Allergen Exposure Planner

Oral immunotherapy works by repeatedly presenting a food protein at a dose below the amount that triggers a reaction, then raising that dose slowly enough for the immune system to shift from an IgE-driven mast cell response toward IgG4 production and regulatory T cell activity. Because tolerance builds multiplicatively rather than additively, protocols escalate geometrically: each step is the previous dose times a fixed factor, so Dose(n) = StartDose x (1 + rate) to the power n, and the number of steps needed is log(Target / Start) divided by log(1 + rate). Doubling at every step reaches a target quickly but concentrates risk; increments of 20 to 30 percent every 14 days are the common compromise between total duration and reaction rate. Starting doses are deliberately tiny - typically 0.1 to 1 mg of allergen protein, below the eliciting dose for most patients - while maintenance targets are commonly 300 mg of peanut protein, roughly one kernel, or 1 to 4 g for milk and egg protocols. The critical limitation is that this arithmetic describes a schedule, not a patient. Real protocols pause or step backward after any reaction, and the reaction threshold is modulated by cofactors: exercise or a hot shower within about two hours of dosing, intercurrent viral illness, NSAIDs, menstruation and dosing on an empty stomach all lower it. A small minority of patients develop eosinophilic esophagitis and must stop - a pooled analysis of oral immunotherapy trials put the figure near 2.7 percent - and desensitization is not a permanent cure - protection fades if daily dosing is interrupted.

The idea is over a century old. In 1908 the English physician Alfred Schofield described in the Lancet how he desensitized a boy with severe egg allergy by feeding him raw egg in doses so small they began as fractions of a drop, increased gradually over several months until he could eat egg freely. Leonard Noon and John Freeman published their injected grass pollen desensitization work in the same journal in 1911, and injection immunotherapy became the dominant model while oral routes for food were largely abandoned after fatal reactions to subcutaneous food extracts. Oral dosing returned through Italian work by Giovanni Patriarca and colleagues, who published structured oral desensitization protocols for food allergy from the 1980s through the late 1990s. Controlled trials followed in the 2000s, including the double-blind milk protocol reported by Justin Skripak and colleagues in 2008 and peanut protocols published in 2009. The Cambridge STOP II trial, reported in the Lancet in 2014, showed that a large majority of treated children could tolerate multiple peanuts after therapy. The pivotal PALISADE trial published in the New England Journal of Medicine in 2018 tested a standardized peanut powder, AR101, and reported that 67.2 percent of treated participants tolerated a 600 mg challenge dose against 4.0 percent on placebo. The FDA approved that product as Palforzia in January 2020, the first licensed food allergy treatment, with a fixed dose ladder running from 0.5 mg to 300 mg.