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Author: Jack M Becker, MD, Chief of Asthma, Allergy and Immunology, Department of Pediatrics, St Christopher's Hospital for Children

Jack M Becker is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, and American College of Allergy, Asthma and Immunology

Editors: C Lucy Park, MD, Director, Allergy and Asthma Center, Associate Professor, Department of Pediatrics, University of Illinois at Chicago; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; John Wilson Georgitis, MD, Consulting Staff, Lafayette Allergy Services; David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville; Harumi Jyonouchi, MD, Associate Professor, Department of Pediatrics, Division of Pulmonary Allergy/Immunology and Infectious Diseases, UMDNJ-New Jersey Medical School

Author and Editor Disclosure

Synonyms and related keywords: allergic rhinitis, AR, hay fever, rose fever, spring cold, sneezing, nasal congestion, stuffiness, rhinorrhea, coughing, nasal itch, itchy eyes, scratchy throat, sinus pressure, sinus headache, epistaxis, asthma, sinusitis, atopic dermatitis, otitis media, allergen, allergy, histamine, prostaglandin D2, heparin, platelet-activating factor, cystic fibrosis, dust mites, cat dander, dog dander, indoor molds, cockroaches, tree pollen, grass pollen, weed pollen

Background

Although allergic rhinitis (AR) is a common disease, the impact on daily life cannot be underestimated. Some patients find AR to be just as debilitating and intrusive as severe asthma. Employees with untreated allergies are reportedly 10% less productive than coworkers without allergies, whereas those using allergy medications to treat AR were only 3% less productive.1 This suggests that effective medications may reduce the overall cost of decreased productivity. AR is caused by an immunoglobulin E (IgE)–mediated reaction to various allergens in the nasal mucosa. The most common allergens include dust mites, pet danders, cockroaches, molds, and pollens.

The allergen present in the outdoor environment varies with the time of year and location. Knowing what allergens are in the environment at a specific time of year helps in diagnosing and treating AR and helps in excluding allergy as a cause of the patient's symptoms. For example, a patient who presents with nasal congestion in November in Boston, Mass cannot have AR attributed to tree pollen allergy, which is prevalent in spring. Allergens bound to allergen-specific IgE antibodies that are bound to mast cells cause a release of a wide range of mediators, which leads to AR symptoms, including sneezing; nasal congestion; stuffiness; rhinorrhea; cough; itching of the nose, eyes, and throat; sinus pressure; headache; and epistaxis.

Allergen exposure likely causes both upper and lower airway inflammation. Many experts believe that a patient's airway needs to be evaluated as a total entity, not as individual parts. Studies have shown that most patients with asthma also have AR. Allergic reactions of the upper airway can trigger lower airway symptoms and vice versa. One study showed that patients with untreated AR and asthma have an almost 2-fold greater risk of having an emergency room visit and almost a 3-fold greater risk of being hospitalized for an asthma exacerbation, respectively.2

See Media files 3-5 for graphs that detail the significant impact of nasal allergies.

Pathophysiology

Understanding the function of the nose is important in order to understand AR. The purpose of the nose is to filter, humidify, and regulate the temperature of inspired air. This is accomplished on a large surface area spread over 3 turbinates in each nostril. A triad of physical elements (ie, a thin layer of mucus, cilia, and vibrissae [hairs] that trap particles in the air) accomplishes temperature regulation. The amount of blood flow to each nostril regulates the size of the turbinates and affects airflow resistance. The nature of the filtered particles can affect the nose. Irritants (eg, cigarette smoke, cold air) cause short-term rhinitis; however, allergens cause a cascade of events that can lead to more significant inflammatory reactions.

In short, rhinitis results from a local defense mechanism in the nasal airways that attempts to prevent irritants and allergens from entering the lungs.

Allergic reactions require exposure and then sensitization to allergens. To be sensitized, the atopic patient must be exposed to allergens for a period of time. Sensitization to highly allergenic indoor allergens can occur in children younger than 2 years. Sensitization to outdoor allergens usually occurs when a child is older than 3-5 years, and the average age at presentation is 9-10 years. The allergic reaction begins with the cross-linking of the allergen to 2 adjacent IgE molecules that are bound to high-affinity Fcε receptors on the surface of a mast cell. This cross-linking causes mast cells to degranulate, releasing various mediators. The best-known mediators are histamine, prostaglandin D2, tryptase, heparin, and platelet-activating factor, as well as leukotrienes and other cytokines.

These substances produce 2 types of reactions: immediate and late-phase. The immediate reactions in the nasal mucosa induce acute allergy symptoms (eg, nasal itch, clear nasal discharge, sneezing, congestion). The late-phase reaction occurs hours later, secondary to the recruitment of inflammatory cells into the tissue by the action of mediators released by the mast cell. Recruited cells are predominated by eosinophils and basophils, which, in turn, release their inflammatory mediators, leading to continuation of the cascade. In very sensitive individuals, this allergen-induced nasal inflammation causes priming of the nasal mucosa. Primed nasal mucosa becomes hyperresponsive, at which point even nonspecific triggers or small amounts of the antigen can cause significant symptoms.

Frequency

United States

Prevalence in the United States is 10-20%.3 One survey demonstrated rates as high as 38.2% when patients were asked if they experienced fewer than 7 days of symptoms. When AR was defined as symptoms lasting more than 31 days, prevalence dropped to 17%.

International

In temperate areas of Europe and Asia, frequency is similar to that in the United States.

Mortality/Morbidity

Mortality is not associated with AR, but significant morbidity occurs. Morbidity is manifested in several ways.

  • Annually, an estimated 824,000 school days are missed, and an estimated 4,230,000 days of reduced quality-of-life functions are reported.4
  • Comorbidity of other atopic diseases (asthma, atopic dermatitis) or upper airway inflammation (sinusitis, otitis media) is significant in AR. Individuals with AR have a higher frequency of these conditions than individuals without AR.
  • Quality-of-life surveys revealed that patients with significant AR found symptoms to be just as debilitating as symptoms in patients with moderate-to-severe asthma. Patients with AR felt they were equally impaired and unable to participate in the activities of normal living similar to those with the moderate-to-severe asthma. They felt that chronic congestion, sneezing, the need to wipe the nose, and a decrease in restful sleep compromised levels of their daily activity.
  • The financial cost of AR is difficult to estimate. Self-treating patients are estimated to spend an average of 56 dollars per year. The direct cost of prescription medication exceeds 6 billion dollars per year worldwide, and lost productivity is estimated at 1.5 billion dollars per year.

Race

AR has no race predilection; however, individuals from non-Caucasian backgrounds seek out medical attention less often than Caucasians.

Sex

AR has no sex predilection.

Age

AR usually presents in early childhood. AR caused by sensitization to outdoor allergens can occur in children older than 2 years; however, sensitization in children aged 4-6 years is more common. Clinically significant sensitization to indoor allergens may occur in children younger than 2 years. This is typically associated with significant exposures to indoor allergens (eg, molds, furry animals, cockroaches, dust mites). Some children may be sensitized to outdoor allergens at this young age if they have significant exposure. Incidence continues to increase until the fourth decade of life, when symptoms begin to fade; however, individuals can develop symptoms at any age.



History

The history of the patient with nasal symptoms may be straightforward or may include a complex set of symptoms. The diagnosis is easy to make in a patient with a new pet or with symptoms that have distinct seasonal variation. Alternatively, younger patients may present with varying signs or symptoms, the family may not appreciate the nasal stuffiness but may note the chronic congestion. In older children, symptoms may have been present for years and, therefore, appear to be less severe because the child has accommodated them.

Physicians should try to identify seasonal variations, provocative elements in the environment, and the timing of events that lead to symptoms. Few patients present soon after the onset of allergic rhinitis (AR) symptoms. Usually, AR symptoms have been present for years and have been slowly worsening during each allergy season. In fact, a patient who describes a sudden onset of nasal allergy symptoms, unless a new exposure to large amounts of allergens is reported (eg, pet, feather pillow), is not experiencing allergic symptoms. Sudden onset of nasal symptoms is often associated with acute sinusitis or acute bacterial sinusitis superimposed on chronic sinusitis. In children younger than 5 years, differentiating allergy symptoms from recurrent upper respiratory viral infection is even more difficult, especially in children who attend daycare and experience frequent rhinitis symptoms.

  • Nature of symptoms
    • Symptoms of rhinitis consist of rhinorrhea, nasal congestion, postnasal drainage, repetitive sneezing, and itching of the palate, nose, or eyes. Snoring, frequent sore throats, constant clearing of the throat, cough, itchy eyes, and headaches are symptoms often associated with rhinitis.
    • When obtaining the history, ascertain the following:
      • Determine which symptoms are reported by the patient or parent.
      • Determine whether the patient has rhinorrhea, sniffling, nasal itching, sneezing, cough, congestion, or nasal discharge. Determine the color of the nasal discharge.
      • Determine whether any associated ocular or respiratory symptoms are present.
  • Timing of symptoms
    • Identify whether symptoms are present or worsen during certain seasons, such as the spring or fall. In addition, try to identify whether symptoms are worse in specific places, such as home, work, or school, or when the patient is around animals.
    • Determine when symptoms occur and whether they occur primarily at night, in school, outdoors, or at a relative's or friend's home.
    • Determine whether symptoms occur only at a certain time of the year or throughout the year.
    • Determine whether symptoms ever improve and, if so, what actions help alleviate symptoms. Most patients have tried over-the-counter antihistamine medication. If these medications help, AR should be suspected; however, a negative response does not eliminate the possibility of AR.
    • Determine whether symptoms improve when the patient is taking antibiotics. Most patients receive antibiotics for various reasons unrelated to nasal symptoms. If symptoms respond to antibiotic therapy, the clinical diagnosis may be sinusitis, which may have been either primary sinusitis or secondary sinusitis caused by AR.
  • Duration of symptoms
    • Determine whether symptoms last for weeks, months, or hours.
    • Most pollen seasons are at least 6 weeks long in more moderate climates. In the south and far north, the season can be longer or shorter, respectively. Symptoms that last less than 2 weeks rarely indicate AR unless concomitant exposure occurs.
    • In winter in the northern regions, virtually all pollens are absent; therefore, any AR-like symptoms are the result of indoor allergen exposure or are not caused by allergen exposure. Although patients are usually exposed to the same allergens throughout the year, AR symptoms triggered by indoor allergens can worsen in winter secondary to longer hours spent indoors during the cold months. This may also be associated with closed windows and doors in winter, resulting in increased recirculation of indoor allergens. An example of winter-only exposure is a person who is allergic to dust mites who uses a down comforter only during the winter (dust mites are highly infested in a down comforter.)
  • Family history
    • Children with parents who have allergies or asthma are more likely to be affected.
    • If a child has one parent with allergies, chances are 30% that a child will have AR. This increases to 50-70% if both parents have allergies or asthma.
  • Related medical history
    • Patients with a history of infantile eczema (atopic dermatitis) have a 70% chance of having AR, asthma, or both.
    • Patients with a history of asthma also have higher incidence of AR.
  • Social and environmental history
    • The patient's environment is very important. Ask about the presence of a pet or feathers (eg, pillow, bedspread, comforter) in the home and the timing of initial exposure. Many times, exposure to feathers or pets coincides with the onset of symptoms, making diagnosis and treatment easier. However, patients could become sensitized to indoor allergens by exposure in places other than the home where they spend a fair numbers of hours (eg, schools, daycare center).
    • Questions must be raised regarding any environment in which the patient spends more than a few hours per week. This includes baby-sitters' and relatives' homes, daycare facilities, and schools (classroom pets).
    • For children younger than 3 years, ask about the child's bed. Cribs or toddler beds that use crib mattresses do not have dust mites because of the plastic covers, but standard bedding (bed mattress) can harbor dust mites.

 

Physical

A full examination should always be performed to detect other diseases, such as asthma, eczema, and cystic fibrosis, which occur in connection with AR. Evaluation involves the head, eyes, ears, nose, and throat. Upon inspection, the following signs can be noted:

  • Head
    • Allergic shiners (dark, puffy, lower eyelids) may be present.
    • Morgan-Dennie lines (lines under the lower eyelid) may be observed.
    • Transverse crease at the lower third of the nose secondary to the allergic salute, which is the upward rubbing of the nose, is commonly seen in parents as well.
  • Eyes
    • Marked erythema of palpebral conjunctivae and papillary hypertrophy of tarsal conjunctivae are observed. Chemosis of the conjunctivae may be present. Patients usually have a watery discharge.
    • Cataracts have occurred from severe rubbing secondary to itching.
  • Ears
    • Tympanic membranes should be examined for the presence of chronic infection or middle ear effusion.
    • The role of AR in chronic otitis media is not clear, but decreased numbers of infections have been noted in children with AR once therapy was instituted.
  • Nose
    • Nasal examination is often helpful in the diagnosis.
    • Turbinates are enlarged and have a pale-bluish mucosa due to edema.
    • Discharge is usually clear but can be white. The discharge is rarely yellow or green. If colored discharge is observed, a diagnosis of viral infection or sinusitis should be considered.
    • Dried blood is commonly observed secondary to trauma from rubbing the nose.
    • Polyps are rarely observed in children. If polyps are noted or suspected, perform rhinoscopy. If polyps are detected, a workup for cystic fibrosis is mandatory in children. Also consider the diagnosis of aspirin sensitivity in adults.
  • Throat
    • Inspection of the dentition can be informative. Discoloration of frontal incisors and a high arched palate are associated with chronic mouth breathing. Malocclusion is commonly associated with chronic mouth breathing.
    • Cobblestoning in the posterior pharynx is also a sign of follicular hypertrophy of mucosal lymphoid tissue secondary to chronic nasal congestion and postnasal drainage.
    • Note the size of tonsillar tissue, which may provide a clue to the size of the adenoids; large adenoids can mimic the signs and symptoms of AR. Chronic nasal congestion due to adenoid hypertrophy is frequently seen in young children with recurrent otitis media and sinusitis.

Causes

  • Perennial symptoms are usually caused by indoor allergens, including the following:
    • Dust mites
    • Cat dander
    • Dog dander
    • Indoor molds
    • Cockroaches
    • Feathers (In most occasions, feather pillows and comforters are highly allergenic, secondary to dust mite infestation.)
    • Other furry animals
  • Seasonal symptoms are usually caused by airborne pollen and outdoor molds, including the following:
    • Tree pollen
    • Grass pollen
    • Outdoor mold spores
    • Weed pollen (Flowers do not cause AR because they do not use wind-borne pollination.)



Agammaglobulinemia
Aspergillosis
Cystic Fibrosis
Gastroesophageal Reflux
Nasal Polyps
Sinusitis

Other Problems to be Considered

Inflammatory causes

Bottle feeding (children >18 mo)
Vasomotor rhinitis
Viral infection

Obstructive causes

Adenoid hyperplasia
Choanal atresia
Foreign body
Deviated septum
Nasal polyps
Neoplasm

Oral Allergy Syndrome

Oral allergy syndrome (OAS) occurs when the body perceives certain foods, primarily fruits and vegetables, as an allergen and causes a contact dermatitis reaction in the mouth. Patients with this condition report an itchy mouth when eating certain fruits or vegetables in their natural form. For example, eating a whole fresh apple causes a reaction, but eating apple pie or apple sauce or drinking apple juice does not. The most common pollens involved are birch tree pollen and ragweed. Birch tree pollen cross-reacts with apples, pears, celery, and carrots, whereas Ragweed cross-reacts with melons and berries.

Making the proper diagnosis is important because OAS can be confused with a potentially life-threatening anaphylactic reaction to food allergens



Lab Studies

  • No studies are needed if the patient has a straightforward history. When the history is confusing, various studies are helpful, including the following:
    • Nasal smear: Eosinophils usually indicate allergy. Neutrophils are more indicative of an infectious process, such as sinusitis.
    • CBC count with differential: A CBC count may reveal an increased number of eosinophils. An eosinophil count within the reference range does not exclude allergic rhinitis (AR); however, an elevated eosinophil count is suggestive of the diagnosis.
    • Immunoglobulin E: Serum IgE values are not routinely recommended to evaluate atopy. An IgE value within the reference range does not exclude AR; however, an elevated IgE value is suggestive of the diagnosis.

Imaging Studies

  • Imaging studies are not needed unless sinusitis is suspected, in which case, a limited CT scan of the sinuses (without contrast) is indicated.

Other Tests

  • Radioallergosorbent testing
    • Radioallergosorbent testing (RAST) for common allergens can be used to identify the patient's triggers. These might include dust mites, cat dander, dog dander, grass pollens, tree pollens, weed pollens, and molds.
    • Foods rarely cause AR, and tests for food allergies are not indicated in patients with AR.
    • RAST testing for allergens, such as dust mites, cat dander, and dog dander, is almost as sensitive and specific as allergy skin testing.

Procedures

  • Skin testing to identify the triggering agent
    • Skin testing has high sensitivity and specificity and is the preferred method of quick allergen identification.
    • Skin testing is helpful if the allergens can be eliminated from the patient's environment or if the patient can avoid them.
    • Skin testing is extremely helpful when patients are unresponsive to standard therapy or are unwilling to acknowledge the trigger, which is especially true if the family pet is a possible trigger.
  • Rhinoscopy: This is helpful in direct examination of the upper airway in identifying whether the etiology of rhinitis is obstructive or infectious and to evaluate for nasal polyps.



Medical Care

Treatment can be divided into 3 categories: avoidance of allergens or environmental controls, medications, and allergen-specific immunotherapy (allergy shots).

  • Use of environmental controls is not adequately explored in most patients. For many patients, the removal of the trigger can have a dramatic effect. Difficulty arises when the trigger needs to be identified and eliminated. Eliminating the trigger may be simple if removal of a feather pillow or blanket is involved; however, it can be very difficult if a family pet needs to be removed. Although avoiding outdoor pollens is impossible, the patient can reduce exposure to pollens to attenuate symptoms.
  • Identification and elimination is easiest for dust mites and feather allergens. Feathered bedding should be removed and replaced with a fiber-filled product. To reduce dust mites, special allergen-proof covers for pillows and mattresses can be obtained either by mail-order or at local stores. The important factor is that the covers must be plastic on one side and have a zippered closure. A bed pad that is placed on top is not adequate and may become another source of dust mite infestation. Less expensive plastic casing may leak allergens through needle holes or between zipper teeth; therefore, more expensive dust mite–proof covers are preferable. The pillow must be covered, which is even more crucial than covering the bed mattress itself because the pillow is where the patient's head usually spends most of the night. Box springs usually do not need to be covered.
  • Pollen is more difficult to avoid because daily activities must be altered to do so.
    • The patient is best advised to remain indoors with air-conditioning during the period of the highest pollen counts of the day. Commonly, remaining indoors is not possible because of patient activities, and many schools are not air-conditioned.
    • An easy intervention is to keep the windows closed, which is easily accomplished in air-conditioned homes and must be done throughout the year. Windows tend to be opened most frequently during fall and spring in moderate climates, but these seasons are the worst possible times for open windows. If windows must be open, open them during the day and close them at night. Many pollen counts are highest during the night, especially for molds and trees.
    • Another intervention is to obtain a window filter or filter fan, which allows air, but not pollen, to enter the room.
    • Advise patients to wash head to toe and to change clothing upon coming in from the outdoors during high pollen season. Avoid hanging cloths outdoors to dry.
  • The most difficult trigger to avoid is the family pet. Ideally, the pet should be removed from the home, but removal is the option, not the rule. Some helpful manipulations include removing the pet from the patient's bedroom and play area, using air cleaners in these areas and, occasionally, frequently sponge-bathing the pet (once per week). Even when these interventions are performed, many patients continue to experience symptoms. Other therapies are necessary in these patients; however, some patients choose to live with the source of offending allergens.
  • See Medication for a discussion of medications and allergen-specific immunotherapy (ie, allergy shots).

Surgical Care

  • No routine surgical care is needed.
  • Some patients may be seen by ear, nose, and throat (ENT) specialists, and turbinectomies may be performed to provide some relief. This is an extreme measure and is reserved for patients in whom all other therapies have failed.
  • Rarely, in adults, if nasal polyps do not respond to topical nasal steroids, surgical removal may be necessary, although the polyps often grow back.

Consultations

  • Primary care physicians can attend to most patients.
  • Patients in whom diagnosis or treatment is more difficult may require consultation with a specialist. This usually starts with an allergist, who performs a complete allergy evaluation, including diagnostic tests. Therapy is instituted, which is a combination of environmental manipulations, medications and, in some patients, allergen-specific immunotherapy.
  • If medical therapies do not produce an adequate result, referral to an ENT specialist should be indicated for possible surgical intervention.

Diet

  • Dietary restrictions do not help because allergic rhinitis (AR) is not triggered by foods.

Activity

  • No limitations are placed on activity.
  • For some pollens, patients with AR benefit from avoiding the outdoors during peak pollen periods of the day. This time varies according to pollens and location. Geographic location and distance from the source have an impact. Patients who are miles away from the source have different peak pollen times than patients near the source.



Many groups of medications are used for allergic rhinitis (AR) (eg, antihistamines, corticosteroids, decongestants, saline, sodium cromolyn, antileukotrienes). These can be further subdivided into intranasal and oral therapies. Intranasal administration has the advantage of directly affecting the site of action, and, in general, intranasal medications have fewer adverse effects and no systemic effects. The main advantage of oral therapy is ease of use. Many patients resist using intranasal medications.

Allergen-specific immunotherapy is an alternative form of therapy that has several advantages. Most importantly, it is the only form of therapy that can cure allergy symptoms. Allergen-specific immunotherapy must be customized to the patient's individual allergies and involves weekly injections of increasing concentrations of an allergen until the maintenance dose is reached and a monthly injection of the maintenance dose for several years. The process usually does not produce clinical results in the first 6 months but results are seen afterwards. The recommended course is usually 4-5 years. Allergen-specific immunotherapy has been demonstrated to be more cost effective and improves the patient's quality of life more efficiently than standard allergy medications.

Saline nasal irrigation is effective in approximately 50% of patients with AR. Irrigation assists the body's natural function of rinsing allergens out of nasal passages. Tap water cannot be used because it is hypotonic and causes edema, leading to greater congestion.

Drug Category: Oral antihistamines

Antihistamines are classified in several ways, including sedating and nonsedating, newer and older, and first- and second-generation antihistamines (most widely accepted classification). First-generation antihistamines are primarily over the counter and are included in many combination products for cough, colds, and allergies. These include brompheniramine (Dimetapp), chlorpheniramine (Atrohist), and diphenhydramine (Benadryl). Loratadine (Claritin) is now available over the counter without a prescription. Second-generation antihistamines are desloratadine (Clarinex), fexofenadine (Allegra), and cetirizine (Zyrtec), which require a prescription.

Drug NameCetirizine (Zyrtec)
DescriptionLow-sedating second-generation medication with fewer adverse effects than first-generation medications. Selectively inhibits peripheral histamine H1 receptors. Available as syr (5 mg/5 mL) and 5- or 10-mg tab.
Adult Dose5-10 mg PO qd
Pediatric Dose6-12 months: 2.5 mg PO qd; not to exceed 2.5 mg/d
12-24 months: 2.5 mg PO qd; may increase to 2.5 mg PO bid, if needed
2-5 years: 2.5-5 mg PO qd or divided bid; not to exceed 5 mg/d
>6 years: 5-10 mg PO qd or divided bid
ContraindicationsDocumented hypersensitivity
InteractionsIncreases toxicity of CNS depressants; theophylline decreases clearance of cetirizine
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsReduce dose in patients with kidney disease; may cause sedation in 5-15% of patients

Drug NameLevocetirizine (Xyzal)
DescriptionHistamine H1-receptor antagonist. Active enantiomer of cetirizine. Peak plasma levels are reached within 1 h, and half-life is about 8 h. Available as a 5-mg breakable (scored) tab. Indicated for seasonal and perennial AR
Adult Dose5 mg PO qd in evening
CrCl 50-80 mL/min: 2.5 mg (half tab) PO qd in evening
CrCl 30-49 mL/min: 2.5 mg PO qod
CrCl 10-29 mL/min: 2.5 mg PO 2 times/wk
Pediatric Dose<6 years: Not established
6-11 years: 2.5 mg (half tab) PO qd in evening
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity; CrCl <10 mL/min or hemodialysis; children aged 6-11 y with renal impairment
InteractionsCoadministration with CNS depressants (eg, alcohol, sedative-hypnotics) may increase somnolence; ritonavir increased plasma AUC of measurable cetirizine by 42% and half-life by 53%
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCommon adverse effects include somnolence, nasopharyngitis, fatigue, xerostomia, and pharyngitis in adults and children >12 y; pyrexia, somnolence, cough, and epistaxis commonly observed in children 6-12 y; caution with activities requiring mental alertness

Drug NameLoratadine (Claritin)
DescriptionNonsedating second-generation antihistamine. Fewer adverse effects than with first-generation medications. Selectively inhibits peripheral histamine H1 receptors. Available as tab, disintegrating tab (Reditab), syr (5 mg/5 mL), or combined with pseudoephedrine in 12- or 24-h preparations. The only one that is presently available without a prescription
Adult DoseLoratadine: 10 mg/d PO
Loratadine and pseudoephedrine:
Claritin-D 12 Hour: 5 mg with 120 mg pseudoephedrine; 1 tab PO bid
Claritin-D 24 Hour: 10 mg with 240 mg pseudoephedrine; 1 tab PO qd
Pediatric DoseLoratadine:
<2 years: Not established
2-5 years: 5 mg PO qd
>6 years: Administer as in adults
Loratadine and pseudoephedrine:
<12 years: Not established
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsKetoconazole, erythromycin, procarbazine, cimetidine, and alcohol may increase loratadine levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMay cause headaches; initiate therapy at lower dose in liver and renal impairment

Drug NameDesloratadine (Clarinex)
DescriptionNonsedating second-generation antihistamine. Fewer adverse effects than with first-generation antihistamines. Selectively inhibits peripheral histamine H1 receptors. Relieves nasal congestion and systemic effects of seasonal allergies. Long-acting tricyclic histamine antagonist selective for H1-receptor. Major metabolite of loratadine, which, after ingestion, is extensively metabolized to active metabolite 3-hydroxydesloratadine. Available as tabs, syr (0.5 mg/mL), or PO disintegrating Reditabs (2.5 and 5 mg).
Adult DoseDesloratadine: 5 mg PO qd
Desloratadine and pseudoephedrine:
Clarinex-D 24 Hour: 5 mg with 240 mg pseudoephedrine; 1 tab PO qd
Pediatric Dose6-11 months: 1 mg (2 mL of syr) PO qd
1-5 years: 1.25 mg (2.5 mL of syr) PO qd
6-11 years: 2.5 mg (5 mL of syr or Reditab) PO qd
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity to desloratadine or loratadine
InteractionsLimited data exist; erythromycin and ketoconazole increase desloratadine and 3-hydroxydesloratadine plasma concentrations, but no increase of clinically relevant adverse effects, including QTc, has been observed
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDecrease dose in hepatic impairment; rarely causes pharyngitis or dry mouth

Drug NameFexofenadine (Allegra)
DescriptionNonsedating second-generation medication with fewer adverse effects than first-generation medications. Competes with histamine for H1 receptors in GI tract, blood vessels, and respiratory tract, reducing hypersensitivity reactions. Available in qd and bid preparations. Also available combined with pseudoephedrine.
Adult DoseFexofenadine: 60 mg PO bid (IR) or 180 mg/d PO (SR)
Fexofenadine and pseudoephedrine:
Allegra-D 12 Hour: 60 mg with 120 mg pseudoephedrine; 1 tab PO bid
Allegra-D 24 Hour: 180 mg with 240 mg of pseudoephedrine; 1 tab PO qd
Pediatric Dose<6 years: Not established
6-11 years: 30 mg PO bid
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsLevels may increase with coadministration of erythromycin and ketoconazole
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAdjust dose in renal impairment (can be used safely in hepatic impairment without dose reduction)

Drug Category: Intranasal antihistamines

These agents are an alternative to oral antihistamines to treat AR. Currently, azelastine is the only agent available in the United States.

Drug NameAzelastine (Astelin)
DescriptionAn effective antihistamine delivered via the intranasal route. Mechanism is similar to PO antihistamines. Systemic absorption occurs and may cause sedation, headache, and nasal burning.
Adult Dose2 sprays/nostril bid (137 mcg/spray)
Pediatric Dose<5 years: Not established
5-11 years: 1 spray/nostril bid (137 mcg/spray)
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsPotentiates CNS depression with alcohol and other CNS depressants; caution with concurrent use of oral antihistamines; when administered PO, serum levels are increased by cimetidine; no effect on QTc when administered PO with ranitidine, theophylline, ketoconazole, or erythromycin
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAvoid contact with eyes; may cause sedation

Drug Category: Intranasal corticosteroids

This class of medications is most effective. Intranasal corticosteroids are potent anti-inflammatory agents shown to decrease AR symptoms in more than 90% of patients. Presently, 9 medications are available in this class, and all are essentially equivalent in efficacy, although few head-to-head studies have been performed. Mometasone (Nasonex) and fluticasone furoate (Veramyst) have been demonstrated to have a somewhat faster onset of action; however, after one week, no difference is found between medications. Most can be used on a once-daily basis, and all have a similar safety profile. Nasonex is the only medication that did not show an affect on growth at one year. Veramyst did not show a growth affect in a 2-week study that is designed to evaluate for growth affects. A longer study is scheduled to begin in late 2007.

Drug NameBeclomethasone (Beconase, Vancenase)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation.
Adult Dose2-4 sprays/nostril bid (42 mcg/spray); titrate to lowest effective dose
Pediatric Dose<6 years: Not established
6-11 years: 1-2 sprays/nostril bid
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses

Drug NameBudesonide (Rhinocort Aqua)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation.
Adult Dose1-4 sprays/nostril qd or divided bid; titrate to lowest effective dose (32 mcg/spray); not to exceed 4 sprays/nostril/d
Pediatric Dose<6 years: Not established
6-11 years: 1 spray/nostril qd; may increase to 2 sprays/nostril qd if needed
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses

Drug NameCiclesonide (Omnaris)
DescriptionCorticosteroid nasal spray indicated for AR. Prodrug that is enzymatically hydrolyzed to pharmacologic active metabolite C21-desisobutyryl-ciclesonide following intranasal application. Corticosteroids have a wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamines, eicosanoids, leukotrienes, cytokines) involved in allergic inflammation. Each spray delivers 50 mcg.
Adult Dose2 sprays (50 mcg/spray) in each nostril qd (ie, 200 mcg/d)
Pediatric Dose<12 years: Not established
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsData limited; PO ketoconazole increases desciclesonide AUC by approximately 3.5-fold at steady state
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution when replacing systemic corticosteroids because of risk of adrenal insufficiency; may decrease growth velocity in pediatric patients; caution with active or quiescent tuberculosis infection or with untreated fungal, viral, or bacterial infections; rare instances of wheezing, nasal septum perforation, cataracts, glaucoma, and increased intraocular pressure reported

Drug NameFlunisolide (Nasalide, Nasarel)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation.
Adult Dose2 sprays/nostril bid or tid; not to exceed 8 sprays/d (25 mcg/spray)
Pediatric Dose<6 years: Not established
6-14 years: 2 sprays/nostril bid; not to exceed 4 sprays/d
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses

Drug NameFluticasone propionate (Flonase)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation.
Adult Dose1-2 sprays/nostril qd or 1 spray/nostril bid (50 mcg/spray); titrate to lowest effective dose; not to exceed 4 sprays (200 mcg)/d
Pediatric Dose<4 years: Not established
>4 years: 1 spray/nostril qd; may increase to 2 sprays/nostril if needed
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with other corticosteroids could increase risk of hypercorticism and/or suppression of HPA; coadministration with CYP450 3A4 isoenzyme inhibitors (eg, amprenavir, atazanavir, darunavir, delavirdine, fosamprenavir, indinavir, ketoconazole, nelfinavir, ritonavir, tipranavir) decreases fluticasone elimination and increases plasma fluticasone levels, case reports of iatrogenic cushingoid symptoms have been reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses

Drug NameFluticasone furoate (Veramyst)
DescriptionIntranasal corticosteroid. Indicated for seasonal and perennial allergic rhinitis. Relieves nasal symptoms associated with allergic rhinitis. Has also demonstrated improvement in allergic eye symptoms. Contains 27.5 mcg/spray.
Adult Dose110 mcg intranasally qd initially (ie, 2 sprays each nostril qd); once symptoms improve, may decrease to 55 mcg qd (ie, 1 spray each nostril qd)
Pediatric Dose<2 years: Not established
2-11 years: 55 mcg intranasally qd (ie, 1 spray each nostril qd)
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration with other corticosteroids could increase risk of hypercorticism and/or suppression of HPA; coadministration with CYP450 3A4 isoenzyme inhibitors (eg, amprenavir, atazanavir, darunavir, delavirdine, fosamprenavir, indinavir, ketoconazole, nelfinavir, ritonavir, tipranavir) decreases fluticasone elimination and increases plasma fluticasone levels, case reports of iatrogenic cushingoid symptoms have been reported
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsPrime before using for first time by shaking contents and releasing 6 test sprays into air away from face; common adverse effects include headache, nose bleed, and nasal sores; fever occurred more frequently in children aged 2-11 years compared with placebo; epistaxis or sensations of nasal burnings may occur; local candidal infections of nasopharynx have been reported with topical steroid use; always consider potential risk of suppression of HPA when using large dose for prolonged periods; rare cases of cataract, glaucoma, and increased intraocular pressure have been reported following intranasal use of corticosteroids; concomitant use of intranasal corticosteroids and other inhaled and/or systemically absorbed corticosteroids may cause hypercorticism and/or HPA suppression; if exposed to measles or chickenpox, consider prophylactic therapy

Drug NameMometasone (Nasonex)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation. Demonstrated no mineralocorticoid, androgenic, antiandrogenic, or estrogenic activity in preclinical trials. Decreases rhinovirus-induced up-regulation in respiratory epithelial cells and modulate pretranscriptional mechanisms. Reduces intraepithelial eosinophilia and inflammatory cell infiltration (eg, eosinophils, lymphocytes, monocytes, neutrophils, plasma cells).
Adult Dose2 sprays (50 mcg/spray) each nostril qd
Pediatric Dose<2 years: Not established
2-11 years: 1 spray (50 mcg/spray) each nostril qd
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses; use with caution in patients with active or quiescent tuberculosis of the respiratory tract; untreated fungal, bacterial, systemic viral infections; or ocular herpes; rare instances of nasal septum perforation and increased IOP have been reported; nasal and inhaled corticosteroids have been associated with development of glaucoma and/or cataracts

Drug NameTriamcinolone (Nasacort AQ)
DescriptionMay decrease number and activity of inflammatory cells, resulting in decreased nasal inflammation.
Adult Dose2 sprays/nostril/d initially; titrate to lowest effective dose
Pediatric Dose<6 years: Not established
6-11 years:
Nasacort: 2 sprays/nostril/d
Nasacort AQ: 1-2 sprays/nostril/d; titrate to lowest effect dose
>12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMay cause adrenal suppression if overused; monitor for growth suppression in children; most common adverse effect is local irritation; exercise great caution when using nasal and inhaled corticosteroids because doses are additive and adverse effects are much more likely to occur as a result; cushingoid symptoms (eg, round [moon] face, weight gain) may occur with high doses

Drug Category: Intranasal decongestants

Decongestants are effective for short-term symptom control. They decrease nasal discharge and congestion and are available without a prescription. The 2 medications in this group are oxymetazoline hydrochloride (Afrin) and ipratropium bromide (Atrovent). Oxymetazoline hydrochloride is an addictive medication that is effective in shrinking nasal membranes and is not recommended for long-term use. Use of oxymetazoline hydrochloride for more than 7-10 d is habit forming. Patients can be addicted for years at a time. Addiction is termed rhinitis medicamentosa. Ipratropium bromide can be used for a prolonged period of time.

Drug NameIpratropium bromide 0.03% or 0.06% (Atrovent)
DescriptionAnticholinergic used for reducing rhinorrhea in patients with AR or vasomotor rhinitis. An excellent medication for decreasing rhinitis. Nonaddictive and lasts for 12 hours. Does not shrink the nasal mucosa, but inhibits secretion that causes rhinitis. Used alone or in conjunction with other medications.
Adult Dose2 sprays/nostril bid/tid (21 mcg/spray)
Pediatric Dose<6 years: Not established
>6 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsDrugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol increases effects
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAvoid contact with eyes; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Category: Intranasal mast cell stabilizers

These are effective therapy for AR in approximately 70-80% of patients. They produce mast cell stabilization and antiallergic effects by inhibiting mast cell degranulation. They have no direct anti-inflammatory or antihistaminic effects and minimal bronchodilator effects. They are effective for prophylaxis. They also clean out antigens mechanically, similar to saline. These products are now available over the counter.

Drug NameCromolyn sodium (Nasalcrom)
DescriptionUsed on a daily basis for seasonal or perennial AR. Significant effect may not be seen for 4-7 d. Administer just before exposure in patients with isolated and predictable periods of exposure (eg, animal allergy, occupational allergy). Generally less effective than nasal corticosteroids. Protective effect lasts 4-8 h; thus, frequent dosing is necessary. If desired, may be used with other medicines, including other allergy medicines.
Adult Dose1 spray/nostril q4-6h (5.3 mg/spray)
Pediatric Dose<2 years: Not established
>2 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsMay take up to 4 wk for maximum efficacy; may cause nasal irritation; do not use in severe renal or hepatic impairment; symptoms may recur when drug is withdrawn

Drug Category: Antileukotrienes

Montelukast has been approved as monotherapy for allergic rhinitis. It has been shown to be most effective in patients in whom significant congestion is a primary complaint. It has also been shown to work as adjunctive therapy with present second-generation antihistamines to provide greater relief of symptoms than antihistamines alone. It is beneficial in patients with symptoms in whom present antihistamines are not adequate. A study has shown a combination with cetirizine is as effective as an intranasal corticosteroid. Antileukotriene can also be added to the treatment plan in patients receiving antihistamines and intranasal therapy.

Drug NameMontelukast (Singulair)
DescriptionInhibits airway cysteinyl leukotriene receptors. Because these receptors are found throughout the airway, the medication can mediate the effect in the upper and lower airway.
Adult Dose10 mg PO qhs
Pediatric Dose6-23 months: 4 mg (oral granules) PO qhs
2-5 years: 4 mg (chewable tab) PO qhs
6-14 years: 5 mg (chewable tab) PO qhs
>15 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsSubstrate of CYP2C9 and CYP3A4; rifampin, phenobarbital, or carbamazepine may increase clearance
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsNot indicated to reverse acute asthma attacks; not for use as monotherapy in management of exercise-induced bronchospasm



Further Outpatient Care

  • Patients with allergic rhinitis (AR) need continuous follow-up care because AR is a chronic disease that waxes and wanes with seasons and age. The fluctuation of symptoms requires adjustment of medications.
  • Patients rarely outgrow AR in childhood.
  • Refer patients in whom AR becomes hard to manage or diagnose to an allergist for complete evaluation and advanced treatment, including institution of allergen-specific immunotherapy.

Deterrence/Prevention

  • The best deterrent is to avoid allergens that trigger symptoms. This means diligent environmental controls and patient compliance with medication use.

Complications

  • Primary complications of AR are associated diseases.
  • Sinusitis is a common complication occurring secondary to the inflamed nasal turbinates that block the ostiomeatal complex of the sinuses and other sinus passages. Blockade of auditory tube is also implicated with otitis media.
  • AR can lead to rhinitis medicamentosa when topical nasal decongestants are used in excess.
  • AR can cause other conditions, such as insomnia, irritability, headache, chronic fatigue, and pharyngitis. These occur secondary to chronic nasal congestion and discharge, mouth breathing, and sleep disturbance.

Prognosis

  • Most patients are able to live normal lives with the symptoms.
  • Only patients who receive allergen-specific immunotherapy are cured of the disease; however, many patients do very well with intermittent symptomatic care.
  • A small percentage of patients improve during the teenage years, but in most, symptoms recur in the early twenties or later. Symptoms begin to wane when patients reach the fifth decade of life.

Patient Education



Media file 1:  Photo demonstrates the allergic salute, which is the action performed when a patient rubs the nose using a motion across the nose.
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Media file 2:  Photo demonstrates allergic shiners. Note the periorbital edema and bluish discoloration seen in allergic rhinitis and sinusitis.
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Media file 3:  Impact of nasal allergies.
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Media file 4:  How patient feel when they have allergy symptoms.
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Media file 5:  Nasal symptoms and affect on work performance.
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Media type:  Graph



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Allergic Rhinitis excerpt

Article Last Updated: Sep 26, 2007