ALLERGC RHNTS

K. Raza Mahmood, MD
Mountainside Pediatrics
Allergic Rhinitis
1. Pathogenesis
2. Clinical
manifestations
& evaluation
3. Diagnosis
4. Management
Epidemiology
9-40% of the US population may have
some form of allergic rhinitis
Prevalence is increasing
2 million lost school days
$ 7 billion cost per year
Bimodal peak: early school & early adult
years.
Pathogenesis
Prior exposure to allergen
inhalation
Antibodies bind to gE receptors
on mast cells in the respiratory
epithelium & to basophils in the
peripheral blood
Degranulation on subsequent
allergen exposure leads to
symptoms
Pathogenesis
IMMUNOGENETICS
Autosomal dominant with incomplete
penetrance
Major histocompatibility complex on
chomosome 6
T- helper 2 cells
Pathogenesis
Allergen inhalation
Antigen presenting cells
(macrophages, CD1+ dendritic cell,
B-lymphocytes) internalize the
allergen
Peptide fragments are exteriorized &
presented with class MHC
molecules to CD4+ T lymphocytes
T lymphocytes send signals to B
lymphos
Pathogenesis: mediators
nterferon gamma
Th-1 cytokine
nhibits B lymphocyte
activation
nhibits gE synthesis
Absent or low in allergic
rhinitis
Pathogenesis
1. L-4 or L-13 stimulate transcription at
the Ce locus in the B lymphocytes.
This locus encodes constant region of
the gE heavy chain.
2. L-4 & L-13 up-regulate vascular cell
adhesion molecule on endothelial
cells
3. CD40 interacts with T lymphocytes to
activate functional gE heavy chain.
4. L 5 (eosinophil growth factor) is also
secreted
Pathogenesis
MAST CELLS
Histamine: mucus secretion,
vasodilatation, sneezing through
nerve stimulation
Phospholipase A2 activation
arachidonic acid metabolites
(Leukotrienes C4, D4, E4,
prostaglandin D2, bradykinin,
platelet activating factor)
GM CSF, TNF d, transforming
growth factor , L 1 to 6, L-13
Pathogenesis: Cells
EOSINOPHILS
Oxygen radicals
Eosinophil major
basic protein
Eosinophil cationic
protein
Eosinophil peroxidase
Pathogenesis
MEDATORS
Substance P (increases
permeability), calcitonin gene
related peptide, vasointestinal
active peptide
Nitric oxide (vasodilator)
RANTES (Regulated on
Activation, Normal T
Expressed and Secreted)
Eotaxins, MCP-3 and MCP-4
(macrophage chemoattractant
proteins)
tyosyl L-arginine methylester
(TAME esterase)
Clinical manifestations
Episodic or intermittent (<4 d/wk, or <4 wk)
Seasonal symptoms 11%
Perennial symptoms 56%
Perennial disease with seasonal
exacerbations 33%
Allergic Rhinitis
Sneezing, cough
Rhinorrhea & post
nasal drip
Nasal congestion,
obstruction, pressure
tching of the eyes,
nose, palate
rritability & fatigue
Dennie Morgan line
Allergic salute
Predisposition to infection
Obstruction of the sinus meatus
Purulent rhinorrhea
Facial or dental pain
Concomitant asthma (up to 50%)
Nasal inflammation
bronchospasm
CAM-1 increase
frequency of rhinovirus
Aspiration of cytokines
T-cell homing to the
lower respiratory tract
Concomitant atopic dermatitis
Up to 30%
Seasonal
exacerbations
Examination
Nasal examination: pale blue, boggy
turbinates
Throat: cobblestoning
Flexible rhinoscopy
Nasal cytology
Neutrophils infection
Eosinophils allergic rhinitis
Eosinophils may also be present in
NARES (non allergic rhinitis with
eosinophilia syndrome)
Rhino mano metry: measures nasal airway
resistance following allergen provocative
challenge
Skin testing
Wheal and flare
reaction at the skin
test site within 20
minutes.
RAST
Serum assay for
specific gE
antibodies
Available as different
panels
maging
X-rays: air fluid
levels or thickening
CT scans
(opacification)
MR imaging
Gold standard for
sinusitis diagnosis:
aspiration (not
used routinely)
Differential diagnoses
Acute infectious
rhinosinusitis
Vasomotor rhinitis
Rhinitis medicamentosa
Non allergic rhinitis with
nasal
eosinophilia syndrome
(NARES)
Unilateral rhinitis or
nasal polyps
Allergen avoidance
ndoor allergens
Outdoor allergens
Peak Pollen Periods
1. Trees (spring)
2. Grasses (summer)
3. Weeds (fall)
'hay fever'
The order is generally
the same:
Tall trees medium
grasses low weeds
Treatment options
Allergen avoidance/environmental control
Cromolyn nasal spray
Topical nasal steroids
Antihistamine spray
Antihistamine/decongestant
Specific immunotherapy
Preventive measures
Relative humidity @ <50% to limit molds
Air conditioning
Pillow covers
Washing bedding in water >130 F
HEPA filters (controversial)
Air cleaners not useful for dust mite
allergens
Decongestants: adverse effects
Nervousness, irritability, insomnia
Headache
Urinary retention
Palpitations, tachycardia
Hypertension
Nausea
Local decongestants
Oxymetazoline, xylometazoline,
naphazoline
Tachyphylaxis
Rhinitis medicamentosa
Useful for short periods in
severe nasal obstruction
ntranasal steroids
Most effective single agent
therapy
'First Iine therapy for AR'
First generation: budenoside,
beclomethasone, flunisolide
Second generation:
fluticasone, mometasone
(very little systemic absorption)
Antihistamines
First generation: benadryl, triprolidine,
chlorpheniramine, brompheniramine
Second generation: cetirizine, loratidine,
Third generation: fexofenadrine,
desloratidine (less sedation than 1
st
generation)
Antihistamines provide inadequate relief from
late phase associated nasal obstruction
Antihistamines: adverse effects
Sedation (or, stimulation)
Dryness (mouth, or eyes)
Urinary retention
Weight gain
Prolonged QT (some
drugs)
Cromolyn & Nedocromil
Chloride channel inhibition
in mast cells, eosinophils
Less effective than nasal
steroids
mmediate and late phase
Large, frequent dosing
required
pratropium
Reduced substance P
release
Reduces rhinorrhea
Used when there is
concomitant allergic
and vasomotor
rhinorrhea
mmunotherapy
Bioequivalent allergy units (BAU)
ncreasing doses of allergens
Cats, mites, short ragweed,
Grasses (Bermuda, red top,
June, rye, orchard, timothy,
sweet vernal)
Mechanism: shift away from Th2
response
Risk of anaphylaxis, most
courses run 3 to 5 years
Cytokine therapy
Modulation of the effects of L-4 & 13
Human monoclonal antibody to gE
(omalizumab)
Leukotriene modifiers
Phosphodiesterase-4 inhibitors: roflumilast
Antifungal agents: amphotericin B
Tryptase inhibitors, sublingual
immunotherapy, phototherapy
Thank you