Glenis K Scadding
MA MD FRCP
Consultant Rhinologist and Allergist
Royal National Throat, Nose and Ear Hospital
Allergic rhinitis is caused by IgE-mediated inflammation in the nasal lining following allergen exposure (see Figure 1). It represents a global health problem since some 10–25% of the population are affected,(1,2) and the prevalence is increasing. It is classified as a major chronic respiratory disease and is a risk factor for asthma.(4)
A recent World Health Organization (WHO) initiative resulted in the document Allergic Rhinitis and its Impact on Asthma (ARIA).(5) This aims to update clinician knowledge of allergic rhinitis, to highlight its impact on asthma, and to provide an evidence-based approach to diagnosis and treatment.
The management of allergic rhinitis includes allergen avoidance, pharmacotherapy, education, occasionally specific immunotherapy, and rarely surgery.(6) The recommendations for therapy are now evidence-based.(5)
Treatment of rhinitis is based on the classification of disease in its intermittent and persistent phase. The effects of available medications on rhinitic symptoms are shown in Table 1. Since the medications have no long-lasting effects following discontinuation, regular long-term treatment is needed for persistent rhinitis.
A recent meta-analysis has shown that intranasal corticosteroids are the most effective treatment for rhinitis.(7) Used in isolation and at recommended doses once daily, the second-generation molecules (ie, excluding betamethasone and dexamethasone) do not have significant corticosteroid side-effects.(8,9) However, it is important to monitor their use, especially in children. The addition of intranasal to inhaled and possibly dermal corticosteroids may result in steroid loading.
Intramuscular or intranasal injection of corticosteroids is not recommended because of possible systemic side-effects and, in the latter case, blindness.(10) Oral corticosteroids are occasionally required at the start of treatment when the nose is significantly blocked or full of nasal polyps. In this case oral steroids should be combined with topical application of intranasal corticosteroid.
Antihistamines usually have effects only on running, itching and sneezing, but do not reverse nasal obstruction. However, some recent molecules, such as desloratadine, appear to have a consistent effect on relief of nasal obstruction.(11) This is one of several new antihistamines (see Drug update section). There is some evidence that these possess certain anti-inflammatory effects in vivo at therapeutic concentrations. None have been compared with topical corticosteroid in a controlled study yet. The criteria for third-generation antihistamines are presently under consideration.
Leukotriene receptor antagonists (LTRAs) are available for the treatment of asthma. In trials they have modest effects on rhinitis and appear to be complementary to antihistamines, decreasing congestion and mucus production. However, the combination of an antihistamine and an LTRA is not superior to corticosteroids.(12)
Specific immunotherapy is effective when administered to the optimum levels. Suitable patients include those with severe disease not responding to pharmacotherapy and in whom allergy is proven by positive skin prick tests that coincide with the clinical history. Subcutaneous immunotherapy can have serious side-effects such as anaphylaxis and death, and should only be practised in centres where full cardiorespiratory resuscitatory facilities are available. However, it is capable of altering the natural course of the disease and has appeared to prevent the progression of rhinitis to asthma in two studies. Patients should be monitored for one hour after injection in the UK, 20 minutes in Europe.(13)
Sublingual-swallow immunotherapy has been shown to be effective with doses at least 50–100 times greater than those used for subcutaneous immunotherapy. Side-effects are few and anaphylaxis has not been reported.(14)
Although rarely necessary for uncomplicated allergic rhinitis, some patients may have a significant septal deviation or grossly protruding bony turbinates, which make the use of topical nasal corticosteroids difficult. Endoscopic sinus surgery can also be used for chronic rhinosinusitis.
The diagnosis of allergic rhinitis is more difficult in childhood where repeated upper respiratory tract infections are common. Skin prick testing can be undertaken at any age. The principles of treatment are the same as those for adults, but care has to be taken over side-effects, especially steroid loading or impairment of academic performance by sedating oral H(1)-antihistamines.(15)
Rhinitis can occur during pregnancy, a side-effect of high oestrogen levels. This form of rhinitis has not been shown to respond to allergic rhinitis therapy.
Pregnant patients with allergic rhinitis may find it exacerbated by pregnancy changes. Care must be taken since most medications cross the placenta. There are no completely safe drugs;(16) however, since inhaled corticosteroids for asthma have been used in thousands of pregnant women without significant ill-effects, it would seem logical to use topical corticosteroids which are least absorbed, such as mometasone and fluticasone.
Allergic rhinitis is less common in the over-65s, but other forms such as cholinergic rhinitis and drug-induced rhinitis (particularly antihypertensives) are usual. Decongestants and anticholinergics may cause urinary retention in patients with prostate problems. Sedative drugs may have greater side-effects. There may also be some renal or hepatic impairment, which must be taken into consideration when giving systemic medication
The treatment of asthma should follow the GINA guidelines.(17) There is evidence that successful treatment of rhinitis can reduce bronchial hyperreactivity and may improve asthma control.(18,19) Oral medication such as glucocorticosteroids and antileukotrienes may affect both nasal and bronchial symptoms. The total dose of corticosteroid reaching the patient may be increased when intranasal corticosteroid is added to inhaled corticosteroid.
It is not yet known whether prevention or early effective pharmacotherapy for allergic rhinitis can reduce or delay the occurrence or severity of bronchial asthma.
Rhinitis sufferers want a cure rather than long-term pharmacotherapy. Immunotherapy appears to alter the natural course of disease, but at present it is difficult, time-consuming and not without risk. It demands good compliance on the part of the patient and the provision of the necessary expertise and resources. Alternative forms of immunotherapy are being explored, and allergen-derived peptides appear promising. Alternative routes such as nasal and sublingual have also proved effective. It may be possible to increase the efficacy of this form of treatment by the appropriate use of adjuvants, largely bacterially derived, which push the immune response away from the TH-2 atopic state.(20)
Short pieces of bacterial DNA appear able to alter immune responsiveness towards a TH-1 state in animal experiments. (21) Human tests are underway.
Other immunological therapeutic techniques are being explored. Anti-IgE is a humanised monoclonal antibody that reacts with IgE and prevents it binding to mast cells or basophils. It has modest therapeutic efficacy in rhinitis, but reduces bronchial asthma.(22) At present it needs to be administered systemically, which along with its cost means that its use will probably be restricted to severely affected individuals. Anti-IL-5 has proved disappointing in asthma(23) but is under trial for nasal polyposis. Other immunological molecules are under investigation. However, for many of these alternative routes exist due to gene duplication, and action at a single site appears unlikely to produce significant therapeutic benefit.
Rhinitis is likely to increase in importance as the ARIA guidelines become established.(5) Accurate allergy diagnosis and specific immunotherapy, at present reserved for severely affected patients, is likely to increase, especially if sublingual immunotherapy plus adjuvant therapy proves significantly effective in clinical trials.
Severely affected patients should be seen in a hospital setting. They may require short courses of oral corticosteroids, subcutaneous immunotherapy or anti-IgE. It is likely that they will have concomitant asthma, and treatment that controls both diseases needs to be considered.
- Nathan RA, et al. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997;99:808.
- Strachan DP, et al. Home environment and severe asthma in adolescence: a population based control study. BMJ 1995;311:1053-6.
- Storms W, et al. The economic impact of allergic rhinitis. J Allergy Clin Immunol 1997;100:592.
- Settipane RJ, et al. Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow up of college students. Allergy 1994;15:215.
- Bousquet J, Van Cauwenberge P. Allergic rhinitis and its impact on asthma. World Health Organization. J Allergy Clin Immunol 2001; (in press).
- Van Cauwenberge P, et al. EAACI Consensus Statement on the treatment of allergic rhinitis. Allergy 2000;55:116-34.
- Weiner JM, et al. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: a systemic review of randomised control trials. BMJ 1998;317:1624-9.
- Allen DB, et al. A meta-analysis of the effect of oral and inhaled corticosteroids on growth. J Allergy Clin Immunol 1994;93:967-76.
- Allen DB. Systemic effects of intranasal steroids: an endocrinologist’s perspective. J Allergy Clin Immunol 2000;106:S179-90.
- Any place for depot triamcinolone in hayfever? Drug Ther Bull 1999:37:17–18.
- Ratner PH, et al. Desloratadine improved asthma symptoms and reduced bronchodilator use in two studies of patients with asthma and SAR. Abstract book of the 2000 Annual Meeting of the American College of Allergy, Asthma and Immunology. Seattle, WA; 3–8 November 2000.
- Pullerits T, et al. Randomised placebo-controlled study comparing a leukotriene receptor antagonist and a nasal glucocorticoid in seasonal allergic rhinitis. Am J Respir Crit Care Med1999;159:1814-18.
- Malling HJ. Allergen specific immunotherapy in allergic rhinitis. Curr Opin Allergic Clin Immunol 2001;1:43-7.
- Guez S, et al. Housedust mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study. Allergy 2000;55:369-75.
- Vuurman EF, Van Veggel LM, Uiterwijk MM, Leutner D, O’Hanlon JF. Seasonal allergic rhinitis and antihistamine effects on children’s learning. Ann Allergy 1993;71:121-6.
- Mazzotta P, et al. Treating allergic rhinitis in pregnancy: safety considerations. Drug J 1999;20:361-75.
- Bousquet J. Global initiative for asthma (GINA) and its objectives. Clin Exp Allergy 2000;30(Suppl):2-5.
- Aubier M, et al. Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyper-responsiveness in patients with allergic rhinitis. Am Rev Respir Dis 1992;146:122-6.
- Simons FER. Allergic rhinosinusitis: the asthma and allergic rhinitis link. J Allergy Clin Immunol 1994;104:534-40.
- Kalliomaki M, et al. Probiotics in primary prevention of atopic disease, a randomised placebo-controlled trial. Lancet 2001;357:1076-9.
- Sparwasser T, et al. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of maurine dendritic cells. Eur J Immunol 1998;28:2045-54.
- Arshad SH, et al. Anti-IgE therapy in asthma and allergy. London: Martin Dunitz; 2000.
- Leckie MJ, et al. Effects of an IL-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness and the response to allergen in patients with asthma. Lancet 2000;356;2144-8.
European Academy of Allergology and Clinical Immunology (EAACI)
Allergic Rhinitis and its Impact on Asthma Guidelines
British Allergy Foundation
British Society for Allergy and Clinical Immunology