Oral allergy syndrome Presented by Rapisa Nantanee, MD.

1. Oral Allergy
Syndrome
Topic Review
17th April 2020
Rapisa Nantanee, M.D.
Pediatric Allergy and Immunology Unit
King Chulalongkorn Memorial Hospital
This Photo by Unknown Author is licensed under CC BY-NC
This Photo by Unknown Author is licensed under CC BY-SA

2. Pollen Morphology
M. Smith and C. Galán. www.eaaci.org

3. Pollen Morphology
JM. Davies, RW. Weber. Middleton 9th ed. 2020. Chapter 27.
All grass pollen grains are
monoporate, having a
single circular to oval pore,
and are indistinguishable
by light microscopy.
Multiple pores
distributed over the
grain surface are
characteristic of the
family Amaranthaceae.
Weed
Tricolporate Ambrosia
pollen is a 20-micron
spheroidal grain with
pores within short
furrows. Surface
texturing is echinate,
with short broad-
based spines.
Ragweed
Tricolporate Artemisia
pollen is 20.5-micron
with pores in longer
furrows. Exine is
tectate, with distinct
roof and floor layers
separated by columns,
giving the grain a
scalloped appearance
in the polar view.
Mugwort

4. Pollen Morphology: Tricolpate pollen
JM. Davies, RW. Weber. Middleton 9th ed. 2020. Chapter 27.
Tricolpate Acer pollen with
long, wide furrows stretching
from pole to pole.
Box elder, Red maple
Tricolpate Salix pollen with
long, wide furrows stretching
from pole to pole, and with
reticulated surface texturing.
White willow
Oak pollen grains are either
tricolpate or tricolporate.

5. Pollen Morphology: Tricolpate pollen
tree
The pollen is
inaperturate with a
“stressed” surface
texturing.

6. Pollen Morphology: Tree
JM. Davies, RW. Weber. Middleton 9th ed. 2020. Chapter 27.
Ulmus pollen, with small
equatorial pores spaced
unevenly, giving a polygonal
shape.
White and red mulberry
trees are strong inducers
of pollinosis, producing
small, diporate pollen.

7. Pollen Morphology
JM. Davies, RW. Weber. Middleton 9th ed. 2020. Chapter 27.
Alder pollen has four or five
pores, frequently with a
square look.
Betula pollen is triporate, rarely
tetraporate, pores with distinct
annulus, aspis, and thickening of
intine beneath (oncus).
Betula verrucosa White birch
Juniperus pollen is 22 to 24
μm, with a thin, easily
ruptured exine and a thick
intine bulging into the
protoplasm in arcs, giving a
stellate appearance.
Ex. mountain cedar
(Juniperus ashei)

8. Outline
Definition
Epidemiology
Pathogenesis
Symptoms
Diagnosis
Treatment
Data in Thailand
Conclusion

9. Oral Allergy Syndrome or Pollen-food Allergy Syndrome
• Patients who have itching of the
mouth and throat, and rarely, other
symptoms, after the ingestion of
fruits and vegetables (usually fresh)
and sometimes nuts, and who also
have pollinosis.
• This phenomenon is almost certainly
caused by cross-reacting allergens
(e.g., profilins) found in the foods
and pollens.
• Many patients with this condition
can safely consume these foods.
J Allergy Clin Immunol 1995;96:275.
• Sensitization to inhaled pollen
is the primary event, with
secondary reactions occurring
after ingestion of the cross-
reactive plant foods.
• Symptoms are provoked
almost exclusively in the
oropharynx and rarely involve
other target organs.
A. Nowak-Węgrzyn, et al.
Middleton 9th ed. Chapter 79.
Other Terms
• Pollen food syndrome
• Food pollen syndrome
• Food pollen allergy
syndrome
• Pollen–related food allergy
• Pollen-fruit allergy
syndrome
• caused by an IgE cross-
reactivity between a prior
aeroallergen sensitization
and a characteristically
difficult to extract and highly
labile plant-derived protein
(class 2 food allergy).
CM. Webber, et al. Ann
Allergy Asthma Immunol.
2010;104:101–108.
A food allergy is defined as an adverse health
effect arising from a specific immune response that
occurs reproducibly on exposure to a given food.
JA. Boyce, et al. J Allergy Clin Immunol 2010;126:S1-S58.

10. Epidemiology
• In US
• The median estimated prevalence of OAS among patients with
rhinitis who were allergic to pollen was estimated to be 5% (range, 0%-
75%) among children and 8% (range, 0%-100%) among adults.
• Defined OAS as “an immediate contact type of allergy caused by
particular fresh (uncooked) fruits and vegetables that cross-react with
pollens.”
S. Ma, et al. J Allergy Clin Immunol 2003;112:784-8.

11. Epidemiology: Children
• In south-west Sydney,
• 163 patients aged between 4 and 17 years with atopic disease
including atopic rhinoconjunctivitis, atopic dermatitis, atopic asthma or
FA.
• 24 of the 163 patients (14.7%) reported a history of OAS.
• The prevalence of PFS was 4.9%. (8 patients)
• Patients reporting oropharyngeal symptoms such as itching, tingling,
stinging, numbness or swelling of the lips, tongue, palate, mouth or
throat upon immediate contact, biting and chewing, or within 5 min of
ingestion of the implicated food were diagnosed with OAS.
• PFS: Patients who reported OAS with pollen and implicated fruit and/or
vegetable sensitization on SPTs.
CEB Brown, et al. Journal of Paediatrics and Child Health 50 (2014) 795–800.

12. Epidemiology: Children
• In Italy,
• 1360 patients age 4–18 yr with a history of pollen-induced AR in one of
the two last pollen seasons, and positive skin-prick tests (SPT) for the
relevant pollen extracts.
• OAS was reported by 325 (24%) of the patients.
• Oral allergy syndrome (OAS) was defined as the occurrence of
immediate oral itching with or without angioedema of the lips and or the
tongue following the ingestion of the food.
A. Dondi, et al. Pediatric Allergy and Immunology 24 (2013) 742–751.

13. Epidemiology: Adults
• In Korea, of the 125 birch pollen sensitive patients
• 20% experienced food allergy.
• OAS was the main clinical manifestation (96.15%).
• Apple, peach and persimmon were identified as frequent triggers.
• Oral allergy syndrome (OAS) is a form of a contact allergic reaction
that mainly occurs when the oropharynx comes in contact with foods.
Chang, Yoon Seok et al. J Allergy Clin Immunol, Volume 141, Issue 2, AB63.

14. Epidemiology: Adults
• In UK,
• 3,590 patients aged 18-75 years
• A validated PFS diagnostic questionnaire (PFSDQ2)
• 555 of these 3,590 subjects (15.45%) reported reactions to foods
(RRF)
• 73 RRF subjects (18-74 years, 73% female) were diagnosed with PFS
giving a population prevalence of 2%.
I. J. Skypala, et al. Clinical & Experimental Allergy, 2013 (43) 928–940.

15. I. J. Skypala, et al. Clinical & Experimental Allergy, 2013 (43) 928–940.

16. Pathogenesis
• Sensitization to inhaled pollen is the primary event
• Secondary reactions occurring after ingestion of the cross-
reactive plant foods.
• Due to the production of cross-reactive specific IgE (sIgE) antibodies
that are directed against structural homologous allergens
• Local contact IgE-mediated mast cell activation
• Provokes the rapid onset of pruritus, tingling, and angioedema of the
lips, tongue, palate, and throat, and it occasionally elicits a sensation of
pruritus in the ears or tightness in the throat.
A. Nowak-Węgrzyn, et al. Middleton 9th ed. Chapter 79.
MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.

17. Plant food
allergens
The prolamin
superfamily
The cupin
superfamily
The
pathogenesis-
related (PR)
proteins family
The profilins
family
2S albumins
Lipid transfer
proteins (LTP)
- No identified aeroallergen
- Have limited role in PFAS
- Pan-allergens
- Resistant to both heat and
digestion
- significant binding to lipid
molecules, which may help
protect them from
degradation.
- Multiple proteins of various
functions as well as seed
storage proteins (7S and 11S)
- No identified 7S or 11S
aeroallergens would function
as the primary sensitizer
- Plays a large role in PFAS, esp.
PR-10.
- Protective mechanism against
pathogenic invasion or noxious
environmental factors.
- These Bet v 1 homologs are
more labile.
- easily degraded by
gastric digestion
G. Carlson, et al. Ann Allergy Asthma Immunol 123 (2019) 359-365.

18. MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.

19. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
Profilin
• Profilin is a structural protein
present in all eukaryotic cells
and does not resist thermal
processing and pepsin
digestion.
• Associated with
symptoms restricted to
the oropharynx.
• Reactions predominantly
involve melon, watermelon,
tomato, banana,
pineapple, and orange.
• In children, kiwi, apricot,
and cucumber seem also to
be involved in profilin-related
allergies.

20. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
Bet v 1 homologues
• Present in the peel and pulp
• Poorly resist both heating
and gastric digestion
• Localized symptoms
restricted to the oropharynx
when eating raw fruits,
vegetables, and nuts.
• Rosacea fruit (eg, apple,
cherry, peach, pear)
• Nuts (eg, hazelnut)
• Vegetables belonging to the
Apiacea family (eg, celery,
carrot)
Birch-fruit-vegetable
syndrome

21. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
ns-LTP
• PR-14 group
• Asymptomatic or only
present a mild phenotype or
severe allergic reactions
• Olive tree, Ole e 7, a
nonspecific lipid transfer
protein (ns-LTP)
• The ns-LTP (Pla a 3) is
assumed to be the most
important allergen causing
cross-reactivity to plant-
derived food in plane tree
allergic patients.
• Mugwort-peach association
ns-LTP syndrome

22. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
Celery-mugwort-spice
syndrome
• Cross-reactivity between
mugwort pollen and
members of the Apiacea,
Solanaceae, Piperaceae,
Anacardiaceae, and the
Liliaceae family
• Caused by a mix of
allergenic proteins, with a
major role for profilins (Art v
4).
• It has been assumed that
also Bet v 1 homologues
play a role in this cross-
reactive syndrome.
Celery-birch-mugwort-
spice syndrome

23. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
Mugwort-mustard
allergy syndrome
• Presents as mild OAS on
ingestion of mustard
• Also vegetables from the
Brassicaceae family (eg,
broccoli, cabbage, and
cauliflower) might cause
allergic symptoms.
• The causative allergens are
still a matter of intense
research, but profilins, ns-
LTPs, and high-molecular-
weight allergens are
assumed as candidates.

24. MA. Faber, et al. J Allergy Clin Immunol
Pract 2018;6:1813-23.
Ragweed-melon-
banana association
• involving members of the
gourd family (melon,
watermelon, zucchini, and
cucumber) and banana.
• It has been thought that this
“ragweed-melon-banana
association” is mainly due to
sensitization to profilin, but
involvement of ns-LTPs and
glycoallergens cannot be
completely ruled out.

25. Other allergens
• Ficus tree
• Sensitization to weeping fig (Ficus benjamina), a common indoor
ornamental plant, can cause respiratory allergies in atopic as in
otherwise nonatopic individuals.
• Thiol proteases are assumed to be important cross-reactive allergens
in this syndrome, as many patients with fig fruit allergy do show sIgE
against papain, a thiol protease from papaya.
MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.

26. Symptoms
• Oropharyngeal symptoms, such as itching, tingling, and
swelling in the oral cavity, immediately after ingesting plant-
derived foods
• 5% had systemic symptoms.
• Symptoms are usually induced by raw fruits and vegetables,
but they are short-lived because of exquisite susceptibility of the
allergens to digestion. The cooked forms of these foods
typically are not capable of inducing symptoms.
• Certain foods have been implicated for a higher risk of
anaphylaxis: almonds, apricots, cherries, celery, lentils,
peaches, plums, and tomatos.
S. Ma, et al. J Allergy Clin Immunol 2003;112:784-8.
G. Carlson, et al. Ann Allergy Asthma Immunol 123 (2019) 359-365.
MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.

27. N. Maeda, et al. Ann Allergy Asthma Immunol. 2010;104:205–210.
• Patients experiencing oropharyngeal
symptoms immediately after
ingesting plant-derived foods and
who also had positive skin prick test
results with the suspected foods
were diagnosed as having OAS.
• 18 of the 436 patients (4.1%)
sensitized to pollens were diagnosed
as having OAS.
• Skin symptoms such as generalized
urticaria, in 3 (16.7%) and facial
angioedema in 6 (33.3%)
• Dyspnea in 3 patients (16.7%)
• Abdominal symptoms in 4 (22.2%)
• Itching of the ear in 4 (22.2%)

28. S. Ma, et al. Food and Agricultural Immunology 2018, 29:1, 281-293.
• Plant food allergy was
diagnosed based on a
convincing history and
confirmed IgE sensitization to
corresponding plant food.
• 83 PFS patients, age 7-62
years
• The food-associated
symptoms with the highest
frequency in PFS patients
were
• oral allergy syndrome
(OAS, 72.3%)
• general urticaria and/or
angioedema (32.5%)
• respiratory symptoms
(24.1%), including
rhinitis, asthma or
tightness of the chest.

29. Diagnosis
• Diagnosis is based on a suggestive history and positive
“prick plus prick” skin tests with the implicated fresh fruits
or vegetables in patients with allergic rhinitis.
• Skin-prick test results with commercial extracts are often
negative, because the responsible allergen is often destroyed in
the manufacturing process.
A. Nowak-Węgrzyn, et al. Middleton 9th ed. Chapter 79.

30. Diagnosis
• Many subjects with an inhalant allergy produce cross-reactive
sIgE antibodies to food allergens without any clinical
significance, in other words demonstrating no allergic
symptoms on exposure.
• Therefore, a positive skin prick test (SPT) or sIgE result should
always be interpreted extremely cautiously as it might merely
reflect (cross) sensitization rather than a genuine clinically
relevant allergy.
• In cases of an unclear history or inconclusive tests, oral
provocations are mandatory to correctly diagnose food allergic
patients and give correct dietary advices.
MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.

31. ENC. Mills. Middleton 9th ed. Chapter 31.

32. Diagnosis
• Basophil activation test (BAT)
• Sulfidoleukotriene release assay
• Combining the cellular antigen stimulation test with an enzyme-linked
immunosorbent assay (CAST-ELISA)
• The value of basophil leukotriene release
CM. Webber, et al. Ann Allergy Asthma Immunol. 2010;104:101–108.

33. CM. Webber, et al. Ann Allergy Asthma Immunol. 2010;104:101–108.

34. Treatment
• Elimination diets
• If the diagnosis of a food allergy due to cross-reactions is confirmed.
• Should never be based on sensitization profiles only
• It is not recommended to preventively avoid potential cross-reactive food
sources.
• No statistical difference in symptoms in patients among those
receiving omalizumab alone, omalizumab with SCIT, or SCIT alone.
• Studies report various effects on reducing or eliminating oral allergy
symptoms with successful immunotherapy for pollen-induced
rhinitis.
• At present secondary food allergies do not justify immunotherapy to
cross-reactive inhalants.
MA. Faber, et al. J Allergy Clin Immunol Pract 2018;6:1813-23.
A. Nowak-Węgrzyn, et al. Middleton 9th ed. Chapter 79.

35. • Summary Statement 9: The potential for benefit in symptoms
related to oral allergy syndrome with inhalant
immunotherapy directed at the cross-reacting pollens has
been observed in some studies but not in others.
• For this reason, more investigation is required to substantiate
that a benefit in oral allergy symptoms will occur with allergen
immunotherapy. C
Treatment
L. Cox, et al. Allergen immunotherapy: A practice parameter third update. 2011.

36. R. Treudler, et al. Allergo J Int (2019) 28:50–56.

37. Data in Thailand
• 6 adult-onset patients who
experienced banana
anaphylaxis without latex
allergy
• Pollen sensitization found in
33.33% (2 of 6 patients)
• Allergic rhinitis in 50% (3 of 6
patients)
• Asthma and chronic eczema
each in 16.67% (1 of 6
patient)
R. Thongkhom, et al. Asia Pac Allergy. 2020 Jan;10(1):e4.

38. R. Thongkhom, et al. Asia Pac Allergy. 2020 Jan;10(1):e4.

39. Conclusion
• Knowing sensitizing pollen allergen components can predict
plant food allergy.
• Clinical symptoms range from mild oropharyngeal symptoms to
severe anaphylaxis.
• Consider treatment for food allergy
• Evidences of immunotherapy are conflicting.

40. Thank you for your attention