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

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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