Persia Pourshahnazari MD, FRCPC Clinical Immunology and Allergy November 3, 2018

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1 Persia Pourshahnazari MD, FRCPC Clinical Immunology and Allergy November 3, 2018

2 UBC couldn t get rid of me Medical school, Internal Medicine residency, Clinical Immunology and Allergy fellowship Current practice Outpatient clinic at Vancouver Pediatric and Allergy Centre (patients >6 years) Primary Immunodeficiency Transition clinic at Saint Paul s Hospital with pediatric immunology Outreach clinics in Masset and Queen Charlotte City (Haida Gwaii) Clinical instructor, UBC

3 Allergy testing is a massive topic! I hope to clarify Commonly available testing methods General indications for different types of testing Discuss a few controversial testing methods Won t have time to discuss Details on performing the tests Interpretation of test results Management of allergic diseases

4 As health care providers, allergy is used to describe hypersensitivity reactions A distinct, immunologic response to an antigen (either exogenous or endogenous) Patients can use allergy to mean absolutely everything and anything Presenting allergic complaint may not be immunologic at all

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7 1. History and physical 2. Skin testing 3. In-vitro testing 4. Supervised graded challenges

8 Fundamental diagnostic tool in any allergy assessment! Positive in-vivo or in-vitro allergy testing in the absence of relevant clinical history is useless Characterize the reaction Identify potential culprit(s) Determine appropriate testing (as required)

9 To detect presence of specific IgE (immediate hypersensitivity): Skin prick testing (SPT) Intradermal testing To detect T-cell response (delayed type hypersensitivity): Patch testing Intradermal testing

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11 Indications Allergic rhinoconjunctivitis Allergic asthma Food allergy Atopic dermatitis (sort of) Latex allergy Others Medications Venoms

12 Rapid (10-15 minutes) Cost effective Sensitive (at the expense of specificity) Aeroallergens: Sensitivity and Specificity >85% Lower for molds Foods: Sensitivity >85%, Specificity 50% Overall negative predictive value: 95% Overall positive predictive value (all types of allergens): <50%

13 Factors affecting skin tests: Age Smaller wheals in infants and elderly Ethnicity Larger wheals in non-atopic black patients Seasonal variation Reactivity peaks during the pollen season Chronic conditions Decreased reactivity with eczema, renal failure/hd, spinal cord injuries, peripheral nerve abnormalities Recent anaphylaxis (anergy)

14 Factors affecting skin tests: Medications Antihistamines Up to 7 days for H1 blockers Up to 48 hours for H2 blockers Tricyclic antidepressants (up to 2 weeks) Omalizumab (up to 6 months) High dose/prolonged systemic corticosteroids

15 Medications that do NOT affect SPT Intranasal steroids or short term OCS Beta agonists Leukotriene receptor antagonists Cromolyn SSRIs Cyclosporine

16 Limitations False positives due to protein or carbohydrate cross reactivity Tree pollens in honeybee allergic patients Dust mites in shellfish allergic patients Peanut in grass pollen allergic patients Caution/Relative contraindications Severe, uncontrolled asthma History of prior severe reaction with minute exposure to antigen (especially latex)

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18 More reproducible and sensitive than SPT, but less specific High rate of false positives due to chemical irritation Can be dangerous Fatalities have been reported Unsafe to do ID testing with foods or latex

19 Indications Medications Useful for penicillin, chemotherapeutic agents, muscle relaxants, insulin and heparin testing Everything else is unvalidated!!! Non-irritating concentrations determined for many drugs Venoms Yellow jacket, yellow hornet, white faced hornet, honeybee, imported fire ant Occasionally for aeroallergens Weaker, non-standardized inhalant allergens (eg. dog)

20 Antigen injected and induration recorded hours later Indications TB skin test Primary immunodeficiency Screening test for function of the cellular immune system Done with recall antigens that a normal (immunized) host should recognize Candida, tetanus toxoid, mumps

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22 Helps identify specific allergen(s) in contact dermatitis May be useful for certain drug reactions Maculopapular drug eruptions, fixed drug eruptions, AGEP Other (more controversial) uses Eosinophilic esophagitis Atopic dermatitis

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24 Generally non-diagnostic of allergic disease Wide ranges and overlap in IgE distribution of both atopic and non-atopic patients Eg. Atopic dermatitis IgE range: 1-65,000 IU/mL Most useful indications: ABPA Omalizumab candidacy Work-up of primary immunodeficiency

25 Quantification of IgE specific to an antigen Less sensitive than SPT, more specific But don t forget positive specific IgE does not equal allergic disease! Sensitization = presence of specific IgE 8-30% of general population when using a standard panel of aeroallergens 25% of general population when testing to venoms 30-60% of sensitized individuals may develop future clinically relevant allergic symptoms Allergy = convincing clinical history + presence of specific IgE

26 Available for: Foods Aeroallergens Natural rubber latex Penicillin (major determinant only) Occupational allergens (TDI and TMA)

27 Short lived, difficult to obtain blood acutely Ex. Plasma histamine level normalizes within 15 minutes Tryptase = most useful mediator Can be used to distinguish anaphylaxis from other causes of systemic symptoms Drawn between 1-3 hours after clinical reaction 24 hour urine collection for histamine metabolites also available

28 Gradual administration of test food/medication under medical supervision For patients where allergy is unlikely May be open, single-blinded, or doubleblinded/placebo controlled Can be done as oral challenge (foods, medications) or parenteral (eg. IV medications) Sting challenge gold standard in venom allergy research studies Rarely performed in the clinical setting

29 For patients where allergy is likely Similar concept to graded challenges Start at much lower doses More graded increments with shorter intervals Treat reactions as they occur continue with the protocol until either can t progress further or desensitization achieved High risk therapeutic procedure, not a diagnostic tool Needs medical supervision/monitoring Used to induce temporary tolerance to a proven allergen for a patient

30 Wide variety of other tests out there that patients may come across Some are currently primarily used in the research setting Majority are unvalidated for diagnosis of allergic disease

31 May become widely used in clinical setting in the future Component resolved diagnostics To determine risk of anaphylaxis with a food versus oral allergy syndrome (ie. protein cross reactivity) Ex. Ara h 2 vs Ara h 8 in peanut allergy Basophil activation tests Incubation of basophils (like mast cells, but in the vasculature as opposed to the tissue) with allergens Flow cytometry to detect markers of activation

32 IgG4 as a marker of success in allergen immunotherapy Decrease in IgE and increase in blocking IgG4 antibodies Correlates with clinical improvement in aeroallergen immunotherapy Not validated as a marker of therapeutic success Correlation with oral immunotherapy (for foods) not yet established

33 Serum specific IgG levels Foods and inhalants are not self-antigens The immune system recognizes them as foreign but in most cases, not as dangerous Serum specific IgG is produced as a marker of exposure Patients often note that the highest values are the foods that they eat the most often.they are correct! No utility in diagnosing any type of allergy or intolerance

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35 Electrodermal testing (eg. Vega testing) Measures electrical impedence of the skin in response to an electric current Performed while foods or inhalant extracts are placed in contact with the circuit (ie. Patient) Change in electrical impedance considered diagnostic of allergy DBPCT data: this method cannot independently distinguish atopic from nonatopic patients

36 Provocation-Neutralization Test doses of various agents (chemicals, allergens, food extracts, etc) given ID, SC, or SL Subjective symptoms recorded for 10 minutes after each dose Increasing dose given if no symptoms If symptoms occur ( provocation ), lower doses are given until symptoms dissipate ( neutralization ) This dose given as therapy/treatment DBPCT found this method to be equivalent to placebo

37 Applied kinesiology Allergens are placed in the patient s hand while a technician assesses subjective muscle strength in the opposite arm A decrease in muscle power indicates allergy Not supported by DBPCT

38 Cytotoxic test and Antigen Leukocyte Cellular Antibody Test (ALCAT) Theory: morphologic changes in leukocytes exposed to allergen in vitro = sensitization to that allergen Centrifuged leukocytes and autologous serum placed on a slide coated with dried allergen extract Cells examined for lack of movement, structural changes (eg. rounding, flattening, change in volume) Data is anecdotal only reports of utility for guiding elimination diets Not supported by DBPCT

39 Sap from commercial rubber tree (Hevea brasiliensis) BIG occupational health epidemic in the 90s Widespread use of powdered latex gloves by healthcare professionals Prevalence: General population: <1% HCP: 1990s: 10-12% Now: 4-7% Latex-exposed patients (e.g. spina bifida): 1990s: 30-35% Now <1%

40 Can cause many allergic manifestations Immediate hypersensitivity/anaphylaxis Allergic rhinoconjunctivitis and asthma Allergic contact dermatitis Allergic contact urticaria Latex-food syndrome Most common adverse reaction with latex exposure in health care professionals is NOT allergic at all Irritant contact dermatitis rubber accelerators and antioxidants

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42 Need to demonstrate sensitization Strict avoidance in sensitized individuals Epinephrine autoinjector and medical alert jewelry for those with a history of anaphylaxis

43 For immediate type hypersensitivity (anaphylaxis, ARC, asthma, urticaria) Skin prick testing No commercially validated extract available in Canada Natural rubber latex used by most allergists Serum specific IgE Commercially available Less sensitive, more specific

44 For delayed type hypersensitivity (ACD) Patch testing Can test for rubber accelerants at the same time For occupational asthma Spirometry and peak flows Do NOT do intradermal testing to latex Cases of severe hypotension/anaphylaxis reported

45 Questions?

46 Canadian Society of Allergy and Clinical Immunology American Academy of Allergy, Asthma & Immunology Food Allergy Canada