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Seasonal Allergies (a detailed review article)

Seasonal allergy refers to allergic rhino-conjunctivitis occurring in response to outdoor airborne allergens only during specific seasons eg. late spring and early summer. Also known as seasonal allergic rhinitis (SAR) or hay fever, the condition is distinguished from perennial allergic rhinitis (PAR) which occurs throughout the year. PAR tends to be associated with regular exposure to indoor allergens such as dust mite, animal dander and moulds. Other causes of PAR include drugs eg. non-steroidal anti-inflammatory drugs (NSAIDs) and occupational exposures eg. bakers. There can be overlap between the two conditions, where SAR can occur in 30% of subjects with chronic rhinitis.

Allergic rhinitis and asthma

Allergic rhinitis (AR) is a clinically defined symptomatic disorder of the nose induced following aero-allergen exposure caused by Immunoglobin E (IgE)-mediated inflammation of the mucous membranes of the nose, the conjunctivae are affected in 70% of cases of SAR. The respiratory tract is a united airway starting at the nose and finishing with the alveoli, inflammation affecting the nose can lead to sympathetic change in the lower airways and vice versa. Nasal allergy may be complicated by bronchial hyperresponsiveness and asthma, sinusitis, nasal polyps and glue ear.

There can be considerable overlap between AR and asthma. One study showed that 58% of patients with AR also had asthma. Conversely, the prevalence of AR in asthma can be as high as 85% in some series. Patients with asthma who deny having nasal allergy symptoms may have inflammatory changes within their nasal mucosa. The pattern of inflammation is similar for both conditions, where eosinophils, mast cells and Tp helper cells predominate. Some investigators have demonstrated direct correlations between eosinophil counts in nasal and bronchial epithelium. The nose and bronchi can both have early and late responses to allergen challenge. Inflammatory mediators such as histamine and leukotrienes have been implicated in both conditions should be considered targets for therapy.

The nasal passages are extensively innervated and there are numerous reflexes some of which may have important clinical and therapeutic implications. The first is the nasal-sinus -bronchial reflex where nasal irritation/inflammation causes increased bronchial hyperresponsiveness. The naso-ocular reflex occurs when nasal/irritation inflammation causes sympathetic itch and streaming in the ipsilateral eye. Separate studies have shown that topical corticosteroid treatment of AR, resulted in reduced bronchial hyperresponsiveness and ablation of the naso-ocular reflex respectively.

In experimental models of AR in humans, allergen nasal challenge produced a dual response in some patients. Nasal lavage implicated histamine, eosinophilic cationic protein, and mast cell tryptase in the early response whereas leukotrienes dominated in the late response four hours later. Pretreatment with topical nasal steroid can abrogate the late response. There is a priming effect where repeated exposure to high levels of allergen leads to a heightening of the inflammatory responses. Clinically, this translates into a deterioration of symptoms as the season progresses.

Prevalence and pharmaco-economics

The International Study of Asthma and Allergies (ISAAC) study in

children) is a worldwide collaboration addressing the epidemiology of asthma, AR and eczema in over 450,000 children aged 13-14 years in 56 countries. The prevalence of AR varies between 1.4% and 39.7%. Irelandhas a high prevelance of AR at almost 25%. It is estimated that SAR affects at least 30% of adult populations in developed countries. Somewhat surprisingly, studies have shown that urban dwellers have consistently higher rates of SAR than rural-dwellers.

SAR is often mistakenly considered a trivial condition because it is so common, self-limiting and can be treated with over the counter (OTC) medications. However, the personal burden of symptoms and the economic or educational effect can be quite considerable. For children, SAR can lead to lost school-time and exercise- limited days. It can exacerbate concurrent asthma. In European andUK studies of the burden of SAR, it was found that between 75-82% of patients reported some impact of the symptoms of AR on daily activities, and health-related quality of life. Both studies highlighted the unmet needs of many patients with a high symptom burden and there was a poor correlation between patients and physicians in the reporting of disease severity.

Grass pollen levels peak in June each year which coincides with important state examinations for secondary school children, thus SAR has the potential to affect a candidate’s results and career choices. Disturbed sleep or inappropriate use of sedating antihistamines may be responsible for daytime drowsiness and may lead to poor performance at work, sick leave and accidents. Pharmaco-economic studies from theUS estimate the direct (physician visits and medications) and indirect costs of AR to range between 5.5-6 billion US dollars.

Aerobiology

Air sampling involves capturing airborne matter using a volumetric suction technique with Burkhard spore trap. Air is sucked into the device at a speed of 10l/min. Airborne particulate matter impacts on an adhesive strip attached to a rotating drum within the device. The strip is then removed allowing moulds, tree and grass pollens to be identified morphologically and quantified by light microscopy. Since pollen can travel long distances through the air, counts are relevant to large areas and a count from one sampling site is typically used as data for an entire city.

A pollen forecast is a prediction of what the pollen levels will be in the future, like a weather forecast. Pollen forecasting often has greater value for allergy suffers than a pollen count, because they can use this information to plan their day, including whether or not to take medication. Pollen forecasting methods consider natural events, besides the recent pollen counts, that will affect future pollen levels. Historical pollen counts (which provide predominant pollen and seasonal trend information for a certain area) temperatures, precipitation, and weather forecasts are all included in the predictive models.

The season in which the condition occurs depends on the kind of tree or grass that an individual is allergic to. For instance, in early spring, trees such as Hazel,Willow, and Birch will pollinate, while grasses such as Timothy,Bermuda, and Orchard pollinate in the summer. Leaf moulds such as Alternaria become more prominent in the autumn months. By far the most common outdoor aero-allergen in Irelandand theUK is grass pollen. However, in parts of the USA the dominant allergen is Ragweed. Outdoor airborne grass-pollen concentrations are not constant during a 24-hour period. It has been suggested by several authors that there is a basic diurnal variation, with a higher pollen concentration in the early morning. The day to day variation in pollen counts is determined by climatic conditions such as rainfall, prevailing winds and atmospheric high-pressure systems. Rapidly changing weather conditions observed inIrelandmay contribute to considerable within day variation in pollen counts. Dry weather, windy conditions and high pressure fronts promote high pollens counts. Smog and air pollution may produce additive effects.

 

 

Clinical Presentation

The diagnosis is essentially clinical. The history should elicit the seasonal nature of symptoms. Typically patients may complain of sneezing, nasal and conjunctival itch, rhinorrhoea, nasal congestion, anosmia, snoring, disturbed sleep, palatal itch, conjunctival itch, head and facial ache. Systemic features may include loss of apetite, irritability and depressed affect. The history should identify the month/season of onset of these symptoms as this may provide a clue to the causative allergen. A careful evaluation for symptoms of asthma is essential. On examination the conjunctivae may be injected and swollen. The nares will be congested. The mucosa will be hyperaemic and may be coated with clear secretions.

Investigations

In most cases of clearcut hayfever where symptoms are mild and infrequent, no investigations are necessary. If there is any doubt as to the causative allergen, there is a background of PAR or the patient has severe disease and is a candidate for immunotherapy then allergy testing is indicated.

Skin prick tests with standardised allergen extracts can be performed rapidly. Panels should include the common grass and tree pollens. They are easy to do, more sensitive than RAST tests and results are available after 15 minutes. Patients need to desist from taking antihistamines 24-72 hours prior to the test, depending on whether they are short or long-acting.

The alternative is measuring specific IgE by radioallergosorbent (RAST) test. Disdavantages of RAST tests are that they require phlebotomy and take several days for the referral laboratory to generate a result. RAST tests can be performed whilst patients are on antihistamines. They are less sensitive than skin prick tests.

 

Treatment

The Allergic Rhinitis & its impact on Asthma (ARIA) guidelines 2008 recognise the united airway theory and the negative effects that uncontrolled nasal allergy may have on the lower airways. They characterise rhinitis according to symptoms and severity . Symptoms are classified as being intermittent or persistent. Severity is classified as mild or not. Severe symptoms include abnormal sleep, impairment of daily activities, problems at school or work and troublesome symptoms not responding to treatment. Treatment guidelines are symptom and evidence based. Another useful document is the British Society of Allergy and Clinical Immunology guidelines on the management of allergic and non-AR.

Allergen avoidance is recommended where possible. Measures may include:

  • Avoiding activity in the early part of the day when pollen counts are high.
  • Avoid going out after storms or very windy days
  • Wearing nasal filters reduce rhinitis symptoms during the pollen season
  • Staying indoors while grass is being cut or when counts are expected to be high
  • Children should not be allowed play in cut grass
  • Keeping windows shut to prevent pollens drifting indoor
  • Pollen filters can be fitted to vehicles
  • Vaseline applied to nostrils may reduce pollen penetration of the nasal mucosa
  • Showering or bathing once in for the day
  • Wear wrap-around sunglasses.

Most of the above recommendations are based on expert consensus rather than randomised clinical trials.

Pharmacotherapy

Oral H1 antihistamines are the first line treatment for all patients irrespective of age. First generation antihistamines should be avoided because of their sedating effects and the potential for them to interfere with academic or work performance. Second generation antihistamines eg. cetirizine, levocetirizine, loratidine, desloratidine, or fexofenadine, are less sedating although drowsiness can occur in some individuals. They are generally safe and well tolerated and are available in both tablet and liquid forms. Azelastine can be used intranasally, has a rapid onset of action and may be used as rescue therapy. Similarly olopatadine eye drops can be used for breakthrough conjunctivitis symptoms.

Topical chromones may be beneficial for eye symptoms, but generally their use has been superceded by other treatments.

If nasal congestion is troublesome then decongestants may be used. Topical agents such xylometazoline, an α-adrenergic agonist, produces vasoconstriction and may be used for short periods. Long-term use is not recommended because of the risks of rebound rhinorrhoea, nasal irritation and rhinitis medicamentosa. Oral decongestants such as pseudoephedrine are not generally recommended and are less effective, but are not associated with any rebound effects. Side-effects include hypertension, insomnia, tachycardia and agitation.

Topical nasal steroids (TNS) are the mainstay of treatment for all but the mildest forms of SAR. They ought to be prescribed with a daily long-acting antihistamine. If SAR has been troublesome during the previous pollen season, both drugs should be started early in the subsequent pollen season before symptoms have commenced, thus reduce the potential for priming. Many of the newer more topically active nasal steroids will ablate to naso-ocular reflex and thus may prevent or relieve symptoms related to conjunctival irritation. Clinical response to TNS may not be apparent for many days and take two weeks to achieve maximal. Side effects of TNS include nasal irritation, sore throat and epistaxis. Systemic absorption from topical administration of fluticazone or mometazone is negligible and high for betamethasone and dexamethsone. Fluticazone, mometazone and budesonide have no significant effects on long term growth. Care must be taken, as adrenal suppression may occur when topical steroids are used at multiple sites eg. asthma, rhinitis and eczema. Short courses of oral steroids are rarely necessary. Long-acting depot steroids such as triamcinolone which require intramuscular injection have no place in the routine management of SAR.

Antileukotriene drugs such as monteleukast and zafirlukast have unpredictable clinical responses. As with asthma, they require a trial period of 6-8 weeks to assess efficacy. They are safe and well tolerated. They can be safely taken in conjunction with oral long-acting H1 antihistamines. Additional efficacy of the drugs used in combination is not universally recognised. They are generally less effective than topical nasal steroids. They may be useful where patients have concurrent asthma or in younger children where co-operation with intranasal therapy may be poor. Adverse effects include behavioural change, sleep disturbance and nightmares in children.

Intranasal ipratropium bromide may be useful in a subgroup of patients with persisting watery rhinorrhoea. Adverse effects include nasal dryness and epistaxis. Only rarely anticholinergic side effects such as urinary retention or glaucoma occur.

Immunotherapy

Long-term regular subcutaneous injection with pollen allergen has the potential to reduce symptoms and medication use. It is the only treatment that offers the prospect of disease modification and long-term disease remission. Only patients with severe disease requiring multiple medications with a single allergen sensitisation are suitable. Anaphylaxis is the main complication.

A promising development is sublingual immunotherapy (SLIT) with grass pollen allergen (Grazax). SLIT is safe and well tolerated. A recent Cochrane meta-analysis concluded that it significantly reduced symptoms and medication requirements. It may be somewhat less efficacious than subcutaneous immunotherapy but anaphylaxis has not been reported. The initial dose of Grazax must be given under physician supervision, subsequent doses can be taken at home.

Learning points

  • Seasonal AR is common
  • Patient symptoms are frequently underestimated by clinicians
  • The direct and indirect economic burden is high
  • Treatment guidelines are available for clinicians
  • Intramuscular steroid injections have not place in the routine management of the condition
  • Sublingual immunotherapy offers significant promise to hay fever sufferers with severe symptoms despite allergen avoidance and maximal pharmacotherapeutic intervention.

References

1. Canonica GW, Bousquet J, Mullol J et al. Assessment of the burden of allergic rhinitis in Europe. Allergy 2007; 62(85): 17-25.

 

2. Scadding GK, Durham SR, Mirakian R et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy 2008; 38(1): 19-42.

 

3. ARIA guidelines. http://www.whiar.org/docs/ARIA_PG_08_View_WM.pdf.