Studies estimate that between 20% and 30% of European adults and potentially up to 40% of children suffer from the distressing condition of allergic rhinitis
Introduction and epidemiology
Hay fever, or seasonal allergic rhinitis, is due to an inflammation of the nasal passages that occurs when the body’s immune system reacts to pollen. Peak pollen season usually occurs from the end of March to September in Ireland. Weather conditions have an impact on the pollen count which is increased by humid, windy, and warm weather. Hay fever is one of the most common conditions in the world. It is difficult, however, to predict its exact prevalence, but some epidemiologic studies estimate that 20 to 30 per cent of European adults are affected. In addition, potentially up to 40 per cent of children suffer from hay fever.
Pathophysiology
The underlying mechanism of hay fever involves immunoglobulin E (IgE) antibodies attaching to pollen, which causes the release of histamine, leukotrienes, and other inflammatory mediators. These immune reactions are induced by type-2 helper T cells. Inflammation in mucous membranes occurs as the body works to remove the pollen. Hay fever should not be considered as an acute response to pollen exposure, but as a complex interaction involving mast cells, T cells, epithelial cells, eosinophils, and basophils.
Symptoms
Hay fever symptoms are generally self-limiting, but they can lead to frustration for patients and have an impact on their quality of life. The main nasal symptoms are sneezing, coughing, runny or blocked nose, itchy nose, and loss of smell. Ocular symptoms – including red, itchy, and watery eyes – are also associated with hay fever. Itch in the mouth, headache, earache, and fatigue are also common symptoms. Patients with asthma may have additional symptoms including shortness of breath, wheeze, and cough. These symptoms can lead to reduced sleep quality, poor performance, and absenteeism at work or school. Symptoms such as anxiety, depression, and fatigue can be observed to a greater extent in patients with severe allergic rhinitis, compared to those with mild allergic rhinitis.
Diagnosis
Diagnosis of hay fever is often made by a GP, following examination of symptoms and medical history. Time of year, triggers, location, and duration of symptoms are all factors to be considered. The patient may also be examined by the GP for nasal polyps – inflammation on the inside of the nose that can result from allergic rhinitis. The GP may initiate treatment with antihistamines. If the patient’s symptoms improve, a diagnosis of hay fever is likely. Commercial allergy testing kits are sometimes used but are not recommended as they can be unreliable and below standard. Laboratory tests can be used to rule out common respiratory viruses.
Allergy testing may be carried out in some cases, particularly if the cause of the symptoms is unclear. Two main allergy tests are used in diagnosing hay fever. Firstly, a skin prick test can be used – where the allergen is placed on the surface of the skin, which is then pricked with a needle to introduce the allergen into the body’s immune system. If the patient is allergic, a small, itchy spot will appear on the skin’s surface. A blood test is the second method, which checks for the presence of IgE in the blood. The main drawback of allergy testing is that it is not definitive, with possibilities of both false positive and negative results.
Figure 1: Table outlining second-generation antihistamines on the market in Ireland
It is also possible to be diagnosed with local allergic rhinitis, where systemic diagnosing methods are negative, but IgE antibodies are produced in the nasal passage. Symptoms tend to be very similar, with an association of local allergic rhinitis with conjunctivitis and asthma. It is estimated that 25 per cent of patients with allergic rhinitis have local allergic rhinitis. This is diagnosed using a nasal allergen provocation test (NAPT).
Prevention
Prevention is vital in controlling symptoms of hay fever. There are several prevention strategies and patients should be thoroughly advised on these. Staying indoors or reducing time outside during peak pollen season is effective. Using Vaseline around the nostrils and wearing wraparound sunglasses are very useful as barrier techniques. Keeping windows and doors closed and not allowing animals into the house are also good techniques. Showering and changing clothes after being outside, not drying clothes outside, and vacuuming regularly are also advised.
The main drawback of allergy testing is that it is not definitive, with possibilities of both false positive and negative results.
Figure 2: Graph showing treatment options available for hay fever.
Treatment
The main objective of treating hay fever is symptom relief. A wide variety of therapeutic options are available for achieving this goal. As hay fever and asthma both contribute to inflamed airways, treatment of asthma is an important consideration in this patient group. Pharmacies are often the first port of call for patients to manage symptoms of hay fever. This can allow community pharmacists to assess patient response to treatment and give information that can help in diagnosing and subsequent treatment of hay fever.
Oral antihistamines
Oral antihistamines are the first-line treatment for hay fever. In Ireland, they are available both over-the-counter (OTC) and on prescription. Antihistamines exert their mechanism of action by being competitive antagonists at the histamine H1 receptors in the body. This reduces the release of histamine that causes inflammation in the nasal passage and leads to symptoms of hay fever. The older, first-generation antihistamines, including diphenhydramine and chlorphenamine, are effective in relieving symptoms. However, due to their sedative nature and the fact that they can negatively impact functioning and cognition, they are not recommended for first-line treatment of hay fever.
The main adverse effects of second-generation antihistamines are headache, fatigue, cough, nausea, and vomiting
Second-generation oral antihistamines can reduce symptoms of hay fever when taken regularly, either at the time of maximal symptoms or before exposure to the allergen. They provide relief from symptoms including sneezing, itch, runny nose, red eyes, and watery eyes. Bilastine, levocetirizine, and desloratadine are examples of second-generation antihistamines that are available on prescription in Ireland. Second-generation antihistamines are generally well tolerated and are not associated with many serious adverse events. They are associated with much less sedation than the first-generation antihistamines. They also provide ease of use due to a possible once-daily dosing schedule. The main adverse effects associated with second-generation antihistamines are headache, fatigue, cough, nausea, and vomiting.
Nasal sprays
Intranasal steroids are a common treatment for hay fever. They act locally by inhibiting the release of cytokines, which reduces inflammation of the nasal mucosa. They have an onset of action within 30 minutes, with maximum effectiveness usually after two-to-four weeks of daily use. Budesonide, beclomethasone, fluticasone, triamcinolone, and mometasone are examples of steroids that can be used intranasally. There is limited evidence to suggest which intranasal steroid is superior and consideration should be given to the patient in question. For example, mometasone may be suitable for a younger population, while budesonide may be more suitable in pregnancy than other steroids. Some adverse effects are possible with this delivery method; however, it is much less likely to have potential systemic adverse effects. Adverse effects are usually local and can include nose bleeds, nasal dryness, headache, and throat irritation.
Intranasal antihistamines can deliver a higher concentration of medication to the targeted area compared to oral antihistamines, which results in fewer adverse events. Azelastine is the most common antihistamine to be used intranasally. Adverse effects can include nose bleeds, headache, and nasal irritation. Their use is limited due to their higher cost compared to oral antihistamines and by their lower efficacy compared to intranasal steroids. Combined steroid and antihistamine nasal sprays are also licensed for use in Ireland. They have been shown to be more effective than the individual components, with a very similar safety profile. A combination fluticasone propionate and azelastine hydrochloride is licensed for twice daily use in people aged over 12. The increase in price is the main drawback with this product.
Oral steroids
Steroids have their effect by reducing inflammatory cytokine production, mast cell proliferation, and cell mediated immune responses. This reduces inflammation in the nasal passage and is effective in reducing symptoms of hay fever. Despite their effectiveness in treating symptoms of hay fever, the use of oral steroids is not recommended for use as first-line treatment due to the associated adverse effects. These adverse effects are wide-ranging and include weight gain, abdominal pain, fluid retention, and altered mood. In certain cases, a short course of systemic steroids may be indicated. These cases include where other treatment options have failed or if a patient is intolerant to intranasal options.
Eye drops
Ocular allergic symptoms can be treated locally using eye drops. In comparison with oral antihistamines, topical antihistamines can directly target the ocular tissue and have a much quicker onset of action – usually between three and 15 minutes. They also have a better safety profile and are better tolerated, due to less systemic absorption. They are effective in symptom relief but generally only for a short period of time. Additionally, they do not have an effect on other inflammatory mediators such as prostaglandins or leukotrienes. They are more effective in the acute phase and can be used as monotherapy or dual therapy. Olopatadine and ketotifen are two antihistamines that are licensed for twice daily use, in the treatment of ocular symptoms of seasonal allergic conjunctivitis.
Sodium cromoglicate is a mast cell stabiliser that is available both OTC and on prescription in Ireland. It works by inhibiting mast cell degranulation which prevents the release of histamine and other inflammatory mediators. It is most effective when used prophylactically and after a loading period of a few weeks before exposure to the allergen.
Steroid eye drops are available for the treatment of steroid-responsive inflammatory conditions of the eye in the short term. They are very effective but are commonly used for short-term therapy only due to increased intraocular pressure and increased risk of cataract development. They can be used as monotherapy or dual therapy, in cases where there is an exacerbation of symptoms. Eye drops containing prednisolone and dexamethasone are licensed and commonly used in Ireland.
Ocular non-steroidal anti-inflammatory drug (NSAID) preparations are not regularly used in the treatment of allergic rhinitis but can be useful in some cases, particularly if symptoms are not controlled or if the patient can’t use a steroid preparation. NSAIDs block the cyclooxygenase pathway and inhibit production of prostaglandins, which are a mediator of inflammation in IgE-mediated allergic responses. After one week of use, topical NSAIDs were found to be effective in significantly reducing symptoms. However, NSAIDs are mainly used to treat inflammation in cataract surgery, and use in allergic rhinitis would be off-licence. Ketorolac and diclofenac are examples of NSAIDs available as ocular preparations. Lubricant eye drops can also be used to dilute and flush pollen away from the tear film, as well as to treat dry eye symptoms that may also be present.
Leukotriene receptor antagonists (LTRAs)
LTRAs can be considered for use in treating hay fever when other treatment options are not well tolerated or are not effective in symptom relief. Montelukast is one such LTRA, which is particularly useful in patients where asthma is a comorbidity. Montelukast blocks leukotriene D4 in the airways and therefore leads to decreased inflammation and smooth muscle relaxation.
Immunotherapy
Immunotherapy is another hay fever treatment option that can be used in cases where symptoms are severe. Immunotherapy is the only treatment option that modifies the disease, rather than treats the symptoms. Allergen immunotherapy involves the administration of gradually increasing doses of the allergen until a dose is reached that can effectively induce immunological tolerance. Subcutaneous therapy has been shown to be effective in reducing symptoms of hay fever. Immunotherapy is generally reserved for patients that can’t tolerate other treatments or whose symptoms are not controlled after other treatments. This treatment carries the risk of anaphylaxis and should therefore only be prescribed and administered by a physician with adequate training and who is properly equipped to manage anaphylactic events. Treatment is typically administered perennially, with weekly dose increases over six to eight months, followed by monthly maintenance injections for three-to-five years. Patients tend to have prolonged protection and therapy may be discontinued. Apart from the risk of anaphylaxis, allergen immunotherapy has a relatively low risk of serious adverse events.
Immunotherapy is another hay fever treatment option that can be used
in cases where symtoms are severe
Immunotherapy can also be administered sublingually and some treatment options are licensed in Ireland. Sublingual immunotherapy involves placing an oral lyophilisate under the tongue until it dissolves. Sublingual treatment offers a better safety profile than subcutaneous treatment. In addition to this, sublingual treatment is generally more acceptable to patients as they can avoid injections and take the medication at home. The most common adverse effects are local and include throat irritation and oral pruritus. These symptoms usually resolve after one week of treatment. Treatment should be initiated at least four months prior to the start of the grass pollen season and continue throughout the season. Asthma is a risk factor for systemic allergic reactions, and therefore this treatment should be avoided in this patient group. Grazax and Oralair are two sublingual allergen immunotherapies used to treat grass pollen-induced rhinitis in adults and children over five years. Both Grazax and Oralair are reimbursed under HSE schemes.
Decongestants
Both oral and topical decongestants can provide relief from nasal congestion associated with hay fever. Pseudoephedrine, phenylephrine, and xylometazoline are the most commonly used decongestants. These work by acting on adrenergic receptors, which results in vasoconstriction in the nasal passage and therefore decreasing inflammation. Duration should be limited to short-term use due to the risk of rhinitis medicamentosa. A combination product containing both pseudoephedrine and cetirizine is licensed for use in Ireland for up to two-to-three weeks. If nasal symptoms are resolved, treatment can be continued with just oral antihistamines.
Non-pharmacological treatment
Nasal irrigation with saline involves rinsing the nasal cavity with hypertonic or isotonic saline. It can relieve some symptoms of hay fever in both adults and children. Nasal saline irrigation is available OTC and can provide a safe and acceptable alternative to pharmacological treatment. It is not unlikely to be associated with adverse effects. It can be used as monotherapy or as an adjunct to other treatments.
References on request
