- CONDITION CENTERS
Brought to you through an educational grant from Aventis, a member of Sanofi-Aventis Group
After completing this continuing education article, the pharmacist should be able to:
Rhinitis is inflammation of the mucous membranes that line the nasal passages and is characterized by rhinorrhea and nasal congestion. Factors contributing to rhinitis include allergies, infection, hormones, and occupational exposures.
Impact of Allergic Rhinitis
Allergic rhinitis affects 40 million Americans-10% to 30% of adults and up to 40% of children and young adults. Allergic rhinitis affects males and females in equal proportion but generally occurs in individuals younger than 45 years, peaking in prevalence between the ages of 21 and 30 years.1 Ranging in severity from mild to debilitating, it is not a life-threatening condition, although it is a significant cause of morbidity. In addition to inflammation of the mucous membranes, rhinorrhea, and nasal congestion, it may also cause fatigue, cognitive impairment, and/or headache. The economic burden of allergic rhinitis is also significant, including substantial medical treatment costs, reduced productivity in the workplace, and missed school days. According to the US Department of Health and Human Services, direct costs for prescription medications and office visits are nearing $1.8 billion and indirect costs related to loss of workplace productivity are approximately $3.8 billion annually.2
Complications of allergic rhinitis are also burdensome and may affect the paranasal sinuses, eustachian tubes, sense of smell, and even the lower airways. Allergic rhinitis is also associated with numerous comorbidities, including sinusitis, otitis, and sleep disturbances. In fact, patients with allergic rhinitis are up to 3 times more likely to develop asthma.3
Causes of Allergic Rhinitis
Several factors increase risk for allergic rhinitis, including family history of allergic rhinitis and family or personal history of atopic dermatitis or asthma, as well as exposure to allergens.4 For allergic rhinitis to develop, the individual must first be exposed to an allergen, which is a protein that elicits an allergic response in a particular individual. Allergic rhinitis can be classified as seasonal or perennial, depending on whether it occurs only in specific seasons or continuously throughout the year.4 Seasonal allergens often include airborne pollen from trees, weeds, and grasses and mold spores on decayed vegetation.4 Pollen allergies may be referred to as rose fever when occurring in the spring and hay fever in late summer and fall. Indoor allergens, including dust mites, pet dander, some types of mold, and cockroaches, are generally responsible for perennial allergic rhinitis.4
There are 2 phases in allergic response. In the early phase, mastcell-bound immunoglobulin E (IgE) antibodies react to the allergen within minutes (Figures 1 and 2). This triggers formation and immediate release of histamine, leukotrienes, bradykinin, and other chemical mediators and causes nasal itching, rhinorrhea, sneezing, and/or congestion.5 Over the next several hours, the lining of the nose becomes infiltrated with white blood cells (eosinophils, basophils, monocytes, and lymphocytes) and the chemical mediators, histamine and leukotrienes, resulting in a "primed" and hyperresponsive nasal mucosa. Subsequent exposure to the offending allergen, even very small amounts, often results in significant allergic response and nasal symptoms in a primed airway.5
The inflammatory response may persist for several weeks after allergen exposure due to the lingering inflammatory infiltrate. Therefore, nasal inflammation may persist for several weeks and may even be continuous in patients with perennial allergic rhinitis.
The chief complaints of patients with allergic rhinitis are usually clear rhinorrhea, sneezing episodes, nasal congestion, nasal and/or eye itching, and postnasal drip. Patients may complain of a cough or an impaired sense of smell and taste.6 Patients may twitch their nose due to itchy mucous membranes. In children, repeated rubbing to relieve itchy symptoms may result in a crease across the bridge of the nose. Chronic mouth breathing may be evident in patients with substantial nasal congestion. A high arched palate may indicate a history of long-term mouth breathing. Patients may also present with red conjunctiva and increased lacrimation.7 Dark rings under the eyes, termed "allergic shiners," are thought to result from lymphatic backflow due to chronic nasal congestion.
Diagnosing Allergic Rhinitis
The differential diagnosis of allergic rhinitis is straightforward.4 A thorough history and physical examination are performed, and diagnostic tests are used in some cases. The history includes description of symptoms, including type and duration, allergen exposures, response to any previous therapies or medications, previous nasal injuries or surgeries, family history, and presence of other medical problems.4 To establish the offending allergens in seasonal allergic rhinitis, it is important to determine the month(s) in which symptoms are most severe. Tree pollen season is generally in early spring, with grass pollen season following in late spring and early summer. Weed pollen season usually starts in mid-August and lasts until early October. Often, it is difficult to identify the specific contributing allergen(s), particularly in perennial rhinitis. If the symptoms are most severe upon wakening, however, dust mites are the likely offenders.8
The physical examination should evaluate the ears, eyes, nose, throat, and lungs. Nasal examination should focus on appearance of the mucous membranes, patency of the airway, and the nasal discharge. The nasal lining in allergic rhinitis is generally pale and edematous. The examination of the nares, nasopharynx, and oral cavity can be made with a light and nasal speculum, but nasal endoscopy is sometimes employed.9
Allergen testing is particularly useful in establishing the diagnosis of seasonal and perennial allergic rhinitis. It aids in identification of the patient's specific offending allergen(s), allowing the patient and health care provider to establish targeted allergen avoidance, immunotherapy, and/or other treatment options. Skin testing is the most widely used and cost-effective method of allergen testing.4 Skin testing confirms the presence of IgE antibodies to allergens. For patients who have perennial symptoms, testing generally includes agents such as dust mites, animal dander, and mold spores. In those with seasonal symptoms, testing will include agents such as weed, grass, and tree pollens. In children, some foods may cause allergic reactions but generally not rhinitis. These are less common in adults but should be investigated if patients complain of itching, hives, or gastrointestinal symptoms after eating.4
The 2 types of skin tests are prick puncture tests and intradermal tests. Prick puncture tests are more commonly used because they are generally safe, cause little discomfort, and are 80% to 85% sensitive. Intradermal tests are used less frequently, because they are overly sensitive to the point of causing nonspecific irritation. They are indicated when absolute (100%) specificity is required or when allergens are likely to have produced negative results via the prick puncture method.10 The patient's allergist, pharmacist, or other health care provider should counsel the patient that antihistamines can interfere with allergy testing and, therefore, should not be used for at least 48 hours prior to testing.10
Skin testing may not be possible in patients with severe dermatologic disease due to lack of normal skin. In these patients, the radioallergosorbent test (RAST), which is an in vitro serum IgE immunoassay, can be used. Because the RAST is more expensive, it should be reserved for those patients unable to tolerate traditional skin testing methods.10
Additional tests are available for establishing the diagnosis of allergic rhinitis. Nasal cytology, an examination of nasal secretions, helps in the identification of inflammatory cells. Elevated eosinophil levels may indicate allergic rhinitis. Some tests used primarily in research are nasal challenge testing and measurement of nasal airway resistance.9
Classification of Allergic Rhinitis
The World Health Organization (WHO) brought together physician experts in December 1999, with an objective of reporting on whether an association exists between allergic rhinitis and asthma. The document they produced was entitled "Allergic Rhinitis and Its Impact on Asthma" (ARIA), and it serves several purposes. First, ARIA emphasizes the impact of allergic rhinitis on asthma. It also provides recommendations with supportive evidence for diagnosis, classification, and a stepwise treatment approach for allergic rhinitis.11 The ARIA document originated the new classification system of allergic rhinitis, which is very similar to that used for asthma.
Before the ARIA guidelines, allergic rhinitis was classified as seasonal, perennial, or occupational.4 This classification made it difficult to distinguish the types of allergic rhinitis, because seasonal allergens often cause symptoms that look like perennial allergic rhinitis, and perennial allergens may be present only during certain parts of the year. Additionally, some patients develop an allergic response to seasonal and perennial allergens, having symptoms of varying severity throughout the year. The ARIA guidelines system has reclassified allergic rhinitis to "intermittent" or "persistent" based on symptom timing and frequency. This system also classifies symptom severity as "mild" or "moderate to severe," taking into account how the symptoms affect the patient's quality of life.11
Poorly controlled allergic rhinitis may lead to comorbid conditions. The incidence of sinusitis and otitis media are clearly more common in patients with allergic rhinitis. This probably results from nasal mucosal hypertrophy infringing on the ostea, which are the draining sites of the paranasal sinuses, and on the eustachian tube leading to the middle ear.
A significant association is evident between allergic rhinitis and asthma.4 More than 80% of patients with asthma also have allergic rhinitis. Allergic rhinitis appears to be a predisposing factor to the development of asthma and also contributes to asthma severity. Appropriate therapy of allergic rhinitis has been shown to impact asthma morbidity favorably. The ARIA guidelines highlight the need to evaluate patients with persistent allergic rhinitis for asthma and to evaluate patients with asthma for allergic rhinitis.11
The goal of treating allergic rhinitis is symptom reduction or prevention, while minimizing side effects and cost of therapy (Table 1). The current management options for allergic rhinitis are organized into a stepwise approach, which includes allergen avoidance, pharmacotherapy to prevent or treat symptoms, and allergenspecific immunotherapy.4
Allergen avoidance is essential to successful treatment of allergic rhinitis, but while it can be very effective, it is often the most difficult treatment approach to achieve. Complete allergen avoidance is usually not possible, but exposure to common allergens such as dust mites, pet dander, pollen, and mold spores can be reduced with relatively simple measures (Table 2).
Avoiding outdoor activities during high pollen season and between 5:00 and 10:00 AM, when the pollen counts are highest, can minimize pollen exposure. When outdoor activities are necessary, filter masks can be worn to provide a barrier against the offending allergens. The use of home and auto air-conditioning instead of open windows markedly reduces pollen and mold exposure during allergy-specific seasons.
Dust mites are microscopic insects that most often reside in warm, humid environments, such as bedding, carpets, and upholstered furniture. Dust mite exposure can be lessened with the use of impermeable bedding covers and weekly washing in very hot (> 130°F) water, which destroys mites and their allergenic feces.8 Maintaining household humidity levels at or below 50% via use of a dehumidifier may also reduce the level of dust-mite allergens. Carpet should be replaced with tile or wood floors and curtains with blinds or nonfabric shades. Stuffed animals may be washed or placed in the freezer overnight weekly to remove mites.
Pet-dander allergens can best be avoided by finding a new home for the pet. However, pet owners are often reluctant to comply with this recommendation, and they should be advised, at minimum, not to allow the pet in the bedroom of the allergic patient. Pet dander resides in soft fabrics, including bedding and carpet. High-efficiency particulate air (HEPA) filters are most effective in removing lighter-weight airborne allergens, including pet dander, pollen, and mold spores.4 Frequent vacuuming with a HEPA vacuum and pet bathing should be recommended.
Medications for allergic rhinitis fall into 2 main categories: those that primarily relieve symptoms and those that target the inflammation and treat the underlying disease. Patients may seek symptom relief with over-the-counter medications before ever addressing the condition with their physicians, because over-the-counter products are more accessible and affordable, particularly for patients without medical or prescription insurance. The pharmacist is the appropriate health care provider to provide thorough education about these products and their role in the treatment of allergic rhinitis. In selecting over-the-counter or prescription treatments, a variety of factors may influence the decision, including type and duration of symptoms, previous therapy success, patient comorbidities, side effects, cost, and patient preference.
Oral Antihistamines. Oral antihistamines are a common pharmacotherapy choice for treatment of allergic rhinitis. These medications work by competitively blocking histamine at the H1 receptor site, thereby reducing many of the classic, histamine-mediated symptoms of allergic rhinitis, including itching, sneezing, rhinorrhea, and allergic conjunctivitis. They are less useful in relieving nasal congestion, however. Many oral antihistamines are available, both with and without a prescription, and they are classified by their selectivity for the H1 receptor as well as their ability to cross the blood-brain barrier.
First-generation antihistamines, such as chlorpheniramine and diphenhydramine, are available without a prescription but cause significant sedation and anticholinergic effects, because they cross the blood-brain barrier easily. It is important to advise patients that these medications can have a considerable effect on coordination, work performance, ability to drive, and information processing.
Second-generation antihistamines are less likely to cause sedation because they do not cross the blood-brain barrier as easily, but they may still be associated with sedation. An expert consensus statement reported that allergic rhinitis should be treated with the newer, second-generation antihistamines because of these significantly impairing side effects.12,13
Patients should be counseled that the sedating antihistamines may augment the sedating effects of other medications and alcohol. First-generation antihistamines are contraindicated in patients with hypersensitivity to any of the medication ingredients, narrowangle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction, and monoamine oxidase inhibitor use.
ARIA guidelines recommend oral antihistamines for mild intermittent, mild persistent, and moderate-to-severe intermittent allergic rhinitis. They are not recommended, however, as first-line treatment in moderate-to-severe persistent cases, where intranasal corticosteroids are considered more useful.10
Decongestants. Both topical (intranasal) and oral decongestants are effective in providing short-term symptom control in that they decrease rhinorrhea and congestion associated with allergic rhinitis. Nasal decongestants cause smooth muscle vasoconstriction via activation of alpha-adrenergic receptors in the nasal mucosa. They can be used alone for symptom relief or in conjunction with antihistamine therapy.14 Although oral systemic decongestants are effective, they are associated with significant side effects, including insomnia, nervousness, tachycardia, elevation of blood pressure and/or blood glucose, and urinary retention. Pseudoephedrine is the most widely used oral decongestant. Topical decongestants act more locally but should only be used for a 3-day period, because prolonged use results in rhinitis medicamentosa, or rebound congestion.
Intranasal Corticosteroids. Intranasal corticosteroids are widely regarded as the most effective treatment for allergic rhinitis. They alleviate all the major symptoms, including sneezing, rhinorrhea, itching, and nasal congestion. Intranasal corticosteroids are recommended for all stages of allergic rhinitis in the ARIA guidelines.10
In a meta-analysis of 16 randomized controlled trials involving more than 2000 patients, researchers evaluated efficacy of intranasal corticosteroids as compared with oral antihistamines in relieving total nasal symptoms, including sneezing, rhinorrhea, itching, and postnasal drip. They found that intranasal corticosteroids produced significantly greater relief of total nasal symptoms than oral antihistamines. The meta-analysis revealed no significant difference between the 2 classes of medications on relief of eye symptoms.15 In an evidence-based evaluation of 13 randomized blinded studies, researchers found that total allergic rhinitis-associated nasal symptoms and nasal obstruction were better relieved with intranasal corticosteroids than with nonsedating antihistamines.16
Intranasal corticosteroids have also been found to be more effective than topical antihistamines in the treatment of allergic rhinitis. Researchers performed a meta-analysis of randomized controlled trials and concluded that intranasal steroids more effectively reduced nasal symptoms (sneezing, rhinorrhea, itching, and nasal blockage) than topical antihistamines.17
A variety of intranasal corticosteroids are on the market and all have been shown to be safe and effective in the treatment of allergic rhinitis. Therefore, patient factors, such as taste and smell, cost, frequency of dosing, and/or previous therapeutic success, should be considered when selecting an intranasal corticosteroid product. Aqueous products are particularly useful in patients who have nasal dryness and significant nasal congestion, whereas nonaqueous preparations work well in patients who have significant rhinorrhea.
Patients should be advised to use these medications prior to allergen exposure on a scheduled basis. Also, the onset of action of intranasal corticosteroids is approximately 12 hours, and maximal benefit may not be seen for 3 to 14 days. Because these medications act locally and have very low systemic absorption, side effects are generally minimal and may include nasal irritation, burning, or dryness. Premedication with saline nasal sprays should be recommended to alleviate these side effects. Researchers showed that mometasone and fluticasone have lower systemic bioavailability, which may reduce the risk of systemic side effects.18 Finally, it is important to counsel patients on the appropriate use/administration of these products (Table 3).
Intranasal Antihistamines. Intranasal antihistamines are effective in controlling sneezing, rhinorrhea, and nasal itching associated with allergic rhinitis and have been shown to be more effective than oral antihistamines and less effective than intranasal corticosteroids in the treatment of congestion.19 ARIA guidelines recommend intranasal antihistamines as an appropriate first-line treatment for mild intermittent, mild persistent, and moderate-to-severe intermittent allergic rhinitis and as an adjunct to intranasal corticosteroids for moderate-to-severe persistent cases.10 Sedation or drowsiness and bitter taste are the most commonly reported side effects.20
Leukotriene Modifiers. Leukotrienes contribute to airway inflammation via bronchial smooth muscle constriction. Additionally, leukotrienes increase nasal blood flow and airway resistance much more drastically than histamine. Although placebo-controlled studies have proven efficacy of leukotriene modifiers, there is little conclusive evidence that they are more effective than oral antihistamines. Additionally, small studies suggest that combination therapy with a leukotriene modifier and an oral antihistamine is no more effective than with the antihistamine alone. In a review of literature to determine the role of leukotriene modifiers in the treatment of allergic rhinitis, researchers concluded that the data do not support widespread use of leukotriene modifiers instead of an intranasal corticosteroid alone or in combination with an antihistamine.21
Mast-Cell Stabilizers. After exposure to a specific antigen, mast-cell degranulation occurs, resulting in the release of multiple inflammatory mediators. Cromolyn, a mast-cell stabilizer, prevents the inflammatory process by inhibiting entry of calcium ions. There are no direct anti-inflammatory or antihistaminic effects.
Cromolyn should be administered intranasally up to 7 days prior to exposure to a known allergen, and maximal benefit is generally seen after 2 to 4 weeks'continuous use. Cromolyn has an excellent safety profile, including safety in pregnancy, and it is available without a prescription. It needs to be taken 4 times daily, however, and patients may have difficulty adhering to this frequent dosing regimen.20
Stepwise Approach to Treatment
The Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology guidelines endorses antihistamines as first-line pharmacotherapy for patients with mild-to-moderate allergic rhinitis and intranasal corticosteroids as first-line treatment for patients with more severe forms of the disease.22 The conclusions of a metaanalysis, however, provided a compelling argument for intranasal corticosteroids to be used first in all classifications of allergic rhinitis.23 If sufficient response is not realized with one or the other, a combination of oral antihistamine and intranasal corticosteroid should be tried next, then other agents added 1 by 1 until the desired response is achieved. If no combination of medications produces adequate response, allergen-specific immunotherapy should then be considered. Immunotherapy is a medical procedure that uses controlled exposure to known allergens to reduce the severity of allergic disease. As increasing quantities of allergen are injected subcutaneously into the patient, there is a corresponding gradual increase in the allergen-specific IgG antibodies and a gradual decrease in allergen-specific IgE antibodies.
Patients who are eligible for immunotherapy are those who have moderate-to-severe allergy symptoms occurring throughout most of the year, have identified allergens via skin test or RAST, have failed pharmacotherapy, cannot avoid allergens, and/or children who do not have chronic irreversible upper airway changes. Immunotherapy usually consists of weekly subcutaneous allergen solution injections in increasing doses until maintenance dose is obtained. The maintenance dose is continued about once every 2 to 4 weeks for 4 or more years.
Durham et al showed that allergen-specific immunotherapy alters the course of allergic rhinitis disease, resulting in long-term efficacy and possibly halting disease progression and preventing the development of comorbid conditions.24 Immunotherapy works to lessen symptoms of allergic rhinitis by reducing the number of mast cells and inflammatory mediators. In the Durham study, 1 group received 3 years of immunotherapy, then 3 years of placebo treatment; another group received 6 years of immunotherapy; and a third group was not treated with immunotherapy. After the 6-year period, a 75% reduction in disease severity was noted in both immunotherapy groups, as compared with the nonimmunotherapy group.24
An important consideration when initiating immunotherapy is the significant time commitment on the part of the patient.
The most serious potential side effect of immunotherapy is anaphylaxis to the injection, so patients should be monitored for 20 to 30 minutes after each injection. Anaphylactic reactions may include sneezing, rhinorrhea, itchy eyes, swelling of the airway, cough, wheezing, shortness of breath, chest tightness, and/or dizziness. These reactions must be treated immediately. Local reactions may include redness and swelling, for which ice packs may be helpful.
The Preventive Allergy Treatment Study, a randomized placebo-controlled trial, evaluated whether use of immunotherapy to treat allergic rhinitis would delay onset of asthma. Researchers studied more than 200 children in Europe and found that, after 3 years, the children who received immunotherapy for allergic rhinitis had significantly fewer asthma symptoms than the placebo-treated group.25
Allergic rhinitis is an extremely common condition that extracts a significant price, both in terms of dollars spent and quality of life. Complications include sinusitis, otitis, and asthma. A careful history, physical examination, and skin testing will not only make the diagnosis but also pinpoint the offending allergens. This can allow the first therapeutic approach, environmental control, to be more effective. The second approach-pharmacologic-includes oral nonsedating antihistamines, decongestants, and topical agents such as corticosteroids and antihistamines. In patients not responding to these measures, immunotherapy (allergy shots) can be used. Patients no longer have to "live with" their allergies. Making an accurate diagnosis and instituting appropriate therapy should result in significant improvement in the vast majority of allergic rhinitis patients.
Lori C. Brown, PharmD: Clinical Assistant Professor, University of North Carolina at Chapel Hill; Clinical Coordinator, Kerr Health Care Center. Raymond G. Slavin, MD, MS: Professor of Internal Medicine and Microbiology, Saint Louis University School of Medicine.
For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: email@example.com.
MWC Office of Continuing Professional Education is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This program is approved for 2 contact hours (0.2 CEU) under the ACPE universal program number of 290-999-05-009-H01. The program is available for CE credit through June 30, 2008.
CE ANSWER FORM INSTRUCTIONS
TESTING AND GRADING PROCEDURES
NEW SCORING OPTIONS
Please print clearlycertificate will be issued from information given.
Please mail completed forms to: Pharmacy Times CE Department, 405 Glenn Drive, Suite 4, Sterling, VA 20164-4432
CE REVIEW QUESTIONS
(Based on the article starting on page 84) Choose the 1 most correct answer.
1. Allergic rhinitis affects what percentage of American children?
2. Which of the following comorbidities is (are) associated with allergic rhinitis?
3. The "early phase" of the nasal allergic response occurs when:
4. Which of the following is not a typical component of the clinical presentation of allergic rhinitis?
5. RJ is an 8-year-old boy who presents to the physician with sneezing episodes, red and teary eyes, and a crease across the bridge of his nose. In order to establish a diagnosis of rhinitis, which is the most cost-effective method of allergen testing?
6. The pharmacist should advise RJ that which of the following medications can interfere with his allergy test and should therefore be discontinued for 48 hours before the testing procedure?
7. ARIA [Allergic Rhinitis and Its Impact on Asthma] guidelines suggest coevaluation for which comorbid condition in all patients who present with allergic rhinitis?
8. After allergen testing and symptom evaluation, it is determined that RJ has severe persistent allergic rhinitis secondary to dust-mite exposure. Which of the following treatments is not recommended as first-line therapy?
9. Weiner et al showed in their metaanalysis that:
10. When selecting an intranasal corticosteroid product, which of the following should be considered?
11. Intranasal antihistamines have been shown to be _______________ in the treatment of nasal congestion.
12. Leukotrienes contribute to the allergic response by all the following methods except:
13. Which of the following is not true of the mast-cell stabilizer cromolyn?
14. Which of the following is not true about immunotherapy?
15. Which of the following intranasal corticosteroids has a recommended dose of 1 to 4 sprays in each nostril once daily?
16. Patients who are eligible for immunotherapy include all of the following groups except:
17. Intranasal corticosteroid side effects generally include which of the following?
18. Rhinitis medicamentosa is the scientific term for a side effect associated with the use of which of the following types of medication?
19. Casale et al showed that second-generation antihistamines have:
20. Hay fever is another term for allergic rhinitis associated with: