MAIN TEXT:
To the Editor:
Food-dependent exercise-induced anaphylaxis (FDEIA) is an immunoglobulin
E (IgE)-mediated food allergy triggered by physical exertion following
the ingestion of the causative food. Foods causing FDEIA differ by
culture and eating habits, and wheat and shrimp are commonly reported
causative foods in Japan. In 95% of patients, the duration between food
consumption and exercise is shorter than 3 h1. Here we
report a unique case of wheat-dependent exercise-induced anaphylaxis
(WDEIA) in a 12-year-old boy who experienced exercise-induced
anaphylaxis 5 h after wheat ingestion and required intramuscular
adrenaline administration.
A 12-year-old boy presented to our emergency department with systemic
urticaria, nasal discharge and dyspnea after running for 20 min. He had
ingested tempura containing wheat and shrimp 5 h before running. He was
administered intramuscular adrenaline by his mother 30 min after the
onset of symptoms. On arrival at the hospital, the patient had diffuse
urticaria and wheezing accompanied by hypoxemia, was diagnosed with
anaphylaxis, and administered hydrocortisone, antihistamines and
intravenous hydration.
The patient had a history of three prior anaphylactic episodes starting
at 7 years of age, with each episode requiring intramuscular adrenaline
injection (Table 1). Prior to all three episodes, he had exercised
within 1 h of wheat ingestion. Other than exercise, none of the common
triggers of FDEIA1 were identified. Although rice,
cow’s milk, beef, pork, chicken, fish, shrimp and vegetables were also
consumed prior to some of the episodes, only wheat was consumed prior to
all four anaphylactic episodes. He regularly consumed wheat and
performed intensive exercise for judo, both of which were always well
tolerated. He had a history of hay fever to cedar and ragweed but no
history of bronchial asthma, other food allergies, or atopic dermatitis.
The anaphylactic episodes were not seasonal; one episode was in March,
one episode was in May, and two episodes were in October. He was
diagnosed with WDEIA and
instructed to refrain from exercise for 3 h after wheat ingestion and to
carry an adrenaline auto-injection for use in case of WDEIA symptoms.
The results of allergen-specific IgE (ImmunoCAP, Thermo Fisher
Scientific, Uppsala, Sweden) were negative for wheat, ω5-gliadin,
gluten, shrimp, cow’s milk, beef, pork, chicken and orchard grass
(cutoff, 0.35 UA/mL). The skin prick test (SPT) using commercial
allergen extracts of wheat (Torii Pharmaceutical, Tokyo, Japan) and the
prick-to-prick method with shrimp revealed a negative reaction with no
measurable wheal.
After obtaining informed consent from his parents, the patient was
admitted for a provocation test using wheat with and without aspirin and
exercise. The test protocol was based on the Japanese guidelines for
food allergy 20202. He experienced no symptoms after
ingesting 5.5 g of wheat protein and running for 15 min. However, a
second provocation test with the combination of 11.0 g of wheat protein
and 500 mg of aspirin followed by a 25-min run induced itching in the
face. The provocation test results confirmed the diagnosis of WDEIA, and
the patient was instructed not to exercise on days of wheat consumption.
However, one month after the positive provocation test, the patient
developed anaphylaxis due to exercising 30 min after wheat ingestion,
which was consistent with the diagnosis of WDEIA (Table 1).
In patients with anaphylactic episodes, identifying the causative foods
based on the clinical history and allergy testing is important before
performing a provocation test3. However,
allergen-specific IgE and SPT are not sufficiently accurate for the
diagnosis of FEDIA, especially in children and young adult patients. The
reported sensitivities of the omega-5 gliadin-specific IgE test and SPT
for WDEIA in children are 46% and 40%,
respectively3,4. In cases where the causative food
cannot be identified through history taking or allergy testing,
determination of the causative food by provocation testing can prevent
the recurrence of anaphylaxis and improve the patient’s quality of life.
The present case was diagnosed with WDEIA based on a positive
provocation test although allergen-specific IgE and SPT did not revealed
wheat sensitization.
The Japanese guidelines for food
allergy 2020 recommend that patients with FDEIA should avoid the
ingestion of causative foods within 2 h prior to
exercise2. Only two cases of FDEIA induced by exercise
performed more than 4 h after eating have been
reported5,6. No information regarding the need for
intramuscular adrenaline injection has been provided in either case. In
the present case, despite the recommended instructions to refrain from
exercise within 3 h of wheat ingestion due to the high frequency of
anaphylactic episodes, the patient exercised 5 h after wheat ingestion,
which triggered the fourth anaphylactic episode and required the
administration of intramuscular adrenaline. Therefore, exercise
restriction for 3 h after wheat ingestion was considered inadequate. The
mechanism of FDEIA remains unclear, and exercise may be one of the many
factors lowering the threshold for food allergy. In the present case, no
known FDEIA triggers except for exercise were identified across the five
anaphylactic episodes, and it remails unclear why the induction of
symptoms could not be prevented despite exercise restriction for 3 h
after wheat ingestion. Future studies are warranted to elucidate the
mechanism of FDEIA and the aggravating factors.
The present case illustrates the unique presentation of anaphylaxis
triggered by exercise 5 h after wheat ingestion, which required
adrenaline self-injection, although allergy tests did not demonstrate
wheat sensitization. This case highlights that severe symptoms can be
triggered even after a long interval between food ingestion and exercise
in patients with FDEIA and that the diet consumed in the 5–6 h before
exercise should be reviewed in patients who develop anaphylaxis during
or after exercise.