Discussion
This study retrospectively analyzed real-world experiences of OIT for CN and peanut allergies. The findings reveal a notable lower incidence of adverse reactions in the CN group, coupled with a high success rate in reaching maintenance. Adverse reactions were generally mild to moderate, with severe reactions primarily occurring in the peanut group. Notably, a substantial proportion of patients who underwent a second OFC demonstrated desensitization, especially in the CN group.
Ensuring safety during OIT is a significant concern, considering the known risk of severe adverse reactions, particularly during the up-dosing phase17 12. In our study, we observed a low frequency and severity of adverse reactions in patients undergoing CN OIT. In contrast, the NUT Cracker study reported a high incidence of side effects (88%) with 18% of patients requiring adrenaline use18. Another study on CN OIT in preschool children recorded no severe reactions, but 70.7% experienced mild reactions19. Our CN group had an even lower rate of mild to moderate adverse effects (33%) with no episodes of anaphylaxis, possibly due, in part, to the low sIgE levels in our study population.
In contrast, the peanut group exhibited a significantly higher rate of side effects, with 13% of patients experiencing anaphylaxis and 63% encountering any side effect. The increased likelihood of severe allergic reactions during peanut OIT, compared to strict avoidance, has been reported in other studies,23 17underscoring the importance of thorough discussions with families to assess the risk-benefit ratio. As reported in previous studies, moderate or severe reactions were associated with higher sIgE levels,24 25 explaining our finding of higher rates of adverse reactions in the peanut group, with greater safety observed in those with lower IgE levels.
In our patients, we did not validate previous findings that associated the severity of adverse effects during OIT up-dosing with the presence of co-existing asthma or allergic rhinitis.2627 However, patients with asthma or other food allergies took significantly longer to reach the maintenance phase. It remains unclear whether this slower progress was intentional for safety reasons, as 70% of asthmatic patients had seasonal symptoms, or if other factors influenced the time required to reach maintenance. This suggests the possibility that seasonal triggers may have contributed to a deceleration during the up-dosing phase, especially during pollen season. Patients undergoing CN OIT reached their maintenance dose quicker, which might be attributed to the significantly lower mean starting dose in the peanut group.
A small proportion (5%) of children discontinued peanut OIT due to aversion to taste, a phenomenon not observed in the CN group, suggesting a potentially better tolerance for the taste of cashews. The introduction of a standardized peanut OIT product may enhance treatment compliance12. The rate of desensitization in CN OIT was high (88%), in line with existing data1819. In contrast, the desensitization rate in the peanut group was lower (69%). However, all patients who didn’t pass the second OFC had mild to moderate reactions and increased their individual reactive dose, indicating partial desensitization.11
Consistent with other studies, a substantial number of patients in the peanut group experienced an initial increase in sIgE levels28 29, with some showing persistent high levels even after years of therapy. This complexity in sIgE dynamics makes it challenging to rely on IgE levels for prognostic purposes.
This study has several limitations, including its retrospective design, potential biases, and missing immunological data. The heterogeneity in starting and up-dosing protocols further complicates therapy duration comparisons. The open OFC format may introduce bias, and the relatively small sample size of patients undergoing a second OFC after the maintenance phase limits statistical power and generalizability. Further evaluations, especially considering the association of low nut-specific IgE with a higher remission rate, may offer additional insights into the study population.15 30 To optimize and standardize CN OIT, prospective studies are needed to evaluate safety, feasibility, and long-term outcomes, enhancing the effectiveness and reliability of this treatment.
In conclusion, CN OIT shows promise as a treatment option, demonstrating a lower rate of severe reactions compared to peanut OIT and good feasibility with low dropout rates. However, careful consideration of immunological parameters and other allergic diseases is crucial when informing families and planning therapy. Further prospective studies will help enhance the safety and effectiveness of OIT as a treatment option for cashew nut allergic children.