Transcript Allergic rhinitis 1014–New R

Allergic Rhinitis
高雄醫學大學附設醫院 耳鼻喉科
高雄市立小港醫院(委託高雄醫學大學經營) 耳鼻喉科
王凌峰
ARIA guideline
2001, Allergic Rhinitis and its Impact on
Asthma in collaboration with the WHO
To update clinician’s knowledge of allergic rhinitis
To highlight the impact of allergic rhinitis on asthma
To provide an evidence-based approach to diagnosis
To provide an evidence-based approach to treatment
To provide a stepwise approach to the management of
the disease
2001. 10
Definition
Rhinitis: a state of persistent nasal symptoms
 allergy, infection, structural anomalies in the
nose, hormone, drug….
Allergic rhinitis: a symptomatic disorder of the
nose, induced after allergen exposure, by an IgEmediated inflammation of the nasal membranes
1. Dykewicz. J Allergy Clin Immunol. 2003;111(suppl):S520.
2. Bauchau and Durham. Eur Respir J. 2004;24:758.
3. Linneberg. BMJ. 2005:331.352.
Allergy and Atopy
“Allergy“： 1906 von Pirquet
Antigens induce changes in reactivity in both：
protective immunity and hypersensitivity reactions.
apply to the "uncommitted" biologic response, immunity
(a beneficial effect) or allergic disease (a harmful effect).
Allergy is an acquired potential to develop
hypersensitivity reactions to a normally innocuous
substance and is mediated by immunological mechanisms
(but not exclusively IgE).
Allergy and Atopy
“Atopy”：Greek atopos, meaning out of place
often used to describe IgE-mediated diseases.
personal or familial (genetic) tendency to produce IgE
antibodies in response to low doses of allergens, usually
proteins, and to develop ‘classic’ allergic diseases such
as asthma, rhinoconjunctivitis or eczemal dermatitis.
Nonatopic allergic diseases：
★ IgE-independent mechanisms： ie. contact
dermatitis and hypersensitivity pneumonitis
★ IgE responses to bee venom and drugs are not more
frequent in atopic families.
Epidemiology
Prevalence
Overall--10-25%, and increasing
In Taiwan: 20~30% of child
Hereditism
One parent (+)--29%(~40%)
Both parents (+)--47%(~75%)
Age
11-20 y/o
Triggers
Allergens
Aeroallergens
Indoor
Mites, dust, animals & insects
Outdoor
Pollens & moulds
Occupational rhinitis
Latex allergy
Triggers
Pollutants
Indoor air pollutants
>80% of time indoors
Tobacco smoke
Outdoor air pollutants
Automobile--ozone, oxides of nitrogen & sulphur
dioxide
Triggers
Aspirin (& NSAIDs)
Classification
Seasonal
a. some specific season
b. usually outdoor allergen: pollen, molds…
c. rhinorrhea
Perennial
a. throughout the year
b. usually indoor allergen: house dust, mite…
c. nasal obstruction
Occupational
Classification
Intermittent
Symptoms
Persistent
Symptoms
< 4 days per week
or < 4 weeks
Mild
normal sleep
normal daily activities, sport,
leisure
normal work and school
no troublesome symptoms
> 4 days per week
and > 4weeks
Moderate-Severe
one or more items
abnormal sleep
impairment of daily activities,
sport, leisure
problems caused at work or
school
troublesome symptoms
Symptoms & signs
Symptoms
a. rhinorrhea
b. nasal obstruction
c. nasal itching
d. sneezing
e. itchy or watery eye
f. anosmia, nasal pain, headache
Symptoms & Signs
Signs
a. Pale bluish turinates, frequently with edema
“ hyperemia” --- acute infection or over use of topical
medication
b. Middle ear involvement: OME, eardrum retraction
c. Prolonged mouth breathing (adenoid face)
- Elevation of the upper lip
- Over-bite
- High arched palate
Symptoms & Signs
Signs
d. Facial signs
- “Allergic shiner”
- Horizontal creases under the eyes (Dannie-Morgan line)
- “Allergic salute”
- supratip nasal crease
e. Nasal polyposis
f. signs of asthma, atopic dermatitis…
Nasal
salute
Nasal
itching
Adenoid
face
Allergic
shiners
Skoner D, Urbach A, Fireman P. In: Atlas of Pediatric Physical Diagnosis. 3rd ed. 1997
Pathophysiology
IgE Ab mediated, type I immune response
Sensitization
IgE adhered to mast cells & basophils
Preformed (stored) mediators
Histamine, kinins, proteases, platelet activating factor,
heparin
Newly formed mediators
Prostaglandin, interleukins, leukotriene, cytokines
Pathogenesis
Early-phase (immediate) response
- The onset of sneezing & itching may occur as
early as ~30 sec, and usually peaks within
minutes
- Mast cell: the predominant cell
- Histamine, leukotriene, prostaglandin, bradykinin,
PAF (platelet activating factor)
- Itching, sneezing, watery rhinorrhea, vasodilation
(nasal congestion)
Pathophysiology
Late/delayed phase response
50%
4~12 Hours
Priming
Eosinophils infiltration
TH2-type cytokines: IL-4, 5 & GM-CSF
Other mediators: IL-8, RANTES, eotaxins & MCPs
Nasal blockage, and nasal hyper-reactivity
Allergy is more than histamine
Minimal persistent inflammation
“The united airways concept”
(One airway, one disease)
Link between rhinitis and other conditions
Co-Morbidities --Asthma
Asthma p’t--60-78% allergic rhinitis
Allergic rhinitis p’t--19-38% asthma
Bronchial challenge--nasal inflammation
Nasal challenge--bronchial inflammation
Co-Morbidities --Asthma
Mechanism
Nasal-bronchial reflex
Mouth breathing caused by N-O
Pulmonary aspiration of nasal contents
Diagnosis
Lung function test
The reversibility of airflow obstruction
Co-Morbidities --Asthma
Medications
Both effective--intranasal steroids, antihistamines,
antileukotrienes
Optimal management of rhinitis may improve
coexisting asthma
Diagnosis
Routine tests
- A typical history
- General ENT examination
i. Nose: boggy turbinate
ii. Ear: OME, eardrum retraction
iii. Eye: injected conjunctivitis with watery discharge, allergic
shiner
iv. Face: adenoid face, supratip nasal crease, Dannie-Morgan fold
- Endoscope: rigid, flexible
Diagnosis
Allergic test
- Skin test
- Serum specific IgE
Nasal cytology
- Eosinophilia >20%
Nasal challenge
- Allergen, aspirin, lysine
Radiology
- usually unnecessary
- X-ray, CT scan
Diagnosis
Optional tests (mainly for research)
- Nasal biopsy
- Nasal swab for bacteriology
- Mucociliary function
i. Nasal mucociliary clearance, ciliary beat frequency,
electronmicroscope
ii. Nasal inspiratory peak flow (NIPF), rhinomanometry,
acoutic rhinometry
iii. Olfaction, nitric oxide measurement
iv. Testing for comobidities
Diagnosis
Total serum IgE test
- a poorly predictive tool for allergy screening in
rhinitis and should rarely be used as a diagnostic tool
- In adult: 60~100 KU/L
- 35~50% of allergic rhinitis have normal IgE level
- 20% of nonatopic individuals have elevated total IgE
Diagnosis
Specific serum IgE
- Phadiatop: for inhalation allergen (23 species)
- MAST (Multiple Antigen Simultaneous Test)
i. Semi-quantitative
ii. 35 species
- CAP
i. CAP-1 ~ CAP-5
ii. 5 items each time
“ Titer of serum IgE is usually unrelated with symptoms”
Diagnosis
Skin test
- Scratch test
- Prick-puncture test
i. (+) in 15~35% of symptom-free persons
- Intradermal test
i. more sensitive, but less safe
ii. Less correlate with symptoms
iii. Positive control: histamine
iv. Negative control: phenol, N/S, glycerin
- Induration (wheal) & surrounding erythema (flare)
Diagnosis
Skin test VS specific IgE test
Advantage
i. greater sensitivity
ii. rapid result
iii. low cost
Disadvantage
i. inability in extensive
eczema
ii. multiple needle pricks
iii. Influenced by drugs:
antihistamine….
iv. maintain the potency of
allergen extract
v. anaphylaxis
Diagnosis
Nasal provocation test
- In vivo and intranasal
- For more stringent criteria are needed to incriminate
the suspected allergen, such as occupational allergy
- Non-specific reaction to pepper or other material
Management
Allergen avoidance
indicated when possible
Immunotherapy
Pharmacotherapy
Safety
Effectiveness
Easy administration
Cost
Effectiveness
Specialist prescription
May alter the
nature course of the disease
Patient education
Always indicated
Management
Allergen avoidance
Oral medication
- Anti-histamine
- Decongestant
- Corticosteroid
Intra-nasal spray
- Intranasal steroid
- Mast cell stabilizer
(Cromolyn)(Intal)
- Antihistamine: Azelastine
- Decongestant
- Anticholinergic
Management
Immunotherapy
Newer agents
- Anti-leukotrienes (zafirlukast®)
- Monoclonal anti-IgE Ab (omalizumab ®)
- Zileuton (Zyflo): 5-Lipoxygenase (LO) inhibitor
Surgery
- SMT(submucosal turbinectomy)
- Inferior turbinate cauterization
- Laser, cryotherapy, chemical agent, electrocautery….
Recommendations for Management of
Allergic Rhinitis: ARIA Guidelines
Moderate
severe
intermittent
Mild
intermittent
Mild
persistent
Moderate
severe
persistent
Intranasal steroid
Local cromone
Second-generation nonsedating H1 antihistamine
Intranasal decongestant (<10 days) or oral decongestant
Allergen and irritant avoidance
ARIA = Allergic Rhinitis and its Impact on Asthma.
Bousquet et al. Allergy. 2002;57:841.
Bousquet et al. Allergy. 2003;58:192.
Immunotherapy
Management
Allergen avoidance
- Encase mattress, hot washing bedding, wooden floor
- Pets, toys
- Cockroaches
- Aeration and heating ducts
- HEPA cleaner
a. Single avoidance intervention is fail to reduce allergen
load
b. Reduce allergen load ≠ symptoms relief
Management
Anti-histamine
a. 1st generation
Longifene, Homoclomin, Vena
b. 2nd generation: 1st line agents for allergic rhinitis
Loratadine(clarityne®), Cetirizine(Zyrtec®),
Fexofenadine(allergra®), Clarinase® (clarityne+Peudo-E)
c. Newer agent
levocetirizine(Xyzal®), Desloratadine(Aerius®)
d. Azelastine(Azela®)nasal spray
“Inverse agonism”
Management --Anti-histamine
Side effect: (doparminergic, serotinergic, cholinergic receptor)
CNS: sedation, sleepy, unable to concentrate
Heart: arrhythmia(Torsades de pointes)Terfenadine,
astemizole, especially in combination with
macolides or ketoconazole
Anti-cholinergic: urinary retention, dryness,
precipitation of narrow-angle glaucoma
GI upset
Intranasal spray: bitter taste: 20% , sedation: 11%
Astelin prescribibg information. Montvale, NJ: Med Pointe Pharmaceuticals: 2000.
Management
Decongestant
- α1- adrenergic agonist (phenylephrine)
- α2- adrenergic agonist (Oxymetazoline,
xylometazoline, naphazoline)
- Nonadrenaline releaser (ephedrine, peudoephedrine,
amphetamine)
- Block re-uptake of noradrenaline (coccaine, TCA,
phenylpropanolamine)
Management
Decongestant
- oral
- Topical
- Pay attention to patients with
CV disease, poorly-controlled hypertension, glaucoma,
older age, BPH, hyperthyroidism, pregnancy
- > 10 days use of topical decongestant
 tachyphylaxis, rebound congestion
(Rhinitis medicamentosa)
Management
Steroid
-Oral
-Intranasal corticosteroids
:1st line for moderate/severe cases or persistent symptoms
and when nasal obstruction is a major concern
: Low Bioavailability
: Local SE: crusting, dryness, and epistaxis
: No Hypothalamic-pituitary-adrenal axis effect
: Children growth delay in one report.
: Pregnancy: safe for inhaled steroid in asthma woman
Management
Newer agents
- Anti-leukotrienes (montelukast)
- Monoclonal anti-IgE Ab (omalizumab )
- Zileuton (Zyflo): 5-Lipoxygenase (LO)
inhibitor
N Eng J Med 1999; 340(3): 197-208
Management
-Immunotherapy
Effective
Indication
Insufficiently controlled by conventional
medications
Do not wish to be on medications
Medications produces undesirable S.E.
Not recommended in children <5 y/o
Management
--Surgery
An adjunctive intervention in a few highly
selected patients
Relief of nasal obstruction
Management
-- Others
Homeopathy, herbalism, acupuncture
No scientific & clinical evidence
Allergic rhinitis in special conditions
Pediatrics
Pregnancy
Elderly patients
Allergies begin in children
Evolution of sensitisation to
grass pollen between the ages
of 0 and 6 years
% sensitised
Evolution of sensitisation to
house dust mite between the
ages of 0 and 6 years
% sensitised
15
25
20
10
15
10
5
5
0
1
2
3
5
6
Age (years)
Bergmann RL et al. Clin Exp Allergy 1998;28:965-70.
0
1
2
3
Age (years)
5
6
“Allergic march”
Children
Allergic rhinitis: unusual < 2 y/o
Allergy tests can be done at any age
Medications
Few medications have been tested in children
< 2 y/o
Avoid oral and intramuscular steroids in
young children
Intranasal steroid, intranasal Cromolyn
Pregnancy
Nasal obstruction may be aggravated
Most medications cross the placenta
FDA Pregnant Category:
B: Cetirizine, loratadine, vena (Diphenhydramine)
Budesonide nasal spray
Cromolyn intranasal spray
Immunotherapy:
may be continued if initiated before pregnancy
Initiating IT during pregnancy is not advised
Pregnancy
1ST line: intranasal Cromolyn(Intal)
Avoid pseudoephedrine in first trimester
abortion or gastroschisis
Aging
Change in connective tissue and
vasculature of the nose
A less common cause in subjects >65 y/o
Atrophic rhinitis is common
Medications cause rhinitis (reserpine,
guanethidine, phentolamine, methyldopa,
prazosin, chlorpromazine or ACE inhibitors)
Aging
2nd-generation antihistamine:1st choice
Topical anticholinergic
For isolated rhinorrhea (ipratropium bromide nasal spray)
Specific S.E.
Decongestants
Drugs with anticholinergic activity, or sedative
effect
Cost per year in Taiwan
1st
2nd
Intranasal Monteluk Omaluzim Zileuton
antihistam steroid
ast
ab (Xolair) (Zyflo)
anti(Singulair)
histamine ine
NT
730
NT
20005000
NT
36004000
NT
16000
NT
400000
NT
70000