The Versatility of LCM SLIT: Approaching the Complex Allergy Patient George F. Kroker MD FACAAI.

The Versatility of LCM SLIT: Approaching the Complex Allergy Patient

George F. Kroker MD FACAAI

Copyright 2011. Allergy Associates of La Crosse

Case Presentation T.D., a 49 y/o Wal-Mart employee from Iron

Mountain Michigan presented 3/25/04 with multiple complaints: ENT: conjunctivitis, peri-orbital swelling,

rhinitis, sinus pressure/congestion, otic pruritis PULMONARY: occasional nocturnal cough GI: urgency & diarrhea after meals, multiple

food reactions SYSTEMIC: chronic fatigue, weight gain,

suboptimal memory & cognitive functioning, headaches


Case Presentation: (cont.) PMH:

Eczema from eggs/dairy as infant Allergic rhinitis as young adult Recurrent sinusitis, vaginitis As young adult began having acute episodes

of angioedema, urticaria & diarrhea from multiple foods

Episodes increased in frequency/intensity and required increasing ER visits


Case Presentation: (cont.) Comment:

“during both of my emergency room visits, I was asked if I was having my period—yes both times…I was asked if I was under heavy stress—yes both times…my husband was in the Navy and both times we were actually moving cross-country”


Case Presentation: (cont.) PMH:

Prior injection immunotherapy in Idaho for multiple inhalant sensitivities

Prior allergy w/u in 1986, 1989, 2001 Recent trials of Clarinex, Flonase, elimination

diets (“pork and rice”) failed to provide significant relief


Case Presentation: (cont.) Environmental History

Seasonal congestion spring & fall Work: store remodeling at Wal-Mart, much

dust exposure, while painting noted ENT SSX flared

Home: has dog; knows cats bother her; yard work aggravates symptoms


Case Presentation: (cont.) Dietary History:

Throat irritation, mouth swelling from multiple foods(especially raw): potatoes, tomatoes, melons, rutabaga, raw carrots & celery, raw cucumber, garlic, apple, oranges, banana, cabbage

“Sugar & bread are what I can eat” Breakfast: eggs & toast Lunch: sandwich Supper: meat, canned vegetable Snacks: 3 Pepsi per day, cupcake, craves

chocolate


Case Presentation: (cont.) Medications:

Up to 8 Sudafed/day for congestion; OTC antihistamines

Epi pen for emergencies


Case Presentation: (cont.)

“Help my energy, and mental functioning” “Keep me from having ER visits—I have to

carry an epi pen everywhere I go…” “I don’t want to be on 8 Sudafed a day…” “Help my food tolerance; I can’t eat the foods

I want to…and I overeat other foods and am gaining weight”

Patient Goals


Case Presentation: (cont)Now what?What do you do??How do I understand what’s really going on??

How can you utilize LCM SLIT to help this patient?


How to approach the complex patient Approaching the complex patient with chronic

illness requires a different paradigm than the acutely sick patient with recent illness

In order to approach complex allergy patients, a specific set of concepts are of help to the practicing allergist


Concepts in Chronic Illness Multiple causation


Concept One: Multiple Causation Acute illness: often one cause Chronic illness: multiple causation is the rule Ask two questions:

1. What is this patient getting too much of, that is not good for them?

2. What is this patient not getting enough of, that is good for them?

AllergensStressChemicalsEtc.

NutrientsExerciseDietSLIT


Concept Two: Total Load Corollary: Treatment of only one isolated

factor in the multiply-sensitized patient may not result in improvement; the erroneous conclusion is “that factor isn’t important because removal/treatment didn’t help”

“Wood sliver analogy” helpful for patients Multiple causation is applied to the complex

patient through the principle of the total load concept


Concepts in Chronic Illness Multiple causation Total load


Total Load Concept


Total Load Concept: “Critical Mass”

Time

Allergic Threshold(“Critical Mass”)


Total Load/Critical Mass Concepts

Time (in months or years)

“Onset of Current Illness”

AllergicThreshold


Critical Mass Concepts

Time (in days)

“Bad Day”AllergicThreshold

“Bad Day”


Critical Mass Concepts

Time


“Bad Day”

The “Sometimes” Patient


The Complex Patient: Natural History of Treatment Course

Time

AllergicThreshold

Stage I“Illness”

“bad days” >>”good days”

Stage 2“Transition”

“bad days”&”good days”

Stage 3

“Recovery”“good days” >>”bad days”


Concepts in Chronic Illness Multiple causation Total load Target organ variability


Concept Three: Target Organ Variability Different allergenic triggers may “target” different end

organ systems in the same patient Disease “labels” are largely irrelevant (!)

Triggers

MED IATORS

“TargetOrgans”

Disease“Labels”

SAR

IBS

Eczema,Urticaria

ENT

GI

DERM

CNSChronicFatigue Syndrome

Trigger 2

Trigger

1

Trigger 3

Disease-ModifyingTreatment--SLIT

Drugs &SymptomaticTreatment


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability


Concept Four: Altered Intestinal Permeability

The “screen inthe window”

metaphor


Concept Four: Altered Intestinal Permeability


Concept Four: Altered Intestinal Permeability Increased intestinal permeability can be

responsible for increased “spread” and severity of food reactions

Causes of increased intestinal permeability include: Acute infectious illness: Viral gastroenteritis, food

poisoning Chronic infectious illness: Protozoal infections, fungal

overgrowth secondary to antibiotics Chronic ingestion of food allergen(s) Drugs: Chronic NSAIDs, alcohol ingestion Acute anaphylactic reaction


Concept Four: Altered Intestinal Permeability Multiple clinical presentations:

White male with prior history of hay fever, --had acute GI bleed secondary to overdose of NSAIDs; shortly afterwards began having multiple food reactions

Alcoholic male with increasing food reactions as drinking increased

White female with chronic antibiotic use for acne, developing yeast vaginitis infections recurrently and simultaneous multiple food reactions

White female with all prior food allergens under good control with SLIT, until trip to California when contracted food poisoning and developed immediate loss of tolerance to all former food allergens


Concept Four: Altered Intestinal Permeability & Chronic Antibiotic Use

Hygiene Hypothesis—infectious disease at early, opportune moments in immunologic development provides protection from atopic disease

“Extended Hygiene Hypothesis”—intestinal microbial flora exposure outweighs that of infections in providing maturational signals

Note: Oral tolerance is defective in germ-free animals


Role of Antibiotics & Fungal Microbiota in Driving Pulmonary Allergic Responses Noverr Et al. Infec & Immunity Sept 2004 pp 4996-5003

Mouse model of antibiotic-induced GI microbial disruption with C. albicans bias; followed by nasal challenge to mold

Mice easily developed CD4 T cell mediated allergic airway response in lungs to subsequent nasal mold exposure without previous systemic antigen priming

Effect is absent in mice challenged with mold not receiving chronic antibiotic administration



“These studies indicate that increased numbers of yeast cells in the microbiota can be a contributing factor in up-regulating Th2 responses to antigen exposure in the lungs. In these studies, Candida was never isolated from the lungs…these studies highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs”

“We have presented a model of a clinically feasible, common scenario that occurs for a number of humans: Antibiotic treatment followed by a non-life-threatening low grade increase in fungal microbiota…”



Question: What happens to an allergic patient with an immune

system that is already up-regulated in Th2 bias, who becomes the recipient of chronic antibiotic usage and Candida overgrowth?

Diagnostic & Therapeutic Implications: Excessive Candida carriage promotes heightened

reaction to mold Excessive mold exposure heightens reaction to

previously asymptomatic Candida carriage


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability Food allergen reactivation


Concept Five: Food Allergy Reactivation “Once an allergen, always a potential

allergen” An allergen early in life causing an acute

reaction (hives, eczema, asthma) may go into remission and then “resurface” in adulthood, causing symptoms once again—often more insidious—and often in a different target organ

Note: Reactivation of an allergen is often a non-IgE mediated, delayed onset sensitivity


Concept Five: Food Allergy Reactivation

Infant with colic & recurrent otitison Cow’s Milk Formula

Changed formula to soy; symptoms resolve

Asymptomatic remission period

New target organ involvement

Dairy re-introduced into diet again; no acute rxn

Reactivated dairy allergy

Allergic/stress load increases


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability Food allergen reactivation Hidden food sensitivities


Concept Six: Hidden Food Sensitivities Frequently eaten foods may be responsible

for chronic, fluctuating symptoms in allergic patients

No immediate reaction consistently reported after eating these foods

Common hidden food sensitivities include milk, wheat, corn, soy, egg, yeast

Diagnostic tests: low or negative titer IgE, may show up with IgG RAST, ALCAT, MRT


Concept Six: Hidden Food Sensitivities Important principle of negative feedback loop:

Hidden food sensitivities worsen intestinal permeability AND increased intestinal permeability worsens hidden food sensitivities!

Food Sensitivities Intestinal Permeability


Concept Six: Hidden Food Sensitivities

Two types of Hidden Food Sensitivities: Delayed onset food allergy Low level IgE mediated food allergy


Concept Six: Hidden Food Sensitivities

Day Number

2 3 4 5 61

Initial Food Ingestion

Total CumulativeFood Allergen Load

AllergicThreshold


Critical Mass Concepts Revisited

Time


“Bad Day”


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability Food allergen reactivation Hidden food sensitivities “The formula”


Concept Seven: “The Formula” When you do a “test” for “allergies,” you are

only measuring one of the two essential items that determine an allergic reaction:

Allergic Reaction =

Our testing Patient’s exposure

Allergic LoadAllergic Sensitivity x


Concept Seven: “The Formula” A corollary: the highly sensitized patient with

a low allergic load may be less in need of treatment than the minimally sensitized patient with a high allergic load!

Example: An bookkeeper with severe mold sensitivity on testing may be less symptomatic than a farmer with mild mold sensitivity on testing


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability Food allergen reactivation Hidden food sensitivities “The formula” The “allergy/nonallergy interface"


Concept Eight: The “allergy/nonallergy interface”

AllergicDiseases

Other Diseases

Insect anaphylaxisUrticariaSeasonal allergicrhinitis,Etc.

Celiac DiseaseFibromyalgiaChronic FatigueIrritable Bowel SyndromeMigraine headachesADD, ADHDEtc.

Aggravation ofChronic Conditions:FibromyalgiaChronic FatigueADD, ADHDIBS“Targeting” effect


The Complex Allergy Patient…Revisited

Let’s reconsider our patient’s history…


Concepts in Chronic Illness Multiple causation Total load Target organ variability Altered intestinal permeability Food allergen reactivation Hidden food sensitivities “The formula” The “allergy/nonallergy interface"


Case Presentation…Revisited T.D., a 49 y/o Wal-Mart employee from Iron

Mountain, Michigan presented 3/25/04 with multiple complaints: ENT: Conjunctivitis, periorbital swelling, rhinitis,

sinus pressure/congestion, otic pruritis PULMONARY: Occasional nocturnal cough GI: Urgency after meals, multiple food reactions SYSTEMIC: Chronic fatigue, weight gain,

suboptimal memory & cognitive functioning, headaches

Multiple Symptoms…Multiple targets…Think Total Load


Case Presentation: (cont.) Comment:

“during both of my emergency room visits, I was asked if I was having my period—yes both times…I was asked if I was under heavy stress—yes both times…my husband was in the Navy and both times we were actually moving cross-country”

Total Allergy Load—hormonal, allergy, stress


Case Presentation, Revisited: PMH:

Eczema from eggs/dairy as infant Allergic rhinitis as young adult Recurrent sinusitis, vaginitis began to develop As young adult began having acute episodes

of angioedema, urticaria & diarrhea from multiple foods,

Episodes increased in frequency/intensity and required increasing ER visits

Reactivated??

Candida load up…

Increased intestinal permeability


Case Presentation, Revisited: PMH: (cont)

Prior injection immunotherapy in Idaho for multiple inhalant sensitivities

Prior allergy w/u in 1986, 1989, 2001 Recent trials of Clarinex, Flonase, “pork and

rice” diet failed to provide significant relief in symptoms

Single approaches fail withMultiple causation…“wood sliver effect”


Case Presentation, Revisited: Environmental History

Seasonal congestion spring & fall Work: Store remodeling at Wal-Mart, much

dust exposure, while painting noted ENT SSX flared

Home: Has dog; knows cats bother her; yard work aggravates symptoms

Big dust exposure…Raises load

Check out dog


Case Presentation, Revisited: Dietary history:

Throat irritation, mouth swelling from multiple foods: potatoes, tomatoes, melons, rutabaga, raw carrots & celery, raw cucumber, garlic, apple, oranges, banana, cabbage

“Sugar & bread are what I can eat” Breakfst: Eggs & toast Lunch: Sandwich Supper: Meat, canned vegetable Snacks: 3 Pepsi per day, cupcake, craves

chocolate

OASPR-10, profilinsConsider ISAC

Narrowed diet..New hidden food rxns??Daily eggs!


Case Presentation, Revisited:

“Help my energy, and mental functioning” “Keep me from having ER visits—I have to

carry an epi pen everywhere I go…” “I don’t want to be on 8 Sudafed a day…” “Help my food tolerance; I can’t eat the foods

I want to…and I overeat other foods and am gaining weight”

Patient Goals

“the allergy/nonallergy Interface”


Case Presentation: IDT TestingDilution # 5 4 3 2 1

Ragweed

Birch

16mm

10mm

Oak

11mm9mm

Grass

10mm

Go after Birch—Bet v 1OAS

Go after RagweedProfilin OAS


Oral Allergy Syndrome (OAS)


Bet v 1 & Profilin (Bet v2) : Cross- Reactivity Pattern in Oral Allergy Syndrome

Wensing, et al. JACI , 435-442, Sept 2002

Birch

Correlations between specificIgE titers of Bet v1, profilin, and 14 plant-derived foods calculated bySpearman rank test

Daily in diet

Daily in diet

Pt’s Oral AllergySyndrome Foods


Case Presentation: IDT TestingDilution # 5 4 3 2 1

Dog

Candida

9mm

7mm

Dust Mite

7mm 9mm

Alternaria

7mm 10mm

9mm 11mm

7mm

Conclusion:Heavy multiple inhalant load:Pollens,dust,dander,molds


Case Presentation: IgE ELISA TestingAntigen Conc IgE

IU/ml(nl<.05)Class

Dust Mite .20 II

Egg White .00 Neg

Wheat .07 I

Corn .07 I

Tomato .14 I

Carrot .01 Neg

Milk .03 Neg

Orange .10 I

Potato .09 I


Case Presentation: IgE ELISA Testing (cont.)Antigen Conc IgE IU/ml

(nl<.05)Class

Yeast .05 Neg

Garlic .11 I

Apple .21 II

Celery .07 I

Melon .05 Neg

Banana .10 I

Milk .03 Neg

Pineapple .01 Neg

Cabbage .07 I

Multiple low grade IgE rxns


Case Presentation: Challenge Testing

Antigen Symptoms Elicited

Egg Fatigue, fell asleep, eye itching

Wheat Eye itching, arm rash

Candida Fatigue, yawning, eye watering

Corn Very fatigued, eye watering, ears flushed

Multiple hidden food sensitivities

Candida Sensitivity


Total Load Concept

Inhalant Allergens

Food Allergens

Nutritional Stressors

Hormonal Stressors

Chemical /toxin stressors

Emotional Stressors

Infectious Stressors

AllergicThreshold


Case Presentation: The Total Load

Oral Allergy Syndrome Foods

Microbial Disruption &Candida Sensitivity

Seasonal Pollen/Mold

Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold


Case Presentation

Time

Milk/eggeczema

Childhood Adulthood

Stress

Dust&Mold PollenAllergy

OralAllergySyndr

NarrowsDiet

Increased

Intestinal Permeability

CandidaAntigenicLoad

FoodAllergy

TotalAllergyLoad

SYMPTOMS

RecurrentSinusitis


LCM SLIT and the Complex PtPrinciples of Administration Utilize multi-antigen threshold dosing initially Always administer SLIT in conjunction with

reduction in Total Allergy Load Advance dose carefully, based on:

Prioritizing advancing “key” allergens Compliance in reduction in allergy load

Later, “Mop up” residual seasonal symptoms with pre-seasonal high dose protocol


Case Presentation: The Total Load

Oral Allergy Syndrome



Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold

= Load x Sensitivity


Consult 3/15/04




Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold


Fix Dust Barrier Covers SLIT

Rx Diflucan, probioticsRefined sugar restriction

SLIT

SLIT

SLITa/c, environ control

“reassurance & hope”

avoidance

Encourage diversificationInto other “safe” food grps

SLIT


Consult 4/14/04 Update




Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold




SLIT

SLIT


Interval Change:Transient cong as SLIT begunNo ER/ visits for angioedema/urticaria/sinusitisLost 13 lb; more energy; diarrhea much improvedMuch personal stress; father killed

SLIT

RDD minus egg, corn,Wheat, refined sugar

Rotate carefully!






Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold




SLIT

SLIT

SLITa/c,environcontrolcontrol

SLIT

RDD minus egg,corn,Wheat, refined sugar Rotate!

Interval ChangeSpring resp ssx much betterNo chronic sinus congestion, rare SudafedDiarrhea in remissionNo urticaria,angioedemaExcellent Energy; Lost 26 poundsTolerating melon, bananas for “first time in years”

Rx Diflucan dc’edProbiotics con’t

Off strict RDD, diversification,restrict eggs, corn, wheatRefined sugars






Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold


Fix Dust Barrier Covers

SLIT

ProbioticsRefined sugar restriction SLIT

SLIT


SLIT

Restricting egg, corn,Wheat, refined sugar

Rotate carefully!

Interval ChangeDoing well except for 1 acute attack of angioedema requiring emergency room visit— “Why did this happen?”

Occurred Sunday 8/22—Weekend spent outdoorsAte cheeseburger & coleslawJust before episode






Perennial Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold


Fix Dust Barrier Covers

SLIT

ProbioticsRefined sugar restriction

SLIT

SLIT


SLIT

Restricting egg, corn,wheat, refined sugar

Rotate carefully!

Interval ChangeNo urticaria/angioedema x 5 monthsNo sudafedLost 30# total; good energyMild PND when ate thanksgiving mealWith raw apple; no hives or angioedema!


Case Presentation: Further f/u Office consult 5/12/05:

“I’ve been great…everyone carries a Kleenex at work but not me…no need for my epi pen; stomach good…can sit out on my deck in spring & fall and enjoy myself without sudafed!”

Office consult 11/21/05: “I did well over the fall, no need for regular sudafed or

antihistamines…no epipen needed…I cheat occasionally on foods with no significant reactions”

Office consult 5/30/06: “No oral allergy problems with fruits provided I don’t overeat

them; no epi pen needed; I need a rare sudafed when I ride my 4-wheeler during allergy seasons! 6 sudafed last year!”


Case Presentation: Further f/u Office consult 5/14/07

“Another good year”…no sudafed needed this spring, outdoors biking…no epi pen needed”

Office consult 8/11/08: “I selectively eat food allergens without reactions…on

picnics I have hotdogs, buns, ice cream, fruits and I’m ok”…I have had no need for my epi-pen or sudafed…my intestines are working fine…”


Treatment Strategy Summary: Lower Total Allergy Load


MicrobialDisruptionCandida Sensitivity


Dust/Dog

Hidden Food Allergy

Stress

Reaction

AllergicThreshold


Dust Barrier Covers SLIT

Rx Diflucan, probioticsSugar restriction SLIT

Rotate Carefully SLIT

RDD minus egg, corn,Wheat, refined sugar SLIT

a/c; environ ctrl SLIT

Reassurance:“A plan for recovery”


Thank you

Next: Exploring the Broader Implications

Of Allergy & Immunity

Vijay Sabnis MD, Benoit Tano MD, Kathryn McMullan MD

The Versatility of LCM SLIT: Approaching the Complex Allergy Patient George F. Kroker MD FACAAI.

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