Treating Allergic Rhinitis: Current
Challenges and Future Approaches
Author: David P. Skoner, MD
MEDSCAPE
Release Date: May 19, 2006; Valid for credit through May 19, 2007
Epidemiology
The prevalence of allergic rhinitis (AR) has risen over the last 10 years.[1] AR ranks among the top
5 chronic medical conditions, affecting 10%-30% of adults and up to 42% of children.[2-5] AR is
most common in children, with a mean age of onset of about 10 years and a peak incidence
between the ages of 13 and 19 years.[6,7] Consequently, approximately one third of those who
suffer from AR are 17 years of age or younger.[8,9] The toll of AR on individuals and society is very
large, including consequences such as missed school and workdays, reduced school
performance, impaired sleep, and a reduced quality of life.[10] Quality-of-life impairments in adults
include fatigue, decreased energy, and disturbances in general health perception and social
function. In children, the impact of AR encompasses learning impairment, inability to integrate
with peers, anxiety, and family dysfunction.[11] Direct expenditures for AR include office visits and
medications that exceeded $4.5 billion in 1997. Indirect costs are also high, as evidenced by an
estimated $13 million in lost productivity of parents who miss work to care for children with AR.[8]
Etiology and Pathophysiology
AR is caused by an IgE-mediated inflammation of the nasal membranes. Symptoms include a
typically clear rhinorrhea, sneezing, congestion, and itching of nasal and non-nasal tissues.
Comorbid conditions include asthma, allergic conjunctivitis, otitis media, and sinusitis. Allergic
individuals are genetically predisposed to produce specific IgE antibodies in response to
normally innocuous environmental exposures. Such exposures include the protein antigens in
seasonal allergens, such as outdoor pollens, and perennial allergens, such as dust mites and
animal dander, that are present throughout the year and are usually found indoors. The IgE
antibodies bind to high-affinity receptors (FCepsilonRIs) on mast cells and basophils and to
lower-affinity receptors on monocytes, eosinophils, and platelets. When allergen binds to the IgE
on mast cells and cross-links FCepsilonRIs, the cells degranulate and release preformed
mediators such as histamine to initiate the early-phase allergic response within minutes of
exposure.[12,13] Newly synthesized mediators, such as the cysteinyl leukotrienes, are also involved.
Such mediators cause vasodilation, increased vascular permeability, and mucus hypersecretion.
These processes generate the typical spectrum of AR symptoms, including sneezing, itching,
congestion, and rhinorrhea. Following the early-phase allergic response, many individuals
experience a second response 4-12 hours later termed the late-phase response. Under the
influence of chemokines and cytokines, inflammatory cells, such as eosinophils and basophils,
are recruited into the nasal tissue to generate the late-phase response. A predominant symptom
in this phase is nasal congestion. Prominent cytokines involved in AR include interleukin-4 (IL-4),
IL-5, and IL-13.
Nasal function is disturbed as a consequence of allergic inflammation. Under normal conditions,
the nose warms, humidifies, and filters incoming air. As such, the air delivered to the lungs of
individuals with AR may be relatively cool, dry and dirty. For this reason, nasal treatment in
individuals with AR and concomitant asthma may result in improvement in the asthma. [14] Other
nasal functions impaired by AR inflammation include olfaction and the ability to function as a
resonating chamber for voice.
Allergic inflammation can cause obstruction of the sinus ostia and the Eustachian tube, [15,16]
predisposing to comorbid conditions such as sinusitis and otitis media. Indeed, AR was present
in 50% of children with chronic otitis media with effusion.[17] AR is nearly ubiquitous in patients
with asthma, affecting approximately 80% of these children. Moreover, asthma is present in AR
sufferers more often than expected, highlighting the unified nature of the airways and
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involvement of systemic immune/inflammatory pathways. Indeed, AR and asthma are now viewed
as clinical manifestations of a disease continuum within a common airway. [18]
Diagnosis
The diagnosis of AR presents a challenge to clinicians who often attribute nasal symptoms to a
common cold rather than to allergy (see Table). This is especially true for children who are unable
to verbalize symptoms. Approximately 50% of all rhinitis symptoms are related to allergy, with the
remainder due to nonallergic conditions such as polyps, adenoidal hypertrophy, nasal septal
deviation, nasal foreign body, benign and malignant tumors, cerebrospinal fluid leak, hormonal
rhinitis, atrophic rhinitis, and systemic immunologic and nonimmunologic diseases that can
affect the nose.[19] The latter category includes granulomas associated with Wegener's
granulomatosis, sarcoid, Churg-Strauss syndrome with eosinophilic granuloma, and infection
(tuberculosis, leprosy, syphilis, sporotricosis, blastomycosis, histoplasmosis, and
coccidiomycosis). Gastroesophageal reflux can manifest as rhinitis, especially in small
children.[20] Rhinitis due to food ingestion has been well described.[21] Cold, dry air can induce a
rhinorrhea, leading to the term "skier's rhinitis."[22] A recently described form of chronic
nonallergic rhinitis is related to chronic fatigue syndrome. [23] In addition to fatigue, these subjects
complain of pain affecting many organs and problems with cognition and short-term memory.
Nasal fullness and congestion, often without nasal pathologic changes, is present in about 70% of
these subjects, and can occur in addition to AR.
Table. Distinguishing Allergic Rhinitis From the Common Cold
Allergic Rhinitis
Common Cold
Symptoms
Rhinorrhea or nasal congestion, sneezing,
watery and itchy eyes
Same as allergic rhinitis, can also
include fever, aches, and pains
Warning
time
Symptoms begin almost immediately after
exposure
Symptoms most severe after a few
days
Duration
Symptoms last as long as exposure
Symptoms resolve within several
continues and until the reaction triggered by days to a week
the allergen ends
Seasonality Yes, if mediated by outdoor allergens
Yes, spring (rhinovirus), winter
(influenza, RSV), and fall (rhinovirus)
viral seasons
Patient History
An accurate diagnosis is dependent on a careful history and physical examination, complemented
by selected laboratory tests.[24,25] The history frequently reveals affected family members, as well
as symptoms (sneezing, itching, rhinorrhea, congestion) of a defined duration (year-round or
seasonal), frequency (daily or less), and severity (mild to severe), which should be documented.
Other symptoms can involve the eyes, ears, and throat, and include postnasal drainage.
Individuals can have perennial symptoms (suggestive of perennial allergen sensitivity) with or
without seasonal exacerbations, or strictly seasonal symptoms (suggestive of pollen allergy). Not
all individuals manifest all symptoms. Nasal congestion is prominent in children with AR and
might be the only complaint.[26] Consequent mouth breathing, a nasal voice, or snoring might be
noted by the parent even if congestion is not specifically reported. Nasal congestion is seen more
commonly in perennial AR than in seasonal AR, but the reverse is true for eye itching.[27]
Physical Exam
Physical examination[28] can identify the classic signs of the allergic salute (upward rubbing of the
nose with the palm of the hand), allergic shiners (darkening of the lower eyelid due to chronic
nasal obstruction), and the allergic crease (a line in the skin above the tip and below the bridge of
the nose caused by constant rubbing). With chronic nasal obstruction, many AR children will
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make use of the oral airway and manifest a gaping mouth appearance. A careful nasal
examination should rule out nonallergic conditions such as septal deviation, nasal polyps, and
foreign bodies. The nasal turbinates in AR typically appear pale and boggy, and secretions are
clear. If there is uncertainty about whether a nasal mass represents a polyp or swollen turbinate, a
topical decongestant can be used to aid in the diagnosis. There, the decongestant will shrink the
turbinate, but not the polyp. The above signs are not uniformly present in all AR sufferers.
Allergen-Specific IgE Antibody, Skin and Blood Testing
When the history and physical examination support an allergic etiology for the symptoms, the
presence of allergen-specific IgE antibody should be confirmed using skin testing or sensitive in
vitro blood testing. Skin testing is the preferred method, but in vitro testing is an acceptable
alternative if skin testing is unavailable. The spectrum of allergens tested (generally, only
perennial allergens in infants and toddlers, and perennial and seasonal allergens in older
individuals as dictated by history) can be modified by age of the individual. These results,
combined with historical details, will permit the clinician to diagnose seasonal AR, perennial AR,
or combined seasonal/perennial AR, and provide advice on appropriate environmental control
measures. Total serum IgE levels are generally not useful in making the diagnosis of AR. In
selected instances, cytologic tests of nasal secretions to detect the presence of eosinophils
(allergic rhinitis) or neutrophils (infection) can be useful. Due to the high degree to which asthma
and AR coexist in the same individual, recent guidelines recommend that AR subjects be
examined for asthma and that asthma patients be examined for AR.[29]
Treatment/Management Issues
There are 4 basic approaches to the management of AR: (1) environmental controls; (2)
education; (3) pharmacotherapy; and (4) allergen immunotherapy.
Environmental Controls
Environmental controls are first-line therapies and need to be tailored to the individual patient's
exposures and sensitivities. Examples of environmental allergen control measures for the home
include: encasing bedding in airtight covers; washing bedding at a temperature above 130
degrees F; getting rid of furred pets or at least keeping them out of the bedroom; reducing
humidity in the house; killing all visible mold; killing cockroaches; using HEPA air filters in the
bedroom and keeping the doors and windows closed; and using air conditioning. Environmental
controls might also need to target nonallergen, irritant triggers in individual patients, including
tobacco smoke, temperature, or weather changes. Unfortunately, environmental controls are not
always practical or effective, and supplemental medical management is usually required.
Education
At all office visits, education about environmental triggering factors and the appropriate use of
medications should be provided. Education and training have been previously demonstrated to
promote adherence and follow-up in an open, randomized, parallel-group stud.[30] Both the patient
and family members should be educated about the chronic, inflammatory nature of the disease,
symptoms, impact on quality of life, avoidance of allergic and irritant triggers, realistic
expectations of the benefits of therapy, possible side effects of therapy (including drugs and
immunotherapy), and the complications of allergic rhinitis such as otitis media and sinusitis.
Indeed, regular follow-up may promote the early detection and management of these
complications. Compliance is enhanced when: (1) a low number of daily medication doses is
required; (2) the patient schedules doses based on an appropriate reminder mechanism, such as
mealtimes or other daily rituals; (3) the patient has a high level of clinician trust; (4) the patient
has written instructions; (5) rhinitis medications are taken with the same dosing frequency as any
other medications the patient may be using; and (6) the patient has a well-designed reminder
chart for the times of dosing intervals.[31-35]
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Pharmacotherapy
The approach to the medical management of AR should be individualized, taking into
consideration factors such as the age, frequency, severity, and spectrum of presenting
symptoms, the degree of impairment of quality of life, the specific allergens to which the
individual is sensitized, the response to previous medications, the presence of comorbid
conditions, and cost. These factors vary among individuals with AR. The patient history provides
a great deal of information about the type and duration of medication(s). Patient history also
provides information about whether the condition is seasonal or perennial, the frequency (daily or
less frequent), severity (mild to severe) and spectrum (1 symptom or many symptoms) of
presenting symptoms, response to and compliance with previous medications, indoor and/or
outdoor allergen exposures, and the presence of symptoms of comorbid conditions such as
allergic conjunctivitis and asthma. Symptoms confined to a defined season allow the institution of
a prophylactic regimen (eg, intranasal corticosteroid) prior to the onset of the same season in the
following year.[2] By contrast, perennial symptoms typically require daily and, frequently, yearround therapy. In that case, medication safety and ease of use are important factors. Furthermore,
a different approach is required for individuals who have perennial symptoms with seasonal
exacerbations. The presence of a comorbid condition makes the use of an intranasal
corticosteroid an attractive first-line treatment option, and might signal the need for additional
medication targeted to a nonallergic condition (eg, antibiotic for concurrent sinusitis).
Tailoring Medication to Patient Needs
When using medications for AR, step-up (if needed in milder patients) and step-down therapy
(after control has been achieved, or maximized in more severe patients) approaches can be
employed.[36-38] Some patients have only 1 symptom, and some medications only benefit 1
symptom. Thus, monosymptomatic patients can be specifically targeted initially with a tailored
therapy highly likely to be effective (such as a decongestant for congestion, an antihistamine or
leukotriene receptor antagonist for sneezing and/or itching, and an anticholinergic for rhinorrhea).
In that regard, second-generation antihistamines or leukotriene receptor antagonists are excellent
choices for initial therapy in patients with mild RA with those symptoms. For moderate to severe
symptoms or symptoms that include congestion, an intranasal corticosteroid is the best choice
for initial therapy. Intranasal corticosteroids have been shown to benefit all 4 major nasal
symptoms of AR. If the first-line medication is unsuccessful in providing relief, a second and third
medication should be added (eg, add an antihistamine or leukotriene receptor antagonist or both
to intranasal corticosteroid). An appropriate, simple, stepwise approach involves the initial
administration of an oral second-generation antihistamine, with the addition or substitution of
agents from other classes of medication when needed for symptom control. First-generation overthe-counter antihistamines are no longer recommended as first-line therapy because of the side
effects, including sedation and performance impairment. If an over-the-counter antihistamine had
been unsuccessfully used previously, changing to a leukotriene receptor antagonist or intranasal
corticosteroid is advisable. If patient adherence to therapy is low or the patient experienced an
adverse event with a particular therapy, then a different treatment strategy should be devised.
Some patients and parents are fearful of medication side effects, and these should be addressed
through education to optimize medication adherence. Intranasal beclomethasone was associated
with a small effect on growth in children, but newer intranasal corticosteroids were shown to have
no effect on 1 year of growth.[39,40]
Intranasal cromolyn sodium, now available over-the-counter, is effective in some patients for
prevention and treatment of AR and is associated with minimal side effects. However, a
requirement for frequent administration limits long-term regular use, but not prophylactic use
prior to known allergen exposures (where its use is recommended). Systemic decongestants can
be useful when added to a second-generation antihistamine, but their use is limited by the
frequent development of systemic side effects. Likewise, topical decongestants can be used
immediately prior to the use of an intranasal corticosteroid for the first 3- to 5 days of therapy in
severely obstructed patients. However, their continued use can lead to rebound nasal congestion
and the condition of rhinitis medicamentosa. Some AR patients with severe symptoms require a
short 3- to 5-day course of oral systemic corticosteroid to gain initial control, while addition of
other medications such as intranasal corticosteroids will help to maintain control. The choice of a
medical regimen can be modified by age of the individual, especially in the very young and old.
Antihistamines and leukotriene receptor antagonists are indicated for use in children as young as
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6 months of age, and intranasal corticosteroids starting at 2 years of age. Special considerations
are warranted for individuals who are pregnant or elderly.[41,42]
Allergen Immunotherapy
Individuals who respond poorly to environmental control measures and optimal medical
management are candidates for allergen immunotherapy.
Referral
Criteria for referral to an allergist-immunologist include: (1) a prolonged history of rhinitis; (2)
symptoms that significantly interfere with the patient's functional ability or reduce quality of life;
(3) prior corticosteroid use or prolonged treatment with multiple medications; (4) treatment that
was ineffective or produced side effects; (5) the presence of comorbid conditions (eg, asthma,
sinusitis, otitis media); and (6) the need to further define allergic/environmental triggers of rhinitis.
Novel Approaches
Much attention has been focused on the prevention of allergic disorders, including AR. The
Canadian Childhood Asthma Primary Prevention Study[43] recently reported the outcomes of a
multifaceted early-intervention program in a group of 7-year-old children (N = 380) and found no
significant impact on the development of AR. The Pollen Immunotherapy Study [44] examined the
ability of a 3-year course of grass or birch pollen immunotherapy to modify the development of
new asthma using an open-label, randomized design. Children (N = 208, ages 6-14 years) who
received the immunotherapy developed asthma less frequently than the group who did not
receive immunotherapy, as defined by the presence of at least 2 of the following in the past 12
months: cough, wheezing, shortness of breath, and bronchial hyperresponsiveness.
Strategies for modulating cytokine production/function are likely to yield major advances in the
future. These include: (1) inhibiting a specific proinflammatory cytokine; (2) monoclonal
antibodies targeted to cytokines or their receptors (eg, anti-IL-5); (3) soluble cytokine receptors
(eg, IL-4 receptors); (4) administering specific anti-inflammatory cytokines; (5) general Th2
cytokine inhibitor (eg, suplatast[45]); and (6) redirecting the immune response to alter the Th1/Th2
balance using DNA vaccination and immunostimulatory sequences. [46] Ciclesonide, a novel agent
with an excellent safety profile as an inhaled corticosteroid for asthma, [47] is now under
development for use in the nasal airway in AR.
Another potential future strategy is subcutaneous anti-IgE therapy, which is now indicated for the
treatment of moderate to severe asthma and has been shown to have efficacy in clinical trials of
AR.[48]
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