TREATING ALLERGIC RHINITIS Prof. Dr. Jean-Baptiste Watelet, MD Department of Otorhinolaryngology Ghent University Hospital Ghent, Belgium Allergic rhinitis (AR) is a nasal disease with the presence of immunologically mediated nasal hypersensitivity symptoms such as itching, sneezing, increased secretion and blockage. The majority of allergic rhinitis are IgE-mediated. The European Community Respiratory Health Survey (ECRHS), investigating adults in 22 countries, reported that the prevalence of nasal allergies ranged from 9.5% to 40.9 %. Allergic rhinitis affects significantly quality of life, quality of sleep, professional activities and school performances. This disease is associated with severe comorbidities such as asthma, rhinosinusitis, conjunctivitis or otitis. Finally, it has a substantial economic impact, based on direct expenditures and on indirect costs linked to productivity loss. 1. Goals of the treatment: The goals of treatment are to reduce the allergy symptoms, to improve quality of life of the patient and to prevent complications. 2. Therapeutic options: 2.1. Allergen avoidance Despites the lack of evidence on their real efficacy in the treatment of allergic rhinitis, avoidance measures are still recommended as first step in patients allergic to house dust mites and pets. The following advices may reduce the exposure to allergens and may prevent symptoms. Page 1
In case of hay fever, during days or seasons when airborne allergens are high: Stay indoors, and if possible, close the windows Use an air conditioner Avoid using fans that draw in air from outdoors Avoid air drying your clothes Bath or shower and change clothes after being outside In case of perennial allergic rhinitis: Cover pillows and mattress with dust mite covers Use an air purifier Avoid pets and other triggers 2.2. Pharmacotherapy If allergen avoidance does not improve significantly the symptoms, pharmacological treatment should be recommended. 2.2.1. Antihistamines Oral antihistamines are rapidly active on sneezing, rhinorrhea and itching. They are also but less effective against nasal congestion. The oral administration allows also a simultaneous control of other allergic clinical expression such as conjunctivitis. The second-generation of antihistamines presents a positive benefit/risk ratio with the absence of sedating effects at therapeutic doses: this has been demonstrated for most of the new compounds. The recent improvement of their pharmacokinetic profile has optimized their onset of action, their duration of activity and their other antiinflammatory properties. Up till now, antihistamines are the only anti-allergic medications that have demonstrated their efficacy in persistent rhinitis and in long-term regimen. Topical antihistamines are directly delivered in the target organ and have a rapid onset of action. Page 2
2.2.2. Corticosteroids Because of their major side effects and because of the safety of the other medications, systemic corticosteroids are not recommended in allergic rhinitis. Their indication is limited to allergic rhinitis complicated with asthma or chronic rhinosinusitis. Intranasal corticosteroids have shown their efficacy on all rhinitis symptoms, and are particularly recommended in cases of nasal congestion. In comparative studies, they were more effective in controlling symptoms of AR than oral antihistamines, intranasal antihistamines, intranasal cromoglycate and oral antileukotrienes. The most frequent side effect is nasal bleeding found in 17 till 23%. When used in combination with inhaled corticosteroids, special caution should be taken with intranasal corticosteroids, even if their new generation seem to have a low systemic bioavailability. 2.2.3. Anti-leukotrienes By blocking the cys-leukotriene receptors during allergic inflammation, antileukotrienes have been shown to be effective alone or in combination with antihistamines. However, their effect is less important than intranasal corticosteroids in seasonal allergic rhinitis. 2.2.4. Others 2.2.4.1. Cromones These drugs have been found to be more effective than placebos for the treatment of allergic rhinoconjunctivitis. They have an excellent safety profile but, in comparative studies, they are less effective than antihistamines and intranasal corticosteroids. 2.2.4.2. Anticholinergics Anticholinergics are indicated in profuse watery rhinorrhea. 2.2.4.3. Decongestants Topical decongestants are highly effective against nasal obstruction. However, they are known to induce rhinitis medicamentosa if the duration of treatment exceeds 10 days. Page 3
When used orally, some sympathetic side effects could occur. 2.2.5. Combinations Oral combination of antihistamines and oral decongestants are more effective than antihistamines alone, especially against nasal obstruction. As already mentioned above, this combination can also induce some side effects such as insomnia or nervousness. Expert opinions suggest that combination of antihistamines and intranasal corticosteroids should have some beneficial effects when compared to intranasal corticosteroids alone. 2.3. Immunotherapy In the WHO position paper on immunotherapy, experts consider that immunotherapy should be proposed in the following situations: Presence of demonstrated IgE-mediated disease (on basis of positive skin prick tests and/or serum specific IgE) Documentation indicating that specific sensitivity is involved in symptoms (eventually after allergen challenge) Characterisation of other triggers that may be involved in symptoms Severe and long-duration of symptoms Poor response to allergen avoidance and pharmacotherapy If standardized or high quality vaccines are available. The efficacy of sub-cutaneous immunotherapy (SCIT) has been demonstrated in birch and betulaceae pollen, grass pollen, ragweed pollen, Parietaria pollen and house dust mites allergies. It has been described that, in children, SCIT could prevent the development of new sensibilizations and asthma when compared to a control group. Because of the potential serious side effects including systemic reactions (severe asthma attacks and anaphylaxis), this procedure must be carried out by or under supervision of trained specialist with access to resuscitation drugs and facilities. Page 4
Finally, regarding sublingual-swallow immunotherapy (SLIT), a metaanalysis from the Cochrane Collaboration demonstrated a significant reduction in both symptoms and medication requirements. In general, SLIT is well tolerated even if, recently, some side effects have been reported. 2.4. Surgery Surgery is only indicated in case of turbinate hypertrophy consequent to allergic rhinitis. In case where morphological abnormalities of the turbinate or nasal septum aggravate rhinitis symptomatology, surgical correction could be envisaged. 3. Decisional algorithms 3.1.Importance of the patient profile An adequate characterization of the allergic patient is needed before initiation of the therapy. The allergic antecedents and co-morbidities should be explored. In case of multiple allergic diseases, a systemic treatment should be preferred to topical administration of anti-allergic drugs. But the well demonstrated efficacy of locally administrated drugs is a strong argument for severe cases, especially if isolated. 3.2.Existing guidelines Several expert panels have proposed guidelines for treating allergic rhinitis. They are based on opinion or on evidence. All of them agree with the concept of a stepwise approach and always start with the most effective allergen avoidance and environmental control possible. The next steps are mainly based on pharmacotherapy. Immunotherapy is reserved for resisting cases. The experts always insist on the necessity to add local medications in case of unsatisfactory control by systemic therapy). Surgery and systemic corticosteroids are proposed in very rare and wellselected cases and should not be used in first line. 3.3. Unmet issues Page 5
Experts are usually agreeing on the fact that the treatment of allergic rhinitis should start before allergen exposure if possible and should persist during the whole period of exposure. However, data are lacking and these therapeutic options must still be considered as opinion-based. Finally, no clear schemes for monitoring the therapy are available. Some authors suggest an evaluation one month after initialization of the treatment. 4. Patient education and integration in the therapeutic process: Interestingly, this aspect of the treatment is only poorly explored in literature. Only limited data are available about patient s compliance in allergic rhinitis. No actual guidelines are integrating the patient s dimension in decision-making and follow-up process of a treatment for allergic rhinitis. Nowadays, patients associations are expecting more information from health care professionals. Adequate information on the disease pathogenesis and therapeutic procedures is becoming more and more a pivotal element for achieving successfully the objectives of improving symptoms and quality of life of allergic patients. A section of this website is fully devoted to some fundamental educational principles for fighting against allergies: physician and patient together. References 1. Johansson SG, Bieber T, Dahl R et al. A revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization. J Allergy Clin Immunol 2004;113:823-826 2. [No author listed]. European Community Respiratory Health Survey. Variations in prevalence of respiratory symptoms self-reported asthma attacks, and use if asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur Respir J 1996;9:687-695 Page 6
3. Bousquet J, Bullinger M, Fayol C et al. Assessment of quality of life in patients with perennial allergic rhinitis with the French version of SF- 36 Health Status questionnaire. J Allergy Clin Immunol 1994; 94:182-188 4. Majani G, Baiardini I, Giardini A et al. Health-related quality of life assessment in young adults with seasonal allergic rhinitis. Allergy 2001;56:313-317 5. Bousquet J, Van Cauwenberge P, Khaltaiev N et ARIA working group. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147-S333. 6. Nathan RA. The burden of allergic rhinitis. Allergy Asthma Proc 2007;28:3-9 7. Heikh A, Hurwitz B. House dust mite avoidance measures for perennial allergic rhinitis: a systematic review of efficacy. Br J Gen Pract 2003;53:318-322 8. Passalacqua G, Bousquet J, Church M et al. Adverse effects of H1 antihistamines. Allergy 1996;51:666-75 9. Bousquet J, Campbell A, Michel F. Antiallergic activities of antihistamines. In: Chruch M, Rihoux J (eds). Therapeutic index of antihistamines. Lewinston, NY Hogrefe and Huber publishers; 1992:pp 57-95 10. Bachert C, Bousquet J, Canonica GW et al. Levocetirizine imporves quality of life and reduces costs in long-term management of persistent allergic rhinitis. J Allergy Clin Immunol 2001; 114:838-44 11. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 1998;317:1624-1629 12. Svensson C, Andersson M, Greiff L et al. Effects of topical budesonide and levocabastine on nasal symptoms and plasma exudation responses in seasonal allergic rhinitis. Allergy 1998;53:367-374 13. Pullerits T, Praks L, Ristioja V et al. Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 202;109:949-955 14. Wilson AM, O Byrne PM, Parameswaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. AM J Med 2004;116:338-344 15. Meltzer EO, Malstrom K, Lu S et al. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: placebocontrolled clinical trial. J Allergy Clin Immunol 2000;105:917-922 16. Di Lorenzo G, Pacor ML, Pelliteri ME et al. Randomized placebocontrolled trial comparing fluticasone plus cetirizine, fluticasone plus Page 7
montelukast, and cetirizine plus montelukast for seasonal allergic rhinitis. Clin Exp Allergy 2004;34:259-267 17. Van Cauwenberge P, Bachert C, Passalacqua G et al. EAACI consensus statement on the treatment of allergic rhinitis. Allergy 2000; 55: 116-134 18. Bousquet J, Lockley R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-562 19. Ross RN, Nelson HS, Finegold I. Effectiveness of specific immunotherapy in the treatment of allergic rhinitis: an analysis of randomized, prospective, single- or double-blind placebo-controlled studies. Clin Ther 2000;22:342-350 20. Des-Roches A, Paradis L, Menardo-Bouges S et al. Immunotherapy with standardized Dermatophagoïdes pteronyssimus extract. VI. Specific immunotherapy prevents the onset of new sensitization in children. J Allergy Clin Immunol 1997;99:450-453 21. Moller C, Dresborg 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 22. Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2003;2:CD002893 23. Plaut M, Valentine M. Allergic rhinitis. N Engl J Med 2005; 353: 1934-1944. Page 8