Allergic Rhinitis

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Allergic Rhinitis

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ARIA guideline

• 2001, Allergic Rhinitis and its Impact on Asthma
  in collaboration with the WHO
• To update clinicians 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

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2001. 10
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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
  IgE-mediated inflammation of the nasal membranes
  

1. Dykewicz. J Allergy Clin Immunol.
2003111(suppl)S520. 2. Bauchau and Durham. Eur
Respir J. 200424758. 3. Linneberg. BMJ.
2005331.352.
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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).

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Allergy and Atopy

• AtopyGreek 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.

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Epidemiology

• Prevalence
• Overall--10-25, and increasing
• In Taiwan 2030 of child
• Hereditism
• One parent ()--29(40)
• Both parents ()--47(75)
• Age
• 11-20 y/o

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Triggers

• Allergens
• Aeroallergens
• Indoor
• Mites, dust, animals insects
• Outdoor
• Pollens moulds
• Occupational rhinitis
• Latex allergy

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Triggers

• Pollutants
• Indoor air pollutants
• gt80 of time indoors
• Tobacco smoke
• Outdoor air pollutants
• Automobile--ozone, oxides of nitrogen sulphur
  dioxide

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Triggers

• Aspirin ( NSAIDs)

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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

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Classification
Intermittent Symptoms lt 4 days per week or lt 4 weeks
Persistent Symptoms gt 4 days per week and gt 4weeks
Moderate-Severe one or more items abnormal sleep impairment of daily activities, sport, leisure problems caused at work or school troublesome symptoms
Mild normal sleep normal daily activities, sport, leisure normal work and school no troublesome symptoms
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Symptoms signs

• Symptoms
• a. rhinorrhea
• b. nasal obstruction
• c. nasal itching
• d. sneezing
• e. itchy or watery eye
• f. anosmia, nasal pain, headache

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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
• .

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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

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Nasal salute
Nasal itching
Allergic shiners
Adenoid face
Skoner D, Urbach A, Fireman P. In Atlas of
Pediatric Physical Diagnosis. 3rd ed. 1997
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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

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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)

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Pathophysiology

• Late/delayed phase response
• 50
• 412 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

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Allergy is more than histamine
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Minimal persistent inflammation
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The united airways concept (One
airway, one disease)

• Link between rhinitis and other conditions

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Co-Morbidities --Asthma

• Asthma pt--60-78 allergic rhinitis
• Allergic rhinitis pt--19-38 asthma
• Bronchial challenge--nasal inflammation Nasal
  challenge--bronchial inflammation

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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

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Co-Morbidities --Asthma

• Medications
• Both effective--intranasal steroids,
  antihistamines, antileukotrienes
• Optimal management of rhinitis may improve
• coexisting asthma

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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

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Diagnosis

• Allergic test
• - Skin test
• - Serum specific IgE
• Nasal cytology
• - Eosinophilia gt20

• Nasal challenge
• - Allergen, aspirin, lysine
• Radiology
• - usually unnecessary
• - X-ray, CT scan

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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

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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 60100 KU/L
• - 3550 of allergic rhinitis have normal IgE
  level
• - 20 of nonatopic individuals have elevated
  total IgE

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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

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Diagnosis

• Skin test
• - Scratch test
• - Prick-puncture test
• i. () in 1535 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)

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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

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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

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Management
Allergen avoidance indicated when possible
Cost
Immunotherapy Effectiveness Specialist
prescription May alter the nature course of the
disease
Pharmacotherapy Safety Effectiveness Easy
administration
Patient education Always indicated
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Management

• Intra-nasal spray
• - Intranasal steroid
• - Mast cell stabilizer
• (Cromolyn)(Intal)
• - Antihistamine Azelastine
• - Decongestant
• - Anticholinergic

• Allergen avoidance
• Oral medication
• - Anti-histamine
• - Decongestant
• - Corticosteroid

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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.

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Recommendations for Management of Allergic
Rhinitis ARIA Guidelines
Moderate severe persistent
Mild persistent
Moderate severe intermittent
Mild intermittent
Intranasal steroid
Local cromone
Second-generation nonsedating H1 antihistamine
Intranasal decongestant (lt10 days) or oral
decongestant
Allergen and irritant avoidance
Immunotherapy
ARIA Allergic Rhinitis and its Impact on
Asthma. Bousquet et al. Allergy.
200257841. Bousquet et al. Allergy.
200358192.
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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

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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
  (claritynePeudo-E)
• c. Newer agent
• levocetirizine(Xyzal),
  Desloratadine(Aerius)
• d. Azelastine(Azela)nasal spray

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Inverse agonism
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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.
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Management

• Decongestant
• - a1- adrenergic agonist (phenylephrine)
• - a2- adrenergic agonist (Oxymetazoline,
• xylometazoline, naphazoline)
• - Nonadrenaline releaser (ephedrine,
  peudoephedrine,
• amphetamine)
• - Block re-uptake of noradrenaline (coccaine,
  TCA,
• phenylpropanolamine)

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Management

• Decongestant
• - oral
• - Topical
• - Pay attention to patients with
• CV disease, poorly-controlled hypertension,
  glaucoma,
• older age, BPH, hyperthyroidism, pregnancy
• - gt 10 days use of topical decongestant
• ? tachyphylaxis, rebound congestion
• (Rhinitis medicamentosa)

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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

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Management

• Newer agents
• - Anti-leukotrienes (montelukast)
• - Monoclonal anti-IgE Ab (omalizumab )
• - Zileuton (Zyflo) 5-Lipoxygenase (LO)
• inhibitor

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N Eng J Med 1999 340(3) 197-208
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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 lt5 y/o

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Management--Surgery

• An adjunctive intervention in a few highly
• selected patients
• Relief of nasal obstruction

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Management-- Others

• Homeopathy, herbalism, acupuncture
• No scientific clinical evidence

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Allergic rhinitis in special conditions

• Pediatrics
• Pregnancy
• Elderly patients

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Allergies begin in children
Evolution of sensitisation to grass pollen
between the ages of 0 and 6 years
Evolution of sensitisation to house dust mite
between the ages of 0 and 6 years
sensitised
sensitised
1 2 3 5 6
1 2 3 5 6
0
0
Age (years)
Age (years)
Bergmann RL et al. Clin Exp Allergy
199828965-70.
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Allergic march
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Children

• Allergic rhinitis unusual lt 2 y/o
• Allergy tests can be done at any age
• Medications
• Few medications have been tested in children lt 2
  y/o
• Avoid oral and intramuscular steroids in young
  children
• Intranasal steroid, intranasal Cromolyn

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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

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Pregnancy

• 1ST line intranasal Cromolyn(Intal)
• Avoid pseudoephedrine in first trimester
• abortion or gastroschisis

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Aging

• Change in connective tissue and
• vasculature of the nose
• A less common cause in subjects gt65 y/o
• Atrophic rhinitis is common
• Medications cause rhinitis (reserpine,
  guanethidine, phentolamine, methyldopa, prazosin,
  chlorpromazine or ACE inhibitors)

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Aging

• 2nd-generation antihistamine1st choice
• Topical anticholinergic
• For isolated rhinorrhea (ipratropium
  bromide nasal spray)
• Specific S.E.
• Decongestants
• Drugs with anticholinergic activity, or sedative
• effect

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Cost per year in Taiwan
1st anti-histamine 2nd antihistamine Intranasal steroid Montelukast (Singulair) Omaluzimab (Xolair) Zileuton (Zyflo)
NT 730 NT 2000-5000 NT 3600-4000 NT 16000 NT 400000 NT 70000
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Thank You!