ARTICLE IN PRESS Current Paediatrics (2005) 15, 228–232

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How dangerous is food allergy? Colin Macdougall, Onajite Etuwewe Department of Paediatrics, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK

KEYWORDS Food allergy; Allergic reactions; Risk; Epinephrine autoinjectors

Summary Food allergy is the inappropriate and harmful response of the immune system to specific food proteins that are normally harmless. In susceptible individuals, adverse reactions can range from mild skin reactions to severe and life-threatening reactions. Food allergy is the most common cause of severe allergic reactions in children. The connection between danger and allergy is deeply ingrained in the public and medical consciousness. Communication of the risks, or lack of risk, of lifethreatening reactions, although important, is not the whole story in managing rapid hypersensitivity. Paramount is the need for a ‘care package’ including advice and backup as well as appropriate treatments. & 2005 Elsevier Ltd. All rights reserved.



Practice points

 



The concepts of danger and allergy have become closely linked in the minds of doctors and the public The term anaphylaxis is used for a broad spectrum of severities of reaction and its use causes anxiety. This may no longer be a useful label The understanding of the epidemiology of fatal and severe reactions is becoming clearer but is still controversial

Corresponding author. Walsgrave Hospital, Clifford Bride

Road, Walsgrave, Coventry CV2 2DX, UK. Tel.: +44 24 7660 2020. E-mail addresses: [email protected], [email protected] (C. Macdougall).



The clinical consultation is often dominated by discrepancies in how people decide to act when presented with risk information Despite the controversy, there is actually a large degree of agreement on current practice, although this is often based on a low level of evidence or is at odds with some published work

Introduction Allergies in general are common and becoming commoner, with 40% of children at some point being diagnosed as having an allergic illness.1 ‘Severe allergy’ is becoming increasingly feared

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ARTICLE IN PRESS How dangerous is food allergy? by professionals and the public.2,3 There are few specialist allergy centres and general training in allergy is often poor.1 As a result, many General Paediatricians feel poorly prepared for the increased numbers of referrals focussed on assessing and managing the perceived risk of food allergy.4 Doctors and families want to know ‘how dangerous is food allergy?’ Before exploring the answers, it is worth considering how the words ‘danger’ and ‘allergy’ have become increasingly linked. In allergy clinics, we are often asked this question or variations of it, although we are almost never asked, e.g., ‘How dangerous is asthma?’ For illustration, in 10 years of ‘Current Paediatrics’, this is the first paper to include the word ‘dangerous’ or ‘danger’ in the title. Clearly, it is not just the lay press that links the term ‘danger’ with allergy in a way that is not done with many other diseases with a higher mortality. To deal with such issues, this review introduces the strengths and limitations of the available literature and considers how parents perceive such uncertainties. In addition, a number of common issues concerning allergy and risk are discussed in brief.

What is food allergy? Medically, the term is reserved for immunologically mediated abnormal reactions to food,5 although it is commonly used by patients to cover a broad range of symptoms perceived to be connected to ingestion of foods or groups of foods. Within the ‘true’ immunologically mediated reactions, some are IgE-mediated (or rapid) hypersensitivity and some involve other immunological mechanisms. Non-immunological mechanisms include toxic, pharmacological, irritant, malabsorbtive and nonorganic. The most useful division, however, is between IgE-mediated reactions and all others; although IgE-mediated reactions can cover a wide range of severities, it is a subset of this group that has the potential to cause severe reactions. The overall prevalence of food allergy is rising and is greatest in the first year of life, affecting up to 5% of young infants,6 falling to about 2% by the end of the first decade as children outgrow their sensitivity.7,8 Eight foods cause up to 90% of IgEmediated food allergy in children: milk, peanuts, soy, egg, wheat, tree nuts (such as pecans and walnuts), fish and shellfish.9 Signs and symptoms of adverse food reactions may include any or several of the following: skin rashes; itching or flushing;

229 nasal congestion, itchiness or sneezing; itchy or teary eyes; intestinal symptoms such as nausea, vomiting, colic, abdominal cramps, diarrhoea; itching, tingling, swelling of the lips, palate, tongue, or throat and bronchospasm.

What is a severe allergic reaction? Despite the levels of anxiety,3 the majority (51%) of patients’ worst ever reactions to peanuts, a food that generates most anxiety, are mild and involve mainly cutaneous features.10 More severe and fatal reactions clearly do occur.11 Describing these is, however, a significant practical and research challenge. Faced with a child with widespread urticaria, significant bronchospasm, pallor and hypoxia, all would agree that they are undergoing a severe reaction requiring rapid action and would probably describe the event as ‘anaphylaxis’. Even this term, however, is used for a surprising range of reaction types in the literature. Derived during animal work testing inoculation a century ago,12 ‘anaphylaxis’ is mostly used to denote severe allergy (‘a potentially fatal multisystem syndrome’).13 Unfortunately, some also use the term for a much broader group of reactions including just urticaria13 or just conjunctivitis and rhinitis.14 Such broad definitions could explain why anaphylaxis is said to affect up to 15.04% of the US population (all causes).15 Where reactions are simply described in research as ‘severe’ this can include, e.g., symptoms that subsided prior to arrival at an emergency room,16 perhaps without treatment. This lack of agreement on what severe means and how it can be measured explains much of the difficulties in interpreting available research.

How common are severe allergic reactions to food? Until recently, such questions were answered using case series14,17,18 and from extrapolations from data covering all ages19,20 with the conclusion that, ‘the disease frequencies of the more serious and systemic allergies, e.g., anaphylaxis, drug and food allergies, are increasing fast’.1 More recently, paediatric surveillance work and admissions data have added clarity,11,21 although this is a controversial area and there has been much discussion about the methodologies.19,22–24 Also, as this work is yet to be repeated, there is no formal

ARTICLE IN PRESS 230 population-based answer to whether severe reactions are getting commoner or not. Between 1990 and 2000 in the UK and Ireland there were eight deaths attributed to an allergic reaction to food, or 0.02 deaths per 100 000 children aged 0–15 per year.11 This represents approximately 1 death per 800 000 food allergic children per year. Areas of uncertainty include whether asthma deaths (which are more common)25 could actually be unrecognised allergy deaths.19 This issue has not been clearly addressed and is a key question for future study. There are between 0.68 and 0.89 admissions per 100 000 children per year in the UK due to food allergy.26 How many of these are ‘severe’ in part gets down to what ‘severe’ means. Restricting it to those with demonstrable evidence of the need for significant treatment limits this to 0.19 severe reactions per 100 000 children aged 0–15 years per year.11 It has been stated that this figure is far too selective, although some much higher suggestions22 would mean very few ‘severe’ cases needed hospital admission.

How do we discuss these issues with parents? The connection between danger and allergy is deeply ingrained in the public consciousness, reflected, or perhaps promoted, by much press attention3 with a best selling novelist even describing peanut allergy as a reliable method for committing undetected murder.27 Indeed, local experience is that many referrals occur following episodes of self-resolving or easily treated urticaria. Most of these would have been previously described as ‘just an allergy’ but now provoke enough anxiety for General Practitioners to feel the need to refer. In numerical terms, the risks are small, with death rates being 1/5 of the rate of sudden asthma death and 1/200 of the rate of unnatural (violence, poisoning, etc.) deaths.25 It would seem straightforward to compare this with other risks in life and with the costs of a given course of action. Often, however, families are ill prepared for handling such information. In part, this is due to a poor overall understanding of statistics and indeed there are tools available to help communicate ‘risk statements’.28 Unfortunately, even when such risks can be explained, most people do not make decisions in such a balanced way,29 tending instead to categorise things simplistically as safe or risky, erring towards risk aversion with decisions based on their

C. Macdougall, O. Etuwewe personal values and beliefs.30 This is clearly compounded when the evidence itself is disputed. In such a context, the challenge is of families wanting to be told either that their child’s food allergy is safe29 or risky. If the answer is the latter, or unclear, they then often want any potential risk removed, thus returning them to a position of certainty. If the discussion is to be useful, however, then patients and their families have to learn to live with uncertainty.30 For example, accepting that even established practices such as allergen avoidance and the availability of epinephrine autoinjectors (EpiPens&)13 do not avoid all risk, with deaths occurring despite all best efforts43 and, therefore, the risks cannot necessarily be removed. This series of dilemmas results in the common situation where a doctor feels that the perceived risk is not in accordance with the actual risk31 and the resultant demands are out of keeping with the need: ‘It is our experience that, in spite of full discussionymany parents prefer, indeed often demand, epinephrine provision on the basis that their anxieties are significantly reduced.’32 The final irony is that even when all agree that the risk is significant, even when epinephrine autoinjectors are prescribed, they may not be available or used,33,34 suggesting that the anxieties expressed in the consultation are handled differently in day-to-day life.

What advice can we give? Despite all these difficulties, there is a surprising amount of agreement amongst UK practitioners10,35–37 and others31 as to the best course of action and on factors that increase and decrease risk within an individual.

Type of allergy Only those with IgE-mediated allergy have any chance of severe reactions. For example, children can present with a variety of IgE-mediated and nonIgE-mediated allergic phenomena where the parents are convinced that if a child reacts to a food then this is potentially dangerous. Simple IgE testing (Skin Prick Testing or specific IgE blood testing) will show which reactions are not IgEmediated (and are therefore ‘safe’) although it should be emphasised that where a child is IgE positive, this does not mean that the given allergy is ‘dangerous’.38

ARTICLE IN PRESS How dangerous is food allergy?

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Food involved

Coexisting asthma

Many children are referred with mild or only suspected allergy on the basis that there was peanut around. Indeed, many parents are so concerned about peanuts that they are visibly relieved when this is shown not to be the case. So does the actual allergen demote severity as some suggest?31 Peanut allergy certainly receives most press attention. Despite being the most common cause of fatal and near-fatal reactions to food in the US,2 peanut allergy covers the full spectrum from mild to severe10 and although deaths from peanut allergy have occurred in UK children, between 1990 and 2000 there were marginally more caused by milk allergy.11 The focus should be on deciding what foods an individual is sensitive to and to what severity. The only way that a particular allergen may be ‘more dangerous’ is if it is hard to avoid and the only way for it to be ‘safer’ is if it is easy to avoid or if children grow out of the given allergy. For example, 80–90% of children go on to tolerate milk.39 Finally, some believe that reacting to a tiny amount of allergen suggests greater sensitisation and should therefore be regarded as higher risk.22,31

This is strongly associated with future risk,11,22,31 so much so that the absence of asthma is very reassuring. It is not known whether close management of asthma reduces risks although most agree it is sensible to try. Indeed, salbutamol via an appropriate inhaler device may be as important for a severe reaction as epinephrine either pre or in hospital.

Severity of previous reactions Many families expect ‘the next reaction to be worse’. The evidence, however, is that subsequent reactions can be more or less severe than the index reaction.10,11 It is clearly reassuring to those who have had a severe reaction that the next one might be milder. The flip side, however, is that there is at least some evidence to support those who say that any one who has had a mild reaction is at risk of a severe reaction.40 Most experts, however, place significant weight on the severity of preceding reactions in predicting risk22,31,35 despite the paucity of clear evidence either way.

Availability of epinephrine autoinjectors Most reject the universal provision of epinephrine autoinjectors suggested by some prominent US authors.40 Some do so because of the perceived risks of epinephrine, particularly in the hands of the poorly trained,41,42 some because widespread prescription would dilute care over a wide group, including those with very mild reactions22 and some because of the huge cost, estimated in Australia to be $51.7 million dollars per life saved.31 At the extremes, whether to prescribe an autoinjector is an easy discussion. Where the reaction is mild, to something that is easy to avoid and there is no asthma, only a very few would suggest autoinjector prescription. At the opposite end, even those who believe the profession is not selective enough agree that there is a role for autoinjectors in some patients. It is the grey area in between that makes this ‘undoubtedly the most tortuous aspect of the consultation’.4 This has resulted in varying local and national protocols.10,29,31,32,36 Given the differences in detail and emphasis the key is that the doctor involved in the discussion has the ability to discuss the individual factors that contribute to heightened or lowered risks with confidence and has an awareness of how risk information is handled and of the broader societal issues. These issues are dealt with in greater detail elsewhere.29

Conclusions Care package Risk discussions often get bogged down with issues surrounding provision of self-injectable epinephrine.32 Even if provided, this is actually a small part of what is needed and it is important to consider a whole ‘care package’32 including written advice, avoidance (backed up with dietetic advice), antihistamines for mild reactions10 and suitable training, including training and backup for schools and child care providers.

Allergy worries many families and to a disproportionate level compared to other risks in life. Many families perceive this as a fight to get medical recognition for their child’s problem. Despite the challenges from research in this area and interpreting the results of such research, there is much that can be said with confidence, although increasingly this is an area becoming complex enough to need interested individuals willing to take on the often-challenging discussions. When

ARTICLE IN PRESS 232 families can be reassured and/or danger reduced, this can be immensely rewarding however.

References 1. Royal College of Physicians of London. Allergy: the unmet need: a blueprint for better patient care: a report of the Royal Colleges of Physicians working party on the provision of allergy services in the UK. London: Royal College of Physicians; 2003. 2. Bock SA, Mua ¨noz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 2001;107(1):191–3. 3. Weale S. Shell shock. In: The Guardian Weekend. London: The Guardian; 2000. p. 26–35. 4. Rosenthal M. How a non-allergist survives an allergy clinic. Arch Dis Child 2004;89(3):238–43. 5. Sheikh A, Walker S. Food allergy. Br Med J 2002;325(7376): 1337. 6. Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics 1987;79(5):683–8. 7. Hourihane JO. Prevalence and severity of food allergy— need for control. Allergy 1998;53(46):84–8. 8. Sampson HA. Epidemiology of food allergy. Pediatr Allergy Immunol 1996;7(9):42–50. 9. Bock SA, Sampson HA, Atkins FM, et al. Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol 1988;82(6): 986–97. 10. Ewan PW, Clark AT. Long-term prospective observational study of patients with peanut and nut allergy after participation in a management plan. Lancet 2001;357(9250): 111–5. 11. Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child 2002;86(4):236–9. 12. Portier M, Richet C. De l’Action anaphylactique de certain venins. Soc Biol 1902:170–2. 13. Young MC. General treatment of anaphylaxis. In: Leung DYM, editor. Pediatric allergy: principles and practice. St. Louis: Mosby; 2003. p. 643–54. 14. Klein JS, Yocum MW. Underreporting of anaphylaxis in a community emergency room. J Allergy Clin Immunol 1995;95(2):637–8. 15. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med 2001;161(1):15–21. 16. Bock SA. The incidence of severe adverse reactions to food in Colorado. J Allergy Clin Immunol 1992;90(4):683–5. 17. Kemp SF, Lockey RF, Wolf BL, Lieberman P. Anaphylaxis. A review of 266 cases. Arch Intern Med 1995;155(16): 1749–54. 18. Ewan PW. Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations. Br Med J 1996;312(7038):1074–8. 19. Hourihane JO, Reading D, Smith P, et al. Incidence of severe and fatal reactions to foods. Arch Dis Child 2002;87(5):450–1 Author’s reply: 450–1. 20. Yocum MW, Butterfield JH, Klein JS, Volcheck GW, Schroeder DR, Silverstein MD. Epidemiology of anaphylaxis in Olmsted County: a population-based study. J Allergy Clin Immunol 1999;104(2):452–6.

C. Macdougall, O. Etuwewe 21. Alves B, Sheikh A. Age specific aetiology of anaphylaxis. Arch Dis Child 2001;85(4):348. 22. Clark AT, Ewan PW. Food allergy in childhood. Arch Dis Child 2003;88(1):79–81. 23. Clark AT, Ewan PW. Food allergy in childhood. Arch Dis Child 2004;89(2):197. 24. Warner JO. How dangerous is food allergy in childhood? Pediatr Allergy Immunol 2002;13(3):149–50. 25. Wren C. Sudden death in children and adolescents. Heart 2002;88(4):426–31. 26. Colver AF, Macdougall C, Cant A. Food allergy in childhood. Arch Dis Child 2003;88(8):742–3. 27. Brown D. The Da Vinci code: a novel. London: Bantam; 2004. 28. Paling J. Strategies to help patients understand risks. Br Med J 2003;327(7417):745–8. 29. Hu W, Kemp A, Kerridge I. Making clinical decisions when the stakes are high and the evidence unclear. Br Med J 2004; 329(7470):852–4. 30. Edwards A. Communicating risks. Br Med J 2003;327(7417): 691–2. 31. Kemp AS. EpiPen epidemic: suggestions for rational prescribing in childhood food allergy. J Paediatr Child Health 2003;39(5):372–5. 32. Williams J. The management of food allergy in children. Curr Paediatr 2002;12:365–9. 33. Gold MS, Sainsbury S. First aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (EpiPen). J Allergy Clin Immunol 2000; 106(1):171–6. 34. Wuthrich B, Ballmer-Weber BK. Food-induced anaphylaxis. Allergy 2001;56:102–4. 35. McLean-Tooke AP, Bethune CA, Fay AC, Spickett GP. Adrenaline in the treatment of anaphylaxis: what is the evidence? Br Med J 2003;327(7427):1332–5. 36. Kelly AM. Anaphylaxis and angioedema and their community management. Curr Paediatr 1996;6:237–41. 37. Sicherer SH. Food allergy. Lancet 2002;360(9334):701–10. 38. Ives AJ, Hourihane JOB. Evidence-based diagnosis of food allergy. Curr Paediatr 2002;12:357–64. 39. Host A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy 1990;45(8):587–96. 40. Sampson HA, Mendelson L, Rosen JP. Fatal and near–fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 1992;327(6):380–4. 41. Unsworth DJ. Adrenaline syringes are vastly over prescribed. Arch Dis Child 2001;84(5):410–1. 42. Huang SW. A survey of Epi-Pen use in patients with a history of anaphylaxis. J Allergy Clin Immunol 1998;102(3): 525–6. 43. Colver AF, Nevantaus H, Macdougall CF, Cant AJ. Severe food allergic reactions in children across the UK and Ireland, 1998–2000. Acta paediatr 2005, in press.

Further Reading 1. Hu W, Kemp A, Kerridge I. Making clinical decisions when the stakes are high and the evidence unclear. Br Med J 2004;329(7470):852–4. 2. Rosenthal M. How a non-allergist survives an allergy clinic. Arch Dis Child 2004;89(3):238–43. 3. Williams J. The management of food allergy in children. Curr Paediatr 2002.