Food Allergies:Food Allergies:What’s New in Clinical, Community, What’s New in Clinical, Community,

School and Food Service ApplicationsSchool and Food Service Applications

Janice M. Joneja, Ph.D., RDJanice M. Joneja, Ph.D., RD

20062006

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Food Allergy in the Past 5 YearsFood Allergy in the Past 5 Years

Nearly 4% of North Americans Nearly 4% of North Americans have food allergies, many more have food allergies, many more than recorded in the pastthan recorded in the past– Incidence of food allergy much higher Incidence of food allergy much higher

in children (>8%) than adults (<2%)in children (>8%) than adults (<2%)

Prevalence of peanut allergy Prevalence of peanut allergy doubled in American children doubled in American children younger than 5 years of age in the younger than 5 years of age in the past 5 yearspast 5 years

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Food Allergy in the Past 5 YearsFood Allergy in the Past 5 Years

Incidence of food intolerances Incidence of food intolerances estimated to be up to 50% of the estimated to be up to 50% of the population, but accurate figures are population, but accurate figures are not available because of the lack of not available because of the lack of appropriate testsappropriate tests– Incidence of food intolerances much Incidence of food intolerances much

higher in adults than in childrenhigher in adults than in children

Many food allergens have been Many food allergens have been characterized at the molecular level, characterized at the molecular level, leading to increased understanding of leading to increased understanding of the causes of many allergic disordersthe causes of many allergic disorders

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Food Allergy & Food Intolerance Food Allergy & Food Intolerance

Food Allergy

• A response of the immune

system to an ingested

food or food additive

• Is not dose-dependent

Food Intolerance• A generic term

describing an abnormal

physiological response

to an ingested food or food

additive which is not a result

of a response of the

immune system

• Is dose-dependent

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Management of Food Allergies and Management of Food Allergies and IntolerancesIntolerances

Management of food sensitivities Management of food sensitivities consists of:consists of:– Accurate identification of the food Accurate identification of the food

causing the problemcausing the problem– Educating clients on how to avoid Educating clients on how to avoid

relevant allergens and intolerance relevant allergens and intolerance triggers in foodstriggers in foods

– Formulating appropriate diets to avoid Formulating appropriate diets to avoid the culprit foods and replacing them with the culprit foods and replacing them with foods of equivalent nutritional valuefoods of equivalent nutritional value

– Educating parents in measures to avoid Educating parents in measures to avoid sensitization of their at-risk babies sensitization of their at-risk babies

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The Allergic DiathesisThe Allergic Diathesis

..

Food Allergy

Atopic dermatitis(Eczema)

Allergic rhinoconjunctivitis

(hay fever)

Asthma(cough;wheeze)

Gastrointestinal symptoms

Sleep deprivation

Anaphylaxis

Mental fogginess

Irritability

Fatigue

In infants: failure to thrive

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Allergy is a Response of the Immune Allergy is a Response of the Immune SystemSystem

Our immune systems are designed to Our immune systems are designed to protect the body from invasion by foreign protect the body from invasion by foreign materialsmaterials

T cell lymphocytes detect foreign proteins T cell lymphocytes detect foreign proteins (antigens) in any form(antigens) in any form

T cells then trigger a series of T cells then trigger a series of immunological reactions, mediated by immunological reactions, mediated by cytokinescytokines

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Antigen RecognitionAntigen Recognition

The first stage of an immune response is The first stage of an immune response is recognition of a “foreign antigen” (protein or recognition of a “foreign antigen” (protein or glycoprotein)glycoprotein)

T cell lymphocytes are the “controllers” of the T cell lymphocytes are the “controllers” of the immune responseimmune response

T helper cells (CD4+ subclass) (Th) identify the T helper cells (CD4+ subclass) (Th) identify the foreign protein as a “potential threat”foreign protein as a “potential threat”

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Education of the Immune SystemEducation of the Immune System

All foods contain proteins – derived from All foods contain proteins – derived from plants and animals – all of which are plants and animals – all of which are foreign to the human bodyforeign to the human bodyIn order for food to be absorbed, In order for food to be absorbed, metabolized, and utilized by the body, the metabolized, and utilized by the body, the immune system needs to be “educated” immune system needs to be “educated” that the foreign material is safethat the foreign material is safeThis involves a complex series of This involves a complex series of immunological reactions immunological reactions

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Immune System of the Digestive TractImmune System of the Digestive Tract

Immune system of the digestive tract is unique – Immune system of the digestive tract is unique – named the gut-associated lymphoid tissue named the gut-associated lymphoid tissue (GALT)(GALT)Recent evidence suggests that the most Recent evidence suggests that the most important cells in the initiation of the recognition important cells in the initiation of the recognition process are the dendritic cells in the intestinal process are the dendritic cells in the intestinal mucosamucosaThey take up dietary proteins and transport them They take up dietary proteins and transport them to the mesenteric lymph nodes (MLN)to the mesenteric lymph nodes (MLN)Differentiation of the T cells takes place in the Differentiation of the T cells takes place in the MLNMLN

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Oral ToleranceOral Tolerance

In most cases this results in “education” of the T In most cases this results in “education” of the T cells to not respond to that food protein when it cells to not respond to that food protein when it enters via the oral route – called enters via the oral route – called oral toleranceoral toleranceContrasts with the active immune responses Contrasts with the active immune responses needed to protect the gut against continual needed to protect the gut against continual bombardment by invading pathogens and their bombardment by invading pathogens and their products (toxins, etc)products (toxins, etc)Also contrasts with the reduced responsiveness Also contrasts with the reduced responsiveness to the millions of microorganisms that are to the millions of microorganisms that are permanent residents of the large bowelpermanent residents of the large bowelT cells involved in these processes are T cells involved in these processes are designated Tdesignated Treg reg

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T cells involved in Oral ToleranceT cells involved in Oral Tolerance

T cell response depends on the type of T helper T cell response depends on the type of T helper cell that is activatedcell that is activatedLatest research indicates that T cells that Latest research indicates that T cells that produce a cytokine called TGF-produce a cytokine called TGF- are important are important in inducing oral tolerancein inducing oral tolerance– Sometimes called Th3 cellsSometimes called Th3 cells

T cells that produce IL-10 may also be involved T cells that produce IL-10 may also be involved in tolerancein toleranceThese also regulate immune response to These also regulate immune response to resident microflora, preventing the usual immune resident microflora, preventing the usual immune inflammatory response to microorganismsinflammatory response to microorganisms

___________________Strobel and Mowat 2006

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T-helper Cell SubclassesT-helper Cell Subclasses

There are two subclasses of T-helper cellsThere are two subclasses of T-helper cells

Type 1: Th1Type 1: Th1

Type 2: Th2Type 2: Th2

Cytokines (the “control chemicals” of the immune Cytokines (the “control chemicals” of the immune system) are releasedsystem) are released

Each subclass produces a different set of Each subclass produces a different set of cytokinescytokines

The types of cytokines generated determine the The types of cytokines generated determine the resulting immune responseresulting immune response

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Role of T-helper Cell SubtypesRole of T-helper Cell Subtypes

Th1 Th1 triggers the triggers the protective response to a protective response to a pathogenpathogen such as a virus or bacterium such as a virus or bacterium

– IgM, IgG, IgAIgM, IgG, IgA antibodies are produced antibodies are produced

Th2Th2 is responsible for the IgE-mediated is responsible for the IgE-mediated hypersensitivity reaction (allergy)hypersensitivity reaction (allergy)

– IgEIgE antibodies are produced antibodies are produced

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Allergic SensitizationAllergic Sensitization

Cytokines associated with Th1 (protective) Cytokines associated with Th1 (protective) response are predominantly:response are predominantly:– INF-INF-– IL-2IL-2

Cytokines associated with allergic (Th2) Cytokines associated with allergic (Th2) response are predominantly:response are predominantly:– IL-4IL-4– IL-13IL-13

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Th1 Th2 InteractionsFactors promoting:

Th1- Bacterial and viral infections - Maturation of the immune system

Th2- Parasite infestations- Immature immune system

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Th1 Th2 InteractionsFactors promoting:

Th1- Bacterial and viral infections - Maturation of the immune system - Antigen tolerance

Th2- Parasite infestations- Immature immune system- Sensitization to antigen

Contributing factors:- Genetic inheritance- Early exposure to allergen- Increased antigen uptake

-“leaky gut”

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Conditions That May Induce Th2 Conditions That May Induce Th2 ResponseResponse

Inherited allergic potentialInherited allergic potentialImmaturity of the immune system Immaturity of the immune system Inflammatory conditions in the gut that Inflammatory conditions in the gut that interfere with the normal antigen interfere with the normal antigen processing pathwayprocessing pathwayImmaturity of the digestive mucosa leading Immaturity of the digestive mucosa leading to hyperpermeability (“leaky gut”)to hyperpermeability (“leaky gut”)Increased uptake of antigensIncreased uptake of antigens

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Th1 Th2 InteractionsTh1 Th2 Interactions Under certain circumstances (eg Under certain circumstances (eg

eczema) Th2 cytokines suppress Th1 eczema) Th2 cytokines suppress Th1 cell activitycell activity

This causes a decrease in the level of This causes a decrease in the level of immune protection against immune protection against microorganismsmicroorganisms

As a result, infection by normally As a result, infection by normally harmless skin bacteria can occurharmless skin bacteria can occur

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Th1 Th2 InteractionsTh1 Th2 Interactions

In contrast, Th1 activity may suppress Th2 In contrast, Th1 activity may suppress Th2 responseresponse

Infection with some common childhood illnesses Infection with some common childhood illnesses may suppress allergy - the “hygiene theory”may suppress allergy - the “hygiene theory”

Certain microorganisms in the large bowel (the Certain microorganisms in the large bowel (the resident microflora) can influence the Th1/Th2 resident microflora) can influence the Th1/Th2 balance – role for probiotics?balance – role for probiotics?

Latest research indicates a possible role for a Latest research indicates a possible role for a new cytokine IL-18 in Th1/Th2 balancenew cytokine IL-18 in Th1/Th2 balance

____________________Cebeci et al August 2006

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IgE-Mediated hypersensitivityIgE-Mediated hypersensitivity Intracellular Granules are ReleasedIntracellular Granules are Released

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Many Inflammatory Chemicals are Released Many Inflammatory Chemicals are Released in the Allergic Reactionin the Allergic Reaction

Preformed:Preformed:– HistamineHistamine– EnzymesEnzymes– Chemo-attractantsChemo-attractants

Newly formedNewly formed– ProstaglandinsProstaglandins– LeukotrienesLeukotrienes

Each chemical has a different effect on tissues: Each chemical has a different effect on tissues:

The allergic response is the combined effect of The allergic response is the combined effect of them all them all

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Action of Inflammatory Mediators on Tissues:Action of Inflammatory Mediators on Tissues: Histamine Histamine

Vasodilation {blood vessels widen}Vasodilation {blood vessels widen}Swelling of tissuesSwelling of tissuesIncreased vascular permeability {blood vessels become Increased vascular permeability {blood vessels become “leaky”}“leaky”}– angioedema (swelling)angioedema (swelling)– rhinitis (stuffy nose)rhinitis (stuffy nose)– rhinorrhea (runny nose)rhinorrhea (runny nose)– urticaria (hives)urticaria (hives)– otitis media (earache)otitis media (earache)

ItchingItchingFlushingFlushingReddeningReddening

Antidote:Antidote: AntihistaminesAntihistamines Block receptors for histamine on reactive cellsBlock receptors for histamine on reactive cells

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Priority Food Allergens In CanadaPriority Food Allergens In CanadaPeanutsPeanutsTree nuts (almonds, Brazil nuts, cashews, Tree nuts (almonds, Brazil nuts, cashews, hazelnuts (filberts), macadamia nuts, pecans, hazelnuts (filberts), macadamia nuts, pecans, pinenuts, pistachios, walnuts)pinenuts, pistachios, walnuts)Sesame seedsSesame seedsMilkMilkEggsEggsFish Fish Shellfish (e.g. clams, mussels, oysters, scallops Shellfish (e.g. clams, mussels, oysters, scallops and crustaceans (e.g. crab, crayfish, lobster, and crustaceans (e.g. crab, crayfish, lobster, shrimp) )shrimp) )SoySoyWheatWheatSulphitesSulphites

These Priority Allergens account for more than These Priority Allergens account for more than 95% of severe adverse reactions related to 95% of severe adverse reactions related to food allergensfood allergens

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Additional Factors Involved in Symptoms Additional Factors Involved in Symptoms of Food Sensitivityof Food Sensitivity

Increased permeability of the digestive tractIncreased permeability of the digestive tract (leaky gut)(leaky gut)

– Inflammation:Inflammation:InfectionInfectionAllergyAllergyAutoimmune diseaseAutoimmune diseaseOther diseasesOther diseases

– Immaturity (in infants)Immaturity (in infants)– Alcohol consumptionAlcohol consumption

Physical exertion:Physical exertion:Exercise-induced anaphylaxisExercise-induced anaphylaxis

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Additional Factors Involved in Additional Factors Involved in Symptoms of Food SensitivitySymptoms of Food Sensitivity

StressStress

Eating several different allergenic foods at the Eating several different allergenic foods at the same timesame time

Other allergies occurring at the same time Other allergies occurring at the same time (e.g. hay fever, asthma)(e.g. hay fever, asthma)

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Classification of Food AllergensClassification of Food Allergens

Class 1:Class 1:– Direct sensitization via the gastrointestinal tract Direct sensitization via the gastrointestinal tract

after ingestionafter ingestion– Water-soluble proteins or glycoproteins Water-soluble proteins or glycoproteins – Stable to heat, proteases, and acidStable to heat, proteases, and acid– Many are lipid transfer proteinsMany are lipid transfer proteins

Class 2:Class 2:– Indirect sensitization by inhalation of air-borne Indirect sensitization by inhalation of air-borne

allergenallergen– Cross-reaction to foods containing structurally Cross-reaction to foods containing structurally

identical proteinsidentical proteins– Heat labileHeat labile– Many are pathogenesis-related proteinsMany are pathogenesis-related proteins

____________Sampson 2003

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Oral Allergy SyndromeOral Allergy Syndrome(OAS)(OAS)

OAS refers to clinical symptoms in the OAS refers to clinical symptoms in the mucosa of the mouth and throat that:mucosa of the mouth and throat that:Result from direct contact with a food allergenResult from direct contact with a food allergenIn an individual who also exhibits allergy to In an individual who also exhibits allergy to inhaled allergens.inhaled allergens.Usually pollens (pollinosis) are the primary Usually pollens (pollinosis) are the primary allergensallergensPollens usually trigger rhinitis or asthmaPollens usually trigger rhinitis or asthmaOccurs most frequently in adultsOccurs most frequently in adults

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Oral Allergy SyndromeOral Allergy SyndromeCharacteristicsCharacteristics

Inhaled pollen allergens sensitize Inhaled pollen allergens sensitize tissues of the upper respiratory tract tissues of the upper respiratory tract Tissues of the respiratory tract are Tissues of the respiratory tract are adjacent to oral tissues, and the mucosa adjacent to oral tissues, and the mucosa is continuousis continuousSensitization of one leads to Sensitization of one leads to sensitization of the othersensitization of the otherOAS symptoms are mild in contrast to OAS symptoms are mild in contrast to primary food allergens and occur only in primary food allergens and occur only in and around the mouth and in the throatand around the mouth and in the throat

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Oral Allergy SyndromeOral Allergy Syndrome

The foods cause symptoms in the oral cavity The foods cause symptoms in the oral cavity and local tissues immediately on contact:and local tissues immediately on contact:– SwellingSwelling– Throat tighteningThroat tightening– TinglingTingling– ItchingItching– “ “Blistering”Blistering”

Foods most frequently associated with OAS Foods most frequently associated with OAS are mainly fruits, a few vegetables, and nutsare mainly fruits, a few vegetables, and nuts

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Oral Allergy SyndromeOral Allergy SyndromeAllergensAllergens

Pollens and foods that cause OAS are Pollens and foods that cause OAS are usually botanically unrelatedusually botanically unrelatedOccurs most frequently in persons allergic Occurs most frequently in persons allergic to birch and alder pollensto birch and alder pollensAlso occurs with allergy to:Also occurs with allergy to:– Ragweed pollenRagweed pollen– Mugwort pollenMugwort pollen– Grass pollensGrass pollens

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Oral Allergy SyndromeOral Allergy SyndromeCross-reacting allergensCross-reacting allergens

Birch pollens with:Birch pollens with:

– AppleApple– Stone Fruits (Apricot, Peach, Nectarine, Plum, Cherry)Stone Fruits (Apricot, Peach, Nectarine, Plum, Cherry)– Kiwi FruitKiwi Fruit– Orange Orange - Peanut- Peanut - Almond- Almond– Melon Melon - Hazelnut- Hazelnut - Walnut- Walnut– Watermelon Watermelon - Carrot- Carrot - Anise- Anise– Potato Potato - Celery- Celery - Caraway seed- Caraway seed– TomatoTomato - Parsnip- Parsnip– Green pepperGreen pepper - Parsley- Parsley– CuminCumin - - BeansBeans– CorianderCoriander - - PeasPeas– DillDill - - LentilsLentils– Sunflower seedSunflower seed - Soy- Soy

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Oral Allergy SyndromeOral Allergy SyndromeCross-reacting allergensCross-reacting allergens

Ragweed pollen with:Ragweed pollen with:– BananaBanana– CantaloupeCantaloupe– HoneydewHoneydew– WatermelonWatermelon– Other MelonsOther Melons– Zucchini (Courgette)Zucchini (Courgette)– CucumberCucumber

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Expression of OAS SymptomsExpression of OAS Symptoms

Oral reactivity to the food significantly Oral reactivity to the food significantly decreases when food is cookeddecreases when food is cookedReactivity of the antigen depends on Reactivity of the antigen depends on ripenessripeness– Antigen becomes more potent as the plant Antigen becomes more potent as the plant

material agesmaterial ages

People differ in the foods which trigger People differ in the foods which trigger OAS, even when they are allergic to the OAS, even when they are allergic to the cross-reacting pollenscross-reacting pollens– Foods contain an antigen that is structurally Foods contain an antigen that is structurally

similar to the allergenic pollen, but not all similar to the allergenic pollen, but not all people will develop OAS to all foods having that people will develop OAS to all foods having that antigenantigen

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Identification of Foods ResponsibleIdentification of Foods Responsible for OAS Symptoms for OAS Symptoms

Skin tests will identify the allergenic plant pollenSkin tests will identify the allergenic plant pollenSkin testing has not been successful in identifying Skin testing has not been successful in identifying persons who react to cross-reacting food antigenspersons who react to cross-reacting food antigens– Plant antigens are unstable and do not survive the Plant antigens are unstable and do not survive the

process of antigen preparationprocess of antigen preparation– Crushing plant material leads to release of phenols and Crushing plant material leads to release of phenols and

degradative enzymesdegradative enzymes

Prick + prick technique are more reliable than Prick + prick technique are more reliable than standard skin testsstandard skin tests– Lancet is inserted in raw fruit or vegetable, withdrawn Lancet is inserted in raw fruit or vegetable, withdrawn

and then used to prick the person’s skinand then used to prick the person’s skin

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Latex-Fruit SyndromeLatex-Fruit Syndrome

Allergy to latex often starts as: Allergy to latex often starts as:

Contact allergy to a latex protein, usually Contact allergy to a latex protein, usually through:through:– Abraded (non-intact) skinAbraded (non-intact) skin– Mucous membraneMucous membrane– Exposed tissue (e.g. during surgery)Exposed tissue (e.g. during surgery)

Inhalant allergy:Inhalant allergy:– Inhaled powder from latex glovesInhaled powder from latex gloves

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Latex AllergyLatex AllergyCross-reacting allergensCross-reacting allergens

As antigen comes into contact with As antigen comes into contact with immune cells, repeated exposure leads to immune cells, repeated exposure leads to IgE mediated allergyIgE mediated allergy

Proteins in foods with the same structure Proteins in foods with the same structure as proteins in latex trigger the same IgE as proteins in latex trigger the same IgE response when they are eatenresponse when they are eaten

In extreme cases can cause anaphylactic In extreme cases can cause anaphylactic reactionreaction

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Latex AllergyLatex AllergyRelated foodsRelated foods

Examples of foods that have been shown to contain Examples of foods that have been shown to contain proteins similar in structure to latex:proteins similar in structure to latex:

– Banana Banana - Mango - Mango - Tomato- Tomato

– Citrus Fruits Citrus Fruits - Melon - Melon - Celery- Celery

– Kiwi Fruit Kiwi Fruit - Pineapple - Pineapple - Avocado - Avocado

– Fig Fig - Papaya - Papaya - Tree Nuts- Tree Nuts

– Passion Fruit Passion Fruit - Peach - Peach - Chestnut - Chestnut

– GrapesGrapes - Potato - Potato - Peanut- Peanut

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Common allergens in unrelated plant Common allergens in unrelated plant materials: materials: SummarySummary

OAS and latex allergy are examples of OAS and latex allergy are examples of conditions in which common antigens, conditions in which common antigens, expressed in botanically unrelated plants, expressed in botanically unrelated plants, are capable of eliciting a hypersensitivity are capable of eliciting a hypersensitivity reactionreaction

In practice, when a specific plant food In practice, when a specific plant food elicits an allergic response, foods in the elicits an allergic response, foods in the same botanic family rarely elicit allergysame botanic family rarely elicit allergy