Otolaryngology - Head and Neck Surgery-2015 - Rhinitis Allergic

561600
ryngologyHead and Neck SurgerySeidman et al

2014 The Author(s) 2010
OTOXXX10.1177/0194599814561600Otola
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Guideline
Clinical Practice Guideline: Allergic Rhinitis
Otolaryngology
Head and Neck Surgery
2015, V
ol. 152(1S) S1S43
American Academy of
OtolaryngologyHead and Neck
Surgery Foundation 2014
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DOI: 10.1177/0194599814561600
http://otojournal.org
Michael D. Seidman, MD1, Richard K. Gurgel, MD2, Sandra Y. Lin, MD3,

Seth R. Schwartz, MD, MPH4, Fuad M. Baroody, MD5,
James R. Bonner, MD6, Douglas E. Dawson, MD7, Mark S. Dykewicz, MD8,
Jesse M. Hackell, MD9, Joseph K. Han, MD10,
Stacey L. Ishman, MD, MPH11, Helene J. Krouse, PhD, ANP-BC, CORLN12,
Sonya Malekzadeh, MD13, James (Whit) W. Mims, MD14,
Folashade S. Omole, MD15, William D. Reddy, LAc, DiplAc16,
Dana V. Wallace, MD17, Sandra A. Walsh18,
Barbara E. Warren, PsyD, MEd18, Meghan N. Wilson, MD19,
and Lorraine C. Nnacheta, MPH20
Sponsorships or competing interests that may be relevant to content are

disclosed at the end of this article.
guideline are not intended to represent the standard of care for

patient management, nor are the recommendations intended
to limit treatment or care provided to individual patients.
Abstract
Action Statements. The development group made a strong recommendation that clinicians recommend intranasal steroids
for patients with a clinical diagnosis of AR whose symptoms
affect their quality of life. The development group also made
a strong recommendation that clinicians recommend oral
second-generation/less sedating antihistamines for patients
with AR and primary complaints of sneezing and itching. The
panel made the following recommendations: (1) Clinicians
should make the clinical diagnosis of AR when patients present with a history and physical examination consistent with an
allergic cause and 1 or more of the following symptoms: nasal
congestion, runny nose, itchy nose, or sneezing. Findings of AR
consistent with an allergic cause include, but are not limited
to, clear rhinorrhea, nasal congestion, pale discoloration of the
nasal mucosa, and red and watery eyes. (2) Clinicians should
perform and interpret, or refer to a clinician who can perform
and interpret, specific IgE (skin or blood) allergy testing for
patients with a clinical diagnosis of AR who do not respond
to empiric treatment, or when the diagnosis is uncertain, or
when knowledge of the specific causative allergen is needed
to target therapy. (3) Clinicians should assess patients with
a clinical diagnosis of AR for, and document in the medical
record, the presence of associated conditions such as asthma,
atopic dermatitis, sleep-disordered breathing, conjunctivitis,
rhinosinusitis, and otitis media. (4) Clinicians should offer, or
refer to a clinician who can offer, immunotherapy (sublingual
or subcutaneous) for patients with AR who have inadequate
response to symptoms with pharmacologic therapy with or
without environmental controls.
Objective. Allergic rhinitis (AR) is one of the most common

diseases affecting adults. It is the most common chronic disease in children in the United States today and the fifth most
common chronic disease in the United States overall. AR is
estimated to affect nearly 1 in every 6 Americans and generates $2 to $5 billion in direct health expenditures annually. It
can impair quality of life and, through loss of work and school
attendance, is responsible for as much as $2 to $4 billion in
lost productivity annually. Not surprisingly, myriad diagnostic tests and treatments are used in managing this disorder,
yet there is considerable variation in their use. This clinical
practice guideline was undertaken to optimize the care of
patients with AR by addressing quality improvement opportunities through an evaluation of the available evidence and an
assessment of the harm-benefit balance of various diagnostic
and management options.
Purpose. The primary purpose of this guideline is to address
quality improvement opportunities for all clinicians, in any setting, who are likely to manage patients with AR as well as to
optimize patient care, promote effective diagnosis and therapy, and reduce harmful or unnecessary variations in care. The
guideline is intended to be applicable for both pediatric and
adult patients with AR. Children under the age of 2 years were
excluded from the clinical practice guideline because rhinitis
in this population may be different than in older patients and
is not informed by the same evidence base. The guideline is
intended to focus on a limited number of quality improvement
opportunities deemed most important by the working group
and is not intended to be a comprehensive reference for diagnosing and managing AR.The recommendations outlined in the
The panel recommended against (1) clinicians routinely performing sinonasal imaging in patients presenting with symptoms
consistent with a diagnosis of AR and (2) clinicians offering
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OtolaryngologyHead and Neck Surgery 152(1S)
oral leukotriene receptor antagonists as primary therapy for

patients with AR.
The panel group made the following options: (1) Clinicians
may advise avoidance of known allergens or may advise environmental controls (ie, removal of pets; the use of air filtration systems, bed covers, and acaricides [chemical agents
formulated to kill dust mites]) in patients with AR who have
identified allergens that correlate with clinical symptoms. (2)
Clinicians may offer intranasal antihistamines for patients with
seasonal, perennial, or episodic AR. (3) Clinicians may offer
combination pharmacologic therapy in patients with AR who
have inadequate response to pharmacologic monotherapy. (4)
Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate reduction in patients with AR with nasal airway
obstruction and enlarged inferior turbinates who have failed
medical management. (5) Clinicians may offer acupuncture, or
refer to a clinician who can offer acupuncture, for patients
with AR who are interested in nonpharmacologic therapy.The
development group provided no recommendation regarding
the use of herbal therapy for patients with AR.
Keywords
allergic rhinitis, allergic rhinitis immunotherapy, surgical management of allergic rhinitis, medical management of allergic
rhinitis, allergic rhinitis and steroid use/antihistamine use/
decongestant use, allergic rhinitis and complementary/alternative/integrative medicine, acupuncture, herbal therapies,
diagnosis of allergic rhinitis, nasal allergies, hay fever, atopic
rhinitis, atrophic rhinitis, pollinosis, catarrh
Received September 18, 2014; revised October 22, 2014; accepted
November 5, 2014.
Introduction
Allergic rhinitis (AR) is one of the most common diseases
affecting adults.1 It is the most common chronic disease in
children in the United States today2 and is the fifth most common chronic disease in the United States overall.3 AR is estimated to affect nearly 1 in every 6 Americans and generates
$2 to $5 billion in direct health expenditures annually.4,5 It can
impair quality of life and, through loss of work and school
attendance, is responsible for as much as $2 to $4 billion in

lost productivity annually.4,5 Not surprisingly, myriad diagnostic tests and treatments are used in managing patients with
this disorder, yet there is considerable variation in their use.
This clinical practice guideline was undertaken to optimize
the care of patients with AR by addressing quality improvement opportunities through an evaluation of the available
evidence and an assessment of the harm-benefit balance of
various diagnostic and management options.
For the purpose of this guideline, AR is defined as an
immunoglobulin E (IgE)mediated inflammatory response of
the nasal mucous membranes after exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or post nasal
drip), nasal congestion, nasal itching, and sneezing. AR can be
seasonal or perennial, with symptoms being intermittent or
persistent. Table 1 summarizes the common terms used for
this guideline.
Defining Allergic Rhinitis

AR is an inflammatory, IgE-mediated disease characterized
by nasal congestion, rhinorrhea (nasal drainage), sneezing,
and/or nasal itching. It can also be defined as inflammation of
the inside lining of the nose that occurs when a person inhales
something he or she is allergic to, such as animal dander or
pollen; examples of the symptoms of AR are sneezing, stuffy
nose, runny nose, post nasal drip, and itchy nose.
AR may be classified by (1) the temporal pattern of exposure
to a triggering allergen, such as seasonal (eg, pollens), perennial/
year-round (eg, dust mites), or episodic (environmental from
exposures not normally encountered in the patients environment,
eg, visiting a home with pets); (2) frequency of symptoms; and
(3) severity of symptoms. Classifying AR in this manner may
assist in choosing the most appropriate treatment strategies for an
individual patient.
In the United States, AR has traditionally been viewed as
either seasonal or perennial, and this is the classification system that the Food and Drug Administration (FDA) uses when
approving new medications for AR. However, it is recognized
that this classification system has limitations, as the length of
the aeroallergen pollen season is dependent on geographic
location and climatic conditions. When the pollen season is
year-round, as in tropical locations, it can be very difficult
based on history to distinguish allergic symptoms provoked
Department of OtolaryngologyHead and Neck Surgery, Henry Ford West Bloomfield Hospital West Bloomfield, Michigan, USA; 2Department of Surgery
OtolaryngologyHead and Neck Surgery University of Utah, Salt Lake City, Utah, USA; 3Johns Hopkins School of Medicine, Department of Otolaryngology
Head and Neck Surgery, Baltimore, Maryland, USA; 4Virginia Mason Medical Center, Seattle, Washington, USA; 5University of Chicago Medical Center,
Department of Otolaryngology, Chicago, Illinois, USA; 6Birmingham VA Medical Center, Birmingham, Alabama, USA; 7Otolaryngology, Private Practice,
Muscatine, Iowa, USA; 8Department of Internal Medicine, St Louis University School of Medicine, St Louis, Missouri, USA; 9Pomona Pediatrics, Pomona, New
York, USA; 10Eastern Virginia Medical School, Norfolk,Virginia, USA; 11Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, USA; 12Wayne State
University, Philadelphia, Pennsylvania, USA; 13Georgetown University Hospital, Washington, DC, USA; 14Wake Forest Baptist Health, Winston Salem, North
Carolina, USA; 15Morehouse School of Medicine, East Point, Georgia, USA; 16Acupuncture and Oriental Medicine (AAAOM), Annandale,Virginia, USA
17
Florida Atlantic University, Boca Raton, Florida and Nova Southeastern University, Davie, Florida, USA; 18Consumers United for Evidence-based Healthcare,
Fredericton, New Brunswick, Canada; 19Louisiana State University School of Medicine, New Orleans, Louisiana, USA; 20Department of Research and Quality,
American Academy of OtolaryngologyHead and Neck Surgery Foundation, Alexandria,Virginia, USA.
Corresponding Author:
Michael D. Seidman, MD, Henry Ford West Bloomfield Hospital, 6777 West Maple Rd, West Bloomfield, MI 48322, USA.
Email: [email protected]
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Seidman et al
Table 1. Abbreviations and Definitions of Common Terms.
Term
Allergic rhinitis (AR)
Seasonal allergic rhinitis (SAR)
Perennial allergic rhinitis (PAR)
Intermittent allergic rhinitis
Persistent allergic rhinitis
Episodic allergic rhinitis
Definition
Disease caused by an IgE-mediated inflammatory response of the nasal mucous membranes after
exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or posterior nasal drainage), nasal
congestion, nasal itching, and sneezing.
Disease caused by an IgE-mediated inflammatory response to seasonal aeroallergens. The length of
seasonal exposure to these allergens is dependent on geographic location and climatic conditions.
Disease caused by an IgE-mediated inflammatory response to year-round environmental aeroallergens.
These may include dust mites, mold, animal allergens, or certain occupational allergens.
Disease caused by an IgE-mediated inflammatory response and characterized by frequency of exposure or
symptoms (<4 days per week or <4 weeks per year).
Disease caused by an IgE-mediated inflammatory response and characterized by persistent symptoms (>4
days per week and >4 weeks per year).
Disease caused by an IgE-mediated inflammatory response that can occur if an individual is in contact with
an exposure that is not normally a part of the individuals environment. (ie, a cat at a friends house).
by exposure to pollen from symptoms caused by exposure to

allergens that are perennial in temperate zones (eg, dust mites).
Mold has been considered to be both a seasonal and a perennial allergen.6 Furthermore, it is recognized that many patients
with AR have perennial AR exacerbated by seasonal pollen
exposure, and many patients are polysensitized so the clinical
implications of seasonal versus perennial are not as clear.6
Classifying a patients symptoms by frequency and severity allows for more appropriate treatment selection. AR symptom frequency has been divided into intermittent (<4 days per
week or <4 weeks per year) and persistent (>4 days per week
and >4 weeks per year).6 However, this classification of symptom frequency has limitations. For example, the patient who
has symptoms 3 days per week year-round would be classified
as intermittent even though she or he would more closely
resemble a persistent patient. It may be advantageous for
the patient and the provider to determine which frequency category is most appropriate and would best guide the treatment
plan. Based on these definitions, it is possible that a patient
may have intermittent symptoms with perennial AR or persistent symptoms with seasonal AR.
AR severity can be classified as being mild (when symptoms are present but are not interfering with quality of life) or
more severe (when symptoms are bad enough to interfere with
quality of life).6,7 Factors that may lead to a more severe classification include exacerbation of coexisting asthma; sleep
disturbance; impairment of daily activities, leisure, and/or
sport; and impairment of school performance or work.
Guideline Purpose
The primary purpose of this guideline is to address quality
improvement opportunities for all clinicians, in any setting,
who are likely to manage patients with AR, as well as to optimize patient care, promote effective diagnosis and therapy,
and reduce harmful or unnecessary variations in care. The
guideline is intended to be applicable for both pediatric and
adult patients with AR. Children under the age of 2 years were
excluded in this clinical practice guideline because rhinitis in
this population may be different than in older patients and is
not informed by the same evidence base.
The guideline is intended to focus on a select number of quality improvement opportunities deemed most important by the
working group and is not intended to be a comprehensive reference for diagnosing and managing AR. The recommendations
outlined in the guideline are not intended be an all-inclusive
guide for patient management, nor are the recommendations
intended to limit treatment or care provided to individual patients.
The guideline is not intended to replace individualized patient
care or clinical judgment. Its goal is to create a multidisciplinary
guideline with a specific set of focused recommendations based
upon an established and transparent process that considers levels
of evidence, harm-benefit balance, and expert consensus to
resolve gaps in evidence.8 These specific recommendations may
then be used to develop performance measures and identify avenues for quality improvement. Table 2 highlights the topics and
issues considered in the development of this guideline.
Healthcare Burden
Incidence and Prevalence
Allergic rhinitis is a worldwide health problem that affects
adults and children. In the United States, AR is the 16th most
common primary diagnosis for outpatient office visits.9 Large
epidemiologic studies consistently show a significantly higher
percentage of the population with rhinitis symptoms than
those with rhinitis symptoms and positive allergy tests.10 In
the 2005-2006 National Health and Nutritional Examination
Survey (NHANES), a sample of 7398 people (selected to
represent the United States population age 6 years and older)
were surveyed for hay fever, current allergies, and current rhinitis and tested for IgE specific to 19 inhalant allergens. One in 3 participants reported rhinitis symptoms within
the last 12 months not associated with an upper respiratory
infection. Of those with rhinitis, 52.7% demonstrated at least
1 positive allergy test.10 By this standard, IgE-mediated AR
may affect 1 in 6 persons within the United States. The United
States population is most commonly sensitized to grass pollen, dust mites, and ragweed pollen.10
The International Study of Asthma and Allergies in
Childhood (ISAAC), a worldwide study of allergies in
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Table 2. Topics and Issues Considered in Allergic Rhinitis (AR) Guideline Development.a
Diagnosis/Testing
Diagnosis of AR
Differentiating
nonallergic nasal
conditions from AR
When should a patient
be referred to an allergy
specialist?
Differentiating perennial
or seasonal AR
Identifying and treating
comorbidities
When is it acceptable
to test for allergic
component(s), and what
type of test should be
performed?
Accuracy of self
diagnosis
Accuracy of clinician
diagnosis based on
clinical assessment
Children age 2 and
older with a diagnosis

of allergies, since age
2 is the earliest age to

consider allergy testing
Role and appropriate
use of imaging
Role of nasal endoscopy
Accurate use of
instruments to measure
symptoms/objective
testing for baseline

When is it necessary to
perform specific allergy
testing and/or IgE test?
Prevention/Education/
Risk Factors
Treatment
First-line therapy upon

diagnosis
When does combining
2 different classes of
allergy pharmacology
benefit the patient?
Pharmacology and the
different medication
classes that offer
additive vs negative
effects
Self-directed therapy
or over-the-counter
medications vs
physician-directed or
prescription medications
Use and safety of nasal,
oral, topical steroids
When is it acceptable
to add a second or
third medication?
Treatment of allergic
conjunctivitis
Role of surgical
management
Managing chronic
inflammation of lung,
sinus, skin, and ears
Role of immunotherapy
Efficacy of different
antihistamines
Measuring response to
therapy and identifying
further need for therapy
Role of environmental
controls
Methods for preventing

the development of AR
Role of patient
education
When is it appropriate
to manage symptoms
over the phone (or
internet)?
Role of dietary
modifications
Value of pollen counts
in determining symptom
severity and selfguidance
Role of stress
management in
the creation of, or
exacerbation of, AR
symptoms
Identification of
risk factors for the
development of AR
Other Therapies
Outcomes
Role of acupuncture
Role of herbal medicines

Role of homeopathy
Role of nasal rinses

Role of capsaicin
Role of antibiotics
Initial evaluation of the

patient
Improvement in
accuracy of diagnosis;
avoidance of
unnecessary testing
Reduction in care
variation and
unnecessary radiation
exposure from sinonasal
imaging
Expenditure reduction
for ineffective
environmental measures
Increased treatment
optimization and
reduced complications
from comorbidities
Optimization of proven
effective therapy
Avoidance of sedating
antihistamine and
promotion of direct
therapy
Improved awareness of
the different classes of
medication for effective
treatment of AR
Reduction in the use of
a less effective first-line
agent
Improved symptom
control and reduction in
care variation
Increased awareness
and appropriate use
of immunotherapy
and reduction in care
variation
Improved nasal
breathing and quality
of life
Increased awareness
of acupuncture as a
treatment option
Increased awareness
of herbal therapy as a
treatment option
This list was created by the Guideline Development Group to refine content and prioritize action statements; not all items listed were ultimately included in
the guideline.
children, found a large variation in the prevalence of AR

between countries, with the lowest rate reported at 1.5% in
Iran and the highest at 39.7% in Nigeria.11 The prevalence of
AR varies with genetics, epigenetics, and environmental
exposure in complex ways we do not fully understand. Allergic

rhinitis is a heterogenic condition in many respects, so the epidemiologic variance is not unexpected. Despite the variation,
the majority of centers found an increasing prevalence of AR
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Seidman et al
in children over time. In the United States, over an 8-year time
period ending in 2002, the prevalence of AR in 2422 children
ages 13 to 14 years increased from 13% to 19%.11 These
results illustrate that AR is both a common and growing global
concern.
Costs, Quality of Life, and Productivity

The financial impact associated with the management of AR
is substantial. Most estimates of the annual direct cost of AR
range from US$2 to $5 billion,4,5 with more than half of AR
direct costs likely coming from prescription medications.4
Data from the 2007 Medical Expenditure Panel Survey suggest that clinic visits and the number of prescriptions filled for
patients with AR are approximately twice the number of those
for patients without AR.12 There are also considerable costs
associated with managing the comorbidities of AR, such as
sinusitis and asthma, which are classified as hidden direct
costs.5
In addition to imposing direct costs, AR exacts a considerable toll on patients quality of life, cognitive function, decision making, and self-perception.13 Indirect costs of AR in
adults include costs associated with decreased work productivity and days absent due to illness. In the United States, AR
results in a loss of 800,000 to 3.5 million workdays per
year.14,15 From a cohort of 8267 US employees at 47 employer
locations, Lamb et al16 reported that AR caused greater loss of
productivity than any other illness and accounted for nearly
one-quarter of all lost productivity. Lost productivity from AR
has been estimated to cost $2 to $4 billion annually in the
United States.4,5 In children, AR and its associated comorbidities are responsible for 800,000 to 2 million lost school days
annually.14,15 Children with AR have also been shown to have
increased disorders of learning performance, behavior, and
attention, especially when common comorbidities such as
sleep-disordered breathing and asthma are present.17-20
Methods
This guideline was developed using an explicit and transparent a priori protocol for creating actionable statements based
on supporting evidence and the associated balance of benefit
and harm.21 The Guideline Development Group consisted of
20 panel members representing experts in otolaryngology,
allergy and immunology, internal medicine, family medicine,
pediatrics, sleep medicine, advanced practice nursing, complementary and alternative medicine (acupuncture and herbal
therapies), and consumer advocacy.
Literature Search
An information specialist conducted 2 literature searches from
June 2013 through November 2013, using a validated filter
strategy, to identify clinical practice guidelines, systematic
reviews, and randomized controlled trials (RCTs). The search
terms used were ((Nasal Allergy[TW] OR Nasal Allergies[TW]
OR Nose Allergy[TW] OR Pollinosis[TW] OR Pollinoses[TW]
OR Catarrh[TW] OR Catarrhs[TW]) OR (Allergic Rhinitis[TW])
OR (((Rhinitis, Allergic, Perennial[MESH]) OR Rhinitis,
Allergic, Seasonal[MESH]) OR Rhinitis, Atrophic[MESH])
AND ((1980/01/01[PDAT]: 2013/12/31[PDAT]) AND

English[LANG])) AND ((Clinical Trial*[PT] AND
(Randomized[TW] OR Randomised[TW])) OR (Randomized
Controlled Trial[PUBLICATION TYPE] OR Randomized
Controlled Trial[TW] OR Randomized Controlled Trial[TW])).
These search terms were used to capture all evidence on the
population, incorporating all relevant treatments and outcomes.
The English-language searches were performed in multiple
databases including the Cochrane Library, EMBASE,
PubMed, and the Cumulative Index to Nursing and Allied
Health Literature (CINAHL). In certain instances, targeted
searches for lower level evidence were performed by panel
members to address gaps from the systematic searches identified in writing the guideline from December 2013 through
May 2014.
1. Clinical practice guidelines were identified by a
PubMed search using guideline as a publication type or
title word. The initial search identified 54 guidelines.
Articles were excluded if they (1) were not on the topic
of the guideline, (2) were not available in English, (3)
did not meet the panels quality criteria (eg, the review
had a clear objective and method), (4) did not possess
an explicit search strategy, and/or (5) did not have valid
data extraction methods. After duplicates, irrelevant
references, and non-English-language articles were
removed, the final tally was 31 guidelines.
2. Systematic reviews were identified through,
EMBASE, the Cochrane Library, CINAHL, and
PubMed. The initial data set included 759 systematic reviews or meta-analyses that were distributed
to the panel members. Articles were excluded if they
(1) were not on the topic of the guideline, (2) were
not available in English, (3) did not meet the panels
quality criteria (eg, the review had a clear objective
and method), (4) did not possess an explicit search
strategy, and/or (5) did not have valid data extraction
methods. The final data set retained was 390 systematic reviews or meta-analyses.
3. The initial set of RCTs identified through PubMed,
EMBASE, CINAHL, and the Cochrane Library
totaled 2446 RCTs articles. These were distributed
among panel members for review. Articles were
excluded if they (1) were unpublished RCTs, duplicate articles, and articles with unavailable abstracts
(2) were not on the topic of the guideline, (3) were
not available in English, (4) did not meet the panels
quality criteria (eg, the review had a clear objective
and method), (5) did not possess an explicit search
strategy, and/or (6) did not have valid data extraction
methods. The total final data set retained after the
panel review was 1605 RCT articles.
The 31 clinical practice guidelines, 390 systematic reviews,
and 1605 RCTs were broken down into the 14 key action
statement categories. This material was supplemented, as
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Table 3. Evidence Levels for Grades of Evidence.a

Grade
A
B
C
D
X
Evidence Quality for Diagnosis
Evidence Quality for Treatment and Harm
Systematic review of cross-sectional studies with consistently Well-designed randomized controlled trials performed on a
applied reference standard and blinding
population similar to the guidelines target population
Individual cross-sectional studies with consistently applied
Randomized controlled trials; overwhelmingly consistent
reference standard and blinding
evidence from observational studies
Nonconsecutive studies, case-control studies, or studies with Observational studies (case control and cohort design)
poor, nonindependent, or inconsistently applied reference
standards
Mechanism-based reasoning or case reports
Exceptional situations where validating studies cannot be performed and there is a clear preponderance of benefit over harm
American Academy of Pediatrics classification scheme25 updated for consistency with current level of evidence definitions.26
needed, with targeted searches to address specific needs identified in writing the guideline through February 2014. After
assessing quality and relevance, we retained 9 of the clinical
practice guidelines, 81 of the systematic reviews, and 177 of
the RCTs.
In a series of conference calls, the working group defined
the scope and objectives of the proposed guideline. During the
12 months devoted to guideline development ending in March
2014, the group met twice, with in-person meetings following
the format previously described,21 using electronic decisionsupport (BRIDGE-Wiz, Yale Center for Medical Informatics,
CT) software to facilitate creating actionable recommendations and evidence profiles.22 Internal electronic review and
feedback on each guideline draft were used to ensure accuracy
of content and consistency with standardized criteria for
reporting clinical practice guidelines.23
American Academy of OtolaryngologyHead and Neck
Surgery Foundation (AAO-HNSF) staff used the Guideline
Implementability Appraisal and Extractor (GLIA) to appraise
adherence of the draft guideline to methodological standards,
to improve clarity of recommendations, and to predict potential obstacles to implementation.24 Guideline panel members
received summary appraisals in April 2014 and modified an
advanced draft of the guideline.
The final guideline draft underwent extensive external peer
review. Comments were compiled and reviewed by the panels chair and co-chairs, and a modified version of the guideline was distributed and approved by the guideline development
panel. The recommendations contained in the guideline are
based on the best available data published through May 2014.
Where data were lacking, a combination of clinical experience
and expert consensus was used. A scheduled review process
will occur at 5 years from publication, or sooner if new compelling evidence warrants earlier consideration.
Classification of Evidence-Based
Statements
Guidelines are intended to produce optimal health outcomes
for patients, to minimize harms, and to reduce inappropriate
variations in clinical care. The evidence-based approach to
guideline development requires that the evidence supporting
a policy be identified, appraised, and summarized and that an
explicit link between evidence and statements be defined.
Evidence-based statements reflect both the quality of evidence and the balance of benefit and harm that is anticipated
when the statement is followed. The definitions for evidencebased statements are listed in Tables 325 and 4.25 Because
much of the guideline dealt with evidence relating to diagnostic tests, Table 3 was adapted to include current recommendations from the Oxford Centre for Evidence-Based
Medicine.26
Guidelines are not intended to supersede professional judgment but rather may be viewed as a relative constraint on individual clinician discretion in a particular clinical circumstance.
Less frequent variation in practice is expected for a strong
recommendation than might be expected with a recommendation. Options offer the most opportunity for practice
variability.25 Clinicians should always act and decide in a way
that they believe will best serve their patients interests and
needs, regardless of guideline recommendations. Clinicians
must also operate within their scope of practice and according
to their training. Guidelines represent the best judgment of a
team of experienced clinicians and methodologists addressing
the scientific evidence for a particular topic.25
Making recommendations about health practices involves
value judgments on the desirability of various outcomes associated with management options. Values applied by the guideline panel sought to minimize harm and diminish unnecessary
and inappropriate therapy. A major goal of the panel was to be
transparent and explicit about how values were applied and to
document the process.
Financial Disclosure and Conflicts of

Interest
The cost of developing this guideline, including travel
expenses of all panel members, was covered in full by the
AAO-HNSF. Potential conflicts of interest for all panel members in the past 2 years were compiled and distributed before
the first conference call. After review and discussion of these
disclosures,27 the panel concluded that individuals with potential conflicts could remain on the panel if they (1) reminded
the panel of potential conflicts before any related discussion,
(2) recused themselves from a related discussion if asked by
the panel, and (3) agreed not to discuss any aspect of the
guideline with industry before publication. Last, panelists
were reminded that conflicts of interest extend beyond financial
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Seidman et al
Table 4. Guideline Definitions for Evidence-Based Statements.
Statement
Strong Recommendation
Recommendation
Option
No Recommendation
Definition
Implication
A strong recommendation means the benefits of the

recommended approach clearly exceed the harms
(or that the harms clearly exceed the benefits in
the case of a strong negative recommendation)
and that the quality of the supporting evidence is
excellent (Grade A or B).a In some clearly identified
circumstances, strong recommendations may be
made based on lesser evidence when high-quality
evidence is impossible to obtain and the anticipated
benefits strongly outweigh the harms.
A recommendation means the benefits exceed the
harms (or that the harms exceed the benefits in
the case of a negative recommendation), but
the quality of evidence is not as strong (Grade B
or C).a In some clearly identified circumstances,
recommendations may be made based on lesser
evidence when high-quality evidence is impossible to
obtain and the anticipated benefits outweigh
the harms.
An option means that either the quality of evidence
that exists is suspect (Grade D)a or that well-done
studies (Grade A, B, or C)a show little clear
advantage to one approach versus another.
No recommendation means there is both a lack of
pertinent evidence (Grade D)a and an unclear
balance between benefits and harms.
Clinicians should follow a strong recommendation

unless a clear and compelling rationale for an
alternative approach is present.
Clinicians should also generally follow a

recommendation but should remain alert to new
information and sensitive to patient preferences.
Clinicians should be flexible in their decision making

regarding appropriate practice, although they may
set bounds on alternatives; patient preference should
have a substantial influencing role.
Clinicians should feel little constraint in their decision
making and be alert to new published evidence that
clarifies the balance of benefit versus harm; patient
preference should have a substantial influencing role.
American Academy of Pediatrics classification scheme.25
relationships and may include personal experiences, how a

participant earns a living, and the participants previously
established stake in an issue.28
Guideline Key Action Statements

Each evidence-based statement is organized in a similar fashion: an evidence-based key action statement in bold, followed
by the strength of the recommendation in italics. Each key
action statement is followed by an action statement profile
of aggregate evidence quality, level of confidence in the evidence, benefit-harm assessment, and statement of costs.
Additionally, there is an explicit statement of any value judgments, the role of patient preferences, clarification of any
intentional vagueness by the panel, exceptions to the statement, any differences of opinion, and a repeat statement of the
strength of the recommendation. Several paragraphs subsequently discuss the evidence base supporting the statement.
An overview of each evidence-based statement in this guideline can be found in Table 5.
The role of patient preference in making decisions deserves
further clarification. For some statements, where the evidence
base demonstrates clear benefit, although the role of patient
preference for a range of treatments may not be relevant (such
as with intraoperative decision making), clinicians should provide patients with clear and comprehensible information on
the benefits to facilitate patient understanding and shared
decision making, which in turn leads to better patient adherence and outcomes. For the purposes of this guideline, shared
decision making refers to the exchange of information regarding treatment risks and benefits, as well as the expression of
patient preferences and values, which result in mutual responsibility in decisions regarding treatment and care.29 In cases
where evidence is weak or benefits are unclear, the practice of
shared decision makingagain where the management decision is made by a collaborative effort between the clinician
and an informed patientis extremely useful. Factors related
to patient preference include (but are not limited to) absolute
benefits (numbers needed to treat), adverse effects (number
needed to harm), cost of drugs or procedures, and frequency
and duration of treatment.
STATEMENT 1. PATIENT HISTORY AND PHYSICAL
EXAMINATION: Clinicians should make the clinical
diagnosis of AR when patients present with a history and
physical examination consistent with an allergic cause and
1 or more of the following symptoms: nasal congestion,
runny nose, itchy nose, or sneezing. Findings of AR consistent with an allergic cause include, but are not limited to, clear
rhinorrhea, nasal congestion, pale discoloration of the nasal
mucosa, and red and watery eyes. Recommendation based on
observational studies, with a preponderance of benefit over
harm.
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Table 5. Summary of Guideline Action Statements.

Statement
Action
Strength
1.Patient history and

physical examination
Clinicians should make the clinical diagnosis of AR when patients present with a
history and physical examination consistent with an allergic cause and 1 or more
of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing.
Findings of AR consistent with an allergic cause include, but are not limited to,
clear rhinorrhea, nasal congestion, pale discoloration of the nasal mucosa, and
red and watery eyes.
2. Allergy testing
Clinicians should perform and interpret, or refer to a clinician who can perform
and interpret, specific IgE (skin or blood) allergy testing for patients with a
clinical diagnosis of AR who do not respond to empiric treatment, or when the
diagnosis is uncertain, or when knowledge of the specific causative allergen is
needed to target therapy.
Clinicians should not routinely perform sinonasal imaging in patients presenting
3.Imaging
with symptoms consistent with a diagnosis of AR.
4.Environmental factors Clinicians may advise avoidance of known allergens or may advise environmental
controls (eg, removal of pets, the use of air filtration systems, bed covers,
and acaricides [chemical agents that kill dust mites]) in AR patients who have
identified allergens that correlate with clinical symptoms.
5.Chronic conditions and Clinicians should assess patients with a clinical diagnosis of AR for, and document
comorbidities
in the medical record, the presence of associated conditions such as asthma,
atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and
otitis media.
6.Topical steroids
Clinicians should recommend intranasal steroids for patients with a clinical
diagnosis of AR whose symptoms affect their quality of life.
Clinicians should recommend oral second-generation/less sedating antihistamines
7.Oral antihistamines
for patients with AR and primary complaints of sneezing and itching.
8.Intranasal
Clinicians may offer intranasal antihistamines for patients with seasonal, perennial,
antihistamines
or episodic AR.
Clinicians should not offer oral leukotriene receptor antagonists as primary
9.Oral leukotriene
therapy for patients with AR.
receptor antagonists
(LTRAs)
10. Combination therapy Clinicians may offer combination pharmacologic therapy in patients with AR who
have inadequate response to pharmacologic monotherapy.
11.Immunotherapy
Clinicians should offer, or refer to a clinician who can offer, immunotherapy
(sublingual or subcutaneous) for patients with AR who have inadequate response
to symptoms with pharmacologic therapy with or without environmental
controls.
12.Inferior turbinate
Clinicians may offer, or refer to a surgeon who can offer, inferior turbinate
reduction
reduction in patients with AR with nasal airway obstruction and enlarged inferior
turbinates who have failed medical management.
13.Acupuncture
Clinicians may offer acupuncture, or refer to a clinician who can offer acupuncture,
for patients with AR who are interested in nonpharmacologic therapy.
14. Herbal therapy
No recommendation regarding the use of herbal therapy for patients with AR.
Recommendation
Recommendation
Recommendation (against)
Option
Recommendation
Strong recommendation
Strong recommendation
Option
Recommendation (against)
Option
Recommendation
Option
Option
No recommendation
Abbreviations: AR, allergic rhinitis; IgE, immunoglobulin E.
Action Statement Profile

Quality improvement opportunity: To promote a
consistent and systematic approach to initial evaluation of the patient with AR
Aggregate evidence quality: Grade C, based on
observational studies
Level of confidence in evidence: High
Benefits: Avoid unnecessary treatment or testing, time referrals appropriately, institute a specific
therapy, improve quality of life and productivity,
improve accurate diagnosis
Risks, harms, costs: Inappropriate treatment, potential

misdiagnosis from using history and physical alone
Benefit-harm assessment: Preponderance of benefit
over harm
Value judgments: Although the Guideline Development Group recognized that a conclusive diagnosis
of AR is difficult without diagnostic testing, making
a presumptive diagnosis of AR based on history and
physical examination alone is reasonable.
Intentional vagueness: The use of the words
clinical diagnosis acknowledges that this is a
presumptive diagnosis not confirmed with testing. The
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Seidman et al
use of the words when patients present with a history

and physical examination consistent with an allergic
cause assumes that a clinician will know how to make
an appropriate diagnosis of AR. Specifics of what constitutes a history and physical examination consistent with
an allergic cause are provided in the supporting text.
Role of patient preferences: LimitedPatient may
request that additional testing be conducted before
deciding on initiation of treatment.
Exclusions: None
Policy level: Recommendation
Differences of opinion: None
Supporting Text
The purpose of this statement is to provide guidance for the
initial clinical diagnosis of AR when a patient first presents to
a health care provider. Since rhinitis is an extremely frequent
complaint, and since this complaint will often be heard first in
the primary care setting, it is important that primary care providers be able to make an initial, if provisional, diagnosis,
especially since first-line, effective, readily available therapies
for AR may differ from those used for nonallergic rhinitis.30
Key elements of the history in patients presenting with AR
include seasonal, perennial or episodic, exposure-associated
itching of the nose, palate, or eyes, sneezing, nasal congestion,
sniffling, clear rhinorrhea, and postnasal drip.31 Children may
only complain of malaise or fatigue, often associated with a
cough, and the history must include specific questions about
rhinorrhea and nasal and ocular itch in order to elicit these complaints.32 Seasonal disease may be caused by exposure to outdoor fungal spores or plant pollens, which vary seasonally in
their appearance; perennial symptoms tend to be associated
with sensitization to indoor allergens, such as dust mites, cockroaches, animal dander, and other molds,33 but may also be
attributed to persistent pollen exposure in some climates.
Associated exposures to specific identifiable allergens, such as
animals, in connection with the sudden appearance and clearing
of symptoms should also be sought. Alternatively, symptoms
that develop on exposure to irritants such as smoke, fumes, and
chemicals are less likely to represent AR. Symptoms of other
sinonasal diseases such as sinusitis, vasomotor rhinitis, and
granulomatous diseases can overlap with AR symptoms and
should be differentiated from AR. Less typical symptoms, such
as epistaxis, unilateral rhinorrhea, unilateral nasal blockage,
severe headache, or anosmia, suggest alternative diagnoses and
should be investigated further. These symptoms could indicate
a more concerning diagnosis, such as cerebrospinal fluid (CSF)
rhinorrhea, sinonasal tumors, or chronic rhinosinusitis. Less
typical symptoms such as epistaxis, unilateral nasal symptoms,
severe headache, or anosmia suggest alternative diagnoses.
Viral upper respiratory infections may produce similar symptoms but tend to be of a shorter duration and often include other
symptoms such as fever and myalgia. Clinicians should pay
attention to a patients medications, such as antihypertensive
drugs, psychotropic agents, and topical decongestants, that may
cause nasal symptoms.34 Moreover, a family history of AR,
asthma, or atopic dermatitis strengthens the diagnosis of AR
in patients with compatible symptoms.35,36 Finally, the severity

of symptoms should be assessed to help guide treatment
decisions.
Findings on physical examination that support the diagnosis of AR include several classic findings, such as clear rhinorrhea and pale pink or bluish swelling of the nasal turbinate
mucosa. Ocular findings are common and include watery eye
discharge, swelling of the conjunctivae and, especially in children, the allergic shiner, with darkening and puffiness of the
lower eyelids, reflecting venous pooling in the lid vessels.
Persistent adenoids may contribute to nasal symptoms and
should be evaluated, especially in children. Frequent throat
clearing is often present as well, reflecting postnasal drip.
These symptoms are nonspecific to AR, and if a patient has
them, clinicians should also rule out other causes, such as
laryngopharyngeal reflux. Chronic AR symptoms can lead to
frequent rubbing of the nose (the allergic salute) and the
development of an allergic crease across the nasal bridge.
When nasal congestion is present from AR, patients, especially children, may develop adenoid facies from chronic
mouth breathing. While many of these findings are, in themselves, nonspecific, their presence in a patient with the appropriate history lends further support to the diagnosis of AR.32
The physical examination should also eliminate other nonallergic causes of nasal obstruction and rhinorrhea, such as foreign bodies, CSF leak, nasal polyps (which can be associated
with AR but may have other infectious or chronic inflammatory origins), tumors, and infection.
Although definitive diagnosis depends on the finding of an
IgE-mediated response to a specific allergen, detected through
cutaneous or blood testing in most patients, it is reasonable to
make an initial diagnosis and begin therapy based on the history and physical examination. This is especially important in
those patients whose school or work performance and quality
of life are compromised by their symptoms.37 A good response
to avoidance of suspected allergens or appropriate empiric
therapy supports the diagnosis of AR and may preclude the
need for further testing.30 Table 6 highlights the history and
physical findings in AR.
STATEMENT 2. ALLERGY TESTING: Clinicians should
perform and interpret, or refer to a clinician who can perform and interpret, specific IgE (skin or blood) allergy
testing for patients with a clinical diagnosis of AR who do
not respond to empiric treatment, or when the diagnosis is
uncertain, or when knowledge of the specific causative
allergen is needed to target therapy. Recommendation based
on RCTs and systematic reviews, with a preponderance of
benefit over harm.

Quality improvement opportunity: Improve accurate
diagnosis and avoid unnecessary testing
Aggregate evidence quality: Grade B, based on randomized controlled trials and systematic reviews
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Table 6. History and Physical Findings in AR.

Presenting Symptoms
Nasal congestion
Sneezing
Rhinorrhea (clear or colored may exist,
although colored rhinorrhea may indicate
a comorbid disease process with AR)
Itching of nose, eyes, palate
Postnasal drip
Frequent throat clearing
Cough
Malaise (may be presenting complaint in
children)
Fatigue (may be presenting complaint in
children)
Historical Findings
Seasonal vs perennial nature of symptoms
Symptoms on exposure to particular agent
(animals, particular plants)
Current medications
Family history of atopic or allergic disease
Symptoms on exposure to irritants (makes
allergic origin less likely)
Symptoms of upper respiratory infection
(makes allergic origin less likely)
Benefits: Confirming diagnosis, directing pharmacologic therapy, directing immunotherapy, avoidance

strategies, avoidance of ineffective therapy, reduce
cost of unnecessary testing
Risks, harms, costs: Cost of testing, adverse events
from testing, misinterpretation of results, inaccurate
test results (false positives and negatives)
over harm
Value judgments: Patients may benefit from identification of specific allergic cause.
Intentional vagueness: We did not specify which specific IgE test (blood or skin) to order. We also did not
specify which allergens to test, as that was beyond
the scope of this guideline. We did not specify what
constitutes empiric treatment, although this is generally treatment that is initiated prior to confirmatory,
IgE-specific testing and could include recommending environmental controls, allergen avoidance, or
medical management. Lack of response to empiric
treatment is not defined to allow the clinician to exercise judgment in making this determination but is
generally thought to include patients with persistent
symptoms despite therapy.
Role of patient preferences: ModerateShared decision making in discussion of harms and benefits of
testing; clinicians and patients should discuss potential costs, benefits, and adverse effects of additional
testing, and type of testing, either skin or blood, if
neither is contraindicated.
Exclusions: None
Supporting Text
The purpose of this statement is to help clinicians decide
when to use IgE-specific allergy testing and to define the
types of testing that may be useful. While a presumptive diagnosis of AR can be made based on a history and physical
Physical Findings
Clear rhinorrhea (clear or colored may
exist, although colored rhinorrhea may
indicate a comorbid disease process with
AR)
Bluish or pale swelling of nasal mucosa
Ocular findings (watery discharge, swollen
conjunctivae, scleral injection)
Frequent throat clearing
Allergic shiners
Nasal crease
Absence of foreign body, tumor, purulence
suggesting infection
examination, the presence of a specific IgE antibody to a

specific inhalant allergen(s) to which the patient has reported
symptoms helps confirm the diagnosis of AR.
Many patients with symptoms of AR can be successfully
treated empirically based solely on history and physical examination, without confirmation of IgE allergy. Empiric treatment is defined as treatment that is initiated prior to
IgE-specific testing and could include environmental controls,
allergen avoidance, or medical management. There are, however, clinical scenarios when confirmatory testing is warranted. These include when patients do not respond to empiric
treatment, when the diagnosis of AR is uncertain, when identification of the specific allergen could affect therapy decisions, or to aid in titration of therapy. According to guidelines
from the World Health Organization (WHO), allergy testing
can be considered as well as other treatment measures such
as immunotherapy in patients in whom antihistamines and
moderate-dose intranasal steroids (INS) insufficiently control
symptoms, with an adequate trial of medications being 2 to 4
weeks in duration.6 In these scenarios, the results of specific
IgE testing (either skin or blood) (see Table 7) provide additional information that can guide targeted therapy or alter
treatment by the clinician.
As AR is an IgE-mediated disease, testing for non-IgE antibodies (ie, IgG) when trying to identify specific allergen triggers is not beneficial. Measurement of total IgE also has
limited diagnostic value in the diagnosis of AR.38 There are 2
main categories of useful IgE-specific tests: skin and blood
testing. Further discussion of these modalities follows.
Skin Testing
Skin testing is a bioassay performed by introducing a specific
allergen into the patients skin. Skin testing allows for direct
observation of the bodys reaction to a specific antigen. The
antigen rapidly activates cutaneous mast cells by interacting
with IgE antibodies on the surface of those cells. This leads to
the release of chemical substances such as histamine from
mast cell granules and results in the development of a wheal
and flare reaction within 15 to 20 minutes.39,40
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Seidman et al
Table 7. Immunoglobulin E (IgE)Specific Tests.
Recommendation
Advantages
Disadvantages
Skin tests
Skin prick, or intradermal
Recommend
Allows for direct observation

of the bodys reaction to a
specific antigen
Considered more sensitive than
blood testing
Intradermal can be used when
additional sensitivity is required
or skin prick negative
Less expensive than blood
testing
Possible systemic allergic reaction

(anaphylaxis)
May be affected by patient
medications
Blood
Recommend
No risk of anaphylaxis
Not affected by patients
medications
Can be used for patients
with skin conditions such
as dermatographism or
severe eczema
Can be used for patients on
-blockers or with comorbid
medical conditions that
preclude skin testing
Requires reliable laboratory,

potential for laboratory errors
IgG or total IgE
Recommend against
Does not yield information helpful

for management of allergic
rhinitis
Other nonspecific tests

No recommendation
Acoustic rhinometry
for or against
Olfactory testing
Microarray testing
Nasal nitric oxide measurements
Nasal allergen challenges
Skin testing is primarily done by either the skin prick/puncture technique or by the intradermal/intracutaneous technique.
Skin prick testing has been shown to be highly sensitive and
specific, typically over 80% for both.38,41,42 Scratch testing, a
form of puncture technique, is rarely done now due to reduced
sensitivity and specificity, poor reproducibility, and greater
patient discomfort.38,43 Intradermal and intradermal dilutional
tests are other forms of skin testing that are used for identifying IgE-specific allergens.44 Intradermal skin tests are particularly helpful when the prick test is negative and there is a high
clinical suspicion for allergic sensitization to a particular allergen or if increased sensitivity is required.38,45 Provocationneutralization testing is a form of intradermal testing that is
primarily of historical interest for inhalant allergy testing, as it
has been shown to produce unreliable results.38
Skin testing can be used in patients of any age. While
infants may have small wheals with both positive controls and
allergens, prick/puncture tests can be performed with a high
degree of reliability. Although the prevalence of positive skin
tests is known to be lower after age 50, significant positive
skin tests can still be detected in the older population.38,42,46,47
Skin testing may be contraindicated when coexistent uncontrolled or severe asthma is present. Skin disease such as
eczema can be a relative contraindication. Other contraindications may include coexisting medical conditions that would
likely compromise survival should skin testing-induced anaphylaxis develop: for example, severe and unstable cardiovascular disease, concurrent use of -blockers.
While adverse reactions such as immediate and delayed
local swelling, redness, pain, and itching have been reported
with skin testing, serious adverse events such as anaphylaxis
and death are extremely rare. There have been no fatalities
reported as a result of prick inhalant testing and 6 fatalities
from intradermal inhalant testing, with 5 of these being asthmatic patients for whom prick testing did not precede intradermal testing.38,48 There is considerable variation in clinical
practice in (1) the number of skin tests performed, (2) the
allergen extract concentration used for testing, (3) selection of
skin testing devices, (4) interpretation and documentation of
results, and (5) quality assurance procedures used.41,49 When
performing prick or intracutaneous skin testing, the clinician
should use standardized allergen extracts when available and
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should record measurements of wheal and erythema for allergen and positive and negative controls at 15 to 20 minutes
after placement. The clinician should also list all medications
the patient has taken within the past week, as many medications, such as antihistamines and some antidepressants (eg,
tricyclics), may suppress the skin test response.38,42,50
Blood Testing
Allergen-specific IgE can be determined by testing the
patients serum with an in vitro test. Using an immunoassay,
allergen-specific IgE in serum is detected by incubating the
serum with the suspected allergen, which has been absorbed
on a solid phase (eg, plastic disc or bead). The bound specific
IgE is then measured by the addition of an anti-IgE antibody
for this specific allergen, which has a label, such as an
enzyme, attached to allow for detection. Anti-IgE antibodies
tagged to radioactive tags, (radioallergosorbent tests, aka
RAST) are seldom used today, making the term RAST an
anachronism.43
Advantages of using immunoassays for allergy testing
include the ability to test for sensitivity to specific antigens
without concern about adverse reactions, including anaphylaxis. Antihistamines and other medications (eg, tricyclic antidepressants and -blockers) do not need to be withheld. Using
blood allergy testing instead of skin testing may be preferred
when special skin conditions, such as dermatographism (skin
writing with reddened and raised skin lines produced by
scratching or stroking) or severe eczema, are present, in that
these conditions may make skin test interpretation very
difficult.38
While both skin prick and serum-specific IgE tests have
similar diagnostic properties, the skin prick test is generally
considered to be more sensitive.38,51,52 Another potential
advantage of skin testing is that it is less expensive than blood
testing,53 and patients are able to see the tangible results of
their testing. Clinicians should use their best judgment when
deciding which method of IgE-specific testing to use for a
given patient. Given the lack of conclusive evidence of superiority of one test over another, in the absence of contraindications to one form of testing, patient preference for and the
availability of skin or blood testing should play a role in deciding which test to use. Clinicians should always be aware that
detection of sensitization to an allergen is not equivalent to a
clinical diagnosis of an allergy to a specific allergen. In the
absence of clinical symptoms, positive skin or blood testing
does not mean that the patient has an allergy to that allergen.
Other Tests
Other diagnostic tests are used to evaluate patients with suspected AR. Those tests include acoustic rhinometry, olfactory
testing, microarray testing, nasal nitric oxide measurements,
testing for food allergy, and nasal allergen challenges. Nasal
smears to evaluate nasal eosinophilia have been used by some
clinicians, although general agreement on their usefulness is
lacking.7,54-56 There is insufficient evidence to make recommendations for or against the use of these tests. As a final
point, the providers knowledge of the patients history, local
allergens, qualities of allergen extracts, and how allergen

immunotherapy is prepared may reasonably lead to the use of
different IgE-specific testing modalities including skin prick
testing, blood or serum testing, intradermal testing, intradermal dilutional testing, or combinations thereof. Table 7 lists
the various types of testing for AR and the advantages and
disadvantages of the different tests.
STATEMENT 3. IMAGING: Clinicians should not routinely perform sinonasal imaging in patients presenting
with symptoms consistent with a diagnosis of AR.
Recommendation against based on observational studies,
with a preponderance of benefit over harm.

Quality improvement opportunity: Reduction of
variation of care, reduction of potential harm from
unnecessary radiation exposure
Benefits: Avoiding unnecessary radiation exposure,
reduction of cost, reducing variation in care
Risks, harms, costs: Inaccurate or missed diagnosis
of pathology with similar presenting symptoms.
over harm
Value judgments: None
Intentional vagueness: The word routine was used
to allow for circumstances where the patient history
may warrant imaging for evaluation of another problem besides AR
Role of patient preferences: None
Exclusions: None
Differences of opinions: None
Supporting Text
The purpose of this statement is to discourage the routine use
of diagnostic imaging for patients with AR. History, physical
examination, and allergy testing are the key aspects of making
the diagnosis of AR. Specific IgE-mediated allergen diagnostic testing is confirmatory. There are no radiological findings
specifically diagnostic for AR. The utility of imaging procedures in AR is undocumented, and no articles were found
regarding the diagnostic yield of imaging studies with AR.
Radiographic imaging is unwarranted in patients who
already meet clinical criteria for the diagnosis of AR. Potential
significant adverse events and unnecessary costs preclude any
benefits of routine imaging. Plain film radiographs and computed tomography (CT) scans expose patients to ionizing
radiation, which may result in future radiation-induced cancers.57,58 Iodinated contrast carries the risk of allergic anaphylactic reactions and nephrotoxicity.59
Radiographic testing may have a role in the diagnosis if the
clinical presentation points to potential sequelae of AR, such
as rhinosinusitis, nasal polyposis, or concerns of a suspected
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Seidman et al
neoplasm. In contrast to AR, which only affects the nasal
mucosa, rhinosinusitis is defined as inflammation of the nasal
cavity and adjacent paranasal sinuses. Complicated sinusitis
implies spread of infection into adjacent structures, which can
result in orbital or intracranial complications, such as orbital
abscess and meningitis.60 Diagnosis of most cases of uncomplicated acute and subacute rhinosinusitis is based on clinical
findings. Sinonasal imaging, specifically CT scans without
contrast, may be indicated in patients who demonstrate signs
and symptoms of recurrent acute rhinosinusitis, nasal polyposis, chronic rhinosinusitis, or complicated rhinosinusitis or to
define sinus anatomy prior to surgery.61 In patients with a suspected sinonasal neoplasm, sinus CT and magnetic resonance
imaging (MRI) may be indicated for further evaluation. CT
scans will define the bony anatomy of the sinuses and patterns
of bone destruction as well as any formation of cartilaginous
or bone matrix. MRI with and without contrast can differentiate soft-tissue densities from postobstructive secretions and
will delineate evidence of perineural, orbital, skull base, or
intracranial extension of tumor.62,63
In summary, the diagnosis of AR is based on clinical presentation, and there is no role for radiographic imaging.
Potential significant costs and possible side effects of imaging
modalities outweigh their utility in the routine evaluation of a
patient with AR.
Intentional vagueness: None

Role of patient preferences: LargeShared decision
making in discussion of evidence for effectiveness
of possible controls and the need to weigh the costs
and benefits
Exclusions: None
Policy level: Option
Difference of opinion: None
Supporting Text
The purpose of this statement is to reduce symptoms of AR

and improve quality of life through environmental controls
that efficiently and effectively reduce allergen exposure while
avoiding measures that are costly, are impractical, and have
not been shown to be beneficial. The term environmental
control refers to implementing one or more interventions to
reduce or eliminate allergens and irritants in the environment
and improve health outcomes for patients with AR. These
control measures focus on preventing the development of
sensitization, progression of disease, allergens triggering
symptoms, and medication use.64 The use of environmental
control measures is a means of actively engaging patients in
treatment strategies designed to reduce exposure to specific
allergens and improve allergy symptoms. The risks and benefits of the various methods need to be discussed with patients
in order for them to make informed decisions about measures
that would be most beneficial and cost-effective over time.
STATEMENT 4. ENVIRONMENTAL FACTORS:
Findings from these studies suggest that an environmental
Clinicians may advise avoidance of known allergens or
control program comprised of multiple strategies may reduce
may advise environmental controls (eg, removal of pets;
exposure to allergens and improve symptoms.
the use of air filtration systems, bed covers, and acaricides
As an environmental control, the protective effect of exclu[chemical agents that kill dust mites]) in AR patients who
sively
breastfeeding infants in the first 3 to 6 months of life on
have identified allergens that correlate with clinical sympthe
development
of AR remains inconclusive. A meta-analysis
toms. Option based on RCTs with minor limitations and
of
6
prospective
studies
with a combined sample of 3303 parobservational studies, with equilibrium of benefit and harm.
ticipants found no significant association between breastfeeding infants and protection from developing AR in later
childhood.65 Kramer66 summarized findings from systematic
Quality improvement opportunity: Reduce expendireviews and meta-analyses on the effects of breastfeeding and
tures on environmental measures that do not improve
the development of allergic disease. The evidence revealed no
symptoms
reduction in the risk of developing AR in breastfed infants.
Aggregate evidence quality: Grade B, based on ranMethodological challenges in designing prospective studies
domized controlled trials with minor limitations and
along with limited follow-up times make it difficult to adeobservational studies
quately study the effect of breastfeeding on AR. The inability
Level of confidence in evidence: Moderatewith
to conduct randomized, double-blind studies limits methodolthe exception of studies on house dust mites, the
ogy to observational designs biased by maternal preferences
majority of the studies were small
related to breastfeeding.67 Inconsistencies in diagnosing AR
Benefits: Decreased allergen levels and possible
by health care providers as well as misclassification of infant
reduction in symptoms
feeding methods and duration further contribute to the chal Risks, harms, costs: Cost of environmental controls,
lenges faced by investigators.66 Thus, breastfeeding continues
emotional effect (eg, recommending animal avoidto be recommended in the literature although its benefits in
ance in pet lovers), cost of ineffective recommendapreventing the development of AR remain unsubstantiated.
tion
Avoidance measures such as removal of pets from the envi Benefit-harm assessment: Equilibrium
ronment can reduce allergen exposure but are often difficult
Value judgments: Many studies have demonstrated a
for patients to adhere to. Several studies have examined meareduction in allergen levels with environmental consures to reduce animal dander. One study by Hodson and coltrols; however, benefits in alleviating symptoms are
leagues68 examined the effectiveness of washing dogs to
limited. Use of multiple avoidance techniques may
reduce Can f1 allergen levels in dog hair and dander as well as
be more effective than individual measures.
in homes. Can f1 allergen levels were significantly reduced
S14
when the animals were washed with shampoo for 5 minutes

and then blown dry. However, prewashed levels of Can f1
returned by days 3 to 4. Thus, in order to be effective in reducing dog allergen, the dog should be washed at least twice a
week. A collective review of studies on washing cats weekly
revealed a reduction in Fel d1 levels; however, these lower
levels were not maintained at 1 week and there was little
change in airborne levels of allergen in the home.64 Thus, the
clinical benefits of washing cats remain unsubstantiated by
current research findings. Although frequent washing of pets
may help reduce these allergens on the animal and in the
home, prewashed levels quickly returned (less than a week)
and the benefit in reducing symptoms of AR has not been
demonstrated in the studies. Findings from a randomized
trial,69 a meta-analysis study of 11 birth cohorts70 and a literature review71 on the role of pet ownership in the early years of
life as either contributing to the development of atopy (a
genetic predisposition to produce elevated levels of IgE to
allergens) or possibly protecting against sensitization were
inconclusive.
The most recent Cochrane review72 on avoidance measures
for house dust mites (HDMs) updated the original Cochrane
review73 and reviews that were published in 200374 and 2007.75
The 2010 review72 evaluated 9 RCTs that investigated the effectiveness of measures to decrease exposures to HDMs, including
use of impermeable covers, air filtration (high-efficacy particulate air [HEPA] filters), acaricides (chemical agents formulated
to kill dust mites), or a combination of treatments.76 Only 2 of
the 9 studies met Cochrane inclusion criteria. Acaricides were
found to be most efficacious as both single therapy and in combination with other environmental control methods in reducing
dust mite exposure and improving symptoms of AR.76
Acaricides are insecticides that are sprayed on furniture, rugs,
and bedding. When acaricides are used, only products appropriate for indoor use should be applied in the home and patients
should read specific instructions for proper application. In a randomized, placebo-controlled trial on the efficacy of impermeable
bed covers in HDM-sensitized patients with AR, researchers
found significant reduction in dust mite levels in mattresses
with impermeable covers versus permeable bedding.77
However, this change in dust mite exposure was not associated
with any improvement in patient symptoms. The protective
effects of mite-impermeable mattress covers on the development of HDM sensitization in newborns was evaluated in a
large randomized controlled European birth cohort study.
Infants in the intervention group slept on mite-impermeable
encased mattresses. At 24 months of age (a young age that may
be a potential limitation of the study), there were no differences
in development of HDM sensitization between infants in the
intervention group versus those in the control group.78 A randomized study79 of 30 patients with AR secondary to HDMs
examined the effect of extensive environmental control measures in the bedroom, such as using vinyl mattress covers,
washing bedding biweekly in hot water (55C), removing
upholstered furniture, and washing floors daily. After 1 month,
this combination of bedroom environmental control methods
significantly reduced dust mite levels in the bedroom. Additionally, patients in the intervention group reported a significant
improvement in nasal symptoms compared with those in the
control group.
The effectiveness of HEPA filtration in reducing symptoms
of AR and medication use was examined in a randomized
double-blind study.80 Thirty-two patients with positive sensitization to HDM used high air filtration in the bedroom for 8
weeks: 4 weeks with HEPA filtration and 4 weeks with placebo filtration. Comparative analysis between the 2 filtration
periods found a reduction in particulate matter in the bedrooms when HEPA filters were used but no improvement in
allergy symptoms or medication use. However, when the
researchers compared the last 2 weeks of each 4-week period,
there were significant reductions in symptom scores in the
HEPA filtration group, indicating some benefit. In another
study,81 35 patients with perennial allergic rhinoconjunctivitis
sensitized to dust mite, cat, or dog allergens participated in a
randomized, double-blind, placebo-controlled crossover design
to determine the effectiveness of a combined therapy using
dust-mite barrier bed pillow encasings and localized HEPA air
filtration. Participants were assigned to either the active filtration group or the placebo group for 2 weeks followed by a
1-week washout period before switching groups for a second
2-week period. Dust samples collected around and under the
bed showed a reduction of 99% in the active filtration group
compared with a reduction of only 7% in the placebo group.
Overnight nasal and ocular symptoms of AR were significantly
reduced in the active group compared with the placebo group;
however, no changes in daytime symptoms were found.
Use of multiple strategies may help reduce dust mite exposure and nasal symptoms in HDM-sensitive patients, although
a single intervention such as using HDM-impermeable covers
on bedding or HEPA filtration has not been shown to be effective.72,77,82 Based on the limited quality of evidence on dust
mite avoidance measures, further research is needed to better
understand the effectiveness of these approaches. Table 8
lists the environmental control measures that can be used to
possibly reduce allergen levels and symptoms.
STATEMENT 5. CHRONIC CONDITIONS AND
COMORBIDITIES: Clinicians should assess patients with
a clinical diagnosis of AR for, and document in the medical
record, the presence of associated conditions such as
asthma, atopic dermatitis, sleep-disordered breathing,
conjunctivitis, rhinosinusitis, and otitis media. Recommendation based on randomized trials with some heterogeneity
and a preponderance of benefit over harm.

Quality improvement opportunity: Identification of
significant comorbid conditions or complications,
potential for treatment optimization
Aggregate evidence quality: Grade B, based on randomized trials with some heterogeneity
Level of confidence in the evidence: High
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Seidman et al
Table 8. Environmental Control Measures to Reduce Allergen Levels and Symptoms.
Evidence Supports Reduction
in Allergen Level
Environmental Control Measure
Yes
Removal of pets
Washing pets twice a week
Acaricides to kill dust mites
Impermeable covers for bedding
Air filtration
Combined use of multiple control measures
No
X
X
X
X
X
X
Benefits: Increased awareness of these conditions;

identification of treatable conditions; knowledge of
these conditions may alter recommendations for AR
treatment as comorbid conditions can alter response
to treatment.
Risks, harms, costs: Potential erroneous diagnosis of
comorbid conditions
over harm
Exclusions: None
Supporting Text
The purpose of this statement is to increase awareness of the
medical conditions that are associated with AR and emphasize
the importance of diagnosing and treating these comorbidities, which include atopic disorders, sleep-disordered breathing, otitis media, and rhinosinusitis.
There is a well-established epidemiologic association
among the atopic disorders, asthma, eczema, and AR, which
share many pathophysiologic mechanisms. Over half of
patients with asthma have AR,83 and 10% to 40% of patients
with AR have asthma. The association between asthma and
AR is especially strong when asthma is documented to have
an allergic cause, a situation where the absence of AR would
be distinctly unusual.84 In children, the risk of asthma is
related to the severity and duration of the patients rhinitis.85,86
Childhood AR not only predisposes to the development of
asthma in childhood but also increases the risk of asthma persisting into adulthood and the onset of allergic asthma in middle age. In contrast, adult-onset, nonallergic asthma is not
necessarily associated with AR.87 Moreover, the presence of
food-associated atopic dermatitis before age 4 is associated
with the development of asthma and AR later in childhood
(after age 7)88; this is a consistent observation that has been
referred to as the allergic march. In one study, 57.6% of
children with early childhood eczema developed AR, 34.1%
Evidence Supports Reduction

in Symptoms
Yes
No
X
X
became asthmatic, and the likelihood of developing the respiratory disorders was related to the severity of the dermatitis.89
The connection between the skin inflammation and later
respiratory disease may be due in part to sensitization to airborne allergens by contact with the skin surface.90 Allergic
conjunctivitis can also be seen in conjunction with AR and can
be treated concurrently.
Recognition of the connections among these atopic diseases has implications for both diagnosis and therapy. A history of atopic eczema or asthma makes an allergic origin more
likely in a patient presenting with persistent or recurrent nasal
symptoms. Evaluation of a patient with AR should always
include an assessment for asthma; inquiry about typical symptoms such as difficulty breathing, cough, wheezing, and ability to exercise; and examination of the chest. This evaluation
should be repeated on follow-up visits, particularly in children, and spirometry should be performed whenever asthma is
suspected. Treatment of AR in patients with concurrent asthma
should be individualized; the use of oral antihistamines91,92
and especially INS93,94 has been shown to reduce bronchial
hyperreactivity and improve asthma control.86,95-97 In addition,
leukotriene receptor antagonists may be an appropriate choice
for patients with both asthma and AR98 even though they are
not first-line therapy for independent AR (see Statement 9 on
LTRAs). Immunotherapy can also benefit both conditions,99-102
and there is evidence that treatment of children with AR with
allergen-specific immunotherapy may prevent the development of asthma103 and sensitivity to new allergens.104 There is
also emerging evidence that immunotherapy for AR may
improve control of atopic dermatitis.105
Nasal blockage and impaired mucociliary clearance106 may
predispose patients with AR to sinus infection; however, a
definite relationship between these disorders is not well established. Adenoid hypertrophy must also be considered in children with AR or sinonasal disease.
There may be an association between AR and otitis media
with effusion,107 with reports of comorbidity varying widely from
16.3 to 89%.108 In a review of patients with both conditions,
allergy treatment using INS, with or without antibiotics, was
found to hasten resolution of otitis media with effusion.109 This
effect may be related to reversing underlying Eustachian tube
dysfunction. AR has been associated with sleep-disordered
S16
breathing110 as well as decreased sleep quality and daytime fatigue

and sleepiness.20,111 While no study has clearly established a
causal relationship between AR and sleep-disordered breathing,
evidence supports the treatment of AR to improve both AR and
sleep-disordered breathing.112 This association may be due to adenoid hypertrophy, but appropriate treatment of AR has been shown
to improve sleep quality and reduce daytime somnolence in both
children and adults.113-116 Although nasal blockage is not usually
the primary causative factor in obstructive sleep apnea, patients
treated for coexistent AR can benefit from mild reductions in the
apnea hypopnea index and reduction in daytime sleepiness.117
STATEMENT 6. TOPICAL STEROIDS: Clinicians
should recommend intranasal steroids for patients with a
clinical diagnosis of AR whose symptoms affect their quality of life. Strong recommendation based on RCTs with minor
limitations and a preponderance of benefit over harm.

Quality improvement opportunity: Optimizing the
use of proven effective therapy
Aggregate evidence quality: Grade A, based on randomized controlled trials with minor limitations
Level of confidence in the evidence: High
Benefits: Improved symptom control, improved
quality of life, better sleep, potential cost saving with
monotherapy, targeted local effect
Risks, harms, costs: Topical side effects, epistaxis,
drug side effects, potential growth concerns in children, septal perforation, and the cost of medication
over harm
Role of patient preferences: LargeThere are multiple
classes of effective therapy with differing risks, adverse
effects, costs, and benefits. The clinician should use his
or her expertise in assisting patients to evaluate the best
treatment and to ensure patient compliance.
Exclusions: None
Policy level: Strong recommendation
Differences of opinions: Minor. There were some differences of opinion regarding the best therapy for mild
or intermittent symptoms, as oral or nasal antihistamines may be adequate therapy for those patients.
Supporting Text
The purpose of this statement is to encourage clinicians to use
INS for AR based on their efficacy, superiority over other
therapies, and good safety record.
Intranasal steroids are very effective for the treatment of AR.
With potent anti-inflammatory properties, INS directly modulate the pathophysiology of AR. In nasal allergen challenge
models, pretreatment with INS results in significant reduction
in mediator and cytokine release along with a significant inhibition in the recruitment of basophils, eosinophils, neutrophils,
and mononuclear cells to nasal secretions.118-120 Moreover, use

of these agents in seasonal disease leads to a reduction in inflammatory cells and cytokines within the nasal mucosa and secretions of patients with AR.121,122 INS also reduce the
antigen-induced hyperresponsiveness of the nasal mucosa to subsequent challenge by antigen123 and histamine release.124,125
Placebo-controlled clinical trials demonstrate the effectiveness of INS in the reduction of nasal symptoms including sneezing, itching, rhinorrhea, and congestion in adults and children
with AR.126-129 By reducing nasal symptoms, INS significantly
improve the quality of life126,127,130 and sleep115,131-134 of patients
with AR. There are no significant differences in efficacy
between the available agents.126 Onset of action starts at time
points ranging from 3-5 hours to 36 hours after first dosing.135-139 The continuous use of INS is recommended and
more efficacious than intermittent use140,141 However, studies
of as-needed use of intranasal fluticasone have shown that
intermittent use is better than placebo.142,143
As far as duration of therapy before INS are considered
ineffective, onset of action starts at time points ranging from
3-5 hours to 36 hours after the first dose, as mentioned above.
The studies suggest that once efficacy is reached after the first
dose, it is maintained for the duration of these trials. Although
there seems to be more reduction in some of these parameters
over the length of therapy, these changes are not statistically
significant compared with the time points when active drugs
reached statistically significant benefit. Therefore, based on
the above data, it is reasonable to assume that efficacy would
be reached after 1 week of therapy at the most and, if none is
observed, the treatment might be considered ineffective.
Along with diminished nasal symptoms, INS have beneficial effects on allergic eye symptoms including itching, tearing, redness, and puffiness.144,145 These symptoms are thought
to occur from the direct effects of allergen on the conjunctiva
and reflexes originating in the nose after allergen exposure.
The reflex response is reduced by INS.146 Some studies have
also suggested that INS improve asthma control in patients
suffering from both AR and asthma97,147 (see Statement 5 on
chronic conditions and comorbidities). Hypertrophic adenoids
can also be reduced in size with INS use.
Comparative studies have shown that INS are superior to
oral H1 antihistamines in controlling nasal symptoms, including
nasal congestion, with no significant difference in the relief of
ocular symptoms.148-150 INS are more effective than leukotriene
receptor antagonists across the range of allergy symptoms.150,151
However, intranasal antihistamines have a more rapid onset of
action than INS in comparison studies.152,153
Different preparations of INS are comparable in efficacy,
making sensory attributes an important factor in patient preference and adherence to therapy.154 These sensory attributes
include aftertaste, nose runout, throat rundown, and smell. To
address some of these concerns, nonaqueous intranasal preparations with hydrofluoroalkane aerosol are now approved for
the treatment of AR in the United States.155-158
The most common side effects of INS are a result of local
irritation and include dryness, burning, stinging, blood tinged
S17
Seidman et al
secretions, and epistaxis. The incidence of epistaxis with different preparations ranges from 4% to 8% over short treatment
periods ranging from 2 to 12 weeks with no differences
between placebo and active therapy.159,160 Higher incidences
of epistaxis (reaching 20%) are reported in studies carried
over a year.161,162 Epistaxis can be minimized with proper INS
positioning and administration, generally pointed away from
the septum within each side of the nose. Septal perforations,
although rare, have been reported.163 Biopsy specimens from
the nasal mucosa of patients with perennial rhinitis who have
been treated with INS continuously for 1 to 5 years showed no
evidence of atrophy.164-171 Studies in adults and children evaluating the effects of INS on the hypothalamic-pituitary axis using
morning cortisol concentrations, cosyntropin stimulation, and
24-hour urinary free cortisol excretion show no adverse
effects.162,172-183 There is some evidence of hypothalamicpituitary-adrenal axis suppression with betamethasone nasal
spray specifically.184,185 Patients with HIV may absorb INS at
a higher rate and need to use caution when using INS or find
an alternative treatment.186-188 Although there have been
reports of an association between the use of INS and the
development of posterior subcapsular cataracts,189 later work
did not corroborate these concerns.190,191 Studies with INS
given over several months have failed to show development of
posterior subcapsular cataracts, significant increases in intraocular pressure, or glaucoma.162,172,180,192
The effect of INS on growth in children has been investigated in controlled studies using both knemometry (a technique able to measure short-term growth by estimating the
distance between heel and knee of the sitting child with an
accuracy of 0.09-0.16 mm) in short-term studies and stadiometry (the accurate measurement of height using an instrument
that provides a direct digital reading of height that is accurate
to the nearest millimeter) in yearlong, placebo-controlled
studies where height is measured monthly. In knemometry
studies, intranasal budesonide reduced lower leg growth rate
in 2 studies, but the difference was statistically significant in
only one of them.193,194 In placebo-controlled studies, fluticasone furoate, triamcinolone acetonide (in 2 doses), and fluticasone propionate for 2 weeks did not affect lower leg growth
rate compared with placebo.195,196 In the yearlong studies
using stadiometry, intranasal beclomethasone dipropionate, at
twice the recommended daily dosage, resulted in growth suppression, but fluticasone propionate and mometasone furoate
showed no effects on growth compared with placebo.197,198 In
a small, nonrandomized, open-label study, children were followed for 2 years while receiving triamcinolone acetonide
nasal spray, and their height was measured by stadiometry and
compared with predicted values; no significant difference was
shown between measured and predicted heights.199 Therefore,
in clinical practice, it seems prudent to use the intranasal steroid preparations that have not been shown to have any negative impact on growth in children, as detailed above.
Short courses of systemic corticosteroids are often used
clinically for patients with severe AR but have not been shown
to be superior to INS.7,200 In nasal challenge studies, systemic
steroids are effective in reducing AR symptoms, mediator

release, and eosinophil influx during the late phase
response.119,201 An open-label study evaluated the effect of 3
different therapies in patients with seasonal AR: oral loratadine,
oral loratadine with mometasone furoate nasal spray, and oral
antihistamine with oral betamethasone.200 Results showed that
both groups with steroid therapy had significantly higher symptomatic improvements in sneezing, nasal obstruction, watery
nasal discharge, and nasal itching over the 7 days of therapy
than the group with loratadine alone, with no significant difference between the 2 steroid groups. While oral corticosteroids
have potent anti-inflammatory effects, they are not recommended for the routine treatment of AR due to known significant systemic side effects and lack of superiority to INS.
INS are strongly recommended for the treatment of AR by
virtue of their superior efficacy in controlling nasal congestion
and other symptoms of this inflammatory condition.
Prophylactic treatment with INS is best initiated several days
before the pollen season in subjects with known seasonal AR.
Beginning treatment at the recommended dose is suggested
followed by evaluation of the patients response on follow-up.
During this visit, the nose should be examined for signs of
local irritation due to the drug or mechanical trauma from the
applicator itself, and the treatment regimen should be modified according to the patients response. A list of FDAapproved INS, by patient age, can be found in Table 9.
STATEMENT 7. ORAL ANTIHISTAMINES: Clinicians
should recommend oral second-generation/less sedating
antihistamines for patients with AR and primary complaints of sneezing and itching. Strong recommendation
based on RCTs with minor limitations and a preponderance of
benefit over harm.

Quality improvement opportunity: Avoidance of
sedating antihistamine use and promotion of use of
effective symptom-directed therapy
Aggregate evidence quality: Grade A, based on randomized controlled trials with minor limitations
Benefits: Rapid onset of action, oral administration,
relief of symptoms, over-the-counter availability,
potential cost saving (generic brand), relief of eye
symptoms
Risks, harms, costs: Systemic side effects (sedation),
dry eyes, urinary retention
over harm
Role of patient preferences: LargeShared decision
making in considering the benefits, harms, costs,
and evaluation of the best treatment options. Clinicians should offer a comparison of evidence for the
effectiveness of oral versus nasal administration of
S18
Table 9. Intranasal Steroids.
Name
Formulation
FDA
Indications
Age
Contraindications Approved
Propellant,
Triamcinolone
acetonidea (Nasacort aqueous
Allergy 24HR), 55 g
per spray
Seasonal and
perennial AR
History of
hypersensitivity
to medication
or components
2 y
Budesonide (Rhinocort Propellant

AQ) 32 g per spray
AR and
nonallergic
rhinitis
History of
hypersensitivity
to medication
or components
6 y
Flunisolideb (Nasalide 0.025%

or Nasarel), 25 g
solution
per spray
Seasonal and
perennial AR
History of
hypersensitivity
to medication
or components
6 y
Fluticasone
propionateb
(Flonase), 50 g
per spray
0.05% nasal AR and

spray
nonallergic
(aqueous)
rhinitis
History of
hypersensitivity
to medication
or components
4 y
Mometasone furoate
(Nasonex), 50 g
per spray
Aqueous
Seasonal and
perennial AR,
nasal polyps
History of
hypersensitivity
to medication
or components
2 y
Ciclesonide
Aqueous
Seasonal and
(Omnaris), 50 g per suspension perennial AR
spray
History of
hypersensitivity
to medication
or components
6 y
Fluticasone furoate
Suspension
(Veramyst), 27.5 g
per spray
Seasonal and
perennial AR
History of
hypersensitivity
to medication
or components
2 y
HFA
Seasonal and
nonaqueous perennial AR
aerosol
History of
hypersensitivity
to medication
or components
History of
hypersensitivity
to medication
or components
12 y
(Qnasl), 80 g per
spray
Ciclesonide (Zetonna), HFA37 g per spray

propelled
aerosol
Seasonal and
perennial AR
12 y
Dosing
Common Side
Effects
OTC or
Prescription
Age 2-5 y: 1 spray Pharyngitis,

OTC
per nostril
epistaxis, cough
every day
Age 6-11 y: 2
sprays per
nostril every
day
Age 12 y: 2
sprays per
nostril 1 or 2
times per day
Age 6 y: 2 sprays Epistaxis, pharyngitis, Prescription
per nostril
bronchospasm,
twice a day or
coughing, nasal
4 sprays per
irritation
nostril in the
morning
Age 6-14 y: 1
Epistaxis, pharyngitis, Prescription
spray per nostril cough, aftertaste,
3 times per day
nasal burning or
or 2 sprays per
stinging
nostril twice a
day
Age >14 y: 2
sprays per
nostril 2 or 3
times per day
Age 4 y to adult: Headache,
Prescription
1 spray per
pharyngitis,
nostril every
epistaxis, nasal
day
burning or
Adult: 2 sprays
irritation, nausea
per nostril
or vomiting,
every day
asthma symptoms,
cough
Age 2-11 y: 1
Headache, viral
Prescription
spray per nostril infection,
every day
pharyngitis,
Age 12 y: 2
epistaxis, cough
sprays per
nostril every
day
Age 18 y with
polyps: 2 sprays
per nostril
twice a day
Age 6 y: 2
Epistaxis, headache, Prescription
sprays per
nasopharyngitis,
nostril every
ear pain,
day
pharyngolaryngeal
pain
Age 2-11 y: 1-2 Epistaxis, headache, Prescription
sprays per
pharyngolaryngeal
nostril every
pain, nasal
day
ulceration, back
Age >11 y: 2
pain, pyrexia, cough
sprays per
nostril every
day
Age 12 y: 2
Nasal discomfort, Prescription
sprays per
epistaxis, headache
nostril every
day
Age 12 y: 1 spray Nasal discomfort, Prescription
per nostril
epistaxis, headache
every day
Abbreviations: AR, allergic rhinitis; HFA, hydrofluoroalkane; OTC, over the counter.
a
Only preparation available OTC.
b
Available in generic form.
S19
Seidman et al
antihistamines and nasal steroids that will provide
good patient adherence and treatment efficacy.
Exclusions: None
Policy level: Strong recommendation
Supporting Text
The purpose of this statement is to define the role and encourage the use of oral antihistamines in the treatment of AR.
These agents have been in use since the 1940s, and numerous
controlled clinical studies have established their effectiveness, in both children and adults, for relief of symptoms
including rhinorrhea, sneezing, itching, and nasal blockage as
well as associated ocular complaints.202-206 While these agents
may not be as effective as INS, they are adequate for many
patients with mild to moderate disease and have the advantage
of lower cost, rapid onset of action, and effectiveness for
intermittent symptoms.
Oral antihistamines, which block the action of histamine
on the H1 receptor, have numerous anti-inflammatory effects206
and can be broadly categorized as first- or second-generation
agents. Older first-generation agents, which are lipophilic and
cross the blood-brain barrier, also have antimuscarinic effects.
Newer second-generation agents are highly selective for the
H1 receptor and have limited penetration of the central nervous system. Examples of first-generation medications
include diphenhydramine, chlorpheniramine, and hydroxyzine. The use of first-generation agents is limited by the side
effects of sedation and mucosal dryness. It is important to recognize that performance impairment may occur even when
patients have no obvious perception of drowsiness.207,208
Commonly used second-generation drugs include fexofenadine, cetirizine, levocetirizine, loratadine, and desloratadine.
In almost all situations, second-generation antihistamines are
preferred. There are relatively few comparative studies among
the various compounds of second-generation antihistamines,
but data indicate that cetirizine and its active enantiomer,
levocetirizine, are the most potent209-212 but carry a modest
risk of sedation not seen with other drugs in this class.208,213,214
Advantages of oral antihistamines include rapid onset of
action,215,216 once-daily dosing, maintenance of effectiveness
with regular use, and the availability of some drugs without a
prescription. Some patients who fail to improve with one
agent may respond to an alternative drug in this category.217,218
Maximum benefit is seen with continuous use,219,220 but use
on an as-needed basis can provide significant symptom relief
and is appropriate for some patients, especially those with
intermittent symptoms.221
Although most studies have shown that INS, used on a continuous basis, is superior to oral antihistamines for treatment
of AR, especially for symptoms of nasal congestion,150,222-226
an antihistamine, used as a single agent either intermittently or
continuously, may provide adequate relief for many individuals. Oral antihistamines usually produce no further improvement when added to treatment with INS, although the addition
of as-needed INS to a regularly taken oral antihistamine is a
viable strategy.227,228 The decision to use oral agents rather
than intranasal sprays is often a matter of patient preference,

and consideration of this preference may promote better
adherence to therapy. Table 10 provides a list of FDAapproved oral antihistamine medications for AR, including
contraindications, common side effects, approval age, and
availability (over the counter or prescription).
STATEMENT 8. INTRANASAL ANTIHISTAMINES:
Clinicians may offer intranasal antihistamines for patients
with seasonal, perennial, or episodic AR. Option based on
RCTs with minor limitations and observational studies, with
equilibrium of benefit and harm.

Quality improvement opportunity: Improve awareness of this class of medications as another effective
treatment for AR that may be an alternative to other
medication classes
Aggregate evidence quality: Grade A, based on randomized controlled trials with minor limitations and
Level of confidence in evidence: High, but most of
the trials were of short duration
Benefits: Rapid onset, increased effectiveness over
oral antihistamines for nasal congestion
Risks, harms, costs: Increased cost relative to oral
antihistamines, poor taste, sedation, more frequent
dosing, epistaxis, local side effects
Benefit-harm assessment: Equilibrium
Value judgments: The Guideline Development Group
felt that in general this class of medications would
represent second-line therapy after failure of nasal
steroids or oral antihistamines due to poor acceptance, taste, and cost but that there may be specific
patients in whom this class would be an appropriate
first-line therapy.
Role of patient preferences: LargeThere is equilibrium of benefits to risks when using intranasal antihistamine. Shared decision making may help ensure
that the patient understands the potential benefits
versus harms of undergoing this treatment, while
also promoting patient compliance with medication.
Exclusions: Not approved for children younger than
5 years.
Differences of opinion: Minor; there are reasonable
data supporting their use, but there was some debate
regarding the harm-benefit ratio leading this to be an
option. Several panel members thought these should be
recommended at the same level as oral antihistamines.
Supporting Text
The purpose of this statement is to address the use of intranasal antihistamines for patients with AR. Antihistamine allergy
medications are H1-receptor antagonists, and 2 intranasal
antihistamines are currently approved by the US FDA for
S20
Table 10. Allergic Rhinitis Oral Antihistamines.
Medication
FDA Indications
(Seasonal,
Perennial)
Contraindications
Approved Ages
Cetirizine
(Zyrtec)
Both
Hypersensitivity
6 months
to cetirizine,
levocetirizine, or
hydroxyzine
Levocetirizine
(Xyzal)
Both
Hypersensitivity
6 months
to levocetirizine,
cetirizine, or
hydroxyzine
Fexofenadine
(Allegra)
Seasonal
Hypersensitivity to 2 years
fexofenadine
Loratadine (Claritin,Both
Alavert)
Desloratadine
(Clarinex)
Both
Hypersensitivity
2 years
to loratadine or
desloratadine
Hypersensitivity to 6 months
desloratadine or
loratadine
Common Side
Effects
Dosing
Occasional
Age 2-5 y: 2.5 mg
sedation, mucosal 1 or 2 times per
dryness, urinary
day
retention
Age 6-12 y: 5-10
mg/d
Age 12-65 y: 10
mg/d
Age 66-76 y: 5-10
mg/d
Age 77 y: 5 mg/d
Occasional
Age 2-5 y, 1.25
sedation, mucosal mg/d
dryness, urinary Age 6-11 y, 2.5
retention
mg/d
Age 12 y, 2.5-5.0
mg/d
Occasional
Age 2-11 y, 30 mg
headache
twice a day
Age 12 y, 60 mg
twice a day or
180 mg/d
Possible sedation Age 2-5 y, 5 mg/d
with higher than Age 6 y, 10 mg/d
usual doses
Possible sedation Age 2-5 y, 1.25
with higher than
mg/d
usual doses
Age 6-11 y, 2.5
mg/d
Age 12 y, 5 mg/d
OTC or
Prescription
OTC
Prescription
OTC
OTC
Prescription
Abbreviation: OTC, over the counter.
treatment of AR. Azelastine and olopatadine are both secondgeneration H1-receptor antagonists and have equal efficacy in
head-to-head, placebo-controlled comparison studies.229 The
formulations of these 2 antihistamines are listed in Table 11.
One of the benefits of intranasal application is targeted
delivery and increased dosage to nasal tissues while limiting
systemic effects.230 For the treatment of nasal symptoms,
intranasal antihistamines have shown equality or superiority
to oral antihistamines in numerous well-designed randomized,
controlled, and blinded studies.231-233 Intranasal antihistamines
show benefit even in patients who fail oral antihistamine
treatment.233,234 Specifically with regard to nasal congestion,
intranasal antihistamines are more efficacious than oral preparations.232,235,236 Intranasal antihistamines also have the advantage of rapid onset of action in the range of 15 to 30 minutes,
which is much faster than in the oral route (average onset 150
minutes).231,237 Numerous studies have compared INS to intranasal antihistamines. The results are conflicting, with some
showing equality238-240 and some showing superiority of
INS.149,241 Heterogeneity, lack of standardized dosing, lack of
validated outcome metrics, and short-term follow-up limit the
applicability of these comparisons.
Formulations and recommended doses for the available

intranasal antihistamines are shown in Table 11. Olopatadine
is FDA approved for treatment of seasonal AR in adults and in
children 6 years and older. Azelastine 0.1% is approved for
age 6 years and older. The azelastine 0.15% solution plus sorbitol and sucralose (added to improve taste) formulation is
approved for both seasonal and perennial AR in adults and in
children 6 years and older.
The most common adverse events related to intranasal antihistamine use are bitter taste, epistaxis, headache, somnolence, and nasal burning. Bitter taste occurs in 2% to 18% of
patients using intranasal antihistamines229,240,242,243 compared
with 0% to 0.2% of patients using INS240,243 and may reduce
patient compliance. While taste aversion has been demonstrated to all intranasal antihistamines, taste varies between
formulations. Therefore, a trial of a second formulation may
be preferred in patients who have had symptomatic benefit.
While early studies quoted somnolence rates around 11%,232
more recent studies have found rates of 0.4% to 3%, which
were equal or only slightly greater than in placebo groups.7,233,234,243,244 In side-by-side comparisons, the somnolence
rates of inhaled antihistamines, inhaled nasal steroids, and
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Seidman et al
Table 11. Allergic Rhinitis (AR) Intranasal Antihistamines.
Medication
FDA Indications
Contraindications
Approved Ages
Dosing
Olopatadine
Seasonal AR
(Patanase) (as
HCl) 0.6% (665
g per spray);
aqueous nasal
spray
Azelastine (Astelin) Seasonal AR,
0.1% solution
vasomotor
(137 g per
rhinitis
spray)
None
6 y
Age 6-11 y: 1 spray

twice a day
Age 12 y: 2 sprays
twice a day
None
6 y
Azelastine
Seasonal AR,
(Astepro) 0.15% perennial AR
solution (205.5
g per spray)
None
6 y
Azelastine plus
Seasonal AR
fluticasone
(Dymista) (137
g of azelastine,
50 g of
fluticasone per
spray)
None
12 y
Age 6-11 y: 1 spray

twice a day
Age 12 y: 1-2
sprays twice a
day or 2 sprays
daily
Age 6-11 y: 1 spray
twice a day
Age 12 y: 1-2
sprays twice a
day or 2 sprays
daily
1 spray per nostril
twice a day
placebo have been equivalent.240,243 Somnolence rate ranges

of intranasal antihistamines (0.9%-11.5%), oral antihistamines (1.3%-14%), and placebo (0.3%-10%) overlap as
well.7,232,234 Caution should be taken at the initiation of intranasal antihistamines for signs of somnolence, and follow-up
with a clinician is advised to assess response and side effects.
Intranasal antihistamines are an effective treatment for AR
and can be used as first- or second-line therapy. Due to the
rapid onset of action and targeted delivery of intranasal antihistamines, they are especially useful in patients with episodic
nasal symptoms or as a pretreatment prior to nasal allergen
exposure. The need for twice-daily dosing and the side effects
of somnolence and bitter taste, however, may lead clinicians
and/or patients to prefer initial treatment with a different class
of medication. Table 11 summarizes a list of FDA-approved
intranasal antihistamine medications for AR which includes
contraindications, common side effects, approval age, and
availability (over the counter or prescription). An AR medication recommendation guideline is summarized in Table 12.
STATEMENT 9. ORAL LEUKOTRIENE RECEPTOR
ANTAGONISTS (LTRAs):Clinicians should not offer
LTRAs as primary therapy for patients with AR.
Recommendation against based on RCTs and systematic
reviews, with a preponderance of benefit over harm.
Common Side
Effects
OTC or
Prescription
Bitter taste
Epistaxis
somnolence
Headache
Prescription
Bitter taste
Epistaxis
Somnolence
Headache
Prescription
Bitter taste
Epistaxis
Somnolence
Headache
Prescription
Bitter taste
Epistaxis
Somnolence
Headache
Prescription

Quality improvement opportunity: Reduced use of a
less effective agent for initial therapy
Aggregate evidence quality: Grade A, based on randomized controlled trials and systematic reviews
Benefits: Avoid ineffective or less effective therapy,
cost saving, decreased variations in care
Risks, harms, costs: There may be a subset of patients
who would benefit from this medication (eg, patients
with both AR and asthma).
over harm
Value judgments: The panel was concerned with the
cost of this medication in combination with the evidence that it is less effective than first-line medications.
Role of patient preferences: LowRare patients
with intolerance of intranasal therapy and concerns
regarding somnolence may benefit from consideration of use of this class of medicine.
Exclusions: Patient with concurrent diagnosis of
asthma. These patients may benefit from oral leukotriene receptor antagonists as a first-line therapy.
S22
The plus symbols indicate the relative effectiveness for each medication class for the various symptoms: for example, most effective for congestion (+++) but also effective for each of the other symptoms (+).
One of the intranasal antihistamines available in the United States (Astepro) is indicated for perennial/persistent AR.
b
Low
Not as
monotherapy
Yes
Yes
No
No
+
+
+
+
Large
+
++
+b
++
++
++
++
++
++
+b
++
Large
No
+
+
++
+
+
++
++
+
++
Large
++
++
++
++
+
++
+++
+++
Intranasal
steroids
Oral
antihistamines
Intranasal
antihistamines
Leukotriene
receptor
antagonist
+++
+++
++
Severe
Mild
Persistent
Intermittent
Episodic
Perennial
Seasonal
Nasal Itching
Sneezing
Congestion Rhinorrhea
Medication
Class
Recommendations
for Symptoms
Table 12. Guideline Medication Recommendations.a
Recommendations for
Exposure to Allergen
Recommendations for
Symptom Frequency
Recommendations for
Symptom Severity
Patient
Preference

Supporting Text
The purpose of this statement is to reduce the use of a more
expensive, less effective agent as first-line treatment of AR.
The LTRA montelukast is FDA-approved for treatment of
symptoms of seasonal AR in adults and pediatric patients 2
years of age and older and perennial AR in adults and pediatric
patients 6 months of age and older. While several other LTRAs
are available in the United States, montelukast is the only LTRA
approved by the FDA for AR. Systematic literature reviews and
meta-analyses (predominantly based on controlled studies of
montelukast in adults with seasonal AR) conclude that LTRAs
are more effective at controlling symptoms and improving quality of life than placebo.245-248 While some studies have shown that
LTRAs are as effective as oral antihistamines,151,245,247,248 others
have shown that LTRAs are less effective246 than oral antihistamines and INS.151,245-248 In a single randomized, double-blind
study, montelukast had a similar effect to pseudoephedrine in
reducing symptoms of AR except the symptom of nasal congestion, for which pseudoephedrine was more effective.249 In patients
having both AR and asthma, montelukast improves both
conditions.250-253
Montelukast is generally well tolerated and is not associated
with drowsiness.254 In placebo-controlled trials, behavior-related
adverse events were infrequent.255 However, some postmarketing
reports have demonstrated rare drug-induced neuropsychiatric
events (including aggression, depression, suicidal thinking, and
behavior).256 Suicidal ideation was reported in 1 of 9929 patients
(0.01%) in clinical trials treated with montelukast.257
Montelukast has traditionally been more expensive than oral
antihistamines,258 although the cost differential has been lessened
with the introduction of generic montelukast. Because montelukast is currently more expensive and equally as effective as or
less effective than oral antihistamines for AR, and because it
is less effective than INS, clinicians should not routinely offer
an LTRA as primary therapy for patients with AR. However,
there may be a subset of patient who have AR and asthma who
may benefit from this medication.
STATEMENT 10. COMBINATION THERAPY: Clinicians
may offer combination pharmacologic therapy in patients
with AR who have inadequate response to pharmacologic
monotherapy. Option based on RCTs with minor limitations and
observational studies, with equilibrium of benefit and harm.

Quality improvement opportunity: Reduce variations
in care, improve symptom control
Aggregate evidence quality: Grade A, based on randomized controlled trials with minor limitations and
Level of confidence in evidence: High. There is
strong evidence supporting the use of some combinations and the ineffectiveness of other combinations.
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Seidman et al
Benefits: Improved effectiveness and symptom control of combined therapy
Risks, harms, costs: Increased cost, overuse of medication, use of ineffective combinations, multiple
medication side effects, drug interactions
Benefit-harm assessment: Equilibrium
Intentional vagueness: The term combination
therapy is nonspecific as there are multiple different combinations. The details are elaborated in the
supporting text. The term inadequate response to
monotherapy also allows for some interpretation by
clinicians and patients.
Role of patient preferences: ModerateShared decision making in consideration of evidence for benefits,
harms and cost of combinations, effective dosing,
and potential medication interactions to assist the
patient in more effective treatment compliance.
Exclusions: Decongestants that are part of some
combined products are not approved for children
under the age of 4 years.
Supporting Text
The purpose of this statement is to promote the use of effective
and decrease the use of ineffective pharmacologic combinations for the treatment of AR. When initial therapy with an INS
does not lead to adequate control of allergic nasal symptoms, or
the patient cannot tolerate INS, the practitioner may choose
combination therapies, of which the most effective additive to
an INS is an intranasal antihistamine. In severe nasal obstruction, adding topical oxymetazoline to INS for a few days has
proven benefit, but due to concerns about nasal rebound, topical oxymetazoline use should be limited to a few days. If nasal
sprays are disliked or not tolerated, combination therapy of an
oral antihistamine and decongestant is the next most effective
pharmacotherapy for AR. The selection of effective pharmacotherapy for AR may be influenced by coexisting conditions of
allergic conjunctivitis or asthma. While oral antihistamines and
INS are common selections for primary monotherapy, their
combination does not offer much clinical benefit.
Intranasal Steroids and Oral Antihistamines

When patients have no response to INS or incomplete control
of nasal symptoms with an INS, oral antihistamines should
not be routinely used as additive therapy. The largest trials
have shown no benefit of taking an INS plus oral antihistamine compared with INS plus placebo in adults.259,260
A Cochrane review including only one study of adequate
quality found no evidence to support this combination in
children.261
Oral Antihistamines and Oral Decongestants

Oral antihistamines and oral decongestant combinations control AR symptoms better than either oral antihistamine or oral
decongestant alone. This benefit has been consistently demonstrated in multiple randomized, placebo-controlled trials,
each with more than 500 subjects enrolled.262-270 Adding an
oral decongestant to a second-generation antihistamine
increases side effects of insomnia, headache, dry mouth, and
nervousness.263,264,267 Additionally, the potential for tolerance
from chronic use of oral decongestants may be seen.
In one study, 24-hour extended-release pseudoephedrine
(240 mg) caused less insomnia than 12-hour extendedrelease pseudoephedrine (120 mg) taken twice daily (4% vs
15%, P < .01).271 A 2005 meta-analysis concluded that
pseudoephedrine caused a small but significant increase in
systolic blood pressure (0.99 mm Hg; 95% CI, 0.08 to 1.90)
and heart rate (2.83 beats/min; 95% CI, 2.0 to 3.6), with no
effect on diastolic blood pressure (0.63 mm Hg, 95% CI,
0.10 to 1.35).272 Oral decongestant use is not recommended for patients under 4 years of age, and the extendedrelease, 120-mg, 12-hour dose is not recommended for
patients under 12 years of age.
Oral Antihistamines and Leukotriene Receptor

Antagonists
There is conflicting evidence as to whether combined treatment
with oral antihistamine and LTRA is superior to either as single
treatment, and therefore routine use of combined therapy is not
recommended. Combinations of oral antihistamines and LTRAs
were equivalent to oral antihistamine alone within arms of several studies.273-277 Alternatively, some trials showed that oral
antihistamine plus LTRA was superior to oral antihistamine
alone278-280 or LTRA alone278,279 for AR symptoms. Other studies
showed a benefit when combining oral antihistamine and LTRA
compared with oral antihistamine or LTRA in preventing symptoms,281 in patients who had poor control with LTRA monotherapy,282 and specifically in nighttime symptoms.276 Combination
of oral antihistamine and LTRA is either inferior to273,283-285 or
less likely equivalent to277 INS monotherapy in control of AR
symptoms.
Intranasal Steroids and Leukotriene Receptor

Antagonists
LTRAs should not routinely be used as additive therapy for
patients benefiting from INS for AR.283,286,287 Three studies
with arms that compared INS to INS + LTRA did not show a
significant benefit to adding LTRA for their primary outcome.
The largest trial enrolled 102 patients.287
Intranasal Steroids and Intranasal

Antihistamines
The combination of INS and intranasal antihistamine is more
effective than INS or intranasal antihistamine monotherapy
for AR.243,288-290 This benefit has been demonstrated across
multiple symptoms of AR and in patients with moderate to
severe symptoms.290 In patients who tolerate INS or intranasal
antihistamine spray and have inadequate control of AR symptoms with a single agent, combined INS + intranasal antihistamine is an effective option.243,288-290
S24

Intra-Nasal steroid (INS)
monotherapy
Oral Antihistamine
monotherapy
Intranasal Antihistamine
monotherapy
Inadequate control of symptoms
Add
Intranasal Antihistamine
or
Oxymetazoline (3 days or less)
Add
Oral Decongestant
(increased side effects of
headache, dry mouth,
hypertension, and nervousness.)
Add
Intranasal steroid
Do not add
Oral Antihistamine
or
Leukotriene Receptor Antagonists
Limited data on other combinations
Could add
Leukotriene Receptor
Antagonoist (evidence mixed)
Do not add
Intra-Nasal steroid
(Reasonable to change to INS, but
adding not helpful)
Figure 1. Recommendations for adding a second medication to treat allergic rhinitis.
Intranasal Steroids and Intranasal

Oxymetazoline
The combination of INS and intranasal oxymetazoline is more
effective in controlling AR symptoms than either monotherapy.291-294 The development of rhinitis medicamentosa
(rebound nasal congestion from overuse of intranasal oxymetazoline) is a concern. The sizes and lengths of the currently available studies are insufficient to draw conclusions
about the risk of rhinitis medicamentosa. Short-term use (<3
days) of this combination in cases of severe nasal congestion
is recommended. Figure 1 illustrates the recommendations
for adding a second medication to treat allergic rhinitis.
STATEMENT 11. IMMUNOTHERAPY: Clinicians
should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with AR
who have inadequate response to symptoms with pharmacologic therapy with or without environmental controls.
Recommendation based on RCTs and systematic reviews, with
a preponderance of benefit over harm.

Opportunity for quality improvement: Increased
appropriate use of immunotherapy and reduced variation in care; increased awareness of immunotherapy
Aggregate evidence quality: Grade A, based on randomized controlled trials and systematic reviews
Benefits: Altered natural history, improved symptom
control, decreased need for medical therapy, longterm cost-effectiveness, may improve or prevent
asthma or other comorbidities, and may prevent new
sensitizations
Risks, harms, costs: Local reactions, systemic reactions including anaphylaxis, increased initial cost,
frequency of treatment (logistics), pain of injection,

delayed onset of symptom control (months)
over harm
Intentional vagueness: We elected to use the term
inadequate response to medical therapy as there
are circumstances where immunotherapy may be
beneficial for symptom control even if there is some
response to medical therapy since immunotherapy
addresses the underlying pathophysiology of atopy.
Role of patient preferences: LargeThere are potential
risks, harms, and costs associated with the use of immunotherapy and a delayed onset. Shared decision making
may help the patient understand the potential harms of
undergoing this treatment. In addition, the efficacy of
using this mode of therapy depends on patient compliance with frequency and duration of treatment as well
as delay in onset of effect with immunotherapy.
Exclusions: Uncontrolled asthma
Policy Level: Recommendation
Differences of opinion: Minor; some panel members

felt that immunotherapy could be offered as first-line
treatment to patients who elect not to use medical
therapy.
Supporting Text
The purpose of this statement is to increase the awareness of
immunotherapy as a treatment for AR, promote its appropriate use, and reduce unnecessary or harmful variation in care.
Allergen-specific immunotherapy (SIT) involves controlled, repetitive dosing of allergen(s) in patients diagnosed
with IgE-mediated AR by history and confirmed with specific
allergy testing in order to increase immune tolerance to the
offending allergen(s). The ultimate goal of SIT is to decrease
S25
Seidman et al
Table 13. Comparison of Features of SCIT and SLIT.
SCIT
SLIT
Effectiveness for allergic

rhinitis
Safety
Rate of systemic reactions
Dosing
Supported by systematic reviews of randomized

controlled trials
Deaths: 1 per 2.5 million injections
0.06%-0.9%
Administered in physicians office
FDA status
FDA approved
Socioeconomic
CPT code exists for SCIT vial preparation and

injections
Covered by most insurance plans
Supported by systematic reviews of randomized

controlled trials
No reported deaths
0.056%
Administered at home
SLIT aqueous dosing not standardized
First dose of SLIT tablet should be administered in
physicians office
SLIT aqueous FDA off-label use
SLIT tablets approved by FDA in April 2014; limited
number of allergens available for treatment
No CPT code exists for SLIT aqueous preparation.
SLIT aqueous not covered by most insurance plans.
SLIT tablet insurance coverage to be determined by
individual insurance carriers.
Abbreviations: CPT, Current Procedural Terminology; SCIT, subcutaneous immunotherapy; SLIT, sublingual immunotherapy.
AR symptoms. SIT is the only proven treatment for AR that

has the potential to change the natural history of the disease.
There is a large role for patient preference in the decision to
undertake immunotherapy, as the therapy carries potentially
serious risks (such as anaphylaxis), has added costs (ie, frequent office visits for injections), and entails delayed onset of
symptom control, and the duration of therapy is several years.
In the United States, 2 forms of immunotherapy are in clinical
use: subcutaneous immunotherapy (SCIT), and sublingual
immunotherapy (SLIT) in aqueous and tablet form.295 The
FDA approved SLIT tablets for use in the United States in
April 2014; however, there are no FDA-approved aqueous
formulations, and therefore using any aqueous SLIT would be
considered an off-label use. Currently there are no US practice
guidelines specifically addressing the dosing of aqueous SLIT,
which is not standardized. Typically, SCIT injections are performed at a physicians office at regular intervals, while SLIT
is administered daily at home with the allergen held under the
tongue for mucosal absorption for a short period of time. It
must be emphasized that demonstration of IgE-mediated
allergy based on history and confirmed by specific allergy
testing (skin or in vitro) is a prerequisite for all forms of
immunotherapy, both SLIT and SCIT. The typical duration of
treatment for either form of immunotherapy is several years,
typically 3 to 5 years.296,297
Both SCIT and SLIT have been shown to be efficacious in
reducing the symptoms of AR in several large-scale systematic
reviews. A 2013 systematic review of the efficacy of SCIT for
AR included 61 RCTs and found high-grade evidence that SCIT
reduces AR symptoms, with moderate evidence that SCIT
decreases medication usage.298 This confirms the findings of
previous systematic reviews of SCIT, which found reductions
in rhinitis symptom scores and medication use.101,299,300 The
efficacy of SLIT for AR has also been confirmed by several
systematic reviews.296,301,302 The most recent of these included
63 RCTs of SLIT, providing a moderate grade level of evidence
that SLIT improves AR symptoms.296 Both forms of SIT have

been shown to improve the control of comorbid conditions,
such as asthma,102,298,303 conjunctivitis,298,303,304 and diseasespecific quality of life298,303; in addition, RCTs have shown that
SIT may prevent the development of asthma305-307 and new
allergic sensitivities.307,308 The positive effects of immunotherapy can continue after discontinuation of SIT, with studies documenting continued beneficial effects at 10 and 8 years after
treatment cessation for SCIT309 and SLIT, respectively.310
Patients on SIT should be monitored on a regular basis for
effectiveness based on clinical parameters such as symptoms
and medication use; typically, positive benefits of immunotherapy on AR symptoms appear from several weeks to 1 year after
initiation of therapy, but repetitive allergy testing is not
recommended.297
While SIT has been shown to be beneficial in AR, the use
of immunotherapy has potential adverse events. These reactions are classified as either local or systemic. In SCIT, local
reactions include redness and induration at the site of injection; in SLIT, local reactions include oral itching and discomfort. The rates of local reactions have been reported to be in
the range of 0.6% to 58% for SCIT and 0.2% to 97% for
SLIT.303 Systemic reactions can be provoked by either form of
SIT and can include urticaria, gastrointestinal upset, wheezing, and anaphylaxis. For SCIT, the rate of systemic reactions
has been reported to be 0.06% to 0.9%311 and deaths have been
reported at 1 per 2.5 million SCIT injections (3.4 deaths per
year)312; for SLIT, systemic reactions are reported at 0.056%,
with no reported deaths.303,311 Due to the potential for serious
reactions, current practice guidelines indicate that SCIT
should not be used in patients with uncontrolled asthma, SCIT
should be administered in a physicians office where serious
reactions can be promptly recognized, and the patient should
be observed for 30 minutes after injection.297 However, a prospective observational study was conducted of 635,000
patients who received more than 1 million injections of
S26
immunotherapy; the injections were either self-administered

by patients at home or administered by medical staff in-office.
No hospitalizations or deaths were reported, and the authors
concluded that home immunotherapy was safe in selected
patients when using appropriate precautions.313 In addition,
the use of -blockers is a relative contraindication as this may
complicate the treatment of anaphylaxis.297 SLIT dosing is
generally done at home because of the perceived improved
safety profile. However, there have been reports of anaphylaxis with SLIT,314 and in Europe there have been calls for the
first dose of sublingual immunotherapy tablets to be given in
a physicians office.315 The recommendations regarding the
SLIT tablets recently approved by the FDA also include the
first administration of the tablet in a physicians office with a
30-minute observation period and prescription of an autoinjectable epinephrine device as a precaution for home administration of the tablet.316-319 The SLIT tablet is contraindicated
in patients with severe, unstable, or uncontrolled asthma.
While the risks of serious systemic adverse events are very
rare for either form of SIT, patients considering immunotherapy should be informed of this risk. The overall benefit-harm
assessment of SIT demonstrates a preponderance of benefit, in
consideration of this effective form of therapy with potential
for disease modification and the very rare risk for serious
reactions.
Both SCIT and SLIT have been shown to be efficacious for
AR, but there is ongoing debate as to whether one form is
superior; systematic reviews have addressed this subject.320-322
The first of these320 concluded that superiority of one mode
over another could not be consistently demonstrated through
indirect comparison. The second systematic review of 8 RCTs
with head-to-head comparisons of SCIT versus SLIT321 provided moderate-grade evidence for greater effectiveness of
SCIT for nasal symptom reduction; however, the authors concluded that additional studies are required to strengthen this
evidence base for clinical decision making. In addition, a
pooled analysis of SCIT studies compared with SLIT studies
for grass allergens showed a significantly higher effect size on
seasonal AR symptoms and medications scores with SCIT
compared with SLIT.322 Table 13 compares some additional
features of SCIT and SLIT.
These guidelines apply to children and adults with AR, diagnosed by history and confirmed by specific allergy testing (see
Key Action Statement 2 regarding allergy testing). SIT should be
offered to patients with AR whose response to pharmacologic
therapy is inadequate. However, immunotherapy may be beneficial for symptom control even if there is partial response to medical therapy, as SIT is currently the only form of treatment with the
potential to alter the natural history of the disease. Other potential
indications for pursuing immunotherapy may include patient
preference, adherence to therapy, medication requirements,
response to avoidance measures, adverse effects of medications,
coexisting allergic asthma, and possible prevention of asthma in
patients with AR. In addition, recent literature suggests there may
be a long-term cost savings with immunotherapy. The economic
considerations regarding immunotherapy were evaluated, and
evidence supports the cost-effectiveness of immunotherapy
(SCIT and SLIT) compared with pharmacotherapy for AR.323 A

recent systematic review found a need for further research to
determine the relative cost-effectiveness in comparing SCIT with
SLIT324; a 2012 US study found a wide variation of cost to the
patient in regard to SCIT by insurance plan, and the cost of SLIT
varied between practices 4-fold.325 While there are significant
benefits of immunotherapy in AR, the decision to pursue immunotherapy should be based on shared decision making between
the physician and the patient.
STATEMENT 12. Inferior Turbinate Reduction:
Clinicians may offer, or refer to a surgeon who can offer,
inferior turbinate reduction in patients with AR with nasal
airway obstruction and enlarged inferior turbinates who
have failed medical management. Option based on observational studies, with a preponderance of benefit over harm.

Quality improvement opportunity: Improved nasal
breathing and quality of life
Level of confidence in the evidence: Moderate
Benefits: Improved symptoms, improved quality of
life, improved medication delivery, reduced medication use, better sleep
Risks, harms, costs: Unnecessary surgery, cost of
surgery, risks of surgery, atrophic rhinitis
Benefit-harm assessment: Balance of benefit and harm
Value judgments: The panel felt that in spite of lack
of head-to-head trials between medical and surgical
therapy, surgery should be reserved for patients failing medical therapy due to the higher risk of any surgical management.
Intentional vagueness: The panel elected to use the
term failure of medical therapy as there are circumstances where inferior turbinate reduction may
be beneficial for symptom control even if there is
some response to medical therapy.
Role of patient preferences: LargeClinicians
should use a shared decision-making process about
the risks, benefits, and costs of undergoing surgery
and associated use of anesthesia.
Exclusions: Patients who are not surgical candidates
Differences of opinion: Minor difference of opinion
whether AR is an independent risk factor for turbinate hypertrophy
Supporting Text
The purpose of this statement is to increase awareness of and
allow for appropriate use of inferior turbinate reduction surgery
as part of the management for AR patients with persistent nasal
symptoms and turbinate hypertrophy despite medical treatment.
The inferior turbinates are tissues located on the lateral
wall of the inside of the nose that consist of bone covered with
tissue that can enlarge and swell in response to inflammation.
S27
Seidman et al
Nasal airway obstruction, secondary to hypertrophic inferior
turbinates, is a common symptom of AR. Several surgical procedures are available for addressing inferior turbinate hypertrophy. These generally involve different methods for
removing either (1) entire portions of the turbinate (turbinectomy) or (2) only the tissues between the mucosal covering
and/or the bone of the turbinate (submucous resection); or
shrinking the volume of the turbinate (tissue ablation). One
prospective randomized study of 382 patients with inferior
turbinate hypertrophy compared turbinectomy, laser cautery,
electrocautery, cryotherapy, submucosal resection, and submucosal resection with inferior turbinate outfracture.326 Of
these methods, submucous resection with outfracture was the
most effective surgical therapy with the fewest complications.
These procedures have been described as being performed
under local anesthetic, sedation, or a general anesthetic.
Currently, the 2 most common techniques for turbinate
reduction are submucous resection and tissue ablation. One
prospective randomized study of 60 patients assessed the
long-term effect of tissue ablation and submucous resection.327
Both techniques reduced subjective nasal obstruction at 3 and
6 months. However, the submucous resection group had
greater nasal patency at 12 months post treatment compared
with the group that underwent tissue ablation.327
A nonblinded randomized trial of 58 perennial AR patients
who had failed oral antihistamines compared inferior turbinate reduction surgery to INS and assessed the outcome of
nasal congestion.328 After 1 year, both groups had reduction in
nasal resistance by acoustic rhinometry. However, the surgical
group had statistically significant improvement in nasal congestion symptoms, while the medical group showed a nonsignificant trend for improvement.
Several uncontrolled studies suggest that inferior turbinate
procedures may also diminish the symptoms of rhinorrhea and
sneezing in patients with AR.329-331 Fukazawa et al330 prospectively evaluated 95 patients who underwent inferior turbinate
reduction for nasal congestion due to AR. The patients had
reduced nasal congestion, rhinorrhea, and sneezing at 1, 3, 6,
and 12 months after the procedure. Another uncontrolled prospective cohort of 60 patients undergoing submucous resection of the inferior turbinates showed a decreased nasal
response to allergy provocation test at 2 and 12 months after
the procedure.329 A second report in this cohort with 3- and
5-year follow-up demonstrated sustained improvement of
symptoms of nasal congestion, sneezing, and rhinorrhea.331
However, patients with persistent symptoms after surgery may
require ongoing medical treatment.
While generally considered to be safe, inferior turbinate
reduction can be complicated by nasal bleeding, synechiae
(scar) formation, or crusting. Rarely atrophic rhinitis (empty
nose syndrome) can be a complication from inferior turbinate
reduction, in which patients have the sensation of nasal
obstruction due to lack of sensations of airflow. Atrophic rhinitis is very rare when only submucous resection, rather than
turbinectomy, is performed. Finally, turbinate reduction is a
surgical procedure with the attendant cost of surgery and the
general risks of anesthesia.
While primary medical management is favored as the initial

treatment for AR due to its high efficacy, low risk, and relatively
low cost, inferior turbinate reduction surgery is a reasonable
option for those AR patients with inferior turbinate hypertrophy
who have continued symptoms despite medical management or
in those patients who cannot tolerate medical treatment.
STATEMENT 13. ACUPUNCTURE: Clinicians may offer
acupuncture, or refer to a clinician who can offer acupuncture, for patients with AR who are interested in nonpharmacologic therapy. Option based on RCTs with limitations,
observational studies with consistent effects, and a preponderance of benefit over harm.

Quality improvement opportunity: Increased awareness of acupuncture as a treatment option for AR
Aggregate evidence quality: Grade B, based on randomized controlled trials with limitations, observational studies with consistent effects
Level of confidence in evidence: Low; the randomized
trials did not show comparison to traditional medical
therapy for AR and had methodological flaws.
Benefits: Effective alternative to medical therapies,
reduction of symptoms, may more closely align with
patient values, improved quality of life, avoidance of
medication use and potential side effects
Risks, harms, costs: Logistics of multiple treatments,
need for multiple needle sticks, cost of treatment,
rare infections
Benefit-harm assessment: Equilibrium of benefit and
harm
Value judgments: Panel members varied in their preconceived bias for or against acupuncture.
Role of patient preferences: LimitedPotential for
shared decision making
Exclusions: None
Supporting Text
The purpose of this statement is to enable patient access to
potentially beneficial nontraditional treatment and increase
awareness of the possible benefit of acupuncture in the treatment of patients with AR.
The NIH National Center for Complementary and Alternative
Medicine (NCCAM) defines acupuncture as a family of procedures involving the stimulation of points on the body. The
technique that has been most often studied involves penetrating the skin with thin, solid, metallic needles that are manipulated by hand or by electrical stimulation. There are no
published estimates of the frequency of acupuncture for AR in
the United States, but a nested case-control study of adults
with allergic disease in Germany reported that lifetime acupuncture use was 17% for those with AR.332 A 2006 systematic review of complementary and integrative medicine by the
S28
Allergic Rhinitis and its Impact on Asthma (ARIA) group

found that most of the studies up to then were uncontrolled,
not randomized, and primarily descriptive.333 Their evaluation
of the RCTs available at the time suggested that results were
inconsistent and found that there was no clear evidence supporting the use of acupuncture in AR.
The only pediatric study included in this review was a randomized controlled study of 72 children with perennial AR who
were 6 years of age and older.334 In this study, the children
undergoing acupuncture had significant improvement in daily
symptoms over 3 months and significantly more symptom-free
days but no decrease in symptomatic medication use. The
investigators also found that the improvements from acupuncture dissipated in the 10 weeks after completing acupuncture.
A subsequent review separated studies that involved seasonal
AR versus perennial AR.335 This review found that trials evaluating acupuncture for seasonal AR did not support specific effects
of acupuncture.336-339 However, for studies investigating the effect
of acupuncture for patients with perennial AR, pooled meta-analysis (N = 152 patients) results suggested that acupuncture patients
had a significant improvement in symptom score when compared
with those treated with sham acupuncture.334,335,340-342 Two RCTs
included in this review compared acupuncture to cetirizine343 or to
saitezan344 for perennial AR. Meta-analysis (N = 193) showed that
the response rate to acupuncture was not significantly better than
conventional medical therapy.335
Several large randomized trials have been conducted since
the publication of the above reviews. One trial of acupuncture
in adults with AR randomized 981 patients to acupuncture versus no treatment; perennial versus seasonal AR was not differentiated in this trial.345 The standard deviation of number of
acupuncture treatments averaged around 10, and patients had as
few as 7 and as many as 13 treatments based on the randomized
acupuncture numbers mentioned above. At 3 months, scores on
the Rhinitis Quality of Life Questionnaire (RQLQ) improved
by a mean of 1.48 in the acupuncture group and 0.5 in the control group (P < .001); changes of 0.5 are considered clinically
relevant, and overall quality of life improvements were statistically greater in the acupuncture group. The RQLQ measures the
influence of AR on quality of life and consists of 28 items in the
7 domains of sleep, nonnasal/eye symptoms, emotional function, practical problems, nasal symptoms, eye symptoms, and
activities. The patients were asked to assess the impact of AR
on these areas during the previous week. Another subsequent
large (N = 422), randomized, controlled, multicenter trial of
acupuncture in patients with seasonal AR compared acupuncture plus rescue medication (cetirizine) to sham acupuncture
with rescue medication to rescue medication alone.346 Patients
undergoing acupuncture were reported to have better RQLQ
and reduced rescue medication scores at 7 to 8 weeks than those
patients with sham acupuncture and rescue medication (P <
.001 for both) or rescue medication alone (P < .001 for both).
Treatment response at 7 to 8 weeks was 71% for acupuncture,
56% for sham acupuncture, and 44% for rescue medication;
however, the confidence intervals for improvement in RQLQ
and rescue medication scores included values below levels considered to be clinically important. A second multicenter RCT of
191 adults with perennial AR reported a significant improvement in Total Nasal Symptom Score at the end of treatment (P
= .029) and 4 weeks after treatment (P = .04), with 3.68 and
3.77 standard deviation, respectively, when compared with
sham acupuncture, and a significant improvement in the Total
Non-Nasal Symptom Score compared with the waitlist group
(P = .0002).347 Throughout the study, 4 nasal symptoms (nasal
obstruction, sneezing, rhinorrhea, and nasal itch) were selfassessed daily and recorded in a diary by participants, using a
5-point scale (0 = no symptom; 1 = mild; 2 = moderate; 3 =
severe; and 4 = very severe). Seven-day individual and Total
Nasal Symptom Scores were determined from the daily symptom scores. No other outcomes were significantly different.347
The use of a placebo control in the medical and immunotherapy treatment trials for AR has shown that placebo effects
are significant and can be greater than 50% for symptom
improvement. For most of the clinical trials reviewed here,
sham acupuncture was used. However, the location, depth,
and manipulation of the sham needles varied widely, and
while some trials report that sham therapy itself might have a
therapeutic effect, several showed no placebo effect from
sham acupuncture.348
The mechanism of action of acupuncture in the treatment
of AR is unknown. Studies suggest that acupuncture inhibits
cytokine synthesis, such as interleukin-10 in patients with AR
and interleukin-6 and interleukin-10 in patients with asthma;
however, it remains unclear whether these findings correlate
with clinical effect.349-352
In summary, one systematic review and several subsequent
large RCTs have found that acupuncture offers some symptom
control and improved quality of life in patients with perennial
AR. Although the systematic reviews of earlier trials did not
find a benefit in seasonal AR, subsequent RCTs found benefit
to acupuncture for symptom control in seasonal AR patients.
Additionally we could find no evidence of significant harms
associated with acupuncture. Accordingly, for patients with an
interest in nonpharmacologic approaches to management of
AR, acupuncture may be offered as an option.
STATEMENT 14. HERBAL THERAPY: No recommendation regarding the use of herbal therapy for patients
with AR. No recommendation based on limited knowledge of
herbal medicines and concern about the quality of standardization and safety.

Quality improvement opportunity: Not applicable
Aggregate evidence quality: Uncertain
Level of confidence in evidence: Low. Many of the
studies were small and of questionable methodology.
The meta-analyses were done in English but looked
at articles from the Chinese literature that are not
available for assessment by the panel.
Benefits: Improved awareness of alternative treatments, improved education of side effects of herbal
therapy
Risks, harms, costs: Not applicable
S29
Seidman et al
Benefit-harm assessment: Not applicable
Value judgments: There are many herbal therapies,
but there is only evidence for a few that have appropriate studies. There is limited knowledge about
these products among most of the panel members,
and accordingly there was a bias against their use.
There is concern about the quality of standardization
of herbal medicines and their safety,
Exclusions: None
Policy level: No recommendation
Supporting Text
The guideline development panel was unable to make a recommendation on the use of herbal therapy for treating patients
with AR due to the lack of English-language translation of the
majority of the literature, the diversity of and lack of standardization of herbal therapies, and a poor understanding by the
panel of the risks and harms of these therapies.
Traditional Chinese herbal medicine has been practiced for
over 80 centuries and continues to evolve. The Chinese pharmacopeia has over 13,000 medicinals and more than 100,000
herbal combinations recorded in ancient literature.353 Although
the prevalence and use of traditional Chinese herbal formulations is on the rise globally,354 there are limited high-quality,
large-scale, multicenter trials validating their safety and effectiveness.355 Studies of traditional Chinese medicine have demonstrated positive benefits in the treatment of AR; however,
many of the studies are small in size, the studies investigate
different medicines, and some of these studies have possible
methodological issues. Therefore, based on the myriad differing herbal therapies, lack of knowledge regarding risks, and
the shortcomings of the existing literature, no recommendation can be made regarding the use of traditional Chinese
medicine in AR.
The ARIA 2006 guideline identified 3 studies of reasonable
quality with an average number of 74 patients evaluating
Butterbur, Biminne, and a Chinese herbal mixture. These all
showed positive results on clinical symptoms and quality of
life for AR, but the ARIA guideline concluded that the studies were too few to make recommendations.333
Many Chinese herbal remedies are commonly prescribed
for AR depending on the traditional Chinese medical diagnosis of the patients signs and symptoms. Various small clinical
trials have reported that those herbal decoctions possess antiallergic, anti-inflammatory, or immunomodulatory actions,
such as inhibition of the release of mast cell mediation, reduction of histamine release, inhibition of inflammation induced
by chemical agents, and modulation of serum IgE levels or of
lymphocyte and/or macrophage activity.356-360 Although progress is ongoing toward global regulation of Chinese herbal
products and improved safety,361,362 currently none of these
herbal remedies are regulated by the FDA.
Safety of Chinese Herbal Medicine

While American clinicians may be skeptical of the safety and
efficacy of herbal therapies for AR with which they are not familiar,354,363,364 there have been no reported deaths due to Chinese
herbal medicine in the United States in the past 40 years.
Implementation Considerations
The clinical practice guideline is published as a supplement to
OtolaryngologyHead and Neck Surgery, which will facilitate reference and distribution. A full-text version of the
guideline will be accessible, free of charge, at http://www.
entnet.org. In addition, all AAO-HNSF guidelines are now
available via the OtolaryngologyHead and Neck Surgery
app for smartphones and tablets. The guideline will be presented to AAO-HNS members as a miniseminar at the 2014
AAO-HNSF Annual Meeting and OTO EXPO. Existing brochures and publication by the AAO-HNSF will be updated to
reflect the guidelines recommendations.
As a supplement to clinicians, an algorithm of the guidelines action statements, Figure 2, and a table with common
allergic rhinitis clinical scenarios, Figure 3, has been provided. The algorithm allows for a more rapid understanding of
the guidelines logic and the sequence of the action statements.
The Guideline Development Group hopes the algorithm can
be adopted as a quick reference guide to support the implementation of the guidelines recommendations.
Research Needs
This guideline was based on the current body of evidence
regarding treatment of AR. While many of the key action
statements were supported by Grade A level evidence, review
of the evidence profile for other statements revealed knowledge gaps and the need for further research. As determined by
the Guideline Development Groups review of the literature,
assessment of current clinical practices, and determination of
evidence gaps, research needs were determined as follows:
1. Research is needed to determine the effect of environmental control strategies on AR. The aggregate
evidence profile for environmental controls was a
Grade B. Controlled trials to identify the efficacy of
environmental controls on measurable AR endpoints
are needed.
2. Research is needed to evaluate the safety and efficacy of SIT, specifically SLIT. There have been
few US-based studies evaluating SLIT, which has
been offered in the United States in an off-label,
non-FDA-approved fashion. With FDA approval of
Oralair, a mixed allergen extract consisting of several pollens (Sweet Vernal, Orchard, Perennial Rye,
Timothy, and Kentucky Blue Grass), Grastek (treatment for Timothy grass pollen) and Ragwitek (treatment for short ragweed pollen) in 2014, prospective
RCTs are needed to properly evaluate the effect of
S30

Paent presents with the
following symptoms: nasal
congeson, runny nose, itchy
nose, sneezing
Physician conducts history and physical

examinaon (KAS1). Including
assessment of chronic condions and
comorbidies (KAS5)
Physician determines
clinical diagnosis of allergic
rhinis
Treatment Needed? - YES

Pharmacologic Treatment
(KAS 6-10):
Refer to Figure 3: Medicaons
Flow Chart for Common
Clinical Scenarios
Environmental
Factors (KAS4):
Clinicians may
advise avoidance of
known or suspected
allergens
Paent prefers Complementary

Medicine
Inadequate control of AR symptoms

with pharmacologic therapy and/or
environmental controls
Allergy Tesng (KAS2);

Clinicians should perform and interpret, or refer to a
clinician who can perform and interpret, specific IgE
(skin or blood) allergy tesng for paents with a
clinical diagnosis of allergic rhinis who do not
respond to empiric treatment, or when the diagnosis is
uncertain, or when knowledge of the specific allergen
could impact therapy decisions
Clinicians may offer

acupuncture (KAS13)
Inferior Turbinate reducon: for Persistent

Nasal Airway Obstrucon (KAS12)
Clinicians may offer, or refer to a surgeon
who can offer, inferior turbinate reducon in
paents with allergic rhinis with nasal
airway obstrucon and enlarged inferior
turbinates who have failed medical
management
Immunotherapy
If Posive Allergy Tesng (KAS11):
Clinicians should offer, or refer to a clinician who
can offer, immunotherapy (sublingual or
subcutaneous) for paents with allergic rhinis who
have inadequate response to pharmacologic
therapy with or without environmental controls
Figure 2. Allergic rhinitis (AR) diagnosis and treatment flow chart for evaluating and managing patients with AR based on this guidelines
recommendations. KAS, key action statement.
the office-sold, physician-diluted, nonstandardized

products and other SLIT preparations.
3. Cost-effectiveness research (including direct and
indirect costs) of SCIT compared with SLIT is
needed. Also needed are better comparisons of SLIT
versus SCIT; such comparisons are very few and far
between, and there are none in the United States.
4. Research is needed to determine the molecular effects
of first-line therapies for AR target end-organ immune
responses (ie, topical steroids and antihistamines for
nasal symptoms). Basic mechanistic research in the
fields of allergy and immunology addressing the
underlying triggers for specific patients is needed,
as well as other immune-modulating treatments that
alter the pathophysiology of AR and its comorbid
conditions.
5. Research is needed to determine the safety and efficacy of acupuncture for AR. There is a relative paucity
of data in the English-language literature regarding
the use of complementary and integrative medicine
for AR. As such, specific recommendations for or
against these treatments could not be made. Higher
levels of evidence regarding these therapies need to
be obtained through well-designed clinical trials and/
or systematic reviews of existing data.
6. The studies on herbal therapies involve use of preparations that combine numerous herbal extracts in
varying amounts; thus, research needs to be conducted on specific herbal extracts along with standardization of dosing to determine efficacy for AR.
7. Controlled trials are needed comparing surgical versus
medical management of inferior turbinate hypertrophy
S31
Seidman et al
10. More research, including basic and/or translational

trials, is needed to evaluate novel forms of immunotherapy such as peptide vaccines, DNA conjugated
vaccines, intradermal injections, and intralymphatic
injections. These are all strategies that are hypothesized to reduce the allergenicity of extracts while
maintaining or enhancing the beneficial effects on
the immune system.
11. Analysis is needed of the impact of immunomodulatory agents for the treatment of asthma on AR.
12. The relationship between AR and comorbid conditions such as otitis media and sinusitis should be
determined. In addition, research is needed to determine the effect of AR on comorbid conditions.
13. It should be determined whether different forms of
allergy testing can provide clinically meaningful
information. It is still unclear whether one form of
testing is superior to the other in identifying clinically relevant allergens.
14. Studies are needed to determine the effect of combined allergen formulations for AR that are standardized, tolerable, and effectively dosed.
15. Outcome measures are needed using SN-5 or other
tools to measure and compare efficacy of medical
and surgical treatments for nasal congestion/AR in
both children and adults.
Disclaimer
Figure 3. Common allergic rhinitis clinical scenarios. The
guidelines task force could not agree on a simple algorithm for
treating allergic rhinitis as variations in patient preferences, severity
of symptoms, duration of symptoms, coexisting conditions, and
allergen sensitizations all influenced reasonable recommendations.
Instead, Figure 3 provides guidance for practitioners using
illustrative clinical scenarios that are consistent with available
evidence and expert advice.
with nasal congestion in patients with AR. In addition,

there is a need for further research regarding the role of
septoplasty in the treatment of AR.
8. Research is needed to determine the relationship
between AR and comorbid conditions such as otitis
media and sinusitis. In addition, research is needed
to determine the effect of AR treatment on comorbid
conditions and the effect of treatment for comorbid
conditions on AR.
9. Research is needed regarding the impact of patient
adherence to different treatments, and treatment
outcomes, which often is neglected in establishing
the evidence base for AR or other treatments in trials. There is a need for increased diversity in trial
subjects and the examination of other factors influencing treatment outcomes such as ease or utility of
treatment administrations, as well as the impact of
patient education aids on patient adherence and subsequent outcomes.
The clinical practice guideline is not intended as the sole source

of guidance in managing patients with AR. Rather, it is designed
to assist clinicians by providing an evidence-based framework
for decision-making strategies. The guideline is not intended to
replace clinical judgment or establish a protocol for all individuals with this condition and may not provide the only appropriate
approach to diagnosing and managing this program of care. As
medical knowledge expands and technology advances, clinical
indicators and guidelines are promoted as conditional and provisional proposals of what is recommended under specific conditions but are not absolute. Guidelines are not mandates; these do
not and should not purport to be a legal standard of care. The
responsible physician, in light of all circumstances presented by
the individual patient, must determine the appropriate treatment.
Adherence to these guidelines will not ensure successful patient
outcomes in every situation. The AAO-HNSF emphasizes that
these clinical guidelines should not be deemed to include all
proper treatment decisions or methods of care or to exclude other
treatment decisions or methods of care reasonably directed to
obtaining the same results.
Acknowledgment
We gratefully acknowledge the support of Janet Waters for her assistance with the literature searches.
Author Contributions
Michael D. Seidman, writer, chair; Richard K. Gurgel, writer,
assistant chair; Sandra Y. Lin, writer, assistant chair; Seth R.
Schwartz, methodologist; Fuad M. Baroody, writer; James R.
S32
Bonner, writer; Douglas E. Dawson, writer; Mark S. Dykewicz,

writer; Jesse M. Hackell, writer; Joseph K. Han, writer; Stacey L.
Ishman, writer; Helene J. Krouse, writer; Sonya Malekzadeh,
writer; James (Whit) W. Mims, writer; Folashade S. Omole, writer;
William D. Reddy, writer; Dana V. Wallace, writer; Sandra A. Walsh,
writer; Barbara E. Warren, writer; Meghan N. Wilson, writer;
Lorraine C. Nnacheta, writer and AAO-HNSF staff liaison.
Disclosures
Competing interests: Michael D. Seidman, medical director
Scientific Advisory BoardVisalus; founder of Body Language
Vitamin Co; National Institutes of Health grant on simulation; 6
patents but related to supplements, aircraft, and the middle ear and
brain implant; Sandra Y. Lin, consultant for Wellpoint; Fuad M.
Baroody, speaker for Merck, Inc; speaker for GlaxoSmithKline and
speaker/consultant for Acclarent/Johnson/Johnson; Mark S.
Dykewicz, consultant for Merck and research contract support to
Saint Louis University for Novartis; Jesse M. Hackell,
GlaxoSmithKline (Speakers Bureau); Sunovion Pharmaceuticals Inc
(Advisory Board) has had discussions regarding nasal corticosteroids; Transit of Venus (Advisory Board); Joseph K. Han, Medtronic
research grant; PI and consultant on clinical study with Intersect; and
speaker for Merck; Stacey L. Ishman, consultant for First Line
Medical; Dana V. Wallace, TEVA (Speakers Bureau); Sanofi
(Advisory Panel and Speakers Bureau); Mylan (Advisory Board
and Speakers Bureau); Sunovian (Speakers Bureau); MEDA
(Advisory Panel and Speakers Bureau); ACAAI Executive
Committee Chair and Board of Regents, Rhinitis/Sinusitis
Committee; AAAAI/ACAAI/JCAAI Practice Parameter Joint Task
Force.
Sponsorships: American Academy of OtolaryngologyHead and
Neck Surgery Foundation.
Funding Source: American Academy of OtolaryngologyHead
and Neck Surgery Foundation.
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Clinical Practice Guideline: Allergic Rhinitis

Michael D. Seidman, MD1, Richard K. Gurgel, MD2, Sandra Y. Lin, MD3,

Sponsorships or competing interests that may be relevant to content are

guideline are not intended to represent the standard of care for

Objective. Allergic rhinitis (AR) is one of the most common

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OtolaryngologyHead and Neck Surgery 152(1S)

oral leukotriene receptor antagonists as primary therapy for

attendance, is responsible for as much as $2 to $4 billion in

Defining Allergic Rhinitis

by exposure to pollen from symptoms caused by exposure to

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OtolaryngologyHead and Neck Surgery 152(1S)

older with a diagnosis

2 is the earliest age to

testing for baseline

First-line therapy upon

Methods for preventing

Role of herbal medicines

Role of nasal rinses

Initial evaluation of the

children, found a large variation in the prevalence of AR

exposure in complex ways we do not fully understand. Allergic

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Costs, Quality of Life, and Productivity

AND ((1980/01/01[PDAT]: 2013/12/31[PDAT]) AND

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OtolaryngologyHead and Neck Surgery 152(1S)

Table 3. Evidence Levels for Grades of Evidence.a

Evidence Quality for Diagnosis

Evidence Quality for Treatment and Harm

Financial Disclosure and Conflicts of

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A strong recommendation means the benefits of the

Clinicians should follow a strong recommendation

Clinicians should also generally follow a

Clinicians should be flexible in their decision making

American Academy of Pediatrics classification scheme.25

relationships and may include personal experiences, how a

Guideline Key Action Statements

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OtolaryngologyHead and Neck Surgery 152(1S)

Table 5. Summary of Guideline Action Statements.

1.Patient history and

Abbreviations: AR, allergic rhinitis; IgE, immunoglobulin E.

Action Statement Profile

Risks, harms, costs: Inappropriate treatment, potential

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use of the words when patients present with a history

in patients with compatible symptoms.35,36 Finally, the severity

Action Statement Profile

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OtolaryngologyHead and Neck Surgery 152(1S)

Table 6. History and Physical Findings in AR.

Benefits: Confirming diagnosis, directing pharmacologic therapy, directing immunotherapy, avoidance

examination, the presence of a specific IgE antibody to a

1.Patient history and