common pitfalls in allergy prof. kiat ruxrungtham, m.d. head, division of allergy and clinical...
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Common Pitfalls Common Pitfalls in Allergyin Allergy
Prof. Kiat Ruxrungtham, M.D.Prof. Kiat Ruxrungtham, M.D.
Head, Head, Division of Allergy and Clinical ImmunologyDivision of Allergy and Clinical ImmunologyDepartment of MedicineDepartment of Medicine
Faculty of MedicineFaculty of MedicineChulalongkorn UniversityChulalongkorn University
Epidemiology of Allergic Diseasesin Thai Children
17.9
4.2
40
13 13
0
5
10
15
2025
30
35
40
45
AtopicDermatitis
AllergicRhinitis
Asthma
Pre
vale
nce
(%
)
1990 1995
AllergyChula
Epidemiology of Allergic Rhinitisin Thai Adults
2320
22
0
5
10
15
20
25
Pre
vale
nce
(%
)
1975 Tuchinda
1983Debhakam
1995 Bunnag
AllergyChula
Allergic Rhinitis: Allergic Rhinitis: The General Perception The General Perception
• Common diseaseCommon disease• Easy to DiagnoseEasy to Diagnose• Easy to treatEasy to treat
““This is partially true”This is partially true”
Common Pitfalls in Common Pitfalls in Managing Allergic Rhinitis Managing Allergic Rhinitis
• UnderdiagnosisUnderdiagnosis
• UndertreatmentUndertreatment
PAR versus SARPAR versus SARCharacteristicCharacteristic SeasonalSeasonal PerennialPerennial
SecretionSecretion +++ +++ (watery)(watery) + /++ + /++ Seromucous,Seromucous,
Post nasal dripPost nasal drip
SneezingSneezing ++++++ + /+++ /++
ObstructionObstruction + /+++ /++ ++++++ predominant predominant
AnosmiaAnosmia 0 /+0 /+ +/ +++/ ++
Eye symptomsEye symptoms ++++++ 0/+0/+
AsthmaAsthma 0/++0/++ ++++
SinusitisSinusitis ++ ++++
AllergyChula Van Cauwenberge P et al Allergy 2000
Clinical Patterns of PARClinical Patterns of PAR Classic Type: Runner/Sneezer Classic Type: Runner/Sneezer <10%<10% Blocker TypeBlocker Type 30 %30 % Combined TypeCombined Type 50 %50 % Under diagnosed TypeUnder diagnosed Type: : ~20 %~20 %
Chronic coughChronic coughPost-nasal drip, throat clearing symptomsPost-nasal drip, throat clearing symptomsChronic headacheChronic headacheShortness of breath or mouth breathingShortness of breath or mouth breathingVertigo, EpistaxisVertigo, EpistaxisProblems in sleep, sleepiness during the dayProblems in sleep, sleepiness during the daySnoringSnoringHyperventilation syndromeHyperventilation syndrome
AllergyChula
Nasal NasalBlockageBlockage
Allergy Chula 1999
UnregnizedUnregnizedNasalNasal
BlockageBlockage
Throat clearing S/SThroat clearing S/SThroat clearing S/SThroat clearing S/S
Chronic HeadacheChronic HeadacheChronic HeadacheChronic Headache
VertigoVertigoVertigoVertigo
Difficulty in BreathingDifficulty in BreathingDifficulty in BreathingDifficulty in Breathing
Snoring or problem in sleeping Snoring or problem in sleeping Snoring or problem in sleeping Snoring or problem in sleeping
Paranasal sinsuses obstParanasal sinsuses obstructionruction
ET dysfucntionET dysfucntion
AllergyChula
Symptoms of Unrecognized ChroSymptoms of Unrecognized Chronic Nasal Blockagenic Nasal Blockage
Chronic CoughChronic CoughChronic CoughChronic Cough Postnasal drip, +/- BHRPostnasal drip, +/- BHR
Severe obstructionSevere obstructionMouth breathingMouth breathingDry mouth, stomatitisDry mouth, stomatitisAggravating asthmaAggravating asthma
Postnasal dripPostnasal drip
Functions of the NoseFunctions of the NoseFUNCTION Airway: upper airw
ay Olfaction Filtration Mucociliary transp
ort Airconditioning Control of middlle
ear pressure
DYSFUNCTIONDYSFUNCTION• Blockage, mouth brBlockage, mouth br
eathingeathing• AnosmiaAnosmia• Cough, infectionCough, infection• Cough, infectionCough, infection
• Headache, Sinusitis Headache, Sinusitis • Eustachian tube dyEustachian tube dy
sfunction, vertigosfunction, vertigo
AllergyChula
The linkThe link : :Noses, Eyes, Ears, and SinusesNoses, Eyes, Ears, and Sinuses
Common Pitfalls in Diagnosis of RhinitisCommonly Unrecognised Symptoms
Chronic cough (including nocturnal cough) The most common cause is rhinitis, not bronchitis Mechanisms: post-nasal drip (PNDS), rhinitis with BHR
Shortness of Breath (requires mouth breathing) “Inadequate air”, relieve by mouthing breathing, some may h
ave “carpo-pedal spasm” due to hyperventilation ~ can be miss-Dx as anxeity neurosis . Mechanism: Severe nasal obstruction
Chronic headache (frontal, periorbital, paranasal) Rhinitis +/- sinusitis is also a common cause of headache Mechanisms: severe nasal congestion, sinus congestion, sinusi
tisVertigo/dizziness (Eustachian tube dysfunction)Post-nasal drip Throat clearing, hoarseness of voice
AllergyChula
Infra-orbital Edema and Discoloration
Allergic ShinerOcular pruritus
Increased lacrimation
Mouth Breathing
Indicating Severe Nasal Obstruction
Will lead to• Dry mouth• Stomatitis• Dental malocclusion
Phenomenon After Allergen Exposure:Immediate, Late Phase Allergic Reactions and
Hyperreactivity
minutes 1 2 3 4 5 6 7 8 9 10 -hrs//------days
Time after Allergen Challenge
Nasal SymptomsNasal
HyperresponsivenessImmediatephase
Latephase
Antigen
Impaired Impaired QOLQOL
Treatment of allergic rhinitis (ARIA)Treatment of allergic rhinitis (ARIA)Allergic rhinitis and its impact on asthma
Mildintermittent
MildpersistentModerate
severeintermittent
Moderatesevere
persistent
Allergen and irritant avoidance
immunotherapyimmunotherapy
Intra-nasal decongestant (<10 days) or oral decongestant
local cromone Intra-nasal steroid
Antihistamines : oral or local non-sedative H1-blocker
<4 days /wk<4 wk /yr
>4 days /wk>4 wk/yr
Treatment of Allergic Rhinitis in AdultsTreatment of Allergic Rhinitis in Adults
Van Cauwenberge P et al Allergy 2000
Drug Itch/sneezing
Rhinorrhea Blockage Anosmia
Antihistamines +++ ++ + -Nasal CS +++ +++ ++/+++ +/++
Oral CS +++ +++ +++ ++/+++
Nasaldecongestants
- - +++ -
Ipratropiumbromide
- +++ - -
Sodiumcromoclycate
+ + + -
Sites of Action of Corticosteroids
GM-CSF, G-CSFIL-6, RANTES,
Eotaxin, etc
T cellT cellTh2Th2
B CellB Cell
Mast cell
Eosinophil
Basophil
Fibroblast
IL-2
IL-5
TNF, IL-1
SCF
Myeloidprecursor
Th2Th2
IL-5 IL-4
IL-3, 5
IL-3
Scadding GK. Allergy 2000Corrigan CJ. 1999
AllergyChula
ICAM-1PGE2, PGF2endothelin, NO
Epithelium
EndotheliumVCAM-1permeability
Mo, DC
LTC4, histamine
Meta-analysis of Intranasal Steroids
AllergyChula
Favors Steroid
Pitfalls in prescribing of the 1st, 2nd and 3rd generation a
ntihistamines
First Generation antihistamines anFirst Generation antihistamines and CNS Side Effectsd CNS Side Effects
Impact of Sedating Antihistamines on Safety and Productivity
• Sedating antihistamines remains commonly use
• Patients taking these agents frequently don’t feel sleepy, but their brain function impaired
• Frequently found to be a causal factor in:– Work-related injuries
– fatal traffic accidents
– aviation fatalities
Kay GG, Quig ME. Allergy Asthma Proc 2001
Antihistamines in Elderly
• Drawsiness, fatigue and may increase risk falling or accident
• The first-generation H1 antagonist should be avoided in patient with glaucoma
• The first-generation H1 antagonist should also be avoided in patient with prostrate hypertrophy
• Be aware of cardiotoxic risk; terfenadine, astemizole should be used with caution
AllergyChula
Common Cold: Antihistamines ?
• Only 1st generation but not the 2nd generation antihistamines is effective on treating clinical symptoms and signs of “COMMON COLD”
• Confirmed both in the natural or experimental “COLDs”
AllergyChulaMuether PS Clin Infect Dis 2001 Nov; 33:1483-8
Clinical Uses of H1 AntagonistsGeneration of Antihistamines
Clinical First Second and Third
Allergic Rhinitis ++ ++ (better compliance)
Urticaria ++ ++ (better compliance)
Atopic dermatitis ++/+++ ++ (better compliance)
Asthma -
-/++ (Meta-analysis= NS)URI/NAR ++ -
Itching dermatosis ++/+++ ++
Anti-motion sickness ++ -
Antiemetic ++ -
Appetite stimulation ++ - (+ for astemizole)
Insomnia ++ -
AllergyChula
Underdiagnosis and treatment in Rhinosinusitis
PAR and Rhinosinusitis PAR and RhinosinusitisConcordance of Aller
gy and Sinusitis25-70 %
Rachelefsky GS et al JACI 1978Shapiro GG Ped Infect Dis J 1985
The Respiratory TractThe Respiratory TractUpper Respiratory Tract
Structures - Nose —> trachea - Sinuses, eustachian tubes - Ciliated mucosal lining
Functions - Conditioning the air - Defense
FiltrationInflammatory reactionImmune reaction
- Smell - Voice
Lower Respiratory Tract
Structures - Trachea —> alveoli
Functions - Inhalation-exhalation - Gas exchange - Acid-base balance
The Link
How to Avoid How to Avoid• Underdiagnosis of ARUnderdiagnosis of AR
– Be aware of non-nasal symptoms or the underrecognized symptomsBe aware of non-nasal symptoms or the underrecognized symptoms
• Undertreatment of ARUndertreatment of AR– Chronic moderate/severe cases required nasal steroid therapy not antihistamineChronic moderate/severe cases required nasal steroid therapy not antihistamine
ss
PAR is easy to diagnose and easy to treat, PAR is easy to diagnose and easy to treat, if we really know about itif we really know about it
AASTHMASTHMA
Common Pitfalls
Asthma: Risk Factors
Environmental Genetic
~5 % in Adults13 % in Children
Clinical Asthma
AeroallergensPollutantsTriggers
ThailandThailand
~19 genes
5q: IL4, CD14, B2ADR
6p: DRB1, TNF
11q: FCERB1, CC16
16p: IL4RA
AllergyChula
Asthma 2002Asthma 2002AirwayAirway
Inflammation Inflammation
SmoothSmooth Muscle Muscle
DysfunctionDysfunction
AirwayAirway Remodeling Remodeling
AsthmaNormal
Barnes PJ 1999
Early and Late Phase Allergic Reactions (EPAR and LPAR)
mins 1 2 3 4 5 6 7 8 9 10 -hrs//------daysTime after Allergen Challenge
FEV1
BHR
AllergyChulaAllergyChulaAntigenAntigen
Pitfalls in Asthma Diagnosis
• Over diagnosis– Shortness of breath is not always caus
ed by asthma– diagnose COPD as asthma
• Under diagnosis–mild asthma–nocturnal asthma
Classification of SeverityClassification of Severity
CLASSIFY SEVERITYClinical Features Before Treatment
SymptomsSymptoms NocturnalNocturnalSymptomsSymptoms
FEVFEV1 1 or PEFor PEF
STEP 4Severe
Persistent
STEP 3
Moderate Persistent
STEP 2Mild
Persistent
STEP 1
Intermittent
ContinuousContinuous
Limited physical Limited physical activityactivity
DailyDailyAttacks affect activityAttacks affect activity
> 1 time a week > 1 time a week but < 1 time a day but < 1 time a day
< 1 time a week< 1 time a week
Asymptomatic Asymptomatic and normal PEF and normal PEF between attacksbetween attacks
FrequentFrequent
> 1 time week> 1 time week
> 2 times a month> 2 times a month
2 times a 2 times a monthmonth2 times a 2 times a monthmonth
60% predicted60% predicted
Variability > 30%Variability > 30%
60 - 80% predicted 60 - 80% predicted
Variability > 30%Variability > 30%
80% predicted80% predicted
Variability 20 - 30%Variability 20 - 30%
80% predicted80% predicted
Variability < 20%Variability < 20%
The presence of one feature of severity is sufficient to place patient in that category.
Part 4: Long-term Asthma Management : GINA 2002
Stepwise Approach to Asthma Therapy - Adults
Reliever: Rapid-acting inhaled β2-agonist prn
Controller: Daily inhaledcorticosteroid
Controller: Daily inhaled
corticosteroid Daily long-
acting inhaled β2-agonist
Controller: Daily inhaled
corticosteroid Daily long –
acting inhaled β2-agonist
plus (if needed)
When asthma is controlled, reduce therapy
Monitor
STEP 1:Intermittent
STEP 2:Mild
Persistent
STEP 3: Moderate Persistent
STEP 4:Severe
Persistent
STEP Down
Outcome: Asthma Control Outcome: Best Possible Results
Alternative controller and reliever medications may be considered (see text).
Controller:None
-Theophylline-SR -Leukotriene -Long-acting inhaled β2- agonist -Oral corticosteroid
The Guidelines : not well implemented
48 yo female, 48 yo female, with chronic persistent aswith chronic persistent asthma for 3 yearsthma for 3 years
• Recently, she has asthmatic attack everyday includRecently, she has asthmatic attack everyday including at night for 6 months.ing at night for 6 months.
• She has been seeking treatment from at least 2 hosShe has been seeking treatment from at least 2 hospitals. The main prescriptions included pitals. The main prescriptions included slow-releasslow-released theophylline and inhaled b-2 agonisted theophylline and inhaled b-2 agonist as needed. as needed.
• The severity of her asthma became more and so seThe severity of her asthma became more and so severe that she had to miss several working days a wvere that she had to miss several working days a week. eek.
• She was eventually forced to leave the job. She was eventually forced to leave the job.
A Case Study (2)
• Baseline Baseline PEFR=150 and 180 L/minPEFR=150 and 180 L/min, pre and post b, pre and post b-2 agonist, respectively. -2 agonist, respectively.
• After 2 weeks of a short course prednisolone follAfter 2 weeks of a short course prednisolone followed by inhaled corticosteroids plus inhaled lonowed by inhaled corticosteroids plus inhaled long-acting b-2 agonist g-acting b-2 agonist
PEFR = 360 L/min. PEFR = 360 L/min. • Her QOL has returned to normal. Her QOL has returned to normal. • Unfortunately, however, she has lost her job.Unfortunately, however, she has lost her job.
AllergyChula
Asthma: A Highly Variable DiseaseAsthma: A Highly Variable Disease
AirwayAirway Inflammation Inflammation
SmoothSmooth Muscle Muscle
DysfunctionDysfunction
AirwayAirway Remodeling Remodeling
Infection
AllergensAllergens
ARAR
PollutantsPollutants
SinusitisSinusitis
Cold airCold air
ExcerciseExcercise
DrugsDrugs
ASA/NSAIDSASA/NSAIDSPsychologicalPsychological
Variable AsthmaticVariable AsthmaticSymptomsSymptoms
• IntermittentIntermittent• PersistentPersistent
• MildMild• ModerateModerate• SevereSevere
• IrreversibilityIrreversibility
TreatmentTreatment
AdherenceAdherence
AvoidanceAvoidance
GeneticsGenetics
AHRAHR
ReversibleReversibleAirwayAirway
ObstructionObstruction
Treating Asthma: Individualized and Dynamics ApproachTreating Asthma: Individualized and Dynamics Approach
Peak Flow Meter
Male : >500 L/minFemale : >400 L/min
Case Study 1Case Study 1: PM, age 44(cont’d): PM, age 44(cont’d)
250
410
230
400
240
120
410
250
0
100
200
300
400
500
Mar-97
Jun-00
July-00
Aug-00
Nov-00
Jan-01
May-01
Jun-01
Peak
flow
rate
(L/m
in)
PEF
Variation of Clinical symptoms and PEFVariation of Clinical symptoms and PEF
SinusitisSinusitis SinusitisSinusitis SinusitisSinusitisLost FULost FU
LABA/ICSLABA/ICS LABA/ICSLABA/ICS
Case Study 2Case Study 2: VN, Male age 60: VN, Male age 60
370
250300 290
230
370
280240
320
230
300
360
300 320390
230
0
100
200
300
400
500
Jan-9
9
Jan-9
9
Mar
-99
May
-99
Aug-99
Dec-9
9
Feb-0
0
Apr-00
May
-00
Oct-0
0
Nov-00
Dec-0
0
Jan-0
1
Apr-01
Jun-0
1
July-
01
Peak
flow
rate
(L/m
in) PEF
Known of Asthma for 30 years, non-smokerKnown of Asthma for 30 years, non-smokerVariation of Clinical symptoms and PEFVariation of Clinical symptoms and PEF
LABA/ICSLABA/ICS LABA/ICSLABA/ICS
Lost FULost FU Lost FULost FU Non-adherenceNon-adherenceworsening ARworsening AR
Case Study 3Case Study 3: PK, male age 35: PK, male age 35
450
620
730690 710
650720 690
650680
350
0
200
400
600
800
Pe
ak
flo
w r
ate
(L
/min
) PEF
Known of Mild Persistent Known of Mild Persistent Asthma and ARAsthma and AR since 17 y-o since 17 y-oVariation of Clinical symptoms and PEFVariation of Clinical symptoms and PEF
Started TreatingStarted TreatingAR onlyAR only
Treated AsthmaTreated Asthma ICSICS
Pitfalls in Asthma managementPitfalls in Asthma management
Undertreatment with inhaled corticosteroids even in developed
countries
Comparable Asthma Severity Comparable Asthma Severity in the Study Populationsin the Study Populations
Europe
Mild 19%
43%
19%
Severe
19%
US
Severe19%
19%
Mild 22%
40%
Severity classified by NIH Symptom Severity Index
ModerateModerate
AllergyChula
AIRE AIA
IntermittentIntermittent
AIREAIRE : Anti-inflammatory uses : Anti-inflammatory uses
23 26 26 30
63
7681
75
0
20
40
60
80
100
AIRE Total SeverePersistent
ModeratePersistent
MildPersistent
% o
f Pat
ient
s
Anti-inflammatory Reliever
N=2803 in 7 European Countries
AllergyChula
Patients and Inhaled CorticosteroidsMedicines Used to Treat Asthma by NIH Severity Index:
Inhaled Corticosteroids vs Quick-Relief Medications
1520 18 16
10
61
80 78
70
40
0
10
20
30
40
50
60
70
80
Total SeverePersistent
ModeratePersistent
MildPersistent
MildIntermittent
% o
f P
atie
nts
Inhaled CS Reliever
Base: All patients (unweighted N=2509).Base: All patients (unweighted N=2509).
American: AIA Study
AllergyChula
Prevention treatment vs. Quick Relief Bronchodilators
41%45%
51%
39% 38%
11%11%13% 15% 18%
0%
10%
20%
30%
40%
50%
60%
AIRIAP Total SeverePersistent
ModeratePersistent
MildPersistent
MildIntermittent
Preventative Treatment Quick Relief Bronchodilators
Asian-Pacifc: AIRIAP 2001
AllergyChula
Comparison of AIRE, AIA and AIRIAPComparison of AIRE, AIA and AIRIAP
25
7
10
29
9
23
30
15
19
0 20 40 60 80 100
Emergent visit
Hospitalized
Emergencyroom visit
Survey Findings (%)
AIRIAP
AIA
AIRE
AllergyChula
AIRE : N=2803 in 7 European Countries
AIA : N= 2509 in USA
AIRIAP: N=3206 in 8 Asian-Pacific countries
1-2 in 10
1 in 10
3 in 10
Comparison of AIRE, AIA and AIRIAPComparison of AIRE, AIA and AIRIAP
63
17
43
64
25
49
52
26
36
0 20 40 60 80 100
Activity limited
Missed work
Missed school
Survey Findings (%)
AIRIAP
AIA
AIRE
AllergyChula
AIRE : N=2803 in 7 European Countries
AIA : N= 2509 in USA
AIRIAP: N=3206 in 8 Asian-Pacific countries
Chronic asthmatics and long term outcomes in lung function
Poorly controlled will lead to irreversible air way obstruction
Increased loss of FEV1 in asthma
Lange P et al, NEJM 1998
No asthma (n= 5480)
Asthma (n= 314)
Age (years)
He
igh
t-ad
just
ed
FE
V1 (
litre
s) Male non-smokers
P <0.001
Airway Remodeling in Asthma
Cells proliferation: smooth muscle cells, mucous glands
Increase matrix protein deposition Reticular basement membrane thic
kening Angiogenesis
AllergyChula
Pathology of AsthmaPathology of AsthmaNormal
Mild Asthma
Busse W, NEJM 2001 Jeffery , Chest 2000
Asthma
Heavy smoker
metaplasia
Ignorance the link of upper and lower airway
The United Airway Diseases
• Patients with persistent allergic rhinitis should be evaluated for asthma by history, chest examination and, if possible and when necessary, assessment of airflow obstruction before and after bronchodilator
• History and examination of the upper respiratory tract for allergic rhinitis should be performed in patients with asthma
• A strategy should combine the treatment of both the upper and lower airway disease in terms of efficacy and safety
ARIA Guidelines recommendations
Co-existence of Asthma and ARCo-existence of Asthma and AR
306 former students 306 former students with with Allergic RhinitisAllergic Rhinitis
84 former students 84 former students with with AsthmaAsthma
AsthmaAsthma
nono ARAR
nono
Greisner WA et al Allergy Asthma Proc 1998; 19:185-8
86 %86 %79 %79 %
21 %21 %
23-Years Follow-up Study of Former Brown University Students (N=738)
Ragweed Hay Fever with Seasonal AsthmaRagweed Hay Fever with Seasonal AsthmaUpper-Lower Airway Linked
PlaceboPlacebo
Welsh et al. Mayo Clin Proc 1987;62:125-34
Mean Changes in FEV1 (Litre)Mean Changes in FEV1 (Litre)in Treated AR with Mild Asthmain Treated AR with Mild Asthma
0
0.05
0.1
0.15
0.2
0.25
Wk 1 Wk 2 Wk 4 Wk 6
Loratadine/Pseudoephredine Placebo
Corren J, et al J Allergy Clin Immuno 1997; Corren J, et al J Allergy Clin Immuno 1997; 100:781-788100:781-788
Morning (AM)
*
*
* P=0.01
***<0.05
Ignorance in Ignorance in Environmental FactorsEnvironmental Factors
Environment and Allergy
ตั�วไร่�ฝุ่นตั�วไร่�ฝุ่น ที่ �กั�กัฝุ่นที่ �กั�กัฝุ่นเกัสร่เกัสร่
ฝุ่นบ้�านฝุ่นบ้�าน เชื้��อร่าเชื้��อร่าฝุ่นบ้ �นอนฝุ่นบ้ �นอน ส�ตัว�ส�ตัว�เลี้ �ยงเลี้ �ยง
อาหาร่อาหาร่
สิ่��งเหล่านี้� มี�อยู่�รอบตั�วเรา มี�ทั้� งในี้บ�านี้แล่ะนี้อกบ�านี้ แตัมี�หล่ายู่อยู่างทั้��เราหล่�กเล่��ยู่งได้� หากเราร� �ว�ธี�ทั้��ถู�กตั�อง
Indoor IrritantsIndoor Irritants
Patient Educationfor
EnvironmentalControl
Pitfalls in Drug Allergy and Drug Sensitivity
Highlight on 3 issues
• Penicillin Skin TestingPenicillin Skin Testing
• Aspirin and NSAIDs sensitivityAspirin and NSAIDs sensitivity
• Cross sensitivity with paracetamol Cross sensitivity with paracetamol
Penicillin Skin testing
• Gold standard testing: (sensitivity >90%)– Major determinant: Pre-Pen (Penicilloyl pol
ylysine)– Minor determinant (MDM)– Penicillin G
• In Thailand: only penicillin G being used for testing (sensitivity <50%)
Aspirin/NSAIDs sensitivity
Underestimated and management
Case study: Diagnosis
Aspirin TriadAspirin Triad Rhinosinusitis witRhinosinusitis wit
h nasal polypsh nasal polyps Chronic asthmaChronic asthma ASA sensitivity ASA sensitivity
AllergyChula
More specific diagnosisMore specific diagnosis: : Aspirin DiseaseAspirin Disease
Clinical Features of NSAIDs/Analgesic Sensitivity
A Thai Cohort (N=31)
3% 3%
10%
10%
17%
13% 44%
Angioedema
Anaphylactoid
Urticaria/angioedema
Asthma with others
Naso-ocular withangioedemaUrticaria
Rash
AngioedemaAngioedema
AnaphylactoidAnaphylactoid
2 Aspirin disease (ASA Triad)2 Aspirin disease (ASA Triad)
Asthma+
Urticaria+angioedema
Nasoocular+angioedema
Ruxrungtham K. 2001
AllergyChula
NSAIDs/Analgesic SensitivityA Thai Cohort
Mixed32%
Dipyrone7%
Paracetamol21%
NSAIDs14%
ASA26%
ASA
NSAIDs
Dipyrone
Paracetamol
Mixed
Ruxrungtham K. 2001
AllergyChula
Type of Agents N=31
NSAIDs/Analgesic SensitivityA Thai Cohort
Cross-reaction with paracetamol
Yes40%No
56%
4% Yes
No
Notknown
N=25
Ruxrungtham K. 2001
AllergyChula
Hospitalization 6/27 (22 %)
Ruxrungtham K. 2001
AllergyChula
A Thai Cohort of NSAIDs/Analgesic Sensitivity
A Thai Cohort of NSAIDs/Analgesic Sensitivity
MedianMedian (Range) (Range) OnsetOnset: : 20 min 20 min (5-360 min)(5-360 min) DurationDuration: : 48 hrs 48 hrs (0.5-168 hrs)(0.5-168 hrs) Episodes of eventEpisodes of event: : 3 3 (1-17 times)(1-17 times)
Onset and Duration of Reactions
Ruxrungtham K. 2001
AllergyChula
Responses to Standard Treatment(Adrenaline, antihistamines, steroids)
in patients with angioedema or anaphylactoid reaction
Total N=14 <30 min : 7 % (n=1) 30-60 min : 21 % (n=3) Not response : 71 % (n=10)
Ruxrungtham K. 2001
AllergyChula
Pitfalls in Urticaria
AllergyChula
Over treat chronic urticaria with systemic corticosteroids
• Problem of rebound
• Systemic side effects of CS
CHRONIC IDIOPATHIC URTICARIACHRONIC IDIOPATHIC URTICARIA
TREATMENTTREATMENT• Antihistamines for Chronic Antihistamines for Chronic IdiopathicIdiopathic urticariaurticaria- Non-sedating- Non-sedating- Sedating- Sedating
CHRONIC IDIOPATHIC URTICARIACHRONIC IDIOPATHIC URTICARIA
TREATMENT Options:TREATMENT Options: If single drug If single drug
therapy ineffectivetherapy ineffective
CombinationsCombinations
- First + second-generation - First + second-generation
antihistaminesantihistamines
- H- H11 antihistamine + H antihistamine + H22-blocking agent-blocking agent
Pitfalls in Anaphylaxis
Mediators of Mast Cells and BasophilsMediators of Mast Cells and Basophils
Histamine
Tryptase
Chymotryptase
Heparin/Chondroitin
Kininogenase
Chemotactic Factors
ProstaglandinsLeukotrienes
PAFHistamine RFs
IL-3, 4, 5, 6, 7, 8GM-CSF, TNF
Chemokines -MCP1, MIP1
Oxygen radicals
Primary MediatorsPrimary Mediators Secondary MediatorsSecondary Mediators
Sim TC, Grant JA 1996 AllergyChula
AllergyChula
Improper treatment• Use antihistamines and/or dexmethasone as fi
rst choice but not adrenaline• Standard of care:
– Adrenaline, Adrenaline, Adrenaline IM !!!! Plus:– Antihistamines– Dexamethasone– H2 blocker, etc
Thank You