Allergic Rhinitis in Focus
Allergy Ireland's Dr Iseult Sheehan features in the Medical Independent in June 2022.
Medical Independent: Allergic Rhinitis in Focus
Allergic Rhinitis (AR) is a common condition with a global impact. In Ireland, at least 1 in 5 people suffer with Allergic Rhinitis.(1) The economic impact is striking. The European Union has recently estimated that the indirect cost of undertreated AR on work productivity may cost between €30 and €50 billion per year.(2)
The symptoms of Allergic Rhinitis are often considered to be trivial and as such Allergic Rhinitis is underdiagnosed and undertreated. However, the burden of this disease is significant with a reduced quality of life for these individuals. It has been shown to affect cognitive and psychomotor function. Though patients describe the impact on sleep as considerably debilitating.
While struggling with Allergic Rhinitis symptoms the ability to participate in social and sporting activities are reduced and missed days at work are a feature.
In addition, Allergic Rhinitis has a worrying impact on a child’s education. Missed or unproductive days at school are common. This becomes particularly apparent during hay fever season which coincides with exam time. A UK study of teenagers found that there was a reduction in exam performance for those with seasonal Allergic Rhinitis compared with other times of the year.(3) This is most relevant for Leaving Certificate students and those in University.
Epidemiology
It is estimated that Allergic Rhinitis affects at least 400 million people worldwide and the prevalence within Europe is between 17 and 29%. The UK has a prevalence of 26% and Ireland is likely to be similar to this. (1)
AR will often begin early in life but prevalence increases with age. The International Study of Asthma and Allergies in Childhood (ISAAC, 2006) phase III study demonstrated this showing a 5% prevalence in those aged 3 years, an 8.5% prevalence in those aged 6-7 years and a 14.6% prevalence in those aged 13-14 years. (4)
What is most concerning is that the prevalence of AR is increasing globally. This was corroborated by this ISAAC study which found an increase in prevalence of AR from 13% to 19% over an 8 year period in a cohort of 13-14yr olds. (4) A smaller study in Cork demonstrated an increase in prevalence from 7.6% to 10.6% over a 5 year period in a cohort of 6-9yr olds. (5)
Nature versus Nurture
The cause for this rising prevalence is unclear although risk factors may include overuse of antibiotics, exposure to air pollution, maternal/passive smoking and climatic factors among other theories (6).
Certainly, environmental exposures are key to understanding the rising prevalence of allergies. The ‘hygiene hypothesis’ was proposed as an explanation whereby the more sterile Western lifestyle was reducing infections and resulting in less type 1 immune responses. More recently, there is a better insight into the development of allergen tolerance with the microbiome during early life being an essential component. Antibiotic use will disrupt this amongst other environmental factors. Exposure to irritants such as cigarette smoke and air pollution particularly diesel exhaust fumes have been shown to contribute to and exacerbate Allergic Rhinitis.
In addition, global warming is seen to be playing a role in Ireland with milder weather resulting in prolongation of pollen and spore seasons. This is confounded by the introduction of new pollens such as ragweed which would usually be a common allergen in North America and Continental Europe.
Nevertheless, Allergic Rhinitis appears to be the consequence of environmental exposures in those with a genetic vulnerability. Indeed, genetic predisposition or atopy accounts for at least 50% of Allergic Rhinitis cases and genetic studies have demonstrated that multiple susceptible loci can contribute to AR alone. (7,8)
Multimorbid Allergic Rhinitis
Multimorbid Allergic Rhinitis is whereby Allergic Rhinitis and asthma or atopic dermatitis co-exist. Interestingly a differing variety of genetically susceptible loci are attributable to multimorbid Allergic Rhinitis for example IL-5 and IL-33 for those with Allergic Rhinitis and asthma (8).
Allergic Rhinitis is a risk factor for asthma. In fact 90% of asthmatics have Allergic Rhinitis and 30-40% of those with Allergic Rhinitis have asthma (9). A ‘united airways’ disease approach to management is the more favoured approach in recent years. Moreover, the treatment of nasal inflammation in asthmatics has been shown to improve outcomes. This highlights the importance of assessing for both asthma and rhinitis in these patients.
Allergic Rhinitis can also be associated with comorbid dermatological conditions such as atopic dermatitis and urticaria upon exposure to an allergen. Interestingly, the treatment of Allergic Rhinitis can very often result in improvements in these dermatological conditions.
Presentation
Allergic Rhinitis is an IgE mediated inflammatory reaction following exposure to an allergen. This results in inflammation of the nasal lining and/or conjunctiva. The symptoms characteristically include rhinorrhoea, nasal obstruction, sneezing and nasal itching.
Additionally symptoms will often include an itchy palate, irritated watery itchy eyes with associated periocular oedema or dark rings under the eyes (allergic shiners!).
Patients can experience fatigue, snoring, mouth breathing due to nasal obstruction and a feeling of heaviness in the head or a ‘fuzzy’ head. If the sinuses are affected the patient may experience sinus pressure and headaches and a post nasal drip. Compression of the olfactory nerve due to oedema within the nasal cavity can result in an altered sense of smell and/or taste.
Pathophysiology
There are two phases which are paramount to the development of an allergy. Phase one occurs when an atopic individual is first exposed to the allergen. The allergen is taken up by antigen presenting cells particularly dendritic cells (DC) and is processed into peptide fragments. The DC will move through the lymphatics towards the lymph node where it will present this peptide fragment to a naïve T cell.
The naïve T cell becomes activated to express cytokines particularly IL-4 which drives the differentiation of these cells to Th2 helper cells.
An environment rich in cytokines IL-4 and IL-13 is created and is responsible for inducing IgE production from B cells. Additionally, IL-5 is responsible for eosinophil recruitment and activation. The cytokine profile is vital as it determines a Th2 immune response.
In the meantime, T cell dependent activation of B cells stimulates further cytokine production particularly IL-4 and promotes irreversible immunoglobulin class switching to allergen specific IgE antibodies.
Allergen specific IgE will attach to mast cells and basophils. This is referred to as primary sensitisation. In addition, memory B cells are generated and a small number of memory T cells remain.
Phase two occurs on subsequent exposure to this allergen. The allergen binds to the sensitised mast cells triggering degranulation of the mast cell releasing pre-stored and newly synthesised inflammatory mediators such as histamine, leukotrienes and prostaglandins. These contribute to vascular permeability, eosinophil infiltration and increased mucus production.
Furthermore, with repetitive allergen exposure nasal priming occurs. This appears to cause an accumulation of effector cells in the nasal mucosa and results in a hyper-responsiveness to the allergen and prolongation of symptoms. In addition, there appears to be a neural component to this hyper-responsiveness. Changes to the sensory nerves of the nose have been demonstrated in those with Allergic Rhinitis. In addition, innate immune responses can be initiated in the nasal epithelium by allergens directly compromising the epithelium and resulting in the release of alarmins such as IL-33 further activating the inflammatory response.
Classification of Allergic Rhinitis
Allergic Rhinitiscan be divided into seasonal and perennial based on allergen triggers. Seasonal rhinitis includes sensitisation to grass, tree or weed pollen and fungal spores. Whereas perennial rhinitis is commonly triggered by house dust mite or animal dander. This classification system is effective at giving a likely diagnosis of the trigger which assists with recommending appropriate avoidance measures.
However, a new classification system focusing on the functional ability of the patient, including the frequency and severity of symptoms, has become a much more effective tool for making treatment decisions. This was developed by Allergic Rhinitis and the Impact on Asthma (ARIA) guideline in collaboration with the World Health Organization. (9)
Diagnosis of Allergic Rhinitis
The diagnosis of Allergic Rhinitisis generally based on clinical symptoms. However skin prick allergy testing or specific IgE blood testing can be used to confirm the allergen trigger.
In addition, it is vital to examine the nose whereby you will often see bulky oedematous turbinates with visible increased mucus production. Pallor of the mucosal lining is often present, particularly in long-standing cases. Occasionally the mucosa will lose its smooth appearance and instead will have ridges and pitting from chronic allergic challenge. Pre-polypoid tissue can occasionally be present.
Non-Pharmacological Management
Allergen avoidance should be discussed. Nevertheless avoidance alone is generally not sufficient to manage symptoms. In cases where the allergen trigger is animal dander avoidance is effective if the animal is removed from the home.
Smoking cessation should be advised always. Smoking can be associated with chronic nasal symptoms and may even be associated with the development of polyposis. Passive smoking or ‘vaping’ appear to carry similar risk.
Saline irrigation is an effective way to directly cleanse the nasal cavity with the resultant reduction of mucus, inflammatory mediators and bacterial burden. It has also been shown to improve mucociliary function.
Pharmacological Management
In patients with mild intermittent symptoms an antihistamine is often effective. Second generation antihistamines are recommended as they carry less cholinergic and sedating side effects. Oral or nasal decongestants can be used as a rescue medication but for no longer than 5 days to avoid rebound symptoms.
The ARIA guideline recommends intranasal corticosteroids as the first line treatment for moderate-severe intermittent or persistent Allergic Rhinitis. (9) A low bioavailability is recommended and so newer generation intranasal corticosteroids are preferred.
If the nasal cavity is very obstructed a nasal spray may not be effective until the oedema has been reduced using intranasal corticosteroid drops. Should this not be effective a combination intranasal treatment is now available combining corticosteroid and antihistamine.
Eye symptoms can be managed conservatively with cold compresses and tear supplements. However, if these symptoms persist, it is advisable to consider oral and topical antihistamines, topical mast cell stabilizers (sodium cromoglicate) or decongestants. Topical corticosteroids should ideally be prescribed under the care of an Ophthalmologist.
If there is evidence of lower airway irritability or asthma, a leukotriene receptor antagonist can be trialed. In severe cases short courses of oral corticosteroids are occasionally required.
Newer Treatment Options: Immunotherapy
Immunotherapy has been shown to significantly reduce symptoms and medication requirements and is recommended by the ARIA guideline. Additionally, the Global Initiative for Asthma (GINA) 2020 guideline recommends immunotherapy can be considered for asthmatics sensitised to dust mite. (11) Immunotherapy involves exposing a patient to minute quantities of the allergen trigger allowing the immune system to build up a tolerance. It is essentially like a vaccination. It can be given as a subcutaneous injection or as a sublingual tablet. Sublingual therapy is used predominantly in Ireland and is currently available for grass pollen, dust mite and tree pollen. Compliance is crucial and regular follow up advised. It is usually a three year process whereby the patient takes it daily. It is highly effective and well tolerated.
Newer Treatment Options: Endonasal Phototherapy
Phototherapy is well established for skin conditions and is now being used within the nasal cavity to manage AR. It uses UV-A (25%), UV-B (< 5%) and visible light (70%) to induce a local immunosuppressive effect by inhibiting allergen induced histamine release from mast cells and inducing apoptosis of T lymphocytes and Eosinophils. It essentially desensitises the nasal cavity thus reducing symptoms. It is particularly useful when pharmacological treatment is insufficient or contraindicated.
Author
Dr. Iseult Sheehan
Clinical Director, Allergy Ireland (www.allergy-ireland.ie)
MICGP, FRACGP, MB BAO, BCh, LRCP&SI, BA (Hons) Biochem & Immunol
References
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2. Zuberbier T, Lötvall J, Simoens S, Subramanian SV, Church MK. Economic burden of inadequate management of allergic diseases in the European Union: a GA(2) LEN review. Allergy 2014; 69(10): 1275-9.
3. Walker S, Khan-Wasti S, Fletcher M, Cullinan P, Harris J, Sheikh A. Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study. J Allergy Clin Immunol 2007; 120(2): 381-7.
4. Asher MI, Montefort S, Björkstén B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006; 368(9537): 733-43.
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8. Lemonnier N, Melén E, Jiang Y, et al. A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents. Allergy 2020; 75(12): 3248-60.
9. Bousquet J, Schünemann HJ, Togias A, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol 2020; 145(1): 70-80.e3.
10. Bousquet J, Anto JM, Bachert C, et al. Allergic rhinitis. Nature Reviews Disease Primers 2020; 6(1): 95.
11. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2020. Available at: https://ginasthma.org/. [Last accessed on 3rd January 2021].