Diagnosis and Management of Rhinitis:
`Complete Guidelines of the Joint Task Force
`on Practice Parameters in Allergy, Asthma
`and Immunology
`
`Mark S Dykewicz, MD,‡ Stanley Fineman, MD, MBA,§ Editors
`David P Skoner, MD,¶¶ Chair, Workgroup on Rhinitis
`Richard Nicklas, MD㛳; Rufus Lee, MD; Joann Blessing-Moore, MD¶; James T Li, MD, PhD**;
`I Leonard Bernstein, MD††; William Berger, MD, MBA‡‡; Sheldon Spector, MD§§; and
`Diane Schuller, MD,㛳㛳 Associate Editors
`
`This document contains complete guidelines for diagnosis and management of
`rhinitis developed by the Joint Task Force on Practice Parameters in Allergy,
`Asthma and Immunology, representing the American Academy of Allergy, Asthma
`and Immunology, the American College of Allergy, Asthma and Immunology and
`the Joint Council on Allergy, Asthma and Immunology. The guidelines are com-
`prehensive and begin with statements on clinical characteristics and diagnosis of
`different forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonal
`rhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from food
`ingestion), and other conditions that may be confused with rhinitis. Recommenda-
`tions on patient evaluation discuss appropriate use of history, physical examination,
`and diagnostic testing, as well as unproven or inappropriate techniques that should
`not be used. Parameters on management include use of environmental control
`measures, pharmacologic therapy including recently introduced therapies and aller-
`gen immunotherapy. Because of the risks to patients and society from sedation and
`performance impairment caused by first generation antihistamines, second genera-
`tion antihistamines that reduce or eliminate these side effects should usually be
`considered before first generation antihistamines for the treatment of allergic rhi-
`nitis. The document emphasizes the importance of rhinitis management for co-
`morbid conditions (asthma, sinusitis, otitis media). Guidelines are also presented on
`special considerations in patients subsets (children, the elderly, pregnancy, athletes
`and patients with rhinitis medicamentosa); and when consultation with an allergist-
`immunologist should be considered.
`
`Ann Allergy Asthma Immunol 1998;81:478–518.
`
`CONTRIBUTORS: Donald W Aaronson, MD;
`Allen D Adinoff, MD; James N Baraniuk, MD;
`Robert
`J Dockhorn, MD; William Dolen,
`MD; Howard M Druce, MD; Marianne Frieri,
`MD, PhD; Morton P Galina, MD; Leon Greos, MD;
`Alfredo A Jalowayski, PhD; Craig F La Force,
`MD; Eli O Meltzer, MD; Robert M Naclerio,
`MD; Keith M Phillips, MD; Gordon Raphael, MD;
`Michael Schatz, MD; Michael J Schumacher,
`MBBS; Howard J Schwartz, MD; Tommy C
`Sim, MD; Chester T Stafford, MD; William W
`Storms, MD; Michael J Tronolone, MD; Mi-
`chael J Welch, MD; Chester C Wood, MD; and
`Robert S Zeiger, MD, PhD
`
`PRINCIPAL REVIEWERS: Jean A Chap-
`man, MD; Robert A Nathan, MD; John Santilli,
`Jr, MD; Michael Schatz, MD; and Betty B Wray,
`MD
`This document was developed by the Joint
`Task Force on Practice Parameters in Allergy,
`Asthma and Immunology,
`representing the
`American Academy of Allergy, Asthma and Im-
`munology (AAAAI), the American College of
`Allergy, Asthma and Immunology (ACAAI) and
`the Joint Council on Allergy, Asthma and Im-
`munology. The AAAAI and the AACAAI have
`jointly accepted responsibility for establishing
`these practice parameters. Because this docu-
`
`ment incorporated the efforts of many partici-
`pants, no single individual, including those who
`served on the Joint Task Force, is authorized to
`provide an official interpretation of this docu-
`ment by the AAAAI or ACAAI. Any request for
`information about or an interpretation of this
`document by the AAAAI or ACAAI should be
`directed to the Executive Offices of the AAAAI,
`ACAAI and the Joint Council on Allergy,
`Asthma and Immunology.
`* This parameter was developed with Dr.
`Nicklas in his private capacity and not in his
`capacity as a medical officer with the Food and
`Drug Administration. No official support or en-
`dorsement by the Food and Drug Administration
`is intended or should be inferred.
`‡ Division of Allergy and Immunology, De-
`partment of
`Internal Medicine, Saint Louis
`University School of Medicine, St. Louis, Mis-
`souri; § Department of Pediatrics, Emory Uni-
`versity School of Medicine, Atlanta, Georgia;
`¶¶ Departments of Pediatrics & Otolaryngology,
`Children’s Hospital of Pittsburgh, University
`of Pittsburgh School of Medicine, Pittsburgh,
`Pennsylvania;
`㛳 Department
`of Medicine,
`George Washington Medical Center, Washing-
`ton, DC; ¶ Departments of Medicine & Pediat-
`rics, Stanford University Medical Center, Palo
`Alto, California; ** Department of Medicine,
`Mayo Clinic & Medical School, Rochester, Min-
`nesota; †† Departments of Medicine & Environ-
`mental Health, University of Cincinnati College
`of Medicine, Cincinnati, Ohio; ‡‡ Department of
`Pediatrics, Division of Allergy and Immunology,
`University of California College of Medicine,
`Irvine, California; §§ Department of Medicine,
`University of California-Los Angeles, Los An-
`geles, California; 㛳㛳 Department of Pediatrics,
`Pennsylvania State University, Milton S. Her-
`shey Medical College, Hershey, Pennsylvania.
`The Joint Task Force has made an intense
`effort to appropriately acknowledge all contrib-
`utors to this parameter. If any contributors are
`inadvertently excluded, the Task Force will in-
`sure that appropriate recognition of such contri-
`butions is subsequently made.
`
`478
`
`ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY
`Exhibit 1019
`IPR2017-00807
`ARGENTUM
`
`000001
`
`

`

`Contents and Organization of this Document
`
`Summary
`Statement
`
`Page
`
`INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`DEFINITION OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`DIFFERENTIAL DIAGNOSIS OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`1
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`2
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`Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`3–12
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`Non-Allergic rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Infectious rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Non-Allergic rhinitis without eosinophilia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Non-Allergic rhinitis with eosinophilia syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Occupational rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Hormonal rhinitis (pregnancy and hypothyroidism) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Drug-induced rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Rhinitis from food ingestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Other conditions that may be confused with rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Nasal polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`EVALUATION OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`23–24
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`Physical examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Testing for specific IgE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Special diagnostic techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Nasal cytology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Total serum IgE, blood eosinophil counts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`Unproven or inappropriate testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`MANAGEMENT OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Environmental control measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Pharmacologic therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`30
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`Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`33–35
`
`Issues with sedation/performance impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Cardiac effects of some antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Intranasal antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Oral and nasal decongestants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Nasal corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Oral and parenteral corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Intranasal cromolyn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Intranasal anti-cholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Oral anti-leukotriene agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Allergen immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Surgical approaches for co-morbid conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Important considerations in management
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Education of patient and caregivers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
`
`Importance of rhinitis management for concomitant asthma, sinusitis, and otitis media . . . . . . . . . . . . . . . .
`
`Special considerations in children, the elderly, pregnancy, athletes, and rhinitis medicamentosa . . . . . . . . .
`
`Consultation with an allergist-immunologist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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`VOLUME 81, NOVEMBER (PART II), 1998
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`INTRODUCTION
`Rhinitis may be caused by allergic,
`non-allergic, infectious, hormonal, oc-
`cupational and other factors. All too
`often, important causes of rhinitis go
`unrecognized by both physicians and
`patients. This leads to suboptimal con-
`trol of the disease.
`Rhinitis is a significant cause of
`widespread morbidity.
`Although
`sometimes mistakenly viewed as a
`trivial disease, symptoms of rhinitis
`may significantly impact the patient’s
`quality of life, by causing fatigue,
`headache, cognitive impairment and
`other systemic symptoms. Appropriate
`management of rhinitis may be an im-
`portant component in effective man-
`agement of co-existing or complicating
`respiratory conditions, such as asthma,
`sinusitis, or chronic otitis media. The
`cost of treating rhinitis and indirect
`costs related to loss of workplace pro-
`ductivity resulting from the disease are
`substantial. The estimated cost of al-
`lergic rhinitis based on direct and in-
`direct costs is 2.7 billion dollars for the
`year 1995, exclusive of costs for asso-
`ciated medical problems such as sinus-
`itis and asthma. Allergic rhinitis, the
`most common form of rhinitis, affects
`20 to 40 million people in the United
`States annually, including 10% to 30%
`of adults and up to 40% of children.
`This document
`reviews clinically
`relevant information about pathogene-
`sis and provides guidelines about diag-
`nosis and management of rhinitis syn-
`dromes. Throughout
`the document,
`summary statements that articulate key
`points precede supporting text and rel-
`evant citations of evidence-based pub-
`lications.
`
`DEFINITION OF RHINITIS
`1. Rhinitis is defined as inflamma-
`tion of the membranes lining the
`nose, and is characterized by na-
`sal congestion, rhinorrhea, sneez-
`ing,
`itching of the nose and/or
`postnasal drainage.
`Rhinitis can be defined as a heteroge-
`neous disorder characterized by one or
`more of the following nasal symptoms:
`sneezing,
`itching, rhinorrhea, and/or
`nasal congestion. Rhinitis frequently is
`
`accompanied by symptoms involving
`the eyes, ears, and throat. Post-nasal
`drainage may also be present
`fre-
`quently.
`
`Reference
`1. Druce HM. Allergic and nonallergic
`rhinitis. In: Middleton EJ, Reed CE,
`Ellis EF, et al, eds. Allergy principles
`and practice, 5th edition. St. Louis:
`Mosby-Year Book
`Inc,
`1998:
`1005–1016.
`
`DIFFERENTIAL DIAGNOSIS OF
`RHINITIS
`2. Rhinitis should be classified by
`etiology as allergic or nonaller-
`gic.
`Allergic rhinitis is a very common
`cause of rhinitis. However, since ap-
`proximately 50% of patients with rhi-
`nitis do not have allergic rhinitis, other
`potential causes must also be ruled
`out.1–3 The following outline lists dif-
`ferent forms of allergic and non-aller-
`gic rhinitis, and conditions that may
`mimic rhinitis.
`I. Allergic rhinitis
`A. Seasonal
`B. Perennial
`C. Episodic
`D. Occupational (may also be non-
`allergic)
`II. Non-allergic rhinitis
`A. Infectious
`1. Acute
`2. Chronic
`B. NARES syndrome
`(Nonallergic rhinitis with eo-
`sinophilia syndrome)
`C. Perennial nonallergic rhinitis
`(Vasomotor rhinitis)
`D. Other rhinitis syndromes
`1. Ciliary dyskinesia syndrome
`2. Atrophic rhinitis
`3. Hormonally-induced
`A. Hypothyroidism
`B. Pregnancy
`C. Oral contraceptives
`D. Menstrual cycle
`4. Exercise
`5. Drug-Induced
`A. Rhinitis medicamentosa
`B. Oral contraceptives
`C. Anti-hypertensive
`apy
`
`ther-
`
`D. Aspirin
`anti-in-
`E. Nonsteroidal
`flammatory drugs
`6. Reflex-Induced
`A. Gustatory rhinitis
`B. Chemical or irritant-in-
`duced
`C. Posture reflexes
`D. Nasal cycle
`E. Emotional factors
`7. Occupational (may be aller-
`gic)
`III. Conditions that may mimic symp-
`toms of rhinitis
`A. Structural/mechanical factors
`1. Deviated septum/septal wall
`anomalies
`2. Hypertrophic turbinates
`3. Adenoidal hypertrophy
`4. Foreign bodies
`5. Nasal tumors
`A. Benign
`B. Malignant
`6. Choanal atresia
`B. Inflammatory/immunologic
`1. Wegener’s granulomatosis
`2. Sarcoidosis
`3. Midline granuloma
`4. Systemic lupus erythemato-
`sus
`5. Sjogren’s syndrome
`6. Nasal polyposis
`C. Cerebrospinal fluid rhinorrhea
`
`References
`1. Lieberman P. Rhinitis. In: Bone RC,
`ed. Current practice of medicine. vol 2.
`Philadelphia: Churchill Livingstone
`1996; VII:5.1–VII:5.10.
`2. Mygind N, Anggard A, Druce HM.
`Definition, classification, and termi-
`nology [of rhinitis]. In: Mygind N,
`Weeke B, eds. Allergic and vasomotor
`rhinitis. Copenhagen, Munksgaard,
`1985;15.
`3. Sibbald B, Rink E. Epidemiology of
`seasonal and perennial rhinitis: clinical
`presentation and medical history. Tho-
`rax 1991;46:895–901.
`
`Allergic Rhinitis
`3. Allergic rhinitis affects 20 to
`40 million people in the United
`States annually, including 10%
`to 30% of adults and up to 40%
`of children.
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`4. The severity of allergic rhinitis
`ranges from mild to seriously
`debilitating.
`5. The cost of treating allergic rhi-
`nitis and indirect costs related to
`loss of workplace productivity
`resulting from the disease are
`substantial. The estimated cost
`of allergic rhinitis based on di-
`rect and indirect costs is 2.7 bil-
`lion dollars for the year 1995,
`exclusive of costs for associated
`medical problems such as sinus-
`itis and asthma. Rhinitis is also a
`significant cause of lost school
`days.
`6. Risk factors for allergic rhinitis
`include:
`(1)
`family history of
`(2) serum IgE > 100
`atopy;
`IU/mL before age 6; (3) higher
`socioeconomic class; (4) expo-
`sure to indoor allergens such as
`animals and dust mites; (5) pres-
`ence of a positive allergy skin
`prick test.
`Rhinitis is reported to be a very fre-
`quent disease, although data regarding
`the true prevalence of rhinitis are dif-
`ficult to interpret. Most population sur-
`veys rely upon physician-diagnosed
`rhinitis for their data, and this may
`give rise to a much lower reporting of
`rhinitis. Some population studies have
`been done with questionnaires admin-
`istered to the subjects followed in
`many cases by telephone interviews to
`try to make a specific diagnosis of
`rhinitis. These studies may reflect a
`more accurate prevalence of rhinitis
`but probably still underreport this dis-
`ease.1–7
`Most epidemiologic studies have
`been directed towards seasonal allergic
`rhinitis, or hay fever, since this symp-
`tom complex with its reproducible sea-
`sonality is somewhat easier to identify
`in population surveys. Perennial aller-
`gic rhinitis is more difficult to identify
`because its symptom complex may
`overlap with chronic sinusitis, recur-
`rent upper respiratory infections, and
`vasomotor rhinitis.
`The prevalence of rhinitis in various
`epidemiologic studies ranges from 3%
`to 19%. Studies suggest that seasonal
`allergic rhinitis (hay fever) is found in
`
`approximately 10% to 20% of the pop-
`ulation.2,8–10 One study showed a prev-
`alence of physician-diagnosed allergic
`rhinitis in 42% of 6-year-old children.3
`Overall, allergic rhinitis affects 20 to
`40 million individuals in the United
`States annually.11,12
`In childhood, males with allergic
`rhinitis outnumber females, but
`the
`gender ratio becomes approximately
`equal in adults and may even favor
`females. Surveys of medical students
`have resulted in a higher prevalence of
`rhinitis, but this may be related to the
`survey technique.1,6,8
`Allergic rhinitis develops before age
`20 in 80% of cases. Studies have
`shown that the frequency of allergic
`rhinitis increases with age until adult-
`hood and that positive immediate hy-
`persensitivity skin tests are significant
`risk factors for the development of new
`symptoms of seasonal allergic rhini-
`tis.1,8,13 There is a greater chance of a
`child developing allergic rhinitis if
`both parents have a history of atopy,
`than if only one parent is atopic. Chil-
`dren in families with a bilateral family
`history of allergy generally develop
`symptoms before puberty; those with a
`unilateral family history tend to de-
`velop their symptoms later in life or
`not at all.5,10
`There tends to be an increased prev-
`alence of allergic rhinitis in higher so-
`cioeconomic classes, in non-whites, in
`some polluted urban areas, and in in-
`dividuals with a family history of al-
`lergy. Allergic rhinitis is more likely in
`first-born children. Studies in children
`in the first years of life have shown
`that the risk of rhinitis was higher in
`those youngsters with early introduc-
`tion of foods or formula, heavy mater-
`nal cigarette smoking in the first year
`of life, exposure to indoor allergens
`such as animals and dust mite, higher
`serum IgE levels (⬎100 IU/mL before
`age 6), and parental allergic disorders.3
`Seasonal allergic rhinitis is appar-
`ently becoming more common. One
`study showed that the prevalence of
`hay fever increased from 4% to 8% in
`the 10 years from 1971 to 1981.14 In
`another study, atopic skin test reactiv-
`
`ity increased from 39% to 50% in dur-
`ing an 8-year period of evaluation.15
`The impact on society is tremen-
`dous.16 The severity of allergic rhinitis
`ranges from mild to seriously debilitat-
`ing. The cost of treating allergic rhini-
`tis and indirect costs related to loss of
`workplace productivity resulting from
`the disease are substantial. The esti-
`mated cost of allergic rhinitis based on
`direct and indirect costs is 2.7 billion
`dollars for the year 1995, exclusive of
`costs for associated medical problems
`such as sinusitis and asthma. The total
`direct and indirect cost estimates for
`allergic rhinitis have been reported to
`be $5.3 billion for 1996. This figure
`included the higher indirect costs asso-
`ciated with increased loss of produc-
`tivity, which, in turn, was related to
`extensive over-the-counter antihista-
`mine use. Such treatment can cause
`drowsiness and impair cognitive and
`motor function (see summary state-
`ment #34).
`Rhinitis is also a significant cause of
`lost school attendance,
`resulting in
`more than 2 million absent school days
`in the US annually. In children, there is
`evidence that symptoms of allergic rhi-
`nitis can impair cognitive functioning,
`which can be further impaired by the
`use of first generation antihistamines.17
`
`References
`1. Hagy GW, Settipane GA. Prognosis of
`positive allergy skin tests in an asymp-
`tomatic population. J Allergy 1971;48:
`200.
`2. Druce HM. Allergic and nonallergic
`rhinitis. In: Middleton EJ, Reed CE,
`Ellis EF, et al. Allergy principles and
`practice, 5th edition. St. Louis: Mosby-
`Year Book Inc, 1998:1005–1016.
`3. Wright AL, Holberg CJ, Martinez FD,
`et al. Epidemiology of physician-
`diagnosed allergic rhinitis in child-
`hood. Pediatrics 1994;94(6):895–901.
`4. Aberg N, Engstrom I. Natural history
`of allergic diseases in children. Acta
`Pediatr Scan 1990;79:206–211.
`5. Aberg N, Engstrom I, Lindberg U. Al-
`lergic diseases in Swedish school chil-
`dren. Acta Paediatr Scan 1989;78:
`246–252.
`6. Fougard T. Allergy and allergy-like
`symptoms in 1,050 medical students.
`Allergy 1991;46:20–26.
`
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`7. Aberg B, Hesselmar B, Eriksson B.
`Increase of asthma, allergic rhinitis
`and eczema in Swedish school chil-
`dren between 1979 and 1991. Clin Exp
`Allergy 1995;25:815–819.
`8. Settipane RJ, Hagy GW, Settipane
`GA. Long-term risk factors for devel-
`oping asthma and allergic rhinitis: a
`23-year follow-up study of college stu-
`dents. Allergy Proc 1994;51:21–25.
`9. Varyonen E, Kalimo K, Lammintausta
`K. Prevalence of atopic disorders
`among adolescents in Turku, Finland.
`Allergy 1992;47:243–248.
`10. Smith JM. A five-year prospective sur-
`vey of rural children with asthma and
`hay fever. J Allergy 1971;47:23–31.
`11. Fireman P. Allergic rhinitis. In: Fire-
`man P, Slavin RG, eds. Atlas of aller-
`gies. Philadelphia, PA: JB Lippincott,
`1991:9.2–9.18.
`12. McMenamin P. Costs of hay fever in
`the United States in 1990. Ann Allergy
`1994;73:35–39.
`13. Tang RB, Tsai LC, Hwang B, et al.
`The prevalence of allergic disease and
`IgE antibodies to house dust mite in
`school children in Taiwan. Clin Exp
`Allergy 1990;20:33–38.
`14. Linna O, Kokkonen J, Lukin M. A
`10-year prognosis for childhood aller-
`gic rhinitis. Acta Pediatr 1992;81:
`100–102.
`15. Sibbald B, Rink E, O’Souza M. Is the
`prevalence of atopy increasing? Br J
`Gen Pract 1990;40:338–340.
`16. Ross RN. The costs of allergic rhinitis.
`Am J Managed Care 1996;2:285–290.
`17. Vuurman EF, van Veggel LM, Uiter-
`wijk MM, et al. Seasonal allergic rhi-
`nitis and antihistamine effects on chil-
`dren’s learning. Ann Allergy 1993;71:
`121–126.
`
`7. The symptoms of allergic rhinitis re-
`sult from a complex allergen-driven
`mucosal
`inflammation
`resulting
`from an interplay between resident
`and infiltrating inflammatory cells,
`and a number of inflammatory me-
`diators and cytokines. Sensory nerve
`activation, plasma leakage and con-
`gestion of venous sinusoids also con-
`tribute.
`The nasal mucosa is designed to hu-
`midify and clean inspired air. The ac-
`tions of epithelium, vessels, glands,
`and nerves are carefully orchestrated to
`perform these functions.1 Dysfunction
`of any of these structures may contrib-
`
`ute to the symptoms of allergic and
`nonallergic rhinitis.2
`
`References
`1. Raphael GR, Baraniuk JN, Kaliner
`MA. How and why the nose runs. J
`Allergy Clin Immunol 1991;87:
`457–467.
`2. Baraniuk JN. Neural control of the up-
`per respiratory tract. In: Kaliner MA,
`Barnes PJ, Kunkel GK, Baraniuk JN,
`eds. Neuropeptides in respiratory med-
`icine. New York: Marcel Dekker, Inc
`1995;79–123.
`
`8. Allergic rhinitis may be character-
`ized by early and late phase re-
`sponses. Each type of response is
`characterized by sneezing, conges-
`tion and rhinorrhea, but congestion
`predominates in the latter.
`Atopic subjects inherit the tendency to
`lympho-
`develop IgE-mast cell-TH2
`cyte immune responses. Exposure to
`low concentrations of dust mite fecal
`proteins, cockroach, cat, dog and other
`danders, pollen grains, or other aller-
`gens for prolonged periods of time
`leads to the presentation of the allergen
`by antigen presenting cells (APC) to
`CD4⫹ lymphocytes that release IL3,
`IL4, IL5, GM-CSF and other cyto-
`kines. These promote IgE production
`against these allergens by plasma cells,
`mast cell proliferation and infiltration
`of airway mucosa, and eosinophilia.
`Early or immediate allergic re-
`sponse. With continued allergen expo-
`sure, increasing numbers of IgE-coated
`mast cells move into the epithelium,
`recognize the mucosally-deposited al-
`lergen, and degranulate.1 Mast cell
`products include preformed mediators
`such as histamine, tryptase (a mast cell
`specific marker), chymase (in “con-
`nective tissue” mast cells only), kini-
`nogenase (generates bradykinin), hep-
`arin,
`and other
`enzymes. Newly
`formed mediators include prostaglan-
`din D2 and the cysteinyl-leukotrienes
`LTC4, LTD4, and LTE4. These media-
`tors stimulate vessels to leak and pro-
`duce edema plus watery rhinorrhea;
`stimulate glands to exocytose their mu-
`coglycoconjugates and antimicrobial
`substances; and dilate arteriole-venule
`anastomoses to cause sinusoidal filling
`
`and occlusion of nasal air passages.
`Sensory nerves are stimulated that con-
`vey the sensations of nasal itch and
`congestion, and initiate systemic re-
`flexes such as sneezing paroxysms.
`Release of these mast cell mediators
`and induction of these reactions occur
`within minutes of allergen exposure,
`and are termed the early or immediate
`allergic response.2 While most subjects
`experience sneezing and copious rhi-
`norrhea after allergen exposure, some
`subjects have sensations of nasal con-
`gestion as their predominant symptom.
`Late phase response. The mast cells
`mediators, including the cytokines, are
`thought to act upon post-capillary en-
`dothelial cells to promote VCAM and
`E-selectin expression that permits cir-
`culating leukocytes to stick to the en-
`dothelial cells. Chemoattractants, such
`as IL-5 for eosinophils, promote the
`infiltration of the superficial
`lamina
`propria of the mucosa with some neu-
`trophils and basophils, many eosino-
`phils, and, at later time points, T lym-
`phocytes and macrophages.3,4 Over the
`course of 4 to 8 hours, these cells be-
`come activated and release their medi-
`ators, which in turn activate many of
`the proinflammatory reactions of the
`immediate response. This late occur-
`ring inflammatory reaction is termed
`the “late phase response”. While this
`reaction may be clinically similar to
`the immediate reaction, congestion
`tends
`to predominate.5 Eosinophil
`products such as major basic protein,
`eosinophil cationic protein, hypochlor-
`ate, leukotrienes and others are thought
`to damage the epithelium and other
`cells, an inflammatory response that
`promotes the tissue damage of chronic
`allergic reactions.
`to
`lymphocytes are thought
`TH2
`play a critical role in promoting the
`allergic response by releasing their
`combination of IL3, IL4, IL5, and
`other cytokines that promote IgE pro-
`duction, eosinophil chemoattraction
`and survival in tissues, and mast cell
`recruitment.6 Cytokines released from
`TH2 lymphocytes, mast cells, eosino-
`phils, basophils and epithelial cells
`may circulate to the hypothalamus and
`promote the fatigue, malaise, irritabil-
`
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`ity, and neurocognitive deficits that
`commonly afflict those suffering from
`allergic rhinitis. Glucocorticoids are
`effective at reducing the release of
`these cytokines during late phase re-
`sponses.7
`Priming response. When allergen
`challenges are given repeatedly,
`the
`amount of allergen required to induce
`an immediate response decreases.8
`This “priming” effect is thought to be
`due to the influx of inflammatory cells
`during ongoing, prolonged allergen ex-
`posure and repeated late phase re-
`sponses. This response is clinically im-
`portant, since exposure to one allergen
`(eg, early spring tree pollen) may pro-
`mote the more exaggerated later re-
`sponses to another allergen (eg, late
`spring grass pollen). This priming ef-
`fect demonstrates the importance of
`knowing the full spectrum of allergens
`to which a patient responds, the sea-
`sons of their allergic responses, and
`highlights the need to initiate effective
`anti-inflammatory
`therapies
`before
`pollen seasons and allergen exposures
`so that the inflammatory allergic phase
`will not occur.
`
`References
`1. Naclerio RM. Allergic rhinitis. N Engl
`J Med 1991;325:860–869.
`2. Mygind N, ed. Allergic and nonaller-
`gic rhinitis clinical aspects. Phila-
`delphia: Saunders, PA, 1993.
`3. Naclerio RM, Proud D, Togias AG, et
`al. Inflammatory mediators in late an-
`tigen-induced rhinitis. N Engl J Med
`1985;313:65–70.
`4. Bascom R, Pipkorn U, Lichtenstein
`LM, Naclerio RM. The influx of in-
`flammatory cells into nasal washings
`during late response to antigen
`challenge: effect of corticosteroid pre-
`treatment. Am Rev Respir Dis 1988;
`138:406–412.
`5. Skoner DP, Doyle WJ, Boehm S, Fire-
`man P. Late phase eustachian tube and
`nasal allergic responses associated
`with inflammatory mediator elabora-
`tion. Am J Rhinol 1988;2:155–161.
`6. Durham SR, Sun Ying M, Varney VA,
`et al. Cytokine messenger RNA ex-
`pression for IL-3, IL-4, IL-5 and gran-
`ulocyte/macrophage-cloning-stimulat-
`ing factor in the nasal mucosal after
`local allergen provocation: relation-
`
`ship to tissue eosinophilia. J Immunol
`1992;148:2390–2394.
`7. Sim TC, Reece LM, Hilsmeier KA, et
`al. Secretion of chemokines and other
`cytokines in allergen-induced nasal
`responses: inhibition by topical steroid
`treatment. Am J Respir Crit Care Med
`1995;152:927–933.
`8. Connell JT. Quantitative intranasal
`pollen changes. III. The priming effect
`in allergic rhinitis. J Allergy 1969;50:
`43–44.
`
`Seasonal and Perennial Allergic
`Rhinitis
`9. Symptoms of allergic rhinitis
`may occur only during specific
`seasons, may be perennial with-
`out seasonal exacerbation, pe-
`rennial with seasonal exacerba-
`tion, or may occur sporadically
`after specific exposures.
`is
`10. Seasonal
`allergic
`rhinitis
`caused by an IgE-mediated re-
`action to seasonal aeroallergens.
`Typical seasonal aeroallergens
`are pollens and molds. The
`length of seasonal exposure to
`these allergens is dependent on
`geographic location.
`is
`rhinitis
`11. Perennial allergic
`caused by an IgE-mediated re-
`action to perennial environmen-
`tal aeroallergens. These may in-
`clude dust mites, molds, animal
`allergens, or certain occupa-
`tional allergens, as well as pollen
`in areas where pollen is preva-
`lent perennially.
`12. Allergic rhinitis often coexists
`with allergic conjunctivitis.
`Symptoms of allergic rhinitis may in-
`clude paroxysms of sneezing, nasal
`pruritus (itching) and congestion, clear
`rhinorrhea and palatal itching. In se-
`vere cases, mucous membranes of the
`eyes, eustachian tube, middle ear and
`paranasal sinuses may be involved.
`This produces conjunctival
`irritation
`(itchy, watery eyes), redness and tear-
`ing, ear fullness and popping, itchy
`throat, and pressure over the cheeks
`and forehead. Malaise, weakness and
`fatigue may be present. The coinci-
`dence of other allergic syndromes such
`as atopic eczema or asthma, and a pos-
`itive family history of atopy, point to-
`
`ward an allergic eti