Separating Fact from Fiction in the Diagnosis and Management of Food Allergy

Abstract

Food allergy is one of the most common chronic conditions of childhood, impacting up to 10% of children.1Soller L. Ben-Shoshan M. Harrington D.W. Fragapane J. Joseph L. St Pierre Y. et al.Overall prevalence of self-reported food allergy in Canada.J Allergy Clin Immunol. 2012; 130: 986-988Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 2Clarke A.E. Elliott S. Pierre Y.S. Soller L. La Vieille S. Ben-Shoshan M. Temporal trends in prevalence of food allergy in Canada.J Allergy Clin Immunol Pract. 2020; 8: 1428-1430Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar, 3Gupta R.S. Warren C.M. Smith B.M. Jiang J. Blumenstock J.A. Davis M.M. et al.Prevalence and severity of food allergies among US adults.JAMA Netw Open. 2019; 2: e185630Crossref PubMed Scopus (303) Google Scholar However, despite the apparent increasing prevalence of this condition, there remain gaps in understanding of the diagnosis and management. There is a common perception held by many regarding a fear of food allergens provoking life-threatening reactions, potentially even fatal food-induced anaphylaxis. Although severe reactions do occur and deaths from food allergy have been reported, fatal food allergy is a very rare event (defined as <1 case per 100 000).4Turner P.J. Jerschow E. Umasunthar T. Lin R. Campbell D.E. Boyle R.J. Fatal anaphylaxis: mortality rate and risk factors.J Allergy Clin Immunol Pract. 2017; 5: 1169-1178Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar,5Baseggio Conrado A. Ierodiakonou D. Gowland M.H. Boyle R.J. Turner P.J. Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018.BMJ. 2021; 372: n251Crossref PubMed Scopus (33) Google Scholar Paradoxically, fear regarding a severe food allergy can cause more morbidity than the food allergy itself.6Nowak-Wegrzyn A. Hass S.L. Donelson S.M. Robison D. Cameron A. Etschmaier M. et al.The Peanut Allergy Burden Study: impact on the quality of life of patients and caregivers.World Allergy Organ J. 2021; 14: 100512Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 7DunnGalvin A. Gallop K. Acaster S. Timmermans F. Regent L. Schnadt S. et al.APPEAL-2: A pan-European qualitative study to explore the burden of peanut-allergic children, teenagers and their caregivers.Clin Exp Allergy. 2020; 50: 1238-1248Crossref PubMed Scopus (16) Google Scholar, 8Couratier P. Montagne R. Acaster S. Gallop K. Patel R. Vereda A. et al.Allergy to Peanuts imPacting Emotions And Life (APPEAL): the impact of peanut allergy on children, adolescents, adults and caregivers in France.Allergy Asthma Clin Immunol. 2020; 16: 86Crossref PubMed Scopus (6) Google Scholar There are also misconceptions in the presentation and diagnosis of food allergy; as urticaria is not pathognomonic of food allergy and diagnostic testing, although sensitive, is not specific. Finally, it is under-recognized that antihistamines have no place in the first-line management of anaphylaxis, nor do oral corticosteroids have a role in prevention of a biphasic reaction. The goal of this commentary is to review important themes that have emerged in our understanding of food allergy management. Anaphylaxis has been defined as a “serious allergic reaction that is rapid in onset and may cause death.”9Boyce J.A. Assa'ad A. Burks A.W. Jones S.M. Sampson H.A. Wood R.A. et al.Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.J Allergy Clin Immunol. 2010; 126: S1-S58Abstract Full Text Full Text PDF PubMed Scopus (1119) Google Scholar However, although it is essential that anaphylaxis be recognized and managed, the risk of fatality from anaphylaxis is very low. Moreover, it has been shown that fatal food anaphylaxis is “rare, and adds little to overall mortality risk, even in young people known to have a food allergy.”4Turner P.J. Jerschow E. Umasunthar T. Lin R. Campbell D.E. Boyle R.J. Fatal anaphylaxis: mortality rate and risk factors.J Allergy Clin Immunol Pract. 2017; 5: 1169-1178Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar The risk of fatal anaphylaxis is about 1 in 10 million (about equivalent to being struck by lightning, and 100-fold lower than death owing to fire or murder).4Turner P.J. Jerschow E. Umasunthar T. Lin R. Campbell D.E. Boyle R.J. Fatal anaphylaxis: mortality rate and risk factors.J Allergy Clin Immunol Pract. 2017; 5: 1169-1178Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar,10Jerschow E. Lin R.Y. Scaperotti M.M. McGinn A.P. Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations.J Allergy Clin Immunol. 2014; 134: 1318-1328.e7Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar In a systematic review and meta-analysis regarding the incidence of fatal food anaphylaxis in people with food allergy in Europe, the incidence of (food-related) fatal anaphylaxis was 1.81 per million person-years (95% CI, 0.94-3.45), which is lower than the incidence of accidental death among the general European population.11Umasunthar T. Leonardi-Bee J. Hodes M. Turner P.J. Gore C. Habibi P. et al.Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis.Clin Exp Allergy. 2013; 43: 1333-1341Crossref PubMed Scopus (160) Google Scholar Even among infants, the risk of anaphylaxis, and fatal anaphylaxis, are both extremely low. Infant anaphylaxis tends to be milder than in older children, and fatality on first ingestion of an allergen in infancy has never been described.12Abrams E.M. Primeau M.-N. Kim H. Gerdts J. Chan E.S. Increasing awareness of the low risk of severe reaction at infant peanut introduction: implications during COVID-19 and beyond.J Allergy Clin Immunol Pract. 2020; 8: 3259-3260Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar A focus on mortality risk often cloaks the importance that there can be considerable morbidity related to food allergy, which is largely psychological and related to its impact on quality of life (QoL).13Shaker M.S. Schwartz J. Ferguson M. An update on the impact of food allergy on anxiety and quality of life.Curr Opin Pediatr. 2017; 29: 497-502Crossref PubMed Scopus (48) Google Scholar Studies of children with food allergy note a significant impact on multiple domains of QoL, including overall QoL, health-related QoL, QoL in school, and emotional QoL (including separation anxiety and bullying).14King R.M. Knibb R.C. Hourihane J.O. Impact of peanut allergy on quality of life, stress and anxiety in the family.Allergy. 2009; 64: 461-468Crossref PubMed Scopus (242) Google Scholar,15Fong A.T. Katelaris C.H. Wainstein B. Bullying and quality of life in children and adolescents with food allergy.J Paediatr Child Health. 2017; 53: 630-635Crossref PubMed Scopus (27) Google Scholar In recent studies, more than 30% of children and adolescents reported being bullied because of their food allergy (although these studies tend to over-rely on clustered samples and self-report).15Fong A.T. Katelaris C.H. Wainstein B. Bullying and quality of life in children and adolescents with food allergy.J Paediatr Child Health. 2017; 53: 630-635Crossref PubMed Scopus (27) Google Scholar, 16Fong A.T. Katelaris C.H. Wainstein B.K. Bullying in Australian children and adolescents with food allergies.Pediatr Allergy Immunol. 2018; 29: 740-746Crossref PubMed Scopus (23) Google Scholar, 17Brown D. Negris O. Gupta R. Herbert L. Lombard L. Bozen A. et al.Food allergy-related bullying and associated peer dynamics among Black and White children in the FORWARD study.Ann Allergy, Asthma Immunol. 2021; 126: 255-263.e1Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 18Lieberman J.A. Gupta R.S. Knibb R.C. Haselkorn T. Tilles S. Mack D.P. et al.The global burden of illness of peanut allergy: a comprehensive literature review.Allergy. 2021; 76: 1367-1384Crossref PubMed Scopus (11) Google Scholar Food allergy impacts many aspects of daily life. In a questionnaire of 87 caregivers of children with food allergy, more than 60% reported that food allergy significantly affected meal preparation, 49% reported that it affected family social activities, 41% reported it had a significant impact on stress levels, and 34% reported that it impacted school attendance (with 10% choosing home schooling because of a food allergy).19Bollinger M.E. Dahlquist L.M. Mudd K. Sonntag C. Dillinger L. McKenna K. The impact of food allergy on the daily activities of children and their families.Ann Allergy Asthma Immunol. 2006; 96: 415-421Abstract Full Text PDF PubMed Scopus (272) Google Scholar The impact of peanut allergy on QoL has been noted to be significantly worse than the impact of other chronic childhood diseases such as rheumatologic disease and type 1 diabetes mellitus.20Primeau M.N. Kagan R. Joseph L. Lim H. Dufresne C. Duffy C. et al.The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children.Clin Exp Allergy. 2000; 30: 1135-1143Crossref PubMed Scopus (328) Google Scholar,21Avery N.J. King R.M. Knight S. Hourihane J.O. Assessment of quality of life in children with peanut allergy.Pediatr Allergy Immunol. 2003; 14: 378-382Crossref PubMed Scopus (355) Google Scholar The burden of food allergy on QoL in food-allergic children and their families is partially, if not largely, related to the concern that accidental exposure could result in fatal anaphylaxis.14King R.M. Knibb R.C. Hourihane J.O. Impact of peanut allergy on quality of life, stress and anxiety in the family.Allergy. 2009; 64: 461-468Crossref PubMed Scopus (242) Google Scholar,22Abrams E.M. Chan E.S. Sicherer S. Peanut allergy: new advances and ongoing controversies.Pediatrics. 2020; 145: e20192102Crossref PubMed Google Scholar In a survey of 305 caregivers of children with food allergy, accurate reaction perception was significantly associated with overall improved QoL score (P = .04).23Howe L. Franxman T. Teich E. Greenhawt M. What affects quality of life among caregivers of food-allergic children?.Ann Allergy Asthma Immunol. 2014; 113: 69-74.e2Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar In a study of 876 families of children with food allergy that assessed parental empowerment and QoL, parental concern in the QoL assessment was greatest for items involving fear of allergen exposure outside of their control (the home).24Warren C.M. Gupta R.S. Sohn M.-W. Oh E.H. Lal N. Garfield C.F. et al.Differences in empowerment and quality of life among parents of children with food allergy.Ann Allergy Asthma Immunol. 2015; 114: 117-125Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar As a result, it is possible that accurate risk perception regarding anaphylaxis may improve QoL. Thus, although much work has focused on the early recognition and management of anaphylaxis to prevent morbidity and even the rare occurrence of mortality, the absolute risk of anaphylaxis fatality is exceptionally low. Living with food allergy remains a challenge for many families, and potentially the greatest source of morbidity facing children with food allergy and their families relates to fear and uncertainty. Cutaneous symptoms (including urticaria, angioedema, and erythema) are the most common presenting symptoms of food allergy and are present in up to 80% of acute food-allergic reactions in children.9Boyce J.A. Assa'ad A. Burks A.W. Jones S.M. Sampson H.A. Wood R.A. et al.Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.J Allergy Clin Immunol. 2010; 126: S1-S58Abstract Full Text Full Text PDF PubMed Scopus (1119) Google Scholar,25Abrams E.M. Sicherer S.H. Diagnosis and management of food allergy.CMAJ. 2016; 188: 1087-1093Crossref PubMed Scopus (32) Google Scholar However, there is a broad differential for urticaria, particularly in children. Thus, although urticaria is commonly equated with a food allergy, food allergy accounts for less than 10% of the causes of all acute urticaria and is not a cause of chronic urticaria.26Sicherer S.H. Sampson H.A. Food allergy.J Allergy Clin Immunol. 2010; 125: S116-S125Abstract Full Text Full Text PDF PubMed Scopus (845) Google Scholar,27Kulthanan K. Chiawsirikajorn Y. Jiamton S. Acute urticaria: etiologies, clinical course and quality of life.Asian Pacific J allergy Immunol. 2008; 26: 1-9PubMed Google Scholar In children, the most common cause of acute urticaria is not food allergy, but viral infection. An observational study of 44 children seen in the emergency department (ED) with acute urticaria found that 90.9% had symptoms of respiratory tract infection and in 45.4% a probable infectious etiology could be identified.28Bilbao A. García J.M. Pocheville I. Gutiérrez C. Corral J.M. Samper A. et al.[Round Table: Urticaria in relation to infections].Allergol Immunopathol (Madr). 1999; 27: 73-85PubMed Google Scholar A study of 54 children with various forms of urticaria documented infection as the most frequent cause of acute urticaria (48.6%), followed by drug allergy (5.4%) and food allergy (2.7%).29Sackesen C. Sekerel B.E. Orhan F. Kocabas C.N. Tuncer A. Adalioglu G. The etiology of different forms of urticaria in childhood.Pediatr Dermatol. 2004; 21: 102-108Crossref PubMed Scopus (145) Google Scholar A review of urticaria and infection documented infections to cause up to 57% of all acute urticaria, with upper respiratory and gastrointestinal infections being the most common etiologies.30Wedi B. Raap U. Wieczorek D. Kapp A. Urticaria and infections.Allergy Asthma Clin Immunol. 2009; 5: 10Crossref PubMed Google Scholar Other common symptoms that are often incorrectly attributed to food allergy include headaches, chronic behavioral symptoms, or chronic nonspecific abdominal pain.25Abrams E.M. Sicherer S.H. Diagnosis and management of food allergy.CMAJ. 2016; 188: 1087-1093Crossref PubMed Scopus (32) Google Scholar There are several elements of the medical history that help to differentiate whether urticaria is attributable to food allergy (Figure 1).31Sampson H.A. 9. Food allergy.J Allergy Clin Immunol. 2003; 111: S540-S547Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar These include the age of the child, the time of onset of the reaction, the food ingested, whether it had been ingested (and tolerated) before, and associated signs and symptoms.25Abrams E.M. Sicherer S.H. Diagnosis and management of food allergy.CMAJ. 2016; 188: 1087-1093Crossref PubMed Scopus (32) Google Scholar,31Sampson H.A. 9. Food allergy.J Allergy Clin Immunol. 2003; 111: S540-S547Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar Foremost, allergic urticaria by definition involves histamine release and typically pruritus; therefore, urticaria in an allergic reaction will usually be itchy or bothersome to the patient (and not just bothersome to the caregiver). Thus, nonbothersome urticarial rashes are less likely to represent an allergic reaction. The timing of onset is another clue to the nature of the finding. Food proteins are digested within several hours; therefore, urticaria associated with a food ingestion will occur within minutes to 2 hours of ingestion, but typically last no more than a few hours (and less with treatment). Thus, urticaria occurring more than 4-6 hours after ingestion and/or urticaria that lasts more than 6-12 hours or that waxes and wanes over the next several days without any reingestion are also unlikely to represent a classical food allergy (although delayed mammalian meat anaphylaxis owing to galactose-α-1,3-galactose allergy is a notable exception). An understanding of the child's state of health is also a clue. Given a very common association of an urticarial exanthem in the setting of a viral illness, assessing if the child has recent sick contacts or has had any upper respiratory illness in the days immediately before or after the event can provide key diagnostic insight. Distribution of the rash is also key. Allergic urticaria is usually not a localized phenomenon (eg, isolated lower extremity and often non bothersome urticarial rash associated with upper respiratory infection symptoms as may be seen in early Henoch-Schoenlein purpura). Acute onset of urticaria in a young child can certainly occur on both first (or subsequent) ingestion of a common allergen (because there could be pre-existing sensitization from environmental exposure), and this phenomenon can occur with or without associated respiratory or gastrointestinal symptoms. This factor notwithstanding, allergic urticaria is unlikely after eating a food that has been tolerated multiple times before, and urticaria arising in this context should immediately raise suspicion that the rash may not be food allergy related (although shellfish allergy and delayed mammalian meat allergy may be notable exceptions). Finally, there are a few common allergens (cow's milk, eggs, soy, peanut, tree nuts, fish, and grains) that account for the vast majority of food allergic reactions in children. In summary, the pediatrician should keep in mind several key points in the history that can help to clarify the diagnosis. A history of recent illness proximal to the onset of urticaria may suggest an infectious etiology. Urticaria that is objectively pruritic or bothersome to the child, or that starts after ingestion of a suspect food should raise concern. Last, regular tolerance to a potential culprit may provide some tentative reassurance; however, realizing that new allergies may develop over time, caution is warranted when reintroducing a potential but unlikely culprit food. An often-misunderstood point regarding allergy testing is how to interpret results. Testing denotes allergic sensitization, for example, the presence of allergen-specific immunoglobulin E (IgE) against whatever the clinician has chosen to test. The body makes IgE for many reasons, one of which is an allergic response, but the presence of a food-specific IgE is not itself indicative of an allergy. Allergy implies that there is a symptomatic response to the allergen (eg, urticaria and/or wheezing after ingestion), occurring in the setting of a sensitized individual. So, more succinctly, isolated positive allergy tests in someone without the context of a symptomatic ingestion do not necessarily translate into a clinical allergy. First-line allergy diagnostic tests are either skin prick tests, serologic food-specific IgE tests (sIgE), or both. Although both skin prick testing and food-specific IgE testing are highly sensitive (>90% for skin prick tests, 70%-90% for sIgE), the specificity and positive predictive values of testing are often very low.9Boyce J.A. Assa'ad A. Burks A.W. Jones S.M. Sampson H.A. Wood R.A. et al.Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.J Allergy Clin Immunol. 2010; 126: S1-S58Abstract Full Text Full Text PDF PubMed Scopus (1119) Google Scholar,39Cox L. Williams B. Sicherer S. Oppenheimer J. Sher L. Hamilton R. et al.Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE test task force.Ann Allergy Asthma Immunol. 2008; 101: 580-592Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar,40Kattan J.D. Sicherer S.H. Optimizing the diagnosis of food allergy.Immunol Allergy Clin North Am. 2015; 35: 61-76Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar The rate of false-positive tests is up to 40%.25Abrams E.M. Sicherer S.H. Diagnosis and management of food allergy.CMAJ. 2016; 188: 1087-1093Crossref PubMed Scopus (32) Google Scholar The tests themselves are very good at detecting sIgE if it is present, but as stated, its presence is not pathognomonic for clinical allergy, and it is difficult to understand the significance of what isolated sIgE means without the context of a suspected reaction to the food in question. Testing is an easily available, generally well-tolerated procedure and is highly used. However, most children with positive allergy testing may in fact be clinically tolerant to the food in question. A retrospective chart review of 125 children, of whom 96% had eczema, noted that 80%-100% of foods that were avoided owing to positive allergy testing could be reintroduced into the diet after an oral food challenge.41Fleischer D.M. Bock S.A. Spears G.C. Wilson C.G. Miyazawa N.K. Gleason M.C. et al.Oral food challenges in children with a diagnosis of food allergy.J Pediatr. 2011; 158: 578-583.e1Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar Among siblings of food allergic children in a Chicago Family Cohort study, 53% had positive allergy testing in the absence of a clinical history of reactivity to that food.42Gupta R.S. Walkner M.M. Greenhawt M. Lau C.H. Caruso D. Wang X. et al.Food allergy sensitization and presentation in siblings of food allergic children.J Allergy Clin Immunol Pract. 2016; 4: 956-962Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Data from the Danish Allergy Research Centre prospective population-based cohort noted that, among children with food allergy (of whom 90% had eczema), 80% were sensitized to other foods which they clinically tolerated, leading the authors to conclude that sensitization in the absence of food allergy in childhood is a “normal phenomenon.”43Eller E. Kjaer H.F. Host A. Andersen K.E. Bindslev-Jensen C. Food allergy and food sensitization in early childhood: results from the DARC cohort.Allergy. 2009; 64: 1023-1029Crossref PubMed Scopus (105) Google Scholar Food allergy testing is only diagnostic within the context of a history of a reaction, and when testing is performed, it should be as narrow as possible. Pre-emptive testing, broad “panel testing” (eg, to a panel of “common” foods), or any food allergy diagnostic testing in the absence of a convincing clinical history has high potential to overdiagnose food allergy and result in unnecessary food avoidances. Because these tests have poor specificity, they are not intended to be used as screening tools to determine to what food someone “could” be allergic. In addition, because early food introduction has a role in food allergy prevention (in particular for egg and peanut),44Fleischer D.M. Chan E.S. Venter C. Spergel J.M. Abrams E.M. Stukus D. et al.A consensus approach to the primary prevention of food allergy through nutrition: guidance from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and the Canadian Society for Allergy and Clinica.J Allergy Clin Immunol Pract. 2021; 9: 22-43.e4Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar there is a risk that screening may inadvertently increase the risk of true food allergy by delaying introduction.45Abrams E.M. Brough H.A. Keet C. Shaker M.S. Venter C. Greenhawt M. Pros and cons of pre-emptive screening programmes before peanut introduction in infancy.Lancet Child Adolesc Health. 2020; 4: 526-535Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Another food allergy diagnostic myth is that food-specific IgG testing has a role in identifying food sensitivities or should be used to direct food avoidances. This trendy fad is offered by many wellness companies or even directly marketed to consumers without having to see a physician. IgG testing for food allergy has been consistently criticized by national allergy associations such as the Canadian Society of Allergy and Clinical Immunology (CSACI) and the American Academy of Allergy Asthma and Immunology (AAAAI) as invalid for the assessment of this condition.46Carr S. Chan E. Lavine E. Moote W. CSACI position statement on the testing of food-specific IgG.Allergy Asthma Clin Immunol. 2012; 8: 12Crossref PubMed Scopus (35) Google Scholar,47Hammond C. Lieberman J.A. Unproven diagnostic tests for food allergy.Immunol Allergy Clin North Am. 2018; 38: 153-163Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar The CSACI, in a position statement about IgG testing, noted it “strongly discourages the practice of food-specific IgG testing for the purposes of identifying or predicting adverse reactions to food.”46Carr S. Chan E. Lavine E. Moote W. CSACI position statement on the testing of food-specific IgG.Allergy Asthma Clin Immunol. 2012; 8: 12Crossref PubMed Scopus (35) Google Scholar There is no evidence that IgG testing marks food sensitivity; in fact, the presence of IgG is both expected and is a potential indicator of ongoing tolerance.46Carr S. Chan E. Lavine E. Moote W. CSACI position statement on the testing of food-specific IgG.Allergy Asthma Clin Immunol. 2012; 8: 12Crossref PubMed Scopus (35) Google Scholar Concerns have been raised that the use of this test results in unnecessary dietary restrictions that can worsen QoL and carries a significant financial cost to the family.46Carr S. Chan E. Lavine E. Moote W. CSACI position statement on the testing of food-specific IgG.Allergy Asthma Clin Immunol. 2012; 8: 12Crossref PubMed Scopus (35) Google Scholar A similar sentiment was expressed by the European Academy of Allergy and Clinical Immunology, and endorsed by the AAAAI, in a report that stated that IgG testing is “irrelevant” for the work up of food allergy or intolerance and “should not be performed in case of food-related complaints.”48Stapel S.O. Asero R. Ballmer-Weber B.K. Knol E.F. Strobel S. Vieths S. et al.Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI task force report.Allergy. 2008; 63: 793-796Crossref PubMed Scopus (225) Google Scholar In conclusion, although first-line food allergy diagnostic testing is highly sensitive, it lacks specificity and should generally only be pursued in the context of a convincing clinical history of a reaction. IgG testing should never be considered in the work up of food allergy. In real-world settings, antihistamines may often be used in the place of epinephrine in the treatment of anaphylaxis, and it is under-recognized that antihistamines have no role in the acute management of a life-threatening reaction and in fact are second- or third-line therapy in anaphylaxis guidelines.49Simons F.E.R. Ardusso L.R.F. Bilo M.B. Dimov V. Ebisawa M. El-Gamal Y.M. et al.2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis.Curr Opin Allergy Clin Immunol. 2012; 12: 389-399Crossref PubMed Scopus (208) Google Scholar Antihistamines are unlikely to relieve upper or lower airway obstruction, shock or hypotension and their onset of action ranges from 1 to 3 hours.50Simons F.E.R. Anaphylaxis.J Allergy Clin Immunol. 2010; 125: S161-S181Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar Their only usefulness is in the treatment of cutaneous symptoms, such as urticaria.50Simons F.E.R. Anaphylaxis.J Allergy Clin Immunol. 2010; 125: S161-S181Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar In addition, there are serious safety concerns with the use of first-generation sedating antihistamines (such as diphenhydramine and hydroxyzine), which can be associated with somnolence, sedation, or a paradoxical stimulatory response in children (Table).32Church M.K. Maurer M. Simons F.E.R. Bindslev-Jensen C. van Cauwenberge P. Bousquet J. et al.Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper.Allergy Eur J Allergy Clin Immunol. 2010; 65: 459-466Crossref Scopus (286) Google Scholar Dizziness and orthostatic hypotension owing to α-adrenergic effects and peripheral vasodilation have been theorized to potentially mask symptoms of allergic reactions that are progressing toward anaphylaxis, which can also be associated with central nervous system effects.50Simons F.E.R. Anaphylaxis.J Allergy Clin Immunol. 2010; 125: S161-S181Abstract Full Text Full Text PDF PubMed Scopus (331) Google Scholar A survey in Canada noted that first-generation antihistamines (diphenhydramine) are the most recommended antihistamines in children.53Prendergast C. Plint A.C. Tang K. Crawford T. Neto G. Alqurashi W. Management of pediatric allergic reaction: practice patterns of Canadian pediatric emergency physicians.CJEM. 2020; 22: 802-810Crossref PubMed Scopus (1) Google Scholar However, a statement by the CSACI notes that newer generation antihistamines are safer and have superior efficacy.51Fein M.N. Fischer D.A. O'Keefe A.W. Sussman G.L. CSACI position statement: newer generation H(1)-antihistamines are safer than first-generation H(1)-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria.Allergy Asthma Clin Immunol. 2019; 15: 61Crossref PubMed Scopus (31) Google Scholar In fact, the CSACI recommends that first-generation antihistamines such as diphenhydramine should be considered for availability only on a behind the counter basis, although the AAAAI and the American College of Allergy Asthma and Immunology have not issued similar statements.TablePotential serious adverse event of first-generation sedating antihistamines32Church M.K. Maurer M. Simons F.E.R. Bindslev-Jensen C. van Cauwenberge P. Bousquet J. et al.Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper.Allergy Eur J Allergy Clin Immunol. 2010; 65: 459-466Crossref Scopus (286) Google Scholar,51Fein M.N. Fischer D.A. O'Keefe A.W. Sussman G.L. CSACI position statement: newer generation H(1)-antihistamines are safer than first-generation H(1)-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria.Allergy Asthma Clin Immunol. 2019; 15: 61Crossr