1. Describe different types of allergy testing; pros and cons of each. AL

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1 Allergy & Immunology (updated 08/06) 1. Describe different types of allergy testing; pros and cons of each. AL The two most common tests used to confirm the diagnosis of allergic rhinitis are skin testing and in vitro testing for serum levels of specific IgE antibodies. Skin testing is performed by applying antigen extracts to the skin either epicutaneously (puncture skin tests) or intradermally (intradermal tests). Intradermal testing is usually not required for the diagnosis of inhalant allergy when standardized extracts are availa- ble266,267 and might induce false-positive reactions. Testing is always accompanied by an introduction of the diluent for the allergen extract, used as negative control, and histamine or codeine (a mast cell degran- ulating agent), used as a positive control. A wheal and flare reaction, seen within 15 minutes of injection, occurs if a patient is sensitive to a specific antigen. A positive reaction indicates the existence of specific IgE antibodies on intradermal mast cells and the reaction of the skin to released mediators. Skin testing is rapid and inexpensive but, like all clinical tests, has certain disadvantages, as follows: (1) skin reactivity might be affected by previous ingestion of antihistamines or other drugs, (2) children often do not tolerate multiple skin needle pricks, (3) prior or coexisting dermatologic conditions, such as eczema or dermatographism, may preclude the performance of skin tests, (4) the potency of antigen extracts needs to be maintained, and (5) systemic reactions may occur. Potentially interfering medications must be discontinued prior to skin testing; montelukast does not appear to affect skin test reactivity, however, and does not need to be discontinued prior to skin testing.268 Most physicians test with a panel of allergens that are prevalent in their areas in addition to allergens that seem relevant from the history, such as cat, dog, and cockroach. Both total and specific serum IgE levels can be measured in vitro. Total IgE is elevated in 30% to 40% of patients with allergic rhinitis, and can be elevated in patients with nonallergic conditions and normal subjects; thus, total IgE determination is of limited use in the diagno- sis of allergic rhinitis. The detection of specific IgE antibodies in the patient s serum is useful in the diagnosis of allergic rhinitis. Although less sensitive than skin testing, in vitro IgE measurements correlate well with the results of skin testing and the clinical picture. These tests eliminate the need for multiple skin pricks but are more expensive, and the results take longer to obtain than those of skin testing. It is impor- tant to obtain simultaneous total IgE levels because false-positive radio- allergosorbent test (RAST) results may occur in sera with extremely high levels of IgE because of nonspecific binding. Other tools, such as nasal challenges and measurement of blood basophil histamine release, other peripheral blood activation markers, or eosinophils in nasal smears, are primarily utilized for research purposes. The clinical history should guide the clinician to test the patient with a panel of the most relevant antigens. Testing with the six most common antigens is effective in picking up 95% of the allergens to which a patient is sensitive. It is always important to remember that a positive in vitro or skin test result alone does not confirm the diagnosis of allergic rhinitis in the absence of supporting clinical history, par- ticularly because the last

2 National Health and Nutrition Examination Survey study showed that a prevalence of positive test results exceeded 50% but full expression of allergic disease affected only 20% of the study population. Skin Allergy Testing Scratch Test: scratch skin with placement of allergen or scratch with allergen, has largely been replaced for more objective and more reliable techniques Prick Test: series of allergens are inserted by needle into skin, positive wheal-andflare reactions are compared to controls; rapid and safe test, risk of anaphylaxis, misses less sensitive allergy, grading is subjective Intradermal Test: similar to prick test except allergen is placed intradermally; more sensitive than prick test, however, more time- consuming and painful, risk of anaphylaxis, and subjective grading Skin Endpoint Titration: series of increasing concentrations of specific allergen are introduced intradermally to titrate to a positive response, useful for determining immunotherapy concentrations, highly sensitive and determines quantitative measurements, however, time-consuming In Vitro Allergy Testing. Radioallergosorbent Test (RAST): serum reacts with a series of known allergens, radiolabeled anti-ige identifies specific antigen-ige complexes. Enzyme-linked Immunosorbent Assay (ELISA): similar to RAST except fluorescing agents are used for markers of antigen-ige complexes. Indications: equivocal skin test results, high risk of anaphylaxis (severe asthma, prior history), skin disorders (eczema), uncooperative patient (children and infants), failed immunotherapy (negative skin test is not an indication for in vitro allergy testing). Advantages: highly specific, no risk of anaphylaxis, no effect from skin condition (skin color, eczema, dermatographia) or medications ( -blockers, antihistamines, tricyclics). Disadvantages: less sensitive, requires up to 1 2 weeks for results, more expensive 2. What are the direct and indirect Coombs tests? CB 3. What are the different types of hypersensitivity reactions? Give examples of each? AL

3 Type I: Anaphylactic, IgE Immediate, self limiting, IgE mediated, stimulates mast cells and basophils which release histamine and other inflammatory mediators Ex: Asthma, anaphylaxis, atopy Type II: Cytotoxic, IgG/IgM IgG, IgM multivalent binding to phagocyte or complement Ex: Transfusion reactions, Goodpasture s Syndrome, Bullous Pemphigoid Type III: Immune Complex, IgG/IgM/IgA Antibody and complement complexes cause increased blood viscosity Removed by reticuloendothelial system Ex: Renal deposition, arthritis, glomerulonephritis, serum sickness Type IV: Cell mediated, T cells Delayed type hypersensitivity reaction (T cell mediated) Ex: Graft rejection, contact dermatitis Type V: Inferference with Receptor, Ig Antibody resembles a ligand and thus blocks or stimulates the receptor Pathophysiology of autoimmunity Ex. Hashimoto s thyroiditis, myasthenia gravis, Grave s disease 4. What are the different antibody isotypes and what is their typical structure? CB 5. Role of inflammatory cells and mediators involved in allergic rhinitis? TT 6. What are medical therapy options for allergic rhinitis (different classes of medications and their effects)? HH 7. What are the common allergens and the times of year that patients are most affected? TT 8. A patient with severe allergic rhinitis that is refractory to medical therapy. What is the role of immunotherapy and the common theories of how it works? Otolaryngol Head Neck Surg 1995;113:597. AL Gordon BR. Immunotherapy Basics. Otolaryngol Head Neck Surg Nov; 113(5): Abstract: Immunotherapy is the use of controlled exposure to allergens to produce durable anti-inflammatory effects, thus reducing the severity of allergic disorders. Immunotherapy is useful when other methods of allergy therapy are not fully satisfactory and can be effectively combined with rhinologic surgical treatment. Immunotherapy should always be considered as a treatment option for allergy patients and can often be

4 of benefit, provided that appropriate indications and contraindications are observed. Physicians caring for patients with allergies should therefore become familiar with methods of allergy diagnosis and with the therapeutic potential of immunotherapy. The history of immunotherapy, possible mechanisms, indications, contraindications, testing methods, and initiation of treatment are reviewed. -Immunotherapy: controlled exposure to known allergens to reduce severity of allergic disorders -last resort when maximal medical tx has failed -Mechanism: allergen specific IgG antibodies may provide protection from allergen exposure in an immunized person -IgG1 and IgG4 both increase, IgG4 correlates with better improvement -after prolonged immunotherapy there is a decrease in allergen specific IgE antibodies -decreased B lymphocyte blastogenesis vs. a specific IgE suppressor factor stimulation -Increase in IgA and IgM: may help with mucosal immune barrier and limit antigen penetration into the body -immunotherapy may alter the relative activity of T lymphocyte helper and suppressor cells -Prevents the chemotactic factors that normally occurs in allergy season -Effects of immunotherapy are both preventative and therapeutic Treatment of rhinitis, asthma, and insect sting allergy Can be used as monotherapy or in combination with medication Indications/Contraindications/Patient Assessment -Must have proven sensitivity to specific allergens -clinical symptoms of allergy that are significant -Should not be used for treatment of trivial, equivocal or evanescent symptoms -Can be used when allergen avoidance has failed or is impossible -useful when Tx with medications is not fully successful or intolerable -Absolute contraindication: negative allergy test -Relative contraindications: -mild symptoms -good Sx control with medication -concomitant use of B blocker (Pro allergic increases severity of Sx s, makes Tx of anaphylaxis more difficult) -Pregnancy potential hypoxic risk to fetus with anaphylaxis -immune dysregulation (ie. Autoimmune disorders) -immune stimulation may accelerate progression of disease -Good Candidates: Pt who is motivated, compliant, reliable, intelligent and has ability to learn, patient, 9. What is allergic fungal sinusitis and how is it treated? CB 10. How would you advise a patient on environmental control? AL Dust Mites: avoid down pillow or comforters, use dust mite proof covers, vacuum or clean covers weekly, wash sheets and blankets in very hot water (130 deg F), avoid

5 upholstered furniture/miniblinkds/carpeting, central or room unit air filters, avoid humidifiers Pollens & Molds: avoid humidifier, ventilate dark/moist places Irritants: no smoking in the house, no wood stoves or wood fireplaces, avoid strong odors (paints, perfume, hair spray, disinfectant, chemical cleaners, air fresheners, glues) Pets: don t have one Cockroach: remove food and water sources that attract cockroaches, seal cracks in walls and floors 11. Tell us about congenital immunodeficieny syndromes CB 12. Review humoral vs. cell-mediated immunity. What are natural killer cells? TT 13. Define and manage anaphylactic shock. HH 14. Common head and neck manifestations of allergic disease. AL. History and Physical Exam Nasal SSx: sneezing, congestion, rhinorrhea Ocular SSx: redness, itchiness, watery, conjunctivitis, burning Otologic SSx: eustachian tube dysfunction, middle ear effusions Laryngeal SSx: scratchiness, dry, irritated, cough Other SSx: seasonal pattern (eg, in the upper Midwest tree pollen allergies occur between April May, grass pollen May July, weed pollen J uly frost, molds year-round), food hypersensitivity, fatigue PE: clear rhinorrhea, congested turbinates, periorbital puffiness, nasal tip crease ( allergic salute ), open-mouthed breathing ( adenoid facies ), prominent pharyngeal lymphoid tissue, conjunctivitis Associated Disorders: chronic sinusitis (obstruction from mucosal edema), nasal polyps, asthma, otitis media with effusion

6 15. Describe the pathophysiology of allergic rhinitis. TT 16. Discuss in vivo vs. in vitro allergy testing. Otolaryngol Head Neck Surg 1995;113:597. HH 17. Educate us on immunotherapy SET vs. RAST based treatment. HH