Allergic Rhinitis is the term given to a group of conditions that cause allergic symptoms in the nose and face. It is a common condition; estimates state that it affects between one in four, and one in six, people in Europe and North America. Originally described as ‘catarrus aestivus’ in the 19th Century, the prevalence is increasing, especially over the last two decades.Rhinitis is defined as nasal hyperfunction and tissue inflammation that leads to nasal congestion, rhinorrhoea, nasal obstruction, pruritus and sneezing. It is associated with a significant loss of productivity and reduced quality of life.
The current recommened classification for allergic rhinitis is the ARIA classification . This replaces terms such as 'seasonal rhinitis' or 'perennial rhinitis'. Rhinitis is now defined as either 'intermittent' or 'persistent' as well as a second term, either 'mild' or 'moderate-severe'.
Allergic rhinitis is triggered by the presence of allergens. Grass pollen is the commonest cause of allergic rhinitis in Britain. During the months of May, June, and July, the level of grass pollen becomes high enough to cause symptoms of seasonal allergic rhinitis, or hayfever, in susceptible people. Allergens are typically soluble low molecular weight proteins, frequently with enzymatic activity, which trigger an immune response with a low dose.
Common allergens in the UK include
Intermittent allergic rhinitis (Seasonal rhinitis)
- Timothy Grass (Phleum pratenes)
- Cockfoot (Dacylis glomerata)
- Birch Hazel
- Cladosporidium mould
- Altenaria mould
- Aspergillus spores
See also allergen calendar
Persistent allergic rhinitis (Perennial rhinitis)
- House Dust Mite faeces (Dermatophagoides pteronysinnus and farinae)
- Cat saliva
- Dog hair dander
The allergic response involves inflammation of the mucous membranes of the eyes and upper aerodigestive tract, including the nose, sinuses, middle ear and pharynx. Typically, there is an early phase response, which occurs between 0 and 30 minutes after exposure. There is sneezing, itching, rhinorrhoea, and some congestion. This is followed by a late phase response, which occurs after 6 to 8 hours. During this phase, there is a chronic itch affecting the nose, nasal cavity and eyes, with nasal congestion and conjunctivitis.
Prior to the early phase, the immune system becomes sensitised to the allergen. It is internalised and processed by antigen presenting cells, including dendritic cells, B lymphocytes and macrophages. Chemokines produced by these cells include Chemokine ligand (CCL) 2, CCL7 and CCL13. These promote class switching of T lymphocytes to a Th2 response. T cell interactions with the antigen presenting cells results in the production of Interleukin 4. This activates B cells to produce Immunoglobulin E (IgE), which becomes attached to the surface of mast cells.
Early phase response
There are several different factors that contribute to the early phase. Two of the most important factors include the role of mast cells and the role of sensory nerves.
During the pollen season, the number of mast cells in human nasal mucosa increases. These cells are sensitive to allergen, which binds to surface IgE and causes mast cell degranulation. Mast cells are sensitive to many other chemical mediators. These include Major Basic Protein (MPB) and Eosinophil Peroxidase, which are both produced by eosinophils. Immunohistochemistry has shown that mast cells also have surface substance P receptors; the level of these increases in allergic rhinitis. During degranulation, mast cells release a wide range of chemical mediators, including enzymes, cytokines, chemokines, lipid mediators and histamine. These all contribute towards the vasodilation of nasal blood vessels and the recruitment of further immune cells.
The role of sensory nerves in allergic rhinitis is less understood than the immune reaction. Sensory nerve endings in nasal mucosa react directly to the presence of antigen, triggering an axonal response. These nerve endings may also respond directly to histamine, Bradykinin and Leukotrienes. Stimulation of these nerves has several different effects. Signals sent to the brain via the pterygopalatine ganglia produce sneezing. Following central stimulation, signals are sent along parasympathetic and sympathetic pathways to the nasal mucosa. Finally, there is a local effect, where the sensory nerves themselves release neuropeptides.
Parasympathetic fibres in the nasal mucosa cause vasodilation of blood vessels and the activation of mucus secreting glands. Acetylcholine is released, and activates muscarinic M1 and M3 receptors, causing these effects. This is not the only contribution from the parasympathetic system. If atropine is used to block these receptors, there is still a strong response. Small diameter cell bodies also release Vasoactive Intestinal Peptide (VIP) as a neuropeptide. VIP causes vasodilation, smooth muscle contraction and glandular secretion in the nasal mucosa; this effect is independent of muscarinic receptors.6 The level of VIP in nasal secretions in allergic rhinitis increases and some studies show that the level of VIP staining fibres increases in allergic rhinitis. The levels of VIP increase in response to an exogenous challenge of histamine, and antihistamines, a common treatment for allergic rhinitis, cause the level of VIP in nasal secretions to fall.
Sensory nerves also release neuropeptides locally as a response to stimulation. Three important peptides are substance P, CGRP and NKA. substance P is an important peptide in the early phase of allergic rhinitis. It acts on Neurokinin 1 receptors (NK1-R) to cause vasodilation. If these are blocked with the synthetic NK1-R antagonist, SR48968, the early phase is significantly diminished. The vasodilation caused by substance P is independent of cholinergic receptors and has a faster response than histamine. The expression of fibres staining for substance P is found to increase in allergic rhinitis and the level of mRNA coding for NK1-R also increases in patients with allergic rhinitis. Certain treatments used to treat allergic rhinitis lower the level of substance P in nasal secretions; these include nasal steroids and antihistamines . Substance P also acts on mast cells directly to cause the release of histamine.
CGRP acts on CGRP-1 receptors and causes vasodilation. NKA acts on NK2 receptors and also causes vasodilation in the human nasal mucosa. Again, these effects are both independent of cholinergic receptors. Blockade of these receptors with synthetic analogues does not seem to affect the early phase response in animal models, however, it does diminish the late phase response.
Substance P, CGRP and NKA are all broken down by the enzyme Neuroendopepsidase (NEP). The NEP antagonist, phosphoramidon, potentiates the effects of all of these neuropeptides in animal models of rhinits, suggesting all of these peptides have a significant role to play.
Late phase response
During the late phase of allergic rhinitis, the number of eosinophils increases in the nasal mucosa. Activated Th2 cells produced IL-3, IL-4 and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), which all stimulate the production and activity of eosinophils. Th2 cells also produce IL-4, which in turn increases the expression of VCAM-1, the primary adhesion molecule required for the migration of eosinophils across endothelium. Antigen presenting cells secrete CCL3, which stimulates eosinophils.
Neuropeptides also play a role in eosinophil migration. Substance P, CGRP, Neurokinin A and VIP all have various effects on eosinophil chemotaxis and migration, which can be blocked by synthetic antagonists to their respective receptors.
Eosinophils release a wide range of mediators that cause the effects seen in the late phase of allergic rhinitis. These include enzymes, toxic mediators, cytokines, chemokines and lipid mediators. Several of these contribute towards mast cell degranulation, including Major Basic Protein and Eosinophil Peroxidase. The various toxins produced also stimulate sensory nerve fibres, either by direct activation, or by causing damage to nearly cells, releasing contents such as potassium ions, which in turn stimulate the nerves.
The cardinal symptoms of allergic rhinitis are sneezing, itching, rhinorrhoea and congestion. Nasal discharge is clear and watery. Pruritis affect the nose, eyes and pharynx. The eyes become sore, and there is conjunctivitis, and periorbital oedema. Asthma and eczema are present in a third of individuals. On examination, the nasal mucosa is livid and pale. In acute stages, the mucosa may be red. The turbinates become swollen and there are large amounts of clear secretion.
Obtaining a full clinical history is important. This should include details of the onset and duration of symptoms, as well as exposure to possible allergens. A family history is supportive of a diagnosis. Effects on the quality of life, including fatigue and the ability to function at work should be recorded.
Clinical tests can support the diagnosis. These include skin-prick allergy testing, where a series of common allergens and controls are used to determine specific sensitivity. An alternative test is the radioallergosobant test (RAST), a blood test which measures the level of IgE present for a specific allergen. Blood testing can also include total IgE level or eosinophil levels, however, these are neither specific nor selective.
The treatment of allergic rhinitis is based around avoidance of allergen and medical treatment of symptoms. Once the causative allergen is known, steps can be taken to avoid it, including the use of filters and allergen resistance fabrics for bedding and clothing.
The medical treatment options are somewhat limited. Antihistamine and corticosteroid therapies make up the main treatment of allergic rhinitis and can be effective monotherapies. Frequently, their use is combined. Other treatments exist, but are less effective.
A variety of antihistamines exist. Most of these are non-sedating second generation antihistamines. These selectively compete with histamine for the H1 receptor, reducing the symptoms of rhinitis. Most are given orally although preparations in the form of nasal sprays exist.
The use of nasal corticosteroids is the other main form of treatment in allergic rhinitis. The steroid ingredient dampens down any immune response. Modern nasal sprays are designed to have low bioavailability; this means they are not rapidly removed from the nasal environment and have long lasting effects. In some cases, oral steroids or subcutaneous long-lasting steroids can be used.
Decongestants are a frequently used over-the-counter remedy. They reduce vasodilation in the nose, and therefore congestion. However, their long-term use can cause long-term problems, especially rhinitis medicamentosa, in which their over-use causes rhinitis.
Intranasal anti-cholinergics have been used as a combination therapy. They are thought to reduce vasodilation.
Topical cromolyns are used in the nose and eye. Their exact mechanism is not known. Traditionally, they are claimed to prevent mast cell degranulation; however, there is no good evidence to show this. Again, they are used in combination with antihistamines and steroids.
Leukotriene inhibitors such as Montelukast have been used successfully as an adjuvant therapy in asthma. Their use is becoming more popular in cases of combined allergic rhinitis and asthma.
Immunotherapy and desensitization
Immunotherapy is an underused mode of treatment. It involves exposure of the individual to an injected or sublingual presentation of antigen. This carries the potential risk of a major allergic response, but modern approaches have reduced these events. It is thought to work by reducing the total level of IgE, decreasing the level of sensitivity of histamine secreting cells and decreasing the responsiveness of lymphocytes. Immunotherapy is aimed at a monoallergy, which must be confirmed on skin testing or serum IgE levels.
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