Allergic Rhinitis

Third Edition

James A. Hadley, M.D. and

J. David Osguthorpe, M.D.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Nasal Airway Insufficiency
(the “stuffy nose”)

• ALLERGY (medically reported as 17 - 22% of population)

• ANATOMIC OBSTRUCTION (septum, turbinate)
• RHINOSINUSITIS (self reported by 10 -13.5% of population)
• NON-ALLERGIC RHINITIS (vasomotor, gustatory, etc.)
• MEDICATION SIDE EFFECT (rhinitis medicamentosa,
anti-HTN, birth control pills, estrogen, etc.)
• PREGNANCY or OTHER ENDOCRINE
SOURCE, FLUID RETENTION
• NEOPLASM, FOREIGN BODY, ETC.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Nasal Insufficienty can be multifactorial.
Nasal
insufficiency
can be
multifactorial
This cigarette
smoker has a
septal deviation,
turbinate
hypertrophy
from allergies,
polyps, &
rhinosinusitis.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Allergic and Non- Allergic Rhinitis

• This educational slide series

will review the
pathophysiology, impact,
diagnosis and management
scenarios of both allergic and
non-allergic rhinitis.
• A summary of the
otolaryngolgist’s perspective
and treatment paradigms.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Impact of Allergic Rhinitis
• 6th most prevalent chronic, & most common
respiratory, disease (most prevalent chronic
condition in those < 18 y/o)
• 2.5% physician office visits, common reason for
both OTC & physician prescriptions
• Diminished QOL (irritability, fatigue, sleep
disturbance, depression)
• Direct costs to US economy of approximately $4.5
billion/year, plus -
• 3.8 million lost work & school days annually

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Allergic Rhinitis : Associated Diseases

Otitis Asthma
Media

Allergic
Laryngitis, Rhinitis
Pharyngitis Rhinosinusitis

Chronic
Rhinitis

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Complications of Allergic Rhinitis

• Rhinosinusitis, Nasal Polyps

• Pharyngitis, Laryngitis
• Otitis Media, Otitis Externa
• Conjunctivitis
• Exacerbation of Asthma, Bronchitis, Vertigo,
Migraine, Eczema
• Impaired Olfaction / Taste, Sleep Apnea,
Facial Growth Abnormalities in
Children (all from nasal obstruction)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Allergic Rhinitis
• Provoked by exposure to antigens
(allergens) in the environment and food
• Symptoms:
– Nasal congestion with nasal mucosal edema or
obstruction (mouth breathing, midfacial
“fullness / pressure” or headache.)
– Sneezing, nasal, conjunctival and/or palatal
pruritis
– Watery rhinorrhea, post nasal drip, lacrimation
– Diminished sense of smell, Eustachian tube
dysfunction

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Definition of Allergy

• Von Pirquet 1906 Allergy

“An altered reactivity to a foreign
substance after prior exposure to the
same material”

• Allergy & Hypersensitivity are used

interchangeably to describe an adverse
clinical reaction to an environmental agent
caused by an immunological reaction
(Antigen-Antibody reaction).

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Hypersensitivity Reactions
(Allergic Rhinitis is primarily a Type I,
IgE mediated reaction)

Type I Immediate (allergic rhinitis, asthma,

immediate onset food reactions)
Type II Cytotoxic (hemolytic anemia, Hashimoto’s)
Type III Immune Complex (serum sicknesss,
delayed onset food reactions,
glomerulonephritis)
Type IV Delayed, Cell Mediated (TB, poison ivy)
Type V Stimulating Antibody Reaction (Graves’)
Type VI Antibody Dependent Cell Cytoxicity
(transplant rejection)
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Definitions Relevant to Allergic Rhinitis

• Hypersensitivity
– A heightened or exaggerated immune response
that develops after >1 exposure to a specific
antigen.
• Allergen (Antigen):
– A foreign substance that when introduced into the
body elicits a specific immunologic response.
• Antibody:
– A protein (immunoglobulin) that selectively binds
to a specific allergen.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Pathophysiology of Allergic Disease

1. Host sensitization to allergen

2. IgE production by host
3. Mast cell sensitization
4. Allergen provocation by further
exposure after sensitizing event
5. Mediator release:
Histamine, kinins, leukotrienes, cytokines
6. End-organ response

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Pathophysiology of Allergic
Inflammation: Sensitization
Phase 1 : Sensitization

Allergens
Antigen-presenting
cell

Processed
allergens

CD4
T cell
B cell

IgE antibodies
Plasma cell

Naclerio, RM. New Engl J Med 1991:325; 860-9

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Pathophysiology of Allergic
Inflammation: Clinical Disease
Phase 2 : Clinical Disease
Early Late
Inflammation Inflammation
Allergens

Late-phase Resolution
IgE antibodies reaction
Cellular
infiltration Hyper-
Mast responsiveness Complications
cell
Eosinophils
Mediator release Basophils Priming
Nerves Monocytes
Blood Irreversible
vessels Lymphocytes
Glands disease (?)

Sneezing
Rhinorrhea
Congestion
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Mast Cells / Basophils and
Inflammatory Cascade
Antigen

Cytokines
-IL-4,5,6,8

Nucleus

Lipid Preformed
Mediators Mediators
-PGs -Histamine
-LTs -Heparin
-Tryptase (Mast Cells)
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Chemical Mediators of Allergic, and Some
Non-Allergic, Rhinitis
(principally from Mast cells & Basophils)

• Pre-formed (stored) • Newly formed mediators

mediators (created by & after reaction)
– Histamine – Leukotrienes
• LTB4, LTC4, LTD4
– Kinins – Cytokines
– Heparin • ECF-A,
– Platelet activating – Prostaglandins
factor (PAF) • PGD2
– Interleukins

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Basic Immunology:
Sensitization vs. Subsequent Exposure
I
Antigen
II
Macrophage

Cytokines

T-cell
TH2

IgE
B-cell Mast Cell Degranulation

Sensitization IgE presentation IgE bridging

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Consequences of Mediator Release
Atg
Mast Cell Mediators

Early Phase Reaction Late Phase Reaction

(maximum 10-30 minutes) (maximum at 10-12 hours)
Pruritis, Sneezing Infiltration with Eosinophils
Smooth muscle contraction Fibrin deposition
Flush, Vascular leakage with Infiltration with Monocytes
Rhinorrhea Tissue destruction
Nasal congestion
Mucous Secretion

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Nasal Response to Inhaled Allergen

Early Phase Late Phase

S
y Response Response
m
p
t
o
m
s

1 3-4 24
Time in Hours from Initial
Challenge
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Types of Rhinitis - 1
• Seasonal allergic rhinitis (classic hayfever with
spring, summer &/or fall symptoms)
• Perennial allergic rhinitis (mite, mold,
cockroach, animal dander)
• Infectious rhinitis (virus, bacteria, fungi)
• Occupational rhinitis (latex)
• Chemical / irritative rhinitis (perfumes,
strong odors, fine particles)
• Anatomic rhinitis (nasal drainage obstruction
by septum, etc.)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Turbinate Hypertrophy/Rhinitis of Pregnancy

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Types of Rhinitis - 2
• Vasomotor rhinitis (temperature variation
induced, either inhaled or with food intake)
• Non-allergic rhinitis with eosinophilia
• Medication-induced rhinitis (rhinitis
medicamentosa, oral contraceptives, anti-
hypertensives)
• Hormonal rhinitis (pregnancy, menopause,
hypothyroidism)
• Atrophic rhinitis (ageing, surgery, infection)
• Gustatory rhinitis (food allergy induced)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 ARIA Classification & Allergic Rhinitis

Intermittent Persistent
• Symptoms < 4 days per week • > 4 days per week
• or Symptoms < 4 weeks • and > 4 weeks

Mild Moderate–severe
Normal sleep One or more items
& no impairment of daily • Abnormal sleep
activities, sport, leisure • Impairment of daily
& normal work and school activities, sport, leisure
& no troublesome symptoms • Abnormal work and school
• Troublesome symptoms

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Symptoms of Allergic Rhinitis
• Provoked by exposure to Antigens (in atopic
context, called Allergens) in environment & food
• Common Symptoms:
– Nasal, conjunctival &/or palatal pruritis
– Sneezing, watery rhinorrhea, post nasal drip,
lacrimation
– Mucosal edema with nasal congestion /
obstruction (mouth breathing, sleep
disturbances), sinus ostial &/or eustachian tube
dysfunction (midfacial pressure/pain, headache,
ear pressure & occasional mild dizzyness), &
diminished olfaction

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Diagnosis and the Allergic Patient

Diagnosis based on:

1. History
2. Physical Examination
3. Laboratory &/or Skin Testing
Note: # 1 & #2 suffice for initiation of
Environmental Measures & Pharmacotherapy,
and may be all that is necessary in mild to
moderate cases; #3 affords definitive diagnosis
& is required prior to Immunotherapy

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Allergies & Past Medical History

• Childhood allergy / asthma • Surgery

• Recurrent OM, recurrent − T &/or A
acute or chronic RS − P E Tubes
• Eczema − Sinus
• Colic / formula intolerance • OTC or Rx
• Anaphylactic reaction (food medications with
or drug) anti-allergy, “cold”
or decongestant
• Seasonal “colds” (spring,
effects
fall)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Allergies & Family History

50
Chance of
40
having
30 atopy
% based on
20
family
10 history
0
None One Two
Number of parents allergic
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Physical Examination of Allergy Patient

• Eyes: conjunctivitis, Dennie’s lines, “shiners”

• Ears: otitis media or externa, retracted
tympanic membrane from ET dysfunction
• Nose: boggy / pale nasal mucosa, clear / thin
mucoid rhinitis, turbinate hypertrophy,
polyps, transverse nasal crease from “allergic
salute”
• Throat: prominent lymphoid patches
(cobblestoning), lateral pharyngeal bands

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 R = “Shiners” & nasal obstruction (mouth
breather) from nasal edema & venous congestion ,
L = Dennie’s Lines

R L
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
R = turbinate congestion & hypertrophy from
allergies; L = allergic conjunctivitis

R L

© 2003 The American Academy of Otolaryngology

. – Head and Neck Surgery Foundation
 Posterior Pharyngeal Cobblestoning (submucosal
lymphoid hyperplasia from chronic post-nasal drip
of inhalant allergies)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Physical Examination
of Allergy Patient
• Dental: crowded teeth, high arched palate
• Nasopharynx: hypertrophic adenoids
(adenoid facies), lateral pharyngeal bands
• Larynx: edematous / polypoid vocal cords
• Lungs: sibilant rales, wheezing suggestive of
bronchospasm
• Skin: eczema or other pruritic rashes
(especially if food allergic)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
L = Rash from Birch Containing Shampoo;
R = Atopic Eczema from Food Sensitivities

L R
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Testing for Allergic Rhinitis
• IgE testing
– Skin “In vivo” (prick or intradermal tests)
– Laboratory “In vitro” antigen specific assay
(radioallergosorbent / RAST Test or enzyme linked
immunosorbent / ELISA Test)
• Other Laboratory testing:
– Eosinophil count (also may be elevated in asthma,
NARES, parasitic infection, etc.)
– Nasal cytology
• Dietary Elimination and Challenge Feeding tests

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 In Vivo or In Vitro Allergy “Screens”
Test Battery of 8 - 12 common Allergens in patient’s
geographic region is 96% efficient & 94.2%
sensitive in detecting those with clinically
significant sensitivities (unless there is an unusual
or occupational exposure, e.g. latex in health care
worker, mice in laboratory worker)

Example of common inhalant “screen”: 2 trees, 1-2

weeds, 1-2 grasses, 1 mite, cockroach, 2 molds,
cat dander
In children with eczema, colic, etc., common foods
can be added to “screen”, such as milk, soybean,
peanut, egg, wheat, corn

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Nasal Cytogram - mucous, epithelial cells and some bacteria,
with leukocytes (& more bacteria) in infection, & eosinophils in allergy
(most of the time)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Clinical Approach to the Allergic Patient
Classic Quartet of Treatment Approaches:
1. Avoidance & Environmental Measures
2. Counseling of Patient & Family
(home, vocation, avocation, school)
3. Physical fitness
4. Pharmacotherapy (e.g., steroids, antihistamines)
5. Eradicate comorbidity
6. Immunotherapy
[if warranted by skin or in vitro testing that
confirms IgE to offending Allergens, plus
inadequate (or unrealistic) control by both #2 & # 3]
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Diagnosis and Treatment of Inhalant Allergy
History and Physical Examination

Seasonal pollens Perennial dust, mold, danders

Education, Environmental Control,

Pharmacotherapy

If Failure

Allergy Testing : Consider “screen”, then if positive, full battery of tests

Immunotherapy
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Air Filtration: Personal, Room, House, Car
Air Filters, in
Consumer
Reports of
1/2002

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Indoor Environmental Allergen Control:
Example for Allergic (Extrinsic) Asthma
• 60-80% with asthma have IgE sensitivities, commonly mite,
cockroach, cat &/or Alternaria species
• Indoor allergen reduction decreases severity of asthma:
– Mite allergen : mite impermeable mattress & pillow
covers; wash comforters, bedding, etc at >130F; mite
killing powders (acaricides) on rugs, upholstered
furniture, drapes; house humidity < 50%
– Cockroach allergen : extermination, cleaning
– Mold : house humidity < 50%; clean bathrooms,
kitchens, laundry rooms; vent moist areas
– High efficiency air filtration & vacuum cleaner bags

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Treatment Considerations in
Allergic Rhinitis
• Pharmacotherapy Factors :
– Effectiveness
– Side effect profile
– Dosing schedule
– Affordability
• Immunotherapy Factors (Allergy shots) :
– Effective in 70-80% with allergic rhinitis, must be continued
for 3-5 years in most (seems to require such for sustainable
levels of “blocking antibodies” & the like; some require
lifelong therapy)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Treatment of Allergic Rhinitis
Type of Drug Action
Antihistamines Block histamine
Intranasal Steroids Local anti-inflammatory
Cromolyn sodium Stabilizes mast cells
Decongestants Vasoconstriction
Leukotrienes Block cytokine action
Immunotherapy Competing antibodies, etc.
IgE specific agents Bind IgE, block receptor
sites, etc.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Effects of Various Pharmacotherapies
Nasal Eye
Therapy0 Sneezing Rhinorrhea Nasal itch
obstruction symptoms
H1-antihistamines
Oral ++ ++ + +++ ++
Intranasal ++ ++ + ++ 0
Intraocular 0 0 0 0 +++
Corticosteroids
Intranasal +++ +++ +++ ++ ++
Cromolyn sodium
Intranasal + + + + 0
Intraocular 0 0 0 0 ++
Decongestants
Intranasal 0 0 ++++ 0 0
Oral 0 0 + 0 0
Anticholinergics 0 ++ 0 0 0
Antileukotrienes ++ ++ + ++ ++
Adapted from van Cauwenberge P, et al. Allergy. 2000;55:116-134 and Nayak AS, et al.
Ann Allergy Asthma Immunol. 2002;88:592-600.
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Management of Allergic Rhinitis
Options Common in a Stepwise Approach
Moderate-
severe
Mild persistent
Moderate- persistent
severe
Mild intermittent
intermittent
Intranasal corticosteroid
Cromolyn Sodium
Patient
Patient education
education andand allergen
allergen and irritant avoidance
avoidance
Intranasal decongestant (<10 days) or oral decongestant
Oral or local nonsedating
antihistamine
Immunotherapy, if other therapies fail
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Traditional Drug Therapies
• Over the Counter (OTC) Allergy Medications:
– Accessible, at modest cost in most cases
– Most current OTC antihistamines, may cause
drowsiness, dry mouth, blurry vision,
constipation & urinary retention
– Oral decongestants may cause agitation &
sleeplessness, or elevate blood pressure
– Topical decongestants can lead to rebound
congestion or rhinitis medicamentosa
– Cromolyn requires frequent dosing prior to &
during exposure

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Topical & Oral Decongestants
(action per alpha adrenergic receptors, do not relieve
rhinitis, pruritis, sneezing)

Topical Decongestants (neosynephrine, oxymetazoline)

Shrink inflamed & swollen mucosa through local
vasoconstriction
Use no longer than 4 - 7 days to avoid rebound
Oral Decongestants (pseudoephedrine)
Reduce nasal blood flow (hence, edema &
hyperemia) & may improve sinus ostial patency
May be used indefinitely (watch BP, sleep, anxiety, & use
with caution if diabetes, glaucoma, prostatic hypertrophy,
ASVD, etc.)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Prescription Antihistamines
• Relieves rhinitis, excess mucous production, as well
as most ocular & non-nasal manifestions, but not
nasal congestion with short term therapy
• Minimal to no sedation (mental alertness &
coordination usually intact)
• Mucosal drying variably present (much less among
than older antihistamines); consider topical
antihistamine alternative in those with severe asthma
or bronchitis
• Costlier than OTC / older generation antihistamines
(though most sedate to varying degrees)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Topical Nasal Steroids
• Topically effective in relieving sneezing, nasal
pruritis, rhinorrhea & reactive mucosal edema
• Minimal systemic absorption for most (in younger
children, use drugs least absorbed & effective with once
daily dosing, particularly if also on steroids for asthma)
• Effectiveness depends on regular use & adequate
nasal airway for delivery; requires at least day or
two before clinical onset of action (may need oral
decongestant for first week to aid penetration); can irritate
nasal mucosa; modest effect on ocular symptoms

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Leukotriene Suppressors

• Leukotriene synthesis inhibitors or receptor

antagonists commonly used for asthma (after
therapies with inhaled steroids & B-agonists fail)
• Consider in patients with persisting symptoms
despite topical steroids &/or antihistamines,
especially in asthmatics or those with ASA triad
• May be useful (variable effect) on polyps or
hyperplastic nasal / sinus mucosa
• Few side effects, safe in children > 2y/o

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Other Therapies for Inhalant Allergies

• Mast Cell Stabilizers: cromolyn or

nedocromil in nasal, ophthalmic or inhaled
preparations
• Anticholinergics: topical atropine or
ipratropium
• IgE Blockers / Binders: omalizumab (as a
periodic shot), many in “pipeline” for
release in next few years
• Saline: saline sprays, pumped irrigations

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Types of Skin Testing

• Patch test • Intradermal Tests

(derm use only) –single intradermal
• Scratch Test –skin endpoint
(poor titration (serial
reproducibility) dilutions, multiple
• Prick Test tests to quantitate
– single prick test sensitivity)
– multi-test devices

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Selection of Antigens for Skin or
Laboratory Testing

• Identify antigens in patient’s environment

(regional, work & home)

• Successful immunotherapy, &

environmental modification, depends
upon accurate determination of all (or
at least the majority) of clinically significant
allergens

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Prick Testing
• Strength of antigen predetermined
– usually 1:10 or 1:20 antigen weight to volume of liquid
• Antigen placed on skin (back or arm) prior to
prick, skin is tented up with sharp instrument &
then pricked
• Reactions are determined after 20 minutes
• Grading system 1+ to 4+, measuring both wheal
and erythema flare responses
• Designed to detect major sensitivities, without
quantitation as to degree; can miss low grade
sensitivities such as molds

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Skin Prick Techniques

Single Prick Options

Multi Prick (various devices, all of which accomplish

simultaneous punctures with different antigens)
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Intradermal Testing : Single Antigen
Concentration Tests
• Strength of antigen predetermined
– usually 0.01 – 0.04cc of 1:500 to 1:1000 antigen weight to
volume injected subcutaneously
• Reaction read after 10-20 minutes
• Grading system 1+ to 4+ , measure both wheal size
& erythema flare responses
• Detects major sensitivities but without quantitative
information; can detect most low grade
sensitivities if 1:500 antigen solution utilized

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Skin Endpoint (Dilutional) Titration
or “SET”
• Intradermal injection of 0.01-0.02 cc of serially
diluted antigen (usually 1:5, starting with the antigen
concentrate) to produce a 4mm wheal
• Reaction read per wheal growth by 10-15 minutes
• If no reaction is detected, progressively more
concentrated antigen solutions are injected until a
2mm or more growth in wheal size occurs or the
highest concentration of antigen (usually 1:100
weight per volume) dilution is reached, signaling no
significant sensitivity to the antigen

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 SET Diagram

• 0.01-.02cc intradermal test 4

produces 4 mm wheal
• Spreads to 5mm by diffusion 5
• If it further enlarges >2mm after
10-15 minutes, test is likely
positive (i.e., patient sensitive to the antigen, 7
but such must be confirmed by yet another 2mm
wheal growth when the next stronger antigen is
injected)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Serial Endpoint (Dilutional) Skin Testing
for Identification and Quantification of
Inhalant Sensitivities

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Skin Endpoint (Dilutional) Titration

Advantages:
Very safe, and can detect low levels of patient
sensitivity to an antigen
Few false positives or false negatives
Both quantitative and qualitative (i.e., identifies
not only patient sensitivities, but magnitude of
those sensitivities)
Safe guide to starting therapy

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Antigen Dose 0.01 ml of
Comparisons among various antigen
Skin Testing dilutions
Techniques delivered by SET
#6 = 0.03 g
Prick 1:10 w/v = .30 g
#5 = 0.16 g
#4 = 0.80 g
0.02ml Single ID 1:1000 w/v = 20 g
#3 = 4.0 g
#2 = 20 g
0.02ml Single ID 1:500 w/v = 40 g
#1 = 100 g
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 In Vitro Testing Procedure
Sandwich Assay Technique
• Allergen coupled to a solid phase : Paper disk
(RAST), Cellulose sponge (ImmunoCAP, etc.)
• Add patient’s serum
• Antigen-Antibody complex formed
• Anti- IgE added
• Anti-IgE Antibody-Allergen complex formed
• Computerized reading of different tags
(radioactive, fluorescence, colorimetric,
enzymatic)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 In Vitro Methodology

Courtesy Scientific American

• Allergen coupled to a solid phase : paper disk or cellulose sponge

• Add patient’s serum, & IgE Antibody-Allergen complexes formed
(& possibly some IgG Antibody-Allergen complexes)
• Add Anti-IgE, & Anti-IgE Antibody-IgE Antibody-Allergen complexes formed
• Computerized reading of different tags (radioactive, fluorescence,
colorimetric, enzymatic)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Modified In Vitro Scoring
(quantifies patient sensitivity per scale that reflects
amount of specific IgE and correlates with SET results;
RAST-specific scale shown )

Class 0 250 - 500 (Not sensitive)

Class 1/0 501 - 750 (Marginally sensitive)
Class 1 751 - 1600 (Low sensitivity)
Class 2 1601 - 3600
Class 3 3601 - 8000
Class 4 8001 - 18000
Class 5 18001 - 40000 (Very sensitive)
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Comparison of
Scoring
Systems

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Relative Advantages:
In Vivo vs. In Vitro Testing
In Vitro (immunoassay) In Vivo (skin tests)
No risk of allergic reaction Greater sensitivity (e.g.,
Not affected by drugs or molds)
skin conditions Larger availability of
Patient convenience antigens
(single venipuncture) Immediate test results
Easy to document quality Moderately less expense
control, reproducibility No laboratory certification
Most convenient for allergy paperwork
“screen”

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Principles Common to SET
In Vivo & In Vitro Methods of Testing
• Testing
– Screens of 8 - 10 antigens can precede full battery
– Testing with individual antigens rather than antigen mixes
• Treatment
– Decision to treat rests on clinical judgement, NOT just + results
– ENDPOINT, a quantification of patient sensitivity, via SET or
Modified RAST score, indicates safe immunotherapy starting
dose
– When enough sensitivities necessitate 2 different treatment
vials, high & low sensitivities are separated & different speeds
of dose escalation are possible (faster with low sensitivity
antigens)
© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Food Allergy
(2 basic types : “Fixed” and “Cyclic”)
• May cause nasal congestion & rhinitis, in
addition to more common food sensitivity
manifestations: GI disturbance, rash,
headache, vertigo
• Consider evaluation if patient has positive
history for food reactions (or colic/eczema
as child), inhalant allergy workup is
unimpressive, or therapy (environmental
modification, pharmacotherapy,
immunotherapy) fails to bring expected relief

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Food Reactions
• Prevalence greatest < 3 years of age, & declines
over next decade
• 90% of food allergy reactions in children are
caused by 6 foods : milk, egg, soy (all of which
can be “outgrown”), & wheat, peanut, tree nuts
• 90% of food allergy reactions in adults are caused
by 4 foods: peanut, tree nuts, fish, shellfish
• Common cross reactions between inhalants &
foods: ragweed & melon / banana; birch &
apple / carrot / potato / hazelnut / almond

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 “Fixed” Food Allergies

• IgE mediated with immediate clinical reaction to

ingestion, frequently angioedema or anaphylaxis
(most frequently shellfish or peanut)
• Diagnosis usually made from patient history
– specific IgE assay will confirm if needed (do NOT skin
test for the food)
• Treatment is avoidance of offending food,
patient should be instructed in use of self
administered, injectable epinephrine

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 “Cyclic” Food Allergies
• Most common type of food sensitivity, with
delayed onset of symptoms (up to 24 hours)
• Mediated by any of the Gell & Coombs
reactions
– Most are immune complex reactions
• Diet and symptom diary identify likely offending foods
– 4 day elimination of the particular food, and then a “Challenge
feeding test” of that food on 5th day
– In vitro tests are alternative in young children (higher
frequency of IgE-mediated food reactions)

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
Elimination Diet and Challenge Food Test
Eliminate suspect food, in all
products, based on patient history

Patient improves
Patient unchanged

Reintroduce suspect
food into diet Evaluate other food(s),
consider other origins to
Symptoms recur symptoms

Eliminate food for 4-5 days,

then Challenge Food Test

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Indications for Immunotherapy
• Avoidance & Environmental Measures fail to control
symptoms, or are impractical (e.g., teacher in moldy
school building, florist sensitive to plant pollens or
veterinarian sensitive to cats)
• Pharmacotherapy fails to fully control symptoms, or
produces bothersome side-effects
• Moderate to severe symptoms in 2 or more seasons, &
Skin or In Vitro tests document IgE mediated
sensitivity
• Contraindications : -blocker or potential problem with
epinephrine, poorly controlled asthma, autoimmune or
immunodeficiency disease, unreliable patient

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Immunotherapy for Allergic Rhinitis

• Regular injections of increasing amounts of Allergen

administered every 5-7 days until symptom relieving
dose or maximum tolerated dose reached, then
maintenance dose q 2-4 weeks, based on symptoms
• Continue maintenance dose until symptoms are
controlled for 3 -5 years, then can discontinue
Immunotherapy in about 75%
• Injections during dose escalation under direct
supervision of physician trained to manage
anaphylaxis

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Immunotherapy Failure:
Common Reasons
• Patient failure to regularly comply with the
immunotherapy regimen
• Incorrect antigen dosing &/or too infrequent shot
intervals
• Food or chemical sensitivities, or inhalants to
which patient was not tested or for which
commercial antigens are unavailable
• Non-allergic rhinitis (vasomotor, occupational,
atrophic, medication-induced)
• Rhinosinusitis, Anatomic airway obstruction

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Allergic Fungal Pansinusitis

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 Summary : Allergic Rhinitis
• Affects 17-25% of US population
• Symptoms / related diseases very relevant to the
otolaryngologists (e.g., nasal congestion,
rhinitis, rhinosinusitis, otitis media,
pharyngitis, laryngitis)
• Initial diagnosis by H & P, with skin or in vitro
tests as needed
• Treatments available : avoidance &/or
environmental measures, patient counseling,
physical fitness, pharmacotherapy, eradicate
comorbidity, immunotherapy

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation
 References
• Fornadley J, Corey J, Osguthorpe J, et al: Allergic
Rhinitis: Clinical Practice Guidelines. Otolaryngol
Head Neck Surg 115:115, 1996 (consensus of American
Academy of Otolaryngology - Head and Neck Surgery & American
Academy of Otolaryngic Allergy).
• Osguthorpe J, Derebery J (guest editors):
Otolaryngic Allergy. Otolaryngol Clin N Am 36(4),
2003.
• Krouse J, Chadwick S, Gordon B, Derebery J:
Allergy and Immunology: An Otolaryngic
Approach. Lippincott Williams & Wilkins. Phil.
2002.

© 2003 The American Academy of Otolaryngology – Head and Neck Surgery Foundation