Dr.

Nabil Galal,MD



This work is a trial to simplify scientific facts to
be as possible understandable to General
practitioners & otolaryngologists concerning
allergic rhinitis.

The main referrences of this subject are:
Recommendations of Am. Academy of
Allergy & Immunology (1993)
Practice parameters for allergy put by The
Joint Task Force for Rhino-sinusitis &
Asthma (1995)
ARIA workshop report (2001) & ARIA
revision 2009.
Rhinitis:
It is an inflammation of the membrane
lining the nose characterized by
Nasal congestion
Rhino rhea
Sneezing
Post nasal discharge
Allergic Rhinitis


It is a symptomatic disorder of the nose
induced by an IgE mediated inflammation
after exposure of the membrane lining the
nose to an allergen.



Atopy:
It is the aptitude of the immune system to
secrete excessive quantities of IgE in response to
minimal allergic stimulation.

It gives a highly +ve skin test to common aero-
allergens

Entopy:
It is the existence of local allergic responcce in
the nasal mucosa in the absence of systemic allergic
reaction.
It gives ve skin test to common aero-allergens

Allergic rhinitis represents a global health
problem. It is an extremely common disease
worldwide affecting up to 25% of the
population, however real figures are much
more, as many patients do not recognize
rhinitis as a disease, therefore they do not
consult physicians.
There are many other conditions associated
with allergic rhinitis, as asthma ,sinusitis
,otitis media , lower respiratory tract infection
& sino-nasal polyposis.

Asthma & rhinitis have common co morbidities
suggesting the concept of one airway one
disease
They are linked by epidemiologic, pathologic &
physiologic characters
common therapeutic
approach.

Patients with persistent All. Rh. Should be
evaluated for Asthma.

Patients with Asthma should be evaluated for All.
Rh.

Classification of Allergic Rhinitis
Less than 4 d./w
Less than 4w/y
Intermittent

More than 4d/w
More than 4w/y
Persistent
Both types are staged according to the severity
of signs & symptoms.







Sleep disturbance Impair. Of work
Impair. of daily act. Troublesome
symp
Mild
Moderate
to
Severe
There are a lot of allergens & trigger
factors that induce allergic rhinitis, but
here in Egypt & other developing
countries,what are the trigger factors that
have an upper hand in inducing allergic
rhinitis ?
House dust mites :
Mites make up a large part of house
dust allergens.
Most of asthmatics & patients with
persistent all. Rhinitis are sensitized to mites.
The most imp. House dust mites are
Dermatophagoides pteronyssinus
Dermatophagoides farinae
Euroglyphus maynei
They feed on human skin dander which are
particularly abundant in mattresses, pillows &
carpets.

Their growth is maximal in hot (> 20 c) &
humid
weather ( 80% relative humidity).

So, Egypt's atmosphere is considered
optimum for maximum growth of House
Dust Mites.
Animal Dander:
Pets take the upper hand in western
countries
Cattle in agricultural countries as Egypt
has an important role.
The allergen are found in dander, fur ,
saliva,
urine & serum.

Insects:
In hot humid weather allergies to
cockroach is
very common in low income housing.
Low Molecular Weight Compounds
Flour dust:
It increases the incidence of
rhinitis & asthma among bakers & those
dealing with flour , baking there own bread
in rural areas.
Outdoor pollutants:
Factories Cement industry
Sugar industry
Rice straw burning
Automobile Pollutants
Oxidant pollutants Co

No

So2
Indoor pollutants:
Fuel burning wood burning stoves
Fuel burning stoves
they induce the following pollutants
Co NO
Co2 No2

Cigarette smoking:
- Irritation of nasal mucosa
-Alteration of muco-ciliary clearance
-Allergic reaction in tobacco sensitive
individuals eosinophilic all.
Inflam. of nasal mucosa
Symptoms of rhinitis
Sneezing Rhino rhea Anosmia Nasal obstruction Post
nasal discharge

Symptoms of Asthma
Wheezy chest
Difficult respiration

Symptoms of other allergic conditions
Conjunctivitis
Urticaria
Exacerbation of symptoms on exposure to
specific allergen exposure to animals
house cleaning

History of drug sensitivity
Aspirin
Non steroidal anti
inflammatories

Family history of any allergic condition
Surroundings & work
Nature of exposure at work
Nature of exposure at home
Pets
Wool blankets
Fixed rugs
Severity of rhinitis
Sleep disturbances
Daily activities
Performance at work
General E.N.T. examination

Nasal Endoscopy
Color of inferior turbinate
Rx to introduction of endoscope serous discharge
sneezing,
nasal engorgement.
IgE is the major isotype of immediate
hypersensitivity reaction. So, in vitro & in vivo
tests for diagnosis of allergic diseases are
directed towards the detection of free or cell-
bound IgE
Skin Tests
If properly done they represent a major
diagnostic tool in the field of allergy.
Pepy,s modified skin prick test was the method
of choice until the European Academy of Allergy
& Clinical immunology (1995 ) & The U.S joint
council of Allergy & Asthma ( 1993 )
recommended skin prick- puncture test as a
major test for the diagnosis of IgE mediated
allergic diseases.
Skin testing 2003 AAOA guidelines
The goal of testing is to identify antigens to which
patients are symptomatically reactive and to
quantify the sensitivity if immunotherapy is
planned
There are a variety of acceptable techniques:
Prick testing, intradermal testing, intradermal dilutional
testing, and in vitro testing
Allergy care shall be directed by a trained and
competent physician who regularly participates in
the care
Members shall practice in an ethical and a
responsible manner
In skin puncture test we use 3 different materials
The allergen
False -ve control the diluent used for allergen preservation
False +ve control Histamine dihydrochloride
(5.43m.mol/litre)

Interpretation of results
They should be read at peak of their reaction ( 15 min).
-ve no wheel
1+ 1 mm. wheel above saline control.
2+ 1-3 mm. wheel above saline control
3+ 3-5 mm. wheel above saline control + flare +ve
4+ > 5 mm wheel above saline control + flare RX


Multitest II
Whealing response
Factors affecting skin testing
Quality of antigen
Age, as extreme of age may yield week
reaction
Drugs, antihistamines & tricyclic
antidepressant can depress or abolish Rx.


Serum specific IgE:
Radio allergosorbent test ( RAST)
Single allergen test
Mixture of allergens test

RAST is useful if per-cutaneous tests are not
practical problems with reagent storage ,.
lack of expertise
patients taking medications interfering with
skin tests.

Soluble allergens bound to solid phase support
(paper disc) to create a stable immunosorbent
media.
The paper disc is incubated with the test sera,
specific IgE antibody will bind to the solid phase
allergen.
The paper disc is then washed to remove all
unbound sera and IgE.
The disc is then exposed to rabbit anti-human IgE
antibodies (IgG) which are radiolabeled. It interacts
with the Fc determinant portion on human IgE
bound to the solid phase allergen.
The unbound anti-IgE is washed off the disc and the
disc is then quantified by a scintillation counter.
Nasal challenge test:
It is used in research & to a lesser extent
in clinical practice
However it is important in diagnosis of
occupational rhinitis & NARES.
So , the important question

is

When to ask for diagnostic tests?
Patients with clear history of allergy but with poor
response to oral antihistamines & local steroid sprays.

Patients with severe symptoms of allergic rhinitis, with
good response to medication but they wish to identify
the causative antigen & consider for immunotherapy.

Patients with allergic fungal sinusitis aiming for
immunotherapy.

Patients with combined allergic rhinitis & asthma.

Patients with long term severe problem aiming for
anther line of ttt.
So a diagnostic approach to allergic rhinitis is
summarized as follows in the majority of patients.
Careful history study
thorough examination
Limited number of allergic tests.

This is all that is required to confirm or exclude an
allergic etiology.

When there is discordance between history & skin
test, further tests including RAST & provocation
tests may be indicated.
PART 2
MANAGEMENT OF ALLERGIC
RHINITIS
Dr. Nabil Galal,MD
MECHANISM OF
ALLERGIC RHINITIS
Fig. 1. Mechanism of action of allergy medications. (From Marple BF,
Fornadley JA, Patel AA,et.al)


ALLERGEN AVOIDANCE
Encase mattress & pillow in impermeable covers which
are routinely washed in hot water weekly.

Carpets are treated with acaricidals

Avoid indoor pets

Good ventilation to reduce humidity
Oral Antihistamines:
They are effective in reducing symptoms of itching ,
sneezing & rhino rhea.

They are the first line of treatment of allergic rhinitis.

They reduce the symptoms of conjunctivitis which are
often associated with allergic rhinitis.

Oral antihistamine have a little objective effect on nasal
congestion.
They were introduced in market in 1942.

they act by binding with H1 Histamine receptors in the
nose but they have no effect on other allergic mediators.

Histamine 1 stimulation leads to the classic symptoms of
allergy
which are sneezing, itching & rhino rhea.

Examples of first generation antihistamines:
Chlorpheniramine
Diphenhydramine
Prometazine
Triprolidine
Side effects of First Generation
Antihistamines:
Sedation:
This is defined as global impairment of
psychomotor performance with tendency to fall
asleep.
Anti cholinergic effect:
Tachycardia, dry mouth & urine voiding.
Second Generation Antihistamines
They are defined as non sedating antihistamines.
They act as H1 blockers & to a little extent as anti allergic
blocking other mediators sharing in allergic reaction, so they
control itching , sneezing rhino rhea & to a little extent nasal
congestion & obstruction.
They have rapid onset of action.
They are administered once per day.
Examples of 2
nd
generation antihistamines:
Loratidine (Claritin)
Cetrizine (Zyrtec)
Fexofenadine (Telfast)
Astemizole (Hismanal)
Ebastine (Evastine)
Desloratidine (Arius)
Levocetrizine (Allear)

Side effects of Second Generation
Antihistamines

Sedation:
It is not considered a major side effect but
some 2
nd
generation antihistamines have a
sedating effect as cetrizine with personal
variation.
Cardiac side effects:
Due to its adverse effect of trans-membrane
ionic movement of k+ ,Na+ & Ca+, some of the
2
nd
generation antihistamines may have an
arrythmogenic effect as astemizole.
Cardiac
Toxicity
Use in
Renal
Disease
Use in
Liver
Disease
Sedatio
n
ETAC Anti-
allergic
effect
Asthm
a
Persisten
t Rhin.
Inter.
Rhin.
Dose Tradenam
e
Agent
-
10mg

reduce

10mg

reduce
- - + - + +
10 mg Claritin Loratidine
-
10mg

reduce
10mg

reduce

- - + - + +
10 mg Arius Desloratidine
-
No
Change
No
Change
- - + - + +
120mg
180mg
Telfast Fexofinadin
-
5mg 5mg
+ + ++ + + +
10mg Zyrtec Cetrizne
-
5mg 5mg
+ + ++ + + +
5mg Allear Levocetrizne
+
No
Change
Avoid
- - + - + +
10mg Hismanil Astemizole
_ 10mg

reduce
10mg

reduce

- - + - + +
10mg Evastine Ebastine


ARIA Revision 2009-GRADE
1. In patients with allergic rhinitis, we recommend second-generation
oral H1antihistamines that do not cause sedation and do not
interact with cytochrome P450 (strong recommendation)


2. In patients with allergic rhinitis, we also suggest second-generation
(mildly sedating and/or interacting with cytochrome P450) oral
H1antihistamines (weak recommendation)

3. We recommend not to use first generation oral H1-antihistamines


Brozek, Bousquet, Schunemann et al

Grade of recommendation:
Strong: benefits clearly outweight risk and burden, or vice versa
Weak: Benefits closely balanced with harm and burden

It was first introduced in market as Beclomethasone
dipropionate in 1972.
It is now the most potent treatment of both allergic & non allergic
rhinitis.
It was initially reserved as a second line of treatment of allergic
rhinitis, but it is now considered as a first line of treatment for
adults with moderate to severe cases of intermittent &
persistent allergic rhinitis.
Glucocorticosteroids can suppress many stages of the
inflammatory cascade , this may explain their strong control of
allergic symptoms especially nasal obstruction which is not
treated successfully with oral antihistamines.
Side effects:
Local side effects:
Nasal crustation Dryness Minor epistaxis Septal
perforation (rare)

Growth in children:
Long term use of beclomethasone dipropionate have shown
mild growth retardation in some children but there were no
growth affection with other products.
Side effects:
Effect on hypothalamo pituitary adrenal axis
(HPA):
Patients on nasal glucocorticosteroid sprays appear to
be at a very low risk of developing HPA suppression
compared to those on oral inhalants for astma.

Effect on pregnancy:
There is recent evidence based studies on the effect of
local glucocorticosteroid sprays on pregnancy & it
proved to be safe (level B).
s
Long Term
Use
Administrati
on in
Children
Growth
Retardation
HPA
Suppressio
n
Efficacy Trade
name
Agent
Unsafe Not
Recommende
d
+ +

+
Beconas
e
Beclonmethazon
e dipropionate
Safe 5 Years
- - ++
Flixonas
e
Flucticazone
Propionate
Safe 4 Years
- - ++
Rhinocor
t
Budesionde
Safe 3 years
- - ++
Avamys Flucticazone
Furoate
Safe 3 Years
- - ++
Nasonex Mometazone
Furoate
Safe 4 Years
- - ++
Nasocort Triamcinolone
Acetonide
Eye Allergies and the Naso-Ocular Reflex
Research demonstrated that histamine release in the nose
does in fact trigger eye allergies. This means that the
pollen or other allergens you inhale are most likely the
culprit in your eye allergy symptoms; while some
allergen does probably get into your eye directly, this
amount is much smaller than the amount you inhale

So proper control of nasal allergy using topical steroids
spray will improve the ocular symptoms.
Systemic Glucocorticosteroids exert their action on broad
spectrum of inflammatory phenomena in the allergic
process , so , they are effective in controlling all allergic
symptoms including nasal obstruction & smell affection.
It can be administered orally or as depot injection, studies
between them were in favor of depot injection, never the
less there are arguments in favor of oral route as the
dose can be adjusted according to the changing needs
for therapy & it can be stopped with emergence of
complications.
The dose of oral steroids is debatable between different
studies but the most acceptable is a short term use of
20-40 mg of prednisolone for a period of 3-7 days.
It is used in severe & intractable cases of allergic rhinitis,
also in cases of sinonasal polyposis.
They cause vasoconstriction & shrinkage of nasal mucosa
by their action on adrenergic receptors.

They are effective in relieving nasal obstruction.

They should not be used for a period longer than 10 days
due to rebound vasodilatation & nasal congestion.

Examples of systemic decongestants are: ephedrine,
pheylephrine, phenyl propanolamine & pseudo
ephedrine.


Side effects: irritability, tremors, tachycardia, arrhythmia&
dizziness.

Contraindications: hypertension thyrotoxicosis elderly.

The combination of antihistamines & systemic nasal
decongestants is suitable for allergic cases presenting with
nasal obstruction.

Individuals are considered appropriate candidates for
immunotherapy if their rhinitis proved to be allergic in origin,
with unavoidable exposure to an allergen or more to which
potent extracts are available .
Indications:
Patients diagnosed as allergic rhinitis clinically & with
demonstrable laboratory evidences of specific Ig E ( skin tests
& in vitro tests ).
These patients can have immunotherapy if:
They have poor response to pharmacotherapy.
Unacceptable response to pharmacotherapy.
Allergic rhinitis with asthma
Desire to avoid long term pharmacotherapy.
Possible prevention of asthma in atopic children.
moving immune system
from CD4+Th2 cell to
Th1 cell pathway
Alter cytokine
production
IL-4, IL-5 as Th2
cytokines
IFN-gamma as Th1
cytokines


Injectable vaccine mainstay of therapy
in the US
Sublingual - used widely in Europe
Wilson et al (2005) performed Cochrane
database meta analysis 22 RCT, found
therapy works, but difficult to compare with
injection immunotherapy. Grade B
Intranasal - currently under investigation
for children and adults with allergic rhinitis.
Limitations:
Many allergens are not identified.

Tedious & costly examinations are required to identify cases
that benefit from immunotherapy.

Immunotherapy must be administered by expert doctors &
personnel due to its possible side effects.

Very high costs.

Contraindications:
Pre school children

Senior citizens
Humanized monoclonal antibodies
against IgE:

It targets the high affinity binding receptor binding sites of IgE, so
bound IgE is not available for basophil binding as a result de-
granulation is attenuated & allergic symptoms are reduced

The drug is taken whether through i.v route or s.c route in a period of 4-
8 weeks.

No serious side effects were noticed apart from mild reaction at site of
injection ,mild upper resp. catarrh & mild pharyngitis.

Arachidonic Acid Metabolism &
Allergy

Arachidonic Acid Synehesis
The first step in the arachidonic acid
pathway is the generation of arachidonic
acid by the action of phospholipase A2.
This derives free arachidonic acid from
lipid bilayers of the cell membrane.
Arachidonic Acid Metablism

Leukotrienes have also demonstrated a significant role in the
pathophysiology of allergic rhinitis. During an allergic response,
leukotrienes are released from the cells. Leukotrienes are
inflammatory mediators that cause vasodilatation and mucosal
swelling, which results in the congestion associated with seasonal
allergic rhinitis. Leukotriene receptor antagonists inhibit leukotrienes,
thereby decreasing congestion associated with seasonal allergic
rhinitis (Gonyeau & Partisano, 2003).

There is one inhibitor of 5-FLAP now in a phase III trial. An inhibitor of the 5-
lipoxygenase (Zileuton) is currently available for treatment of asthma. It is
effective in inhibiting the leukotriene production, but it also has to be
monitored closely because of hepatic toxicity.
There are no inhibitors of B-LT1 or B-LT2 available at this time. CysLT
antagonists are available today;
[11]
the substances known are Montelukast,
Zafirlukast and Pranlukast. These drugs have a variety of effects on asthma
in children and adults. Although the efficiency concerning pulmonal function
and exacerbation of asthma as well as quality of life is inferior to that of
inhaled corticosteroids and long-acting beta-agonists, the antileukotrienes
are a useful add-on or even substitute in the case of insufficient steroid
compliance or effect. Studies in asthma and allergic rhinitis revealed that
patients with coexisting asthma and allergic rhinitis might have special
benefit by the treatment with Montelukast. There are also good effects in
exercise-induced asthma. Several studies show the benefit of
antileukotriene treatment in patients with aspirin sensitivity. However, the
effects of aspirin challenge cannot be suppressed completely


The leukotriene modifiers are the first classification of drugs that are
mediator-specific therapy for asthma (Krawiec & Wenzel, 1999). The
Food and Drug Administration (FDA) approved three leukotriene
modifiers divided into two classes. The first class leukotriene-
receptor antagonists prevent leukotriene binding and includes
zafirlukast (Accolate) and montelukast (Singulair). The second
classification is leukotriene-receptor inhibitors, which focus on
synthesis inhibition and include zileuton (Zyflo)
Leukotriene modifiers appear to have a beneficial role in the
treatment of both asthma and allergic rhinitis and are currently
recommended as alternative therapy to inhaled corticosteroids or in
combination depending on severity of symptoms. The use of
leukotrienes as monotherapy for asthma or allergic rhinitis is being
debated. In a systematic review comparing the use of inhaled
glucocorticoids with leukotriene antagonists as monotherapy in the
treatment of asthma, Ducharme (2003) concluded that leukotriene
antagonists are less effective than inhaled glucocorticoids when
used as a single agent in the treatment of asthma. Gonyeau and
Partisano (2003), in their review of leukotriene antagonists as a
treatment for seasonal allergic rhinitis, also concluded that
leukotriene antagonists appear to have a primary role, not as a
single treatment agent, but as an adjunct to intranasal steroids and
antihistamines.
Remember always that it is a united airway, so external
stimulus that may cause allergic rhinitis may also induce
asthma.

Studies proved that allergic rhino-conjunctivitis is a
precursor of asthma in children.

Control of allergic rhinitis has a role in asthma treatment.

In treatment of allergic rhinitis with asthma , two lines of
treatment may take place more than if we treat allergic
rhinitis alone
Antileukotriens
Immunotherapy

Algorithm for management of allergic rhinitis
Good history & Exam.
Antihistamines

Local steroids
Poor
response
Skin
Prick
test
+ve
Good
respons
e
-ve
Skin
Prick
test
-ve
+ve
RAST
or
PRIST
-ve
+ve
Chang
e
Line of
ttt
Non
Allergi
c
rhinitis
Allergi
c
rhinitis
Algorithm for management of allergic rhinitis
Management of Allergic Rhinitis
Intermittent Rhinitis Persistent Rhinitis
Mild Moderate to Severe
Mild
Moderate to Severe
Dripper Blocker
2
nd
G.A.H
2
nd
G.A.H +
Sys.N.D
2
nd
G.A.H + Local
Spray
Mild Moderate to Severe
Dripper Blocker
2
nd
G.A.H +
Sys.N.D
2
nd
G.A.H + Local Spray
2
nd
G.A.H
Intermittent Rhinitis
Review after 3 Weeks
Improvement Failure
Stop ttt Add Local Steroids
Review after 3 Weeks
Improvement
Failure
Step Down Treatment
( (1 Month Local Spray
Look for Infection
Doubling Local
Steroids
Management of Allergic Rhinitis
Intermittent Rhinitis Persistent Rhinitis
Mild Moderate to Severe
Mild
Moderate to Severe
2
nd
G.A.H + Local Spray 2
nd
G.A.H + Local Spray
Syst. Decongestants

Anti leukotriens
Mild Moderate to Severe
2
nd
G.A.H + Local Spray
Persistent All. Rhinitis
Review after 3 Weeks
Improvement Failure
Step Down Treatment
( (1 Month Local Spray
Look for Infection
Doubling Local
Steroids
Review after 3 Weeks
Improvement Failure
Step Down Treatment
( (1 Month Local Spray
Look for Infection
Doubling Local Steroids
Systemic Steroids
Immunotherapy


2
nd
G.A.H + Local Spray
A broad range of medications exists for the treatment of patients with allergic
rhinitis. The most appropriate medical therapy depends upon the nature
of each patients specific rhinitis symptoms, his or her tolerance to and
preference for certain classes of medications, and the response to treatment

.
The various pharmacotherapeutic options available affect symptoms of allergic
rhinitis through a variety of mechanisms .


Through an appreciation of these various physiological mechanisms, the physician
can select the treatment option or options that will most likely effectively
manage the patients symptoms.
Conclusion