Etiopathogenesis and Management of Perennial Allergic Rhinitis

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Abstract
Perennial allergic rhinitis is an inflammatory disorder characterized by symptoms of nasal congestion, rhinorrhea, sneezing, and itching. The prevalence of allergic rhinitis is quite common and affects 20% or more of various populations. Some patients with allergic rhinitis are symptomatic only during the pollen season, while many others are allergic to multiple allergens including indoor allergens such as house dust mites, animal dander, cockroaches, and fungi, which lead to perennial symptoms. Immunoglobulin (Ig)-E is the proximate cause of perennial allergic rhinitis. Circulating IgE antibodies bind to the high affinity IgE receptor on mast cells and basophils. IgE antibodies, bound to the receptors crosslinked by allergen, initiate the secretion of inflammatory mediators including histamine, leukotrienes, and cytokines. These mediators can induce both acute and chronic changes that result in symptoms of allergy. Many therapies are approved for the treatment of allergic rhinitis including intranasal corticosteroids, antihistamines with or without decongestants, and nasal cromolyn sodium (sodium cromoglicate). Allergen avoidance is the mainstay of therapy for many patients but is not always practical. For those patients who have not responded to appropriate medications, allergen specific immunotherapy may also be effective. A number of studies with omalizumab have shown that it is effective in the treatment of seasonal allergic rhinitis induced by pollen such as ragweed and birch pollen. Omalizumab is a molecularly cloned humanized monoclonal antibody inhibiting human IgE. It binds specifically to the region of the IgE molecule that binds to the IgE receptor on the mast cell or basophils. Because omalizumab cannot bind IgE molecules that are already bound to the surface receptors on mast cells and basophils, it does not stimulate secretion of mediators from these cells. Omalizumab does not appear to stimulate an immune response against itself. It rapidly reduces free serum IgE levels by over 95% when administered at therapeutic doses and also results in the reduction of IgE receptors on mast cells and basophils. The combined effects of reduction of both free IgE in serum and the receptor density on the mast cells or basophils results in decreased allergen-stimulated mediator release. Preliminary studies in the treatment of perennial allergic rhinitis supports omalizumab’s efficacy and safety. The compound has been well tolerated. Aside from urticarial reactions, adverse effects appear to be minimal. Omalizumab is the first of several new immune-based specifically targeted molecules that may prove to be extremely valuable in the treatment of perennial allergic rhinitis, as it is often unresponsive to traditional therapies.

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