ALLERGY ON ADULT AND

CHILDREN

YANTI NURROKHMAWATI

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 Allergy
• Allergy is generally caused by a sustained over
production of IgE in response to common
environmental antigens such as pollen, foods,
house dust mite, animal danders, fungal spores
and insect venom.

• Elevated levels of serum IgE are thus a hall

mark of atopic diseases like allergic rhinitis
Allergic rhinitis (AR): a symptomatic disorder of
the nose, induced after allergen exposure, by
an IgE-mediated inflammation of the nasal
membranes

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 Allergy in Children

•Affected more than one

site Classification allergic in
Children :
•Atopic dermatitis
•The Condition Can •Atopic gastrointestinal
Progress disease
•Atopic respiratory disease
•ISAAC Study : 32% •Anaphylaxis
asthma, 9% eczema, 40 % •Urticaria
•Drug Allergy
allergic Rhinitis

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Relevant Anatomy and Physiology:
•The Short relatively horizontal eustachian tube nasal disease
frequently impinges on middle ear in children

•Most children under 2-3 years ( due to the time of maturation of the
IgG2 response and delayed maturation of IgA) allergic respiratory
disease is often accompanied by infection

•Children relatively tolerant of severe allergic reactions (anaphylaxis) and

of epinephrine treatment atheroma free cardiovascular system
•Drug metabolism can differ  paradoxical excitement with
antihistamines
•Many drug  have not adequately tested in childhood

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Pathophysiology of Allergic Inflammation

Three phases :
Sensitization phase
Early Phase Allergic Reaction
Late Phase Allergic Reaction

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Allergy
Allergen
Mastosit
A
C
U IgE
IgE
T
Rhinorea E
Histamine
S Tryptase
Sneezing Y IgE
M PGD2 LTs Antibody
P Cytokines
Congestion T
O

IgE
M
S
CD4+

Allergen
CD25+
Th2 EOS C
Class II MHC H
T cell r R
O I
Basic proteins N
N
LTs
Cytokines
I F Rhinorea
IF C L
Fragment A
S M Sneezing
Y A
Histamine M T
IL-1 CD4+ LTs P I Congestion
ANTIGEN Th1 Cytokines T O
O N
M

PRESENTING Baso
S

CELLS

(APC) Early- and late-phase allergic reactions

Adapted from: Sumarman. The rational manag of AR & its impact on asthma
 Mast cell-T cell interaction
Mekori & Metclaf. JACI 1999;104: 517-23
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 Equilibrum mechanism hypothesis between
Th1 (IFNγ) Response with Th2 (IL-4) Response

Durham SR. Till SJ. Immunologic changes associated with allergen immunotherapy.
J Allergy Clin Immunol 1998;102:157-64
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 TregCell Role in Control
Specific Immune response to Alergen
Akdis M, Blasser K, and Akdis CA. T regulatory cells in allergy:
Novel concept in the pathogenesis, prevention and treatment of allergic diseases.
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J Allergy Clin Immunol. 2005;116:961-8
 Immunity In Children
• Intra Uterine Period
– Deviated immune system
to Th2 to prevent fetal DC (-)
rejection. Baby born with IL-12
(-)
Th2 biased immune
system
T
– During pregnancy
H (+)
cortisol↑ N
IL-4
K
– Ig M production 10-12 Th Th
2
weeks intrauterine 1

– IgA  30 weeks

Cortisol (+) : Increase (-) : Inhibit

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 Immunity In Children

Post Natal Period

Cell Function
T cell function in neonatus <
Th2 more dominant in Antibody Production
children Ig M, at birth 10%
Equilibrum Th1-Th2 at 5 1-2 years old 75%
years old IgG  at first 6 months of life
Level IgA and IgG=adult 10
Cytokines Production years old
IL-12 production 
IFNγ
IL 4 at age 3,6,9,18 months

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 Allergen
Allergens Pollutants
Aeroallergens Indoor air pollution
mites, pollens, animal domestic allergens,
danders, insects, plant origin, indoor gas pollutants
moulds (tobacco smoke)
Food allergens Outdoors air pollution
Occupational rhinitis Automobile pollution
Latex allergy

•Children rarely exhibit allergy to occupational allergen

•Many children being initially food allergic ( milk, egg,
wheat, soya)
develop inhalant allergies around age 4-6 years
 Diagnostic Of Allergy
Typical History
General examination
Diagnostic Test
• In Vivo Test : Skin tests
Patch test
• In Vitro Test : Allergen-specific IgE,
PRIST,RAST, ELISA, ImmunoCap
Endoscopy
Cytology
Nasal challenge test
Imaging
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CLASSIFICATION OF RHINITIS
ALLERGY

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Allergy Diagnostic in Children
History
•Complaint , duration,timing, provoking factors etc
•History of pregnancy, birth, postnatal issues, development,
presence/absence of colic, failure to thrive, decrease
concentration, poor sleep etc
•Family history, enviromental history

Physical Examination
•Spending More time
•Quiet Observation can be useful
•Weight and height recorded at each visit medications dosage
•Examine : Skin, Chest, abdomen

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Investigation
Skin Prick Test
•Can be undertaken in children from a few months of age
•Small Children : back, Older Children : Forearm
•Positive SPT : 2 mm larger than negative control
•With history of anaphylaxis : SPT undertaken with care and allergen may
need to be tested in dilutional titers

Nitrit Oxide
Laboratory Test
Useful pointer to underlying
• Antigen specific Ig E test
asthma
•Test for Immune deficiency
•CBC<WBC
Nasal Nitrit Oxide
•Total IgG,IgA, IgM, IgG
Suspicion primary dyskinesia
subclasses

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 Managements
1. Allergen avoidance
2. Medications ( Pharmacotherapy )
3. Specific Immunotherapy
4. Education
Improving The Physical Fitness

5. Optional therapy:
Other medications and/or surgery for complications

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 Therapeutic considerations
Allergen
avoidance
indicated when
possible

Immunotherapy
Pharmacotherapy effectiveness
safety specialist prescription
effectiveness may alter the natural
easy administration course of the disease

Patient
education
always indicated
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 Allergen avoidance
Avoidance of allergen and trigger factors:
Although there is no definite demonstration that
allergen avoidance measures are effective in the
treatment of AR, it is indicated when possible

Improving The Physical Fitness:

•Induce the Th1 on anti inflammatory cytokines
production
•Improve adrenaline production by cortex adrenal

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 Treatment of Allergic Rhinitis
Allergic Rhinitis and its Impact on Asthma

moderate
moderate mild severe
severe persistent persistent
intermittent
mild
intermittent intra-nasal steroid
local cromone

oral or local non-sedative H1-blocker

intra-nasal decongestant (<10 days) or oral decongestant
allergen and irritant avoidance

immunotherapy
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 Stepwise treatment proposed

moderate moderate
mild mild
severe severe
intermittent persistent
intermittent persistent

Oral H1- AH Nasal Oral H1-AH Nasal

Beclomethasone Beclomethasone
high dose or high dose
(300-400 μg (300-400 μg /daily)
/daily)after Nasal
If needed Beclomethasone
Severe
1 week treat low dose symptoms
add (100-200 μg add
/daily)
Oral H1-AH Oral H1-AH
and / or and / or
Oral CS Oral CS
Ideal Antihistamine: Anti-inflammatory Profile

Should inhibits:
 Histamine release from basophils
 TNF release from mast cells
 PGD2, LTC4 release from FcERI positive cells
 IL-6/IL-8 release from endothelial cells
 Histamine-induced P-selectin expression
 TNF-induced RANTES release
 IL-4/IL-13 release from human basophils
 Superoxide-synthesis from eosinophils
 PAF-induced chemotaxis of eosinophils
 Adhesion to endothelial cells
 ICAM-1 expression
(ARIA WHO Consensus 2001)

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Antihistamines in Children
•First Generation :diphenhydramine and chlorpheniramine, 
sedating for routine use decreased school performance and
learning in children.

•Second generation antihistamines  first-line therapy for

children with allergic rhinitis
• cetirizine ,fexofenadine and desloratadine are indicated
down to six months of age in children
• Loratadine is indicated for use in children as young as
two

•Topical intranasal antihistamines effective for rhinitis in

children

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 Name Mechanism of Side Effects Adult Dose Child Dose
Action
Antihistamin
Diphenhydrami - Blockage H1 Sedation, arritmia, 25 to 50 mg 2 to 6:
ne receptor antikcholinergic every 4 to 6 6.25 mg 3-
effect, BW↑, retensi hours 4x/day
- Blockage histamin
urine 6 to 12:
release 12.5 to 25 mg
- Direct action to 6 to 12 yo:
Chlorpeniramine
cytokines and 4 mg every 4 to 2 mg every 4 to
inflammation 6 hours; up to
6 hours; up to
12 mg/day
process
2 to 6:
24mg/day 1 mg every 4 to
6 hours

Cyproheptadine 4 mg up to 3 2 to 6 years old:

times / day 0.25 mg/kg/day
Age 7 to 14:
increase to 4
mg every 8 to

12 hours

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 Name Mechanism of Side Effects Adult Dose Child Dose
Action
Antihistamin
Loratadine - Blockage H1 Non Sedating, 1 x 10 mg Age 2 to
receptor arritmia, 6: 5mg daily
antikcholinergic Age> 7 :10mg
- Blockage histamin daily
release effect, BW↑, retensi
Cetirizine urine 10 mg/day 6 to 23 months:
- Direct action to 1/2 tsp. (2.5mg) 1-
cytokines and 2x/day
inflammation 2-5 yo: 1/2 tsp.
process [2.5 mg] 1-2x/day
>6 yo 5 or 10 mg
1x1
Desloratadine One 5 mg 6-11 yo : 2.5mg
tablet daily daily
6months and
older:
½ tsp(1.25mg)
Fexofenadine 60 mg twice 6 to 11 yo:
daily; 30 mg twice
180 mg once a daily
day for allergic
rhinitis 31
 Name Mechanism of Side Effects Adult Dose Child Dose
Action
Antihistamin
Topical - Blockage H1 Sedation, arritmia,
receptor antikcholinergic
- Blockage histamin effect, BW↑, retensi
Azelastine 2 x 2 spray
release urine
- Direct action to
Levocabastine cytokines and 2 x 2 spray
inflammation
process

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 Decongestan

Oral decongestant :
•Alpha Adrenergic agonist : decrease vascular congestion
in nose an d less respiratory tract obstruction
•Very effective (especially for nasal congestion)
•Combined with antihistamine  more effective
• than alone

Topical decongestant :
Rebound effect (Rhinitis medicamentosa)
if used >7-10 days;  Need a steroid therapy
 use it < twice/month

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 Name Mechanism of Action Side Effects Adult Dose Child
dose

Decongestan
Pseudoefedrine - Stimulation α adrenergik Top: rebound rhinitis, 180-240 >12 yo
 vasokonstriction of efek sistemik mg/day =adult

Phenylpropanola inferior turbinate Sist.: stimulasi CV, Maks. 150

mine - Sympatomimetic CNS, anoreksia mg/day
Phenylephrine 40 mg/day
Oxymetazoline 2 x 2-3 spray
Phenylephedrine
Ephedrine

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 Topical Steroid
AR clinical symptoms
Eosinophilia (EG2+) (nasal epithelium and submucous)
through product inhibition of IL-5 by T cells CD3+
T CD3+ submucous number or not increasing

IL-5 dan GM-CSF mRNA expression T cells

Inhibition of IL-5 secretion from blood peripher T cells

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 Corticosteroid Use in Children

•Topical use  inhaled nasal and dermal routes

•Microgram amounts can become sufficient to cause

adrenal suppresion and other CS effects  monitoring

•First generation CS (bethamethason, dexamethason)

should be avoided. Highly systemical available

•Recent CS (Fluticasone/mometasone) the least absorbed

from the nose

•Barlan et al1997budesonide use in children w/ ARS 

improvement in cough and nasal secretion
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 Corticosteroid Use in Children

•One disease control establishdose of CS should be

reduced

•For rhinitis nasal steroid w/ low systemic bioavailability

at lowest possible dose

•Oral CS highly effective, use w/ extreme

cautionsystemic side effect used at the start of
treatment when airway obstruction very severe (0,5-1
mg/kgbw)

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 Name Mechanism of Action Side Effects Adult Dose Child
Dose

Corticosteroid Prophylactic

Beclomethasone - early & late phase dryness, epistaksis, 2x200-400 -

- Permeability endotel & sneezing mcg/day
epitel ↓ Mental retarded, 1-2x200mcg
- Tonus simpatis ↑ delay development.
Budesonide - Hiperreactivity ↓ 2x200mcg 1x1-2
spray/day
Fluticasone 2x2 spray 1x1-2
propionate spray

Mometasone 2x2 spray 1x1-2

spray
Triamcinolone 2x2 spray

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 Name Mechanism of Side Effects Adult Dose Child
Action Dose

Intranasal
Anticholinergik
Ipratropium Blockage acetylcholin dryness,, sneezing 3-4 x 0,4-2 ml 3-4 x 0,4-1
bromide effect ml

Name Mechanism of Action Side Effects Adult Dose Child

Dose
Leukotrienes
modifiers
Pranlukast, Inhibitor enzim 5- Age 2 to 5: one oral
granule packet or 4
Zafirlukast lipoxygenase at early mg chewable tablet
Montelukast phase once a day
Age 6 to 14: one 5 mg
tablet once daily
Age 15 and above:
one 10 mg tablet once
daily

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 Mast Cell Stabilizer
• Recombinant humanized IgG1 monoclonal anti IgE antibody
•Early/Late phase response
•Omalizumab (Genentech,Xolair)
•Dose subcutaneously monthly/twice a month

Name Mechanism of Side Effects Adult Dose Child

Action Dose
Mast Cell Prophylactic
Stabilizers
Cromolyn sodium - Prevent release of dryness, sneezing 4-6 x/day 4 x/day
mast cell mediators
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MANAGEMENT

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 Side effects of medications in Allergy

Borish LC, Steinke JW. Cytokines and chemokines. 42

J Allergy Clin Immunol. 2003;111:S460-75
 Allergen specific immunotherapy

Allergen specific immunotherapy:

Has a place in selected patient with demonstrable
IgE-mediated diseases:
• who either have a long duration of symptoms, or
• in whom insufficiently controlled by conventional
pharmacotherapy, or
• in whom pharmacotherapy produce undisirable
side effect, or
• in patients who do not wish to be on
pharmacotherapy, or
• in patients who do not want to receive long-term
pharmacological treatment
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IL-4 / IFN-γ Ratio

The hypothesis of immunotherapy mechanism

TH1 response changes which occurred either as a consequently of decreasing of
regulation TH2 response (anergy), or immune deviation be influenced by IL-12.
(Adapted from Durham and Till, 1998)

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Patient Selection For Immunotherapy

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 Immunotherapy in Children :

Classical Immunotherapy :
•Immunotherapy in nonasthmatic children relatively safe
•Has been reported reducing progression from allergic
rhinitis to asthma and reducing new allergic sensitization

Other Form of Immunotherapy

•Oral, Nasal, Sublingual, Swallow Immunotherapy
•Sublingual immunotherapy proved positive in several
trial
Far Safer, can be given at home
SE : sore throat
expensive
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THANK
YOU

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