Treating Allergic Rhinitis: Current Challenges and Future ...



Treating Allergic Rhinitis: Current Challenges and Future Approaches

Author: David P. Skoner, MD

MEDSCAPE

Release Date: May 19, 2006; Valid for credit through May 19, 2007

Epidemiology

The prevalence of allergic rhinitis (AR) has risen over the last 10 years.[1] AR ranks among the top 5 chronic medical conditions, affecting 10%-30% of adults and up to 42% of children.[2-5] AR is most common in children, with a mean age of onset of about 10 years and a peak incidence between the ages of 13 and 19 years.[6,7] Consequently, approximately one third of those who suffer from AR are 17 years of age or younger.[8,9] The toll of AR on individuals and society is very large, including consequences such as missed school and workdays, reduced school performance, impaired sleep, and a reduced quality of life.[10] Quality-of-life impairments in adults include fatigue, decreased energy, and disturbances in general health perception and social function. In children, the impact of AR encompasses learning impairment, inability to integrate with peers, anxiety, and family dysfunction.[11] Direct expenditures for AR include office visits and medications that exceeded $4.5 billion in 1997. Indirect costs are also high, as evidenced by an estimated $13 million in lost productivity of parents who miss work to care for children with AR.[8]

Etiology and Pathophysiology

AR is caused by an IgE-mediated inflammation of the nasal membranes. Symptoms include a typically clear rhinorrhea, sneezing, congestion, and itching of nasal and non-nasal tissues. Comorbid conditions include asthma, allergic conjunctivitis, otitis media, and sinusitis. Allergic individuals are genetically predisposed to produce specific IgE antibodies in response to normally innocuous environmental exposures. Such exposures include the protein antigens in seasonal allergens, such as outdoor pollens, and perennial allergens, such as dust mites and animal dander, that are present throughout the year and are usually found indoors. The IgE antibodies bind to high-affinity receptors (FCepsilonRIs) on mast cells and basophils and to lower-affinity receptors on monocytes, eosinophils, and platelets. When allergen binds to the IgE on mast cells and cross-links FCepsilonRIs, the cells degranulate and release preformed mediators such as histamine to initiate the early-phase allergic response within minutes of exposure.[12,13] Newly synthesized mediators, such as the cysteinyl leukotrienes, are also involved. Such mediators cause vasodilation, increased vascular permeability, and mucus hypersecretion. These processes generate the typical spectrum of AR symptoms, including sneezing, itching, congestion, and rhinorrhea. Following the early-phase allergic response, many individuals experience a second response 4-12 hours later termed the late-phase response. Under the influence of chemokines and cytokines, inflammatory cells, such as eosinophils and basophils, are recruited into the nasal tissue to generate the late-phase response. A predominant symptom in this phase is nasal congestion. Prominent cytokines involved in AR include interleukin-4 (IL-4), IL-5, and IL-13.

Nasal function is disturbed as a consequence of allergic inflammation. Under normal conditions, the nose warms, humidifies, and filters incoming air. As such, the air delivered to the lungs of individuals with AR may be relatively cool, dry and dirty. For this reason, nasal treatment in individuals with AR and concomitant asthma may result in improvement in the asthma.[14] Other nasal functions impaired by AR inflammation include olfaction and the ability to function as a resonating chamber for voice.

Allergic inflammation can cause obstruction of the sinus ostia and the Eustachian tube,[15,16] predisposing to comorbid conditions such as sinusitis and otitis media. Indeed, AR was present in 50% of children with chronic otitis media with effusion.[17] AR is nearly ubiquitous in patients with asthma, affecting approximately 80% of these children. Moreover, asthma is present in AR sufferers more often than expected, highlighting the unified nature of the airways and involvement of systemic immune/inflammatory pathways. Indeed, AR and asthma are now viewed as clinical manifestations of a disease continuum within a common airway.[18]

Diagnosis

The diagnosis of AR presents a challenge to clinicians who often attribute nasal symptoms to a common cold rather than to allergy (see Table). This is especially true for children who are unable to verbalize symptoms. Approximately 50% of all rhinitis symptoms are related to allergy, with the remainder due to nonallergic conditions such as polyps, adenoidal hypertrophy, nasal septal deviation, nasal foreign body, benign and malignant tumors, cerebrospinal fluid leak, hormonal rhinitis, atrophic rhinitis, and systemic immunologic and nonimmunologic diseases that can affect the nose.[19] The latter category includes granulomas associated with Wegener's granulomatosis, sarcoid, Churg-Strauss syndrome with eosinophilic granuloma, and infection (tuberculosis, leprosy, syphilis, sporotricosis, blastomycosis, histoplasmosis, and coccidiomycosis). Gastroesophageal reflux can manifest as rhinitis, especially in small children.[20] Rhinitis due to food ingestion has been well described.[21] Cold, dry air can induce a rhinorrhea, leading to the term "skier's rhinitis."[22] A recently described form of chronic nonallergic rhinitis is related to chronic fatigue syndrome.[23] In addition to fatigue, these subjects complain of pain affecting many organs and problems with cognition and short-term memory. Nasal fullness and congestion, often without nasal pathologic changes, is present in about 70% of these subjects, and can occur in addition to AR.

Table. Distinguishing Allergic Rhinitis From the Common Cold

|  |Allergic Rhinitis |Common Cold |

|Symptoms |Rhinorrhea or nasal congestion, sneezing, watery and itchy eyes |Same as allergic rhinitis, can also include fever, |

| | |aches, and pains |

|Warning time |Symptoms begin almost immediately after exposure |Symptoms most severe after a few days |

|Duration |Symptoms last as long as exposure continues and until the |Symptoms resolve within several days to a week |

| |reaction triggered by the allergen ends | |

|Seasonality |Yes, if mediated by outdoor allergens |Yes, spring (rhinovirus), winter (influenza, RSV), and |

| | |fall (rhinovirus) viral seasons |

Patient History

An accurate diagnosis is dependent on a careful history and physical examination, complemented by selected laboratory tests.[24,25] The history frequently reveals affected family members, as well as symptoms (sneezing, itching, rhinorrhea, congestion) of a defined duration (year-round or seasonal), frequency (daily or less), and severity (mild to severe), which should be documented. Other symptoms can involve the eyes, ears, and throat, and include postnasal drainage. Individuals can have perennial symptoms (suggestive of perennial allergen sensitivity) with or without seasonal exacerbations, or strictly seasonal symptoms (suggestive of pollen allergy). Not all individuals manifest all symptoms. Nasal congestion is prominent in children with AR and might be the only complaint.[26] Consequent mouth breathing, a nasal voice, or snoring might be noted by the parent even if congestion is not specifically reported. Nasal congestion is seen more commonly in perennial AR than in seasonal AR, but the reverse is true for eye itching.[27]

Physical Exam

Physical examination[28] can identify the classic signs of the allergic salute (upward rubbing of the nose with the palm of the hand), allergic shiners (darkening of the lower eyelid due to chronic nasal obstruction), and the allergic crease (a line in the skin above the tip and below the bridge of the nose caused by constant rubbing). With chronic nasal obstruction, many AR children will make use of the oral airway and manifest a gaping mouth appearance. A careful nasal examination should rule out nonallergic conditions such as septal deviation, nasal polyps, and foreign bodies. The nasal turbinates in AR typically appear pale and boggy, and secretions are clear. If there is uncertainty about whether a nasal mass represents a polyp or swollen turbinate, a topical decongestant can be used to aid in the diagnosis. There, the decongestant will shrink the turbinate, but not the polyp. The above signs are not uniformly present in all AR sufferers.

Allergen-Specific IgE Antibody, Skin and Blood Testing

When the history and physical examination support an allergic etiology for the symptoms, the presence of allergen-specific IgE antibody should be confirmed using skin testing or sensitive in vitro blood testing. Skin testing is the preferred method, but in vitro testing is an acceptable alternative if skin testing is unavailable. The spectrum of allergens tested (generally, only perennial allergens in infants and toddlers, and perennial and seasonal allergens in older individuals as dictated by history) can be modified by age of the individual. These results, combined with historical details, will permit the clinician to diagnose seasonal AR, perennial AR, or combined seasonal/perennial AR, and provide advice on appropriate environmental control measures. Total serum IgE levels are generally not useful in making the diagnosis of AR. In selected instances, cytologic tests of nasal secretions to detect the presence of eosinophils (allergic rhinitis) or neutrophils (infection) can be useful. Due to the high degree to which asthma and AR coexist in the same individual, recent guidelines recommend that AR subjects be examined for asthma and that asthma patients be examined for AR.[29]

Treatment/Management Issues

There are 4 basic approaches to the management of AR: (1) environmental controls; (2) education; (3) pharmacotherapy; and (4) allergen immunotherapy.

Environmental Controls

Environmental controls are first-line therapies and need to be tailored to the individual patient's exposures and sensitivities. Examples of environmental allergen control measures for the home include: encasing bedding in airtight covers; washing bedding at a temperature above 130 degrees F; getting rid of furred pets or at least keeping them out of the bedroom; reducing humidity in the house; killing all visible mold; killing cockroaches; using HEPA air filters in the bedroom and keeping the doors and windows closed; and using air conditioning. Environmental controls might also need to target nonallergen, irritant triggers in individual patients, including tobacco smoke, temperature, or weather changes. Unfortunately, environmental controls are not always practical or effective, and supplemental medical management is usually required.

Education

At all office visits, education about environmental triggering factors and the appropriate use of medications should be provided. Education and training have been previously demonstrated to promote adherence and follow-up in an open, randomized, parallel-group stud.[30] Both the patient and family members should be educated about the chronic, inflammatory nature of the disease, symptoms, impact on quality of life, avoidance of allergic and irritant triggers, realistic expectations of the benefits of therapy, possible side effects of therapy (including drugs and immunotherapy), and the complications of allergic rhinitis such as otitis media and sinusitis. Indeed, regular follow-up may promote the early detection and management of these complications. Compliance is enhanced when: (1) a low number of daily medication doses is required; (2) the patient schedules doses based on an appropriate reminder mechanism, such as mealtimes or other daily rituals; (3) the patient has a high level of clinician trust; (4) the patient has written instructions; (5) rhinitis medications are taken with the same dosing frequency as any other medications the patient may be using; and (6) the patient has a well-designed reminder chart for the times of dosing intervals.[31-35]

Pharmacotherapy

The approach to the medical management of AR should be individualized, taking into consideration factors such as the age, frequency, severity, and spectrum of presenting symptoms, the degree of impairment of quality of life, the specific allergens to which the individual is sensitized, the response to previous medications, the presence of comorbid conditions, and cost. These factors vary among individuals with AR. The patient history provides a great deal of information about the type and duration of medication(s). Patient history also provides information about whether the condition is seasonal or perennial, the frequency (daily or less frequent), severity (mild to severe) and spectrum (1 symptom or many symptoms) of presenting symptoms, response to and compliance with previous medications, indoor and/or outdoor allergen exposures, and the presence of symptoms of comorbid conditions such as allergic conjunctivitis and asthma. Symptoms confined to a defined season allow the institution of a prophylactic regimen (eg, intranasal corticosteroid) prior to the onset of the same season in the following year.[2] By contrast, perennial symptoms typically require daily and, frequently, year-round therapy. In that case, medication safety and ease of use are important factors. Furthermore, a different approach is required for individuals who have perennial symptoms with seasonal exacerbations. The presence of a comorbid condition makes the use of an intranasal corticosteroid an attractive first-line treatment option, and might signal the need for additional medication targeted to a nonallergic condition (eg, antibiotic for concurrent sinusitis).

Tailoring Medication to Patient Needs

When using medications for AR, step-up (if needed in milder patients) and step-down therapy (after control has been achieved, or maximized in more severe patients) approaches can be employed.[36-38] Some patients have only 1 symptom, and some medications only benefit 1 symptom. Thus, monosymptomatic patients can be specifically targeted initially with a tailored therapy highly likely to be effective (such as a decongestant for congestion, an antihistamine or leukotriene receptor antagonist for sneezing and/or itching, and an anticholinergic for rhinorrhea). In that regard, second-generation antihistamines or leukotriene receptor antagonists are excellent choices for initial therapy in patients with mild RA with those symptoms. For moderate to severe symptoms or symptoms that include congestion, an intranasal corticosteroid is the best choice for initial therapy. Intranasal corticosteroids have been shown to benefit all 4 major nasal symptoms of AR. If the first-line medication is unsuccessful in providing relief, a second and third medication should be added (eg, add an antihistamine or leukotriene receptor antagonist or both to intranasal corticosteroid). An appropriate, simple, stepwise approach involves the initial administration of an oral second-generation antihistamine, with the addition or substitution of agents from other classes of medication when needed for symptom control. First-generation over-the-counter antihistamines are no longer recommended as first-line therapy because of the side effects, including sedation and performance impairment. If an over-the-counter antihistamine had been unsuccessfully used previously, changing to a leukotriene receptor antagonist or intranasal corticosteroid is advisable. If patient adherence to therapy is low or the patient experienced an adverse event with a particular therapy, then a different treatment strategy should be devised. Some patients and parents are fearful of medication side effects, and these should be addressed through education to optimize medication adherence. Intranasal beclomethasone was associated with a small effect on growth in children, but newer intranasal corticosteroids were shown to have no effect on 1 year of growth.[39,40]

Intranasal cromolyn sodium, now available over-the-counter, is effective in some patients for prevention and treatment of AR and is associated with minimal side effects. However, a requirement for frequent administration limits long-term regular use, but not prophylactic use prior to known allergen exposures (where its use is recommended). Systemic decongestants can be useful when added to a second-generation antihistamine, but their use is limited by the frequent development of systemic side effects. Likewise, topical decongestants can be used immediately prior to the use of an intranasal corticosteroid for the first 3- to 5 days of therapy in severely obstructed patients. However, their continued use can lead to rebound nasal congestion and the condition of rhinitis medicamentosa. Some AR patients with severe symptoms require a short 3- to 5-day course of oral systemic corticosteroid to gain initial control, while addition of other medications such as intranasal corticosteroids will help to maintain control. The choice of a medical regimen can be modified by age of the individual, especially in the very young and old. Antihistamines and leukotriene receptor antagonists are indicated for use in children as young as 6 months of age, and intranasal corticosteroids starting at 2 years of age. Special considerations are warranted for individuals who are pregnant or elderly.[41,42]

Allergen Immunotherapy

Individuals who respond poorly to environmental control measures and optimal medical management are candidates for allergen immunotherapy.

Referral

Criteria for referral to an allergist-immunologist include: (1) a prolonged history of rhinitis; (2) symptoms that significantly interfere with the patient's functional ability or reduce quality of life; (3) prior corticosteroid use or prolonged treatment with multiple medications; (4) treatment that was ineffective or produced side effects; (5) the presence of comorbid conditions (eg, asthma, sinusitis, otitis media); and (6) the need to further define allergic/environmental triggers of rhinitis.

Novel Approaches

Much attention has been focused on the prevention of allergic disorders, including AR. The Canadian Childhood Asthma Primary Prevention Study[43] recently reported the outcomes of a multifaceted early-intervention program in a group of 7-year-old children (N = 380) and found no significant impact on the development of AR. The Pollen Immunotherapy Study[44] examined the ability of a 3-year course of grass or birch pollen immunotherapy to modify the development of new asthma using an open-label, randomized design. Children (N = 208, ages 6-14 years) who received the immunotherapy developed asthma less frequently than the group who did not receive immunotherapy, as defined by the presence of at least 2 of the following in the past 12 months: cough, wheezing, shortness of breath, and bronchial hyperresponsiveness.

Strategies for modulating cytokine production/function are likely to yield major advances in the future. These include: (1) inhibiting a specific proinflammatory cytokine; (2) monoclonal antibodies targeted to cytokines or their receptors (eg, anti-IL-5); (3) soluble cytokine receptors (eg, IL-4 receptors); (4) administering specific anti-inflammatory cytokines; (5) general Th2 cytokine inhibitor (eg, suplatast[45]); and (6) redirecting the immune response to alter the Th1/Th2 balance using DNA vaccination and immunostimulatory sequences.[46] Ciclesonide, a novel agent with an excellent safety profile as an inhaled corticosteroid for asthma,[47] is now under development for use in the nasal airway in AR.

Another potential future strategy is subcutaneous anti-IgE therapy, which is now indicated for the treatment of moderate to severe asthma and has been shown to have efficacy in clinical trials of AR.[48]

REFERENCES

1. Salib RJ, Drake-Lee A, Howarth PH. Allergic rhinitis: past, present and the future. Clin Otolaryngol Allied Sci. 2003;28:291-303.

2. Dykewicz MS, Fineman S, Skoner DP, et al. Diagnosis and management of rhinitis: complete guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology. American Academy of Allergy, Asthma, and Immunology. Ann Allergy Asthma Immunol. 1998;81:478-518.

3. D'Alonzo GE Jr. Scope and impact of allergic rhinitis. J Am Osteopath Assoc. 2002;102-S2-S6.

4. Management of Allergic and Nonallergic Rhinitis. Summary, Evidence Report/Technology Assessment: Number 54, May 2002; Rockville, Md: U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality. Available at:

clinic/epcsums/rhinsum.htm. Accessed May 11, 2006.

5. Wright AL, Holberg CJ, Martinez FD, et al. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994; 94:895-901.

6. Druce HM, Kaliner MA. Allergic rhinitis. JAMA 1988:259:260-263.

7. Fagin J, Friedman R, Fireman P. Allergic rhinitis. Pediatr Clin North Am. 1981;28:797-806.

8. Malone DC, Lawson KA, Smith DH, et al. A cost of illness study of allergic rhinitis in the United States. J Allergy Clin Immunol. 1997;99:22-27.

9. Ricketti AJ. Allergic rhinitis. In: Grammer LC, Greenberg PA, eds. Patterson's Allergic Diseases. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2002: 159-182.

10. Blaiss M. Current concepts and therapeutic strategies for allergic rhinitis in school-age children. Clin Ther. 2004;26:1876-1889.

11. Meltzer EO. Quality of life in adults and children with allergic rhinitis. J Allergy Clin Immunol. 2001; 108:S45-S53.

12. Naclerio RM. Allergic rhinitis. N Engl J Med. 1991;125:860-869.

13. Kay AB. Allergy and allergic disease. N Engl J Med. 2001;344:30-37.

14. Crystal-Peters J, Neslusan C, Crown WH, Torres A. Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalizations and emergency department visits. J Allergy Clin Immunol. 2002;109:57-62.

15. Skoner DP, Doyle WJ, Fireman P. Eustachian tube obstruction (ETO) after histamine nasal provocation: a double-blind dose-response study. J Allergy Clin Immunol. 1987;79:27-31.

16. Skoner, DP, Doyle WJ, Chamovitz AH, et al. Eustachian tube obstruction after intranasal challenge with house dust mite. Arch Otolaryngol Head Neck Surg. 1986;112:840-842.

17. Tomonaga K, et al. The role of nasal allergy in otitis media with effusion. A clinical study. Acta Otolaryngol Suppl. 1988;458:41-47.

18. Grossman J. One airway, one disease. Chest. 1997;111:11S-16S.

19. Falkoff RJ. Nasal Manifestations of Systemic immunologic Diseases. In: Schatz M, Zeigler RS, Settipane GA, eds. Nasal Manifestations of Systemic Diseases. Chapter III, Providence, RI: Oceanside; 1991. Available at: .

20. Halstead LA. Role of gastro-oesophogeal reflux in paediatric upper airway disorders. Otolaryngol Head Neck Surg. 1999;120:208-214.

21. James JM. Common respiratory manifestations of food allergy: a critical focus on otitis media. Curr Allergy Asthma Rep. 2004;4:294-301.

22. Silvers WS. The skier's nose: a model of cold-induced rhinorrhea. Ann Allergy. 1991;67:32-36.

23. Baraniuk JN, Clauw DJ, Gaumond E. Rhinitis symptoms in chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1998;81:359-365.

24. Scadding GK. Non-allergic rhinitis: diagnosis and management. Curr Opin Allergy Clin Immunol. 2001;1:15-20.

25. Staevska M, Baraniuk J. Persistent nonallergic rhinosinusitis. Curr Allergy Asthma Rep. 2005; 5:233-242.

26. Meltzer EO. Treatment options for the child with allergic rhinitis. Clin Pediatr (Phil). 1998;37:1-10.

27. Rachelefsky GS. National guidelines needed to manage rhinitis and prevent complications. Ann Allergy Asthma Immunol. 1999;82:296-305.

28. Gentile DA, Michaels M, Skoner DP. Allergy and immunology. In: Zitelli BJ, Davis HW, eds. Atlas of Pediatric Physical Diagnosis. London: Mosby-Wolfe; 2002.

29. Bousquet J. The Allergic Rhinitis and its Impact on Asthma (ARIA) Workshop Group. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108:S147-S336.

30. Gani F, Pozzi E, Crivellaro MA, et al. The role of patient training in the management of seasonal rhinitis and asthma: clinical implications. Allergy. 2001;56:65-68.

31. Horwitz RI, Horwitz SM. Adherence to treatment and health outcomes. Arch Intern Med. 1993;153:1863-1868.

32. Botelho RI, Dudrach II R. Home assessment of adherence to long-term medication in the elderly. J Fam Pract. 1992;35:61-65.

33. Weinstein AG. Clinical management strategies to maintain drug compliance in asthmatic children. Ann Allergy. 1995;74:305-310.

34. Cramer JA. Optimizing long-term patient compliance. Neurology. 1995;45:825-828.

35. Raynor DK, Booth TG, Blenkinsopp A. Effects of computer generated reminder charts on patients compliance with drug regimens. Br Med J. 1993;306:1158-1161.

36. Gelfand EW. Pediatric allergic rhinitis: factors affecting treatment choice. Ear Nose Throat J. 2005;84:163-168.

37. Prenner BM, Schenkel E. Allergic rhinitis: treatment based on patient profiles. Am J Med. 2006;119:230-237.

38. Berger WE. Allergic rhinitis in children: diagnosis and management strategies. Pediatr Drugs. 2004;6:233-250.

39. Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate [ no. e23]. Pediatrics. 2000;105:415-416.

40. Krahnke J, Skoner D. Benefit and risk management for steroid treatment in upper airway diseases. Curr Allergy Asthma Rep. 2002;2:507-512.

41. Hansen J, et al. Pharmacological management of allergic rhinitis in the elderly. Drugs Aging. 2005;22:289-296.

42. The use of newer asthma and allergy medications during pregnancy. The American College of Obstreticians and Gynecologists (ACOG) and The American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy Asthma Immunol. 2000;84:475-480.

43. Chan-Yeung M, Ferguson A, Watson W, et al. The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age. J Allergy Clin Immunol. 2005;116:49-55.

44. Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002;109:251-256.

45. Tamaoki J, Kondo M, Sakai N, et al. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Lancet. 2000;356:273-278.

46. Broide D, Schwarze J, Tighe H, et al. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. J Immunol. 1998;161:7054-7062.

47. Georgitis JW, Galant S, Lloyd BK. Once-daily ciclesonide does not cause HPA-axis suppression in pediatric asthma patients. Pediatr Crit Care Med. 2004;5:511.

48. Holgate ST, Djukanovic R, Casale T, Bousquet J. Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy. Clin Exp Allergy. 2005;35:408-416.

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download