At the American College of Allergy, Asthma, and Immunology's 2000 Annual Meeting, a panel of three leaders in adult and pediatric allergy and immunology presented the most recent advances in the management of allergic rhinitis and allergic conjunctivitis. Topics discussed included the impact of allergic rhinitis and conjunctivitis on quality of life, optimal treatment approaches, and patient education strategies.
This program was supported by an unrestricted educational grant from Dura Pharmaceuticals.
Optimizing Allergy Treatment Choices
Emerging new therapies for the treatment of allergic rhinitis and allergic conjunctivitis are offering great promise of relief for the more than 40 million Americans who are afflicted with these diseases. "When assessing the treatment options for allergic rhinitis and conjunctivitis, a primary goal is to establish that the patient can tolerate and accept the treatment regimen," said Bruce M. Prenner, MD, Associate Professor, Division of Immunology and Allergy, Department of Pediatrics, University of California, La Jolla. According to Dr. Prenner, patient acceptance is key in overcoming non-compliance and effectively treating allergic diseases and their symptoms.
About Allergic Rhinitis and Conjunctivitis
Allergic rhinitis is characterized by an itchy, runny, or stuffy nose; sneezing; and itchy or watery eyes. This disease affects all age groups, but is most common in persons 18 to 44 years of age. Often referred to as hay fever, allergic rhinitis can occur on a seasonal or perennial basis. Seasonal allergic rhinitis tends to be triggered by an allergy to pollen, while year-round disease is often the result of an allergy to dust, mites, mold, and animal dander.
The signs and symptoms of allergic conjunctivitis, which often occurs with allergic rhinitis, include seasonal or perennial hyperemia, itching, and tearing of the eyes, sometimes with edema and mucous discharge. Most cases of allergic conjunctivitis occur in young adults; however, one third of affected patients are younger than 12 years old. The pathogenesis of allergic conjunctivitis is similar to that of allergic rhinitis, involving the cross-linking of immunoglobulin (Ig) E with antigen and mast cell degranulation. This process is mediated by a number of entities, including histamine, PGD-2, mast cells, interleukin (IL)-4, and ICAM-1.
Each of these diseases affects 16% to 25% of the American population, and together result in more than $5.9 billion in direct medical cost and more than 10 million days of school and work lost each year.
Treatment Options for Allergic Rhinitis
In addition to avoidance of allergens, the appropriate pharmacologic therapy is often essential in managing allergic rhinitis. According to Dr. Prenner, the goals of treating persons with this disease are to minimize or eliminate symptoms; reduce inflammation and alter the course of underlying disease; ensure the safety and tolerability of the therapy; and ensure appropriate dosing and patient compliance with the therapy. Treatment options, used alone or in combination, include oral and topical antihistamines and decongestants; topical nasal corticosteroids; and topical cromolyn sodium (Table 1).
Cromolyn sodium. This agent, a mast cell stabilizer delivered as a nasal spray, is effective in preventing the release of histamine and other chemicals from the mast cell, thereby blocking both early- and late-phase allergic reaction. A disadvantage with cromolyn sodium is that it requires four or more administrations per day and sometimes an induction period of up to 2 weeks before an effect is observed.
Nasal decongestants. Topical nasal decongestants are used to reduce the swelling of nasal tissue and relieve nasal congestion. However, repetitive use can be associated with rebound nasal congestion and irritation. Oral decongestants, such as pseudo-ephedrine, can be used for the same purpose, often in combination with antihistamines. Oral decongestants can be associated with insomnia and nervousness, and may be contraindicated in certain patient populations.
Antihistamines. Antihistamines have long been used in the treatment of allergic rhinitis. These agents act to counter the effects of histamine, as it is released from mast cells. However, these drugs also have significant anticholinergic effects and can cause sedation. Several studies have found an association between oral first-generation antihistamine use and work-related and other injuries. Many second-generation antihistamines appear to have minimal effects on the central nervous system, with a greatly reduced potential for sedation. The bioavailability of these agents can sometimes be affected by food, antacids, and other factors.
Nasal corticosteroids. Topical nasal coriticosteroids are used to relieve most of the symptoms of allergic rhinitis, including pruritus of the face and palate and ocular pruritus, tearing, and redness. These agents inhibit inflammation by affecting early- and late-phase allergic reaction, and decreasing vascular permeability, secretions, exudate, and edema. Indeed, biopsy results 1 year or more after treatment with one of these agents show improvement in the nasal anatomy and a decrease in mast cells and eosinophils. "Data show that topical nasal corticosteroids not only relieve symptoms, but also influence nuclear genetic coding, addressing the underlying disease process," said Dr. Prenner. The topical application of nasal corticosteroids allows the minimization of side effects that might be observed with oral corticosteroids. Adverse effects may include epistaxis (5% to 8%) and atrophy (uncommon). Beclomethasone dipropionate use in children 6 to 12 years is associated with interference in growth velocity. "Most nasal corticosteroids are safe and extremely effective when administered properly," Dr. Prenner explained.
Treatment Options for Allergic Conjunctivitis
Allergic conjuctivitis often occurs concomitantly with allergic rhinitis. While nasal corticosteroids, such as flunisolide nasal solution, can minimize the symptoms of allergic conjunctivitis, additional therapy is needed in some cases. Treatment options include artificial tears, vasoconstrictors, antihistamines, nonsteroidal anti-inflammatory drugs, corticosteroids, mast cell stabilizers, and combination products (Table 1). The therapy to emerge most recently is a new type of mast cell stabilizer, a pyranoquinolone called nedocromil sodium.
Nedocromil is a fast-acting agent that relieves allergic conjuctivitis-associated pruritus, with a twice-daily dosing regimen. "Nedocromil provides the benefit of convenience over the traditional mast cells stab- ilizers, which require four or administrations per day," Dr. Prenner explained. One recent study of nedocromil versus levocabastine and placebo demonstrated the drug's efficacy against inflammation and symptoms of allergic conjuctivitis. Results showed a significant reduction in ocular pruritus, hyperemia, and tearing with both nedocromil and levocabastine. However, laboratory results showed a decrease only in ICAM-1 with levocabastine and a decrease in histamine, PGD-2, mast cells, and IL-4 with nedocromil.
In conclusion, Dr. Prenner noted that a combination of drugs and therapies, such as a nasal corticosteroid and a mast cell stabilizer ocular preparation, is often most efficacious in treating the signs and symptoms of concomitant allergic rhinitis and allergic conjunctivitis. A combination of currently available agents, as well as newly emerging leukotriene antagonists, second-generation antihistamine metabolites, and monoclonal antibodies, holds promise for greater relief of these common allergic diseases.
Table 1. Select Types of Treatment Options for Allergic Rhinitis and Conjunctivitis
Allergic Rhinitis
o Antihistamines (oral and topical)
o Nasal corticosteroids
o Combination antihistamine/ decongestants
o Nasal decongestants
o Mast cell stabilizers
Allergic Conjunctivitis
o Mast cell stabilizers
o Topical vasoconstrictors
o Antihistamines
o NSAIDs
o Corticosteroids
o Artificial tears
Optimal Allergy Management: Outcomes That Make Sense
Allergic rhinitis is associated with detrimental effects on the health-related quality of life of persons who suffer from this prevalent and chronic disease. Understanding the quality of life data available allows clinicians to offer patients the most effective treatment options and thereby improve the standard of care, said Warren W. Pleskow, MD, FACP, Assistant Clinical Professor of Pediatrics, University of California at San Diego School of Medicine, and Medical Director of Radiant Research, San Diego.
Allergic Rhinitis and Quality of Life
Allergic rhinitis has an impact not only on healthcare costs, but also on the functional ability of the persons who suffer with this disease. Indeed, allergic rhinitis can cause irritability, fatigue, restlessness, limitation of day to day activities, and changes in concentration, taste and smell perception, and interpersonal relationships. One study of children with allergic rhinitis showed that associated behavior problems resolve with treatment of the allergy. Another study showed impaired memory during the allergy season in persons with allergic rhinitis. "These studies indicate that allergic rhinitis has a profound impact on the patients' health-related quality of life, and this impact can be altered by treatment of the allergy," Dr. Pleskow explained.
Using a general quality of life survey, the SF-36, researchers have been able to measure the impact of allergic rhinitis and its treatment from the patient's perspective. Measuring parameters of physical, psychological, and social functioning, several studies have shown a significantly reduced quality of life in persons with allergic rhinitis. Indeed, one study demonstrated that perennial allergic rhinitis inflicts more quality of life impairment than asthma.
A new survey, the Rhino-Conjunctivitis Quality of Life questionnaire, developed by Juniper, specifically addresses allergic rhinitis. Measuring 28 different items (eg, sleep deprivation, emotional dysfunction, eye symptoms, typical nasal symptoms, day to day activity limitations), Juniper again found a significantly reduced quality of life in persons with allergic rhinitis versus controls.
Treatment Options and Quality of Life
When treating persons with allergic rhinitis, it is imperative to consider the patient perspective, according to Dr. Pleskow. Therapies should be assessed for three factors: efficacy, side effect profile, and impact on quality of life. Nasal corticosteroids and antihistamines are two of the most common pharmacologic treatments used against allergic rhinitis.
Nasal corticosteroids. Placebo-controlled studies have shown that topical nasal corticosteroids, such as flunisolide nasal solution, are effective in reducing almost all of the symptoms of allergic rhinitis as well as preventing seasonal symptoms from occurring. "The data show that nasal corticosteroids are extremely effective in treating allergic rhinitis, and indeed offer the greatest improvements in quality of life," said Dr. Pleskow. In terms of choosing a specific nasal corticosteroid, patient preferences are important. A recent survey showed that patients prefer a solution that is fragrance-free, does not require shaking, and does not require chlorofluorocarbons. Interestingly, said Dr. Pleskow, only flunisolide nasal solution, which is administered twice daily, is truly aqueous and does not require shaking.
Antihistamines. Antihistamines are also effective in treating allergic rhinitis. However, side effects may include nervousness, restlessness, headache, nausea, urinary problems, and most importantly sedation and performance impairment. Data show that impairments with antihistamines can occur in hand/eye reaction time, driving, office skills, and learning ability. Dr. Pleskow pointed out that sedation may occur on an EEG reading, without subjective clinical symptoms of sedation. Importantly, performance impairment and drowsiness can also occur independently of each other, and both can occur without patient awareness. The second-generation antihistamines do not penetrate the blood- brain barrier, and therefore cause less sedation. Some symptoms, such as allergic rhinitis-associated learning impairment in children, are improved with a second-generation antihistamine over no treatment, but a deficit may still exist in comparison with non-allergic children.
Several studies comparing nasal corticosteroids with non-sedating antihistamines show that "topical nasal corticosteroids are superior in relieving the nasal symptoms of allergic rhinitis," said Dr. Pleskow. In fact, five studies and a meta-analysis indicate that topical nasal corticosteroids provide significantly more relief from the total nasal symptom complex than do antihistamines. Dr. Pleskow also noted that 52% of those taking a nasal corticosteroid do not require further treatment, while 87% of those taking a non-sedating antihistamine eventually require a nasal corticosteroid. In terms of overall quality of life improvement, studies by Blackwell and by Candemi again show that topical nasal corticosteroids offer a significant advantage over non-sedating antihistamines.
Conclusion
In closing, Dr. Pleskow noted that measuring the health-related quality of life is important in ensuring the highest standard of care for patients being treated for allergic rhinitis. "Currently, topical nasal corticosteroids are our most effective therapy in improving health-related quality of life in persons with allergic rhinitis," he said.
Taking Control: Making the Most of Patient Education
The most proactive component in helping patients manage and control their allergies is patient education, said Edwin A. Bronsky, MD, Clinical Professor of Family and Preventive Medicine, University of Utah, Salt Lake City. "Establishment of a good patient-physician relationship is essential in educating patients about avoiding allergens and employing environmental controls to prevent the occurrence of or reduce the severity of allergies," said Dr. Bronsky. He pointed out that patient education is not an event, but an ongoing process, requiring time and followup.
The first steps in educating patients about their disease are making an accurate diagnosis, clearly defining the suspected allergens, and explaining the treatment components, including avoidance therapy, pharmacotherapy, and immunotherapy.
Immunotherapy and Pharmacotherapy
When pharmacotherapy or immunotherapy is needed to manage allergic rhinitis or allergic conjunctivitis, explaining the advantages and disadvantages ahead of time will help avoid common pitfalls and hopefully improve patient compliance. According to Dr. Bronsky, the use of immunotherapy may be helpful earlier, rather than later, in the treatment process.
Patients should also be warned in advance of the potential side effects and multiple daily dosing required with many over-the-counter and prescription medications. In terms of antihistamines, patients should understand the difference between the sedating and non-sedating preparations. They should be informed of the potential insomnia and rebound disease that occur with repeated use of nasal decongestants. In terms of topical nasal corticosteroids, clinicians need to take the time to show patients how to deliver the drug effectively. With proper administration, nasal corticosteroids can provide excellent relief from the overall symptoms of allergic rhinitis. However, patients with concomitant allergic rhinitis and conjunctivitis should be informed that a combination of a topical nasal corticosteroid and another agent, such as a mast cell stabilizer ocular drop, is sometimes needed to provide optimal relief. In addition, clinicians should explain to patients with seasonal allergic rhinitis or conjunctivitis the benefits of pretreatment, of pre-empting the allergic reaction before it strikes.
Avoidance Therapy
Care, enthusiasm, and followup on the physician's part can help motivate the patient to avoid allergens, and thus avoid or reduce the severity of allergic rhinitis and conjunctivitis symptoms (see Table 1). In providing recommendations for environmental control efforts, Dr. Bronsky emphasized that these measures must be reasonable and economically feasible for the patient. For example, in avoiding allergic symptoms due to pollen, pretreatment should be initiated a week before the allergy season begins. In addition, patients should be encouraged to invest in air conditioning and try to minimize outdoor activity during peak pollen hours (4:00-8:00am and again at dusk). However, patients are not likely to comply with a recommendation to avoid outdoor activities entirely during the high-pollen season.
Ensuring patient compliance is essential in allergy management. To maximize patient compliance, Dr. Bronsky recommended: 1) keeping explanations simple; 2) avoiding problematic medications, such as first- generation antihistamines; 3) reviewing the dosing and delivery techniques of medications; 4) providing written instructions; 5) encouraging patients to be proactive in their treatment and pretreatment; and 6) linking treatment strategies with patient lifestyle and following up on progress.
In closing, Dr. Bronsky emphasized that successful avoidance of allergens is an effective strategy in preventing or reducing allergic responses and in minimizing the need for medications. "In establishing a strong patient-physician relationship and providing the needed education, clinicians can help patients proactively and successfully manage their allergic disease," he concluded.
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