Allergic rhinitisFahad zakwan

MD5

Definition

•hypersensitivity of the sinonasal mucosa to antigenic materials.•Characterized by recurrent attacks of:SneezingItchingRhinorrhea (thin watery discharge from the nose)

Nasal obstruction

Types•seasonal (hay fever)•Perennial•Perennial with seasonal exacerbations

Predisposing factors:

•Genetic (50%) atopic patient•Temperature changes•Emotional (anxiety)

The atopic syndrome•The atopic syndrome is a hereditary disorder of variable penetrance.•Subjects are particularly susceptible to the development of IgE-mediated allergic reactions manifested by:• infantile eczema;•allergic asthma;•nasal and conjunctival allergy

Exciting factors: (antigen)

• Inhalants: pollens (seasonal), house dust mites (perennial)• Ingestants: fish, milk, eggs.• Injectants: penicillin.• Infectants: fungal (allergic fungal sinusitis)•Contactants: face powder.

Exposure to

allergens

PATHOPHYSIOLOGY

Mechanism (pathogenesis):

•When allergens are inhaled (1st time), the body produces antibodies (IgE) which become fixed to the mast cells of nasal mucosa. •On re-exposure these antibodies cause the release of a chemical mediators mainly histamine by the degranulation of mast cells that leads to: • swelling and edema of the nasal mucosa• Vasodilatation and increased capillary dilatation• Increased secretions• Cellular infiltration (esinophils)

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

EARLY ALLERGIC RESPONSE• Histamine results in Rhinorrhea, Sneezing, Itching, and some

nasal obstruction (Early allergic response)• Edema, 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

LATE 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

Symptoms

recurrent attacks of • itching, • sneezing, • rhinorrhea (runners), • obstruction (blockers), •mild facial pain and headache.• other allergic manifestations (conjunctivitis, bronchial asthma, eczema)

Signs•Enlarged turbinates (pale bluish)•Polyps (bilateral, multiple, glistening, pale bluish, soft, mobile, insensitive, middle meatus)

PHYSICAL EXAMINATION

•The physical examination should focus on the nose, but examination of facial features, eyes, ears, oropharynx, neck, lungs, and skin is also important. •Look for physical findings that may be consistent with a systemic disease that is associated with rhinitis.

General facial features• "Allergic shiners" are dark circles around the eyes and are related to vasodilation or nasal congestion.• "Nasal crease" is a horizontal crease across the lower half of the bridge of the nose that is caused by repeated upward rubbing of the tip of the nose by the palm of the hand (ie, the "allergic salute")

Nose• The nasal examination is best accomplished with a

nasal speculum or an otoscope with nasal adapter. A rigid or flexible rhinolaryngoscope may be used.• The mucosa of the nasal turbinates may be swollen

(boggy) and have a pale, bluish-gray color. Some patients may have predominant erythema of the mucosa, which can also be observed with rhinitis, infection, or vasomotor rhinitis. • While pale, boggy, blue-gray mucosa is typical for

allergic rhinitis, mucosal examination findings cannot definitively distinguish between allergic and nonallergic causes of rhinitis.

•Assess the character and quantity of nasal mucus. •Thin and watery secretions are frequently associated with allergic rhinitis. • thick and purulent secretions are usually associated with sinusitis; •however, thicker, purulent, colored mucus can also occur with allergic rhinitis.

• Examine the nasal septum to look for any deviation or septal perforation, which may be present due to chronic rhinitis, granulomatous disease, cocaine abuse, prior surgery, topical decongestant abuse, or, rarely, topical steroid overuse.• Examine the nasal cavity for other masses such as polyps or tumors. • Polyps are firm gray masses that are often attached

by a stalk, which may not be visible. • After spraying a topical decongestant, polyps do not

shrink, while the surrounding nasal mucosa does shrink

Ears and eyes

•Perform otoscopy to look for tympanic membrane retraction, air-fluid levels, or bubbles. Performing pneumatic otoscopy can be considered to look for abnormal tympanic membrane mobility. These findings can be associated with allergic rhinitis.•Ocular examination may reveal findings of injection and swelling of the palpebral conjunctivae, with excess tear production which are associated with allergic rhinitis.

Neck•Look for evidence of lymphadenopathy or thyroid disease.

Lungs•Look for the characteristic findings of asthma.

Skin•Evaluate for possible atopic dermatitis.

Investigations•Skin prick test•Serum IgE•Nasal cytology: esinophils•Nasal challenge test•RAST•C.T scan (polyps)

Allergy skin tests

• allergen introduced into skin causes mast cell degranulation, formation of wheal and flare• mean wheal diameter at

15 mins• >2 mm in children <5yrs,• > 3 mm in older children

and adults

Total serum IgE• This is a measurement of the total level of IgE in the blood.•While patients with allergic rhinitis are more likely to have an elevated total IgE level than the normal population, this test is neither sensitive nor specific for allergic rhinitis.• Therefore, this test is generally not used alone to establish the diagnosis of allergic rhinitis, but the results can be helpful in some cases when combined with other factors.

Total blood eosinophil count

•As with the total serum IgE, an elevated eosinophil count supports the diagnosis of allergic rhinitis, but it is neither sensitive nor specific for the diagnosis. •The results can sometimes be helpful when combined with other factors.

Nasal cytology• A nasal smear can sometimes be helpful for establishing

the diagnosis of allergic rhinitis. • A sample of secretions and cells is scraped from the

surface of the nasal mucosa using a special sampling probe. • Secretions that are blown from the nose are not

adequate. • The presence of eosinophils is consistent with allergic

rhinitis but also can be observed with NARES. • Results are neither sensitive nor specific for allergic

rhinitis and should not be used exclusively for establishing the diagnosis.

Imaging StudiesRadiography•While radiographic studies are not needed to establish the diagnosis of allergic rhinitis, they can be helpful for evaluating possible structural abnormalities or to help detect complications or comorbid conditions, such as sinusitis or adenoid hypertrophy.

CT scanning• Coronal CT scan images of the sinuses can be very helpful for evaluating acute or chronic sinusitis. • In particular, obstruction of the ostiomeatal complex (a confluence of drainage channels from the sinuses) can be seen quite clearly. • CT scanning may also help allocate polyps, turbinate swelling, septal abnormalities (eg, deviation), and bony abnormalities (eg, concha bullosa).

MRI•For evaluating sinusitis, MRI images are generally less helpful than CT scan images, largely because the bony structures are not seen as clearly on MRI images. •However, soft tissues are visualized quite well, making MRI images helpful for diagnosing malignancies of the upper airway.

PROCEDURESRhinoscopy:

•While not routinely indicated, upper airway endoscopy (rhinolaryngoscopy) can be performed if a complication or comorbid condition may be present. • It can be helpful for evaluating structural abnormalities (eg, polyps, adenoid hypertrophy, septal deviation, masses, foreign bodies) and chronic sinusitis (by visualizing the areas of sinus drainage).

Nasal provocation (allergen challenge) testing: • This procedure is essentially a research tool and is rarely

indicated in the routine evaluation of allergic rhinitis. • The possible allergen is inhaled or otherwise inoculated into

the nose. • The patient can then be monitored for development of

symptoms or production of secretions, or objective measurements of nasal congestion can be taken. • Some consider this test the criterion standard test for the

diagnosis of allergic rhinitis.However, it is not a practical test to perform routinely, and only an appropriately trained specialist should perform this test

Management3-major treatment strategies:-•Environmental control & allergen avoidance•Pharmacologic management•Immunotherapy

1.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

2.Pharmacologic management

• Most cases of allergic rhinitis respond to pharmacotherapy. • Patients with intermittent symptoms are often treated adequately with oral

antihistamines, decongestants, or both as needed. • Regular use of an intranasal steroid spray may be more appropriate for patients with

chronic symptoms. • Daily use of an antihistamine, decongestant, or both can be considered either instead of

or in addition to nasal steroids. • The newer, second-generation (ie, nonsedating) antihistamines are usually preferable to

avoid sedation and other adverse effects associated with the older, first-generation antihistamines.

• Ocular antihistamine drops (for eye symptoms), intranasal antihistamine sprays, intranasal cromolyn, intranasal anticholinergic sprays, and short courses of oral corticosteroids (reserved for severe, acute episodes only) may also provide relief.

SECOND-GENERATION ANTIHISTAMINES• They compete with histamine for histamine receptor type 1

(H1) receptor sites in the blood vessels, GI tract, and respiratory tract, which, in turn, inhibits physiologic effects that histamine normally induces at the H1 receptor sites• All are efficacious in controlling symptoms of allergic rhinitis

(ie, sneezing, rhinorrhea, itching) but do not significantly improve nasal congestion. For this reason, some second-generation antihistamines are available as combination preparations containing a decongestant. • They are often preferred for first-line therapy of allergic

rhinitis, because of their excellent efficacy and safety profile. • They can be used prn or daily

Cetirizine

• Competes with histamine for H1 receptors in GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. • Once-daily dosing is convenient. • Bedtime dosing may be useful if sedation is a problem. DOSE:

• <2 years: Safety and efficacy not established• 2-6 years: 2.5 mg (0.5 teaspoon) oral solution PO qDay; can increase

to 5 mg PO qDay or 2.5 mg PO twice daily; not to exceed 5 mg qDay• >6 years: 5-10 mg PO qDay, depending on severity of symptoms;

not to exceed 10 mg qDay

Levocetirizine

DOSE:•<6 months: Safety and efficacy not established•6 months to 5 years: 1.25 mg PO qDay (evening)•6-12 years: 2.5 mg PO qDay (evening)•>12 years: 5 mg PO qDay (evening)

Fexofenadine

DOSE:•<2 years: Use not recommended•2-12 years: 30 mg PO BID•>12 years: 60 mg PO BID OR 180 mg PO qDay

LoratadineDOSE:•<2 years: Safety and efficacy not established•2-6 years: 5 mg PO qDay•>6 years: 10 mg PO qDay; not to exceed 10 mg qDay

LEUKOTRIENE RECEPTOR ANTAGONISTS•Alternative to oral antihistamine to treat allergic rhinitis. •One of the leukotriene receptor antagonists, montelukast (Singulair), has been approved in the United States for treatment of seasonal and perennial allergic rhinitis.•When used as single agent, produces modest improvement in allergic rhinitis symptoms

Montelukast

• Selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene (CysLT 1) receptor. • Selectively prevents action of leukotrienes released by mast

cells and eosinophils. • When used as a single agent, has been shown to result in a

reduction of seasonal allergic rhinitis symptoms, similar in degree to that of loratadine. • <2 years: Safety and efficacy not establishedDOSE:

• 2-6 years: 5 mg (chewable tablet) or 4 mg (granules) PO once daily• 6-15 years: 5 mg (chewable tablet) PO once daily• >15 years: 10 mg (conventional tablet) PO once daily

FIRST-GENERATION ANTIHISTAMINES•The older, first-generation H1 antagonists (eg, diphenhydramine, hydroxyzine) are effective in reducing most symptoms of allergic rhinitis, but they produce a number of adverse effects (eg, drowsiness, anticholinergic effects). •They can be used prn, but adverse effects may limit their usefulness when taken on a daily basis

Chlorpheniramine

• One of the safest antihistamines to use during pregnancy. • Competes with histamine on H1-receptor sites on effector cells in blood

vessels and respiratory tract. DOSE:• <2 years: Safety & efficacy not established• 2-6 years: 1 mg PO q4-6hr; not to exceed 6 mg/day• 6-12 years: 2 mg PO q4-6hr; not to exceed 12 mg/day or sustained release

HS• >12 years

• Tablets or syrup: 4 mg PO q4-6hr; not to exceed 24 mg/day• Extended-release tablets: 8 mg PO q8-12hr or 12 mg q12hr; not to exceed 24 mg/day• Extended-release capsules: 12 mg PO qDay; not to exceed 24 mg/day• Sustained-release capsules: 8-12 mg PO q8-12hr, up to 16-24 mg/day

Diphenhydramine

DOSE:•2-6 years old: 6.25 mg q4-6hr; not to exceed 37.5 mg/day•6-12 years old: 12.5-25 mg PO q4-6hr; not to exceed 150 mg/day•>12 years old: 25-50 mg PO q4-6hr; not to exceed 300 mg/day

Hydroxyzine

DOSE:•<6 years old: 50 mg/day PO divided q6hr•>6 years old: 50-100 mg/day PO divided q6hr

DECONGESTANTS• Stimulate vasoconstriction by directly activating alpha-adrenergic

receptors of the respiratory mucosa. • Pseudoephedrine produces weak bronchial relaxation (unlike

epinephrine or ephedrine) and is not effective for treating asthma. • Increases heart rate and contractility by stimulating beta-adrenergic

receptors. • Used alone or in combination with antihistamines to treat nasal

congestion.• Numerous preparations are available containing combinations of

various decongestants, expectorants, or antihistamines. • Alternatively, a separate decongestant and antihistamine can be

administered to allow for individual dose titration of each drug.

Pseudoephedrine• Stimulates vasoconstriction by directly activating alpha-

adrenergic receptors of the respiratory mucosa.DOSE:Nasal Congestion• <2 years: Safety and efficacy not established• 2-6 years: 5-30 mg PO q4-6hr PRN• 6-12 years: 30 mg PO q4-6hr, OR 4 mg/kg/day divided

q6hr; not to exceed 120 mg/day • >12 years: 60 mg PO q6hr PRN (immediate release);

alternatively, 120 mg PO q12hr (extended release) or 240 mg PO q24hr (extended release)

NASAL CORTICOSTEROIDS• Nasal steroid sprays are highly efficacious in treating

allergic rhinitis.• They control the 4 major symptoms of rhinitis (ie,

sneezing, itching, rhinorrhea, congestion). • They are effective as monotherapy, although they do

not significantly affect ocular symptoms. • Greater benefit may occur when nasal steroids are used

with other classes of medication. • They are safe to use and not associated with significant

systemic adverse effects in adults

EXAMPLES:•Mometasone (Nasonex)•Beclomethasone (Beconase AQ, QNASL)•Budesonide inhaled (Rhinocort Aqua)•Fluticasone (Flonase)•Ciclesonide (Omnaris)•Fluticasone furoate (Veramyst)•Triamcinolone (Nasacort AQ)

INTRANASAL ANTIHISTAMINES

AzelastineDOSE:•<6 years: Safety and efficacy not established•6-12 years: 1 spray per nostril q12hr•>12 years: 1-2 sprays per nostril q12hr

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.

3.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.

Reference

• Diseases of the Ear, Nose and Throat (P.D. BULL MBBCh, FRCS),University of Sheffield(Ninth Edition)

• Mediscape references, Allergic rhinitis (full article)