1. Allergic Rhinitis

2. References Allergic rhinitis management pocket reference 2008.
Allergy 2008: 63: 990–996.
Pharmacotherapy: A pathophysiologic Approach. 7th Edition 2008.
Safety of Antihistamines in Children. Drug Safety 2001; 24 (2):
Second-Generation Antihistamines Actions and Efficacy in the Management of Allergic Disorders. Drugs 2005; 65 (3): 2

3. allergic rhinitis
<immunology> An inflammatory response in the nasal passages to an allergic stimulus. Often includes: nasal congestion, sneezing, runny or itchy nose

4. Allergic Rhinitis The most common atopic disease
The hallmark of ~: a temporal relationship between the exposure to allergens & the development of nasal symptoms
It takes at least 2 years of exposure to aeroallergens (airborne environmental allergens) to develop AR (thus, very rare in children <1 year)
The prevalence of AR: lowest in children < 5 yrs
highest 2nd---- 4th decades
Genetic predisposition (60%)

5. •
In a sensitized individual, allergic rhinitis occurs when mucous membranes are exposed to inhaled allergenic materials that elicit a specific response mediated by immunoglobulin E (IgE). 5

6. Exposure to antigen stimulates IgE production and
Allergen
sensitization and the allergic response. A.
Exposure to antigen stimulates IgE production and
sensitization of mast cells with antigen specific
IgE antibodies. B. Subsequent exposure to the same antigen produces an allergic reaction when mast cell mediators are
released. 6

7. Mast cells degranulating and releasing vasoactive amines.

8. Classification persistent AR is classified as seasonal or perennial
Seasonal: repetitive and predictable symptoms (severe)
Perennial: symptoms persist throughout the year without any obvious seasonal pattern
WHO: replace terms with intermittent or
persistent

9. symptoms symptoms lntermiHent Persistent Mild Moderate-Severe
<4 days per week
or <4 consecutive weeks
Persistent
symptoms
>4 days/week
and >4 consecutive weeks
Mild
all of the following
normal sleep
Moderate-Severe
one or more items
sleep disturbance
impairment of doily activities, sport, leisure
impairment of school or work
troublesome symptoms
no impairment of doily activities, srrt, leisure
no impairment of work and schoo
symptoms present but not troublesome

10. Allergic Rhinitis Most patients develop symptoms before age 30
Asthma develops in about 19% of children with rhinitis (more likely with perrenial allergic rhinitis)
The term “rhinitis” refers to the inflammation of the nasal mucous membranes. Whenever a a causative allergen can be identified-7 allergic rhinitis
It is difficult sometimes to distinguish between different types of rhinitis
Comparison between different types of rhinitis

11. Features of Common Rhinitis Symptoms
Allergic rhinitis
Infectious rhinitis
Vasomotor rhinitis
Rhinitis Medicamentosa
Etiology
Allergen
Viral or bacterial
Unknown
Tachyphylaxis to topical decongestants
Symptoms
Rhinorrhea, congestion, sneezing, pruritis, cough with postnasal drip ocular itching etc
Fever (more common in children), mucupurulent rhinorrhea, scratchy throat, congestion, cough
Rhinorrhea, congestion
Congestion
Pattern
Perennial or seasonal
Any time
Temporal relationship with use of topical decongestant
Associated Factors
Concurrent atopic disease, family history
None
Affects women primarily, strong odours, alcohol, stress, change in humidity and temperature
Overuse of topical decongestants, concurrent use of antihypertensive therapy

12. Perennial Allergic Rhinitis 1
Caused by continuous exposure to many different types of allergens
Dust Mite-7 the most common cause of perennial allergic rhinitis
Commonly: household dust mites, molds, cockroaches, house pets
Less commonly: cottonseed & flaxseed (found in fertilizers, hair setting preparations and foods); some vegetable gums (found in hair setting prep & foods)

13. Caused by:
Dust mites

14. Perennial Allergic Rhinitis 2
Dust mite: thrive in carpets, beddings & reproduce best in warm (18-21ºC) humid (>50%) environment found in most homes
Mites feed on human skin scales and their own faeces.
Mite itself is not allergen, the main allergen is the
glycoprotein that coats their faeces.
Dust mite remain airborne for about 30 minutes after being disturbed
Molds: grow best in warm, moist environment
Cat-derived allergens: light small proteins secreted through the sebaceous glands in the skin. May remain airborne for up to 6 hrs. Can be detected at home even 6 months after removal of the cat.

15. Seasonal Allergic Rhinitis
Caused by wind-borne plant pollens (e.g. tree, grass. etc)
“hay fever”, and “rose fever” are terms related to seasons associated grass pollinosis and NOT associated with FEVER!

16. -
Nasal
Passages
AOc(gCfls , -

17. Complications Sinusitis Recurrent otitis media & hearing loss
Patients who develop:
fever, •
purulent nasal discharge, frequent HA,
earache
refer to Dr. for evaluation and treatment

18. Symptoms of Allergic Rhinitis
Ocular: itching, lacrimation, mild soreness, puffiness
& conjuctival erythema
Nasal: congestion, watery rhinorrhea, itching, sneezing, postnasal drip and nasal pruritus
Head & Neck: loss of taste and smell, mild sore throat due to postnasal drip, earache, sinus HA, itching of the palate and throat
Systemic: malaise & fatigue:

19. Physical Assessment “allergic shiners” -7 venous/lymphatic congestion
Chronic mouth breathing-7 highly arched palate
A horizontal crease across the lower third of the nose (in patients repeatedly rub their noses upward) called “nasal salute”
Nasal mucosa: pale & swollen
Nasal secretions: clear & watery
Eyes: watery with scleral & conjuctival erythema and periorbital edema

20. Allergic shiners
Arched palate because of mouth breathing
Periorbital edema

21. Repooted performan of the allergic lute (a)
r ults 1n a n al cr aso (b).
lute (a)

22. Allergic Rhinitis Questionnaire
Response Choices
1. Do you have any of the following symptoms?
Symptoms on only one side of your nose
Yes No
Thick,green or yellow discharge from your nose (see NOTE)
Postnasal drip (down the back of your throat) with thick mucus and/or runny nose (see NOTE}
Facial pain (see NOTE}
Recurrent nosebleeds
oss of smell (see NOTE}
2. Do you have any of the follow ing symptoms for at least one hour on most days (or on most days during the season if your symptoms are seasonal)?
Watery runny nose
Sneezing, especially violent and in bouts
Nasal obstruction
Nasal itching
Conjunctivitis (red,itchy eyes) 22

23. The ymptom
de cribed in Que tion 1 are u ually
OT found in allergic rhiniti . The pre ence of ANY ONE of them ugge t that alternative diagno e hould be inve tigated. Con ider alternative diagno­ e and/or referral to a peciali t.
NOTE: Purulent di charge po tna al drip facial
pain and lo of n1ell are common
ymptom of
inu iti al o
inu iti . Becau e mo t patient with
have rhiniti (though not alway allergic in origin) in
thi ituation the clinician po
hould al o evaluate the
i bili ty of allergic rhini ti .
The pre ence of watery runny no e with ONE OR
MORE of the other
ympto1n li ted in Que tion 2
ugge t patient n1ent.
allergic rhiniti and indicate
that the
hould undergo further diagno tic a e -
The pre ence of watery runny no e ALONE
ugge t
that the patient MAY have allergic rhiniti . (Addi ­ tionally on1e patient with allergic rhiniti have only na al ob truction a a cardinal ymptom.)

24. Medication Class Symptoms Controlled Comments
TABLE Pharmacotherapeutic Options For Allergic Rhinitis
Medication Class Symptoms Controlled
Comments
Antihistamines
Systemic
Sneezing, rhinorrhea, itching,
For seasonal allergic rhinitis, begin treatment before allergen exposure.
Nonsedating agents should be tried first. If ineffective or too expensive for the patient,the older agents may be used. For perennial allergic rhinitis, use an intranasal steroid as an alternative to or in combination with systemic antihistamines.
Logical addition to nasal steroids if ocular symptoms are present.
Option for seasonal allergic rhinitis.Warn patients of potential drowsiness.
conj unctivitis
Ophthalmic Intranasal Decongestants Systemic Topical
I ntranasal corticosteroids
Conjunctivitis
Sneezing, rhinorrhea,nasalpruritus
Nasal congestion Nasal congestion
Only needed w hen nasal congestion is present.
Only needed w hen nasal congestion is present. Do not exceed 3-5 days. For seasonal allergic rhinitis, an option w hen congestion is present. Must
begin therapy before allergen exposure. Excellent choice for perennial rhinitis.
Prevents symptoms; therefore,for seasonal allergic rhinitis,use before offending allergen's season starts. For perennial rhinitis, improvement may not be seen for up to 1 month.
Sneezing, rhinorrhea, itching,
nasal congestion
Mast cell stabilizers
See comments
Intranasal ant icholinergics
Rhinorrhea
Reserve for use w hen above therapies fa il or cannot be tolerated.

25. Oral H, antihistamines H,-blockers 2nd generation blockage of H1
Name and Also known as
Generic name
Mechanism of ac­ tion
Side effects
Comments
Oral H, antihistamines H,-blockers
2nd generation
blockage of H1
receptor
-some anti-allergic activity
new generation drugs can be used once daily
no development of
tachyphylaxis
2nd generation
no sedation for
most drugs
-no anti-cholinergic effect
no cardiotoxicity
acrivasti ne has
sedative effects
oral azelasti ne may induce
sedation and a bitter taste
Firsine therapy except in Moderate/ Severe Persistent Allerg ic Rhinitis
-2nd generation oral HI­
blockers are preferred for
their favorable efficacy/ safety ratio and pharma­ cokinetics;first generation molecules are no longer recommended because of their unfavorable safety/ efficacy ratio
Rapidly effective (less than 1hr)
on nasal and ocular symptoms
• Moderately effective on nasal congestion
* Cardiotoxic drugs
(astemizole,terfenadine)
are no longer marketed in most countries
Cetirizine Ebastine
Fexofenadine
Loratadine Mizolastine Acr ivasti ne Azelastine
Mequitazine
New products
Desloratadine
Levocetirizine
Rupatadine

26. half-life; tmax = time after oral dose
Table Ill. Pharmacokinetic and pharmacodynamic properties of second-generation antihistamines
tmax (h)
Cetirizine
Fexofenadine
Desloratadine
Loratadine ]
,137] ] ]
Onset of action (h) ]
, ] ] ]
F (%)
,135]
921154]
871155]
::: ]
F, food effects
Delayl1561
Decreased 25%11571
No effect1158l
Increased 43%11591
Vd (Ukg)
,160,161] ] NA
,161]
Protein binding (%) ]
,163] ]
First-pass metabolism
Limited1162l
Moderate1155l
Extensive1162l
Hepatic metabolism
Negligiblel1641
CYP3A411651
CYP3A4 CYP2D61166·1671
Active metabolites
None11621
Hydroxylated 11551
Descarboethoxy
(desloratadine )11621
Elimination
renal (%) 70 12 44
:::.20 unchanged
fecal (%)
101135)
801154]
44 (as metabolites)I155J
40 (as metabolites)l1641
t•h (h) ]
,137]
,142,143,168,169]
,143]
Duration of action (h)
24188,149,160, ]
241146,147,149]
241151]
<241173,174]
CYP = cytochrome P450; F = fraction absorbed orally ; NA = not available; t•h = elimination
half-life; tmax = time after oral dose
administration until maximal plasma concentration ; Vd = volume of distribution.

27. Table VIII. Adverse effects (% of patients) with second-generation antihistamines
Cetirizine
(n = 2034)l3601
Desloratadine
(n = 1655)l155l
Fexofenad ine (n = 679)l3581
Loratadine
(n = 1926)[3591
Drowsiness/somnolence
13.7
2.1
1.3 8
Insomnia
< 1
<2
Headache
>2
10.6 12
Fatigue
5.9 4
Dry mouth
5.0
3.0 3
Pharyngitis
2.0
4.1
3.2
Dizziness
<2.2
Gastrointestinal distress
Dysmenor rhoea
1.5

28. NS = not stated in product labelling.
Table XV. Recommended dailya oral dosage of second-generation antihistamines
Drug
Adults
Children
Elderly
Renal impairment
Hepatic impairment
Cetirizine
5-1Omg
6-11 years: 5-1Omg
0.5-5 years: 2.5- Smg
5mg
Desloratadine
>12 years: 5mg
5mg every 48 hours
Fexofenadine
180mg
6-11 years: 30mg twice daily
60mg
Loratadine
10mg
>6 years: 1Omg
2-5 years: 5mg NS
1Omg every 48 hours
a Unless specified.
NS = not stated in product labelling.

29. Azelastine Levocabastine Olopatadine
- blockage of H1
receptor
-some anti-ollergic activity for azelastine
-Minor local side effects
- Azelastine : bitter taste
in some patients
Rapidly effective (less than 30 min) on nasal or ocular symptoms
local H, antihistamines (in­ tranasal,
intraocular)
Intranasal glucocortico­ steroids
Beclomethasone dipropionate
Budesonide Ciclesonide Flunisolide
Fluticasone
propionate Fluticasone furoate Mometasone furoate Triamcinolone
acetonide
-potently reduce nasal inflammation
- reduce nasal hyperreactivity
-Minor local side effects
-Wide margin for systemic side
effects
- Growth concerns with BDP only
-In young children
consider the combination of intranasal and inhaled drugs
The most effective pharmacologic treatment of allergic rhinitis;first-line treatment for Moder­ ate/ Severe Persistent Allergic Rhinitis
Effective on nasal
congestion
Effective on smell
Effect observed after hrs but maximal effect after a few days
Patients should be advised on the proper method of administering intranasal glucocortico­ steroids, including the importance of directing the spray laterally rather than medially (toward the septum) in the nose

30. 30 Oral I IM glucocortico- steroids
Dexamethasone Hydrocortisone Methylpredisolone Prednisolone Prednisone Triamcinolone Betamethasone Deflazacort
- Potently reduce
nasal inflammation
-Reduce nasal hyperreactivity
- Sffstemic side
e ects common in
particular for IM drugs
-Depot injections may cause local
tissue atrophy
When possible, intranasal glucocortico- steroids should replace oral or IM drugs
However, a short course of oral gluco- corticosteroids may be needed if moderate/ severe symptoms
Local cromones (intranasal, intraocular)
Cromoglycate Nedocromil Naaga
-mechanism of action poorly known
-Minor local side effects
Intraocular cromones are very effective
Intranasal cromones are less effective and their effect is short lasting
Overall excellent
safety
Oral decongestants
E hedrine
P enylephrine
Phenyl-
propanolamine
Pseudoephedrine
Oral Hl- antihistam ine- decongestant combinat ion
- drmpathomimetic
rug
-relieve symptoms of nasal
congestion
Hypertension
Palpitations
Restlessness
-Agitation
-Tremor
-Insomnia
-Headache
Dry mucous
membranes
-Ur inary retention
Exacerbation of
aucoma or yrotoxicos is
Use oral decongestants with caution in patients with heart disease
Oral Hl- antihistamine decongestant combination
products may be more
effective than either product alone but side effects are combined 30