Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)

INTRODUCTION — The oral allergy syndrome (OAS) (pollen-food allergy syndrome [PFAS or PFS]) describes allergic reactions that typically occur upon ingestion of certain uncooked fruits, nuts, vegetables, or spices in pollen-sensitized individuals [1,2]. The causative allergens in these plant foods are homologous to pollen allergens. The symptoms result from contact urticaria of the mucosal surface that touches the food, and symptoms are usually limited to the mouth and throat. Symptoms appear quickly after eating raw forms of the food because the responsible allergens are rapidly inactivated by cooking and digestion, although this is not always true.

This topic review presents the management and prognosis of patients with PFS. The clinical manifestations, diagnosis, and pathogenesis of PFS are reviewed separately. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)".)

TERMINOLOGY — In this topic review, the term "oral allergy syndrome" (OAS) is used to describe reactions limited to the oropharynx that are caused by food proteins that are homologous to pollen proteins. "Pollen-food allergy syndrome," "pollen-food syndrome," and "pollen-associated food allergy syndrome" (abbreviated PFAS or PFS) are broader terms that encompass both oropharyngeal and systemic symptoms. In this review, PFS is the preferred term for the spectrum of reactions caused by allergens in plant foods that are homologous to pollen allergens.

OVERVIEW OF MANAGEMENT — The approach presented in this topic review is based upon the author's experience because there are limited guidelines for the management of PFS, and clinicians vary considerably in their practices [1,3-6]. A questionnaire mailed to 226 randomly selected allergy specialists across the United States illustrated the variability in approach to this disorder [3]. Of the 122 allergists who responded, 53 percent recommended complete avoidance of causal foods to all patients, whereas 9 percent did not advocate any restrictions. Sixty-six percent of allergists prescribed epinephrine for PFS on a case-by-case basis, 30 percent never prescribed it, and 3 percent always did. (See 'Indications for epinephrine' below.)

Avoidance — Dietary avoidance of the offending plant food(s) in the form in which it causes symptoms is the most common approach to management. However, strict avoidance may not be uniformly necessary if symptoms are mild. Additionally, patients may continue to eat forms of the foods that do not cause symptoms. Cooked, processed, and sometimes frozen forms of the foods typically do not cause symptoms of PFS, but there are exceptions (eg, roasted nuts). The purpose of avoidance is the prevention of future reactions. However, there are no studies reporting the impact of avoidance on the natural history of the condition. (See 'Prognosis' below.)

Risk of systemic reactions — Systemic reactions are possible but uncommon. A review of multiple studies, which included over 1000 patients, estimated that between 2 and 10 percent of patients with PFS experience systemic symptoms [7]. This study is discussed in more detail separately. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Systemic reactions'.)

Peanuts, tree nuts, peaches, and mustard are associated with more systemic reactions than other foods. In the future, component-resolved diagnostic testing to determine if the patient's immunoglobulin E (IgE) is binding to labile (eg, profilins) or stable food proteins (eg, lipid transfer proteins, seed storage proteins) may assist in determining the risk of systemic reactions, as labile proteins more typically cause PFS [8]. The use of component testing and the pathophysiology of PFS are reviewed separately. (See "Component testing for pollen-related, plant-derived food allergies", section on 'Allergen-specific use/interpretation' and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)".)

Possible risk factors — Possible risk factors for systemic reactions include antiulcer medications, large amounts of the food in question, periods of fasting, and other factors known to augment food allergic reactions.

Antiulcer therapies — Antiulcer drugs increase gastric pH and may impair digestion of food proteins [9,10]. There are no published studies directly examining the clinical effect of antiulcer therapies on PFS, although the results of studies of other food allergies are of interest [11-14]:

●In a mouse model, antiulcer drugs were reported to predispose to allergic reactions to caviar caused by unstable allergens that would be normally destroyed by digestion [12].

●Following a three-month course of antiulcer drugs, 5 of 153 patients developed IgE to hazelnut, and 2 developed clinical allergy to hazelnut [13]. In addition, specific IgE increased in 10 percent of the patients, and 15 percent showed de novo IgE formation toward numerous digestion labile dietary compounds, such as milk, potato, celery, carrots, apple, orange, wheat, and rye flour [14].

●Proton pump inhibitors (PPIs) were identified as relevant cofactors for systemic reactions in a case-control study from Italy; 17 (19 percent) patients were taking a PPI when the systemic reaction occurred versus 5 percent of controls [11].

These observations, although preliminary, suggest that patients with PFS may be at risk for more severe reactions while being treated with antiulcer drugs and should practice more careful food avoidance if these medications are required.

Large amounts of related foods — A case of a 16-year-old girl with birch pollen allergy and peanut allergy caused by exclusive Bet v1-Ara h 8 cross-reactivity (negative Ara h 1, 2, 3, and 9) was reported [15]. The girl tolerated a double-blind, placebo-controlled food challenge (DBPCFC) to peanut and subsequently ingested regular amounts (30 to 40 g) of peanut without any symptoms over the three years following the DBPCFC. However, on one occasion, she skipped lunch and instead ingested a large amount (ie, 300 g) of roasted peanuts and developed a severe systemic reaction with low blood pressure, difficulty breathing, swollen lips, and generalized urticaria. She was treated with two doses of intramuscular epinephrine, oral antihistamine, and betamethasone. Repeat evaluation showed undetectable serum peanut-specific IgE, Ara h 1, 2, 3, and 9-IgE but positive Ara h 8-IgE. The girl spontaneously resumed eating small amounts of peanuts (30 to 40 g/serving) without any further reactions. In addition, the Italian study mentioned previously also identified excessive amounts of the ingested allergen as a risk factor for systemic reactions [11]. Thus, it is possible that the ingestion of large amounts of the food, especially on an empty stomach, can overload the digestive capacity and lead to a systemic reaction. It is prudent to caution patients to avoid such situations. The specific allergens in peanut are reviewed in more detail separately. (See "Peanut, tree nut, and seed allergy: Clinical features", section on 'Pathogenesis'.)

Other augmenting cofactors — In our experience (unpublished), ingestion of alcohol may also lead to systemic symptoms in patients with birch pollen cross-reactive allergy to peanut. Since pollen cross-reactive proteins undergo degradation in stomach and the intestine, any factors that alter intestinal permeability or speed absorption, such as alcohol, exercise, or nonsteroidal anti-inflammatory drugs (NSAIDs), may result in systemic reactions, and it is prudent to caution patients to avoid these substances if eating cross-reactive foods.

Indications for epinephrine — Practices regarding prescribing epinephrine vary among allergists, and our approach is presented here. We advise patients with one or more of the following characteristics to carry epinephrine autoinjectors:

●Systemic symptoms in the past.

●Pharyngeal anatomy that may predispose to severe obstruction even with a mild degree of swelling, such as large tonsillar tissue or large tongue.

●Dysphagia or significant throat discomfort during the past reactions.

●Reactions of any severity to cooked plant foods, since this suggests the patient is sensitized to a heat-stable protein and may be at higher risk for a systemic reaction.

●Established allergy (regardless of the severity of past reactions) to peanut, tree nuts, or mustard, as these foods are associated with higher rates of systemic reactions. Similarly, certain foods are considered higher risk in specific regions of the world (peach in Mediterranean countries and apple in Spain). The phenomenon of certain foods causing more severe reactions in patients in specific geographic locales is discussed in more detail elsewhere. (See "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Peach' and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Apple'.)

For patients with positive skin prick testing using a commercial extract (versus the fresh food) to the causative food, we discuss the uncertain risk of systemic reactions with the patient/parent. If the patient/parent's preference is to have access to epinephrine following that discussion, then we generally supply it. The role of skin testing in the diagnosis of PFS is reviewed elsewhere. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Objective testing for food allergy'.)

Specific clinical scenarios — Our approach to management depends upon the patient's past symptoms, the foods to which he/she is sensitized, and his/her interest in continuing to eat the causative food(s).

Patients with past systemic symptoms — Patients with PFS who have experienced systemic reactions to a raw food should avoid raw and dehydrated forms of that food. Dehydrated forms of the food may be used in seasonings and can cause reactions (eg, patients allergic to raw celery may react to celery spice, which is dried and powdered celery) [16,17].

The decision to avoid cooked versions of the culprit food is influenced by the severity of the patient's reaction, the patient's recent history of tolerating cooked versions, and the preferences of the patient and clinician. This decision is usually made on a case-by-case basis.

Tolerance to cross-reactive foods should be carefully evaluated in any patient who has experienced systemic symptoms, so that the foods that must be avoided are clearly defined (figure 1). If a cross-reactive food is being ingested on a regular basis without adverse symptoms, it is not necessary to test or restrict that food. In contrast, if the cross-reactive food is not a usual part of the diet, a clinician-supervised oral food challenge may be needed to determine tolerance.

Patients with oral symptoms to high-risk foods — We suggest that all patients with established allergies to certain high-risk foods, regardless of the severity of past symptoms, avoid the foods that cause symptoms and learn to use and carry an epinephrine autoinjector. High-risk foods include peanut, tree nuts, and mustard because these foods are associated with serious systemic reactions [18]. In addition, peach and apple, which are usually not considered high-risk in most areas of the world, are associated with systemic reactions in the Mediterranean region and Spain, respectively, where patients are usually sensitized to lipid transfer proteins. Thus, clinicians in these areas of the world should be cautious about these foods as well. (See 'Indications for epinephrine' above and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Apple' and "Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Peach'.)

Advice regarding avoidance for patients who have had very mild oropharyngeal symptoms to one of these foods is less clear, especially if the individual wishes to continue eating cooked forms of the food that are not currently causing symptoms. We typically explain to the patient that the culprit food is more likely to cause dangerous reactions compared with other foods and suggest that he/she convert to strict avoidance if the symptoms seem to be worsening over time.

Patients with oral symptoms to low-risk foods — Based on guidelines and our experience, we manage patients with isolated oral symptoms based on severity [1,2,6]. In most cases of PFS with isolated uncomfortable oropharyngeal symptoms, we advise patients to avoid the raw foods that cause symptoms, but we do not restrict potentially cross-reactive foods. We advise patients who tolerate cooked or otherwise thermally processed (microwaved, pasteurized, or baked) fruits and vegetables to continue to eat these forms of the food. When making this recommendation, however, the clinician must be certain that patients are not experiencing other types of reactions to the plant foods in question (such as worsening of atopic dermatitis). (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)", section on 'Patients with concomitant atopic dermatitis'.)

Many patients with PFS choose to avoid the causative foods, but some want to continue ingesting fruits that are causing mild oral symptoms. Such patients should be advised to avoid eating large amounts of the food, such as in a fruit shake or during apple picking, and to stop if their symptoms appear to be worsening over time. The symptoms may worsen temporarily during or following the pollen season, and food should be avoided during such periods. H1 antihistamines may help reduce symptoms. We explain to such patients that the impact of ongoing exposure on the natural history of the disease is unknown.

OTHER MANAGEMENT ISSUES

Antihistamines — We do not suggest routinely premedicating with H1 antihistamines in order to eat the fruit/vegetable in question, although antihistamines may reduce the symptoms of PFS, and there is no clear evidence that this approach is unsafe. In a randomized, placebo-controlled clinical trial, patients with birch allergy and hazelnut PFS who received a two-week course of the H1-receptor antagonist, astemizole, had significantly reduced symptoms on oral challenge compared with placebo, although symptoms did not resolve completely [19]. Still, the long-term effects of continuing to eat a food sporadically that causes PFS have not been evaluated. For patients with more significant oropharyngeal symptoms or abdominal discomfort, we advise them to eat only cooked or processed forms of the food that do not cause symptoms, instead of premedication with antihistamines.

Immunotherapy — Several forms of immunotherapy have been studied for the treatment of PFS, but this approach is limited by inconsistent efficacy. Although the efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and allergic asthma is well established, the benefits for PFS are uncertain. We do not suggest administering pollen immunotherapy solely for the purpose of treating PFS, although we would consider it if the patient is very troubled by the symptoms and accepts that clinical improvement as a result of immunotherapy is uncertain. This is consistent with the recommendations of European guidelines and American practice parameters [2,6].

Injection immunotherapy with pollen extracts — Trials of SCIT with pollen extracts in patients with PFS have shown mixed results [20-23]:

●In a prospective study of 49 birch-allergic patients with apple-induced PFS, subjects were treated with 12, 24, or 36 months of SCIT and compared with 26 control subjects who did not receive SCIT [21]. Skin prick testing and nonblinded oral challenges with apple were performed before and after SCIT. Of those treated with SCIT, 41 (84 percent) reported a significant or total disappearance of PFS symptoms, with similar response rates regardless of the length of SCIT therapy. Skin reactivity to fresh apple was reduced in 88 percent. In contrast, none in the control group experienced decreased symptoms to apple or reduced skin reactivity. This trial was neither randomized nor blinded. The same group reported that following discontinuation of SCIT, skin test reactivity to apple gradually increased, although about 50 percent of patients who benefited from SCIT still tolerated raw apple more than two years after discontinuation [24]. The researchers hypothesized that immunotherapy might work best for PFS in adults monosensitized to birch tree pollen rather than to multiple pollens and in those treated with birch pollen extracts containing relatively high doses of Bet v 1 [25].

●In a second positive study, 25 adults with birch pollen allergy and PFS to apple were randomly assigned to birch pollen SCIT or medical management [20]. Double-blind, placebo-controlled food challenges (DBPCFC) were performed at baseline and at 12 months. In the SCIT group, 9 of 13 patients improved significantly, while 4 did not. In the control group, no patients improved.

However, other studies were negative [23,26]:

●In a carefully controlled (ie, double-blind, double-dummy, and placebo-controlled) study, 74 birch-allergic patients (of whom 74 percent had PFS to apple) were randomized to either SCIT, sublingual immunotherapy (SLIT), or placebo immunotherapy [23]. Apple-induced symptoms were assessed by open-food challenges before and after two years of immunotherapy. Forty patients were included in the final evaluation. There was a significant decrease in rhinitis symptoms and use of medications in the immunotherapy groups. Apple challenges were positive in 10 (SCIT), 4 (SLIT), and 10 (placebo) patients before treatment and 9 (SCIT), 6 (SLIT), and 8 (placebo) patients after treatment. The severity of symptoms to apple decreased in all groups but only significantly in the placebo group. Thus, despite a significant effect on allergic rhinitis, immunotherapy was not accompanied by a meaningful decrease in the severity of allergy to apple compared with placebo. One weakness of this study was the high rate of dropouts, although this is not unusual in immunotherapy.

In addition to negative studies, there are a small number of case reports of PFS developing during SCIT or SLIT [27,28].

Other forms of immunotherapy — Other forms of immunotherapy have been evaluated for the treatment of PFS, although all require further study.

Sublingual pollen immunotherapy — Sublingual immunotherapy (SLIT) with pollen allergens appears to be less effective than injection immunotherapy.

●A trial of SLIT for birch pollen allergy did not show efficacy for alleviating PFS symptoms. However, this study used a very low maintenance dose of Bet v 1 (4.5 mcg) [29].

●In a small study comparing injection and sublingual forms of immunotherapy for PFS, complete tolerance to raw apple was achieved in two of eight and one of seven patients receiving injection and oral immunotherapy, respectively [25,30]. An additional three of eight and two of seven patients tolerated increased doses of raw apple.

Oral immunotherapy with food — The question of whether it is possible to induce oral tolerance in patients with PFS by repeatedly ingesting the causative food was addressed in a randomized-controlled trial of 40 adults [31]. Subjects had birch pollen-induced rhinitis and oral symptoms to apple and underwent oral food challenge with fresh apple to determine the highest tolerated dose at baseline (1 to 64 grams). They were then randomized to active treatment (daily consumption of fresh apple) or control (no treatment). The study was performed outside of birch pollen season. A specific amount of apple was chewed carefully for one to two minutes and swallowed daily, and the amount ingested was doubled every two to three weeks. No treatment was given to 13 control patients. The primary endpoint was the proportion of patients achieving tolerance to at least 128 grams of apple at eight months. Those who achieved tolerance continued to eat a whole apple at least three times per week. Exploratory endpoints were questionnaires about symptoms to cross-reactive foods and pollen allergy symptoms, a conjunctival provocation test with birch pollen and Bet v 1, and in vitro tests (total immunoglobulin E [IgE], specific IgE, immunoglobulin G4 [IgG4] to Mal d 1 and Bet v 1, and basophil activation test with both allergens).

Seventeen of 27 patients (63 percent) in the active group could tolerate a whole apple by the end of the study, compared with 0 of 13 patients in the control group. Two patients withdrew (one developed diarrhea and the other had worsening oral symptoms), but none experienced anaphylaxis. Differences in exploratory endpoints related to systemic immune reactivity did not reach statistical significance. Among those who achieved tolerance, two had interruptions in apple ingestion of two to four weeks duration, with recurrence of symptoms in both cases, indicating that the tolerance was dependent upon ongoing exposure. Thus, this approach appears to be effective in a subset of patients but requires ongoing exposure once tolerance is induced. Larger studies are needed to better define the risks involved and determine if this approach is practical for a subset of patients.

Sublingual immunotherapy with recombinant food allergens — Sublingual immunotherapy (SLIT) with recombinant food allergens is an experimental approach to treating PFS to certain foods, such as apple, which has shown promise [9]. A randomized, placebo-controlled trial compared SLIT with a daily dose of 25 micrograms of recombinant Mal d 1 (rMal d 1), rBet v 1, or placebo in 60 Austrian adults with PFS to raw apple and birch pollen allergic rhinitis [32]. Sublingual challenges with a standardized dose of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG4 antibodies were performed before and after 16 weeks of SLIT. SLIT with rMal d 1 was safe; no systemic reactions occurred. SLIT with rMal d 1 reduced oral symptoms upon sublingual challenge with rMal d 1, compared with placebo and rBet v 1 SLIT, respectively. SLIT with rMal d 1 was associated with reduced rMal d 1 skin test reactions and increased IgG4/IgE. Oral reactivity to raw apple was not evaluated.

Anti-IgE therapy — Although no information regarding PFS in patients receiving anti-IgE therapy for allergic rhinitis or asthma has been published, it appears to be an attractive potential approach in view of the central role of immunoglobulin E (IgE) reactions in the pathomechanism of PFS. However, data from clinical trials are lacking. (See "Anti-IgE therapy".)

Genetically modified foods — It is theoretically possible to genetically modify foods to reduce the content of specific allergens responsible for food allergy. This was successfully done with an apple line, in which the Mal d 1 genes were silenced using RNA interference [33]. In a study of 21 adults with PFS to apple, single-blind oral challenges of the two lines containing the lowest content of Mal d 1 produced no symptoms in 43 and 63 percent of subjects, respectively [34]. Thus, this approach may offer a future alternative to avoidance.

PATIENT EDUCATION

Important teaching points — Our approach is to inform patients and caregivers about the following:

●Based on available data, between 2 and 10 percent of patients with PFS experience systemic symptoms [7]. We prescribe an epinephrine autoinjector to patients with any of the indications listed above. (See 'Indications for epinephrine' above.)

●A period of fasting followed by ingestion of the culprit plant food, ingestion of large amounts of the culprit food, and the use of proton pump inhibitors (PPIs) were identified as risk factors for systemic reactions in an Italian study [11]. For patients sensitized to birch pollen, soy beverages (eg, soy milk) represented a risk for systemic symptoms and should be avoided. Nonsteroidal anti-inflammatory drugs (NSAIDs) and exercise have been implicated in augmenting food reactions in other settings (eg, food-dependent exercise-induced anaphylaxis), although the data from patients with PFS are mixed [11].

●Although rare, systemic reactions to first ingestions of pollen-related foods have been reported. Specifically, severe reactions upon the first ingestion of a soy beverage with high concentration of birch cross-reactive proteins was described in a group of children during the birch pollen season [16].

PRIMARY PREVENTION — There are no known strategies to prevent development of PFS. In theory, early pollen immunotherapy in children sensitized to pollens prior to the onset or promptly at the onset of PFS might be beneficial, and some preliminary results in mice support this approach [35]. However, there are no data in humans evaluating the impact of pollen immunotherapy on preventing sensitization to plant food allergens.

PROGNOSIS — Studies on the long-term natural history and prognosis of PFS are lacking. In our experience, PFS is usually a persistent condition. In an Italian study of 67 adults with pollen-food allergy with sensitization to LTP, 27 percent reported new food allergies over 12 to 18 months follow-up. The new systemic allergies were to tree nuts (4), saffron (2), and 1 each to peeled peach, apple, plum, cherry, kiwi, mandarin, rice, and broccoli [36]. Little data are available about long-term outcomes in patients who respond to pollen immunotherapy initially.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Oral allergy syndrome (Beyond the Basics)" and "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)" and "Patient education: Food allergen avoidance (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definitions – Oral allergy syndrome (OAS) (pollen-food allergy syndrome [PFAS or PFS]) is an immunoglobulin E (IgE)-mediated allergic reaction that occurs upon ingestion of certain raw fruits, nuts, vegetables, or spices in pollen-sensitized individuals. The symptoms result from contact urticaria of the mucosal surface that touches the food and are caused by allergens in plant foods that are homologous to pollen allergens (figure 1). OAS is used to describe reactions limited to the oropharynx, while PFS is a broader term that encompasses both oropharyngeal and systemic symptoms. (See 'Introduction' above and 'Terminology' above.)

●Management – Dietary avoidance of the offending plant food(s) in the form in which it causes symptoms is the most common approach to management. However, strict avoidance may not be uniformly necessary if symptoms are mild. Additionally, patients may continue to eat forms of the foods that do not cause symptoms. Cooked, processed, and sometimes frozen forms of the foods typically do not cause symptoms of PFS, but there are exceptions (eg, roasted nuts). (See 'Avoidance' above.)

●Systemic reactions – Certain foods (peanuts, tree nuts, peaches, and mustard) are associated with more systemic reactions than other foods. In general, systemic reactions appear to occur in 2 to 10 percent of patients with PFS. Patients should be informed of this and of the possibility of reacting to related foods upon first exposure. Patients with PFS and systemic symptoms should avoid the raw form of the responsible food. We suggest that such patients also avoid cooked forms of the responsible food (Grade 2C). (See 'Patients with past systemic symptoms' above and 'Risk of systemic reactions' above.)

●Risk factors for systemic reactions – Possible risk factors for systemic reactions include eating large quantities of the offending foods (especially on an empty stomach), taking medications that alter normal digestion (such as proton pump inhibitors), and possibly taking nonsteroidal anti-inflammatory drugs (NSAIDs), drinking alcohol, or exercising vigorously in close proximity to eating the causative foods. (See 'Possible risk factors' above.)

●Need for epinephrine autoinjectors

•We prescribe epinephrine autoinjectors for any patient with PFS who has experienced systemic symptoms in the past. (See 'Patients with past systemic symptoms' above.)

•We suggest that patients who have not experienced systemic reactions carry epinephrine autoinjectors if any of the following are true (Grade 2C) (see 'Indications for epinephrine' above and 'Patients with oral symptoms to high-risk foods' above):

-Allergy to peanut, tree nuts, or mustard has been objectively established.

-The patient experienced an oropharyngeal reaction to a cooked plant food.

-The patient had a positive skin prick test to a commercial extract for the culprit food.

-The patient reacted to a food that is associated with higher rates of systemic reaction in the geographic area in question (eg, peach in Mediterranean countries or apple in Spain).

●Antihistamines – H1 antihistamines can reduce symptoms, although the risks of suppressing symptoms and continuing to ingest the food have not been studied. Patients with systemic symptoms or PFS to high-risk foods should not use antihistamines in this manner. (See 'Antihistamines' above.)

●Pollen immunotherapy – Subcutaneous immunotherapy (SCIT) with pollen allergens is a well-established therapy for allergic rhinoconjunctivitis and allergic asthma, but studies of its effects on PFS are mixed. We do not suggest administering pollen SCIT solely for the purpose of treating PFS (Grade 2C). (See 'Immunotherapy' above.)