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Fawzeia Abo Ali
Prof. of Internal Medicine & Immunology
Allergy is a hypersensitivity reaction
initiated by mainly antibody- or
occasionally via cell-mediated response.
About 30 -40% of individuals in
developed countries have allergy,
1. asthma ,(5 - 10%),
2. Rhinitis (10 - 20%)
3. food allergy (1 - 3%).
Asthma
A.rhinitis
Anaphlaxis
hives
Allergy Diagnosis
1. Asthma
2. Seasonal allergic
rhinitis/conjunctivits
3. Allergic & fungal sinusitis
Major Indications for Allergy
Testing
Necessary indications of allergy testing
Indicatios of allergy testing in
Asthma
1. Patients exposed to indoor allergens
with persistent asthma
2. To improve management of patients
with:
– Moderate to severe persistent asthma
– Poor control despite appropriate therapy
– Using excessive amounts of medications
– Associated rhinitis or sinusitis
3. Identifying role of agent
– Occupational exposure ,food or drug
4. Before immunotherapy
Allergy tests
• In vitro testing:
 Total &specific IgE tests),
 basophil histamine
release test
 Serum mast cell
tryptase .
• In vivo testing:
 ((skin prick testingskin prick testing,
intradermal testing,
 patch testing,
 bronchial provocation
tests,
food challengesfood challenges.
1. Skin prick test
1. Skin prick test
rhinoconjunctivitis,
asthma,
urticaria,
anapylaxis,
atopic eczema
food and drug allergy.
Contraindications:
:
Severe atopic dermatitis
Dermatographism. •
severe reaction to some
allergens
Pregnancy.
Anaphylaxis
B blockers
Indications:
IgE mediated allergy
Drug Suppression
Abstinence before
testing
Antihistamines
1st generation H1-blocker
+++ > 2 days
Hydroxyzine
2nd generation H1-blocker
+++ 7 days
Cetirizine, Loratadine, etc.
Ketotifen +++ > 5 days
H2-blocker 0 - + Ø
Glucocorticosteroids
  Topical (in test area) + > 1 week 1
  NasalInhaled  0 Ø
  Systemic/short term (up to 10 d) 0 / (+)
Topical calcineurin inhibitors + > 1 week
Omalizumab ++ > 4 weeks
•Patients unable to discontinue antihistamines
Patients with extensive dermatitis/dermatographia
Patients unable to discontinue beta-blockers
•Patients with an anaphylactic
2) Allergen-specific IgE
SPT compared with specific IgE
SPT
•  more rapidly obtained,
• less expensive, and more
sensitive
• Immediate results
• Generally more sensitive
• Side effect
Specific IgE
• Completely safe
• Not affected by drugs
• It is not affected by skin
disease:
Should I do a “blood" test or a
skin test???
• Skin testing remains the "gold
standard" for detection of allergen-
specific IgE
• Positive "RAST" indicate the presence of
allergen-specific IgE in the peripheral
blood (ie that the patient is "sensitised" to
the allergen),NOT necessarly allergic.
• sensitivities of 70% to 80% have been noted
when compared with skin tests.
Total IgE levels — 
• Although an elevated total IgE may indicate that
the patient has an atopic condition, yet, there is
a large degree of overlap between IgE levels in
people with and without allergic disease, the
utility of total IgE in diagnosing these common
conditions is limited
Patch test
• Basophil histamine release 
•  The basophil histamine release test measures
the release of histamine from human peripheral
blood basophils incubated with allergen, basophil
histamine release is not standardized and is
considered an investigative tool for drug, food,
and environmental allergens.
The Double blind food challenge
test
(DBPCFC)
 The gold standard for food allergy
diagnosis.
• These consist of double-blind, placebo-controlled
challenges using encapsulated food.
• This test allow diagnosis of food hypersensitivity
whatever its pathogenesis .
• Sequentially increasing doses of the suspected
food are administered at intervals of 30 to 60 minutes
until the patient consumes an amount equivalent to a
standard serving size of the food.
• If the patient demonstrates objective evidence of an
allergic reaction then the procedure is halted .
Indicated when there is
discordance between the
clinical history and the
results of objective tests.
4. Provocation Testing
The patient inhales saline, and the pulmonary functions are repeated. If
the baseline FEV1 remains stable, the patient inhales increasing doses of
the challenge substance at15- to 30-minute intervals. A decrease in FEV1
of at least 20% following a dose of the substance is considered a positive
response.
Case 1
• A 25-year-old nonsmoking graduate student recently
moved into a ground-floor apartment.
• He had a history of childhood asthma that easily
managed by the use of inhaled -agonist as needed.
• Within 1 month, he began to experience nocturnal
attacks, and increased need for his -agonist,β
• Physical examination revealed a pale, boggy nasal
mucosa and diffuse expiratory wheezes.
• Prick skin testing to inhalant allergens revealed 4+
reaction to house dust mite, and 2+ to tree pollen.
Case 2
• A 25-year-old woman with a long history of asthma
develops nasal stuffiness. Initial blood tests reveal an
elevated serum IgE (550 kU/L) and eosinophilia 18%.
• Respiratory allergic disease is suspected but RAST and
skin prick testing are negative.
• She subsequently develops fevers, weight loss, foot drop
and pulmonary infiltrates.
• Other causes of eosinophilia elevated IgE were
investigated.
• In this case, specific anti-neutrophil antibodies were
detected, which indicated Churg-Strauss syndrome.
Case 3
A .42-year-old nurse is assessed for antibiotic
allergy one week after having developed
generalised urticaria associated with dyspnoea
and near syncope following ingestion of
amoxycillin.
What is the safest initial test for penicillin
allergy?
– Skin prick test
– RAST testing to penicillin
Case 4
A six-year-old girl who has history of egg allergy
since she was 12 months, develops +ve (SPT) to
egg white.
• Does the positive skin prick test mean this girl is
still allergic to egg? If not, are there any further
tests that should be performed?
 The majority of egg-allergic children will
lose their allergy to egg by age seven, some of
these children may not lose their SPT reactivity
 Graded challenge is confirmatory
Take home messege
• History + skin prick testing remain
the "gold standard" for identifying
relevant allergens.
• A positive RAST in the absence of a
consistent history indicates
sensitisation, not allergy.
• Double blind food challenge test
demonstrates objective evidence for
allergic food reaction .
Take home messege (cont.)
• Bronchoprovocation challenges for
asthma are indicated in some situations.
• In the absence of allergic disease,
Elevations of IgE and eosinophilia
,should be investigated.
• In vitro tests offer advantages in some
situations.
• REFERENCES
• Simons FE, Frew AJ, Ansotegui IJ, et al. Risk assessment in anaphylaxis: current and future
.
• Pereira B, Venter C, Grundy J, et al. Prevalence of sensitization to food allergens, reported a
• Stevenson MD, Sellins S, Grube E, et al. Aeroallergen sensitization in healthy
children: racial and socioeconomic correlates. J Pediatr 2007; 151:187.
• Golden DB, Tracy JM, Freeman TM, et al. Negative venom skin test results in
patients with histories of systemic reaction to a sting. J Allergy Clin Immunol 2003;
112:495.
• Hamilton RG, Biagini RE, Krieg EF. Diagnostic performance of Food and Drug
Administration-cleared serologic assays for natural rubber latex-specific IgE antibody.
The Multi-Center Latex Skin Testing Study Task Force. J Allergy Clin Immunol 1999;
103:925.
• Sampson HA. Update on food allergy. J Allergy Clin Immunol 2004; 113:805.
• Wood RA, Segall N, Ahlstedt S, Williams PB. Accuracy of IgE antibody laboratory
results. Ann Allergy Asthma Immunol 2007; 99:34.
• . Clin Exp Allergy 2003; 33:259.
Gold standards in allergy diagnosis

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Gold standards in allergy diagnosis

  • 1. Fawzeia Abo Ali Prof. of Internal Medicine & Immunology
  • 2. Allergy is a hypersensitivity reaction initiated by mainly antibody- or occasionally via cell-mediated response. About 30 -40% of individuals in developed countries have allergy, 1. asthma ,(5 - 10%), 2. Rhinitis (10 - 20%) 3. food allergy (1 - 3%).
  • 5. 1. Asthma 2. Seasonal allergic rhinitis/conjunctivits 3. Allergic & fungal sinusitis Major Indications for Allergy Testing
  • 6. Necessary indications of allergy testing
  • 7. Indicatios of allergy testing in Asthma 1. Patients exposed to indoor allergens with persistent asthma 2. To improve management of patients with: – Moderate to severe persistent asthma – Poor control despite appropriate therapy – Using excessive amounts of medications – Associated rhinitis or sinusitis 3. Identifying role of agent – Occupational exposure ,food or drug 4. Before immunotherapy
  • 8.
  • 9. Allergy tests • In vitro testing:  Total &specific IgE tests),  basophil histamine release test  Serum mast cell tryptase . • In vivo testing:  ((skin prick testingskin prick testing, intradermal testing,  patch testing,  bronchial provocation tests, food challengesfood challenges.
  • 11. 1. Skin prick test rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema food and drug allergy. Contraindications: : Severe atopic dermatitis Dermatographism. • severe reaction to some allergens Pregnancy. Anaphylaxis B blockers Indications: IgE mediated allergy
  • 12. Drug Suppression Abstinence before testing Antihistamines 1st generation H1-blocker +++ > 2 days Hydroxyzine 2nd generation H1-blocker +++ 7 days Cetirizine, Loratadine, etc. Ketotifen +++ > 5 days H2-blocker 0 - + Ø Glucocorticosteroids   Topical (in test area) + > 1 week 1   NasalInhaled  0 Ø   Systemic/short term (up to 10 d) 0 / (+) Topical calcineurin inhibitors + > 1 week Omalizumab ++ > 4 weeks
  • 13.
  • 14.
  • 15.
  • 16. •Patients unable to discontinue antihistamines Patients with extensive dermatitis/dermatographia Patients unable to discontinue beta-blockers •Patients with an anaphylactic 2) Allergen-specific IgE
  • 17. SPT compared with specific IgE SPT •  more rapidly obtained, • less expensive, and more sensitive • Immediate results • Generally more sensitive • Side effect Specific IgE • Completely safe • Not affected by drugs • It is not affected by skin disease:
  • 18. Should I do a “blood" test or a skin test??? • Skin testing remains the "gold standard" for detection of allergen- specific IgE • Positive "RAST" indicate the presence of allergen-specific IgE in the peripheral blood (ie that the patient is "sensitised" to the allergen),NOT necessarly allergic. • sensitivities of 70% to 80% have been noted when compared with skin tests.
  • 19. Total IgE levels —  • Although an elevated total IgE may indicate that the patient has an atopic condition, yet, there is a large degree of overlap between IgE levels in people with and without allergic disease, the utility of total IgE in diagnosing these common conditions is limited
  • 21. • Basophil histamine release  •  The basophil histamine release test measures the release of histamine from human peripheral blood basophils incubated with allergen, basophil histamine release is not standardized and is considered an investigative tool for drug, food, and environmental allergens.
  • 22. The Double blind food challenge test (DBPCFC)  The gold standard for food allergy diagnosis. • These consist of double-blind, placebo-controlled challenges using encapsulated food. • This test allow diagnosis of food hypersensitivity whatever its pathogenesis .
  • 23. • Sequentially increasing doses of the suspected food are administered at intervals of 30 to 60 minutes until the patient consumes an amount equivalent to a standard serving size of the food. • If the patient demonstrates objective evidence of an allergic reaction then the procedure is halted .
  • 24. Indicated when there is discordance between the clinical history and the results of objective tests. 4. Provocation Testing The patient inhales saline, and the pulmonary functions are repeated. If the baseline FEV1 remains stable, the patient inhales increasing doses of the challenge substance at15- to 30-minute intervals. A decrease in FEV1 of at least 20% following a dose of the substance is considered a positive response.
  • 25. Case 1 • A 25-year-old nonsmoking graduate student recently moved into a ground-floor apartment. • He had a history of childhood asthma that easily managed by the use of inhaled -agonist as needed. • Within 1 month, he began to experience nocturnal attacks, and increased need for his -agonist,β • Physical examination revealed a pale, boggy nasal mucosa and diffuse expiratory wheezes. • Prick skin testing to inhalant allergens revealed 4+ reaction to house dust mite, and 2+ to tree pollen.
  • 26. Case 2 • A 25-year-old woman with a long history of asthma develops nasal stuffiness. Initial blood tests reveal an elevated serum IgE (550 kU/L) and eosinophilia 18%. • Respiratory allergic disease is suspected but RAST and skin prick testing are negative. • She subsequently develops fevers, weight loss, foot drop and pulmonary infiltrates. • Other causes of eosinophilia elevated IgE were investigated. • In this case, specific anti-neutrophil antibodies were detected, which indicated Churg-Strauss syndrome.
  • 27. Case 3 A .42-year-old nurse is assessed for antibiotic allergy one week after having developed generalised urticaria associated with dyspnoea and near syncope following ingestion of amoxycillin. What is the safest initial test for penicillin allergy? – Skin prick test – RAST testing to penicillin
  • 28. Case 4 A six-year-old girl who has history of egg allergy since she was 12 months, develops +ve (SPT) to egg white. • Does the positive skin prick test mean this girl is still allergic to egg? If not, are there any further tests that should be performed?  The majority of egg-allergic children will lose their allergy to egg by age seven, some of these children may not lose their SPT reactivity  Graded challenge is confirmatory
  • 29. Take home messege • History + skin prick testing remain the "gold standard" for identifying relevant allergens. • A positive RAST in the absence of a consistent history indicates sensitisation, not allergy. • Double blind food challenge test demonstrates objective evidence for allergic food reaction .
  • 30. Take home messege (cont.) • Bronchoprovocation challenges for asthma are indicated in some situations. • In the absence of allergic disease, Elevations of IgE and eosinophilia ,should be investigated. • In vitro tests offer advantages in some situations.
  • 31. • REFERENCES • Simons FE, Frew AJ, Ansotegui IJ, et al. Risk assessment in anaphylaxis: current and future . • Pereira B, Venter C, Grundy J, et al. Prevalence of sensitization to food allergens, reported a • Stevenson MD, Sellins S, Grube E, et al. Aeroallergen sensitization in healthy children: racial and socioeconomic correlates. J Pediatr 2007; 151:187. • Golden DB, Tracy JM, Freeman TM, et al. Negative venom skin test results in patients with histories of systemic reaction to a sting. J Allergy Clin Immunol 2003; 112:495. • Hamilton RG, Biagini RE, Krieg EF. Diagnostic performance of Food and Drug Administration-cleared serologic assays for natural rubber latex-specific IgE antibody. The Multi-Center Latex Skin Testing Study Task Force. J Allergy Clin Immunol 1999; 103:925. • Sampson HA. Update on food allergy. J Allergy Clin Immunol 2004; 113:805. • Wood RA, Segall N, Ahlstedt S, Williams PB. Accuracy of IgE antibody laboratory results. Ann Allergy Asthma Immunol 2007; 99:34. • . Clin Exp Allergy 2003; 33:259.