Allergic rhinitis (hayfever) is

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1 Facts Behind the Fact Card Pharmacist CPE Hayfever by Lynn Gould Allergic rhinitis (hayfever) is a common disorder, affecting up to 40% of Australians. Its prevalence has doubled over the past 25 years. Although often perceived as trivial or inconvenient, untreated allergic rhinitis has a significant impact on quality of life, work or school performance and other medical conditions such as asthma and sinusitus. 1,2 Causes 1,3 There are two main types of allergic rhinitis: Seasonal allergic rhinitis ( hayfever ) is triggered by wind-borne pollen from grasses, weeds and trees. Symptoms occur mostly during spring and summer. Pollen exposure is highest in the morning, when outside, on windy days and after thunderstorms. Perennial allergic rhinitis occurs throughout the year and is most commonly triggered by exposure to house dust mites. Symptoms are often worse in the early morning or at night. Animal dander (especially cat), mould spores and, occasionally, cockroaches may trigger similar Aetiology 2-5 The symptoms of allergic rhinitis (AR) develop as a result of inflammation induced by an IgE-mediated immune response to an inhaled allergen. The allergic inflammatory cascade has three phases: Sensitisation initial contact with an allergen, such as pollen, sensitises the immune system and leads to the production of IgE. Antigen-specific IgE then binds to high-affinity receptors on mast cells. Early-phase response on further exposure to the allergen, triggering of sensitised mast cells occurs when two molecules of IgE, bound to the surface of a mast cell, are cross-linked by antigen. This results in the release of chemical mediators, including histamine, kinins, neutral proteases, cytokines (such as tumour necrosis factor α) and several interleukins, and the production of leukotrienes and prostaglandins from arachidonic acid. Together, these mediators result in the characteristic symptoms of AR within minutes of allergen exposure. Mucous glands are stimulated, leading to increased secretions. Vascular permeability is increased, leading to plasma exudation. Pollen seen through an electron microscope Immunoglobulin E (IgE) is one of the five classes of antibodies produced by the body. It is concentrated in the lungs, skin and mucous membranes. IgE interacts with mast cells; bridging of two IgE molecules by allergen may cause degranulation of the cells, with the release of chemical mediators that cause an allergic response. IgE levels are elevated in atopic diseases (e.g. asthma, hayfever and atopic dermatitis), parasitic diseases, advanced Hodgkin s disease and IgE-monoclonal myeloma. IgE is thought to have a role in the body s defence against parasites. 5,8,9 5

2 Practice Points Practice Point 1 Ask questions to aid diagnosis 1 Information which may help with diagnosis includes: the type and duration of symptoms; whether the symptoms are perennial or seasonal; aggravating and relieving factors; use of and compliance with medication; other allergic disease e.g. asthma, eczema; family history; occupation and hobbies; home and work environments; and the presence or absence of systemic Allergic rhinitis should be considered in patients with: recurrent upper respiratory or middle ear infections, particularly in children; frequent sore throats; mouth breathing and snoring; a feeling of pressure over the sinuses; recurrent infective sinusitis; and headaches. Facts Behind the Fact Card Hayfever Vasodilation occurs, leading to congestion and pressure. Sensory nerves are stimulated, leading to sneezing and itching. Late-phase response over the next few hours the nasal mucosa is infiltrated by eosinophils, neutrophils, basophils, T lymphocytes and macrophages. These cells release inflammatory mediators which produce continued inflammation. The symptoms are essentially the same as in the early-phase response, but less sneezing and itching and more congestion and mucus production tend to occur. The late phase may persist for hours or days. The inflammatory response can cause systemic effects, including fatigue, sleepiness and malaise. These symptoms often contribute to impaired quality of life. Risk factors 3,6 Family history is the primary risk factor for developing allergic rhinitis; if both parents have allergic rhinitis, there is a 75% chance of developing it. If only one parent has it, the risk is 50%. Other allergies and medical conditions the most common allergies or conditions associated with allergic rhinitis include eczema, asthma and food allergies. Age although allergic rhinitis often first appears in childhood, it may appear at any age. In general, if the condition occurs in early childhood it may not recur in Reduced tolerance to allergens When patients are repeatedly challenged with an allergen, the amount of allergen necessary to lead to an allergic response decreases. This is thought to be due to a positive feedback loop high IgE levels are associated with increased numbers of high-affinity IgE receptors on mast cells and basophils. This leads to augmented mast cell and basophil degranulation and an increased release of cytokines, which in turn produces increased IgE levels and IgE receptor density. 4 adulthood. However, if the initial onset is at age 20 or older it may continue through middle age. Living environment there are some studies that indicate that people in Westernised countries may be at higher risk for developing allergic rhinitis, possibly due to more highly sanitised living conditions and reduced exposure to diverse allergens. Exposure to cigarette smoke may increase sensitivity to allergens. Occupation allergic rhinitis may be more prevalent in people who are exposed to the following allergens during work: Seed dust Chemicals Rubber latex Wood dust Animal dander Storage mites Textile dust Certain foods and spices Table 1: ARIA guidelines for classification of allergic rhinitis 2,7,10 Timing of symptoms Intermittent Persistent Symptoms present for: four days per week; or four weeks at a time. Symptoms present for: > four days per week; and > four weeks at a time. Severity and quality of life Mild no impairment of sleep, daily activities, leisure or sport, school or work; no troublesome Moderate to severe One or more of the following are present: impairment of sleep; impairment of daily activities, leisure or sport; impairment of school or work; troublesome ARIA = Allergic Rhinitis and its Impact on Asthma. 6

3 Facts Behind the Fact Card Hayfever Symptoms 1,3,7,11 The classic symptoms of allergic rhinitis are: Clear rhinorrhoea and nasal congestion (which increases during the late phase) Sneezing Watery, itchy eyes Itchy nose, ears, or throat. Other possible symptoms include: Sinus pressure Headache Dark circles under the eyes (also known as allergic shiner ) Post-nasal drip Fatigue Decreased sense of smell and taste. Diagnosis 1,3,6,11 Accurate diagnosis is important as similar symptoms can be caused by other conditions. These include: Viral infection Vasomotor (non-allergic) rhinitis Sinusitis, acute or chronic Nasal polyps Rhinitis medicamentosa (e.g., due to topical decongestants, antihypertensives, cocaine abuse) Hormonal rhinitis (e.g., related to pregnancy, hypothyroidism, oral contraceptive use) Anatomic rhinitis (e.g., deviated septum, adenoid hypertrophy, foreign body, nasal tumour) Cystic fibrosis Granulomatous rhinitis (e.g., Wegener s granulomatosis, sarcoidosis). Testing for allergic rhinitis may include: Skin test An allergen particle is placed under the skin with a needle. An allergic response is confirmed if the skin becomes raised or red within 20 minutes. Antihistamines can interfere with allergy testing and should not be used for at least 48 hours prior to testing. 12 Radioallergosorbent Test (RAST) used to measure the amount of allergen-specific IgE in a sample of blood. The amount of specific IgE produced in response to a particular allergen approximately correlates with the allergic sensitivity to that substance. Nasal smear A sample of the nasal secretions may be taken and examined to determine the cause of the rhinitis; the presence of eosinophils indicates an allergic reaction. Nasal endoscopy A tiny fibre-optic camera may be used inside the nose to view 14 : the nasal mucosa; pale, thick blue-grey mucosa is typical of allergic rhinitis nasal septum; deviated or perforated? mucus secretions; thin, watery secretions are associated with allergic rhinitis while thick, purulent secretions are usually associated with sinusitis nasal cavity; presence of polyps or tumours. Complications 1,6 Possible complications of untreated or inappropriately treated allergic rhinitis include otitis media, eustachian tube dysfunction and acute or chronic sinusitis. Severe allergic rhinitis can also: exacerbate asthma impair learning and behaviour in children due to poor quality sleep, fatigue and daytime sleepiness increase snoring and the potential for sleep apnoea in adults cause bad breath, a husky voice and a sore throat result in eye infections from rubbing itchy eyes cause abnormal development of the mouth and teeth from chronic mouth breathing. Management Oral antihistamines Histamine release causes vasodilation and increases capillary permeability. Antihistamines antagonize the action of histamine at H 1 receptors. They reduce nasal itching, sneezing and rhinorrhoea but are less effective than INCS in controlling nasal obstruction. Individual response to specific antihistamines varies widely and it may be necessary to try several agents to determine which is the best tolerated and most effective. Response to one member of a class does not predict response to another member of that class. In the elderly there is an increased risk of sedation and anticholinergic effects, particularly with the sedating antihistamines. The sedating antihistamines may occasionally cause paradoxical CNS stimulation, especially in children. Practice Points Practice point 2 When to refer 2,7,10 The patient should be referred to their doctor if: treatment with an antihistamine and an intranasal corticosteroid (INCS) has not controlled symptoms; symptom control requires long-term (>one month) treatment; the patient has co-morbidities; the patient s quality of life is being seriously affected; the nasal obstruction is unilateral or there is nasal obstruction without rhinorrhea; there are symptoms such as facial pain (may indicate sinusitis), anosmia (impaired sense of smell), recurrent nosebleeds, hearing loss or earache (may indicate otitis media); there are symptoms of infection (mucopurulent discharge, sore throat, myalgia, fever); or there are symptoms of asthma (wheezing, shortness of breath). 7

4 Practice Points Practice point 3 Prevention 6,12,20,21 The following strategies to minimise exposure to allergens may help to prevent allergic rhinitis: Stay inside during the morning hours, when pollen counts are highest. Avoid outside activities when the trees, flowers or moulds which trigger the allergy are blooming. Take a shower after outdoor exposure to remove pollen that is stuck to the hair and skin. Keep the windows of the house and car closed to exclude pollen. Prevent mould and mildew growth by using an air conditioner to reduce indoor humidity during the warmer months; clean the air conditioner filters regularly. Use vacuum cleaners and air conditioners with HEPA (high efficiency particulate air) filters to trap allergens. Cover pillows and mattresses with impermeable covers to reduce exposure to house dust mites. Wash bedding weekly in hot water (>55 C). Reduce dust-collecting furnishings such as curtains, bed skirts, carpeting and stuffed animals, especially in the bedroom. Vacuum frequently. Exposure to smoke, fumes and strong perfumes, rapid changes in temperature and outdoor pollution can be non-specific triggers in patients with allergic rhinitis and should, if possible, be avoided if they seem to aggravate Facts Behind the Fact Card Hayfever Table 2: Allergic rhinitis treatment algorithm 2 Intermittent Less sedating antihistamines The newer antihistamines are peripherally selective H 1 -receptor antagonists and do not cross the blood-brain barrier to a significant degree. They also have a lower binding affinity for the cholinergic and alpha-adrenergic receptor sites. This eliminates many of the adverse effects caused by the older sedating antihistamines, including CNS depression, blurred vision, dry mouth and tachycardia. Loratadine is metabolised by the liver and its dose should be reduced in severe hepatic impairment. It is approved for use in children one year and over. Desloratadine is the active metabolite of loratadine and appears to have similar therapeutic and adverse effects. At present it is only approved for use in children 12 years and over. Fexofenadine should preferably not be taken within two hours of antacids containing aluminium or magnesium hydroxide as concurrent use may decrease its bioavailability. The dose should be reduced in severe renal impairment. It may be used in children six years and over. Frequency of symptoms Severity of symptoms Persistent Mild Moderate to severe Mild Moderate to severe First-time treatment Antihistamine INCS INCS INCS If incomplete or poor response Add INCS Add antihistamine Add antihistamine Immunotherapy In all patients consider: Intranasal saline to counteract drying from using INCS; also has mucus-diluting properties. Anti-allergy eyedrops if allergic conjunctivitis persists despite treatment. Ipratropium bromide effective in cases of intractable rhinorrhoea. Avoid: Intranasal decongestants except for short-term use. Oral decongestants where contraindicated (e.g., hypertension, coronary artery disease). Cetirizine is less sedating than the older antihistamines, but may produce sedation in some patients; the effect appears to be dosedependent. The dose should be reduced in moderate to severe renal impairment. It is approved for use in children one year and over. Sedating antihistamines First-generation H 1 -receptor blockers enter the CNS, causing sedation. They are also potent inhibitors of muscarinic receptors and may cause anticholinergic effects such as blurred vision, dry mouth and tachycardia. They should be avoided by patients with closed angle glaucoma, increased intraocular pressure, pyloroduodenal obstruction, bladder neck obstruction and hyperthyroidism. In addition, they disrupt cortical neurotransmission and block fast sodium channels. These effects exacerbate sedation and seizure activity and may cause cardiac conduction delays. The different classes of sedating antihistamines include: Alkylamines, e.g. dexchlorpheniramine, brompheniramine, pheniramine, chlorpheniramine have fewer sedative and gastrointestinal adverse affects, but are more likely to cause paradoxical CNS stimulation. 8

5 Facts Behind the Fact Card Hayfever Phenothiazines, e.g. promethazine, methdilazine, trimeprazine the most anticholinergic antihistamines. They have significant sedative affects, may lower the seizure threshold and cause respiratory depression. They also have alpha-adrenergic blocking activity and may cause hypotension. Piperidines, e.g., cyproheptadine the least sedative of the sedating antihistamines. Cyproheptadine has antiserotonin activity and may cause weight gain. Monoethanolamines, e.g. dimenhydrinate, diphenhydramine, doxylamine have significant sedative effects and are not generally used for allergic rhinitis. Intranasal corticosteroids (INCS) 2,11,12,13,15,18 INCS (beclomethasone, budesonide, fluticasone, mometasone (S4), triamcinolone) have local anti-inflammatory effects, decrease capillary permeability and mucus production and produce local vasoconstriction. They are very effective for the relief of all rhinitis symptoms (including nasal congestion) and often relieve eye INCS are the recommended therapy for persistent AR and for moderate to severe intermittent AR in adults. Some sources also recommend INCS as the drugs of choice in children, as concerns that they may cause systemic side effects, such as suppression of growth and bone metabolism, have been allayed. 2 Other sources, however, suggest that a mast cell stabiliser (e.g., sodium cromoglycate) may be the preferred therapy in children. 10,15 INCS have a slow onset of action and they should be used continuously for maximum effect. A topical or oral decongestant may be used concomitantly to provide symptom relief during the first 24 to 48 hours. There is no clear evidence that one preparation is more effective than another. They are well tolerated and can be used long term without atrophy of the nasal mucosa. Studies have revealed no systemic steroid effect on the hypothalamic-pituitary-adrenal axis. Side effects are mostly due to local irritation and include nasal stinging, sore throat, dry mouth, cough and, occasionally, nasal bleeding. If the allergens causing the rhinitis cannot be avoided, INCS may be prescribed for prevention of Patients should be advised to shake the device and to clear the nasal passages before using the nasal spray (the use of a saline nasal spray may be helpful). For more detailed instructions on the use of nasal sprays refer APF 20, page 37. Other medications: 2,10,11,13,15 Intranasal/ocular antihistamines (azelastine, levocabastine) treatment is specific to the site of administration and may be useful for localised symptoms or as a prn treatment in addition to a continuous medication. They have similar efficacy to oral antihistamines, with a faster onset of action. Intraocular antihistamine/mast cell stabiliser/eosinophil inhibitor (ketotifen) may be useful for ocular Intranasal anticholinergic agent (ipratropium) effective for controlling watery nasal discharge but not sneezing or nasal obstruction. It has a rapid onset of action and a prolonged effect (four to 12 hours) and may be used in addition to an antihistamine if there is marked rhinorrhoea. Because of its anticholinergic action it should be avoided by people with closed angle glaucoma or bladder obstruction. Practice Points Practice point 4 Allergic rhinitis and asthma 7,12 Epidemiological studies consistently show that allergic rhinitis and asthma often co-exist. More than 80% of patients with asthma also have allergic rhinitis and 20-30% of people with allergic rhinitis also have asthma. Allergic rhinitis appears to be a predisposing factor to the development of asthma and also contributes to asthma severity. Appropriate treatment of allergic rhinitis has been shown to have a favourable impact on asthma morbidity. Therefore, if a patient has persistent allergic rhinitis, they should be asked about the presence of other symptoms e.g., wheezing a chronic cough, especially at night coughing or wheezing after exercise chest tightness. If there is any suspicion of undiagnosed asthma, the patient should be referred to a doctor. 9

6 Practice Points Practice point 5 Immunotherapy 7,22,23 Patients whose symptoms remain uncontrolled despite drug treatment may benefit from allergen injection immunotherapy which uses controlled exposure to known allergens to reduce the severity of allergic disease. Allergen injection immunotherapy usually consists of weekly subcutaneous injections in increasing doses until a maintenance dose is obtained followed by maintenance doses about once every 2 to 4 weeks for three to five years. The most commonly prescribed allergen vaccines in Australia are house dust mite; five-grass pollen mix; 12-grass pollen mix; cat; couch grass, ryegrass and plantain pollens; Alternaria mould; cockroach and olive/privet pollen. The evidence from about 200 randomised controlled trials shows that allergen injection immunotherapy significantly reduces symptoms and medication usage in both allergic rhinitis and asthma and may reduce the progression from allergic rhinitis to asthma in some children. In addition, monotherapy for one specific allergen reduces the risk of development of new sensitisation to other allergens. Allergen injection immunotherapy has a relatively low risk of adverse events, with mild to moderate effects (rhinitis, mild bronchospasm, urticaria) occurring in one in 1500 injections. Safety can be enhanced by adhering strictly to the requirement that patients remain in the clinic for a minimum of 30 minutes (ideally, 45 minutes) after each injection (even maintenance doses). Facts Behind the Fact Card Hayfever Intranasal decongestants (oxymetazoline, phenylephrine, tramazoline, xylometazoline) should only be used as temporary additional therapy to reduce severe nasal blockage. To avoid rebound congestion, they should not be used for longer than four days. They should not be used by people who are taking MAOIs, nor in infants under six months of age (if nasal congestion interferes with feeding, saline nasal drops may be used just before a feed to loosen and liquefy the mucus). Oral decongestants (phenylephrine, pseudoephedrine) are less effective than intranasal decongestants but do not produce rebound congestion. They are not recommended as first-line treatment of AR but, if antihistamines alone fail to relieve nasal congestion, a dose of an oral decongestant may provide temporary relief. Adverse effects are usually related to their CNS effects and include insomnia, agitation and anxiety. They should be avoided by people with hypertension, coronary artery disease or taking MAOIs and used with caution by people with heart disease, prostatic hypertrophy, hyperthyroidism, closed angle glaucoma and psychiatric disorders. Intranasal mast cell stabiliser (sodium cromoglycate) prevents the release of histamine and leukotrienes. It is safe for medium- to long-term use and for use in children and may be useful as prophylactic treatment in mild rhinitis. However, it requires frequent and regular application for optimal results, which may result in low compliance. See Table 1. on page 14 for examples of available products. References 1. Management of allergic rhinitis; information for health professionals. Australasian Society of Clinical Immunology and Allergy (ASCIA). Last revised Feb management_allergic_rhinitis.htm 2. Walls R et al. Optimising the management of allergic rhinitis: an Australian perspective; MJA Vol. 182 No. 1, 3 Jan issues/182_01_030105/wal10248_fm.html 3. Badash M. Conditions InDepth: Allergic Rhinitis; Brigham and Women s Hospital Health Information, last reviewed Sept org/browsing/browsecontent.asp 4. Hansen I, Klimek L, Mösges R, Hörmann K. Mediators of Inflammation in the Early and the Late Phase of Allergic Rhinitis; Curr Opin Allergy Clin Immunol 4(3): , viewarticle/478213_1 5. LaForce C. Inflammatory Nature of Allergic Rhinitis: Implication for Future Therapies; Medscape Allergy & Clinical Immunology, 2006;8(1). com/viewarticle/532192_1 6. Sheikh J. Rhinitis, Allergic; emedicine, last updated 22 Nov Allergic Rhinitis and Its Impact on Asthma (ARIA) Management of Allergic Rhinitis Symptoms in the Pharmacy At: ARIA_Pharm_Guide.pdf 8. Harris P. Mosby s Dictionary of Medicine, Nursing & Health Professions; Elsevier Australia, The Merck Manual of Diagnosis and Therapy 17th edition, Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001; 108: S147-S334. Copyright 2001, American Academy of Allergy, Asthma and Immunology. 11. Management of allergic rhinitis; National Prescribing Service Limited, Sept At: resources/pharmacy_letter/rhinitispharmacyletter.pdf 12. Brown L, Slavin R. Improving Quality of Life in Patients with Allergic Rhinitis: The Pharmacist s Role. Pharmacy Times CE, At: pharmacytimes.com/lessons/ asp 13. Australian Medicines Handbook, McCann D. Toxicity, Antihistamines; emedicine, last updated May topic38.htm 15. etherapeutic Guidelines, March Martindale: the complete drug reference; 35th edition, Lehman J, Blaiss M. Selecting the Optimal Oral Antihistamine for Patients with Allergic Rhinitis. Drugs 2006; 66 (18): AusDI, March Drugs and Pregnancy; Pharmacy Dept., The Royal Women s Hospital, Melbourne; Carson-DeWitt R. Allergic Rhinitis; Brigham and Women s Hospital Health Information, Last reviewed September Allergen avoidance, ASCIA Education Resources patient information, Last updated March 2003 www. medeserv.com.au/ascia/aer/infobulletins/allergen_ avoidance.htm 22. Weiner J. Allergen injection immunotherapy. MJA Practice Essentials Allergy. MJA 2006; 185 (4): 234. At: wei10219_fm.html 23. Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database of Systematic Reviews 2007, Issue 1. At: 10

7 Facts Behind The Fact Card assessment For Pharmacy Self Care members only Questions Select one correct answer from each of the following questions. Answers due 30 November 2007 Submit answers online To submit your response to these questions online, go to and follow the link on the front page or in the PSC section (via the Navigate button). Please answer the following multiple choice questions using the information in Facts Behind the Fact Card and Practice Points. This activity is recognised under the PSA CPD & PI Program. ONE credit point will be awarded to pharmacists with five out of six answers correct. To receive your credit submit your answers to these questions online at 1. During an allergic reaction there may be systemic effects such as fatigue and sleepiness. These occur: a) When initial contact with an allergen sensitises the immune system and leads to the production of IgE. b) During the early-phase response, due to the release of histamine. c) During the early-phase response, due to vasodilation and the stimulation of sensory nerves. d) During the late-phase response due to the release of inflammatory mediators. 2. A person with symptoms of allergic rhinitis on three days a week which impair their daily activities would have their allergic rhinitis classified as: a) Mild intermittent b) Moderate to severe intermittent c) Mild persistent d) Moderate to severe persistent. 3. The classic symptoms of allergic rhinitis include: a) Watery, itchy eyes b) Headache c) Dark circles under the eyes d) Sinus pressure 4. Regarding the use of less-sedating antihistamines in children: a) Desloratadine is approved for use in children two years and over. b) Cetirizine is approved for use in children six years and over. c) Loratadine is approved for use in children one year and over. d) Fexofenadine is approved for use in children 12 years and over. 5. Oral antihistamines and intranasal corticosteroids are first-line treatment for allergic rhinitis. Other medications which may be used include: a) Levocabastine, an intranasal mast cell stabiliser which may be useful as preventative treatment in mild allergic rhinitis. b) Ipratropium, an intranasal anticholinergic agent with a rapid onset of action and a prolonged effect. c) Tramazoline, an intranasal antihistamine, which may be useful for localised d) Sodium cromoglycate, an intranasal mast cell stabiliser which is not recommended for use in children. 6. Which of the following statements regarding the treatment of allergic rhinitis is correct? a) Evidence from clinical trials has shown that allergen injection immunotherapy significantly reduces symptoms in allergic rhinitis but not in asthma. b) Brompheniramine is one of the most sedating antihistamines. c) Intranasal corticosteroids are very effective for the relief of nasal rhinitis symptoms but do not relieve eye d) The bioavailability of fexofenadine may be reduced if it is taken within two hours of an antacid containing aluminium or magnesium hydroxide. Answers for the Hayfever Special Edition Facts Behind the Fact Card Questions can only be submitted on-line at 11