알레르기질환관련 진단적검사의이해 분당서울대병원알레르기내과 김세훈

Transcription

1 알레르기질환관련 진단적검사의이해 분당서울대병원알레르기내과 김세훈

2 What is allergy? Von Pirquet(1906): Greek allos (altered) + ergos (response) Exposure to foreign antigen (allergen) beneficial Harmful altered response Immunity No response Hypersensitivity (Allergy) Allergy: aberrant or excessive immune response generated against foreign antigens

3 Atopy vs. Allergy Atopy - tendency for exaggerated IgE response - defined clinically by presence of positive skin prick test for one or more common inhalant allergen - predisposition to develop allergy Allergy (esp. IgE-mediated allergic disease) - clinical expression of atopic disease - including asthma, rhinitis, eczema and food allergy

4 Mechanisms of allergic disease

5 Allergens Inhalants Foods Drugs Insect venom Occupational allergens 항원

6 Manifestation of allergy Site Disease Symptoms Respiratory Allergic rhinitis rhinorrhea, obstruction, sneezing mucosa asthma cough, dyspnea, wheezing GI mucosa Food allergy cramping, diarrhea, vomiting Skin Systemic Contact dermatitis eczema, pruritis Urticaria hives, pruritis Anaphylaxis hives/edema, hypotension (LOC), bronchospasm, cramping

7 Diagnosis of allergic disease History taking : most important!! Physical examination Diagnostic test for target organ disease status (e.g. asthma) - reversible airway obstruction: spirometry, bronchodilator response - airway hyperresponsiveness: methacholine bronchial provocation test - airway inflammation: induced sputum analysis Evaluation of causative allergen - Skin test : prick, intradermal, patch test - Serum specific IgE : MAST, RAST, ImmunoCAP - specific allergen provocation test: nasal, bronchial, oral

8 Focus of Allergy diagnosis Is the patient atopic? Does allergy contribute to patient s symptom? What are the clinical relevant allergens? allergen avoidance environmental control immunotherapy, desensitization (if avoidance is impossible)

9 Allergy History Taking Main dominant symptoms Associated symptoms Frequency and severity of symptoms, impact on lifestyle Seasonal or perennial? Triggering factors : allergic or non-allergic factor Occupation, hobbies Food, drug consumption history Possible allergen exposure in home Personal or family history of allergic disease Prior treatment response, side-effects

10 Skin test Purpose - identification of causative allergens - standardization of allergens : allergenic potency - immunotherapy dosing and response evaluation Advantages - easy to perform, fast - not expensive - high sensitivity

11 Technique Skin prick test ( 피부단자시험 ) - clean the test skin surface(back, forearm volar surface) with cotton moistened with 75% alcohol and dry up - place a small drop of each test extract and positive/negative control solution 3-5cm apart - prick with 25 or 26G needle and lift gently needle tip upward - read the wheal and flare reaction 15min later Intradermal test ( 피내시험 ) - clean the test skin surface(back, forearm volar surface) with cotton moistened with 75% alcohol and dry up - intradermal injection of allergen extract with 1ml syringe and 26G needle (approximately 2-4mm diameter bleb, 0.02ml injection) - perform with positive/negative control solution - read the wheal and flare reaction 15min later

12 Controls Negative control diluent or saline false positive - dermographism - needle irritation Positive control Histamine (1mg/ml) (intradermal: 1/100 diluted) false negative - medication (e.g. antihistamine) - underlying disease - technical error

13 Skin test : method Prick test Intradermal test Scratch test

14 Skin prick test

15 Skin prick test : method

16 Factors affecting skin test Allergen extract Area of body - back >> arm - upper back >> lower back - ulnar side of arm >> radial side of arm Age - significant wheal detect after 3mo of age in infants - increase from infancy to adulthood - decline after age of 50 Sex, Race Seasonal variation Pathologic conditions

17 Drugs affecting skin test H1 antihistamine - 1 st generation (pheniramine, hydroxyzine): 1-3days - 2 nd generation: (cetrizine, fexofenadine etc.) : 3-10days Imipramies, Phenothiazines: > 10days Systemic steroid - short-term( 1wk) : no effect - long-term : possible effect H2 blocker, leukotriene antagonist, theophylline, beta-agonist: no clinical significance

18 Positive criteria Size of wheal and erythema(flare) - prick test: wheal size ( 3mm) and flare( 10mm) regarded as clinically significant allergy - intradermal test : wheal size 5mm Grading (relative size compared with positive control) - Allergen/Histamine ratio

19 Interpretation Clinical relevancy - positive skin test clinical allergic disease - consider asymptomatic sensitization, insignificant cross-reaction (sensitization rate: 30-40% of general population) Correlation with other allergy diagnostic test - more sensitive, less specific than in vitro allergen-specific IgE test Diagnostic value of skin test - inhalant : most cheapest and effective method for respiratory allergy - food : low sensitivity(20-60%) and specificity(30-70%) due to insignificant cross-reaction and food protein instability - drug : variable, low sensitivity except penicillin (PPL+MDM)

20 Prick vs. intradermal Factor Prick test Intradermal test Simplicity Speed Interpretation of positive and negative reactions Discomfort False-positive reactions Rare Possible False-negative reactions Possible Rare Reproducibility Sensitivity Specificity Detection of IgE antibodies Yes Yes Safety Testing of infants Yes Difficult

21 Skin test Precautions 1. Skin tests should never be performed unless a physician is available immediately to treat systemic reactions. 2. Have emergency equipment readily available, including epinephrine. 3. Be careful with patients having current allergic symptoms. 4. Determine the value of allergenic extracts used and assess their stability. 5. Be certain that the test concentrations are appropriate. 6. Include a positive and a negative control solution. 7. Perform tests in normal skin. 8. Evaluate the patient for dermographism. 9. Determine and record medications taken by the patient and time of last dose. 10.Record the reactions at the proper time.

22 Immediate reaction Induced by chemical mediators (e.g. histamine, tryptase) realeased from mast cell degranulation Wheal and flare reaction Reading: 15-20min after injection (peak)

23 Late phase reaction Induced by inflammatory cell infiltration due to cytokine, chemokines release from mast cell erythema, induration, edema, dysthesia Reading: 6-12hr after injection (peak reaction)

24 Prick to prick test Useful in food allergy, oralallergy syndrome Food allergens such as fresh fruits and vegetables related with easy enzymatic degradation of relevant allergen

25 Patch test Evaluation of delayed-type cell mediated reaction Contact dermatitis, delayed-type drug hypersensitivity reaction Patch apply for 48hrs Reading: 48hrs after apply (20min after removal) 72hrs after apply (24hr after removal)

26 In vitro test for specific serum IgE 1967, RAST introduced - noncompetitive, heterogeneous solidphase radioallergosorbent assay - semi-quantitative - less affected by medication, patients factor - low sensitivity, relatively high specificity - expensive FAST, MAST ELISA ImmunoCAP system

27 MAST(Multiple allergen simultaneous test) MAST-CLA TM, Hitachi RIDA TM allergyscreen, r-biopharm - low sensitivity, semi-quantitative

28 ImmunoCAP system (Pharmacia) FEIA-fluoroenzyme immuno assay Cellulose polymer sponge structure high sensitivity and specificity Quantitative, reliable measure of specific IgE ImmunoCAP 100, 250, 1000 Inhalants, Foods, Drugs, Occupational allergen, Insects

29 Serum specific IgE in food allergy Predictive value of food allergen-specific IgE levels Sampson HA, JACI, 2004;113:805-19

30 Serum specific IgE in food allergy 95% Positive Predictive value of specific IgE levels and skin prick test diameter Lack G, NEJM, 2008;358:

31 Serum specific IgE in food allergy Suggested decision levels for challenge ku A /L Neg Egg Egg 95% Probability of positive reaction Milk Peanut Fish Milk 90% Probability of negative reaction Fish

32 Serum total IgE PRIST, ImmunoCAP etc. kiu/l or IU/ml (1IU=2.44ng/ml) Highly variable in normal children and adults Affected by age, sex, smoking, environmental factors etc. Wide overlap in IgE concentration between atopic and non-atopic individuals Can be elevated in non-allergic disease e.g. parasitic infection, malignancy, HIV infection etc. Increasing serum total IgE are strongly related with the risk of asthma

33 Serum total IgE Values suitable to rule out allergic disease were not founded Little value as a test for atopy and allergic disease Can be used to confirm clinical histories suggestive of allergic disease * Predictive value of total serum IgE for a positive allergen specific IgE Sinclair D et al. J Clin Pathol, 2004;57:

34 Phadiatop TM Screening atopy vs. non-atopy ImmunoCAP system for allergen mixture Qualitative report : positive or negative Phadiatop infant (0-4yr) : foods, inhalants Phadiatop ( 5yr) : common inhalants

35 Serum Tryptase Useful in diagnosis of anaphylaxis Persist longer than plasma histamine Peak 60-90min after onset of anaphylaxis Can be detected as long as 4-5hrs after onset of symptoms Can be elevated in other allergic disease, systemic mastocytosis

36 Common inhalant allergens In Korea Kim TB et al. 천식및알레르기 2003.

37 Important inhalant allergens in Korea House dust mite (D. pteronyssinus, D farinae) Mould (alternaria, aspergillus etc.) Cockroach (German cock, American cock.) Animal dander (cat, dog) Tree pollen (birch, beech, oak, hazel, alder etc.) Grass pollen (rye, timothy, kentucky blue grass etc.) Weed pollen (ragweed, mugwort, Hop Japanese etc.) Geographical factor: 예 ) 제주도 : Panonychus citiri( 귤응애 ), Japanese cedar( 일본삼나무 )

38 Important food allergens Infant and children - egg, milk, seafood (shrimp, crab), peanut, wheat Adults - seafood (shrimp, crab, lobster), fruits, peanut, treenut, wheat, buckwheat, meat (pork, beef), fish

39 When to refer to a specialist allergy clinic Investigation and management of anaphylaxis If diagnosis of allergy is in doubt, e.g. there is discord between the history and skin test/specific serum IgE test To evaluate allergy as a suspected cause of nonspecific illness If occupational allergy is suspected For consideration of more sophisticated test or specific provocation test Uncontrolled asthma, rhinitis, urticaria, food allergy For consideration of immunotherapy For specialist allergen-avoidance advice