Allergic rhinitis

Dr Ahlam Alzuway
Otorhinolaryngologist
 

 Epidemiology:

 Most common atopic disease, affects up to 20% of adult population in US.

 Sixth most prevalent chronic condition in US.

 Prevalence is increasing, theories:

- Increase in outdoor pollutants include.

- Increase in indoor allergens. “Western”-style housing with weatherproofing and

- Decrease in infections in early childhood which have a protective effect for the development of allergy.

 Symptoms of allergic rhinitis can begin at any age but are most frequently first reported in adolescence or
young adulthood.

 Rates of prevalence are similar for males and females, and no racial variations are reported.
 Genetic component:

 If one parent has allergies, the chances of the child’s having rhinitis are 30% and increase to
50% when both parents have the disease.

 To date, no chromosomal loci have been conclusively identified for association with allergic
rhinitis. However, positive associations of certain HLA (human leukocyte–associated
antigens = major histocompatibility complex [MHC] with dust and mite allergens have been
reported.
 Pathophysiology:
 Sensitization:

 In an individual with a susceptibility for developing allergic disease, an initial contact with
allergen a Macrophages and other antigen-presenting cells process the allergen a presenting it to
T-helper cells a differentiation of B lymphocytes into IgE-producing plasma cells a IgE bind to
high-affinity receptors located on mast cells and basophils and to low-affinity receptors located
on eosinophils, monocytes, and platelets.

 Process involving interleukin IL-4 and IL-13.

 Mast cells are usually found within the mucosal connective tissue stroma, in the vicinity of
blood vessels and glandular structures.

 Seasonal exposure increases the number of mast cells located close to the surface in the nasal
epithelium without affecting their overall number, suggesting that these cells migrate from the
deeper to the more superficial layers of the nasal mucosa during the pollen season.
 Early (Immediate) response:

 Occurs in sensitized individual, within seconds after another encounter with the same
allergen (priming) or other stimuli (hyper-reactivity).

 Antigens interact with specific IgE molecules on the surface of mast cells a Cross-linking of
two adjacent IgE molecules by antigen a mast cell degranulation a release of mediators a
symptoms.

 Mediators:

o Preformed: present in cytoplasmic granules within mast cells, include histamine, tryptase,
heparin.

o Newly formed: synthesized from the phospholipids of the cell membrane subsequent to mast cell
activation, include platelet activating factor (PAF), prostaglandins (PGs), and leukotrienes.
 Late response:

 If one continues to monitor the response for several hours, symptoms recur.

 Caused by inflammatory cell infiltration (basophils, eosinophils, neutrophils, and

mononuclear inflammatory cells).

 Associated with an elevation of levels of inflammatory mediators.

 There is increases in vascular cell adhesion molecule 1 (VCAM-1). This molecule is

expressed on the surface of vascular endothelial cells, stimulate eosinophils migration
from the circulation into allergic inflammatory sites.
 Associated with release of Cytokines & Chemokines: Important mediators of allergic
inflammation originate mainly from lymphocytes
 Nonspecific Nasal Reactivity:

 Increased responsiveness to non-antigenic substances during allergy season.

 Studies showed a positive correlation between the number of eosinophils 24 hours after antigen
challenge and the magnitude of the hyper-responsiveness.

 Neural Reflexes:

 Sneezing and itching seen during the early response to allergen provocation involve the nervous
system.

 Studies showed that stimulating one nasal cavity with histamine led to bilateral nasal secretions.

 There are several neuropeptides in the nasal mucosa, secreted by sympathetic and
parasympathetic nerve endings, including (tachykinins, neurokinin A [NKA], and vasoactive
intestinal protein [VIP]).

 These peptides produce symptoms and inflammatory responses similar to those obtained after
exposure to antigen.
 Allergens:

 Allergens are foreign substances capable of provoking an IgE-mediated response.

 Most allergens are between 5 and 20 μm in diameter.

 They are proteins with molecular weights between 10 and 40 kD.

 Categorized into indoor and outdoor types. In general, outdoor allergens are responsible
for seasonal allergic rhinitis, whereas indoor allergens usually cause perennial rhinitis.

 Pollens:

- Causing allergy in temperate climates are released into the air from plants, trees, weeds,
and grasses and are carried over great distances.

- Pollination, and hence the allergy season, occurs in a predictable annual pattern for
different regions of the country. In some areas, pollination may be a year-round
process.
 Indoor allergens:

- The most frequent perennial allergens are animal dander, dust mites, cockroaches.

- Dust mites are microscopic, eight-legged organisms. They are the major allergens in “house
dust.”

- Bedding provides an ideal environment for proliferation of dust mites. Other sites are
furniture, carpets, and stuffed toys.

- Dust mite feces, the source of the allergen, are relatively large particles that remain airborne
for short periods, unlike outdoor pollen. When an individual sits on a bed, the particles
become airborne and are inhaled. Because these particles are large, they settle from the air
rapidly, and air filtration systems cannot effectively remove them.

- Lowering the indoor relative humidity to less than 50% during the summer months has a
profound effect on the mite population, suggesting a role for dehumidifiers even in homes
with central air conditioning.
 CLINICAL PRESENTATION:
 HISTORY:

 Antigen exposure causes itching within seconds, which is soon followed by sneezing.
Rhinorrhea ensues, and within about 15 minutes, nasal congestion peaks.

 Ocular pruritus, tearing, pharyngeal itching, throat clearing, cough, ear popping,
postnasal drip, dry cough, red eyes, headaches over the paranasal sinus areas, and loss of
smell or taste.

  
 EXAMINATION:

 Examination of allergic individuals often appears normal, and the primary importance of the physical
examination is to rule out other causes of or contributors to the symptoms.

 Allergic facies: occur especially in children, includes mouth breathing, allergic “shiners” (resulting
from periorbital venous stasis from chronic nasal obstruction), and a transverse supra-tip nasal crease
from long-term rubbing of the nose upward to relieve itching.

 Ocular examination may demonstrate injection of the conjunctiva or swelling of the eyelids.

 Examination of the nose:

- Character and consistency of nasal secretions should be noted. These can vary from thin and clear to
thick and whitish.

- Mucosa may be swollen and pale-bluish, although these signs are not pathognomonic of the disease, as
previously thought.

- Nasal polyps are infrequent in allergic rhinitis (< 2%) but are found in up to 20% of patients with cystic
fibrosis.
 DIAGNOSTIC TESTS:
  

 1. SKIN TESTING:

 Evaluates the presence of specific IgE antibodies on skin mast cells, the reactivity of these
cells, and the reaction of skin to released mediators.

 Aadvantages include greater sensitivity, rapidity, and low cost.

 Disadvantages include the inability to perform the test in patients with dermatologic problems
such as eczema, poor tolerance of many children for multiple needle pricks, inhibitory effect
of certain drugs such as antihistamines on skin test reactivity, need to maintain the potency of
the allergen extracts, and possibility of systemic reactions.

 Begins with puncture testing, small drop of concentrated allergen is placed on the skin
(usually on the volar surface of the forearm or the back), and a minute quantity is introduced
into dermis with a sharp object.
 Positive responses occur within 10 to 15 minutes and produce a characteristic raised central area of
induration (wheal), with a surrounding zone of erythema (flare).

 Response is graded in comparison with a positive histamine response, positive control ensures that the
patient can show a reaction to histamine, and the absence of a reaction can unmask interference by
medications, decreased skin reactivity, or technical problems.

 Negative puncture tests are usually confirmed by intra-dermal tests, which are more sensitive. Small
(0.01 to 0.05 mL) quantity of dilute allergen is injected into the superficial dermis, and the same wheal
and flare responses are observed and graded in comparison with a positive histamine control.

 Antihistamines can interfere with the results of skin testing, should be stopped for 2 days before skin
testing. Tricyclic antidepressants suppress responses for several weeks, as can tranquilizers and
antiemetics of the phenothiazine class through intrinsic anti-H1 activity. Short-term oral corticosteroid
treatment has no effect on skin test reactivity but may have an inhibitory effect if the agent is taken for
long periods.

 Testing with extracts that are standardized (ragweed, grass pollens) is more reliable than for
nonstandardized antigens such as foods and chemicals.
 2. MEASUREMENT OF SPECIFIC IgE: (Radio-allergo-sorbent assay or RAST)

 Comparing results of skin testing and RAST in allergic subjects suggest a good correlation between
the two, with a higher sensitivity for skin testing.

 Disadvantages include cost, slightly lower sensitivity, and the time delay before obtaining the results.

  

 3. PREPHIRAL ESINOPHILIA:

 Although nonspecific, may indicate the presence of other atopic diseases.

  

 4. NASAL CYTOLOGY:

 Elevated eosinophils and may be helpful in differentiating an infectious from an allergic cause
during a clinical exacerbation of symptoms.

 A value greater than 10% is suggestive of allergic disease.

 Eosinophils, however, may also be present in the absence of IgE-mediated disease.
Approximately 25% of patients with chronic rhinitis and negative skin tests
demonstrate eosinophilia on nasal cytologic study, and this entity is known as the
nonallergic rhinitis with eosinophilia syndrome (NARES).

 Regardless of the cause, the presence of eosinophilia usually implies a favorable

clinical response to corticosteroid therapy.
 THERAPY:
 ENVIRONMENTAL MODIFICATIONS:

 In seasonal allergic rhinitis, keeping windows closed on days when pollen counts are high and limiting
physical activity outdoors in the early morning and evening when pollen counts peak. Pollen counts are
often given during daily weather reports.

 Air conditioning can help, and the addition of special filters can prevent pollen grains and mold spores
from entering home.

 Measures to reduce exposure to dust mites concentrate on bedding include replacing feather pillows and
bedspreads with synthetic ones that can be washed in hot water and covering mattresses with plastic
covers.

 Removing carpets and frequent vacuuming also help. Where carpets cannot be removed, acaricidal
products can directly kill mites.

 Stuffed toys can be placed in the freezer for 2 days to reduce the number of dust mites.

 In subjects with allergies to animal dander, removal of a domestic pet is the best step.
 Use of high-efficiency particulate air (HEPA) filters and of electrostatic filters
effectively removes particulates larger than 1 μm in diameter. Particles, however, must
be airborne for removal, such as pollens, whereas heavy particles that settle from the air
rapidly, such as dust mites, are not eliminated.

 Pesticide application are necessary to eliminate cockroaches.

 ANTIHISTAMINES:

 3 Types of histamine receptors:

- H1 receptors are found on blood vessels, sensory nerves, smooth muscles of the respiratory and digestive tracts, and in
central nervous system. Stimulation leads to vasodilatation, increased vascular permeability, sneezing, pruritus,
glandular secretion, and increased intestinal motility. Largely mediated in early allergic response.

- H2 receptors principally involved in the regulation of gastric acid secretion.

- H3 receptors are located principally in the brain.

 Classification of H1 antihistamines:

o First-generation (sedating): effective, but they have some undesirable side effects because of their lack of selectivity
and subsequent nonspecific stimulation of other receptors. Among these side effects are sedation, anticholinergic
effects, and gastrointestinal distress. Eg.

- Chlorophexamine (Allergex)

- Chlorophenramine maleate (Allergyl)

- Clemastil (Tavagyl)

- Dimethinidine maleate (Fenestil)

- Third generation of antihistamines (desloratadine).

o Second-generation (non-sedating): less lipophilic, and do not penetrate the blood-brain
barrier. Therefore, they produce no more somnolence than does placebo. Their greater
receptor selectivity also reduces the incidence of anticholinergic side effects. Eg.

- Loratidine (Claritine, Lortan)

- Fexofenadine (Telfast)

- Citirizine (Zyrtec)

- Azelastine (Zalastin) & Levocapastine (Livostin) intranasal preparations.

o Third generation: Desloratidine (Areus)

 Treatment with some antihistamines also reduces the production of leukotrienes and
kinins (anti-inflammatory effect).

 Oral antihistamines are readily absorbed. Their onset of action is rapid, usually within
60 minutes, and maximum benefit occurs within hours.
 DECONGESTANTS:

 Sympathetic nervous activity regulates nasal patency through stimulation of α1- or α2-adrenergic
receptors present on vessels to maintain sinusoids contracted to approximately half maximal
capacity. The resting state is affected by the nasal cycle.

 Decongestants exert their effect through stimulation of α1- or α2-adrenergic receptors.

 Oral decongestants exert their effects directly and by stimulating norepinephrine release.

- Eg. Pseudoephedrine.

- Available combined with antihistamines (eg. Clarinase,..)

- Because also stimulate adrenergic receptors other than those in the nasal vasculature, overdosage
has been associated with hypertensive crisis. When given in prescribed doses, however, they do not
induce hypertension in normotensive patients, nor do they alter the pharmacologic control of stable
hypertensive patients. Should not be used in patients with uncontrolled hypertension, in those with
coronary artery disease, hyperthyroidism, closed-angle glaucoma, prostatic hypertrophy.

- Major side effect is insomnia, which occurs in approximately 25% of patients.

 Topical decongestants:

- Eg. Xylometazoline (Otrovin), Oxymetazolone (Afrin).

- Prolonged use can bring about rhinitis medicamentosa, which is characterized by

reduced duration of action and rebound nasal congestion after cessation of therapy.
Because this phenomenon can appear even after a short period, use of these agents
should be limited to a few days.
 TOPICAL INTRANASAL CORTICOSTEROIDS:

 Mechanism of action: penetrate the interior of the cell, where they are bound by a glucocorticoid
receptor in the cytoplasm. Glucocorticoid-receptor complex then penetrates the nucleus, where it
inhibits the synthesis of the proinflammatory cytokines IL-1-6; interferon-γ; tumor necrosis factor-α
and induces the synthesis of anti-inflammatory substances such as vasocortin and lipocortin.

 Eg. Fluticasone propionate (Flixonase), Mometazone foroate (Nasonex), Beclometazone

dipropionate (Beconaze), Rhinocort (Budesonide).

 More effective for perennial allergic rhinitis than second-generation antihistamine.

 The most frequent is nasal irritation, which occurs in approximately 10% of patients. Other very
rare include septal perforation, cataract.

 FDA approved to be used starting at the ages of 3 (mometasone) and 4 years (fluticasone), with the
recommended dose being half that used for adults.

  
 SYSTEMIC CORTICOSTEROIDS:

 Administered to patients during severe exacerbations of allergic symptoms when total nasal
obstruction prevents the introduction of a topical intranasal corticosteroid.

  

 N.B. Corticosteroid injections into the turbinates are also perceived as clinically effective but
have rarely been used since the advent of intranasal corticosteroids and because of a small
associated risk of blindness. Although this complication can be minimized by use of a
corticosteroid with small particle size.

  
 SODIUM CHROMOGLYCATE:

 Eg. Nasotal spray, Cromolyn drops.

 It exerts a protective effect on the allergic response when given four to six times daily beginning before
the development of symptoms.

 Although it was initially thought to prevent mast cell degranulation, the exact mechanism of action of
this agent is unknown.

 Its effectiveness approximates that of antihistamines, but the need for frequent dosing limits compliance.

 Like antihistamines, cromolyn is more helpful for sneezing, rhinorrhea, and nasal itching than for nasal
congestion.

 Its safety profile, however, makes it an attractive treatment, especially in children and pregnant women.

  
 TOPICAL ANTI-CHOLINERGIC AGENTS:

 Ipratropium bromide (Atrovent).

 Inhibit parasympathetic stimulation of glandular secretion by competing for muscarinic

receptors on glands. Thus, highly effective in reducing rhinorrhea but have no effect on the
other symptoms.

 May be beneficial in some cases of allergic and nonallergic rhinitis, as well as the
rhinorrhea precipitated by exposure to cold, windy environments, often referred to as
“skiers’ nose.”
 Excessive drying of the nasal mucosa and epistaxis are the most frequent side effects.
 LEUKOTRIENE MODIFIERS = LEUKOTRIENE RECEPTOR ANTAGONISTS:
Montelukast (Singulair)

 Block the receptor for the Cystenyle LTs.

 May be useful in the treatment of patients with allergic rhinitis and concomitant asthma.

 Combination of a leukotriene modifier with an antihistamine increases the efficacy of

both medications. This combination can be considered as an alternative in patients who
do not tolerate intranasal corticosteroids.

  
 IMMUNOTHERAPY:
 Indications:

 Primary indication is symptoms not adequately controlled by avoidance measures and

pharmacotherapy.

 Patients with perennial symptoms may prefer immunotherapy to yearlong daily medication.

 Technique:

 Choice of allergens for treatment is made after a careful diagnostic workup.

 Begins with low-dose injections of allergen extracts till reaching a maintenance dose. Injections usually
begin at weekly intervals and are then reduced in frequency when maintenance doses are reached.

 Improvement begin after 3 months, but an optimal effect takes 1 year.

 Patients who do not achieve symptomatic improvement after 1 year of immunotherapy should
discontinue.
 Most physicians treat for 2 to 5 years. Improvement persists for several years after
the end of treatment.

 Injections should be administered under the supervision of a qualified medical

practitioner, and patients should be observed for at least 30 minutes after every
injection. Proper resuscitative equipment should be present because anaphylactic
reactions can occur at any time during treatment, even in patients receiving
maintenance dosages.

 Local reactions at the site of injection are frequent with effective dosages and require
no therapy.
 Repeated strong reactions persisting for 24 hours should lead to consideration of dose
reduction
 Disadvantages:

 Sow in onset

 Effective only for the allergens for which the patient is treated.

 Precautions:

 Immunotherapy of asthmatic patients should be administered with extreme caution because these
patients have the greatest morbidity.

 Immunotherapy should not be started in pregnant women because of the risk of anaphylaxis and the
resultant effect of hypotension on the fetus.

 Patients who are taking beta blockers should not receive immunotherapy because, if anaphylaxis
occurs, they cannot be resuscitated. 

 FUTURE THERAPIES:

 Anti-human IgE antibody (rhuMAb-E25) showed promise in early trials.

 Development of drugs combining antihistamines and antileukotriene agents.

 SPECIAL CONSIDERATIONS
 Pregnancy:
 • American College of Allergy, Asthma and Immunology (ACAAI) make the
following recommendations.
 • Pseudoephedrine is the decongestant to be used, but to avoid oral
decongestants during the first trimester.
 • First generation antihistamines can be used even in first trimester.
 • Cetirizine and loratidine but not fexofenadine (according to experimental
works) can be used in patients who do not tolerate chlorpheniramine and who
fail other therapies.
 • Sodium cromoglycate is a safe drug during pregnancy.
 • No data exist on the teratogenicity of intranasal corticosteroids in humans,
although they are thought to be safe.
 • Leukotriene modifiers show adverse effects in animals and cannot be
recommended in pregnancy.
 • Maintenance immunotherapy may be safely continued during pregnancy in
patients who are not prone to systemic reactions. Immunotherapy should not be
initiated during pregnancy.
THANKS