Post on 17-Oct-2020
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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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↑
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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.