Oral allergy syndrome Presented by Sadudee Boonmee, MD. November9, 2012

1. Oral allergy syndrome
(Pollen-Food syndrome)
L/O/G/O
Sadudee Boonmee,MD
9/11/12

2. Contents
1. Introduction
2. Clinical manifestration
3. Epidemiology
4. Pathogenesis
5. Diagnosis
6. Treatment

3. 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 Food
Allergy in the United States: Report of the NIAID-Sponsored
Expert Panel , J Allergy Clin Immunol 2010;126:S1-S58

4. OAS 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: 461–476
2 Allergology International. 2009;58:485-491

5. Oral allergy syndrome (OAS)
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 Food
Allergy in the United States: Report of the NIAID-Sponsored
Expert Panel , J Allergy Clin Immunol 2010;126:S1-S58
• Middleton’s Allergy principles & practice 7th edition, p 1150-51

6. 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

7. Birch pollen
Mugwort
pollen
Ragweed pollen

8. 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

9. Pathogenesis
• Sensitization to inhaled pollen proteins via
the respiratory tract is believed to be the
initial pathogenic event (Class 2 food
allergy)
Current Allergy and Asthma Report 2008,8:413-17

10. Cross-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)
Current Allergy and Asthma Report 2008,8:413-17

11. 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

12. Pathogenesis-related protein (PRs)
• 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
Current Allergy and Asthma Report 2008,8:413-17

13. Pathogenesis-related protein (PRs)
Fruit of the Rosaceae
Vegetable of the Apiaceae
Hazel nut Cor a1
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

14. Pathogenesis-related protein (PRs)
• 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
Current Allergy and Asthma Report 2008,8:413-17

15. Latex food syndrome
Middleton’s Allergy principles &
practice 7th edition, p 1150-51

16. Pathogenesis-related protein (PRs)
• 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
Current Allergy and Asthma Report 2008,8:413-17

17. Cross reactivity of latex-allergic pt. to
avocado,chestnut, and banana
Middleton’s Allergy principles &
practice 7th edition, p 1150-51

18. Pathogenesis-related protein (PRs)
• PRs-5  Thaumatin-like protein
- antifungal in plantgive plants resist
against freeze and drough
(Minor allergen)
(Major allergen)
Current Allergy and Asthma Report 2008,8:413-17
Middleton’s Allergy principles &
practice 7th edition, p 1150-51

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

20. • 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 )
Current Allergy and Asthma Report 2008,8:413-17

21. Cherry Pru av 3
Hazelnut Cor a 8
Orange Cit s 3
Strawberry Fra a 3
Mugwort Art v 3
Middleton’s Allergy principles &
practice 7th edition, p 1150-51

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

23. Mugwort Art v 4 Profilin
Middleton’s Allergy principles &
practice 7th edition, p 1150-51

24. 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
Current Allergy and Asthma Report 2008,8:413-17

26. 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

27. • 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

28. • Mugwort profilin Art v4 celery mugwort
spice syndrome
• Bet v2  birch-celery association cross
reactive of celery Api g 4

29. Allergy 2006;61:461

30. Allergy 2006;61:461

33. Apiaceae (Umbelliferae)

34. Ragweed 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

35. cucurbitaceae musaceae
Ragweed
Allergy 2006;61:461

36. Allergy 2006;61:461

37. Allergy 2006;61:461

38. Allergy 2006;61:461

39. Allergy 2006;61:461

40. • 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

42. Allergy 2006;61:461

43. Dignosis
• 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?

44. Clinical & Experimental Allergy, 41, 1001–1011

45. Diagnosis
• Skin prick test
- Prick to prick
- Commercial extract
• Specific IgE (immunoassays)
• Oral food challenges :

46. DDx
• 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

47. 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

48. • 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 recentlyclinician-supervised
oral food challenge to determine tolerance

49. • 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

50. • 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)

51. • 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 Clinical and Experimental Allergy, 1998, Volume
28, pages 1368–1373
- 87% of birch allergic pt.with PFAS treat with SCIT could
eat significant more apple or hazelnut without sign and
symptom (small amount) Allergy 2004,59;1272-1276

52. • 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

54. Allergology International 2009;58:485-491

55. Class 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

56. 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

57. Allergen in specific food
Apple -Mal d 1, Bet v 1 homolog - highly unstable
(heating, processing, and
digestion)
-Mal d 3, LTPs - 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 -central and northern Europe, oral
- Pru p 3, LTPs symptom
-Spanish pt. with anaphylatic
Soy Gly m 4,homologous to Bet v 1 -Content depent on processing
More process low reaction

58. Allergen in specific food
carrot - Dau c 1,Bet v 1 homolog - cross react with celery,
-profilin, a Bet v 6 cross- watermelon, apiaceous spices
reactive allergen (fennel, coriander, caraway,
- CCD aniseed), and birch and
mugwort pollens
Kiwi fruit -Act c 1;actinidin (cysteine -OAS and severe systemic
protease family) reactions, cross reactions with
celery, rye, birch, mugwort, and
timothy grass pollen, and latex
- allergens in pollen-related kiwi
-Act d 8,Bet v 1 homolog, allergy manifesting with less
- Act d 9, profilin, severe symptoms.

59. Thank You!
L/O/G/O
www.themegallery.com