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Allergic Disorders

Anne-Marie Irani, MDVirginia Commonwealth University

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Allergic DisordersIgE-mediated immune reactionsClinical entities include:– asthma– allergic rhinitis– atopic dermatitis– urticaria and angioedema– anaphylaxis (foods, drugs, venom,

idiopathic)

3IgE production

armmast cells

& basophils

triggermediatorrelease

clinical effects

Development of Immediate Hypersensitivity

TH

Be

APC

AnaphylaxisAnaphylaxisHivesHives

AsthmaAsthmaRhinitisRhinitis

ConjunctivitisConjunctivitis

processing

presentation

help

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IgE-dependent Release of Inflammatory Mediators

IgEAllergens

FcεRI

Over MinutesLipid mediators: ProstaglandinsLeukotrienes

WheezingBronchoconstriction

Over HoursCytokine production:Specifically IL-4, IL-13

Mucus productionEosinophil recruitment

Immediate ReleaseGranule contents:Histamine, TNF-α, Proteases, Heparin

Sneezing Nasal congestionItchy, runny noseWatery eyes

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Immediate and Late Reactions in IgE-mediated Hypersensitivity

Adapted from Hadley JA. Med Clin North Am. 1999;83(1):13-25.Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81:478-518.Squillance SP. Otolaryngol Head Neck Surg. 1992;107:831-834.Urval KR. Primary Care. 1998;25:649-662.Adapted from American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Vol 1. Milwaukee, Wis: 2000.

Immediate Reactions

Late Reactions

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ILIL--22

INFINF--γγILIL--33

GMGM--CSFCSF

TNFTNF--αα

ILIL--4 (IL4 (IL--13)13)

ILIL--55ILIL--33

GMGM--CSFCSF

TNFTNF--αα

Delayed Hypersensitivity Allergic Inflammation

TH1/TH2 Paradigm

TH1 TH2

BalanceBalance

IFNIFN--γγ

ILIL--1010

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Why is the Prevalence of Asthma and Allergic Disorders Increasing Worldwide ?

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TH1TH1

TH2TH2

IFNIFN--γγ

ILIL--4 4 ILIL--55

Cytokine Imbalance or Dysregulation

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Developmental Component

? Normalize ? Normalize later in later in

ChildhoodChildhood

Delay in Delay in MaturationMaturation

Differences Differences at Birthat Birth

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BirthBirthTh2Th2

AllergiesAllergiesStill Th2Still Th2

Only childOnly childFew infectionsFew infections

No allergiesNo allergiesTh1Th1

Older sibsOlder sibsMany infectionsMany infections

(Th1 stimuli)(Th1 stimuli)

The Hygiene Hypothesis

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Diagnostic Testing: Allergen-specific IgE

Total IgE level not diagnosticImmediate Hypersensitivity Skin Tests– epicutaneous (prick) /intradermal– results read within 15-20 minutes– more sensitive, less specific

Serum Specific IgE Tests– less sensitive, more specific– RAST: radioallergosorbent test; qualitative– immunocap: quantitative

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Allergy Skin Testing

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Epidemiology, Diagnosis, and Pharmacologic Management of Allergic Rhinitis

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AR and Comorbid Airway Disease

Spector, J Allergy Clin Immunol. 1997; 99: S773-S780.16

Allergic Rhinitis and Asthma:One Airway, One Disease

ARIA. J Allergy Clin Immunol. 2001;108:S148-61; Guerra et al. J Allergy Clin Immunol. 2002;109:419-25;

Asthmaalone

Allergicrhinitis

+ asthma

Allergic rhinitis alone

Allergic rhinitis affects :– 25% of the general

population – 40% of children

Of 478 patients with allergic asthma, 99% of adults and 93% of adolescents reported concomitant allergic rhinitisIn patients with allergic rhinitis, asthma present in 19% - 40%

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Nasalitching

Reprinted from:Skoner et al. In: Zitelli et al. Atlas of Pediatric Physical Diagnosis. 1997.By permission of the publisher Mosby-Wolfe.

Mouth breathing

Repeated nose rubbing

(“allergic salute”)

Allergicshiners

Allergic Rhinitis: Clues

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Normal Nasal Cytology

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Eosinophilic Rhinitis

↑

↑

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Pharmacotherapy for RhinitisOral– antihistamines– decongestants– combination drugs– leukotriene

modifiers– corticosteroids

Subcutaneous– anti-IgE antibody

Intranasal– corticosteroids– antihistamines– anticholinergics– decongestants– saline– cromolyn sodium

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Medications: Targeting Symptoms

++++++Intranasal corticosteroids

++––Topical anticholinergics

+++Intranasal mast cell stabilizers

–++–Intranasal decongestants

–+–Oral decongestants

++/–+Nasal antihistamines

+++/–++Oral antihistamines

RhinorrheaRhinorrheaCongestionCongestionSneezingSneezingAgent Agent

– = provides no benefit+/– = provides little or minimal benefit+ = provides modest benefit++ = provides substantial benefitAmerican Academy of Allergy, Asthma, and Immunology. The Allergy Report. Vol 1. Milwaukee, Wis: 2000. 22

Intranasal Corticosteroids in Allergic Rhinitis: An Overview

Intranasal Intranasal CorticosteroidsCorticosteroids

Require careful patient instruction to ensure proper useMay cause nasal dryness, irritation, and/or bleedingReports of nasal septal perforation and limited suppression of bone growth

Most effective medication class for controlling symptoms of allergic rhinitisRelieve sneezing, rhinorrhea, and mucosal edema leading to nasal congestionAssociated with minimal side effects

DrawbacksBenefits

Physicians should routinely monitor the growth of children taking nasal corticosteroids and weigh the benefits of corticosteroid therapy against the possibility of effects on growth velocity.

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Total Systemic Exposure

Liver

Post First-Pass Metabolism

GI Tract Absorption

NASAL CORTICOSTEROIDNasal Absorption

Excretion

Adapted from Pedersen S, et al. Allergy. 1997;52(suppl 39):1-34.24

First and Second generation H1 Histamine Receptor Antagonists

Minimal effect on rhinorrheaHigher costs

Reduce itching, sneezing, rhinorrheaSome effect on nasal congestionNon-sedatingMinimal anticholinergicactivityOnce daily dose

Second Second GenerationGeneration

Have little effect on nasal congestion Can cause sedationAnticholinergic activityShort duration of action

Reduce itching, sneezing, rhinorrheaLower costs

First First GenerationGeneration

DrawbacksBenefits

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Immunotherapy for Allergic Rhinitis: An Overview

Must be administered in facilities equipped to handle adverse reactions (urticaria, laryngeal edema, bronchospasm, and anaphylaxis)Requires high level of patient compliance

Especially effective for grass pollen, ragweed pollen, and house-dust mitesImprovement of childhood allergies in childrenMay prevent progression of rhinitis to asthmaMay reduce need for symptomatic pharmacotherapy

DrawbacksBenefits

Report of BSACI Working Party. Clin Exp Allergy. 1993;23(suppl 3):1-44.Canonica GW, et al. Allergy. 1998;53(suppl 41):7-31. 26

Atopic Dermatitis“Chronic relapsing, highly pruritic,

inflammatory skin disease.”

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Diagnostic Features of AD Clinical

Atopy– personal Hx / FHx

of eczema, hay fever, asthma.

PruritusEczema (Spongiosis)– acute– subacute– chronic

(Vascular instability)

XerosisKeratosis pilarisPityriasis albaAllergic shinersMorgan-Dennie lines Palmar / plantar hyperlinearityAnterior Capsular CataractsKeratoconus

Essential Essential NonessentialNonessential

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Immunologic pathways involved in the progression of AD. LC,Langerhans cells; MC, mast cells; CLA, cutaneous lymphoid antigen.

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Food Allergy and AtopicDermatitis

Children: – moderate - Severe AD (33%) have food

allergy– increasing severity of AD ~ increasing risk of

FAAdults:– low incidence (< 2%)

Foods responsible (~ 85% of cases):– outgrown: milk, egg, soy, wheat– persistent: peanut, nuts, fish, shellfish 30

Evaluation of Food Allergy in AD

Allergy prick skin tests:Negative is very reliablePositive carries 50-80% false positive rateLaboratory studies:– specific IgE (pharmacia immunoCAP-RAST

system)• predictive value (> 95% reaction rate) in

children –egg, milk, peanut, codfish

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Evaluation of Food Allergy in AD

Clinical evaluation:– elimination diets– oral food challenges

• physician supervised• open, single blind, double-blind, placebo-

controlled

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Treatment

Skin hydration & moisturizersAvoidance of irritantsAvoidance of allergensTopical corticosteroidsTopical calcineurin inhibitors

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Incidence of different types of atopy. AD peaks in the first years of life and declines after that time. Asthma and allergic rhinitis increase over time as sensitization develops.