ALLERGIC RHINITIS

DEFINITION

● RHINITIS IS DEFINED AS AN INFLAMMATION OF THE LINING OF THE NOSE, CHARACTERISED BY NASAL SYMPTOMS, INCLUDING:

– ANTERIOR OR POSTERIOR RHINORRHOEA

– SNEEZING

– NASAL BLOCKAGE

– ITCHING OF THE NOSE

DEFINITION OF ALLERGIC RHINITIS

● ALLERGIC RHINITIS IS DEFINED AS A SYMPTOMATIC DISORDER OF THE NOSE INDUCED AFTER ALLERGEN EXPOSURE,

● BY AN IgE MEDIATED INFLAMMATION,

● CHARACTERISED BY RHINORRHOEA, NASAL OBSTRUCTION, NASAL ITCHING, AND SNEEZING;

● WHICH ARE REVERSIBLE SPONTANEOUSLY OR WITH TREATMENT.

● - ARIA, 2008, 2010 UPDATE

CLASSIFICATION

● BASED ON THE FREQUENCY OF EPISODES,

–INTERMITTENT

–PERSISTENT

● BASED ON THE SEVERITY OF SYMPTOMS,

–MILD

–MODERATE/SEVERE

INTERMITTENT & PERSISTENT ALLERGIC RHINITIS

INTERMITTENT PERSISTENT

Symptoms are present:

< 4 days a week > 4 days a week

Or <4 consecutive weeks And > 4 consecutive weeks

MILD & MODERATE/SEVERE ALLERGIC RHINITIS

MILD MODERATE/ SEVERE

Sleep disturbance - +

Impairment of daily activities, leisure or sport

- +

Impairment of school or work

- +

Troublesome symptoms

- +

Exposure to allergens

PATHOPHYSIOLOGY

• Antigen-presenting cells, which include macrophages and Dendritic cells similar to Langerhans cells in the skin, take up allergen by endocytosis

• APCs process allergens, and co-present it along with HLA Class 2 molecules to CD4+ T cells (Th2 lymphocytes)

• T cells undergo clonal expansion

• They get activated

• They produce cytokines

• Signal B cells, causing differentiation into plasma cells

• Plasma cells produce IgE class antibodies

• Allergen specific IgE produced by Plasma cells, bind to mast cells, and Basophils, resulting in Antigen priming.

• Subsequent exposure to allergen leads to cross linking of IgE on cell surface

• Opening of Calcium channels

• Degranulation

• Release of preformed mediators

• Histamine

• Prostaglandins

• Leukotrienes

• Kinins

• Cytokines

• Histamine results in Rhinorrhoea, Sneezing, Itching, and some nasal obstruction (Early allergic response)

• Oedema, vasodilatation and plasma exudation; Increases glandular secretion

• Upregulation of Adhesion molecules on vascular endothelial cells, increased production of cytokines

• Other mediators of importance in Allergic Rhinitis:

• Prostaglandin D2 – Sustained nasal obstruction

• Leukotrienes (SRS-A) – Vascular permeability, Oedema,

• Eosinophil recruitment

• Kinins-Rhinorrhoea, Sneezing, Obstruction, Pain

• TH2 cytokines-IL-4, 5, 13, 6, 8, 10, TNF-alpha are important in regulation of immune response

EARLY ALLERGIC RESPONSE

• Severe exposure to allergens can result in a late phase response

• Eosinophils-Activated, increase local vascular permeability, mucus secretion, further inflammatory cell influx, alteration of nasal epithelium

• Endothelial cells recruit leukocytes by releasing chemotactic factors and modulation of adhesion factors.

• Trap circulating inflammatory cells at the site of allergic response, especially eosinophils and basophils

• Basophils are a major source of histamine in the late phase response.

• Epithelial cells – Activated, and show increased expression of adhesion molecules, expression and production of inflammatory mediators

LATE ALLERGIC RESPONSE

DIAGNOSIS

• HISTORY-SYMPTOMS OF NASAL ALLERGY

• PHYSICAL EXAMINATION

• ALLERGIC NASAL MUCOSA-SWOLLEN BILATERALLY, PALE OR BLUISH, OEDEMATOUS, WATERY DISCHARGE

• FEATURES OF BRONCHIAL ASTHMA, OR ATOPY

SKIN PRICK TESTS

• MEAN WHEAL DIAMETER AT 15 MINS

• >2 MM IN CHILDREN <5YRS,

• > 3 MM IN OLDER CHILDREN AND ADULTS

• ALLERGEN INTRODUCED INTO SKIN CAUSES MAST CELL DEGRANULATION, FORMATION OF WHEAL AND FLARE

TREATMENT GUIDELINES (ARIA 2008, 2010)INTERMITTENT

MILD

SEVERE

• ORAL H1 BLOCKERS• INTRANASAL H1

BLOCKERS• +/-

DECONGESTANT/LTRA

• ORAL H1 BLOCKERS• INTRANASAL H1 BLOCKERS• +/- DECONGESTANT/LTRA

• INTRANASAL STEROIDS• LTRA

• OR CHROMONE

PERSISTENT

MILD

REVIEW AFTER 2-4 WEEKS

REASSESS

IMPROVED FAILURE

CONTINUE FOR 1 MONTH STEP UP

• INTRANASAL STEROIDS

SEVERE PERSISTENT

• H1 BLOCKERS OR LTRA

REASSESS

AFTER 2-4WKS

FAILUREIMPROVED

STEP DOWN AND CONTINUE FOR >1 MONTH

• REVIEW DIAGNOSIS• REVIEW COMPLIANCE

• QUERY INFECTIONS OR OTHER CAUSES

ADD OR INCREASE

INTRANASAL CS

ADD IPRATROPIUM

FOR RHINORRHOEA

ADD IPRATROPIUM

FOR RHINORRHOEA

ADD DECONGESTANT OR ORAL SHORT

TERM CS

ALLERGEN AVOIDANCE

CONSIDER IMMUNOTHER

APY

ALLERGEN AVOIDANCE AND ENVIRONMENTAL CONTROL

• VARIOUS RECOMMENDATIONS FOR ALLERGEN AVOIDANCE HAD BEEN SUGGESTED IN THE PAST

• TOTAL AVOIDANCE OF EXPOSURE TO PASSIVE SMOKING IN PREGNANT WOMEN

• NO ‘ANTIGEN AVOIDANCE DIET’ IS RECOMMENDED

• REDUCE EARLY LIFE EXPOSURE TO HOUSE DUST MITE

• NO SPECIAL AVOIDANCE OF EXPOSURE TO PETS AT HOME IN INFANTS AND PRESCHOOL CHILDREN

• SPECIFIC PREVENTION MEASURES ELIMINATING OR REDUCING OCCUPATIONAL ALLERGEN EXPOSURE

• CLINICIANS SHOULD NOT ADMINISTER AND PATIENTS DO NOT USE CURRENTLY AVAILABLE SINGLE CHEMICAL OR PHYSICAL PREVENTIVE METHODS AIMED AT REDUCING EXPOSURE TO HOUSE DUST MITES

• AVOID EXPOSURE TO INDOOR MOULDS AT HOME

• AVOID EXPOSURE TO ANIMAL DANDER

ANTIHISTAMINES• Rapidly relieve nasal discharge, sneezing itching (early phase response)

• Minimal effect on nasal blockage (except desloratidine, levocetirizine) (late phase response)

• Avoid first generation

• Azelastine can be given intranasally

• Chronic nasal congestion and headache caused by edema of the paranasal sinus mucosa are often refractory to antihistamine therapy.

• Single-ingredient products generally are safer than combination products,100while also facilitating dosage adjustment.

• Oral antihistamine combinations containing an analgesic-antipyretic and/or nasal decongestant; an antitussive and nasal decongestant; an analgesic-antipyretic, antitussive, and nasal decongestant; or an antitussive may be rational if each ingredient has demonstrated clinical effectiveness 

• Side effects: sedation, toxicity, Anticholinergic effects

• Rarely, agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, and pancytopenia have been reported

• Acrivastine, desloratadine, fexofenadine, loratadine, and, possibly, cetirizine and levocetirizine appear to cause fewer adverse CNS effects

• Antihistamines can cause sensitivity reactions (e.G., Sensitization, hypersensitivity) following topical application

• Antihistamines can act as haptens and cause Ig E-mediated (type I) hypersensitivity reactions or T cell-mediated (type IV) sensitization reactions.

• Adverse cardiovascular effects are uncommon and usually limited to overdosage situations. 

• Patients who were receiving therapy with an azole (ketoconazole] and triazole derivative [itraconazole]) antifungal, a macrolide (e.G., Clarithromycin, erythromycin), quinine appeared to be at substantial risk of such toxicity, probably secondary to interference with metabolism of theantihistamine.

TOPICAL ANTIHISTAMINES• Azelastine hydrochloride spray is used intranasally to provide

symptomatic relief of allergic rhinitis

• Intranasal azelastine was more effective than placebo and at least as effective as oral antihistamines in relieving symptoms

• Administered intranasally, using a spray pump.

• For adults and children 12 years of age or older dose is 2 sprays (274 mcg) in each nostril twice daily (1096 mcg of azelastine hydrochloride total daily, equivalent to 1 mg of azelastine base daily).

• Principal adverse effects of intranasal azelastine are local (e.G., Bitter taste, nasal burning, pharyngitis, paroxysmal sneezing),

• Adverse systemic effects (e.G., Somnolence, headache) also can occur.

TOPICAL GLUCOCORTICOIDS• Most effective treatment for allergic rhinitis

• Regular treatment is necessary

• Generally provides symptomatic relief of watery rhinorrhea, nasal congestion, sneezing, postnasal drip, and nasalitching.

• Slow onset of action. Maximal effect after several days

• Administration of a topical nasal decongestant about 5-15 minutes before intranasal corticosteroid administration may be useful during the first 2 or 3 days of therapy in patients with blocked nasalpassages to ensure adequate penetration of the drug.

• Lowest bioavailability is seen with fluticasone and mometasone

ADMINISTRATION• Patients should tilt the head slightly

forward, insert the nasal adapter into one nostril, and point the tip of the adapter toward the inflamed nasal turbinates and away from the nasal septum. 

• Patients should pump the drug into one nostril while holding the other nostril closed and should concurrently inspire through the nose. 

• Repeat for the other nostril.

• If sneezing occurs, patients should wait until sneezing has stopped, then clear the nasal passages and repeat administration of the dose.

FLUTICASONE PROPIONATE• Synthetic trifluorinated corticosteroid

• Used for the symptomatic treatment of intermittent or persistent allergic rhinitis.

• Administered by nasal inhalation using a metered-dose nasal spray pump.

• Intranasal fluticasone propionate (200 mcg daily given in 1 or 2 divided doses in adults and adolescents) is effective in allergic rhinitis

• Children 6-11 years of age with allergic rhinitis, intranasal fluticasone propionate (100 mcg once or twice daily) 

• 200 mcg of fluticasone propionate given once daily is as effective as 100 mcg of the drug given twice daily.

MOMETASONE FUROATE• NON FLUORINATED STEROID

• USEFUL IN PROPHYLAXIS AND TREATMENT OF ALLERGIC RHINITIS

• MAXIMUM BENEFIT USUALLY OCCURS WITHIN 1-2 WEEKS

• AS EFFECTIVE AS OTHER INTRANASAL CORTICOSTEROIDS (E.G., BECLOMETHASONE DIPROPIONATE, FLUTICASONE PROPIONATE) IN RELIEVING MODERATE TO SEVERE NASAL SYMPTOMS, INCLUDING STUFFINESS, RHINORRHEA, ITCHING, AND SNEEZING

• ADMINISTERED BY NASAL INHALATION USING A SPECIAL NASAL INHALER.

•  PRIOR TO INITIAL USE OF THE INHALER, THE PUMP SHOULD BE PRIMED BY ACTUATING 10 TIMES OR UNTIL A FINE SPRAY APPEARS.

• DOSAGE OF MOMETASONE FUROATE IN ADULTS AND CHILDREN 12 YEARS OF AGE OR OLDER IS 100 MCG (2 SPRAYS) IN EACH NOSTRIL DAILY (TOTAL DAILY DOSAGE OF 200 MCG).

• DOSAGE IN CHILDREN 2-11 YEARS OF AGE, 50 MCG (1 SPRAY) IN EACH NOSTRIL DAILY (TOTAL DAILY DOSAGE OF 100 MCG)

CROMOLYN SODIUM (DISODIUM CROMOGLYCATE)

• MAST CELL STABILIZER

• SAFE FOR YOUNGER CHILDREN

• NEEDS TO BE SPRAYED FOUR TIMES A DAY

• ALSO USEFUL IN BRONCHIAL ASTHMA

NASAL DECONGESTANTS• Very short term topical decongestants are useful in reducing nasal obstruction

• Some degree of rebound congestion usually results.

• Prolonged use can cause rhinitis medicamentosa (tachyphylaxis and rebound symptoms)

• Oxymetazoline drops/spray applied topically to relieve nasal congestion 

• Sprays may be preferable to drops because of the lesser risk of swallowing the drug and resultant systemic absorption.

• Drops should be applied to the dependent (lower) nostril, with the patient in a lateral, head-low position. The patient should remain in the same position for 5 minutes

• 0.05% oxymetazoline hydrochloride nasal solution should be used only in adults and children 6 years of age and older. 

• 2 or 3 drops or sprays in each nostril every 10-12 hours

• Systemic decongestants are relatively ineffective, and may cause hypertension in adults, hyperreactivity and insomnia in young children

IPRATROPIUM BROMIDE

• SYNTHETIC ANTOMUSCARINIC AGENT

• USED AS A 0.03% OR 0.06% NASAL SPRAY FOR THE SYMPTOMATIC RELIEF OF RHINORRHEA

• ADVERSE ANTICHOLINERGIC EFFECTS MAY OCCUR IN OVERDOSE- INCREASED INTRAOCULAR PRESSURE, MYDRIASIS, URINARY RETENTION, CHEST PAIN, PALPITATION, DIZZINESS, HEADACHE

SYSTEMIC CORTICOSTEROIDS

• RARELY USED TO UNBLOCK THE NOSE AT THE START OF TREATMENT FOR VERY SEVERE SYMPTOMS

• REGULAR USE ASSOCIATED WITH SERIOUS SIDE EFFECTS, AND NOT RECOMMENDED

LEUKOTRIENE MODIFIERS

• MODEST IMPROVEMENT IN NASAL CONGESTION, NASAL ITCHING, RHINORRHEA, NASAL PRURITUS, SNEEZING) COMPARED WITH PLACEBO.

• THERAPY WITH MONTELUKAST ALONE OR IN COMBINATION WITH LORATADINE HAS BEEN ASSOCIATED WITH IMPROVED OCULAR MANIFESTATIONS, DAYTIME NASAL SYMPTOMS, NIGHTTIME SYMPTOMS, QUALITY OF LIFE 

• ZAFIRLUKAST ALSO PRODUCES REDUCED NASAL CONGESTION, SNEEZING, AND RHINORRHEA COMPARED WITH THE PLACEBO GROUP.

IMMUNOTHERAPY• Involves repeated administration of an allergen extract subcutaneously

to induce immunological tolderance with reduction in clinical symptoms and medication requirement suring subsequent natural allergen exposure.

• Indicated in patients with patients with severe allergic rhinitis whose symptoms fail to respond to conventional treatment.

• More useful in patients with a limited spectrum of allergies, esp in seasonal hayfever, inability to avoid allergens.

• Mechanism appears to be modulation of T lymphocyte functions• IgE sensitivity should be confirmed before starting.• Reduction in risk of bronchial asthma, may prevent development of

new allergies• Special protocols are available, which includes an updosing phase

of weekly injections for 8-16 weeks, followed by maintainence injections at 4-8 weekly intervals for 3-5 years.

• Local reactions may occur• Systemic reactions are rare, may lead to rhinitis and asthma, which

responds to treatment.• Rarely anaphylaxis may occur.