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Food dependant exercise induced anaphylaxis a retrospective study from 2 allergy clinics in Colombo, Sri Lanka

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Abstract

The aetiology of anaphylaxis ranges from food, insect venom, drugs and various chemicals. Some individuals do not develop anaphylaxis with the offending agent unless ingestion is related temporally to physical exertion, namely food dependent exercise induced anaphylaxis (FDEIA). The foods implicated are wheat, soya, peanut, milk and sea food. A retrospective study on patients with FDEIA from two Allergy clinics in Sri Lanka from 2011 to 2015 is reported. Patients were selected who fulfilled the following criteria: clinical diagnosis of anaphylaxis according to the World Allergy Organization (WAO) criteria, where the onset of symptoms was during exertion, within 4 h of ingesting a food, the ability to eat the implicated food independent of exercise, or exercise safely, if the food was not ingested in the preceding 4 h and an in vitro (ImmunoCap serum IgE to the food) or in vivo (skin prick test) test indicating evidence of sensitivity to the food. There were 19 patients (12 males: 7 females). The ages ranged from 9 to 45 (mean 22.9, median 19 years). Eight patients (42.1%) were in the 9-16 age group. Those below 16 years had a male:female ratio of 3:5, while for those above 16 years it was 9:2. Wheat was the only food implicated in FDEIA in all patients and was confirmed by skin prick testing, or by ImmunoCap specific IgE to wheat or ω - 5 gliadin. All patients had urticaria, while 5/19 (26.3%) had angioedema of the lips. Fifteen patients (78.9%) had shortness of breath or wheezing, while 8 (42.1%) had lost consciousness. Nine patients (47. 3%) had hypotension. Fourteen (73.6%) of our patients had severe reactions, with loss of consciousness or hypotension, while 5 (26.3%) had symptoms related to the gastrointestinal tract. One patient developed anaphylaxis on two occasions following inhalation of ganja, a local cannabis derivative along with the ingestion of wheat and exertion. Wheat is the main food implicated in FDEIA in Sri Lanka. A local cannabis derivative, ganja has been implicated as a cofactor for the first time.
de Silva et al. All Asth Clin Immun (2015) 11:22
DOI 10.1186/s13223-015-0089-6
CASE REPORT
Food dependant exercise induced
anaphylaxis a retrospective study from2 allergy
clinics inColombo, Sri Lanka
Nilhan Rajiva de Silva1*, Wasala Mudiyanselage Dhanushka Kumari Dasanayake1, Chandima Karunatilleke1
and Gathsauri Neelika Malavige2
Abstract
The aetiology of anaphylaxis ranges from food, insect venom, drugs and various chemicals. Some individuals do not
develop anaphylaxis with the offending agent unless ingestion is related temporally to physical exertion, namely
food dependent exercise induced anaphylaxis (FDEIA). The foods implicated are wheat, soya, peanut, milk and sea
food. A retrospective study on patients with FDEIA from two Allergy clinics in Sri Lanka from 2011 to 2015 is reported.
Patients were selected who fulfilled the following criteria: clinical diagnosis of anaphylaxis according to the World
Allergy Organization (WAO) criteria, where the onset of symptoms was during exertion, within 4 h of ingesting a food,
the ability to eat the implicated food independent of exercise, or exercise safely, if the food was not ingested in the
preceding 4 h and an in vitro (ImmunoCap serum IgE to the food) or in vivo (skin prick test) test indicating evidence
of sensitivity to the food. There were 19 patients (12 males: 7 females). The ages ranged from 9 to 45 (mean 22.9,
median 19 years). Eight patients (42.1%) were in the 9–16 age group. Those below 16 years had a male:female ratio
of 3:5, while for those above 16 years it was 9:2. Wheat was the only food implicated in FDEIA in all patients and was
confirmed by skin prick testing, or by ImmunoCap specific IgE to wheat or ω 5 gliadin. All patients had urticaria,
while 5/19 (26.3%) had angioedema of the lips. Fifteen patients (78.9%) had shortness of breath or wheezing, while 8
(42.1%) had lost consciousness. Nine patients (47. 3%) had hypotension. Fourteen (73.6%) of our patients had severe
reactions, with loss of consciousness or hypotension, while 5 (26.3%) had symptoms related to the gastrointestinal
tract. One patient developed anaphylaxis on two occasions following inhalation of ganja, a local cannabis derivative
along with the ingestion of wheat and exertion. Wheat is the main food implicated in FDEIA in Sri Lanka. A local can-
nabis derivative, ganja has been implicated as a cofactor for the first time.
Keywords: Anaphylaxis, FDEIA, Wheat, Food allergy, Exercise
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Background
Anaphylaxis is a potentially fatal, systemic hypersensi-
tivity reaction [1]. e aetiology of anaphylaxis ranges
from food, insect venom, drugs and various chemicals.
In some cases of anaphylaxis, the individual does not
develop anaphylaxis with the offending agent unless
ingestion is related temporally to physical exertion [2].
e initial case report described a patient who developed
anaphylaxis during exertion after ingesting shellfish
[3]. is condition was termed food dependent exer-
cise induced anaphylaxis (FDEIA) [4]. A number of food
items have been implicated in FDEIA such as wheat,
soya, peanut, milk and sea food [5]. Anaphylaxis follow-
ing exertion, without concomitant intake of food was also
described, termed exercise induced anaphylaxis (EIA)
[6]. EIA constitutes 5–15% of all cases of anaphylaxis [5].
A third or half of EIA are due to FDEIA [2].
In FDEIA, anaphylaxis develops only if a specific food,
or in some instances, any food, is ingested up to 4 h
before exertion. In some instances, ingestion of the food
may be after exertion [2]. Ingesting the food without
Open Access
*Correspondence: nilhanrajivadesilva@yahoo.com
1 Department of Immunology, Medical Research Institute, Colombo 08,
Sri Lanka
Full list of author information is available at the end of the article
Page 2 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
exertion, or exertion in the absence of preceding inges-
tion of food does not lead to symptoms. Although the
exact pathogenesis of FDEIA is not clear, changes in
serum osmolality and the pH, changes in permeability
of the intestinal epithelium and blood flow re distri-
bution are thought to play a role [7]. It is believed that
co factors may influence the process in two ways, by
either increasing bioavailability of the food by increas-
ing intestinal permeability or by reducing the thresh-
old for mast cell degranulation [8]. Exercise, alcohol
and certain drugs have been shown to increase the
intestinal absorption of allergens, by inducing a leak-
age of the intestinal barrier [8], and exercise provoca-
tion has shown a dose dependent reactivity [9]. It is well
documented that exercise may reduce the threshold
for mast cell and basophil activation, even though the
exact mechanism is still unclear [8]. Increased plasma
osmolality, or activation of intestinal tissue transglu-
taminase (tTG) have been postulated. An increase in IL
6 (increased 50–100 times in marathon runners) upreg-
ulates tTG, which then causes aggregation of ω 5
gliadin, a wheat component implicated in FDEIA. e
aggregated product can more efficiently cross link Fcε
receptors on mast cells and basophils [10].
FDEIA has been described in the West [11], and in
South East Asia, including Japan [12, 13], Korea [14], Sin-
gapore [15] and ailand [16]. Here we report for the first
time, a series of cases of FDEIA due to wheat allergy in
Sri Lanka.
Case presentations
Methods
is is a retrospective review of patients diagnosed at 2
allergy clinics in Colombo, one at the Medical Research
Institute (RdeS), and the other at Asiri Surgical Hospital
(GNM) between 2011 and 2015.
FDEIA was diagnosed if the patients fulfilled the crite-
ria presented in Table1 [13].
Case records were analysed, including clinical history
and results of skin prick testing and invitro testing for
the implicated food. As this is a retrospective study, ethi-
cal clearance was obtained to collect data from the Ethics
Committee of the Medical Research Institute, Colombo.
However, the patients were traced and written informed
consent was obtained for publication.
Results
Nineteen patients were diagnosed with FDEIA. All had
wheat dependent exercise induced anaphylaxis. No other
food was identified to cause FDEIA in the two clinics
during the study period, even though two patients, in
addition to wheat dependent exercise induced anaphy-
laxis, developed anaphylaxis without ingesting wheat on
1 and 2 occasions, respectively (Table2).
Skin prick testing (SPT) was carried out in 7/19
patients, and all seven were found to be sensitized to
wheat. Wheat specific IgE was determined by Immu-
noCap in 15 patients: 10 with whole wheat and 5 with
ω5-gliadin as it was only available from 2014. Eight
out of 10 patients tested with whole wheat ImmunoCap
(80%) gave positive results. All 5 patients tested with
ω5-gliadin were positive. In 2/10 patients, where the
whole wheat ImmunoCap gave a negative result, the SPT
was positive. In one patient, both tests were positive.
Of the 19 patients, 12 were males and 7 females. e
ages ranged from 9 to 45 (mean 22.9, median 19years).
Eight patients (42.1%) were in the 9–16 age group, 5 in
the 20–29 age group, and only 4 were in the 41–45 age
group. ose below 16years had a male: female ratio of
3:5, while for those above 16years it was 9:2. Seventeen
patients had not developed any symptoms when ingest-
ing wheat, prior to the development of anaphylaxis. One
patient (No. 16) gave a history of developing urticaria fol-
lowing ingestion of wheat; however, on one occasion, the
ingestion of a wheat based product followed by exertion
resulted in anaphylaxis. Another patient (No. 19) could
eat wheat without developing symptoms, except on one
occasion, when ingestion of a bun resulted in urticaria.
However, it is possible that another allergen was involved.
Two patients (No. 7, 13) developed urticaria following
exertion alone on 7 and 2 occasions respectively, but ana-
phylaxis developed when the exertion was preceded by
the ingestion of wheat.
One patient (No. 19), developed anaphylaxis on 6 occa-
sions following ingestion of a wheat based product, fol-
lowed by exertion. On 2 occasions, food other than
wheat also resulted in anaphylaxis, when the intake was
followed by exertion. However, there have been occa-
sions where ingestion of wheat followed by exertion did
not result in anaphylaxis. On 6 of the 8 occasions where
anaphylaxis had developed, the patient was having her
Table 1 Criteria fordiagnosis ofFDEIA [13]
1. Clinical diagnosis of anaphylaxis according to the World Allergy Organization (WAO) criteria [1]
2. Onset of symptoms during exertion, within 4 h of ingesting the implicated food
3. Ability to eat the implicated food independent of exercise, or exercise safely, if the food was not ingested in the preceding 4 h
4. In vitro (ImmunoCap serum IgE to the implicated food) or in vivo (skin prick test) evidence of sensitivity to the food
Page 3 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
Table 2 Clinical Characteristics ofthe patients
No Age (years) Sex Food Exertion Latent period Clinical Skin prick test
forwheat (Posi-
tive—wheal >3mm
diameter overnega-
tive control)
ImmunoCap results
For wheat kUA/L
(>0.35 positive)
Skin Respiratory Cardiovascular GIT
01 11 F (1). Biscuit Playing 15 min U S 8 mm ND
(2). 4 other episodes
with wheat
02 29 M (1). Chicken sandwich Cycling 60 min Pr, U SLOC AP ND IgE to wheat 12.1
(2). 1 other episode,
trigger not certain
03 25 M (1). Vegetable rotti* Badminton 30 min U LOC ND IgE to wheat 2.06
(2, 3). Pizza (x2) Walking (x2) 1.5 and
2 km U
(4). Noodles* Dancing 30 min U LOC, H
04 10 M (1). Fishbun Playing 30 min U LOC, H, no Pulse ND IgE to wheat 2.33
05 20 M (1). Rotti* Walking 60 min U, A S H ND IgE to wheat 5.6
06 42 F (1). Rotti* Cleaning 15 min U, A W AP ND IgE to wheat 2.8
(2). Bread Walking 30 min U, A W V
07 12 M (1). Cream bun Cycling, sweeping 120 min U W LOC AP, V ND IgE to wheat 8.3
(2). Cake Cycling 7 km 60 min U, A
(3–10). No food X 7 playing U
08 14 F (1). Rotti* Volleyball 15 min U S LOC 3 mm IgE to wheat 0.07
(2). Egg bun Walking 30 min U
09 14 F (1). Sandwich Football 45 min U, A SLOC 5 mm IgE to wheat 0.07
(2). Pasta Climbed 2 flights of
steps on a rock 30 min (after 5 min
at rest) U
10 11 M (1). Chinese roll, cake Playing 30 min U W V, AP 5 mm ND
11 42 M (1). Rotti* Walking 30–45 min U S, W ND IgE to wheat 5.47
12 45 M (1). Noodles* Walking rapidly and
cleaning garden 30 min U AP, V 4 mm ND
13 16 F (1). No food Swimming (x2) U 5 mm IgE to wheat 11.4
(1). Fish bun Badminton 20 min U S Faintness, H
14 19 M (1). Paratha* + Ganja
(cannabis for the
first time)
Walked 30 min 30 min U S Faintness BP unre-
cordable IgE to ω 5-gliadin
1.63
(2). Rotti* + ganja Football 30 min U S
Bilateral rhonchi Dizzines, reduced BP
Anaphylactic shock
Page 4 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
U urticaria, A angioedema, AP abdominal pain, BP blood pressure, D dizziness, H hypotension, LOC loss of consciousness, P palpitations, Pr pruritus, R rhonchi, S shortness of breath, V vomiting, W wheeze.
*Wheat based food: Rotti=wheat, scrapped coconut and salt containing at bread; Paratha=wheat, coconut oil and salt containing unleavened at bread; Kotthu=wheat, vegetables, chicken/beef containing dish;
Wadé=Wheat based vegetable pastry.
Table 2 continued
No Age (years) Sex Food Exertion Latent period Clinical Skin prick test
forwheat (Posi-
tive—wheal >3mm
diameter overnega-
tive control)
ImmunoCap results
For wheat kUA/L
(>0.35 positive)
Skin Respiratory Cardiovascular GIT
15 18 M (1). Kotthu Walked 1 km 1 h (15 min after walk) U S 3 mm ND
(2). Doughnut Exercise 4 h (1 hour after exer-
tion) U S D, H
(3). Paratha* Orbitract (1 km) U
16 9 F (1). Noodles*, cake,
biscuits, bread, roti x9
times)
No exertion 30 min after ingestion U IgE wheat ω 5-glia-
din 35.7
(2). Wafers, cookies Played 30 min U W, R D, BP 80/58 mm Hg
17 26 M (1). Fish bun Cycling 3 km 30 min U S Faintness IgE wheat ω 5-glia-
din 10.6
(2). Rice and curry.
Later, wheat based
pastry (Wadé*) after
walk
Walked 100 yards. 10 min after eating
pastry U
(3). Rice, coconut
sambol, eggs (break-
fast)—8 am
Household chores for
1 ½ h 5 min after lunch U Blurring of vision, LOC
Rice, fish, dhal (lunch)
12.30 pm 2 h after breakfast
(10–11.30 am) S
18 44 M (1). Rotti* Walked 1 km 25 min U Faintness, H IgE wheat ω 5-glia-
din 3.4
19 27 F (1). Rotti* Walked 10 min up a hill 90 min U, A P, H IgE wheat ω 5-glia-
din 5.4
(2). Noodles* Running 15 min 45 min U, A W H
(3). Bun No exertion U
(4). Green gram Gardening for 30 min 120 min U W H
(5). Bun Climbing hill for 10 min 15 min U H, LOC
(6). Sandwich Exertion for 15 min 60 min U P, H
(7). Rice, carrot, potato,
beans Exertion 240 min U P
(8). Chinese roll Exertion 15 min U W P, H, LOC
(9). Roll Exertion U LOC
Page 5 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
monthly periods. Another patient developed anaphy-
laxis, 5min after ingesting a meal which did not contain
wheat. He had finished exertion an hour before the meal.
He subsequently developed anaphylaxis following inges-
tion of wheat. e onset was 5min to 4h after ingesting a
meal (mean 51.6min, median 30min). Fourteen patients
(73.6%) reported symptoms within 30min of eating wheat
based food. e episodes occurred during exertion in 18
patients. In one patient, anaphylaxis developed 15 and
60 min after exertion. e exertions ranged from mild
(domestic cleaning/sweeping) to moderate/severe (bad-
minton, football and volleyball). e rigorousness of the
exertion played a part in the clinical symptoms in three
patients. One patient developed urticaria (No. 9) when
resting for 5min after mild exertion (climbing 2 flights of
stairs situated on a rock) previously; subsequently she had
anaphylaxis after more severe exertion (football). A sec-
ond patient (No. 3) had 2 episodes of urticaria while walk-
ing (1.5 and 2km), while he had 2 episodes of anaphylaxis
after severe exertion (badminton, dancing). A third
patient (No 0.13) had developed urticaria while swim-
ming on 2 occasions, and anaphylaxis after badminton.
One patient (No. 14) had eaten wheat based food
and exerted without symptoms. However, on the first
occasion he had smoked ganja (local cannabis), he had
ingested wheat containing food and walked for 30 min
and developed anaphylaxis. On a second occasion, he had
smoked ganja, ingested wheat and played football with
similar results. He has smoked ganja without any symp-
toms subsequently provided wheat was not consumed in
relation to exertion.
All patients had urticaria, while 5/19 (26.3%) had angi-
oedema of the lips. Fifteen patients (78.9%) had shortness
of breath or wheezing, while 8 (42.1%) had lost con-
sciousness. Nine patients (47.3%) had hypotension. Four-
teen (73.6%) of our patients had severe reactions, with
loss of consciousness or hypotension, while 5 (26.3%) had
symptoms related to the gastrointestinal tract.
ere was no association with stress, humidity, cold
weather, or use of non steroidal anti inflammatory drugs.
However, one patient developed anaphylaxis on 6 occa-
sions when FDEIA was during menstruation, whereas
she could eat the wheat based food and exercise without
symptoms at other times.
Eleven patients had only one episode, while one patient
each had 8 (No. 19) and 5 episodes (No. 1) of anaphylaxis
respectively. Among the group, one patient had 7 previ-
ous episodes of urticarial.
Discussion
During a 2 ½ year period, FDEIA was diagnosed in 19
patients, who had consulted two Immunologists, serving
two allergy clinics in Colombo, Sri Lanka. ese clinics
cater to patients from the entire island. All patients with
FDEIA were allergic to wheat. Two of the patients, in
addition, developed anaphylaxis following exertion after
eating food other than wheat. Wheat is the commonest
food responsible for FDEIA in Japan [12], Korea [14] and
ailand [16]. However, the genetic makeup is different
in these countries. Shellfish has been reported to be the
commonest allergen implicated in FDEIA in Singapore
[17], but wheat is also being described [15]. e situa-
tion is different in the west, where tomatoes, cereal and
peanuts are the commonest foods implicated in FDEIA
[11]. e geographical variation may be due to the use
of wheat flour in popular dishes [15], such as hoppers,
string hoppers and the increasing consumption of west-
ern foods, such as sandwiches and fast foods among the
urban population in Sri Lanka, replacing or supplement-
ing rice based meals.
In a study among junior high school students in Japan,
the male: female ratio was 11: 2 [13]. Eight of our patients
(42.1%) were aged 9–16years, and in contrast, the male
to female ratio was 3:5. However, when patients over 16
were considered, the male: female ratio was 9: 2. e rea-
son for the discrepancy is unclear. In the total cohort,
the male: female ratio was 12:7, similar to an European
study which included children as well as adults, the male:
female ratio being 31:23 [11].
All patients had skin manifestations, and respiratory
manifestations were seen in the majority (15/19). is is
in agreement with other studies [13, 16, 18]. Eight out of
19 (42.1%) lost consciousness. Fourteen (73.6%) of our
patients had severe reactions, with loss of consciousness
or hypotension. Severe reactions, with hypotension, has
been reported in the majority of patients (60–77.7%) in
some [16, 18] but not all (25%) studies [13]. Only 5/19
patients developed gastrointestinal symptoms, similar to
other studies [16].
Eighteen patients developed anaphylaxis during exer-
cise. One patient (patient no. 15) developed anaphylaxis
15 min and 1 h, respectively, after completion of the
exercise. Anaphylaxis may occur soon after exertion and
it is recommended that wheat should not be ingested
up to 1h after exertion [7]. Two patients (patient no. 7,
13) developed urticaria during exertion, without the
ingestion of wheat containing food; the intake of wheat
resulted in anaphylaxis.
Exercise increases absorption of allergens from the gas-
trointestinal tract and induces mast cell degranulation.
More intense exercise may provoke a more severe allergic
reaction [19]. Two patients (patient no. 3, 8) developed
urticaria with mild exertion (climbing 2 flights of stairs,
walking 1.5km); another (patient no. 13) developed urti-
caria while swimming. However, more vigorous activity
(badminton, dancing, football) resulted in anaphylaxis.
Page 6 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
All patients developed anaphylaxis during or after exer-
tion, with wheat being ingested prior to the exercise.
However, one patient (patient no. 17) developed ana-
phylaxis after eating wheat following exertion, on one
occasion. On a previous occasion, he had developed ana-
phylaxis while cycling. FDEIA may occur, rarely, if food is
ingested soon after exercise [2].
One co factor was noted in a patient during the epi-
sodes of FDEIA. is patient (no. 14) developed severe
FDEIA if ganja (locally produced cannabis) was smoked.
is happened on two occasions. e mere ingestion of
wheat, even if associated with exertion did not give rise
to anaphylaxis. To the best of our knowledge, this is the
first report of cannabis as a co factor in FDEIA. Cannabis
contains many compounds, including at least 60 cannabi-
noids, which are active components of cannabis. Cannab-
inoids act via the CB1 and CB2 receptor [20]. e CB2
receptor is found on immune and other cells, and when
stimulated leads to immune cell migration and cytokine
release both in the central nervous system, and peripher-
ally [21]. Cytokine release may be a possible mechanism
for cannabis acting as a cofactor in this patient. However,
there are many more compounds and receptors impli-
cated in the diverse activities of cannabis. For example,
cannabidiol, a prominent psychoinactive component of
cannabis has been shown to activate a rat basophil leu-
kaemia mast cell line in a Ca2+ dependent manner alone
or together with FcεRI stimulation, bypassing the CB 1
and CB 2 receptors [22]. Cannabis has also been impli-
cated, albeit rarely, in IgE mediated allergic reactions
[23]. Drugs that can evoke IgE mediated symptoms may
function as a co factor in anaphylaxis, such as iodinated
contrast media and muscle relaxants [8]. We did not do
skin prick testing for cannabis in this patient due to the
legal issues involved.
e other co factors implicated in FDEIA are humidity/
cold, stress, menstruation and use of non steroidal anti
inflammatory drugs [11]. However, Sri Lanka, a tropi-
cal country, is humid throughout the year except in the
temperate central mountains. Interestingly, none of our
patients were from the central hills. One patient devel-
oped anaphylaxis on 8 occasions, 6 of which occurred
during menstruation. She had ingested wheat prod-
ucts and exercised on a few occasions without symp-
toms; menstruation may be considered a co factor in her
situation.
e patients were diagnosed on the basis of the clini-
cal history, and results of invitro testing for wheat spe-
cific IgE or ω5-gliadin by ImmunoCap, and with skin
prick testing. Eight out of 10 patients tested (80%) had
ImmunoCap IgE levels to whole wheat above the cut off
level (kUA/L >0.35 positive). Five patients tested positive
for ω5 gliadin. In one study, wheat Cap detected only
41% of patients with wheat dependent exercise induced
anaphylaxis [24]. Wheat protein contains salt soluble
albumins and globulins, and insoluble glutens. Of the
glutens, the gliadins are soluble in 70% ethyl alcohol,
while the glutenins are not. Using immunoblotting, the
wheat proteins ω5 gliadin and high molecular weight
glutenins were found to be the major antigens respon-
sible for wheat dependent EIA [25]. Using recombinant
ω5 gliadin protein as an Immunocap, its sensitivity for
wheat dependent EIA was 80%, compared to 48% for the
wheat ImmunoCap [26]. In our study, 5/5 patients tested
positive.
e Gold standard for the diagnosis of FDEIA is a
challenge test. A standard 3day challenge protocol has
been used [16]. Due to logistic reasons as well the risk
involved, we did not attempt challenge testing in our
patients.
A number of hypothesis have been postulated regard-
ing the pathophysiology of FDEIA, including increased
allergen absorption from the gastrointestinal system
during exercise; increase in osmolality in the villus bases
activating mast cells; and blood redistribution to skin
and muscle exposing sensitive mast cells in these areas to
food allergens [2].
All patients were advised to avoid ingesting wheat
based food 4 h before and one hour after exercise [2].
Some patients were prescribed the autoinjectable adrena-
line pen (“Epipen”). Many patients were unable to afford
this device as it is not supplied free of charge by the Min-
istry of Health. Attempts are being made to supply this
vital drug, on a named patient basis, to patients at risk of
anaphylaxis.
Conclusion
Wheat is the main food item implicated in FDEIA in Sri
Lanka. A local cannabis product, ganja, was implicated as
a co factor in one patient, the first report in the literature.
Lack of awareness of FDEIA may lead to an inaccurate
diagnosis by the physician and the patient may be placed
on unnecessary dietary restrictions and exercise. ere-
fore, we feel that all the primary care physicians must be
educated on this important disease entity.
Consent
Case records were analysed, including clinical history
and results of skin prick testing and invitro testing for
the implicated food. As this is a retrospective study, ethi-
cal clearance was obtained to collect data from the Ethics
Committee of the MedicalResearch Institute, Colombo.
However, the patients were traced and written informed
consent was obtained for publication.
Page 7 of 7
de Silva et al. All Asth Clin Immun (2015) 11:22
Authors’ contributions
NRDS—Concept, design of study, diagnosis, drafting of paper. WMDKD—
Diagnosis, drafting of paper. CK—Diagnosis. GNM—Concept, design of
study, diagnosis, drafting of paper. All authors read and approved the final
manuscript.
Author details
1 Department of Immunology, Medical Research Institute, Colombo 08, Sri
Lanka. 2 Department of Microbiology, Faculty of Medical Sciences, University
of Sri Jayewardenapura, Nugegoda, Sri Lanka.
Acknowledgements
We thank the staff of the Department of Immunology, Medical Research Insti-
tute, and the Allergy Clinic of the Asiri Surgical Hospital, Colombo.
Compliance with ethical guidelines
Competing interests
The authors declare that they have no competing interests.
Received: 6 May 2015 Accepted: 13 July 2015
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... However, there were some reports of a dose-response such that the same patient developed stand-alone cutaneous symptoms with exercise of lower intensity or duration, but experienced anaphylaxis when exercising harder or longer. 7,8 Conversely, in 2 patients, similar exercise and food intake resulted in stand-alone urticaria and/or angioedema on one occasion and anaphylaxis on another. 7,9 More studies are needed to better characterize dose-response relevance and mechanisms. ...
... 7,8 Conversely, in 2 patients, similar exercise and food intake resulted in stand-alone urticaria and/or angioedema on one occasion and anaphylaxis on another. 7,9 More studies are needed to better characterize dose-response relevance and mechanisms. The rates of patients who develop wheals and/or angioedema, anaphylaxis, or both in response to exercise after eating is currently unknown. ...
... The aforementioned data and findings highlight the considerable gaps in our understanding of the clinical manifestations, culprit foods and exercises, the effect of comorbidities and cofactors, and the use and efficacy of treatment in patients with food-dependent exercise-induced allergic reactions, including FDEIA. 1,3,7,10,17,18 The reasons for this knowledge gap include the absence of controlled studies and the lack of a comprehensive review of the many case reports and case series that have been published on FDEIA, especially in recent years. In an effort to bridge this gap, we set forth to systematically review reports specific to food-dependent exercise-induced wheals, angioedema, and anaphylaxis to characterize the clinical manifestations, the laboratory investigations that confirm the diagnosis, the culprit foods and exercises that trigger reactions, the comorbidities, the treatment options, and the outcomes of treatment in this patient population. ...
Article
Background: Food-dependent exercise-induced wheals, angioedema, and anaphylaxis remain insufficiently characterized. Objective: We systematically reviewed the literature on clinical manifestations, laboratory investigations, culprit foods, triggering exercise, comorbidities, and treatment outcomes. Methods: Using predefined search terms and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) recommendations, we searched three electronic databases to identify relevant literature published before July 2021. Results: Of 722 patients (median age: 25 years, 55.4% male) from 231 studies (43 cohort studies, 15 cases series, and 173 case reports), 79.6% and 3.7% had anaphylaxis with and without wheals/angioedema, respectively. The remaining 16.6% had wheals/angioedema without anaphylaxis. The duration from eating to exercising and from exercising to symptom onset ranged from 5 minutes to 6 hours (median: 1 hour) and from 5 minutes to 5 hours (median: 30 minutes), respectively, and virtually all patients exercised within 4 hours after eating and developed symptoms within one hour after exercising. Wheat was the most common culprit food. Running was the most common trigger exercise. Most patients were atopic, and one in three had a history of urticaria. Aspirin and wheat-based products were the most frequent augmenting factors. On-demand antihistamines, corticosteroids, and epinephrine were commonly used and reported to be effective. Patients who stopped eating culprit foods before exercise no longer developed food-dependent exercise-induced allergic reactions. Conclusions: Food-dependent exercise-induced allergic reactions are heterogeneous in their clinical manifestations, triggers, and response to treatment. Patients benefit from avoidance of culprit foods before exercise, which highlights the need for allergological diagnostic workup and guidance.
... While many foods have been implicated, wheat is responsible for FDEIA in Sri Lanka. 10 Alpha gal allergy is responsible for allergy to red meats. A tick bite sensitizes a patient to a carbohydrate moiety (alpha gal), which is present in the saliva of ticks and in non-primate mammals. ...
... While wheat is the commonest allergen, other foods are also implicated elsewhere. 10 Red meat was the commonest allergen in the 5-12-year age group, and was the second most common in adults. In addition, patients with red meat allergy developed allergic reactions including anaphylaxis, to vaccines containing bovine/porcine components such as the measles, mumps, and rubella (MMR) and the live Japanese encephalitis (JE) vaccine. ...
Article
Full-text available
Background The incidence of IgE mediated food allergy (FA) is increasing in the west. Cow's milk (CM), hen's egg, wheat, soy, peanut, tree nut, fish, and shellfish are responsible for 90% of food allergy in the west; however, local dietary habits may result in specific allergies. Data on food allergies in South Asia is scarce. The present study aims to evaluate the foods that cause immediate type hypersensitivity in Sri Lanka, and to compare with Asia and the developed west. Methods Records of patients referred to an Immunology clinic from 2010–January 2022 were reviewed. The diagnosis of food allergy was based on standard guidelines. Confirmation of the specific food implicated was based on the history and the presence of specific IgE or component resolved diagnostics by in vitro methods (Phadia ImmunoCap) or by skin prick testing with commercial extracts (Alk Abello). Prick to prick testing was performed for fruits and vegetables when commercial extracts were unavailable. Results Three hundred and forty-six patients were confirmed with food allergy. CM allergy (CMA) was the commonest (31.2%) followed by red meat allergy (27.7%) and food dependent exercise induced anaphylaxis (FDEIA) (17.9%). Allergy to alpha-gal crustaceans, eggs, gelatin, wheat, coconut milk, and mollusks were seen in 2–10% of patients. The onset of CMA was mainly in childhood. However, in 23/108 patients, onset was after 5 years, including 8 patients in adulthood, and in 14 of the 23, it was preceded by red meat allergy. Onset of primary red meat allergy was predominantly in children, but in 33/96 (34.3%) of patients, it was in adults. Most patients with alpha-gal allergy (21/29, 72.4%) had initial symptoms in childhood and adolescence. Anaphylaxis was diagnosed in 213 patients. FDEIA is the commonest cause (24.7%) followed by red meat allergy (23%), CMA (21.5%) and alpha-gal allergy (10.3%). Allergy to peanuts and fruits were rare. Patients with red meat allergy and/or CMA developed allergy, including anaphylaxis, to vaccines containing bovine/porcine products. Conclusion CM was the most common food allergy in children, but egg allergy was uncommon. Primary red meat allergy was the second most common, and was associated with allergy to vaccines containing bovine products, such as the measles, mumps and rubella (MMR) vaccine. Allergy to peanuts and fruits were rare. Primary red meat allergy may be responsible for late onset CMA.
... Some evidence suggests that Tri tu 14, LTP of Triticum turgidum (used for pasta, pizza, bulgur, semolina and couscous), rather than Tri a 14 is associated with WDEIA, as well as with Pru p 3-mediated food allergy (16). Additional co-factors reported as facilitator for WDEIA are both menstruation, for which the pathological mechanism is not yet fully understood (52,53), and cannabis consumption (55), probably due to the cytokine release mediated by the stimulation of CB2 receptors on the immune cells by cannabinoids (56). Even though there are no reports about the specific effect on human mast cells, it may be relevant to state also that cannabidiol, which is another component of cannabis, promotes a Ca2+ dependent activation of a rat basophil leukaemia mast cell line, alone or together with FcϵRI stimulation (57). ...
Article
Full-text available
Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector.
... We recorded only one case in 236 women where menstruation was a cofactor. Nevertheless, single cases have been reported, indicating beyond any doubt, a significant effect of menstruation on the onset of anaphylaxis [66]. ...
Article
Full-text available
Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction that is still rarely diagnosed. For safety reasons, patients should visit an allergologist to identify potential causes and cofactors of this reaction. This paper presents the analysis of data from the Anaphylaxis Registry gathered over ten years at the Allergy Clinic, Pomeranian Medical University (PMU). A questionnaire-based survey was used for patients visiting the Allergy Clinic to identify potential augmentation factors/comorbidities and/or cofactors of anaphylaxis in patients with a history of moderate to severe anaphylaxis. The registry comprised patients with grade II or higher anaphylaxis. The gathered data concerned chronic comorbidities (cardiovascular diseases, respiratory diseases, and others), recurrence of anaphylaxis, and potential cofactors in anaphylaxis. In the analyzed group, the incidence rate of anaphylaxis was the highest for women aged 19–60 years. Most common comorbidities in patients with moderate to severe anaphylaxis included: cardiovascular diseases, respiratory tract diseases, features of atopy, and thyroid diseases. More than 30% of drug-induced reactions were anaphylactic reactions due to the re-exposure to the same drug, which points to the need for educational initiatives in this area. The incidence rate of anaphylaxis induced by Hymenoptera stings was comparable in patients who had a previous generalized reaction and those who had good tolerance to the previous sting. It is important to take these cofactors into consideration when evaluating patients with anaphylaxis as they may play a role in future anaphylactic reactions.
... 4,16 The Gold standard for the diagnosis of FDEIA is a 3-day challenge test. 17 A retrospective study from Sri Lanka used the following diagnostic criteria: 3,5,18,19 • Clinical diagnosis of anaphylaxis as outlined by World Allergy Organization (WAO) criteria 18 • Onset of symptoms during exertion with ingestion of the implicated food within 4 hours • Ability to eat the implicated food independent of exercise, or ability to exercise safely if the food was not ingested in the preceding 4 hours • Evidence of sensitivity to the food by in vitro (ImmunoCap serum IgE to the implicated food) or in vivo (skin prick test). ...
Article
Full-text available
Allergic reactions can be mild or life threatening. Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe form of allergic reaction in which symptoms develop only after exercising within a few hours of eating a specific food. The condition is, at times, underdiagnosed. Proper history taking is essential, especially when patients present with allergic reactions after exertion following food intake. The patient being described developed FDEIA because of exercising after eating nuts.
... 8 The Gold standard method for the diagnosis of FDEIA is a 3 day oral challenge test. 9 The diagnostic criteria which was used in a retrospective study from Sri Lanka are 2,3,10,11 • World Allergy Organization (WAO) outlined criteria for clinical diagnosis of anaphylaxis 10 • The onset of symptoms occurred on exertion within 4 hours of ingesting the implicated food • The ability to eat the implicated food independent of exercise, or ability to exercise safely if the food was not taken in the preceding 4 hours ...
Article
Full-text available
Exercise has been associated with several systemic reactions. These reactions can vary from mild symptoms to life threatening situations like anaphylaxis. In many of these cases, a predisposing factor in the form of food has been noticed. People may develop anaphylaxis on exercising after consumption of a nonspecific or specific food item. The patient being described developed anaphylaxis with seizure on exercising after having his meal. Nonspecific food dependant exercise-induced anaphylaxis is a rare scenario. Proper history taking is essential, as it can be lifesaving.
... Additionally, one in three cannabis allergic patients reported cofactor mediated reactions to plant-foods with cofactors defined as the use of non-steroidal inflammatory drugs (NSAIDs), alcohol intake or physical exercise. On the other hand, de Silva et al. [59] report on a case in which cannabis itself is put forward as a possible cofactor in a history of wheat-mediated anaphylaxis. ...
Article
Introduction: Although the use of cannabis dates back millennia, the first description of cannabis allergy is relatively recent (1971). Recent large-scale data show that cannabis allergy can manifest severe and generalized symptoms with extensive cross-reactions. Thus, it is essential to become familiarized with its clinical presentation, diagnostic aids, and adequate therapeutic guidance. Areas covered: Here we provide a hands-on overview on cannabis allergy focusing on symptomatology and the reliability of diagnostic options. Recent advances in proteomics are discussed in detail, elucidating the link with nsLTP-related allergies. The proteomics advancements have paved the way for more reliable diagnostics, especially component-based tools. Finally, the current experience in treatment options is highlighted. Expert opinion: Cannabis allergy is an allergy entity which can significantly impact the quality of life. For optimal diagnosis, we advise to start with a validated and standardized crude-extract based test such as sIgE hemp complemented by component-based diagnostics such as sIgE Can s 3 quantifications where available. Future research should lift the veil on the true prevalence of cannabis allergy and the importance of other cannabis allergens to further guide our practice.
Chapter
Although allergic diseases were historically reported more commonly in industrialized populations, in the past decades, their rates have been on the rise globally, especially in developing countries. Trends observed in various developing countries in Africa, the Middle East, Asia, and Latin America show this increasing prevalence has been attributed to the effects of modernization in those countries. Multiple risk factors of allergic diseases, such as obesity, tobacco exposure, living in close proximity of factories, or simply overcrowding, are linked to urbanization and modern life styles. It is important to note that despite lower disease rates, the impact of allergic diseases is potentially higher in developing countries with limited resources than that observed in developed countries. This is at least partly due to a lack of knowledge and inadequate access to health care. The lack of awareness about the rise of allergies must be addressed in order to decrease the burden of these diseases.
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Introduction: Food-dependent, exercise-induced anaphylaxis (FDEIA) is a rare type of anaphylaxis with a growing incidence. Although the precise mechanism by which the patient reacts only in a combination of a culprit food and cofactors are not currently understood, many advances in diagnosis and management have been made since their first description. Areas covered: A literature search in PubMed was performed to review the diagnosis and management of FDEIA. Clinicians should have a high level of suspicion for identification of the culprit foods and the cofactors involved. Component-resolved diagnosis and more accurate provocation tests have revolutionized the diagnosis accuracy. Management is not easy and involves educating the patient to evict the combination of exposure to the culprit foods and the cofactors that elicit anaphylaxis, and how to act and treat if a reaction occurs. Expert opinion: FDEIA is currently misdiagnosed and the authors believe that there are many FDEIA patients labelled as idiopathic anaphylaxis with unnecessary evictions and with a poor quality of life because of the fear of an imminent reaction. Due to recent advances in diagnostic tools and the use of monoclonal antibodies for prophylaxis in persistent cases, FDEIA can have a better prognosis improving the quality of life of the patients and their families.
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Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.
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Full-text available
Food-dependent exercise-induced anaphylaxis (FDEIAn) is induced by different types and various intensities of physical activity, and is distinct from food allergies. It has been shown that consumption of allergenic food followed by exercise causes FDEIAn symptoms. Intake of allergenic food or medication before exercise is a major predisposing factor for FDEIAn. Urticaria and severe allergic reactions are general symptoms of FDEIAn. Dermatological tests and serum IgE assays are the typical prescreening methods, and have been used for several decades. However, these screening tests are not sufficient for detecting or preventing FDEIAn. It has been found that exercise may stimulate the release of mediators from IgE-dependent mast cells that can result in FDEIAn when a certain threshold level has been exceeded. Mast cell degradation might be a major factor to induce FDEIAn but this has not been determined. A number of foods have been reported to be involved in the onset of FDEIAn including wheat, eggs, chicken, shrimp, shellfish, nuts, fruits, and vegetables. It is also known that aspirin increases the occurrence of type I allergy symptoms when combined with specific foods. Moreover, high intensity and frequent exercise are more likely to provoke an attack than low intensity and less frequent exercise. In this paper, we present the current views of the pathophysiological mechanisms underlying FDEIAn within the context of exercise immunology. We also present a detailed FDEIAn definition along with etiologic factors and medical treatment for cholinergic urticaria (UC) and exercise-induced anaphylaxis (EIA).
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Full-text available
Wheat is a common cause of food allergy. Wheat-induced anaphylaxis (WIA) and wheat-dependent exercise induced anaphylaxis (WDEIA) are severe forms of immunoglobulin E (IgE) mediated allergic reaction to wheat protein. As the diagnosis of WIA or WDEIA is not easy because of the risk of oral challenge, identification of specific IgE of various wheat proteins is helpful for diagnosis. In Korea, there are only a few reports on WIA in adults. We report six cases of WIA diagnosed on the basis of clinical history and specific IgE of wheat proteins or provocation test. For immunologic evaluation of severe wheat allergy including WIA and WDEIA, it is important to measure specific IgE to each component of wheat including gluten and ω-5 gliadin not just measuring wheat-specific IgE.
Article
Introduction: Food-dependent exercise-induced anaphylaxis (FDEIA) is an uncommon and under-recognised syndrome that clinicians may not consider in a patient presenting with ana- phylaxis. Clinical Picture: We describe here 5 patients aged 9 to 20 years old who presented at a local tertiary hospital over a 2-year period from August 2006 to July 2008. All presented with urticaria, 4 were hypotensive, 2 had angioedema and another 2 had dyspnoea. The symptoms occurred between 15 and 150 minutes (mean, 81) after exercising and consuming various food. All had consumed shellfish. All patients were admitted with the diagnosis of anaphylaxis of undefined aetiology. Diagnosis of FDEIA was only reached upon referral to an allergist. Treat- ment and Outcome: Patients were treated with standard medicines for anaphylaxis including adrenaline, antihistamines, steroids and fluid flushes. Symptoms resolved in 2 to 3 days with no further episodes. At discharge, patients were prescribed epinephrine auto-injectors and given written anaphylaxis management plans. Conclusions: More public awareness and strategies to ensure accurate diagnosis and management of this condition are necessary. Key words: Anaphylaxis, Epinephrine, Exercise, Food
Article
Background Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy caused by the combination of wheat ingestion and physical exercise and has been reported in other parts of Asia. At present, there are no published reports of WDEIA in Singapore. The objective of this study is to characterise the common local clinical and laboratory manifestations of WDEIA. Methods This was a retrospective descriptive study of all WDEIA who presented to a tertiary Singaporean Hospital over a 5-year-period from 1 January 2009 to 30 June 2013. Results Eight patients aged 9–41 years old were characterised. Six were males and the majority (5) was of Chinese ethnicity. An atopic history was found in four patients. The symptoms of anaphylaxis included cutaneous manifestations such as urticaria (n=7), angioedema (n=6), respiratory symptoms of dyspnoea and wheezing (n=5) and hypotension (n=5). The symptoms occurred 20–75 min after consumption of wheat-based products, often upon cessation of exercise [running (n=3), walking (n=4) and swimming (n=1)]. The WDEIA was recurrent in seven patients. The skin prick tests were positive to wheat in seven patients, and ω-5 gliadin test to wheat was positive in five patients. Conclusions With the emergence of wheat allergy in East Asian countries, WDEIA has become an important condition for physicians and Singapore is no exception. Under-recognition combined with life-threatening symptoms warrants better public awareness measures. In addition, further studies are necessary to identify possible unique genetic and environmental exposures that could explain the inter-regional differences of WDEIA.
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The risk to develop anaphylaxis depends on the sensitization pattern, the proportion of the involved immunoglobulin classes, the avidity and affinity of immunoglobulins to bind an allergen, characteristics of the allergen, the route of allergen application, and, last but not least, the presence of cofactors of anaphylaxis. To be able to calculate the risk to develop anaphylaxis and to anticipate the severity of the reactions under certain conditions, it is necessary to understand how all these factors interact with each other. Important progress for risk assessment in anaphylaxis is based on component-resolved stratified diagnostics, which allow to (i) determine a patient's sensitization pattern on a molecular basis, (ii) correlate clinical responses to defined sensitization patterns, and (iii) better identify cross-reactive allergens. Together with the increasing knowledge regarding the role and mode of action of cofactors of anaphylaxis, these data pave the way to unscramble the complex interactions determining the clinical relevance of sensitizations, the risk of anaphylaxis, and the severity of reactions. As a consequence, this understanding allows to better determine the individual risk in response to an identified allergen and results in more specific advices and education for our patients to prevent further life-threatening anaphylactic reactions.
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Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as 'wheat-dependent exercise-induced anaphylaxis' (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.
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Allergic sensitization to Cannabis sativa is rarely reported, but the increasing consumption of marijuana has resulted in an increase in the number of individuals who become sensitized. To date, little is known about the causal allergens associated with C sativa. To characterize marijuana allergens in different components of the C sativa plant using serum IgE from marijuana sensitized patients. Serum samples from 23 patients with a positive skin prick test result to a crude C sativa extract were evaluated. IgE reactivity was variable between patients and C sativa extracts. IgE reactivity to C sativa proteins in Western blots was heterogeneous and ranged from 10 to 70 kDa. Putative allergens derived from 2-dimensional gels were identified. Prominent IgE reactive bands included a 23-kDa oxygen-evolving enhancer protein 2 and a 50-kDa protein identified to be the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. Additional proteins were identified in the proteomic analysis, including those from adenosine triphosphate synthase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and luminal binding protein (heat shock protein 70), suggesting these proteins are potential allergens. Deglycosylation studies helped refine protein allergen identification and demonstrated significant IgE antibodies against plant oligosaccharides that could help explain cross-reactivity. Identification and characterization of allergens from C sativa may be helpful in further understanding allergic sensitization to this plant species.
Article
Little is known about the cause of food-induced anaphylaxis in children or about the factors that might affect its clinical severity. The aim of this study was to investigate the cause of food-induced anaphylaxis in children in Italy and to identify factors that could influence the appearance of symptoms and the severity of anaphylaxis. One hundred and sixty-three children with anaphylaxis consecutively attending 29 outpatient allergy clinics throughout Italy were enrolled in this prospective study. Information about past anaphylaxis episodes was collected with a standardized questionnaire. Food sensitization was evaluated by skin-prick test. A clinical history of asthma increased the risk of wheezing [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5] and respiratory arrest (OR 6.9; 95% CI 1.4-34.2). A clinical history of chronic/relapsing gastrointestinal symptoms increased the risk of vomiting (OR 2.1; 95% CI 0.9-4.3), hypotension (OR 7.9; 95% CI 1.9-32.0), and bradycardia/cardiac arrest (OR 9.2; 95% CI 0.9-91.3). The severity of present and previous episodes was similar only in patients with mild or moderate anaphylaxis. Peanut and egg were the most frequent causes of severe anaphylaxis. A clinical history of asthma and chronic/relapsing gastrointestinal symptoms (probably linked to food allergy) may predict the development of respiratory and gastrointestinal symptoms and the severity of anaphylaxis.