ALLERGY & IMMUNOLOGY

IN CHILDREN
ATOPIC DERMATITIS
Definition:
Atopic dermatitis is a genetically transmitted, chronic inflammatory
skin disease that is often associated with other atopic disorders, such
as allergic rhinitis and asthma.
Akdis CA et al, EAACI/AAAAI/PRACTALL Consensus Report. JACI
2006;118:152-69

Chronic, relapsing form of skin inflammation

Disturbance of epidermal-barrier function leading to dry skin (xerosis)
IgE-mediated sensitization to food and environmental allergens

Epidemiology of Atopic Dermatitis

Often the prelude to an atopic diathesis that includes asthma and
other allergic diseases

50-70% of children with AD go on to have asthma and allergic rhinitis

Pathophysiology of AD
EPITHELIAL-BARRIER DYSFUNCTION
AD is characterized by:
Dry skin, even involving nonlesional skin
Increased transepidermal water loss

The “Outside-Inside” Paradigm: AD is primarily a skin disease driven by an

intrinsic epidermal defect

The brick wall analogy of the stratum corneum of the epidermal barrier. In
healthy skin the
corneodesmosomes (iron rods) are intact throughout the stratum corneum.
At the surface, the corneodesmosomes start to break down as part of the
normal desquamation process, analogous to iron rods rusting (A).
In an individual genetically predisposed to AD, premature breakdown of the
corneodesmosomes leads to enhanced desquamation, analogous to having
rusty iron rods all the way down through the brick wall (B). If the
iron rods are already weakened, an environmental agent, such as soap, can
corrode them much more easily.
The brick wall starts falling apart (C) and allows the penetration of allergens
(D).
Triggers of AD

AD patients have “twitchy skin”

Xerosis
Stress
Contact and aeroallergens: dust mites, contact > aeroallergens; furry
animals (cat>dog); pollens (seasonal); molds; human dander (dandruff)
Microorganisms: viral infections, S. aureus, Malassezia furfur
Irritant factors: rough clothing, lipid solvents (ie, soaps, detergents);
disinfectants (ie, chlorine), occupational irritants; household fluids (eg,
juices from fresh fruits, meats), chemical agents
Others:
Foods (as contact irritants > vasodilators > allergens)
33% of children with moderate to severe AD have food
allergies
Climate
Hormones (eg, menstrual cycle)
Adapted from Beltrani VS. JACI 1999;104:S87-S98
Diagnosis of Atopic Dermatitis
Hanifin & Rajka Criteria for Atopic Dermatitis (1991)
Major Features (must have 3)
Pruritus – “an itch, that, when scratched, erupts!”, worse in the early evening and night
Typical morphology and distribution:
Facial and extensor involvement during infancy and childhood
Flexural lichenification and linearity in adults
Chronic or chronically relapsing dermatitis
Personal or family history of atopy (asthma, allergic rhinoconjunctivitis, atopic dermatitis)

Minor Features (3 or more)

• Cheilitis • Xerosis
• Hand or foot dermatitis • Nipple eczema
• Ichthyosis • Ptyriasis alba
• Palmar hyperlinearity
• Keratosis pilaris
• IgE reactivity
• Periauricular fissures
• Perifollicular accentuation
• Scalp dermatitis
• Susceptibility to cutaneous infection
Keratoconus – association with atopy and vernal
catarrh has led to the speculation that vigorous and
frequent eye rubbing may aggravate and even
cause kc; often manifests in late teens or early 20s
and progresses slowly for the next decade or two as
the cornea scars and becomes more elongated;
non-inflamed condition characterized by the change
in eye from normal round shape to cone shape;
cone shape results from the bilateral central or axial
ectasia of the corneal anterior protrusion of the
cornea; kc presents when the cornea thins and
protrudes; abnormal eye shape distorts visual
images.
Management of Atopic dermatitis
Successful management requires a systematic, multipronged
approach that includes:
• anti-pruritic therapy
• skin hydration
• topical anti-inflammatory medications
• identification and possible elimination of exacerbating
factors

BASIC TREATMENT
• Skin hydration – lukewarm soaking baths for 20 minutes
• Emollients - mainstay of general management of AD;
applied continuously even if no actual inflamed skin lesions
are obvious; in lotion, cream or ointment preparations
Identification and elimination of triggering factors
• Avoidance of common irritants (eg, soaps, toiletries, wool, chemicals)
• Control of temperature and humidity
• Aeroallergens may cause flares and exposure to them must be minimized
• Food allergens trigger AD more commonly on young infants and children
than in adults

Leung DYM et al. Disease management of atopic dermatitis: an updated

practice parameter. Ann Allerg, Asth Immunol . 2004;93:S1-S21

Topical corticosteroids
• First line treatment of acute flare-ups of AD
• Reduce inflammation and pruritus in both acute and chronic components
of AD by suppressing pro-inflammatory genes
• Reduce also skin colonization of S. aureus
• Available in low-potency to high-potency preparations; vehicles vary
TOPICAL CALCINEURIN INHIBITORS
• Inhibits calcineurin à inhibits activaiton of key cells – T
cells, DC, MC, keratinocytes
• Tacrolimus and pimecrolimus
• Steroid-free, anti-inflammatory
• Tacrolimus effective and safe in both adults and
children for the treatment of mild-moderately severe
AD, decreased pruritus within 3 days of initiating
therapy
Kang S et al. J Am Acad Derrmatol.2001;44(Suppl):S58-
S64; Reitamo S et al. Arch Dermatol;136:999-1006
Good safety profile; side effect: transient burning
sensation of skin; no skin atrophy; currently not
recommended for children 2 years and below.
ANTIHISTAMINES
Some patients may benefit from the use of
antihistamines for the relief of pruritus associated
with AD
MICROBE CONTROL
Appropriate systemic or topical antibiotic for
patients heavily colonized or infected with S. aureus
PSYCHOLOGICAL COUNSELLING
PATIENT EDUCATIONTAR PREPARATIONS
No randomized controlled studies that have
demonstrated their efficacy
Class 1: food allergens penetrating the GI barrier;
above allergens 90% of FA during childhood

Class 2: fruit or plant proteins similar to pollen

proteins; penetrate the respiratory tract; also
referred to as pollen-associated FA syndrome, is a
form of localized IgE-mediated food allergy, usually
to raw fruits or vegetables, with symptoms confined
to the lips, mouth and throat. OAS most commonly
affects patients who are allergic to pollens.
Symptoms include itching of the tongue, lips, roof
of the mouth and throat, with or without swelling,
and/or tingling of the lips, mouth, roof of the
tongue and throat.
IgE-mediated Reactions
Anaphylaxis
• A severe systemic or generalized allergic reaction that
is potentially life-threatening
• Symptoms involve the skin and one or more target
organs: gastrointestinal tract, respiratory tract and/or
the cardiovascular system

Gastrointestinal symptoms:
• Lip swelling, oral pruritus, tongue swelling and
sensation of tightness in the throat (OAS)
• Stomach and upper intestine: nausea, vomiting, and
colicky abdominal pain
• Lower intestinal tract: abdominal pain, diarrhea, and
occasional bloody stools
Mixed mechanism: IgE- and cell-mediated
Atopic Dermatitis
• 90% start age <5 years
• Relapsing, pruritic, vesiculopapular rash in a typical distribution
• Food allergy in around 35% of children with moderate-severe AD

Allergic Eosinophilic Esophagitis

• Allergic inflammatory disease with elevated eosinophils in the
esophagus
• Newly recognized disease; increasingly diagnosed in children and
adults; usually persists
• Commonly occurs with other allergic disease: rhinitis, asthma,
and/or eczema
• Symptoms of chronic GERD and failure to respond to conventional
reflux medications
• Diagnosis: GI biopsy demonstrating eosinophilic infiltration (>15
eos/40x hpf); (+) Prick Skin Test/Specific IgE in 50%; patch testing
may help; eosinophilia
Non-IgE-Mediated (Late Onset) Reactions
Food protein-induced enterocolitis syndrome
(FPIES)
Usually begin in early infancy, 1-4 weeks following
introduction of CM/soy
2 phases:
• chronic-while food is ingested regularly (emesis,
diarrhea, weight loss and FTT);
• acute -if ag is removed and re-ingested —>
profuse repetitive vomiting, diarrhoea,
dehydration, lethargy, hypotension within 1-4 hrs
• around 30% develop atopic disease; family
history of atopic disease in 40-80%
Food Protein-Induced Proctocolitis
• Presents in the first few months of life (<6 months)
• Frequently in breast-fed infants; do not appear ill
• Presence of blood in normally formed stools

Respiratory
• Milk-Induced Chronic Pulmonary Disease (Heiner’s
Syndrome)
• Rare syndrome
• Recurrent episodes of pneumonia with pulmonary
infiltrates, hemosiderosis, GI blood loss Fe-deficiency
anemia and FTT
• Precipitating antibodies to cow’s milk
Diagnosis of FA
History and Physical Examination
Signs and symptoms, amount of food ingested,
timing of reaction to ingestion, most recent
reaction, most severe reaction, treatment,
personal history of atopy: asthma, AD, AR;
family history of food allergy and atopy
Middleton 7th Edition
Nutritional status, vital signs, examination of
skin and respiratory system
Elimination Diet  Challenge

Diagnosis of Non-IgE-Mediated FA
• Atopy Patch test
Subject of on-going research; needs to be
standardized

Additional Procedures
Endoscopy and Biopsy for gastrointestinal
syndromes:
• Allergic eosinophilic esophagitis
• Dietary protein-induced enteropathy
Oral food Challenge (OFC)
• In vivo diagnostic tests performed to confirm a
suspicion of FA
• OFCs can be performed in 3 ways
– Open : simplest, decreased costs; CM administered
openly in increasing doses; clinical observation for 2
hours (immediate reactions) and at home (delayed); a
(+) result is considered sufficient evidence of FA in
younger children; 50% of (+) open FC are not
reproduced in DBPCFC (Fiocchi A, 2002)
– Single-blinded: pediatrician aware of which food is
being given; possible bias or subjective interpretation
by observer
– DBPCFC: “Gold Standard”; test of choice; third party
prepares test; randomizes offering of food or placebo
Treatment of Food Allergy
• Identification and elimination of food responsible
for reactions
• Epinephrine
• Anti-IgE immunoglobulin therapy

Other Modes of Treatment

• Oral immunotherapy – administration of
increasing doses of food to induce tolerance;
under study
• Not established whether this is true tolerance
(long lasting decrease in IgE production) or
temporary reduction of food-specific IgE levels
Reasons for increased prevalence and persistence
of food allergies Hygiene hypothesis
• Changes in components of the diet (antioxidants,
fats, and nutrients – vitamin D)
• Use of antacids – exposure to more intact protein
• Food processing
• Extensive delay of oral exposure, increasing
topical (possibly sensitizing) rather than oral
(possibly tolerizing)
Sicherer SH, et al. J Allergy Clin Immunol
2007;120:491-503
Lack G. J Allergy Clin Immunol 2008;121:1331-6
 Definition"of"asthma

Asthma"is"a"heterogeneous"disease,"usually"characterized"
by"chronic"airway"inflammation."

It"is"defined"by"the"history"of"respiratory"symptoms"such"as"
wheeze,"shortness"of"breath,"chest"tightness"and"cough"
that"vary"over"time"and"in"intensity,"together"with"variable"
expiratory"airflow"limitation.

GINA%
2017 ©"Global"Initiative"for"Asthma
 Patient'with'
respiratory'symptoms
Are$the$symptoms$typical$of$asthma?

NO
YES

Detailed'history/examination'
for'asthma
History/examination supports$
asthma$diagnosis?
Further"history"and"tests"for"
NO alternative"diagnoses
Clinical"urgency,"and"
YES Alternative*diagnosis*confirmed?
other"diagnoses"unlikely

Perform'spirometry/PEF'
with'reversibility'test
Results$support$asthma$diagnosis?

Repeat"on"another"
NO
occasion"or"arrange"
NO
YES other"tests
Confirms"asthma"diagnosis?

Empiric"treatment"with" YES NO YES

ICS"and"prn"SABA
Review"response
Consider"trial"of"treatment"for"
Diagnostic"testing" most"likely"diagnosis,"or"refer"
within"1@
3"months for"further"investigations

Treat'for'ASTHMA Treat'for'alternative'diagnosis

GINA*2017,*Box*1=1*(4/4) ©"Global"Initiative"for"Asthma
 ! Increased
"

"
"
"

! Decreased
"
"
"

"
"

GINA-2017
 Diagnosis"of"asthma"– physical"examination

! Physical"examination"in"people"with"asthma
"Often"normal
"The"most"frequent"finding"is"wheezing"on"auscultation,"especially"
on"forced"expiration
! Wheezing"is"also"found"in"other"conditions,"for"example:
"Respiratory"infections
"COPD
"Upper"airway"dysfunction
"Endobronchial obstruction"
"Inhaled"foreign"body
! Wheezing"may"be"absent"during"severe"asthma"exacerbations"
(‘silent"chest’)

GINA%
2017 ©"Global"Initiative"for"Asthma
 !
"
"

!
"

"

"

"

"

GINA%
2017,%
Box%
1.2
 A.#Symptom control Level#of#asthma#symptom#control
Well; Partly# Uncontrolled
In#the#past#4#weeks,#has#the#patient#had:
controlled controlled

! !
! !

! !
! !

B.#Risk#factors#for#poor#asthma#outcomes

ASSESS#PATIENT’S#RISKS#FOR:

GINA%
2017%
Box%
2-2B%
(1/4)
 Assessing"asthma"severity

! How?
"Asthma"severity"is"assessed"retrospectively"from"the"level"of"
treatment"required"to"control"symptoms"and"exacerbations
! When?
"Assess"asthma"severity"after"patient"has"been"on"controller"
treatment"for"several"months
"Severity"is"not"static"– it"may"change"over"months"or"years,"or"as"
different"treatments"become"available
! Categories"of"asthma"severity
"Mild%asthma:%wellDcontrolled"with"Steps"1"or"2"(asDneeded"SABA"or"
low"dose"ICS)
"Moderate% asthma:% wellDcontrolled"with"Step"3"(lowDdose"ICS/LABA)
"Severe% asthma:%
requires"Step"4/5"(moderate"or"high"dose"
ICS/LABA"± addDon),"or"remains"uncontrolled"despite"this"treatment

GINA%
2017 ©"Global"Initiative"for"Asthma
Initial"controller"treatment"for"adults,"adolescents"
and"children"6–11"years
! Start"controller"treatment"early
"For"best"outcomes,"initiate"controller"treatment"as"early"as"possible"
after"making"the"diagnosis"of"asthma
! Indications"for"regular"low?dose"ICS"?any"of:
"Asthma"symptoms"more"than"twice"a"month
"Waking"due"to"asthma"more"than"once"a"month
"Any"asthma"symptoms"plus"any"risk"factors"for"exacerbations
! Consider"starting"at"a"higher"step"if:
"Troublesome"asthma"symptoms"on"most"days
"Waking"from"asthma"once"or"more"a"week,"especially"if"any"risk"
factors"for"exacerbations
! If"initial"asthma"presentation"is"with"an"exacerbation:
"Give"a"short"course"of"oral"steroids"and"start"regular"controller"
treatment"(e.g."high"dose"ICS"or"medium"dose"ICS/LABA,"then"step"
down)

©"Global"Initiative"for"Asthma
Stepwise"management"8pharmacotherapy
UPDATED)
2017

Diagnosis
Symptom"control"&"risk"factors
(including"lung"function)
Inhaler"technique"&"adherence
Patient"preference

Symptoms
Exacerbations
Side8effects Asthma"medications
Patient"satisfaction Non8pharmacological"strategies
Lung"function Treat"modifiable"risk"factors

STEP)5

STEP)4

STEP)3 Refer"for" *Not"for"children"<12"years

PREFERRED) STEP)1 STEP)2 add8on" **For"children"6811"years,"the"
CONTROLLER) treatment" preferred"Step"3"treatment"is"
CHOICE Med/high"
e.g."
tiotropium,*! medium"dose"ICS
ICS/LABA anti8IgE,"
#For"patients"prescribed"
Low"dose" anti8IL5*
Low"dose"ICS BDP/formoterol or"BUD/"
ICS/LABA**
formoterol maintenance"and"
reliever"therapy
*!
!Tiotropium by"mist"inhaler"is"
an"add8on"treatment"for"
patients"≥12"years"with"a"
As8needed"short8acting"beta28agonist"(SABA) As8needed"SABA"or" history"of"exacerbations
RELIEVER
low"dose"ICS/formoterol#

©"Global"Initiative"for"Asthma
 UPDATED%
2017

•
REMEMBER%
•
TO...
•
•

•
Managing"exacerbations"in"primary"care
PRIMARY'CARE'' Patient'presents'with'acute'or'sub8acute'asthma'exacerbation

Is"it"asthma?
ASSESS'the'PATIENT Risk"factors"for"asthma=related"death?
Severity"of"exacerbation?

MILD'or'MODERATE SEVERE
Talks'in'phrases,'prefers'
LIFE8THREATENING
Talks'in'words,'sits'hunched'
sitting'to'lying,'not'agitated forwards,'agitated Drowsy,"confused"
Respiratory'rate'increased Respiratory'rate'>30/min or"silent"chest
Accessory'muscles'not'used Accessory'muscles'in'use
Pulse'rate'100–120'bpm Pulse'rate'>120'bpm
O2'saturation'(on'air)'90–95% O2'saturation'(on'air)'<90%
PEF'>50%'predicted'or'best PEF'≤50%'predicted'or'best URGENT

START'TREATMENT
SABA 4–10"puffs"by"pMDI"+"spacer," TRANSFER'TO'ACUTE'
repeat"every"20"minutes"for"1"hour CARE'FACILITY
WORSENING
Prednisolone: adults"1"mg/kg,"max."
50"mg,"children"1–2"mg/kg,"max."40"mg While'waiting: give"inhaled"
SABA"and"ipratropium"bromide,"
Controlled'oxygen (if"available):"target" O2,"systemic"corticosteroid
saturation"93–95%"(children:"94=98%)

CONTINUE'TREATMENT'with"SABA"as"needed
WORSENING
ASSESS'RESPONSE'AT'1'HOUR'(or"earlier)

IMPROVING

ASSESS'FOR'DISCHARGE ARRANGE'at'DISCHARGE
Symptoms improved,"not"needing"SABA Reliever: continue"as"needed
PEF improving,"and">60=80%"of"personal" Controller: start,"or"step"up."Check"inhaler"
best"or"predicted technique,"adherence
Oxygen saturation">94%"room"air Prednisolone: continue,"usually"for"5–7"days"
(3=5"days"for"children)"
Resources'at'home adequate
Follow'up:'within"2–7"days

FOLLOW'UP'
Reliever:'reduce"to"as=needed
Controller: continue"higher"dose"for"short"term"(1–2"weeks)"or"long"term"(3"months),"depending"
on"background"to"exacerbation
Risk'factors:'check"and"correct"modifiable"risk"factors"that"may"have"contributed"to"exacerbation,"
including"inhaler"technique"and"adherence"
Action'plan: Is"it"understood?"Was"it"used"appropriately?"Does"it"need"modification?

©"Global"Initiative"for"Asthma
 Diagnosis%
and%management%
of%
asthma%in%
children%
5%years%
and%younger

GINA%Global%
Strategy%
for%
Asthma%
Management%and%Prevention%
2017
This%slide%
set%is%
restricted%for%
academic% and% educational%
purposes%
only.%
%Use%of%the%slide%set,%or%
of%
individual%slides,%
for%
commercial%or%
promotional%purposes% requires%approval%from% GINA.%

GINA%
2017 ©"Global"Initiative"for"Asthma
Probability"of"asthma"diagnosis"or"response"to"
asthma"treatment"in"children"≤5"years

©"Global"Initiative"for"Asthma
Symptom"patterns"in"children"≤5"years"

©"Global"Initiative"for"Asthma
 Features"suggesting"asthma"in"children"≤5"years

Feature Characteristics,suggesting,asthma
Cough Recurrent"or"persistent"non?productive"cough"that"may"be"worse"at"
night""or"accompanied"by"some"wheezing"and"breathing"difficulties.
Cough"occurring"with"exercise,"laughing,"crying"or"exposure"to"
UPDATED, tobacco"smoke"in"the"absence"of"an"apparent"respiratory"infection
2017 Prolonged"cough"in"infancy,"and"cough"without"cold"symptoms,"are"
associated"with"later"parent?reported"physician?diagnosed"asthma,"
independent"of"infant"wheeze
Wheezing Recurrent"wheezing,"including"during"sleep"or"with"triggers"such"as"
activity,"laughing,"crying"or"exposure"to"tobacco"smoke"or"air"pollution
Difficult"or"heavy" Occurring"with"exercise,"laughing,"or"crying
breathing"or"
shortness"of"breath
Reduced"activity Not"running,"playing"or"laughing"at"the"same"intensity"as"other"
childrenK"tires"earlier"during"walks"(wants"to"be"carried)
Past"or"family"history Other"allergic"disease"(atopic"dermatitis"or"allergic"rhinitis)
Asthma"in"first?degree"relatives
Therapeutic"trial"with" Clinical"improvement"during"2–3"months"of"controller"treatment"and"
low"dose"ICS"and" worsening"when"treatment"is"stopped
as?needed"SABA
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Condition Typical-features
 Common"differential"diagnoses"of"asthma"in"
children"≤5"years"(continued)

Condition Typical-features
Cystic"fibrosis Cough"starting"shortly"after"birth>"recurrent"chest"infections>"
failure"to"thrive"(malabsorption)>"loose"greasy"bulky"stools
Primary"ciliary"dyskinesia Cough"and"recurrent"mild"chest"infections>"chronic"ear"infections"
and"purulent"nasal"discharge>"poor"response"to"asthma"
medications>"situs inversus (in"~50%"children"with"this"
condition)
Vascular"ring Respirations"often"persistently"noisy>"poor"response"to"asthma"
medications
Bronchopulmonary" Infant"born"prematurely>"very"low"birth"weight>"needed"prolonged"
dysplasia mechanical"ventilation"or"supplemental"oxygen>"difficulty"with"
breathing"present"from"birth
Immune"deficiency Recurrent"fever"and"infections"(including"nonJrespiratory)>"failure"
to"thrive

©"Global"Initiative"for"Asthma
 A.#Symptom control Level#of#asthma#symptom#control
Well; Partly# Uncontrolled
In#the#past#4#weeks,#has#the#child#had:
controlled controlled

! !

! !

! !

! !
B.#Risk#factors#for#poor#asthma#outcomes
ASSESS#CHILD’S#RISK#FOR:

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 STEP)4

PREFERRED) STEP)3
STEP)1 STEP)2
CONTROLLER)
CHOICE
Double)
low)dose
Daily)low)dose)ICS ICS

RELIEVER

CONSIDER)
THIS)STEP)FOR)
CHILDREN)WITH:
 ‘Low"dose’"inhaled"corticosteroids"(mcg/day)"
for"children"≤5"years

Beclometasone"dipropionate (HFA) 100

Budesonide"(pMDI +"spacer) 200
Budesonide"(nebulizer) 500
Fluticasone"propionate"(HFA) 100
Ciclesonide" 160
Mometasone"furoate" Not"studied"below"age"4"years
Triamcinolone"acetonide Not"studied"in"this age"group

!This"is"not"a"table"of"equivalence
!A"low"daily"dose"is"defined"as"the"dose"that"has"not"been"associated"
with"clinically"adverse"effects"in"trials"that"included"measures"of"safety

GINA%2017,%
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 Initial"assessment"of"acute"asthma"exacerbations"
in"children"≤5"years

Symptoms Mild Severe*

Altered"consciousness No Agitated,"confused"or"drowsy

Oximetry"on" >95% <92%

presentation"(SaO2)**
Speech† Sentences Words

Pulse"rate <100"beats/min >200 beats/min"(0–3"years)

>180"beats/min"(4–5"years)
Central"cyanosis Absent Likely"to"be"present

Wheeze"intensity Variable Chest"may"be"quiet

*Any"of"these"features"indicates"a"severe"exacerbation
**Oximetry"before"treatment"with"oxygen"or"bronchodilator
† Take"into"account"the"child’s"normal"developmental"capability"

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 PRIMARY'CARE''

ASSESS'the'CHILD

MILD'or'MODERATE SEVERE'OR'LIFE'THREATENING

START'TREATMENT
Salbutamol'

Controlled'oxygen
URGENT

MONITOR'CLOSELY'for'182'hours TRANSFER'TO'HIGH'LEVEL'CARE'
(e.g.'ICU)'
Worsening,'
or'lack'of' While&waiting&give:
improvement
While&waiting&give:
 Primary"prevention"of"asthma

! The"development"and"persistence"of"asthma"are"driven"by"
gene:environment"interactions
! For"children,"a"‘window"of"opportunity’"exists"in#utero#and"in"
early"life,"but"intervention"studies"are"limited
! For"intervention"strategies"including"allergen"avoidance
"Strategies"directed"at"a"single"allergen"have"not"been"effective
"Multifaceted"strategies"may"be"effective,"but"the"essential"
components"have"not"been"identified
! Current"recommendations"are
"Avoid"exposure"to"tobacco"smoke"in"pregnancy"and"early"life
"Encourage"vaginal"delivery
"Advise"breast:feeding"for"its"general"health"benefits
"Where"possible,"avoid"use"of"paracetamol"(acetaminophen)"and"
broad:spectrum"antibiotics"in"the"first"year"of"life

GINA#2017,#Box#741 ©"Global"Initiative"for"Asthma
Allergic Rhinitis
• AR is clinically defined as a symptomatic disorder of the nose after
allergen exposure of the membranes of the nose.
• Presence of nasal inflammation, nasal hyperreactivity

Typical Symptoms:
• sneezing
• clear rhinorrhea
• nasal itching
• nasal congestion
• which are reversible spontaneously or with treatment

Hidden symptoms:
• chronic unproductive cough / throat clearing
• sleep disturbance
• sinus headache
• eustachian tube dysfunction
Physical Examination:
• Facial grimace
• Allergic hand salute
• Nasa; crease
• Allergic shiners
• Dennie Morgan Line
• Dental malocculusion
• High-arched palate
• Pale, boggy turbinates
• Many associated with allergic conjunctivitis

Allergic Rhinitis and Asthma

• Approximately 80% of asthmatics have allergic rhinitis
• Approximately 40% of allergic rhinitis patients have asthma

Co-morbidities of Allergic Rhinitis

• When considering a diagnosis of rhinitis or asthma, an evaluation of both
the lower and upper airways should be made
 Mild
Normal sleep; no impairment of daily,
leisure, or sport activities; normal
work or school; no troublesome
symptoms

Symptoms
Rhinorrhea
Blocked nose
< 4 days per week Itchy nose > 4 days / week
Intermittent or <4 weeks Sneezing Persistent
and >4 weeks
Itchy eyes

Moderate-Severe
One or more of the following:
abnormal sleep; impairment of daily,
leisure, or sport activities; abnormal
work or school; troublesome
symptoms

Classification of Allergic Rhinitis (ARIA)

 Treatment of Allergic Rhinitis
(stepwise approach)

Moderate
Mild severe
Moderate persistent
severe persistent
Mild intermittent
intermittent
Intra-nasal steroid / chromone

Antileukotrienes
Oral or local non-sedative antihistamine
Intra-nasal decongestant (< 10 days) or oral decongestant
Allergen and irritant avoidance

Immunotherapy/ anti-IgE

Frequency and Severity of Symptoms

 Development of Atopic
Atopic March
Disease
Rhinitis Typical Evolution of Allergic Diseases

Adapted from Holgate S. Church MK. Eds. Allergy. London: Gower Medical Publishing. 1993
TYPE I HYPERSENSITIVITY (Immediate hypersensitivity, IgE-mediated
hypersensitivity)

Some people who are genetically predisposed develop allergic reaction

when they are exposed to an environmental antigen such as dust or
pollen. This is mediated by IgE antibodies.

The allergic reaction first requires sensitization to a specific allergen.

Let us say for example to a common respiratory allergen- the protein
Der p-1 found in the fecal pelllets of the house dust mite

The allergen is inhaled and then the dust mite allergen is taken up and
processed by the dendritic cell, the antigen presenting cell and
presented to a T helper cell. where they prime naive TH cells (TH0
cells) that bear receptors for the specific antigen
Tissues under the mucus membranes are rich in B cells
committed to IgE production and IgE producing cells are more
abundant in persons susceptible to allergens or what we
termed atopic.

The T helper cells produces cytokines like IL-4 to stimulate B

cells to proliferate and differentiate in producing class
switched plasma B cells producing Der P-1 specific IgE
IgE producing plasma cells.

The antigen-specific IgE antibodies can then bind to high-

affinity receptors located on the surfaces of mast cells and
basophils

Mast cell contains granules that are packed with chemicals

that induce a hypersensitivity response.
Once attached , The igE molecule once formed can survive for
many weeks.
The individual is now sensitized to that specific allergen (dust
mite)

When exposed to the dust mite allergen for a second time,

the allergen binds to the specfic IgE for dust mite on the mast
cell,

To trigger a response, two cell bound IgE molecule must react

with a specific allergen.

Within seconds of the reaction, the mast cell will release

preformed mediators like Histamine, proteases such as
chymase and tryptase, acid hydrolases, and proteoglycans.
These mediators can produce:
Vasodilation increased vascular permeability,
bronchospasm increased mucous secretion and edema.
This is the early allergic response.
Immediate or early phase reaction:
occur within minutes of exposure to allergen in sensitized
individuals; mast cells degranulate, releasing preformed
mediators: smooth muscle constriction, mucus secretion,
vascular permeability, sensory nerve stimulation

The late allergic response occurs within 2-4 Hours, with

the release other inflammatory cytokines promoting cell
activation and cell recruitment which perpetuates further
the inflammatory response.
Begin 2-4 hours after exposure to allergen and
can last for 24 hours before subsiding
Newly-formed mediators promote:
outflow of plasma à localized edema
infiltration of tissues by eosinophils,
neutrophils and basophils
Eosinophils produce mediators that promote
tissue damage (MBP, ECP, LT)
TH2 cells release cytokines that promote IgE
production, eosinophil chemoattraction,
increased numbers of mucosal mast cells
Preformed Mediators:
Biogenic amine
Histamine – effects on smooth muscle
(contraction), endothelial cells, nerve endings, and
mucous secretion
Neutral Proteases –
Tryptase – cleaves C3 and C3a, activate fibroblasts,
and promote accumulation of inflammatory cells.
Others- chymase, carboxypeptidase, and
cathepsin G
Acid hydrolases –acts on carbohydrates
Proteoglycans –
Heparin- anticoagulant
Newly Formed Mediators (lipid mediators)
Cyclooxygenase Pathway:
Prostaglandin D2- bronchoconstrictor; peripheral vasodilator,
inhibition of platelet aggregation; neutrophil chemoattractant
Thromboxane A2 – vasoconstrictor; aggregates platelets;
bronchoconstrictor
Lipooxygenase Pathway:
Leukotrienes- neutrophil chemotaxis, vascular permeability,
bronchoconstrictor

Cytokines:
TNF-α- up-regulates expression of endothelial and epithelial
adhesion molecules; promotes chemokine secretion
IL-5- maturation, activation, and survival of eosinophils
IL-4 – stimulates and maintains Th2 cell proliferation and B cell
production of IgE
Others: IL-13 (like IL-4), IL-6 (promotes mucus production), IL-
8, GM-CSF
 Allergy In the Family Is The Most Important
Risk Factor For The Development Of Atopic Diseases

50 – 80%
Both parents atopic
HIGH with same manifestations
40 – 60%
Both parents atopic

Either parent atopic

20 – 40%
MODERATE
One sibling atopic
25 – 35%

LOW Neither parent atopic 5 – 15%

Aberg N, Sundell J, Eriksson B, Hessellmar B. 1996

de Weck AL, Proost P.1997
Olderam H et al. JNM 1995
Cookson WO. 1998
SKIN PRICK TEST

After 15-20 minutes:

Skin Prick Tests
are the diagnostic tests of choice for many allergic disease. This test is
the most convenient and precise methods of eliciting IgE antibodies
How is this done?

Usually the volar surface of the forearm is used.

Histamine is the preferred agent for positive control. Saline or extract
diluent may be used for negative control.

A drop of extract is placed on the skin surface,

a needle is gently penetrated into the epidermis through the drop/

Then the epidermis is gently raised without causing any bleeding.
Immediate response elicited by skin testing peaks in 15 to 20 minutes.
Thus, after 15 to 20 minutes, the tests should be
read.
In general, a wheal of 3 mm or greater than the
negative control is considered positive.

The reaction involves production of the wheal and

flare reaction characteristic of atopic sensitization.

In-Vitro test: Specific IgE levels

The blood test measures the levels of allergy

antibody, or IgE, produced when your blood is
mixed with a series of allergens in a laboratory.
MANAGEMENT OF ALLERGIES:
In general:
Allergen avoidance
Pharmacotherapy
Specific Immunotherapy – for inhalant allergies

• House dust mite reduction

• Wash pillows and beddings in hot water (55-60⁰C) q 1-2 weeks
• Encase pillows and mattresses with protective coverings
• Provide sufficient ventilation to decrease humidity
• Use damp cloth duster when cleaning surfaces
• No carpets. Only linoleum or wooden floors which can be wiped clean
• Remove/reduce curtains and soft furnishings in the bedroom
• Replace fabric covered seating with leather or vinyl
• Remove soft toys from the bedroom. Wash at 5-60⁰C or freeze them to kill
house dust mites
• No pets inside bedroom
• Expose mattresses and rugs to strong direct sunlight for >3 hours to kill
mites
Cockroach allergen avoidance:
• Eradicate cockroaches with appropriate insecticides
• Seal cracks in floors and ceilings
• Remove sources of food Control dampness
• Scrub floors with water and detergent to remove allergens
• Bedding, curtains, and clothi Keep windows closed in the evening
when airborne pollen counts are high

Pollen avoidance
• Keep windows closed in the evening when airborne pollen counts
are high
• Wear glasses or sunglasses to prevent pollen entering the eye
• Consider wearing a mask over nose and mouth to prevent
inhalation of pollen at peak times
• Pollen-allergic individuals should not cut grass
• Keep windows closed when the grass has been mown
• Use air conditioning if possible
Pet allergen avoidance
• Remove animals from the home
• Exclude pets from bedrooms and if possible, keep pets outdoors

Mold allergen avoidance

Indoors
• Ensure ventilation or air conditioning systems are properly
maintained
• Use 5% ammonia solution to remove mold from bathrooms and
other contaminated
• surfaces
• Replace carpets with hard flooring: replace wall paper with paint
• Repair indoor water damage immediately
Outdoors
• Avoid cutting grass when mould spores are present in decaying
vegetations
Allergen Immunotherapy
• Is the only current therapeutic method that alters the natural
course of allergic disease
• Failure or unacceptability of other treatment modalities
• Patient wants long-term benefits May be useful for patients with
allergic rhinitis, asthma and hymenoptera sensitivity (not food
allergy or atopic dermatitis)
• Should be administered under the direction of an allergy-
immunology specialist

85% long lasting relief from IT; 60% of all patients continue to derive
symptomatic benefit with reduced use for medications after
immunotherapy is discontinued

Sublinglual immunotherapy
• FDA-approved SLIT products for the treatment of allergic
rhinitis/rhinoconjunctivitis; in Europe -asthma, AR
• Available: Timothy grass, ragweed pollen, dust mite
• Drops, tablets, spray
• Efficacy SCIT vs. SLIT: SCIT has the edge