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Diagnosis and Management of Inhalant Allergens Steven T. Wright MD Shawn Newlands MD, PhD June 11, 2003.

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Presentation on theme: "Diagnosis and Management of Inhalant Allergens Steven T. Wright MD Shawn Newlands MD, PhD June 11, 2003."— Presentation transcript:

1 Diagnosis and Management of Inhalant Allergens Steven T. Wright MD Shawn Newlands MD, PhD June 11, 2003

2 Diagnosis and Management of Inhalant Allergens Anatomy Anatomy Immunology Immunology Diagnosis Diagnosis Treatment Treatment Environmental control Environmental control Pharmocotherapy Pharmocotherapy Immunotherapy Immunotherapy Allergic Emergencies Allergic Emergencies

3 Inhaled Allergens 5-22% annual prevalence of seasonal allergic rhinitis 5-22% annual prevalence of seasonal allergic rhinitis 9% of all visits to physicians 9% of all visits to physicians

4 History First described by John Bostock in 1819 as “seasonal catarrah” First described by John Bostock in 1819 as “seasonal catarrah” 1873, Blackley observed the first reaction by applying pollen to excoriated skin 1873, Blackley observed the first reaction by applying pollen to excoriated skin 1911, treatment began by Leonard Noon on the assumption of “antitoxins” 1911, treatment began by Leonard Noon on the assumption of “antitoxins”

5 History Cooke is said to have been the father of modern intradermal testing. Cooke is said to have been the father of modern intradermal testing. French Hansel developed the optimal dose concept by starting at lower concentrations. French Hansel developed the optimal dose concept by starting at lower concentrations. Herbert Rinkel first identified the “endpoint for titration” Herbert Rinkel first identified the “endpoint for titration”

6 Inhaled Allergens Identified by their portal of entry via the respiratory tree which is richly supplied with IgE. Identified by their portal of entry via the respiratory tree which is richly supplied with IgE. Essentially all inhalant allergy is IgE mediated, producing a Type I Gell and Coomb’s reaction. Essentially all inhalant allergy is IgE mediated, producing a Type I Gell and Coomb’s reaction.

7 Immune System Components Lymphocytes, Phagocytes, Complement, and mediator cells and their products. Lymphocytes, Phagocytes, Complement, and mediator cells and their products. Functions to distinguish self from nonself. Functions to distinguish self from nonself.

8 Gell and Coomb’s reactions Type I- Immediate Hypersensitivity Type I- Immediate Hypersensitivity Immediate Immediate Allergen binds 2 molecules of IgE Allergen binds 2 molecules of IgE Intracellular degranulation and immediate release of products Intracellular degranulation and immediate release of products Ex. Allergic rhinitis, anaphylactic shock, asthma Ex. Allergic rhinitis, anaphylactic shock, asthma

9 Gell and Coomb’s Type II- Cytotoxic reaction Type II- Cytotoxic reaction Immediate Immediate Binding of either IgM or IgG to cell bound antigen and activation of complement cascade. Binding of either IgM or IgG to cell bound antigen and activation of complement cascade. Ex. Hemolytic anemia. Ex. Hemolytic anemia.

10 Gell and Coomb’s Type III- Immune complex reaction Type III- Immune complex reaction Delayed Delayed Antigen-antibody complexes deposit on tissue Antigen-antibody complexes deposit on tissue

11 Gell and Coomb’s Type IV- Delayed hypersensitivy Type IV- Delayed hypersensitivy Delayed Delayed Tissue injury involving presensitized T- Lymphocytes. Tissue injury involving presensitized T- Lymphocytes.

12 Acute Phase Degranulation of preformed and newly synthesized mediators, most importantly, Histamine. Degranulation of preformed and newly synthesized mediators, most importantly, Histamine. Sneezing, watery discharge, itchy eyes, nose and throat. Sneezing, watery discharge, itchy eyes, nose and throat.

13 Transitional Phase Asymptomatic Asymptomatic Activation and recruitment of leukocytes into nasal tissue from the blood. Activation and recruitment of leukocytes into nasal tissue from the blood.

14 Late Phase Local Leukocyte infiltration. Local Leukocyte infiltration. 4-6hrs after allergen exposure. 4-6hrs after allergen exposure. Nasal congestion is the most characteristic symptom. Nasal congestion is the most characteristic symptom.

15 History The most important method of establishing the diagnosis of inhalant allergy. The most important method of establishing the diagnosis of inhalant allergy. What symptoms occur? What allergen exposure? When do they occur? What symptoms occur? What allergen exposure? When do they occur? Symptoms include sneezing, itchy eyes/nose, rhinnorhea, postnasal drip, congestion, headache, loss or diminished smell or taste. Symptoms include sneezing, itchy eyes/nose, rhinnorhea, postnasal drip, congestion, headache, loss or diminished smell or taste. Itching and Sneezing are the most distinctive complaints. Itching and Sneezing are the most distinctive complaints.

16 History PMHx: Asthma, allergic reactions, eczema Hypertension, Depression PMHx: Asthma, allergic reactions, eczema Hypertension, Depression Medications: B-Blockers, TCA, MAOi, OTC- antihistamines/nasal sprays Medications: B-Blockers, TCA, MAOi, OTC- antihistamines/nasal sprays FH: Asthma, allergies, immune disorders FH: Asthma, allergies, immune disorders SH: Geographical area, Work environment, smoker or smoker in the house, toxic/irritant exposures SH: Geographical area, Work environment, smoker or smoker in the house, toxic/irritant exposures

17 Physical Exam Nasal mucosa tends to be pale/bluish, congested, covered by watery mucosa. Nasal mucosa tends to be pale/bluish, congested, covered by watery mucosa. Infraorbital edema or “allergic shiner” Infraorbital edema or “allergic shiner” Open mouth breathing, nasal crease, infraorbital crease Open mouth breathing, nasal crease, infraorbital crease Lymphoid hyperplasia Lymphoid hyperplasia

18 Physical Exam Also rule out anatomic factors aggravating the allergic condition. Also rule out anatomic factors aggravating the allergic condition. Septal deviation Septal deviation Nasal Valve Collapse Nasal Valve Collapse Sinusitis Sinusitis Choanal Stenosis Choanal Stenosis

19 Nasal Cytology Anterior Inferior turbinate has shown to be the most representative. Anterior Inferior turbinate has shown to be the most representative. 5:1 Ratio of columnar to goblet cells in normal nasal epithelium. 5:1 Ratio of columnar to goblet cells in normal nasal epithelium. 1:4 Ratio in an allergic response. 1:4 Ratio in an allergic response. 20% or more Eosinophils suggest inhalant allergy. 20% or more Eosinophils suggest inhalant allergy.

20 Skin Endpoint Titration (SET) Intradermal skin test technique using 1:5 serial dilutions of allergenic extract. Intradermal skin test technique using 1:5 serial dilutions of allergenic extract. Advantages Advantages Safe Safe Readable Readable Standardization Standardization

21 SET Intradermal injections of 0.01ml allergenic extract applied to the upper lateral arm. Intradermal injections of 0.01ml allergenic extract applied to the upper lateral arm. Wheal and Flare beyond 5mm suggest positive response. Wheal and Flare beyond 5mm suggest positive response. Maximal whealing occurs at 15 minutes. Maximal whealing occurs at 15 minutes.

22 SET The endpoint is defined as the antigen dilution which yields a wheal at least 2mm larger than the preceding negative wheal, and which is followed by a wheal at the next stronger dilution. The endpoint is defined as the antigen dilution which yields a wheal at least 2mm larger than the preceding negative wheal, and which is followed by a wheal at the next stronger dilution. The confirming wheal is important for determining the true endpoint. The confirming wheal is important for determining the true endpoint.

23 SET controls Negative Controls Negative Controls Diluent Diluent Preservative (2% Glycerin) Preservative (2% Glycerin) Positive Controls Positive Controls No. 3 Histamine dilution No. 3 Histamine dilution

24 Abnormal Whealing Occur in 5-15% of tests applied Occur in 5-15% of tests applied Most common include: Most common include: Flash Response Flash Response Hourglass Hourglass Plateau Plateau

25 Flash Response Huge whealing response to a dilution that is weaker than the true endpoint. Huge whealing response to a dilution that is weaker than the true endpoint. Day 1: Day 2:

26 Plateau Response A 7mm or larger wheal that is followed by the same size wheal on progressively stonger dilutions until an additional 2mm increment is observed A 7mm or larger wheal that is followed by the same size wheal on progressively stonger dilutions until an additional 2mm increment is observed

27 Hourglass Response A large response of an initial weak dilution that is followed by progressively smaller reactions on stronger dilutions until a normal reaction occurs. A large response of an initial weak dilution that is followed by progressively smaller reactions on stronger dilutions until a normal reaction occurs

28 Factors influencing SET Volume injected Volume injected Skin reactivity Skin reactivity Increased allergen exposure Increased allergen exposure Food Allergens Food Allergens Antihistamines Antihistamines Age Age

29 Food Ingestants Ragweed: Milk, Melons, Bananas Ragweed: Milk, Melons, Bananas Sage: Potato Sage: Potato Grass: Beans, Peas, Soybeans Grass: Beans, Peas, Soybeans Cedar: Beef Cedar: Beef Oak: Egg Oak: Egg

30 Antigen Selection Seasonals Seasonals Pollens- short ragweed most common Pollens- short ragweed most common Trees Trees Grasses Grasses Weeds Weeds Perennials Perennials Dust mites Dust mites Molds- Alternaria, Hormodendrum Molds- Alternaria, Hormodendrum Cockroach allergens Cockroach allergens Dog and Cat dander Dog and Cat dander

31 SET Immunotherapy Individualized treatment sets are developed based on weak solutions of high sensitivities and stronger solutions of low sensitivities. Individualized treatment sets are developed based on weak solutions of high sensitivities and stronger solutions of low sensitivities. Increased strengths until the patient has relief of symptoms or serious local reactions occur. Increased strengths until the patient has relief of symptoms or serious local reactions occur. Length of treatment generally 3-5 years. Length of treatment generally 3-5 years.

32 In Vitro Testing Eliminates Variables associated with skin testing. Eliminates Variables associated with skin testing. non specific whealing, effects of medications, skin types. non specific whealing, effects of medications, skin types. More specific but less sensitive. More specific but less sensitive.

33 Indications for In Vitro Testing Impracticality of skin testing Impracticality of skin testing Skin disorder, drug inhibition, uncooperatvie patients Skin disorder, drug inhibition, uncooperatvie patients Clarification of skin test results Clarification of skin test results Bizarre or borderline reactions Bizarre or borderline reactions Prevention of systemic reactions Prevention of systemic reactions Prior history of anaphylactic reaction, severe asthma, stinging hypersensitivity Prior history of anaphylactic reaction, severe asthma, stinging hypersensitivity Convenience Convenience

34 Inappropriate Use of In Vitro Testing Delayed food hypersensitivity Delayed food hypersensitivity Penicillin hypersensitivity Penicillin hypersensitivity Improper Indications Improper Indications Routine screening Routine screening Patients who are not candidates for immunotherapy Patients who are not candidates for immunotherapy

35 Radioimmunosorbant Assay (RAST) Allergen is couple to a paper disc and incubated with the patients serum Allergen is couple to a paper disc and incubated with the patients serum Disc washed and radioactive IgE added Disc washed and radioactive IgE added Gamma counters quantitates the radioactivity. Gamma counters quantitates the radioactivity.

36 Modified RAST (MRT) Involves an additional washing procedure in order to reduce non immunologically bound radioactivity. Involves an additional washing procedure in order to reduce non immunologically bound radioactivity. Increased sensitivity to RAST Increased sensitivity to RAST

37 MRT MRT system is divided into 5 classes from 1-5, each representing approximately a fivefold increase in the amount of serum specific IgE antibody present in the sample. MRT system is divided into 5 classes from 1-5, each representing approximately a fivefold increase in the amount of serum specific IgE antibody present in the sample. ClassCounts0.1ml ClassCounts0.1ml Class :500 Class :2500 Class :12500 Class : Class : 312,500

38 MRT Immunotherapy Before starting immunotherapy, it is mandatory that an intradermal skin challenge of the initial vial be tested. Before starting immunotherapy, it is mandatory that an intradermal skin challenge of the initial vial be tested. After the initial doses have been administered and tolerated, the injections are increased until the dose reaches maximum level. After the initial doses have been administered and tolerated, the injections are increased until the dose reaches maximum level.

39 Specific Nasal Immunotherapy (SNIT) Applies the same principles as conventional immunotherapy. Applies the same principles as conventional immunotherapy. Now listed by the WHO as an alternative therapeutic option to the subcutaneous or intradermal route. Now listed by the WHO as an alternative therapeutic option to the subcutaneous or intradermal route. Data is still somewhat limited. Data is still somewhat limited.

40 Environmental control Best treatment is prevention. Best treatment is prevention. Animal dander Animal dander Dust mites Dust mites High filtration air filters High filtration air filters Hot water laundry Hot water laundry Special bedding Special bedding Pollen Pollen Pollen Masks Pollen Masks Avoiding irritants such as tobacco smoke. Avoiding irritants such as tobacco smoke.

41 Pharmacologic treatment Alpha-adrenergic agonists Alpha-adrenergic agonists Inhaled Cromylyn Inhaled Cromylyn Antihistamines Antihistamines Leukotrienes Leukotrienes Inhaled Nasal Corticosteroids Inhaled Nasal Corticosteroids Systemic and Intraturbinal Corticosteroid injections Systemic and Intraturbinal Corticosteroid injections

42 Alpha adrenergic agonists Pseudoephedrine Pseudoephedrine Vascular constriction Vascular constriction Wide variation of patient tolerance due to insomnia and irritability. Wide variation of patient tolerance due to insomnia and irritability.

43 Cromolyn Sodium Inhibits the degranulation of sensitized mast cells. Inhibits the degranulation of sensitized mast cells. Inhibits both the early and late phase Inhibits both the early and late phase Mainly prophylactic Mainly prophylactic OTC- 4% Nasal spray four times daily OTC- 4% Nasal spray four times daily Very safe Very safe

44 Antihistamines Currently the primary drug for treatment of nasal allergy. Currently the primary drug for treatment of nasal allergy. Compete with Histamine for the H1 receptor. Compete with Histamine for the H1 receptor. Most effective when taken prophylactically Most effective when taken prophylactically Anticholinergic, antiserotatonergic, and anti alpha adrenergic. Anticholinergic, antiserotatonergic, and anti alpha adrenergic. Lipid soluble and cross the Blood Brain Barrier Lipid soluble and cross the Blood Brain Barrier Most effective at reducing symptoms of sneezing, nasal itching, and rhinorrhea. Most effective at reducing symptoms of sneezing, nasal itching, and rhinorrhea.

45 Second generation Antihistamines Loratidine, Fexofenadine, Cetrizine, and azelastine. Loratidine, Fexofenadine, Cetrizine, and azelastine. Cross BBB less and have reduced CNS effects. Cross BBB less and have reduced CNS effects. Longer half lives Longer half lives

46 Antihistamine Costs AntihistamineCost per month Allegra 60mg$47 Allegra 180mg$78 Clarinex$78 Zyrtec$67

47 Leukotriene inhibitors Act similar to antihistamines by competetive inhibition of the leukotriene receptor. Act similar to antihistamines by competetive inhibition of the leukotriene receptor. Singular Singular Very successful in Asthma Very successful in Asthma The data available to date do not clearly support a unique role of leukotriene inhibitors in the treatment of allergic rhinitis. The data available to date do not clearly support a unique role of leukotriene inhibitors in the treatment of allergic rhinitis.

48 Intranasal Corticosteroids Primarily block the late phase reaction. Primarily block the late phase reaction. Only a small fraction is absorbed locally Only a small fraction is absorbed locally Side effects Side effects Atrophy Atrophy Epistaxis 5-8% Epistaxis 5-8%

49 Intranasal Corticosteroids Bedesonide, Mometasone, fluticasone Bedesonide, Mometasone, fluticasone Increased potency Increased potency Reduced systemic availability and activity Reduced systemic availability and activity Quicker onset of action Quicker onset of action More effective than oral antihistamines at relieving all nasal symptoms as well as improving the total nasal symptom score More effective than oral antihistamines at relieving all nasal symptoms as well as improving the total nasal symptom score May be appropriate for replacing antihistamines as first line therapy for management of nasal allergy. May be appropriate for replacing antihistamines as first line therapy for management of nasal allergy.

50 Intranasal Corticosteroid Costs SteroidCost per month Flonase$72 Nasonex$87 Rhinocort AQ$79

51 Systemic Corticosteroids The most potent agents for relieving the symptoms of allergic rhinitis. The most potent agents for relieving the symptoms of allergic rhinitis. Because of the side effects, they are reserved for severe or chronic symptoms. Because of the side effects, they are reserved for severe or chronic symptoms.

52 Intraturbinal injection Concern over vasospasm or retrograde embolization of the retinal vasculature. Concern over vasospasm or retrograde embolization of the retinal vasculature. Now considered safe and effective with proper procedure. Now considered safe and effective with proper procedure. Side effects: Side effects: 2% nasal bleeding 2% nasal bleeding Facial flushing occurs the following day due to steroid induce vasodilation. Facial flushing occurs the following day due to steroid induce vasodilation.

53 Pregnancy and Allergic Rhinitis Therapy Increased levels of progesterone lead to exacerbations of nasal congestion. Increased levels of progesterone lead to exacerbations of nasal congestion. Astemizole and Cromolyn Astemizole and Cromolyn Intranasal steroids Intranasal steroids

54 Surgery Minor role Minor role Septoplasty Septoplasty Partial Turbinate resections Partial Turbinate resections The effects of submucosal fibrosis on allergic rhinitis is still unproven. The effects of submucosal fibrosis on allergic rhinitis is still unproven.

55 Allergic Emergencies Immediate Immediate Delayed Delayed Local Local Systemic Systemic

56 Allergic Emergencies Delayed Local reactions range on a spectrum of pain and induration Local reactions range on a spectrum of pain and induration Systemic reactions usually manifest as exacerbation of the patients symptoms Systemic reactions usually manifest as exacerbation of the patients symptoms Treatment consists of antihistamines and reassurance, with steroids for more severe symptoms. Treatment consists of antihistamines and reassurance, with steroids for more severe symptoms.

57 Allergic Emergencies Diagnosis Vasovagal Vasovagal Most common Most common Slow pulse, normal BP, pale cool skin Slow pulse, normal BP, pale cool skin Anaphylactic Anaphylactic Involvement of more than one organ system, always including the cardiovascular system Involvement of more than one organ system, always including the cardiovascular system Rapid pulse, low BP, increased secretions/nasal congestion/hoarseness or wheezing, Flushed warm skin. Rapid pulse, low BP, increased secretions/nasal congestion/hoarseness or wheezing, Flushed warm skin.

58 Allergic Emergencies Management Keep patient recumbent, loosen tight clothing Keep patient recumbent, loosen tight clothing Oxygen as needed Oxygen as needed Check pulse and BP Check pulse and BP Get Help and call ambulance Get Help and call ambulance Place touniquet above the injection site (loosen every 20min) Place touniquet above the injection site (loosen every 20min) Epinephrine (1:1000) 0.3ml in the opposite arm, may repeat in 10 min intervals up to 1ml Epinephrine (1:1000) 0.3ml in the opposite arm, may repeat in 10 min intervals up to 1ml Assess airway- more deaths result from airway obstruction than from cardiovascular collapse Assess airway- more deaths result from airway obstruction than from cardiovascular collapse Oral airway Oral airway Inhaled albuterol Inhaled albuterol Intubate or sugical airway if glottic obstruction threatens Intubate or sugical airway if glottic obstruction threatens Start IV Start IV Diphenhydramine 50mg IV Diphenhydramine 50mg IV Dexamethasone 4mg IV Dexamethasone 4mg IV Transport to Hospital ASAP Transport to Hospital ASAP

59 Conclusion Allergic Rhinitis is very common. Allergic Rhinitis is very common. Thorough history and physical examination including visualization of the nasal anatomy. Thorough history and physical examination including visualization of the nasal anatomy. Approach to therapy Approach to therapy Environmental control Environmental control First line pharmacotherapy First line pharmacotherapy Nasal Steroids, systemic steroids Nasal Steroids, systemic steroids Immunotherapy Immunotherapy Adequate counseling of the patient Adequate counseling of the patient


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