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Food Allergies in Pediatric Atopic Dermatitis
Atopic dermatitis (AD) is a chronic relapsing condition, with a significant impact on patient and family quality of life. For dermatologists and families alike, avoiding triggers is a mainstay of AD treatment. Families frequently inquire about potential food triggers for their child’s AD and may have questions about the complex relationship between AD and food allergies. For example, families may have tried elimination diets or may be avoiding a specific food in hopes of improving their child’s eczema. Families of younger children and infants may have questions as to when, and how, to safely introduce foods to their children.
For dermatologists in a busy practice, these conversations can be time consuming and overwhelming. However, dermatologists have a complex understanding of the pathogenesis of AD, including the role of potential triggers. This specialized knowledge allows us to play a unique role in the prevention of comorbid food allergy in our pediatric patients with AD, as well as counsel families with concerns about food triggers. With a focus on the data, dermatologists can ease the burden on families of children at high risk for food allergies.
Why Are Pediatric Patients With AD At Risk for Developing Food Allergy?
Infants with early onset eczema, particularly in the first 1 to 6 months of life, are at the highest risk for developing food allergies.2,3Â IgE-mediated food allergy is 5 times more likely in infants with atopic dermatitis than in those without AD.3 Certainly, these infants are genetically predisposed to atopy and, therefore, all atopic disease, but the defective skin barrier in AD plays a critical role in predisposing these patients to food allergies.
Mutations in the gene encoding filaggrin are known to be major predisposing factors for AD. The filaggrin gene encodes an important epidermal protein, and mutations in this gene cause disruption in the barrier function of the skin. Interestingly, data have shown that filaggrin mutation is more predictive of peanut allergy (odds ratio 5.3) than of AD (odds ratio 3.1).4 This supports the theory that a defective skin barrier alone is susceptible to food allergies, even in infants and children without AD.
The dual-allergen-exposure hypothesis states that allergic sensitization is enhanced when a child is exposed to a food antigen via the skin. Cutaneous exposure to food proteins is prone to induce a T-helper 2 (TH2) cell response and produce specific IgE antibodies to that food. Conversely, oral exposure to foods is inclined to induce immune tolerance. This tolerance is proposed to occur via TH1 and regulatory T-cell responses within gut-associated lymphoid tissue.5
Infant skin is inherently more permeable than adult skin, with decreased ceramides and increased transepidermal water loss compared with adults.6 For infants with AD, this is coupled with an impaired skin barrier and cutaneous inflammatory signaling. All this creates a perfect storm for infants with eczema to have increased cutaneous exposure to food allergens, placing these infants at high risk for developing food allergy.
What Can Dermatologists Do to Prevent Food Allergy in Pediatric Patients With AD?
Dermatologists play a significant role in the prevention and awareness of food allergies. We have all seen many visual iterations of the atopic march, with AD as the first manifestation of atopy, typically beginning just a few months before the development of food allergy.7 When we look carefully at the diagrams, we see a small window of time between onset of AD and then food allergy; as dermatologists, this is our chance to intervene.
Introducing allergenic foods through the oral or gastrointestinal route induces food tolerance and decreases the risk of allergy to those foods.5 For infants with AD, the goal is to introduce highly allergenic foods early in life before food antigens are inadvertently introduced through the skin. Numerous studies support early introduction of allergenic foods as prevention of food allergies.
Results of the LEAP trial, a large, randomized controlled trial including infants at high risk for atopic disease (ie, severe eczema, egg allergy, or both), showed that early and sustained introduction to peanuts dramatically reduced the development of peanut allergy.8 This was in stark contrast to previous guidelines, which recommended excluding allergenic foods from the diets of infants at high risk for allergies.9 However, within 10 years of this evasion, the number of patients with peanut allergy doubled, and peanut allergy became the leading cause of anaphylaxis and death caused by food allergy.8,10 At the time the LEAP trial was published in 2015, existing guidelines suggested that solid foods should be introduced between ages 4 and 6 months and that highly allergenic foods “may” be introduced once a few typical complementary foods are tolerated, without specific recommendations on the exact age for introduction of peanuts.9
The LEAP trial investigators examined 2 groups: infants with a negative peanut skin-prick test at baseline (nonsensitized) and infants with a mild wheal after skin-prick test at baseline (sensitized). These infants were then randomly assigned to either early consumption of peanuts or strict peanut avoidance. Early introduction of peanuts to the nonsensitized group resulted in an 86% relative reduction in the prevalence of peanut allergy at age 5 years.8 Interestingly, early introduction of peanuts to the sensitized group also reduced the prevalence of peanut allergy at age 5 years, with a 70% relative risk reduction.8 The guidelines were then updated, recommending early introduction of peanuts for infants at risk for food allergies. The practicing dermatologist, therefore, has a huge potential to recommend the early introduction of peanuts in these high-risk patients, in turn preventing peanut allergy.
Which Infants With AD Are Good Candidates for Early Introduction of Peanut?
The National Institute of Allergy and Infectious Diseases has clear guidelines for which infants should be introduced to peanuts at home.11 For infants without eczema or food allergies, peanuts should be introduced at home in accordance with family preferences. For infants at risk for food allergies, namely those with mild to moderate AD, peanuts should be introduced at home around age 6 months.
To introduce peanuts to infants, parents can mix 2 teaspoons of peanut butter or peanut powder with breastmilk or formula, start with a small sip, and monitor for 30 minutes, looking for an immediate IgE-mediated reaction, such as urticaria, lip swelling, or vomiting within minutes of eating the food. If no reaction is noted after 30 minutes, parents can feed the infant the remainder of the thinned peanut mixture and continue to feed 2 teaspoons of peanut butter at least 3 times per week.
For infants with severe eczema, egg allergy, or both, guidelines recommend either a direct referral to an allergist, a skin-prick test, or serum IgE screening for peanuts, with early introduction at age 4 to 6 months if negative (and referral to an allergist if positive).
It is important to note that these guidelines define “severe eczema” as “persistent or frequently recurring eczema, assessed as severe by a health care provider, and requiring frequent need for prescription-strength topical corticosteroids, calcineurin inhibitors, or other anti-inflammatory agents despite appropriate use of emollients.”11
When ordering blood tests (such as peanut-specifi c IgE) for an infant, health care providers may be tempted to order additional tests to avoid future blood draws. Parents/guardians may also request testing for other foods before introduction. However, extensive allergy panels are not recommended because of the low positive predictive values and potential for several false positives. Future allergy testing should be directed to foods of concern, rather than broad panels. For families with concerns about multiple foods, referral to an allergist is warranted.
What About Other Foods?
The most common food allergens are cow’s milk (2.5% of the general population), peanuts (1.4%–5%), egg (1.3%–10.1%), tree nuts, hen’s egg, shellfish, wheat, fish, soy, and sesame.12 Together, these allergens account for 90% of all food allergies in the United States.13 Although no guidelines to date have been established for early introduction of other food allergens besides peanuts, data have demonstrated decreased incidence of food allergies with early introduction of other allergens as well. The HealthNuts study, a population-based study of 2500 infants, found that introduction of a cooked egg between ages 4 and 6 months decreased the risk of food allergies compared with introduction at age 10 months or later.14 Another large observational study including more than 13,000 infants found that infants with early exposure to cow’s milk within 14 days of life with regular consumption afterward had a lower risk of IgE-mediated cow’s milk protein allergy compared with those exposed after age 3 months.15
The literature suggests that the magic window for introducing nonpeanut–containing allergenic foods, such as egg and wheat, to high-risk infants is at age 4 to 6 months.16,17 To date, no studies have demonstrated any harm with allergen introduction within this window.16 Additionally, during this time, infants have the lowest potential for sensitization to new foods, as evidenced by the decreased incidence of food allergies when introduced within this time compared with later introduction.17
However, introducing all of these allergenic foods early and regularly can be challenging for families. In a large, randomized controlled trial (the Enquire About Tolerance, or EAT, trial), exclusively breastfed infants were randomly assigned to early introduction of 6 common allergenic foods (ie, peanuts, a cooked egg, cow’s milk, sesame, whitefish, and wheat) starting at age 3 months vs standard introduction at age 6 months.18 The intention-to-treat analysis showed a nonstatistically significant 20% decrease in food allergies in the early introduction group. However, adherence to consistently including all 6 foods in the diet was challenging, and this likely resulted in the lack of statistical significance. The perprotocol analysis showed a significant decrease in prevalence of any food allergy overall, specifically in egg and peanut allergies, with early introduction. Infants with moderate AD (SCORAD 15–40) showed the clearest benefit from early introduction in this trial.18 Moreover, contrary to popular belief, early introduction of allergens did not interfere with breastfeeding.19 Further randomized controlled trials are needed to support the early introduction of other common allergens, but current observational data have supported this approach.
How Can Dermatologists Approach Concerns About Food Allergies?
Avoiding foods impairs tolerance, particularly in young infants with AD who will likely be inadvertently exposed to food antigens via their skin. If a parent/guardian reports an immediate reaction to a food, referral to an allergist for testing sensitivity to that specific food is recommended. However, in infants with no immediate reactions (such as hives within minutes of consuming the food in question, immediate vomiting, or wheezing), elimination diets are not recommended.
Parents/guardians often ask about elimination diets in hopes of identifying triggers for their child’s AD. These diets can appeal to caregivers as a safer approach compared with a slew of prescription ointments. However, avoiding foods can increase the risk of sensitization to those foods over time and should not be considered risk-free. A retrospective study of 300 children with concerns of food-triggered eczema found that after avoiding a food of concern, most commonly cow’s milk and egg, 19% of patients developed new immediate reactions to these foods.20 As for the reactions, 70% were cutaneous, but 30% were anaphylaxis.20 Avoidance of a food significantly increased the risk of developing an immediate reaction to that food. Therefore, elimination diets are not typically recommended, unless patients have immediate reactions to certain foods.
Conclusion
At first, it may seem daunting to include a discussion about food allergies in a visit for AD. However, many of these families have real concerns about food allergies, and they may even already be avoiding foods without their health care provider knowing. It is important to tell families that food allergies are not causing their eczema, but their eczema may be causing food allergies. A discussion of the facts, including the robust data regarding prevention of food allergies and the risks of elimination diets, may be a successful way to pivot these concerns into actionable prevention of allergic comorbidities.
References
1. Eigenmann PA, Beyer K, Lack G, et al. Are avoidance diets still warranted in children with atopic dermatitis? Pediatr Allergy Immunol. 2020;31(1):19-26. doi:10.1111/pai.13104
2. Shoda T, Futamura M, Yang L, et al. Timing of eczema onset and risk of food allergy at 3 years of age: a hospital-based prospective birth cohort study. J Dermatol Sci. 2016;84(2):144-148. doi:10.1016/j.jdermsci.2016.08.003
3. Martin PE, Eckert JK, Koplin JJ, et al. Which infants with eczema are at risk of food allergy? Results from a population-based cohort. Clin Exp Allergy. 2015;45(1):255-264. doi:10.1111/cea.12406
4. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315-1327. doi:10.1056/NEJMra1011040
5. Lack G. Epidemiologic risks for food allergy. J Allergy Clin Immunol. 2008;121(6):1331-1336. doi:10.1016/j.jaci.2008.04.032
6. Oranges T, Dini V, Romanelli M. Skin physiology of the neonate and infant: clinical implications. Adv Wound Care (New Rochelle). 2015;4(10):587-595. doi:10.1089/wound.2015.0642
7. Czarnowicki T, Krueger JG, Guttman-Yassky E. Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol.2017;139(6):1723-1734. doi:10.1016/j.jaci.2017.04.004
8. Du Toit G, Roberts G, Sayre PH, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803-813. doi:10.1056/NEJMoa1414850
9. Fleischer DM, Spergel JM, Assa’ad AH, Pongracic JA. Primary prevention of allergic disease through nutritional interventions. J Allergy Clin Immunol Pract. 2013;1(1):29-36. doi:10.1016/j.jaip.2012.09.003
10. Sicherer SH, Muñoz-Furlong A, Godbold JH, Sampson HA. US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol. 2010;125(6):1322-1326. doi:10.1016/j.jaci.2010.03.029
11. Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. J Allergy Clin Immunol. 2017;139(1):29-44. doi:10.1016/j.jaci.2016.10.010
12. Savage J, Sicherer S, Wood R. The natural history of food allergy. J Allergy Clin Immunol Pract. 2016;4(2):196-204. doi:10.1016/j.jaip.2015.11.024
13. Dunlop JH, Keet CA. Epidemiology of food allergy. Immunol Allergy Clin North Am. 2018;38(1):13-25. doi:10.1016/j.iac.2017.09.002
14. Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126(4):807-813. doi:10.1016/j.jaci.2010.07.028
15. Katz Y, Rajuan N, Goldberg MR, et al. Early exposure to cow’s milk protein is protective against IgE-mediated cow’s milk protein allergy. J Allergy Clin Immunol. 2010;126(1):77-82.e1. doi:10.1016/j.jaci.2010.04.020
16. Abrams EM, Chan ES. Prevention of non-peanut food allergies. Curr Allergy Asthma Rep. 2019;19(12):60. doi:10.1007/s11882-019-0891-1
17. Ierodiakonou D, Garcia-Larsen V, Logan A, et al. Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis. JAMA. 2016;316(11):1181-1192. doi:10.1001/jama.2016.12623
18. Perkin MR, Logan K, Tseng A, et al. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374(18):1733-1743. doi:10.1056/NEJMoa1514210
19. Perkin MR, Logan K, Marrs T, et al. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137(5):1477-1486.e8. doi:10.1016/j.jaci.2015.12.1322
20. Chang A, Robison R, Cai M, Singh AM. Natural history of food-triggered atopic dermatitis and development of immediate reactions in children. J Allergy Clin Immunol Pract. 2016;4(2):229-36.e1. doi:10.1016/j.jaip.2015.08.006
