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.