Rhinitis, Allergic

Introduction
Background

Rhinitis is defined as inflammation of the nasal membranes1 and is characterized by a symptom complex that consists of any combination of the following: sneezing, nasal congestion, nasal itching, and rhinorrhea.2 The eyes, ears, sinuses, and throat can also be involved. Allergic rhinitis is the most common cause of rhinitis. It is an extremely common condition, affecting approximately 20% of the population. While allergic rhinitis is not a life-threatening condition, complications can occur and the condition can significantly impair quality of life,3,4 which leads to a number of indirect costs. The total direct and indirect cost of allergic rhinitis was recently estimated to be $5.3 billion per year.5
Pathophysiology
Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, eustachian tubes, middle ear, sinuses, and pharynx. The nose invariably is involved, and the other organs are affected in certain individuals. Inflammation of the mucous membranes is characterized by a complex interaction of inflammatory mediators but ultimately is triggered by an immunoglobulin E (IgE)–mediated response to an extrinsic protein.6

The tendency to develop allergic, or IgE-mediated, reactions to extrinsic allergens (proteins capable of causing an allergic reaction) has a genetic component. In susceptible individuals, exposure to certain foreign proteins leads to allergic sensitization, which is characterized by the production of specific IgE directed against these proteins. This specific IgE coats the surface of mast cells, which are present in the nasal mucosa. When the specific protein (eg, a specific pollen grain) is inhaled into the nose, it can bind to the IgE on the mast cells, leading to immediate and delayed release of a number of mediators.6,7,8

The mediators that are immediately released include histamine, tryptase, chymase, kinins, and heparin.7,8 The mast cells quickly synthesize other mediators, including leukotrienes and prostaglandin D2.9,10,11 These mediators, via various interactions, ultimately lead to the symptoms of rhinorrhea (ie, nasal congestion, sneezing, itching, redness, tearing, swelling, ear pressure, postnasal drip). Mucous glands are stimulated, leading to increased secretions. Vascular permeability is increased, leading to plasma exudation. Vasodilation occurs, leading to congestion and pressure. Sensory nerves are stimulated, leading to sneezing and itching. All of these events can occur in minutes; hence, this reaction is called the early, or immediate, phase of the reaction.

Over 4-8 hours, these mediators, through a complex interplay of events, lead to the recruitment of other inflammatory cells to the mucosa, such as neutrophils, eosinophils, lymphocytes, and macrophages.12 This results in continued inflammation, termed the late-phase response. The symptoms of the late-phase response are similar to those of the early phase, but less sneezing and itching and more congestion and mucus production tend to occur.12 The late phase may persist for hours or days.

Systemic effects, including fatigue, sleepiness, and malaise, can occur from the inflammatory response. These symptoms often contribute to impaired quality of life.
Frequency
United States

Allergic rhinitis affects approximately 40 million people in the United States.13 Recent US figures suggest a 20% cumulative prevalence rate.14,15
International

Scandinavian studies have demonstrated a cumulative prevalence rate of 15% in men and 14% in women.16 The prevalence of allergic rhinitis may vary within and among countries.17,18,19,20 This may be due to geographic differences in the types and potency of different allergens and the overall aeroallergen burden.
Mortality/Morbidity

While allergic rhinitis itself is not life-threatening (unless accompanied by severe asthma or anaphylaxis), morbidity from the condition can be significant. Allergic rhinitis often coexists with other disorders, such as asthma, and may be associated with asthma exacerbations.21,22,23

Allergic rhinitis is also associated with otitis media, eustachian tube dysfunction, sinusitis, nasal polyps, allergic conjunctivitis, and atopic dermatitis.1,2,24 It may also contribute to learning difficulties, sleep disorders, and fatigue.25,26,27

Numerous complications that can lead to increased morbidity or even mortality can occur secondary to allergic rhinitis. Possible complications include otitis media, eustachian tube dysfunction, acute sinusitis, and chronic sinusitis.
Allergic rhinitis can be associated with a number of comorbid conditions, including asthma, atopic dermatitis, and nasal polyps. Evidence now suggests that uncontrolled allergic rhinitis can actually worsen the inflammation associated with asthma21,22,23 or atopic dermatitis.24 This could lead to further morbidity and even mortality.
Allergic rhinitis can frequently lead to significant impairment of quality of life. Symptoms such as fatigue, drowsiness (due to the disease or to medications), and malaise can lead to impaired work and school performance, missed school or work days, and traffic accidents. The overall cost (direct and indirect) of allergic rhinitis was recently estimated to be $5.3 billion per year.5

Race

Allergic rhinitis occurs in persons of all races. Prevalence of allergic rhinitis seems to vary among different populations and cultures, which may be due to genetic differences, geographic factors or environmental differences, or other population-based factors.
Sex

In childhood, allergic rhinitis is more common in boys than in girls, but in adulthood, the prevalence is approximately equal between men and women.
Age

Onset of allergic rhinitis is common in childhood, adolescence, and early adult years, with a mean age of onset 8-11 years, but allergic rhinitis may occur in persons of any age. In 80% of cases, allergic rhinitis develops by age 20 years.28 The prevalence of allergic rhinitis has been reported to be as high as 40% in children, subsequently decreasing with age.14,15 In the geriatric population, rhinitis is less commonly allergic in nature.
Clinical
History

Obtaining a detailed history is important in the evaluation of allergic rhinitis. Important elements include an evaluation of the nature, duration, and time course of symptoms; possible triggers for symptoms; response to medications; comorbid conditions; family history of allergic diseases; environmental exposures; occupational exposures; and effects on quality of life. A thorough history may help identify specific triggers, suggesting an allergic etiology for the rhinitis.

Symptoms that can be associated with allergic rhinitis include sneezing, itching (of nose, eyes, ears, palate), rhinorrhea, postnasal drip, congestion, anosmia, headache, earache, tearing, red eyes, eye swelling, fatigue, drowsiness, and malaise.2
Symptoms and chronicity
Determine the age of onset of symptoms and whether symptoms have been present continuously since onset. While the onset of allergic rhinitis can occur well into adulthood, most patients develop symptoms by age 20 years.28
Determine the time pattern of symptoms and whether symptoms occur at a consistent level throughout the year (ie, perennial rhinitis), only occur in specific seasons (ie, seasonal rhinitis), or a combination of the two. During periods of exacerbation, determine whether symptoms occur on a daily basis or only on an episodic basis. Determine whether the symptoms are present all day or only at specific times during the day. This information can help suggest the diagnosis and determine possible triggers.
Determine which organ systems are affected and the specific symptoms. Some patients have exclusive involvement of the nose, while others have involvement of multiple organs. Some patients primarily have sneezing, itching, tearing, and watery rhinorrhea (the classic hayfever presentation), while others may only complain of congestion. Significant complaints of congestion, particularly if unilateral, might suggest the possibility of structural obstruction, such as a polyp, foreign body, or deviated septum.
Trigger factors
Determine whether symptoms are related temporally to specific trigger factors. This might include exposure to pollens outdoors, mold spores while doing yard work, specific animals, or dust while cleaning the house.
Irritant triggers such as smoke, pollution, and strong smells can aggravate symptoms in a patient with allergic rhinitis. These are also common triggers of vasomotor rhinitis. Many patients have both allergic rhinitis and vasomotor rhinitis.
Other patients may describe year-round symptoms that do not appear to be associated with specific triggers. This could be consistent with nonallergic rhinitis, but perennial allergens, such as dust mite or animal exposure, should also be considered in this situation. With chronic exposure and chronic symptoms, the patient may not be able to associate symptoms with a particular trigger.
Response to treatment
Response to treatment with antihistamines supports the diagnosis of allergic rhinitis, although sneezing, itching, and rhinorrhea associated with nonallergic rhinitis can also improve with antihistamines.29
Response to intranasal corticosteroids supports the diagnosis of allergic rhinitis, although some cases of nonallergic rhinitis (particularly the nonallergic rhinitis with eosinophils syndrome [NARES]) also improve with nasal steroids.
Comorbid conditions
Patients with allergic rhinitis may have other atopic conditions such as asthma21,22 or atopic dermatitis.24 Of patients with allergic rhinitis, 20% also have symptoms of asthma. Uncontrolled allergic rhinitis may cause worsening of asthma23 or even atopic dermatitis.24 Explore this possibility when obtaining the patient history.
Look for conditions that can occur as complications of allergic rhinitis. Sinusitis occurs quite frequently. Other possible complications include otitis media, sleep disturbance or apnea, dental problems (overbite), and palatal abnormalities. The treatment plan might be different if one of these complications is present. Nasal polyps occur in association with allergic rhinitis, although whether allergic rhinitis actually causes polyps remains unclear. Polyps may not respond to medical treatment and might predispose a patient to sinusitis or sleep disturbance (due to congestion).
Investigate past medical history, including other current medical conditions. Diseases such as hypothyroidism or sarcoidosis can cause nonallergic rhinitis. Concomitant medical conditions might influence the choice of medication.
Family history
Because allergic rhinitis has a significant genetic component,30 a positive family history for atopy makes the diagnosis more likely.
In fact, a greater risk of allergic rhinitis exists if both parents are atopic than if one parent is atopic. However, the cause of allergic rhinitis appears to be multifactorial, and a person with no family history of allergic rhinitis can develop allergic rhinitis.
Environmental and occupational exposure
A thorough history of environmental exposures helps to identify specific allergic triggers. This should include investigation of risk factors for exposure to perennial allergens (eg, dust mites, mold, pets).31,32 Risk factors for dust mite exposure include carpeting, heat, humidity, and bedding that does not have dust mite–proof covers. Chronic dampness in the home is a risk factor for mold exposure. A history of hobbies and recreational activities helps determine risk and a time pattern of pollen exposure.
Ask about the environment of the workplace or school. This might include exposure to ordinary perennial allergens (eg, mites, mold, pet dander) or unique occupational allergens (eg, laboratory animals, animal products, grains and organic materials, wood dust, latex, enzymes).
Effects on quality of life
An accurate assessment of the morbidity of allergic rhinitis cannot be obtained without asking about the effects on the patient's quality of life. Specific validated questionnaires are available to help determine effects on quality of life.3,4
Determine the presence of symptoms such as fatigue, malaise, drowsiness (which may or may not be related to medication), and headache.
Investigate sleep quality and ability to function at work.

Physical

The physical examination should focus on the nose, but examination of facial features, eyes, ears, oropharynx, neck, lungs, and skin is also important. Look for physical findings that may be consistent with a systemic disease that is associated with rhinitis.

General facial features
"Allergic shiners" are dark circles around the eyes and are related to vasodilation or nasal congestion.2,33
"Nasal crease" is a horizontal crease across the lower half of the bridge of the nose that is caused by repeated upward rubbing of the tip of the nose by the palm of the hand (ie, the "allergic salute").2,33
Nose
The nasal examination is best accomplished with a nasal speculum or an otoscope with nasal adapter. In the specialist's office, a rigid or flexible rhinolaryngoscope may be used.
The mucosa of the nasal turbinates may be swollen (boggy) and have a pale, bluish-gray color. Some patients may have predominant erythema of the mucosa, which can also be observed with rhinitis medicamentosa, infection, or vasomotor rhinitis. While pale, boggy, blue-gray mucosa is typical for allergic rhinitis, mucosal examination findings cannot definitively distinguish between allergic and nonallergic causes of rhinitis.
Assess the character and quantity of nasal mucus. Thin and watery secretions are frequently associated with allergic rhinitis, while thick and purulent secretions are usually associated with sinusitis; however, thicker, purulent, colored mucus can also occur with allergic rhinitis.
Examine the nasal septum to look for any deviation or septal perforation, which may be present due to chronic rhinitis, granulomatous disease, cocaine abuse, prior surgery, topical decongestant abuse, or, rarely, topical steroid overuse.
Examine the nasal cavity for other masses such as polyps or tumors. Polyps are firm gray masses that are often attached by a stalk, which may not be visible. After spraying a topical decongestant, polyps do not shrink, while the surrounding nasal mucosa does shrink.
Ears, eyes, and oropharynx
Perform otoscopy to look for tympanic membrane retraction, air-fluid levels, or bubbles. Performing pneumatic otoscopy can be considered to look for abnormal tympanic membrane mobility. These findings can be associated with allergic rhinitis, particularly if eustachian tube dysfunction or secondary otitis media is present.
Ocular examination may reveal findings of injection and swelling of the palpebral conjunctivae, with excess tear production. Dennie-Morgan lines (prominent creases below the inferior eyelid) are associated with allergic rhinitis.34
The term "cobblestoning" is used to describe streaks of lymphoid tissue on the posterior pharynx, which is commonly observed with allergic rhinitis. Tonsillar hypertrophy can also be observed. Malocclusion (overbite) and a high-arched palate can be observed in patients who breathe from their mouths excessively.35
Neck: Look for evidence of lymphadenopathy or thyroid disease.
Lungs: Look for the characteristic findings of asthma.
Skin: Evaluate for possible atopic dermatitis.
Other: Look for any evidence of systemic diseases that may cause rhinitis (eg, sarcoidosis, hypothyroidism, immunodeficiency, ciliary dyskinesia syndrome, other connective tissue diseases).
Causes
The causes of allergic rhinitis may differ depending on whether the symptoms are seasonal, perennial, or sporadic/episodic. Some patients are sensitive to multiple allergens and can have perennial allergic rhinitis with seasonal exacerbations. While food allergy can cause rhinitis, particularly in children, it is rarely a cause of allergic rhinitis in the absence of gastrointestinal or skin symptoms.

Seasonal allergic rhinitis is commonly caused by allergy to seasonal pollens and outdoor molds.
Pollens (tree, grass, and weed)
Tree pollens, which vary by geographic location, are typically present in high counts during the spring, although some species produce their pollens in the fall. Common tree families associated with allergic rhinitis include birch, oak, maple, cedar, olive, and elm.
Grass pollens also vary by geographic location. Most of the common grass species are associated with allergic rhinitis, including Kentucky bluegrass, orchard, redtop, timothy, vernal, meadow fescue, Bermuda, and perennial rye. A number of these grasses are cross-reactive, meaning that they have similar antigenic structures (ie, proteins recognized by specific IgE in allergic sensitization). Consequently, a person who is allergic to one species is also likely to be sensitive to a number of other species. The grass pollens are most prominent from the late spring through the fall but can be present year-round in warmer climates.
Weed pollens also vary geographically. Many of the weeds, such as short ragweed, which is a common cause of allergic rhinitis in much of the United States, are most prominent in the late summer and fall. Other weed pollens are present year-round, particularly in warmer climates. Common weeds associated with allergic rhinitis include short ragweed, western ragweed, pigweed, sage, mugwort, yellow dock, sheep sorrel, English plantain, lamb's quarters, and Russian thistle.
Outdoor molds
Atmospheric conditions can affect the growth and dispersion of a number of molds; therefore, their airborne prevalence may vary depending on climate and season.
For example, Alternaria and Cladosporium are particularly prevalent in the dry and windy conditions of the Great Plains states, where they grow on grasses and grains. Their dispersion often peaks on sunny afternoons. They are virtually absent when snow is on the ground in winter, and they peak in the summer months and early fall.
Aspergillus and Penicillium can be found both outdoors and indoors (particularly in humid households), with variable growth depending on the season or climate. Their spores can also be dispersed in dry conditions.
Perennial allergic rhinitis is typically caused by allergens within the home but can also be caused by outdoor allergens that are present year-round.36 In warmer climates, grass pollens can be present throughout the year. In some climates, individuals may be symptomatic due to trees and grasses in the warmer months and molds and weeds in the winter.
House dust mites
In the United States, 2 major house dust mite species are associated with allergic rhinitis. These are Dermatophagoides farinae and Dermatophagoides pteronyssinus.31
These mites feed on organic material in households, particularly the skin that is shed from humans and pets. They can be found in carpets, upholstered furniture, pillows, mattresses, comforters, and stuffed toys.
While they thrive in warmer temperatures and high humidity, they can be found year-round in many households. On the other hand, dust mites are rare in arid climates.
Pets
Allergy to indoor pets is a common cause of perennial allergic rhinitis.31,32
Cat and dog allergies are encountered most commonly in allergy practice, although allergy has been reported to occur with most of the furry animals and birds that are kept as indoor pets.
Cockroaches: While cockroach allergy is most frequently considered a cause of asthma, particularly in the inner city, it can also cause perennial allergic rhinitis in infested households.37,38
Rodents: Rodent infestation may be associated with allergic sensitization.39,40,41
Sporadic allergic rhinitis, intermittent brief episodes of allergic rhinitis, is caused by intermittent exposure to an allergen. Often, this is due to pets or animals to which a person is not usually exposed. Sporadic allergic rhinitis can also be due to pollens, molds, or indoor allergens to which a person is not usually exposed. While allergy to specific foods can cause rhinitis, an individual affected by food allergy also usually has some combination of gastrointestinal, skin, and lung involvement. In this situation, the history findings usually suggest an association with a particular food. Watery rhinorrhea occurring shortly after eating may be vasomotor (and not allergic) in nature, mediated via the vagus nerve. This often is called gustatory rhinitis.
Occupational allergic rhinitis, which is caused by exposure to allergens in the workplace, can be sporadic, seasonal, or perennial. People who work near animals (eg, veterinarians, laboratory researchers, farm workers) might have episodic symptoms when exposed to certain animals, daily symptoms while at the workplace, or even continual symptoms (which can persist in the evenings and weekends with severe sensitivity due to persistent late-phase inflammation). Some workers who may have seasonal symptoms include farmers, agricultural workers (exposure to pollens, animals, mold spores, and grains), and other outdoor workers. Other significant occupational allergens that may cause allergic rhinitis include wood dust, latex (due to inhalation of powder from gloves), acid anhydrides, glues, and psyllium (eg, nursing home workers who administer it as medication).

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