11/10/2016

OBJECTIVES
 To discuss the principles of allergic disorders in
children
 To discuss the clinical presentation of allergic
ALLERGIC DISORDERS IN disorders and appropriate diagnostic work-up
 To discuss common allergic disorders and plan of
CHILDREN treatment
 Allergic rhinitis
Jasmin Escaño-Dumbrique, MD, DPPS, DPAPP  Bronchial asthma

General Pediatrics-Pulmonology  Anaphylaxis

Types of Hypersensitivity states

HYPERSENSITIVITY REACTIONS (Gell and Coombs Classification)
state of altered reactivity in which the TYPE I – ANAPHYLACTIC REACTIONS
body reacts with an exaggerated immune TYPE II – CYTOTOXIC REACTIONS
response to a foreign agent TYPE III - IMMUNE-COMPLEX REACTIONS
i.e. anaphylaxis and allergy TYPE IV – CELL-MEDIATED REACTIONS

Types of Hypersensitivity states

(Gell and Coombs Classification)  Type 2 CYTOTOXIC REACTIONS
 Type 1 hypersensitivity:
 caused by an interaction of antibody and antigens on cell sur
 an immediate, abnormal reaction occurring when an Ag
faces
reacts with an antibody (e.g. IgE)attached to a mast cell or
 Examples: Graves' disease, myasthenia gravis
basophil
 Type 3 (immune-complex mediated hypersensitivity)
 Leads to the release of specific chemical mediators of allergy
 mediated by a combination of antigen-antibody.
(e.g. histamine) that react
with target organs throughout the body  Example: systemic lupus erythematosus.

 systemic signs: itching, lacrimation, skin rash,  Type 4 (T cell-mediated hypersensitivity)

possibly haemodynamic collapse and shock  a delayed reaction (several days to develop) mediated by T l
 Ex: Allergic conjunctivitis ymphocytes
 Example: rheumatoid arthritis

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KEY ELEMENTS OF ALLERGIC DISEASES

ALLERGY
“altered state of reactivity” to common
environmental antigens
represents the clinical expression of IgE-
mediated allergic disease
such individuals have a familial predisposition
to allergic diseases that manifest as
hyperresponsiveness in their target organs
such as the lung, skin, or nose
1. ALLERGENS
antigen that triggers an IgE response in
genetically predisposed individuals
this includes a number of major allergens
such as Dermatophagoides pteronyssinus
allergen I (Der p 1) from the house dust
mite.

Allergens are found outdoors and indoors

2. T CELLS.
 Outdoor
T-helper type 1 (Th1) cells
Trees
Grasses non-atopic subjects
Weeds secrete cytokines, including interferon (IFN)–
γ, that are involved in the elicitation of
 Indoor allergen-specific IgG antibodies;
Dust mites
activate phagocytes  promote production
Pets of opsonizing and complement-fixing
Cockroaches antibodies  eradicate intracellular
Molds organisms such as mycobacteria

T helper type 2 (Th2) cells

 genetically predisposed atopic individuals
 respond with a brisk expansion of cells that
secrete cytokines favoring IgE synthesis and
eosinophilia
 Th2 cytokines play an important role in the
pathogenesis of asthma and allergic diseases; Th2
cells infiltrate into the affected tissues of acute
allergic tissue reactions.

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3. Antigen-presenting cells
 dendritic cells, Langerhans cells, monocytes, and
macrophages
 induction of allergic inflammation by presenting
allergens to T cells and by contributing to the local
recruitment of effector cells.
 heterogeneous group of cells with the common
property of presenting antigens in the context of
the major histocompatibility complex (MHC)
5. EOSINOPHILS
 contain dense intracellular granules that are sources
of inflammatory proteins
 proteins damage epithelial cells, induce airway
hyperresponsiveness, and cause degranulation of
basophils and mast cells
 Produce cysteinyl leukotriene C4, which contracts
airway smooth muscle and increases vascular
permeability
 Other secretory products : cytokines (IL-4, IL-5, tumor
necrosis factor [TNF]–α), proteolytic enzymes, and
reactive oxygen intermediates
 enhance allergic tissue inflammation
MECHANISMS OF ALLERGIC
TISSUE INFLAMMATION
Three patterns of reaction
1. early-phase response
2. late-phase response
3. chronic allergic disease
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4. IgE AND ITS RECEPTORS
 induction of IgE synthesis involves two major
signals
 initial signal: activation of germline transcription at
the ε immunoglobulin locus by IL-4 or IL-
13dictates isotype specificity
 second signal: involves the engagement of CD40 on
B cells by CD40 ligand expressed on T cells
activation of the recombination machinery
6. MAST CELLS
 derived from CD34 hematopoietic progenitor cells
 arise in the bone marrowenter the circulationtravel to
peripheral tissue (undergo tissue-specific maturation)
 Lungs, small intestinal mucosa, skin, gastrointestinal
submucosa, and blood vessels
 Produce mediators (histamine, serine proteases,
proteoglycans); membrane-derived lipids, cytokines, and
chemokines
 most important mast cell–derived lipid mediators with
potent inflammatory activities
 cyclo-oxygenase: prostaglandin D 2
 lipoxygenase products: sulfidopeptide leukotrienes- LTC 4
and its peptidolytic derivatives LTD4 and LTE4
I. EARLY-PHASE RESPONSE
 results from mast cell degranulation
 occurs within 10 min after allergen exposure and
resolves within 1–3 hr
 increased local vascular permeabilityleakage of
plasma proteins, tissue swelling, increased blood
flow
 itching, sneezing, wheezing, and acute abdominal
cramps in the skin, nose, lung, and gastrointestinal
tract
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The Allergic Response

II. Late-phase response

 occur within hours of allergen exposure, reaching a maximum at Hours
6–12 hr and resolving by 24 hr Minutes
 Cutaneous: edema, redness, and induration; NOSE: sustained Secretion
nasal blockage; LUNGS: wheezing Degranulation
 early infiltration of neutrophils and eosinophils followed by
basophils, monocytes and macrophages, and Th2-type cells. Histamine Cytokines
 several hours after allergen exposure, TNF-α (released by
Leukotrienes Chemokines
Proteases
activated mast cells) induces the vascular endothelial
expression of cell adhesion molecules the transendothelial
migration of various inflammatory cells, accumulation of
eosinophils Immediate Rxn Late Phase Rxn
 Chemokines: chemotactic cytokines that play a central role in
tissue-directed migration of inflammatory cells

III. Chronic allergic disease

 tissue inflammation can persist for days to years
 recurrent exposure to allergens and microbial agents with
repeated stimulation of allergic effector cells such as mast
cells, basophils, eosinophils, and Th2 cells
 Tissue remodeling irreversible changes in target organs DIAGNOSIS OF ALLERGIC
 Th2 cytokines contribute to tissue remodeling by activating
resident cells in target organs: IL-4, IL-9, and IL-13 can
DISEASES
induce mucus hypersecretion and metaplasia of mucus cells;
IL-4 and IL-13 stimulate fibroblast growth and synthesis of
extracellular matrix proteins; and IL-5 and IL-9 increase
subepithelial fibrosis

 Presence of characteristic behavior

ALLERGY HISTORY
1. Elicit a description of all symptoms along with their
timing and duration, exposure to common
allergens, and responses to previous therapies
2. Elicit presence or absence of other allergic diseases
including allergic rhinitis, allergic conjunctivitis,
asthma, food allergy, and atopic dermatitis should
be determined
3. A family history of allergic disease (50% when one
parent is allergic; 66% when both parents are
allergic) Allergic Hand Salute

4

Characteristicvigorous grinding of the eyes
with the thumb and side of the fist
allergic cluck : an effort to scratch the palate
timing of onset and the progression of
symptoms are relevant
PHYSICAL EXAMINATION
 Peak flow analysis or spirometry  evidence of airway
obstruction
 Pulse oximetry respiratory distress
 Poor weight gain in a child with chronic chest
symptoms cystic fibrosis
 blood pressure to check for steroid-induced hypertension
 allergic shiners (bluish-gray to purple discoloration
beneath eyelids)
 Dennie lines (Dennie-Morgan folds) prominent
symmetric skinfolds that extend in an arc from the inner
canthus beneath and parallel to the lower lid margin.
Ear examination
Nasal exam transverse crease,
Nasal patency septal deviation, turbinate
hypertrophy, septal spurs, or nasal polyps
nasal mucosa in allergic rhinitis: pale to
purple
Facial tenderness: frontal and maxillary
sinuses
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a history of episodic acute symptoms, review
the setting in which symptoms occur as well
as the activities and exposures that
immediately precede their onset
Reproducible reactions after the ingestion of
a specific foodpossibility of food allergy
Age of patient– impt in identifying specific
allergen
Environmental survey
Allergic Shiner
 Chest findings in asthmatic children
 Normal or hyperinflation, tachypnea, cyanosis, use of
accessory muscles, wheezing, and decreased air
exchange with a prolonged expiratory time
 Decreased airflow or rhonchi and wheezes over the right
chest may be noted in children with mucus plugging and
right middle lobe atelectasis
 Unilateral wheezing after an episode of coughing and
choking in a small child without a history of previous
respiratory illness suggests aspiration of a foreign
body
 Digital clubbing chronic disease
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Skin:urticaria/angioedema or atopic
dermatitis
Xerosis, or dry skin, is the most common skin
abnormality of allergic children
exaggerated palmar and plantar creases in
some allergic children.
 Nasal and bronchial secretions examination
 presence of eosinophils in the sputum of asthmatic
patients is classic
 increased number of eosinophils in a smear of
nasal mucus stained with Hansel stain more
sensitive indicator of nasal allergies than peripheral
blood eosinophilia
 young children, nasal eosinophilia is defined as >4%
eosinophils in nasal mucus smears, finding of >10%
eosinophils in adolescents and adults
 Skin testing
 ALLERGENS INTRODUCED HiSTAMINE
RELEASEDWHEAL WITH ERYTHEMA
 time course of these reactions is rapid in onset, reaching
a peak within ≈20 min and usually resolving over the
next 20–30 min, some dEvelop an erythematous base
over the next 6–12 hr (late-phase response)
 1. PRICK/PUNCTURE
 2. intradermal technique
 when the prick/puncture skin test is negative and the
history is suggestive of allergy
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DIAGNOSTIC TESTING
IN VITRO TESTS
1. EOSINOPHILIA: presence of >450
eosinophils/μL in peripheral blood,
The number of circulating eosinophils can be
suppressed by certain infections and the
systemic corticosteroids
Increased numbers of eosinophils are
observed in a wide variety of disorders in
addition to allergy
 ELEVATED IgE LEVELS
 the presence of IgE specific for a particular allergen can
be documented in vivo by skin testing or in vitro by the
measurement of allergen-specific IgE levels in the serum,
radioallergosorbent test (RAST)
 RAST is not as sensitive as the skin test, however, results
not influenced by skin disease or medications
 In patients with histories of life-threatening reactions to
foods, insect stings, drugs, or latex, skin testing is still
required because of its higher sensitivity even if the
RAST is negative
Skin Testing confirms sensitivity to allergens
After 15 minutes:
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Other tests
 Provocation test– methacholine challenge testing
 Food challenges Common Allergic
 involve the ingestion of gradually increasing
amounts of the suspected food at set time intervals Disorders
until the patient either experiences a reaction or
tolerates a normal portion of the food openly

ALLERGIC RHINITIS ALLERGIC RHINITIS

Typical Symptoms:
Definition: sneezing

a symptomatic disorder of the nose clear rhinorrhea

induced by an IgE mediated nasal itching
inflammation after allergen exposure of nasal congestion
the membranes of the nose
which are reversible
spontaneously or
with treatment

ALLERGIC RHINITIS ALLERGIC RHINITIS

Signs / Symptoms: Signs / Symptoms:
mouth breathing or frequent throat
snoring clearing
sleep disturbance chronic postnasal
abnormalities of drip
facial development, chronic,
dental malocclusion nonproductive
and allergic facies cough

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ALLERGIC RHINITIS
ALLERGIC RHINITIS

Facial Grimace Allergic Hand Salute

ALLERGIC RHINITIS ALLERGIC RHINITIS

Signs / Symptoms:
red, itchy eyes
itchy throat, ears and
palate
swollen nasal
turbinates
Allergic Shiner

Allergic Response in Allergic Rhinitis

ALLERGIC RHINITIS
Immediate Rhinitis
Signs / Symptoms: •Sneezing
•Pruritus
eustachian tube
•Rhinorrhea
dysfunction “Runners”
ear fullness
sinus headache Chronic Rhinitis
•Congestion
malaise, weakness •Nasal hyperreactivity
and daytime fatigue •Loss of smell
“Blockers”

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Skin Testing confirms sensitivity to allergens

“Runners” “Blockers
”
Sneezing especially little or
paroxysmal After 15 minutes:
none
Rhinorrhea watery thick mucus
anterior and posterior more posterior

Itching yes no

Nasal Blockage variable often severe

Diurnal Rhythm worse during day constant,day

improving at night and night, may
be worse at
night
Conjunctivitis often present

Allergens are found outdoors and indoors

 Outdoor
ALLERGIC RHINITIS
Trees  Allergic inflammation does not necessarily limit itself
to the nasal passages
Grasses
Weeds
 Multiple co-morbidities have been associated with
 Indoor rhinitis
Dust mites  asthma

Pets  sinusitis

Cockroaches  conjunctivitis
 otitis media
Molds

Allergic Rhinitis as Risk Factor for

ALLERGIC RHINITIS
Allergic rhinitis is correlated to and constitutes
a risk factor for the occurrence of asthma
Strong epidemiologic, pathophysiological and
clinical evidences of a relationship between
Asthma
Settipane et al : Allergy Proc 1994
 Incidence of asthma over the 23 years between the 2
surveys was 10.5% in those with rhinitis compared to 3.6%
in those without rhinitis. Patients with allergic rhinitis have
3-fold increased risk of developing asthma.
Guerra et al : J Allergy Clin Immunol 1997

rhinitis and asthma  OR = 2.9 for developing asthma if rhinitis was present
 OR = 6.28 for developing asthma if sinusitis was present
 Risk for asthma increased with increasing severity of
rhinitis

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Histologic Evidences: Nasal versus Lung Physiologic Evidences: Nasal versus Lung

Allergen Challenge

Epithelium + + Histamine + +
Glands + + Leukotrienes + +
Nerves + + Eosinophils + +
_
Venous sinusoids + Sanico et al. J Allergy Clin Immunol abst
_ 2000 et al. Am J Respir Crit Care Med
Jarjour
Smooth muscle + 1997
Wenzel et al. Am Rev Respir Dis 1990

Clinical Evidences: One Airway, One Disease Clinical Evidences: One Airway, One
Nasal Allergen Challenge
Disease
Nasal Biopsy Bronchial Biopsy

Pre Pre

24h 24h
Post Post

ICAM-1 E Selectin ICAM-1 E Selectin

VCAM-1 CD31 VCAM-1 CD31

PNIF: Peak Nasal Inspiratory Flow

Braunstahl et al. J Allergy Clin Immunol 2001 PEF: Peak Expiratory Flow Braunstahl et al. J Allergy Clin Immunol 2001

Clinical Evidences: One Airway, One Clinical Evidences: One Airway, One
Disease Disease
Placebo Flunisolide Beclomethasone
nasal spray nasal spray nasal spray

Treatment 6 p=0.001
15 1200
Untreated Rhinitis
5
1000
Daily Treated Rhinitis
Percent(%)

Asthma 10 4
score
800 ragwee
differenc 5 600 d pollen 3
p=0.001
e from count 2
400 (grain/m
baseline 0 3) 1
200
0
-5 0
11 24 7 21 4 18 ER Visits Hospitalization
July August September

Treatment of allergic rhinitis improves Welsh et al. Mayo Clinic Proc 1987 Treatment of allergic rhinitis improves asthma
Crystal-Peters et al. J Allergy Clin Immunol 2002

asthma

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Allergic Rhinitis and Asthma

Allergic
Rhinitis

Asthma + AR

Asthma

 Approximately 80% of asthmatics have allergic rhinitis

 Approximately 40% of allergic rhinitis patients have asthma

Allergic rhinitis adversely affects asthma

n=1,261 asthmatics ALLERGIC RHINITIS

70 p<0.001
Mild or no rhinitis
60 New Subdivision in ARIA:
Severe rhinitis
Percentage

50 based on duration
40
(%)

30 p<0.001 intermittent
p<0.001
20 persistent
10

0
symptoms and quality of life parameters:
Weekly Nightly Related
attacks awakenin work loss
mild
g moderate-severe
Huse et al. Amer J Respir Crit Care Med 1996

Classification of Treatment of allergic rhinitis

Allergic Rhinitis (Stepwise approach)

Intermittent Persistent Moderate

symptoms symptoms Mild severe
Moderate persistent
persistent
• < 4 days per week • > 4 days / week severe
intermittent
• or <4 weeks • and >4 weeks Mild
intermittent Intra-nasal steroid / chromone
Mild Moderate-Severe
Antileukotrienes
one or more items
•Normal sleep •Abnormal sleep Oral or local non-sedative antihistamine
•Normal daily activities, •Impairment of daily Intra-nasal decongestant (< 10 days) or oral decongestant
sport, leisure activities sport, leisure
Allergen and irritant avoidance
•Normal work and school •Problems caused at work
•No troublesome or school Immunotherapy/ anti-IgE
symptoms •Troublesome symptoms
Frequency and Severity of Symptoms

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DEFINITION OF ASTHMA
 a heterogeneous disease, characterized by chronic
airway inflammation
 wheeze, shortness of breath, chest tightness and
cough that vary over time and in intensity together
ASTHMA IN CHILDREN with variable expiratory airflow limitation
 Usually associated with airway hyperresponsiveness
and airway inflammation, but these are not
necessary or sufficient to make the diagnosis

GINA 2015

Criteria Clinical Asthma Phenotypes

Age of onset Transient infant wheezing (began and ended before 3 years) ALGORITHM FOR THE DIAGNOSIS OF ASTHMA
Non-atopic wheezing of the toddler and early school years
Persistent IgE-mediated wheezing/ asthma (began before 3y/o,
Cough
continued beyond 6 years)
Late-onset childhood asthma (symptoms began before the age
and/or wheeze DIAGNOSIS
of 3) and/or chest tightness POSSIBLE
and/or breathlessness
Airway Eosinophilic asthma – assoc with allergic asthma
inflammation Non-eosinophilic asthma – assoc with refractory asthma & and/or gurgly chest (“halak”)
chronic airflow obstruction
Paucigranulocytic
Mixed inflammatory
Associated with any or all of the ff.:
Severity pattern Mild exercise
Severe
nocturnal occurrence
Brittle
episodic / seasonal occurrence DIAGNOSIS
Near-fatal asthma
Asthma with fixed airflow obstruction- long-standing asthma personal or family history of atopy PROBABLE
due to airway remodeling recognizable triggers
Corticosteroid-resistant asthma
Etiologic factors Aspirin- and NSAID sensitive (2-5%)
Persistent respiratory infections
Occupational factors ASTHMA SUSPECT
Toxic exposures
Exercise-induced
Menses-related

ALGORITHM FOR THE DIAGNOSIS OF ASTHMA

Diagnosis
ASTHMA SUSPECT Spirometry
 Recommended in the initial assessment of patients
suspected to have asthma
Spirometry Spirometry  Usually feasible in children from age >5 years
available/feasible NOT available/feasible
 Useful in assessing
 Degree of airway obstruction
 Disturbances in gas exchange
Peak Flow Meter Peak Flow Meter
available/feasible NOT available/ feasible  Response of airways to inhaled allergens/
chemicals/exercise
see Figure 1-1 see Figure 1-2 see Figure 1-3  Assessing response to therapeutic agents
 Evaluating long-term course of disease

Philippine Consensus for the Management

of Childhood Asthma, 2002

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ASTHMA SUSPECT Spirometry

Diagnosis Figure 1-1 available/feasible

Spirometry FEV1 below normal FEV1 normal

Inhaled short acting Beta2*

FEV1 is the single best measure for

FEV1 increases FEV1 increase
assessing severity of airflow obstruction by 15% or more less than 15%

FEV1 measurements <80% of predicted

Exercise challenge test
value is evidence of airway obstruction ASTHMA Methacholine/Histamine challenge
Peak flow variability > 20%
and reversibility with use of inhaled ß2- DEFINITE
5-day systemic oral steroid and bronchodilator course
agonist (increase in FEV1 by 15%) makes a
definitive diagnosis of asthma POSITIVE response NEGATIVE response
ASTHMA Consider
other diagnosis
*short acting oral B2 agonists may be used, but the inhaled form is preferred
because of the delay and variability of response to the oral form

ASTHMA SUSPECT Spirometry

Peak Flow Meter NOT available/feasible
Figure 1-2
available/feasible

Portable Peak Flow Meter Below normal Normal

 measure PEFR where spirometry is not available Inhaled short acting Beta2*

 less sensitive, but correlates well with FEV1 > 20% increase < 20% increase
 offers an acceptable alternative to assess response
to exercise challenge and peak flow variability Exercise challenge test
ASTHMA Peak flow variability > 20%
 The predicted normal PEFR for Filipino children 5-day systemic oral steroid and bronchodilator course

between 6 and 17 years of age with height of at

least 100 cm can be calculated: POSITIVE response NEGATIVE response

 Males: (Height in cm - 100) 5 + 175 ASTHMA Consider

other diagnosis
 Females: (Height in cm - 100) 5 + 170 *short acting oral B2 agonists may be used, but the inhaled form is preferred
because of the delay and variability of response to the oral form

ASTHMA SUSPECT Spirometry

Peak Flow Meter NOT available/feasible
Figure 1-3
NOT available/feasible

Inhaled short acting Beta2*

Diagnosis of Asthma
GOOD response POOR response  Other Tests to help establish the diagnosis of asthma
Presume as ASTHMA Consider
1) Methacholine/Histamine bronchoprovocation test
and start treatment** other diagnosis 2) Exercise challenge test
5-day systemic oral steroid 3) Twice daily recording of peak flow to determine diurnal
and bronchodilator course*** variation
4) Therapeutic trial of five days steroid and bronchodilator
GOOD response Equivocal POOR response course
Presume as ASTHMA Refer toCenter with Consider
and start treatment** Diagnostic Technology other diagnosis
* short acting oral B2 agonists may be used, but the inhaled form is preferred
because of the delay and variability of response to the oral form
** needs follow-up as initial episodes of wheezing responsive to bronchodilators may be
transient
*** in prescribing corticosteroids in patients with probable asthma and concomitant
infections, specific therapy for the infection must be administered

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Management Exacerbations are episodes

of Acute characterized by progressive
Exacerbation in increase in symptoms of
Children shortness of breath, cough,
wheezing or chest tightness
and progressive decrease in
lung function.

 Treatment should be started as soon as an

asthma attack is recognized.
 Initial treatment will include inhaled short-acting
2 and if necessary, oxygen.

 Factors that increase the risk of asthma-

related deaths
 History of near-fatal asthma requiring
intubation and MV Brief but focused history PE should be done to determine
 Hospitalization or emergency care visit for pertinent to the attack severity of exacerbation
asthma in the past year
 Currently using or have recently stopped
using OCS
 Not currently using ICS This will serve as a guide to
 Over-use of SABAs the type of management
appropriate for the case.
 Poor adherence with asthma medications

Severity of Asthma Exacerbations

Particular attention should be given to
patients who present with the following Clinical Features
features, as they are the ones most Mild Moderate Severe Resp. Arrest Imminent
prone to develop acute respiratory
Walking Talking Infant – At rest Infant –
failure: Breathless
softer, shorter cry; stops feeding
1) cyanosis difficulty feeding
Can lie down Prefers sitting Hunched forward
2) absence of wheeze
Talks in Sentences Phrases Words
3) bradycardia and bradypnea
4) paradoxical thoraco-abdominal movement Alertness May be agitated Usually agitated Usually agitated Drowsy or confused

5) drowsiness or confusion Respiratory Increased Increased Often >30/min Bradypnea

rate
6) a normal or elevated pCO2 in a patient with
severe Acc muscles& None Present Present Paradoxical thoraco-
abdominal movement
distress suprasternal
retractions
Wheeze Audible with Audible with Audible without (-) wheeze with
stethoscope stethoscope stethoscope /(-) breath sounds
Pulse/min < 100 100-120 > 120 Bradycardia

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Management of asthma exacerbation in acute care facility

Severity of Asthma Exacerbations INITIAL ASSESSMENT ARE ANY OF THE FOLLOWING
Objective Measures PRESENT? Drowsiness, Confusion, Silent Chest
Mild Moderate Severe Respiratory Arrest
Imminent NO YES
Further TRIAGE BY CLINICAL
Pulsus Absent May be present Often present Absence suggests Consult ICU, start SABA and O2
Paradoxus 20-4- mm Hg respiratory muscle
STATUS and prepare for intubation
<10 mm Hg 10-20 mm Hg
fatigue according to worst feature
PEF  80% 60-79% < 60 %
%predicted or
MILD OR MODERATE
%personal best
Short-acting beta2-agonists SEVERE
paO2 (on air) Normal 60 mm Hg < 60 mm Hg Consider ipratropium bromide Short-acting beta2-agonists
Test not Possible Controlled O2 to maintain sats ipratropium bromide
and/or usually cyanosis 94-98% Controlled O2 to maintain sats
paCO2 necessary  45 mm Hg 45 mm Hg Oral corticosteroids 94-98%
 45 mm Hg Possible resp Oral or IV corticosteroids
failure Consider IV magnesium
Consider high dose ICS
SaO2% (on air)  95% 90-94% < 90%
GINA 2015

If continuing deterioration, treat

Management of Acute Exacerbation
as severe and re-assess for ICU  OXYGEN
 INHALED SHORT-ACTING BETA2 AGONISTS
ASSESS CLINICAL PROGRESS FREQUENTLY  E.g. salbutamol- give 1 nebule every 20 minutes for 3
MEASURE LUNG FUNCTION doses, then re-assess, decrease to Q4 for 2-3 days
In all patients one hour after initial treatment
 EPINEPHRINE (for anaphylaxis)
 SYSTEMIC CORTICOSTEROIDS
 Route of delivery
FEV1 or PEF < 60% of predicted or
FEV1 or PEF 60-80% of predicted or  Oral as effective as intravenous
personal best or lack of clinical
personal best and symptoms  IV: when patients are too dyspneic to swallow,
response
improved
SEVERE vomiting, or require non-invasive ventilation or
MODERATE
Continue treatment as above and intubation
Consider for discharge planning re-assess frequently
 Dosage
 OCS dose 1-2mg/kg day (max 40 mg) as single
morning,0-2 years (max 20 mg), 2-5 years (max
GINA 2015
30mg)
 IV: 4mg/kg/dose Q6

IPRATROPIUM BROMIDE MAGNESIUM

 IV Mg sulfate is not routinely
recommended in asthma exacerbation
 Treatment with both SABA and  25-75mg/kg (as single 2 g infusion over 20
ipratropium was associated with min)  reduces hospital admissions in
some patients who fail to respond to initial
fewer hospitalizations and greater treatment, persistent hypoxemia, and
improvement in PEF and FEV1 whose FEV1 fails to reach 60% predicted
compared with SABA alone after 1 hour of care (Evidence A)

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LEUKOTRIENE RECEPTOR ANTAGONISTS

 Limited evidence to support role in
acute asthma
ANTIBIOTICS:
LONG-TERM
 Not recommended
MANAGEMENT
SEDATIVES
OF ASTHMA IN
 Not recommended (should be strictly
CHILDREN
avoided)
NON-INVASIVE VENTILATION
 Evidence regarding role in acute asthma
is weak

PHARMACOLOGIC APPROACH FOR INITIATING THERAPY

Classification of Asthma by Severity Before Initiation of Treatment ‡

GOALS OF ASTHMA Intermittent

Mild
Persistent
Moderate Severe
MANAGEMENT Symptoms ≤ 2 days/week >2 days/week Daily Daily
Interference with none Less than Affects daily Limits daily activities
normal activity daily activities
 To achieve good control of Nighttime ≤ 2x/ month 3-4x/month >1x/week but nightly
symptoms and maintain normal awakenings not nightly
Short acting B2 ≤ 2 days/week >2 days/week Daily Several times per day
activity levels agonist use for but not daily
symptom control
(not prevention
EIB)

 To minimize risk of flare-ups, PEFR ≥80%

predicted
≥80%
predicted
60-79%
predicted
< 60% predicted

impaired lung development and PEFR variability < 20% 20-30% > 30% > 30%
FEV 1 ≥ 80% ≥80% 60-79% < 60% predicted
medication side-effects predicted predicted predicted
FEV1 / FVC > 85% >80% 75-80% < 75%
Exacerbations 0 – 1 / year ≥2 in one year
requiring oral
systemic steroids

PHARMACOLOGIC APPROACH FOR INITIATING THERAPY

Recommended Steps for Initiating Therapy LEVELS OF ASTHMA CONTROL
Intermittent Persistent
Characteristics Controlled Partly Controlled Uncontrolled
Mild Moderate Severe (All of the (Any measure
Asthma Education following) present in any
Environmental Control week)

As needed rapid-acting B2-agonist Daytime symptoms None (twice or More than Three or more
less/week) twice/week features of partly
Preferred Low-dose inhaled Low-dose ICS ( 100-200 ug)* plus controlled asthma
Limitations of None Any
Controller ICS (100-200 ug) long- acting B2 agonist present in any week
activities
Alternative OR OR
Controller Nocturnal symptoms/ None Any
Leukotriene Low-dose ICS (100-200 ug)* plus
Options awakening
modifier leukotriene modifier
OR Need for reliever/ None (twice or More than
rescue treatment less/week) twice/week
Low-dose ICS (100-200 ug)* plus
sustained release theophylline Lung function Normal <80% predicted or
OR (PEF or FEV1) personal best (if
known)
Medium dose ICS (>200- 400 ug)*
Exacerbations None One or more/year One in any week
And consider short course of systemic
corticosteroids
lung function is not a reliable test for children 5 years and younger
In 2-4 weeks, evaluate level of asthma control that is achieved, and adjust therapy
accordingly based on level of control.

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Management Approach Based on Control

For children 5 years and older, and adolescents

Management Approach Based on Control Reduce TREATMENT STEPS Increase

For children 5 years and older, and adolescents STEP STEP STEP STEP STEP
1 2 3 4 5
Asthma Education
Environmental Control
LEVEL OF CONTROL TREATMENT OF ACTION
As needed rapid As needed rapid – acting B2-agonist
acting B2
controlled maintain an find lowest agonist
controlling step
Controller Select one Select one Add one or more Add one or both
partly controlled consider stepping up to Options*** Low-dose ICS Low-dose ICS Medium-or high- Oral
gain control plus LABA dose ICS plus glucocorticosteroid
uncontrolled step up until controlled LABA (lowest dose)
LRTA Medium-or high- LRTA Anti-IgE
exacerbation treat as exacerbation dose ICS Treatment
Low-dose ICS SR theophylline
plus LRTA
Low-dose ICS
plus SR
theophylline
Refer to asthma specialist if asthma is uncontrolled at step
3 care or if step 4 care or higher is required

DEFINITION
Potentially fatal multisystem
syndrome resulting from massive
ANAPHYLAXIS release of inflammatory
mediators from mast cells and
basophils

EPIDEMIOLOGY THE ALLERGY CASCADE

True incidence of anaphylaxis is unknown

Antigen
(Allergen)
Antigen-
Estimates of the risk of anaphylaxis per Presenting Cell

person in US is < 1-3%

T-Cell TH2 B-Cell
Occurs in all age groups but is more Mast Cell

common in adults due to increased time TH1

IgE Antibody
Inflammatory
for exposure and sensitization Mediators

Cytokines (Allergic Inflammation)

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ALLERGIC REACTIONS ROLE OF MAST CELL & BASOPHIL MEDIATORS

Wheeze,urticaria,angio
Smooth muscle spasm,mucus
Histamine and AA edema,flush,itch,
Minutes Hours secretion,vasodilation,inc
products diarrhea.hypotension,
vascular permeability,etc rhinorrhea
Degranulation Secretion
Cleavage of complement,
Histamine
chemoaatractant for Hypertension
Leukotrienes Cytokines
Cytokines Chemokines Neutral proteases eosinophil and Magnification of mast
Proteases
neutrophil,conversion of cell responses
angiotensin 1
Immediate Rxn Late Phase Rxn
Anrticoagulation, complement Prevent intravaascular
Chemotaxis
inhibition,chemoattractant for coagulation and
Proteoglycans
Cell Influx Mediators eosinophil,activator of kinin recruitment of
Middleton 2003

system complement

DYNAMICS OF CARDIOVASCULAR ABNORMALITIES IN

ETIOLOGIC and PATHOPHYSIOLOGIC CLASSIFICATION
ANAPHYLACTIC SHOCK of Anaphylaxis and Anaphylactoid Reaction in Children
EARLY STAGE WITH NO
PARAMETER AT 0NSET OF REACTION
TREATMENT
PROLONGED SHOCK Anaphylaxis – IgE mediated reaction
Drugs,
Blood pressure ↓ ↓↓ ↓↓↓ Food
Insect bite
Pulse ↑ ↑ ↑↑ Latex
Some cases of exercise:
Cardiac output ↑ ↓ ↓↓ exercise-induced
food-dependent exercise -induced
Peripheral vascular
resistance ↓ →↓ →↑↓

Intravascular volume →↓ ↓ ↓↓↓

Middleton 2003

ETIOLOGIC and PATHOPHYSIOLOGIC CLASSIFICATION

of Anaphylaxis and Anaphylactoid Reaction in Children
CLINICAL MANIFESTATIONS

Anaphylactoid
 the signs and symptoms are highly
• Direct release of mediators from mast cells and
basophils
variable and can range from mild
Drugs , immune aggregates
Radiocontrast media cutaneous sx to a fatal reaction
Idiopathic
Exercise  reaction begins within seconds or minutes
Physical Factors
• Activation of complement after exposure to the allergen
Transfusion reactions
 initial fright or sense of impending doom
• Disturbances in arachidonic acid metabolism
ASA/NSAIDS

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FREQUENCY OF OCCURRENCE CRITERIA FOR RAPID RECOGNITION

SIGNS/SYMPTOMS PERCENT (%)

1. Exposure to an allergen within 1 hour & 1 systemic sign
Urticaria and Angioedema 99

Dyspnea/wheeze 60 2. Urticaria or angioedema & 1 systemic sign

Dizziness, syncope, hypotension, nausea, vomiting, diarrhea 49

Cramping abdominal pain 46

Systemic signs:
Flush 28
hypotension
Upper airway edema 24

Rhinitis 16 bronchospasm or dyspnea

Headache 5
laryngeal/pharyngeal edema, stridor or dysphonia
Substernal pain 6

Itch without rash 4.5 increased gastrointestinal tract motility

Seizure 1.5

Kemp et al, Arch Int Med 155:1749-1754,1995

PATTERNS FATAL

 Occurs in <2% of patients with anaphylaxis

Acute – explosive onset within seconds to minutes of
 Most common etiology in children is food allergy
exposure to triggering event

Biphasic – followed by a reaction 3 to 8 hours after

 Anaphylaxis due to drug allergy increases with age

initial reaction (5-20% of cases)  A history of asthma is a risk factor due to its greater
Protracted – lasts 3 to 21 days from onset of acute reactivity to mediators released e.g. histamine,
reaction
leukotrienes and prostaglandins

 Failure to administer epinephrine OR lack of

epinephrine seen in 90- 100% of cases

Differential Diagnosis Laboratory Findings

1. Vasodepressor reactions
2. Flush syndrome (carcinoid,post menopausal)  Immediate emergency treatment should
3. “Restaurant syndrome” (MSG, sulphites) never be delayed pending results of
4. Other forms of shocks
laboratory studies
5. Non-organic diseases (panic attack, munch-hausen’s
stridor, globus hystericus)  Elevated plasma histamine
6. Histamine syndrome (scombroid fish  Elevated serum tryptase - longer half-life
poisoning,systemic mastocytosis)
7. Miscellaneous(hereditary angioedema,
pheochromocytoma, neurologic)
8. Foreign body aspiration, severe asthma,
hyperventilation

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Treatment
EPINEPHRINE IS THE DRUG OF CHOICE!
 potent cathecholamine with both α and
β adrenergic properties
 Reverses all pathophysiologic features
of anaphylaxis
α-hypotension,peripheral vasodilation, increased
vasopermeability, urticaria, angioedema
β-positive inotropic & chronotropic effects,
bronchodilation, increase cAMP
Therapeutic Principles
Immediate Therapy
 Rapid ABC’s of resuscitation
 Epinephrine IV (1:100,000) = 0.01 mg/kg or
continuous drip 0.1-0.2 μg/kg/min titrated q 0.1
μg/kg/min to max of 1.5 μg/kg/min
 Separate IV line no HCO3 infusion
 Continuous monitoring of CVS status and O2
 Rapid HX of triggering event, current
medications, HX of asthma, allergies and
concomitant medical conditions
Therapeutic Principles
Secondary
 H2 blocker – Ranitidine IV or PO 2-4
mg/kg/day q 8 h
 Glucagon 0.1 mg/kg IV if refractory to initial
TX
 Observe at least 4 hours for biphasic
anaphylaxis
11/10/2016
Treatment
EPINEPHRINE IS THE DRUG OF CHOICE!
 Epinephrine 1:1000 0.01 ml/kg SC/ IM
(ped) or 0.3 to 0.5 ml (adult) given q 20
mins prn
 Px on β blockers may be resistant to
epinephrine so higher does may be
required or glucagon given
 insect sting or injected drug: infiltrate
0.1 - 0.2 ml locally to retard absorption
of the residual allergen
 tourniquet applied proximally if
injection or sting is on an extremity
Therapeutic Principles
Subacute
 H1 blocker – Diphenhydramine 1-2 mg/kg
PO,IM,IV
Chlorpheniramine 10-20 mg
IV,IM
 Corticosteroids – Hydrocortisone 4-8
mg/kg/dose or methylprednisolone 1-2 mg/kg
Iv q 6 h
 Β2 agonist nebulization q 20 mins Or
continuous
Therapeutic Principles
 Fluids – Loss of up to 50% intravascular
volume may occur resulting in profound
hypotension not responsive to epinephrine
 Antihistamines are not appropriate
monotherapy for the Tx of acute anaphylaxis
 Corticosteroids are used to prevent the
biphasic response and to control
bronchospasm
 Bronchodilators are useful adjuncts in TX esp
in those with asthma
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Therapeutic Principles Therapeutic Principles

Disposition
Complications
 If still symptomatic admit for further tx
 permanent brain damage - hypoxia
 If unstable VS, laryngeal edema or refractory
 myocardial infarction
bronchospasm admit to ICU
 abortion (for pregnant women)
 If Sx resolve with no biphasic response
 renal failure
discharge on 72 hrs of antihistamine, oral CS

and inhaled β2 agonist

 Discuss allergen trigger and avoidance

 Follow up with allergist

Basic principles in treatment of

allergic Diseases
Therapeutic Principles
 avoidance of exposure to allergens and irritants that
Prognosis
trigger symptoms
Usually assumed that in anaphylaxis each
 pharmacologic management of symptoms caused
succeeding exposure may occasionally
by inadvertent acute and chronic allergen exposures
result in a more severe reaction stressing
 For those refractory to avoidance measures and
importance of patient education and
optimal pharmacologic management, allergen
avoidance measures
immunotherapy may be considered

In summary
Basic principles of allergic diseases, its
pathophysiology and the several cells
involved in its mechanism
Diagnosis of allergic diseases through review
THANK YOU!
of history, pertinent physical examination
findings and laboratory work-up
Discussed the common emergency allergic
diseases and their treatment

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