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The physical examination can also provide evidence to suspect a peanut allergy and help focus the evaluation, although its findings alone are not sufficient evidence to be diagnostic for a peanut allergy.30 The presence of physical symptoms can verify the presence of an atopic disorder, such as urticaria or atopic dermatitis, and can also reveal symptoms that may be more suggestive of a nonallergic disorder and point to further evaluation and testing.30

It is important to note that self-reported symptoms have a low positive predictive value for peanut allergy, with multiple studies demonstrating that 50% to 90% of presumed food allergies of all types are not allergies on further examination.30 Therefore, although the medical history and physical symptoms are critical components of the diagnostic process, they alone do not provide enough information to be diagnostic.30

The most common subsequent steps in the diagnosis of peanut allergy include an evaluation of peanut-specific IgE by means of skin-prick testing or serum testing. These can help the clinician decide whether it is reasonable to perform an oral food challenge with peanuts.28 A skin-prick test is a safe, convenient, and inexpensive test used to elicit a localized IgE-mediated allergic reaction.14,30 A positive skin-prick test correlates with the presence of serum-specific IgE (sIgE) levels bound to the surface of cutaneous mast cells.30 To perform the test, a drop of peanut extract is typically placed on the forearm or back, and the skin is pricked with some form of skin-prick device, such as a lancet. This is an epicutaneous test and does not penetrate the epidermal/dermal junction. Negative (saline) and positive (histamine) controls are also placed at the same time. Results of the test are read 15 minutes after placing the test; a result is considered positive when the wheal from the extract has a mean diameter of 3 mm greater than the negative (saline) control, with a larger wheal diameter more suggestive of a clinically relevant allergy, although not necessarily a more severe reaction. In general, a skin-prick test has a high sensitivity and high negative predictive value, but low specificity and positive predictive value, compared with an oral food challenge.14,28,30 Therefore, the use of skin-prick tests alone can lead to over-diagnosis of peanut allergy; it is important to remember that a significant number of patients may have a positive skin-prick test but no clinical allergy.1

Evaluation of peanut-specific IgE in vitro can also assist in determining the likelihood of peanut allergy. Skin-prick testing and sIgE evaluation both identify the presence of allergen-specific antibodies, although, because sIgE measures the serum and skin-prick testing reflects IgE bound to cutaneous mast cells, the results may not correlate.30 Serum testing can be especially useful when skin-prick testing cannot be done (ie, if the patient has extensive skin conditions or is actively taking antihistamines).14,30 In this assay, peanut-specific IgE results are measured quantitatively, with a range of less than 0.35 kUA/L to greater than 100 kUA/L (although some labs report down to 0.10 kUA/L), with higher levels correlating with a higher probability of clinical reactivity but not severity of reaction.14,28 Data suggest that approximately 95% of patients will react during a peanut challenge if their peanut-specific IgE level is equal to 15 kUA/L or greater.14 However, the presence of sIgE represents an allergic sensitization and not always a true clinical allergy.30 Compared to skin-prick testing, sIgE measurement has a similar sensitivity but may have a greater positive predictive value.14,30 Therefore, serum sIgE represents an additional tool that may be useful in the diagnosis of peanut allergy, but it is not a diagnostic test alone for food allergy. Future research is being conducted to evaluate IgE binding to specific peanut proteins (such as Ara h 2) in distinct populations and may provide a more specific and accurate diagnostic test in certain populations.32,33

Oral food challenge is considered the gold standard for diagnosis of peanut allergy.28,34 Before initiating a food challenge, the suspected food should be fully eliminated from the diet for several weeks.30 The double-blind, placebo-controlled food challenge is the most rigorous and typically used in research settings.28,30 This process involves the patient ingesting incremental portions of peanut or placebo, hidden in a masking vehicle, at 15- to 30-minute intervals. Any signs and symptoms of an allergic reaction should be documented throughout the challenge, and, if a reaction occurs, the challenge should be stopped and patient symptoms should be managed.35 However, this process can be both labor and time intensive in a clinical setting, so an open oral food challenge is commonly done instead, although this introduces the risk of patient and physician bias.34

Studies suggest that some infants with allergic reactions to peanuts will outgrow their allergy, especially if they have low levels of sIgE.7,28,36 These children should be evaluated again by school age (4-6 years) to determine whether the allergy has been outgrown, although their skin-prick test and sIgE levels may remain positive for years even if they have outgrown their allergy. Therefore, an evaluation every 1 to 2 years may be appropriate.28

Prevention of Peanut Allergy

Previous clinical practice guidelines from organizations including the American Academy of Pediatrics have recommended delaying introduction of peanuts, especially in children considered high-risk for peanut allergy, for at least the first year of life or longer.37 In 2010, the “Guidelines for the diagnosis and management of food allergy in the United States” were published by an expert panel and coordinating committee that was convened by the National Institute of Allergy and Infectious Diseases (NIAID).30 These guidelines did not present a strategy for the prevention of peanut allergy because of a lack of definitive studies available. The guidelines differed from previous recommendations, however, by stating that “insufficient evidence exists for delaying introduction of solid foods, including potentially allergenic foods, beyond 4 to 6 months of age, even in infants at risk of developing allergic disease.”30

In 2015, the New England Journal of Medicine published the landmark results of the Learning Early About Peanut Allergy (LEAP) trial.38 The trial was based on a previous study by Du Toit and colleagues that was published in 2008, which found that the prevalence of peanut allergy was 10-fold higher among Jewish children in London compared with Jewish children in Tel Aviv, with the difference not accounted for by differences in atopy, social class, genetic background, or peanut allergenicity. In Israel, foods that contain peanuts are introduced into the diet in high quantities during the first year of life, while in the United Kingdom, children did not typically consume any peanuts during the first year of life. The findings raised the question of whether introduction of peanuts early in the first year of life would prevent the development of peanut allergy versus the standard practice of avoidance in many Western countries.39

The LEAP trial randomized 640 children aged 4 to 11 months with severe eczema, egg allergy, or both to either consume or avoid peanut-containing foods until age 60 months.38 At that time, a peanut oral food challenge was administered to determine the prevalence of peanut allergy. Patients in the LEAP trial were stratified upon study entry into 2 separate cohorts based on preexisting sensitivity to peanut extract, which was determined by skin-prick testing. One cohort consisted of infants with no measurable skin test wheal to peanut and the other consisted of infants who developed a wheal measuring 1 to 4 mm in diameter. Infants with a wheal measurement 5 mm or greater in diameter were not included in the study because these infants were presumed to be allergic to peanut. Among the 530 patients in the intent-to-treat population with a negative baseline skin-prick test, the prevalence of peanut allergy at age 60 months was 13.7% in the peanut avoidance group and 1.9% in the peanut consumption group (P <.001), equating to an 86.1% relative risk reduction in the prevalence of peanut allergy. Among the 98 patients with a positive skin-prick test result, the prevalence of peanut allergy at age 60 months was 35.3% in the peanut avoidance group and 10.6% in the peanut consumption group (P = .004), equating to a 70% relative risk reduction in the prevalence of peanut allergy.38

In 2016, the Enquiring about Tolerance trial was published, examining the effects of early introduction (at age 3 months) of several allergenic foods in the diet of breastfed infants on the development of food allergy in the general population. The results of the per protocol analysis were consistent with the LEAP trial and found the prevalence of peanut allergy between age 1 and 3 years to be 0% in the early introduction group versus 2.5% in the standard introduction group (P = .003).40

The LEAP study was the first randomized trial to study the use of early peanut introduction as a preventive strategy. Considering these data, the NIAID published an addendum to its 2010 guidelines in 2017 entitled, “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.”41 The addendum provides 3 separate guidelines for infants in varying risk categories for development of peanut allergy. A summary of the guidelines is illustrated in Table 4.41 The guidelines recommend evaluation of patients with severe eczema, egg allergy, or both with peanut sIgE, a skin-prick test, or both before introduction of peanuts to determine if peanut should be introduced. For these children, the guidelines recommend introduction of age-appropriate foods containing peanuts as early as age 4 to 6 months, after other solid foods have been introduced, to reduce the risk of peanut allergy.41

To reduce the risk of peanut allergy in children with mild to moderate eczema, the guidelines recommend introduction of peanut-containing foods around age 6 months, after other solid foods have been introduced and in accordance with family preferences. This introduction can occur at home if the family is comfortable, or the infant may have an in-office supervised feeding if that is preferable. For children without eczema or any other food allergy, the guidelines recommend that peanut-containing foods be introduced in the diet without restriction along with other solid foods in accordance with family preferences.41

 
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