Atopic Disease

Syamsu
Division of Allergy and Immunology
Department of Internal Medicine
Medical Faculty Hasanuddin University
Makassar

Atopy is the propensity of an individual to produce IgE

in response to various environmental antigens and to
develop strong immediate hypersensitivity (allergic)
People who have allergies to environmental antigens
such as pollen or house dust, are said to be atopic.
Allergic rhinitis and allergic asthma are the most common
manifestation. Atopic dermatitis is less common, and
allergic gastroenteropathy is rare. These manifestation may
simultaneously coexist in the same patient or at different
time. Atopy can also be asymptomatic

The etiology of atopy is unknown.

There is substantial evidence for
complex of genes with variable degree
of expression encoding protein factors,
some of which are
pathogenic and others protective.

COMPARISON OF ALLERGY WITH OTHER RESPONSES

Disease

Mechanism

Result

Immunologic

Antigen
Source
Foreign

Allergy
Immunity

Immunologic

Foreign

Prophylaxis

Autoimmu
nity
Toxicity

Immunologic

Self

Disease

Toxic

Foreign

Disease

Disease

Allergic Asthma

Definition
Chronic inflammatory disorder of the airways
leading to episodes that are associated to
airflow obstruction which is often reversible.
Increased bronchial hyperresponsiveness
Multiple cells and cellular components
involved
Reversibility may be incomplete

General consideration
A. Extrinsic Asthma (allergic, atopic, or immunologic)
Generally develop early in life, usually in infancy or
childhood, often coexist with eczema or allergic rhinitis.
A family history of atopic disease is common.
Skin test show positive reaction to the causative allergen
Total serum IgE elevated , but sometimes normal
B. Intrinsic Asthma (nonallergic or idiopathic)
Appears first during adult life, usually after respiratory
infection, but sometimes develop during chidhood.
Skin test are negative to the usual allergens,
The serum IgE concentration is normal.
Blood and sputum eosinophilia is present.
Personal and family history for atopic disease usually
negative

Mechanisms of the late phase allergic

reaction
0

Early phase

24

Very late phase

Late phase

APC
Ag

MBP, ECP,
EDN, CLC etc

FceRI

Th2 B cells

IL-4

Eos
Histamin, PGD2,
LTs etc

Th0

TNF-
IL-4
IL-5
IL-8
GM-CSF
MIP-1
MCP-3

ICAM-1
VCAM-1
E-selection Eos

Epithelium

RANTES
MCP-4
Eotaxin

MBP, ECP,
EDN, CLC etc

IL-3
IL-4
IL-5
IL-6
IL-13
RANTES

Th2

RANTES
Ectaxin
IL-8
GM-CSF
Endothelium PAF

TNF-
IL-

IL-3
IL-4
IL-5
IL-8
GM-CSF

Mast cells

48 (h)

Baso
Histamin, LTC4

IL-4
IL-13
MIP-1
VCAM-1

RANTES
Eotaxin
IL-8
GM-CSF
PAF

Endothelium
Th2

Baso

Eos

Mediators and cytokines involved in chronic

allergic inflammation

Nonspecifictrigger
Infection : Viral resp. infection
Physiological Factors : . Exercise, Hyperventilation, Deep
breathing, Psychologic factors
Atmospheric factors : SO2, NH2, Cold air, O2, dest.water
Ingestants, Propanolol, aspirin, NSAID, Sulfit
Experimental inhalants : hypertonic solution, citric acid,
histamine, metacholine, PGF2
Occupational inhalant : isocyanate, wool, cotton, coffee,
fragrance etc

Clinical Features
A. Symptoms
Attack of wheezing, dyspnea, cough and tightness of chest
Fever is absent but fatigue, malaise, irritability, palpitations
and sweating are occasional systemic complaints
B. Sign
Tachypnea, audible wheezing, expiration >>inspiration.
Use of the accessory muscles of respiration.
Pulsus paradoxus indicate severe asthma
In severe attack with high grade obstruction breath sound
and wheezing may both absent

C. Laboratory Findings
- Increased total eosinophil count in peripheral blood
in nasal secretion, sputum, Charcot Leyden crystals and
Curschmans spiral
- CXR may be normal or show hyperinflation
- Total serum IgE is usually elevated in childhood allergic
asthma and normal in adult intrinsic asthma, but this test
lack specificity for diagnosis
- PFT : PFR and FEV1 are decreased
VC may be normal or decreased
Bronchodilatation test (+) if FEV1 > 15 %

ImmunologicDiagnosis
Diagnosis made by history, physical examination and PFT
to show reversible bronchial obstruction.
Blood and sputum eosinophilia is confirmatory.
CXR is useful to exclude other cardipulmonary diseases
Metacholin challenge test for instances which history and
PFT is normal
Skin Prick test or RAST for trigger allergens

CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN

YOUTHS > 12 YEARS AND ADULTS

Components of
Severity

EPR-3, p74, 344

Classification of Asthma Severity

Intermittent

Impairment
Normal
FEV1/FVC
8-19 yr 85%
20-39 yr 80%

Symptoms

<2 days/week

Nighttime
Awakenings

<2x/month

SABA use for sx

control

60-80 yr 70%

<2 days/week
none

Lung Function

Normal FEV1
between
exacerbations

FEV1 > 80%

Risk

Exacerbation
s
(consider
frequency
and severity)

Recommended Step for

Initiating Treatment

>2 days/week
not daily
3-4x/month

Severe
Continuous

Daily
>1x/week

Often nightly

not nightly

Interference with
normal activity

40-59 yr 75%

Mild

Persistent
Moderate

FEV1/FVC
normal

0-2/year

>2

Daily

days/week
not daily
Minor limitation

FEV1 >80%

FEV1/FVC
normal

> 2 /year

Several times daily

Some limitationExtremely limited

FEV1 >60%

but < 80%

FEV1/FVC
reduced
5%

FEV1
<60%

FEV1/FVC
reduced
> 5%

Frequency and severity may vary over time for patients in any category
Relative annual risk of excaerbations may be related to FEV

Step 1

Step 2

Step 3

Step 4 or 5

Consider short course of oral steroids

In 2 -6 weeks, evaluate asthma control that is achieved and adjust therapy

21
accordingly

EPR-3, p77,
345

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN

YOUTHS > 12 YEARS OF AGE AND ADULTS

Classification of Asthma Control

Components of Control
Symptoms
Nighttime awakenings

IMPAIRMENT

< 2 days/week
day
< 2/month

Interference with
normal activity
SABA use

> 80% predicted/

personal best

Very Poorly
Controlled
Throughout the
> 4/week
Extremely limited

> 2 days/week

Several times/day

60-80% predicted/
personal best

<60% predicted/
personal best

0/> 20

ATAQ/ACT
Exacerbations
Progressive loss of lung
function
Rx-related adverse effects

0- 1 per year

1-2/16-19

3-4/< 15

2 - 3 per year

> 3 per year

Evaluation requires long-term follow up care

Consider in overall assessment of risk

For Treatment

1-3/week
Some limitation

< 2 days/week

Validated questionnaires

Recommended Action

> 2 days/week

none

FEV1or peak flow

RISK

Not Well
Controlled

Well Controlled

Maintain current
step

Consider step
down if well
controlled at least
3 months

Step up 1 step
Reevaluate in 2 6 weeks

Consider oral
steroids

Step up 1-2
weeks and
22 in 2
reevaluate
weeks

SEVERITY OF ASTHMA EXACERBATION

GINA 2006

23

24

Pharmacologic Treatment
Reliever
- Rapid acting inhaled 2
-

agonist
Anticholinergic
Theophylline
Short- acting oral 2 -- agonist

Controller
- Inhaled glucocorticoid
- Oral antileucotrienes
- inhaled long-acting 2-

agonist
Cromones
( Theophylline )
Oral long-acting 2-agonist
Oral anti-Ig.E
Systemic glucocorticoid
Oral antiallergic
Allergen specific immunotherapy

25

Other drugs
-Other anti inlammation : methotrexate,
gold salt, cyclosporine, anti TNF
- Anti leukotrine : zafirlukast, montelukast
- Anti IgE : omalizumab

EPR-3, p333-343

STEPWISE APPROACH FOR MANAGING ASTHMA

IN YOUTHS > 12 YEARS AND ADULTS
Intermittent
Asthma

Persistent Asthma: Daily Medication

Consult with asthma specialist if step 4 or higher care is required
Consider consultation at step 3
Step up if
needed (check
adherence,
Preferred:
environmental
Step 5
High-dose ICS control and
Preferred:
+ LABA + oral
High dose ICS Corticosteroid comorbidities)
+ LABA

Step 6

Step 4
Step 3
Step 2
Step 1
Preferred:
SABA prn

Preferred:
Medium-dose
ICS OR

Preferred:
Low-dose ICS Low-dose ICS+
either LABA,
Alternative:
LTRA,
LTRA
Theophylline
Cromolyn
Or Zileutin
Theophylline

Preferred:
Medium-dose
ICS+LABA
Alternative:
Medium-dose
ICS+either
LTRA,
Theophlline
Or Zileutin

AND
AND
Consider
Olamizumab
for
patients with
allergies

Consider
Olamizumab
for
patients with
allergies

Assess
Control

Step down if
possible
(asthma well
controlled
for 3
months)

Patient Education and Environmental Control at Each Step

EPR-3, p333-343

27

Terima Kasih