Allergic rhinitis, the second leading cause of chronic disease in the United States, affects up to 60 million Americans, approximately one person in every four households. Of those affected, more than half have experienced symptoms for longer than 10 years (1
). Allergic rhinitis has a substantial effect on patient’s quality of life, sleep, school performance, and productivity. Physicians should also be aware of the association of allergic rhinitis with other conditions such as asthma. Asthma is both underdiagnosed and suboptimally controlled in the United States (2
). This chapter focuses on the epidemiology, diagnosis, and treatment of allergic rhinitis.
DEFINITION AND GENETICS
Allergic rhinitis is clinically defined in the 2008 Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines as “a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation” (3
). Normally, harmless particles elicit an unnecessary immune response in patients with allergies. It is the inflammation that causes their symptoms. When harmless nonself substances cause inflammation, they are called hypersensitivity reactions. Atopy is the genetic predisposition to develop allergic hypersensitivity reactions. Examples of allergic disease are allergic rhinitis, allergic asthma, atopic dermatitis, and food allergies. One atopic condition tends to put individuals at risk for others.
Atopic conditions occur more frequently in children when parents are atopic, but do not follow simple Mendelian patterns of inheritance. The genetics of allergic rhinitis is complex and not well understood. Initial speculation was that the genetics of allergy was based in alterations of the inflammatory process. Single-nucleotide polymorphisms (SNPs) of inflammatory mediator genes were targeted. Some allergic individuals were found to have more SNPs in genes coding for allergic inflammation including interleukins IL-4, IL-13, and T-cell receptors than nonallergic controls (4
). Many SNPs of inflammatory mediators have been found to be weakly associated with allergic patients, but these findings have been hard to reproduce (4
). Broader studies such as the Genome Wide Association studies have identified gene candidates that were not directly linked to the allergic inflammatory cascade (5
). It is likely that a combination of factors of innate immunity and variable changes in the regulation of inflammation may both contribute toward allergic hypersensitivity.
Allergic rhinitis is genetically a heterogeneous disease. As such, the predisposition for allergic rhinitis is influenced by multiple, perhaps hundreds, of genetic variables. An example of a gene affecting innate immunity influencing allergic disease can be seen in atopic dermatitis. A defect in the protein filaggrin has been identified in about one-third of those with atopic dermatitis (6
). Filaggrin is a protein that helps connect or seal the outer layer of keratinocytes, and it is speculated that the genetic “loss of function” makes the skin barrier more porous. A filaggrin barrier defect may augment any genetic tendency toward promoting inflammation through increased allergen exposure through the more porous keratinocyte connections.
BASIC IMMUNOLOGY OF ALLERGY
IgE-mediated hypersensitivity (Gel and Coombs Type 1) defines allergic disease. An allergen is recognized by an antigen-presenting cell (APC) then processed and presented to a T-helper cell lymphocyte. Specific human leukocyte antigen receptors on the APC and a specific T-cell receptor are both necessary for this communication to take place. TH2 cells, a specific type of T-helper cell, are predisposed toward promoting allergic inflammation (7
). TH2 cells present the allergen (or allergic epitope) to a B lymphocyte, which must also have a B-cell receptor for
that specific allergen. All of these specific receptors must be present to form an allergic response. IL-4 and other “allergic” cytokines can induce the B cell to change into an IgE-producing plasma cell. IgE can then travel via the circulatory system and bind to IgE receptors on basophils and mast cells throughout the body.
Reexposure to the specific allergen can cause an IgE-mediated degranulation of basophils and mast cells. This releases inflammatory mediators such as histamine. Histamine binds to histamine receptors on endothelial cells and vascular smooth muscle causing vasodilation and increased permeability (8
). Patients then experience rhinorrhea, sneezing, and nasal congestion. Other proinflammatory mediators are released including IL-5, which recruit eosinophils and leukotrienes that promote “late phase” inflammation. The promotion of more inflammation is balanced by factors that down-regulate inflammation such as IL-10 and regulatory T cells (9
Allergic rhinitis is a common condition throughout the world, as well as in the United States. The prevalence of the disease is rising in developed countries (10
). The widespread prevalence of allergic rhinitis places a significant burden on our health care system. There is evidence of an “allergic march” in which infant atopy leads to later problems with allergies. Also, the controversial “hygiene hypothesis” may explain the increase of allergies.
The prevalence of allergic rhinitis is difficult to precisely estimate for several reasons, including regional differences and how allergic rhinitis is diagnosed. Allergic rhinitis is frequently quoted to affect between 10% and 30% of adults, and up to 40% of children (11
). In some countries, over 50% of adolescents report symptoms of rhinitis (1
). However, larger epidemiologic studies suggest a lower prevalence. In the United States, the 2009 National Health Interview Survey conducted by the Centers for Disease Control reported that 17.7 million adults or 7.8% of those surveyed had been diagnosed with “hay fever” in the last 12 months (12
). Over 7 million children were reported to have “hay fever” and 8.2 million (11%) were reported to have “respiratory allergy” in the last 12 months (13
). There is often a difference in reported rates by questionnaire and by actual allergy testing. For example, in Sweden, by questionnaire alone 14.2% were allergic when compared to 9.1% who were positive by questionnaire and skin test (3
The direct cost of allergic rhinitis includes physician charges and medications used to treat rhinitis, both prescription and over-the-counter. In 2011, Meltzer estimated the direct medical cost of allergic rhinitis at $3.4 billion in the United States (14
). A 2002 study estimated direct and indirect costs related to rhinitis in the United States to be $11.58 billion (15
). These costs, especially indirect costs, are hard to calculate. But given the prevalence of the disease, allergic rhinitis presents a significant burden in terms of cost.
The “atopic march” refers to the observation that young children with atopic dermatitis and food allergies are at risk of developing asthma and allergic rhinitis in later years (16
). Identifying children at risk for allergic rhinitis and asthma can provide an opportunity for early detection and intervention. However, allergic rhinitis and asthma also commonly occur in individuals with no history of early childhood atopy.
The “hygiene hypothesis” is a controversial theory that may explain the increasing prevalence of allergic disease. It is postulated that exposure to infections early in life decreases the chance of atopy later in life. Different studies provide conflicting evidence to this theory (17
). Evidence supporting the “hygiene hypothesis” includes decreased atopy associated with helminth eradication programs (19
), measles vaccinations (20
), day care attendance in the first 6 months of life (21
), living on a farm during early life (22
), and having multiple siblings (23
). The controversy arises as published exceptions to the hygiene hypothesis are plentiful, including no observed change in atopic disease after an effective decrease in parasitic disease in Ecuador (24
) or the increase in atopy observed after Streptococcus pneumonia
vaccination in South Africa (25
). One explanation for the hygiene hypothesis is that early infections shift the bias of T cells from allergic inflammation (TH2) at birth to a nonallergic bias (TH1) (18
). If the TH2 (proallergic) bias persists, individuals are more likely to develop allergic hypersensitivity to otherwise harmless exposures.