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米国での食物アレルギーの診断と管理のためのガイドライン:米国国立アレルギー感染症研究所(NIAID)専門家委員会の報告/Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.

Author:Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FE, Teach SJ, Yawn BP, Schwaninger JM.
Title:Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.
Citation:Journal of Allergy Clinical Immunology. 2010 Dec;126(6 Suppl):S1-58. doi: 10.1016/j.jaci.2010.10.007.
URL:http://www.ncbi.nlm.nih.gov/pubmed/ 21134576
Abstract:Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.
Section 1. Introduction
In summary, the Guidelines:
• list-behavior=unordered prefix-word= mark-type=disc
• Provide concise recommendations (guidelines numbered 1 through 43) to a wide variety of health care professionals on how to diagnose FA, manage ongoing FA, and treat acute FA reactions
• Identify gaps in the current scientific knowledge to be addressed through future research
• Identify and provide guidance on points of current controversy in patient management
A companion Summary of the NIAID-Sponsored Expert Panel Report has been prepared from the Guidelines. This Summary contains all 43 recommendations, all “In summary” statements, definitions (section 1.3.5), 1 diagnostic table for FA, and 1 summary table for the pharmacologic management of anaphylaxis. It does not contain background information, supporting evidence for the recommendations and “In summary” statements, and other summary tables of data. The Summary is not intended to be the sole source of guidance for the health care professional, who should consult the Guidelines for complete information.
Finally, these Guidelines do not address the management of patients with FA outside of clinical care settings (for example, schools and restaurants) or the related public health policy issues. These issues are beyond the scope of this document.
Section 2. Definitions, prevalence, and epidemiology of food allergy
A food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food.
Section 3. Natural history of food allergy and associated disorders
In summary: Most children with FA eventually will tolerate milk, egg, soy, and wheat; far fewer will eventually tolerate tree nuts and peanut. The time course of FA resolution in children varies by food and may occur as late as the teenage years. A high initial level of sIgE against a food is associated with a lower rate of resolution of clinical allergy over time.
An important part of the natural history of FA is determining the likelihood and the actual time of resolution of the FA.
• list-behavior=unordered prefix-word= mark-type=disc
• In children, a drop in sIgE levels over time is often a marker for the onset of tolerance to the food. In contrast, for some foods, the onset of allergy can occur in adult life, and the FA may persist despite a drop in sIgE levels over time.
• Changes in immediate SPTs in association with resolution of the FA are less well defined, since an SPT response to a food can remain positive long after tolerance to the food has developed. Nevertheless, a reduction in the size of the SPT wheal may be a marker for the onset of tolerance to the food.
Because the natural history of FA varies by the food, the natural history of each of the most common FAs for which data are available is addressed below.
Section 4. Diagnosis of food allergy
Guideline 1: The EP recommends that FA should be considered:
・In individuals presenting with anaphylaxis or any combina- tion of symptoms listed in Table IV that occur within min- utes to hours of ingesting food, especially in young children and/or if symptoms have followed the ingestion of a spe- cific food on more than 1 occasion
・In infants, young children, and selected older children diag- nosed with certain disorders, such as moderate to severe AD, EoE, enterocolitis, enteropathy, and allergic proctocolitis (AP)
・In adults diagnosed with EoE
Rationale: Sufficient evidence exists to support the evaluation of FA in patients presenting with specific allergic signs and symptoms following the ingestion of food or with certain disorders frequently associated with allergic reactions to food, even in some cases without an apparent relationship to eating.
Balance of benefits and harms: Identification and avoidance of foods responsible for food-induced allergic reactions improve quality of life and potentially prevent life-threatening reactions and dis- orders. With the appropriate evaluation, there is a low risk of erroneously diagnosing someone as food allergic and adversely affecting his or her nutritional well-being and social interactions.
Quality of evidence: Moderate

Contribution of expert opinion: Significant

Guideline 2: The EP recommends using medical history and physical examination to aid in the diagnosis of FA.
・ Medical history: The EP recommends using a detailed medical history to help focus the evaluation of an FA. Al- though the medical history often provides evidence for the type of food-induced allergic reaction and the potential causative food(s) involved, history alone cannot be considered diagnostic of FA.
・ Physical examination: The EP recommends performing a focused physical examination of the patient, which may provide signs consistent with an allergic reaction or disorder often associated with FA. However, by itself, the physical examination cannot be considered diagnostic of FA.
Rationale: Medical history is useful for identifying food aller- gens that may be responsible for IgE-mediated allergic reactions, but it lacks sufficient sensitivity and specificity to definitively make a diagnosis of FA. Moreover, medical history is more useful in diagnosing immediate food-induced allergic reactions com- pared with delayed reactions. Further evaluation, for example lab- oratory studies or oral food challenges, is required to confirm a diagnosis of FA.
Balance of benefits and harms: The medical history and phys- ical examination provide evidence for suspecting FA and focus the evaluation. However, basing the diagnosis of FA on either his- tory or physical examination alone may lead to an erroneous di- agnosis of FA and unnecessarily restrictive diets that could have adverse nutritional and social consequences.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 3: The EP recommends that parent and patient re- ports of FA must be confirmed, because multiple studies demonstrate that 50% to 90% of presumed FAs are not allergies.
Rationale: Given the low positive predictive value of self- reported symptoms, it is important that all suspected FA be confirmed by appropriate evaluation (for example, oral food challenge or tests for allergic sensitization).
Balance of benefits and harms: Because unnecessary food avoidance affects quality of life and nutrition, there is possible harm in over-diagnosing FA.
Quality of evidence: High

Contribution of expert opinion: Minimal
Guideline 4: The EP recommends performing an SPT (also known as a skin puncture test) to assist in the identification of foods that may be provoking IgE-mediated food-induced allergic reactions, but the SPT alone cannot be considered diagnostic of FA.
Rationale: SPTs are safe and useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions, but they have a low positive predictive value for the clinical diagnosis of FA.
Balance of benefits and harms: The reagents and methods for performing SPTs are not standardized. Nevertheless, SPTs effectively detect the presence of sIgE, but many patients have sIgE without clinical FA. Compared with oral food challenges, SPTs have low specificity and low positive predictive value for making an initial diagnosis of FA. Thus, use of SPTs in the clinical setting may lead to over-diagnosis. However, in a patient with confirmed FA, an SPT is valuable in identifying the food(s) responsible for IgE-mediated FA. In the clinical setting, when compared with oral food challenges, SPTs have high sensitivity and high negative predictive values.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 5: The EP recommends that intradermal testing should not be used to make a diagnosis of FA.
Rationale: Insufficient evidence exists to support the use of intradermal testing for the diagnosis of FA. Moreover, intradermal tests carry a higher risk of adverse reactions than SPTs.
Balance of benefits and harms: Although intradermal testing may be more sensitive than skin prick testing for the diagnosis of IgE-mediated FA, there is no evidence to support such claims for protein-induced FA and insufficient evidence to support its routine use in diagnosing carbohydrate-induced FA. In addition, there is a greater risk of systemic adverse allergic reactions from intradermal tests compared with SPTs.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 6: The EP recommends that the routine use of measuring total serum IgE should not be used to make a diagnosis of FA.
Rationale: Insufficient evidence exists to support the proposal that measurements of total serum IgE levels can be a sensitive and specific test for FA.
Balance of benefits and harms: Although an elevated total se- rum IgE level is frequently found in atopic individuals and some investigators suggest that it may be useful when interpreting allergen-specific IgE levels, the EP could find no studies to sup- port such a claim. In addition, the sensitivity and specificity of this test compared with the outcome of oral food challenges is in- sufficient to warrant routine use in evaluating FA.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 7: The EP recommends sIgE tests for identifying foods that potentially provoke IgE-mediated food-induced aller- gic reactions, but alone these tests are not diagnostic of FA.
Rationale: sIgE tests are useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions, and specified ‘‘cutoff’’ levels, defined as 95% predictive values, may be more predictive than SPTs of clinical reactivity in certain populations, but when used alone they are not diagnostic of FA.
Balance of benefits and harms: sIgE tests are very useful for detecting the presence of sIgE antibodies, which indicates the presence of allergic sensitization. Fluorescence-labeled antibody assays have comparable sensitivity to that of SPTs, and the absolute levels of sIgE antibodies may directly correlate with the likelihood of clinical reactivity when compared with oral food challenges for the identification of foods provoking IgE- mediated FA.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 8: The EP suggests that the APT should not be used in the routine evaluation of non-contact FA.
Rationale: Insufficient evidence exists to support the use of the APT for the evaluation of FA.
Balance of benefits and harms: Although a number of studies have reported that the APT may be useful in the evaluation of FA in patients with AD and EoE, there is no agreement on the appropriate reagents, methods, or interpretation of these tests. When compared with oral food challenges, APTs show highly variable sensitivity and specificity among different studies.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 9: The EP suggests not using the combination of SPTs, sIgE tests, and APTs for the routine diagnosis of FA.
Rationale: No literature supports the proposal that the use of SPTs, sIgE tests, and APTs in combination for the evaluation of FA provides any significant advantage over the use of SPTs or sIgE tests alone.
Balance of benefits and harms: Combining the results of SPTs, sIgE tests, and APTs may provide higher positive and negative predictive values than any test alone, but use of all 3 tests is time consuming, inconvenient for the patient, and provides marginally improved positive and negative predictive values that may not be clinically relevant. However, a combination of 2 of these methods is sometimes more helpful for identifying foods likely to induce allergic reactions.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 10: The EP suggests that elimination of 1 or a few specific foods from the diet may be useful in the diagnosis of FA, especially in identifying foods responsible for some non-IgE-mediated food-induced allergic disorders, such as FPIES, AP, and Heiner syndrome, and some mixed IgE- and non-IgE-mediated food-induced allergic disorders, such as EoE.
Rationale: The use of an elimination diet in combination with a convincing history may be sufficient to diagnose FA in several food-induced allergic disorders, including FPIES, AP, and Heiner syndrome, and some mixed IgE- and non-IgE-mediated food- induced allergic disorders, such as EoE.
Balance of benefits and harms: In several non-IgE-mediated FA disorders and EoE, a suggestive medical history plus the elimination of the suspected food resulting in the resolution of symptoms provides evidence for the diagnosis of FA. In these situations, there are no known laboratory tests that are diagnostic of the causative food, and the oral food challenge, while a poten- tially useful diagnostic test, may provoke significant morbidity. Thus, many health care professionals base the initial diagnosis on history and clearing of symptoms while on the elimination diet, and reserve the oral food challenge for evaluating the eventual resolution of the disorder (ie, development of tolerance).
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 11: The EP recommends using oral food challenges for diagnosing FA. The DBPCFC is the gold standard. However, a single-blind or an open-food challenge may be considered diagnos- tic under certain circumstances: if either of these challenges elicits no symptoms (ie, the challenge is negative), then FA can be ruled out; but when either challenge elicits objective symptoms (ie, the challenge is positive) and those objective symptoms correlate with medical history and are supported by laboratory tests, then a diagnosis of FA is supported.
Rationale: DBPCFC is the most specific test for diagnosing FA. However, due to the expense and inconvenience of DBPCFCs, single-blind and open-food challenges may be used in the clinical setting.
Balance of benefits and harms: The DBPCFC markedly reduces potential bias of patients and supervising health care professionals that may interfere with the appropriate interpretation of oral food challenges, and corresponds most closely to the natural ingestion of food. Other diagnostic tests lack specificity and may lead to the unnecessary exclusion of foods from patients’ diets. However, the DBPCFC is time consuming, expensive, and, like any form of oral food challenge, subjects the patient to potential severe allergic reactions. Single-blind and open-food challenges are frequently used to screen patients for FA. When negative, they may be considered diagnostic in ruling out FA, and when positive (ie, when ‘‘immediate’’ objective allergic symptoms are elicited), they may be considered diagnostic in patients who have a supportive medical history and laboratory data.
Quality of evidence: High
Contribution of expert opinion: Moderate
Guideline 12: The EP recommends not using any of the following nonstandardized tests for the routine evaluation of IgE-mediated FA:
・ Basophil histamine release/activation
・ Lymphocyte stimulation
・ Facial thermography
・ Gastric juice analysis
・ Endoscopic allergen provocation
・ Hair analysis
d Applied kinesiology

・ Provocation neutralization
・ Allergen-specific IgG4

・ Cytotoxicity assays

・ Electrodermal test (Vega)

・ Mediator release assay (LEAP diet)
Rationale: There is a lack of evidence demonstrating that any of these nonstandardized tests has any value in the diagnosis of FA. However, although basophil histamine release/activation is not a routine diagnostic test for IgE-mediated FA, it is commonly used as a research tool.
Balance of benefits and harms: The utility of these tests has not been validated for the diagnosis of FA and may result in false positive or false negative diagnoses, leading to unnecessary dietary restrictions or delaying the appropriate diagnostic workup, respectively.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 13: The EP suggests that SPTs, sIgE tests, and APTs may be considered to help identify foods that are associated with EoE, but these tests alone are not sufficient to make the diagnosis of FA. The role of these tests in the diagnosis of other EGIDs has not been established.
Rationale: SPTs, sIgE tests, and APTs alone are insufficient to establish a causal role for FA in EoE, but they may be useful in identifying foods that should be investigated further with other di- agnostic tests, such as dietary elimination, oral food challenge, and endoscopy and esophageal biopsy.
Balance of benefits and harms: Some studies suggest that SPTs, sIgE tests, and APTs may be of value in identifying foods that cause symptoms of EoE. However, the utility of these tests has not been validated for the diagnosis of FA in EoE or other EGIDs and may result in false positive or false negative diagnoses.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 14: The EP recommends using the medical history and oral food challenge to establish a diagnosis of FPIES. However, when history indicates that infants or children have experienced hypotensive episodes or multiple reactions to the same food, a diagnosis may be based on a convincing history and absence of symptoms when the causative food is eliminated from the diet.
Rationale: FPIES is diagnosed based on a supportive medical history, resolution of symptoms with the elimination of the causative food, and, in many cases, provocation of symptoms following an open or single-blind oral food challenge.
Balance of benefits and harms: There are no laboratory studies with demonstrated specificity and sensitivity to diagnose FPIES, so an oral food challenge is necessary to establish the diagnosis. Al- though the oral food challenge may induce significant symptoms, there are no alternative methods with adequate predictability to diagnose FPIES. However, when the history is very compelling (for example, 2 or more reactions with classic symptoms to the same food in a 6-month period and elimination of symptoms when the causative food is removed from the diet), an oral food challenge may not be necessary to make the diagnosis. Because this disorder often lasts only a few years, however, subsequent oral food challenge is warranted to determine when FPIES has resolved and the food elimination diet can be terminated.
Quality of evidence: High

Contribution of expert opinion: Moderate
Guideline 15: The EP recommends using the medical history, resolution of symptoms when the causative food is eliminated from the diet, and recurrence of symptoms following an oral food challenge to diagnose AP.
Rationale: The evidence supports the conclusion that food protein-induced AP can be diagnosed based on a supportive medical history, resolution of symptoms with the elimination of the causative food, and recurrence of symptoms following an oral food challenge. Balance of benefits and harms: Because there are no laboratory studies with sufficient specificity and sensitivity to diagnose food protein-induced AP, an oral food challenge is necessary to establish the diagnosis. Although the food challenge may induce blood in the stools, symptoms of AP are generally benign, and there are no alternative methods with adequate predictability to diagnose AP. In cases with a classic history of AP, a normal physical examination and resolution of symptoms following elimination of the causative food leads many investigators to believe that an oral food challenge is not required to establish the diagnosis. Since this disorder often lasts only 1 to 2 years, repeated challenges are warranted to determine when food elimination diets can be terminated.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 16: The EP recommends using the medical history, including the absence of symptoms while the causative food is avoided, and positive patch tests to diagnose ACD.
Rationale: There are a limited number of well-controlled studies demonstrating the utility of these methods in diagnosing ACD. However, the concept that patch testing can be useful in establishing the diagnosis of ACD is based on both the underlying immunologic mechanism involved in the disease and observations from general medical practice.
Balance of benefits and harms: Traditionally, patch testing has been used to support history in diagnosing ACD. Although there are insufficient well-controlled studies to demonstrate the benefits of these methods in diagnosing ACD, the concept of patch testing largely fits with the immunopathogenic mechanism involved. The harm of avoiding contact with the food identified by this method appears minimal.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 17: The EP suggests using the medical history, including the resolution of symptoms while the causative food is avoided, and positive patch tests to establish the diagnosis of systemic contact dermatitis.
Rationale: Insufficient well-controlled studies exist to demonstrate the utility of these methods in diagnosing systemic contact dermatitis.
Balance of benefits and harms: Traditionally, patch testing has been used to support a suggestive history in diagnosing this rare condition. Although there are few well-controlled studies to demonstrate the benefits of these methods in diagnosing systemic contact dermatitis, those that exist support the utility of these methods. The harm of eliminating a small number of foods on this basis appears minimal.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 18: The EP suggests using the medical history, including the absence of symptoms while the causative food is avoided, positive sIgE tests or SPTs, and positive immediate epicutaneous skin tests (for example, positive immediate responses to APTs), to establish the diagnosis of food-induced IgE-mediated contact urticaria.
Rationale: There are a limited number of well-controlled studies demonstrating the utility of these methods in diagnosing IgE- mediated contact urticaria, but traditionally these methods have been used and found to correlate with clinical symptoms.
Balance of benefits and harms: Although there are few well- controlled studies to demonstrate the benefits of these methods in diagnosing IgE-mediated contact urticaria, test results appear to correlate with clinical symptoms. The potential harm of avoiding contact with foods provoking contact urticaria appears to be minimal.
Quality of evidence: Low

Contribution of expert opinion: Significant
Section 5. Management of nonacute allergic reactions and prevention of food allergy
Guideline 19: The EP recommends that individuals with documented IgE-mediated FA should avoid ingesting their specific allergen or allergens.
Rationale: The EP recognizes that allergen avoidance is a strategy that is unproven in RCTs. However, allergen avoidance is currently the safest strategy for managing FA.
Balance of benefits and harms: For individuals with FA, ingesting food allergens can cause allergic reactions ranging in se- verity from mild to life-threatening. Carefully planned allergen- free diets can provide sufficient nutrients to maintain a healthy and active life. In addition, there is no evidence that strict food avoidance (compared with less strict avoidance) has any effect on the rate of natural remission to a specific food allergen.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 20: The EP recommends that individuals with documented non-IgE-mediated FA should avoid ingesting their specific allergen or allergens.
Rationale: The literature cannot readily be divided on the basis of IgE-mediated and non-IgE-mediated reactions. In general, the management of non-IgE-mediated FA is similar to that of IgE- mediated FA, in that the medical history, the age of the individual, and the specific food allergen are all-important considerations in developing the management plan. Although there are relatively few high-quality studies regarding treatment for non-IgE- mediated FA, the bulk of the evidence suggests that food avoidance is the best management plan.
Balance of benefits and harms: For individuals with FA, ingesting trigger foods can cause allergic reactions and serious illness. Carefully planned allergen-free diets can provide sufficient nutrients to maintain a healthy and active life. In addition, there is no evidence that strict food avoidance (compared with less strict avoidance) has any effect on the rate of natural remission to a specific food allergen.
Quality of evidence: Low
Contribution of expert opinion: Significant
Guideline 21: In individuals with documented or proven FA who also have 1 or more of the following—AD, asthma, or EoE —the EP recommends avoidance of their specific allergen or allergens.
Rationale: Only limited study data exist on this issue. In appropriately diagnosed individuals with FA, food allergen avoidance may reduce the severity of AD or EoE. Current evidence is not available to indicate whether food allergen avoidance will alter the course of AD, asthma, or EoE.
Balance of benefits and harms: This approach is not an additional burden for individuals already practicing food avoidance to manage FA.
Quality of evidence: Low
Contribution of expert opinion: Significant
Guideline 22: In individuals without documented or proven FA, the EP does not recommend avoiding potentially allergenic foods as a means of managing AD, asthma, or EoE.
Rationale: No conclusive evidence exists to suggest that avoiding food allergens reduces the severity of AD, asthma, or EoE in individuals who are not sensitized and have not demonstrated specific clinical reactivity to foods.
Balance of benefits and harms: Unnecessary food avoidance could place individuals at risk for nutritional deficiencies and growth deficits. There is no known benefit to avoiding potentially allergenic foods (such as (cow’s) milk, egg, peanut, tree nuts, wheat, soy, fish, and crustacean shellfish).
Quality of evidence: Moderate

Contribution of expert opinion: Moderate
Guideline 23: The EP recommends nutritional counseling and regular growth monitoring for all children with FA.
Rationale: Although few studies have evaluated whether food allergen avoidance results in nutritional deficiency, the EP acknowledges that obtaining adequate nutrition is a concern in this population.
Balance of benefits and harms: Avoidance of specific allergens can limit the availability of nutritious food choices. Nutrition counseling can help patients plan and consume an allergen-free yet nutritionally adequate diet.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 24: The EP suggests that individuals with FA and their caregivers receive education and training on how to interpret ingredient lists on food labels and how to recognize labeling of the food allergens used as ingredients in foods. The EP also suggests that products with precautionary labeling, such as ‘‘this product may contain trace amounts of allergen,’’ be avoided.
Rationale: Although current requirements under the Food Allergen Labeling and Consumer Protection Act (FALCPA) require food labels to disclose the presence of any of the 8 major food allergens when used as ingredients, the law does not address pre- cautionary labeling. Precautionary labeling is voluntary and is used at the manufacturer’s discretion. Ingredient labeling is not completely effective in preventing unintentional exposure to allergens.
Balance of benefits and harms: Ingredient lists on food pack- ages can help consumers identify the contents of products, but may be difficult to interpret. FALCPA provides for the use of plain-language labels for ingredients that are, or that contain, major food allergens. Difficult-to-interpret voluntary precautionary labeling statements place individuals at risk for unintentional exposure to allergens.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 25: The EP suggests follow-up testing for individuals with FA depending on the specific food to which the individual is allergic. Whether testing is done annually or at other intervals depends on the food in question, the age of the child, and the intervening medical history.
Rationale: Insufficient evidence exists to make a specific recommendation as to the timing for re-evaluating individuals for FA.
Balance of benefits and harms: It is recognized that children will likely outgrow allergies to certain foods, such as milk, egg, soy, and wheat, and be less likely to outgrow allergies to other foods, such as peanut, tree nuts, fish, and crustacean shellfish. Results of follow-up testing can guide decision making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 26: There are no medications currently recommended by the EP to prevent IgE-mediated food-induced allergic re- actions from occurring in an individual with existing FA.
Rationale: The current evidence does not support the use of pharmacologic therapy for IgE-mediated reactions to food.
Balance of benefits and harms: Pharmacologic agents have the potential to prevent or lessen the severity of food-induced allergic reactions by altering the immune response, but these agents may display significant side effects and predispose individuals to an increased risk for infection. Only limited safety and cost- effectiveness data are currently available.
Quality of evidence: Moderate
Contribution of expert opinion: Significant
Guideline 27: There are no medications currently recommended by the EP to prevent non-IgE-mediated food-induced allergic reactions from occurring in an individual with existing FA.
Rationale: The current evidence does not support the use of pharmacologic therapy to prevent non-IgE-mediated FA reactions. Balance of benefits and harms: The use of swallowed corticosteroids has the potential to lessen the severity of or prevent future food-induced allergic reactions, but these medications may cause significant side effects and predispose individuals to an increased risk for infection. Nevertheless, swallowed corticosteroids have
been shown to be beneficial in the treatment of EoE.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 28: The EP does not recommend using allergen- specific immunotherapy to treat IgE-mediated FA.
Rationale: Allergen-specific immunotherapy improves clinical symptoms of FA while on treatment. However, it is currently difficult to draw conclusions on the safety of such an approach and whether clinical tolerance (ie, improvement in clinical symptoms that persists even after allergen-specific immunotherapy is dis- continued) will develop with long-term treatment.
Balance of benefits and harms: Allergen-specific immunotherapy can improve clinical symptoms of FA for some patients. How- ever, additional safety and efficacy data are needed before such treatment can be recommended. Because of the risk of severe reactions, the approach should only be used in highly controlled settings.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 29: The EP does not recommend immunotherapy with cross-reactive allergens for treating IgE-mediated FA.
Rationale: Although some evidence exists to suggest that specific immunotherapy with cross-reactive allergens is beneficial in treating FA, additional safety and efficacy data are needed before such treatment can be recommended.
Balance of benefits and harms: It has been hypothesized that immunotherapy with cross-reactive antigens could benefit patients with FA, yet the safety of this approach has been evaluated in a highly controlled setting in only 1 study to date. Replication of these findings with additional safety and efficacy data in clinical practice settings is needed.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 30: The EP recommends that patients with FA and their caregivers be provided with information on food allergen avoidance and emergency management that is age and culturally appropriate.
Rationale: Food-allergen avoidance and the risk of severe allergic reactions can have substantial daily consequences for patients and their caregivers.
Balance of benefits and harms: Patients with FA and their caregivers (especially mothers) can experience anxiety and diminished quality of life because of the risk of anaphylaxis and the burden of selecting or preparing allergen-free foods. Concerns may change as patients with FA mature. Knowledge and skills related to management of FA may improve patient and caregiver self-efficacy, quality of life, and successful allergen avoidance.
Quality of evidence: Low
Contribution of expert opinion: Significant
Guideline 31: The EP recognizes the varying consensus recommendations of the different organizations on this particular vaccine
and recommends that children with egg allergy, even those with a
history of severe reactions, receive vaccines for measles, mumps,
and rubella (MMR) and for MMR with varicella (MMRV). The
safety of this practice has been recognized by ACIP and AAP and
is noted in the approved product prescribing information for these vaccines.
Rationale: MMR and MMRV vaccines are safe for children with egg allergy, even for those with a history of severe reactions. Balance of benefits and harms: Vaccinations can prevent severe disease, and in most states proof of MMR vaccination is required for school entry. Varicella vaccine also is required in most states. The measles component of the vaccine is produced in chicken-embryo fibroblasts, which may be of concern to parents of children with egg allergy. However, MMR and MMRV vaccines are safe to administer to these children because the egg protein content of these vaccines is very low. Severe allergic adverse events attributable to varicella vaccination are extremely rare, and serious allergic reactions could be due to non-egg vaccine components, including gelatin.

Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 32: The EP suggests that patients at risk for developing FA do not limit exposure to potential nonfood allergens (for ex- ample, dust mites, pollen, or pet dander). Patients at risk for developing FA are defined as those with a biological parent or sib- ling with existing, or history of, allergic rhinitis, asthma, AD, or FA. This definition of ‘‘at risk’’ is used throughout sections 5.2 and 5.3.
Rationale: Insufficient evidence exists to suggest that avoidance of allergens that are not food allergens has any effect on the natural history of FA.
Balance of benefits and harms: It has been hypothesized that exposure to nonfood allergens could increase the likelihood of developing an FA in patients at risk for atopic disease, but there are insufficient data to support this hypothesis.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 33: The EP suggests that patients at risk for developing FA do not need to limit exposure to foods that may be cross-reactive with the 8 major food allergens in the United States (milk, egg, peanut, tree nuts, soy, wheat, fish, and crustacean shellfish).
Rationale: Insufficient evidence exists to determine whether eating foods that cross-react with the major allergenic foods will cause symptoms.
Balance of benefits and harms: It has been hypothesized that exposure to possible cross-reactive foods could result in an allergic response. However, unnecessary food avoidance can result in inadequate nutrient intake and growth deficits.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 34: The EP suggests that the general population of children not be tested for FA to highly allergenic foods prior to their introduction into the diet. The general population of children does not have pre-existing severe allergic disease and also does not have a family history of FA.
Rationale: Insufficient evidence exists to suggest whether, or which, foods should be tested prior to introduction.
Balance of benefits and harms: Testing prior to introduction could potentially prevent allergic reactions, but there is currently no practical consensus on which (if any) foods should be tested.
Quality of evidence: Low
Contribution of expert opinion: Significant
Guideline 35: The EP suggests that children less than 5 years old with moderate to severe AD be considered for FA evaluation for milk, egg, peanut, wheat, and soy, if at least 1 of the following conditions is met:
・ The child has persistent AD in spite of optimized management and topical therapy.
・ The child has a reliable history of an immediate reaction after ingestion of a specific food.
Rationale: Insufficient evidence exists to determine the appropriate age to test for response to foods known to commonly cause IgE-mediated FA in infants or young children with AD or other risk factors. In spite of the lack of evidence, the opinion of the EP is that if a child is less than 5 years old and has persistent AD, there is benefit to finding out whether the child is allergic to a food.
Balance of benefits and harms: Early diagnosis can lead to better management of FA and reduce the risk of exposure to food antigens. However, testing is time-consuming and costly for patients and their families. In addition, severely restrictive diets may be harmful. Care should be taken to ensure these children are clinically allergic to a food prior to removing it completely from their diet.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 36: The EP does not recommend restricting maternal diet during pregnancy or lactation as a strategy for preventing the development or clinical course of FA.
Rationale: Insufficient evidence exists that maternal diet during pregnancy or lactation affects the development or clinical course of FA.
Balance of benefits and harms: Restricting exposure to food antigens either during pregnancy or through breast milk has been hypothesized as a means of preventing the development of FA, but it has not been shown conclusively to prevent FA. Adequate nutritional status during pregnancy and lactation is essential for optimal infant health, growth, and development.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 37: The EP recommends that all infants be exclusively breast-fed until 4 to 6 months of age, unless breast- feeding is contraindicated for medical reasons.
Rationale: There is not strong evidence that breast-feeding has a protective role in preventing atopic disease. However, because of other benefits of breast-feeding, it is recommended that all infants, including those with a family history of atopic disease, be exclusively breast-fed until 4 to 6 months of age, unless breast- feeding is contraindicated for medical reasons.
Balance of benefits and harms: Whether exclusive breast- feeding has a beneficial role in preventing atopic disease is un- clear, but there are no potential harms associated with exclusive breast-feeding until 4 to 6 months of age.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 38: The EP does not recommend using soy infant formula instead of cow’s milk infant formula as a strategy for preventing the development of FA or modifying its clinical course in at-risk infants (‘at risk’ is defined in Guideline 32, section 5.2.1).
Rationale: The literature reports little difference between soy infant formula and cow’s milk infant formula for the prevention of FA in at-risk infants.
Balance of benefits and harms: There appears to be neither long-term harm nor significant benefit in using soy infant formula.
Quality of evidence: Moderate

Contribution of expert opinion: Minimal
Guideline 39: The EP suggests that the use of hydrolyzed infant formulas, as opposed to cow’s milk formula, may be considered as a strategy for preventing the development of FA in at-risk infants who are not exclusively breast-fed (‘‘at risk’’ is defined in Guideline 32, section 5.2.1). Cost and availability of extensively hydrolyzed infant formulas may be weighed as prohibitive factors.
Rationale: Only a limited number of studies exist to indicate that extensively or partially hydrolyzed infant formulas reduce the development of CMA in at-risk infants.
Balance of benefits and harms: The preventive effects of hydrolyzed infant formulas on allergy in infants and children vary considerably from study to study. Evidence from a small number of large-population studies shows that feeding hydrolyzed infant formulas, as compared with cow’s milk infant formula, to at-risk infants may reduce, albeit to a small extent, allergy in infants and children and CMA in infants. None of the studies show reduction in allergy to foods other than cow’s milk.Practical and cost considerations of extensively hydrolyzed infant formulas may limit their use to infants who are at risk and not being exclusively breast-fed. There is no evidence to suggest exclusive feeding with a hydrolyzed infant formula is more likely to prevent atopic disease than exclusive breast-feeding. The influence of duration of use on the effect of hydrolyzed infant formula on the development of allergy is not known.
Quality of evidence: Moderate

Contribution of expert opinion: Moderate
Guideline 40: The EP suggests that the introduction of solid foods should not be delayed beyond 4 to 6 months of age. Potentially allergenic foods may be introduced at this time as well.
Rationale: 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 (as defined in Guide- line 32, section 5.2.1) of developing allergic disease.
Balance of benefits and harms: Restricting exposure to food antigens during infancy has been hypothesized as a means of pre- venting development of FA. However, restricting developmentally appropriate solid food variety beyond age 6 months can lead to in- adequate nutrient intake, growth deficits, and feeding problems.
Quality of evidence: Low

Contribution of expert opinion: Significant
Section 6. Diagnosis and management of food-induced anaphylaxis and other acute allergic reactions to foods
Guideline 41: The EP recommends that the health care professional considering a diagnosis of food-induced anaphylaxis should understand:
・The signs and symptoms characteristic of anaphylaxis
d The timing of symptoms in association with food ingestion/
exposure

・Comorbid conditions, such as asthma, that may affect treat-
ment and outcome

・The limited utility of laboratory parameters in the acutecare setting
Rationale: The evidence and expert opinion support prompt recognition and diagnosis of food-induced anaphylaxis.
Balance of benefits and harms: Prompt recognition and diagnosis of food-induced anaphylaxis are essential and necessary to ensure appropriate health outcomes and to prevent progression to life-threatening reactions. Potential harm, including the possibility of death, exists if the diagnosis is delayed or not recognized.
Quality of evidence: Low

Contribution of expert opinion: Significant
Guideline 42: The EP recommends that treatment for food- induced anaphylaxis should focus on the following:
・ Prompt and rapid treatment after onset of symptoms (see Table VI for a summary of treatment in an outpatient or hospital setting)
・ Intramuscular (IM) epinephrine as first-line therapy

・ Other treatments, which are adjunctive to epinephrine
dosing
Rationale: Evidence supports the implementation of rapid re- sponse and treatment for food-induced anaphylaxis and the use of IM epinephrine as first-line therapy.
Balance of benefits and harms: The benefits of appropriate treatment for anaphylaxis begin with IM epinephrine injection. Benefits of epinephrine treatment far outweigh the risks of unnec- essary dosing. Delays in instituting therapy with epinephrine are associated with risks of death and morbidity.
Quality of evidence: Moderate

Contribution of expert opinion: Significant
Guideline 43: The EP recommends that the management of food-induced anaphylaxis should focus on the following:
・ Dosing with IM epinephrine followed by transfer to an emergency facility for observation and possible further treatment
・ Observation for 4 to 6 hours or longer based on severity of the reaction
・ Education for patient and family on:
– Allergen avoidance
– Early recognition of signs and symptoms of anaphylaxis
– Anaphylaxis emergency action plan implementation
– Appropriate IM epinephrine administration
– Medical identification jewelry or an anaphylaxis wallet 
card
・ Epinephrine auto-injector prescription and training provided at the time of discharge

・ Continuation of adjunctive treatment after patient discharge:
– H1 antihistamine: diphenhydramine every 6 hours for 2- 
3 days; alternative dosing with a non-sedating second 
generation antihistamine
– H2 antihistamine: ranitidine twice daily for 2-3 days
– Corticosteroid: prednisone daily for 2-3 days
・ Follow-up appointment with primary health care professional (after the food-induced anaphylactic reaction), with consideration for additional follow-up with a clinical specialist such as an allergist/immunologist
Rationale: Despite the lack of evidence, the EP recommends close monitoring, scheduled follow-up, and patient education for effective management following anaphylaxis.
Balance of benefits and harms: The benefits of appropriate management following food-induced anaphylaxis should serve to further protect the patient through long-term follow-up care and education, with the benefit of preventing subsequent events. The potential harm is minimal if appropriate education is employed.
Quality of evidence: Low
Contribution of expert opinion: Significant
邦文タイトル:米国での食物アレルギーの診断と管理のためのガイドライン:米国国立アレルギー感染症研究所(NIAID)専門家委員会の報告
一般向け要約食物アレルギーは小児にも成人にも影響する重要な公衆衛生の課題で、現在増加傾向にある。致命的でもある重篤なアレルギー反応の危険性があるにもかかわらず、食物アレルギーの有効な治療法は存在せず、抗原の除去と症状への対処のみである。診断や対応方法についても診療体制によってまちまちである。さらにしばしば患者は食物による非アレルギー性の反応に戸惑うため、実際よりも食物アレルギーが世間に多いと誤解されている。そこでNIAIDでは臨床ガイドラインを作成した。ガイドラインは広く医療従事者に使用してもらえるようになっている。ガイドラインでは食物アレルギーの定義、合併症についても取り上げ、IgE依存性とIgE非依存性とに焦点を当てている。項目は疫学、自然経過、診断、管理法に加えて重篤症状やアナフィラキシーの対応についても述べ、臨床上の43の推奨分も掲載している。
専門医コメント米国の国立アレルギー・感染症研究所が出したガイドラインです。食物アレルギーの罹患率や疫学について、食物アレルギーの自然経過については知識のギャップについて指摘し、治療と管理に関しては推奨されている43の事項について根拠の質を3段階に分類して評価しています。科学的根拠に乏しい推奨事項もあり、今後の研究でさらに検討が必要であるとしています。