Title: Basics in paediatric allergology: IgE-mediated allergy in respiratory illness
1Basics in paediatric allergology IgE-mediated
allergy in respiratory illness
- Prof. Dieter Koller, M.D.
- University Childrens Hospital of Vienna, Austria
2Themes
- Definition of allergy
- Overview on IgE-mediated allergies
- Methods in diagnosis
- Skin Prick testing, intradermal testing, atopy
patch test, provocation testing - Allergy prevention
- Primary, sekundary,tertiary prevention
- Overview on studies dealing with prevention
- Treatment
- Symptomatic
- causale (specific immuntherapy SCIT und SLIT)
- Studies dealing with SCIT und SLIT
3Allergic reaction
- Manifestation of symptoms after repeated exposure
to an allergen after (latent) period of
sensitization - IgE-mediated release of mediators and zytokines
from effector cells like mast cells, eosinophils
and T-lymphocytes - Symptoms may occur in single organ but also
systemically (allergic - Symptome zwar abhängig vom Zielorgan -systemisch
allergische Reaktion jedoch immer möglich (z.B.
allergische Rhinitis u. zeitgleiche
Asthmasymptome)
4Pseudoallergy and/or anaphylaktoid reactions
- Symptoms similiar to allergic reaction but not
immunological mediated (Allergy tests negative)-
and partially dependent on dosis - Histamine intolerance
- Reaction auf radiocontrast agents,i.v.
anaesthetics, antibiotics - Food adverse reactions to additives
5Atopya-topos
being on the wrong
place
ill-making
reaction of the immune systeme
Clemes von Pirquet (Head of the University
Childrens Hospital Vienna1911-1929) defined the
terminus Allergy/Atopy
6Definition
- Atopy enhanced production of IgE in asymptomatic
subjects - Allergy Presence of symptoms corresponding to
specific IgE antibodies
7Manifestations of allergic diseases
- Eyes - allergic conjunctivitis
- Nose - allergic rhinitis
- larynx- angioedema
- Lung - allergic bronchial asthma
- Skin urticaria, rash
- Gastrointestinal - diarrhea, abdominal cramps
- Systemic - Anaphylaxis
8House dust mite
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10Flow of systemic allergic reactions
- Seconds to minutes after exposure of minimal
amounts of allergen, sometimes after up to two
hours - Biphasic reactions
?rapide improvement after treatment
further reaction - Prolonged reaction
?Perstistence of symptoms under treatment
11Allergic diseases
- Bronchial asthma (extrinsic)
- Allergic rhinoconjunctivitis (hay fever)
- Atopic dermatitis
- Food allergy
- Insect sting allergy
- Oral Allergy Syndrome (cross reactivity between
pollens and certain fruits, like tree pollens
and nuts, latex and banana, mango, house dust
mite and snails, mussels, shrimps)
12Prevalence of allergic diseases in the paediatric
population
- Atopic eczema 10
- Allergic rhinoconjunctivitis 10-20
- Bronchial asthma 10
- Insect sting Allergy 0.8 -1
- Food allergy 3-4
- Anaphylaxis1-4
- Drug allergy ?
(in 90 of children with
positive history no detection of specific)
13Genetics of allergic diseases
- Until now, 79 genes have been identified to
associated with the asthma and/or atopy phenotype
in different populations. - Two major genes with association to the same
phenotype independent of the population - Arg 110Gln variation of IL-13 (Th2-cytokine)
encoded Gene is associated with increaseed IgE
production - R510X Gene variation causing lost of function
of filagrin atopic eczema
14Diagnostic procedure
Patients history
in vivo, in vitro testing
Provocation testing
15Anamnesis
- Which symptoms
- Since when
- When
- How long
- How frequent
- Where
- Which medication so far (improvement?)
16Which symptoms may be associated with allergic
diseases
-
- ? Eczema ? Itching
- ? Erythema ? urticaria
- ? recurrent diarrhea ? abdominal pain
- ? dystrophia
-
- ? Wheezing ? coughing
- ? shortness of breath
- ? chronic sticky nose
- ? sneezing
-
- ? recurrent redness of eyes or itching
-
-
17Diagnostics in allergy
- In vivo (Skin-Prick testing,intradermal testing)
- In vitro (spezific IgE, total IgE, tryptase )
18Skin Prick Testing (SPT)
19SKIN PRICK TESTING
20 218 a old child rhinoconjunctivitis since 2 years
, end of May to middle of June
22When are skin prick test false positive/negative?
- Medication antihistamines, steroids,
immunosuppression - diseases mastocytosis, atopic eczem, chronic
urticaria, sunburn
23Positive SPT result
- negative no wheal reaction, similar to the
negative control - positive wheal reaction of at least 3mm and
equivalent to the histamine reaction.
24Intradermal testing
- Suspicion of hymenoptera allergy (drug allergy)
- More sensitive than SPT but also more painful
25In-vitro- testing
- total IgE ?
- specific IgE ?
- ECP (eosinophil cationic protein)
- tryptase
26Total IgE Indications
- Indirect-diagnostic parameter if aspergillosis,
parasitic infections, Job-syndrome - Detection of atopy(nice to know but no need to
know) - Total IgE is no screening test (sensitivity lt60)
27Primary indications for IgE measurement
- Contraindications for skin prick testing
- Diagnostics in infants and toddlers
28Indication for using recombinant allergens
(component)
- ???? (no therapeutic consequences)
- Exception
- hymenoptera allergy (Api m1, Ves v1, Ves v5)
- peanut allergy (Ara h2 high risk for severe
reactions)
29In-Vitro-diagnostics- advantages -
- Accurate and reproducable results
- WHO controlled standards
- Simple quantification (classes, Kilounits/l)
30In-Vitro-diagnostics- disadvantages -
- Measurement of circulating IgE-Ab, only
- The level of antibodies does not correlate with
clinical severity.
31Provocation testing
- Nasal
- Conjunktivale
- Bronchial
- Oral
- S.c.
- i.v.
32Nasal provocation testing
- Especially with perennial allergens (mould, house
dust mite) - Information about clinical relevance
- Discrepancy between symptoms and SPT/IgE
33conjunctival provocation testing
- No screening test
- Detection of allergic reactions of the eyes
- Very sensitive, prove of allergy also when SPT or
IgE negative - Einfach und meist risikolos
34Bronchial provocation testing
- Can a suspected allergen induce an asthma attack
and in which dosage?
35Why early diagnosis?
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38Conclusion!
- In children with a positive family history for
atopy an early sensitization against allergens
is a significant risk factor for the development
of brochial asthma.
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47TREATMENT
48Austrian Allergy Report 2006, T Dorner, A Rieder,
K Lawrence,M Kunze,
49Treatment of allergic diseases
- Symptomatic topical and/or systemic
- antihistamines (H1-receptorblockers)
- Dinatriumcromoglycate (nose, eye, lung)
- topical steroids (nose, eye, lung, skin)
- Causal
- Allergen avoidance if possible
- Spezific immuntherapy SIT
50Allergic rhinitis and its impact on asthma ARIA
Bousquet J et al. J Allergy Clin Immunol 2001
108 (5 Suppl) S 147-334
51A.R.I.A. Allergic Rhinitis and its Impact on
Asthma WHO Position Statement
- AR and asthma One Airway- One Disease
- Early treatment of AR reduces the development of
asthma or diminishes the severity of symptoms. - Optimal management of AR can improve
co-existent asthma - SIT is an additive therapy and should be offered
early in the course of disease
Bousquet J, van Cauwenberge P J Allergy Clin
Immunol, 2001108S 147-S 334
52Stufenplan nach ARIA
- Symptoms lt 4 days/ week
- or lt 4 Weeks
moderatel- severe persistent
mild persistent
Moderate- severe recurrent
topical steroids
Mild recurrent
Cromones
Non-sedating antihistamines
Decongestiva ( nose drops lt10 days)
Allergen avoidance
Spezific Immuntherapy
53Causal treatment
- Specific immunotherapy
- Allergen avoidance
54Specific immunotherapy (SIT)
Vaczinationsimmunotherapy(VIT) Hyposensitization
55Indications
- IgE-mediated disease (Rhinoconjunctivitis,allergic
bronchial asthma) - At least 2 years seasonal or perennial symptoms
when allergen avoidance can not b achieved or
symptoms persist - Older then 5 years of age
- Atopic family history early initiation to
prevent the developement of asthma and
polysensitization ftallergie
56Contraindications
- Immunodeficieny
- Severe, uncontrolled bronchial asthma
- severe cardiovascular diseases
57Applications
- Subcutaneous
- Sublingual (drops)
- Soluble tablets
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59SCIT
60Grass pollen immunotherapy as an effective
therapy for childhood seasonal allergic asthma
.Roberts G, Hurley C, Turcanu V, Lack G, J
Allergy Clin Immunol. 2006 Feb117(2)263-8.
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62Conclusion
- SCIT with grass pollens leads to significant
improvement of rhinitis- and asthma symptoms in
children. - In comparison to placebo skin test, conjunctival
and bronchial reactivity decreased.
63SCIT
- Prevention of new sensitizations
64Development of new sensitizations after SCIT with
house dust mites
Des Roches A. et al. JACI 199799450-53
65SCIT
- Prevention of bronchial asthma
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68PAT-Prevention of Asthma by Treatment
Specific immunotherapy has long-term preventive
effect of seasonal and perennial asthma 10-year
follow-up on the PAT study.Jacobsen L, Niggemann
B, Dreborg S et al. Allergy. 2007
Aug62(8)943-8.
69Immunological mechanisms of SCIT
APC
70Sublingual Immunotherapy (SLIT)
- Drops for sublingual application
- Allergen dosage much higher than used in SCIT
- Mechanism not totally solved
71SLIT indications
- Repeated systemic reactions during SCIT??
- Incompliant patients, trypanophobia???
Allergic Rhinitis and its Impact on Asthma ARIA
Bousquet J, Cauwenberge P editors, J Allergy
Clin Imunol 2001108S 147-336
72Demands when prescribing SLIT
- cumulative allergen-dosage at least 100-fold
higher than using SCIT - Accurate information of the patient about
potential side-effects (treatment will be
performed at home)
Allergic Rhinitis and its Impact on Asthma ARIA
Bousquet J, Cauwenberge P editors, J Allergy
Clin Imunol 2001108S 147-336
73 Ann Allergy Asthma Immunol. 200697141-48
74Rhinitis score
Rescue medication score
75Different IgG- antibody response after SCIT and
SLIT
76Until now, unsolved questions regarding SLIT in
children
- Ideal dosage duration of therapy ?
- Direct comparison SLIT and SCIT regarding
efficacy, prevention and immunological effects? - Reproducability of studies in a larger study
population?
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