Allergic Disorders. Allergic Disorders. IgE-dependent Release of Inflammatory Mediators. TH1/TH2 Paradigm

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1 Allergic Disorders Anne-Marie Irani, MD Virginia Commonwealth University Allergic Disorders IgE-mediated immune reactions Clinical entities include: asthma allergic rhinitis atopic dermatitis urticaria and angioedema anaphylaxis (foods, drugs, venom, idiopathic) 1 2 Development of Immediate Hypersensitivity processing APC presentation Anaphylaxis Hives Asthma Rhinitis Conjunctivitis IgE-dependent Release of Inflammatory Mediators IgE FcεRI Allergens T H help B e IgE production arm mast cells & basophils trigger mediator release clinical effects 3 Immediate Release Granule contents: Histamine, TNF-α, Proteases, Heparin Sneezing Nasal congestion Itchy, runny nose Watery eyes Over Minutes Lipid mediators: Prostaglandins Leukotrienes Wheezing Bronchoconstriction Over Hours Cytokine production: Specifically IL-4, IL-13 Mucus production Eosinophil recruitment 4 Immediate and Late Reactions in IgE-mediated Hypersensitivity TH1/TH2 Paradigm Immediate Reactions TH1 IL-10 IFN-γ TH2 Late Reactions IL-2 IL-4 4 (IL-13) INF-γ IL-3 Balance IL-5 IL-3 GM-CSF GM-CSF Adapted from Hadley JA. Med Clin North Am. 1999;83(1): Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: Squillance SP. Otolaryngol Head Neck Surg. 1992;107: Urval KR. Primary Care. 1998;25: Adapted from American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Vol 1. Milwaukee, Wis: TNF-α Delayed Hypersensitivity TNF-α Allergic Inflammation 6 1

2 Why is the Prevalence of Asthma and Allergic Disorders Increasing Worldwide? IFN-γ TH1 Cytokine Imbalance or Dysregulation IL-4 IL-5 TH2 7 8 Developmental Component The Hygiene Hypothesis Birth Th2 Differences at Birth? Normalize later in Childhood Delay in Maturation Older sibs Many infections (Th1 stimuli) No allergies Th1 Only child Few infections Allergies Still Th Diagnostic Testing: Allergen-specific IgE Allergy Skin Testing Total IgE level not diagnostic Immediate Hypersensitivity Skin Tests epicutaneous (prick) /intradermal results read within minutes more sensitive, less specific Serum Specific IgE Tests less sensitive, more specific RAST: radioallergosorbent test; qualitative immunocap: quantitative

3 Epidemiology, Diagnosis, and Pharmacologic Management of Allergic Rhinitis AR and Comorbid Airway Disease Allergic Rhinitis and Asthma: One Airway, One Disease 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 rhinitis In patients with allergic rhinitis, asthma present in 19% - 40% Allergic rhinitis alone Allergic rhinitis asthma Asthma alone Spector, J Allergy Clin Immunol. 1997; 99: S773-S ARIA. J Allergy Clin Immunol. 2001;108:S148-61; Guerra et al. J Allergy Clin Immunol. 2002;109:419-25; 16 Allergic Rhinitis: Clues Normal Nasal Cytology Nasal itching Repeated nose rubbing ( allergic salute ) Mouth breathing Allergic shiners Reprinted from: Skoner et al. In: Zitelli et al. Atlas of Pediatric Physical Diagnosis By permission of the publisher Mosby-Wolfe

4 Eosinophilic Rhinitis Pharmacotherapy for Rhinitis 19 Oral antihistamines decongestants combination drugs leukotriene modifiers corticosteroids Subcutaneous anti-ige antibody Intranasal corticosteroids antihistamines anticholinergics decongestants saline cromolyn sodium 20 Medications: Targeting Symptoms Agent Intranasal corticosteroids Oral antihistamines Nasal antihistamines Oral decongestants Intranasal decongestants Intranasal mast cell stabilizers Sneezing Congestion / / Rhinorrhea Intranasal Corticosteroids in Allergic Rhinitis: An Overview Intranasal Corticosteroids Benefits Most effective medication class for controlling symptoms of allergic rhinitis Relieve sneezing, rhinorrhea, and mucosal edema leading to nasal congestion Associated with minimal side effects Drawbacks Require careful patient instruction to ensure proper use May cause nasal dryness, irritation, and/or bleeding Reports of nasal septal perforation and limited suppression of bone growth Topical anticholinergics = provides no benefit / = provides little or minimal benefit = provides modest benefit = provides substantial benefit American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Vol 1. Milwaukee, Wis: 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. 22 Total Systemic Exposure NASAL CORTICOSTEROID Nasal Absorption First and Second generation H1 Histamine Receptor Antagonists Benefits Drawbacks GI Tract Absorption Liver Adapted from Pedersen S, et al. Allergy. 1997;52(suppl 39):1-34. Post First-Pass Metabolism Excretion 23 First Generation Second Generation Reduce itching, sneezing, rhinorrhea Lower costs Reduce itching, sneezing, rhinorrhea Some effect on nasal congestion Non-sedating Minimal anticholinergic activity Once daily dose Have little effect on nasal congestion Can cause sedation Anticholinergic activity Short duration of action Minimal effect on rhinorrhea Higher costs 24 4

5 Immunotherapy for Allergic Rhinitis: An Overview Benefits Especially effective for grass pollen, ragweed pollen, and house-dust mites Improvement of childhood allergies in children May prevent progression of rhinitis to asthma May reduce need for symptomatic pharmacotherapy Drawbacks Must be administered in facilities equipped to handle adverse reactions (urticaria, laryngeal edema, bronchospasm, and anaphylaxis) Requires high level of patient compliance Atopic Dermatitis Chronic relapsing, highly pruritic, inflammatory skin disease. Report of BSACI Working Party. Clin Exp Allergy. 1993;23(suppl 3):1-44. Canonica GW, et al. Allergy. 1998;53(suppl 41): Diagnostic Features of AD Clinical Essential Atopy personal Hx / FHx of eczema, hay fever, asthma. Pruritus Eczema (Spongiosis) acute subacute chronic (Vascular instability) Nonessential Xerosis Keratosis pilaris Pityriasis alba Allergic shiners Morgan-Dennie lines Palmar / plantar hyperlinearity Anterior Capsular Cataracts Keratoconus 27 Immunologic pathways involved in the progression of AD. LC, Langerhans cells; MC, mast cells; CLA, cutaneous lymphoid antigen. 28 Food Allergy and Atopic Dermatitis Children: moderate - Severe AD (33%) have food allergy increasing severity of AD ~ increasing risk of FA Adults: low incidence (< 2%) Foods responsible (~ 85% of cases): outgrown: milk, egg, soy, wheat Evaluation of Food Allergy in AD Allergy prick skin tests: Negative is very reliable Positive carries 50-80% false positive rate Laboratory studies: specific IgE (pharmacia immunocap-rast system) predictive value (> 95% reaction rate) in children egg, milk, peanut, codfish persistent: peanut, nuts, fish, shellfish

6 Evaluation of Food Allergy in AD Clinical evaluation: elimination diets oral food challenges physician supervised open, single blind, double-blind, placebocontrolled Treatment Skin hydration & moisturizers Avoidance of irritants Avoidance of allergens Topical corticosteroids Topical calcineurin inhibitors 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. 33 6

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