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Basics in paediatric allergology: IgE-mediated allergy in respiratory illness

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Title: Basics in paediatric allergology: IgE-mediated allergy in respiratory illness


1
Basics in paediatric allergology IgE-mediated
allergy in respiratory illness
  • Prof. Dieter Koller, M.D.
  • University Childrens Hospital of Vienna, Austria

2
Themes
  • 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

3
Allergic 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)

4
Pseudoallergy 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

5
Atopya-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
6
Definition
  • Atopy enhanced production of IgE in asymptomatic
    subjects
  • Allergy Presence of symptoms corresponding to
    specific IgE antibodies

7
Manifestations of allergic diseases
  • Eyes - allergic conjunctivitis
  • Nose - allergic rhinitis
  • larynx- angioedema
  • Lung - allergic bronchial asthma
  • Skin urticaria, rash
  • Gastrointestinal - diarrhea, abdominal cramps
  • Systemic - Anaphylaxis

8
House dust mite
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Flow 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

11
Allergic 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)

12
Prevalence 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)

13
Genetics 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

14
Diagnostic procedure
Patients history
in vivo, in vitro testing
Provocation testing
15
Anamnesis
  • Which symptoms
  • Since when
  • When
  • How long
  • How frequent
  • Where
  • Which medication so far (improvement?)

16
Which 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

17
Diagnostics in allergy
  • In vivo (Skin-Prick testing,intradermal testing)
  • In vitro (spezific IgE, total IgE, tryptase )

18
Skin Prick Testing (SPT)
19
SKIN PRICK TESTING

20

21
8 a old child rhinoconjunctivitis since 2 years
, end of May to middle of June
22
When are skin prick test false positive/negative?
  • Medication antihistamines, steroids,
    immunosuppression
  • diseases mastocytosis, atopic eczem, chronic
    urticaria, sunburn

23
Positive SPT result
  • negative no wheal reaction, similar to the
    negative control
  • positive wheal reaction of at least 3mm and
    equivalent to the histamine reaction.

24
Intradermal testing
  • Suspicion of hymenoptera allergy (drug allergy)
  • More sensitive than SPT but also more painful

25
In-vitro- testing
  • total IgE ?
  • specific IgE ?
  • ECP (eosinophil cationic protein)
  • tryptase

26
Total 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)

27
Primary indications for IgE measurement
  • Contraindications for skin prick testing
  • Diagnostics in infants and toddlers

28
Indication 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)

29
In-Vitro-diagnostics- advantages -
  • Accurate and reproducable results
  • WHO controlled standards
  • Simple quantification (classes, Kilounits/l)

30
In-Vitro-diagnostics- disadvantages -
  • Measurement of circulating IgE-Ab, only
  • The level of antibodies does not correlate with
    clinical severity.

31
Provocation testing
  • Nasal
  • Conjunktivale
  • Bronchial
  • Oral
  • S.c.
  • i.v.

32
Nasal provocation testing
  • Especially with perennial allergens (mould, house
    dust mite)
  • Information about clinical relevance
  • Discrepancy between symptoms and SPT/IgE

33
conjunctival 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

34
Bronchial provocation testing
  • Can a suspected allergen induce an asthma attack
    and in which dosage?

35
Why early diagnosis?
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Conclusion!
  • 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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TREATMENT
48
Austrian Allergy Report 2006, T Dorner, A Rieder,
K Lawrence,M Kunze,
49
Treatment 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

50
Allergic rhinitis and its impact on asthma ARIA
Bousquet J et al. J Allergy Clin Immunol 2001

108 (5 Suppl) S 147-334
51
A.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
52
Stufenplan 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
53
Causal treatment
  • Specific immunotherapy
  • Allergen avoidance

54
Specific immunotherapy (SIT)
Vaczinationsimmunotherapy(VIT) Hyposensitization
55
Indications
  • 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

56
Contraindications
  • Immunodeficieny
  • Severe, uncontrolled bronchial asthma
  • severe cardiovascular diseases

57
Applications
  • Subcutaneous
  • Sublingual (drops)
  • Soluble tablets

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SCIT
  • Clinical efficacy

60
Grass 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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Conclusion
  • 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.

63
SCIT
  • Prevention of new sensitizations

64
Development of new sensitizations after SCIT with
house dust mites
Des Roches A. et al. JACI 199799450-53
65
SCIT
  • Prevention of bronchial asthma

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PAT-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.
69
Immunological mechanisms of SCIT
APC

70
Sublingual Immunotherapy (SLIT)
  • Drops for sublingual application
  • Allergen dosage much higher than used in SCIT
  • Mechanism not totally solved

71
SLIT 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
72
Demands 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
74
Rhinitis score
Rescue medication score
75
Different IgG- antibody response after SCIT and
SLIT
76
Until 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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