Anaphylactic Reactions to Novel Foods: Case Report of a Child With Severe Crocodile Meat Allergy - Pediatrics
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Anaphylactic Reactions to Novel
Foods: Case Report of a Child With
Severe Crocodile Meat Allergy
Natalia Ballardini, MD, PhD,a,b,c Anna Nopp, PhD,d Carl Hamsten, MSc, PhD,d Mirja Vetander, MD, PhD,a,b,e
Erik Melén, MD, PhD,a,b Caroline Nilsson, MD, PhD,b,f Markus Ollert, MD, PhD,g,h Carsten Flohr, MD, PhD,i
Annette Kuehn, MD, PhD,g Marianne van Hage, MD, PhDd
Availability of “exotic” foods is steadily increasing. In this report, we abstract
describe the first case of anaphylaxis to crocodile meat. The patient was
a 13-year-old boy with severe immunoglobulin E–mediated allergy to
chicken meat. When tasting crocodile meat for the first time, he developed
an anaphylactic reaction. Cross-reactivity between chicken and crocodile
meat was suspected to have triggered this reaction. Basophil activation and
immunoglobulin E testing confirmed the boy’s allergic reaction to crocodile
aInstitute of Environmental Medicine, eCentre for
meat proteins. Molecular analysis identified a crocodile α-parvalbumin, Allergy Research, and fDepartment of Clinical Science
with extensive sequence homology to chicken α-parvalbumin, as the and Education, Södersjukhuset, Karolinska Institutet,
Stockholm, Sweden; dClinical Immunology and Allergy Unit,
main cross-reactive allergen. We conclude that crocodile meat can be a
Department of Medicine Solna, Karolinska Institutet, and
potent food allergen and patients with allergy to chicken meat should be Karolinska University Hospital, Stockholm, Sweden bSachs’
advised to avoid intake of meat from crocodile species. Both foods and Children and Youth Hospital, Södersjukhuset, Stockholm,
Sweden; cSt John’s Institute of Dermatology, King’s College
people travel around the world and accessibility to exotic foods is steadily London, London, United Kingdom; gDepartment of Infection
growing. As a result, novel allergic cross-reactivities are likely to become a and Immunity, Luxembourg Institute of Health, Esch-sur-
Alzette, Luxembourg; hDepartment of Dermatology and
challenge in the management of food allergy and, as our report illustrates, Allergy Center, Odense Research Center for Anaphylaxis,
cross-reactivity has to be considered even between foods that might not University of Southern Denmark, Odense, Denmark; and
iSt John’s Institute of Dermatology, Guy’s and St Thomas’
intuitively be perceived as related. Hospital NHS Foundation Trust and King’s College London,
London, United Kingdom
Dr Ballardini conceptualized and designed the
study, was responsible for care of the patient, and
drafted the first manuscript; Dr van Hage designed
Food allergy is an increasing PRESENTATION the study and was responsible for the initial
problem in the pediatric population immunoglobulin E (IgE) analyses, immunoblots,
and cross-inhibition experiments, and critically
and is estimated to affect 8% of A 13-year-old boy presented to the
reviewed and revised the manuscript; Drs Kuehn
children with a high negative pediatric emergency department and Ollert planned and carried out the molecular
impact on quality of life.1–3 Allergy at Sachs’ Children and Youth experiments, subsequent IgE analysis, immunoblots,
to chicken meat has been reported Hospital in Stockholm, Sweden, and cross-inhibition tests, and critically reviewed
both in children and adults and is due to an anaphylactic reaction and revised the manuscript; Dr Nopp conceptualized
and designed the study, performed basophil
estimated to be rare, but reliable to crocodile meat. He had been a
allergen threshold sensitivity analysis, and reviewed
prevalence data are missing.4–8 regular outpatient at the hospital’s and revised the manuscript; Dr Hamsten carried
Cross reactivity between chicken pediatric allergy department since 5 out the initial IgE analyses, immunoblots, and cross-
and duck, turkey, and goose has years of age when he was diagnosed inhibition experiments and critically reviewed and
been described.4 Little is known with chicken meat allergy (specific revised the manuscript; Dr Vetander performed
the literature review and reviewed and revised the
about the causative allergens for immunoglobulin E [IgE], 19 kUA/L).
manuscript; Dr Nilsson participated in patient care
chicken meat allergy. There are He was otherwise healthy and ate
no reports of allergic reactions to all foods except poultry. At 7 years
crocodile meat. Although crocodiles of age, an adrenaline autoinjector To cite: Ballardini N, Nopp A, Hamsten C, et al.
belong to the reptile group, they was prescribed after an anaphylactic Anaphylactic Reactions to Novel Foods: Case
Report of a Child With Severe Crocodile Meat
are also the closest living relatives reaction due to accidental
Allergy. Pediatrics. 2017;139(4):e20161404
of birds.9 consumption of turkey. Although strict
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PEDIATRICS Volume 139, number 4, April 2017:e20161404 CASE REPORTavoidance of chicken and turkey meat for content of DNA and protein from crocodile extract at a concentration
was recommended, he continued to chicken and turkey. In addition, the of 1 mg inhibitor/mL for immunoblot
experience anaphylactic reactions crocodile filet was used to prepare a and 200 μg inhibitor/mL for ELISA.
due to accidental consumption of protein extract.11 Briefly, the muscle Parvalbumins were detected by using
foods contaminated by chicken or tissue was grinded in liquid nitrogen an antiparvalbumin IgG antibody mix
turkey. As a consequence, he was followed by extraction in lysis buffer (Swant, Marly, Switzerland; Abcam,
reluctant to eat foods outside of (50 mM Tris-HCl, pH 8, 150 mM Cambridge, MA).
his home, which had a significant NaCl, and 1% Triton X-100). Extract
impact on his social life. More supernatants were dialyzed against Biomolecular Allergen
recently, his father, a professional phosphate-buffered saline (pH 7.2) Characterization
chef, bought and prepared crocodile before basophil activation assay and Chicken and crocodile parvalbumins
meat to create a novel meal for his specific IgE–binding analysis. For were isolated by ion exchange and
son. The boy reacted at first bite the basophil activation assay and gel filtration chromatography as
with itch in the mouth and throat, measurements of allergen-specific previously reported.7,14 Protein
facial urticaria, conjunctivitis, IgE, muscle tissue was homogenized purity of chicken and crocodile
angioedema, chest tightness, and followed by extraction in phosphate- parvalbumins was confirmed by
breathing difficulties. Intramuscular buffered saline (pH 7.4). silver-stained, two-dimensional
adrenaline and β-2 agonist inhalation SDS-PAGE.11 Crocodile parvalbumin
was administered at home by the Measurement of Allergen-Specific isoforms were additionally separated
parents. At the pediatric emergency IgE by isoelectric focusing (Offgel,
department, he presented with IgE antibodies against chicken Agilent, Diegem, Belgium) before
facial urticaria, angioedema around (f83), turkey (f284), and crocodile an intact mass measurement by
the eyes, bilateral redness of the meat proteins (5 μg of biotinylated mass spectrometry (MS) analysis.
sclera, and heavy breathing but no crocodile extract coupled to Parvalbumins were trypsinized for
bronchoconstriction. After 4 hours of Streptavidin ImmunoCAP) and total MS peptide mass fingerprint analysis,11
observation, he was free of symptoms IgE were measured by ImmunoCAP which revealed the complete
and discharged. (Phadia AB/Thermo Fisher Scientific, sequence of 1 crocodile parvalbumin
Uppsala, Sweden). isoform. Unidentified peptides of
Reviewing the literature, we found
the other isoform were sequenced
no reports of allergic reactions Basophil Activation Assay de novo on a second MALDI TOF/
to crocodile. We had previously
Basophil allergen threshold TOF instrument (AB Sciex 5800,
identified α-parvalbumin as a
sensitivity (CD-sens) was performed Framingham, MA), identifying 92%
relevant chicken meat allergen7 and
as previously described.12,13 Briefly, of the protein sequence. Protein
because another report showed that
cells were stimulated with increasing structures were calculated using
parvalbumin is expressed in the tail
concentrations of crocodile or Modeller 9v2 software,15,16 and
muscle of Alligator mississippiensis,10
chicken extracts (0.5–500 ng chicken parvalbumin (P43305; 2KYF)
we hypothesized that the reaction
protein/mL) or negative controls was used to establish the surface
to crocodile was due to IgE cross-
(peanut, birch, casein) and then model.
reactivity between α-parvalbumins in
chicken and crocodile meat. analyzed by flow cytometry.
Allergen Analysis by IgE Immunoblot RESULTS
and Enzyme-Linked Immunosorbent No contamination of the crocodile
METHODS Assay meat by chicken or turkey residues
Written informed consent was Chicken and crocodile meat was demonstrated. The boy’s
obtained from the patient and his extracts were separated by serum immunoglobulin E (sIgE)
parents. SDS-PAGE (sodium dodecyl levels were 40 kUA/L to chicken,
sulfate polyacrylamide gel 14 kUA/L to turkey, and 6 kUA/L
Allergen Preparation
electrophoresis).11 Patient serum to crocodile meat extract, whereas
Crocodile filet was purchased was diluted 5× in 3% bovine total serum-IgE was 190 kU/L.
from the same store that sold the serum albumin (Sigma-Alderich, CD-sens was clearly positive to both
crocodile meat that caused the Bornem, Belgium) for immunoblot crocodile and chicken meat extracts
allergic reaction. It was analyzed and 5–10× for IgE enzyme-linked (Fig 1A). In immunoblot analysis,
by the certified laboratory of the immunosorbent assay (ELISA).11 For the patient’s IgE bound to chicken
Swedish National Food Agency IgE cross-inhibition, patient serum (14 kDa, 19/22 kDa, 30 kDa) and
(Livsmedelsverket; Uppsala, Sweden) was preincubated with chicken or crocodile meat proteins (18–50 kDa)
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e2 BALLARDINI et al(Fig 1B). IgE-binding to chicken phylogenetic relationship. In another allergens was not inhibited by recent publication, we reported on preincubation with crocodile extract, 36 patients (including 17 children whereas IgE-binding was inhibited
ABBREVIATIONS
CD-sens: basophil allergen
threshold sensitivity
ELISA: enzyme-linked immuno-
sorbent assay
IgE: immunoglobulin E
MS: mass spectrometry
sIgE: serum immunoglobulin E
FIGURE 2
Comparison of chicken and crocodile α-parvalbumin. A, Three-dimensional model of chicken parvalbumin, protein surface coloring by identity to crocodile
parvalbumin. Red, identical residues; gray, variable residues. B, Amino acid sequence alignment of chicken and crocodile parvalbumins as allergens
involved in the clinical cross-reaction to both meats.
Agency (Uppsala, Sweden) for and turkey DNA by real time PCR. We also thank Dr K. Arumugam
analysis of crocodile meat for (1) We thank D. Revets (Luxembourg (Luxembourg Institute of Health) for
detection of poultry protein by use Institute of Health) for excellent establishing the structural model of
of ELISA and (2) detection of chicken technical support with MS analysis. chicken and crocodile parvalbumin.
and reviewed and revised the manuscript; Drs Melén and Flohr provided intellectual input and reviewed and revised the manuscript; and all authors approved
the final manuscript as submitted.
DOI: 10.1542/peds.2016-1404
Accepted for publication Sep 22, 2016
Address correspondence to Natalia Ballardini, MD, PhD, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, SE-171 77 Stockholm, Sweden.
E-mail: natalia.ballardini@ki.se
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2017 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: This work was supported by research grants from the Swedish Research Council, the Stockholm County Council, the Swedish Asthma and Allergy
Association’s Research Foundation, the Swedish Cancer and Allergy Foundation, the Hesselman Foundation, Karolinska Institutet, the Karin and Sten Mörtstedt
Initiative on Anaphylaxis, and the Ministry of Higher Education and Research in Luxembourg.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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PEDIATRICS Volume 139, number 4, April 2017 e5Anaphylactic Reactions to Novel Foods: Case Report of a Child With Severe
Crocodile Meat Allergy
Natalia Ballardini, Anna Nopp, Carl Hamsten, Mirja Vetander, Erik Melén, Caroline
Nilsson, Markus Ollert, Carsten Flohr, Annette Kuehn and Marianne van Hage
Pediatrics originally published online March 8, 2017;
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/early/2017/03/06/peds.2
016-1404
References This article cites 18 articles, 2 of which you can access for free at:
http://pediatrics.aappublications.org/content/early/2017/03/06/peds.2
016-1404#BIBL
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Downloaded from www.aappublications.org/news by guest on January 22, 2020Anaphylactic Reactions to Novel Foods: Case Report of a Child With Severe
Crocodile Meat Allergy
Natalia Ballardini, Anna Nopp, Carl Hamsten, Mirja Vetander, Erik Melén, Caroline
Nilsson, Markus Ollert, Carsten Flohr, Annette Kuehn and Marianne van Hage
Pediatrics originally published online March 8, 2017;
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/early/2017/03/06/peds.2016-1404
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