Allergic Rhinitis

Definition

• Allergic rhinitis is inflammation of the nasal mucous membrane caused by exposure to inhaled allergenic materials that elicit a specific immunologic response mediated by immunoglobulin E. There are two types.
  • Seasonal (hay fever): occurs in response to specific allergens (pollen from trees, grasses, and weeds) present at predictable times of the year (spring and/or fall blooming seasons) and typically causes more acute symptoms.
  • Perennial (intermittent or persistent): occurs year round in response to nonseasonal allergens (e.g., dust mites, animal dander, molds) and usually causes more subtle, chronic symptoms.
• Some patients have both types, with symptoms year round and seasonal exacerbations.

Pathophysiology

• The initial reaction occurs when airborne allergens enter the nose during inhalation and are processed by lymphocytes, which produce antigen-specific immunoglobulin E, thereby sensitizing genetically predisposed hosts to those agents. On nasal reexposure, immunoglobulin E bound to mast cells interacts with airborne allergens, triggering release of inflammatory mediators.
• An immediate reaction occurs within minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade. Mediators of immediate hypersensitivity include histamine, leukotrienes, prostaglandin, tryptase, and kinins. These mediators cause vasodilation, increased vascular permeability, and production of nasal secretions. Histamine produces rhinorrhea, itching, sneezing, and nasal obstruction.
• From 4 to 8 hours after the initial exposure to an allergen, a late-phase reaction may occur, which is thought to be due to cytokines released primarily by mast cells and thymus-derived helper lymphocytes. This inflammatory response likely is responsible for persistent, chronic symptoms including nasal congestion.

Clinical presentation

• Symptoms include clear rhinorrhea, sneezing, nasal congestion, postnasal drip, allergic conjunctivitis, and pruritic eyes, ears, or nose.
• Patients may complain of loss of smell or taste, with sinusitis or polyps the underlying cause in many cases. Postnasal drip with cough or hoarseness can also be bothersome.
• Untreated rhinitis symptoms may lead to insomnia, malaise, fatigue, and poor work or school efficiency.
• Allergic rhinitis is a risk factor for asthma; as many as 78% of asthma patients have nasal symptoms, and about 38% of allergic rhinitis patients have asthma.
• Recurrent and chronic sinusitis and epistaxis are complications of allergic rhinitis.

Diagnosis

• Physical examination may reveal dark circles under the eyes (allergic shiners), a transverse nasal crease caused by repeated rubbing of the nose, adenoidal breathing, edematous nasal turbinates coated with clear secretions, tearing, conjunctival injection and edema, and periorbital swelling.
• Microscopic examination of nasal scrapings typically reveals numerous eosinophils. The peripheral blood eosinophil count may be elevated, but it is nonspecific and has limited usefulness.
• Allergy testing can help determine whether rhinitis is caused by an immune response to allergens. Immediate-type hypersensitivity skin tests are commonly used. Percutaneous testing is safer and more generally accepted than intradermal testing, which is usually reserved for patients requiring confirmation. The radioallergosorbent test (RAST) can be used to detect immunoglobulin E antibodies in the blood that are specific for a given antigen, but it is less sensitive than percutaneous tests.

Desired outcome

• The goal of treatment is to minimize or prevent symptoms with minimal or no side effects and reasonable medication expense.
• Patients should be able to maintain a normal lifestyle, including participation in outdoor activities and playing with pets as desired.

Treatment

Allergen avoidance

• Avoidance of offending allergens is difficult. Mold growth can be reduced by keeping household humidity below 50% and removing obvious growth with bleach or disinfectant.
• Patients sensitive to animals benefit most by removing pets from the home, if feasible. Exposure to dust mites can be reduced by encasing mattresses and pillows with impermeable covers and washing bed linens in hot water. Washable area rugs are preferable to wall-to-wall carpeting.
• High-efficiency particulate air (HEPA) filters can remove lightweight particles such as pollens, mold spores, and cat allergen, thereby reducing allergic respiratory symptoms.
• Patients with seasonal allergic rhinitis should keep windows closed and minimize time spent outdoors during pollen seasons. Filter masks can be worn while gardening or mowing the lawn.

Pharmacologic therapy

Antihistamines

• Histamine H1-receptor antagonists bind to H1 receptors without activating them, preventing histamine binding and action. They are more effective in preventing the histamine response than in reversing it.
• Oral antihistamines can be divided into two major categories: nonselective (first-generation or sedating antihistamines) and peripherally selective (second-generation or nonsedating antihistamines). However, individual agents should be judged on their specific sedating effects because variation exists among agents within these broad categories. The central sedating effect may depend on the ability to cross the blood-brain barrier. Most older antihistamines are lipid soluble and cross this barrier easily. The peripherally selective agents have little or no central or autonomic nervous system effects.
• Symptom relief is caused in part by anticholinergic properties, which are responsible for the drying effect that reduces nasal, salivary, and lacrimal gland hypersecretion. Antihistamines antagonize capillary permeability, wheal-and-flare formation, and itching.
• Drowsiness is the most frequent side effect, and it can interfere with driving ability or adequate functioning at the workplace. Sedative effects can be beneficial in patients who have difficulty sleeping because of rhinitis symptoms.

TABLE. Relative Adverse-Effect Profiles of Antihistamines

Medication Relative Sedative Effect Relative Anticholinergic Effect Alkylamine class, nonselective Brompheniramine maleate Low Moderate Chlorpheniramine maleate Low Moderate Dexchlorpheniramine maleate Low Moderate Ethanolamine class, nonselective Carbinoxamine maleate High High Clemastine fumarate Moderate High Diphenhydramine hydrochloride High High Ethylenediamine class, nonselective Pyrilamine maleate Low Low to none Tripelennamine hydrochloride Moderate Low to none Phenothiazine class, nonselective Promethazine hydrochloride High High Piperidine class, nonselective Cyproheptadine hydrochloride Low Moderate Phenindamine tartrate Low to none Moderate Phthalazinone class, peripherally selective Azelastine (nasal only) Low to none Low to none Piperazine class, peripherally selective Cetirizine Low to moderate Low to none Piperidine class, peripherally selective Desloratadine Low to none Low to none Fexofenadine Low to none Low to none Loratadine Low to none Low to none

• Although anticholinergic (drying) effects contribute to efficacy, adverse effects such as dry mouth, difficulty in voiding urine, constipation, and potential cardiovascular effects may occur (Table Relative Adverse-Effect Profiles of Antihistamines). Antihistamines should be used with caution in patients predisposed to urinary retention and in those with increased intraocular pressure, hyperthyroidism, and cardiovascular disease.
• Other side effects include loss of appetite, nausea, vomiting, and epigastric distress. Taking medication with meals or a full glass of water may prevent gastrointestinal side effects.
• Antihistamines are more effective when taken approximately 1 to 2 hours before anticipated exposure to the offending allergen.
• Table Oral Dosages of Commonly Used Antihistamines and Decongestants lists recommended doses of commonly used oral agents.
• Azelastine (Astelin) is an intranasal antihistamine that rapidly relieves symptoms of seasonal allergic rhinitis. However, patients should be cautioned about its potential for drowsiness because systemic availability is approximately 40%. Patients may also experience drying effects, headache, and diminished effectiveness over time.
• Levocabastine (Livostin) and olopatadine (Patanol) are ophthalmic antihistamines that can be used for allergic conjunctivitis that is often associated with allergic rhinitis. However, systemic antihistamines are usually effective for allergic conjunctivitis, making an ocular product unnecessary. They may be a logical addition to nasal glucocorticoids when ocular symptoms occur.

TABLE. Oral Dosages of Commonly Used Antihistamines and Decongestants

Medication Dosage and Intervala Adults Children Nonselective (first-generation) anthihistamines   Chlorpheniramine maleate, plainb 4 mg every 6 h 6-12 yr: 2 mg every 6 h 2-5 yr: 1 mg every 6 h Chlorpheniramine maleate, sustained-release 8-12 mg daily at bedtime or 8-12 mg every 8 h 6-12 yr: 8 mg at bedtime <6 yr: Not recommended Clemastine fumarateb 1.34 mg every 8 h 6-12 yr: 0.67 mg every 12 h Diphenhydramine hydrochlorideb 25-50 mg every 8 h 5 mg/kg/day divided every 8 h (up to 25 mg per dose) Peripherally selective (second-generation) antihistamines Loratadineb 10 mg once daily 6-12 yr: 10 mg once daily 2-5 yr: 5 mg once daily Fexofenadine 60 mg twice daily or 180 mg once daily 6-11 yr: 30 mg twice daily Cetirizineb 5-10 mg once daily >6 yr: 5 mg once daily infants 6-11 monthsc Oral decongestants Pseudoephedrine, plain 60 mg every 4-6 h 6-12 yr: 30 mg every 4-6 h 2-5 yr: 15 mg every 4-6 h Pseudoephedrine, sustained-released 120 mg every 12 h Not recommended Note: Fexofenadine and cetirizine are available by prescription only. aDosage adjustment may be needed in renal/hepatic dysfunction. Refer to manufacturers’ prescribing information. bAvailable in liquid form. c0.25 mg/kg orally demonstrated to be safe. dControlled-release product available: 240 mg once daily (60-mg immediate-release with 180-mg controlled-release).

Decongestants

• Topical and systemic decongestants are sympathomimetic agents that act on adrenergic receptors in the nasal mucosa to produce vasoconstriction, shrink swollen mucosa, and improve ventilation. Decongestants work well in combination with antihistamines when nasal congestion is part of the clinical picture.
• Topical decongestants are applied directly to swollen nasal mucosa via drops or sprays (Table Duration of Action of Topical Decongestants). They result in little or no systemic absorption.
• Prolonged use of topical agents (more than 3 to 5 days) can result in rhinitis medicamentosa, which is rebound vasodilation with associated congestion. Patients with this condition use more spray more often with less response. Abrupt cessation is an effective treatment, but rebound congestion may last for several days or weeks. Nasal steroids have been used successfully, but they take several days to work. Weaning the patient off the topical decongestant can be accomplished by decreasing the dosing frequency or concentration over several weeks. Combining the weaning process with nasal steroids may be helpful.
• Other adverse effects of topical decongestants include burning, stinging, sneezing, and dryness of the nasal mucosa.
• These products should be used only when absolutely necessary (e.g., at bedtime) and in doses that are as small and infrequent as possible. Duration of therapy should always be limited to 3 to 5 days.

TABLE. Duration of Action of Topical Decongestants

Medication Duration (h) Short-acting Phenylephrine hydrochloride Up to 4 Intermediate-acting Naphazoline hydrochloride 4-6 Tetrahydrozoline hydrochloride   Long-acting Oxymetazoline hydrochloride Up to 12 Xylometazoline hydrochloride

• Pseudoephedrine is an oral decongestant that has a slower onset of action than topical agents but may last longer and cause less local irritation. Also, rhinitis medicamentosa does not occur with an oral decongest- ant.
• Pseudoephedrine is the safest systemic decongestant; doses up to 180 mg produce no measurable change in blood pressure or heart rate. However, higher doses (210 to 240 mg) may raise both blood pressure and heart rate. Systemic decongestants should be avoided in hypertensive patients unless absolutely necessary. Severe hypertensive reactions can occur when pseudoephedrine is given concomitantly with monoamine oxidase inhibitors. Pseudoephedrine can cause mild central nervous system stimulation, even at therapeutic doses.
• Use of combination oral products containing a decongestant and antihistamine is rational because of the different mechanisms of action.

Nasal Corticosteroids

• Intranasal corticosteroids effectively relieve sneezing, rhinorrhea, pruritus, and nasal congestion with minimal side effects (Table Dosage of Nasal Corticosteroids). They reduce inflammation by blocking mediator release, suppressing neutrophil chemotaxis, causing mild vasoconstriction, and inhibiting mast cell-mediated late-phase reactions.

TABLE. Dosage of Nasal Corticosteroids

Medication Dosage and Interval Beclomethasone dipropionate >12 yr: 1 inhalation (42 mcg) per nostril 2-4 times a day (maximum, 336 mcg/day) 6-12 yr: 1 inhalation per nostril 3 times/day Beclomethasone dipropionate, monohydrate >12 yr: 1-2 inhalations once daily 6-12 yr: 1 inhalation per nostril (42 mcg) twice daily to start Budesonide >6 yr: 2 sprays (64 mcg) per nostril in AM and PM or 4 sprays per nostril in AM (maximum, 256 mcg) Flunisolide Adults: 2 sprays (50 mcg) per nostril twice daily (maximum, 400 mcg)   Children: 1 spray per nostril 3 times a day Fluticasone Adults: 2 sprays (100 mcg) per nostril once daily; after a few days decrease to 1 spray per nostril   Children > 4 yr and adolescents: 1 spray per nostril once daily (maximum, 200 mcg/day) Mometasone furoate >12 yr: 2 sprays (100 mcg) per nostril once daily Triamcinolone acetonide >12 yr: 2 sprays (110 mcg) per nostril once daily (maximum, 440 mcg/day)

• These agents are an excellent choice for perennial rhinitis and can be useful in seasonal rhinitis, especially if dosed in advance of symptoms. Some authorities recommend nasal steroids as initial therapy over antihistamines because of their high degree of efficacy when used properly along with allergen avoidance.
• Side effects include sneezing, stinging, headache, epistaxis, and rare infections with Candida albicans.
• Some patients improve within a few days, but peak response may require 2 to 3 weeks. The dosage may be reduced once a response is achieved.
• Blocked nasal passages should be cleared with a decongestant before administration of glucocorticoids to ensure adequate penetration of the spray.

Cromolyn Sodium

• Cromolyn sodium (Nasalcrom), a mast cell stabilizer, is available as a nonprescription nasal spray for symptomatic prevention and treatment of allergic rhinitis.
• It prevents antigen-triggered mast cell degranulation and release of mediators, including histamine.
• The most common side effect is local irritation (sneezing and nasal stinging).
• The dosage for individuals at least 2 years of age is one spray in each nostril 3 to 4 times daily at regular intervals. Nasal passages should be cleared before administration, and inhaling through the nose during administration enhances distribution to the entire nasal lining.
• For seasonal rhinitis, initiate treatment just before the start of the allergens season and continue throughout the season.
• In perennial rhinitis, the effects may not be seen for 2 to 4 weeks; antihistamines or decongestants may be needed during this initial phase of therapy.

Ipratropium Bromide

• Ipratropium bromide (Atrovent) nasal spray is an anticholinergic agent useful in perennial allergic rhinitis.
• It exhibits antisecretory properties when applied locally and provides symptomatic relief of rhinorrhea associated with allergic and other forms of chronic rhinitis.
• The 0.03% solution is given as two sprays (42 mcg) 2 to 3 times daily. Adverse effects are mild and include headache, epistaxis, and nasal dryness.

Montelukast

• Montelukast (Singulair) is a leukotriene receptor antagonist approved for treatment of seasonal allergic rhinitis. It is effective alone or in combination with an antihistamine.
• The dosage for adults and adolescents older than 15 years is one 10-mg tablet daily. Children aged 6 to 14 years may receive one 5-mg chewable tablet daily. Children aged 2 to 5 may be given one 4-mg chewable tablet or oral granule packet daily. The timing of administration can be individualized. The dose should be given in the evening if the patient has combined asthma and seasonal allergic rhinitis.
• Although leukotriene antagonists represent a new therapeutic alternative, published studies to date have shown them to be no more effective than peripherally selective antihistamines and less effective than intranasal corticosteroids.

Immunotherapy

• Immunotherapy is the slow, gradual process of injecting increasing doses of antigens responsible for eliciting allergic symptoms in a patient with the intent of increasing tolerance to the allergen when natural exposure occurs.
• The effectiveness of immunotherapy probably results from diminished immunoglobulin E production, increased immunoglobulin G production, changes in T lymphocytes, reduced inflammatory mediator release from sensitized cells, and diminished tissue responsiveness.
• Because immunotherapy is expensive, has potential risks, and requires a major time commitment from patients, it should only be considered in selected patients. Good candidates include patients who have a strong history of severe symptoms unsuccessfully controlled by avoidance and pharmacotherapy and patients who have been unable to tolerate the adverse effects of drug therapy. Poor candidates include patients with medical conditions that would compromise the ability to tolerate an anaphylactic-type reaction, patients with impaired immune systems, and patients with a history of nonadherence to therapy.
• In general, very dilute solutions are given once or twice per week. The concentration is increased until the maximum tolerated dose is achieved. This maintenance dose is continued every 2 to 6 weeks, depending on clinical response. Better results are obtained with year-round rather than seasonal injections.
• Common mild local adverse reactions include induration and swelling at the injection site. More severe reactions (generalized urticaria, bronchospasm, laryngospasm, vascular collapse, and death from anaphylaxis) occur rarely. Severe reactions are treated with epinephrine, antihistamines, and systemic corticosteroids.

Evaluation of therapeutic outcomes

• Patients should be monitored regularly for reduction in severity of identified target symptoms and the presence of side effects.
• Patients should be questioned about their satisfaction with the management of their allergic rhinitis. Management should result in minimal disruption to their life.
• The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and the Rhinoconjunctivitis Quality of Life Questionnaire measure not only improvement in symptoms but also parameters such as sleep quality, nonallergic symptoms (e.g., fatigue, poor concentration), emotions, and participation in a variety of activities.