Allergic Rhinitis: Definition, Classification, and Management, Including Immunotherapy


Allergic Rhinitis: Definition, Classification, and Management, Including Immunotherapy

Pascal Demoly, Wytske Fokkens, and Ingrid Terreehorst


This chapter discusses the definition, diagnosis, comorbidities, and treatment of allergic rhinitis. The Allergic Rhinitis and Its Impact on Asthma (ARIA) initiative has published diagnostic procedures and new treatment recommendations based on a new classification of allergic rhinitis. ARIA constitutes a fundamental step in the profession′s approach to quality practice and is the basis of this chapter.13

The treatment of allergic rhinitis should consider the severity and duration of the disease and the patient′s preference, as well as the efficacy, availability, and costs of medications. A stepwise, tailored approach depending on the severity and duration is required. Levels of evidence of each class of treatment and a list of options are given in the ARIA recommendations.


Allergic rhinitis is a common disease worldwide, affecting up to 50% of the population, and its prevalence is increasing. It affects adolescents and young adults more often. Although allergic rhinitis is not usually a severe disease, it alters the social life of patients and affects school performance and work productivity. Moreover, it is a major risk factor for developing asthma, and the costs incurred are substantial.

In the current medical practice, the manifestation of allergic rhinitis is easily identifiable. It is not the same for the immunoglobulin E (IgE)–dependent inflammation of the nasal mucous membranes. Only a firm diagnosis can allow proper management, differentiating as clearly as possible nonallergic and allergic rhinitis. The management of these two entities often differs and is now better codified. The search for associated comorbidities such as asthma must be systematic. Recommendations have been proposed by professional societies and governing bodies to guide physicians in their daily practice to diagnose allergic rhinitis properly and to allow patients to benefit from quality care supported by evidence-based science. Among these guidelines, the ARIA initiative offers diagnostic procedures and new treatment recommendations based on a new classification of allergic rhinitis.4 This document represents an exhaustive review of current knowledge. The recommendations are as much for the specialist as for the general practitioner; they are based on the latest scientific evidence in the literature. Recently, ARIA has been updated using the GRADE assessment of evidence.1,3 ARIA constitutes a fundamental step in the profession′s approach to quality practice and is the basis of this chapter.

Definition of Allergic Rhinitis

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure due to an IgE-mediated inflammation of the membranes lining the nose. The diagnosis of allergic rhinitis is based on the typical history of symptoms of sneezing, watery rhinorrhea, and nasal blockage. Often nasal symptoms are combined with eye symptoms and lower airway symptoms.


By definition, allergic rhinitis is the symptomatic disorder of the nose induced after allergen exposure due to an IgE-mediated inflammation of the membranes lining the nose.

Definition of Atopy

Atopy refers to a genetic predisposition to produce IgE in response to minute amounts of environmental protein allergens. Nonatopic individuals can produce IgE but normally do so only transiently. In atopic individuals, the production continues and leads to various atopic disorders, such as

  • Atopic dermatitis or eczema

  • Asthma

  • Allergic rhinitis

Anaphylaxis is an acute, multisystem, severe IgE-mediated allergic reaction.


Hyperreactivity describes the heightened (nasal) responsiveness to nonspecific physical and chemical triggers in inspired air. It occurs in allergic and nonallergic rhinitis.


Hypersensitivity is a state of altered reactivity in which the body reacts with an exaggerated response to what is perceived as a foreign substance. When the immune system is involved, by means of immunoglobulins, cellular responses, or a combination of both, this is called an allergic hypersensitivity response (e.g., allergic rhinitis, atopic eczema). If the immune system is not involved, it is called nonallergic hypersensitivity (e.g., lactose intolerance). The allergic hypersensitivity can be further categorized by the Gell and Coombs classification.


Hyperreactivity describes the heightened (nasal) responsiveness to nonspecific physical and chemical triggers in inspired air. It occurs in both allergic and nonallergic rhinitis.

Hypersensitivity is a state of altered reactivity in which the body reacts with an exaggerated response to what is perceived as a foreign substance.

Allergic Hypersensitivity Reactions According to Gell and Coombs

Type I (immediate) hypersensitivity allergic reaction occurs when a sensitized individual comes in contact with a specific antigen. IgE has a strong affinity for mast cells, and the cross-linking of two adjacent IgE molecules by the antigen triggers mast cell degranulation. This, in turn, causes the release of various preformed and newly formed mediators of the inflammatory cascade, including histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These inflammatory mediators, together with various chemotactic factors, result in increased vascular permeability and migration of eosinophils and neutrophils. Allergic rhinitis is a type I hypersensitivity allergic reaction.

Type II hypersensitivity allergic reaction is autoimmune and may be complement mediated. This type of reaction may be the underlying cause of various ocular conditions, such as cicatricial pemphigoid and Mooren ulcer.

Type III hypersensitivity allergic reaction results in antigen–antibody immune complexes, which deposit in tissues and cause inflammation. The classic type III reaction systemically is the Arthus reaction. Ocular type III hypersensitivity reactions include marginal infiltrates of the cornea.

Type IV hypersensitivity allergic reaction, also known as cell-mediated immunity, is mediated by T lymphocytes. It is also known as delayed-type hypersensitivity, as its onset is generally after 48 hours. Type IV implies immunocompetence on the part of the individual, as an intact immune system is required to mount the cell-mediated response. Ocular examples of type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection, contact dermatitis, and some forms of drug allergy.

Seasonal or Perennial Allergic Rhinitis: The Old Classification

In most of the Western world, for a long time allergic rhinitis was divided into seasonal and perennial allergic rhinitis. Because seasonal allergic rhinitis in these countries was often based on pollen allergy and perennial allergic rhinitis based primarily on house dust mite allergy, this seemed to be an effective classification.

However, in certain areas, pollens and molds are perennial allergens (e.g., grass pollen allergy in Southern California and Florida and Parietaria pollen allergy in the Mediterranean area), and symptoms due to perennial allergens may not always be present year-round, as is the case in a large number of patients allergic to house dust mites in Scandinavia and the Mediterranean. Moreover, many patients are sensitized to many different allergens and therefore exposed throughout the year to overlapping allergen seasons.

Intermittent or Persistent Rhinitis: ARIA Subdivision of Allergic Rhinitis

For these reasons, the World Health Organization (WHO) initiative ARIA proposed in 2001 a new subdivision of allergic rhinitis,4 with patients categorized as having

  • Intermittent or persistent rhinitis (superseding the prior categories of seasonal and perennial) based on the number of days per week and consecutive weeks per year the patients are bothered

  • Mild or moderate/severe rhinitis, based on the impact on the quality of life of patients ( Fig. 14.1 )

Severe Chronic Upper Airway Diseases

Although the majority of patients with allergic rhinitis have controlled symptoms during treatment, some have severe chronic upper airway disease (SCUAD).5 SCUAD defines those patients whose symptoms are inadequately controlled despite effective, safe, and acceptable pharmacological treatment based on guidelines. These patients have impaired quality of life, social functioning, sleep, and school/work performance. Severe uncontrolled allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis (CRS), aspirin-exacerbated respiratory diseases, and occupational airway diseases are defined as SCUADs.

Classification of allergic rhinitis according to Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. (Adapted from Bousquet J, Van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108(5 Suppl):S147–334, with permission.)


Allergic rhinitis is one of the most prevalent chronic diseases in the world. The prevalence has been increasing in the last decades. Several prevalence studies have been conducted, some especially focusing on allergic rhinitis,6 some primarily on asthma. Worldwide, the prevalence of seasonal allergic rhinitis, based on data and questionnaire results from 1990 until now, ranges from 4 to 40%. The prevalence of perennial allergic rhinitis varies from 1 to 13%. Total prevalence in the Western world is seldom 10% and usually ~25%. The prevalence of seasonal allergic rhinitis is higher in children and adolescents than in adults. Perennial rhinitis is more common in adults than in children, but few reliable data exist. In many parts of the world, pollen allergy is very common, but in Eastern Asia, Latin America, and tropical areas, mite allergy is more common.

Increase in the Prevalence of Allergic Rhinitis

The prevalence of allergic rhinitis is increasing worldwide. In Europe and the United States, prevalence has increased over the past 40 years; in countries in Africa and Asia, the increase seems to have started more recently.

Genetic Factors

With one atopic parent, the risk of atopy in the child is doubled, with maternal influence being greater than paternal. If both parents are atopic, the risk is quadrupled. Several genes are involved, and children probably inherit a predisposition for atopic disease in general, for specific organ involvement, and for disease severity. Thus, a child with one parent with hay fever is likely to be less severely affected than one whose parents have severe eczema and asthma. For more information on genetics, see Chapter 5.

Hygiene Hypothesis

Allergic rhinitis and asthma seem to be associated with the adoption of an urbanized, “Western” lifestyle. In 1989, David Strachan showed that younger children raised in large families (and, in a later study, children visiting day care) developed fewer allergies than older children in the family or children who were the only child. Both of these observations suggested that lifestyle could be an important factor in the development of allergies.7 After the fall of the Berlin wall, Erica von Mutius and her colleagues devised a study comparing the prevalence of allergic rhinitis and asthma in Munich (the cleanest city in the former West Germany) and Leipzig (one of the most polluted cities in the former East Germany) because it was thought that allergic rhinitis and asthma were caused by air pollution.8 Totally contrary to what was expected, children in Munich showed a higher prevalence of allergic rhinitis and asthma than children in Leipzig.

The hygiene hypothesis was proposed by Strachan to explain his observation that allergic diseases were less common in the younger children from larger families, who were presumably exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis suggests that an early-life environment with exposure to infections primes the immune system in the Th1 (T helper 1) direction (nonallergic), whereas a “sterile” environment tends to promote the development of allergy (Th2 [T helper 2] direction). The hygiene hypothesis has been extensively endorsed by epidemiological and immunologic data. It is used to explain the increase in allergic diseases that has been seen since industrialization, as well as the higher incidence of allergic diseases in more developed countries.

Rural–Urban Differences

Studies in different parts of the world have shown that the prevalence of atopy and allergic rhinitis is higher in urban than in rural areas. This is particularly the case for pollinosis (hay fever). Surprisingly, pollen counts are usually not higher in rural areas. Most consistently, the “protective” farm effect was related to livestock farming and thus to microbial and endotoxin exposure. Airborne pollutants, such as diesel exhaust particles, ozone, nitrogen dioxide, and sulfur dioxide, have been implicated in the initiation and exacerbation of allergic airway diseases. Traffic-related pollution has been confirmed in both cross-sectional and longitudinal studies to be associated with increased asthma morbidity and cardiopulmonary mortality. Data on rhinitis and air pollution are limited. In one study, patients living in congested areas due to automobile traffic had more severe symptoms of rhinitis and conjunctivitis than those living in uncongested areas. Outdoor pollution appears to induce symptoms in patients with allergic but especially nonallergic rhinitis. Diesel exhaust particles can both induce and exacerbate in vivo allergic responses. They can also modify the immune system′s handling of the allergen.

Etiology: Allergens and Nonspecific Factors

Sensitization to Allergens

House Dust Mite

The house dust mite is a cosmopolitan guest in human habitation. The most important species are Dermatophagoides pteronyssinus (Der p) and D. farinae (Der f). House dust mites feed on human skin danders, which are particularly abundant in mattresses, bed bases, pillows, carpets, upholstered furniture, and fluffy toys. Their growth is maximal in warm (20°C/68°F) and humid conditions (80% relative humidity). When humidity is 50%, mites dry out and die. This is why they are practically nonexistent above 1800 m (5906 ft) in European mountains, but this is not the case in South American mountains (too humid, even at high altitudes). Even though mites are present in the home year-round, there are usually peak seasons, in autumn in particular. House dust mite allergen is contained in fecal pellets (10–20 m). The prevalence of sensitization to mites in the general population is more important in humid than in dry regions.


Pollen grains are the male gametes of plants and need to be transferred from one plant to another. Wind-pollinated plants release large quantities of small pollen grains and are the major cause of allergy. Because the majority of pollen grains (20–30 m in size) are trapped in the nose, rhinitis is the usual result. However, only a small percentage of pollen produced is allergenic. For the pollen of any plant to be important in seasonal allergies, it must meet the criteria set forth in Thommen′s postulates9:

  1. The pollen must be wind-borne (anemophilous).

  2. The pollen must be produced in large quantities, which is a characteristic of wind-pollinated plants.

  3. The pollen must be sufficiently buoyant to be carried considerable distances.

  4. The plant producing the pollen must be widely and abundantly distributed.

  5. The pollen must contain specific excitants or allergens for hypersensitivity.

Grass Pollen

Grass pollen is the most common cause of pollinosis worldwide. Pollen is released early in the morning, rises high into the atmosphere, and descends in the evening as the air cools. The pollen season travels northward at ~5 degrees longitude per week; thus, it may be possible to plan a pollen avoidance holiday. Because grass species cross-react extensively, the number of extracts needed for diagnosis and treatment is limited. Bermuda grass, however, is a separate entity.

Tree Pollen

Trees pollinate mainly in winter and in the spring; the season is short. In northern Europe, Asia, and North America, birch pollen is the main cause of allergy. It is cross-reactive with hazel pollen and elder pollen, and some patients suffer birch/apple syndrome, in which fresh apples and certain vegetables and soft fruit cause oral allergy symptoms. In Mediterranean areas, cypress and olive trees are the major cause of pollen allergy. These are cross-reactive with peach and privet, respectively. In the United States, mountain cedar is an important allergen in some areas.


Ragweeds (Ambrosia) are a genus of flowering plants from the sunflower family (Asteraceae). Ragweed is a major cause of seasonal allergic rhinitis in North America, most prevalent in the Midwest region of the United States. Its season runs between mid-August and September. The season is later in more southerly areas, in contrast to the grass pollen season.

In Europe, mugwort and parietaria, and more and more often also ragweed, are important weed allergen sources. Parietaria is a perennial weed found in Mediterranean countries.


Molds or microfungi are microscopic organisms that produce very large numbers of small spores (2–5 m) and volatile organic compounds. These spores can reach the lower airway and thus tend to cause not only rhinitis but also asthma.

Molds need conditions of high relative humidity to grow. They are therefore prevalent in temperate climates during the late summer, but are present in the tropics in large quantities year-round. In buildings with damp indoor areas, molds can be a problem, particularly if disseminated via the air-conditioning system. The main pathogens are Cladosporium, Alternaria, Aspergillus, Penicillium, and Mucor.

Animal Dander

Over 50% of homes in northern Europe and North America have at least one cat or dog; allergy to these pets is a common cause of symptoms.

In cats, the major allergen (Fel d1) is produced in the salivary glands. Dried saliva in the pelt becomes airborne as small, sticky allergenic particles, which become attached to carpets, furniture, and walls. These particles remain in the home for ~6 months after the removal of the cat. Cat dander is present in schools and workplaces, having been carried there on the owners’ clothes, so sensitive patients who are not cat owners can still be troubled by cat allergy.

In dogs, the major (Can d1) allergens are from the salivary glands, skin scales, and urine. Hair itself is not allergenic.


Hamsters, guinea pigs, mice, and rats are popular as pets and are also widely used in medical research. The major allergen occurs in their urine. Atopic subjects commonly become sensitized and react within 1 year of first exposure.

Occupational Allergens

Occupational rhinitis is an inflammatory disease of the nose that is characterized by intermittent or persistent symptoms (i.e., nasal congestion, sneezing, rhinorrhea, and itching), variable nasal airflow limitation, and/or hypersecretion due to causes and conditions attributable to a particular work environment and not to stimuli encountered outside the workplace.10 Work-related rhinitis can be categorized as occupational rhinitis, which is due to causes and conditions attributable to a particular work environment, and work-exacerbated rhinitis, preexisting or concurrent rhinitis exacerbated by workplace exposures. Prevalence rates of occupational rhinitis varied from 2 to 87% in workforces exposed to high molecular weight agents and from 3 to 48% in those exposed to low molecular weight agents. Occupational allergens are listed in Table 14.1 ; they include small mammals (e.g., rats and mice in laboratory workers), foodstuffs (e.g., wheat in bakers and pineapple in factory workers), drugs (e.g., penicillin in nurses), and latex (e.g., health care workers). Occupational rhinitis can also be nonallergic (see Chapter 13 for the main potential determinants for the development of occupational rhinitis).

Occupational rhinitis is associated with an increased risk of asthma, although the proportion of subjects with occupational rhinitis who will develop occupational asthma remains uncertain. Available data indicate that occupational rhinitis is usually two to four times more prevalent than occupational asthma. Complete avoidance of exposure to the agent causing allergic occupational rhinitis should still be recommended as the safest and most effective therapeutic option. When complete elimination of causal exposure is expected to induce important adverse socioeconomic consequences, reduction of exposure with relevant pharmacotherapy may be considered an alternative approach, especially in workers with a lower risk of developing asthma (e.g., workers without nonspecific bronchial hyperresponsiveness, with mild/recent disease or a short expected duration of exposure); these workers should benefit from close medical surveillance aimed at early detection of occupational asthma.10

Occupational allergens

Agent (hmw/lmw)


Prevalence (%)

Grain dust (hmw)

Agricultural workers


Diisocyanates (lmw)

Industrial painters, urethane mold workers


Flour (hmw)



Anhydrides (lmw)

Epoxy resin production, chemical workers


Wood dust (lmw)

Carpentry, wood workers


Drugs (psyllium, spiramycin, piperacillin) (lmw)

Health care workers


Latex (hmw)

Health care workers, textile/factory workers


Laboratory animals (hmw)

Laboratory workers


Other animal-derived allergens (hmw)

Swine confinement workers


Other plant allergens (hmw)

Plant (tobacco, cacao, carpet) workers


Fish and seafood protein (hmw)

Fish workers, aquarists, fishfood factory workers


Biological enzymes (lmw)

Pharmaceutical and detergent industry workers


Chemicals (lmw)

Hairdressers, shoe manufacturers


Insects and mites (hmw)

Laboratory workers


hmw, high molecular weight; lmw, low molecular weight.


Small particles of latex attach to the powder in latex gloves and become airborne when gloves are handled, with consequent eye and nose sensitization ( Fig. 14.2 ). Latex can also cause an irritant contact dermatitis. Latex allergy results from IgE (immune)–mediated reactions to proteins found in the Hevea brasiliensis, a type of rubber tree. Rhinoconjunctivitis is often the first symptom of latex allergy, together with contact urticaria. The most serious and rare form, anaphylaxis, is an IgE-mediated, potentially life-threatening reaction, comparable to the severe reaction some people have to bee stings or peanuts. Such reactions account for a significant proportion of perioperative anaphylactic reactions. The recognition of latex allergy and substitution with nonpowdered or nonlatex gloves in hospitals have reduced the alarming rise in severe allergy and anaphylaxis due to latex, an example of allergen avoidance producing significant benefit. Some people who have latex allergy also have an allergic response to any of several plant products, usually fruits. This is known as the latex–fruit syndrome. Fruits involved in this syndrome include banana, pineapple, avocado, kiwi fruit, mango, passion fruit, and strawberry, but also food such as chestnut, buckwheat, and soy.

Latex gloves. (Photo by Alexander Fischer.)

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Jun 28, 2020 | Posted by in OTOLARYNGOLOGY | Comments Off on Allergic Rhinitis: Definition, Classification, and Management, Including Immunotherapy

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