Discussion
1. Patient characteristics
The results suggest that we could not predict severe anaphylaxis from patients’ backgrounds. Almost half of the patients had no history of anaphylaxis in response to the causative food. A previous study evaluating the predictive factors of reactions during OFCs also reported that the clinical history of anaphylaxis to peanuts was not significantly associated with severe allergic reactions during OFCs [9]. In our study, the patients were older, and displayed a high rate of asthma complications, which is consistent with previous case reports [10]. Although there have only been a limited number of reports to date, it is necessary to pay attention to severe symptoms in children who are older and have a history of asthma.
2. Symptoms during OFCs, and treatment
Severe anaphylactic symptoms can develop suddenly or worsen rapidly, leading to anaphylactic shock. In our patients, while IM adrenaline was mostly administered 30–90 minutes after ingestion, two patients presented with severe symptoms immediately after food ingestion or exercise. Of note, all patients had cardiovascular symptoms. Considering the rapid worsening of allergic reactions, we acknowledged that providing prompt therapeutic intervention, and consensus on the treatment strategy must have been a crucial prerequisite for providing safe OFC.
We standardized the treatment corresponding to severe refractory anaphylaxis to multiple IM adrenaline injections; therefore, we adopted a 0.03 µg/kg/min starting dose for continuous adrenaline infusion. This decision was based on the expectation that the risk of anaphylaxis is mitigated in the OFC because the challenged dose was set based on severity and immunological parameters, and the treatment was applied without delay. Therefore, we set this infusion rate to minimize the risk of treatment with adrenaline. Even in the two cases in which the required dose was increased, the patients were able to overcome anaphylaxis with appropriate dose increases based on their symptoms, and no serious sequelae were observed.
According to the current guideline, adrenaline infusion should be applied to patients who require repeated IM doses of adrenaline, but the appropriate infusion rate is not standardized [8]. The Japanese guidelines for food allergy recommends 0.1–1.0 µg/kg/min as the starting dose [6]. Barach et al. recommended an infusion rate of 0.1 µg/kg/min for children and infants [11]. Brown and Alviani suggested 0.085–0.17 µg/kg/min as the initial rate depending on the severity of the reaction [5, 12]. The doses recommended in previous studies were relatively high compared to those used in our study. However, none of the patients presented with serious adverse events and all patients recovered completely. In addition, continuous adrenaline administration was discontinued in all the patients within a few hours. These facts suggest that the high infusion rate recommended in previous studies or guidelines might not be needed if appropriate therapy is provided. However, because of the small number of cases examined, this suggestion would need to be confirmed after studying further cases.
This was a case-series study performed during OFCs, and the amount of challenged food was determined based on the characteristics of previous episodes of the patients. Our results cannot be applied directly to accidental anaphylaxis in emergency departments; however, they will certainly be valuable in considering treatment options for severe anaphylaxis.