Allergic rhinitis

AR is a multifactorial disease with genetic and environmental components. AR is highly heritable.[15]

The risk of developing atopic disease in the absence of parental family history has been reported to be 13%.[16] The risk increased to 29% if one parent or sibling is atopic, 47% if both parents are atopic, and 72% if both parents have the same atopic manifestation.[16]

One genome-wide association study, which included 59,762 cases of European ancestry, identified 41 risk loci for AR. Genes involved in various immune pathways were implicated in AR pathogenesis; fine mapping of the HLA region suggested specific amino acid variants that are important for antigen binding.[17]

Environmental factors and gene-environment interactions may play an important role in AR development.[18][19][20] Epidemiological studies implicate exposure to aeroallergens, indoor dampness-related exposures, and living in an urban environment.[21][22][23][24] Changes to the intestinal microbiome may contribute to increased prevalence of allergic disease in industrialised nations (the 'microflora hypothesis').[25][26][27][28][29] According to this hypothesis, the intestinal microbiome of Westerners may be altered by certain lifestyle factors (e.g., antibiotic use and dietary factors) that may predispose to the development of allergy.[25]

In susceptible individuals, exposure to a variety of environmental aero-allergens leads to allergic sensitisation, which is characterised by the production of specific IgE directed against these proteins. This process begins with the binding of the allergen by antigen-presenting cells, such as dendritic cells, in the nasal mucosa that process the captured allergen and present it to T cells. Ultimately, this may lead to the production of allergen-specific IgE, which binds to high-affinity IgE receptors present on the surface of mast cells in the nasal mucosa.

Once mast cells are sensitised to specific allergens, re-exposure to the allergen in quantities sufficient to cause cross-linking between allergen and adjacent IgE molecules will lead to degranulation of the mast cell and initiation of various pro-inflammatory events, such as synthesis of interleukins and inflammatory cell infiltration. The effects of mast cell activation may be separated into two separate processes termed the early phase and the late-phase response.

The early phase begins within minutes of allergen exposure and is primarily due to mast cell release of pre-formed mediators, including histamine, tryptase, chymase, kinins, and heparin. Other substances that are rapidly synthesised include cysteinyl leukotrienes (CysLTs) and interleukins, among others. Clinically, this process results in mucous gland stimulation leading to rhinorrhoea, sensory nerve stimulation (which leads to sneezing and itching), and vasodilation (which results in mucosal and sinusoidal swelling and nasal obstruction).

Over 4 to 8 hours, the events of the early phase result in the recruitment and migration of other inflammatory cells to the nasal mucosa, including eosinophils, lymphocytes, and macrophages. These cells become activated and release their mediators into the milieu, perpetuating and amplifying the inflammatory process. Symptoms of the late-phase response are characterised less by sneezing and itching than the early phase and more by congestion and mucus production.

Allergic Rhinitis and its Impact on Asthma (ARIA) classification[1][2]

The ARIA classification of AR is based on severity, duration of symptoms, and impact of social life, school, and work.

Intermittent: symptoms are present

<4 days a week or for <4 consecutive weeks/year.

Persistent: symptoms are present

≥4 days a week and for ≥4 consecutive weeks/year.

Mild: none of the following items are present

Sleep disturbance
Impairment of daily activities, leisure, and/or sport
Impairment of school or work
Troublesome symptoms.

Moderate/severe: one or more of the following items are present

Sleep disturbance
Impairment of daily activities, leisure, and/or sport
Impairment of school or work
Troublesome symptoms.

Classification by symptom severity[1][3][4]

Mild rhinitis severity: present when symptoms are not interfering with quality of life such as impairment of daily activities, work or school performance, and sleep.

Moderate/severe rhinitis: present when symptoms are troublesome or there is a negative impact on any of these parameters.

Classification by temporal pattern of allergen exposure[3][5]

AR can be classified as being seasonal or perennial, depending on whether an individual was sensitised to cyclic pollen or year-round allergens such as dust mites, pets, cockroaches, and moulds.

This classification scheme has been shown to be artificial and often inconsistent, because, depending on the locale, allergic sensitisation to multiple seasonal allergens can result in year-round disease, and, conversely, allergic sensitisation to 'perennial' allergens such as animal dander can result in symptoms during only a limited period of time. Thus, medical management of these patients is better informed by considering patients as having intermittent or persistent symptoms.

Aetiology

Pathophysiology

Classification