Ultra-low-dose allergen drops helped children with severe peanut and walnut allergies start oral immunotherapy

Children whose peanut or walnut allergies are so severe that they cannot tolerate even milligram-level amounts of allergen during oral food challenges have traditionally had only one option: strict avoidance. A new multicenter observational cohort study from Japan reports that an ultra-low-dose induction phase, administered before conventional oral immunotherapy (OIT), allowed nearly all such children enrolled in the study to transition successfully to standard OIT and tolerate milligram-level powder ingestion.

The study enrolled participants aged 3 to 15 years who were unable to start conventional OIT because of an extremely low reaction threshold or fear related to previous anaphylactic reactions. The induction phase consisted of individually adjusted diluted allergen extracts given as drops containing allergen proteins at the picogram-to-nanogram level — doses far below those used in conventional OIT protocols. The primary endpoint was the proportion of patients who successfully transitioned to conventional OIT. Secondary endpoints included changes in drop threshold doses, skin prick test wheal sizes, allergen-specific and component-specific immunoglobulin E (IgE) levels, and adverse events.

In total, ten patients with peanut allergy and eleven patients with walnut allergy were enrolled, most of whom had a history of anaphylaxis. During the study period, all patients with peanut allergy and 90.9 percent of patients with walnut allergy successfully transitioned to conventional OIT and tolerated milligram-level powder ingestion. Most evaluated indicators, including threshold protein doses in drop challenges, skin prick test wheal sizes, and component-specific IgE levels, were consistent with this outcome, according to the study’s results.

Safety findings were a central part of the report. Adverse reactions during home-based drop maintenance were rare, occurring at rates of 0.02 percent for peanuts and 0.09 percent for walnuts. Higher reaction rates were observed during initial drop challenges and the in-clinic build-up phases, but most reactions were mild to moderate, and adrenaline administration was not required, the researchers reported.

The authors note that peanut and tree nut allergies are increasing worldwide and have become a major cause of anaphylaxis in Japan. Although OIT is considered a promising treatment, conventional OIT cannot be initiated in patients with an extremely low reaction threshold because they fail to tolerate oral food challenges requiring milligram-level protein ingestion. For these patients, strict avoidance has remained the only option, resulting in persistent anxiety regarding accidental exposure. The ultra-low-dose induction phase was designed specifically to address this gap by allowing the immune system to be gradually exposed to allergen at doses far below the reaction threshold before any conventional OIT attempt.

The study was registered with the University Hospital Medical Information Network Center (R000052813). As an observational cohort study without a control group, it demonstrates feasibility and safety within the enrolled population rather than proving superiority over other approaches, and the results are based on a small number of participants — twenty-one children in total. The article was published as an open-access paper in Allergy, Asthma & Clinical Immunology on 28 September 2026, and the version shared at publication is subject to further edits before the final version of record.

According to the study’s conclusions, the ultra-low-dose induction phase appears to be a promising treatment strategy for children with severe peanut or walnut allergies who have extremely low reaction thresholds, and the approach may render conventional OIT feasible for patients who were previously unable to initiate treatment. The findings suggest that starting immunotherapy at picogram-to-nanogram protein doses, delivered as individually adjusted diluted allergen extracts, could open a treatment pathway for a group of patients for whom strict avoidance and the persistent anxiety of accidental exposure had been the only reality.

Subject of Research: An ultra-low-dose induction phase enabling oral immunotherapy in children with severe peanut and walnut allergies

Article Title: Ultra-low-dose induction phase in oral immunotherapy for children with severe peanut and walnut allergies: a multicenter observational cohort study

Article References: Nishikage, K., Imai, Y., & Shinoda, S. (2026). Ultra-low-dose induction phase in oral immunotherapy for children with severe peanut and walnut allergies: a multicenter observational cohort study. Allergy, Asthma & Clinical Immunology. https://doi.org/10.1186/s13223-026-01066-6

Image Credits: AI Generated

DOI: 10.1186/s13223-026-01066-6

Keywords: peanut allergy, walnut allergy, oral immunotherapy, ultra-low-dose induction, food allergy, anaphylaxis, children, allergen-specific IgE, skin prick test, adverse events, observational cohort study, Japan