Advanced Topics in
Sublingual Immunotherapy
Diagnostics & Delivery
George F. Kroker, MD FACAAI
Case Report
 J.L. was a 26 year old graduate student
at U of Penn who presented in Oct
2009 with the recent diagnosis of
eosinophilic esophagitis and
recalcitrant dysphagia unimproved on a
strict elimination diet
Copyright 2015 Allergy Associates of La Crosse
Past Medical History
 As infant, suffered from chronic
dermatitis affecting back of knees, trunk
 Trouble on introducing solids with
vomiting—extended breast feeding
 By age 2, recurrent o.m. with pe tubes
 As child, vomiting from restaurant food,
especially Chinese food
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Past Medical History (cont.)
 Chronic vaginal rashes
 Asthma beginning in 1st grade
 Worse in elementary school
 Saw allergist—told allergic to peanuts,
tree nuts, weeds, grasses, trees, mite,
cats
 Took SCIT for a few years
Copyright 2015 Allergy Associates of La Crosse
Past Medical History (Cont.)
 In 2002 severe reaction to nut ingestion
over holidays; required ER treatment
 In 2004 severe reaction to Mango lassi
 2007 began experiencing constant
heartburn unresolved with OTC Rx
 Began graduate school, periods of
feeling as if “swallowing broken glass”
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Past Medical History (cont.)
 2007 Endoscopy revealed 12 eos/HPF
 No dx EoE, given Nexium
 Sudden crisis July 4th weekend, 2009:
 At
holiday cottage, no air conditioning
 Had cottage cheese dip with raw celery
and had immediate severe dysphagia
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Past Medical History (cont.)
 Repeat Endoscopy 2009
 Eosinophilic Esophagitis confirmed
 >20
Eos/HPF mid esophagus
 15-20 Eos/HPF proximal esophagus
 Rx Flovent swallowed; allergy consult
Copyright 2015 Allergy Associates of La Crosse
Allergy Testing 2009
Food/Inhalant
Result (kU/L)
Beef
<.35
Casein
.56
Chicken
<.35
Chocolate
.76
Corn
1.84
Egg white
<.35
Milk
.74
Orange
.47
Peanut
2.04
Potato
.70
Rice
1.60
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Allergy Testing 2009
Food/Inhalant
Result (kU/L)
Soybean
2.63
Tomato
1.50
Wheat
1.34
Pork
<.35
Tuna
<.35
Banana
1.04
Apple
1.48
Turkey
<.35
Copyright 2015 Allergy Associates of La Crosse
Allergy Testing 2009
Food/Inhalant
Result (kU/L)
Almond
<.35
Brazil nut
1.30
Coconut
<.35
Pecan
2.45
Sesame seeds
7.09
Cashew
1.99
Walnut
1.47
Pistaschio
3.14
Pine Nut
<.35
Clam
2.04
Crab
3.70
Copyright 2015 Allergy Associates of La Crosse
Allergy Testing 2009
Food/Inhalant
Result (kU/L)
Lobster
4.13
Oyster
2.29
Shrimp
4.68
Blue Mussel
1.91
Scallops
1.69
Crayfish
4.27
Cucumber
0.69
Grape
<.35
Oat
2.43
Quinoa
1.89
Copyright 2015 Allergy Associates of La Crosse
Allergy Recommendation: 2009
 “Eliminate the following foods from your
diet for 90 days: soy, carrot, peas,
beans, legumes, peanut, celery,
sesame, milk, corn, rice, wheat, tomato,
tree nuts shellfish. Then repeat
endoscopy”.
Copyright 2015 Allergy Associates of La Crosse
Case Presentation (cont.)
 On strict elimination diet patient felt no
improvement in dysphagia
 Other symptoms present:
 Fluctuating
upper respiratory congestion
 Migratory pruritic skin rashes
 Episodic diarrhea
 SOB with exercise
 No definite pollen-food oral symptoms
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Case Presentation (cont.)
 Medications:
 Prilosec
 Zoloft
 Yaz
Oral Contraceptive
 OTC antihistamine prn
 Physical Exam
 No
urticarial, angioedema, wheezing
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Patient Concerns
 Why am I not getting better when I’m
avoiding so many food allergens?
 How can I possibly be sensitive to so
many items, and how can I treat them?
 I’m confused and discouraged…
 ……..please
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help me
The Total Load Concept
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Case Presentation: Blood tests
 Vitamin D 28.9
 CBC wnl; hb 13.6, hct 42, WBC 4900
 No
eosinophilia
 Serum iron 131 wnl
 AST 14, wnl
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Intradermal Skin Testing
Antigen
Mm diameter
Dilution #
Dust Mite Mix
18
3
Ragweed
16
5
Grass
15
5
Dog
10
4
Alternaria
11
4
8
3
Aspergillus
13
3
Penicillium
10
3
Candida
12
2
Histamine Control 10
2
Cladosoporium
Copyright 2015 Allergy Associates of La Crosse
IgE ELISA
Antigen
Conc IU/ml
Class
Dust Mite Mix
9.50
IV
Baker’s Yeast
1.96
III
Grass
(Kentucky/June)
13.82
V
Candida albicans
3.40
IV
Alternaria
16.21
V
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Phadia Component Testing—
Positive Results
Allergen
Component
Classification
Birch
rBetv1
PR-10
Celery
rApi g 1
PR-10
Carrot
rDau c 1
PR-10
Apple
rMal d 1
PR-10
Peach
rPru p 1
PR-10
Peanut
rAra h 8
PR-10
Soybean
rGly m4
PR-10
Shrimp
rPen a 1
Tropomysin
Dust Mite
rDer p 10
Tropomysin
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Time
Working Medical Hypothesis
Chronic
Dermatitis
Dairy/soy allergic
infancy
Pollen food
Cross-rxns
Inhalant allergies
“atopic march”
Increased
Intestinal Permeability
Secondary food
Allergies
Lower GI Tract
Eosinophilic
Esophagitis
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Recurrent
Otitis Media
asthma
Recurrent
Antibiotics
Intestinal
Dysbiosis
Reassurance
Hope
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Patient Presentation: SLIT
Priorities in Treatment
 Inhalants (can’t control exposure)
 Super-Antigens
(Birch, Ragweed) due to
pollen—food connection
 Perennial allergens—dust, molds
 Foods hard to avoid—grains, dairy,
legumes/soy
 Foods easier to avoid—nuts, shellfish
 (Rxns
from Total Allergy Load)
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Sublingual Testing at #7
Dilution
Antigen
Result
Corn
Itchy throat
Milk
Itchy throat
Soy
unchanged
Tomato
unchanged
Rice
unchanged
Wheat
Tight chest
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Diet strategy in Patient
 RDD for patient avoided milk, soy,
wheat, corn, orange, chocolate, peanut,
tree nuts & seeds for 6 months
 Gradually converted to “modified”
rotation (“zone approach”)
 “red
zone” avoid
 “yellow zone” proceed with caution! Rotate
 “green zone” eat freely
Copyright 2015 Allergy Associates of La Crosse
Case Presentation (cont)
Treatment




Environ control
SLIT inhalants
SLIT foods
Rotation Diet
 Fluconazole
 Probiotics
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Strategy
 Lower dust/pollen load
 Help dysphagia
 Help food tolerance
 Minimize new food
sensitivities short term
 Lower Candida, help GI
tract heal
 Help GI tract heal
Case Presentation (cont)
Treatment
Strategy
 Zyrtec D
 Flovent Orally
 Gastrocrom before
 Help congestion
 Prn EoE exacerbation
 Minimize risk of


restaurant meals
ProAir available
Vitamin D, multiple
vitamin replacement
Copyright 2015 Allergy Associates of La Crosse


reaction eating out
At risk for EIA
Aid in immune
modulatioin
SLIT Strategy in Patient:
inhalants
 Use threshold dosing for inhalants
 Use ½ bottles of antigens
 Establish priorities in inhalant treatment
 Superantigens
 Perennial
antigens
 Every 6 weeks, increase inhalants by 1
(or fraction of 1) dilution on “out of
season” allergens
Copyright 2015 Allergy Associates of La Crosse
SLIT Strategy in Patient: foods
 Use dosing based on ELISA
 Use ½ bottles of antigens
 Establish priorities in food treatment
 Add 3-5 new foods to each new bottle
 For PR-10 allergy, don’t need to add
these foods, Rx inhalant superantigen
Copyright 2015 Allergy Associates of La Crosse
Reaction = sensitivity x load
Reduce sensitivity:
Use SLIT
Dilution #
1
2
3
Dust
Dust Mite—
Dust mite barrier covers
Pollen
Mold
Pollen & Mold-Use Air Conditioning
Foods
Food Allergens—
Follow Hypoallergenic Diet
Candida
Candida—
Fluconazole, Diet
4
5
6 wks
Copyright 2015 Allergy Associates of La Crosse
Reduce load
Patient Progress—Jan 2010
 October 2009—treatment begun
 Reduced dysphagia
 More energy
 Diarrhea gone
 Breathing easier
Copyright 2015 Allergy Associates of La Crosse
Patient Progress—April 2010
 Only one episode of dysphagia:
 Tested chocolate brownie—immediate
pain between shoulder blades, fatigue
 Compliant with diet, treatment
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Patient Progress—Dec 2010
 No further dysphagia
 As baseline improved, patient realized
most reactive to wheat, chocolate
 Tried wheat/chocolate without
gastrocrom and ok with small
amounts
 Compliant with diet, treatment
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Patient Progress—July 2011
 No further dysphagia
 Mild spring SAR during grass season
 Chocolate continues to cause fatigue
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Patient Progress—Dec 2011
 Dysphagia/EoE flare up
 Occurred when ate former allergens
consecutively over weekend at
boyfriends house
 Boyfriend had cat
 Cat test positive: 13 mm Dil#5
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Patient Progress—July 2013
 No dysphagia
 All foods tolerated ad lib except for
nuts, soy, wheat and chocolate
 Spring grass season went well
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Patient Progress—May 2014
 Excellent Grass season; no flare-ups
 Vitamin d level rechecked; 42.8
 No dysphagia
 Reviewed diet with patient:
 Red
zone—wheat, sugar, nuts, shellfish
 Yellow zone—soy, corn, dairy
 Green foods—all others
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Patient Presentation—May 2014
 Energy, quality of life have returned
 Married in July!
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Patient Presentation—Nov 2014
 Got married—able to eat wedding cake!
 Traveled to Mexico, did fine with food
 Mild ear plugging in fall, otherwise ok
 Endpoints found for nuts by challenge:

Cashew #9—itching lip; #10 ok
 Sesame #9 ok
 Peanut #9 ok
 Walnut #9 ok
 Endpoints found for shellfish/mollusk by challenge

Shrimp #9 fatigue; #10 ok
 Scallop #9 ok
Copyright 2015 Allergy Associates of La Crosse
Beginning to Current
 Inhalant Treatment
2009
2014
Multi-Inhalants
TX
Dilution
TX
Dilution
Mite
5
3
Ragweed
5
1
Grass Mix
5
1
Birch
5
1
Tree Mix
5
1
Alternaria
5
2
Copyright 2015 Allergy Associates of La Crosse
Beginning to Current
 Food Treatment
2009
2014
Food
TX
Dilution
TX
Dilution
Corn
6
1
Milk
6
1
Soy
5
1
Tomato
5
1
Rice
4
1
Wheat
4
1
Chocolate
4
1
Yeast
5
3
Egg
4
2
Chicken
3
2
Copyright 2015 Allergy Associates of La Crosse
Key Points from Case Study re:
Eosinophilic Esophagitis
 Food sensitivity AND inhalant allergy may



BOTH play a role in triggering EoE
Clinical correlation needs to be made when
Eos/HPF elevated but not diagnostic
Don’t ignore non-esophageal symptoms in
EoE pt! Other target organs may be involved
“Food-Pollen Syndrome” may involve
Esophagus
Copyright 2015 Allergy Associates of La Crosse
Key Points from Case Study re:
The Pan-Allergic Patient
 A thorough, chronological history is
essential
 Total load concept explains history!
 Pan-allergic patients may be
successfully treated with SLIT
 Establish
treatment priorities
 Use threshold dosing
 Frequent incremental changes
Copyright 2015 Allergy Associates of La Crosse
Thank you
Next:
Lessons Learned in 35 Years of
Experience
George Kroker MD
Copyright 2015 Allergy Associates of La Crosse