Egg-allergic patients can be safely vaccinated against influenza.
- [Show abstract] [Hide abstract]
ABSTRACT: The most serious form of type I or IgE-mediated hypersensitivity reaction is anaphylaxis. A standardized case definition of anaphylaxis as an adverse event after immunization has been developed. Such reactions to vaccines, including influenza vaccine, are rare but potentially life-threatening. Until recently, all influenza vaccines were manufactured in eggs. Residual egg protein in the vaccines was thought to pose a risk to egg-allergic vaccine recipients. However, a large number of recent studies have demonstrated that egg-allergic recipients are no more likely than those without egg allergy to suffer such reactions. Published guidelines have been updated to recommend that patients with egg allergy receive annual influenza vaccination. Any patient who has an anaphylactic reaction to influenza vaccine should be carefully evaluated by an allergist for guidance on subsequent immunization.Expert Review of Vaccines 06/2014; · 4.22 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Excipients are substances in pharmaceuticals other than the active ingredients. Some excipients are foods or substances derived from foods, raising the possibility that these substances would pose a hazard to patients with food allergy. This review describes which food-derived substances are used as pharmaceutical excipients in which medications and reviews published data regarding the safety of the administration of these medications to recipients with food allergy. Such reactions are rare, usually because the amount of food protein is not present in a large enough quantity to elicit a reaction. When a food protein appears as an unintentional contaminant, the amount, if any, that is present might be variable and might elicit reactions only from some lots of medication or only in some patients. In most circumstances these medications should not be routinely withheld from patients who have particular food allergies because most will tolerate the medications uneventfully. However, if a particular patient has had an apparent allergic reaction to the medication, potential allergy to the food component should be investigated.Journal of Allergy and Clinical Immunology 06/2014; 133(6):1509–1518. · 11.25 Impact Factor
Article: Allergic reactions to vaccines[Show abstract] [Hide abstract]
ABSTRACT: Anaphylactic reactions to vaccines are rare but do occur, and have been reported for nearly every vaccine. And while the reaction rate per each dose of vaccine is low, this is a common clinical question due in large part to the enormous numbers of vaccines administered. Reactions are most often due to vaccine constituents rather than the microbial components of the vaccine, but in many instances, the specific ingredient triggering the reaction cannot be definitively identified. Evaluation of patients with suspected vaccine reactions should begin by determining whether the symptoms and timing of the reaction were consistent with a true allergic reaction, followed by an assessment to determine whether the patient needs further doses of the vaccine in question, or similar vaccines, in the future. Skin and serologic testing to vaccines and vaccine constituents can then be performed to further assess the potential cause of the reaction and to develop a plan for future immunizations. Specific guidelines for the administration of influenza vaccines to egg allergic patients have been revised to allow virtually all patients to receive this vaccine in a straightforward manner.Pediatric Allergy and Immunology 09/2013; 24(6). · 3.86 Impact Factor
that additional factors are required. Our study also confirmed the
association of FLG mutations and early-onset infantile eczema,
which is in line with previous work.6
Our ability to interrogate the role of sensitization in the
relationship between FLG mutations and food allergy in a large
population-based, age-matched, challenge-proved food allergy
cohort is a major and novel strength of this work. There is some
potential participation bias among negative control subjects
(higher immediate family history of allergic diseases compared
with the general population); however, such a bias would be
more likely to create a false-negative than a false-positive
In conclusion, FLG mutations do not increase the risk of
food allergy over and above that of food sensitization among
1-year-old infants. These results confirm the biological plausi-
bility that decreased skin barrier function increases the risk of
food sensitization in early life, but other as yet undetermined
factors are important in the conversion from food sensitization
We acknowledge the contribution of all the parents and children who
participated in the study. We thank Dr Benjamin Ong for assistance with
Sequenom assay design and the Royal Children’s Hospital Outpatient
Pathology staff for blood collection. We thank ALK-Abell? o S.A., Madrid,
Spain, for supplying the SPT reagents and the HealthNuts safety committee:
Associate Professor Noel Cranswick (Australian Paediatric Pharmacology
Research Unit/Murdoch Childrens Research Institute, Melbourne, Australia),
Dr Jo Smart (Department of Allergy and Immunology, Royal Children’s
Hospital, Melbourne, Australia), and Associate Professor Jo Douglass (Head
of Allergy, Alfred Hospital, Melbourne, Australia).
Hern-Tze Tina Tan, BBiomedSca,b
Justine A. Ellis, PhDa,c
Jennifer J. Koplin, PhDa
Melanie C. Matheson, PhDd
Lyle C. Gurrin, PhDa,d
Adrian J. Lowe, PhDa,d
Pamela E. Martin, BBiomedSc (Hons)a,b
Thanh D. Dang, BBiomedSc (Hons)a,b
Melissa Wake, MD, FRACP, MBBSa,b,e
Mimi L. K. Tang, MBBS, FRACP, FRCPA, FAAAAI, PhDa,b,f
Anne-Louise Ponsonby, BMedSci, MBBS, PhD, FAFPHM, FRACPa,b
Shyamali C. Dharmage, MBBS, MSc, MD, PhDa,d
Katrina J. Allen, MBBS, FRACP, PhDa,b,f
for the HealthNuts Study Investigators*
Fromathe Murdoch Childrens Research Institute,ethe Centre for Community Child
Health, andfthe Department of Allergy and Immunology, Royal Children’s Hospital,
and the Departments ofbPaediatrics andcPhysiology anddthe Centre for Molecular,
Environmental, Genetic and Analytic Epidemiology, University of Melbourne,
Melbourne, Australia. E-mail: firstname.lastname@example.org.
Supported by the Australian National Health & Medical Research Council (NHMRC),
the Ilhan Food Allergy Foundation, AnaphylaxiStop, and the Victorian Government’s
Operational Infrastructure Support Program. K.J.A. is a Viertel Senior Medical Re-
search Fellow, J.A.E. and J.J.K. are supported by an NHMRC Capacity Building
Grant in Population Health, and M.C.M., L.C.G., A.J.L., M.W., A.-L.P., and S.C.D.
hold NHMRC Awards. H.-T.T.T. is a recipient of a Malaysian Government ASTS
Scholarship, and T.D.D. is an Australian Postgraduate Award scholar.
Disclosure of potential conflict of interest: A. J. Lowe, M. Wake, and A.-L. Ponsonby
have been supported by one or more grants from the National Health & Medical Re-
search Council of Australia. M. L. K. Tang receives research support from Phadia. K.
J. Allen receives speaker’s fees from Nutricia/Danone, Pfizer, Wyeth, and Abbott. The
rest of the authors declare that they have no relevant conflicts of interest.
*The HealthNuts investigators include Nicholas Osborne, David Hill, Leone Thiele,
Helen Czech, Deborah Anderson, Marnie Robinson, Dean Tey, Jeeva Sanjeevan,
John Zurzolo, Lucy Miles, Kate Birch, Kelley Mancer, Marg Sutherland, and Marjo-
lein Slaa. Ethics approval was obtained from the Office for Children HREC (reference
no. CDF/07/492), the Department of Human Services HREC (reference no. 10/07),
and the Royal Children’s Hospital HREC (reference no. 27047).
1. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and
allergic diseases. N Engl J Med 2011;365:1315-27.
2. Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao Y, Liao H, et al. Loss-of-function
variants in the filaggrin gene are a significant risk factor for peanut allergy. J Allergy
Clin Immunol 2011;127:661-7.
3. Osborne NJ, Koplin JJ, Martin PE, Gurrin LC, Thiele L, Tang ML, et al. The Health-
Nuts population-based study of paediatric food allergy: validity, safety and accept-
ability. Clin Exp Allergy 2010;40:1516-22.
4. Sporik R, Hill DJ, Hosking CS. Specificity of allergen skin testing in predicting pos-
itive open food challenges to milk, egg and peanut in children. Clin Exp Allergy
5. Koplin JJ, Tang ML, Martin PE, Osborne NJ, Lowe AJ, Ponsonby AL, et al. Prede-
termined challenge eligibility and cessation criteria for oral food challenges in the
HealthNuts population-based study of infants. J Allergy Clin Immunol 2012;129:
6. Flohr C, England K, Radulovic S, McLean WH, Campbel LE, Barker J, et al. Fil-
aggrin loss-of-function mutations are associated with early-onset eczema, eczema
severity and transepidermal water loss at 3 months of age. Br J Dermatol 2010;
7. Lack G, Fox D, Northstone K, Golding J. Avon Longitudinal Study of Parents and
Children Study Team. Factors associated with the development of peanut allergy in
childhood. N Engl J Med 2003;348:977-85.
Available online September 7, 2012.
Egg-allergic patients can be safely vaccinated
To the Editor:
As the influenza vaccine contains residual egg protein, its
administration to egg-allergic patients had always raised theoret-
ical concerns about anaphylaxis.1We report our experience with
seasonal influenza vaccine administered during 5 seasons (2007-
2011) and summarize the current published clinical experience
with these patients.
We conducted a prospective cohort study recruiting and
vaccinating egg-allergic patients in 2010-2011 and 2011-2012
in 5 Canadian hospitals (Montreal, Quebec City, Sherbrooke,
Edmonton, and Vancouver). Egg allergy was defined as a history
of at least 1 sign or symptom of allergy (cutaneous, ocular, respi-
ratory, gastrointestinal, or cardiovascular symptoms) occurring
within 60 minutes of egg ingestion, and the confirmation of per-
sistent sensitization to egg (within 6 months of vaccination)
shown by a skin prick test response to egg at least 3 mm larger
than that of the saline control within 10 to 15 minutes, or an
egg-specific IgE level of 0.35 kU/L or more (UniCAP, Pharma-
cia). In 2010-2011, we recruited all patients with allergy to egg,
whereas in 2011-2012, the recruitment focused on patients with
severe allergic reaction defined as the occurrence of anaphylaxis
or cardiorespiratory symptoms upon egg ingestion. In both years,
patients (or their parents/legal guardian if minor patients) had to
provide written consent for the collection of data on adverse
events occurring within 24 hours following vaccination. We
also performed a retrospective cohort study of all egg-allergic
patients referred for administration of seasonal influenza at the
Sainte-Justine Hospital in Montreal, during the 2007-2008,
2008-2009, and 2009-2010 vaccination seasons. The definition
of egg allergy and the threshold for skin prick test were the
same as previously described, but the method of detection of
J ALLERGY CLIN IMMUNOL
VOLUME 130, NUMBER 5
LETTERS TO THE EDITOR 1213
TABLE I. Published studies with 25 or more egg-allergic patients vaccinated against influenza
No. of patientsNo. of doses
Bierman CW, Shapiro GG, Pierson WE, Taylor JW, Foy HM, Fox JP, et al. Safety of influenza vaccination
in allergic children. J Infect Dis 1977;136:S652-55.
James JM, Zeiger RS, Lester MR, Fasano MB, Gern JE, Mansfield LE, et al. Safe administration of influenza
vaccine to patients with egg allergy. J Pediatr 1998;133:624-8.
Zeiger RS. Current issues with influenza vaccination in egg allergy. J Allerg Clin Immunol 2002;110:834-40.
Dorsey MJ, Song L, Geha T, Timmons A, Oettgen H, Schneider L. Influenza vaccine in 55 patients with egg
allergy. J Allergy Clin Immunol 2005;115:S250.
Hotte SL, Lejtenyi C, Primeau MN. A 6 years experience with influenza vaccination in egg allergic patients.
J Allergy Clin Immunol 2008;121:S239.
Esposito S, Gasparini C, Martelli A, Zenga A, Tremolati E, Varin E, et al. Safe administration of an inactivated
virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy. Vaccine 2008;26:4664-8.
Park AY, Pien GC, Stinson R, Brown-Whitehorn, Spergel JM. Administration of influenza vaccine to patients
with egg allergy. J Allergy Clin Immunol 2008;121:S240.
Saltzman RW, Park AY, Pien GC, Stinson R, Spergel JM. Administration of influenza vaccine to pediatric
patients with egg allergy. J Allergy Clin Immunol 2009;123:S175.
Thanik ES, Cox AL, Sampson HA. Administration of a low egg-containing influenza vaccine [Fluarix] in an
egg-allergic pediatric population. J Allergy Clin Immunol 2010;125:AB25.
Chung EY, Huang L, Schneider L. Safety of influenza vaccine administration in egg-allergic patients. Pediatrics
Gagnon R, Primeau MN, Des Roches A, Lemire C, Kagan R, Carr S, et al. Safe vaccination of patients with
egg allergy with an adjuvanted pandemic H1N1 vaccine. J Allergy Clin Immunol 2010;126:317-23.
Greenhawt MJ, Chernin AS, Howe L, Li JT, Sanders G. The safety of the H1N1 influenza A vaccine in egg
allergic individuals. Ann Allergy Asthma Immunol 2010;105:387-93.
Leo SH, Dean J, Chan ES. Safety of H1N1 and seasonal influenza vaccines in egg allergic patients in British
Columbia. Allerg Asthma Clin Immunol 2010;6:P4.
Pien GC, LeBenger KS, Carotenuto DR, Difilippi M, Scolpino D, Simmons JM, et al. Coordination of
multidisciplinary resources for vaccination of egg-allergic individuals during an H1N1 (novel) influenza
pandemic. Allergy Asthma Proc 2010;31:507-10.
Siret-Alatrista A, Bouali F, Demoly M, Bousquet PJ, Demoly P. The 2009-2010 H1N1 vaccination campaign
for patients with egg allergy in a region of France. Allergy 2011;66:298-9.
Boden SR, LaBelle VS, Sedlak DA, Kim EH, Vickery BP, Burks AW. Safe administration of flu vaccine in
egg-allergic patients. J Allergy Clin Immunol 2011;127:AB114.
Paschall VL, Siles RI, Bhatti H, Nolder PJ, Melton AL. Do egg-specific IgE levels predict reactions to
seasonal influenza or H1N1 vaccination? J Allergy Clin Immunol 2011;127:AB182.
Owens G, MacGinnitie A. Higher-ovalbumin-content influenza vaccines are well tolerated in children with
egg allergy. J Allergy Clin Immunol 2011;127:264-5.
Howe LE, Conlon AS, Greenhawt MJ, Sanders GM. Safe administration of seasonal influenza vaccine to
children with egg allergy of all severities. Ann Allergy Asthma Immunol 2011;106:446-7.
Webb L, Petersen M, Boden S, LaBelle V, Bird JA, Howell D, et al. Single-dose influenza vaccination of
patients with egg allergy in a multicenter study. J Allergy Clin Immunol 2011;128:218-9.
Pitt T, Kalicinsky C, Warrington R, Cisneros N. Assessment of epicutaneous testing of a monovalent
influenza A (H1N1) 2009 vaccine in egg allergic patients. Allergy Asthma Clin Immunol 2011;7:3.
Schuler JE, King WJ, Dayneka NL, Rastelli L, Marquis E, Chad Z, et al. Administration of the adjuvanted
pH1N1 vaccine in egg-allergic children at high risk for influenza A/H1N1 disease.
Can J Pub Health 2011;102:196-9.
Forsdahl BA. Reactions of Norwegian children with severe egg allergy to an egg-containing influenza
A (H1N1) vaccine: a retrospective audit. BMJ Open 2012;2:e000186.
Fung I, Spergel JM. Administration of influenza vaccine to pediatric patients with egg-induced anaphylaxis.
J Allergy Clin Immunol 2012;129:1157-9.
Khan FS, Virant FS, Furukawa CT, Altman LC, Williams PV, Kennedy MS, et al. Influenza vaccine
administration in egg allergic children. J Allerg Clin Immunol 2012;129:AB70.
Wainwaring Upton JE, Hummel DB, Kasprzak A, Atkinson AR. No systemic reactions to influenza vaccination in
egg-sensitized tertiary care pediatric patients. Allerg Asthma Clin Immunol 2012;8:2.
Des Roches A, Paradis L, Gagnon R, Lemire C, Begin P, Carr S, et al. Egg-allergic patients can be
safely vaccinated against influenza. J Allergy Clin Immunol 2012 (current study).
83 27 8327
4411 44 11
53 NR 53
59 NR 59
62 NR 62
80 19 80 19
5656 119 119
643 NR 643
7717 77 17
NR, Not reported.
*Number of doses, as number of patients not reported.
J ALLERGY CLIN IMMUNOL
1214 LETTERS TO THE EDITOR
specific IgE was the Immulite immunoassay system (Siemens,
For both cohorts, patients were examined immediately before
vaccination, remained under observation for 60 minutes post-
vaccination, and were then reexamined for any sign of allergic
reaction. The vaccine used during all 5 seasons was the
split-virion trivalent inactivated influenza vaccine Fluviral
manufactured by GSK (Quebec City, Quebec, Canada). The
ovalbumin content for the lots used was provided by the
manufacturer: 0.09 mg/mL in 2007-2008, 0.03 mg/mL in 2008-
2009, 0.31 mg/mL in 2009-2010, up to 0.2 mg/mL in 2010-2011,
and up to 0.06 mg/mL for 2011-2012. The primary outcome was
the occurrence of anaphylaxis according to the Brighton Col-
laboration definition.2The study was approved by the ethics
boards of all participating hospitals.
Over 5 influenza seasons, 457 doses of trivalent inactivated
seasonal influenza vaccines were administered to 367 patients
among whom 132 (153 doses) had a history of severe allergy to
egg (see Table E1 in this article’s Online Repository at www.
jacionline.org). Four patients reported mild allergic-like symp-
toms after previous influenzavaccination (1urticaria, 2 vomiting,
and 1 eczema), but none experienced an adverse event when
gic-like symptoms in the 24 hours following vaccination, none of
the 367 patients developed anaphylaxis.
We then did a literature review and retrieved articles in English
or French in which at least 25 egg-allergic patients had been
vaccinated. PubMed was searched with the following MESH:
(influenza AND (vaccination or vaccine)) AND (egg AND
(allergy OR allergic)). Further studies or conference abstracts
were identified by citations in retrieved articles and by consulta-
tion with experts. Among the 87 articles retrieved from PubMed,
16 were studies including the vaccination of 25 or more egg-
26 studies and the current study have enrolled 4172 patients
including 513 who were identified as patients with a history of
severe reactions (Table I). These patients received a total of 4729
4729 doses of vaccine, the 95% Clopper-Pearson exact CI of the
risk of anaphylaxis ranges from 0% to 0.08% (or 0 to 1 of 1250
doses).3For the 597 doses administered to the 513 patients with
a history of severe allergic reaction to egg, the exact 95% CI of
the risk of anaphylaxis ranges from 0% to 0.62% (or 0 to 1 of
161 doses). Their risk of anaphylaxis is in fact smaller as many
studies in Table I had patients with severe allergy but simply did
not report the information regarding their number.
The clinical experience with influenza vaccination in egg-
allergic patients in our cohorts and in other studies displayed in
Table I has limitations. The amount of ovalbumin varied in the
different influenza vaccines used and was sometimes unknown
or low. Patients rarely had a recent positive food challenge con-
firming the persistence of egg allergy. Some studies included
young children with atopic conditions (eg, atopic dermatitis)
who had never eaten eggs but had a positive skin test result
and high levels of egg-specific IgE. These sensitized patients
are typically managed with recommendations of food avoidance
as if they were allergic, although the diagnosis of allergy for
these patients may be inaccurate. Despite these limitations, the
patients in Table I are representative of patients managed as
egg-allergic and the large number vaccinated with no ensuing
anaphylaxis constitutes a strong scientific basis for new
Egg allergy is the second most frequent food allergy and
affects 1% to 2% of young children.4While most patients will
eventually develop tolerance to eggs, it will still be present in
more than 60% by 6 years of age.5In the United States, this
grossly corresponds to 150,000 to 250,000 influenza vaccine–el-
igible preschoolers. Many of these patients have not benefited
from the influenza vaccine in the past because of the fear of an-
aphylaxis or the difficulty of accessing an allergist as is often
recommended.1Paradoxically, given their young age and the
high rate of concurrent asthma, these patients have a higher
risk of complications from influenza and are among those
most likely to benefit from this vaccine.6The evidence gathered
over the past 15 years is overwhelmingly reassuring that this
risk is minimal. The published number of egg-allergic patients
safely vaccinated against influenza is nearly 4 times as large
as the number that ended the precautions regarding measles,
mumps and rubella (MMR) vaccine (4172 vs 1227).7There
will always be a very small risk of anaphylaxis associated
with influenza or any other vaccination, but there is now robust
evidence that egg-allergic patients, even those with severe al-
lergy, can be safely vaccinated against influenza. The risk of an-
aphylaxis appears sufficiently low for patients with egg allergy
to be vaccinated like all other individuals, without requiring ad-
ministration by an allergist.
We are thankful to collaborators from the different sites—H^ opital Sainte-
Justine(M.Blaqui? ereandA.Kukhta),CHUQ-CHUL(J.H? ebert,P.M.B? edard,
A. Lavoie, J. P. Drolet, and N. Verreault), CHUS (M. Plante, D. Leduc, A.
Farrand, and C. Nault), Stollery Children’s Hospital (T. Vander Leek and P.
Lidman), and BC Children’s Hospital (J. Dean)—and to T. Koerner from
Anne Des Roches, MD, FRCPC, FAAAAIa
Louis Paradis, MD, FRCPC, FAAAAIa,b
Remi Gagnon, MD, FRCPCc
Chantal Lemire, MD, FRCPCd
Philippe B? egin, MD, FRCPC, MSca
Stuart Carr, MD, FRCPC, FAAAAIe
Edmond S. Chan, MD, FRCPC, FAAAAIf
Jean Paradis, MD, FRCPCb
Lyne Frenette, MD, FRCPc
Manale Ouakki, MScg
M? elanie Beno^ ıt, BScc
Gaston De Serres, MD, PhDc,g
on behalf of the PCIRN (Public Health Agency of Canada/Canadian
Institutes of Health Research Influenza Research Network)
FromaH^ opital Sainte-Justine andbCentre hospitalier universitaire de Montr? eal, Univer-
sity of Montr? eal, Montr? eal, Qu? ebec, Canada;
Qu? ebec (CHUQ), Laval University, Qu? ebec City, Qu? ebec, Canada;dCentre hospital-
ier universitaire de Sherbrooke (CHUS), University of Sherbrooke, Sherbrooke,
Qu? ebec, Canada;eStollery Children’s Hospital, University of Alberta, Edmonton, Al-
berta, Canada;fBC Children’s Hospital, University of British Columbia, Vancouver,
British Columbia, Canada; and
Qu? ebec, Canada. E-mail: email@example.com.
This study was funded by the PCIRN (Public Health Agency of Canada/Canadian Insti-
tutes of Health Research Influenza Research Network).
Disclosure of potential conflict ofinterest:P.B? egin has received one or moregrants from
or has one or more grants pending with the Canadian Allergy and Immunology Foun-
dation and AllerGen NCE. M. Beno^ ıt was employed by and owns stock/stock options
in Janssen-Ortho and Johnson & Johnson. S. Carr has been supported by one or more
grants from CIHR. E. S. Chan has been supported by one or moregrants from the Pub-
lic Health Agency of Canada. G. De Serres has been provided with medicines by
GlaxoSmithKline and has received one or more grants from Sanofi and
GlaxoSmithKline. C. Lemire has received one or more payments for lecturing from
cCentre hospitalier universitaire de
gInstitut national de sant? e publique du Qu? ebec,
J ALLERGY CLIN IMMUNOL
VOLUME 130, NUMBER 5
LETTERS TO THE EDITOR 1215
or is on the speakers’ bureau for Abbott, Merck, and Nestl? e. The rest of the authors
declare that they have no relevant conflicts of interest.
1. Centers for Disease Control and Prevention. Prevention and control of influenza with
vaccines: recommendations of the Advisory Committee on Immunization Practices
(ACIP), 2011. MMWR Morb Mortal Wkly Rep 2011;60:1128-32.
2. Ruggeberg JU, Gold MS, Bayas JM, Blum MD, Bonhoeffer J, Friedlander S, et al.
Anaphylaxis: case definition and guidelines for data collection, analysis, and presen-
tation of immunization safety data. Vaccine 2007;25:5675-84.
3. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the
case of the binomial. Biometrika 1934;26:404-13.
4. Eggesbo M, Botten G, Halvorsen R, Magnus P. The prevalence of allergy to egg: a
population-based study in young children. Allergy 2001;56:403-11.
5. Savage JH, Matsui EC, Skripak JM, Wood RA. The natural history of egg allergy.
J Allergy Clin Immunol 2007;120:1413-7.
6. Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, et al.
Influenza and the rates of hospitalization for respiratory disease among infants
and young children. N Engl J Med 2000;342:232-9.
7. James JM, Burks AW, Roberson PK, Sampson HA. Safe administration of the mea-
sles vaccine to children allergic to eggs. N Engl J Med 1995;332:1262-6.
Available online September 27, 2012.
Obesity is not a risk factor for repeat epineph-
rine use in the treatment of anaphylaxis
To the Editor:
forms of anaphylaxis.1,2Approximately 10% to 20% of the pa-
tients treated with epinephrine for anaphylaxis receive a second
dose,3-6but the risk factors associated with repeat epinephrine
use remain poorly defined. Previous studies have suggested that
epinephrine administration with autoinjectors may be influenced
by a patient’s body habitus.7Therefore, we sought to determine
whether obesity increases the risk for requiring 21 epinephrine
doses among patients who present to the emergency department
(ED) with anaphylaxis due to food allergy or stinging insect
We performed a chart review at 4 New England teaching
hospitals: Brigham and Women’s Hospital (January 1, 2001, to
December 31, 2006), Children’s Hospital Boston (January 1,
2001, to December 31, 2006), Hasbro Children’s Hospital (Jan-
uary 1, 2004, to December 31, 2009), and Massachusetts General
Hospital (January 1, 2001, to December 31, 2006). We identified
hypersensitivity by using relevant International Classification of
Diseases, Clinical Modification Codes, Ninth Revision,8includ-
ing 558.3 (allergic gastroenteritis), 693.1 (dermatitis due to
food), 708.0 to 708.9 (urticaria), 989.5 (toxic effect due to
venom), 995.0 (other anaphylactic shock), 995.1 (angioneurotic
edema), 995.3 (allergy, unspecified), 995.60 (anaphylactic shock
due to unspecified food), 995.61 to 995.69 (anaphylactic shock
due to a specified food), and 995.7 (other adverse food reactions,
not elsewhere classified). Cases were confirmed by allergist re-
view. We focused on the total number of epinephrine treatments
the ED visit) and the patient’s anthropomorphic data. Weight and
height measurements documented at the ED visit were preferen-
tially used. If measurements had been taken more than 3 months
from the ED visit, height/weight at the time of the ED visit was
estimated by using Centers for Disease Control and Prevention
growth charts in children (<18 years) and estimates of average
weight gain in US adults. Calculated body mass indexes were
classified according to Centers for Disease Control and Preven-
tion growth indicators as underweight, healthy, overweight, or
obese. Medians with interquartile ranges were presented for con-
tinuous variables that were not normally distributed. Compari-
sons between groups were evaluated by using Kruskal-Wallis
rank sum tests for continuous variables and the x2test or the
Fisher exact test for categorical variables, as appropriate. Multi-
variable models were performed using logistic regression. A 2-
sided P value of less than .05 was considered statistically
The study population comprised 321 ED patients (261 children
and 60 adults) who received epinephrine for anaphylaxis and had
data for both height and weight; 267 (83%) received 1 dose of
epinephrine, while 54 (17%) received 21 doses. There was no
difference intheneed foradditional dosesofepinephrine between
children and adults (P 5.94) and no difference among the 4 insti-
tutions (P 5 .60). Demographic data, reaction history, and ED
treatments are summarized in Table I. Patients had a median age
of 8.5 (intraquartile range 3.0-16.4) years, and 47% were males.
When comparing patients who received 1 and 21 doses of epi-
nephrine, there was no difference in the inciting allergen, organ
receiving 21 doses of epinephrine were more likely to receive
b-agonists, there was no significant difference in other adjunctive
medications, including corticosteroids (85% vs 79%; P 5.38).
weight, 57 (18%) overweight, and 69 (22%) obese. The distribu-
tion of body mass index categories was similar in those receiving
1 versus 21 doses (P 5.83). There was no difference when sep-
arately examining these distributions among children (P 5 .92)
and adults (P 5 .81). There was also no significant association
when comparing categories of underweight/healthy versus over-
weight/obese (data not shown). Finally, when adjusting for age
and sex, there remained no significant association between
obesity (vs nonobesity) and receiving 21 doses (odds ratio
1.22; 95% CI 0.77-1.93; P 5.40).
Anaphylaxis is a potentially life-threatening medical emer-
gency that is frequently incited by exposure to foods or stinging
insects.1The primary treatment for anaphylaxis is the prompt ad-
ministration of epinephrine. Current practice guidelines recom-
mend that all patients at risk for anaphylaxis receive a
prescription for an epinephrine autoinjector and education on
its proper use.1,2Furthermore, on the basis of recently published
data that 10% to 20% of the patients require repeat dosing,3-6ex-
perts now recommend that patients at risk for anaphylaxis always
carry 2 doses.2Our current analysis—based on a partially over-
lapping population of ED patients who were included in our pre-
vious studies5,6—is consistent with the reported percentages of
anaphylaxis patients who require repeat doses of epinephrine.
Repeat dosing could be a result of biphasic reactions or
inadequate treatment response. In prior work,5we reported that
most patients received the second dose within 1 hour of the first
dose, suggesting that inadequate treatment response was the
more likely explanation. Lack of response to epinephrine could
be a result of failure to administer it in a timely manner or a rapid
progression of the anaphylactic event. Other studies have sup-
treatments, which may be a reflection of increased reaction sever-
ity.4,6In the current study, all patients had reactions that met crite-
ria for anaphylaxis and organ system involvement was similar
among patients who received 1 versus 21 doses of epinephrine.
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1216 LETTERS TO THE EDITOR
TABLE E1. Characteristics of egg-allergic patients vaccinated against seasonal influenza between 2007 and 2011
All patients Patients with severe allergy
Total (N 5 367) Retrospective
Total (N 5 132)
(n 5 137)
(n 5 187)
(n 5 43)
(n 5 31)
(n 5 58)
(n 5 43)
Skin prick test to egg
> _3 mm
> _10 mm
Egg IgE (kUA/L)*
Tolerate baked goods?
Naive to flu vaccine
2 doses (10% 1 90%)
Allergic symptoms < _24 h
vaccination (all were mild)
87 (63) 98 (52) 28 (65)213 (58)23 (74) 29 (50)28 (65)80 (61)
0 7 (12)
Significant differences with P values <.05 between severe and nonsevere egg-allergic patients are indicated in bold characters.
*Measured with UniCAP for 2010-2011 and 2011-2012 and with Immulite for 2007-2010.
?There were 114 patients (including 36 severe cases) who had challenge with a baked good and tolerated it well. While the tolerance to baked goods in patients with severe allergy
may suggest milder severity, this does not rule out the risk of severe reaction to uncooked egg proteins.
?Some patients had more than 1 dose over several seasons. Percentage calculated on the total number of doses administered.
J ALLERGY CLIN IMMUNOL
1216.e1 LETTERS TO THE EDITOR