIT (LOIT) may have promise as a treatment. Recently, an abstract has attracted attention at the AAAAI [4] . In this study, yet to be reported unblinded, it appeared that there was little difference in clinical and immunological outcomes in young children randomized to low-dose (300 mg) or high-dose (3,000 mg) OIT to peanut. Previous to that study, the same center initially targeted a maintenance dose of 300 mg of peanut protein and 93% who completed the protocol passed a challenge of 3,900 mg Published online: January 21, 2016

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