Acute and Chronic Rhinitis: Tina Penick Brock and Dennis M. Williams

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LWBK915-25 LWW-KodaKimble-educational November 21, 2011 21:2
Acute and Chronic Rhinitis 25

Tina Penick Brock and Dennis M. Williams
C O R E P R I N C I P L E S
CHAPTER CASES
1 Rhinitis is a common disorder and refers generally to inflammation in the nasal Cases 25-1, 25-8, 25-9
cavity. Common manifestations can include nasal discharge, itching, sneezing,
congestion, and postnasal drip. Rhinitis can be caused by allergic, nonallergic, or
mixed allergic and nonallergic triggers. Distinguishing the subtype can be helpful in
targeting symptomatic treatment.
2 Oral antihistamines are the most common therapies used for treating allergic Case 25-1
rhinitis. They are convenient and effective for most rhinitis symptoms including
rhinorrhea, sneezing, and itching.
3 Second-generation antihistamines are preferred over first-generation agents based Case 25-1 (Question 4)
on a superior side-effect profile and convenience of dosing.
4 Intranasal antihistamines offer an alternative to oral agents, with the advantage of Case 25-1 (Question 5)
efficacy for congestion and for symptoms from some nonallergic causes. Side
effects challenge patient acceptance, however.
5 Intranasal corticosteroids are the most effective therapies available for treating a Case 25-3
variety of rhinitis disorders. They are safe, well tolerated, and are highly effective in
reducing itching, sneezing, rhinorrhea, and congestion.
6 Proper administration technique is important for intranasal therapies in order to Cases 25-1, 25-2, 25-3
maximize effectiveness and minimize the risk of side effects and toxicities.
7 Leukotriene modifiers have similar efficacy to oral antihistamines for seasonal Case 25-4
allergic rhinitis and may be beneficial for selected patient populations (e.g., those
with concomitant asthma or aspirin sensitivity).
8 The duration of use of topical decongestants should be limited to 5 or fewer days Case 25-7 (Question 1)
due to the risk of rebound congestion.
9 Ophthalmic therapies may be indicated if ocular itching, tearing, and redness are Case 25-1 (Question 7)
the primary complaint or continue to be bothersome despite appropriate therapy
for nasal symptoms.
10 Many patients seek complementary and alternative therapies to treat rhinitis Case 25-5
conditions despite limited evidence regarding their effectiveness.
DEFINITION ing, congestion, and postnasal drainage (postnasal drip). These

nasal symptoms can be accompanied by ocular symptoms such
Rhinitis is defined as an inflammatory condition affecting the as redness, itching, and discharge and can be exacerbated by the
mucous membranes of the nose and upper respiratory system. development or presence of sinusitis. The most common form
In clinicial practice, however, the term is used broadly to encom- of rhinitis occurs in response to an allergen, although a variety
pass a heterogeneous group of nasal disorders characterized by of other subtypes, some of which are not predominantly inflam-
periods of rhinorrhea (nasal discharge), pruritus (itching), sneez- matory, have been demonstrated.1–3
619
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620
RHINITIS
SYMPTOMS
Foreign
Infections
bodies • Viral
• Coins • Bacterial
• Candy ACUTE • Fungal
CHRONIC
• Beans
Allergic Nonallergic
Hormones
Drugs • Pregnancy
• Table 25-9
Section 3
• Hypothyroidism
Intermittent Persistent
NARES Idiopathic
(Seasonal) (Perennial)
Anatomic
• Polyps
• Tumors
• Septal defects
Pulmonary Disorders
FIGURE 25-1 Possible causes of rhinitis symptoms. NARES, nonallergic rhinitis with eosinophilia syndrome.
CAUSES AND CLASSIFICATIONS Chronic rhinitis can be classified as allergic, nonallergic, or

mixed allergic and nonallergic.3 Allergic rhinitis, the most com-
Rhinitis is not a single disease but rather has multiple causes and mon subtype, is typically associated with atopy, an inherited ten-
underlying pathophysiologic mechanisms.1,4 Figure 25-1 depicts dency to develop a clinical hypersensitivity condition, and its
common causes of acute and chronic rhinitis symptoms, includ- symptoms are a result of immunoglobulin E (IgE)–dependent
ing some conditions that mimic rhinitis (e.g., nasal polyps). The events.2 There is not a single, uniform standard for classify-
most common cause of acute rhinitis is a viral upper respiratory ing allergic rhinitis. Traditionally, patients have been classified
infection, that is, the common cold. as having seasonal or perennial disease, based on frequency of
symptoms and potential offending allergens.1 An alternative clas-
sification system categorizes allergic rhinitis based on severity
(e.g., mild, moderate, and severe) and frequency (e.g., intermit-
For visuals of rhinitis, go to tent or persistent) of symptoms.11 This classification system is
http://thepoint.lww.com/AT10e. summarized in Figure 25-2. Clinicians are likely to encounter a
combination of these classifications when evaluating the clinical
literature and participating in patient care activities.
In most patients, these viral infections are self-limited and Several categories exist for nonallergic causes of rhini-
require only symptomatic treatment.4 Nasal foreign bodies are tis including idiopathic rhinitis, nonallergic rhinitis with
another frequent cause and should be suspected when a pedi- eosinophilia syndrome (NARES), and anatomic abnormalities.4
atric patient presents with acute, unilateral symptoms.5 Hor- Idiopathic rhinitis, also called vasomotor rhinitis, refers to symp-
monal and medication-related rhinitis are also common acute toms associated with environmental stimuli, including tempera-
syndromes.6–10 ture changes, strong odors, tobacco smoke, stress, or emotional
Intermittenta Disease Persistentb Disease

Symptoms occur: Symptoms occur:
Fewer than 4 days/week or At least 4 days/week and
for fewer than 4 weeks for at least 4 weeks
Mild Moderate–Severe
All of the following: At least one of the following:
• Normal sleep • Impaired sleep
FIGURE 25-2 ARIA classification of
• No impairment of usual daily activities, • Impairment of daily activities, sports, and allergic rhinitis. ARIA, Allergic Rhinitis and
sports, and leisure leisure its Impact on Asthma. (Source: Bousquet J
• No interference with work or school • Interference at work or school et al. Allergic rhinitis and its impact on
asthma [ARIA] 2008 update [in
• No troublesome symptoms • Troublesome symptoms
collaboration with the World Health
aFormerly Organization, GA(2)LEN and AllerGen].
“seasonal” symptoms.
bFormerly Allergy. 2008;63[Suppl 86]:8.)
“perennial” symptoms.
factors.12 NARES occurs frequently in middle-aged patients who gic diseases are the most frequent contributor to the total cost 621
have no evidence of allergic disease excepting the presence of of health-related absenteeism and presenteeism (i.e., being phys-
eosinophils in the nasal smear. In these cases, increased perme- ically present at the workplace, but not being fully functional
ability of the nasal mucosa is likely caused by non–IgE-mediated because of disruptive medical symptoms), with allergic rhini-
inflammation, and neurogenic mechanisms may play a role in tis being the most prevalent of the allergic diseases. Employ-
membrane hyperreactivity.4 ees report annual allergic symptoms on average of 52.5 days,
Mixed rhinitis is a subset of allergic rhinitis in which features absence 3.6 days, and lack of productivity 2.5 hours/day when
of both allergic and nonallergic disease are present, and trig- experiencing symptoms.18 The Agency for Healthcare Research
gers include allergens as well as other irritants.3 The presence and Quality reported that in 2005, a total of $11.2 billion was
of mixed disease should not be overlooked when evaluating the spent on allergic rhinitis–associated health care and prescription
presentation of a patient or assessing the response to therapy. medications.21 Rhinitis is an important health problem because
of its prevalence and its impact on patients’ social life, school
performance, and work productivity.3
EPIDEMIOLOGY AND IMPACT
Prevalence rates for rhinitis are difficult to quantify because the ANATOMY AND PHYSIOLOGY
Chapter 25
condition is often undiagnosed, different definitions are used, and
data collection methods vary.13,14 In addition, because rhinitis in The external nose is pyramidal and consists of paired nasal bones
its mildest form is largely self-managed, it is likely that health and associated cartilage. Its base has two elliptical-shaped open-
statistics underrepresent the actual scope of the problem.15,16 ings called nares, or nostrils. Internally, a septum separates the
Despite these confounders, a conservative estimate suggests that nasal cavity into two halves and consists of bone and cartilage cov-
up to 30% of adults (and even more children) are affected by ered by a mucosal membrane.22 The lateral walls of the internal
Acute and Chronic Rhinitis

allergic rhinitis, making it the sixth most common chronic illness cavity contain the conchae, or turbinates. These bony projec-
in the United States.17,18 In recent decades, prevalence in Western tions increase surface area substantially and contribute to tur-
societies has increased and studies from around the world are bulence of airflow, which is useful in filtering and conditioning
reporting similar trends.19 Although studies have traditionally inspired air. Sinuses and eustachian tubes open into the nasal
reported a 3:1 ratio of allergic to nonallergic rhinitis, recent data cavity near the turbinates, as do the lacrimal drainage ducts.22
suggest that up to 87% of patients may experience symptoms Figure 25-3 shows a lateral view of the head with the nasal
from mixed causes.3 anatomy labeled.
Rhinitis can lead to sleep disorders, loss of appetite, general The membranes of the nasal cavity consist primarily of ciliated
weakness, fatigue, mood disorders, decreased concentration, and columnar epithelial cells with mucus-producing goblet cells inter-
difficulty learning.1,15,20 Despite the impact of symptoms and the spersed among them. The tiny cilia beat rhythmically to transport
burden of disease, less than half (47%) of nasal allergy sufferers mucus across the upper airway membrane to the nasopharynx.
reported seeing a health care practitioner about their symptoms The cilia-lined mucous membranes of the nose provide a physical
in the last 12 months.14 Although symptom severity is associated barrier of defense to microorganisms and other particles in the
positively with seeking treatment, 41% of patients who reported inspired air.5 In addition, respiratory secretions residing on these
severe nasal allergy symptoms in the past week had not seen a mucous membranes contain immunoglobulin A (IgA), which
health practitioner about this within the last year.14 Most nasal serves as an immunologic defense.22
allergy sufferers report taking medication for their condition; The autonomic nervous system controls the vascular sup-
with more than half (53%) using a nonprescription medication ply and the secretion of mucus to the nasal membrane. Sym-
and more than a third (36%) receiving a prescription nasal spray pathetic activation results in vasoconstriction, which decreases
in the past 4 weeks.14 A large proportion (38%–48%) of patients nasal airway resistance. Parasympathetic stimulation results
taking medications for their symptoms, however, report that they in glandular secretion and nasal congestion.6 The mucosa is
are only somewhat satisfied with the products they use.14 also innervated by the nonadrenergic–noncholinergic system.
Although rhinitis does not lead to the mortality associated Neuropeptides from these nerves (e.g., substance P and
with some illnesses, its prevalence and negative health impact neurokinins) play a role in vasodilation, mucus production
make it an important health problem in the United States. Aller- and inflammation, although their significance is unclear. The
Superior Turbinate Frontal Sinus

and Meatus
Middle Turbinate
and Meatus Pharyngeal Orifice of
Inferior Turbinate Eustachian Tube
and Meatus
Vestibule
FIGURE 25-3 Lateral view of the head with nasal

anatomy. (Reprinted with permission from the
LifeArt Human Anatomy II collection.)
622 trigeminal nerve also provides sensory innervation; the stimula- In patients with seasonal or intermittent allergic rhinitis, pol-
tion of which can result in sneezing and itching.6 lens and airborne mold spores are the most common allergens.
The primary functions of the nose and upper airway are smell, Although the pollen season varies with geographic location,
speech, and conditioning of inspired air, that is, humidifying and grasses, trees, and weeds can be problematic for many people dur-
filtering it before delivery to the lungs.5 These processes are ing active pollination. In the United States, ragweed is a primary
disrupted in the presence of inflammation, increased mucus, and cause of intermittent symptoms and sensitivity to this pollen is
congestion. historically referred to as “hay fever.”4
In patients with persistent allergic rhinitis, the major aller-
gens are house dust mites, indoor molds, animal dander, and
ETIOLOGY OF ALLERGIC RHINITIS cockroach antigen. Another common cause is occupational expo-
sure, in which symptoms can be precipitated by agents such as
Genetic, environmental, and lifestyle influences are associated flour, wood, and detergents.4
with the development of allergic rhinitis.23 Candidiate genes
have not been identified23 ; however, atopy is a significant inher-
itable factor, and the risk of a child experiencing allergic symp-
toms is 50% with one atopic parent and 66% with two atopic PATHOPHYSIOLOGY
Section 3
parents.24 Environmental exposures, particularly early in life, are

also important in the development of symptoms.25 In addition, The pathogenesis of allergic rhinitis and asthma includes numer-
lower socioeconomic status may be a risk factor for development ous areas of commonality. Inflammation is a central mechanism
of allergic rhinitis.26 and the role of cytokines is similar. This has led many scien-
One etiologic theory, referred to as the hygiene hypothesis, tists and clinicians to adopt the concept of “one airway, one
suggests that the initial differentiation of lymphocytes early in life disease.”23 Further evidence for this association include the fact
Pulmonary Disorders
has either positive or negative influences on the development of that rhinitis is a known risk factor for asthma, some patients
subsequent allergies. In the normal development of the immune with rhinitis exhibit bronchial hyperresponsiveness, viral upper
system, the lymphocytes differentiate into either helper T (TH 1 respiratory tract infections are a common cause of asthma exac-
or TH 2) cells based on environmental stimuli. Factors associated erbations, and sinusitis can worsen asthma.23 Some treatment
with a TH 1 (allergy protective) response include exposures to var- strategies, including pharmacotherapy, have a role in both rhini-
ious bacteria and viruses, the presence of older siblings, and early tis and asthma.
attendance in day care. Factors associated with a TH 2 (predispo- Allergic rhinitis is characterized by an IgE-mediated re-
sition to allergies) response include environmental exposures to sponse that involves three primary steps: sensitization, early-
house dust mites, cockroaches, or early, frequent antimicrobial phase events, and late-phase events. This process is depicted in
use.24,27 Figure 25-4. The nonallergic pathogenic course is less well
Antigen
⫹ Presenting
Cell
Allergen Processed Allergen

S
E
N
S
I
T
I TH0
Z
A
T
I
O
N
IL-3,-4,-5
IL-4,-5,-13 GM-CSF
IgE B cell TH2 Expression of Cell Adhesion Molecules
on Eosinophils, Vascular Endothelium
L
⫹ A
Cell Migration and Accumulation T
E
Mast P
E H
A Cell Leukotrienes, Prostaglandins A
R S
L E
Y Chemotaxis
P
H
A Sensory Nerve Endings Itching, Sneezing Hyperresponsiveness
S
Priming
E Histamine Vasculature →↑ Permeability and Leakage Rhinorrhea, Congestion
Mucosal Glands Rhinorrhea
FIGURE 25-4 Pathophysiology of allergic rhinitis.

understood. It is not IgE-mediated, although in some subtypes patient interview, including medication history, pertinent phys- 623
inflammatory cells and mediators can cause similar effects to ical examination, and a limited number of relevant laboratory
those seen in the allergic form.3 assessments.32
In allergic rhinitis, sensitization occurs after initial allergen
exposure in a susceptible patient and involves the production of
IgE antibodies. These antibodies bind to receptors on various
History, Signs, and Symptoms
cells, including mast cells. On subsequent exposure, an interac- A history should be obtained from the patient that includes a dis-
tion occurs between the complex of the allergen, IgE antibody, cussion of the onset, character, frequency, duration, and sever-
and the mast cell, such that a cross-linking occurs that results ity of the patient’s symptoms and any identifiable factors that
in activation and initiation of the inflammatory response. The provoke or relieve these symptoms.1,4,32 Past medical history
events can occur early after exposure if the mediators are pre- (including age of onset of symptoms) and family history (e.g.,
formed or late if mediators are synthesized after the process atopy) are also helpful. The presence of nasal obstruction as a
begins or are attracted to the area through chemotaxis.28 sole symptom, mucopurulent rhinorrhea, chronic sinus pain,
recurrent epistaxis, and anosmia may be important in differenti-
ating rhinitis from other problems.6
Sensitization
Chapter 25
Because both allergic and nonallergic forms of rhinitis are
In an atopic patient, the result of initial exposure to allergens is common and can potentially coexist, some experts suggest that
production of IgE. After initial exposure, antigen-presenting cells distinguishing rhinitis subtype during initial evaluation can help
of the immune system react to allergens deposited on the nasal to target initial treatment.4,33 Diagnostic criteria suggestive of
mucosa. This results in helper T-lymphocyte differentiation into allergic rhinitis include sneezing, itchy nose, seasonal symp-
TH 2 cells, which are associated with production of cytokines toms, itchy eyes, clear rhinorrhea, family history of allergic
rhinitis, eczema, and food allergy. Persistent congestion and/or

and other mediators of inflammation. As a result, memory cells
programmed for IgE production are produced.23,24,28 rhinorrhea without itch/sneeze, poor response to oral antihis-
tamines, symptoms exacerbated by weather changes, temper-
ature extremes/changes, foods, perfumes/odors, smoke/fumes,
Early Response late age of onset, absence of cat/dog/pet triggers are suggestive
When a susceptible patient is exposed to an allergen to which pre- of nonallergic causes. Ear popping, frequent upper respiratory
vious sensitization has occurred, an early-phase allergic response tract infection, fatigue, headache, and sleep disturbance are fea-
generally occurs. This reaction is attributed largely to the interac- tures commonly associated with both allergic and nonallergic
tion between the allergen, IgE, and the sensitized mast cell, result- rhinitis. These are summarized succinctly in a checkbox-type
ing in mast cell degranulation. Other cells, including basophils, diagnostic worksheet developed by the Respiratory and Allergic
play an important role as well. As a result, mediators of the Disease Foundation.34
allergic response, including histamine, are released along with The negative impact of rhinitis on a patient’s quality of
various chemotactic factors, which amplify and perpetuate the life can be substantial, and it is important to assess this during
allergic response. Because these mediators are already present the patient interview. Symptoms and symptom-induced inter-
in the mast cell, they act within minutes to cause the common ference with necessary (i.e., work, school) and enjoyable (e.g.,
symptoms of allergic rhinitis, including itching, sneezing, and hobbies, family events) activities can lead to patient irritability,
congestion.28–30 anxiety, and exhaustion.35 The questions listed in Figure 25-5 pro-
Histamine receptors (H1 ) are present throughout the nasal vide a guide to collecting the information needed to initiate and
mucosa and their activation results in vascular engorgement, modify therapy based on the underlying causes of the rhinitis
leading to nasal congestion, direct stimulation of mucus secre- symptoms.
tion, and increased glandular secretion.30 In addition, parasym-
pathetic nervous system stimulation results in cholinergically Physical Examination
mediated nasal secretions. Finally, stimulation of peripheral nerve
receptors results in itching and sneezing reflexes.31 During a physical examination for rhinitis, the patient’s nose
should be inspected for nasal patency, position of the sep-
tum, appearance of the nasal mucosa (especially over the
Late Response turbinates), quantity and appearance of secretions, and abnormal
growths.1,4,32 If the nasal passage is extremely occluded, appli-
Up to one-third of patients with allergic rhinitis also experience cation of a topical vasoconstrictor (e.g., oxymetazoline 0.025%)
a late response that develops approximately 8 hours after ini- allows better visualization. Common physical characteristics of
tial exposure and may persist for up to 4 hours. In this phase, patients with allergic rhinitis are clear nasal discharge and pale,
the nature of inflammation is even more complex, and nasal boggy, swollen nasal mucosa.18,19,32
congestion is a prominent feature. Numerous cells and medi- The patient’s eyes, ears, pharynx, sinuses, and chest should
ators, including T lymphocytes, cytokines, eosinophils, neu- also be examined.1,19,31 Chronic mouth breathing because of
trophils, macrophages, mast cells, and leukotrienes, play impor- nasal obstruction can cause recognizable facial characteristics
tant roles. These additional mediators, attracted to the area (e.g., adenoid face, allergic shiners, and nasal crease) and den-
through chemotaxis, sustain the inflammatory response. This tal abnormalities (e.g., crowded, crooked teeth, gingivitis, and
response is also perpetuated through continued exposure to the cavities).32
offending allergen.31
Laboratory Tests
CLINICAL PRESENTATION AND Several diagnostic tests are available for confirming a diagnosis of
ASSESSMENT OF RHINITIS allergic rhinitis in patients who present with a suggestive history
and symptoms. Microscopic examination of nasal secretions can
The diagnosis of rhinitis is not defined by one specific laboratory be performed, but current recommendations suggest that this is
test; rather, it is related to the coordinated results of a thorough more commonly used by subspecialists or in research.4 In allergic
624
1. Which of the common symptoms of rhinitis is the patient experiencing?
• Sneezing, nasal itching, runny nose, nasal congestion, postnasal drip, altered sense
of smell, watery eyes, itching eyes, ear “popping”
2. What color are the nasal secretions?

• Clear, white, yellow, green, blood-streaked, rusty brown
3. When did the symptoms first appear?

• Infancy, childhood, adulthood
4. Were the symptoms associated with a change in state/environment?

• After a viral upper respiratory infection, after a traumatic blow to the head or face, upon
moving into/visiting a new dwelling, after obtaining a new pet
Section 3
5. How often do the symptoms occur?

• Daily, episodically, seasonally, constantly
6. For how long has this symptom pattern persisted?

• Days, weeks, months, years
Pulmonary Disorders
7. Which factors or conditions precipitate symptoms?

• Specific allergens, inhaled irritants, climatic conditions, food, drinks
8. Which specific activities precipitate symptoms?

• Dusting, vacuuming, mowing grass, raking leaves
9. Are other members of the family experiencing similar symptoms?
10. Which of the following are prevalent in the household?

• Carpeting, heavy drapes, foam or feather pillows, stuffed toys, areas of high moisture
(basements, bathrooms), tobacco use (by patient or others), pets
11. Does the patient have other medical conditions that can cause similar symptoms?
12. Is the patient taking any medications that might cause or aggravate these symptoms?
13. What prescription and nonprescription medications have been used for these symptoms in
the past? Were they effective? Did they cause any unwanted effects?
14. What is the patient's occupation?
15. What are the patient's typical leisure activities?
16. To what extent have the symptoms interfered with the patient's lifestyle (i.e., are they
disabling or merely annoying)?
• Greatly, somewhat, not much
FIGURE 25-5 Patient history interview.
conditions, the clinician would expect numerous eosinophils to of differentiation between pure allergic versus nonallergic disease
be present in the sample; however, this could also be true of is the presence of a serum IgE level greater than 100 international
NARES or nasal polyps.1 units/mL (especially before age 6), which is consistent with aller-
Immediate hypersensitivity skin tests are used to demonstrate gic rhinitis.24 However, a clinical diagnosis of either allergic or
an IgE-mediated response of the skin. This provides confirmatory nonallergic disease is often made in the absence of a serum IgE
evidence for a specific allergy.36 A variety of skin test methods and is based on the nature of symptoms and triggers.
are available; however, the prick and puncture test (in which the Testing for IgE sensitivity to specific antigens is useful in
wheal and flare reaction is evaluated 15 minutes after allergen many patients where the exact etiology is unclear or possi-
administration) is the preferred technique.23,36 A primary point ble sensitivity to multiple agents is present. Skin testing for
specific IgE sensitivity is preferred over immunoassays.3 In ing for patients with both conditions.11,39 The ARIA document 625
selected cases, other diagnostic tests, such as sinus x-ray study, has also been updated to include information about the use of
computed tomography (CT), rhinomanometry, and spirometry complementary and alternative therapies, rhinitis in developing
may be useful.6,36,37 countries, rhinitis in athletes, and grading the evidence used to
establish the guidelines.23,40,41
The treatment goals for rhinitis, including that from allergic
GENERAL MANAGEMENT OF causes, are to prevent or relieve symptoms, and improve qual-
RHINITIS ity of life without prohibitory concerns about adverse effects or
expense. These goals should be achievable through the establish-
Practice parameters for the diagnosis and management of aller- ment of a therapeutic partnership with a competent and caring
gic and nonallergic rhinitis were updated in 2008 by a joint task clinician. With appropriate treatment, the patient should be able
force representing the American Academy of Allergy, Asthma, to maintain a normal lifestyle and perform desired activities.41
and Immunology (AAAAI); the American College of Allergy, Common management strategies include patient education,
Asthma, and Immunology (ACAAI); and the Joint Council on allergen and irritant avoidance, and pharmacotherapy.23 Fig-
Allergy, Asthma, and Immunology.3 In addition, evidence link- ure 25-6 depicts an algorithm for the general management of
Chapter 25
ing asthma and allergic rhinitis epidemiologically, pathologically, allergic rhinitis.
and physiologically has been published, suggesting that upper
respiratory allergic disorders and asthma represent components
of a single inflammatory airway syndrome.38 This prompted the
Patient Education
development of the Allergic Rhinitis and Its Impact on Asthma An increasing trend seen in health care is to limit clinical rec-
(ARIA) document, which provides guidance for clinicians car- ommendations to those based on sound evidence.42,43 Despite

Evaluate for asthma,
Diagnosis of allergic rhinitis especially in patients with severe
or persistent rhinitis
Provide education and allergen/irritant avoidance strategies
Intermittent Persistent
symptoms symptoms
Moderate– Moderate–
Mild severe Mild severe
Not in preferred order In preferred order

H1-blocker (oral, intranasal CS
Not in preferred order
intranasal) and/or oral H1-blocker (oral, H1 -blocker (oral, intranasal) or LTRA
decongestant or intranasal) and/or
LTRA Assess the patient’s
decongestant or
response after 2–4 weeks.
intranasal CS or LTRA
or mast cell stabilizer
Improved Failure
In persistent rhinitis
assess the patient’s Review diagnosis
Step-down Review adherence
response after
and continue Query infections
2–4 weeks treatment or other causes
for >1 month
If failure: step-up
If improved: continue
for 1 month
Blockage
Add or increase add
Rhinorrhea
intranasal CS decongestant
add ipratropium
dose or oral CS
(short term)
Failure
referral to specialist
If conjunctivitis
Add
H1-blocker (intraocular, oral)
or intraocular mast cell stabilizer
or intraocular saline
Consider specific immunotherapy
FIGURE 25-6 Treatment algorithm for allergic rhinitis. Treatment should be directed at predominant symptoms (i.e.,
for eye symptoms in absence of other symptoms use ophthalmic preparation). Prevention strategies are more effective
than treatment strategies. For intermittent symptoms, begin treatment several weeks before antigen exposure and
discontinue when no longer needed. CS, corticosteroid; LTRA, leukotriene receptor antagonist (leukotriene modifier).
(Source: Bousquet J et al. Allergic rhinitis and its impact on asthma [ARIA] 2008 update [in collaboration with the World
Health Organization, GA(2)LEN and AllerGen]. Allergy. 2008;63[Suppl 86]:8.)
626 the paucity of data about the benefits of patient education in the classes of therapy, excepting the second generation antihis-
patients with rhinitis, it is likely to play a significant role in treat- tamines and nasal corticosteroids, which have both been shown
ment adherence.1 Considerations for patient education include to be cost-effective.46,47 Table 25-1 summarizes the effectiveness
instruction about the disease and specific triggers, the range of of agents for specific symptoms used in the treatment of allergic
symptoms, and the role of various treatments. An appropriate rhinitis.
understanding of prevention versus treatment strategies is critical
to achieving optimal outcomes. The recent practice parameters
for treating allergic rhinitis suggest that a rhinitis action plan may ANTIHISTAMINES
be useful for some patients.3 Antihistamines are the most common treatment for allergic
rhinitis and are effective for relieving sneezing, itching, and rhi-
norrhea. They also diminish eye symptoms, but when taken
Allergen and Irritant Avoidance orally, have minimal effects on nasal congestion.1,11 Although
first-generation antihistamines (FGAs) are efficacious, their use is
Although the benefit of allergen avoidance has proved difficult
limited by anticholinergic, sedative, and performance-impairing
to document, this strategy is considered central in a comprehen-
effects which challenge their cost-effectiveness.48 As a result,
sive management plan for allergic rhinitis.44 Various strategies
second-generation antihistamines (SGAs) are preferred over
Section 3
for minimizing exposure to known allergens (e.g., pollens, house

FGAs in most cases where an antihistamine is desired.1,2,41 Anti-
dust mites, molds, animal dander, and cockroaches) are com-
histamines are available in oral, ophthalmic, and intranasal for-
monly used for prevention. Because little evidence supports a
mulations and can also be found in combinations with oral
single physical or chemical intervention to reduce allergen expo-
decongestants. They are most effective when administered before
sure, a multifaceted approach should be used.23 Efforts to reduce
allergen exposure.
exposure to irritants (e.g., tobacco smoke, indoor or outdoor pol-
Although oral antihistamines represent the most commonly
Pulmonary Disorders
lutants) should also be recommended, as it is anticipated that this

used therapy for allergic rhinitis, there is some evidence that
would have similar benefits as allergen avoidance.45
intranasal antihistamines are effective in treating symptoms of
both allergic and nonallergic rhinitis. Further, they appear to
relieve symptoms of congestion, which is not a feature of oral
Pharmacotherapy antihistamines.3 The basis for improved efficacy of intranasal
Several classes of medications are used in the management of antihistamines over oral agents in certain rhinitis conditions is
rhinitis disorders. Choices should be based on goals of treatment, unclear but may be related to direct administration to the affected
safety, efficacy, cost-effectiveness, adherence, severity, comorbid- site. However, the currently available product is associated with
ity, and patient preferences.41 Common therapies are adminis- significant sedation, suggesting that it is well absorbed across the
tered either orally or topically, and used on a regular schedule or nasal mucosa. This side effect may limit the usefulness of this
an as-needed basis.1 Few cost-effectiveness data exist comparing formulation for persistent symptoms.41
TA B L E 2 5 - 1
Effectiveness of Agentsa Used in Management of Allergic Rhinitis
Rhinorrhea Nasal Pruritus Sneezing Nasal Congestion Eye Symptoms Onset
Antihistamines
Nasal Moderate High High Moderate 0 Rapid
Ophthalmic 0 0 0 0 Moderate Rapid
Oral Moderate High High 0/Low Low Rapid
Decongestants
Nasal 0 0 0 High 0 Rapid
Ophthalmic 0 0 0 0 Moderate Rapid
Oral 0 0 0 High 0 Rapid
Corticosteroids
Nasal High High High High High Slow (days)
Ophthalmic 0 0 0 0 High Slow (days)
Mast-cell stabilizers
Nasal Low Low Low 0/Low Low Slow (weeks)
Ophthalmic Low Low Low Low Moderate Slow (weeks)
Anticholinergics
Nasal High 0 0 0 0 Rapid
Leukotriene modifiers
Oral Low 0/Low Low Moderate Low Rapid
a
Immunotherapy can lead to significant responses in all symptom categories; however, onset of action is delayed (months).
High, significant effect; moderate, moderate effect; low, low effect; 0, no effect.
Source: van Cauwenberge P et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy.
2000;55:116; Bousquet J et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA[2]LEN and
AllerGen). Allergy. 2008;63(Suppl 86):8.
Adapted with permission from Facts & Comparisons eAnswers. http://online.factsandcomparisons.com/index.aspx?. Accessed December 15, 2010.
INTRANASAL CORTICOSTEROID AGENTS IMMUNOTHERAPY 627

Intranasal corticosteroids are the most effective medication class Specific allergen immunotherapy (SIT) should be considered for
for the treatment of allergic rhinitis, and are particularly useful patients who have severe symptoms despite optimal pharma-
for more severe or persistent symptoms.6,37 Although achiev- cotherapy, require systemic corticosteroids, or have coexisting
ing optimal outcomes depends on the patient’s ability to use conditions such as sinusitis and asthma.1 The clinical efficacy of
the device correctly, if administered as intended, these agents immunotherapy by subcutaneous injection (SCIT), sometimes
are appropriate for all symptoms, are generally well tolerated, called “allergy shots,” is well established.54 Traditional SCIT
and have few adverse effects.41 They are most beneficial when presents some disadvantages, however, such as cost, adherence,
dosed on a regular schedule; some evidence indicates, how- and rare adverse systemic reactions. Because regular injections
ever, that they are effective when used on an as needed basis.49 can be unacceptable to some patients, alternative methods of
Intranasal corticosteroids are also useful for treating nonallergic delivering antigens, such as sublingual immunotherapy (SLIT)
rhinitis. and nasal immunotherapy (NIT) have been investigated.55,56
Recent reviews of studies using equivalent dosing strategies (e.g.,
LEUKOTRIENE MODIFIERS the dose of allergen needed for SLIT is much higher than that
Leukotriene modifiers are effective in relieving many of the nasal required for SCIT) have found that SLIT is a safe, convenient
Chapter 25
symptoms of allergic rhinitis.50,51 For seasonal symptoms, these treatment that significantly reduces symptoms and medication
agents can be considered as an alternative to oral antihistamines requirements in allergic rhinitis.4,57,58 Less evidence is found
based on similar efficacy profiles.41 Selected patients might ben- about the efficacy of NIT, but a multicenter trial in children sug-
efit from the combination of an antihistamine and a leukotriene gests improvement in nasal symptom scores as compared with
modifier.51 These agents may have a role in concomitant asthma placebo.56 Neither SLIT nor NIT is currently available in the
and allergic rhinitis, particularly if both diseases are relatively United States, though in Europe SLIT has become the standard
for immunotherapy because of proven efficacy and advantages

mild.52 There is no evidence that these agents are helpful for
symptoms from nonallergic causes. in both cost and compliance.55
ANTI-IgE Therapy
CROMOLYN Omalizumab is a recombinant humanized monoclonal anti-IgE
Intranasal cromolyn, a nonsteroidal agent, acts as a mast-cell sta- antibody that complexes free circulating IgE in the body. The
bilizer and, although safe, it is generally less efficacious than other complex cannot interact with mast cells and basophils, thus
therapies and only useful for symptoms related to allergic causes. reduces IgE-mediated allergic reactions. When administered as a
It should be administered multiple times daily and requires sev- subcutaneous injection once or twice monthly, omalizumab has
eral weeks to be effective. Based on its excellent safety profile, it been shown to decrease all nasal symptoms and improve quality
is best reserved for acute prophylaxis before exposure to a known of life in patients with allergic rhinitis.59 Currently, this therapy
allergen and for use by children or in pregnancy.53 is approved only for people 12 years of age and older with mod-
erate to severe allergy-related asthma inadequately controlled
DECONGESTANTS
with inhaled corticosteroids. The product is labeled with a black
Oral and nasal decongestants can effectively reduce nasal conges- box label warning to alert users that omalizumab can cause
tion produced by allergic and nonallergic forms of rhinitis.1 Oral potentially life-threatening allergic reactions after any dose, up to
agents are often combined with antihistamines and are generally 24 hours after the dose is given and even if there was no reaction
well tolerated, but their use can lead to insomnia, nervousness, to the first dose.60
urinary retention, and palpitations which may be problematic
for some patients. Subsequently, these agents should be used Special Considerations of Medications
with caution in elderly patients and in those with arrhythmias,
hypertension, and hyperthyroidism. Nasal agents are not typi- in Pregnancy
cally associated with these effects, but should be limited to short- The majority of data about the risks of various pharmacothera-
term use to avoid rebound nasal congestion.2 Recent restrictions pies are derived from animal studies. There are limited human
on the sale of nonprescription formulations containing pseu- data; however, cohort and case control studies have been used to
doephedrine and questions regarding the efficacy of phenyl- support therapeutic decision-making. Antihistamines, intranasal
ephrine have resulted in challenges to the optimal use of oral steroids, montelukast, and cromolyn are considered safe to
decongestants. use during pregnancy. Oral decongestants should generally be
avoided in the first trimester, although topical decongestants may
be used on a short-term basis.3
ANTICHOLINERGIC AGENTS
Intranasal ipratropium bromide is an anticholinergic agent effec-
tive in reducing watery, nasal secretions in allergic rhinitis, Nondrug Therapies
nonallergic rhinitis, and viral upper respiratory infections.1,11
Anticholinergic agents have no significant effects on other symp- Supportive care is the foundation of treatment for patients with
toms. symptoms of rhinitis.1 These strategies can be helpful during
an acute worsening of symptoms as well as for the patient who
suffers chronically. Supportive care can ameliorate discomfort,
OPHTHALMIC THERAPIES relieve mild symptoms, and assist with side effects from phar-
Ophthalmic products used to treat symptoms of allergic con- macotherapies. Examples include the application of compresses
junctivitis include antihistamines, decongestants, mast-cell stabi- to the sinuses or external nasal passages and humidification of
lizers, and nonsteroidal anti-inflammatory agents. These agents mucous membranes with artificial tears or nasal saline solutions.
are effective in reducing ocular symptoms and may be used in Many patients with chronic symptoms of rhinosinusitis report
combination with oral and intranasal agents. subjective improvement with nasal irrigation.61
628 SPECIFIC THERAPEUTIC OPTIONS ing humidity in the home to below 50%. In addition, replacing
carpets with linoleum, tile, or wood floors and replacing cur-
tains and heavy draperies with blinds that can be wiped clean are
Antihistamine Therapy commonly recommended.1
DIAGNOSIS OF ALLERGIC RHINITIS Mold avoidance is difficult when outdoor humidity levels
are high, but removing carpeting may be effective. Live plants
CASE 25-1 should be removed from the home to reduce mold contamina-
QUESTION 1: L.B. is a 57-year-old man with a history of tion from the soil. Air conditioners should be used, and filters
hypertension for 10 years and intermittent allergic rhinitis should be changed frequently to reduce humidity and assist with
since childhood (confirmed sensitivity to birch tree pollen air filtration.1
via skin testing). L.B. presents with complaints of nasal itch- Because L.B. has recently moved into an older home, he may
ing, sneezing, clear rhinorrhea, and stuffiness. He usually not have used these avoidance strategies. These should be rec-
experiences similar symptoms with added ocular itching ommended and explained during the initial clinical consultation.
every spring, but has noticed that the problem has become
persistent since he moved into an older home in the his- THERAPEUTIC OBJECTIVES FOR ALLERGIC RHINITIS
toric district of town. In the past, L.B. has successfully self-
Section 3
medicated his seasonal symptoms with an over-the-counter CASE 25-1, QUESTION 3: What are the therapeutic objec-
(OTC) antihistamine and decongestant (diphenhydramine tives in treating L.B.?
50 mg and pseudoephedrine 60 mg twice a day to four
times a day as needed for symptoms), although “nothing The therapeutic objectives for the treatment of allergic rhini-
seems to help much with the itchy eyes.” L.B.’s hypertension tis are to control symptoms and permit all usual daily activities
with no adverse effects of therapy. In patients with seasonal exac-
Pulmonary Disorders
has been well controlled with hydrochlorothiazide 25 mg

every morning and amlodipine 10 mg every day. He denies erbations, another objective is to prevent the onset of symptoms
any other medical problems, is afebrile, and his blood pres- by anticipating the patient’s season of sensitivity. In L.B.’s case, he
sure is 128/82 mm Hg. He has no history of adverse drug should use environmental measures to reduce exposure and then
reactions or drug allergies. He does not smoke, but drinks begin chronic treatment with possible add-on therapy instituted
alcohol socially. What elements of L.B.’s presentation indi- 2 weeks before the start of pollen season.
cate a probable diagnosis of allergic rhinitis?
CHOICE OF THERAPEUTIC AGENT
L.B. is exhibiting the classic symptoms of persistent (peren-
nial) allergic rhinitis with intermittent (seasonal) exacerbations: CASE 25-1, QUESTION 4: L.B. has used diphenhydramine
nasal itching, sneezing, watery (often profuse) rhinorrhea, and for many years with good symptom relief and, as he recalls,
congestion.3 His history of positive skin tests and that his symp- only minimal daytime sedation. He asks your opinion regard-
toms previously responded to antihistamine or decongestant also ing whether this is the best treatment for his allergic symp-
support the diagnosis. In the past, L.B. has experienced symptoms toms. He specifically requests the most cost-effective treat-
predictably at the onset of the tree pollination season, with only ment available because he must pay cash out-of-pocket for
minimal symptoms during the remainder of the year. Moving any medications. What therapy do you recommend and how
into an older home, however, has likely triggered latent sensitivi- should it be initiated?
ties to dust mite allergens and mold spores. A treatment approach
can be developed based on these presumptions. If this strategy Based on effectiveness and convenience, including nonpre-
is not effective, skin testing or additional laboratory assessments scription availability, oral antihistamines are the most frequent
are warranted. initial therapy recommended for patients with allergic rhinitis,
particularly those with mild symptoms.65 They reduce symp-
ALLERGEN AVOIDANCE MEASURES toms of nasal itching, sneezing, and rhinorrhea, with variable
effectiveness on ocular symptoms but no efficacy for nasal con-
CASE 25-1, QUESTION 2: What allergen avoidance strate- gestion. FGAs (e.g., diphenhydramine, brompheniramine, chlor-
gies could L.B. use to minimize his exposure to triggers? pheniramine, and clemastine) lack specificity for the H1 receptor
and can cause significant sedation, various anticholinergic side
Allergen avoidance is important for reducing symptoms in effects, and can impair performance, all of which limit their use-
patients with known sensitivities. Avoiding these triggers should fulness. Although at times these effects are considered desirable
lead to an improvement of symptoms; however, little evi- (e.g., to aid in sleep and dry nasal secretions), the SGAs (e.g.,
dence supports the effectiveness of a single physical or chem- loratadine, desloratadine, fexofenadine, cetirizine, and levoceti-
ical method.44,55 To achieve effective control, a multifaceted rizine), are preferable in most instances.23,66
approach to the control of environmental triggers is usually Antihistamines block the effects of histamine by one of two
needed.62–65 Although total allergen avoidance is often imprac- mechanisms: (a) as an H1 -receptor antagonist and (b) as an
tical to implement, simple changes that can reduce exposure to inverse agonist of the H1 -receptor.67 Whereas all marketed anti-
many perennial triggers, such as house dust mites, animal dander, histamines have sufficient effects on the histamine receptor to
and mold, can assist with symptom control.1 provide clinical benefits, the SGAs are more specific for the
Dust-mite avoidance (e.g., the use of impermeable covers on peripheral histamine receptor than are the FGAs68 and, for this
box springs, mattresses, and pillows) has traditionally been used reason, they present a lower risk for adverse effects.
as a method of reducing allergen exposure. Although this prac- In general, SGAs include agents with one or more of the
tice continues to be recommended frequently, a recent study following properties: (a) improved H1 -receptor selectivity, (b)
demonstrated that despite reduced exposure to antigen this strat- absent or reduced sedative effects, and (c) antiallergic properties
egy alone did not reduce symptoms in patients with allergic separate from antihistamine effects.65 Early SGAs, astemizole
rhinitis.64 Other methods of reducing antigen exposure include and terfenadine, were withdrawn from the market because of the
washing bedding at least weekly in hot water (>130◦ F) and reduc- risk of cardiovascular toxicity, usually related to higher doses and
interactions with agents metabolized via the cytochrome P-450 sistent use over time they perceive less symptomatic relief. 629
system.68 This is not a significant concern with currently available Although no pharmacologic explanation exists to support these
SGAs; however, many of the current agents undergo substantial observations,72 patients may experience benefit from switching
hepatic metabolism and some evidence exists of potential drug therapies if this perception presents.
interactions or variability in metabolic capacity associated with The major advantages of SGAs are their selectivity to
this.69 the H1 -receptor and their reduced central nervous system
L.B. has experienced a good response to an FGA without com- sedative effects.73 Desloratadine, fexofenadine, loratadine, and
plaints of excessive drowsiness. However, sedation includes both levocetirizine—at recommended doses—are reported to have
drowsiness (i.e., the subjective state of sleepiness or lethargy) an incidence of sedation that does not differ from placebo for
and impairment (i.e., an objective decrease in specific physical or both somnolence and performance impairment.74 Cetirizine and
mental abilities)61 and evidence indicates that cognitive impair- intranasal azelastine are not considered to be entirely nonsedat-
ment can occur, even in the absence of overt drowsiness.70,71 ing, although the incidence of sedation is less than with FGAs.73,75
Although patients can exhibit tolerance to sedative properties Another advantage of SGAs is that most products can be dosed
of FGAs, they may not perceive the performance impairment once daily to improve patient adherence to therapy. Specific anti-
that is still present. This has led to a consensus opinion among histamines are compared in Table 25-2. Second-generation agents
Chapter 25
experts that SGAs are preferred to FGAs when treating allergic prevent the onset of symptoms better than they reverse symp-
rhinitis.41,69 toms that are already present. Also, the maximal antihistamine
Essentially, all the antihistamines listed in Table 25-2 are effects occur several hours after the drug’s serum concentration
equally effective.41 Therefore, the choice of agent is based on peaks.73 For maximal effect, therefore, the SGA should be admin-
duration of action, side-effect profile (especially drowsiness and istered before allergen exposure, whenever possible. For the same
anticholinergic effects), risk of drug interactions, and cost.72 reason, chronic dosing is preferred to intermittent dosing.
Some patients claim that a kind of “tolerance” to the ther- In the case of L.B., it would be reasonable to begin ther-

apeutic effects occurs with antihistamines, in that with con- apy with loratadine 10 mg daily, because as an SGA it has
TA B L E 2 5 - 2
Oral Antihistaminesa,b Commonly Used in Allergic Rhinitis
Generic Name
(Example Brand
Product) Adult Dose Pediatric Dosec Other Effects
First Generation Sedative Antiemetic Anticholinergic
Chlorpheniramine 4 mg every 4–6 hours Children 6–12 years: 2 mg every 4–6 hours + 0 ++
(Chlor-Trimeton)
Clemastine 1.34 mg every 12 hours Children 6–12 years: 0.67 mg every 12 hours ++ ++ +++
(Tavist)
Diphenhydramine 25–50 mg every Children 6–12 years: 12.5–25 mg every +++ ++ +++
(Benadryl) 4–6 hours 4–6 hours
Second Generation Sedative Antiemetic Anticholinergic
Cetirizine 5–10 mg once daily Children 6–12 years: 5–10 mg once daily + 0 ±
(Zyrtec Allergy) Children 2–5 years: 2.5–5 mg once daily or
2.5 mg every 12 hours
Desloratadined 5 mg once daily Children 6–11 years: 2.5 mg once daily ± 0 ±
(Clarinex) Children 1–5 years: 1.25 mg once daily
Children 6–11 months: 1 mg once daily
Fexofenadine 60 mg every 12 hours Children 2–11 years: 30 mg every 12 hours ± 0 ±
(Allegra) or 180 mg once daily
Levocetirizined 5 mg once daily in the Children 6–11 years: 2.5 mg once daily in ± 0 ±
(Xyzal) evening the evening
Children 2–5 years: 1.25 mg once daily in
the evening
Loratadine 10 mg once daily Children 6–12 years: 10 mg once daily ± 0 ±
(Claritin) Children 2–5 years: 5 mg once daily
a
Many oral antihistamines are sold as combination products with the oral decongestants pseudoephedrine and phenylephrine. The addition of the decongestant may alter
the dosing scheme for the product. As of 2005, pseudoephedrine products have been placed behind the pharmacy counter in the United States. Federal law limits the
quantity available for purchase to 9 g/mo, 3.6 g/d with signature and photo identification. Individual states may have additional restrictions regarding the sale of
pseudoephedrine, consult local boards of pharmacy for details.
b
Some oral antihistamines are available in both short-acting and extended- or sustained-release formulations. Refer to package insert for specific dosing instructions for
long-acting products.
c
In 2008, the FDA issued an advisory alert recommending that OTC cough and cold agents (e.g., products containing antitussives, expectorants, decongestants, and
antihistamines) not be used in infants and children younger than 2 years of age because of the potential for serious and possibly life-threatening adverse events. More
recently, in October 2008, leading pharmaceutical manufacturers voluntarily modified product labels on OTC cough and cold preparations to state “do not use” in children
younger than 4 years of age. Further safety reviews by the FDA regarding the use of these agents in children between the ages of 2 and 11 are ongoing.
d
Currently available by prescription only.
630 demonstrated efficacy with minimal side effects and is also avail- congestion may require a combination of an antihistamine with
able without a prescription (as he requested) and as a generic a decongestant. The combination of an antihistamine and an oral
formulation, which will further control costs. decongestant is more effective than either component alone in
the treatment of allergic rhinitis.66
INTRANASAL ANTIHISTAMINES Both the topical (intranasal) and the oral decongestants are
sympathomimetics that directly stimulate α 1 -adrenergic recep-
CASE 25-1, QUESTION 5: L.B. reports that a friend with sim- tors, resulting in vasoconstriction. Local effects on the nasal
ilar symptoms had experienced relief from an antihistamine mucosa include decreased tissue hyperemia, decreased tissue
nasal spray. Is it possible to give antihistamines by this route, swelling, decreased nasal congestion, and improved nasal air-
or is L.B. confusing this with other topical therapies, such way patency.66 Oral decongestants include phenylephrine and
as decongestants or corticosteroids? Are intranasal antihis- pseudoephedrine. Until 2005, pseudoephedrine was the more
tamines appropriate for L.B.? popular agent; however, because of the potential to use it in
the manufacturer of illicit substances (e.g., methamphetamine),
Topical formulations of the antihistamine azelastine have restrictions on the allowable quantity and methods for pur-
been shown beneficial in allergic rhinitis and conjunctivitis.76–80 chasing pseudoephedrine-containing products have been imple-
In studies comparing intranasal azelastine with oral antihis- mented at both the state and federal levels. These restrictions
Section 3
tamines and placebo, this agent has been found to be equally effec- have resulted in the reformulation of many oral decongestant
tive to oral antihistamines, although a meta-analysis comparing products to include phenylephrine as an alternative deconges-
azelastine with intranasal corticosteroids suggests that intranasal tant. A meta-analysis of phenylephrine used as a decongestant
corticosteroids were superior in efficacy for all but ophthalmic in doses approved for nonprescription use has raised concerns
symptoms.76 In contrast to oral antihistamines, intranasal azelas- about its efficacy as an oral agent81 ; however, the FDA has deter-
tine has also been proven effective for patients with nonallergic mined that there are adequate data to support its continued use.
Pulmonary Disorders
or mixed rhinitis, relieving a variety of symptoms, including nasal The available oral and topical decongestants, all of which are
congestion.3 available without prescription, are compared in Table 25-3.
The side effects of azelastine are comparable to the FGAs in Oral decongestants can cause systemic side effects, particu-
terms of somnolence (10%–15%) and headache (15%–30%).79 larly those associated with central nevous system stimulation
Intranasal azelastine can also cause local side effects, includ- (e.g., nervousness, restlessness, insomnia, tremor, dizziness, and
ing nasal irritation, dry mouth, sore throat, and mild epistaxis. headache).6 Cardiovascular stimulation (e.g., tachycardia, palpi-
An objectionable aftertaste is a significant problem, occurring tations, increased blood pressure) also can occur, so patients with
in up to 20% of patients, even those using the ophthalmic hypertension should be monitored carefully while taking oral
formulations.78 The original intranasal product (Astelin) was decongestants.82 Because oral decongestants are not associated
saline-based; but a newer formulation (Astepro) includes sor- with the development of rebound congestion, in most patients
bitol and sucralose to mask this bitter taste.80 Patient complaints they are appropriate for chronic use except during pregnancy.83
are fewer with the newer product, but still present. Topical administration of decongestants generally does not lead
Dosing recommendations for azelastine for adults and chil- to systemic side effects; however, these agents are not appropriate
dren older than 12 years of age with perennial symptoms are two for chronic use in rhinitis because of their potential for causing
sprays in each nostril twice a day. Before the first use and any- rebound congestion (see Case 25-7).
time when the product has not been used for 3 days or more, the Because L.B. is complaining of nasal congestion, he will
dosage form must be primed. This is accomplished by pumping require a decongestant in addition to the loratadine. He may
the spray mechanism two to four times until a consistent mist is choose to use a once-daily fixed-dose combination product (e.g.,
expelled. loratadine 10 mg + pseudoephedrine extended-release 240 mg)
A potential role for intranasal antihistamines is for patients or to supplement the daily loratadine with pseudoephedrine as
who do not respond adequately to oral antihistamines.3 In addi- needed. Although L.B. has used pseudoephedrine in the past
tion, some patients may prefer the intranasal route of adminis- without a problem, he may require education regarding the new
tration or benefit from concomitant therapy with intranasal anti- procedures for purchasing this product while assuring him that
histamines and intranasal corticosteroids. As a prescription-only the new restrictions are not related to the drug’s safety as a decon-
product, an intranasal antihistamine would be more expensive gestant. In addition, although his hypertension is controlled, his
than many oral alternatives. Because of the expense associated blood pressure should be monitored regularly to detect any dete-
with prescription-only status, increased risk of side effects, and rioration. If he’s ready to consider a prescription product, an
objectionable taste, topical azelastine is not an optimal therapeu- intranasal steroid (discussed subsequently) would also be a rea-
tic option for L.B. sonable option for L.B.
Decongestant Therapy Ocular Therapies

CASE 25-1, QUESTION 6: What role do decongestants have RELATIONSHIP BETWEEN OCULAR AND
in L.B.’s treatment? NASAL SYMPTOMS
Nasal congestion is often much less severe in patients who CASE 25-1, QUESTION 7: L.B.’s new therapies are effective
experience only intermittent symptoms, but as L.B.’s symptoms for his persistent nasal symptoms; however, in the spring he
have become persistent since his move, the exact frequency and complains that his eyes are itchy and watery and that the
severity of his nasal congestion should be assessed before rec- loratadine and pseudoephedrine do not seem to be help-
ommending drug therapy. In patients with only mild, intermit- ing. How are L.B.’s ocular symptoms related to his allergic
tent symptoms, saline irrigation (administered as frequently as rhinitis?
needed) is helpful in soothing and moisturizing irritated nasal
mucosa but may be impractical. Antihistamines do little to relieve Allergic ocular disease is part of the full range of allergic
nasal congestion; therefore, patients with moderate to severe diseases, including rhinitis, eczema, and asthma, which share
631
TA B L E 2 5 - 3
Decongestantsa,b Commonly Used in Allergic Rhinitis
Generic Name
(Example Brand Product) Adult Dose Pediatric Dosec
Orala
Pseudoephedrine (Sudafed) 60 mg every 4–6 hours (max 240 mg/d) Children 6–12 years: 30 mg every 4–6 hours (max 120 mg/d)
Children 2–5 years: 15 mg every 4–6 hours (max 60 mg/d)
Phenylephrine (Sudafed PE) 10–20 mg every 4 hours (max 120 mg/d) Children 6–11 years: 10 mg every 4 hours (max 60 mg/d)
Topicald
Naphazoline (Privine) 0.05% solution: 1–2 drops or sprays/nostril Children <12 years: Avoid, unless under physician direction
every 6 hours
Phenylephrine (Neo-Synephrine) 0.25%–1.0% solution: 2–3 sprays or drops/ Children 6–11 years: 2–3 sprays or drops (0.25% solution)/
Chapter 25
nostril every 3–4 hours nostril every 4 hours
Children 2–5 years: 2–3 drops (0.125% solution) into each
nostril not more than every 4 hours
Oxymetazoline (Afrin) 0.05% solution: 2–3 sprays/nostril every Children 6–12 years: 2–3 sprays/nostril every 12 hours
10–12 hours
Xylometazoline (Triaminic) 0.1% solution: 2–3 sprays into each nostril Children 2–12 years: 1–2 sprays (0.05% solution) into each

every 8–10 hours nostril every 8–10 hours
a
Many oral decongestants are sold as combination products with the oral antihistamines. The addition of the antihistamine may alter the dosing scheme for the product. As
of 2005, pseudoephedrine products have been placed behind the pharmacy counter in the United States. Federal law limits the quantity available for purchase to 9 g/mo,
3.6 g/d with signature and photo identification. Individual states may have additional restrictions regarding the sale of pseudoephedrine, consult local boards of pharmacy
for details.
b
Some oral decongestants are available in both short-acting and extended- or sustained-release formulations. Refer to package insert for specific dosing instructions for
long-acting products. Note that some extended-release formulations are not recommended for children younger than 12 years of age.
c
In 2008, the FDA issued an advisory alert recommending that OTC cough and cold agents (e.g, products containing antitussives, expectorants, decongestants, and
antihistamines) not be used in infants and children younger than 2 years of age because of the potential for serious and possibly life-threatening adverse events. More
recently, in October 2008, leading pharmaceutical manufacturers voluntarily modified product labels on OTC cough and cold preparations to state “do not use” in children
younger than 4 years of age. Further safety reviews by the FDA regarding the use of these agents in children between the ages of 2 and 11 are ongoing.
d
Limit duration of treatment to less than 5 days to minimize risk of rebound congestion. Topical decongestants should never be used in infants younger than 6 months of
age because they are obligate nose breathers and the resulting rebound congestion could cause obstructive apnea.
a common pathophysiology and inflammatory presentation.84 episodic versus chronic treatment). Nonpharmacologic treat-
The most common of the allergic ocular diagnoses is seasonal ment includes avoidance of aeroallergens to the extent possible,
(intermittent) allergic conjunctivitis, which accounts for up to cold compresses or the use of refrigerated eye drops, and lubrica-
50% of all ocular allergy cases. The symptoms of both inter- tion with frequent application of saline or tear substitutes. Part of
mittent and persistent allergic conjunctivitis are identical in that the effectiveness of all of the ocular preparations, including lubri-
they are caused by allergic response in the conjunctiva to airborne cating eye drops, is attributable to physical dilution and irrigation
allergens. Seasonal symptoms commonly occur in response to of aeroallergens from the eye.84
pollens, whereas perennial symptoms are more often associated The available therapeutic options for management of allergic
with house dust mites. The symptoms of allergic conjunctivi- conjunctivitis include topical ocular administration of antihis-
tis are itchy eyes, with or without a burning sensation, and a tamines, vasoconstrictors, mast-cell stabilizers, and nonsteroidal
watery discharge or tearing. Physical examination reveals con- anti-inflammatory drugs (Table 25-4). Randomized, controlled
junctival surfaces that are mildly injected (reddened) with vary- trials have demonstrated that these agents significantly reduce
ing degrees of conjunctival edema. Swelling of the eyelids can ocular symptoms, including itching, and improve sleep.84–87
also occur. The symptoms are usually bilateral, but not always These ocular medications act by the same mechanisms as
symmetric.84 their nasal counterparts. In addition, topical ophthalmic cortico-
Because of the potential for long-term damage to vision, per- steroids have a limited role in the acute management of aller-
sistent ocular conditions should always be assessed by an eye gic conjunctivitis; however, they are not indicated for prolonged
care professional. Other ocular problems that can be confused use because of the risk of serious infectious complications in the
with allergic conjunctivitis include atopic keratoconjunctivitis, eye.88
keratopathy, and giant papillary conjunctivitis (see Chapter 54, In the case of L.B., a trial of antihistamine + vasoconstric-
Eye Disorders). tor combination eye drops (e.g., pheniramine maleate 0.3% +
naphazoline hydrochloride 0.025%) one to two drops in affected
CHOICE OF THERAPEUTIC AGENT eyes up to 4 times a day for management of acute symptoms is an
appropriate recommendation for short-term use. Note that the
CASE 25-1, QUESTION 8: What are the treatment options overuse of ocular vasoconstrictors can lead to rebound conjunc-
for L.B.’s allergic conjunctivitis, and how does the clinician tivitis, similar to that occurring with nasal decongestants (see
choose between the available options? Drug-Induced Nasal Congestion: Rhinitis Medicamentosa sec-
tion). If the patient exhibits chronic symptoms, consider a switch
Seasonal and perennial allergic conjunctivitis are treated simi- to an intranasal corticosteroid (which may have better efficacy
larly with only the duration of the treatment course differing (i.e., for combination symptoms)89 or refer to specialist care.
632
TA B L E 2 5 - 4
Topical Ophthalmic Medications Commonly Used for Allergic Conjunctivitis
Generic Name Available Dosage

(Example Brand Product) Forms/Strength Dose
Antihistamines
Azelastine (Optivar) Ophthalmic solution: 0.05% Adults and children ≥3 years: 1 drop in the affected eye(s) every 12 hours
Emedastine (Emadine) Ophthalmic solution: 0.05% Adults and children ≥3 years: 1 drop in the affected eye(s) up to
4 times daily
Antihistamine/Decongestant Combinations
Pheniramine + Naphazoline Ophthalmic solution: naphazoline Adults and children ≥6 years: 1–2 drops in the affected eye(s) every 6 hours
(Naphcon-A)a HCl 0.025% + pheniramine for up to 3 days
maleate 0.3%
Antihistamine/Mast-Cell Stabilizers
Section 3
Ketotifen (Zaditor)a Ophthalmic solution: 0.025% Adults and children ≥3 years: 1 drop in the affected eye(s) every
8–12 hours
Olopatadine (Pataday) Ophthalmic solution: 0.2% Adults and children ≥3 years: 1 drop in the affected eye(s) daily
Mast-Cell Stabilizers
Cromolyn Sodium (Crolom) Ophthalmic solution: 4% Adults and children ≥4 years: 1–2 drops in the affected eye(s)
Pulmonary Disorders
4–6 times daily

Lodoxamide (Alomide) Ophthalmic solution: 0.1% Adults and children ≥2 years: 1–2 drops in affected eye(s)
4 times daily for up to 3 mos
Nedocromil (Alocril) Ophthalmic solution: 2% Adults and children ≥3 years: 1–2 drops in the affected eye(s) every
12 hours
Pemirolast (Alamast) Ophthalmic solution: 0.1% Adults and children ≥3 years: 1–2 drops in the affected eye(s) 4 times daily
Nonsteroidal Anti-Inflammatory Drugsb
Ketorolac (Acular) Ophthalmic solution: 0.5% Adults and children ≥3 years: 1 drop in the affected eye(s) 4 times daily
Corticosteroids
Loteprednol (Alrex) Ophthalmic suspension 0.2% Adults: 1 drop in the affected eye(s) 4 times daily
a
Available without a prescription.
b
Other ophthalmic nonsteroidal anti-inflammatory drugs (diclofenac, flurbiprofen, suprofen) indicated for intraoperative miosis and for postcataract surgery, but not
approved for allergic conjunctivitis.
Cromolyn Therapy backs to this are its out-of-pocket cost, its technique-dependent
administration, its multiple daily dosing requirements (up to six
CASE 25-2 times daily), and its reduced effectiveness compared with other
treatments.53
QUESTION 1: J.C. is a 10-year-old girl who has been expe-
riencing rhinorrhea and sneezing when visiting her father in CASE 25-2, QUESTION 2: What strategies should J.C.’s
another state a couple of times each year. On questioning, father use to minimize exposure to the allergic triggers?
J.C.’s mother reveals that although J.C. has not complained
of symptoms previously, her father adopted a puppy from To minimize J.C.’s exposure to allergens, the dog should be
the local animal shelter about a year ago and the symptoms kept out of the child’s bedroom at all times and, when possible,
correspond to the times that the child spends with the dog. kept outside or confined to an uncarpeted area of the home. J.C.’s
J.C. will be visiting her father again next month, and she father should use a high-quality air filter and should vacuum the
is hoping to purchase something without a prescription to home with a double-filter system while J.C. is out of the house.
prevent her from “getting sick and missing out on her sum- Although evidence of benefit is unclear, it may be helpful to wash
mer vacation.” What options are available to treat J.C.’s the dog weekly while the child visits. The additional expense of
intermittent symptoms of allergic rhinitis? regular, commercial cleaning of air ducts is not cost justified.1
J.C. appears to have mild allergic rhinitis triggered by exposure INSTRUCTIONS FOR USE
to animal dander. When it is possible to anticipate symptoms, as
in J.C.’s case, initiating prophylactic therapy can help lessen the CASE 25-2, QUESTION 3: How should J.C. be advised to
impact of allergen exposure.1 J.C. appears to be a good candi- use cromolyn nasal spray to prevent her symptoms?
date for treatment with intranasal corticosteroids or cromolyn
sodium, administered regularly beginning several weeks before To be effective, cromolyn nasal spray must be dosed several
each trip. Because the mother indicates that she wants to select an times each day, which can hinder adherence.53 The initial dose
OTC product, allergen avoidance strategies plus cromolyn nasal for the 4% cromolyn sodium nasal spray is one spray in each
spray would be a reasonable choice for initial therapy. The draw- nostril four to six times daily. In some patients, symptom control
633
TA B L E 2 5 - 5
Additional Oral and Topical Agents for Rhinitis
Available Dosage
Generic (Brand Product) Forms/Strength Adult Dose Pediatric Dose
Oral
Leukotriene modifiers Tablets: 10 mg 10 mg once daily Children 6–14 years: 5 mg once daily
Montelukast Tablets, chewable: 4 mg, 5 mg Children 2–5 years: 4 mg once daily
(Singulair) Oral granules: 4 mg Children 6–23 months: 4 mg once daily
Intranasal
Antihistamine Nasal spray: 137 mcg/spray 1–2 sprays/nostril every 12 hours Children 5–11 years: 1 spray/nostril
Azelastine Nasal spray: 205.5 mcg/spray (for seasonal symptoms) every 12 hours
(Astelin) 2 sprays/nostril every 12 hours (for Not indicated for children <12 years
perennial symptoms)
Chapter 25
(Astepro) 2 sprays per nostril once daily or
1–2 sprays per nostril every
12 hours (for seasonal symptoms)
2 sprays per nostril every 12 hours
(for perennial symptoms)
Mast-cell stabilizer Nasal spray: 5.2 mg/spray 1 spray/nostril every 4–6 hours (max Children ≥2 years: 1 spray/nostril every
Cromolyn sodium 6 times daily) 4–6 hours (max 6 times daily)

(Nasalcrom)a
Anticholinergic Nasal spray: 21 mcg/spray (for 2 sprays/nostril up to 4 times daily Children ≥5 years: 2 sprays/nostril up
Ipratropium bromide perennial symptoms), 42 mcg/ (max = 672 mcg/day) to 4 times daily (max = 672 mcg/
(Atrovent)b spray (for seasonal symptoms) day)
a
Available without a prescription.
b
Optimum dosage varies with the response of the individual patient, however. It is always desirable to titrate an individual to the minimum effective dose to reduce the risk of
side effects. In addition, the safety and efficacy of the use of ipratropium 42 mcg nasal spray beyond 3 weeks in patients with seasonal allergic rhinitis has not been established.
can be maintained with dosing two to three times per day. J.C.
allergies. While you are talking to her, you note that A.R.
should be instructed to begin therapy at least two weeks before
breathes exclusively through her mouth, sniffs frequently,
her planned visit because of the delay in the onset of action for
and rubs her nose. You also notice dark circles under her
this agent.
eyes. What signs and symptoms of allergic rhinitis is A.R.
The clinician should ensure that both parent and child can
displaying?
demonstrate appropriate administration technique before ther-
apy is initiated. On first use, the device should be primed until a A.R. is showing the classic signs of allergic airways disease in
consistent spray is achieved. J.C. should be instructed to gently children. She is sniffing and snorting in response to nasal itching
blow her nose and then spray the cromolyn sodium solution into and discharge. The frequent upward rubbing of the nose (gener-
each nostril in a slightly upward direction, parallel to the nasal ally with the palm of the hand) is known as the “allergic salute”
septum. and is caused by nasal itching. Long-standing symptoms can lead
Topical nasal cromolyn has an excellent safety profile, includ- to facial abnormalities, including the formation of a transverse
ing minimal incidence of adverse effects. Local irritation occurs crease across the bridge of the nose. Generalized facial swelling
in less than 10% of patients, with burning, stinging, and sneez- with associated venous congestion can also result in infraorbital
ing being the most common manifestations. The safety of cro- discoloration. These dark circles under the eyes are commonly
molyn has made it widely used as initial therapy for children with known as “allergic shiners” and they can be further aggravated
allergic rhinitis and for treating rhinitis during pregnancy.53,83 by the frequent rubbing of the eyes associated with severe ocular
Table 25-5 includes information about intranasal cromolyn dos- itching.2
ing and availability.
CASE 25-3, QUESTION 2: Given her concomitant asthma,
Intranasal Corticosteroid Therapy are there any special considerations for treating A.R.’s aller-
gic rhinitis?
CASE 25-3
QUESTION 1: A.R. is an 8-year-old girl with allergic rhinitis Based on the relationship between inflammation in the upper
and asthma. She has been treated with orally inhaled budes- and lower airways, and the similar immunologic mechanisms
onide for asthma and oral loratadine for rhinitis. Her mother involved in allergic rhinitis and asthma, it is a reasonable assump-
reports that she frequently sneezes, complains of an itchy tion that poor control of upper airway allergies can have a nega-
nose and eyes, and does not sleep well at night because of tive impact on asthma control.90–92 In fact, rhinitis is a risk factor
nasal congestion. She also reports that she cannot give her for asthma development,93 and poorly controlled rhinitis can
cetirizine on a daily basis because it “makes her drowsy at aggravate asthma control.94 In a patient with asthma, like A.R.,
school.” Her asthma has been well controlled in the past; treatment of allergic rhinitis can also reduce airway hyperrespon-
however, she is concerned that she is experiencing some siveness and symptoms of asthma.95
shortness of breath and that this might be related to her Historically, the use of antihistamines (FGAs) was consid-
ered problematic for patients with asthma because of a theoretic
634 concern about excessive drying of airway secretions caused by antihistamines for various nasal symptoms and total nasal symp-
the anticholinergic properties of these agents. It is now clear that tom scores.101
most patients with asthma can take any of the antihistamines
without adverse pulmonary effects. Oral antihistamines (SGAs) MECHANISM OF ACTION
would currently be a logical first addition to an asthma regimen
because of their convenient dosing, but A.R.’s experience with CASE 25-3, QUESTION 4: How do intranasal corticosteroids
these agents in the past has not been positive. For this reason, work to reduce the symptoms of allergic rhinitis?
intranasal corticosteroids should be considered for A.R.
Corticosteroids interact with a specific steroid receptor in the
ROLE IN THERAPY cytoplasm of a cell, and the steroid receptor complex then moves
into the cell nucleus where it influences protein synthesis.102
CASE 25-3, QUESTION 3: What would be the role of Among the proteins synthesized is lipocortin, which inhibits the
intranasal corticosteroids in A.R.? breakdown of phospholipids to arachidonic acid; this, in turn,
inhibits the formation of prostaglandins and leukotrienes. Topi-
Based on the frequency and severity of symptoms, and the cal corticosteroids reduce the number of eosinophils, basophils,
lack of control/side effects with oral antihistamine therapy, and mast cells in the nasal mucosa and epithelium; directly inhibit
Section 3
intranasal corticosteroids are an appropriate consideration for the release of mediators from mast cells and basophils; reduce
A.R. Intranasal corticosteroids are the most effective therapy mucosal edema and vasodilation; stabilize the endothelium and
available for the treatment of allergic rhinitis. They are safe, well epithelium, resulting in decreased exudation; and reduce the sen-
tolerated, and are highly effective in reducing itching, sneezing, sitivity of irritant receptors, resulting in decreased itching and
rhinorrhea, and congestion.96 Intranasal corticosteroids may also sneezing.36 Topical corticosteroids inhibit both the early-phase
and late-phase reactions to antigen challenge, in contrast to sys-
Pulmonary Disorders
be beneficial in relieving cough associated with postnasal drip in

patients with allergic rhinitis.97 In addition to improving all nasal temic corticosteroids, which inhibit only the late-phase reaction
symptoms, evidence also suggests that intranasal administration in allergic rhinitis.103
of corticosteroids effectively relieves ocular symptoms.98 These
agents also have demonstrated efficacy for nonallergic rhinitis, CHOICE OF THERAPEUTIC AGENT
rhinitis medicamentosa, and nasal polyposis.10,12 The currently
available intranasal corticosteroids are listed in Table 25-6. CASE 25-3, QUESTION 5: What intranasal corticosteroid
Intranasal corticosteroids are consistently more effective than products are appropriate to manage A.R.’s allergic rhinitis?
other therapeutic options. They are frequently rated as more
effective than antihistamines, although the benefit from therapy Currently marketed intranasal corticosteroid products vary
requires correct use of the administration device.99,100 In a sys- in the pharmacologic characteristics that can influence patient
tematic review of the medical literature performed by the Agency acceptance and adherence; however, there do not appear to be sig-
for Healthcare Research and Quality, intranasal corticosteroids nificant advantages with regard to efficacy among them.104 Top-
provided significantly greater relief of symptoms compared with ical application is very effective in controlling nasal symptoms
TA B L E 2 5 - 6
Intranasal Corticosteroidsa Commonly Used for Rhinitis
Generic Name Available Dosage

(Example Brand Product) Forms/Strengths Adult Dosea Pediatric Dosea
Beclomethasone dipropionate 42 mcg/spray 1–2 sprays/nostril twice daily Children 6–12 years: 1 spray/nostril twice daily
(Beconase AQ) (max 2 sprays/nostril daily)
Budesonide 32 mcg/spray 1 spray/nostril once daily (max Children 6–12 years: 1 spray/nostril once daily
(Rhinocort Aqua) 4 sprays/nostril daily) (max 2 sprays/nostril daily)
Ciclesonide 50 mcg/spray 2 sprays/nostril once daily Children 6–12 years: 2 sprays/nostril once daily
(Omnaris) (approved for seasonal symptoms in ages >6,
and for perennial symptoms for ages >12)
Fluticasone propionate 50 mcg/spray 2 sprays/nostril once daily or Children 4–17 years: 1–2 sprays/nostril once daily
(Flonase) 1 spray/nostril twice daily (max 2 sprays/nostril daily)
Fluticasone furoate 27.5 mcg/spray 2 sprays/nostril once daily Children 2–11 years: 1–2 sprays/nostril once daily
(Veramyst) (max 2 sprays/nostril daily)
Flunisolide 29 mcg/spray 2 sprays/nostril two or three Children 6–14 years: 1 spray/nostril three times
(no brand product available) times daily (max 8 sprays/ daily or 2 sprays/nostril twice daily (max
nostril daily) 4 sprays/nostril daily)
Mometasone furoate 50 mcg/spray 2 sprays/nostril once daily Children 2–11 years: 1 spray/nostril once daily
(Nasonex)
Triamcinolone acetonide 55 mcg/spray 2 sprays/nostril once daily Children 2–5 years: 1 spray/nostril once daily
(Nasacort AQ) (max 1 spray/nostril daily)
Children 6–11 years: 1–2 sprays/nostril once daily
(max 2 sprays/nostril daily)
a
It is always desirable to titrate an individual patient to the minimum effective steroid dose to reduce the risk of side effects. When the maximum benefit has been achieved
and symptoms have been controlled, reducing the steroid dose might be effective in maintaining control of rhinitis symptoms.
with minimal risks of systemic effects.105 Primary differences intranasal corticosteroids does not impose a significant risk for 635
among products include potency, dosing regimens, delivery sys- mucosal atrophy, histologic changes in nasal mucosa have not
tems, spray volume, and patient preference.106 For sensitive been demonstrated, and intranasal candidiasis has never been
patients, there may be some theoretical advantage to products documented.115 Although the effects of systemic corticosteroids
that are benzalkonium chloride (BKC)–free or alcohol-free.3,23 on the eyes are well-established, nasal steroids have not been
The method to determine potency among topical cortico- shown to increase intraocular pressure.116 A report from the
steroids is to measure topical vasoconstrictive activity on the National Registry of Drug-Induced Ocular Side Effects linked
skin. Cutaneous vasoconstriction may not consistently correlate 21 cases of bilateral posterior subcapsular cataracts to the use of
with anti-inflammatory potency in the nasal mucosa, however.107 intranasal or inhaled corticosteroids117 ; however, several of these
Potency can also be described as a measure of lipophilicity patients were also on systemic corticosteroids or had used high-
because agents that are highly lipophilic may have faster absorp- dose beclomethasone for more than 5 years. The risk of cataracts
tion and longer residence at the receptor in the mucosa. The with the newer agents has not been established.117
lipophilicity from lowest to highest among current products is It may be important for the clinician to consider the total
flunisolide, triamcinolone, budesonide, beclomethasone, flutica- corticosteroid load in atopic patients who may be treated with
sone, mometasone, and ciclesonide.107,108 The topical-to- an inhaled or systemic preparation for asthma, intranasal prepa-
Chapter 25
systemic potency relationship should also be considered because ration for rhinitis, and dermatologic preparation for eczema,
the ideal agent should exhibit high topical potency and low sys- although no guidelines to follow exist in this area. Although
temic activity. After topical administration, the corticosteroid intranasal steroids are considered safe and are sometimes avail-
may reach the systemic circulation by absorption across the nasal able without a prescription from pharmacies outside the United
mucosa or through gastrointestinal absorption of the swallowed States, a joint task force for the American Academy of Allergy,
portion of the dose.107 Among the available agents, mometasone, Asthma, and Immunology issued a position statement recom-
fluticasone, and ciclesonide have the lowest systemic bioavailabil- mending that these agents remain prescription-only and pre-

ity, ranging from 0.1% to less than 2%.109 Beclomethasone may scribed under the direct supervision of a physician.118
exert greater systemic effects owing to its metabolism to an active
metabolite (beclomethasone 17-monopropionate). For this rea- INSTRUCTIONS FOR USE
son, newer agents are often favored over beclomethasone.110
Studies have shown that varying sensory attributes (e.g., taste, CASE 25-3, QUESTION 7: A.R. is given a prescription for
smell, aftertaste, throat rundown, nose runout, and feel of spray budesonide, two actuations in each nostril twice daily. How
in nose and throat) affect acceptability of, and preference for, should she be counseled to use this drug?
particular nasal corticosteroid products.104,106 Although more
patients rated aftertaste as the most important feature deter- Although intranasal corticosteroids have an excellent safety
mining their preference,104 no head-to-head trials have directly profile, some local adverse effects can occur. The currently avail-
compared the available products, and thus some degree of exper- able products are all aqueous solutions delivered via a man-
imentation may be required to find the optimal product for A.R. ual spray pump; these are much less drying than the original
propellant-based aerosol formulations of the same products. The
SAFETY most commonly reported side effect is epistaxis, with excessive
nasal dryness and crusting also reported.32 A more serious con-
CASE 25-3, QUESTION 6: How safe are intranasal cortico- cern is the risk for nasal septal perforation. Proper technique in
steroids in this situation? using the nasal corticosteroid products can reduce the risks for
these side effects.1
The corticosteroids currently available for intranasal admin- Patient education is important to ensure proper use of,
istration are listed in Table 25-6. Among available prod- and response to, the intranasal corticosteroids. A.R. should be
ucts, intranasal corticosteroids have similar efficacy in clinical instructed to blow her nose gently before using the nasal inhaler
trials.99 Budesonide, ciclesonide, flunisolide, triamcinolone, and as severe blockage of the nasal passage may prevent deposition
beclomethasone are indicated for ages 6 years or older. Flutica- of the drug at the intended site of action. The patient should be
sone and mometasone are labeled for ages 4 years and older and instructed to direct the spray away from the nasal septum. This
2 years and older, respectively.109 is accomplished by pointing the applicator nozzle straight and
A common concern regarding the use of corticosteroids back using the contralateral hand to ensure application is parallel
in children is the risk of growth suppression. Current US to the septum.32
Food and Drug Administration (FDA) labeling for inhaled and Therapeutic benefit to intranasal steroids is generally evident
intranasal corticosteroid preparations include wording that use in as few as 2 days, although some newer agents may begin to
of these products in children may reduce their rate of growth. relieve symptoms within hours.98 Fluticasone has been effective
Although beclomethasone may be associated with reduced when used on an as-needed basis.49 Nonetheless, it is reasonable
growth velocity,111 numerous studies have shown no growth to advise patients that full benefit may not be realized for up to
delay in children treated long term with newer intranasal 3 weeks.
steroids.112–114
In 2003, the FDA approved revised labeling for fluticasone
nasal spray, indicating no adverse effect on growth even with use Systemic Corticosteroids
for up to 1 year. Data are lacking, however, about the potential
risk of reduced growth velocity associated with a combination of CASE 25-3, QUESTION 8: What is the role of systemic
intranasal and orally inhaled corticosteroids. With this in mind, it corticosteroid therapy in the managment of A.R.’s allergic
is appropriate to recommend agents with low systemic bioavail- rhinitis?
ability and to utilize the lowest effective dose.
Other potential adverse effects of chronic intranasal cor- In contrast to the minimal side effects of the topical cor-
ticosteroids have been investigated. Prolonged topical use of ticosteroids, systemic administration of these drugs can cause
636 numerous, and at times serious, side effects. Systemic adminis- around the urethra, enlargement of the gland can obstruct urine
tration, therefore, must be reserved for only short-term, adjunc- flow.123
tive therapy in cases of severe, debilitating rhinitis. In such cases, The bladder and urethra are made up of smooth muscle tis-
a short course of relatively high-dose corticosteroid, so-called sue that is innervated by the sympathetic and parasympathetic
burst therapy, can be administered. Prednisone 40 mg/day for divisions of the autonomic nervous system. The detrusor muscu-
adults or 1 to 2 mg/kg/day for children (or an equivalent dose lature is predominantly innervated by β-adrenergic and choliner-
of a comparable compound) every morning for up to 7 days gic receptors, whereas the bladder neck (or outlet) is innervated
effectively relieves acute, severe rhinitis symptoms. If A.R. were predominately by α-adrenergic receptors. Sympathetic stimula-
to have a particularly severe exacerbation of her allergic rhinitis tion causes relaxation of the detrusor muscle to allow bladder
such that it interfered with sleep or ability to attend school, an filling, closure of the urethra, and decreased bladder emptying.
oral corticosteroid burst would be indicated. More likely, A.R. Cholinergic stimulation of the detrusor causes contraction of the
would require a short course of systemic corticosteroids for an detrusor to cause bladder emptying. Initially, the detrusor mus-
acute asthma exacerbation which should also result in improved culature can compensate for the urethral obstruction in BPH.
nasal symptoms. Eventually, however, the detrusor muscle fibers hypertrophy and
decompensate, resulting in urinary retention and detrusor hyper-
reflexia manifesting as urinary frequency, urgency, urge inconti-
Section 3
Combination Therapy nence, and nocturia.123

When K.H. took diphenhydramine, the anticholinergic prop-
CASE 25-3, QUESTION 9: Would there be an advantage in erties of the drug blocked detrusor contraction and precipitated
combining various therapies for allergic rhinitis in A.R.? acute urinary retention.124 In this case, therapy with a SGA (i.e.,
fexofenadine) is more appropriate because these agents have little
The rationale for combining agents to treat allergic rhinitis to no anticholinergic side effects.
Pulmonary Disorders
is based on the theoretic benefit of additive or synergistic reac-

tions. Various combinations have been studied. Concomitant use EFFICACY
of antihistamines and decongestants has been shown to relieve
individual nasal symptoms as well as the total symptom score as CASE 25-4, QUESTION 2: What is the rationale and evi-
compared with either agent alone. When combinations of anti- dence that a leukotriene modifier might be beneficial in the
histamines and nasal corticosteroids were compared with either managment of K.H.’s allergic rhinitis?
agent alone, the combination was superior to antihistamine
monotherapy but not to treatment with nasal corticosteroids Leukotrienes are important inflammatory mediators in the
alone.119 In one study using an algorithm for treatment, this com- upper and lower airways and are present in nasal secretions of
bination, however, was the standard for severe rhinitis.120 Stud- patients with allergic rhinitis. They serve as inflammatory medi-
ies evaluating the combination of antihistamines and leukotriene ators that result in increased vascular permeability, tissue edema,
modifier therapies have yielded inconsistent results.121,122 There- mucus secretion, and increased eosinophils. These actions lead
fore, it is unclear that the combination is superior to monother- to the symptoms of allergic rhinitis, as well as those of asthma.50
apy with either agent alone and it is likely less effective than In clinical trials, leukotriene modifiers relieve nasal symptoms in
treatment with nasal steroids alone.100 When combination ther- patients with allergic rhinitis44 with similar efficacy to SGA52 and
apy of any kind is used, once symptoms are controlled, one agent less efficacy than nasal corticosteroids.125
should undergo a trial for discontinuation. In actual use, the benefit of leukotriene modifiers has been
modest; therefore, their role is typically adjunctive to the use of
first-line agents for allergic rhinitis.126 Clinical decisions about
Leukotriene-Modifying Agent Therapy the value of combining treatments should be based on the spe-
cific clinical situation. Because K.H. has experienced intoler-
CASE 25-4
ance to FGAs and a lack of efficacy with SGAs, a trial with
QUESTION 1: K.H. is a 58-year-old man with allergic rhini- an intranasal corticosteroid or a leukotriene-modifying agent is
tis. He has experienced symptoms during ragweed pollen appropriate. Specifically, a patient with mild asthma and allergic
season for several years. He has used various antihistamines rhinitis may benefit from therapy with a leukotriene modifier
for his symptoms during this time with moderate success. At with or without an antihistamine. If used, however, a risk exists
times, K.H. has self-medicated with nonprescription medica- of a rare complication known as Churg-Strauss syndrome, which
tions, including clemastine and diphenhydramine. This year, is characterized by eosinophilia, vasculitic rash, worsening pul-
he initiated therapy with diphenhydramine 1 week before monary symptoms, cardiac complications, and neuropathy.109
the pollen season, but began experiencing symptoms of Table 25-5 includes information about the use and availability of
urinary retention after 10 days. His physician advised him montelukast, which is currently the only leukotriene modifier
that this might be related to the antihistamine aggravat- approved for allergic rhinitis.
ing his enlarged prostate and he was advised to use fex-
ofenadine 60 mg twice daily. After 1 week, K.H. com-
plains that the medication is not working. After seeing an Complementary and Alternative
advertisement on television, he inquires about the use of Therapies
a leukotriene modifier for his allergic rhinitis. What is the
mechanism for the K.H.’s urinary discomfort attributed to CASE 25-5
the diphenhydramine? QUESTION 1: C.L., a 25-year-old woman presents in mid-
August complaining that her allergies are worsening daily.
K.H. is exhibiting symptoms of urinary outflow obstruction Symptoms are nasal discharge and obstruction, repetitive
or prostatism. Common features of this are frequency, hesitancy, sneezing, and itching of the nose, eyes, and throat. She
slow urine stream, dribbling, and bladder fullness after void- is fatigued and has difficulty concentrating. Her symptoms
ing. The most common cause of obstruction is benign prostatic have been occurring in late spring and summer since high
hyperplasia (BPH). Because the prostate is located anatomically
sunflowers, daisies, and ragweed—all members of the Composi- 637

school, and she has used a variety of medications inter-
tae (Asteraceae) family.137 The possibility that cross-sensitivity
mittently (clemastine, fexofenadine, beclomethasone nasal,
between echinacea and other environmental allergens may trig-
ketotifen ophthalmic) over the years. C.L. is a competitive
ger allergic reactions is supported by an Australian review of all
runner but has been unable to run as far or as often as
adverse drug reports, including cases of anaphylaxis, associated
usual due to bothersome symptoms. She is also reluctant
with echinacea.137 Patients with known allergy to these plants
to use medications as they may be prohibited by her race
should be cautioned regarding the use of echinacea products.
sponsors. A running partner mentioned that she could con-
A few herbal therapies, including butterbur138–140 and
trol her allergy symptoms with diet, exercise, and herbal
spirulina,141 potentially hold some promise but more investi-
remedies purchased at a local nutritional supplement shop.
gation is needed before they can be included in recommended
What, if any, alternative treatments have been shown to be
treatment algorithms.23 No good clinical data are available on
efficacious in allergic rhinitis?
the efficacy of supplements containing vitamin C, grapeseed
Alternative treatments are common among adults with rhini- extract, bee pollen and honey, probiotics, burdock, ginger, freeze-
tis and should be taken into account by health care providers. dried stinging nettle leaves, or quercetin (a bioflavonoid found
A survey of 300 adults indicated that herbal agents, caffeine- in apples, buckwheat, grapes, red onions, red wine, and white
grapefruit).40
Chapter 25
containing products, homeopathy, acupuncture, aromatherapy,
reflexology, and massage were common alternative treatments
OTHER
for respiratory conditions.127 Still, because allergic rhinitis is
Reports regarding the use of intranasal zinc for upper respira-
largely a self-managed disease, it is likely that reported use of
tory symptoms, particularly those associated with the common
these agents is underestimated. For these reasons, patients should
cold, have been conflicting. Although zinc gels and sprays are
always be questioned specifically about the use of alternative
popular OTC products, they have been shown to be ineffective

therapies during the patient interview. Although some alterna-
in a double-blind, placebo-controlled clinical trial142 and have
tive approaches have been deemed to be safe, efficacy for many
been associated in zinc-induced anosmia syndrome, particularly
modalities has not been clearly established.23,40 In addition, some
when the products are sniffed deeply.143 Some products have been
complementary therapies have been associated with side effects
removed from the market because of this problem.
and potential drug interactions.128–130 Because of C.L’s reluc-
Some studies have shown that patients with allergic rhinitis
tance to use medications, other strategies are appropriate to
who received homeopathic dilutions of allergens had significantly
consider to help her manage her rhinitis symptoms.
better nasal air flow than those in the placebo group, but overall
no difference was seen in subjective measurement on a visual ana-
LIFESTYLE CHANGES log scale.144 Further investigation is needed before homeopathy
Some reports have indicated that patients with allergic rhinitis can be recommended for allergic rhinitis.
may benefit from hydration and a diet low in sodium, omega-6 Although a variety of alternative remedies are widely avail-
fatty acids, and transfatty acids, but high in omega-3 fatty acids able and used frequently in self-treatment, based on evaluation
(e.g., fish, almonds, walnuts, pumpkin, and flax seeds), and at of these data, there is no firm recommendation for C.L. regard-
least five servings of fruits and vegetables per day.131 These rec- ing the use of alternative therapies in allergic rhinitis.40,130 C.L.
ommendations are not without merit, because they may be ben- should be advised to consult with the specific regulating agency
eficial for the population at large, but insufficient evidence exists that governs her sporting activities (e.g., the World Anti-Doping
to support specific value for allergic rhinitis symptoms. Agency for Olympic events) to gain a clear understanding of
medicines that are banned in all cases as compared to those that
PHYSICAL TECHNIQUES may be used with medical exemptions or used outside of the
For the motivated patient, mind–body interventions, such as competitive window. This may allow her to use many conven-
yoga, hypnosis, and biofeedback-assisted relaxation and breath- tional treatments (e.g., intransal steroids) with confidence. Saline
ing exercises, are beneficial for stress reduction in general which irrigation would also be a safe, noncontroversial option that may
may improve the quality of life associated with rhinitis symp- offer some efficacy.
toms and treatment.128 Acupuncture has been shown to have an
attributive effect in inflammatory diseases such as rhinitis; how-
ever, data are not sufficient to recommend this therapy at this Immunotherapy
time.132 EFFICACY
Menthol-delivered rubs have been shown to have an amelio-
rating effect on nasal congestion; however, the effects are short- CASE 25-6
lived.133 Other forms of aromatherapy suggested to relieve nasal
QUESTION 1: R.C. is a 25-year-old schoolteacher who has
congestion include massaging the essential oils of lavender and
experienced allergic symptoms since childhood, but noticed
niaouli around the sinuses, or inhaling eucalyptus and pepper-
a worsening after she graduated from college and moved
mint oils.134 Data are also lacking about the efficacy of these
to a new area of the country. Although she has mild symp-
treatments.
toms year-round, she has severe exacerbations during April
Phototherapy for allergic rhinitis has been investigated with
through June and August through October each year. Dur-
positive results135 but simpler methods are needed for this to
ing these periods, she feels that exposure to cut grass
be useful outside of the research arena.23 Saline nasal irrigation
and weeds provoke profound nasal symptoms. She also
(e.g., neti pot) is simple, inexpensive and has been shown to have
notes that when she spends more time outdoors in spring
some efficacy.23,61
and early fall, her regular therapy, fluticasone nasal spray
(2 sprays per nostril once daily), is less effective. She has
HERBAL MEDICINES added loratadine (10 mg daily) during this time, but is
It has been suggested that herbs that support improved immune frustrated by having to take so many medications while
function could also help to ease symptoms of allergy.136 With this continuing to experience symptoms. R.C. asks your opin-
in mind, echinacea has become one of the top-selling herbal prod- ion about allergy shots, remarking that she started them as
ucts in the United States. Echinacea, however, is closely related to
638 pollinate at about the same time each year: trees in the spring,
a child with some relief, but moved after a year and never
grasses from early to midsummer, and weeds from late summer
resumed treatment. Is allergen immunotherapy effective for
into fall before the first killing frost. The onset and potency of
reducing symptoms of allergic rhinitis?
the pollen season varies with geographic location and weather,
Allergen-specific immunotherapy has long-term efficacy, particularly with respect to temperature and moisture. Season-
induces clinical and immunologic tolerance, and may prevent ality can be misleading, however, because settled pollen particles
progression of allergic disease.145,146 This process usually involves from a previous season may be resuspended in the air following
subcutaneous injection (sometimes called “allergy shots”) of the spring snow melt or periods of heavy winds.
dilute solutions of allergen extracts to increase tolerance to aller- Mold spores also are common airborne allergens. The out-
gens so that the threshold for symptoms is increased (i.e., subse- door molds release their spores from early spring through late
quent exposure elicits no or mild symptoms). fall. Within this long season, spore counts increase and decrease,
Immunotherapy administered via SIT has been used empiri- depending on the presence of local flora on which these molds
cally since the early 1900s, and its efficacy has been documented in grow (e.g., grain and other crops, forests, and orchards). Some
many controlled trials.147 A meta-analysis of 51 published studies perennial allergens (e.g., house dust mites, insect and animal
involving 2,871 patients concluded that SIT is effective in the treat- dander, and some indoor molds) occur consistently across all
ment of allergic rhinitis.54 In addition, studies of immunotherapy geographic distributions. In each case, skin test results must be
Section 3
for allergic rhinitis in children suggest that immunotherapy may correlated with the patient’s clinical history.145
prevent the onset of asthma.148,149 Taken together, these studies R.C.’s perennial symptoms with seasonal exacerbations indi-
show that SIT should be considered a supplement to drug ther- cate sensitivity to the common perennial allergens with a particu-
apy in specific patients and possibly be used earlier in the course lar sensitivity to seasonal allergens such as tree, grass, and weed
of allergic disease to achieve maximal benefit.2 pollen, but these subjective relationships should be confirmed
with skin testing.
Pulmonary Disorders
An alternative to skin testing is the radioallergosorbent test

ALLERGEN TESTING
(RAST), in which the patient’s serum is tested for allergen-specific
IgE antibodies. However, this test is less sensitive and more expen-
CASE 25-6, QUESTION 2: How can the clinician determine
sive than skin testing.151 It is indicated only in selected clinical
R.C.’s specific sensitivities?
situations: when a patient consistently reacts positively to the neg-
ative control skin test (dermatographism), when antihistamine
Skin testing using the modified prick test method or a prick- therapy cannot be discontinued, or when the patient has exten-
puncture method is used to confirm the diagnosis of allergic sive atopic dermatitis or other skin lesions. Blood eosinophil
rhinitis and to determine specific allergen sensitivities. Skin test- counts and total serum IgE antibody measurements are neither
ing is a highly sensitive and a relatively inexpensive objective sensitive nor sufficiently specific to be useful in the diagnosis of
measurement of allergen sensitivity. Small quantities of aller- allergic rhinitis.1
gen are introduced into the skin by pricking or puncturing the
skin in the immediate presence of the diluted allergen extract. CASE 25-6, QUESTION 3: R.C. is currently using medica-
Fifteen to 35 tests are placed on the upper portion of the back or tions (fluticasone nasal spray and loratadine) for her symp-
the palmar surface of the forearms. A positive skin test produces a toms. Should these be discontinued before skin testing?
wheal and flare at the site within 15 to 30 minutes of application.
An experienced clinician, usually an allergist, should conduct skin Antihistamines blunt the wheal-and-flare reaction by blocking
testing using high-quality allergen extracts and should interpret the effects of histamine on capillaries. Different antihistamines
the results.150 vary in the extent to which they can inhibit wheal formation and
The allergens tested vary with geographic location, empha- in the duration of the inhibitory effect (Table 25-7). Depending
sizing the most common offending plant species that generate on the agent selected, antihistamines must be discontinued from
airborne particles. Pollen, the primary particle, is produced by 24 hours to 10 days before skin testing, and even then considerable
trees, grasses, and weeds. Each of these plant groups generally interpatient variability exists in blocking effects.152,153 For best
TA B L E 2 5 - 7
Effects of Antihistamines on Allergen Skin Tests1,23,109,147,149,150,151,153,154
Drug Extent of Suppressiona Half-Life (hours)b Duration of Suppression (days)
Azelastine (intranasal) +/– 22 0

Brompheniramine + 24.9 1–4
Cetirizine +++ 7.4–11 (7) 3–10
Chlorpheniramine + 24.4 (11) 1–4
Clemastine ++ 21.3 1–10
Cyproheptadine +/– 16 1–4
Desloratadine +/++ 27 (27) 3–10
Diphenhydramine +/– 4–9 1–4
Fexofenadine ++ 14 (18) 3–10
Hydroxyzine ++ 20 (7.1) 1–10
Loratadine +/++ 11–24 (3.1) 3–10
Promethazine + 12 1–4
a
+++, extensive; ++ moderate; +, mild; +/–, minimal to none.
b
Parenthetical numbers indicate half-life in children.
Adapted with permission from Facts & Comparisons eAnswers. http://online.factsandcomparisons.com/index.aspx?. Accessed
December 15, 2010.
After identifying the offending allergens via skin testing, sub- 639
TA B L E 2 5 - 8
General Recommendations for Discontinuation of cutaneous immunotherapy is generally administered in two
Antihistamines Before Allergen Skin Testing phases. During the build-up phase, increasing doses of allergen
are given once or twice a week until a predetermined target or
1. Remind patient that allergic symptoms may return during the maintenance dose is achieved. This usually takes 3 to 4 months
antihistaminefree period, but that reliable skin tests cannot be (e.g., 16–18 injections). Once this maintenance dose is reached,
performed in a patient taking antihistamines.
shots are usually administered every 2 to 3 weeks for the
2. Discontinue any short-acting antihistamine (i.e., those in Table 25-7
with a duration of suppression ≤4 days) 4 days before skin testing.
ensuing several years of treatment. Clinical improvement with
3. Discontinue longer-acting antihistamines (i.e., those in Table 25-7 immunotherapy usually occurs in the first year. In a small percent-
with a duration of suppression >4 days) at an interval appropriate age of patients, there is no improvement and immunotherapy is
to their duration of effect (e.g., hydroxyzine should be discontinued discontinued. If symptoms are reduced, however, injections are
10 days before skin testing). usually continued for 4 to 5 years of maintenance therapy.145
4. Before applying the full battery of skin tests, apply histamine Although immunotherapy can lead to long-term remission
(positive) control and glycerinated diluent (negative) control tests. of symptoms, one drawback is the lengthy treatment period.
Application of a 1 mg/mL histamine base equivalent should yield Preliminary data involving a 2-year study of 19 patients aller-
wheal-and-flare diameters of 2–7 mm and 4.5–32.5 mm, respectively,
Chapter 25
gic to ragweed who underwent one allergy shot per week for
to be considered a normal histamine reaction. A normal cutaneous
6 weeks before the ragweed season suggest that significant relief
reaction to histamine control suggests that accurate skin testing can
be performed.
can be obtained from a shorter term of treatment.156 SIT alters
the natural course of disease and evidence suggests that efficacy
Source: Bousquet J et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 persists long after therapy ends.157
update (in collaboration with the World Health Organization, GA[2]LEN and
AllerGen). Allergy. 2008;63(Suppl 86):8.
RISKS

results, R.C.’s loratadine should be discontinued 10 days before CASE 25-6, QUESTION 6: R.C. is interested in proceeding
her skin testing. but concerned about the time commitment associated with
Other allergy medications, including cromolyn and nasal the office visits required for immunotherapy. She inquires
corticosteroids, have no effect on skin tests. Likewise, most whether it would be safe to have her boyfriend (who is
asthma medications, including leukotriene modifiers, inhaled studying to be an accupuncturist) administer the injections.
β 2 -agonists, cromolyn, theophylline, and inhaled and short- How should you respond to R.C.’s query?
course systemic (burst) corticosteroids have no effect on skin
tests.23,150,154 R.C. can continue the use of fluticasone nasal spray Local adverse reactions (i.e., redness, swelling) to
while she waits to be skin tested. immunotherapy can be common, but the risk of severe
Other medications can interfere with skin testing by blocking reaction (i.e., anaphylaxis) is low. A classification system for
the cutaneous wheal and flare reactions or increasing skin reactiv- grading systemic reactions has been proposed, which categorizes
ity. These include: oral β 2 -agonists, long-term systemic corticos- these into immediate (occurring within 30 minutes) and late
teroids, and high-potency topical corticosteroids (applied to the (occurring after 30 minutes).145 In addition, pretreatment with
skin testing sites), tricyclic antidepressants, phenothiazine-type antihistamines during immunotherapy induction has been
antipsychotics and antiemetics.23,150 Depending on the indica- shown to reduce the incidence of such adverse events. In view of
tion for drug therapy, however, discontinuation of these drugs the occasional occurrence of systemic side effects, it is important
before skin testing is not always advisable. Recommendations that R.C.’s injections be administered by personnel who are fully
for discontinuing antihistamines before allergen skin testing are trained and experienced in the early recognition and treatment
listed in Table 25-8. of such reactions.54
CASE 25-6, QUESTION 4: Is R.C. a candidate for immuno-

therapy injections? DRUG-INDUCED NASAL
CONGESTION: RHINITIS
Immunotherapy via SCIT is indicated for patients with evi- MEDICAMENTOSA
dence of sustained, clinically relevant IgE-mediated disease and
a limited spectrum of allergies (i.e., one or two clinically relevant
allergens) and in whom pharmacotherapy and avoidance mea- CASE 25-7
sures are insufficient.155 Further considerations are the patient’s QUESTION 1: L.K. is a 27-year-old man who has suffered
attitude to available treatment modalities, costs of treatment, and intermittent symptoms of allergic rhinitis for several years.
the quality of allergen vaccines available for treatment.145 In the He reports that his symptoms are most bothersome in the
case of R.C., she has year-round symptoms with seasonal exac- spring and associated with blooming of various grasses.
erbations, she has not experienced symptom relief when using During these periods, he has typically used oral chlor-
appropriate therapies, and she is motivated to try immunother- pheniramine (4 mg every 6 hours), which relieves his symp-
apy. In addition, a previous trial in childhood was beneficial. For toms but makes him drowsy at work. This season, he reports
these reasons, skin testing and a trial of immunotherapy with that his symptoms have been more severe, with sneezing,
specific allergens are reasonable. runny nose, and extreme itching in his nose. He tried oral
loratadine (10 mg daily) with partial relief of symptoms. He
LENGTH OF THERAPY also states that nasal congestion has been more of an issue
with this episode and to address this he has used xylometa-
CASE 25-6, QUESTION 5: If R.C. decides to proceed with zoline nasal spray (0.1% solution) for the past 3 weeks.
immunotherapy, how long should her therapy continue and Despite increasing the use of nasal spray from two sprays
how long will the effects last? per nostril twice daily to three sprays per nostril four times
640 Topical decongestants are indicated for short-term use. When

a day, however, he reports that the congestion is getting
used acutely, sympathomimetic (adrenergic) agents stimulate
worse. What might be an explanation for L.K.’s increasing
α-adrenergic receptors on blood vessels, resulting in vasocon-
need for nasal decongestant?
striction (which serves to relieve nasal congestion associated with
Selected medications and some drugs of abuse can cause nasal edematous, congested blood vessels). But when these agents
congestion through a variety of mechanisms.10 Table 25-9 lists are used chronically, this can result in (a) overstimulation of
agents associated with drug-induced nasal symptoms. In this case, α-adrenergic receptors leading to tachyphylaxis, (b) stimulation
L.K. is likely experiencing rebound nasal congestion as a result of β-adrenergic receptors causing vasodilation, and (c) decreased
of a specific form of drug-induced rhinitis called rhinitis medica- production of endogenous norepinephrine through a negative
mentosa (RM). feedback mechanism.158–160 RM has also been associated with the
presence of BKC as a preservative in some nasal products.159,160
When RM occurs, many patients will attempt to treat the
rebound congestion by using the offending topical decongestant
For a visual of rhinitis medicamentosa, go to more frequently and/or at increased doses, creating a vicious
http://thepoint.lww.com/AT10e. cycle. L.K.’s description of using the xylometazoline for an
extended period of time (3 weeks), more frequently (from twice
Section 3
daily to four times daily) and at high doses (from two sprays per
nostril to three sprays per nostril) support the diagnosis of RM.
TA B L E 2 5 - 9
Drugs Capable of Causing Nasal Symptoms Strategies for Resolution
Pulmonary Disorders
Local Inflammatory Mechanisms

CASE 25-7, QUESTION 2: How should L.K.’s rhinitis medica-
Aspirin mentosa be managed?
Nonsteroidal anti-inflammatory drugs
Neurogenic Mechanisms The best strategy for managing RM is prevention, by lim-
iting the duration of topical decongestant use to fewer than
Centrally Acting Sympatholytics 5 days. When these medications must be used for longer than
Clonidine
Methyldopa
5 days, the patient should be advised to take a 1- to 2-day holiday
Reserpine during which the topical agent is not used before resuming treat-
ment. Patients should be counseled about this whenever topical
Peripherally Acting Sympatholytics
Prazosin
decongestants are recommended or purchased. When preventa-
Guanethidine tive strategies fail, several options for treatment exist.158
Doxazosin The first step is to discontinue the offending topical decon-
Phentolamine gestant and, if necessary, substitute another therapy that will
Vasodilators not cause nasal symptoms.10 Because abrupt discontinuation of
Sildenafil an agent that has been used long-term may cause the patient
Tadalafil considerable discomfort for up to 7 days, it is recommended
Vardenafil to add an intranasal corticosteroid or a short course of an oral
Idiopathic Mechanisms decongestant (e.g., pseudoephedrine 120 mg twice daily for one
week).10,159 Saline nose drops or spray can be added to moistur-
Antihypertensives ize and alleviate any nasal irritation. In refractory cases, a short
Amiloride course of systemic corticosteroids may be necessary.10 Note that
Angiotensin-converting enzyme inhibitor class if the patient has used the topical decongestant continuously for
β-Blocker class many months or even years, the nasal mucosa may have under-
Calcium-channel blockers
gone irreversible changes.
Chlorothiazide
Hydralazine An alternative to abrupt cessation of the topical decongestant
Hydrochlorothiazide is to recommend that the patient discontinue use of the topical
decongestant in a stepwise manner (i.e., one nostril at a time). For
Hormonal Products
Exogenous estrogens example, have the patient substitute normal saline nasal spray for
Oral contraceptives decongestant spray in the right nostril every other dose. Later, use
saline twice for each decongestant dose. Eventually, the decon-
Neuropsychotherapeutic Agents
Alprazolam gestant is discontinued totally in the right nostril and saline is
Amitriptyline substituted. Repeat the process for the left nostril. Saline can be
Chlordiazepoxide used as often as needed throughout this process and after the
Chlorpromazine topical decongestant is completely withdrawn. This method has
Gabapentin been suggested in several reviews, although no prospective trial
Risperidone results are available to support it.10,160 Thus, this method should
Perphenazine be combined with careful patient education, support, and fre-
Thioridazine quent follow-up.
Source: Dykewicz MS et al. Diagnosis and management of rhinitis: complete In the case of L.K., because he not only needs treatment for
guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and the RM but also for the original symptoms (sneezing, runny and
Immunology. American Academy of Allergy, Asthma, and Immunology. Ann itchy nose) that occur seasonally, a reasonable option would be
Allergy Asthma Immunol. 1998;81(5 Pt 2):478; Ramey JT et al. Rhinitis to discontinue the xylometazoline, and begin treatment with
medicamentosa. J Investig Allergol Clin Immunol. 2006;16:148; Varghese M et al.
Drug-induced rhinitis. Clin Exper Allergy. 2010;40:381.
mometasone nasal spray (2 sprays in each nostril daily) with as
needed saline nasal spray.
IDIOPATHIC RHINITIS Mast cells may be present in the nasal smear; however, by def- 641
inition, nasal eosinophilia is not present. Skin tests are usually
negative.8
Diagnosis M.S.’s symptoms of bothersome watery rhinorrhea, nasal
congestion, and headache without itching or sneezing are typ-
CASE 25-8 ical. His complaint of worsening symptoms with exposure to
QUESTION 1: M.S., a 29-year-old man, complains of profuse noxious inhalants, cold air, and hot beverages supports the diag-
watery rhinorrhea that has been a chronic and progressively nosis of idiopathic rhinitis. The nasal smear, which notably lacks
worsening problem for the past 5 years. He also experiences large numbers of eosinophils, initially differentiates this disease
some nasal congestion with the rhinorrhea, but denies nasal from NARES.
itching or sneezing. Although the symptoms tend to remit
and exacerbate, they do not occur in any definable sea-
sonal pattern. His symptoms are worsened by exposure to Choice of Therapeutic Agent
tobacco smoke, strong fumes such as paint or ammonia,
and cold air. These often are associated with headaches. CASE 25-8, QUESTION 2: M.S. asks what causes idiopathic
Chapter 25
M.S. has no other medical problems and no family history rhinitis and what can be done to alleviate his symptoms.
of allergies. He does not smoke and rarely drinks alcohol. His What nonpharmacologic and pharmacologic treatments are
only medication, mometasone (50 mcg/spray, two sprays in appropriate to manage M.S.’s idiopathic rhinitis?
each nostril once daily as needed), only partially relieves the
symptoms. M.S. sniffs and blows his nose several times dur- Nasal symptoms in patients with idiopathic rhinitis have been
ing the medical history taking. Physical examination reveals shown to be influenced by psychological factors. Some therapeu-
tic benefit may be realized by establishing an ongoing, trusting

a mildly erythematous nasal mucosa and a minimally ede-
matous inferior turbinate. Copious nasal discharge is clear relationship between the health care provider and the patient.
and watery and air movement through the nose is rela- This should include a thorough explanation of the disease state
tively good. There is no sinus tenderness. The remainder and the realistic outcomes of therapy for most patients. Psy-
of his physical examination is normal. Microscopic examina- chotherapy is helpful in some cases. In addition, patients should
tion of a nasal smear demonstrates only a few neutrophils be instructed to avoid as many aggravating factors as possible,
and no eosinophils. What information about M.S. supports such as smoking, exposure to smoke or other irritants, and very
the diagnosis of idiopathic rhinitis? cold or very hot beverages. Saline irrigation is valuable as a gen-
eral soothing and moisturizing treatment. Exercise may be par-
Idiopathic rhinitis is a diagnosis of exclusion encompassing ticularly helpful for patients with idiopathic rhinitis because it
those patients with nasal mucous membrane inflammation with increases sympathetic tone.8
no proved immunologic, microbiologic, pharmacologic, hor- Pharmacotherapy for idiopathic rhinitis should be directed
monal, or occupational cause.8,12 The syndrome is sometimes toward the predominant symptoms of the individual patient.8,12
called “vasomotor rhinitis”, but using this terminology can be For patients with predominant nasal congestion and minimal
confusing because the cause of the symptoms has still not been rhinorrhea, the intranasal corticosteroids may be helpful. The
clearly identified.1,4,161 The prevailing theory holds that an imbal- addition of oral decongestants may improve nasal obstruction in
ance in the autonomic nervous system exists in which the cholin- some patients with idiopathic rhinitis, but objective measures of
ergic parasympathetic activity exceeds the α-adrenergic activity improvement are affected variably and side effects can be prob-
in the nasal mucosa.8 Theoretically, this is the reason that stimuli lematic.
that normally increase parasympathetic activity in the nose, such M.S.’s case is typical of the often frustrating course in treat-
as cold air and inhaled irritants, aggravate symptoms.161 Still, sub- ing idiopathic rhinitis.8,12 Commonly, multiple therapeutic plans
stantial debate exists over whether idiopathic rhinitis represents fail, and M.S. has responded incompletely and unsatisfactorily
a localized allergic response in the absence of systemic atopic to intranasal corticosteroids. There is some older evidence sug-
markers162 as well as the evidence for inflammatory pathophys- gesting topical nasal capsaicin may be effective, but this option
iology in the disease.163 has not garnered widespread support.12 Surgical treatments have
The symptoms of idiopathic rhinitis are variable. Most been attempted for patients in whom medical management fails,
patients experience perennial nasal obstruction accompanied by although recent clinical evidence is limited primarily to case
profuse, watery nasal and postnasal discharge. Many patients reports.164
complain of nasal obstruction as the primary symptom, whereas In patients such as M.S., who have rhinorrhea as their pre-
for others it is rhinorrhea. Sneezing is usually not a prominent dominant symptom, FGAs may be helpful because of their anti-
symptom and nasal itching is uncommon.8,12 Headache may cholinergic drying effects. In general, however, FGAs are less
occur and usually is frontal or localized over the bridge of the effective in the treatment of idiopathic rhinitis than for allergic
nose. In patients with chronic nasal obstruction, chronic sinusitis rhinitis, and patients may have difficulty adhering to therapy
and significant morbidity can result. In contrast to allergic rhini- because of side effects.165 Of note, the nonsedating SGAs have
tis, the onset of symptoms in patients with idiopathic rhinitis little value in idiopathic rhinitis because they lack anticholinergic
usually occurs in adulthood.4 properties. Another option for decreasing nasal secretions is nasal
Patients report worsening of their symptoms when exposed ipratropium bromide, a topically active congener of atropine.8
to nonspecific irritants, including tobacco smoke, industrial pol- Ipratropium bromide’s quaternary ammonium structure makes
lutants, strong odors and perfumes, newsprint, and chemical it lipophobic; therefore, it is absorbed poorly from the nasal
fumes; cold, dry air; changes in humidity; and ingestion of very mucosa and gastrointestinal tract and does not cross the blood–
cold or very hot beverages or spicy foods. Most patients have no brain barrier. It significantly reduces rhinorrhea (as measured by
history or evidence of atopy.4 the number of nose-blowing episodes or daily number of tissues
The appearance of the nasal mucosa also is variable. The used), but has no effect on sneezing or nasal obstruction.165
turbinates are usually erythematous and, during an exacerbation, The recommended dose of ipratropium bromide is two sprays
considerable quantities of nasal secretions usually are present. of the 0.03% nasal solution (42 mcg) in each nostril two to
642 three times per day, but dosage individualization (from 168 to oral antihistamine), suggest that D.W. may be exhibiting a mixed
1,600 mcg/day) is often required to achieve symptomatic relief.110 allergic–nonallergic rhinitis presentation.
A 0.06% nasal formulation is also available, but its use is typically
reserved for short-term treatment of common cold symptoms. CASE 25-9, QUESTION 2: How should D.W.’s mixed rhinitis
Table 25-5 includes information about intranasal ipratropium be treated? How is this different from the management of
dosing and availability. allergic rhinitis?
In general, intranasal ipratropium bromide is well tolerated,
although its use is associated with dose-related side effects.1 The high prevalence and importance of nonallergic causes
The most common side effects are nasal dryness, nasal burning, of rhinitis has been recognized in recent years. A recent study
bloody nasal discharge (epistaxis), dry or sore throat, and dry suggests that knowledge and opinions about the prevalence
mouth.110 Theoretically, elderly men with BPH may experience and relative importance of nonallergic rhinitis varies among
difficulty in urinating, but the risk is low because of negligible sys- physicians.166 Among those who had an allergy specialist in
temic absorption. No significant adverse cardiovascular or blood their practice, there was a greater awareness that treatment
pressure effects have been observed. approaches might vary between allergic and nonallergic trig-
In the case of M.S., because he has been comfortable using gers as compared to physicians who did not also have an allergist
an intranasal product (mometasone) in the past, it would be resource.
Section 3
reasonable to initiate a trial of ipratropium bromide 0.03% two The important point about nonallergic triggers, or new onset
sprays in each nostril three times daily. Once the rhinorrhea is triggers such as those present in D.W., is that oral anthistamines
controlled, he should be advised to reduce the dosage to twice and other therapies directed primarily at allergic responses may
daily. Nasal saline can also be used as needed if excessive dryness be ineffective in relieving symptoms. Good clinical evidence sug-
occurs during dosage optimization. gests that intranasal steroids are an effective option, and some
Pulmonary Disorders
limited evidence suggests that these patients may benefit from

intranasal antihistamine therapy.23 Avoidance or minimization
of exposure to the triggers is also an important strategy. For
MIXED ALLERGIC–NONALLERGIC D.W., a 4-week therapeutic trial of a BKC-free intranasal steroid
RHINITIS (e.g., ciclesonide 2 sprays in each nostril once daily) with coun-
seling about appropriate administration is warranted. Intransal
steroid therapy may improve the response to both allergic and
CASE 25-9
nonallergic triggers.
QUESTION 1: D.W. is a 56-year-old woman with a long-
standing history of allergic rhinitis related to triggers with
seasonal ragweed. Her primary symptoms are rhinorrhea SUMMARY
and sneezing, which she has relieved by using various oral
anthistamines (clemastine 1.34 mg daily and, more recently, The initial management of rhinitis should be directed at pre-
cetirizine 10 mg daily) which she takes several weeks each venting symptoms, which can be achieved through a variety
autumn. Recently (during winter), she has experienced new of pharmacologic and nonpharmacologic methods. Treatment
rhinitis symptoms associated with the weather and various plans for allergic rhinitis, the most common subtype, should
odors that were not a problem in the past, specifically, per- include patient education, allergen or irritant avoidance, and the
fumes and food spices. When she encounters these, she appropriate medications, including immunotherapy, if indicated.
exhibits watery rhinorrhea and profound congestion. She Control of the disease process is the expected outcome, so that
has tried a combination of cetirizine with pseudoephedrine patients are able to live their lives comfortably without symp-
for these episodes, but reports that it “doesn’t seem to toms or impairment. Customizing therapy for each patient based
help much and it makes me feel jumpy.” Are D.W.’s new on symptom history and response to treatments is important.
symptoms the result of breakthrough (uncontrolled) aller- Rhinitis can be controlled and effective management can greatly
gic rhinitis or do they represent something new? improve the quality of patients’ lives.
Distinguishing between allergic rhinitis and nonallergic rhini-

tis may be difficult in clinical practice, and the presence of ACKNOWLEDGMENTS
concomitant allergic and nonallergic rhinitis in some patients
confounds the diagnosis further.33,34 A careful history should The authors acknowledge the assistance of Margrit B. Rosado-
be gathered from the patient and an assessment made of the Duroisin and Caroline A.R. Lindsay in the preparation of this
temporal nature of the symptoms and various exposures. The chapter.
Clinical Presentation and Assessment of Rhinitis section in this
chapter includes diagnostic criteria that can be used to distin-
guish between allergic and nonallergic causes of rhinitis. When KEY REFERENCES AND WEBSITES
a patient presents with characteristics suggestive of both types,
especially in the case of new symptoms or triggers despite opti- A full list of references for this chapter can be found at
mized therapy, mixed rhinitis should be considered. http://thepoint.lww.com/AT10e. Below are the key references
Although D.W. has a confirmed history of ragweed pollen for this chapter, with the corresponding reference number in this
sensitivity (supporting the allergic rhinitis diagnosis), the timing chapter found in parentheses after the reference.
of the more recent symptoms and the new triggers (i.e., odors)
suggest that she may have developed sensitivities of a nonallergic Key References
(non–IgE-based) nature. The patient’s age also is consistent with
the development of vasomotor rhinitis (nonallergic) which can Bousquet J et al. Allergic rhinitis and its impact on asthma (ARIA)
present around the time of menopause. This, combined with 2008 update (in collaboration with the World Health Organiza-
the lack of efficacy from a previously successful therapy (i.e., tion, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8. (23)

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P1: Trim: 8.375in × 10.875in Top: 0.373in Gutter: 0.

Acute and Chronic Rhinitis 25

DEFINITION ing, congestion, and postnasal drainage (postnasal drip). These

CAUSES AND CLASSIFICATIONS Chronic rhinitis can be classified as allergic, nonallergic, or

Intermittenta Disease Persistentb Disease

Acute and Chronic Rhinitis

Superior Turbinate Frontal Sinus

FIGURE 25-3 Lateral view of the head with nasal

parents.24 Environmental exposures, particularly early in life, are

Allergen Processed Allergen

FIGURE 25-4 Pathophysiology of allergic rhinitis.

Acute and Chronic Rhinitis

2. What color are the nasal secretions?

3. When did the symptoms first appear?

4. Were the symptoms associated with a change in state/environment?

5. How often do the symptoms occur?

6. For how long has this symptom pattern persisted?

7. Which factors or conditions precipitate symptoms?

8. Which specific activities precipitate symptoms?

9. Are other members of the family experiencing similar symptoms?

10. Which of the following are prevalent in the household?

14. What is the patient's occupation?

15. What are the patient's typical leisure activities?

FIGURE 25-5 Patient history interview.

Acute and Chronic Rhinitis

Provide education and allergen/irritant avoidance strategies

Not in preferred order In preferred order

Consider specific immunotherapy

for minimizing exposure to known allergens (e.g., pollens, house

lutants) should also be recommended, as it is anticipated that this

Rhinorrhea Nasal Pruritus Sneezing Nasal Congestion Eye Symptoms Onset

INTRANASAL CORTICOSTEROID AGENTS IMMUNOTHERAPY 627

Acute and Chronic Rhinitis

has been well controlled with hydrochlorothiazide 25 mg

Acute and Chronic Rhinitis

First Generation Sedative Antiemetic Anticholinergic

Decongestant Therapy Ocular Therapies

Acute and Chronic Rhinitis

Generic Name Available Dosage

4–6 times daily

Acute and Chronic Rhinitis

be beneficial in relieving cough associated with postnasal drip in

Generic Name Available Dosage

Acute and Chronic Rhinitis

Combination Therapy nence, and nocturia.123

is based on the theoretic benefit of additive or synergistic reac-

sunflowers, daisies, and ragweed—all members of the Composi- 637

Acute and Chronic Rhinitis

An alternative to skin testing is the radioallergosorbent test

Drug Extent of Suppressiona Half-Life (hours)b Duration of Suppression (days)

Azelastine (intranasal) +/– 22 0

Acute and Chronic Rhinitis

CASE 25-6, QUESTION 4: Is R.C. a candidate for immuno-

640 Topical decongestants are indicated for short-term use. When

Local Inflammatory Mechanisms

Acute and Chronic Rhinitis

limited evidence suggests that these patients may benefit from