In atopic patients, antigen exposure stimulates the production of allergen-specific immunoglobulin E (IgE). This IgE attaches to mucosal mast cells. Subsequent exposure to the allergen leads to the formation of antigen-IgE complexes on mast cells and basophils. The formation of antigen-antibody complexes triggers an acute-phase degranulation reaction, with the release of histamine, cytokines, kinins, leukotrienes, prostaglandins, and esterases in concentrations proportional to the intensity of the antigen challenge. Hours later, a late-phase response can be demonstrated in persons with more severe disease, manifested by a rerelease of mediators (minus prostaglandins), an influx of leukocytes, eosinophils, and mononuclear cells, and an increased responsiveness to antigenic and nonantigenic stimuli. With continued allergen exposure, there is a heightened mucosal responsiveness due to an increase in the population of mast cells. The leukotriene pathway, which is active in aspirin-induced disease, can produce both early and late allergy symptoms, including sneezing, nasal itching, runny nose, and congestion.

In addition to environmental stimuli, genetic factors play a role. Antigen-specific responses are controlled by regulatory genes, and allergic rhinitis is much more common in persons with a positive family history. The relation of allergic rhinitis to reactive lower airway disease (asthma) is a subject of debate, but it appears that allergic rhinitis is neither a cause nor a consequence of it, although activation of one often accompanies activation of the other.

Nasal congestion, sneezing, and profuse watery discharge dominate the initial clinical presentation. Itching of the nose, throat, and eyes is common, as is postnasal drip, tearing, and conjunctival injection. Often the nasal mucosa appears pale and edematous. Symptoms typically vary over the course of the day. They are most severe on arising in the morning, lessen in the afternoon, and may worsen again by evening. Nighttime nasal obstruction may impede restful sleep. With continued allergen exposure, there is increased sensitivity both to allergens and to nonallergenic stimuli.

Onset of allergic rhinitis is usually during childhood but may occur at any age. Childhood cases frequently continue into adulthood. Often, the condition improves with time. The condition is seasonal when the antigen is a pollen (“hay fever”) and perennial when the allergens are dusts, molds, or animal danders. Patients living in the northern half of the United States who are sensitive to tree pollen will become symptomatic in late March and early April, and those sensitive to grasses will become symptomatic in mid-May to late June. Patients affected by ragweed and other summer weeds experience difficulty in late August until the first frost. Patients with seasonal allergic rhinitis outnumber those with perennial complaints by a ratio of about 10:1. Individuals may be allergic to a number of antigens.

In some instances, the patient has all the earmarks of allergic rhinitis but no evidence of IgE mediation, and skin tests for inhaled allergens are negative. Such patients have been designated as having nonallergic rhinitis, even though their nasal secretions often contain large numbers of eosinophils and they respond to corticosteroids.

The pathophysiology is poorly understood but is believed to involve abnormal autonomic responsiveness and vascular dilation of the submucosal vessels. IgE levels are normal, and the number of eosinophils in nasal secretions is usually, but not always, normal. Abnormal autonomic reactivity is believed to account for the nasal stuffiness or rhinorrhea sometimes occurring with emotional upset and sexual arousal. The condition may mimic perennial allergic rhinitis and is believed by some clinicians to be a diagnosis of exclusion when no allergen is identified. Others consider the condition to be a readily distinguishable entity characterized by a normal-appearing nasal mucosa and persistent nasal stuffiness without itching that is worsened
by changes in ambient temperature and humidity. Although congestion is the most prominent symptom, profuse watery discharge may also be present. Sneezing is relatively absent.

Midline granuloma (also known as polymorphic reticulosis), an uncommon illness, causes ulcerative destruction of upper respiratory tract structures and may present as nasal stuffiness, crusting, and granulations. Steady progression leads to ulcers of the nasal septum. Most patients are older than 50 years, and many have a history of allergic rhinitis. More recently, this has been identified as a type of cutaneous T-cell lymphoma. Wegener granulomatosis, an immune-mediated disease of middle-aged persons, may have a similar insidious presentation with nasal obstruction, rhinorrhea, or chronic sinusitis. Necrotizing granulomatous lesions and vasculitis are found in the upper and lower airways. Sarcoidosis may present as bilateral nasal obstruction (see Chapter 51).

Hypothyroidism and pregnancy may cause the turbinates to become pale and edematous, leading to nasal congestion. Hypothyroidism may otherwise be subclinical save for the chronic nasal obstruction. Symptoms resolve with the correction of the hypothyroidism or with delivery.

Unilateral congestion, discharge, and recurrent episodes of sinusitis are characteristic of mechanical obstruction due to tumor, polyp, or deviated septum. Neoplasm is rare but is suggested by a blood-tinged discharge. Polyps can occur in association with allergic and vasomotor rhinitis, chronic sinusitis, aspirin-induced asthma, cystic fibrosis, and drug use. The mechanism of formation is unknown. Polyps move freely because they are pedunculated and nontender and appear as soft, pale gray, smooth structures. Patients with asthma and nasal polyps are often hypersensitive to aspirin (so-called triad asthma). Polyps do not regress spontaneously and may become large or multiple, causing considerable obstruction. A deviated septum is sometimes the source of obstructive symptoms. Most are developmental and not traumatic in origin. Associated sinus occlusion is rare.

Obstruction due to crusting is seen with atrophic rhinitis. The condition is of unknown etiology, appears mostly in women, and is characterized by dry atrophic nasal turbinates, mucosal crusts, and a foul or fetid greenish discharge referred to as ozena. The purulent discharge is believed to be due to secondary infection. Atrophic rhinitis can also be caused by excessive nasal surgery (i.e., turbinate resection) or nasal necrosis after cocaine abuse.

The timing of symptoms can be helpful diagnostically. Nasal congestion that coincides with periods of pollination is virtually diagnostic of seasonal allergic rhinitis. Continuous waxing and waning of symptoms throughout the year, with exacerbations during the hay fever season, suggests a combination of perennial and seasonal allergic disease. When symptoms occur chronically without respect to seasons, one may be dealing with vasomotor rhinitis, perennial allergy, mechanical obstruction, or a chronic inflammatory condition. Perennial rhinitis is a possibility when the patient reports frequent “colds.”

Aggravating and alleviating factors should be noted. Patients bothered by dusts are generally atopic, whereas those whose symptoms are aggravated by quick changes in temperature, emotion, or drugs fall into the vasomotor category. Use of antihypertensive agents and topical nasal decongestants needs to be explored, as does exposure to fur-bearing animals (especially cats), feathers, other possible sources of animal danders, or chemical irritants. Pollutants are often more irritating to allergic patients, but they may also cause symptoms in nonatopic people. Wood-burning stoves and fireplaces are associated with chronic rhinitis and sinonasal polyposis.

Associated symptoms of potential importance include fever and a purulent nasal discharge, which suggest an infectious etiology. A cold is the most likely cause of acute discharge, but chronic discharge that is fetid, foul smelling, and accompanied by crusting indicates secondary infection as in atrophic rhinitis, Wegener granulomatosis, and midline granuloma. Chronic sinusitis may also present with a primary symptom of nasal congestion/obstruction. Bloody discharge and unilateral obstruction suggest tumor. Mechanical obstructions are often unilateral as well. The presence of asthma or aspirin sensitivity increases the likelihood of nasal polyps and/or chronic sinusitis. Sneezing and postnasal drip are nonspecific and of little help in distinguishing among etiologies, but associated itching of the eyes, tearing, and conjunctival redness suggest an allergic mechanism.

Epidemiologic data need to be considered. Onset in childhood is typical of allergic disease, but onset of symptoms during adulthood does not rule out atopy. When chronic progressive nasal congestion develops in a middle-aged patient, particularly a woman, one must consider atrophic rhinitis or one of the necrotizing inflammatory diseases. The allergy histories of the patient’s parents should be ascertained because a positive family history strongly suggests allergic disease.

Drug use and concurrent conditions are important to review, including abuse of cocaine or nasal decongestants, hypothyroidism, sarcoidosis, and pregnancy. Some intranasal medications such as intranasal migraine medications and intranasal calcitonin may also cause localized rhinitis.

Antigen challenge is sometimes helpful when the differentiation between allergic and nonallergic disease remains difficult. In vivo and in vitro methods are used. When history provides ready identification of allergens, there is little need for skin testing, but if drastic environmental measures are being contemplated, documentation of the specific allergens is indicated.

The procedure of choice for the detection of allergen-specific IgE continues to be skin testing. For environmental allergens, an epicutaneous (needle prick) test is used. (Intradermal injection should not be used because it generates a high frequency of false positives and risks severe systemic reactions.) Preparations of commonly inhaled allergens (dusts, molds, animal danders, and local pollens) are introduced by needle prick into the skin. A positive test is a wheal-and-flare reaction within 20 minutes. A positive reaction does not prove causation, only that there is sensitization to the allergen and allergen-specific IgE present. Correlation with history and physical examination is needed to establish an etiologic role for the antigen.

Antihistamines must be omitted for 12 to 24 hours before testing to avoid a false-negative result. Dermatographism is a common cause of false-positive results, occurring in 15% to 20% of the population and necessitating the use of a saline control injection. Eczema and concurrent use of antipsychotic drugs can also interfere with interpretation. The size of the wheal and flare correlates well with the level of allergen-specific IgE. However, allergen preparations need to be standardized to avoid impairing interpretation and comparison of results.

Although many of the allergens tested by skin prick are inhaled, inhalation challenge remains predominantly a research method, used to evaluate nasal resistance after mucosal exposure.

When skin prick testing is not available, serum tests can contribute to diagnosis. Determination of total serum IgE is helpful if the level is markedly elevated, but test sensitivity is low because some cases of allergic rhinitis are not associated with high serum concentrations. The same is true for the total eosinophil count. A count at the time of an exacerbation that is greater than 500 cells/mm³ suggests an allergic etiology, but the absence of peripheral eosinophilia does not rule out allergic rhinitis. Radioallergosorbent testing (RAST) is an in vitro means of identifying and quantifying an allergen-specific IgE. The test involves adding the patient’s serum to a purified allergen absorbed to an inert particle. If the serum contains high concentrations of specific IgE antibodies to the allergen, it gives a positive test. The shortcomings of RAST are its expense and only modest sensitivity (less than that of skin testing); however, specificity is high. The test is best reserved for patients whose skin tests are equivocal and for those who cannot undergo skin testing. IgE immunoassays represent an alternative in vitro means of testing for specific IgE antibodies; a positive test that correlates with symptoms on natural exposure is often sufficient grounds for initiating environmental therapy.