Allergic Rhinitis

References

2

• 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): 119-147.

• Second-Generation Antihistamines Actions and Efficacy in the Management of Allergic Disorders. Drugs 2005; 65 (3): 341-384

• allergic rhinitis• <immunology> An inflammatory response in

the nasal passages to an allergic stimulus. Often includes: nasal congestion, sneezing, runny or itchy nose

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 yrshighest 2nd---- 4th decades

• Genetic predisposition (60%)

•• 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

Allergen

6released.

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

Mast cells degranulating and releasing vasoactive amines.

Classification• 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

lntermiHentsymptoms

• <4 days per week• or <4 consecutive weeks

Persistentsymptoms

• >4 days/week• and >4 consecutive weeks

Mildall of the following

• normal sleep• no impairment of doily activities, s r r t , leisure• no impairment of work and schoo• symptoms present but not troublesome

Moderate-Severeone or more items

• sleep disturbance• impairment of doily activities, sport, leisure• impairment of school or work• troublesome symptoms

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

Features of Common Rhinitis SymptomsAllergic 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 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

Perennial Allergic Rhinitis1• 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)

Caused by:

Dust mites

Perennial Allergic Rhinitis2• 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.

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!

-

NasalPassages

AOc(gCfls

,-

Complications1. Sinusitis

2. Recurrent otitis media & hearing loss

3. Patients who develop:• fever,

•

•

•

purulent nasal discharge,

frequent HA,

earache

refer to Dr. for evaluation and treatment

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:

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

Allergic shiners

Arched palate because of mouth breathing

Periorbital edema

Repooted performan of the allergicr ults 1n a n al cr aso (b).

lute (a)

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Allergic Rhinitis Questionnaire

Question 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) Yes No

• Postnasal drip (down the back of your throat) with thick mucus and/or runny nose (see NOTE}

Yes No

• Facial pain (see NOTE} Yes No

• Recurrent nosebleeds Yes No• oss of smell (see NOTE} Yes No

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 Yes No

• Sneezing, especially violent and in bouts Yes No

• Nasal obstruction Yes No• Nasal itching Yes No

• Conjunctivitis (red,itchy eyes) Yes No

• Theymptom

de cribed in Que tion 1 are u uallyOT 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 dripfacialpain and lo of n1ell are common ymptom of

inu iti al o

inu iti . Becau e mo t patient withhave rhiniti (though not alway allergic in origin) inthi ituation the clinicianpo

hould al o evaluate thei bili ty of allergic rhini ti

.• The pre ence of watery runny no e with ONE ORMORE of the other

ympto1n li ted in Que tion 2ugge t

patient n1ent.

allergic rhiniti and indicate that thehould undergo further diagno tic a e -

• The pre ence of watery runny no e ALONE

ugge tthat the patient MAY have allergic rhiniti . (Addi tionally on1e patient with allergic rhiniti have only na al ob truction a a cardinal ymptom.)

TABLE 93 -2. Pharmacotherapeutic Options For Allergic Rhinitis

Medication Class Symptoms ControlledComments

AntihistaminesSystemic

Ophthalmic Intranasal Decongestants Systemic TopicalI ntranasal corticosteroidsMast cell stabilizers

Intranasal ant icholinergics

Sneezing, rhinorrhea, itching,conj

unctivitis

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.

ConjunctivitisSneezing, rhinorrhea, nasal pruritus

Nasal congestion Nasal congestionSneezing, rhinorrhea, itching,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.Reserve for use w hen above therapies fa il or cannot be

tolerated.

See comments

Rhinorrhea

Name and Also known asOral H, antihistamines H ,-blockers

Mechanism of ac tion

- blockage of H1

receptor-some anti-allergic

activity- new generation

drugs can be used once daily

- no development oftachyphylaxis

Side effects

2nd generation- no sedation for

most drugs-no anti-cholinergic

effect- no cardiotoxicity- acrivasti ne has

sedative effects- oral azelasti ne

may inducesedation and a bitter taste

Comments

- Firs ine therapy except in Moderate/ Severe Persistent Allerg ic Rhinitis

-2nd generation oral HI blockers are preferred fortheir 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

Generic name

2nd generationCetirizine EbastineFexofenadineLoratadine M izolastine Acr ivasti ne AzelastineMequitazineNew productsDesloratadineLevocetirizineRupatadine

Table Ill. Pharmacokinetic and pharmacodynamic properties of second-generation antihistamines

CYP = cytochrome P450; F = fraction absorbed orally ; NA = not available; t •h = elimination

half-life; tmax = time after oral doseadministration until maximal plasma concentration ; Vd = volume of distribution.

tmax (h) Cetirizine Fexofenadine Desloratadine Loratadine

0.81133-135] 1.21136,137] 41138-140] 1.51140-142]Onset of action (h) 1-1.51143-146] 1-21137,147-150] 0.5-31151-153] 1.51143]

F (%) 70-961134,135] 921154] 871155] :::.851140]

F, food effects Delayl1561 Decreased

25%11571No effect1158l Increased 43%11591

Vd (Ukg) 0.51133,160,161] 5.61161] NA 74-1201142 ,161]

Protein binding (%) 88-9011611 50-701161-163] 73-771162,163] 971161-163]

First-pass metabolism Limited1162l Limited1162l Moderate1155l Extensive1162lHepatic metabolism Negligiblel1641 Negligiblel1641 CYP3A411651 CYP3A4

CYP2D61166·1671Active metabolites None11621 None11621 Hydroxylated 11551 Descarboethoxy

(desloratadine )11621Elimination

renal (%) 70 12 44 :::.20 unchanged

fecal (%) 101135) 801154] 44 (as metabolites)I155J 40 (as metabolites)l1641t•h (h) 71133-135] 12-151136,137] 13-301138-

140 ,142,143,168,169]11-141140,143]

Duration of action (h) 24188,149,160,170-174]

241146,147,149] 241151] <241173,174]

Table VIII. Adverse effects (% of patients) with second-generation antihistamines

Adverse effect 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 2.1 1.3 4

Dry mouth 5.0 3.0 3

Pharyngitis 2.0 4.1 3.2 <2

Dizziness 2.0 <2.2 <2

Gastrointestinal distress >2 1.3 <2

Dysmenor rhoea 2.1 1.5

Table XV. Recommended dailya oral dosage of second-generation antihistamines

a Unless specified.

NS = not stated in product labelling.

Drug Adults Children Elderly Renal impairment

Hepatic impairment

Cetirizine 5-1Omg

6-11 years: 5-1Omg0.5-5 years: 2.5-Smg

5-1Omg

5mg 5mg

Desloratadine

5mg >12 years: 5mg 5mg 5mg every 48 hours

5mg every 48 hours

Fexofenadine

180mg 6-11 years: 30mg twice daily

180mg 60mg 180mg

Loratadine

10mg >6 years: 1Omg2-5 years: 5mg

NS 1Omg every 48 hours

1Omg every 48 hours

Azelastine Levocabastine Olopatadine

- blockage of H1receptor

-some anti-ollergic activity for azelastine

-Minor local side effects

- Azelastine : bitter tastein 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 FlunisolideFluticasone

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 childrenconsider 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 nasalcongestion

- Effective on smell- Effect observed after

6-12 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

Oral I IM glucocortico- steroids

Dexamethasone Hydrocortisone Methylpredisolone Prednisolone Prednisone Triamcinolone Betamethasone Deflazacort

- Potently reducenasal inflammation

-Reduce nasal hyperreactivity

- Sffstemic sidee ects common inparticular 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 excellentsafety

Oral decongestants

E hedrineP enylephrinePhenyl-

propanolaminePseudoephedrine

Oral Hl- antihistam ine- decongestant combinat ion

- drmpathomimeticrug

-relieve symptoms of nasal

congestion

- Hypertension- Palpitations- Restlessness-Agitation-Tremor-Insomnia-Headache- Dry mucousmembranes

-Ur inary retention- Exacerbation

ofaucoma or yrotoxicos is

Use oral decongestants with caution in patients with heart disease

Oral Hl- antihistamine decongestant combinationproducts may be moreeffective than either product alone but side effects are combined

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