Food Allergy Update:Food Allergy Update: Overview for SCAFP Overview for SCAFP

Suzanne S. Teuber, M.D.ssteuber@ucdavis.eduProfessor of Medicine

Training Program Director, Allergy and Immunology

Sometimes tough Sometimes tough to avoid…to avoid…

DefinitionsDefinitions

Adverse Food Reactions Adverse Food Reactions

Toxic / PharmacologicToxic / Pharmacologic Non-Toxic / IntoleranceNon-Toxic / Intolerance• Bacterial food

poisoning• Heavy metal poisoning• Scombroid fish

poisoning• Caffeine• Alcohol• Histamine

Non-immunologic

• Lactase deficiency• Galactosemia• Pancreatic insufficiency• Gallbladder / liver

disease • Hiatal hernia• Gustatory rhinitis• Anorexia nervosa• IdiosyncraticAdapted from Sicherer S, Sampson H. J Allergy Clin Immunol

2006;117:S470-475.

• Eosinophilic esophagitis

• Eosinophilic gastritis

• Eosinophilic gastroenteritis

• Atopic dermatitis

Adverse Food Reactions Adverse Food Reactions

IgE-MediatedIgE-Mediated(most common)(most common)

Non-IgE MediatedNon-IgE MediatedCell-MediatedCell-Mediated

Immunologic

• Systemic (Anaphylaxis)

• Oral Allergy Syndrome

• Immediate gastrointestinal allergy

• Asthma/rhinitis

• Urticaria

• Morbilliform rashes and flushing

• Contact urticaria

• Protein-Induced Enterocolitis

• Protein-Induced Enteropathy

• Eosinophilic proctitis

• Dermatitis herpetiformis

• Contact dermatitis

Sampson H. J Allergy Clin Immunol 2004;113:805-9, Chapman J et al. Ann Allergy Asthma & Immunol 2006;96:S51-68.

PathophysiologyPathophysiology

AllergensAllergens• Proteins or glycoproteins (not fat or carbohydrate as

primary immunogens)– Generally heat resistant, acid stable

• Major allergenic foods (>85% of allergy)– Children: milk, egg, soy, wheat, peanut, tree nuts– Adults: peanut, tree nuts, shellfish, fish, fruits and

vegetables– commonly stated that “90% of food allergies are

caused by the “Big 8””, this was true for children with atopic dermatitis, not the general population with anaphylaxis. ER studies in US: FRUITS and VEGGIES same % as peanut, crustaceans highest

Emergency Department Visits for Emergency Department Visits for Food AllergyFood Allergy

(Clark et al. JACI 2004;113:347)

Crustaceans: 19%

Peanuts: 12%

Fruits and Veggies: 12%

Are these counted in food allergy prevalence estimates?

-NO

CASE: Crustacean Allergy: IgE Towards CASE: Crustacean Allergy: IgE Towards Protein in the Food, NOT Iodine Protein in the Food, NOT Iodine

• 79 year old man had anaphylaxis to shrimp at age 20, 25• Doctors told him he was allergic to iodine in seafood• Avoided seafood, iodized salt for years• Age 70: retirement dinner, hostess picked shrimp out of

his portion and gave it to him --- ER visit for anaphylaxis• At age 79, specific IgE measurement extremely high to

shrimp: >100 kU/L • On follow-up after education on avoidance, happily

consuming foods with iodized salt because he didn’t have to screen salt source any more

Pan-allergensPan-allergens• Proteins in food, pollen or plants that possess

homologous IgE binding epitopes across species• Tropomyosins: crustacea, dust mites, cockroach,

mollusks– Storage mites in flour: anaphylaxis reported!

• Parvalbumins: fish• Bovine IgG: beef, lamb, venison, cow’s milk• Lipid transfer protein: fruits (peach, apple),

vegetables, peanut, tree nuts• Profilin: fruits, vegetables• Class 1 chitinases: fruits, wheat, latex

IgE-MediatedIgE-MediatedIgE-receptorIgE-receptor

HistamineHistamine

Protein digestionProtein digestion Antigen processingAntigen processing Some Ag enters bloodSome Ag enters blood

Mast cellMast cellAPC

B cell T cell

TNF-TNF- IL-5IL-5

Non-IgE MediatedNon-IgE Mediated

Immune MechanismsImmune Mechanisms

Risk FactorsRisk Factors

Risk Factors for Development of Food Risk Factors for Development of Food AllergyAllergy

Local Factors (Rodent Models)• Pepsin digestion • Gastrointestinal infections? • Malabsorption• Rate of absorption• Antigen processing• Nature and dose of Ag• Transdermal exposure

Host Factors• Age (esp neonates)• Genetic susceptibility• FHx of atopy• FHx of food allergy• Atopic dermatitis• Transdermal food exposure (peanut)

Chapman J et al. Ann Allergy Asthma & Immunol 2006;96:S51-68.

Food Allergy DisordersFood Allergy Disorders

Anaphylaxis SyndromesAnaphylaxis Syndromes

• Food-induced anaphylaxis– Food allergy = #1 cause of anaphylaxis in the ED– Rapid-onset, up to 30% biphasic– May be localized (single organ) or generalized– Potentially fatal– Do DNA Allergy Relief Treatments for these high

risk foods:• peanut, tree nut, seafood (cow’s milk and egg

in young children)• Food-dependent, exercise-induced: 2 forms

– Specific foods (wheat, celery most common)– Any food (post-prandial)

Fatal Food AnaphylaxisFatal Food Anaphylaxis• Frequency: ~ 150 deaths / year

• Clinical features:– Biphasic reaction can contribute –initially better, then

recurs

– Cutaneous symptoms may not be present

– Respiratory symptoms prominent

• Risk factors:

– Underlying asthma – Delayed epinephrine

– Symptom denial – Previous severe reaction

– Adolescents, young adults

• History: known food allergen

• Key foods: peanuts and tree nuts dominate (~90% of fatalities), fish,crustaceans, few milk, few misc.

• Most events occurred away from homeBock SA, et al. J Allergy Clin Immunol 2001;107:191-3.

Cutaneous ReactionsCutaneous Reactions• Acute urticaria/angioedema – common• Contact urticaria - common• Food allergy rarely causes chronic

urticaria/angioedema• 1/3 of kids with moderate to severe atopic

dermatitis may have food allergy (especially cow’s milk, egg, soy, wheat). Morbilliform rashes may be seen in these children upon food challenge.

• Contact dermatitis (food handlers)

Respiratory ResponsesRespiratory Responses• Upper and lower respiratory tract symptoms may

be seen (rhinoconjunctivitis, laryngeal edema, asthma)

• Rarely isolated, usually accompany skin and GI symptoms

• Inhalational exposure may cause respiratory symptoms that can be severe

• Occupational

• Restaurants

• Kitchen/Home Example: crabs to be boiled

BirchBirch Apple, carrot, celery, cherry, pear, hazelnut Apple, carrot, celery, cherry, pear, hazelnut RagweedRagweed Banana, cucumber, melonsBanana, cucumber, melonsGrassGrass Melon, tomato, orangeMelon, tomato, orangeMugwortMugwort Melon, apple, peach, cherryMelon, apple, peach, cherry

Pollen-Food Syndrome or Pollen-Food Syndrome or Oral Allergy SyndromeOral Allergy Syndrome

• Clinical features: rapid onset oral pruritus, rarely progressive

• Epidemiology: prior sensitization to pollens

• Key foods: raw fruits and vegetables

• Allergens: Profilins and pathogenesis–related proteins

– Heat labile (cooked food usually OK)

• Cause: cross reactive proteins pollen/food

GI Syndromes of Children and Adults:GI Syndromes of Children and Adults:

Celiac Disease (Gluten-sensitive enteropathy) – In children:

• FTT, or weight loss• Malabsorption, diarrhea, abdominal pain• May be subtle

– In adults, average 10 years of nonspecific symptoms:• Diarrhea, abdominal pain• GERD• Malabsorption• May present atypically with osteoporosis, infertility, neurologic sx

Pathophysiology: an immune-mediated enteropathy triggered by gluten peptides in genetically predisposed patients (DQ2 or DQ8) – Lymphocytic infiltration of small bowel– Villus atrophy

Celiac Disease (Gluten-sensitive Celiac Disease (Gluten-sensitive enteropathy) Cont’d:enteropathy) Cont’d:

• Diagnosis– ~1/133 people in US have celiac disease – many are

currently undiagnosed– IgA anti-tissue transglutaminase (IgG if IgA-deficient),

anti-endomysial Ab, little role for anti-gliadin Ab currently due to poor specificity

– Upper endoscopy with biopsy;

• Management– Strict, lifelong, gluten avoidance (wheat, barley, rye)– Rare risk of GI lymphoma– Oats almost always OK– Link with resources: dietician, local support groups,

national organizations (listed at www.celiac.nih.gov)

GI Syndromes of Children and AdultsGI Syndromes of Children and Adults

Gastrointestinal Anaphylaxis or Immediate Gastrointestinal Allergy– IgE-mediated – Acute emesis/diarrhea/abdominal pain– Can present without other signs or symptoms of an

allergic reaction to food

GI Syndromes of Children and AdultsGI Syndromes of Children and AdultsEosinophilic Gastrointestinal Disorders:

eosinophilic esophagitis/gastritis/gastroenteritis

• Prevalence increasing, eosinophilic esophagitis is the most common syndrome, all rare in adults

• Symptoms– Post-prandial N/V/D/abdominal pain, weight loss– FTT in infants and young children, irritability, sleep

disturbance– GER, often refractory, may be seen– In teens/adults: dysphagia, food impaction

Eosinophilic Gastrointestinal Disorders: eosinophilic esophagitis/gastritis/gastroenteritis cont’d:

• Diagnosis– Biopsy: eos infiltration (mucosa serosa): >15/HPF– Presence of eos doesn’t necessarily invoke food allergy– May affect esophagus to rectum

• Response to specific food elimination found in a subset of patients (especially eosinophilic esophagitis): can screen for food allergy with prick/in vitro IgE, patch testing with food is currently under investigation

Disorders Not Proven to be Disorders Not Proven to be Related to Food AllergyRelated to Food Allergy

• Migraines

• Behavioral / Developmental disorders

• Arthritis

• Seizures

• Inflammatory bowel disease

Prevalence and Natural HistoryPrevalence and Natural History

Prevalence of Food Prevalence of Food AllergyAllergy

• Perception by public: 20-25%• Confirmed allergy (oral challenge)

– Adults: 3-4%– Infants/young children: 6-8%

• Specific Allergens– Dependent upon societal eating and cooking patterns

• Prevalence higher in those with:– Atopic dermatitis– Certain pollen allergies– Latex allergy

• Prevalence seems to be increasing

Estimated Prevalence of Food AllergyEstimated Prevalence of Food AllergyFood Children (%) Adults (%)

Cow’s milk 2.5 0.3

Egg 1.3 0.2

Soy 0.3-0.4 0.04

Peanut 0.8 0.6

Tree nut 0.2 0.5

Crustaceans

Fish

0.1

0.1

2.0

0.4Sampson H. J Allergy Clin Immunol;113:805-19.

Prevalence of Clinical Cross Reactivity Prevalence of Clinical Cross Reactivity Among Food “Families”Among Food “Families”

Food AllergyPrevalence of Allergy to > 1 Food in Family

FishFish 30% -100%30% -100%

Tree NutTree Nut 15% - 40%15% - 40%

GrainGrain 25%25%

LegumeLegume 5%5%

AnyAny 11%11%

Sicherer SH. J Allergy Clin Immunol. 2001 Dec;108(6):881-90.

Natural HistoryNatural History

• Dependent on food & immunopathogenesis• ~ 85% of cases of cow milk, soy, egg and

wheat allergy remit by age 3 yrs – numbers may be worse now for milk and egg – Declining/low levels of specific-IgE favorable – IgE binding to conformational epitopes

favorable

• Non-IgE-mediated GI allergy– Infant forms resolve in 1-3 years– Toddler / adult forms more persistent

Natural History (cont’d)Natural History (cont’d)• Allergies to peanuts, tree nuts, seafoods,

and seeds typically persist• ~20% of cases of peanut allergy resolve

by age 5 years.Prognostic factors include:– PST <6mm– ≥2 years avoidance– History of mild reaction– Few other atopic diseases– Low levels of peanut-specific IgE– Rarely re-develop allergy: role for regular ingestion?

Diagnosis and ManagementDiagnosis and Management

Evaluation: History & Physical ExamEvaluation: History & Physical Exam• History: most important

– Symptoms, timing, reproducibility, treatment and outcome– Concurrent exercise, NSAIDs, EtOH

• Diet details / symptom diary– Subject to recall– “Hidden” ingredient(s) may be overlooked

• Physical exam: assess for other allergic and alternative disorders

• Identify general mechanism– Allergy vs intolerance– IgE versus non-IgE mediated

Evaluation of Food AllergyEvaluation of Food Allergy• Suspect IgE-mediated

– Panels/broad screening should NOT be done without supporting history because of high rate of false positives.

– Prick skin tests (prick-prick with fresh food if pollen-food syndrome)

– In vitro tests for food-specific IgE • Suspect non-IgE-mediated

– Consider biopsy of gut, skin• Suspect non-immune, consider:

– Breath hydrogen– Sweat test– Endoscopy

Interpretation of Laboratory TestsInterpretation of Laboratory Tests• Positive prick test or specific IgE

– Indicates presence of IgE antibody NOT clinical reactivity

– ~90% sensitivity – ~50% specificity– ~50% false positives– Larger skin tests/higher IgE correlates with

likelihood of reaction but not severity

• Negative prick test or specific IgE– Essentially excludes IgE antibody

(>95% specific)

Unproven/Experimental TestsUnproven/Experimental Tests• Intradermal skin test with food

– Risk of systemic reactions and death– Not predictive (high false positive rate)

• Provocation/neutralization, cytotoxic tests, applied kinesiology (muscle response testing), hair analysis, electrodermal testing, food-specific IgG or IgG4 (IgG “RAST”)

• Note: industry/restaurants have no way of ascertaining whether a consumer was “diagnosed” by these methods or has a true food allergy. Science does not enter until a lawsuit is filed….

Diagnosis: Elimination Diets & Food ChallengesDiagnosis: Elimination Diets & Food Challenges

• Elimination diets (1 - 6 weeks) most useful for chronic disease (eg. AD, GI syndromes)– Eliminate suspected food(s) or– Prescribe limited “eat only” diet or– Elemental diet

• Oral challenge testing (MD supervised, emergency meds available)– Open– Single-blind– Double-blind, placebo-controlled (DBPCFC)

* Unless convincing history warrants supervised challenge* Unless convincing history warrants supervised challenge

Diagnostic Approach: IgE-Mediated AllergyDiagnostic Approach: IgE-Mediated Allergy

• If test for specific-IgE antibody is– Negative: reintroduce food*

– Positive: start elimination diet

• If elimination diet is associated with– No resolution: reintroduce food*

– Resolution• Open / single-blind challenges to “screen”• DBPCFC for equivocal open challenges

Treatment of Food AllergyTreatment of Food Allergy

• Complete avoidance of specific food trigger• Ensure nutritional needs are being met• Education• Anaphylaxis Emergency Action Plan if

applicable– most accidental exposures occur away from

home

This frozen dessert could have peanut, tree nut, cow’s milk, egg, wheat

Peanut allergen exposure through saliva: Peanut allergen exposure through saliva: assessment and interventions to reduce assessment and interventions to reduce exposure.exposure. Maloney JM et al. JACI 2006:118:719-24Maloney JM et al. JACI 2006:118:719-24..• In our UC Davis group of patients with severe tree nut

or peanut allergy, 5.3% volunteered that they had a reaction from kissing, sometimes several hours after partner had eaten food. 1/3 in dating situation.

• This study: Waiting 60 min, then brushing still did not remove peanut allergen completely

• Authors suggest waiting several hours and ingesting a peanut-free meal to be more effective than tooth-brushing or gum-chewing.

Treatment: Dietary EliminationTreatment: Dietary EliminationEducation• Hidden ingredients in restaurants/homes (peanut in

sauces,egg rolls)• Labeling issues (“spices”, changes, errors)• Cross contact (shared equipment)• Seeking assistance

– Food allergy specialist– Registered dietitian: (www.eatright.org)– Food Allergy & Anaphylaxis Network (www.foodallergy.org;

800-929-4040) and local support groups

Treatment: Dietary EliminationTreatment: Dietary Elimination

Education• Hidden ingredients in restaurants/homes (peanut

in sauces,egg rolls)– International products

– Restaurants: outsourced dressings/desserts a problem• Woman with near-fatal reaction after patisserie cake

– Secret ingredients

FALCPA won’t help this: “No Nuts in It!” FALCPA won’t help this: “No Nuts in It!” swore the chefswore the chef

-- Meal served. Told specifically that there were no nuts in it

36 yr old woman with tree nut allergy – peanuts OK36 yr old woman with tree nut allergy – peanuts OK

Upscale bistro; chef in chargeUpscale bistro; chef in charge

Told waitress of life-threatening allergy – Told waitress of life-threatening allergy – asked to check with chef to make sure asked to check with chef to make sure dishes she was ordering were safe. Was dishes she was ordering were safe. Was told, “No problem.”told, “No problem.”

Highly Educated Expert Chef

Ate a few bites and started to have

tingling in the mouth

Called the waitress over and asked if there was Called the waitress over and asked if there was any way there were nuts in the dish – was told any way there were nuts in the dish – was told “No”“No”

Reaction progressed over minutes, trouble Reaction progressed over minutes, trouble breathing and speaking, used her Epi-Pen, breathing and speaking, used her Epi-Pen, 911 called911 called

HospitalizedHospitalized

Jambalaya

• After discharge, she spoke to the chef, who repeatedly denied to her that there were nuts in the dish

• Important to find out the cause, because if it was a new allergy she would have to track it down to avoid it in future along with tree nuts

• Threatened a lawsuit

Chef only then disclosed ground cashews Chef only then disclosed ground cashews were used as a were used as a secret ingredientsecret ingredient

• “Didn’t know it could be so serious”• The chef maintained that he had been

residing on planet earth despite an address in San Francisco

Hospitality literatureHospitality literature

• Wait staff: majority thought it was OK to pick an allergen off a dish and serve it to the customer

• 80% of managers said they were familiar with food allergy but only about 50% could define it. Others gave examples of things like spoiled food.

Treatment: Dietary EliminationTreatment: Dietary EliminationEducation• Hidden ingredients in restaurants/homes (peanut in

sauces,egg rolls)• Labeling issues (“spices”, changes, errors)• Cross contact (shared equipment)• Seeking assistance

– Food allergy specialist– Registered dietitian: (www.eatright.org)– Food Allergy & Anaphylaxis Network (www.foodallergy.org;

800-929-4040) and local support groups

Contain cow’s milk: Artificial butter flavor, butter, butter fat, buttermilk, casein, caseinates (sodium, calcium, etc.), cheese, cream, cottage cheese, curds, custard, Half&Half®, hydrolysates (casein, milk, whey), lactalbumin, lactose, milk (derivatives, protein, solids, malted, condensed, evaporated, dry, whole, low-fat, non-fat, skim), nougat, pudding, rennet casein, sour cream, sour cream solids, sour milk solids, whey (delactosed, demineralized, protein concentrate), yogurt. MAY contain milk: brown sugar flavoring, natural flavoring, chocolate, caramel flavoring, high protein flour, margarine, Simplesse®.

AS of January 1, 2006, all food containing “Big Eight Allergens” (cow’s milk, peanut, tree nut, hen’s egg, soy, wheat, fish, crustacean) in the U.S. MUST declare the ingredient on the label in COMMON language. Does NOT apply to non-Big 8 allergens (e.g., sesame).

Label reading used to be very challenging Label reading used to be very challenging Example: Cow’s MilkExample: Cow’s Milk

Food Allergen Labeling and Consumer Protection Act of 2004 (P.L. 108-282) (FALCPA)

Geographic UnitGeographic Unit United StatesUnited States(U.S. Public Law (U.S. Public Law

2004)2004)

European Union European Union (European (European Commission Commission 2003)2003)

Australia-New Australia-New Zealand Zealand (Australia New (Australia New Zealand Food Zealand Food Authority 2001)Authority 2001)

Canada Canada (pending (pending law, Health law, Health Canada Canada 2008)2008)

Japan Japan (Ministry (Ministry of Health of Health 2001)2001)

Cow’s milkCow’s milk √√ √√ √√ √√ √√

Hen’s eggHen’s egg √√ √√ √√ √√ √√

WheatWheat √√ √√ √√ √√ √√

SoySoy √√ √√ √√ √√

PeanutPeanut √√ √√ √√ √√ √√

Tree nutsTree nuts √√ √√ √√ √√

FishFish √√ √√ √√ √√

CrustaceanCrustacean √√ √√ √√ √√

MolluscsMolluscs √√ √√

SesameSesame √√ √√ √√

Mustard seedMustard seed √√

celerycelery √√

buckwheatbuckwheat √√

Undeclared food (allergens)Undeclared food (allergens)• Current laws don’t help people with allergy to

less common food allergens that are present in small amounts. – Example: spices. UCD: personally have patients

with oregano, cumin, garlic allergy. Virtually any food can be an allergen• Prefer not to experiment with finding a threshold in

an uncontrolled setting!– FULL disclosure of all ingredients would be helpful– Gets back to fact that we need more data on

meaningful thresholds for a reaction• E.g., soy lecithin

May Contain..May Contain..

• FDA mandated to publish results of follow-up studies on utility and consumer preferences for “may contain” labeling.

• Should be available soon.

• Consumers “hate it”

• As detection kits improve, can the use of these terms decrease? Need thresholds

Treatment: Dietary EliminationTreatment: Dietary EliminationEducation• Hidden ingredients in restaurants/homes (peanut in

sauces,egg rolls)• Labeling issues (“spices”, changes, errors)• Cross contact (shared equipment)• Seeking assistance

– Food allergy specialist– Registered dietitian: (www.eatright.org)– Food Allergy & Anaphylaxis Network (www.foodallergy.org;

800-929-4040) and local support groups

Cross-ContactCross-Contact• We need to do a better job teaching patients

• And restaurant staff– Utensils

– Surfaces

– Pans/pots

– Deep fryers

– Scatter

• No need to “eliminate” allergens when there is a “safe” area for all and knowledgeable staff.

Treatment: Dietary EliminationTreatment: Dietary EliminationEducation• Hidden ingredients in restaurants/homes (peanut in

sauces,egg rolls)• Labeling issues (“spices”, changes, errors)• Cross contact (shared equipment)• Seeking assistance

– Food allergy specialist– Registered dietitian: (www.eatright.org)– Food Allergy & Anaphylaxis Network (www.foodallergy.org;

800-929-4040) and local support groups

Emergency Treatment: AnaphylaxisEmergency Treatment: Anaphylaxis

• Epinephrine: drug of choice– Self-administered epinephrine readily available at all times– If administered, seek medical care IMMEDIATELY– Train patients, parents, contacts: indications/technique

• Anti-histamines: secondary therapy only: WILL NOT STOP ANAPHYLXAXIS

• Written Anaphylaxis Emergency Action Plan– Schools, spouses, caregivers, mature sibs / friends

• Emergency identification bracelet

MYTH: Prior Episodes MYTH: Prior Episodes Predict Future ReactionsPredict Future Reactions

• No predictable pattern

• Severity depends on:– Sensitivity of the individual – Dose of the allergen– Other factors (e.g., food matrix effects, exercise,

concurrent medications, airway hyperresponsiveness) • Must always be prepared for an emergency

.

Patients with severe food allergy may not receive education on avoidance, self-injectable epinephrine or referral to an allergist at emergency department visits. It is imperative for primary care doctors and allergists to recognize the risks and help patients avoid a future accident.

Emergency Department Management of Food Allergy

Clark S, et al. J Allergy Clin Immunol 2004;113:347-352.

Future Immunomodulatory TherapiesFuture Immunomodulatory Therapies

• Recombinant anti-IgE antibody

• Mutated B-cell epitopes

• Minimal T-cell epitopes

• Immune-modulating adjuvants (ISS)

• Probiotics

• T lymphocyte manipulation to induce tolerance

• Heat-killed E. coli encoding mutated allergens

• Chinese herbal remedies (Food Allergy Herbal Formula)

• Oral tolerance induction

Induction of tolerance after establishment of peanut allergy Induction of tolerance after establishment of peanut allergy by the food allergy herbal formula-2 is associated with up-by the food allergy herbal formula-2 is associated with up-regulation of IFN-regulation of IFN-γγ. . Qu et al. CEA 2007;37:846Qu et al. CEA 2007;37:846..

• Murine model of peanut anaphylaxis• Treatment by gavage bid x 6 weeks started AFTER mice

allergic completely blocks reactions• Still blocked reactions to peanut 4 weeks after treatment

stopped• IL-4, IL-5, IL-13 significantly decreased in mesenteric lymph

nodes of treated mice• IFN-γ significantly increased in mesenteric lymph nodes of

treated mice• An apparently synergistic combination of phytochemicals is

present

Phamacological and immunological effects of Phamacological and immunological effects of individual herbs in the Food Allergy Herbal Formula-2 individual herbs in the Food Allergy Herbal Formula-2 (FAHF-2) on peanut allergy.(FAHF-2) on peanut allergy. Kattan JD et al. Phytotherapy Res Kattan JD et al. Phytotherapy Res 2008;epub ahead of print 4/082008;epub ahead of print 4/08

• The nine separate “herbs” were individually tested as in the previous studies in the murine model

• No single herb offered full protection• One offered statistically signif (but only 4 mice) protection (only

¼ mice had a reaction to peanut): Huang Bai: Phellodendron bark

• Huang Bai also reduced plasma histamine levels, but no change in IgE or specific IgG2a levels, whereas FAHF-2 results in decreased IgE and increased IgG2a

• Tried a simplified formula with only Huang Bai and 2 other “herbs”, but 2/5 mice had anaphylactic reactions to peanut

• Best results with full formula

Food Allergy Initiative and NIH-NIAID Food Allergy Initiative and NIH-NIAID Food Allergy ConsortiumFood Allergy Consortium

• Funding to Xiu-Min Li and Hugh Sampson at Mt. Sinai. • Food Allergy Herbal Formula 2 is a bitter-tasting

decoction/tea. Now, a tablet form has been developed (12 small tablets tid is the human dose). Phase I trial scheduled to start now – announced that patients were now being enrolled at 2008 AAAAI meeting: just tolerability/safety.

• They plan to seek FDA approval via Phase II, III trials.

• If the safety profile is good, since it is an herbal supplement, it could be available OTC with no health claims by the end of 2008 according to a recent Food Allergy Initiative mailer.– This needs to be thought through very carefully

though

– Knock-offs could proliferate with claims for all kinds of allergies• Lead, arsenic, cadmium, adulteration (remember

Zencor/sildenafil??)

• Takes time for FTC to catch up with those who illegally make claims

A randomized, double-blind, placebo-controlled study A randomized, double-blind, placebo-controlled study of Milk Oral Immunotherapy (MOIT) for cow’s milk of Milk Oral Immunotherapy (MOIT) for cow’s milk

allergy. allergy. Skripak JM et al. JACI 2008;S137Skripak JM et al. JACI 2008;S137

• 20 randomized to milk or placebo (2:1 ratio) after baseline studies

• Build up day: started with 0.4 mg milk protein, final dose 50 mg

• Daily dosing with eight weekly dose increases to maintenance of 500 mg

• Continued daily for 3-4 mo• 11 completed, 5 active, 6 placebo• Baseline OFC: all 11 reacted to 40 mg milk protein (the

initial dose)

Cont’d: MOITCont’d: MOIT

• Post OFC active group: cumulative median dose to elicit reaction in active group: 5,140 mg (range 2,540 – 6,140)– 1 patient tolerated final dose of 8,140 mg with no

symptoms.

• Post OFC placebo group: still reactive at 40 mg• 968 total active MOIT doses: 9.9% local reactions,

3.8% systemic, epi given in 2 reactions• 994 placebo doses: 11.3% local reactions, 1.2%

systemic, no epi given.

Rush specific oral tolerance induction in peanut Rush specific oral tolerance induction in peanut allergic patients at high risk of anaphylactic reactions. allergic patients at high risk of anaphylactic reactions.

Blumchen K et al. JACI 2008:S136Blumchen K et al. JACI 2008:S136..

• 6 children, ages 3-10• Peanut ImmunoCAP range 85->100 kU/l, median >100• All asthmatic, all “high risk”• DBPCFC median provoking dose 470 mg peanut• Inpatient rush protocol, allergic symptoms appeared at 96

mg to 480 mg, 3/6 had lower respiratory symptoms, multiple reactions requiring treatment

• Discharged after 6 days: on maintenance doses from 24 mg to 160 mg of peanut

• NOT protective doses!• Conclusion: not a good approach for this type of pt.