Lecture 9 Therapeutics of Allergic Rhinitis Miller

Rhinitis = inflammation of membranes lining nose

Allergic rhinitis = immunologically (IgE) mediated

Initiated by antigen-antibody reactions

upon exposure to inhaled allergens

Non-allergic types

Classification of allergic rhinitis

Type Seasonal

Perennial

Perennial w/ seasonal exacerbation

Episodic

Frequency Intermittent <4 days/wk or <4 consecutive wks

Persistent > 4 days/wk or > 4 consecutive wks

Severity Mild Normal sleep, daily activities, no troublesome sx

Moderate/ Severe

≥1 of: decreased sleep, impaired daily activities, troublesome sx

Vasomotor rhinitis: sx complex of sneezing &

watery rhinorrhea w/ or w/o nasal congestion

when no allergic basis can be found

Triggers include cold dry air, odors, emotions

Cholinergic hyper-respnsiveness maybe cause

o Anticholinergic txt: ipratroprium

bromide intranasal spray

Non-allergic rhinitis w/ eosinhophilia (NARES):

similar sx to allergic rhinitis but no evidence of

IgE-mediated hypersensitivity

Eosinophils abundant in nasal secretions

Cause unknown

Responds to intranasal corticosteroids

Common features of allergic rhinitis

Seasonal Perennial Common cold

Duration Weeks-months

Continuous One week

Discharge Watery Not so copious

Mucopurulent

Sore throat

Rare Uncommon (irritated)

Sore throat, cough

Itch/ sneeze

Itchy, sneezing

Less common

Mild sneeze, rarely itchy

Predisposing factors

Family history of atopy (asthma, allergic

rhinitis, atopic dermatitis)

o Greater risk of both parents affected

Higher socioeconomic class

Allergen exposure

PRIMING RESPONSE: with repeated exposure to

allergens, amount of allergen to induce

immediate response decreases

Symptom pattern:

Develop within 2-3

years following

sensitizing exposure

Often escalate in

severity, then plateau

or diminish

May diminish with age

Presenting sx:

Nasal congestion

Clear rhinorrhea (anterior &

postnasal drip)

Sneezing & itching (nasal &

palatial)

Conjunctivitis & periorbital

swelling

Postnasal drip coughing

Systemic manifestations

(fatigue, irritability

,depression)

Diagnostic signs

General: facial pallor, allergic shiners

& mouth breathing, transverse crease

on nose bridge (allergic salute)

Dennie-Morgan lines & conjunctivitis

Nasal mucosal swelling, bluish

appearance

Ears – fluid in middle ear (otitis media)

Diagnostic test

Skin tests (wheal & flare response to allergen

extracts)

Nasal cytology (for eosinophils & neutrophils)

Serology (serum IgE increase 2-6x normal in

30-40% pts)

Skin tests: most sensitive, cost-effective & fast results

Identifies clinically relevant allergens that may be used

in immunotherapy

Test only in persistent or severe cases

False negatives with antihistamines, tricyclic

antidepressants, oral or topical steroids

o Need to be DC prior to testing (1 wk before)

Lecture 9 Therapeutics of Allergic Rhinitis Miller

Complications of allergic rhinitis

Recurrent upper respiratory

infections (colds)

Nasal polyps (small sac like

growths of inflamed nasal

mucosa)

Loss of smell and/or taste

Facial and dental abnormalities

o Transverse crease across

nose

o Allergic shiners

o Dental malocclusions

Epistaxis (nose bleeds)

Sleep disorders

ASSOCIATED WITH OTHER

DISORDESR: asthma, sinusitis, otitis

media with effusion

Treatment of allergic rhinitis

1. Allergen avoidance

2. Palliative therapy – humidification, saline irrigation

3. Education – reassurance of chronic disease; expectations with

therapy; options for management

4. Pharmacotherapy

a. Antihistamines

b. Decongestants

c. Topical corticosteroids

d. Cromolyn (mast cell stabilizers)

e. Leukotriene receptor agonists

f. Oral corticosteroids

Nasal irrigation: Neti-pot (device to administer saline solution to flush

nasal passageways)

Relieves sx, adjunct to treatment, well-tolerated by majority

Infection risk: naegleria fowleri (amoeba) in tap water

meningoencephalitis

Antihistamines: competitive blockers of H1 receptors; don’t prevent release of histamine

Nasal responses primarily result of histamine release

o Not very effective for congestion

o Oral – can decrease non-nasal sx

Need to take before exposure or continuously (although effective as prn)

Patient will not be as responsive if chronic sx or high allergen exposure or prolonged exposure

1st generation oral antihistamines:

chlorpheniramine, diphenhydramine

Sedation & anticholinergic properties most

pronounced

Can lower seizure threshold

GI disturbance – ethylenediamines

Impair children’s learning & academic

performance

Drivers of fatal car accidents 1.5x more likely to

be taking 1st generation antihistamine

Auto-induction of hepatic microsomal enzymes

tolerance

Concomitant CNS depressants can potentiate

these effects

2nd generation oral antihistamines: loratidine,

desloratidine, fexofenadine, cetirizine

Large & lipophobic don’t cross BBB = non-

sedating (except cetirizine) at regular doses

o Not shown to potentiate effects of

other CNS depressants

Long-acting once or twice daily dosing

Equal efficacy

Topical antihistamines

Levocabastine intranasal

o For nasal or ocular sx – clinically

significant effect on nasal congestion

o Equal efficacy or superior to oral

antihistamines

o Faster onset

Azelastine/fluticasone propionate

o Combination: one spray bid (>12 yo)

o More effective than either agent alone

Lecture 9 Therapeutics of Allergic Rhinitis Miller

Decongestants: act on alpha-adrenergic receptors

vasoconstriction to reduce nasal congestion

Topical: LIMIT TO 3-7 DAYS (rebound congestion = rhinitis

medicamentosa)

o Short-acting: phenylephrine

o Long-acting: oxymetazoline, xylometazoline, naphazoline

Oral

o Phenylephrine – feeble orally

o Pseudoephedrine 60 mg tid

Effective to reduce severe obstructive congestion impairing

absorption of intranasal steroids

Adverse effects: increase BP, stimulate CNS, interact with

MAOIs

Avoid in: pregnancy, hypertension, cardiomyopathy,

hyperthyroidism, benign prostatic hypertrophy, glaucoma,

psychiatric disorders, patients on MAOIs or beta-blockers

Combo products: ANTIHISTAMINE +

DECONGESTANT

Antihistamine dries nasal

secretions; decongestant reduces

congestion

MORE EFFECTIVE relief of nasal

congestion than antihistamines

alone

More insomnia and nervousness

(even with sedating

antihistamines)

Difficult to titrate dose when in

combination

Some patients may find combo

convenient for short periods of

time

Intranasal corticosteroids: local anti-inflammatory effects;

decreases both early & late phase response

Beclomethasone, budesonide, flunisolide, fluticasone,

mometasone, ciclesonide, triamcinolone

More effective than antihistamines

Decreases ALL Sx (congestion, itching, sneezing,

rhinorrhea, similar effect on ocular sx as oral AH)

Use prophylactically or as needed

Well tolerated

Local side effects: nasal irritation, stinging, burning,

dryness, minor epistaxis, septal perforation (rare – due

to improper technique), candida albicans infection (rare)

o HPA suppression: rare with dexa or beta methasone

Slow onset of relief (3 days and max effect at 2 weeks)

o Once sx controlled, can decrease frequency

COMBOs:

o With intranasal antihistamine – superior to either

agent alone

o No benefit when combined with oral AH or LTRA

Technique for topical intranasal steroids

1. Hold head in neutral upright position

2. Clear nose of thick or excessive mucus

by gently blowing nose

3. Insert spray nozzle into nostril

4. Direct spray laterally or to side (away

from middle of nose aka septum, and

toward outer portion of eye or top of

ear on that side)

a. CONTRALATERAL HAND

TECHNIQUE: use right hand to

spray left nostril and vice versa

5. Activate device as recommended by

manufacturer and with # of sprays as

recommended by dr

6. Gently breathe in or sniff during

spraying

7. Breathe out through nose

Oral corticosteroids: NOT FIRST LINE (little data to

support use)

Dose: prednisone 20-40 mg/d for 5-7 days for very

severe or intractable nasal sx or nasal polyposis

Local depot administration not recommended (ex//

methylprednisolone – Depo Medrol)

Systemic side effects

Anticholinergics: block cholinergic receptors to

decrease watery nasal secretions

Ipratropium nasal spray

Evidence lacking for use in allergic rhinitis

Onset: 15-30 min

SE: nasal and oral dryness, irritation, burning

Dose: 1 spray per nostril TID – QID

Lecture 9 Therapeutics of Allergic Rhinitis Miller

Cromolyn: stabilizes mast cell membranes to prevent

release of inflammatory mediator

Effective in mild – moderate conditions (and prior

to allergen exposure in episodic cases)

o Delayed effect of 4-7 days (or 2 wks if

severe or perennial) = need to start at least

1 wk before allergy season

1 spray each nostril 6 times daily decrease to bid

or tid

Safe with few SEs (sneezing, stinging, or nasal

burning rarely)

Ocular and nasal solutions 2%

Steroids superior in efficacy and compliance

Leukotriene Receptor Antagonists: Montelukast

Similar efficacy to antihistamines

Less effective than nasal corticosteroids

Combination of antihistamine + LRTA superior

to either alone

Weak as monotherapy in allergic rhinitis

o Use as adjunct when inadequate

response to antihistamines or refuse

to use intranasal corticosteroids

o Use if concurrent diagnosis of asthma

Immunotherapy: production of IgG blocking antibodies

(block IgE from binding to antigen inhibits mast cell

rupture)

SC administration of standardized extract of

allergen

Build-up of dose and maintenance phase

Treatment remains for several years (3 yrs

injections protection for 3 more years after DC)

Effective adjunctive therapy to medications

especially for pollen & dust mite antigens

Use if non-responsive to pharmacotherapy or

unable to tolerate side effects, or unable to avoid

allergens

Frequent injections, extract strengths unclear

Risk of anaphylaxis (5% with high-potency extracts)

Special populations

Pregnancy

o 1st line: intranasal corticosteroids –

beclomethasone, budenoside (low

systemic absorption)

o Antihistamines: chlorpheniramine &

2nd generation antihistamines

o Mast cell stabilizer: cromoglycate

safe but weak efficacy

o LTRA: montelukast safe

o AVOID: oral decongestants during

first trimester

Breast feeding

o Pseudoephedrine concentrates in

breast milk but no reports of adverse

effects on breastfed infant

Refer to allergist or immunologist

Inadequate control of sx despite adherence and correct use of therapies

ADRs to medications

Reduces QOL or ability to function secondary to the condition

Desire to identify sensitizing allergents and receive advice on environmental control

Comorbidity (asthma, recurrent sinusitis)

Allergen immunotherapy