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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 from2 allergy
clinics inColombo, 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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(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
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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 Table1 [1–3].
Case records were analysed, including clinical history
and results of skin prick testing and invitro 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 (Table2).
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
ω−5-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
ω−5-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 19years).
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 16years had a male: female ratio of
3:5, while for those above 16years 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 fordiagnosis ofFDEIA [1–3]
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 ofthe patients
No Age (years) Sex Food Exertion Latent period Clinical Skin prick test
forwheat (Posi-
tive—wheal >3mm
diameter overnega-
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
forwheat (Posi-
tive—wheal >3mm
diameter overnega-
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, 5min 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 5min to 4h after ingesting a
meal (mean 51.6min, median 30min). Fourteen patients
(73.6%) reported symptoms within 30min 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 5min 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 2km), 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 9–16years, 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 1h 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 1.5km); 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 invitro 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 ω−5 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 3day 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 invitro 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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