Adverse Food Reactions—An Emerging Issue for Adults

RESEARCH Review Meets Learning Need Codes 2000, 2060, 3005, and 5110. To take the Continuing Professional Education quiz for this article, log in to ADA’s Online Business Center at www.eatright.org/obc, click the “Journal Article Quiz” button, click “Additional Journal CPE Articles,” and select this article’s title from a list of available quizzes.

Adverse Food Reactions—An Emerging Issue for Adults ISABEL SKYPALA, PhD

ABSTRACT Adverse reactions to foods are classified according to the presence or absence of involvement of the immune system, which may or may not include the production of immunoglobulin E (IgE) antibodies. This review focuses on the epidemiology, diagnosis, and management of adverse food reactions, primarily in adults, and excluding celiac disease and lactose intolerance. Reported reactions to foods are often believed to be manifestations of a food allergy; however, IgE-mediated food allergy only affects 1% to 4% of adults, with seafood, tree nuts, peanuts, fruits, and vegetables being the most common triggers. Diagnosis is challenging and most commonly achieved through careful evaluation of clinical history followed by elimination and reintroduction or challenge with the suspected offending food. With acute-onset allergic reactions, estimation of food-specific IgE antibodies is frequently used to confirm or refute the diagnosis. Recent developments, such as single allergen assays, enhance the diagnosis of IgE-mediated food allergy, but the gold standard remains oral food challenge. Despite recent advances in the management of food allergy, including the promotion of oral tolerance, the mainstay of management is still the avoidance of food triggers. Dietary management can be compromised by nutritional inadequacy, accidental exposure, food labeling, and quality of life or adherence issues. It is essential that adults with confirmed food allergy receive optimal nutrition and dietetic support to enable them to manage their condition. J Am Diet Assoc. 2011;111:1877-1891.

I. Skypala is director of rehabilitation and therapies, Royal Brompton & Harefield NHS Foundation Trust, London, UK. Address correspondence to: Isabel Skypala, PhD, Royal Brompton & Harefield NHS Foundation Trust, Sydney St, London, England SW3 6NP. E-mail: [email protected] Manuscript accepted: May 20, 2011. Copyright © 2011 by the American Dietetic Association. 0002-8223/$36.00 doi: 10.1016/j.jada.2011.09.001

© 2011 by the American Dietetic Association

F

ood allergy and intolerance describe a wide range of adverse reactions to foods. In 2010, an expert panel sponsored by the National Institute of Allergy and Infectious Diseases published guidelines for the diagnosis and management of food allergy in the United States (1). These guidelines define food allergy as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. A food is defined as any substance intended for human consumption, including drinks, food additives, and dietary supplements. They propose that all adverse food reactions be classified as either immune-mediated (food allergy and celiac disease) or nonimmune mediated (formerly known as food intolerances), which are themselves subdivided into four categories (see the Figure). The four categories of immune-mediated adverse food reactions are immunoglobulin E (IgE)-mediated, non–IgE-mediated, mixed–IgEand non–IgE-mediated, and cell-mediated. Nonimmune mediated conditions include metabolic, pharmacologic, toxic, and other/idiopathic/undefined. This new definition is similar to one published in 2004 by a taskforce of the European Academy of Allergy and Clinical Immunology (2), which proposed all nontoxic adverse reactions foods be termed food hypersensitivity and categorized as immune or nonimmune mediated conditions. The two sets of definitions both include celiac disease in the immunemediated section, and lactose intolerance as a nonimmune mediated condition; however, the US guidelines do not advocate the use of the term “food hypersensitivity” (FHS). The mechanisms of immune-mediated adverse food reactions involve recognition of harmless antigens, or allergens, from pollen or food proteins by the cells of adaptive immunity, the T and B lymphocytes (3). IgEmediated reactions involve antigen recognition, which promotes the differentiation of naive T cells into Th2 cells. The Th2 cells stimulate the B lymphocytes to produce allergen-specific IgE antibodies; these attach themselves to the surfaces of mast cells and blood basophils by way of a receptor, a process known as sensitization (4-6). Not all sensitized individuals will experience symptoms when next exposed to the allergen. However, where recognition of an allergen by the specific IgE antibodies occurs, the mast cell de-granulates, releasing histamine, prostaglandins, and leukotrienes

Journal of the AMERICAN DIETETIC ASSOCIATION

1877

Adverse Food Reactions

Non Immune-mediated (primarily food Intolerance)

Immune-mediated (Food Allergy and Celiac Disease)

Non IgEmediated Urticaria Angioedema Anaphylaxis Immediate GI hypersensitivity Oral allergy syndrome Including pollenfood syndrome and latex allergy Food-dependent, exercise-induced anaphylaxis

Metabolic

Cellmediated

IgE-mediated

Food protein– induced proctocolitis Food protein– induced enterocolitis Food proteininduced enteropathy Celiac disease Cow-milk inducedpulmonary haemosideroisis

Toxic Pharmacological

Mixed IgE and Non IgEmediated

Dermatitis herpetiformis Contact dermatitis

Eosinophiilic esophagitis and gastritis Atopic dermatitis

Other Idiopathic

Lactose intolerance

Vasoactive amines Salicylates Caffeine Theobromines

Scombroid poisoning Food additive hypersensitivity

Figure. Presentation of the many forms of adult-onset food hypersensitivity. IgE⫽Immunoglobulin E. Adapted with permission from Guidelines for the Diagnosis and Management of Food Allergy in the United States (1).

that provoke the characteristic symptoms of IgE-mediated food allergy. The allergen epitope is a specific peptide domain within a protein, associated with allergenic potential, which links to the specific IgE antibody to effect degranulation (7). Epitopes can either be linear (sequential) or conformational; linear epitopes are not degraded as easily as conformational epitopes, allowing the allergen to bind with the antibody even after heating (8). Non–IgE-mediated food allergic responses are usually delayed and most often involve the differentiation of naïve T cells into Th1 cells, or other cells of the immune system such as eosionophils. Initial allergen exposure leads to the sensitization of Th1 cells, with subsequent contact leading to cytokine release and chronic inflammation (9). The pathogenic mechanisms underlying the reactions of nonimmune mediated adverse food reactions are diverse, and some remain unknown. Food allergies are most prevalent in pediatric populations; pediatric allergists have played a prominent role in the development of diagnostic and management strategies. However, Deisner and colleagues (10) contend that the pediatric focus of most epidemiologic studies creates an impression that food allergies do not occur in the older population; they propose age-related changes can affect the immune system, increasing the potential for newly diagnosed food allergy in older adults (10). Möhrenschlager and Ring (11) suggest that as populations’ age, allergic reactions in older adults will become more frequent, but potentially masked by

1878

December 2011 Volume 111 Number 12

age-associated symptoms such as vitamin D deficiency and gastric pH increase. The presentation of adverse food reactions in adults is often more disparate, involving reactions to a wide range of foods (12); severe or life-threatening symptoms (13); and cofactors such as exercise, alcohol, and aspirin (7). This review will focus on adverse food reactions in adults, excluding celiac disease and lactose intolerance. The review will outline the current knowledge of the prevalence of adverse food reactions in adults, consider the pathophysiology and food triggers involved, analyze current and future diagnostic tools, and apprise the management issues involved. METHODS This subject review was not conducted as a systematic review; potentially relevant studies were identified by using electronic databases, including PubMed, Medline, and Google Scholar. The search terms included “allergy,” “food,” “diet,” “oral,” “diagnosis,” “prevalence,” and “nutrition” and individual foods, food additives, and naturally occurring food components. Studies were principally selected from the years 2000 to 2010, although occasionally evidence from the two preceding decades was included due to a lack of more recent evidence to support current knowledge or practices. Studies were principally from scientific journals with an impact factor of four or above; they were almost exclusively in English or were available as a translation. The following types of articles were selected in the order given below:

1. 2. 3. 4. 5. 6. 7.

randomized controlled trials; nonrandomized controlled clinical trials; before and after clinical trials; prevalence studies employing oral food challenge; systematic reviews and other meta-analyses; observational studies— cohort or case reports; and other subject reviews.

Prevalence The prevalence of allergic disorders is associated with age and commonly referred to as the allergic march; food allergy and atopic dermatitis traditionally predominate in early years with asthma and allergic rhinitis peaking in teenage and adult years, most often in the second or third decade (14). Most IgE-mediated food allergy is considered to be acquired during the first 1 to 2 years of life; it is unknown whether the condition in adults primarily represents a persistence of childhood symptoms or a new entity manifesting in adult life (15). The prevalence of food allergy was first determined by Bock in 1987 (16), who reported that 8% of infants and young children in the United States had a diagnosed food allergy, compared to 2.3% in Denmark (12), 4.2% in Germany (17), and 6% in the United Kingdom (18). The prevalence of adult food allergy is less well established; unlike pediatric studies that can utilize birth cohort data, studies in adults have often been questionnaire-based, occasionally supported by diagnostic test data. A meta analysis conducted by Rona and colleagues (19) concluded that many prevalence studies are based on perceptions of food allergy and do not include diagnosis made using oral food challenge (OFC), in particular the gold standard of diagnosis: double-blind, placebo-controlled food challenge (DBPCFC). Because approximately 20% of the population alters their diet on the suspicion of an adverse reaction to a food or food component (20), there is often great disparity between the reported prevalence as captured by questionnaire surveys and diagnosed food allergy. Only 1.0% of British 15-year-olds and 1.7% of Danish young adults were diagnosed with a food allergy using oral food challenges, despite a reported incidence of 18.7% and 19.6%, respectively (21,22). Through the analysis of Food Safety Survey data from a US Food and Drug Administration 2001 survey, Vierk and colleagues (23) reported a 9.1% prevalence of selfreported allergy among US adults, although only 5.3% of these subjects had doctor-diagnosed food allergy. Some studies have utilized OFC to provide actual prevalence data for adult food allergy. In 1994, Young and colleagues (24) sent a questionnaire to two random samples of 7,500 households in the United Kingdom. Of the 12,195 responses, 2,257 (18%) reported reactions to a food and 93 symptomatic subjects underwent oral challenge, following which a prevalence rate of 1.4% to 1.8% was determined (24). Ten years later, Zuberbier and colleagues (17) undertook a well-designed postal questionnaire survey of a similar magnitude involving 13,000 subjects from the population register of Berlin, Germany. Of those who responded, 2,298 (17%) reported reactions to foods, almost identical to the reported rate by Young and colleagues’ study (24). The results from 141 open OFCs and 216 DBPCFC indicated that the actual prevalence of food allergy in the adult subjects was 3.7%. The highest frequency for proven IgE-mediated reactions was seen in the 20- to 39-year age group, but

surprisingly for proven non–IgE-mediated reactions to foods, those aged 60 years or older had the highest rate. There is a strong association between food allergy in adults and other manifestations of atopy; Schafer and colleagues (25) reported that 73.1% of subjects reporting adverse food reactions also had hay fever. The most prevalent food allergy affecting adults is observed in people with concomitant seasonal hay fever. Oral allergy syndrome (OAS), first described by Amlot and colleagues in 1987 (26), is characterized by localised oropharyngeal symptoms related to the ingestion of any food (27,28). It manifests in people with seasonal allergic rhinitis due to structural homologies between pollen allergens and plant food proteins (29,30). The main food allergens involved in pollen food syndrome (PFS), the pathogenesis-related 10 proteins, and profilins, are usually susceptible to digestion and proteolysis, which means they cannot sensitize in the gut and cause a primary food allergy (27). However, the high shared degree of conserved surface residues and domains with pollen allergens allows them to bind to pollen-specific IgE antibodies on mast cells and trigger classic PFS symptoms (31). There is a growing consensus that pollen-related OAS should be specifically labeled as pollen-food allergy or PFS to distinguish it from other forms of OAS (32-34). The incidence of reported allergic rhinitis has tripled during the past 3 decades in the United Kingdom (35) and may continue to rise in some countries and continents in line with projected increases in pollen sensitization, possibly due to global warming changing the species and spread of pollen-bearing plants (36). This could lead to an epidemic of PFS in years to come. In summary, robust data for the actual prevalence of adult food allergy is sparse, especially for older adults, and the most recent figure of 3.7% may an underestimate. Therefore, the burden of food allergy in adults could become substantial, and more data on the etiology of food allergy diagnosed in later life is needed. PRESENTATION AND TRIGGERS OF ADVERSE FOOD REACTIONS Symptoms Adult-onset FHS can manifest in many forms (see the Figure); IgE-mediated food allergic symptoms (see the Figure) most commonly include pruritis, urticarial rash or hives, flushing, and angioedema although tachycardia, hypotension, throat tightness, bronchospasm, shortness of breath, and collapse can also occur in some individuals. The most severe reaction is anaphylaxis, defined as a life-threatening generalized or systemic hypersensitivity reaction that often includes multiple organ failure, hypotension, and shock (37). Zuberbier and colleagues (17) found the most common reported symptoms in 2,298 adults to be gastrointestinal (12.8%) and dysaesthesia of the tongue (11.9%) with eczema, urticaria, allergic rhinitis, and angioedema of the lips all reported to affect ⬎7% of respondents (17). Other studies suggest that the most common symptom in adults are oropharyngeal symptoms, characteristic of PFS. Erikkson and colleagues (38) surveyed 600 subjects with pollen allergy; the most frequent symptoms reported by the 390 with adverse food reactions were oral pruritis (72%) and rhinoconjunctivitis (39%). Osterballe and colleagues (12) showed that of those adults with a confirmed food allergy through oral

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1879

food challenge, 86% had OAS symptoms. Although IgEmediated food allergic symptoms in adults are anecdotally reported to appear within 30 to 120 minutes after ingestion of the primary sensitizing allergen, Ortalani and colleagues’ (29) careful characterization of OAS and PFS subjects demonstrated that these symptoms usually occur within 5 minutes of eating. Both immediate and delayed-onset reactions can occur in non–IgE-mediated food allergy (39). Apart from celiac disease, the other most common manifestation of non– IgE-mediated food allergy in adults is eosinphilic esophagitis (EoE), a chronic disorder characterized by eosinophilic infiltration of the esophageal mucosa (see the Figure). Very few studies have been published on adults with this condition, but the small amount of evidence available suggests that presentation in adults usually involves dysphagia and food impaction (40,41). Some nonimmune mediated conditions, such as lactose intolerance, have well recognized symptoms. Others are less easy to detect through symptom history. Pharmacologic reactions involving naturally occurring substances in foods or beverages may occur within 30 minutes of consumption and symptoms may be analogous to those of IgE-mediated food allergy. Attaran and Probst (42) describe how histamine fish poisoning, also known as scombroid poisoning, can commonly be mistaken for food allergy due to the symptoms of flushing, sweating, urticaria, gastrointestinal symptoms, palpitations, and bronchospasm. Food additive hypersensitivity reactions may occasionally be immediate, as in the case of sulfite hypersensitivity, but reactions to other additives such as colorings, flavor enhancers, and other preservatives are usually delayed. In summary, adult FHS can manifest in many forms and, although different physiological mechanisms are involved, symptoms of both immune and nonimmune-mediated FHS may share similarities that can hamper diagnosis. Food Triggers The main triggers of IgE-mediated food allergy in adults are most commonly considered to be seafood, peanuts, tree nuts, fruits, and vegetables (see Tables 1 and 2 for a summary of individual foods). Most immune-mediated food allergy in infancy and early childhood is provoked by cow’s milk or egg (79,80), and often resolves in childhood or adolescence (81,82); presentation in adults is rare. Despite this, cow’s milk is frequently reported by adults to provoke adverse food reactions (17), especially in foodrelated irritable bowel syndrome (83) and respiratory conditions (84). Zuberbier and colleagues (17) found that 15.9% of their subjects had non–IgE-mediated reactions to cow’s milk confirmed through DBPCFC. Eggs are rarely reported to cause adverse food reactions in adults, although newly diagnosed egg allergy can occur as a result of cross-reactivity between birds and eggs. Bird egg syndrome was described in 13 egg-allergic adults by Szépfalusi and colleagues (85); all subjects were sensitized to the egg yolk allergen Alpha livetin and 92% were also sensitized to allergens in bird’s feathers. Some food triggers can provoke severe reactions; seafood (Table 1) is reported to cause 10% of all cases of anaphylaxis to foods in France and 8% of fatal anaphylaxis in the United Kingdom (86,87). Shellfish were implicated in 24% of all reported reactions in Ross and

1880

December 2011 Volume 111 Number 12

colleagues’ (13) analysis of 20,821 emergency department hospital visits, including 2,333 for anaphylaxis, from the US National Electronic Injury Surveillance System (13). Although most reactions to fruits and vegetables will be PFS involving mild symptoms, Ross and colleagues’ data (13) also showed fruit was implicated in 12% of reported severe reactions to foods compared to 7% for peanuts and 4% for tree nuts. Other plant-food cross reactions include those to latex (Table 2) and nonspecific lipid transfer proteins (nsLTP). Sensitization to lipid transfer protein allergens is most prevalent in southern Europe. A panEuropean study reported results from 389 patients demonstrating that apple allergy in The Netherlands, Austria, and Italy is associated with sensitization to Bet v 1 and its apple homologue, Mal d 1, whereas in Spain apple allergy is related to peach allergy and sensitization to the apple lipid transfer protein Mal d 3 (88). Although wheat allergy (Table 1) is predominantly a pediatric disease, wheat can precipitate IgE-mediated food allergy in adults, most notably as a common trigger of food-dependent, exercise-induced anaphylaxis (FDEIA) (89), a condition first reported in 1979 (90). Those affected are asymptomatic to the trigger food except when it is consumed in close proximity with exercising. The prevalence is unknown, although studies suggest that ⬎80% of anaphylaxis cases involving exercise could be food related (91,92). Jogging is the most common exercise known to provoke FDEIA, but data presented by Shaddick and colleagues (93) from their 10-year follow-up survey of FDEIA cases showed that low-level exercise such as walking, shopping, or sweeping can also generate a response. Although wheat is a common trigger food, shellfish, tomatoes, celery, peanuts, corn, soy, strawberries, and cheese have all been reported to provoke FDEIA (89-91,93). Aside from its role in celiac disease, wheat is also reported to provoke gastrointestinal symptoms in other conditions. Monsbakken and colleagues (83) studied perceived food intolerance in subjects with irritable bowel syndrome and reported that 14.3% of subjects associated wheat with abdominal symptoms. Nonimmune mediated food triggers, summarized in Table 3, have been rarely studied in a robust manner. Food additives in particular are commonly perceived to be a problem by the public, but only sulfites have been studied in depth. Vally and colleagues (113) surveyed 366 adult subjects with asthma and demonstrated a significant association between wine-induced asthma and asthma triggered by sulphite-containing foods. However, in a separate study, only 16% of 24 self-reporting wine-sensitive asthmatics responded when challenged to sulfite, and then only at the highest dose (114). A study on recurrent chronic idiopathic urticaria showed that sensitivity to food additives may be of the order of 1% to 3% in this group (95). Of 838 patients with recurrent idiopathic urticaria, 116 (14%) had positive DBPCFC to mixed challenges containing tartrazine, erythrosine, monosodium benzoate, p-hydroxybenzoate, sodium metabisulphite, and monosodium glutamate. However when DBPCFC using incremental doses of single allergens were performed, only 24 subjects (2.8%) had a positive test to single food allergens given. Pharmacologic food reactions (Table 3) are also poorly understood. Hypersensitivity to acetyl salicylate (aspirin) is well characterized, but less is known about the effects

Table 1. Prevalence and features of food triggers commonly provoking primary adverse food reactions in adults Food trigger

Prevalence (%)

Natural history

Common sensitizing allergens/foods

Cross reactivity

␤-Parvalbumin—high levels in fish are associated with increased allergenicity (44) Cod is the most allergenic fish (45) ␤-Parvalbumin may be denatured by extreme heat (46) Invertebrate tropomyosin—Pen a 1, the dominant shrimp allergen, is the best characterized tropomyosin, and shares common allergenic determinants with other crustaceans and mollusks (48) Heat stable and remain potent after cooking (49) Ara h 2 is most common sensitizing peanut allergen (54)

Strong cross-reactivity between invertebrate fresh and salt water fish

Mono-sensitization to Ara h 2 linked to less severe allergy (55) Ara h 1 linked to severe peanut allergy (56) Walnuts commonest primary nut allergy in US (50) and Brazil nut in UK (52)

30% cross-reactivity to other legumes (58)

Fish

0.5 (43)a 0.2 (12)b 0.6 (23)c

Does not resolve (7)

Shellfish (crustaceans and mollusks)

2.5 (43)a 0.3 (12)b 1.1 (23)c

Does not resolve (47)

Peanuts

1.3% (50)a 0.4 (12)b 0.3 (23)c

8%-10% diagnosed in adulthood (51, 52) 20% resolution in adult life (53)

Tree nuts Seeds Wheat

1.1 (50)a 1.4 (59)b 0.4 (23)c Sesame ⬍1.0 (59)a 0.0 (12)b 0.4 (23)c

9% resolution (60) 0.1 (50)a ⬍1.0 (59)b 65% resolution (62)

Cross-reactivity between crustaceans and molluscs but not between vertebrate fish and shellfish

Cross-reactivity to tree nuts (57)

Cross-reactivity to peanuts (57)

Mustard 0.8%b (61) n-5 gliadin and other gliadins are important markers of wheat allergy (63) n-5 gliadin important marker of wheatdependent, exercise-induced anaphylaxis (64)

Cross-reacts with grass (21)

a

Reported prevalence. Actual prevalence. c US self-reported doctor-diagnosed prevalence in the United States. b

of its natural counterpart salicylic acid, a signaling molecule in plant foods (115). Dahlén and colleagues (116) reported that most aspirin-intolerant asthmatics are not affected by dietary salicylic acid (salicylate) in large amounts (116). There is currently no published evidence on the prevalence of salicylate hypersensitivity or the efficacy of dietary avoidance. Naturally occurring biogenic (vasoactive) amines in foods may also precipitate nonimmune-mediated pharmacologic reactions. This was refuted by Jansen and colleagues (117), but Maintz and Novak (118) concluded that histamine-intolerance has possibly been underestimated. Alcohol, coffee, and chocolate have also been reported to provoke adverse reactions. Alcohol can also be a cofactor in precipitating or exacerbating adverse food reactions. DIAGNOSIS Clinical History Clinical history can elicit detailed information essential to the formulation of a diagnosis. A thorough history

includes ascertainment of suspected or known food triggers, the quantity likely to provoke reactions, the range of symptoms observed (see the Figure), speed of symptomonset, reproducibility of reactions, and involvement of cofactors such as alcohol, exercise, or medication (7,13). Guidelines for the diagnosis and management of food allergy in the United States (1) found little published robust evidence to support the use of clinical history, but expert opinion on the panel recommended its use, provided it was not the sole diagnostic tool. Diagnostic questionnaires or diet and symptom diaries can supplement clinical history to aid identification of problem foods or assess the accuracy of food avoidance measures, but their efficacy has rarely been evaluated (119,120). The interpretation of a clinical history can be confounded by crossreactions, inaccurate recollection of events, and the involvement of multiple foods or the presence of cofactors. Clinical history alone is not diagnostic; a retrospective review of German adults investigated for reported allergic reactions to foods found that only 50% of those reporting adverse food reactions were diagnosed with IgE-me-

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1881

Table 2. Prevalence and features of plant food triggers commonly provoking cross-reactions in adults Primary sensitizing allergen Pollen

Prevalence

Food trigger Common sensitizing allergens/foods

8% (33)a Peanuts and 50% of birch-sensitized legumes individuals (65)a

96% of peanut-sensitized individuals had concomitant reactions to grass pollen (66) Reactions will most commonly involve raw peanuts Precipitant allergens are Ara h 5 (67) and Ara h 8 (68) Cross-reactions between homologous epitopes in the soybean allergen Gly m 4 and Bet v 1, the dominant allergen in birch pollen, are most common cause of soy symptoms in adults (69) Tree nuts Hazel nut allergen Cor a 1 commonly cross reacts with birch pollen allergen Bet v 1 (65) Other cross-reacting nuts include walnuts, almonds and Brazil nuts (38) Fruits and Pathogenesis-related proteins, the PR10 group (70-73) main allergen involved in vegetables pollen food sensitivity PR 10 allergens have high homology with Bet v 1 Profilins—affect 10-30% of those with PFS (70,74) Main foods—tree nuts, apples and stone fruits such as peaches and cherries (30) Latex 30%-50% in those with Fruits and Homologous profilin and PR3 allergens in natural rubber latex (Hevea brasilienisis) latex allergy (75)a vegetables cross-reacting with plant foods, including tomatoes, kiwifruit, avocado, pear, melon, chestnuts, bananas, and bell peppers (76) Lipid transfer Unknown All Plant food Primary sensitizing allergens, resistant to proteolysis, pH change and thermal protein groups treatments (77) Peach nonspecific lipid transfer protein allergen Pru p 3 linked with clinical crossreactivity to nonspecific lipid transer proteins in other foods (78) Lipid transfer proteins have so far been identified in the following foods: cabbage, mustard, tomato, carrot, lettuce, peaches, plums, apricots, cherries, strawberries, apples, pears, raspberry, orange, grapes, hazelnuts, almonds, walnuts, chestnuts, peanuts, wheat, corn, and barley a

Estimated or reported prevalence.

diated food allergy (121). Therefore, other tests are required to avoid unnecessary food restriction or misdiagnosis. An OFC is considered the definitive test for those who have a history of adverse foods reactions (1,122). However, other tests and dietary measures are helpful in providing additional information to supplement the clinical history. Tests for IgE-mediated Food Allergy Testing for the presence and level of specific IgE antibodies is helpful in establishing if the reactions are IgEmediated. A negative test suggests that the reaction is not IgE-mediated, but a diagnosis of non–IgE-mediated food allergy or a nonimmune-mediated condition cannot be ruled out. Food-specific IgE estimation can be ascertained by undertaking skin prick testing (SPT) or testing a serum sample (still often referred to as a radio-allergosorbant test), but a more correct term for techniques used today is immunoassay. When undertaking SPT, liquid commercial food extracts are placed on the skin and pricked through with a lancet. A resultant wheal of ⱖ3mm is considered to be a positive result (1,122,123). Some advocate the use of fresh foods for SPT in place of reagents; known as the prick-by-prick test method (PPT). Rancé and colleagues (124) demonstrated that using fresh milk, egg, and peanuts gave superior predictive values when compared with reagents. Others have dem-

1882

December 2011 Volume 111 Number 12

onstrated the efficacy of this method for testing foods that are likely to contain highly labile allergens such as fruits and vegetables (125). However, by their nature, PPTs lack standardization, and some believe the use of fresh foods may increase the risk of inducing severe reactions (126). An analysis by Codreneau and colleagues (127) of 34,905 PPT from 1,138 food-allergic patients of all ages showed that there were no severe reactions; the authors estimated the risk of a systemic reaction from PPT was 0.008%, very similar to the 0.005% for SPT using reagents. Both SPT and specific IgE tests have been well validated and the negative predictive value of either test is usually of the order of 95%. However undetectable serum food-specific IgE levels might occur in 10% to 25% of clinical reactions; therefore, negative results for this test need to be interpreted with caution (128). The positive predictive value of both tests is less impressive, often only 50% to 60%, (129,130). Several studies have examined the predictive value of SPT wheal diameters and levels of specific IgE with widely differing results. In addition, Wang and colleagues (131) showed that specific IgE results for predictive values from the test of one manufacturer cannot be applied to the results from other assays. Most of the data in all of these studies were from patients younger than age 18 years; thus, the relevance of these diagnostic decision points in adults is unknown. Guide-

Table 3. Prevalence and features of triggers of nonimmune mediated adverse food reactions Trigger Food additives

Salicylates

Prevalence (%)

At risk groups and symptoms

Foods involved

1.3 (12)a 0.1 (12)b 0.3 (23)c

1%-3% patients with urticaria (94) 5% asthmatics (sulphites) (95)

Unknown

Patients with lower gastrointestinal tract disease and a pre-existing intolerance of non-steroidal anti inflammatory drugs (96)

Sulfites—wine, vinegar, pectin, clear or light colored fruit juices such as grape juice and dehydrated foods such as dried fruit, dried onions, and coconut Tea, coffee, dried herbs, oranges, berries.

Biogenic amines

Unknown

Unknown

Dietary Methylxanthines

Chocolate

Anxiety and disordered sleep (102-104) Caffeine also reported to trigger allergic symptoms (105,106)

Alcohol

6.6 (24)a 0.07 (17)b 0.3 (23)c Unknown

Alcohol dehydrogenase deficiency prevalent in those of Asian ethnicity (108)

Variation in published levels due to differences in analytical techniques, varietal and growing conditions (97-99) Strong cheeses (eg, Parmesan, Roquefort), red wine, spinach, eggplant, yeast extract, and scombroid fish such as tuna and mackerel (100) Intakes of 36-250 mg are most likely to provoke a response (101) Caffeine in coffee Theobromine in chocolate Allergy to refined chocolate unlikely due to extensive processing (107) Allergy to pure alcohol very rare (109) Biogenic amines, salicylates, nonspecific lipid transfer protein allergens from barley, wheat, and grapes or added sulfite in alcoholic beverages may precipitate reactions (110-112)

a

Reported prevalence. Actual prevalence. c US self-reported doctor-diagnosed prevalence. b

lines suggest that SPT and specific IgE estimation are interchangeable; either can be used to good effect with clinical history or to confirm or refute negative tests (132). However, correlation between results from SPT and specific IgE tests may be less likely in adults; an evaluation of tests for egg, milk, peanut, walnut, and sesame by Pongracic and colleagues (133) found a significant correlation between the weal size of SPT and specific IgE levels in children but not in adults. A major advance in the diagnosis of FHS has been the sequencing of allergens and allergen epitopes. Assessing sensitization to specific allergens and allergen epitopes may aid diagnosis and predict resolution, although published studies have principally focused on milk and egg allergy in children (134-137). Specific allergen estimation using individual recombinant or native allergens can also support and refine the diagnosis of allergy to plant foods, in particular those foods that have poor positive predictive values using standard reagents such as wheat and soy (138). Palouso and colleagues (139) identified that the major allergen involved in wheat-dependent, exerciseinduced anaphylaxis is n-5 gliadin; estimation of this individual allergen has been shown to be useful in the diagnosis of this condition (63,64). Recombinant allergen technology is most helpful when differentiating between a primary allergy to peanuts or tree nuts and symptoms caused by cross-reactions to tree

and grass pollen. Flintermann and colleagues (140) evaluated hazelnut allergy in Holland; their data showed that subjects reporting mild symptoms were sensitized to the birch homologous allergen Cor a 1, whereas those reporting severe, systemic symptoms were sensitized to the nsLTP allergen Cor a 8. Most individuals with peanut allergy appear to be sensitized to the allergen Ara h 2, compared to ⬍10% of those tolerant of peanuts (54,55, 141). Those with cross-reacting PFS triggered by peanuts are more likely to be sensitized to the pathogenesis-related 10 Bet v 1 homologous allergen Ara h 8 (69). Such technology also enables geographical differentiation in terms of allergen sensitization; Krause and colleagues (142) reported that 19 out of 42 subjects (45%) in the Mediterranean area with peanut allergy had specific IgE to the nsLTP Ara h 9 but only 4.8% recognized Ara h 1, 2, and 3. Vereda and colleagues (143) data showed that peanut allergic subjects from Spain (n⫽50) were more likely to be sensitized to Ara h 9, whereas those from Sweden (n⫽70) and the United States (n⫽30) more frequently had antibodies to Ara h 1, 2, and 3. Diagnosis using micro array-based IgE technology, many individual allergens or allergen epitopes in a single chip, has been evaluated in children with suspected allergy to milk or egg. Results suggest microarrays can be used to predict the outcome of food challenge tests, but further studies are needed (144). However, this technol-

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1883

ogy is currently not routinely available and does not overcome the common difficulty of interpreting sensitization without clinical symptoms. An Italian cross-sectional survey on 23,077 subjects reported that 71% had positive specific IgE to one or more of the 75 allergens tested. (145). Test results using single allergens may still be confounded by cross-reactivity; Ebo and colleagues (146) found sensitization to Bet v 1 to be associated with sensitization to Mal d 1, the homologous allergen in apples. Sensitization to Mal d 1 was common both in birch-allergic subjects who reported PFS, but also in those who did not report food-related symptoms. Sensitization may be a predictor of the development of food allergy in adults; Schnable and colleagues (147) found that in children early sensitization was a strong risk for doctor-diagnosed food allergy at age 6 years. Understanding the relevance of sensitization, which is clearly commonplace in many populations, will assist in the correct diagnosis of adult food allergy. Tests for Non–IgE-Mediated Food Allergy There are few tests for non–IgE-mediated food allergy, apart from the standardized tests for celiac disease. The atopy patch test is principally recommended for use in the diagnosis of delayed non–IgE-mediated food allergy such as atopic dermatitis. Combining the atopy patch test with specific IgE estimation may improve the sensitivity and specificity of SPT and specific IgE tests to foods with a poor positive predictive values such as wheat, although this has only been tested in children (148). For EoE, the usual test is an esophageal biopsy to establish the presence of eosionophils. A positive test is usually indicated by ⱖ15 eosinophils per high powered field (149). Tests for Nonimmune Mediated Adverse Food Reactions Apart from tests for lactose intolerance, there are few, if any, validated tests for other forms of nonimmune mediated conditions. It has been postulated that another antibody, immunoglobulin G (IgG) and its subclass IgG4, could predict the presence or absence of adverse food reactions, although the evidence is contradictory and highly controversial (150,151). IgG antibodies to foods are commonly found in healthy adults; it is likely that IgG levels reflect the level of food exposure rather than the presence of clinically manifest allergy to the relevant food (7,152,153). A European position paper published in 2008 (154) stated that testing for IgG4 against foods is not recommended as a diagnostic tool, a stance supported by the United States (1,7,155). In a review of the reasons for the lack of clinical utility of food-specific IgG/IgG4 measurements in allergy diagnosis, Hamilton (156) concluded that a patient’s clinical history remains the principal arbiter that determines the final diagnosis of allergic disease. Other commercially available tests have not been scientifically investigated or validated for the accurate diagnosis of either immune or nonimmune mediated adverse food reactions (1,157,158). Elimination Diets Elimination diets involve the avoidance of single or multiple food triggers or encompass a highly limited or total

1884

December 2011 Volume 111 Number 12

exclusion of foodstuffs, with the use of elemental formulae to support nutritional adequacy. For all types of adverse food reactions, elimination diets can be effective in assisting the formulation of a diagnosis. Although there are no studies supporting the use of such diets, guidelines issued in 2010 (1) suggest that the elimination of one or a few specific foods from the diet may be useful in the diagnosis of FHS, with the caveat that OFCs are used for the diagnosis of most FHS. The standard length of avoidance may vary, but is usually a 4- to 6-week abstinence if a single food is involved, and 2 to 4 weeks for multiple food avoidance or total elimination diets (159-162). Due to lack of awareness of the range of foods that contain small quantities of allergen, reported avoidance of the trigger food may not in fact be complete exclusion (163). VliegBoerstra and colleagues (164) reported that the diets of 13 out of 38 children (34%) undergoing OFC contained small amounts of allergenic food. Complete exclusion of the suspected food can be effectively achieved through expert evaluation of the current diet, with individual advice on suitable alternative foods as appropriate. Compliance to the diet may be measured through the use of food and symptom diaries to obtain objective measures of the outcome of the dietary exclusion. Although commonly advocated as a diagnostic device, published evidence for all elimination diets is scant, but there are some examples in the literature. Mageri and colleagues (165) placed 140 subjects with urticaria on a 3-week pseudo allergen-free diet, eliminating all processed food, food additives, preservatives, phenols, foods naturally rich in aromatic compounds, alcohol, spices and herbs, sweets, eggs, seafood, and most fruits and vegetables. Nearly one third of subjects had objective improvement of symptoms due to the dietary intervention. Other evidence comes from studies on dietary approaches to the diagnosis of EoE; a six-food elimination diet was effective in controlling symptoms and reducing eosionophils in adults with EoE (166). Kagalwalia and colleagues (167) compared results for both six-food elimination and elemental formula in 60 children with EoE, and the groups showed similar histologic and clinical improvements. Food Challenge US and European guidelines recommend that the OFC, and in particular the DBPCFC, is the gold standard for food allergy diagnosis (1,2,7,122). The control over dosage, recording of symptoms, and blinding where appropriate make OFC distinguishable from mere reintroduction of foods. Because any form of FHS can be diagnosed using an OFC, it is recommended that a positive OFC be accompanied by a demonstration of immune involvement to label the reaction a food allergy. The DBPCFC fulfils an important function; objective responses may occur during OFC but it can be difficult to assess if such responses are related to the ingestion of the allergen unless blinding has occurred. Vlieg-Boerstra and colleagues (168) reported that during 132 DBPCFC challenges in 105 children, 17 placebo events occurred, including 11 that resulted in objective symptoms. However, DBPCFC are complex and require accurate blinding procedures in order to be effective. Both US and European guidelines recommend that open or single-blind food challenge are suitable for use where immediate-onset

IgE-mediated food allergy is suspected, with objective symptoms reported that can be seen and measured independently. This type of challenge may be also used as a precursor to the more robust DBPCFC, with a negative OFC negating the need for DBPCFC (1,123,169). In a review of the subject, Niggemann (170) proposed that challenges should be continued until objective and/or severe, reproducible, persisting symptoms occur. He noted that the sooner symptoms appear, the more likely the challenge is to be a true positive reaction and that the beginning of a clinical reaction is often a change in demeanor. There are a number of issues that need to be considered when undertaking an OFC, including challenge type, location of challenge, presentation of challenge material, dosage, duration, and blinding in the instance of a DBPCFC (162). MANAGEMENT Medical Nutrition Therapy Although pharmacotherapy has a role to play in most types of FHS, the key to the management is the avoidance of foods known or suspected of causing a reaction, with dietetics practitioners providing a pivotal educational and supportive role (2). It is recognized anecdotally that the mainstay of treatment, exclusion of trigger food(s), may be complicated by work or social situations and co-factors such as exercise, drugs, or alcohol. There may also be difficulties advising on the degree of avoidance, especially if more than one food is involved. Dietary exclusion is greatly assisted by legislation; the Food Allergen Labeling and Consumer Protection Act of 2004 (171) mandated the use of clear labeling and source labeling of ingredients likely to contain major food allergens; cow’s milk, egg, fish, crustaceans, tree nuts, wheat, peanuts, and soybeans are all required to be labeled (172). European legislation also covers these major food allergens, but in addition requires all cereals containing gluten, mollusks, lupine, celery, mustard, sesame seed, and sulfur dioxide and sulfites at more than 10 mg/liter/kg to be listed if present (173). The greatest difficulties occur when foods are not labeled or when there is accidental exposure through inhalation of aerosolized allergens, transfer of allergens during cooking or by touch, and absorption through the skin. It has been estimated that 5% to 12% of accidental exposures causing reactions are due to kissing (174). Maloney and colleagues (175) demonstrated that the major peanut allergen Ara h 1 is detectable in the saliva even after interventions such as brushing teeth and chewing gum. Adults with FHS may not be at risk of nutritional compromise to the same degree as children, although case reports do illustrate that nutritional deficiency states can occur (176-180). However, long-term avoidance of one or more major food groups such as wheat or milk increases the risk of suboptimal nutritional intakes and the development of conditions such as osteopenia, and may be particularly prevalent in individuals with a respiratory or gastrointestinal complaint (181,182). Other nutrition-related issues may arise, for example where PFS involves reactions to multiple fruits and vegetables, or those seafood-allergic individuals who require a supplement of n-3 fats. The female to male dominance in self-reported allergic

disease (183) suggests more adults with FHS may be women who may seek advice on allergy prevention for their offspring. Children born to mothers with a food allergy have an increased risk of developing atopy or allergy (184-186). The maternal diet can influence the development of allergic disease in infants because nutrients, such as vitamin A (187), iron (188), selenium (189), zinc (190,191), and vitamin D (192), affect the general development of the fetal immune system (193). Guidelines suggest at risk infants should be exclusively breastfed for 4 to 6 months, or given formula milk with documented reduced allergenicity for the first 4 months of life (194,195). For those who are unable to breastfeed, Berg and colleagues (196) reported that early intervention with hydrolyzed formulae can compensate up to 6 years of age for the enhanced risk of eczema due to familial disposition in children with a history of atopy. Traditionally, it has been considered that the introduction of foods perceived to be of high allergenic risk into an infant’s diet should be delayed. However, Sariachvili and colleagues (197) reported that early exposure to solid foods, within the first 4 months of life, was associated with reduced risk of eczema up to age 4 years, although this effect was only observed in children with allergic parents (197). Other birth cohort studies assessing the effects of early introduction of fish (198) and delayed introduction of wheat (199) suggest that early introduction of high allergenic foods may be beneficial, whereas a delay could increase the risk of developing an allergy. Guidelines issued in 2008 by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (200) recommend weaning should not commence before 17 weeks with foods added singly and at regular intervals to allow for detection of reactions. A review by Grimshaw and colleagues (201) examining worldwide recommendations established that the effect of breastfeeding in prevention is not conclusive, and that evidence for use of hydrolyzates is weak, but that early complementary feeding in breastfed infants may hasten and maintain tolerance. Age-Related Considerations Another group of adults who may require special consideration are elderly people. Deisner and colleagues (10) consider that deficiencies in micronutrients, especially zinc and iron, as well as vitamin D, in elderly people may contribute to the development of allergies. There is a growing appreciation of the importance of vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. Vassallo and Camargo (202) suggest that, concurrent with the increase in FHS, there is an epidemic of vitamin D deficiency caused by decreased sunlight/ultraviolet B ray exposure. A further risk factor for the development of food allergies in elderly persons could be the decreased digestive ability due to atrophic gastritis or antiulcer medication (10). Promotion of Oral Tolerance Orally administered food-specific immunotherapy, in the form of daily up-dosing with increasing quantities of the relevant food protein followed by a maintenance dose,

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1885

appears to be effective in allowing permanent tolerance of a food previously proven to provoke symptoms. Data from studies on milk- (203,204), egg- (205,206), and peanutallergic (207,208) children demonstrate that induction of tolerance is possible. A meta-analysis conducted by Fisher and colleagues (209) concluded that the long-term efficacy, safety, and cost-effectiveness of this technique need to be assessed before it can be recommended in routine practice. The burden of daily dosing and shortlived effect of the maintenance dose may not make it an effective alternative to avoidance in adults, more able than children to manage dietary exclusion. For those with PFS to multiple foods, the development of oral immunotherapy may enable liberalization of the diet. Subcutaneous immunotherapy to birch pollen has been reported to protect against the development of symptoms to apple, although this effect is often negated once immunotherapy is stopped, and other studies have not reported similar findings (210-212). A robust study by Kinaciyan and colleagues (213), who utilized OFC to apple in nine birch-allergic individuals before and after 1 year of sublingual immunotherapy with birch pollen, found no effect on PFS symptoms to apple because the immune response to Mal d 1 was not significantly altered. Immunotherapy utilizing food allergens has been evaluated in patients with an allergy to peaches. In a randomized, double-blind, placebo-controlled clinical trial, FernándezRivas and colleagues (214) studied the efficacy and safety of sublingual immunotherapy with a peach extract quantified for the peach lipid transfer protein Pru p 3. After 6 months of sublingual immunotherapy, the active group tolerated a significantly higher amount of peach, decrease in SPT wheal size, and increase in IgE and IgG(4) to Pru p 3 compared with no change in the placebo group (214).

Quality of Life Dietary exclusion can significantly affect quality of life (215); conversely, those who re-introduce foods back into their diet enjoy an improvement of their social life (216). There have been significant advances in the measurement of health-related quality of life in FHS. Flokstra-de Blok and colleagues (217) reported food allergic adolescents and adults experience more pain, poorer overall health, more limitations in social activity, and less vitality than the general population, with the health-related quality of life of food-allergic subjects being more impaired than subjects with diabetes and rheumatoid arthritis. This may explain why adolescents and young adults with food allergy appear to indulge in risk-taking behavior. Sicherer and colleagues (218) reviewed 174 subjects with a food allergy, 54% of whom reported that they had knowingly and purposefully ingested a potentially unsafe food and 42% who were willing to eat a food labelled that it “may contain” and allergen. This behavior was not affected by variables such as age, sex, or severity of reactions. Walker and colleagues (219) showed that discussing concerns and anxieties can help individuals with food allergy live with a high degree of confidence and a feeling of being in control of their life.

1886

December 2011 Volume 111 Number 12

CONCLUSIONS The umbrella of adverse food reactions encompasses a huge variety of different conditions, some of which are well characterized, while for others there is very little objective assessment or testing available. The prevalence of these conditions in adults may be rising, especially when escalating levels of pollen sensitization put adolescents and young adults at greater risk of developing PFS. The increasing longevity of the population may also result in more food allergy developing in elderly persons, an area currently significantly underresearched. Further robust studies are needed to establish the prevalence of adult FHS, although the EuroPrevall partnership is undertaking a series of studies (220) using common protocols to obtain robust estimates of the prevalence of food allergy and identify the major foods involved. Although new assay techniques and recombinant allergens help to refine allergy diagnosis, they have yet to render the oral food challenge obsolete. The diagnosis and management of adult FHS should include expert nutrition and dietetic support to ensure improved quality of life and minimize the effects of dietary measures on health and well-being. Dietetics practitioners are ideally placed to provide such support and a new network, the International Network for Diet and Nutrition in Allergy (www.indana-allergy network.org), has been established during the past 2 years to support the development of dietetic and nutritional aspects of food allergy. Further research into nutritional compromise in adults with FHS will improve outcomes for patients and allow evidence-based recommendations to be made regarding the prevention of suboptimal intakes. Newly diagnosed food allergy is no longer just part of the pediatric allergic march confined to the early years of life, but a growing burden for many adolescents and adults. The presenting features are often severe, the diagnostic issues complex, and the spectrum extremely diverse. The paucity of research in the prevalence, diagnosis, and management of FHS in adults needs to be addressed. STATEMENT OF POTENTIAL CONFLICT OF INTEREST: No potential conflict of interest was reported by the author. References 1. Boyce JA, Assa’ad A, Burks WA, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Carnargo CA, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, levy BD, Lieberman P, Luccioli S, McCall KM, Schneider LC, Simon RA, Simons FER, Teach SJ, Yawn BP, Schwaninger JM. Guidelines for the diagnosis and management of food allergy in the United States: Summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. 2010;126(suppl):S1S58. 2. Johansson SGO, Bieber T, Dhal R, Friedmann PS, Lanier BO, Lockey RF, Motala C, Ortega Martnell JA, Platts-Mills TAE, Ring J, Thien F, van Cauwenberge P, Williams HC. Revised nomenclature for allergy for global use: Report of the nomenclature review committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113:832-836. 3. deFranco AL, Locksley RM, Robertson M. Immunity: The Immune Response in Infectious and Inflammatory Disease. Oxford, UK: Oxford University Press; 2007. 4. Chaplin DD. Overview of the human immune response. J Allergy Clin Immunol. 2006;117(suppl):S430-S435.

5. Maggi I, Parronchi P, Manetti R, et al. Reciprocal regulatory effects of IFN␥ and IL-4 on the in vitro development of human Th1 and Th2 clones. J Immunol. 1992;148:2142-2147. 6. Sutton BJ, Gould HJ. The human IgE network. Nature. 1993;366: 421-428. 7. Chapman JA, Bernstein IL, Lee RE, Oppenheimer J, Nicklas RA, Portnoy JM, Sicherer SH, Schuller DE, Spector SL, Khan D, Lang D, Simon RA, Tilles SA, Blessing-Moore J, Wallace D, Teuber SS. Food allergy: A practice parameter. Ann Allergy, Asthma, Immunol. 2006; 96(suppl):S1-S68. 8. Lin J, Sampson HA. The role of immunoglobulin E-binding epitopes in the characterization of food allergy. Curr Opin Allergy Clin Immunol. 2009;9:357-363. 9. Hamelmann E, Wahn U. Immune responses to allergens early in life: When and why do allergies arise? Clin Exp Allergy. 2002;32:16791681. 10. Diesner SC, Untersmayr E, Pietschmann P, Jensen-Jarolim E. Food allergy: Only a pediatric disease? Gerontology. 2011;57:28-32. 11. Möhrenschlager M, Ring J. Food allergy: An increasing problem for the elderly. Gerontology. 2011;57:33-36. 12. Osterballe M., Hansen TK, Mortz CG, Høst A, Bindeslev-Jensen C. The prevalence of food hypersensitivity in an unselected population of children and adults. Pediatr Allergy Immunol. 2005;16:567-573. 13. Ross MP, Ferguson M, Street D, Klontz K, Schroeder T, Luccioli S. Analysis of food-allergic and anaphylactic events in the National Electronic Injury Surveillance System. J Allergy Clin Immunol. 2008;121:166-171. 14. Bergmann R, Wahn U, Bergmann K. The allergy march: From food to pollen. Env Toxicol Pharmacol. 1997;4:79-83. 15. Crespo JF, Rodriguez J. Food allergy in adulthood. Allergy. 2003;58: 98-113. 16. Bock SA. Prospective appraisal of complaints of adverse reactions to foods in children during the first 3 years of life. Pediatrics. 1987;79: 683-688. 17. Zuberbier T, Edenharter G, Worm M, Ehlers I, Reimann S, Hantke T, Roehr CC, Bergmann KE, Niggemann B. Prevalence of adverse reactions to food in Germany—A population study. Allergy. 2004;59: 338-345. 18. Venter C, Pereira B, Voigt K, Grundy J, Clayton CB, Higgins B, Arshad SH, Dean T. Prevalence and cumulative incidence of food hypersensitivity in the first three years of life. Allergy. 2007;63:354359. 19. Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, Sigurdardottir ST, Lindner T, Goldhahn K, Dahlstrom J, McBride D, Madsen C. The prevalence of food allergy: A meta-analysis. J Allergy Clin Immunol. 2007;120:638-646. 20. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol. 2006;117:S470-S475. 21. Pierera B, Venter C, Grundy J, Clayton CB, Arshad SH, Dean T. Prevalence of sensitization to food allergens, reported adverse reaction to foods, food avoidance, and food hypersensitivity among teenagers. J Allergy Clin Immunol. 2005;116:884-992. 22. Osterballe M, Mortz CG, Hansen TK, Andersen KE, Bindslev-Jensen C. The prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol. 2009;20:686-689. 23. Vierk KA, Koehler KM, Fein SB, Street DA. Prevalence of selfreported food allergy in American adults and use of food labels. J Allergy Clin Immunol. 2007;119:1504-1510. 24. Young E, Stoneham MD, Petuckevitch A, Barton J, Rana R. A population study of food intolerance. Lancet. 1994;343:1127-1130. 25. Schäfer T, Böhler E, Ruhdorfer S, Weigl L, Wessner D, Heinrich J, Filipiak B, Wichmann HE, Ring J. Epidemiology of food allergy/food intolerance in adults: Associations with other manifestations of atopy Allergy. 2001;56:1172-1179. 26. Amlot PL, Kemeny DM, Zachary C, Parkes P, Lessof MH. Oral allergy syndrome (OAS): Symptoms of IgE-mediated hypersensitivity to foods. Clin Allergy. 1987;17:33-42. 27. Fernández-Rivas M, Benito C, González-Mancebo E, de Durana DA. Allergies to fruits and vegetables. Pediatr Allergy Immunol. 2008; 19:675-681. 28. Katelaris HC. Food allergy and oral allergy or pollen-food syndrome. Curr Opin Allergy Clin Immunol. 2010;10:246-251. 29. Ortolani C, Ispano M, Pastorello E, Bigi A, Ansaloni R. The oral allergy syndrome. Ann Allergy. 1988;61:47-52. 30. Kondo Y, Urisu A. Oral allergy syndrome. Allergol Int. 2009;58:485491. 31. Bohle B. The impact of pollen-related food allergens on pollen allergy. Allergy. 2007;62:3-10.

32. Egger M, Mutschlechner S, Wopfner N, Gadermaier G, Briza P, Ferreira F. Pollen-food syndromes associated with weed pollinosis: An update from the molecular point of view. Allergy. 2006;61:461476. 33. Ma S, Sicherer SC, Nowark-Wegrzyn A. A survey on the management of pollen-food allergy syndrome in allergy practices. J Allergy Clin Immunol. 2003;112:784-788. 34. Konstantinou GN, Grattan CEH. Food contact hypersensitivity syndrome: The mucosal contact urticaria paradigm. Clin Dermatol. 2008;33:383-389. 35. Gupta R, Sheikh A, Strachan DP, Anderson HR. Time trends in allergic disorders in the UK. Thorax. 2007;62:91-96. 36. Emberlin J. Grass, tree and weed pollen. In: Kay AB, ed. Allergy and Allergic Diseases. 2nd ed. Oxford, UK: Wiley Blackwell; 2008. 37. Johansson SGO, Hourihane JO’B, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wüthrich B. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56:813-874. 38. Eriksson NE, Formaren H, Svenonius E. Food hypersensitivity in patients with pollen allergy. Allergy. 1982;37:437-443. 39. Hill DJ, Duke AM, Hosking CS, Hudson IL. Clinical manifestations of cows’ milk allergy in childhood. II. The diagnostic value of skin tests and RAST. Clin Allergy. 1988;18:481-490. 40. Chehade M, Aceves SS. Food Allergy and Eosinophilic Esophagitis. Curr Opin Allergy Clin Immunol. 2010;10:231-237. 41. Funula GT, Liacouras CA, Collins MH. Eosinophilic eosophagitis in children and adults: A systemicatic review and consensus recommendations for diagnosis and treatment. Gastroenterol. 2007;133: 1342-1363. 42. Attaran RR, Probst F. Histamine fish poisoning: A common but frequently misdiagnosed condition. Emerg Med J. 2000;19:474-475. 43. Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States determined by a random telephone survey. J Allergy Clin Immunol. 2004;114:159165. 44. Hansen TK, Bindslev-Jensen C, Skov PS, Poulsen LK. Codfish allergy in adults: IgE cross-reactivity among fish species. Ann Allergy Asthma Immunol. 1997;78:187-194. 45. Griesmeier U, Vázquez-Cortés S, Bublin M, Radauer C, Ma Y, Briza P, Fernández-Rivas M, Breiteneder H. Expression levels of parvalbumins determine allergenicity of fish species. Allergy. 2010;65:191198. 46. Bernhisel-Broadbent J, Scanlon SM, Sampson HA. Fish hypersensitivity. In vitro and oral challenge results in fish-allergic patients. J Allergy Clin Immunol. 1992;89:730-737. 47. Daul CB, Morgan JE, Lehrer SB. The natural history of shrimpspecific immunity. J Allergy Clin Immunol. 1990;86:88-93. 48. Reese G, Ayuso R, Lehrer SB. Tropomyosin: An invertebrate pan– allergen. Int Arch Allergy Immunol. 1999;119:247-258. 49. Lehrer SB, Kim L, Rice T, Saidu J, Bell J, Martin R. Transfer of shrimp allergens to other foods through cooking oil. J Allergy Clin Immunol. 2007;119(suppl):S112. 50. 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;125:1322-1326. 51. Mullins RJ, Dear KB, Tang ML. Characteristics of childhood peanut allergy in the Australian Capital Territory, 1995 to 2007. J Allergy Clin Immunol. 2009;123:689-693. 52. Ewan PW. Clinical study of peanut and nut allergy in 62 consecutive patients: New features and associations. BMJ. 1996;312:1074-1078. 53. Skolnick HS, Conover-Walker MK, Sampson CB, Koerner HA, Wesley Burks W, Wood RA. The natural history of peanut allergy. J Allergy Clin Immunol. 2001;107:367-374. 54. Astier C, Morisset M, Roitel O, Codreanu F, Jacquenet J, Frank P, Ogier V, Petit N, Proust B, Moneret-Vautrin DA, Burks AW, Bihain B, Sampson HA, Kanny G. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. J Allergy Clin Immunol. 2006;118:250-256. 55. Peeters KABM, Kopplemann SJ, van Hoffen E, van der Tas CWH, den Hartog Jager CF, Penniks AH, Hefle SL, Bruijnzeel-Koomen CAFM, Knol EF, Knuist AC. Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy? Clin Exp Allergy. 2007;37:108-115. 56. Burks AW, Cockrell G, Stanley JS, Helm RM, Bannon GA. Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. J Clin Invest. 1995;96:17151721.

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1887

57. Bock SA, Munoz-Furlong A, Sampson HA. Further fatalities caused by anaphylactic reactions to food, 2001-2006. J Allergy Clin Immunol. 2007;119:1016-1018. 58. Ballmer-Weber BK, Holzhauser T, Scibilia J, Mittag D, Zisa G, Ortolani C, Oesterballe M, Poulsen LK, Vieths S, Bindslev-Jensen C. Clinical characteristics of soybean allergy in Europe: A double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol. 2007;119:1489-1496. 59. Zuidmeer L, Goldhahn K, Rona RJ, Gislason D, Madsen C, Summers C, Sodergren E, Dahlstrom J, Lindner T, Sigurdardottir ST, McBride D, Keil T. The prevalence of plant food allergies: A systematic review. J Allergy Clin Immunol. 2008;121:1210-1218. 60. Fleischer D, Conover-Walker M, Matsui E, Wood R. The natural history of tree nut allergy. J Allergy Clin Immunol. 2005;116:10871093. 61. Morisset M, Moneret-Vautrin D-A, Maadi F, Fremont S, Gunard L, Croizier A, Kanny G. Prospective study of mustard allergy: First study with double-blind placebo-controlled food challenge trials (24 cases) Allergy. 2003;58:295-299. 62. Keet CA, Matsui EC, Dhillon G, Lenehan P, Paterakis M, Wood RA. The natural history of wheat allergy. Ann. Allergy Asthma Immunol. 2009;102:410-415. 63. Matsuo H, Dahlström J, Tanaka A, Kohno K, Takahashi H, Furumura M, Morita E. Sensitivity and specificity of recombinant x-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis. Allergy. 2008;63:233-236. 64. Wong GK, Huissoon AP, Goddard S, Collins DM, Krishna MT. Wheat dependent exercise induced anaphylaxis: Is this an appropriate terminology? J Clin Pathol 2010;63:814-817. 65. Veiths S. Scheurer S, Ballmer-Weber B. Current understanding of cross-reactivity of food allergens and pollen. Ann N Y Acad. Sci. 2002;964:47-68. 66. Mortz CG, Andersen KE, Bindeslev-Jensen C. Prevalence of peanut sensitization and the association to pollen sensitization in a cohort of unselected adolescents—The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Pediatr Allergy Immunol. 2005;16:501-506. 67. Kleiber-Janke T, Crameri R, Scheurer S, Veiths S, Becker WM. Patient–tailored cloning of allergens by phage display: Peanut (Arachis Hypogaea) profilin, a food allergen derived from a rare mRNA. J Chromatogr B Biomed Sci Appl. 2001;756:295-305. 68. Mittag D, Akkerdass J, Ballmer-Weber B, Vogel L, Wensing M, Becker WM, Koppelman SJ, Knulst AC, Helbling A, Hefle SL, Van Ree R, Vieths S. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol. 2004;114:1410-1417. 69. Mittag D, Veiths S, Vogel L, Becker W-M, Rhis H-P, Hebling A, Ballmer-Webber B. Soybean allergy in patients allergic to birch pollen: Clinical investigation and molecular characterization of allergens. J Allergy Clin Immunol. 2004;113:148-154. 70. Breiteneder H, Radauer C. A classification of plant food allergens. J Allergy Clin Immunol. 2004;113:821-830. 71. Jarolim E, Rumpold H, Endler AT, Ebner H, Breitenbach M, Scheiner O, Kraft D. IgE and IgG antibodies of patients with allergy to birch pollen as tools to define the allergen profile of Betula verrucosa. Allergy. 1989;44:385-395. 72. Breiteneder H, Ebner C. Molecular and biochemical classifications of plant-derived food allergens. J Allergy Clin Immunol. 2000;106:27-36. 73. Holmann A, Burks W. Pollen food syndrome: Update on the allergens. Curr Allergy Asthma Rep. 2008;8:413-417. 74. Valenta R, Duchene M, Ebner C, Valent P, Sillaber C, Deviller P, Ferreira F, Tejkl M, Edelmann H, Kraft D, Scheiner O. Profilins constitute a novel family of functional plant pan-allergens. J Exp Med. 1992;175:377-385. 75. Wagner S, Breiteneder H. The latex-fruit syndrome. Biochem Soc Tans. 2002;30:935-940. 76. Raulf-Heimsoth M, Rihs HP, Rozynek P, Cremer R, Gaspar A, Pires G, Yeang HY, Arif SAM, Hamilton RG, Sander I, Lundberg M, Bruning T. Quantitative analysis of immunoglobulin E reactivity profiles in patients allergic or sensitised to natural rubber latex (Hevea brasiliensis). Clin Exp Allergy. 2007;37:1657-1667. 77. Salcedo G, Sanchez-Monge R, Diaz-Perales A, Garcia-Casado G, Barber D. Plant non-specific lipid transfer proteins as food and pollen allergens. Clin Exp Allergy. 2004;34:1336-1341. 78. Asero R, Mistrello G, Roncarolo D, Amato S. Relationship between peach lipid transfer protein specific IgE levels and hypersensitivity to non-Rosaceae vegetable foods in patients allergic to lipid transfer protein. Ann Allergy Asthma Immunol. 2004;92:268-272.

1888

December 2011 Volume 111 Number 12

79. Høst A. Frequency of cow’s milk allergy in childhood. Ann Allergy Asthma Immunol. 2002;89:33-37. 80. de Boissieu D, Dupont C. Natural course of sensitization to hen’s egg in children not previously exposed to egg ingestion. Eur Ann Allergy Clin Immunol. 2006;38:113-117. 81. Isolauri E, Suomalainen H, Kaila M, Jalonen T, Soppi E, Virtanen E. Arvilommi H. Local immune response in patients with cow milk allergy: Follow-up of patients retaining allergy or becoming tolerant. J Pediatr. 1992;120:9-15. 82. Potamianou-Taprantzi P, Zanikou S, Psarros P, Syrigou E, Manoussakis M, Saxoni-Papageorgiou P. Relationship between egg-specific serum IgE concentration and the outcome of specific provocation to egg allergic children. Allergy. 2002;57:79 83. Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome—Aetiology, prevalence and consequences. Eur J Clin Nutr. 2006;60:667-672. 84. Wuthrich B, Schmid A, Walther B, Seiber R. Milk consumption does not lead to mucus production or occurrence of asthma. J Am Coll Nutr. 2005;24(suppl):547S-555S. 85. Szépfalusi Z, Ebner C, Pandjaitana R, Orlicek F, Scheiner O, BoltzNitulescu G, Ebner H. Egg yolk ␣-livetin (chicken serum albumin) is a cross-reactive allergen in the bird-egg syndrome. J All Clin Immunol. 1994;93:932-942. 86. Moneret-Vautrin DA, Morisset M. Adult food allergy. Curr Allergy Asthma Rep. 2005;5:80-85. 87. Pumphrey RSH. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30:1144-1150. 88. Fernández–Rivas M, Bolhaar S, González-Moncebo E, Asero R, van Leeuwen A, Bohle B, Ma Y, Ebner C, Rigby N, Sancho A, Miles S, Zuidmeer L, Knulst A, Breiteneder H, Mills C, Hoffmann-Sommergruber K, van Ree R. Apple allergy across Europe: How allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol. 2006;118:481-488. 89. Beaudouin E, Renaudin JM, Morisset M, Codreanu F, Kanny G, Moneret-Vautrin DA. Food-dependent, exercise-induced anaphylaxis— Update and current data. Allerg Immunol Paris. 2006;38:45-51. 90. Maulitz RM, Pratts DS, Schocket AL. Exercise-induced anaphylactic reaction to shellfish. J Allergy Clin Immunol. 1979;63:433-434. 91. Romano A, Di Fonso M, Guiffreda F, Papa G, Artesani MC, Viola M, Venuti A, Palmieri V, Zeppilli P. Food-dependent exercise-induced anaphylaxis: Clinical and laboratory findings in 54 subjects. Int Arch Allergy Immunol. 2001;125:264-272. 92. Yang Mk, Lee SH, Kim TW, Kwon JW, Lee SM, Kim SH. Kwon HS, Park CH, Park HW, Kim SS, Cho SH, Min KU, Kim YY, Chang YS. Epidemiologic and clinical features of anaphylaxis in Korea. Ann Allergy Asthma Immunol. 2008;100:31-36. 93. Shadick NA, Laing MH, Partridge AJ, Bingham C, Wright E, Fossel AH, Sheffer AL. The natural history of food-dependant exerciseinduced anaphylaxis: Survey results from 10-year follow-up study. J Allergy Clin Immunol. 1999;104:123-127. 94. Di Lorenzo G, Pacor ML, Mansueto P, Matrinelli N, Esposito-Pellitteri M, Lo Banco C, Ditta V, Leto-Barone MS, Napoli N, Di Fede G, Rini GB, Corrocher R. Food additive-induced urticaria: A survey of 838 patients with recurrent chronic idiopathic urticaria. Int Arch Allergy Immunol. 2005;138:235-242. 95. Bush RK, Taylor SL, Holden K, Nordlee JA, Busse WW. The prevalence of sensitivity to sulfiting agents in asthmatics. Am J Med. 1986;81:816-820. 96. Raithel M, Baenkler HW, Naegel A, Buchwald F, Schultis HW, Backhaus B, Kimpel S, Koch H, Mach K, Hahn EG, Konturek PC. Significance of salicylate intolerance in diseases of the lower gastrointestinal tract. J Physiol Pharmacol. 2005;56:89-102. 97. Baxter GJ, Graham AB, Lawrence JR, Wiles D, Paterson JR. Salicylic acid in soups prepared from organically and non-organically grown vegetables. Eur J Nutr. 2001;40:289-292. 98. Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet Assoc. 1985;85:950-960. 99. Scotter MJ, Roberts DPT, Wilson LA, Howard FAC, Davis J, Mansell N. Free salicylic acid and acetyl salicylic acid content of foods using gas chromatography-mass spectrometry. Food Chem. 2007;105:273279. 100. Fritz SB, Baldwin JL. Pharmacologic food reactions. In: Metcalfe DD, Sampson HJ, Simon RA. Food Allergy: Adverse Reactions to Foods and Food Additives. Oxford, UK: Blackwell Publishing Ltd; 2003:324-341. 101. Malone MH, Metcalfe DD. Histamine in foods: its possible role in non-allergic adverse reactions to ingestants. Allergy Asthma Proc. 1986;7:241-245.

102. Broderick P, Benjamin AB. Caffeine and psychiatric symptoms: A review. J Okla State Med Assoc. 2004;97:538-542. 103. Mathew RJ, Wilson WH. Behavioral and cerebrovascular effects of caffeine in patients with anxiety disorders. Acta Psychiatrica Scandinavica. 1990;82:17-22. 104. Pollak CP, Bright D. Caffeine consumption and weekly sleep patterns in US seventh-, eighth-, and ninth-graders. Pediatrics. 2003; 111:42-46. 105. Infante S. Baeza ML, De Barrio M, Rubio M, Herrero T. Anaphylaxis due to caffeine. Allergy. 2003;58:681-682. 106. Fernandez-Nieto M, Sastre J, Quirce S. Urticaria caused by cola drink. Allergy. 2002;57:967. 107. Zak DL, Keeney PG. Changes in cocoa proteins during ripening of fruit, fermentation and further processing of cocoa beans. J Agric Food Chem. 1976;24:483-486. 108. Agarwal DP, Harada S, Goedde HW. Racial differences in biological sensitivity to ethanol: The role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes. Alcohol Clin Exp Res. 1981;5:12-16. 109. Ehlers I, Hipler UC, Zuberbier T, Worm M. Ethanol as a cause of hypersensitivity reactions to alcoholic beverages. Clin Exp Allergy. 2002;32:1231-1235. 110. Asero R, Mistrello G, Roncarolo D, Amato S, van-Ree R. A case of allergy to beer showing cross-reactivity between lipid transfer proteins. Ann Allergy Asthma Immunol. 2001;87:65-67. 111. Herzinger T, Kick G, Ludolph-Hauser D, Przybilla B. Anaphylaxis to wheat beer. Ann Allergy Asthma Immunol. 2004;92:673-675. 112. Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, Papasteriades CA. Grape anaphylaxis: A study of 11 adult onset cases. Allergy Asthma Proc. 2005:26:53-58. 113. Vally H, de Klerk N, Thompson PJ. Alcoholic drinks: Important triggers for asthma. J Allergy Clin Immunol. 2000;105:462-467. 114. Vally H, Thompson PJ. Role of sulfite additives in wine induced asthma: Single dose and cumulative dose studies. Thorax. 2001;56: 763-69. 115. Hare LG, Woodside JV, Young IS. Dietary salicylates. J Clin Pathol. 2003;56:649-650. 116. Dahlén B, Boréus LO, Anderson P, Andersson R, Zetterström O. Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin-sensitive subjects. Allergy. 1994;49:43-49. 117. Jansen SC, van-Dusseldorp M, Bottema KC, Dubois AEJ. Intolerance to dietary biogenic amines: A review. Ann Allergy Asthma Immunol. 2003;91:233-240. 118. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85:1185-1196. 119. Kueper T, Martinelli D, Konetzki W, Stamerjohn RW, Magill JB. Identification of problem foods using food and symptom diaries. Otolaryngol Head Neck Surg. 1995;112:415-420. 120. Alvarado MJ, Pérez M. Study of food allergy in the Spanish population. Allergol Immunopathol. 2006;34:185-193. 121. Seitz CS, Pfeuffer P, Raith P, Bröcker E-B, Trautmann A. Food allergy in adults: An over- or underrated problem? Dtsch Arztebl Int. 2008;105:715-723. 122. Bindslev-Jensen C, Ballmer-Webber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B, Osterballe M, Ortolani C, Ring J, Schnopp C, Werfel T; European Academy of Allergology and Clinical Immunology. Standardisation of food challenges in patients with immediate reactions to foods—Position paper from the European Academy of Allergology and Clinical Immunology. Allergy. 2004;59:690-697. 123. Rusznak C, Davies RJ. Diagnosing allergy. Br Med J. 1998;316:686689. 124. Rancé F, Juchet A, Brémont F, Dutau G. Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy. 1997:32;1031-1035. 125. Anhøj C, Backer V, Nolte H. Diagnostic evaluation of grass- and birch-allergic patients with oral allergy syndrome. Allergy. 2001;56: 548-552. 126. Liccardi G, Salzillo A, D’Amato G. The risk of generalized allergic reactions to skin prick testing may be higher in poly-sensitized individuals and in those who underwent SPT with fresh foods. Pediatr Allergy Immunol. 2010;21:656-657. 127. Codreanu F, Moneret-Vautrin DA, Morisset M, Guénard L, Rancé F, Kanny G, Lemerdy P. The risk of systemic reactions to skin pricktests using food allergens: CICBAA data and literature review. Eur Ann Allergy Clin Immunol. 2006;38:52-54. 128. Ives AJ, Hourihane J. Evidence-based diagnosis of food allergy. Current Paed. 2002;12:357-364. 129. Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, Bush RK, Metcalfe DD. Double-blind, placebo-controlled food chal-

130. 131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

142.

143.

144.

145.

146.

147.

148. 149.

lenge (DBPCFC) as an office procedure. J Allergy Clin Immunol. 1988;82:986-997. Sampson HA. Update on food allergy J Allergy Clin Immunol. 2004; 113:805-819. Wang J, Godbold JH, Sampson HA. Correlation of serum allergy (IgE) tests performed by different assay systems. J Allergy Clin Immunol. 2008;121:1219-1224. Hts´t A, Andrae S, Charkin S, Diaz-Vázquez C, Dreborg S, Eigenmann PA, Friedrichs F, Grinsted P, Lack G, Meylan G, Miglioranzi P, Muraro A, Nieto A, Niggemann B, Pascual C, Pouech MG, Rancé F, Rietschel E, Wickman M. Allergy testing in children: Why, who, when and how? Allergy 2003;58:1-11. Pongracic JA, Ouyang F, Kim JS, Caruso D, Wang H, Wang X. Associations between prick skin tests and allergen specific IgE in children and adults. J Allergy Clin Immunol. 2007;119(suppl):S121. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA. Tolerance to extensively heated milk in children with cow’s milk allergy. J Allergy Clin Immunol. 2008;122: 342-347. Vila L, Beyer K, Järvinen KM, Chatchatee P, Bardina L, Sampson HA. Role of conformational and linear epitopes in the achievement of tolerance in cow’s milk allergy. Clin Exp Allergy. 2001;31:1599-1606. Jarvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA. Specificity of IgE antibodies to sequential epitopes of hen’s egg ovomucoid as a marker for persistence of egg allergy. Allergy. 2007: 62:758-765. Ando H, Movérare R, Kondo Y, Tsuge I, Tanaka A, Borres MP, Urisu A. Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy. J Allergy Clin Immunol. 2008;122:583-588. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001;107:891896. Palosuo K, Alenius H, Varjonen E, Koivuluhta M, Mikkola J, Keskinen H, Kalkkinen N, Reunala T. A novel wheat gliadin as a cause of exercise-induced anaphylaxis. J Allergy Clin Immunol. 1999;103: 912-917. Flinterman AE, Akkerdaas JH, den Hartog Jager CF, Rigby NM, Fernandez-Rivas M, Hoekstra MO, Bruijnzeel-Koomen CA, Knulst AC, van Ree R, Pasmans SG. Lipid transfer protein–linked hazelnut allergy in children from a non-Mediterranean birch-endemic area. J Allergy Clin Immunol. 2008;121:423-428. Beyer KB, Ellman-Grunther L, Jarvinen KM, Wood RA, Hourihane J, Sampson HA. Measurement of peptide-specific IgE as an additional tool in identifying patients with clinical reactivity to peanuts. J Allergy Clin Immunol. 2003;112:202-207. Krause S, Reese G, Randow S, Zennaro D, Quaration D, Palazzo P, Ciardello MA, Petersen A, Becker W-M, Mari A. Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol. 2009;124:771778. Vereda A, van Hage M, Ahlstedt S, Ibañez MD, Cuesta-Herranz J, van Odijk J, Wickman M, Sampson HA. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions. J Allergy Clin Immunol. 2011;127:603-607. Ott H, Baron JM, Heise R, Ocklenburg C, Stanzel S, Merk H-F, Niggemann B, Beyer K. Clinical usefulness of microarray-based IgE detection in children with suspected food allergy. Allergy. 2008;63: 1521-1528. Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, Quaratino D, Rasi C, Zaffiro A, Zennaro D, Mari A. Cross-sectional survey on immunoglobulin E reactivity in 23 077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy. 2010;40:911-921. Ebo DG, Bridts CH, Verweji MM, De Knopp KJ, Hagendorens MM, De Clerck LS, Stevens WJ. Sensitization profiles in birch pollenallergic patients with and without oral allergy syndrome to apple: Lessons from multiplexed component-resolved allergy diagnosis. Clin Exp Allergy. 2009;40:339-347. Schnabel E, Sausenthaler S, Schaaf B, Schäfer T, Lehmann I, Behrendt H, Herbarth O, Borte M, Krämer U, von Berg A, Wichmann HE, Heinrich J; LISA Study Group. Prospective association between food sensitization and food allergy: Results of the LISA birth cohort study. Clin Exp Allergy. 2010;40:450-457. Niggemann B, Beyer K. Diagnostic pitfalls in food allergy in children. Allergy. 2005;60:104-107. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME. Eosinophilic esophagitis in children and adults: A systematic review

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1889

150. 151. 152. 153. 154.

155. 156. 157.

158. 159. 160. 161. 162. 163.

164.

165. 166.

167.

168. 169. 170. 171. 172. 173.

174. 175.

1890

and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133:1342-1363. Jenkins M., Vickers A. Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance. Clin Exp Allergy. 1998;28:15261529. Dixon HS. Treatment of delayed food allergy based on specific immunoglobulin G RAST testing. Otolayrngol. 2000;123:48-54. Spickett G. Oxford Handbook of Clinical Immunology and Allergy. Oxford, UK: Oxford University Press; 2006:392393. Bahna SL. The diagnosis of food allergy. Ann Allergy Asthma Immunol. 2003;90:80. Stapel S, Asero R, Ballmer-Webber B, Knol E, Strobel S, Vieths S, Kleine-Tebbe J. Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force report. Allergy. 2008: 63:793-796. Bock SA. AAAAI support of the EAACI Position Paper on IgG4. J Allergy Clin Immunol. 2010;125:1410. Hamilton RG. Clinical laboratory assessment of immediate-type hypersensitivity. J.Allergy Clin Immunol. 2010;125:S284-S296. Ortolani C, Bruijnzeel-Koomen C, Bengtsson U, Bindslev-Jensen C, Björkstén B, Høst A, Ispano M, Jarish R, Madsen C, Paganelli R, Poulsen LK, Wüthrich B. Controversial aspects of adverse reactions to food. Allergy. 1999;56:27-45. Niggemann B, Grüber C. Unproven diagnostic procedures in IgEmediated allergic diseases. Allergy. 2004;59:806-808. Sicherer SH, Teuber SS. Academy practice paper: Current approaches to the diagnosis and management of adverse food reactions. J Allergy Clin Immunol. 2004;114:1146-1150. Minford AMB, MacDonald A, Littlewood JM. Food intolerance and food allergy in children: A review of 68 cases. Arch Dis Child 1982; 67:474-477. Atherton DJ. Dietary Treatment in Childhood Atopic Eczema, Proceedings of the Second Food Allergy Workshop Oxford, UK: The Medicine Publication Foundation. 1983:109-110. Venter C, Vlieg-Boerstra B, Carling C, The diagnosis of food hypersensitivity. In: Skypala IJ, Venter C, eds. Food Hypersensitivity. Oxford, UK: Wiley Blackwell; 2009:85. Tuokkola J, Kaila M, Kronberg-Kippilä C, Sinkko HK, Klaukka T, Pietinen P, Veijola R, Simell O, Ilonen J, Knip M, Virtanen SM. Cow’s milk allergy in children: Adherence to a therapeutic elimination diet and reintroduction of milk into the diet. Eur J Clin Nutr. 2010;64:1080-1085. Vlieg-Boerstra BJ, van der Heide S, Bijleveld CM, Kukler J, Duiverman EJ, Wolt-Plompen SA, Dubois AE. Dietary assessment in children adhering to a food allergen avoidance diet for allergy prevention. Eur J Clin Nutr. 2006;60:1384-1390. Magerl M, Pisarevskaja D, Scheufele R, Zuberbier T, Maurer M. Effects of a pseudoallergen-free diet on chronic spontaneous urticaria: A prospective trial. Allergy. 2010;65:78-83. Gonsalves N, Yang G, Doerfler B. A prospective clinical trial of six-food elimination diet and reintroduction of causative agents in adults with eosinophilic esophagitis. Gastroenterology. 2008;134: A104-A105. Kagalwalia AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Melin-Aldana H, Li BU. Effect of six-food elimination diet on clinical and histological outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006;4:1097-1102. Vlieg-Boerstra BJ, van der Heide S, Bijleveld CM, Kukler J, Duiverman EJ, Dubois AE. Placebo reactions in double-blind, placebocontrolled food challenges in children. Allergy. 2007;62:905-912. Roberts S. Challenging times for food allergy tests. Archives Dis Child. 2005;90:564-566. Niggemann B. When is an oral food challenge positive? Allergy. 2010;65:2-6. US Food and Drug Administration. Food Allergen Labeling and Consumer Protection Act of 2004. Pub Law 108-282, Title II. Congressional Record. Vol. 150; 2004. Taylor SL, Hefle SL. Food allergen labeling in the USA and Europe. Curr Opin Allergy Clin Immunol. 2006;6:186-190. Commission Directive 2006/142/EC of 22 December 2006 amending Annex IIIa of Directive 2000/13/EC of the European Parliament and of the Council listing the ingredients which must under all circumstances appear on the labeling of foodstuffs. OJL 2006;368:110-111. Eriksson NE, Moller C, Werner S, Magnusson J, Bengtsson U. The hazards of kissing when you are food allergic. J Invest Allergol Clin Immunol. 2003;13:149-154. Maloney JM, Chapman MD, Sicherer SH. Peanut allergen exposure through saliva: Assessment and intervention to reduce exposure. J Allergy Clin Immunol. 2006;118:719-724.

December 2011 Volume 111 Number 12

176. Christie L, Hine J, Parker JG, Burks W. Food allergies in children affect nutrient intake and growth. J Am Diet Assoc. 2002;102:16481651. 177. Fox AR, Du Toit G, Lang A, Lack G. Food allergy as a risk factor for nutritional rickets. Pediatr Allergy Immunol. 2004;15:566-569. 178. Noimark L, Cox HE. Nutritional problems related to food allergy in childhood. Pediatr Allergy Immunol. 2008;19:188-195. 179. Vieira MC, Morais MB, Spolidoro JV, Toporovski MS, Cardoso AL, Araujo GT, Nudelman V, Fonseca MC. A survey on clinical presentation and nutritional status of infants with suspected cow’s milk allergy. BMC Pediatr. 2010;23;10-25. 180. des Roches A, Paradis L, Paradis J, Singer S. Food allergy as a new risk factor for scurvy. Allergy. 2006;61:1487-1488. 181. Woods RK, Weiner JM, Abramson M, Thien F, Walters EH. Patients’ perceptions of food-induced asthma. Austr New Zeal J Med. 1996; 26:504-512. 182. Kershaw R. Nutritional consequences of avoidance and practical approaches to nutritional management. In: Food Hypersensitivity. Skypala IJ, Venter C, eds. Oxford, UK: Wiley Blackwell; 2009:243. 183. DunnGalvin A, Hourihane JO’B, Frewer L, Knibb RC, Oude Elberink JNG, Klinge I. Incorporating a gender dimension in food allergy research: A review. Allergy. 2006;61:1336-1343. 184. Kjellman NI. Atopic disease in seven-year-old children. Incidence in relation to family history. Acta Paediatr Scand. 1977;66:465-471. 185. Kurukulaaratchy R, Fenn M, Matthews S, Hasan Arshad S. The prevalence, characteristics of and early life risk factors for eczema in 10-year-old children. Pediatr Allergy Immunol. 2003;14:178-183. 186. Muraro A, Dreborg S, Halken S, Host A, Niggemann B, Aalberse R, Arshad SH, Berg Av A, Carlsen K, Duschén K, Eigenmann P, Hill D, Jones C, Mellon M, Oldeus G, Oranje A, Pascual C, Prescott S, Sampson H, Svartengren M, Vandenplas Y, Wahn U, Warner JA, Warner JO, Wickman M, Zeiger RS. Dietary prevention of allergic diseases in infants and small children. Part I: Immunologic background and criteria for hypoallergenicity. Pediatr Allergy Immunol. 2004;15:103-111. 187. Chew BP, Park JS. Carotenoid action on the immune response. J Nutr. 2004;134:257S-261S. 188. Jason J, Archibald LK, Nwanyanwu OC, Bell M, Jensen RJ, Gunter E, Buchanan I, Larned J, Kazembe PN, Dobbie H, Jarvis WR. The effects of iron deficiency on lymphocyte cytokine production and activation: Preservation of hepatic iron but not at all cost. Clin Exp Immunol. 2001;126:466-473. 189. Jackson MJ, Dillon SA, Broome CS, McArdle A, Hart CA, McArdle F. Are there functional consequences of a reduction in selenium intake in UK subjects? Proc Nutr Soc. 2004;63:513-517. 190. Wieringa FT, Dijkhuizen MA, West CE, van d, V, van der Meer JW. Reduced production of immunoregulatory cytokines in vitamin Aand zinc-deficient Indonesian infants Eur J Clin Nutr. 2004;58:14981504. 191. Osendarp SJ, West CE, Black RE. The need for maternal zinc supplementation in developing countries: An unresolved issue. J Nutr. 2003;133:817S-827S. 192. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004;80:1717S-1720S. 193. Tricon S, Williers S, Smit HA, Burney PG, Devereuz G, Frew AJ, Halken S, Hs´t A, Nelson M, Shaheen S, Warner JO, Calder PC. Nutrition and allergic disease. Clin Exp Allergy Rev. 2006;6:117-188. 194. IUIS/WHO Allergen Nomenclature Subcommittee Bulletin. World Health Org. 1994;72:797-806. 195. Høst A, Halken S, Muraro A, Dreborg S, Niggemann B, Aalberse R, Arshad SH, von Berg A, Carlsen KH, Duschén K, Eigenmann PA, Hill D, Jones C, Mellon M, Oldeus G, Oranje A, Pascual C, Prescott S, Sampson H, Svartengren M, Wahn U, Warner JA, Warner JO, Vandenplas Y, Wickman M, Zeiger RS. Dietary prevention of allergic diseases in infants and small children. Pediatr Allergy Immunol. 2008:19:1-4. 196. Berg A, Krämer U, Link E, Bollrath C, Heinrich J, Brockow I, Koletzko S, Grübl A, Filipiak-Pittroff B, Wichmann HE, Bauer CP, Reinhardt D, Berdel D; GINIplus study group. Impact of early feeding on childhood eczema: Development after nutritional intervention compared with the natural course—The GINIplus study up to the age of 6 years. Clin Exp Allergy. 2010;40:627-636. 197. Sariachvili M, Droste J, Dom S, Wieringa M, Hagendorens M, Stevens W, van Sprundel M, Desager K, Weyler J Early exposure to solid foods and the development of eczema in children up to 4 years of age. Pediatr Allergy Immunol. 2010;21:74-81. 198. Kull I, Bergstrom A, Lilja G, Pershagen G, Wickman M. Fish con-

199. 200.

201.

202. 203.

204. 205.

206.

207. 208.

209.

sumption during the first year of life and development of allergic diseases during childhood. Allergy. 2006;61:1009-1015. Poole JA, Barriga K, Leung DYM, Hoffmann M, Eisenbarth GS, Rewers M, Norris JM. Timing of initial exposure to cereal grains and the risk of wheat allergy. Pediatrics. 2006;117:2175-2182. Agostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B, Michaelsen KF, Moreno L, Puntis J, Rigo J, Shamir R, Szajewska H, Turck D, van Goudoever J; ESPGHAN Committee on Nutrition. Complementary feeding: A commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2008;46:99-110. Grimshaw KE, Allen K, Edwards CA, Beyer K, Boulay A, van der Aa LB, Sprikkelman A, Belohlavkova S, Clausen M, Dubakiene R, Duggan E, Reche M, Marino LV, Nørhede P, Ogorodova L, Schoemaker A, Stanczyk-Przyluska A, Szepfalusi Z, Vassilopoulou E, Veehof SH, Vlieg-Boerstra BJ, Wjst M, Dubois AE. Infant feeding and allergy prevention: A review of current knowledge and recommendations. A EuroPrevall state of the art paper. Allergy. 2009;64:1407-1416. Vassallo MF, Camargo CA Jr. Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children. J Allergy Clin Immunol. 2010;126:217-222. Skripak JM, Nash SD, Rowley H, Bereton NH, Oh S, Hamilton, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo controlled study of milk oral immunotherapy for cow’s milk allergy J Allergy Clin Immunol. 2008;122:1154-1160. Zapatero L, Alonso F, Fuentes V, Martinez MI. Oral desensitization in children with cow’s milk allergy. J Investig Allergol Clin Immunol. 2008;18:389-396. Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, Steele PH, Pons L, Helm RM, Lee LA, Burks AW. Egg oral immunotherapy in non-anaphylactic children with egg allergy. J Allergy Clin Immunology. 2007;119:199-205. Staden U, Rolinick-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: Efficacy and clinical patterns of reaction. Allergy. 2007; 62:1261-1269. Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW. Successful oral tolerance induction in severe peanut allergy. Allergy. 2009;64:1218-1220. Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009;124:292. Fisher HR, Toit GD, Lack G. Specific oral tolerance induction in food

210. 211. 212. 213.

214.

215. 216. 217.

218. 219. 220.

allergic children: Is oral desensitisation more effective than allergen avoidance? A meta-analysis of published RCTs. Arch Dis Child. 2011;96:259-264. Asero R. How long does the effect of birch pollen injection SIT on apple allergy last? Allergy. 2003;58:435-438. Hansen KS, Khinchi MS, Skov PS, Bindeslev-Jensen C, Poulsen LK, Malling HJ. Food allergy to apple and specific immunotherapy with birch pollen. Mol Nutr Food Res. 2004;48:441-448. Bucher X, Pichier WJ, Dahinden CA, Heibling A. Effect of tree pollen specific subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut. Allergy. 2004;59:1272-1276. Kinaciyan T, Jahn-Schmid B, Radakovics A, Zwolfer B, Scheiber C, Francis JN, Ebner C, Bohle B. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol. 2007;119:937-943. Fernández-Rivas M, Garrido Fernández S, Nadal JA, Díaz de Durana MD, García BE, González-Mancebo E, Martín S, Barber D, Rico P, Tabar AI. Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy. 2009;64:876-883. Sicherer SH, Noone SA, Muñoz-Furlong A. The impact of childhood food allergy on quality of life. Ann Allergy Asthma Immunol. 2001; 87:461-464. Eigenmann PA, Caubert JC, Zemore SA. Continuing food-avoidance diets after negative food challenges. Pediatr Allergy Immunol. 2006; 17:601-605. Flokstra-de Blok BM, Dubois AE, Vlieg-Boerstra BJ, Oude Elberink JN, Raat H, DunnGalvin A, Hourihane JO, Duiverman EJ. Health-related quality of life of food allergic patients: Comparison with the general population and other diseases. Allergy. 2010;65: 238-244. Sampson MA, Munoz-Furlong Anne, Sicherer SH. Risk-taking and coping strategies of adolescents and young adults with food allergy. J Allergy Clin Immunol. 2006;117:1440-1445. Walker S, Sheikh A. Managing anaphylaxis: Effective emergency and long-term care are necessary. Clin Exp Allergy. 2003;33:10151018. Kummeling I, Mills EN, Clausen M, Dubakiene R, Pérez CF, Fernández-Rivas M, Knulst AC, Kowalski ML, Lidholm J, Le TM, Metzler C, Mustakov T, Popov T, Potts J, van Ree R, Sakellariou A, Töndury B, Tzannis K, Burney P. The EuroPrevall surveys on the prevalence of food allergies in children and adults: Background and study methodology. Allergy. 2009;64:1493-1497.

December 2011 ● Journal of the AMERICAN DIETETIC ASSOCIATION

1891