Allergic rhinitis

The characteristic symptoms of allergic rhinitis are: rhinorrhea (excess nasal secretion), itching, sneezing fits, and nasal congestion/obstruction. Nasal endoscopy may show findings such as pale and boggy inferior turbinates from mucosal edema, stringy mucus throughout the nasal cavities, and cobblestoning. There can also be behavioral signs; in order to relieve the irritation or flow of mucus, people may wipe or rub their nose with the palm of their hand in an upward motion: an action known as the "nasal salute" or the "allergic salute". This may result in a crease running across the nose (or above each nostril if only one side of the nose is wiped at a time), commonly referred to as the "transverse nasal crease", and can lead to permanent physical deformity if repeated enough. People might also find that cross-reactivity occurs. For example, people allergic to birch pollen may also find that they have an allergic reaction to the skin of apples or potatoes. A clear sign of this is the occurrence of an itchy throat after eating an apple or sneezing when peeling potatoes or apples. This occurs because of similarities in the proteins of the pollen and the food. There are many cross-reacting substances. Hay fever is not a true fever, meaning it does not cause a core body temperature in the fever over . ==Cause==

Pollen is often considered as a cause of allergic rhinitis, hence called hay fever (See sub-section below). Predisposing factors to allergic rhinitis include eczema (atopic dermatitis) and asthma. These three conditions can often occur together which is referred to as the atopic triad. Additionally, environmental exposures such as air pollution and maternal tobacco smoking can increase an individual's chances of developing allergies. • Grasses (Family Poaceae): especially ryegrass (Lolium sp.) and timothy (Phleum pratense). An estimated 90% of people with hay fever are allergic to grass pollen. • Weeds: ragweed (Ambrosia), plantain (Plantago), nettle/parietaria (Urticaceae), mugwort (Artemisia Vulgaris), Fat hen (Chenopodium), and sorrel/dock (Rumex) Allergic rhinitis may also be caused by allergy to Balsam of Peru, which is in various fragrances and other products. Genetic factors The causes and pathogenesis of allergic rhinitis are hypothesized to be affected by both genetic and environmental factors, with many recent studies focusing on specific loci that could be potential therapeutic targets for the disease. Genome-wide association studies (GWAS) have identified a number of different loci and genetic pathways that seem to mediate the body's response to allergens and promote the development of allergic rhinitis, with some of the most promising results coming from studies involving single-nucleotide polymorphisms (SNPs) in the interleukin-33 (IL-33) gene. The IL-33 protein that is encoded by the IL-33 gene is part of the interleukin family of cytokines that interact with T-helper 2 (Th2) cells, a specific type of T cell. Th2 cells contribute to the body's inflammatory response to allergens, with specific ST2 receptors—also known as IL1RL1—on these cells binding to the ligand IL-33. This IL-33/ST2 signaling pathway has been found to be one of the main genetic determinants in bronchial asthma pathogenesis, and because of the pathological linkage between asthma and rhinitis, the experimental focus of IL-33 has now turned to its role in the development of allergic rhinitis in humans and mouse models. Recently, it was found that allergic rhinitis patients expressed higher levels of IL-33 in their nasal epithelium and had a higher concentration of ST2 serum in nasal passageways following their exposure to pollen and other allergens, indicating that this gene and its associated receptor are expressed at a higher rate in allergic rhinitis patients. In a 2020 study on polymorphisms of the IL-33 gene and their link to allergic rhinitis within the Han Chinese population, researchers found that five SNPs specifically contributed to the pathogenesis of allergic rhinitis, with three of those five SNPs previously identified as genetic determinants for asthma. Another study focusing on Han Chinese children found that certain SNPs in the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene can be associated with childhood allergic rhinitis and allergic asthma. The encoded PTPN22 protein, which is found primarily in lymphoid tissue, acts as a post-translational regulator by removing phosphate groups from targeted proteins. Importantly, PTPN22 can affect the phosphorylation of T cell responses, and thus the subsequent proliferation of the T cells. As mentioned earlier, T cells contribute to the body's inflammatory response in a variety of ways, so any changes to the cells' structure and function can have potentially deleterious effects on the body's inflammatory response to allergens. To date, one SNP in the PTPN22 gene has been found to be significantly associated with allergic rhinitis onset in children. On the other hand, CTLA-4 is an immune-checkpoint protein that helps mediate and control the body's immune response to prevent overactivation. It is expressed only in T cells as a glycoprotein for the Immunoglobulin (Ig) protein family, also known as antibodies. There have been two SNPs in CTLA-4 that were found to be significantly associated with childhood allergic rhinitis. Both SNPs most likely affect the associated protein's shape and function, causing the body to exhibit an overactive immune response to the posed allergen. The polymorphisms in both genes are only beginning to be examined, therefore more research is needed to determine the severity of the impact of polymorphisms in the respective genes. Finally, epigenetic alterations and associations are of particular interest to the study and ultimate treatment of allergic rhinitis. Specifically, microRNAs (miRNA) are hypothesized to be imperative to the pathogenesis of allergic rhinitis due to the post-transcriptional regulation and repression of translation in their mRNA complement. Both miRNAs and their common carrier vessel exosomes have been found to play a role in the body's immune and inflammatory responses to allergens. miRNAs are housed and packaged inside of exosomes until they are ready to be released into the section of the cell that they are coded to reside and act. Repressing the translation of proteins can ultimately repress parts of the body's immune and inflammatory responses, thus contributing to the pathogenesis of allergic rhinitis and other autoimmune disorders. There are many miRNAs that have been deemed potential therapeutic targets for the treatment of allergic rhinitis by many different researchers, with the most widely studied being miR-133, miR-155, miR-205, miR-498, and let-7e. Air pollution Numerous studies confirm that ambient air pollution particularly traffic-related pollutants like nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and fine particulate matter (PM2.5 and PM10) is significantly associated with both the prevalence and severity of allergic rhinitis. One Taiwanese study found that a 10 ppb increase in NOx corresponded to an 11% higher odds of physician‑diagnosed allergic rhinitis, with smaller yet significant associations for CO, SO2, and PM10. Chinese meta-analysis data echoed this trend: increases in SO2 (OR ≈ 1.03), NO2 (OR ≈ 1.11), PM10 (OR ≈ 1.02), and PM2.5 (OR ≈ 1.15) all correlated with heightened risk of childhood allergic rhinitis, while ozone exposure showed no significant association. Air pollutants impair the respiratory epithelial barrier, increasing permeability and inflammation. This occurs through mechanisms such as oxidative stress, immune modulation, and epigenetic changes. Diesel exhaust particles (DEP), for example, have been shown to enhance allergic inflammation by boosting eosinophil activation when allergens are present. Meanwhile, damaged nasal mucosa facilitates deeper allergen penetration, intensifying rhinitis symptoms. Urbanization, vehicle emissions, and fossil fuel combustion have accelerated in recent decades, coinciding with a steady rise in allergic rhinitis prevalence. For instance, in Southeast Asia and parts of Latin America, higher AR rates align strongly with poorer air quality. ==Pathophysiology==

The pathophysiology of allergic rhinitis involves Th2 Helper T cell and IgE mediated inflammation with overactive function of the adaptive and innate immune systems. The process begins when an aeroallergen penetrates the nasal mucosal barrier. This barrier may be more permeable in susceptible individuals. The allergen is then engulfed by an antigen presenting cell (APC) (such as a dendritic cell). The APC then presents the antigen to a Naive CD4+ helper T cell stimulating it to differentiate into a Th2 helper T cell. The Th2 helper T cell then secretes inflammatory cytokines including IL-4, IL-5, IL-13, IL-14, and IL-31. These inflammatory cytokines stimulate B cells to differentiate into plasma cells and release allergen specific IgE immunoglobulins. The IgE immunoglobulins attach to mast cells. The inflammatory cytokines also recruit inflammatory cells such as basophils, eosinophils and fibroblasts to the area. The person is now sensitized, and upon re-exposure to the allergen, mast cells with allergen specific IgE will bind the allergens and release inflammatory molecules including histamine, leukotrienes, platelet activating factor, prostaglandins and thromboxane with these inflammatory molecules' local effects on blood vessels (dilation), mucous glands (secrete mucous) and sensory nerves (activation) leading to the clinical signs and symptoms of allergic rhinitis. Disruption of the nasal mucosal epithelial barrier may also release alarmins (a type of damage associated molecular pattern (DAMP) molecule) such as thymic stromal lymphopoietin, IL-25 and IL-33 which activate group 2 innate lymphoid cells (ILC2) which then also releases inflammatory cytokines leading to activation of immune cells. ==Diagnosis==

Allergy testing may reveal the specific allergens to which an individual is sensitive. Skin testing is the most common method of allergy testing. Even if a person has negative skin-prick, intradermal and blood tests for allergies, they may still have allergic rhinitis, from a local allergy in the nose. This is called local allergic rhinitis. Specialized testing is necessary to diagnose local allergic rhinitis. Classification • Seasonal allergic rhinitis (hay fever): Caused by seasonal peaks in the airborne load of pollens. • Perennial allergic rhinitis (nonseasonal allergic rhinitis; atopic rhinitis): Caused by allergens present throughout the year (e.g., dander). Allergic rhinitis may be seasonal, perennial, or episodic. Seasonal allergic rhinitis occurs in particular during pollen seasons. It does not usually develop until after 6 years of age. Perennial allergic rhinitis occurs throughout the year. This type of allergic rhinitis is commonly seen in younger children. Allergic rhinitis may also be classified as mild-intermittent, moderate-severe intermittent, mild-persistent, and moderate-severe persistent. Intermittent is when the symptoms occur 4 days/week and >4 consecutive weeks. The symptoms are considered mild with normal sleep, no impairment of daily activities, no impairment of work or school, and if symptoms are not troublesome. Severe symptoms result in sleep disturbance, impairment of daily activities, and impairment of school or work. Local allergic rhinitis Local allergic rhinitis is an allergic reaction in the nose to an allergen, without systemic allergies. So skin-prick and blood tests for allergy are negative, but there are IgE antibodies produced in the nose that react to a specific allergen. Intradermal skin testing may also be negative. In several studies, over 40% of people having been diagnosed with nonallergic rhinitis were found to actually have local allergic rhinitis. ==Prevention==

Prevention often focuses on avoiding specific allergens that cause an individual's symptoms. These methods include not having pets, not having carpets or upholstered furniture in the home, and keeping the home dry. Specific anti-allergy zippered covers on household items like pillows and mattresses have also proven to be effective in preventing dust mite allergies. ==Treatment==

The goal of rhinitis treatment is to prevent or reduce the symptoms caused by the inflammation of affected tissues. Measures that are effective include avoiding the allergen. Intranasal corticosteroids (eg, flunisolide) are the preferred medical treatment for persistent symptoms, with other options if this is not effective. It is best to take oral antihistamine medication before exposure, especially for seasonal allergic rhinitis. In the case of nasal antihistamines like azelastine antihistamine nasal spray, relief from symptoms is experienced within 15 minutes allowing for a more immediate 'as-needed' approach to dosage. There is not enough evidence of antihistamine efficacy as an add-on therapy with nasal steroids in the management of intermittent or persistent allergic rhinitis in children, so its adverse effects and additional costs must be considered. Ophthalmic antihistamines (such as azelastine in eye drop form and ketotifen) are used for conjunctivitis, while intranasal forms are used mainly for sneezing, rhinorrhea, and nasal pruritus. Pseudoephedrine is also indicated for vasomotor rhinitis. It is used only when nasal congestion is present and can be used with antihistamines. In the United States, oral decongestants containing pseudoephedrine must be purchased behind the pharmacy counter in an effort to prevent the manufacturing of methamphetamine. Desloratadine/pseudoephedrine can also be used for this condition. Steroids Intranasal corticosteroids are used to control symptoms associated with sneezing, rhinorrhea, itching, and nasal congestion. Systemic steroids such as prednisone tablets and intramuscular triamcinolone acetonide or glucocorticoid (such as betamethasone) injection are effective at reducing nasal inflammation, but their use is limited by their short duration of effect and the side-effects of prolonged steroid therapy. Others Other measures that may be used second line include: decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies such as nasal irrigation. Nasal saline irrigation (a practice where salt water is poured into the nostrils), may have benefits in both adults and children in relieving the symptoms of allergic rhinitis and it is unlikely to be associated with adverse effects. Allergen immunotherapy Allergen immunotherapy, also called desensitization, treatment involves administering doses of allergens to accustom the body to substances that are generally harmless (pollen, house dust mites), thereby inducing specific long-term tolerance. Allergen immunotherapy is the only treatment that alters the disease mechanism. Immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous). Subcutaneous immunotherapy is the most common form and has the largest body of evidence supporting its effectiveness. Alternative medicine There are no forms of complementary or alternative medicine that are evidence-based for allergic rhinitis. Therapeutic efficacy of alternative treatments such as acupuncture and homeopathy is not supported by available evidence. While some evidence shows that acupuncture is effective for rhinitis, specifically targeting the sphenopalatine ganglion acupoint, these trials are still limited. Overall, the quality of evidence for complementary-alternative medicine is not strong enough to be recommended by the American Academy of Allergy, Asthma and Immunology. ==Epidemiology==

Allergic rhinitis is the type of allergy that affects the greatest number of people. In Western countries, between 10 and 30 percent of people are affected in a given year. It is most common between the ages of twenty and forty. ==History==

The first accurate description is from the 10th-century Persian physician Rhazes. Pollen was identified as the cause in 1859 by Charles Blackley. In 1906 the mechanism was determined by Clemens von Pirquet. The link with hay came about due to an early (and incorrect) theory that the symptoms were brought about by the smell of new hay. Although the scent per se is irrelevant, the correlation with hay checks out, as peak hay-harvesting season overlaps with peak pollen season, and hay-harvesting work puts people in close contact with seasonal allergens. ==See also==