CASE PRESENTATION

A 4-year-old boy has exhibited transient peanut allergy over the past few months, associated with itching around the mouth and face after eating peanuts, with one episode of urticaria after ingestion that resolved after one day. His mother now ensures that he avoids peanuts. There is no history of asthma or anaphylaxis in the child and no family history of peanut or other tree nut allergy. His father had childhood asthma.
Discussion Question

If the mother became pregnant with another child, would you recommend that she avoids eating peanuts during pregnancy and breastfeeding? Why or why not?
COMMUNITY FEEDBACK

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CASE DISCUSSION

Food allergy is a major public health issue and its prevalence has increased in recent years, with an 18% reported increase in children between 1997 and 2007 according to the CDC.[1,2] For example, the prevalence of self-reported peanut allergy increased from 0.4% to 1.4% between 1997 and 2008.[3] Prevalence estimates for food allergies vary widely depending on method of diagnosis of the food allergy (self-report, IgE positive, skin prick test positive, sensitization and food challenge). One metaanalysis reported a range from 1.2% to 17% for milk, 0.12% to 7% for egg, 0% to 2% for peanuts, 0% to 10% for shellfish allergies, and 3% to 35% for any food allergy among both children and adults.[4] Another study on plant food allergies[5] confirmed these findings, showing a wide

range of prevalence between studies regardless of the food type. In this study, the range was 0.1% to 1.4% for vegetables and 0.1% to 4.3% for fruits and tree nuts using food challenge tests, and less than 1% when assessed by skin prick test. Nonetheless, food allergy is the most common cause of anaphylaxis evaluated in the emergency room and a major cause of food-induced anaphylaxis which has increased 3-fold in the past decade in both the United Stated and the United Kingdom.[1,6] Food allergy prevalence among children is currently estimated at around 6%[2] and the rise mirrors the rise of other allergic conditions such as asthma, atopic dermatitis, and allergic rhinitis. Both genetic and environmental factors are believed to contribute to the rising incidence and the hygiene hypothesis has been postulated as a contributor, although it does not explain the immunological changes observed. The major causes of food allergies accounting for over 90% of cases in the United States are: milk, egg, peanuts, tree nuts, soybeans, fish, and shellfish.[7] Food allergy to egg, milk, wheat, and soy typically resolve with age (in around 85%)

but allergy to peanuts, tree nuts, and seafood is often lifelong[8] and only 15% to 20% of children with peanut, tree nut, fish, and shellfish allergy will develop spontaneous tolerance.[9] The most commonly used method to assess food-specific allergy is skin prick testing.[10] Intradermal testing has poor specificity and a greater risk of adverse reaction and is not appropriate for initial evaluation. Food challenge may be performed open or blinded and should be administered by an experienced clinician as interpretation may be problematic if reactions occur days later or the challenge is not designed correctly. Patients with a reported anaphylaxis to food do not need a food challenge if IgE testing is confirmatory.[10] Elimination diets are well tolerated by parents and may be used at any age with the aid of a dietician, and may result in marked improvement in symptoms without further treatment. Currently there are no specific diagnostic tests that can predict the spontaneous development of oral tolerance (including IgE-specific antibodies or skin prick tests), and tests are needed that can distinguish those with transient vs persistent forms of food allergy. There are 3 phenotypes

of children with IgE-mediated food allergy[9]: transient, persistent, and food pollen (oral allergy) syndrome. Transient food allergy is most likely to respond to therapy, and treatment increases the likelihood of tolerance developing and improved quality of life. Persistent food allergies are more challenging with greater likelihood of failure to desensitize, failure of oral tolerance and need for more prolonged treatment, and more severe adverse effects during treatment.
POLLING QUESTION RESPONSES

Two thirds of 46 respondents chose to continue avoidance of peanuts as the only strategy for the child, one fifth chose oral immunotherapy, and 13% chose subcutaneous immunotherapy. The majority chose avoidance because of the mild reaction seen so far in the child (urticaria and pruritis). Some respondents advocated for injectable epinephrine for the child as a precaution, and others recommended avoidance and use of antihistamines as needed, as the initial strategy. The period of peanut avoidance recommended was also uncertain, ranging from 7 years of age to adulthood. For a pregnant mother who already has a child with peanut

allergy, some respondents advocated exposure of the mother to peanuts during pregnancy and induction of tolerance early during infancy as a new approach toward preventing later allergies, while others recommended complete avoidance of peanuts not only for the child and mother but also the entire family, as a way to prevent allergic reaction in the index child. The wide range of responses indicates controversy and the continuing development of new approaches toward food allergies in children.
CASE RESOLUTION

Although the current mainstay of treatment for food allergies in children is prevention (elimination) and avoidance of exposure to the food, accidental ingestion may still occur and prevention of anaphylaxis is a major concern among parents. Diets that involve extensively heating foods such as milk or egg represent an alternative approach to allergen-specific immunomodulation of food allergy in some patients. For example, when baked goods were added to diets of tolerant children after exposure to heat treatment, no increases in acute allergic reactions or atopic disease were seen over 3 to 6 months[9] and often wheal sizes on skin prick tests decreased to levels seen in children treated with oral immunotherapy.

Desensitization is the ability to increase the amount of food protein required to induce a clinical reaction, while tolerance is the ability to consume large amounts of the protein after the treatment. Tolerance is the goal of immunotherapy. Approaches other than avoidance are being currently considered for treating food allergies, including oral (OIT), sublingual (SLIT), and epicutaneous (EPIT, or desensitization) immunotherapy with native food allergens and mutated recombinant proteins. In one trial subcutaneous immunotherapy for peanut allergy was found to reduce the rate of systemic reactions and to increase tolerance and desensitization over 12 months, but an accidental administration caused death by anaphylaxis in one subject resulting in study termination.[11] In OIT trials escalation of peanut doses has been found to be problematic, with many children not tolerating the higher doses and a high rate of adverse reactions causing dropouts and withdrawals. However, when OIT occurred successfully, peanutspecific IgE levels were found to be decreased by 12 to 18 months, and treated children were able to tolerate up to 1000 mg of peanut compared with only 190 mg for untreated children.[9] OIT has been reported to be successful for egg-induced anaphylaxis but adverse reactions are common (up to 25% of doses may be associated with adverse reactions). Food is usually mixed in a safe food vehicle and dose escalation occurs in a controlled setting until maintenance dosing is achieved and maintained at home. Children with allergy to milk, egg, fish, fruit, peanut, and celery have been

desensitized this way, but permanent tolerance may not be achieved.[12] Overall the data on OIT suggests that 10% to 20% of patients fail the initial rush/escalation phase (desensitization failure) and withdraw, 10% to 20% do not achieve the full planned maintenance dose, and overall 50% to 75% achieve and tolerate the maintenance dose. It is still unclear whether tolerance can be maintained for longer with longer duration of OIT. SLIT has been described for kiwi fruit, peach, and cows milk allergy. One study involved peanut allergy and children treated with SLIT (with the protein administered sublingually, held for 2 minutes and then swallowed) were found to react at a threshold 20 times greater than the placebo group after 12 months of therapy, and IgE levels also decreased after 4 months, indicating successful desensitization.[13] However, local oropharyngeal side effects were common and longer term studies are needed to assess for tolerance. Newer therapies for peanut and other food allergies include the use of allergen-nonspecific therapy, such as humanized monoclonal anti-IgE murine IgG1 antibody, but concerns have been expressed about the lack of effect in some patients and the high rate of severe allergic reactions during treatment.[9] Modified recombinant engineered food proteins have also been combined with bacterial adjuvants and administered like vaccines through the oral, nasal, subcutaneous, and rectal routes, but effectiveness for peanut allergies has been variable and unreliable[9] and studies are still

underway. A specific Chinese herbal tea has been shown to be highly effective in preventing peanut allergies in animals and phase 1 human studies are currently being evaluated.[14,15] Patients with even a single attack of anaphylaxis to food should be provided with injectable epinephrine pens with instruction for administration and follow-up technical assessment of skill. A second pen is recommended because the first dose may wear off after 20 minutes, and patients should wear a medical identification bracelet about their allergy. Children should have access to diphenhydramine or other antihistamines for more minor reactions such as urticaria.[10] In the school setting a personalized emergency action plan should be provided to the childs family to share with the school with instruction to call for activation of emergency medical services as soon as there is a need for using the autoinjector.[16] A majority of fatalities occurring in schools are attributed to delays in administering epinephrine. The child should be transported in supine position and should not be raised from supine to upright position during transportation because of a documented risk of the empty ventricle syndrome with risk of blood pooling in the legs leading to sudden death.[16] The importance of avoiding food sharing during school should be emphasized as well as meticulous hand washing by food handlers to prevent passing peanuts or other food allergens between dishes. It should also be noted that adolescents are at

highest risk of fatal food-induced anaphylaxis among children. The issue of preventing food allergies in the infant starting from the time of the mothers pregnancy has been controversial. European and American pediatric societies have now changed their recommendations for mothers and newborns because of a lack of effect of avoidance of peanuts and other potential allergens during pregnancy and breastfeeding on subsequent allergy.[17] Indeed recent evidence suggests that early introduction of peanut, milk, and egg into an infants diet may decrease the risk of IgE-mediated allergy to those foods.[9,18] Currently mothers are recommended not to avoid allergenic foods during pregnancy or breastfeeding. CME TEST To receive AMA PRA Category 1 Credit, you must receive a minimum score of 75% on the posttest. Which of the following best describes the prevalence of peanut allergy in the United States? Prevalence has remained stable over the past 20 years

Prevalence of self-reported allergy increased 3fold over 10 years Prevalence ranges from 4% to 6% Prevalence is higher among adults than in children A 6-year-old child has food allergy to milk and egg. Which of the following best describes the natural history of this condition? In 85% of children allergy will resolve with age In 50% of children allergy will resolve with age Only 20% will develop spontaneous tolerance 40% of children will develop spontaneous tolerance In a child with peanut allergy, which of the following treatments would be considered most effective for desensitization? Sublingual immunotherapy Chinese herbal medicine Humanized monoclonal anti-IgE murine IgG1 antibody

Immunotherapy using recombinant engineered food proteins