Mechanisms of allergy

Allergic Rhinitis is one of the most common diseases, with a worldwide prevalence ranging from 2.2% to 45.5% in children between the ages of 6 and 14 (1) and in adults (2). Symptoms include nasal obstruction, rhinorrhoea, nasal itching and sneezing, which can be disruptive to sleep and lead to negative impacts on daily function and performance (3). Avoidance of allergens is the first-line treatment but often is not feasible.

The clinical signs and symptoms of allergic inflammation are mediated by the release of histamine by mast cells (4). Mast cells are produced in bone marry from myeloid progenitor and then migrate to tissues. The function of mast cells is not yet discovered, but the hypothesis is that they play role in tissue reparation as well as take part in anti-parasitic immune response.

Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma (5).

In allergy mast cell activation is IgE dependent. To trigger the release of histamine and other mediators two neighbouring receptors with specific IgE antibodies to the same allergens need to be crosslinked with that specific allergen in this case there will be allergen specific degranulation that we emulate when doing skin prick test.

When histamine is released it bind local receptors on blood vessels and nerves resulting in itchiness and leakage of fluid out of the blood vessels resulting in swelling. This manifests as symptoms nasal obstruction itching. Seasonal/perennial allergic conjunctivitis is the most common allergic conjunctivitis, usually with acute manifestations when a person is exposed to allergens and with typical signs and symptoms including itching, redness, and tearing (4).

Diagnostic tests

Diagnostic tests that are currently used include skin prick test and evaluation of specific IgE antibodies to whole allergens or parts (allergenic components) (by classic ImmunoCAP or micro-array technique ImmunoCAP ISAC) (6).

Skin prick testing is performed in allergy clinics, it is quick test (results are available within 15 minutes), but has limitations as the results are affected (false negative results) by use of antihistamines and other mediation with antihistamine activity (sleeping tablets antidepressants), but occasionally can be inconclusive due to dermatographism (false positive results).

Measurement of specific IgE is a useful method that gives slightly different information to SPT as it measures total and specific IgE in the blood stream. Results need to be reviewed in light of clinical history, as the detection can be affected by non-specific binding (in patients with high total IgE), levels of specific IgE do not necessarily correlate with severity of symptoms. Component test ISAC can be used in patients with high total IgE situation and non specific binding in immunocap test.

Serum eosinophil percentage (cut-off value, 3.8%) was associated with the newly developed allergic nasal symptoms (sensitivity, 77.9; specificity, 41.8). A high serum TIgE concentration (cut-off value, 17.7 IU/mL) was also associated with the risk for allergic sensitization (sensitivity, 46.3; specificity, 85.3) (7).

Nasal/Ocular Challenge is done when it is difficult to identify the allergen that is triggering symptoms and specific immunotherapy is planned. It is usually done in graded manner until measurable symptoms occur (nasal obstruction documented by rhinomanometry or exhaled nasal peakflow) or appreciation of redness in case of ocular challenge.

Treatment options

Treatment options depend on severity of symptoms. Nasal irrigation is confirmed useful by the first evidence that nasal lavage with isotonic saline relieved the nasal symptoms of children with allergic rhinitis and improved the parental perception of the disease (8).

Histamine antagonists (also called antihistamines) inhibit the action of histamine by blocking histamine H1 receptors, antagonising the vasoconstrictor, and to a lesser extent, the vasodilator effects of histamine. Mast cell stabilisers inhibit degranulation and consequently the release of histamine by interrupting the normal chain of intracellular signals.

Antihistamines are molecules that bind histamine receptors on blood vessels and nerves, but do not activate them, thus prevent symptoms by occupation of receptors not allowing histamine to bind with the receptors. This process is dose dependent and there were studied that showed that higher dose of the same antihistamine will work better, comparing to use of two different molecules at the same time due to competition between the structures for the histamine receptors.

Topical treatments include eye drops with antihistamines, mast cell stabilisers, non-steroidal anti-inflammatory drugs, combinations of the previous treatments, and corticosteroids. Standard treatment is based on topical antihistamines alone or topical mast cell stabilisers alone or a combination of treatments (4). It was shown that combination therapy further improves symptom reduction (9).

Atopic conjunctivitis is treated with antihistamines, cromoglycate and short courses of corticosteroids, in severe cases with subcutaneous or sublingual immunotherapy (10).

Experience for 30 years and a long series of controlled studies have shown that the treatment with intranasal steroids is highly effective and that the side effects are few. However, the exact mechanism behind the marked clinical effect remains unclear. Topical glucocorticosteroids are highly effective in diseases characterised by eosinophil-dominated inflammation (allergic rhinitis, nasal polyposis), but not in diseases characterized by neutrophil-dominated inflammation (11).

While the high efficacy of this class of medication is well known, the wide range of adverse effects, both local and systemic, is not well elucidated. It is imperative to monitor total steroid burden in its varied forms as well as tracking for possible side effects that may be caused by a high cumulative dose of steroids (12).

Mast cell stabilising drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for treatment, there still remains an urgent need to design new substances (13)

Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Moreover, specific products for allergen specific immunotherapy have shown to have disease-modifying capacities being able to prevent the progression of allergic diseases, as in the case of hay fever that may frequently lead to asthma and to reduce the risk of new sensitisations (14).