An observational cohort study found that ultra-low-dose induction may render conventional oral immunotherapy (OIT) feasible for children who were previously unable to initiate treatment.
Researchers collected data between 2021–2024, which included 21 children older than 3 years with physician-diagnosed severe peanut or walnut allergy.
Participants had either a history of Grade ≥ 2 allergic reactions, including anaphylaxis, or reactions to trace amounts of the allergen indicating an extremely low reaction threshold preventing conventional OIT initiation or progression, and were also required to have a positive skin prick test or elevated allergen-specific immunoglobulin E (IgE) levels
Participants were divided into two groups; peanut allergy and walnut allergy. Both groups underwent the ultra-low-dose induction phase protocol, with the starting treatment dose individually determined using serial 5-fold dilutions of allergen extract.
Participants ingested the selected extract dose twice daily for one month and at monthly clinic visits, the dose was increased by increasing the number of drops and by progressing to more concentrated extract dilutions if tolerated.
Participants with peanut allergy and 90.9% of patients with walnut allergy successfully transitioned to conventional OIT and tolerated mg-level powder ingestion with a median time to transition of 16 and 8 months for peanuts and walnuts, respectively.
Most participants could tolerate higher doses in the allergen-drop challenges after treatment and adverse reactions during home-based drop maintenance were rare (0.02% for peanuts and 0.09% for walnuts), with reactions being mostly mild to moderate, and no adrenaline was needed at any stage.
Researchers found that 30% and 27.3% of patients with peanut and walnut allergies could consume allergen-containing commercial products, respectively.
Researchers suggested that the benefits of treatment may extend beyond an increase in reaction threshold, as they may also reduce anxiety related to accidental exposure in daily life.
The researchers concluded that an ultra-low-dose induction phase may help children with severe peanut or walnut allergies progress to conventional OIT and tolerate milligram-level protein doses. However, the absence of a randomised comparison group and standardised allergen extracts suggest that further research is needed to confirm these findings.
Reference
Nishikage K et al. Ultra-low-dose induction phase in oral immunotherapy for children with severe peanut and walnut allergies: a multicenter observational cohort study. Allergy Asthma Clin Immunol.2026. DOI;10.1186/s13223-026-01066-.
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