Guideline for the Diagnosis and Management of Pollen Food Syndrome in the UK

Overview

This new Guidelines summary of the British Society for Allergy and Clinical Immunology’s pollen food syndrome (PFS) guideline covers recommendations on diagnosing and managing PFS, including information on different allergy tests. It includes useful tables and algorithms to assist understanding and diagnosis.

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Pollen Food Syndrome in the UK: Visual Summary

Introduction

• PFS is a common, IgE-mediated food allergy, characterised by immediate, mild oropharyngeal symptoms after the consumption of raw plant foods due to cross reactions between pollen antibodies and unstable plant food allergens
• This condition can often be managed in primary care, and this guidance contains a leaflet specifically designed for use by GPs.

Diagnosis

Clinical Presentation

• Typically, PFS provoked by Bet v 1 or profilins (common pollen allergens) presents as reported reactions only to raw/uncooked plant foods, although some individuals may react to roasted peanuts and/or tree nuts
• Symptoms usually occur immediately or within 5–15 minutes of eating, and typically include tingling, itching, or soreness in the mouth, throat, or ears, and/or mild angioedema of lips and oral mucosa
• Patients may also experience itchy hands/sneezing/eye symptoms when peeling potatoes or other root vegetables. Minor angioedema of the tongue or pharynx, peri-oral rash, mild cough, and occasionally ocular/nasal symptoms, abdominal pain, and nausea may occur
• The consumption of PFS trigger foods can exacerbate existing eczema, and in young children, skin symptoms of itch and rash may be predominant
• While throat tightness/closure and breathing difficulties due to marked localised oedema can occur, systemic symptoms (for example, chest tightness, wheeze, urticaria, or erythema) are much less common
• Symptom severity may vary depending on the individual, quantity of allergen consumed, how long the product has been stored, whether the food has been peeled, and how well-cooked it is. Systemic or more severe symptoms could indicate a primary allergy to peanuts and/or tree nuts, or sensitisation to nonspecific lipid-transfer protein (nsLTP), which ranges from relatively mild-to-moderate allergic reactions to anaphylaxis
• Symptoms of a primary allergy to peanut and tree nuts are generally consistent at each exposure, and differ from nsLTP allergy—which can be unpredictable—because reactions may be dependent on cofactors such as exercise, alcohol, or nonsteroidal anti-inflammatory drugs.

Diagnostic Clinical History

• The diagnosis of PFS mediated by Bet v 1 or profilins can be made through clinical history alone (see Algorithm 1). If the answer to the following five questions is affirmative, then the diagnosis is almost certainly PFS:

1. Are the foods provoking symptoms raw fruits, raw nuts, or raw carrot/celery?
2. Are the same trigger foods tolerated when well-cooked or roasted?
3. Do the symptoms occur immediately or within a few minutes of eating?
4. Are the symptoms localised to the oropharynx and include tingling, itching, or swelling?
5. Does the patient experience seasonal allergic rhinitis, or, if not, are they sensitised to pollen?

Algorithm 1: Algorithm for the Diagnosis of Birch Pollen-mediated PFS—Making a Diagnosis of Pollen Food Syndrome on the Basis of the Clinical History Alone

Allergy Tests

Pollen Sensitisation

• Individuals reporting reactions to plant foods should be assessed for sensitisation to birch and grass pollens (see Table 1).

Table 1: Recommended Allergy Tests for the Diagnosis of PFS

• A diagnosis of PFS is associated with sensitisation to multiple pollens and a larger skin prick test (SPT) wheal size or higher levels of specific immunoglobulin E (sIgE) to these aeroallergens
• In young children, the grass profilin Phl p 12 has been demonstrated to be a reliable biomarker for PFS, with Bet v 1 being a marker of PFS in older children and adults, especially those not reporting seasonal allergic rhinitis
• If the profile of reported food triggers is not consistent with birch cross-reactivity, then SPT to mugwort or ragweed should be undertaken
• Severe reactions involving banana, kiwifruit, avocado, or chestnuts may indicate latex-food allergy, so testing with latex SPT or a prick-to-prick skin test (PPT) with a latex glove is helpful.

Skin Prick Tests and Specific IgE Antibody Tests

• In all cases, only those foods reported to provoke symptoms should be tested
• If fruits and vegetables have been reported to provoke symptoms, but the symptoms are atypical, severe, or to both raw and cooked fruits/vegetables, or when present in a composite dish, then PFS is less likely. However, in the case of severe reported reactions to fruits (for example, jackfruit), and/or fresh fruit/vegetable juices/smoothies, a positive PPT to raw but not to cooked fruits and vegetables is diagnostic of PFS. A PPT to soya milk can also confirm PFS when accompanied by sensitisation to birch, and a convincing history
• If hazelnut is a reported trigger, then a PPT with roasted hazelnut may be useful if available, with a negative test confirming the diagnosis. If the test is positive, then a diagnosis of a primary allergy to hazelnut needs to be considered. If PPT is not an option, then a commercial extract of hazelnut can be utilised, but a positive test may still indicate PFS, so symptom history is key to the diagnosis
• Undertaking PPT to raw and roasted nuts can also be utilised for almonds and peanuts, or, if PPT is not available, SPTs with commercial extracts
• Commercial SPT extracts are reasonable predictors of walnut allergy, whereas the value of Brazil nut extracts is less certain, although an SPT of 6 mm or below for Brazil nut suggests that a primary allergy is less likely
• It has been reported that individuals with PFS are commonly sensitised but not allergic to macadamia nuts, with an SPT of less than or equal to 8 mm or an sIgE of less than or equal to 15 kUA/l ruling out a primary allergy to macadamia nuts
• There are little or no published data on the likelihood of birch-sensitised individuals experiencing PFS reactions to cashew and pistachio nuts, so, if they have been reported as a trigger food, sIgE or SPT tests using reagents are good predictors of a primary allergy to cashew nut and/or pistachio nut.

Component-resolved Diagnosis

• A detailed clinical history and PPT/SPT can achieve diagnosis, but should there be any concerns regarding the presence of either a primary tree nut/legume allergy, or a combination of PFS and a primary tree nut/legume allergy, then component-resolved diagnosis (CRD) tests are useful (see Table 1 above and Table 4 in the full guideline).

Soya

• Patients who have experienced more severe or systemic reactions to soya should be tested to Gly m 4 (PR10), Gly m 5, Gly m 6, and Gly m 8 (major soy allergens).

Peanuts

• The poor sensitivity and specificity of the peanut PR10 allergen Ara h 8 make it a less useful test, and it may be positive in those with a primary peanut allergy who are sensitised to birch pollen. It should only be tested in those with suspected PFS who have a negative test to the major peanut allergens Ara h 2 and Ara h 6
• If suspicion of primary peanut allergy is high, but tests to these allergens are negative, more comprehensive tests against Ara h 1, 3, and 9 can be helpful, especially in children.

Tree Nuts

• The hazelnut allergens Cor a 9 and Cor a 14 are the best markers of primary hazelnut allergy, in both children and adults
• If they are negative, and the PR10 allergen Cor a 1 is positive, this confirms a diagnosis of PFS since Cor a 1 has good sensitivity, albeit low specificity
• If there is any doubt about whether reactions to walnut and Brazil nut are due to birch-related PFS, then the major allergens in walnut (Jug r 1) and Brazil nut (Ber e 1) have the best diagnostic accuracy
• Although individual allergens responsible for allergic reactions to almond and macadamia nut have been identified, there are no individual component allergens available for almond or macadamia nut.

Excluding nsLTP Allergy

• If more severe or atypical reactions have occurred to fruits and vegetables, a diagnosis of nsLTP allergy should be considered. A correct diagnosis is essential as the advice given differs significantly to that for PFS
• Testing with specific peach SPT reagents containing the peach nsLTP, Pru p 3, can determine likely sensitisation to nsLTP, although they might contain other peach allergens such as Pru p 7, the gibberellin-related protein
• If the specific SPT extracts are not available, then testing for Pru p 3 is recommended as it is a useful surrogate marker of sensitisation to nsLTP, even if the reported trigger food is not peach (see Table 1)
• If nsLTP allergy is suspected, then testing to mugwort and plane tree can support the diagnosis of nsLTP allergy
• Birch-sensitised individuals reporting reactions to peanuts or tree nuts atypical for PFS, with negative tests to the major allergens, should also be tested with Pru p 3 and the relevant nsLTP allergens in walnut (Jug r 3), hazelnut (Cor a 8), or peanut (Ara h 9) to exclude nsLTP allergy. However, patients with PFS or a primary peanut or tree nut allergy may also have clinically irrelevant sensitisation to nsLTP, so tests should only be undertaken if there is strong suspicion of nsLTP allergy from the clinical history.

Oral Food Challenge

• An oral food challenge (OFC) is rarely required for the diagnosis of PFS, except when history and diagnostic tests are inconclusive and there is a pressing need to eliminate unnecessary dietary restrictions or alleviate anxiety in the patient and their family
• Individuals avoiding multiple foods (for example, all fruits, vegetables, and nuts) or those who already have a very limited diet due to religious reasons, patient choice, (vegetarian or vegan), poor eating habits, or anxiety, may also require an OFC
• The difficulty with OFC for suspected PFS is the high probability of a positive outcome when testing to the raw fruits/vegetables or nuts, and the often-subjective nature of PFS symptoms. Since early-onset oropharyngeal symptoms could either be due to PFS or a primary food allergy, it may be necessary to continue the challenge if such symptoms occur, to ascertain the final diagnosis.

Foods Used in OFC

• It is recommended that in clinical practice the tested food should be administered in its natural state, for example raw fruit/vegetables, soy milk, roasted or blanched tree nuts, roasted peanuts.

Tree Nuts and Peanuts

• Blanched (without skin) hazelnuts and almonds and roasted peanuts should be used, as small amounts might be tolerated in individuals with PFS in whom a primary nut allergy has been ruled out
• If roasted/blanched nuts are tolerated, a limited challenge with low doses of raw hazelnuts/almonds/peanuts might be helpful, to demonstrate that accidental exposure to traces of nuts will not provoke significant reactions. Standard dosing schedules based on protein content can be used for challenges to tree nuts, peanuts, and soy.

Fruit and Vegetables

• Varietal differences, peeling, and heat processing may diminish/eliminate reactions. Challenging with different types or varieties of fruit, or with peeled or cooked fruit, can increase intake in individuals excluding multiple foods
• Challenge doses based on protein content are unsuitable for fruit and vegetables, so challenges should focus on giving incremental doses of the food up to an age-appropriate portion.

Prevention and Management of Reactions

Dietary Advice

• Only the specific raw plant foods which trigger symptoms should be avoided (see Table 2).

Table 2: Dietary Management of Birch-related PFS

For a table detailing classical sensitisation patterns in PFS relating to peanut, tree nuts, and soy, refer to the full guideline.

Fruits and Vegetables

• The most common birch-related PFS triggers are raw apple, pear, kiwi fruit, strawberry, peach, plum, cherry, tomato, celery, and carrot, but cosensitisation to profilins can involve a wider range of fruits and vegetables
• Organic or frozen raw fruit or vegetables can still provoke reactions. Cooked, canned, or processed fruit and vegetables, and commercially produced, pasteurised fruit and vegetable juices are usually tolerated, although some ‘lighter’ cooking methods such as stir-frying or steaming may be insufficient to denature the PR10 or profilin allergens
• Some varieties of fruits or vegetables are more likely to provoke symptoms than others: Golden Delicious, Granny Smith, Starking, and Cox’s Orange Pippin apple varieties have been shown to be more allergenic due to the increased amount of the Bet v 1 homologous protein Mal d 1
• The level of the PR10 allergen in apples is low when freshly harvested and increases during storage, so eating local fruit and vegetables in season is advised, but avoid organic or pesticide-free plants as the level of PR10 allergens may be greater
• The allergens are mainly in the peel and pips so peeled and deseeded raw fruits and vegetables may provoke fewer or no symptoms; however, peeling foods such as potatoes or other root vegetables can result in itching/swelling of hands and eyes.

Tree Nuts, Legumes, and Seeds

• Hazelnut, walnut, almond, and, less often, peanut are common PFS triggers, but may be tolerated in small amounts if well roasted or when present in composite foods, such as chocolate hazelnut spread
• Foods with ‘may contain nuts’ warnings do not need to be avoided, and pistachio, cashew, and macadamia nuts are often tolerated
• Soya milk affects around 10% of birch-sensitised individuals and can provoke severe reactions, so an assessment should be undertaken to determine individual risk and whether other plant-based milks (oat, coconut, or rice milk) would be preferable
• Other raw or lightly cooked legumes more likely to provoke symptoms include beansprouts, sugar snap peas, and mangetout
• Sunflower and pumpkin seeds have been linked to PFS but often only in those sensitised to mugwort pollen, and sesame seeds are usually tolerated.

Nutritional Issues

• Everyone with a diagnosis of PFS will benefit from individual dietary counselling from a qualified dietitian, but this is imperative for those who report multiple food triggers, have a concomitant primary food allergy, or already have dietary restrictions due to religious/personal reasons.

Management of Reactions

• Although dietary avoidance is the mainstay of PFS management, antihistamines are recommended to treat symptoms in case of exposure and are generally sufficient for individuals with PFS mediated by Bet v 1 and/or profilins, who have mild symptoms
• Those rare patients experiencing severe PFS reactions may require adrenaline auto-injectors
• Severe reactions may be more likely in the birch pollen season, especially in those patients who have perennial or seasonal asthma; therefore, optimal management of allergic rhinitis and asthma is important for patients with PFS
• Other issues which may also increase the severity of reactions include the presence of cofactors, for example:
  • exercise
  • pain relief
  • reactions which occur:
    • during the pollen season
    • in individuals on acid suppressant medication
    • in individuals who have had bariatric surgery
• Those who also suffer from concomitant eczema will benefit from well-controlled symptoms, so they can evaluate whether some PFS-cooked foods are causing a worsening of their eczema.

For recommendations on other treatments, and a table detailing nutritional issues and supplementation, refer to the full guideline.

Quality of Life

• Although PFS is often perceived to be a mild condition that needs no specialist input, the avoidance of multiple foods and fear of reactions to new foods can hugely impact the health-related quality of life (HRQoL) of sufferers
• Anxiety has been shown to be associated with strict avoidance of foods in individuals and could result in the avoidance of all pollen-associated foods
• Individuals with PFS usually have concomitant seasonal allergic rhinitis, which has a high morbidity due to reductions in outdoor activity, sleep quality, emotional wellbeing, and work/school performance, and therefore additionally affects HRQoL
• Thus, it is important that healthcare professionals address the psychological needs of the PFS-affected individual to help improve their HRQoL.