Common%20Pitfalls%20in%20Allergy

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Common Pitfalls in Allergy
Prof. Kiat Ruxrungtham, M.D. Head, Division of
Allergy and Clinical ImmunologyDepartment of
MedicineFaculty of MedicineChulalongkorn
University
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Epidemiology of Allergic Diseasesin Thai Children
AllergyChula
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Epidemiology of Allergic Rhinitisin Thai Adults
AllergyChula
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Allergic RhinitisThe General Perception

• Common disease
• Easy to Diagnose
• Easy to treat
• This is partially true

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Common Pitfalls inManaging Allergic Rhinitis

• Underdiagnosis
• Undertreatment

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PAR versus SAR

• Characteristic Seasonal Perennial
• Secretion (watery) / Seromucous,
• Post nasal drip
• Sneezing /
• Obstruction / predominant
• Anosmia 0 / /
• Eye symptoms 0/
• Asthma 0/
• Sinusitis

Van Cauwenberge P et al Allergy 2000
AllergyChula
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Clinical Patterns of PAR

• Classic Type Runner/Sneezer lt10
• Blocker Type 30
• Combined Type 50
• Under diagnosed Type 20
• Chronic cough
• Post-nasal drip, throat clearing symptoms
• Chronic headache
• Shortness of breath or mouth breathing
• Vertigo, Epistaxis
• Problems in sleep, sleepiness during the day
• Snoring
• Hyperventilation syndrome

AllergyChula
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Nasal Blockage
Allergy Chula 1999
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Symptoms of Unrecognized Chronic Nasal Blockage
Chronic Cough
Postnasal drip, /- BHR
Paranasal sinsuses obstruction
Chronic Headache
Postnasal drip
Throat clearing S/S
Unregnized Nasal Blockage
Severe obstruction Mouth breathing Dry mouth,
stomatitis Aggravating asthma
Difficulty in Breathing
Vertigo
ET dysfucntion
Snoring or problem in sleeping
AllergyChula
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Functions of the Nose

• FUNCTION
• Airway upper airway
• Olfaction
• Filtration
• Mucociliary transport
• Airconditioning
• Control of middlle ear pressure

• DYSFUNCTION
• Blockage, mouth breathing
• Anosmia
• Cough, infection
• Cough, infection
• Headache, Sinusitis
• Eustachian tube dysfunction, vertigo

AllergyChula
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The link Noses, Eyes, Ears, and Sinuses
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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 have 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, sinusitis
• Vertigo/dizziness (Eustachian tube dysfunction)
• Post-nasal drip Throat clearing, hoarseness of
  voice

AllergyChula
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Infra-orbital Edema and Discoloration
Allergic Shiner Ocular pruritus Increased
lacrimation
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Mouth Breathing

• Will lead to
• Dry mouth
• Stomatitis
• Dental malocclusion

Indicating Severe Nasal Obstruction
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Phenomenon After Allergen ExposureImmediate,
Late Phase Allergic Reactions and Hyperreactivity
Nasal Symptoms
Nasal Hyperresponsiveness
Late phase
Immediate phase
Antigen
minutes 1 2 3 4 5 6 7 8 9 10 -hrs//------days
Time after Allergen Challenge
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Treatment of allergic rhinitis (ARIA) Allergic
rhinitis and its impact on asthma
gt4 days /wk gt4 wk/yr
lt4 days /wk lt4 wk /yr
Impaired QOL
Moderate severe persistent
Mild persistent
Moderate severe intermittent
Mild intermittent
Intra-nasal steroid
local cromone

Antihistamines oral or local non-sedative
H1-blocker
Intra-nasal decongestant (lt10 days) or oral
decongestant
Allergen and irritant avoidance
immunotherapy
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Treatment of Allergic Rhinitis in Adults
Van Cauwenberge P et al Allergy 2000
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Sites of Action of Corticosteroids
Scadding GK. Allergy 2000 Corrigan CJ. 1999
Epithelium
ICAM-1 PGE2, PGF2a endothelin, NO
Fibroblast
GM-CSF, G-CSF IL-6, RANTES, Eotaxin, etc
SCF
Mo, DC
TNFa, IL-1
Mast cell
T cell Th2
IL-2
IL-3
Myeloid precursor
B Cell
IL-5
IL-4
Th2
IL-3, 5
IL-5
Endothelium
Basophil
VCAM-1 permeability
LTC4, histamine
Eosinophil
AllergyChula
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Meta-analysis of Intranasal Steroids
Favors Steroid
AllergyChula
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Pitfalls in prescribing of the 1st, 2nd and 3rd
generation antihistamines
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First Generation antihistamines and CNS Side
Effects
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Impact of Sedating Antihistamines on Safety and
Productivity
Kay GG, Quig ME. Allergy Asthma Proc 2001

• Sedating antihistamines remains commonly use
• Patients taking these agents frequently dont
  feel sleepy, but their brain function impaired
• Frequently found to be a causal factor in
• Work-related injuries
• fatal traffic accidents
• aviation fatalities

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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
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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

Muether PS Clin Infect Dis 2001 Nov 331483-8
AllergyChula
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Clinical Uses of H1 Antagonists

• Generation 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
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Underdiagnosis and treatment in Rhinosinusitis
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PAR and Rhinosinusitis
Concordance of Allergy and Sinusitis 25-70
Rachelefsky GS et al JACI 1978 Shapiro GG Ped
Infect Dis J 1985
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The Respiratory Tract

• Upper Respiratory Tract
• Structures
• - Nose gt trachea
• - Sinuses, eustachian tubes
• - Ciliated mucosal lining
• Functions
• - Conditioning the air
• - Defense
• Filtration
• Inflammatory reaction
• Immune reaction
• - Smell
• - Voice

The Link

• Lower Respiratory Tract
• Structures
• - Trachea gt alveoli
• Functions
• - Inhalation-exhalation
• - Gas exchange
• - Acid-base balance

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How to Avoid

• Underdiagnosis of AR
• Be aware of non-nasal symptoms or the
  underrecognized symptoms
• Undertreatment of AR
• Chronic moderate/severe cases required nasal
  steroid therapy not antihistamines

PAR is easy to diagnose and easy to treat, if we
really know about it
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ASTHMA

• Common Pitfalls

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Asthma Risk Factors
5q IL4, CD14, B2ADR 6p DRB1, TNF 11q
FCERB1, CC16 16p IL4RA
Environmental
Genetic
19 genes
Aeroallergens Pollutants Triggers
5 in Adults 13 in Children
Clinical Asthma
Thailand
AllergyChula
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Asthma 2002
Airway Inflammation
Smooth Muscle Dysfunction
Airway Remodeling
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Normal
Asthma
Barnes PJ 1999
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Early and Late Phase Allergic Reactions (EPAR and
LPAR)
FEV1
BHR
mins 1 2 3 4 5 6 7 8 9 10 -hrs//------days
Time after Allergen Challenge
Antigen
AllergyChula
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Pitfalls in Asthma Diagnosis

• Over diagnosis
• Shortness of breath is not always caused by
  asthma
• diagnose COPD as asthma
• Under diagnosis
• mild asthma
• nocturnal asthma

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Classification of Severity
CLASSIFY SEVERITY Clinical Features Before
Treatment
Nocturnal Symptoms
FEV1 or PEF
Symptoms
Continuous Limited physical activity
STEP 4 Severe Persistent
lt 60 predicted Variability gt 30
Frequent
60 - 80 predicted Variability gt 30
STEP 3 Moderate Persistent
Daily Attacks affect activity
gt 1 time week
gt 80 predicted Variability 20 - 30
gt 2 times a month
STEP 2 Mild Persistent
gt 1 time a week but lt 1 time a day
lt 1 time a week Asymptomatic and normal PEF
between attacks
STEP 1 Intermittent
gt 80 predicted Variability lt 20
gt 2 times a month
The presence of one feature of severity is
sufficient to place patient in that category.
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Part 4 Long-term Asthma Management GINA
2002 Stepwise Approach to Asthma Therapy - Adults
Outcome Best Possible Results
Outcome Asthma Control

• Controller
• Daily inhaled corticosteroid
• Daily long acting inhaled ß2-agonist
• plus (if needed)

• When asthma is controlled, reduce therapy
• Monitor

• Controller
• Daily inhaled corticosteroid
• Daily long-acting inhaled ß2-agonist

• Controller
• Daily inhaled
• corticosteroid

• Controller
• None

-Theophylline-SR -Leukotriene -Long-acting
inhaled ß2- agonist -Oral corticosteroid
Reliever
Rapid-acting inhaled ß2-agonist prn
STEP 2 Mild Persistent
STEP 3 Moderate Persistent
STEP 4 Severe Persistent
STEP 1 Intermittent
STEP Down
Alternative controller and reliever medications
may be considered (see text).
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The Guidelines not well implemented

• 48 yo female, with chronic persistent asthma for
  3 years
• Recently, she has asthmatic attack everyday
  including at night for 6 months.
• She has been seeking treatment from at least 2
  hospitals. The main prescriptions included
  slow-released theophylline and inhaled b-2
  agonist as needed.
• The severity of her asthma became more and so
  severe that she had to miss several working days
  a week.
• She was eventually forced to leave the job.

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A Case Study (2)

• Baseline PEFR150 and 180 L/min, pre and post b-2
  agonist, respectively.
• After 2 weeks of a short course prednisolone
  followed by inhaled corticosteroids plus inhaled
  long-acting b-2 agonist
• PEFR 360 L/min.
• Her QOL has returned to normal.
• Unfortunately, however, she has lost her job.

AllergyChula
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Asthma A Highly Variable Disease
Infection
AR
Avoidance
Sinusitis
Allergens
Treatment
Airway Inflammation
Adherence
Pollutants
AHR
Variable Asthmatic Symptoms
Genetics
Smooth Muscle Dysfunction
Airway Remodeling
Reversible Airway Obstruction

• Intermittent
• Persistent
• Mild
• Moderate
• Severe
• Irreversibility

Drugs
Psychological
ASA/NSAIDS
Cold air
Excercise
Treating Asthma Individualized and Dynamics
Approach
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Peak Flow Meter
Male gt500 L/min Female gt400 L/min
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Case Study 1 PM, age 44(contd)
Variation of Clinical symptoms and PEF
LABA/ICS
LABA/ICS
Lost FU
Sinusitis
Sinusitis
Sinusitis
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Case Study 2 VN, Male age 60
Known of Asthma for 30 years, non-smoker Variation
of Clinical symptoms and PEF
LABA/ICS
LABA/ICS
Non-adherence worsening AR
Lost FU
Lost FU
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Case Study 3 PK, male age 35
Known of Mild Persistent Asthma and AR since 17
y-o Variation of Clinical symptoms and PEF
Treated Asthma ICS
Started Treating AR only
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Pitfalls in Asthma managementUndertreatment
with inhaled corticosteroids even in developed
countries
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Comparable Asthma Severity in the Study
Populations
AIRE
AIA
Moderate
Moderate
Intermittent
Intermittent
Severity classified by NIH Symptom Severity Index
AllergyChula
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AIRE Anti-inflammatory uses
N2803 in 7 European Countries
AllergyChula
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Patients and Inhaled CorticosteroidsMedicines
Used to Treat Asthma by NIH Severity
IndexInhaled Corticosteroids vs Quick-Relief
Medications
American AIA Study
Base All patients (unweighted N2509).
AllergyChula
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Prevention treatment vs. Quick Relief
Bronchodilators
Asian-Pacifc AIRIAP 2001
AllergyChula
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Comparison of AIRE, AIA and AIRIAP
AIRE N2803 in 7 European Countries AIA N
2509 in USA AIRIAP N3206 in 8 Asian-Pacific
countries
1-2 in 10
1 in 10
3 in 10
AllergyChula
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Comparison of AIRE, AIA and AIRIAP
AIRE N2803 in 7 European Countries AIA
N 2509 in USA AIRIAP N3206 in 8
Asian-Pacific countries
AllergyChula
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Chronic asthmatics and long term outcomes in lung
functionPoorly controlled will lead to
irreversible air way obstruction
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Increased loss of FEV1 in asthma
Male non-smokers
P lt0.001
Height-adjusted FEV1 (litres)
No asthma (n 5480)
Asthma (n 314)
Age (years)
Lange P et al, NEJM 1998
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Airway Remodeling in Asthma

• Cells proliferation smooth muscle cells, mucous
  glands
• Increase matrix protein deposition
• Reticular basement membrane thickening
• Angiogenesis

AllergyChula
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Pathology of Asthma
Asthma
Normal
Mild Asthma
Heavy smoker
metaplasia
Busse W, NEJM 2001
Jeffery , Chest 2000
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Ignorance the link of upper and lower airway

• The United Airway Diseases

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ARIA Guidelines recommendations

• 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

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Co-existence of Asthma and AR
23-Years Follow-up Study of Former Brown
University Students (N738)
21
no
Asthma
no
79
AR
86
306 former students with Allergic Rhinitis
84 former students with Asthma
Greisner WA et al Allergy Asthma Proc 1998
19185-8
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Ragweed Hay Fever with Seasonal
AsthmaUpper-Lower Airway Linked
Placebo
Welsh et al. Mayo Clin Proc 198762125-34
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Mean Changes in FEV1 (Litre)in Treated AR with
Mild Asthma
Morning (AM)
P0.01
lt0.05




Corren J, et al J Allergy Clin Immuno 1997
100781-788
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Ignorance in Environmental Factors
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Environment and Allergy
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Indoor Irritants
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Patient Education for Environmental Control
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Pitfalls in Drug Allergy and Drug Sensitivity
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Highlight on 3 issues

• Penicillin Skin Testing
• Aspirin and NSAIDs sensitivity
• Cross sensitivity with paracetamol

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Penicillin Skin testing

• Gold standard testing (sensitivity gt90)
• Major determinant Pre-Pen (Penicilloyl
  polylysine)
• Minor determinant (MDM)
• Penicillin G
• In Thailand only penicillin G being used for
  testing (sensitivity lt50)

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Aspirin/NSAIDs sensitivityUnderestimated and
management
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Case study Diagnosis

• Aspirin Triad
• Rhinosinusitis with nasal polyps
• Chronic asthma
• ASA sensitivity

More specific diagnosis Aspirin Disease
AllergyChula
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Clinical Features of NSAIDs/Analgesic
SensitivityA Thai Cohort (N31)
Nasoocular angioedema
Angioedema
Asthma
Anaphylactoid
Urticaria angioedema
2 Aspirin disease (ASA Triad)
Ruxrungtham K. 2001
AllergyChula
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NSAIDs/Analgesic SensitivityA Thai Cohort
Type of Agents N31
Ruxrungtham K. 2001
AllergyChula
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NSAIDs/Analgesic SensitivityA Thai
CohortCross-reaction with paracetamol
N25
Ruxrungtham K. 2001
AllergyChula
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A Thai Cohort of NSAIDs/Analgesic Sensitivity

• Hospitalization
• 6/27 (22 )

Ruxrungtham K. 2001
AllergyChula
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A Thai Cohort of NSAIDs/Analgesic Sensitivity
Onset and Duration of Reactions

• Median (Range)
• Onset 20 min (5-360 min)
• Duration 48 hrs (0.5-168 hrs)
• Episodes of event 3 (1-17 times)

Ruxrungtham K. 2001
AllergyChula
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Responses to Standard Treatment(Adrenaline,
antihistamines, steroids)in patients with
angioedema or anaphylactoid reaction

• Total N14
• lt30 min 7 (n1)
• 30-60 min 21 (n3)
• Not response 71 (n10)

Ruxrungtham K. 2001
AllergyChula
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Pitfalls in Urticaria
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Over treat chronic urticaria with systemic
corticosteroids

• Problem of rebound
• Systemic side effects of CS

AllergyChula
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CHRONIC IDIOPATHIC URTICARIA

• TREATMENT
• Antihistamines for Chronic Idiopathic urticaria
• - Non-sedating
• - Sedating

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CHRONIC IDIOPATHIC URTICARIA
TREATMENT Options If single drug therapy
ineffective Combinations - First
second-generation antihistamines - H1
antihistamine H2-blocking agent
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Pitfalls in Anaphylaxis
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Mediators of Mast Cells and Basophils
Secondary Mediators
Primary Mediators

• Prostaglandins
• Leukotrienes
• PAF
• Histamine RFs
• IL-3, 4, 5, 6, 7, 8
• GM-CSF, TNFa
• Chemokines -MCP1, MIP1
• Oxygen radicals

• Histamine
• Tryptase
• Chymotryptase
• Heparin/Chondroitin
• Kininogenase
• Chemotactic Factors

AllergyChula
Sim TC, Grant JA 1996
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Improper treatment

• Use antihistamines and/or dexmethasone as first
  choice but not adrenaline
• Standard of care
• Adrenaline, Adrenaline, Adrenaline IM !!!!
• Plus
• Antihistamines
• Dexamethasone
• H2 blocker, etc

AllergyChula
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Thank You