An International Delphi Consensus on the Management of Pollen-Food Allergy Syndrome: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee

Abstract

Background:

Pollen-food allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable.

Objective:

To develop consensus recommendation statements for managing patients with PFAS.

Methods:

An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by three authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements.

Results:

After two Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS, and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention.

Conclusions:

We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

Introduction

Pollen-food allergy syndrome (PFAS) or pollen-food syndrome (PFS), previously known as oral allergy syndrome (OAS), is a syndrome of type I hypersensitivity to plant-based foods secondary to pollen sensitization.¹ PFAS is characterized by a constellation of symptoms often limited to the oropharynx such as oropharyngeal pruritus, and angioedema and is frequently observed among patients with pollinosis.¹ The estimated prevalence of PFAS varies by geographic region, paralleling the prevalence of pollen sensitization ranging from 2% to 10.8%.^2–7 PFAS occurs due to the structural homology and consequent cross-reactivity between pollen proteins and heat-labile proteins, such as pathogenesis-related class 10 (PR-10) proteins and profilins, found in plant-based foods.⁸ Due to the nature of these cross-reactive panallergens, which are largely heat and acid labile, symptoms are generally limited to the oropharynx, and systemic type I hypersensitivity reactions, including anaphylaxis, are extremely rare.⁹ Nonetheless, some patients can develop more severe and even systemic symptoms and certain risk factors or co-factors have been implicated as increasing the risk of such severe manifestations.¹⁰

The current management approach to patients with PFAS includes dietary avoidance, epinephrine autoinjectors (EAI) prescription, and consideration of allergen immunotherapy (AIT); however, these practices and recommendations vary considerably and there are no conclusive studies to guide such treatment recommendations.^11–14 To address this unmet need, the American Academy of Allergy, Asthma, and Immunology (AAAAI) Plant Food Allergy Workgroup of the Adverse Reactions to Foods Committee set out to develop consensus management statements to guide practicing physicians caring for patients with PFAS. These statements are focused on patients with PFAS with sensitivity to the heat-labile PR-10 or profilin antigens.

Methods

Panel selection

An international panel of 25 experts with a particular interest in PFAS (allergists, scientists, and dietitians) from 25 different institutions across 11 countries convened and participated in a Delphi consensus process. This was conducted electronically using REDCap, an electronic data capture tool, hosted at Penn State Health Server.¹⁵

The Delphi consensus process

We followed the RAND/University of California Los Angeles methodology.¹⁶ During the first round of the Delphi consensus process, participants were asked to rate the level of appropriateness/agreement of 22 statements pertinent to PFAS management using a scale of 1 (extremely inappropriate or strongly disagree) to 9 (extremely appropriate or strongly agree). These statements were generated based on a review of the literature and previously published practice management guidelines. These statements covered different domains such as education, dietary avoidance, treatment of acute reactions, need for EAI prescription, and allergen immunotherapy. Participants had the option of indicating “non-applicable” if they did not have the expertise to rate a particular statement. Participants were also given the option to submit comments and suggest statement revision if they rated a particular statement <7.

For each statement, we calculated the median appropriateness level, and each statement was categorized as either inappropriate (median appropriateness level of 1–3.4), uncertain (median appropriateness level of 3.5 to 6.9), or appropriate (median appropriateness level of 7.0 to 9.0). We also calculated the disagreement index (DI) as previously described.¹⁷ A DI of less than 1 was used to indicate agreement among the group. In the second Delphi round, experts ranked the level of appropriateness of new and revised statements. A consensus or acceptable statement for inclusion in our final management statements was defined as having a median appropriateness level of at least 8 and a DI of less than 1. We used these stringent criteria as our goal was to generate statements that are more likely to be adopted by practicing clinicians. A consensus was reached after the second round, and therefore, a third round was not conducted. Authors T.A-S., I.S., and A.N-W. drafted the initial and revised statements. Further, we examined comments and incorporated these comments into the discussion section.

Results and Discussion

In total, 22 statements were distributed electronically, and all 25 panel members responded to the first Delphi round. The level of appropriateness and DI of the original 22 statements are presented in Table E1. Of the initial 22 statements, 14 revised/new statements were drafted considering the results and feedback received during the initial round. These 14 statements were then distributed for a second Delphi round and nearly all (23/25;92%) panel members responded. Two members were not available during the second round. A consensus on the revised 14 statements was reached. These statements are presented here verbatim except for subtle modifications to ensure consistent language and terminology across the manuscript (Table 1). In particular, the panel members favored the use of PFAS as a more proper terminology in lieu of the old designation OAS. Using these statements, we suggest an algorithm for the management of PFAS (Figure 1).

Table 1.

Round 2 Delphi exercise

Statement	Appropriateness, median	Disagreement index (DI)
Individuals with pollen-food allergy syndrome (PFAS) may benefit from education about the mechanistic basis of their PFAS.	9	0
Reactions in PFAS are mostly benign, and limited to the oropharynx, although, rarely, more severe symptoms may occur.	9	0.050
Certain foods associated with PFAS (nuts, soy milk, smoothies/fresh juices), especially if consumed rapidly or in large amounts might rarely trigger systemic symptoms.	9	0.132
Certain factors have been reported to increase the severity of PFAS symptoms including medications (e.g., PPIs, NSAIDs), bariatric surgery, uncontrolled asthma, fasting, and exercise)	8	0.132
Individuals with PFAS limited to oral symptoms may choose to avoid only the raw forms of the responsible fruit/vegetable.	9	0.132
Patients with PFAS limited to oral symptoms may choose to continue to ingest the responsible fruit and vegetable if well-cooked but cautioned that roasting may not eliminate the risk of reaction with nuts.	9	0.132
Lighter cooking methods (e.g., steaming or stir-frying) may be insufficient to fully denature the allergens relevant to PFAS.	8	0.132
Patients should be educated on the higher allergen contents in the peels and seeds of fruits but cautioned peeling and removing the seeds is usually insufficient to prevent symptoms of PFAS.	9	0.132
Patients with PFAS characterized by systemic reactions (i.e., symptoms extending beyond the oropharynx) should strictly avoid the responsible fruits and vegetables.	9	0.132
When possible, modifiable risk factors for systemic reactions should be identified and mitigated in patients with PFAS to decrease the risk of life-threatening anaphylaxis.	9	0
Mild symptoms of PFAS limited to oropharynx often resolve without treatment; a non-sedating antihistamine can be used for uncomfortable symptoms.	9	0
PFAS with a history of systemic reaction (defined as having symptoms that extend beyond the oropharynx) may be at a higher risk for future severe reactions. An emergency treatment plan and a prescription of epinephrine autoinjector (EAI) should be offered.	9	0
Individuals with PFAS limited to the oropharynx and who have risk factors for systemic reactions (PPI or beta-blockers use, gastric bypass surgery, or asthma) benefit from a shared decision-making approach when discussing the need for an epinephrine autoinjector (EAI).	9	0.132
Pollen allergen immunotherapy (AIT) via subcutaneous or sublingual route is not proven to alleviate symptoms of PFAS. PFAS is not an indication for pollen AIT.	9	0.132

Figure 1.

Approach for managing patients with PFAS. EAI, epinephrine autoinjector.

Patient education

Statement 1:

Individuals with pollen-food allergy syndrome (PFAS) may benefit from education about the mechanistic basis of their PFAS.

Statement 2:

Reactions in PFAS are mostly benign, and limited to the oropharynx, although, rarely, more severe symptoms may occur.

Statement 3:

Certain foods associated with PFAS (nuts, soy beverage, smoothies/fresh juices), especially if consumed rapidly or in large amounts might rarely trigger systemic symptoms.

Statement 4:

Certain factors have been reported to increase the severity of PFAS symptoms including medications [e.g., proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs)], bariatric surgery, uncontrolled asthma, fasting, and exercise)

Understanding the mechanism of PFAS could reinforce for patients the benign nature of PFAS and the basis of dietary and treatment recommendations. Anaphylaxis as a manifestation of PFAS was first reported to only affect 1.7% of patients with PFAS,³ although subsequently, other studies have reported a much higher figure.^{6, 18} In a nationwide study on PFAS in Korea by Kim and colleagues, 8.9% experienced anaphylaxis.¹⁸ In another study from Italy, 5% of patients with PFAS experienced systemic symptoms.⁶ Considering this, the panel agreed that patients should be offered the opportunity to learn about the mechanistic basis of PFAS and be made aware that PFAS is rarely severe and often limited to the oropharynx. Although experts considered that the sharing information about more severe reactions with patients with PFAS may provoke undue anxiety among PFAS patients, the panel agreed that it was important for patients to be aware that there is a rare chance of systemic reaction including anaphylaxis. Patients with PFAS need to be aware that severe reactions are more likely during the corresponding peak pollen season.¹⁹ Although there is a low risk of anaphylaxis amongst those with PFAS, these patients would nonetheless benefit from education about the signs and symptoms of severe reactions. Although not addressed in our Delphi consensus process, the panel notes that confirming PFAS with prick-to-prick testing with fresh food could be especially important in patients with more severe reactions and that when feasible, consideration of component-resolved diagnostics to elucidate primary sensitization or sensitization to more stable components such as the non-specific lipid transfer protein (nsLTP), as identifying such sensitization could alter treatment recommendations.¹¹

The panel agreed to counsel patients with PFAS that certain foods and factors may be associated with increased severity of PFAS reactions and to educate patients that avoiding these factors, when possible, might serve as an opportunity to mitigate their rare risk of more severe reactions. Several case reports and studies have attempted to explore factors associated with the rare risk of severe PFAS reactions, particularly drug risk factors.^{10, 20} In a multicenter, retrospective study aimed at identifying co-factors associated with systemic reactions to labile plant-food allergens, the authors identified that the use of PPIs was more prevalent among patients with PFAS who experienced systemic reactions.¹⁰ NSAID use was similarly more prevalent among patients with systemic reactions (3% versus 0%), but this was not statistically significant.¹⁰ In another study evaluating adult patients with acute hypersensitivity reaction to NSAIDs, authors identified a subset of patients with history of PFAS limited to the oropharynx who experienced systemic reactions related to co-exposure to NSAIDs and had no reaction upon drug challenge to the culprit NSAID without ingesting the food.²¹ Ingestion of peanuts, tree nuts, fasting, and excessive ingestion such as with liquid forms (e.g., soy beverage, and fresh smoothies) were also factors associated with systemic reactions.¹⁰ Wolters and colleagues described 9 patients with PFAS who had bariatric surgery and experienced systemic reactions to Rosaceae fruit, tree nuts, and peanuts that were either tolerated completely or caused only mild oropharyngeal symptoms before gastric bypass surgery.²⁰ In another study, 2 of 18 patients with PFAS transitioned from only experiencing mild oropharyngeal symptoms to more generalized allergic reactions after gastric bypass surgery.²² Lastly, although not specifically examined in the context of PFAS, alcohol consumption, exercise, and uncontrolled asthma are recognized co-factors for food-induced anaphylaxis and might; therefore, increase the severity of PFAS reactions.^{21, 23}

Dietary avoidance and food processing recommendations

Statement 5:

Individuals with PFAS limited to oral symptoms may choose to avoid only the raw forms of the responsible fruit/vegetable.

Statement 6:

Patients with PFAS limited to oral symptoms may choose to continue to ingest the responsible fruit and vegetable if well-cooked but cautioned that roasting may not eliminate the risk of reaction with nuts.

Statement 7:

Lighter cooking methods (e.g., steaming or stir-frying) may be insufficient to fully denature the allergens relevant to PFAS.

Statement 8:

Patients should be educated on the higher allergen content in the peels and seeds of fruits but cautioned that peeling and removing the seeds are usually insufficient means for preventing symptoms of PFAS.

Statement 9:

Patients with PFAS characterized by systemic reactions (i.e., symptoms extending beyond the oropharynx) should strictly avoid the responsible fruits and vegetables.

Avoidance of the culprit food is a key consideration in the management of Immunoglobulin E (IgE)-mediated food allergy.¹² However, the nature of cross-reactive proteins responsible for PFAS, being both heat- and acid-labile, and the consequent self-limited nature of the PFAS reaction, which is often confined to the oropharynx, requires special consideration.³ There is considerable variability among US allergists in their recommendations regarding dietary avoidance.¹⁴ In one survey study of US allergists, 53% recommended complete avoidance of responsible food, but ~40% indicated a case-by-case approach.¹⁴ In a survey of healthcare professionals in the United Kingdom, 80% recommended avoidance of the triggering food.²⁴ In this Delphi exercise, the panel agreed that avoidance of the raw form of the culprit fruit/vegetable is advisable for most patients, particularly those with a history of systemic reaction, for whom strict avoidance of the culprit food is recommended. While these foods are easily identifiable, the panel members pointed to the major risk of inadvertent ingestion in “juice bars” and commercial salads. Aside from avoiding the plant-derived food responsible for the index reaction, the panel disagreed that patients with PFAS should be provided with a list of fruits and vegetables that they may potentially react to on the basis of their index reaction history (Table E1). The panel cited the positive health impact of ingesting fruits and vegetables²⁵ and the concern of provoking undue anxiety.²⁶ The panel cautioned that such a practice might lead to unnecessary avoidance. On the contrary, one of the panel members suggested offering a graded challenge should the patient have a concern. Similarly, the avoidance of the cross-reactive fruit/vegetable based on the original food inciting the reaction did not meet our appropriateness cutoff of >7 (Table E1).

While a few panel members acknowledged that some patients with mild PFAS may tolerate the responsible raw fresh fruit or vegetable and only experience tolerable symptoms, a consensus was reached that patients should only consider ingesting the culprit fruit and vegetables when well-cooked, tinned, or as jams. Patients should be educated about the ineffectiveness of only removing the peels and of lighter cooking techniques such as steaming or stir-frying in completely denaturing the allergen responsible for PFAS and that roasting may similarly be inadequate in removing the culprit allergen responsible for nut-induced PFAS.²⁷ In a double-blind, placebo-controlled food challenge (DBPCFC) with roasted hazelnuts (140° C for 40 minutes) performed on 17 birch pollen-allergic patients, 5/17 experienced PFAS.²⁸ In another study, 17 of 20 patients developed PFAS after the DBPCFC with roasted hazelnut.²⁹ However, both of these studies indicated a higher threshold dose for eliciting a reaction.^.30 As the process of nut roasting is not standardized, and there might be a high risk of cross-contamination in roasting facilities, in combination with the lack of studies demonstrating absolute tolerability of roasted nuts in patients with PFAS, patients would benefit from education on this fact to avoid false reassurance.³⁰

Treatment of acute reactions and consideration of epinephrine autoinjector prescription

Statement 10:

When possible, modifiable risk factors for systemic reactions should be identified and mitigated in patients with PFAS to decrease the risk of life-threatening anaphylaxis.

Because anaphylaxis has been reported secondary to PFAS, patients with PFAS might benefit from measures to mitigate the risk of severe reactions.^{6, 18} In addition to co-factors that have been specifically associated with the occurrence of systemic reactions in patients with PFAS such as the use of PPIs, NSAIDs, other generic factors commonly linked to severe food-induced anaphylaxis (e.g., uncontrolled asthma), or factors linked to refractory anaphylaxis (e.g., the use of beta-blockers or angiotensin-converting enzyme inhibitors) would need to be identified and, when possible, mitigated to lessen the risk of anaphylaxis from PFAS.^{10, 20, 23} The panel acknowledged that these medications could be important to patients’ overall health and thus a shared-decision making balancing the risks and benefits of continuation versus discontinuation of such medications along with the involvement of the respective specialty are advisable.

Statement 11:

Mild symptoms of PFAS limited to oropharynx often resolve without treatment; a non-sedating antihistamine can be used for uncomfortable symptoms.

Symptoms of PFAS that are confined to the oropharynx are often self-limited to 30 minutes or less and do not require treatment with medication.³¹ However, antihistamines are frequently advised by treating physicians with 18 out of 28 otolaryngologists indicating that they would recommend antihistamines as a treatment for PFAS in one survey study.³² Further, the panel members considered that oropharyngeal symptoms might induce panic and apprehension that could further exacerbate throat symptoms with complaints that the throat is tightening or becoming restricted. Taken together, while the panel agreed that patients should be reassured of the self-limited nature of PFAS, non-sedating antihistamines may be used by patients who experience uncomfortable symptoms. This is in line with the British Society of Allergy and Clinical Immunology (BSACI) guidelines for the diagnosis and management of PFAS in the UK.¹¹ While there is no supporting evidence, in theory, liquid or chewable non-sedating antihistamines may act more rapidly in relieving the oropharyngeal symptoms of PFAS.³³

Statement 12:

PFAS with a history of systemic reaction (defined as having symptoms that extend beyond the oropharynx) may be at a higher risk for future severe reactions. An emergency treatment plan and a prescription of epinephrine autoinjector (EAI) should be offered.

Statement 13:

Individuals with PFAS limited to the oropharynx and who have risk factors for systemic reactions (PPI or beta-blockers use, gastric bypass surgery, or asthma) benefit from a shared decision-making approach when discussing the need for an epinephrine autoinjector (EAI).

EAI is a lifesaving intervention in patients with anaphylaxis due to food.²³ However, our panel members raised concerns about the cost and reluctance of some patients to carry an EAI.³⁴ While anaphylaxis is considered a rare manifestation of PFAS,¹⁸ 82 out of 122 US allergists surveyed indicated that they would prescribe EAI for patients with PFAS on a case-by-case basis with symptoms affecting the throat being the most common reason for prescribing EAI followed by facial edema and generalized urticaria.¹⁴ A higher proportion of otolaryngologists consider EAI prescription. Of the 28 otolaryngologists who were familiar with PFAS, 14 prescribed EAI.³² The tendency to prescribe EAI is less common among UK allergists (18% of the surveyed allergists).²⁴ In keeping with the 2014 practice parameter update on food allergy, which suggests prescribing EAI in patients with PFAS with a history of laryngeal swelling or respiratory compromise,^{12, 23} a consensus has been reached among panel members that patients with PFAS who have experienced a systemic reaction would benefit from EIA.

Because several studies and anecdotal reports suggested that certain factors could be associated with increased severity of PFAS reaction,^{10, 20, 22, 23} the panel agreed that patients with PFAS who have non-modifiable risk factors for systemic reactions, e.g., gastric bypass surgery, or asthma, a shared decision-making regarding the prescription of EAI should be adopted.¹⁰ As the burden of carrying an EAI was cited by panel members as one reservation to prescribing EAI, the novel non-injectable epinephrine forms (intranasal, sublingual) under development may alter the threshold for prescribing rescue epinephrine for patients with PFAS.³⁵

Immunotherapy for PFAS

Statement 14:

Pollen allergen immunotherapy (AIT) via subcutaneous or sublingual route is not proven to alleviate symptoms of PFAS. PFAS is not an indication for pollen AIT.

Subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) are effective in alleviating symptoms of allergic rhinitis, allergic conjunctivitis, allergic asthma, and atopic dermatitis in patients.^{36, 37} The benefit of AIT in alleviating symptoms of PFAS remains uncertain. Limited studies have explored the utility of SCIT for the treatment of PFAS.^38–48 While several small-scale studies suggested benefit from SCIT in completely or partially alleviating symptoms of PFAS^{38, 39, 42, 45, 47}, other studies failed to demonstrate such benefits, or only a fraction of patients benefited from this intervention.^{40, 43, 46, 48} In a double-blind placebo-controlled study, 1-year of allergen immunotherapy with the folding variant of recombinant Bet v 1 in 56 patients with birch-related soy allergy resulted in higher threshold for eliciting objective signs of reaction; however, results were not statistically significant.⁴⁹ Further, re-sensitization to apple occurred after discontinuation of SCIT, although persistent tolerance has also been reported.⁵⁰ Taken together, the small sample size of studies exploring SCIT as a treatment of PFAS and the focus of these studies on apple-induced PFAS in birch-sensitive individuals limit the overall generalizability of these study findings.

Even more limited studies have explored the impact of aeroallergen SLIT on PFAS.^{46, 51–53} In one small study from Kinaciyan and colleagues, nine patients with apple-induced PFAS received SLIT with birch pollen extract (administered as drops; maintenance dose, 4.5 μg Bet v 1) which was successful in ameliorating their rhinoconjunctivitis symptoms, but symptoms of apple-induced PFAS did not significantly decrease.⁵² Authors noted that while specific IgE and IgG₄ to Bet v1 were increased, Mal d 1-specific IgE and IgG₄ levels were not altered, concluding that SLIT did not alter the immune response to the pollen-related food allergen.⁵² However subsequent studies were more promising. In an open-label observational study of 102 patients with pollen-induced rhinoconjunctivitis and PFAS, approximately 75% of patients responded to SLIT with a decrease in their symptom score of ≥50%, and PFAS was rated as much or very much improved in ~73% of these patients.⁵¹ In another placebo-controlled study, investigators randomized patients with PFAS to either a placebo or sublingual tree pollen tablet and examined the impact of SLIT on PFAS through an open-label challenge to apple noting improved tolerance suggesting a beneficial effect for SLIT.⁵³ De novo PFAS to apple, with progression to peaches, cherry, and carrot, has been reported in one 40-year-old female patient a few months after starting birch-specific SLIT.⁵⁴ Considering the limited evidence for both SCIT and SLIT as a treatment for PFAS, consensus was reached that PFAS should not be considered an indication for AIT. In patients with allergic rhinoconjunctivitis, clinicians should counsel patients that there is insufficient evidence that pollen-specific AIT alleviates PFAS. Future larger studies with DBPCFC and assessment of such intervention on quality of life are needed to characterize the benefit of pollen AIT in PFAS, and as suggested by one panel member, whether AIT in early childhood would prevent the onset of PFAS.

Other treatment considerations

Other considerations that did not meet the consensus criteria included oral immunotherapy (OIT) and omalizumab use for PFAS. OIT has transformed our approach to patients with peanut allergy.⁵⁵ The role of OIT in patients with PFAS has been explored. In one study, 40 birch-sensitive patients with allergic rhinitis and PFAS limited to the oropharynx were randomized to either daily consumption of incremental amounts of raw apple or no treatment (avoidance) and after 8 months, 17 out of the 27 patients randomized to active apple consumption, were able to tolerate 128 grams of apple as opposed to zero patients in the placebo arm, suggesting a role for OIT in the management of PFAS.⁵⁶ Another Phase II pilot study evaluated the effectiveness of incremental daily apple consumption in 16 patients with birch pollen allergy. After 8 months, a provocative challenge demonstrated increased tolerance to apple and was accompanied by a decrease in skin reactivity to apple.⁵⁷ SLIT with recombinant Mal d 1, but not with recombinant Bet v1 reduced clinical reactivity to apple.^{58, 59} Similarly, in a case series of 7 patients, sublingual drops with increasing concentrations of profilin resulted in decreased skin test wheal size in five patients and promoted tolerance to several foods that they couldn’t tolerate before the induction phase in all 7 patients.⁶⁰ In our Delphi exercise, agreement among the panel members has been reached that OIT might be offered in a research capacity, however, the appropriateness level did not meet our cutoff >7 (Table E1).

Few cases have been reported of patients with PFAS who responded to omalizumab therapy, an anti-IgE monoclonal antibody. One described a birch-sensitive individual with apple-induced PFAS and another described an individual who experienced intractable lip edema and was sensitive to multiple fresh fruits including orange, apple, peach, and tomato.^{36, 61} Given the prohibitive cost of omalizumab, and limited evidence to support the use of omalizumab, the panel did not agree on using omalizumab for the sole purpose of treating PFAS (Table E1).

Conclusion

Through an international Delphi exercise, we established a consensus to guide treatment recommendations for patients with PFAS. Our panel members agreed on educating patients about the mechanistic basis of the disease, emphasizing the usual benign self-limited nature of the reaction, while providing the necessary education for prompt recognition of a worsening reaction and its treatment, recommending avoidance of the culprit raw plant-derived foods, discussing appropriate treatment options, and considering shared decision-making when prescribing EAI for patients who have experienced severe reactions or have risk factors for severe reactions. At present, there is insufficient evidence to recommend PFAS as an indication for allergen immunotherapy (Figure 1).

Abbreviations:

AAAAI

American, Academy of Allergy, Asthma, & Immunology

AIT

allergen immunotherapy

BSACI

British Society of Allergy and Clinical Immunology

DI

disagreement index

DBPCFC

double-blind, placebo-controlled food challenge

EAI

epinephrine autoinjector

PFAS

pollen-food allergy syndrome

OAS

oral allergy syndrome

OIT

oral immunotherapy

PPI

proton pump inhibitor

SCIT

subcutaneous immunotherapy

SLIT

sublingual immunotherapy

NSAIDs

non-steroidal anti-inflammatory drugs