Oral allergy syndrome

L/O/G/O

Oral allergy syndrome (Pollen-Food syndrome)

Sadudee Boonmee,MD 9/11/12

ContentsContents

1. Introduction1. Introduction

2. Clinical manifestration2. Clinical manifestration

3. Epidemiology3. Epidemiology

4. Pathogenesis4. Pathogenesis

5. Diagnosis5. Diagnosis

6. Treatment6. Treatment

Oral allergy syndrome (OAS)Oral allergy syndrome (OAS)

• Oral allergy syndrome (OAS), referred to as pollen associated FA syndrome

• localized IgE mediated allergy, usually to raw fruits or vegetables

• OAS most commonly affects patients who are allergic to pollens

Guidelines for the Diagnosis and Management of FoodAllergy in the United States: Report of the NIAID-SponsoredExpert Panel , J Allergy Clin Immunol 2010;126:S1-S58

OAS vs PFASOAS vs PFAS• Some pt. experience reaction to foods without pollinosis and symptom are

not limited to oral cavity but may be range from oral and GI symptom to severe systemic reaction eg. Laryngeal edema, urticaria, bronchial asthma and food-induced anaphylaxis

• Mari et al. defined OAS as

complex of symptoms induced by exposure of the oral and pharyngeal mucosa to food allergens including symptoms of increasing severity1

• OAS is not restricted to pollen-associated food allergies1

• OAS due to a cross-reaction between pollen antigen and fruit or vegetable antigen has been called the more specific term “pollen-food allergy syndrome” (PFAS)2

1 Allergy 2006: 61: 461–4762 Allergology International. 2009;58:485-491

Clinical manifestration

- usually restrict to oral cavity

- After contact of fruit or vegetable rapid onset of itching of the lips, tongue, roof of the mouth, and throat, with or without swelling, and/or tingling of the lips, tongue, roof of the mouth, and throat

- occassionally a sensation of pruritus in the ear and/or tightness in the throat

- symptom are generally short-lived• Guidelines for the Diagnosis and Management of FoodAllergy in the United States: Report of the NIAID-SponsoredExpert Panel , J Allergy Clin Immunol 2010;126:S1-S58• Middleton’s Allergy principles & practice 7th edition, p 1150-51

Oral allergy syndrome (OAS)Oral allergy syndrome (OAS)

Epidemiology Epidemiology

• Estimated about 5% of general population in central Europe suffer from PFAS

• PFAS affects up to 50-70% of adults suffering from pollen allergy, esp. to birch, ragweed, and mugwort pollens

• Geographic and dietary influences complicate epidemiologic studies on pollinosis-associated food allergy, no exact data on the frequency of PFS is available

• Middleton’s Allergy principles & practice 7th edition, p 1150-51• Current Allergy and Asthma Report 2008,8:413-7

Birch pollen

Mugwortpollen

Ragweed pollen

Pathogenesis Pathogenesis • Cross reactivity occur when a specific antibody formed in

response to one epitope react to another similar or identical epitope on anothor antigen

• These pollen and foods are not botanically related but share highly conserved homologous protein called

pan allergen (widely distributed throught the plant and animal kingdom)

• IgE directed against common cross-reactive structures shared by pollen and plant-derived food

Current Allergy and Asthma Report 2008,8:413-17

• Sensitization to inhaled pollen proteins via the respiratory tract is believed to be the initial pathogenic event (Class 2 food allergy)

Pathogenesis Pathogenesis


Cross-reactive Pan AllergensCross-reactive Pan Allergens• Widely distributed throughout the plant kingdom

and are involed in the extensive IgE cross-reactivity between antigen from unrelated plant species

• Plant protein involved in PFAS

- pathogenesis-related proteins (PRs)

- lipid transfer protein (LTPs)

- profilins

-(cross-reactive carbohydrate determinant : CCD)


Pathogenesis-related protein (PRs)Pathogenesis-related protein (PRs)

• 14 PRs familly• related to defense response to infection, wound

healing, or environmental stress (drought, flood, freezing and ozone) in higher plant

• Small molecular weight 5-70 kDa • Express different amount of PRP depending on

environmental condition

: ripeness, chemical, pesticides increase PRP expression (may enhance allergenicity)

• Current Allergy and Asthma Report 2008,8:413-17

• Bet.v1 is major allergenic protein in birch tree (Betula verrucosa)

- PRP 10

- Most PFAS in birch pollen allergic pt. cause by protrein that have IgE cross-reactivity to Bet v1 and its food homologues

: Rosacea fruit apple (Mal d 1), cherry(Pru av 1), apricort (Pru ar 1),pear (Pyr c 1), plum

: Apiaceae vegetables celery(Api g 1), carrot(Dua c 1)

- Mal d 1, major apple allergen, 63% homolog to Bet v1




These protein share a high degree of amino acid sequence similarity (28%-67%)to Bet v1

Middleton’s Allergy principles & practice 7th edition, p 1150-51

Fruit of the Rosaceae

Hazel nut Cor a1

Vegetable of the Apiaceae

• PRs-2

- beta 1,3 glucanases

- plant cell wall, these protein express during pollen germination and induced upon wounding, cold, ozone and UVB expose

- Hev b 2 (latex allergen) sequence similar to beta 1,3 glucanases-like allergen in banana, potato, and tomato



Latex food syndrome


• PRs-3 chitaneses class I, II, IV

- only chitaneses class I associated with allergy

- found in exoskeleton insect and cell wall of fungi

- chitaneses class I have an N-terminal hevein domain that shared by latex prohevein (Hev b 6.02)

- avocado, chestnut, and banana have sequence similar to chitaneses class I



Cross reactivity of latex-allergic pt. to avocado,chestnut, and banana


• PRs-5 Thaumatin-like protein

- antifungal in plantgive plants resist against freeze and drough

(Minor allergen)

(Major allergen)




PR-14 : LTPs (lipid transfer proeins)PR-14 : LTPs (lipid transfer proeins)• 9 kDa polypeptides (plant antifungal and antibacterial)

• Pan-allergen : widely distributed throughout the plant kingdom

• Potent food allergen : thermostability and extreme resistance to pepsin digestion cause both PFAS and class 1 food anaphylaxis

• LTPs retain allergenicity in process foods such as sterilized peach juice, cooked apple, beer, and ferment product such as wine

• Sensitization to LTPs associated with higher rate of systemic reaction


• May responsible for fruit allergy in absence of pollen allergy • found in outer cell layer (peel > pulp)

- Prunoideae family : peach (Pru p1 in peach skin and Pru p 3 in peach fruit), apricort (Pru ar 3), cherry (Pru av 3)

- Rosaceae family : apple (Mal d 3), pear (Pyr c 3)

- Gly m 1, a major allergen in soy bean

• Apple allergic pt. without birch hypersensitivity frequence sensitized to apple LTPs (Mal d 3) (in southern Europe)

• Mugwort pollen LTPs (Art v3) cross-react with peach LTPs(Pru p3) mugwort-peach association (esp. in Mediteranean area )


Cherry Pru av 3Hazelnut Cor a 8Orange Cit s 3Strawberry Fra a 3Mugwort Art v 3


ProfilinProfilin

• 12–15 kDa actin-binding and cytoskeleton regulating protein

• pan-allergen : prominent allergens in pollen of tree, grass, and weed

• sensitization to profilin found 20% of pollen allergic pt.• First profilin identified was named Bet v2, IgE of birch

pollen-food allergic individual cross-reacts with Bet v2 homologous protein from

- apple ,pear, melon, carrot, celery, potato and mugwort


Mugwort Art v 4 Profilin


High-molecular weight allergens and cross-reactive carbohydrate determinants (CCD)High-molecular weight allergens and cross-reactive carbohydrate determinants (CCD)

• 45–60 kDa• N-glycan stability to proteolysis & processing /

thermostable

• N-glycans containing 1,3-fucose & 1,2-xylose (glycoallergen) form the key IgE-binding epitope of celery protein (Api g 5) (cross-react with mugwort glycoprotein)

• Celery-mugwort-spice syndrome in Mediterranean (rare Birch pollen): variable frequency of anaphylaxis


SYNDROMES ASSOCIATED WITH SYSTEMIC REACTIONS SYNDROMES ASSOCIATED WITH SYSTEMIC REACTIONS

• Celery-birch-mugwort-spice syndrome

- potentially severe form of celery allergy seen in patients who are sensitized to both birch and mugwort

- Patients may react to the Apiaceae family (carrot, caraway, parsley, fennel, coriander, fenugreek, cumin, dill, and aniseed), as well as paprika, pepper, mango, garlic, leek, and onion

Allergy 2006;61:461

• Can devide into at least 4 group

1. Api g 1,Bet v 1 homologous proteins demonstrated that IgE reactivity is based on primary sensitization to Bet v 1 in a central European population

2. Api g 4, profilin in celery display IgE cross-reactivity with birch Bet v 2 and mugwort Art v 4 profilins

3. Art v 60 kDa high MW allergens and/or CCDs (glycoallergens) recognized by IgEs cross –reacttivity from celery allergen Api g 5

4. Little known about cross reactions with Solanaceae or Piperaceae family

Allergy 2006;61:461

• Mugwort profilin Art v4 celery mugwort spice syndrome

• Bet v2 birch-celery association cross reactive of celery Api g 4

Allergy 2006;61:461

Apiaceae (Umbelliferae)

Ragweed melon banana associationRagweed melon banana association

• Lack of molecular data on melon allergens possible cross-reactive allergen were identified in sera from OAS pt.

- Profilin : allergenic conpound in other Cucurbitaceae fruit and vegetable eg. Zucchini, Cucurbita pepo

- LTPs: 10% of melon allergic pt. display severe anaphylatic reaction (no melon LTPs has been idetified yet !!! )

- MW 15 to 60 kDa as allergens in melon, zucchini, cucumber, and watermelon seem to harbor complex asparagine-linked glycans comprising xyloxyl and fucosyl residues, which may act as CCDs

Allergy 2006;61:461

Ragweed

cucurbitaceae musaceae

Allergy 2006;61:461

Allergy 2006;61:461

• Latex-fruit syndrome- Approximately 30 % to 50 %of individuals who are allergic to natural rubber latex (NRL) show an associated hypersensitivity to some plant-derived foods, especially fresh fruits, such as avocado, banana, chestnut, kiwi, peach, tomato, white potato, and bell pepper

- Allergens involved in the latex-fruit syndrome include hevein (Hev b 6.02), Hev b 7, and the panallergen profilin Hev b 8

Allergy 2006;61:461

DignosisDignosis• No diagnostic criteria

- A history of symptoms consistent with PFAS

- Evidence of allergic sensitization to the plant food in question

- Evidence of allergic sensitization to pollen

- A known correlation between the plant food(s) in question and a pollen(s) to which the patient is sensitize

• History

- Has the patient experienced oropharyngeal symptoms, systemic symptoms, or both?

- Are symptoms of pollen allergy present?

- Has the patient reacted to other plant foods related to the one in

question?

- Are cooked forms of the food tolerated?

Clinical & Experimental Allergy, 41, 1001–1011

DiagnosisDiagnosis

• Skin prick test

- Prick to prick

- Commercial extract • Specific IgE (immunoassays)• Oral food challenges :

DDxDDx

• Isolated food allergy• Local irritation of the mouth, tongue, or throat (spicy, tart,

or gritty foods)• Contact urticaria (tomato sauce, citrus fruit, garlic, and

berries local irritant contact urticaria of the lips and perioral skin esp. in children

• Perioral dermatitis or oral contact dermatitis • Gastroesophageal reflux disease (GERD) • Eosinophilic esophagitis (EE) • Burning mouth syndrome

Treatment Treatment • Avoidance

- specific raw fruits or vegetables or the nuts (roasted or raw) that have caused symptoms in the past

- patients with mild symptoms limited to the oropharynx and wish to continue eating foods that cause symptom not restricting food intake

- Patients with PFAS and systemic symptoms must avoid the raw form of the responsible food, should avoid cooked forms also

• If a patient wishes to continue eating cross-reactive foods

- evaluate for allergy to the foods in question, If the test positive and patient wishes to continue eating foods, but have not eaten recentlyclinician-supervised oral food challenge to determine tolerance

• Antihistamines

- not suggest premedicating with antihistamines in order to eat the fruit/vegetable masking symptoms by antihistamine may seduce pts to consume larger amounts of offending food & may lead to more severe symptom

• patients not experienced systemic reactions who should carry epinephrine autoinjectors ?

- 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 SPT 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 geographical area (eg, a patient with allergy to apple living in Spain)

• Immunotherapy

- 84% of birch pollen sensitive pt with birch pollen SCIT report significant reduction or disappearance of oral symptom to apple

- 88% of these pt. experience marked reduction in SPT reactivity to apple

- 87% of birch allergic pt.with PFAS treat with SCIT could eat significant more apple or hazelnut without sign and symptom (small amount)

Clinical and Experimental Allergy, 1998, Volume 28, pages 1368–1373

Allergy 2004,59;1272-1276

• Immunotherapy

- SLIT with birch pollen on PAFS to apple may enhance therapeutic efficacy in PFAS ??? no improvement in oral symptom to apple ingestion was note (in 9 pt.), improved nasal provocation score to birch pollen after SLIT

J Allergy Clin Immunol 2007;119:937-43

Debate continue on therapeutic benefit of pollen immunotherapy for pollen food syndrome

Allergology International 2009;58:485-491

Class 1 food allergyClass 1 food allergy

• Allergens eliciting class 1 food allergy (also termed complete food allergens) share special features, like resistance to gastric digestion, leading to the postulation that the sensitization process takes place in the gastrointestinal tract.

• Major allergen are water soluble glycoprotein, molecular weight 10-70 kDa

Class 2 food allergy Class 2 food allergy • class 2 food allergens : more sensitive to heat and

digestive enzymes and cannot cause per-orally sensitizations, but instead provoke allergic reactions in already sensitized patients Incomplete sensitization or non sensitizing elicitors

• According to their stability during the digestive process, they can cause symptoms ranging from mild oral reactions (typical for the birch-fruit syndrome) to anaphylatic shock (rare within the celery-mugwart-spice syndrome

• Major allergen are plant-derived protein

Allergen in specific foodAllergen in specific food

Apple -Mal d 1, Bet v 1 homolog

-Mal d 3, LTPs

- highly unstable(heating, processing, and digestion)- highly resistant to heating

Hazelnut -Cor a 1, Bet v1 homolog- Cor a 2,profilins - Cor a 8, LTPs - heat-stable systemic

reaction

Peanut Ara h 8, Bet v1 homologous partially disrupted by roated and complete destroyed by gastric enzyme

Peach - Profilin - Pru p 3, LTPs

-central and northern Europe, oral symptom -Spanish pt. with anaphylatic

Soy Gly m 4,homologous to Bet v 1 -Content depent on processing More process low reaction

carrot - Dau c 1,Bet v 1 homolog -profilin, a Bet v 6 cross-reactive allergen- CCD

- cross react with celery, watermelon, apiaceous spices (fennel, coriander, caraway, aniseed), and birch and mugwort pollens

Kiwi fruit -Act c 1;actinidin (cysteine protease family)

-Act d 8,Bet v 1 homolog, - Act d 9, profilin,

-OAS and severe systemic reactions, cross reactions with celery, rye, birch, mugwort, and timothy grass pollen, and latex

- allergens in pollen-related kiwi allergy manifesting with less severe symptoms.

Allergen in specific foodAllergen in specific food

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Oral allergy syndrome

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