Allergic Rhinitis: The Disease Immunology and Translation to Modern Medicine

Allergic rhinitis (AR) is a common inflammatory airway disorder triggered by airborne-related allergens. While this is not a life-threatening medical condition, it can be debilitationg — affecting a person’s quality of life; causing poor quality of sleep, suboptimal work performance and social interaction impairment.

In this article, we want to understand the background science and immunology of allergic rhinitis and make sense of the current treatments available, including the exciting option of immunotherapy.

What is allergic rhinitis?

Allergic rhinitis is an upper airway disease resultant from sensitisation of allergens and proteins in the air during breathing. The classical symptoms involve the upper respiratory airway such as sneezing, nasal itch, increase nasal secretion, blocked nose and etc. Common inhalant allergens that can trigger allergic rhinitis include house dust mite particles, mould, animal dander, grass, birch and pollen, cockroach particles and more.

Immune Response in Allergic Rhinitis

In allergic rhinitis, following exposure to allergens, the immune response undergoes 2 phases:

1. Early phase

The inhaled allergen protein will be ‘carried’ and ‘presented’ by a type of specialised cells known as Antigen Presenting Cells (APCs) to the nearby lymph nodes. Lymph nodes are ‘checkpoints’ in our body that store immune cells. 

The allergen proteins then trigger a cascade of inflammatory response from the immune cells. Immune cells that are commonly involved in this phase include T cells, B cells, IgE antibodies, mast cells, ILK-4, IL-13, histamine, prostaglandins, leukotrienes, TNF-alpha and etc.

2. Delayed phase

Following 4-6 hours of exposure to allergen protein, there will be further chemical inflammatory response involving cells such as monocytes, granulocytes, protein elastase and etc.

*Understanding the involvement of immune cells is imperative as this becomes the target area of modern medicine in allergic rhinitis. 

The surge of inflammatory response in the early and delayed phase can be translated to the clinical symptoms of allergic rhinitis such as acute sneezing, itching, runny and block nose. Symptoms tend to abate when the allergen is withdrawn or avoided. 

Over time, with recurring exposure and recurring inflammatory immune response, repeated wax and wane of condition, remodeling of the affected airway can occur. This explains the association of chronic allergic rhinitis with more complicating ENT conditions such as nasal polyps, nasal hyperplasia, eosinophilic sinusitis and more.

Association of Allergic Rhinitis, Asthma and Chronic Rhinosinusitis

Interestingly, allergic rhinitis can be associated with asthma and chronic rhinosinusitis. The actual cause of association remains not fully understood. However, in these conditions, when one is exposed to allergens, there are similar inflammatory immune response demonstrated. 

Statistics show 10-40% of people with allergic rhinitis have concurrent allergic asthma, while 60-80% of asthma people have concurrent allergic rhinitis. In chronic allergic rhinitis, when there is repeated and resolution of airway inflammation, remodeling of the airway anatomy can result in chronic rhinosinusitis or nasal polyps and other ENT conditions.

Modern Treatment of Allergic Rhinitis

The ideal treatment of allergic rhinitis is to eliminate the triggering allergen from the environment. This, unfortunately, even with strict lifestyle allergenic control is not achievable and not practical.

Current management of allergic rhinitis involved a holistic approach of combining modern medicine with lifestyle control of environmental allergen to alleviate the condition.

• Antihistamines — Antihistamines are used commonly to abort and alleviate the allergic respiratory symptoms. There are currently newer generation anti-histamine with better safety profile (non-drowsy, safe for the heart and kidney), faster and longer acting in managing allergic rhinitis.
  
• Leukotriene receptor antagonists —  Leukotriene receptor antagonists, such as montelukast, can be used concurrently with antihistamine to reduce inflammatory response leading to less mucus production and nasal congestion.
  
• Nasal sprays — Nasal sprays with combination of decongestants and corticosteroids can be safely used to reduce nasal cells and mucosal swelling and reduce inflammation in the nose.

• Sodium chloride solution — Sodium chloride solution nasal wash can be recommended as a treatment to complement the effect of the medications above.

Despite current conventional treatment is beneficial in controlling symptoms of allergic rhinitis, one may find taking daily pills, nose sprays or nasal irrigation a challenge and burden to our daily living. 

In addition, the symptomatic medications may even be limited in efficacy in some patients. To address these concerns, immunotherapy can be considered as a potential therapeutic option.

Allergen Specific Immunotherapy

Not all patients with allergic rhinitis find conventional medical treatment useful. Allergen specific immunotherapy (AIT) may come in useful and serve as a safe alternative treatment. AIT is a desensitization treatment where the triggering allergen is repeatedly introduced to the affected person over time to modify the immune response, inducing desensitization and amelioration of allergic symptoms after exposed to allergen.

AIT is arguably to achieve immune tolerance against allergen in the affected person over time following repeated re-exposure. In immunology terminology, with repeated exposure to the allergen, the body is able to normalised its own immune and inflammatory cells, preventing them from being triggered by allergens. AIT also produces allergen-neutralising antibodies that prevent allergen from triggering allergic inflammatory response. In clinical setting, 

Here, we can observe the treatment of allergic rhinitis has shifted from conventionally controlling symptoms with symptomatic medication to management and re-education of the immune response to an allergen, hence transforming the immune system that is exaggeratingly overactive to 'normal' immune reaction towards allergen protein. 

It is worth to note that in order to consider AIT, it is mandatory to identify the specific culprit allergen that causes the symptoms. Thankfully, again with modern medicine and technology, many of the common allergens can be picked up with skin prick test or IgE RAST blood test.

Overall Effectiveness of Allergen Specific Immunotherapy

Medical literature over the years has shown consistently that AIT is useful in alleviating allergic rhinitis symptoms and standard medication burden. Currently, AIT can be considered in allergic rhinitis patients with specific IgE allergy that present with significant symptoms that affect their daily life, sleep despite conventional pharmacological treatment.

AIT demonstrates effective management of allergic rhinitis with concurrent allergic asthma. AIT has shown clinical significance in reduction of both allergic rhinitis and asthma symptoms, asthma exacerbations and hospitalisation. AIT also shows good clinical improvement in those with allergic rhinitis and concurrent rhinosinusitis disorders.

Furthermore, AIT when introduced during the early phase of allergic disease can prevent progression of allergic rhinitis to asthma or new allergen sensitisation. This is particularly useful and a beneficial option for the younger group people with allergic rhinitis. This can also serve as a backbone theory in further research and medical advancement into immuno-desensitisation related treatment.

What have I learnt today?

• Allergic rhinitis is a common upper airway inflammatory disorder that can be triggered by airborne related allergens.
  
• A person with allergic rhinitis is more predisposed towards other upper respiratory allergic disorders such as asthma, rhinosinusitis, nasal polyps and etc.
  
• Upon exposure to allergen particles, there can be a downstream trigger of allergic inflammatory response of the immune system, leading to clinical symptoms of allergic rhinitis.
  
• Conventional treatment of allergic rhinitis include lifestyle reduction in exposure of airborne allergens and symptomatic medications to reduce inflammation and clinical symptoms. 
  
• Allergen specific immunotherapy modifies the body's immune response towards allergen, strives towards down-regulation and normalisation of immune system towards allergen upon repeated exposure towards the allergen.
  
• There is increasing evidence to support allergen specific immunotherapy in effective management of allergic rhinitis with specific IgE-rleated allergen. This is also beneficial in those with concurrent asthma and chronic rhinosinusitis.

References:

1. Sharma K, Akre S, Chakole S, Wanjari MB. Allergic rhinitis and treatment modalities: a review of literature. Cureus. (2022) 14(8):e28501. 
2. Bousquet J, Anto JM, Bachert C, Baiardini I, Bosnic-Anticevich S, Walter Canonica G, et al. Allergic rhinitis. Nat Rev Dis Primers. (2020) 6:95. 
3. Guerra S, Sherrill DL, Martinez FD, Barbee RA. Rhinitis as an independent risk factor for adult-onset asthma. J Allergy Clin Immunol. (2002) 109(3):419–25.
4. Bousquet J, Schünemann HJ, Togias A, Bachert C, Erhola M, Hellings PW, 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. 
5. Husna N, Tan SM, Md Shukri HT, Mohd Ashari NS, Wong KK. Allergic rhinitis: a clinical and pathophysiological overview. Front Med (Lausanne). (2022) 9:874114.