Diagnosis and Management of Rhinitis: Complete Guidelines ... · 2. Atrophic rhinitis 3....

41
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; 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, 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; 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; 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

Transcript of Diagnosis and Management of Rhinitis: Complete Guidelines ... · 2. Atrophic rhinitis 3....

Page 1: Diagnosis and Management of Rhinitis: Complete Guidelines ... · 2. Atrophic rhinitis 3. Hormonally-induced A. Hypothyroidism B. Pregnancy C. Oral contraceptives D. Menstrual cycle

Diagnosis and Management of Rhinitis:Complete Guidelines of the Joint Task Forceon Practice Parameters in Allergy, Asthmaand ImmunologyMark S Dykewicz, MD,‡ Stanley Fineman, MD, MBA,§ EditorsDavid P Skoner, MD,¶¶ Chair, Workgroup on RhinitisRichard Nicklas, MD�; Rufus Lee, MD; Joann Blessing-Moore, MD¶; James T Li, MD, PhD**;I Leonard Bernstein, MD††; William Berger, MD, MBA‡‡; Sheldon Spector, MD§§; andDiane Schuller, MD,�� Associate Editors

This document contains complete guidelines for diagnosis and management ofrhinitis developed by the Joint Task Force on Practice Parameters in Allergy,Asthma and Immunology, representing the American Academy of Allergy, Asthmaand Immunology, the American College of Allergy, Asthma and Immunology andthe Joint Council on Allergy, Asthma and Immunology. The guidelines are com-prehensive and begin with statements on clinical characteristics and diagnosis ofdifferent forms of rhinitis (allergic, non-allergic, occupational rhinitis, hormonalrhinitis [pregnancy and hypothyroidism], drug-induced rhinitis, rhinitis from foodingestion), 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 shouldnot be used. Parameters on management include use of environmental controlmeasures, pharmacologic therapy including recently introduced therapies and aller-gen immunotherapy. Because of the risks to patients and society from sedation andperformance impairment caused by first generation antihistamines, second genera-tion antihistamines that reduce or eliminate these side effects should usually beconsidered 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 onspecial considerations in patients subsets (children, the elderly, pregnancy, athletesand 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 CSim, MD; Chester T Stafford, MD; William WStorms, MD; Michael J Tronolone, MD; Mi-chael J Welch, MD; Chester C Wood, MD; andRobert 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,MDThis document was developed by the Joint

Task Force on Practice Parameters in Allergy,Asthma and Immunology, representing theAmerican Academy of Allergy, Asthma and Im-munology (AAAAI), the American College ofAllergy, Asthma and Immunology (ACAAI) andthe Joint Council on Allergy, Asthma and Im-munology. The AAAAI and the AACAAI havejointly accepted responsibility for establishingthese practice parameters. Because this docu-

ment incorporated the efforts of many partici-pants, no single individual, including those whoserved on the Joint Task Force, is authorized toprovide an official interpretation of this docu-ment by the AAAAI or ACAAI. Any request forinformation about or an interpretation of thisdocument by the AAAAI or ACAAI should bedirected 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 hiscapacity as a medical officer with the Food andDrug Administration. No official support or en-dorsement by the Food and Drug Administrationis intended or should be inferred.‡ Division of Allergy and Immunology, De-

partment of Internal Medicine, Saint LouisUniversity 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, Universityof Pittsburgh School of Medicine, Pittsburgh,Pennsylvania; � Department of Medicine,George Washington Medical Center, Washing-ton, DC; ¶ Departments of Medicine & Pediat-rics, Stanford University Medical Center, PaloAlto, California; ** Department of Medicine,Mayo Clinic & Medical School, Rochester, Min-nesota; †† Departments of Medicine & Environ-mental Health, University of Cincinnati Collegeof Medicine, Cincinnati, Ohio; ‡‡ Department ofPediatrics, 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; �� 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 areinadvertently excluded, the Task Force will in-sure that appropriate recognition of such contri-butions is subsequently made.

478 ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGYExhibit 1019IPR2017-00807ARGENTUM

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Contents and Organization of this DocumentSummaryStatement

Page

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480

DEFINITION OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 480

DIFFERENTIAL DIAGNOSIS OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 480

Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3–12 480

Non-Allergic rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 484

Infectious rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 485

Non-Allergic rhinitis without eosinophilia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 485

Non-Allergic rhinitis with eosinophilia syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 486

Occupational rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 486

Hormonal rhinitis (pregnancy and hypothyroidism) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 487

Drug-induced rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 487

Rhinitis from food ingestion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 487

Other conditions that may be confused with rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 488

Nasal polyps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 489

EVALUATION OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489

History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23–24 489

Physical examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 491

Testing for specific IgE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 492

Special diagnostic techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 493

Nasal cytology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 494

Total serum IgE, blood eosinophil counts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 495

Unproven or inappropriate testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 495

MANAGEMENT OF RHINITIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497

Environmental control measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 497

Pharmacologic therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 500

Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33–35 501

Issues with sedation/performance impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 501

Cardiac effects of some antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 501

Intranasal antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 505

Oral and nasal decongestants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 505

Nasal corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 506

Oral and parenteral corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 506

Intranasal cromolyn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 507

Intranasal anti-cholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 508

Oral anti-leukotriene agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 510

Allergen immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 510

Surgical approaches for co-morbid conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 511

Important considerations in management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 511

Education of patient and caregivers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 511

Importance of rhinitis management for concomitant asthma, sinusitis, and otitis media . . . . . . . . . . . . . . . . 47 512

Special considerations in children, the elderly, pregnancy, athletes, and rhinitis medicamentosa . . . . . . . . . 48 513

Consultation with an allergist-immunologist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 518

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INTRODUCTIONRhinitis may be caused by allergic,non-allergic, infectious, hormonal, oc-cupational and other factors. All toooften, important causes of rhinitis gounrecognized by both physicians andpatients. This leads to suboptimal con-trol of the disease.Rhinitis is a significant cause of

widespread morbidity. Althoughsometimes mistakenly viewed as atrivial disease, symptoms of rhinitismay significantly impact the patient’squality of life, by causing fatigue,headache, cognitive impairment andother systemic symptoms. Appropriatemanagement of rhinitis may be an im-portant component in effective man-agement of co-existing or complicatingrespiratory conditions, such as asthma,sinusitis, or chronic otitis media. Thecost of treating rhinitis and indirectcosts related to loss of workplace pro-ductivity resulting from the disease aresubstantial. The estimated cost of al-lergic rhinitis based on direct and in-direct costs is 2.7 billion dollars for theyear 1995, exclusive of costs for asso-ciated medical problems such as sinus-itis and asthma. Allergic rhinitis, themost common form of rhinitis, affects20 to 40 million people in the UnitedStates 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 keypoints precede supporting text and rel-evant citations of evidence-based pub-lications.

DEFINITION OF RHINITIS1. Rhinitis is defined as inflamma-tion of the membranes lining thenose, and is characterized by na-sal congestion, rhinorrhea, sneez-ing, itching of the nose and/orpostnasal drainage.

Rhinitis can be defined as a heteroge-neous disorder characterized by one ormore of the following nasal symptoms:sneezing, itching, rhinorrhea, and/ornasal congestion. Rhinitis frequently is

accompanied by symptoms involvingthe eyes, ears, and throat. Post-nasaldrainage may also be present fre-quently.

Reference1. Druce HM. Allergic and nonallergicrhinitis. In: Middleton EJ, Reed CE,Ellis EF, et al, eds. Allergy principlesand practice, 5th edition. St. Louis:Mosby-Year Book Inc, 1998:1005–1016.

DIFFERENTIAL DIAGNOSIS OFRHINITIS2. Rhinitis should be classified byetiology as allergic or nonaller-gic.

Allergic rhinitis is a very commoncause of rhinitis. However, since ap-proximately 50% of patients with rhi-nitis do not have allergic rhinitis, otherpotential causes must also be ruledout.1–3 The following outline lists dif-ferent forms of allergic and non-aller-gic rhinitis, and conditions that maymimic rhinitis.I. Allergic rhinitisA. SeasonalB. PerennialC. EpisodicD. Occupational (may also be non-allergic)

II. Non-allergic rhinitisA. Infectious1. Acute2. Chronic

B. NARES syndrome(Nonallergic rhinitis with eo-sinophilia syndrome)

C. Perennial nonallergic rhinitis(Vasomotor rhinitis)

D. Other rhinitis syndromes1. Ciliary dyskinesia syndrome2. Atrophic rhinitis3. Hormonally-inducedA. HypothyroidismB. PregnancyC. Oral contraceptivesD. Menstrual cycle

4. Exercise5. Drug-InducedA. Rhinitis medicamentosaB. Oral contraceptivesC. Anti-hypertensive ther-apy

D. AspirinE. Nonsteroidal anti-in-flammatory drugs

6. Reflex-InducedA. Gustatory rhinitisB. Chemical or irritant-in-duced

C. Posture reflexesD. Nasal cycleE. Emotional factors

7. Occupational (may be aller-gic)

III. Conditions that may mimic symp-toms of rhinitisA. Structural/mechanical factors1. Deviated septum/septal wallanomalies

2. Hypertrophic turbinates3. Adenoidal hypertrophy4. Foreign bodies5. Nasal tumorsA. BenignB. Malignant

6. Choanal atresiaB. Inflammatory/immunologic1. Wegener’s granulomatosis2. Sarcoidosis3. Midline granuloma4. Systemic lupus erythemato-sus

5. Sjogren’s syndrome6. Nasal polyposis

C. Cerebrospinal fluid rhinorrhea

References1. Lieberman P. Rhinitis. In: Bone RC,ed. Current practice of medicine. vol 2.Philadelphia: Churchill Livingstone1996; 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 vasomotorrhinitis. Copenhagen, Munksgaard,1985;15.

3. Sibbald B, Rink E. Epidemiology ofseasonal and perennial rhinitis: clinicalpresentation and medical history. Tho-rax 1991;46:895–901.

Allergic Rhinitis3. Allergic rhinitis affects 20 to40 million people in the UnitedStates annually, including 10%to 30% of adults and up to 40%of children.

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4. The severity of allergic rhinitisranges from mild to seriouslydebilitating.

5. The cost of treating allergic rhi-nitis and indirect costs related toloss of workplace productivityresulting from the disease aresubstantial. The estimated costof allergic rhinitis based on di-rect and indirect costs is 2.7 bil-lion dollars for the year 1995,exclusive of costs for associatedmedical problems such as sinus-itis and asthma. Rhinitis is also asignificant cause of lost schooldays.

6. Risk factors for allergic rhinitisinclude: (1) family history ofatopy; (2) serum IgE > 100IU/mL before age 6; (3) highersocioeconomic class; (4) expo-sure to indoor allergens such asanimals and dust mites; (5) pres-ence of a positive allergy skinprick test.

Rhinitis is reported to be a very fre-quent disease, although data regardingthe true prevalence of rhinitis are dif-ficult to interpret. Most population sur-veys rely upon physician-diagnosedrhinitis for their data, and this maygive rise to a much lower reporting ofrhinitis. Some population studies havebeen done with questionnaires admin-istered to the subjects followed inmany cases by telephone interviews totry to make a specific diagnosis ofrhinitis. These studies may reflect amore accurate prevalence of rhinitisbut probably still underreport this dis-ease.1–7Most epidemiologic studies have

been directed towards seasonal allergicrhinitis, or hay fever, since this symp-tom complex with its reproducible sea-sonality is somewhat easier to identifyin population surveys. Perennial aller-gic rhinitis is more difficult to identifybecause its symptom complex mayoverlap with chronic sinusitis, recur-rent upper respiratory infections, andvasomotor rhinitis.The prevalence of rhinitis in various

epidemiologic studies ranges from 3%to 19%. Studies suggest that seasonalallergic 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 allergicrhinitis in 42% of 6-year-old children.3Overall, allergic rhinitis affects 20 to40 million individuals in the UnitedStates annually.11,12In childhood, males with allergic

rhinitis outnumber females, but thegender ratio becomes approximatelyequal in adults and may even favorfemales. Surveys of medical studentshave resulted in a higher prevalence ofrhinitis, but this may be related to thesurvey technique.1,6,8Allergic rhinitis develops before age

20 in 80% of cases. Studies haveshown that the frequency of allergicrhinitis increases with age until adult-hood and that positive immediate hy-persensitivity skin tests are significantrisk factors for the development of newsymptoms of seasonal allergic rhini-tis.1,8,13 There is a greater chance of achild developing allergic rhinitis ifboth parents have a history of atopy,than if only one parent is atopic. Chil-dren in families with a bilateral familyhistory of allergy generally developsymptoms before puberty; those with aunilateral family history tend to de-velop their symptoms later in life ornot at all.5,10There tends to be an increased prev-

alence of allergic rhinitis in higher so-cioeconomic classes, in non-whites, insome polluted urban areas, and in in-dividuals with a family history of al-lergy. Allergic rhinitis is more likely infirst-born children. Studies in childrenin the first years of life have shownthat the risk of rhinitis was higher inthose youngsters with early introduc-tion of foods or formula, heavy mater-nal cigarette smoking in the first yearof life, exposure to indoor allergenssuch as animals and dust mite, higherserum IgE levels (�100 IU/mL beforeage 6), and parental allergic disorders.3Seasonal allergic rhinitis is appar-

ently becoming more common. Onestudy showed that the prevalence ofhay fever increased from 4% to 8% inthe 10 years from 1971 to 1981.14 Inanother study, atopic skin test reactiv-

ity increased from 39% to 50% in dur-ing an 8-year period of evaluation.15The impact on society is tremen-

dous.16 The severity of allergic rhinitisranges from mild to seriously debilitat-ing. The cost of treating allergic rhini-tis and indirect costs related to loss ofworkplace productivity resulting fromthe disease are substantial. The esti-mated cost of allergic rhinitis based ondirect and indirect costs is 2.7 billiondollars for the year 1995, exclusive ofcosts for associated medical problemssuch as sinusitis and asthma. The totaldirect and indirect cost estimates forallergic rhinitis have been reported tobe $5.3 billion for 1996. This figureincluded the higher indirect costs asso-ciated with increased loss of produc-tivity, which, in turn, was related toextensive over-the-counter antihista-mine use. Such treatment can causedrowsiness and impair cognitive andmotor function (see summary state-ment #34).Rhinitis is also a significant cause of

lost school attendance, resulting inmore than 2 million absent school daysin the US annually. In children, there isevidence that symptoms of allergic rhi-nitis can impair cognitive functioning,which can be further impaired by theuse of first generation antihistamines.17

References1. Hagy GW, Settipane GA. Prognosis ofpositive allergy skin tests in an asymp-tomatic population. J Allergy 1971;48:200.

2. Druce HM. Allergic and nonallergicrhinitis. In: Middleton EJ, Reed CE,Ellis EF, et al. Allergy principles andpractice, 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 historyof allergic diseases in children. ActaPediatr 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-likesymptoms 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 rhinitisand eczema in Swedish school chil-dren between 1979 and 1991. Clin ExpAllergy 1995;25:815–819.

8. Settipane RJ, Hagy GW, SettipaneGA. Long-term risk factors for devel-oping asthma and allergic rhinitis: a23-year follow-up study of college stu-dents. Allergy Proc 1994;51:21–25.

9. Varyonen E, Kalimo K, LammintaustaK. Prevalence of atopic disordersamong adolescents in Turku, Finland.Allergy 1992;47:243–248.

10. Smith JM. A five-year prospective sur-vey of rural children with asthma andhay 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 inthe United States in 1990. Ann Allergy1994;73:35–39.

13. Tang RB, Tsai LC, Hwang B, et al.The prevalence of allergic disease andIgE antibodies to house dust mite inschool children in Taiwan. Clin ExpAllergy 1990;20:33–38.

14. Linna O, Kokkonen J, Lukin M. A10-year prognosis for childhood aller-gic rhinitis. Acta Pediatr 1992;81:100–102.

15. Sibbald B, Rink E, O’Souza M. Is theprevalence of atopy increasing? Br JGen 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-drivenmucosal inflammation resultingfrom an interplay between residentand infiltrating inflammatory cells,and a number of inflammatory me-diators and cytokines. Sensory nerveactivation, 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 toperform these functions.1 Dysfunctionof any of these structures may contrib-

ute to the symptoms of allergic andnonallergic rhinitis.2

References1. Raphael GR, Baraniuk JN, KalinerMA. How and why the nose runs. JAllergy 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, Inc1995;79–123.

8. Allergic rhinitis may be character-ized by early and late phase re-sponses. Each type of response ischaracterized by sneezing, conges-tion and rhinorrhea, but congestionpredominates in the latter.

Atopic subjects inherit the tendency todevelop IgE-mast cell-TH2 lympho-cyte immune responses. Exposure tolow concentrations of dust mite fecalproteins, cockroach, cat, dog and otherdanders, pollen grains, or other aller-gens for prolonged periods of timeleads to the presentation of the allergenby antigen presenting cells (APC) toCD4� lymphocytes that release IL3,IL4, IL5, GM-CSF and other cyto-kines. These promote IgE productionagainst these allergens by plasma cells,mast cell proliferation and infiltrationof airway mucosa, and eosinophilia.Early or immediate allergic re-

sponse. With continued allergen expo-sure, increasing numbers of IgE-coatedmast cells move into the epithelium,recognize the mucosally-deposited al-lergen, and degranulate.1 Mast cellproducts include preformed mediatorssuch as histamine, tryptase (a mast cellspecific marker), chymase (in “con-nective tissue” mast cells only), kini-nogenase (generates bradykinin), hep-arin, and other enzymes. Newlyformed mediators include prostaglan-din D2 and the cysteinyl-leukotrienesLTC4, 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 antimicrobialsubstances; and dilate arteriole-venuleanastomoses to cause sinusoidal filling

and occlusion of nasal air passages.Sensory nerves are stimulated that con-vey the sensations of nasal itch andcongestion, and initiate systemic re-flexes such as sneezing paroxysms.Release of these mast cell mediatorsand induction of these reactions occurwithin minutes of allergen exposure,and are termed the early or immediateallergic response.2 While most subjectsexperience sneezing and copious rhi-norrhea after allergen exposure, somesubjects have sensations of nasal con-gestion as their predominant symptom.Late phase response. The mast cells

mediators, including the cytokines, arethought to act upon post-capillary en-dothelial cells to promote VCAM andE-selectin expression that permits cir-culating leukocytes to stick to the en-dothelial cells. Chemoattractants, suchas IL-5 for eosinophils, promote theinfiltration of the superficial laminapropria 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 thecourse of 4 to 8 hours, these cells be-come activated and release their medi-ators, which in turn activate many ofthe proinflammatory reactions of theimmediate response. This late occur-ring inflammatory reaction is termedthe “late phase response”. While thisreaction may be clinically similar tothe immediate reaction, congestiontends to predominate.5 Eosinophilproducts such as major basic protein,eosinophil cationic protein, hypochlor-ate, leukotrienes and others are thoughtto damage the epithelium and othercells, an inflammatory response thatpromotes the tissue damage of chronicallergic reactions.TH2 lymphocytes are thought to

play a critical role in promoting theallergic response by releasing theircombination of IL3, IL4, IL5, andother cytokines that promote IgE pro-duction, eosinophil chemoattractionand survival in tissues, and mast cellrecruitment.6 Cytokines released fromTH2 lymphocytes, mast cells, eosino-phils, basophils and epithelial cellsmay circulate to the hypothalamus andpromote the fatigue, malaise, irritabil-

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ity, and neurocognitive deficits thatcommonly afflict those suffering fromallergic rhinitis. Glucocorticoids areeffective at reducing the release ofthese cytokines during late phase re-sponses.7Priming response. When allergen

challenges are given repeatedly, theamount of allergen required to inducean immediate response decreases.8This “priming” effect is thought to bedue to the influx of inflammatory cellsduring 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, latespring grass pollen). This priming ef-fect demonstrates the importance ofknowing the full spectrum of allergensto which a patient responds, the sea-sons of their allergic responses, andhighlights the need to initiate effectiveanti-inflammatory therapies beforepollen seasons and allergen exposuresso that the inflammatory allergic phasewill not occur.

References1. Naclerio RM. Allergic rhinitis. N EnglJ 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, etal. Inflammatory mediators in late an-tigen-induced rhinitis. N Engl J Med1985;313:65–70.

4. Bascom R, Pipkorn U, LichtensteinLM, Naclerio RM. The influx of in-flammatory cells into nasal washingsduring late response to antigenchallenge: 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 andnasal allergic responses associatedwith 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 afterlocal allergen provocation: relation-

ship to tissue eosinophilia. J Immunol1992;148:2390–2394.

7. Sim TC, Reece LM, Hilsmeier KA, etal. Secretion of chemokines and othercytokines in allergen-induced nasalresponses: inhibition by topical steroidtreatment. Am J Respir Crit Care Med1995;152:927–933.

8. Connell JT. Quantitative intranasalpollen changes. III. The priming effectin allergic rhinitis. J Allergy 1969;50:43–44.

Seasonal and Perennial AllergicRhinitis9. Symptoms of allergic rhinitismay occur only during specificseasons, may be perennial with-out seasonal exacerbation, pe-rennial with seasonal exacerba-tion, or may occur sporadicallyafter specific exposures.

10. Seasonal allergic rhinitis iscaused by an IgE-mediated re-action to seasonal aeroallergens.Typical seasonal aeroallergensare pollens and molds. Thelength of seasonal exposure tothese allergens is dependent ongeographic location.

11. Perennial allergic rhinitis iscaused by an IgE-mediated re-action to perennial environmen-tal aeroallergens. These may in-clude dust mites, molds, animalallergens, or certain occupa-tional allergens, as well as pollenin areas where pollen is preva-lent perennially.

12. Allergic rhinitis often coexistswith allergic conjunctivitis.

Symptoms of allergic rhinitis may in-clude paroxysms of sneezing, nasalpruritus (itching) and congestion, clearrhinorrhea and palatal itching. In se-vere cases, mucous membranes of theeyes, eustachian tube, middle ear andparanasal sinuses may be involved.This produces conjunctival irritation(itchy, watery eyes), redness and tear-ing, ear fullness and popping, itchythroat, and pressure over the cheeksand forehead. Malaise, weakness andfatigue may be present. The coinci-dence of other allergic syndromes suchas atopic eczema or asthma, and a pos-itive family history of atopy, point to-

ward an allergic etiology. Around 20%of cases are accompanied by symp-toms of asthma.1When all the typical rhinitis symp-

toms are not expressed, the diagnosisis more difficult to make. Chronic na-sal obstruction alone may be the majorsymptom of perennial rhinitis due toongoing inflammation and late-phaseallergic reactions.2 Distinct temporalpatterns of symptom production mayaid diagnosis. Symptoms of rhinitiswhich occur whenever the patient isexposed to a furry pet suggest IgE-mediated sensitivity to that pet. Pa-tients who are exquisitely sensitive toanimal proteins may develop symp-toms of rhinitis and asthma when en-tering a house or laboratory eventhough the animal is no longer present.Exposure to airborne allergens in theworkplace may produce symptomsonly at work with symptom-free peri-ods away from work. Seasonal and pe-rennial forms of allergic rhinitis oftencoexist in the same individual. Symp-toms may be chronic and persistentand patients may present with second-ary complaints of mouth-breathing,snoring, or symptoms of sinusitis.3Seasonal allergic rhinitis symptoms

typically appear during a defined sea-son in which aeroallergens are abun-dant in the outdoor air. Familiaritywith the pollinating season of the ma-jor trees, grasses and weeds of the lo-cale makes the syndrome easier to di-agnose.4,5 Certain outdoor mold sporesalso display seasonal variation, withhighest levels in the summer and fallmonths.6 Tree (eg, birch, oak, maple,mountain cedar), grass, and weed (eg,ragweed) pollens, and fungi (“molds”:Alternaria, Aspergillus, Cladospo-rium) are common seasonal allergens.Priming effects, increases in sensorynerve irritability, and mucosal infiltra-tion by activated eosinophils, mastcells, and TH2 lymphocytes have beenidentified. Hyperresponsiveness to ir-ritant triggers such as tobacco smoke,noxious odors, changes in temperature,and exercise may persist beyond theactual pollen season.In studies of allergic seasonal rhini-

tis, a correlation between the daily pol-

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len count and overall daily symptomscore and medication score has beenfound. The symptoms on any particu-lar day will be influenced by exposureon that day but also on previous daysdue to the priming phenomenon. As aconsequence, at the end of the pollenseason, it is usual to observe a declinein symptoms which is slower than thatof the pollen counts themselves.7 Indi-vidual sensitivity will also influencethe intensity of symptoms. In highlysensitive individuals, many symptomsoccur with pollen counts of 15 to 75pollen grains/m3 per 24 hours, whereasin the less sensitive, 4 to 10 times thisexposure may be necessary to provokeequivalent symptoms.8 The levels ofpollen counts that cause symptomsmay vary with an individual’s degreeof sensitivity and with different pol-lens.9In perennial allergic rhinitis the re-

sponsible allergens are present in theenvironment throughout the year, andare usually indoor. Chronic exposureto dust mites (Dermatophagoidespteronyussinus, D. farinae), cock-roach, perennial molds, cat, dog andother danders leads to persistent tissueedema and infiltration with eosino-phils, mast cells, TH2 lymphocytes,and macrophages.10 Chronic allergenexposure with unremitting recruitmentof inflammatory cells often requirescorticosteroids for control. In somesubjects, nasal congestion and mucusproduction (post-nasal drip) symptomspredominate, and sneezing and wateryrhinorrhea may be minimal.

References1. Evans III R. Epidemiology and naturalhistory of asthma, allergic rhinitis, andatopic dermatitis. In: Middleton E, Jr,Reed CE, Ellis EF, et al, eds. Allergy:principles and practice. 4th edition. St.Louis: Mosby, 1993:1109–1136.

2. Skoner DP, Doyle WJ, Boehm S, Fire-man P. Late phase eustachian tube andnasal allergic responses associatedwith inflammatory mediator elabora-tion. Am J Rhinol 1988;2:155–161.

3. Lucente FE. Rhinitis and nasal ob-struction. Otolaryngol Clin North Am1989;22:307–318.

4. Jelks M. Allergy plants that cause

sneezing and wheezing, Tampa:Worldwide Publications, 1986.

5. Lewis WH, Vinay P, Zenger VE. Air-borne and allergic pollen of NorthAmerica, Baltimore: Johns HopkinsUniversity Press, 1983.

6. Platts-Mills TAE, Hayden ML, Chap-man MD, Wilkins SR. Seasonal varia-tion in dust mite and grass pollen al-lergens in dust from the houses ofpatients with asthma. J Allergy ClinImmunol 1987;79:781–791.

7. Brostrom G, Moller CA. A newmethod to relate symptom scores withpollen counts. A dynamic model forcomparison of treatments of allergy.Grana 1990;28:123–128.

8. Taudorf E, Moseholm L. Pollen count,symptom and medicine score in birthpollinoses. A mathematical approach.Int Arch Allergy Appl Immunol 1988;86:225–233.

9. Solomon WR, Platts-Mills TAE. Aer-obiology and inhalant allergens. In:Middleton EJ, Reed CE, Ellis EF, et al,eds. Allergy principles and practice,5th edition. St. Louis: Mosby-YearBook Inc, 1998;367–403.

10. Bradding P, Feather IH, Wilson S, etal. Immunolocalization of cytokines inthe nasal mucosa of normal and peren-nial rhinitis subjects. J Immunol 1993;151:3853–3865.

Non-Allergic Rhinitis13. Nonallergic rhinitis is character-

ized by sporadic or persistent pe-rennial symptoms of rhinitis thatdo not result from IgE-mediatedimmunopathologic events. Exam-ples of nonallergic rhinitis areinfectious rhinitis, hormonal rhi-nitis, vasomotor rhinitis, nonaller-gic rhinitis with eosinophilia syn-drome (NARES), certain types ofoccupational rhinitis, and gusta-tory and drug-induced rhinitis.

The differential diagnosis of nonaller-gic rhinitis is extensive.1 The mecha-nisms in each are poorly understood.Nonallergic rhinitis with inflammatorycells present in the mucosa can be clas-sified by inflammatory cell type.Nonallergic rhinitis with eosino-

philia syndrome (NARES) is charac-terized by nasal congestion and prom-inent nasal eosinophilia. (see summarystatement #15) The mechanism of theeosinophil infiltration is not known.

Eosinophilia is also prominent whennasal polyps are present, but again themechanism of eosinophil recruitmentis not known. Subjects with aspirinsensitivity have nasal eosinophilia. As-pirin and other nonsteroidal antiin-flammatory drugs (NSAIDs) block cy-clooxygenase activity, and shuntarachidonic acid to the 5-lipoxygenasepathway that increases production ofthe potent proinflammatory cysteinylleukotrienes (LTC4, LTD4, and LTE4).2Neutrophilic infiltrates usually indi-

cate the presence of bacterial rhinosi-nusitis, especially when humoral im-munodeficiency or ciliary dysmotilityare present. LTB4, IL8, bacterial prod-ucts, and complement fragments maycontribute to their recruitment and ac-tivation. Neutrophilic infiltrates mayalso be present in rhinoviral and otherviral rhinitis syndromes. Early in rhi-novirus infections there is an increasein vascular permeability that is likelydue to bradykinin. Later, there may bean increase in glandular secretion, par-ticularly of locally synthesized secre-tory IgA.There are several causes of nonaller-

gic rhinitis without inflammation/in-flammatory cells. Endocrine changesof hypothyroid and hyperthyroid dis-ease, and pregnancy can lead to unre-mitting nasal congestion. Damage tosympathetic nerves, as in Horner’ssyndrome, can ablate sympathetic va-soconstrictor tone and lead to unop-posed vasodilatory parasympathetic re-flexes and chronic nasal congestion.Overuse of topical-adrenergic ago-nists/nasal decongestants also leads tochronic nasal congestion (“rhinitismedicamentosa”).Vasomotor rhinitis is unrelated to

allergy, infection, structural lesions,systemic disease, or drug abuse. (seesummary statement #16) Although theterm vasomotor implies increased neu-ral efferent traffic to the blood vesselssupplying the nasal mucosa, this hasnever been proven. Subjects with va-somotor rhinitis fall into two generalgroups: “runners” who have “wet” rhi-norrhea, and “dry” subjects with pre-dominant symptoms of nasal conges-tion and blockage to airflow, and

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minimal rhinorrhea. These reactionscan be provoked by nonspecific irritantstimuli such as cold dry air, perfumes,paint fumes, and cigarette smoke. Sub-jects with predominantly rhinorrhea(sometimes referred to as cholinergicrhinitis) appear to have enhanced cho-linergic glandular secretory activity,since atropine effectively reduces theirsecretions.3 Subjects with predomi-nantly nasal congestion and blockagemay have nociceptive neurons thathave heightened sensitivity to innocu-ous stimuli.Emotional factors such as stress and

sexual arousal are known to have aneffect on the nose, probably due toautonomic stimulation.4

References1. Mygind N, Naclerio RM, eds. Allergicand nonallergic rhinitis. Philadelphia,PA: 1993.

2. Christie PE, Tagari P, Ford-Hutchin-son AW, et al. Urinary leukotriene E4concentrations increase after aspirinchallenge in aspirin sensitive subjects.Am Rev Respir Dis 1991;143:1025–1102.

3. Stjarne P, Lundblad L, Lundberg JM,Anggard A. Capsaicin and nicotinesensitive afferent neurons and nasal se-cretion in healthy human volunteersand in patients with vasomotor rhinitis.Br J Pharmacol 1989;96:693–701.

4. Eiser N. The hitch-hikers guide to na-sal airway patency. Respir Med 1990;84:179–183.

Infectious Rhinitis14. Infectious rhinitis may be acute

or chronic. Acute infectious rhi-nitis is usually due to one of alarge number of viruses, but sec-ondary bacterial infection withsinus involvement is a commoncomplication. Symptoms ofchronic infectious rhinosinusitisinclude mucopurulent nasal dis-charge, facial pain and pressure,olfactory disturbance, and post-nasal drainage with cough.

Acute rhinitis is usually associatedwith a viral upper respiratory infection,but may follow trauma.1 Symptoms ofacute viral rhinitis include rhinorrhea,nasal obstruction, and fever. Initially,

viral rhinitis is characterized by clear,watery rhinorrhea that is accompaniedby sneezing and nasal obstruction.Edema of the nasal mucosa producesocclusion of the sinus ostia with result-ing facial pain or of the eustachian tubewith resulting ear fullness. The nasaldrainage may become cellular andcloudy due to the presence of organ-isms, white blood cells and desqua-mated epithelium. Responsible virusesinclude rhinoviruses, respiratory syn-cytial virus, parainfluenza, influenzaand adenoviruses. Unless there is bac-terial superinfection, the condition isself-limiting and usually resolveswithin 7 to 10 days. Acute bacterialrhinitis may occur de novo or mayfollow viral rhinitis. Nasal obstruction,cloudy drainage, vestibular crustingand facial pain occur. Not all patientsreport fever. Bacteria frequently recov-ered from nasal or sinus cultures in-clude Streptococcus pneumoniae,group-A beta-hemolytic Streptococciand Hemophilus influenzae.2 In pa-tients with immunodeficiency, HIVpositivity, or acquired immunodefi-ciency syndrome (AIDS), mycobacte-rial, fungal, and other opportunistic or-ganisms may be involved.The symptoms of allergic rhinitis

are frequently confused with infectiousrhinitis when patients complain of aconstant cold. Purulent nasal drainagemay be present in either infectious ornon-infectious rhinitis. Symptoms per-sisting longer than two weeks shouldprompt a search for causes other thaninfection. Foreign body rhinitis shouldbe considered in the differential diag-nosis, especially in children. Symp-toms may be acute or chronic, unilat-eral or bilateral, and the nasaldischarge may be blood-stained orfoul-smelling.Exacerbations of rhinitis symptoms

with predominant clear rhinorrhea inpatients with a known history of aller-gic rhinitis may prove to be a diagnos-tic difficulty. The distinction betweenactive infection and allergy should bemade. When the history or physicalexamination is not diagnostic, a nasalsmear may be obtained to aid in dif-ferentiation.

There is controversy about whetherchronic infectious rhinitis (diagnosedafter 8 to 12 weeks of symptoms) canexist in the absence of chronic sinus-itis. Symptoms of chronic infectiousrhinosinusitis can include nasal con-gestion, predominantly purulent nasaldischarge, facial pain, and pressure, ol-factory disturbances and post-nasaldrainage with cough.3Allergy, mucociliary disturbance and

immune deficiency may predispose cer-tain individuals to the development ofchronic infection.4,5 Mucociliary abnor-malities may be congenital, as in primaryciliary dyskinesia,6 Young’s syndrome,7or cystic fibrosis, or secondary to infec-tion. Similarly, immune deficiency maybe congenital or acquired.

References1. Noble SL, Forbes RC, WoodbridgeHB. Allergic rhinitis. Am Fam Physi-cian 1995;51:837–846.

2. Gwaltney JM, Scheld M, Sande MA,Sydnor A. The microbial etiology andantimicrobial therapy of adults withacute community-acquired sinusitis: afifteen-year experience at the Univer-sity of Virginia and review of otherselected studies. J Allergy Clin Immu-nol 1992;90:457–462.

3. Kaliner MA, Osguthorpe JD, FiremanP, et al. Sinusitis: bench to bedside. JAllergy Clin Immunol 1997;99:S289–S847.

4. MacKay IS, Cole P. Rhinitis, sinusitisand associated chest disease. In:MacKay IS, Null TR, eds. Scott-Brown’s otolaryngology. vol. 4. Rhi-nology. London: Butterworths. 1987;61–92.

5. Lund VJ, Scadding GK. Immunologicaspects of chronic sinusitis. Can J Oto-laryngol 1991;105:181–185.

6. Afzelius BA. A human syndromecaused by immotile cilia. Science1976;193:317–319.

7. Young D. Surgical treatment of maleinfertility. J Reprod Fertil 1970;23:541–542.

Non-Allergic Rhinitis WithoutEosinophilia15. Nonallergic, noninfectious rhini-

tis, generally termed vasomotorrhinitis, comprises a heteroge-neous group of patients with

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chronic nasal symptoms that arenot immunologic or infectious inorigin and usually not associatedwith nasal eosinophilia. Most ofthese patients develop rhinitis inresponse to environmental con-ditions, such as cold air, highhumidity, strong odors and in-haled irritants.

The term vasomotor rhinitis has beenused loosely to describe patients withperennial rhinitis whose symptoms areintensified by changes in temperatureor relative humidity, alcohol, odorssuch as bleach, perfume or solvents,bright lights or hot spicy foods, andirritants such as tobacco smoke, dustsand automotive emission fumes. Thisdisorder is not due to allergy or infec-tion, nor is it associated with nasaleosinophilia. The symptoms are vari-able, consisting mainly of nasal ob-struction and increased secretion.Sneezing and pruritus are less com-mon. Although the term vasomotor im-plies increased neural efferent traffic tothe blood vessels supplying the nasalmucosa, this has never been proven.Some investigators prefer to use thedescriptive term “nonallergic” or “id-iopathic” rhinitis that does not implyknown pathophysiology.

Reference1. Druce HM. Allergic and nonallergicrhinitis. In: Middleton EJ, Reed CE,Ellis EF, et al, eds. Allergy principlesand practice, 5th edition. St. Louis:Mosby-Year Book Inc, 1998:1005–1016.

Non-allergic Rhinitis withEosinophilia Syndrome16. The nonallergic rhinitis with eo-

sinophilia syndrome (NARES) ischaracterized by nasal eosino-phils in patients who have pe-rennial symptoms and occasion-ally loss of sense of smell. Thesepatients lack evidence of allergicdisease as demonstrated by lackof clinically significant positiveskin tests and/or specific IgE an-tibodies in the serum.

In the NARES syndrome, individualsexperience perennial symptoms of

sneezing paroxysms, profuse wateryrhinorrhea and nasal pruritus and oc-casional loss of smell.1,2 Patients aretypically middle-aged and have a char-acteristic perennial course but withparoxysmal episodes. Nasal smears re-veal eosinophils during symptomaticperiods. Patients lack evidence of al-lergic disease as determined by skintesting or by serum levels of IgE anti-body to specific allergens. It is difficultto assess the prevalence of this syn-drome in the general population. Theetiology of the syndrome is obscure,but may be an early stage of aspirinsensitivity.3

References1. Jacobs RL, Freedman PM, BoswellRN. Non-allergic rhinitis with eosino-philia (NARES syndrome): clinicaland immunologic presentation. J Al-lergy Clin Immunol 1981;67:253.

2. Mullarkey MF. Eosinophilic nonaller-gic rhinitis. J Allergy Clin Immunol1988;82:941–949.

3. Moneret-Vautrin DA, Shieh V, Way-off M. Non-allergic rhinitis with eosin-ophilia syndrome (NARES)—a pre-cursor of the triad. Ann Allergy 1990;64:513–518.

Occupational Rhinitis17. Occupational rhinitis refers to

rhinitis arising in response toairborne substances in theworkplace, which may be medi-ated by allergic or nonallergicfactors, eg, laboratory animalantigen, grain, wood dusts, andchemicals. It often coexists withoccupational asthma.

Occupational rhinitis may be definedas sneezing, nasal discharge and/orcongestion caused by exposure to anairborne agent present in the work-place. Triggering substances may beirritants, such as tobacco smoke, coldair, formaldehyde, hair sprays, orchemicals acting apparently throughnon-immunologic mechanisms. Alter-natively, occupational exposure mayinvolve IgE-mediated reactions trig-gered by allergens such as laboratoryanimals (rats, mice, guinea pigs, etc.),animal products, grain (bakers and ag-ricultural workers), coffee beans, wood

dusts (particularly hard woods such asmahogany, western red cedar, iroko),latex, chemicals (eg, acid anhydrides,platinum salts, glues), mites, moldspores, pollen, psyllium, enzymes, anda litany of other substances. This dis-order frequently coexists with occupa-tional asthma. Occupational rhinitismay precede development of occupa-tional asthma.Symptoms may occur acutely at

work after intermittent exposure ormore chronically at work after contin-uous exposure. Occupational rhinitisshould be suspected in patients withnasal symptoms which are temporallyrelated to exposure at work and whichimprove away from the workplace. Foroccupational allergens, skin testingmay confirm sensitivity, if appropriatereagents are available. The most spe-cific diagnostic test for occupationalrhinitis is a challenge with the sus-pected agent, either naturally in theworkplace setting or in a medical set-ting. Optimally, in addition to symp-tom scores, such a challenge could in-clude pre-challenge and post-challengemeasures of nasal airway resistance us-ing anterior rhinomanometry.The optimal management of occupa-

tional rhinitis is avoidance of the oc-cupational trigger, either by modifyingthe workplace, use of filtering masks,or removing the patient from the ad-verse exposure. If this is impossible,pharmacologic therapy as discussed inearlier sections should be instituted,recognizing that chronic use of medi-cation will probably be required foradequate relief and prevention ofsymptoms. Strategies to prevent or re-duce symptoms may include the dailyuse of anti-inflammatory intranasalcorticosteroids or the administration ofantihistamines and/or intranasal cro-molyn immediately prior to allergenexposure. It is also important to insti-tute avoidance measure for non-occu-pational allergens that may contributeto rhinitis symptoms.

References1. Murphy EE, Slavin RS. Occupationalrhinitis: when to suspect, what to do. JRespir Dis 1995;16:135–142.

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2. Lund VJ, Aaronson D, Bousquet J andThe International Rhinitis Manage-ment Working Group. InternationalConsensus Report on the Diagnosisand Management of Rhinitis. Allergy1994;49(Suppl 19):1–34.

3. Druce HM. Allergic and nonallergicrhinitis. In: Middleton EJ, Reed CE,Ellis EF, et al, eds. Allergy principlesand practice, 5th edition. St. Louis:Mosby-Year Book Inc, 1998:1005–1016.

Hormonal Rhinitis18. Causes of hormonal rhinitis in-

clude pregnancy and hypothy-roidism. Although symptoms ofrhinitis, in particular nasal con-gestion, may occur during preg-nancy, most notably from thesecond month to term, thesesymptoms usually disappearrapidly after delivery. Othercauses of rhinitis such as allergicrhinitis, infectious rhinitis andrhinitis medicamentosa are alsocommon during pregnancy.

Pregnancy,1 puberty, the use of oralcontraceptives, hypothyroidism,2 orconjugated estrogens can be associatedwith nasal obstruction and/or hyperse-cretion. Evidence linking thyroid dis-ease directly with nasal pathology islimited.2 Increased nasal secretion inhypothyroidism has been reported onan anecdotal basis. The frequency ofrhinitis symptoms was unclear. Symp-toms of hypothyroidism such as leth-argy, constipation, and cold intoler-ance, should be sought. No clear dataexist which indicate that thyroid re-placement treatment alone leads to res-olution of an associated rhinitis.During pregnancy, rhinitis symp-

toms, especially congestion, often de-velop during the second month andpersist to term, but usually disappearshortly after delivery.2 These symp-toms are likely related to hormone-induced intranasal vascular engorge-ment and mucosal hypersecretion.3However, non-hormonal causes of rhi-nitis such as allergic rhinitis, vasomo-tor rhinitis, rhinitis medicamentosa andsinusitis are more common causes ofrhinitis in pregnancy.

References1. Mabry RL. Rhinitis in pregnancy.South Med J 1986;79:965–971.

2. Incaudo GA, and Schatz M. Rhinosi-nusitis associated with endocrineconditions: hypothyroidism and preg-nancy, In: Schatz M, Zeigler RS, Set-tipane GA, eds. Nasal manifestationsof systemic diseases, Providence:Oceanside, 1991.

3. Georgitis JW. Allergic and non-allergic rhinitis. Current concepts andtreatment. Immunol Allergy ClinNorth Am 1987;7:211–234.

Drug-Induced Rhinitis19. Drug-induced rhinitis may be

caused by a number of medica-tions, including ACE (angioten-sin-converting enzyme) inhibi-tors, reserpine, guanethidine,phentolamine, methyldopa andprazosin, as well as beta block-ers, chlorpromazine, aspirin,other NSAIDs (non-steroidal an-ti-inflammatory drugs) and oralcontraceptives. Rhinitis medica-mentosa commonly refers tothe over-use of nasally inhaledvasoconstrictor (decongestant)agents such as the OTC (over-the-counter) products, oxymeta-zoline or phenylephrine. Re-peated use of cocaine may alsoproduce rhinitis.

Medications may induce symptoms ofnasal congestion and/or rhinorrhea.1Antihypertensive medications are mostfrequently incriminated. Reserpinewas thought to be the major cause ofnasal obstruction, but guanethidine,phentolamine, methyldopa, ACE in-hibitors (angiotensin-converting en-zyme) and prazosin (alpha receptor an-tagonist) have been implicated. Otherantihypertensive drugs from variedpharmacologic classes have been doc-umented to have similar side effects.Oral contraceptives, chlorpromazineand beta blockers have also been im-plicated.2 Aspirin and non-steroidal an-ti-inflammatory agents (NSAIDs) mayproduce rhinorrhea. The rhinorrheamay be isolated, or part of a complexinvolving hyperplastic rhinosinusitis,nasal polyposis and asthma. Drugs ofabuse, such as cocaine, should also be

considered potential causes of rhinitis.Nasal irritation and inflammation mayproduce a rhinitis picture before theend-stage effects, such as nasal septalperforation, occur.3The repetitive use of topical alpha-

adrenergic nasal decongestant spraysfor more than 5 to 7 days may inducerebound nasal congestion upon with-drawal. These agents include over thecounter products containing oxymeta-zoline or phenylephrine. Also, patientsmay develop tachyphylaxis, due to theneed for more frequent doses to pro-vide adequate decongestion. Prolongedusage may lead to a hypertrophy of thenasal mucosa termed “rhinitis medica-mentosa”. The nasal mucosa is oftenbeefy-red, appears inflamed, andshows areas of punctate bleeding andscant mucus. This condition may becaused by down regulation of the nasalmucosal alpha-adrenergic receptors.Similar consequences may occur withprolonged use of other vasoconstrictoragents such as cocaine.Management of rhinitis medicamen-

tosa is discussed in text for summarystatement #48.

References1. Druce HM. Allergic and nonallergicrhinitis. In: Middleton EJ, Reed CE,Ellis EF, et al. Allergy principles andpractice, 5th edition. St. Louis: Mosby-Year Book Inc, 1998:1005–1016.

2. Ammar-Kohdja A. Influence des con-traceptifs oraux sur la muqueuse na-sale. Revue de Laryngologie OtologieRhinologie 1971;92:40–42.

3. Dax EM. Drug dependence in the dif-ferential diagnosis of allergic respira-tory disease. Ann Allergy 1990;64:261.

Rhinitis from Food Ingestion20. Rhinitis may occur after inges-

tion of foods or alcoholic prod-ucts. This may be due to vagallymediated mechanisms, nasal va-sodilation, food allergy and/orother undefined mechanisms.Food allergy is a rare cause ofrhinitis without associated gas-trointestinal, dermatologic orsystemic manifestations.

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Foods can provoke rhinitis symptomsby a variety of different mechanisms.1,2Ingested food allergens rarely produceisolated IgE mediated rhinitis withoutinvolvement of other organ systems.Urticarial rash, facial or lip swelling,or bronchospasm, strongly suggest anIgE mediated reaction.3 Symptomswhich promptly follow eating foods orfood additives may suggest a causaletiology, but this may or may not beIgE-mediated. In adults, food skin testsmay be appropriate in occasional casesif a careful history suggests food-re-lated rhinitis symptoms, particularly ifrhinitis symptoms are associated withother systemic symptoms. Although avariety of opinions have been ex-pressed in the literature,1–10 there is lit-tle or no credible data available to jus-tify routine performance of food skintests in the evaluation of rhinitis inadults. In the evaluation of rhinitis inchildren where the history may bemore difficult to interpret and food al-lergy is more common, there is greaterjustification to consider performanceof limited food skin testing. Beer, wineand other alcoholic drinks may pro-duce symptoms by nasal vasodilation.The syndrome of copious watery rhi-norrhea occurring immediately afteringestion of foods, particularly hot andspicy foods, has been termed “gustato-ry rhinitis” and is vagally mediated.10

References1. Metcalfe DD. The diagnosis of foodallergy: theory and practice. In: Spec-tor S, ed. Provocative challengeprocedures: bronchial, oral, nasal andexercise. vol. 2. Boca Raton: CRCPress. 1983:119–125.

2. Bock SA, Lee WY, Remigio LK, MayCD. Studies of hypersensitivity reac-tions to food in infants and children. JAllergy Clin Immunol 1978;62:327–334.

3. Atkins FM, Steinberg SS, and Met-calfe DD. Evaluation of immediate ad-verse reactions to foods in adult pa-tients. I. Correlation of demographic,laboratory, and prick skin test datawith response to controlled oral foodchallenge. J Allergy Clin Immunol1985;75:348.

4. Hendrick DJ, Davies RJ, D’Souza MF,

Pepys J. An analysis of skin prick re-actions in 656 asthmatic patients. Tho-rax 1975;30:2–8.

5. Foucard T. Allergy and allergy-likesymptoms in 1050 medical students.Allergy 1991;46:20–26.

6. Novembre E, de Martino M, VierucciA. Foods and respiratory allergy. J Al-lergy Clin Immunol 1988;81:1059–1065.

7. Pastorello E, Ortolani C, Luraghi MT,et al. Evaluation of allergic etiology inperennial rhinitis. Ann Allergy 1985;55:854–856.

8. Pelikan Z, Pelikan-Filipek M. Bron-chial response to the food ingestionchallenge. Ann Allergy 1987;58:164–172.

9. Heiner DC. Respiratory diseases andfood allergy. Ann Allergy 1984;53:657–664.

10. James JM, Bernhisel-Broadbent J,Sampson HA. Respiratory reactionsprovoked by double-blind food chal-lenges in children. Am J Respir CritCare Med 1994;149:59–64.

11. Raphael GD, Hauptschein-Raphael M,Kaliner M. Gustatory rhinitis: a syn-drome of food-induced rhinorrhea. JAllergy Clin Immunol 1989;83:110–115.

Other Conditions that May BeConfused with Rhinitis21. Signs and symptoms suggestive

of rhinitis can be produced byother conditions including: na-sal septal deviation, tumors, ad-enoidal hypertrophy, hypertro-phy of the nasal turbinates.

Nasal obstruction may be caused bycongenital or acquired anatomic abnor-malities, which may mimic symptomsof rhinitis. Reduced air flow throughthe nasal passages in infants may bedue to congenital choanal atresia. Themost common acquired anatomiccause of nasal obstruction in infantsand children is adenoidal hypertrophy.Nasal septal deviation, and nasal

turbinate or adenoidal hypertrophymany block flow of nasal secretions,leading to rhinorrhea or postnasal drip,as well as causing nasal blockage.Although comparatively rare, both

benign and malignant tumors maycause rhinitis symptoms.1 Lesions mayocclude the nasal airway, often unilat-erally and invariably. Rapidly growing

nasal malignancies may cause nasalobstruction early in the disease. Le-sions arising in the maxillary sinuspresent intranasally in the late stages ofthe disease, after the tumor has pene-trated the medial wall of the antrum.Bleeding may occur, as well as hypos-mia or anosmia, pain and otalgia. Pro-longed occupational exposure to chem-icals such as nickel, wood or leatherdusts, chromate, formaldehyde andchlorophenol, have been associatedwith hypertrophic rhinosinusitis, meta-plasia and carcinoma. Refractory clearrhinorrhea may be due to CSF leakeven in the absence of trauma or recentsurgery.Nasal mastocytosis presents with

symptoms of rhinorrhea and nasal con-gestion without pruritus.2 Patients withnasal mastocytosis display an espe-cially pale mucosa, which contains in-creased numbers of mast cells, and feweosinophils. Skin tests and other testsfor IgE-mediated disease are negative.Primary atrophic rhinitis occurs in

elderly patients who report nasal con-gestion and a constant bad smell (oze-na) in the nose.3 This persistent condi-tion is characterized by progressiveatrophy of the nasal mucosa and un-derlying bone of the conchae.4 Thickcrusts form that produce the character-istic foul odor. The nasal cavities areenlarged and squamous metaplasia ofthe surface epithelium is detectable.Patients report associated headachesand chronic sinusitis. The syndromeshould be separated from secondaryatrophic rhinitis, developing as a directresult of chronic granulomatous nasalinfections, chronic sinusitis, radical na-sal surgery, trauma and irradiation.The incidence of atrophic rhinitis indeveloped countries has declined, butthe disease is still prevalent in EasternEurope, Greece, Egypt, India, andChina. The etiology of primary atro-phic rhinitis has not yet been estab-lished. Theories include infection withKlebsiella ozaenae5 and other bacteria.Despite the sensation of congestion,rhinomanometric studies have shownno evidence of increased resistance toairflow.

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Systemic immunologic and non-im-munologic diseases may affect thenose. In uremia and diabetes, ischemiamay cause an anterior rhinitis. Othersinclude Wegener’s granulomatosis,sarcoidosis, relapsing polychondritisand midline granuloma.6 In certainsyndromes, the systemic symptomsmay be absent or undetected when pa-tients present with nasal complaints.Infections such as tuberculosis, syphi-lis, leprosy, sporotricosis, blastomyco-sis, histoplasmosis, and coccidiomyco-sis also may cause granulomatousnasal lesions. These are usually ulcer-ative, and crust formation may lead tonasal obstruction or bleeding. Rhino-scleroma is a rare chronic granuloma-tous disease associated with the bacte-rium Klebsiella rhinoscleromatis.Rhinoscleroma is endermic to EasternEurope and Central America, but isnow increasing in incidence in the US.Symptoms include purulent nasal dis-charge, crusting and nodule formationproducing nasal obstruction.

References1. Komisar A. Nasal obstruction due tobenign and malignant neoplasms. Oto-laryngol Clin North Am 1989;22:351–365.

2. Connell JT. Nasal mastocytosis [Ab-stract]. J Allergy 1969;43:182.

3. Zohar Y, Talmi YP, Strauss M, et al.Ozena revisited. J Otolaryngol 1990;19:345–349.

4. Goodman WS, deSouza FM. Atrophicrhinitis. In: English GM, ed. Otolaryn-gology. Philadelphia: JB Lippincott,1987;2:1–11.

5. Ferguson JL, McCaffrey TV, Kern EB,et al. Effects of Klebsilla ozaenae onciliary activity in vitro: implications inthe pathogenesis of atrophic rhinitis.Otolarygol Head Neck Surg 1990;102:207.

6. Falkoff RJ. Nasal manifestations ofsystemic disease, Providence: Ocean-side, 1991.

Nasal Polyps22. Nasal polyps may occur in con-

junction with chronic rhinitis orsinusitis and may contribute sig-nificantly to the patient’s symp-toms. Nasal polyps should al-

ways be considered in thedifferential diagnosis of patientswho present with invariant na-sal congestion and its sequelae.Allergy as a cause of nasal pol-yps has not been established butnasal polyps may occur in con-junction with allergic rhinitis.

Nasal polyps present as invariable na-sal obstruction and may occur in asso-ciation with chronic allergic rhinitis orsinusitis. They may occur in associa-tion with cystic fibrosis in children1and adults,2 asthma and as part of as-pirin idiosyncracy3 (acetylsalicylicacid sensitivity, sinusitis and asthma),but they most commonly occur alone.Allergy does not appear to predisposeto polyp formation, but mast cell reac-tions and eosinophil activation withsubsequent inflammation seem to beimportant and may explain why corti-costeroids are therapeutically effec-tive. Between 10% and 15% of pa-tients with allergic rhinitis also havenasal polyps.4

References1. Stern RC, Boat TF, Wood RE. Treat-ment and prognosis of nasal polyps incystic fibrosis. Am J Dis Child 1982;136:1067–1070.

2. DiSant’Agnese PA, David PB. Cysticfibrosis in adults: 75 cases and a re-view of 232 cases in the literature.Am J Med 1979;66:121–132.

3. Stevenson DD, Simon RA. Sensitivityto aspirin and nonsteroidal anti inflam-matory drugs. In: Middleton E, Jr,Reed CE, Ellis EF, et al, eds. Allergy:principles and practice. 4th edition. St.Louis: Mosby, 1993:1747–1766.

4. Fireman P. Allergic rhinitis. In: Fire-man P, Slavin RG, eds. Atlas of aller-gies, ed 2. London: Mosby-Wolfe,Times Mirror International PublishersLimited, 1996:141–159.

EVALUATION OF RHINITIS

History23. Full evaluation of the patient

with rhinitis should include adetermination of the pattern,chronicity, and seasonality ofsymptoms (or lack thereof), re-sponse to medications, presence

of coexisting conditions, occupa-tional exposure, a detailed envi-ronmental history and identifi-cation of precipitating factors.

A careful history will usually suggestthe diagnosis of rhinitis (Table 1). Athorough general medical historyshould be followed by questions spe-cific to rhinological symptoms, includ-ing information on environmental andoccupational factors and family his-tory. Allergic rhinitis can occur at anyage, including infancy, and the physi-cian should note the onset of symp-toms. Most patients with allergic rhi-nitis develop their symptoms prior tothe age of 20 years.1,2 The frequency ofsymptoms should be noted andwhether they are daily, episodic, sea-sonal or perennial. The duration andseverity of the symptoms should alsobe mentioned, and whether the severityhas increased, decreased, or remainedthe same over a period of time.Presentation of allergic rhinitis may

vary considerably. Some patientspresent primarily with symptoms ofsneezing and rhinorrhea whereas oth-ers present with nasal blockage withlittle or no itching or sneezing.Symptoms may be perennial, with

or without seasonal exacerbations. Inevaluating the patient, it is important toobtain a detailed account of when andwhere the symptoms arise. Commonseasonal allergens include tree, grassand weed pollens, and airborne molds.In seasonal allergic rhinitis, there is adistinct relation between timing of pol-len release at various geographic loca-tions and the appearance of symptoms.It is important to ask about the as-

sociation of acute symptoms with ex-posure to specific allergens such asmites during house cleaning, episodicexposures to animals or mold spores,which are present in increased amountsduring harvesting, mowing, or leaf rak-ing. Perennial allergens, such as dustmites, cockroaches, pet danders andmold spores can cause chronic symp-toms.Frequently, unsuspected occupa-

tional allergens can stimulate an IgE-mediated response, and inquiriesshould be made about this and poten-

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tial exposures to irritants in the work-place. (see Summary Statement #17)Consistent obstruction on the same

side suggests a polyp, foreign body,structural problem, or rarely, a tumor.Hyposmia and anosmia are most oftenassociated with nasal polyps or severedisease. Symptoms related to blockageof the airways include: frequent sorethroats, dryness of the mouth and oro-pharynx, a nasal quality to the voiceand snoring. An allergic salute may becharacterized by an upward or side-ways thrust of the palm of the handagainst the tip of the nose when wateryrhinorrhea and itching are significant,resulting in a transverse crease in theskin of the lower third of the externalnose. If sneezing is present, it oftenoccurs in paroxysms.The allergens, irritants and weather

conditions that precipitate or aggravatesymptoms should be detailed. Peren-nial symptoms more commonly occurwhen there are indoor pets, dust mitesor mold spores present throughout theyear. Moisture favors the growth ofmites and molds. Mattresses, pillows,upholstered furniture, curtains and car-pets are frequent sources of dust mites.House plants and stored paper goodsfavor mold growth. There is a directrelationship between the amount ofpollen exposure and severity of symp-toms.3 As the season progresses, thereis a gradual increase in severity ofsymptoms in relation to the pollencount due to immunologic enhance-ment of sensitivity or “priming.”4 Cer-tain foods can induce rhinitis symp-toms as has been confirmed by doubleblind challenges.5 Irritants can potenti-

ate the symptoms of allergic rhinitis.Emotional upsets can also exacerbaterhinitis symptoms. In an allergic indi-vidual, an upper respiratory infectioncan either mimic allergies or worsen orprolong the effects of allergies or othernon-specific irritants.6,7 Hormonal fac-tors or medications/drugs, such as anti-hypertensives or cocaine, can be re-sponsible for a persistent rhinitis. Apositive family history makes it morelikely that an allergy will develop,8 butthe pattern of inheritance seems to bepolygenic and a negative family his-tory by no means rules out the diagno-sis of allergic rhinitis. The level ofresponse to previous medication trialsis also important to assess. For exam-ple, a favorable response to antihista-mines would support a diagnosis ofallergy, while such a response to intra-nasal corticosteroids could support anyof a number of diagnoses, includingrhinitis due to allergy, or the NARESsyndrome.

References1. Haahtela R, Heiskala M, Slonemi I.Allergic disorders and immediate skintest reactivity in Finnish adolescents.Allergy 1980;35:433–441.

2. Hagy GW, Settipane GA. Bronchialasthma, allergic rhinitis and allergyskin tests among college students. JAllergy 1969;44:323.

3. Norman PS. Allergic rhinitis. J AllergyClin Immunol 1985;75:531–548.

4. Connell JT. Quantitative intranasalpollen changes. III. The priming effectin allergic rhinitis. J Allergy 1969;50:43–44.

5. Bock SA. Prospective appraisal ofcomplaints of adverse reactions to

foods in children during the first 3years of life. Pediatrics 1987;79:683–688.

6. Lemanske RF, Dick EC, Swenson C,et al. Rhinovirus upper respiratory in-fection increases airway hyperreactiv-ity and late asthmatic reactions. J ClinInvest 1989;83:1–10.

7. Doyle WJ, Skoner DP, Seroky JT, etal. Effect of experimental rhinovirus39 infection on the nasal response tohistamine and cold air challenges inallergic and non-allergic subjects. J Al-lergy Clin Immunol 1994;93:534–542.

8. Van Arsdel PP Jr, Motulsky AG. Fre-quency and hereditability of asthmaand allergic rhinitis in college students.Acta Genet 1959;9:101–114.

Taking History of Impact onQuality of Life24. Symptoms of rhinitis may signif-

icantly impact the patient’squality of life, by causing fa-tigue, headache, cognitive im-pairment and other systemicsymptoms. An assessment of thedegree to which these symptomsinterfere with the patient’s abil-ity to function should be made.

The “individuals subjective assessmentof his/her physical, physiologic and so-cial well being”1 is the cornerstone ofevaluating the effect of the varioustherapies provided by physicians. Inrhinitis, it is not only the clinical out-come—relief of sneezing, itching, rhi-norrhea or congestion—or the effecton measures of nasal patency studieswhich define success of treatment, butalso it is the functional impact of thetreatment on the patients daily lifewhich defines successful treatment.Diseases have a variety of impacts onpatients in addition to making themfeel ill. They also interfere in a varietyof ways with carrying out ones day today responsibilities. In patients withrhinitis, loss of sleep and concomitantfatigue, headache, poor concentration,repeated nose blowing, itchy wateryeyes and general irritability all impactnegatively on their ability to carry outphysical, social and work/school re-sponsibilities effectively.There are several surveys which

have been used to measure the out-

Table 1. Important Historical Points in the Evaluation of Rhinitis

● Symptoms: magnitude, duration, timing in relation to exposure (ie, early and/or late-phaseallergic reactions), effects on daily living

● Triggers/seasonality● Environment, including home, job and school or day care for children● History of other allergic symptoms (eg, asthma, conjunctivitis, eczema)● Past medical history, including trauma● Feeding history in young children● Past treatment experience● Current treatment● Family history, including allergic diseases● Review of systems

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comes of treatment on a variety ofdiseases. The Medical OutcomesStudy Short Form Healthy Survey (SF-36) has been used to measure the out-comes on specific functions such asphysical and role functioning and onemotional well being. On the otherhand specific rhinitis questionnaires,such as the Rhinoconjunctivitis Qual-ity of Life Questionnaire (RQLQ),have been validated in the measure-ment of the effects of treatment of na-sal disease on important parameters ofevery day living.2,3Another look at the Rhinoconjuncti-

vitis Quality of Life Questionnaire re-veals that a questionnaire specificallydesigned for 12 to 17-year old patientsis necessary to determine significantquality of life impacts of different ther-apies for this age group.4Another quality of life study evalu-

ated the impact of the relief of rhinor-rhea on moods and daily activities inpatients with non-allergic rhinitis. Thisstudy revealed that patients treatedwith topical ipratropium had substan-tially greater improvement in moodthan those on placebo.5Finally, one must note that numer-

ous studies have demonstrated thatbetter health outcomes occurred in pa-tients who adhere to treatment recom-mendations as compared to those whoare not compliant with recommendeddrug regimens.6 This fact is worrisomein evaluating the results of clinicaldrug trials which require patients to becompliant with drug administrationand do not make allowances for thenon-compliant patient.Allergic rhinitis, particularly when

perennial, can cause restrictions on thephysical, psychological, and socialwell-being of patients. In one studythat used the SF-36 questionnaire toevaluate the quality of life in patientswith perennial allergic rhinitis, valuesfor patients with moderate to severeperennial allergic rhinitis were signifi-cantly different from those for healthysubjects for 8 of 9 variables.7 Indeed,patients with allergic rhinitis had de-creased physical and social function-ing, energy, mental health, and generalhealth perception. They had increased

physical and emotional limitations andexperience of pain.

References1. Coons SJ, Kaplan RM. Assessinghealth related quality of life; applica-tion to drug therapy. Clin Therap 1992;14:850–858.

2. Juniper EF, Guyatt GH. Developmentand testing of a new measure of healthstatus for clinical trials in rhinocon-junctivitis. Clin Exp Allergy 1991;21:77–83.

3. Juniper EF, Guyatt GH, Archer B, etal. Aqueous beclomethasone dipropi-onate in the treatment of ragweed pol-len-induced rhinitis; further explora-tion of “as needed” use. J Allergy ClinImmunol 1993;92:66–72.

4. Juniper EF, Guyatt GH, Dolovich J. As-sessment of quality of life in adolescentswith allergic rhinoconjunctivitis: devel-opment and testing of a questionnaire forclinical trials. J Allergy Clin Immunol1993;93:413–423.

5. Georgitis JW, Banov C, Boggs PB, etal. Ipratropium bromide nasal spray innon-allergic rhinitis, efficacy, nasalcytological response and patient eval-uation on quality of life. Clin Exp Al-lergy 1994;24:1049–1055.

6. Horwitz R, Horwitz SM. Adherence totreatment and health outcomes. ArchIntern Med 1993;153:1863–1868.

7. Bousquet J, Bullinger M, Fayol C, etal. Assessment of quality of life inpatients with perennial allergic rhinitiswith the French version of the SF-36health status questionnaire. J AllergyClin Immunol 1994;94:182–188.

Physical Examination25. An examination of the nose

should be performed in patientswith a history of rhinitis. Thisshould include examination ofthe nasal passageways, secre-tions, turbinates, septum, anddetermination of whether nasalpolyps are present.

Examination of the nose is indicated inall cases of rhinitis (Table 2). This isaccomplished with a nasal speculumwith appropriate lighting, otoscopewith nasal adapter, rigid Hopkins rodor flexible nasopharyngoscope.1 Use ofthe latter procedure may be limited inthe pediatric population. If it is used,the middle meatus should also be ex-

amined, if possible, to evaluate bony ormucosal crowding with obstruction ofthe sinus ostia. The presence of muco-purulent material in this region is sug-gestive of sinusitis. “Cobblestoning”of the pharynx with lymphoid tissuemay be seen. A nasal speculum shouldbe inserted gently, since the septummay be tender. Elevating the end of thenose with the other hand provides abetter view of the nasal passage.On physical examination, the patient

with rhinitis may appear quite uncom-fortable and distressed with mouthbreathing. On nasal examination, thetypical mucosa of the allergic patientappears pale and swollen, with a blu-ish-gray appearance when the mucosaledema is severe. Occasionally, the mu-cosa can be hyperemic. The mucosa isusually reddened in acute infectionsand with overuse of topical medica-tions. Mucosal appearance may notdistinguish between allergic and non-allergic rhinitis, because non-allergicrhinitis may also present with mucosalpallor, edema or hyperemia.The quantity and quality of nasal

secretions should be noted. With aller-gic rhinitis, there may be watery mu-cus on the epithelial surface or on thefloor of the nasal passage. With abnor-mal mucociliary clearance or total na-sal obstruction, thick secretions can beseen pooling in the floor of the nose.An examination of the nasal cavity

may identify polyps, tumors, foreignbodies, or septal deflections. Unlikethe nasal turbinates with which theyare often confused, polyps appear glis-tening, mobile, and opaque and areinsensitive to touch.3 Nasal polyps maybe differentiated from severely edem-atous mucosa by applying a smallamount of a topical vasoconstrictorsuch as phenylephrine to the mucosa,and reexamining the mucosa 5 to 10minutes later. Nasal polyps will notshrink in size after topical vasocon-strictor has been applied, unlike edem-atous mucosa. Crusting on an inflamedmucosa may suggest atrophic rhinitisor a systemic disease such as sarcoid-osis. The presence of a septal perfora-tion should raise the possibility of co-caine abuse, previous surgery or,

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again, systemic granulomatous dis-eases.In allergic rhinitis associated with

conjunctivitis, the palpebral conjuncti-vae may be injected with watery dis-charge and puffiness of the eyelids.Subconjunctival edema may bepresent. With chronic or severe acuteallergic rhinitis, a transverse crease isoften seen across the bridge of thenose, particularly in children, as a re-sult of rubbing of the nose to relievenasal obstruction and itching. Thecharacteristic gesture in which the pa-tient elevates the tip of the nose withthe palm of the hand to relieve itchingand obstruction has acquired the name“the allergic salute.” Allergic “shiners”(infraorbital dark skin discoloration),3and facial pallor may be present. Theeyes and periorbital region also shouldbe examined for evidence of Dennie-Morgan lines (accentuated lines orfolds below the margin of the inferioreyelid) and cataracts, particularly ifatopic dermatitis is present.With prolonged nasal obstruction

and constant mouth breathing in child-hood, an individual may have eleva-tion of the upper lip, an overbite (den-tal malocclusion) and a high archedpalate.4 The tympanic membranes

should be examined for evidence ofassociated middle-ear disease, includ-ing middle-ear effusion and tympanicmembrane retraction or immobility.5This may provide evidence of allergen-induced Eustachian tube dysfunction.6The examination should also focus onthe possible involvement of the si-nuses. Evidence of associated allergicdiseases, such as asthma and atopicdermatitis, should be sought. Examina-tion of the lungs may reveal wheezingor a persistent cough, since there areoften accompanying symptoms andsigns of asthma when allergic rhinitisis present.7 In the evaluation of patientswith rhinitis it may be necessary to ruleout involvement of any other relevantorgan system.

References1. Rohr A, Hassner A, Saxon A. Rhino-pharyngoscopy for the evaluation ofallergic-immunologic disorders. AnnAllergy 1983;50:380–384.

2. Slavin RG. Nasal polyps and sinusitis.In: Middleton E Jr, Reed CE, Ellis EF,et al, eds. Allergy principles and prac-tice, 5th ed. St. Louis: Mosby-YearBook, 1998:1024–1035.

3. Marks MB. Significance of discolora-tion in the lower orbitopalpebralgrooves in allergic children (allergic

shiners). Ann Allergy 1963;21:26–32.4. Bresolin D, Shapiro CG, Shapiro PA,et al. Facial characteristics of childrenwho breathe through the mouth. Pedi-atrics 1984;73:622–625.

5. Badhwar AK, Druce HM. Allergic rhi-nitis. Med Clin North Am 1992;76:789–803.

6. Skoner DP, Doyle WJ, Chamovitz A,Fireman P. Eustachian tube obstruc-tion (ETO) after intranasal challengewith house dust mite. Arch Otolaryn-gol 1986;112:840–842.

7. Noble SL, Forbes RC, WoodbridgeHB. Allergic rhinitis. Am Fam Physi-cian 1995;51:837–846.

Testing for Specific IgE26. The demonstration of specific

IgE antibodies to known aller-gens by skin testing or in-vitrotests (as delineated in the “Pa-rameters for Diagnostic Test-ing”1) is of particular impor-tance in determining whetherthe patient has allergic rhinitisand for identifying specific aller-gens for which avoidance mea-sures and/or allergen immuno-therapy are warranted.

A careful history is the most importantstep toward the diagnosis of allergicdisease. Skin testing to allergens is in-dicated to provide evidence of an al-lergic basis for the patient’s symptoms,to confirm suspected causes of the pa-tient’s symptoms, or to assess the de-gree of sensitivity to a specific aller-gen. The simplicity, ease and rapidityof performance, low cost, and highsensitivity of these tests makes themfavorable for use in patients with rhi-nitis. Quality control measures andproper performance of skin testing arevital to produce accurate and reproduc-ible results. The number of skin teststhat are necessary may vary dependingon the age, potential allergen expo-sures, and area of the country. To prop-erly interpret skin tests or in vitro testsfor specific IgE, it is essential to knowwhich aeroallergens are present lo-cally, are clinically important and haveallergenic cross-reactivity with botani-cally related species (see “Practice Pa-rameter for Allergy Diagnostic Test-ing”).

Table 2. Elements of Physical Examination and Procedures to Consider in Patients WithRhinitis

● General observations: facial pallor, “allergic shiners”, mouth breathing, and nasal crease,evidence of systemic disease (e.g. nail clubbing).

● Growth percentiles for children.● Eyes: evidence for conjunctivitis, Dennie-Morgan lines (accentuated lines or folds belowthe margin of the inferior eyelid).

● Nose: presence or absence of external deformity, nasal mucosal swelling, nasal polyps,deviated septum, septal perforation, discharge (noting color and consistency), blood.Consider examining the nasopharynx using indirect mirror visualization or fiberopticendoscope

● Ears: Consider pneumatic otoscopy to look for abnormalities of tympanic membranes,including abnormal mobility patterns, retraction, air-fluid levels, bubbles behind tympanicmembrane; consider tympanometry to confirm the presence or absence of effusion andmiddle ear under- or over-pressures.

● Mouth: Observe for malocclusion or high arched palate associated with chronic mouthbreathing, tonsilar hypertrophy, lymphoid “streaking” in the oropharynx, pharyngealpostnasal discharge, halitosis, and pain upon mouth occlusion suggestive of temporo-mandibular joint syndrome.

● Neck: Lymphadenopathy, thyroid enlargement.● Chest: Signs of asthma.● Skin: Eczema, skin dryness, dermographism.● Other relevant organ systems.

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Reference1. Bernstein IL, Storms WW. Practiceparameters for allergy diagnostic test-ing. Joint Task Force on Practice Pa-rameters for the Diagnosis and Treat-ment of Asthma. The AmericanAcademy of Allergy, Asthma and Im-munology and the American Collegeof Allergy, Asthma and Immunology.Ann Allergy Asthma Immunol 1995;75:543.

Special Diagnostic Techniques27. In selected cases, special tech-

niques such as fiberoptic nasalendoscopy and/or rhinomanom-etry may be useful in evaluatingpatients presenting with rhinitissymptoms. These tests may re-quire special expertise for ap-propriate administration and in-terpretation. Patients with nasaldisease require appropriate ex-amination for associated dis-eases, such as sinusitis and otitismedia.

History and routine physical examina-tion are usually sufficient for a defini-tive diagnosis of rhinitis. Patients withupper airway complaints may initiallyreport symptoms suggestive of rhinitis.When symptoms or physical findingsare atypical, complications or otherconditions are suspected, or whensymptoms do not respond appropri-ately to therapy, endoscopy may beindicated. Traditional examination ofthe nasal cavity consists of inspectionwith a nasal speculum following mu-cosal decongestion; mirrors are usedfor examination of the nasopharynxand larynx. Unfortunately, it is notpossible to view many of the importantrecessed structures of the upper airwayby these methods. A more completeupper airway examination can easilybe performed endoscopically, using ei-ther the rigid Hopkins instruments orthe flexible fiberoptic endoscope. Ra-diologic imaging techniques, such asplain films, computed tomography(CT), and magnetic resonance imaging(MRI) have limited use in the evalua-tion of patients with uncomplicatedrhinitis which responds well to ther-apy.

Upper Airway Endoscopy. Upperairway endoscopy (rhinolaryngos-copy) is the most useful diagnosticprocedure in an evaluation for ana-tomic factors causing upper airwaysymptoms. Endoscopy provides a clearview of the nasal cavity and allows fordetailed examination of the middle me-atus, superior meatus, sphenoeth-moidal recess, and posterior nasophar-ynx, as well as structures of theoropharynx and larynx.1,2 The proce-dure is usually performed in the officefollowing decongestion and topical an-esthesia. Some children may requiresedation. Analysis of videotaped fiber-optic upper airway endoscopy has alsobeen used as a research technique tomeasure cross sectional area of the na-sal cavity.3Imaging Techniques. The primary

goals of radiologic imaging of the up-per airway are to provide an accuratereproduction of the regional anatomyand to establish the presence and ex-tent of anatomic disease. This informa-tion may assist in planning medicaltherapy and provide an anatomic guideto facilitate subsequent surgical treat-ment.3Standard radiographs. Although

standard radiographs have traditionallybeen the most frequently used radio-logic modality for evaluating diseaseof the upper airway and paranasal si-nuses, they are not indicated in theevaluation of patients with uncompli-cated rhinitis. The Caldwell (anterior-posterior) and Waters views best dem-onstrate the frontal and maxillarysinuses. The lateral view is the bestchoice for visualization of the sphe-noid sinus. These projections are notuseful for demonstration of structuresof the nasal cavity, and are of limiteduse in demonstration of structures ofthe nasopharynx, oropharynx, and lar-ynx. Lateral views are sometimes usedfor evaluation of the soft tissues of thenasopharynx, adenoids, oropharynx,and larynx, but are generally notneeded when endoscopy is available.Computed tomography and mag-

netic resonance imaging. Computer-ized tomographic scanning (CT) andmagnetic resonance imaging (MRI) us-

ing coronal sections for imaging ofsinuses frequently identify turbinatecongestion, concha bullosa, polyps andseptal deviation as causes of nasal air-way obstruction. Although CT andMRI have been used to validate acous-tic rhinometry (see below) as amethod, they are expensive and maynot correlate well with functional ob-struction.High resolution computed tomogra-

phy can demonstrate disease that is notshown on routine x-ray films. It canalso delineate pathologic variationsand demonstrate anatomic structuresinaccessible by physical examinationor endoscopy. Because of its superbcontrast resolution, CT is an excellentmethod for examining the complexanatomy of the upper airway, particu-larly the ostiomeatal complex. The ca-pability of CT to display bone, softtissue, and air facilitates accurate def-inition of regional anatomy of the noseand paranasal sinuses. The main indi-cations for the CT are chronic sinusitisnot responding to appropriate medicaltherapy, acute recurrent sinusitis, ab-normal diagnostic nasal endoscopicexamination and persistent facial pain.4In some centers, a limited CT studyincluding only 4 to 5 views can beperformed as a cost effective alterna-tive to sinus radiographs.Magnetic resonance imaging (MRI)

provides better imaging of soft tissuethan CT, but it is less suited to imagingthe bony anatomy of this region. Be-cause bone and air yield similar signalintensities on MRI, precise definitionof the ostiomeatal air passages andtheir bony perimeter is difficult. Fur-thermore, in the patient with extensiveinflammatory disease, the signal inten-sity of this pathologic process is indis-tinguishable from the appearance ofthe normal mucosa in the edematousphase of the nasal cycle. These factorslimit the MRI evaluation of underlyinganatomy in a patient with upper airwaydisease. MRI is useful, however, inevaluation of upper airway malignan-cies.Aerodynamic methods for estima-

tion of nasal airway obstruction. Re-sistance to air flow through the nose

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(or conductance, the inverse of resis-tance) may be measured by rhinoma-nometry. Rhinomanometry objectivelymeasures functional obstruction to air-flow in the upper airway, although thetechnique has not been fully standard-ized. Subjective perception of nasalstuffiness may correlate only looselywith measured nasal airway resis-tance,5 but rhinomanometry may beused in the assessment of the severityof symptoms. In addition, rhinoma-nometry may provide objective infor-mation on results of therapeutic inter-ventions. The objective informationobtained from rhinomanometry may beparticularly important when it is sus-pected that occupational exposure re-sults in nasal symptoms including na-sal congestion. Rhinomanometry is nota substitute for careful endoscopy ofthe nose because significant pathologyin the nose can occur with nasal airwayresistance values in the normal range.Rhinomanometry may be used to as-

sess the severity of anatomical abnor-malities that are causing airway ob-struction in the nose, including nasalvalve abnormalities, septal deviation,and polyposis. This application re-quires measurements before and aftertreatment with a potent intranasal de-congestant agent.Other indications for rhinomanom-

etry include the evaluation of patientswith obstructive sleep apnea.6Acoustic Rhinometry. Acoustic

rhinometry depends on reflection ofacoustic signals from structures in thenasal cavity.7–9 It is currently not atechnique used in the routine evalua-tion of patients with rhinitis. It pro-duces an image that represents varia-tions in the cross sectional dimensionsof the nasal cavity and closely approx-imates nasal cavity volume and mini-mal cross sectional area. It also allowsidentification of the distance of theminimal cross section area of the nasalcavity from the naris. Changes in nasalgeometry measured by acoustic rhi-nometry during histamine challengetesting have been documented10,11 andthe results of parallel determinationsby acoustic rhinometry and rhinoma-nometry are comparable.11 However,

nasal airway resistance cannot be eas-ily computed from the acoustic rhi-nometry data.Nasal Provocation Testing. Identi-

fication of sensitivity of the nose to aparticular aeroallergen can be usuallybased on a history of symptoms ofallergic rhinitis provoked by exposureto the allergen and confirmed by skintesting. Nasal provocation testing withallergen is unnecessary unless morestringent criteria are needed to incrim-inate the suspected allergen. For ex-ample, nasal provocation testing withallergen may be required for confir-mation of sensitivity to allergens in theworkplace. Testing of sensitivity toallergens requires that responses to in-cremental doses of allergens are as-sessed.12 Single dose allergen provo-cation measures nasal reactivity toallergens, not sensitivity. Since nasalreactions to instillation of placebo ma-terials may occur, response to diluentmust be measured before provocationwith allergens.Nasal sensitivity/hyperresponsive-

ness to histamine and methacholinehas been found in allergic rhinitis13–15and vasomotor rhinitis.16 Although thismay be a marker for these diseases, theclinical utility of nasal provocationtesting with histamine or methacholinemay be limited to trials of the efficacyof drugs and allergen immunotherapyon nasal irritability, because of a con-siderable overlap between allergic andnonallergic patients in their sensitivityto these agents.

References1. Stafford CT. The clinician’s view ofsinusitis. Otolaryngol Head Neck Surg1990;103:870–875.

2. Dolen WK, Selner JC. Endoscopy ofthe upper airway. In: Middleton E,Reed CE, Ellis EF, eds. Allergy prin-ciples and practice, 5th ed. St. Louis:Mosby-Year Book, 1998:1017–1023.

3. Zinreich SJ. Radiologic diagnosis ofthe nasal cavity and paranasal sinuses.In: Druce HM, ed. Sinusitis: patho-physiology and treatment. New York:Marcel Dekker, 1993.

4. Bingham B, Shankar L, Hawke M. Pit-falls in computed tomography of theparanasal sinuses. J Otolaryngol 1991;

20:414–418.5. Naito K, Cole P, Fraschetti J, Hum-phrey D. Nasal patency: subjective andobjective. Am J Rhinol 1989;3:93–97.

6. Anch AM, Remmers JE, Bunce H, III.Supraglottic airway resistance in nor-mal subjects and patients with occlu-sive sleep apnea. J Appl Physiol 1982;53:1158–1163.

7. Grymer LF, Hilberg O, Pedersen OF,Rasmussen TR. Acoustic rhinometry:values from adults with subjective nor-mal nasal patency. Rhinology 1991;29:35–47.

8. Fisher EW, Lund VJ, Scadding GK.Acoustic rhinometry in rhinologicalpractice: discussion paper. J Royal SocMed 1994;87:411–413.

9. Pedersen OF, Berkowitz R, YamagiwaM, Hilberg O. Nasal cavity dimensionsin the newborn measured by acousticreflections. Laryngoscope 1994;104:1023–1028.

10. Kano S, Pedersen OF, Sly PD. Nasalresponse to inhaled histamine mea-sured by acoustic rhinometry in in-fants. Pediatr Pulmonol 1994;17:312–319.

11. Austin CE, Foreman JC. Acoustic rhi-nometry compared with posterior rhi-nomanometry in the measurement ofhistamine- and bradykinin-inducedchanges in nasal airway patency. Br JClin Pharmacol 1994;37:33–37.

12. Schumacher MJ, Pain MCF. Nasalchallenge testing in grass pollen hayfever. J Allergy Clin Immunol 1979;66:202–208.

13. Birchall MA, Phillips I, Fuller RW,Pride NB. Intranasal histamine chal-lenge in normality and nasal rhinitis.Otolaryngol Head Neck Surg 1993;109:450–456.

14. Majchel AM, Proud D, Friedhoff L, etal. The nasal response to histaminechallenge: effect of the pollen seasonand immunotherapy. J Allergy ClinImmunol 1992;90:85–91.

15. Hilberg O, Grymer LF, Pederson OF.Nasal histamine challenge in nonaller-gic and allergic subjects evaluated byacoustic rhinometry. Allergy 1995;50:166–173.

16. Hallen H, Juto JE. Correlation betweensubjective and objective assessment ofnasal hyperreactivity. Orl J Otorhino-laryngol Relat Spec 1994;56:51–54.

Nasal Cytology28. Nasal cytology may aid in differ-

entiating allergic rhinitis and

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NARES from other forms of rhi-nitis, eg, vasomotor, infectiousrhinitis, if the correct procedureis followed and the appropriatestains are utilized.

Visualization of large numbers of eo-sinophils may be helpful in narrowingthe differential diagnosis between al-lergic rhinitis and non-allergic rhinitiswith eosinophilia from other types ofrhinitis. The presence of neutrophilsmay support a diagnosis of infectiousrhinosinusitis, but secretion neutro-philia is not uncommon in apparentlynormal subjects.1 There is lack of ex-pert consensus about whether nasal cy-tology should be routinely performedin the evaluation of rhinitis.

Reference1. Malmberg H. Symptoms of chronicand allergic rhinitis and occurrence ofnasal secretion granulocytes in univer-sity students, school children and in-fants. Allergy 1979;34:389–394.

Total Serum IgE, Blood EosinophilCounts29. Neither total serum IgE nor to-

tal circulating eosinophil countsare routinely indicated in the di-agnosis of rhinitis.

Serum total IgE has been measured inindividuals with a variety of diseaseconditions.1 It has often been used as ascreening test for allergy. Adults andchildren with allergic rhinitis andasthma tend to have more elevated to-tal serum total IgE levels.2 In spite ofits wide use, however, it is neither verysensitive nor very specific. There isconsiderable overlap in total IgE levelsbetween atopic and nonatopic individ-uals, making the test results difficult tointerpret in many instances.3–7 In gen-eral, between 35% to 50% of individ-uals with allergic rhinitis have normaltotal IgE levels, while as many as 20%of nonatopic individuals have elevatedtotal IgE levels. In one study of 244individuals with allergic rhinitis, thespecificity and sensitivity of total se-rum IgE determinations using a cutofflevel of 200 IU/mL were 85% and 50%respectively.8 A similar result was alsoobserved in a study with pediatric pa-

tients.9 Although significant elevations(greater than 50 IU/mL in infants orgreater than 200 IU/mL in older chil-dren and adults) may correlate with thepresence of atopy, a variety of nona-topic conditions can also be associatedwith these elevated levels of serumtotal IgE.1 Recently, there have beenseveral investigations done to evaluatethe association respiratory symptomswith serum total IgE and skin-test re-activity.10–12 The overall results ofthese studies revealed a poor correla-tion, especially with allergic rhinitis.Although serum IgE levels may havethe advantage of providing some indexof overall allergy and can identify theindividuals who are least “allergic,”they have the disadvantage of measur-ing all types of IgE, not all of whichappear relevant to the respiratorysymptoms and skin-test reactivity.Hence, there is still no convincing ev-idence to support the routine use oftotal serum IgE measurement in pa-tients suspected of having allergic rhi-nitis and other related atopic diseases.The routine measurement of total

circulating eosinophil counts in the di-agnosis of allergy is subject to similarlimitations as for serum total IgE.13

References1. Ownby DR. Clinical significance ofIgE. In: E. Middleton Jr, CE Reed, EFEllis, eds. Allergy: principles and prac-tice, 5th ed. St. Louis: Mosby, 1998:770–782.

2. Johnson EE, Irons JJ, Patterson R,Roberts M. Frequency of elevated se-rum IgE concentrations in eczema withand without respiratory allergy. J Al-lergy Clin Immunol 1974;54:94.

3. Grundbacher FJ. Causes of variation inserum IgE levels in normal popula-tions. J Allergy Clin Immunol 1974;56:104.

4. Henderson LL, Swedlund HA, VanDellen RG, et al. Evaluation of IgEtests in an allergy practice. J AllergyClin Immunol 1971;48:361.

5. Marsh DG, Bias WB, Ishizaka K. Ge-netic control of basal serum immuno-globulin level and its effect on specificreaginic sensitivity. Proc Natl AcadSci USA 1974;71:3588.

6. Haahtela T, Suoniemi I, Jaakonmaki I,et al. Relationship between serum IgE

concentration and occurrence of im-mediate skin test reactions and allergicdisorders in young people. Allergy1982;37:597.

7. Klink M, Cline MG, Halonen M, et al.Problems in defining normal limits forserum IgE. J Allergy Clin Immunol1990;85:440.

8. Wittig HJ, Belloit J, De Fillippi I,Royal G. Age-related serum immuno-globulin E levels in healthy subjectsand in patients with allergic disease. JAllergy Clin Immunol 1980;66:305.

9. Ownby DR, Anderson JA, Jacobs GL,et al. Development and comparativeevaluation of a multiple-antigen RASTas a screening test for inhalant allergy.J Allergy Clin Immunol 1984;73:466.

10. Burrows B, Sears MR, Flannery EM,et al. Relations of bronchial respon-siveness to allergy skin test reactivity,lung function, respiratory symptoms,and diagnoses in thirteen-year-oldNew Zealand children. J Allergy ClinImmunol 1995;95:548.

11. Sears MR, Burrows B, Flannery EM,et al. Relation between airway respon-siveness and serum IgE in childrenwith asthma and in apparently normalchildren. N Engl J Med 1991;325:1067.

12. Sherrill DL, Lebowitz MD, HalonenM, et al. Longitudinal evaluation of theassociation between pulmonary func-tion and total serum IgE. Am J RespirCrit Care Med 1995;152:98.

13. Mygind N, Dirksen A, Johnsen NJ,Weeke B. Perennial rhinitis: an analy-sis of skin testing, serum IgE, andblood and smear eosinophilia in 201patients. Clin Otolaryngol 1978;3:189–196.

Unproven or InappropriateDiagnostic Techniques30. Cytotoxicity testing, provocative

and neutralization testing car-ried out by either intracutane-ous or subcutaneous injection orsublingual administration, andmeasurement of specific andnon-specific IgG4 are controver-sial, unproven and/or not appro-priate for diagnostic use in eval-uation of rhinitis.

Those techniques summarized beloware considered controversial or un-proven because they have not beensubjected to validation by acceptedstandards of scientific evaluation or are

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not appropriate for diagnostic use inIgE-mediated disease. The techniquesare cytotoxicity testing, provocativeand neutralization testing carried outby either intracutaneous or subcutane-ous injection or sublingually and mea-surement of specific and nonspecificIgG4.I. Cytotoxicology TestingLeukocytotoxic testing is based on theclaim that the addition of specific al-lergen in vitro to whole blood or toserum leukocyte suspensions will re-sult in reduction in white blood cellcount or death of the leukocytes. In1960, Bryan and Bryan1 published thefirst of a series of articles describingthe method. Hence, this has also beencalled Bryan’s Test. The test is per-formed by removing the buffy coatfrom whole blood and the cells arethen added to a mixture containingsterile distilled water and serum. Thesuspension is then applied to a micro-scope slide containing dried antigenwithin a ring of petrolatum jelly. Acontrol slide is used containing a mix-ture of the patient’s cells, serum andwater. The slides are examined at in-tervals up to 2 hours for any changes inthe appearance of the leukocytes or adecrease in motility. These changes areclaimed to be the consequence of anallergic reaction, and the test is usedfor diagnosis of both food and inhalantallergy.The test has never been proven ef-

fective by controlled studies nor has ascientific basis for its use been demon-strated. The results of numerous pub-lished control trials indicate that theprocedure is not effective for diagnosisof food or inhalant allergy. In serum-leukocyte preparations from patientssensitive to a variety of specific aller-gens, there are no consistent differ-ences between leukocytes exposed toallergens to which the patients are clin-ically sensitive and those exposed toallergens to which the patients are notsensitive.2,3 In a controlled study of thecytotoxic effect of specific allergenson white cells and plasma suspensions,tests did not correlate with atopic re-actions to foods or with other untoward

reactions to foods (headache, diarrhea,fatigue), and the test was dependent onsubjective interpretation and inconsis-tent end results when repetitive resultswere performed on the same patient. Ina double-blind controlled study,4 asimilar cytotoxic test afforded no reli-able help in establishing the diagnosisof food allergy because positive cyto-toxic effects were frequently obtainedto foods that produced no clinicalsymptoms, and negative cytotoxic re-actions were obtained to foods that didproduce clinical symptoms.The test is not performed under stan-

dardized conditions and the interpreta-tion of changes is entirely subjective.Leukocytotoxic changes in IgE-medi-ated hypersensitivity have not beenconfirmed. Therefore, there is no proofthat cytotoxic testing is a valid tech-nique for diagnosing inhalant allergyand a number of controlled trials haveindicated that this test is ineffective fordiagnostic purposes.5

II. Provocation–Neutralization testing(Intracutaneous or subcutaneous)Intracutaneous or subcutaneous provo-cation neutralization testing is claimedto be a method of diagnosing allergicdisease.6 In this technique, an intracu-taneous or subcutaneous injection ofantigen is administered in increasingconcentrations to elicit symptoms thatcorrespond to the patient’s complaints.As soon as symptoms appear, weakerdilutions of the same antigen are in-jected at intervals until a dose is foundthat relieves the provoked symptoms.The patient is observed for 10 minutesafter each dilution and all symptomsare recorded. The symptoms can takemany forms including drowsiness,chills and muscle pain. Thus, there are2 phases to the process, provocationand neutralization. A modification ofthe provocative intracutaneous test todiagnose inhalant allergy was devel-oped using wheal size. However, theprinciple of provoking and neutralizingsymptoms remained the basis for theprocedure. One double-blind study of61 atopic subjects was unable to con-firm and reproduce the validity of re-sults from subcutaneous provocative-

neutralization testing.7 A study ofsymptoms, chest auscultation and peakexpiratory flow rates in 20 asthmaticchildren after provocation skin testingfound no correlation of these measure-ments with skin tests.8 No attempts atscientific establishment of the possiblemechanisms involved have been pub-lished. Moreover, from what is knownabout IgE-mediated reactions, there isno immunologic basis for a therapeuticresponse to a neutralizing dose of al-lergenic extract. Therefore, there is norationale or immunologic basis forsubcutaneous or intracutaneous provo-cation and neutralization testing to beused as a method for the diagnosis ofallergic disease in patients with rhini-tis.9

III. Provocation–NeutralizationTesting (Sublingual)Sublingual antigen administration hasbeen advocated as a technique for thediagnosis of food induced respiratorysymptoms.8 The method consists ofplacing drops of an allergenic extractin various dilutions under the tongue ofthe patient and waiting 10 minutes forthe appearance of symptoms and anysymptom is interpreted as a positivetest. When the symptoms occur, a neu-tralizing dose is administered which isusually drops of a more dilute solutionof the same extract. Symptoms are ex-pected to disappear in approximatelythe same temporal sequence in whichthey appeared. Two separate con-trolled studies carried out by the FoodAllergy Committee of the AmericanCollege of Allergy, Asthma and Im-munology revealed that sublingualprovocative testing did not discrimi-nate between placebo controls and al-lergenic extracts.10,11 Another studyevaluated this technique with 5 physi-cians, all of whom had been using thismethod of testing for at least 7 years.12The technique was performed accord-ing to a double-blind protocol andthere was no distinction of reactionsbetween placebo and active extracts.Another study obtained similar nega-tive results.13 Therefore, there are nocontrolled clinical studies indicatingthat sublingual antigen administration

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has diagnostic efficacy for humanatopic disease. Moreover, there are noknown immunologic mechanisms thatcan account for the neutralizing effectsof dilute solutions of allergenic ex-tracts.IV. Specific and Non-Specific IgG4Measurement of nonspecific and spe-cific IgG4 has been advocated as adiagnostic test for clinical allergy. Be-cause of controversial and inconclu-sive scientific evidence,14–18 the mea-surement of IgG4 should not be part ofthe diagnosis of patients with allergicnasal disease.19

References1. Bryan WTK, Bryan MP. The applica-tion of in vitro cytotoxic reactions toclinical diagnosis of food allergy. La-ryngoscope 1960;70:810.

2. Chambers VV, Hudson BH, Glaser J.A study of the reactions of humanpolymorphonuclear leukocytes to var-ious antigens. J Allergy 1958;29:93.

3. Lieberman P, Crawford L, Bjelland J,et al. Controlled study of the cytotoxicfood test. JAMA 1974;231:728.

4. Benson TE, Arkins JA. Cytotoxic test-ing for food allergy: evaluations of re-producibility and correlation. J AllergyClin Immunol 1976;58:471.

5. Lowell FC. Some untested diagnosticand therapeutic procedures in clinicalallergy [Editorial]. J Allergy Clin Im-munol 1975;56:168–169.

6. Lee CH, Williams RI, Binkley EL.Provocative inhalant testing and treat-ment. Arch Otolaryngol 1969;90:173.

7. Crawford LV, Lieberman P, Harfi HA,et al. A double-blind study of subcuta-neous food testing sponsored by theFood Allergy Committee of the Amer-ican Academy of Allergy. J AllergyClin Immunol 1976;57:236.

8. Bronsky EA, Burkley DP, Ellis EF.Evaluation of the provocative skin testtechnique [Abstract]. J Allergy 1971;47:104.

9. Morris DL. Use of sublingual antigenin diagnosis and treatment of food al-lergy. Ann Allergy 1971;27:289.

10. Breneman JC, et al. Report of the FoodAllergy Committee on the sublingualmethod of provocative testing for foodallergy. Ann Allergy 1973;31:382.

11. Breneman JC, et al. Final report of theFood Allergy Committee of the Amer-ican College of Allergists on the clin-

ical evaluation of sublingual provoca-tion testing method for diagnosis offood allergy. Ann Allergy 1974;33:164.

12. Kailin EW. “Relieving” therapy forantigen exposure. JAMA 1971;217:78.

13. Lehman CW. A double-blind study ofsublingual provocative food testing: Astudy of its efficacy. Ann Allergy1980;45:144.

14. Gwynn CM, Ingram J, Almosawi T,Stanworth DR. Bronchial provocationtests in atopic patients with allergen-specific IgG4 antibodies. Lancet 1982;1:254.

15. Lee TH, Durham SR, Merrett J, Mer-rett TG, Kay AB. Allergen-specificIgG4 in bronchial asthma. Lancet1982;2:1048.

16. Homburger HA, Mauer K, Sachs MI,et al. Serum IgG4 concentrations andallergen-specific IgG4 antibodies com-pared in adults and children withasthma and nonallergic subjects. J Al-lergy Clin Immunol 1986;77:427.

17. Stanworth DR. Immunochemical as-pects of human IgG4. Clin Rev Al-lergy 1983;1:183.

18. Perelmutter L. IgG4 and the immunesystem. Clin Rev Allergy 1983;1:267.

19. American Academy of Allergy andImmunology. Measurement of specificand nonspecific IgG4 levels as diag-nostic and prognostic tests for clinicalallergy. Position statement. J AllergyClin Immunol 1995;95:652–654.

MANAGEMENT OF RHINITIS

Environmental Control Measures31. Avoidance of inciting factors, eg,

allergens, irritants, medications,is fundamental to the manage-ment of rhinitis. Triggers shouldbe identified and avoidancemeasures instituted.

General ConsiderationsThere are five major categories of IgE-dependent triggers for allergic rhinitis:pollens, molds, house dust mites, ani-mals and insect allergens. In patientssensitive to multiple allergens, it is im-portant to institute avoidance measuresfor all relevant allergens. This may im-prove tolerance to unavoidable expo-sure to aeroallergens, eg, pollens. Al-though sensitive immunochemicaltechniques permit direct quantitationof actual changes in allergen level, the

effectiveness of environmental controlprocedures is judged primarily by pa-tient symptoms and medicationscores.1,2

Clinical SciencePollens. Pollen triggering allergic rhi-nitis is principally derived from wind-pollinated (anemophilus) trees, grassesand weeds though insect-pollinated(entemophilus) plants may producesymptoms if encountered at closerange. Pollen allergens are quicklyeluted from pollen grains on contactwith ocular or respiratory mucosa.Similar allergens may be found onfragments derived from other portionsof the plant. Pollen allergens, possiblyeluted from pollen grains and passivelyborne on plant debris and soil particles,can be found on air sampling evenwhen pollen grains are no longer beingrecovered. Pollens responsible forsymptoms vary widely with locale, cli-mate and introduced plantings. In tem-perate regions of North America, treepollen generally predominates in earlyto mid-spring, grasses in late springand early summer, and weeds from latesummer until early fall. The dose ofpollen allergen necessary to elicitsymptoms exhibits considerable vari-ability depending on level of allergicsensitization and degree of extant al-lergic nasal mucosal inflammation(“priming”). Reducing pollen exposureis important in the effective manage-ment of allergic rhinitis.Windows and doors must be kept

closed and air conditioning used, ifnecessary, on indoor cycle (closedvents) to keep the home or vehiclecomfortable.3 Indoor pollen levels areincreased by window or attic fans.Though remaining entirely indoors isimpractical, it is helpful to reduce out-door exposure during periods of highpollen counts. Activities involving ex-tended time out-of-doors, such ascamping trips, may need to be avoidedduring offending pollen seasons. Ingeneral, limiting outdoor activity onsunny, windy days with low humidityis also advisable whereas such activi-ties may be well-tolerated following agentle, sustained rain. Because the in-

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terplay of different weather factors (eg,wind currents, sunshine, rain, humid-ity) is complex, it is not possible toreliably predict levels of outdooraeroallergens from the influence of asingle weather factor.4 A shower orbath following outdoor activity re-moves pollen from the hair and skinand avoids contamination of bedding.In highly sensitive patients whosesymptoms are triggered by very lowpollen levels, effective allergen avoid-ance may necessitate severely curtail-ing outdoor activity. Medications andallergen immunotherapy are requiredin such patients.Molds. Molds or fungi are ubiqui-

tous and important allergens. Thesesaprophytic organisms exist in greatnumbers outdoors but also may heavilycontaminate indoor environments.Most mold allergens are encounteredthrough inhalation of spores althoughfragments of hyphal elements may alsocontribute. Though displaying a poorlydefined summer-early autumn seasonalpattern in the northern US, moldspores are recovered on outdoor airsampling year-round in the southernUS except during periods of snowcover. Outdoor molds grow on bothviable and decaying vegetation, andare strongly influenced by local vege-tation. Abundant mold is also found insoil and is released when the earth isdisturbed by plowing, excavation, etc.Harvesting activities are also associ-ated with increased mold counts. Moldspore levels are affected by tempera-ture, wind, rain and humidity. Somefungi require the action of water drop-lets for spore release. High levels ofthese spores appear during rainyweather and with dew formation atnight. “Wet weather” molds includeFusarium, Phoma and Cephalospo-rium. Other common allergenic molds,such as Alternaria and Cladosporium,are released by wind as humidity falls.Rain or high humidity lowers “dry re-lease” mold spore counts, but countsrise rapidly when the rainy periodends.4Like pollens, avoidance of outdoor

molds consists of remaining in a closedenvironment as much as practical. Air

conditioning on indoor cycle is help-ful4 though air conditioning units maybe heavily contaminated with mold.Mold exposure is increased by walkingin uncut fields and may reach veryhigh levels with activities such asmowing or threshing. Working withcompost, silage or dry soil commonlytriggers symptoms in mold sensitivepatients as does raking leaves. The lat-ter activities may also involve expo-sure to resuspended pollens and insectdebris. Face masks are recommendedfor such outdoor activities though theirvalue is limited by entrainment of airaround the edges of the mask. Also,they offer no protection for the eyes.Many factors influence the amount

of indoor mold, including age and con-struction of the dwelling, presence of abasement or crawl space, type of heat-ing system, and use of humidifiers andair conditioning. Damp homes, base-ments, cold outside walls and windowmoldings provide favorable conditionsfor mold growth as do sinks, showerstalls, non-refrigerated vegetable stor-age areas and garbage pails. Fungi-cides to kill and retard mold growth,such as Clorox� or Lysol�, should beused in these locations. Mold sporesalso are present in carpeting, beddingand upholstered furniture and are re-duced by dust mite avoidance mea-sures. Console humidifiers and coolmist vaporizers may be reservoirs formold and are best avoided by moldsensitive patients. If employed, suchequipment must be kept scrupulouslyclean. If the home is constructed over acrawl space, a plastic vapor barrierover exposed soil and keeping founda-tion vents open will reduce moistureand mold. If a basement is damp ortends to flood, carpeting and furnish-ing the basement should be avoided, adehumidifier employed at all times andany standing water evacuated asquickly as possible. Chemical andphysical measures to control indoormold will usually fail if relative hu-midity and condensation are not re-duced.House dust mites. The fecal residue

of dust mites, belonging to the genusDermatophagoides, is the major

source of allergen in house dust. Theirprincipal food source is exfoliated hu-man skin scale. Consequently, mitesexist in reservoirs of skin scale: bed-ding, fabric covered furniture, soft toysand carpeting.1 Aside from availabilityof food, the major factors influencingmite growth are temperature and hu-midity. To replicate, a relative humid-ity of 50% or greater (absolute humid-ity of �8 g/kg) is required.5 Recentchanges in home construction andhousecleaning methods including moreenergy-efficient buildings with re-duced ventilation and increased hu-midity, wall-to-wall carpeting, wideruse of furnished basements, centralheat, and use of cool water detergentsfor laundering bedding all favor dustmite growth.Vigorous measures are required to

reduce dust mite allergen. Ordinaryvacuuming and dusting have little ef-fect.6 To achieve effective reduction inmite allergen, the bedroom and mainliving areas (eg, family room) shouldbe simply furnished without carpets.Whenever feasible, mite-sensitive pa-tients should avoid vacuuming or mak-ing beds. If vacuuming is required, usea vacuum cleaner with an efficientdouble filtration system. Patients whodo their own cleaning should wear aface mask while cleaning and for 10 to15 minutes afterward. Better still,housecleaning should be carried outwhile the patient is not at home. Thereis no evidence that electrostatic purifi-ers and conflicting evidence thatHEPA air purifiers reduce symptomsin dust mite allergy.7,8 At most, suchfilters are of modest benefit.9 Like-wise, cleaning heating ducts is of nodemonstrated value. On the other hand,air conditioning reduces mite numbersby lowering indoor humidity. Humid-ifier use should be minimized.All mattresses, box springs and pil-

lows in the patient’s bedroom must beencased in zippered, allergen-proof en-casings. Vinyl encasings are effective,but cloth encasings with semi-perme-able plastic backing are more comfort-able and durable. If a mattress is old,replacement should be considered buteven new “hypoallergenic” mattresses

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and pillows must be encased since mitecolonization occurs within weeks.Bedclothes should be washed in hotwater (greater than 130 degrees F) atleast every 2 weeks to remove miteallergen and kill mite ova. Quilts andcomforters should be avoided or cov-ered with an allergen-proof duvet.Stuffed toys that cannot be washedshould be eliminated or replaced with awashable toy. Avoid storing items un-der beds.Mites may be abundant in fabric

covered furniture and presently, no ef-fective means exist in the US for elim-inating mites in upholstered furniture.Plastic, leather or wood furniture isbest. When fabric upholstered furni-ture cannot be avoided, a 3% tannicacid solution can be used to denaturemite and other allergens on these fur-nishings. This solution does not killmites, however, so mite allergen re-accumulates rapidly and requires re-treatment.1Since thorough vacuuming removes

only surface dirt and mite allergen,carpeting is best removed from thebedroom and replaced with smoothfinish wood, tile or vinyl flooring.6 Ifthis is impractical, one may considertreating carpets with Acarosan�, a spe-cial carpet treatment containing benzylbenzoate.10 However, the effects oftreatment do not appear to be main-tained for long periods and are notdramatic.11 If Acarosan� is used, itshould be repeatedly brushed into thecarpet over 12 hours followed by care-ful vacuuming to remove all powder.Efficacy of allergen removal and needfor re-treatment can be ascertainedwith a kit (Acarex�) that measuresguanine, a fecal excretion product ofdust mites, in house dust. Carpetinginstalled over a concrete slab is a par-ticularly potent source of mite allergenand is best avoided, if possible. Acaro-san� and other treatments may notcontrol mite allergen in carpets that aredamp from seepage or condensation.12Animal allergens. Because of the

popularity of indoor pets, cats, dogsand other domestic animals are impor-tant causes of allergic rhinitis. Allwarm-blooded animals, including

birds, potentially are capable of sensi-tizing susceptible allergic patients.Positive skin test reactivity to cat anddog is found in 1/4 to 1/3 of allergicindividuals, and animal allergens are asignificant occupational hazard forworkers exposed to mice, rats, guineapigs, etc. Farm workers may developsensitivities to farm animals. In innercity areas, rodent urine may be an im-portant source of animal allergen.Though furs processed for use in cloth-ing are no longer allergenic, featherproducts retain significant allergenic-ity. Because allergen-bearing particlesof animal origin are generally quitesmall and low density, they remainsuspended in air for extended periodsand disseminate widely in homes andother facilities. Symptoms of allergicrhinoconjunctivitis may occur withinminutes of entering a contaminatedarea.The major antigen in cat allergen,

Fel d I is found on cat skin/dander andin saliva and urine. Cat albumin is alsoallergenic but a less frequent cause ofsensitivity than Fel d I. Fel d I andalbumin are common to all breeds ofcats. Cat allergen has been identified inhomes and other locations where catswere never present and occasionallymay reach concentrations found inhomes where cats are kept.2 This ispresumed to be passive contaminationfrom cat allergen borne on clothing.Such contamination may be an unsus-pected cause of symptoms in sensitiveindividuals.13Allergy to dogs, though common,

appears less frequent than cat allergy.The major dog allergen, Can f I, isfound in dog skin/dander and salivaand is present in varying amounts in allbreeds tested. Still, many dog-sensitivepatients claim to respond differently tovarious breeds of dogs or even specificdogs of a single breed. Like cat aller-gen, Can f has been found in rooms inwhich dogs were never present.2,13Analysis of the location of this allergensuggests passive transport on clothing.Levels may be sufficient to elicitsymptoms in sensitized patients.13Avoidance clearly remains the most

effective way of dealing with animal

sensitivity. If the pet producing symp-toms is in the home, the patient andfamily should be counseled to considerremoving the animal to avoid possibleprogression of symptoms. A “trial” re-moval of a pet for a few days or evenweeks may be of little value or, worse,misleading since, in the case of catallergen, an average of 20 weeks (andin some cases much longer) is requiredfor allergen levels to reach levelsfound in homes without cats. This de-crease can be accelerated by removingcarpeting and discarding upholsteredfurniture, but this is generally imprac-tical. Steam cleaning of carpets andupholstered furniture following re-moval of the animal seems to havelittle advantage over routine vacuum-ing with a double filter vacuum sys-tem. If despite vigorous counseling thepatient and/or family refuses to removethe pet, confining the animal to an un-carpeted room (other than the bed-room) with a HEPA or electrostatic airpurifier may reduce airborne allergenin the remainder of the home by 90%.13Some14,15 but not all16 studies havedemonstrated reduced airborne cat al-lergen by washing the animal on aweekly basis. Whether frequent bath-ing of dogs reduces airborne dog aller-gen is uncertain. Litter boxes should beeliminated whenever feasible or placedin an area unconnected to the air sup-ply for the rest of the home. If notremoved, caged pets (birds, rodents,guinea pigs, etc.) also should be kept inan uncarpeted area of the home andremote from the patient’s bedroom.Insect allergens. Allergic rhinocon-

junctivitis and asthma have been re-ported with exposure to debris of nu-merous insects including cockroaches,crickets, caddis flies, house flies,midges and moths. Because of theirprevalence and indoor living habits,cockroaches are a significant cause ofrespiratory allergy, especially in innercity populations. Up to 60% of dust-sensitive patients from urban areas re-act to cockroach allergens. The majorcockroach allergens, Bla g I and Bla gII, are found on the insect’s body andits feces. Cockroach allergen is mostabundant in kitchen floor dust and may

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reach high levels in poorly maintainedhomes and apartments. Eliminatingcockroaches requires careful sanitationsuch as not allowing food to standopen or remain on unwashed dishes,promptly wiping up food spills andstoring garbage in tightly closed con-tainers. Use of “roach traps” has beenadvocated since these permit removalof the allergen-containing bodies of theinsects. If the infestation is heavy,however, repeated applications of in-secticide by a professional extermina-tor or changing homes may be re-quired.Miscellaneous and non-allergic fac-

tors. A host of other environmentalfactors may incite or worsen rhinitis.Agents producing occupational asthmaby IgE-dependent mechanisms com-monly trigger nasal and ocular symp-toms. Because asthma may be moredebilitating, occupational rhinocon-junctivitis is often ignored. Measuresto control occupational asthma usuallyreduce occupational rhinitis and willnot be discussed further. Rhinitis hasalso been attributed to irritants eg, to-bacco smoke, formaldehyde, perfumeand other strong odors, and newspaperink. Some persons display increased“sensitivity” to environmental tobaccosmoke.17 The headache, nasal andchest symptoms do not appear to in-volve IgE. Avoidance of passive to-bacco smoke is mandatory for suchpatients. The capacity of formaldehydeto cause stinging and burning of theeyes and nose, lacrimation, and de-creased nasal mucous flow is well-es-tablished.18 This appears to be irritanteffect since even prolonged, high-levelformaldehyde exposure only rarely re-sults in IgE to formaldehyde-proteinconjugates and this does not correlatewith clinical symptoms.18,19 Since re-spiratory symptoms generally occur atconcentrations well above those atwhich the odor of formaldehyde is de-tectable, it is unlikely that formalde-hyde would be an unsuspected cause ofrhinitis. Perfume and newsprint areclaimed to elicit symptoms in somerhinitis sufferers. The mechanism isuncertain but felt to be irritant.20 Iftroublesome, avoidance is indicated.

References1. Platts-Mills TAE, Thomas WR, Aal-berse RC, et al. Dust mite allergensand asthma: report of a second inter-national workshop. J Allergy Clin Im-munol 1992;89:1046–1060.

2. Wood RA, Eggleston PA, Lind P, et al.Antigenic analysis of household dustsamples. Am Rev Resp Dis 1988;137:358–363.

3. Solomon WR, Burge HA, Boise JR.Exclusion of particulate allergens bywindow air conditioners. J AllergyClin Immunol 1980;65:305–308.

4. Solomon WR, Platts-Mills TAE. Aer-obiology and inhalant allergens. In:Middleton EJ, Reed CE, Ellis EF, et al,eds. Allergy: principles and practice.5th ed. St. Louis: Mosby-Year Book,1998:367–403.

5. Pollart S, Chapman MD, Platts-MillsTAE. House dust mite and dust con-trol. Clin Rev Allergy 1988;6:23–33.

6. Burr UL, Dean BV, Merrett TG, et al.Effects of anti-mite measures on chil-dren with mite-sensitive asthma: acontrolled trial. Thorax 1980;35:506–512.

7. Nelson HS, Hirsch SR, Ohman JLJ, etal. Recommendations for the use ofresidential air-cleaning devices in thetreatment of allergic respiratory dis-ease. J Allergy Clin Immunol 1988;82:661–669.

8. American Thoracic Society. Achievinghealthy indoor air; report of the ATSworkshop: Santa Fe, New Mexico, No-vember 16–19, 1995. Am J Respir CritCare Med 1997;156:S33–S64.

9. Reisman RE, Mauriello PM, DavisGB, et al. A double-blind study of theeffectiveness of a high efficiency par-ticulate air (HEPA) filter in the treat-ment of patients with perennial allergicrhinitis and asthma. J Allergy Clin Im-munol 1990;85:1050–1057.

10. Hayden ML, Rose G, Diduch KB, etal. Benzyl benzoate moist powder: in-vestigation of acarical activity in cul-tures and reduction of dust mite aller-gens in carpets. J Allergy ClinImmunol 1992;89:536–545.

11. Woodfolk JA, Hayden ML, Couture N,Platts-Mills TA. Chemical treatment ofcarpet to reduce allergen: comparisonof the effects of tannic acid and othertreatments on proteins derived fromdust mites and cats. J Allergy ClinImmunol 1995;96:325–333.

12. Rose G, Woodfolk JA, Hayden ML, etal. Testing of methods to control mite

allergen in carpets fitted to concreteslabs [Abstract]. J Allergy Clin Immu-nol 1992;89:315.

13. Munir AKM, Einarsson R, Schou C, etal. Allergens in school dust. I. Theamount of the major cat (Fel d I) anddog (Can f I) allergens in dust fromSwedish schools is high enough toprobably cause perennial symptoms inmost children with asthma who aresensitized to cat and dog. J AllergyClin Immunol 1993;91:1067–1074.

14. deBlay F, Chapman MD, Platts-MillsTAE. Airborne cat allergen (Fel d I):Environmental control with the cat insitu. Am Rev Respir Dis 1991;143:1334–1339.

15. Glinert R, Wilson P, Wedner HJ. Fel dI is markedly reduced following se-quential washing of cats [Abstract]. JAllergy Clin Immunol 1990;85:327.

16. Klucka CV, Ownby DR, Green J, et al.Cat shedding of Fel d I is not reducedby washings, Allerpet-C spray oracepromazine. J Allergy Clin Immunol1995;95:1164–1171.

17. Bascom R, Kulle T, Kagey-Sobotka A,et al. Upper respiratory tract environ-mental tobacco smoke sensitivity. AmRev Respir Dis 1991;143:1304–1311.

18. Bardana EJ, Montanaro A.Formaldehyde: an analysis of its respi-ratory, cutaneous, and immunologiceffects. Ann Allergy 1991;66:441–452.

19. Dykewicz MS, Patterson R, CugellDW, et al. Serum IgE and IgG toformaldehyde–human serum albumin:lack of relation to gaseous formalde-hyde exposure and symptoms. J Al-lergy Clin Immunol 1991;87:48–57.

20. Theander C, Bende M. Nasal hyperre-activity to newspapers. Clin Exp Al-lergy 1989;19:57–58.

Pharmacologic Therapy32. Pharmacologic management

should be considered in relationto the etiology and pathophysi-ology of the condition. If it ispossible to anticipate the onsetof symptoms, eg, seasonal rhini-tis or rhinitis triggered by spo-radic exposure, initiating prophy-lactic use of medications maylessen the impact of such expo-sure on the patient.

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Antihistamines33. Oral antihistamines are effective

in reducing symptoms of itching,sneezing, and rhinorrhea, andare first line therapy for treat-ment of allergic rhinitis. How-ever, oral antihistamines havelittle objective effect on nasalcongestion. Antihistamines re-duce symptoms of allergic con-junctivitis, which are often asso-ciated with allergic rhinitis.

Issues with sedation/performanceimpairment34. Sedation and performance im-

pairment are undesirable andpotentially dangerous side ef-fects of first generation antihis-tamines. Consequently, secondgeneration antihistamines thatare associated with less risk orno risk for these side effectsshould usually be considered be-fore sedating antihistamines forthe treatment of allergic rhinitis,and are even mandated in somesegments of the transportationindustry. Studies have demon-strated that many patients maynot perceive performance im-pairment that is associated withfirst generation (classical) anti-histamines. In the majority ofstates, patients taking sedatingantihistamines are legally con-sidered “under the influence ofdrugs.”

Adverse cardiac effects of somesecond generation antihistamines35. Some older non-sedating anti-

histamines such as astemizoleand terfenadine (the latter with-drawn from the US market in1998) may cause prolongation ofthe QTc interval that may leadto the ventricular arrhythmiatorsade de pointes especiallywith overdose, administrationwith certain concomitant medi-cations (eg, some macrolide an-tibiotics, azole anti-fungalagents), and in the presence ofsevere liver disease.

Although many chemical mediators ofinflammation play a role in producingthe various symptoms and signs of al-lergic rhinitis, there is strong evidencethat histamine is a mediator of majorimportance in this disorder. Once re-leased from mast cells and basophils,histamine dilates blood vessels, in-creases vessel permeability, and stim-ulates sensory nerve endings and re-flexes through the parasympatheticsystem that cause glandular secretion.Histamine given intranasally can re-produce all the symptoms of allergicrhinitis (sneezing, pruritus, rhinorrhea,blockage),1 and therefore, H1 hista-mine receptor antagonists (ie, H1 anti-histamines) are generally effective incontrolling many of the symptoms ofallergic rhinitis. Antihistamines areless efficacious (if at all) in other formsof rhinitis (eg, vasomotor, infectious),thereby making it important to estab-lish a correct diagnosis before initiat-ing therapy.A major limitation of the use of the

first generation (classical) antihista-mines has been sedation. However,second generation antihistamines havebeen developed that in recommendeddoses significantly reduce or eliminatethis problem. The availability of thesesecond generation antihistamines hasgreatly improved the usefulness of an-tihistamines as pharmacotherapeuticagents since patients who otherwisewould avoid antihistamine therapy dueto sedation, can now utilize them andobtain significant benefit.Mechanism/pharmacokinetics. Both

first and second generation H1 antihis-tamines are pharmacologic antagonistsof histamine at the H1-receptor site andact by competitively binding to the H1receptor, thus blocking the H1 re-sponse. Certain H1-receptor antago-nists have metabolites that are activeand as relevant, or even more relevant,than their parent compound (eg, lora-tadine, terfenadine, astemizole, hy-droxyzine).2 In addition to being antag-onists of histamine, some of the secondgeneration antihistamines may inhibitrelease of mast cell and basophil in-flammatory mediators resulting in anti-allergic and anti-inflammatory effects.

Some of this action may be due to theability of some, but not all, antihista-mines to prevent release of histamineafter antigen challenge.3Oral antihistamines are readily ab-

sorbed, with peak serum concentra-tions usually occurring within 2 to 3hours after a dose. The metabolism ofall first generation and several secondgeneration antihistamines is via the he-patic cytochrome P450 system. Clear-ance rates of H1 antagonists are quitevariable (2 hours to 10 days) but gen-erally, serum elimination half-lives areshorter in children than in adults,longer in the elderly, but in all agesserum half-lives are less than their du-ration of bioactivity. In studies of theability of antihistamines to suppresshistamine- or antigen-induced whealand flare reactions, peak suppressionby antihistamines usually occurs 5 to 7hours after an oral dose. Histaminesuppressive effects can persist for up to24 to 36 hours and longer (eg, hy-droxyzine, cetrizine), even when se-rum concentrations of the parent com-pound have declined to their lowestlimit of detection, probably secondaryto the presence of active metabolitesand/or high tissue drug concentra-tions.2 Astemizole is unique in that itbinds to peripheral H1-receptor siteswith far greater affinity than do otherH1-receptor antagonists. As a result, asingle dose of astemizole produces se-rum and tissue levels that persist fordays to weeks, with skin test suppres-sion noted to last up to at least 6weeks.4Clinical efficacy. Oral antihista-

mines are capable of decreasing all thesymptoms of allergic rhinitis (especial-ly sneezing, itching, and nasal dis-charge) but are least effective in reliev-ing nasal blockage. Numerous firstgeneration antihistamines are availableover-the-counter or by prescription.All first generation antihistamines be-long to one of 6 different chemicalclasses based on their specific sidechain substitution. There generally islittle difference in clinical efficacyamongst these classes, although chlor-pheniramine (alkylamine class) andhydroxyzine (piperazine class) have

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been found to be more effective incertain studies when compared to otherfirst generation antihistamines.5Adverse Effects. Many patients with

significant allergy symptoms wouldrather tolerate their symptoms than usean antihistamine for relief because ofthe associated sedation, performanceimpairment and other adverse effects.This phenomenon has great inter-patient variability. Some patients willbe completely free of drowsiness,whereas others are heavily sedatedeven after a small dose. After contin-ued use of antihistamines, it has beenreported that some individuals may de-velop tolerance to sedation or perfor-mance impairment effects from theseagents, but other studies report little orno reduction in these side effects.6Many patients deny sedation with

the use of first generation antihista-mines but an increasing body of infor-mation suggests that CNS impairmentcan exist even when sedation is notreported.7 The major objective param-eters used to detect CNS effects withantihistamines are reduced sleep la-tency (greater sleepiness) and perfor-mance impairment. Measurementsused to assess performance impairmentinclude reaction time, visual-motor co-ordination, arithmetical exercises,memory, learning, and driving tests (eg,ability to avoid obstacles and drive in astraight line). Using these measure-ments, first generation antihistamineshave been clearly associated with CNSdepression and impairment, and theseeffects can be independent of any sub-jective complaints by the patient. First

generation antihistamines have beendemonstrated to impair children’slearning and academic performance.8,9First generation antihistamines alsomay cause driving impairment and fa-tal automobile accidents.10–14 Onelarge epidemiologic study has demon-strated that drivers responsible for fatalautomobile accidents were 1.5 morelikely to be taken first-generation anti-histamines than drivers killed but notresponsible for accidents.15 In the ma-jority of states, patients taking sedatingantihistamines are legally considered“under the influence of drugs.”16Workers taking first generation anti-histamines have decreased work per-formance and productivity and are alsomore likely to be involved in occupa-tional accidents, a risk greater than thatattributable to narcotics and sedativehypnotics.17–20 Other CNS active sub-stances such as alcohol, sedatives, hyp-notics and anti-depressants may poten-tiate the performance impairment fromantihistamines. Similar effects on per-formance and sleep latency have notbeen observed with the standard dosesof available “non-sedating” second-generation antihistamines describedbelow. Consequently, second genera-tion antihistamines that are associatedwith less risk or no risk for these sideeffects should usually be consideredbefore sedating antihistamines for thetreatment of allergic rhinitis, and areeven mandated in some segments ofthe transportation industry.Adverse effects other than drowsi-

ness can occur with first generationantihistamines, and are related mainly

to the peripheral and central cholin-ergic nervous system; antiserotoninand anti-bradykinin effects may alsobe important. Peripheral anticholin-ergic effects including dry mouth, dryeyes, and urinary retention are not un-common; tachycardia, impotence,worsening of glaucoma, and headachealso rarely occur. Central effects inaddition to somnolence may includecoma, seizures, dyskinesia and behav-ioral changes. An atropine-like “psy-chosis” can result from overdose.Second-Generation Antihistamines.

Second generation H1-receptor antago-nists are relatively lipophobic, have alarge molecular size, and possess anelectrostatic charge, all of which con-tribute to poor penetration of the CNS,thereby decreasing or eliminatingsedation. Other advantages of thesesecond generation antihistamines in-clude preferential binding to peripheralH1-receptors over central ones and thefeature of possessing minimal antise-rotonin, anticholinergic and alpha-ad-renergic blocking activity.21The present list of available second

generation antihistamines includesastemizole, loratadine, cetirizine, andfexofenadine; terfenadine marketing inthe US ceased in 1998 (Table 3). Theseagents have proven effective in de-creasing symptoms of sneezing, itch-ing, and nasal discharge, and the ocularsymptoms of allergic conjunctivitis of-ten associated with allergic rhinitis.Although they possess an improvedsafety profile, most evaluations show,however, that this new class of antihis-tamines is no more effective than thefirst generation H1-receptor antago-nists.22Pharmaceutical manufacturers rec-

ommend the following adult doses toprovide optimal efficacy with minimallikelihood of causing sedation or otheradverse effects: astemizole, 10 mgQD; cetirizine, 5 to 10 mg QD; fexo-fenadine, 60 mg BID; and loratadine10 mg QD. Cetirizine, fexofenadineand loratadine have serum half-livesand duration of histamine-inducedwheal and flare suppression in therange of 8 to 24 hours. Astemizole hasan initial half-life of 7 to 9 days, and a

Table 3. Second Generation Oral Antihistamines

AgentUsual adult

dosing*Available withdecongestant

Reduce dosewith liverdisease?

Reduce dosewith renal

impairment?

Pregnancycategory

Astemizole*(Hismanal�)

10 mg QD No Avoid No change C

Cetirizine(Zyrtec�)

5–10 mg QD No 5 mg QD 5 mg QD B

Fexofenadine(Allegra�)

60 mg PO BID Yes 60 mg QD No change C

Loratadine(Claritin�)

10 mg PO QD Yes Start at 10 mgQOD

Start at 10mg QOD

B

* For pediatric dosing, see Table 6.

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terminal half-life of 19 days, account-ing for its ability to suppress skin testresponses for a month or longer inmany subjects.Although comparison trials of sec-

ond generation agents are limited innumber, overall clinical efficacy andpatient acceptance appear similaramong the different non-sedating orless sedating preparations. Astemizoledoes have a longer time for peak onsetof symptom relief making it less usefulas a prn medication.23 When compar-ing antihistamine therapy with intrana-sal corticosteroids, both first and sec-ond generation oral antihistamines areless potent in improving allergic rhini-tis symptoms, although, they providemore relief of ocular symptoms. Intra-nasal cromolyn and intranasal antihis-tamines provide comparable control ofallergic rhinitis. Therefore, while anti-histamine therapy is useful in the treat-ment of mild to moderate allergic rhi-noconjunctivitis, patients with moresevere disease will usually require anintranasal corticosteroid or combina-tion regimen.24Administration of standard doses of

some second generation antihistamines(astemizole, fexofenadine, loratadine)result in no greater incidence of seda-tion than that seen with placebo.Therefore, these preparations havebeen termed “nonsedating.” However,some nonsedating agents have been re-ported to cause sedation or CNS dys-function at higher than usual doses (eg,with loratadine), or at recommendeddoses in certain individuals.25 The in-cidence of sedation with the secondgeneration antihistamine cetrizine at astandard adult dose of 10 mg is higherthan with placebo, although it is sig-nificantly less sedating than most firstgeneration antihistamines.Non-sedating antihistamines have

not been shown to potentiate the CNSeffects of alcohol or diazepam. Astem-izole has the additional property of ap-petite stimulation in certain patients re-sulting in unwanted weight gain.Previous concerns about the potentialadverse effects of antihistamines in pa-tients with asthma have not been sub-stantiated with the second generation

antihistamines. In fact, some othernon-sedating antihistamines appear tohave some mild anti-asthma effects26(see “Summary Statement #47”).Astemizole (and the no longer mar-

keted terfenadine) can rarely produceserious cardiovascular effects if usedin doses that exceed the manufactur-er’s recommendations. Patients withhepatic dysfunction, hypokalemia, hy-pocalcemia, congenital QT syndrome,or who are using certain concomitantmedications that interfere with the me-tabolism of astemizole (or terfena-dine), are also at risk.27 The cardiovas-cular events seen include ventriculartachyarrhythmias (particularly torsadesde pointes but also ventricular tachy-cardia, and ventricular fibrillation orflutter), cardiac arrest, sudden neardeath and death. The serious rhythmchanges that occur are likely due toprolongation of the QT interval as adirect effect of elevated tissue levels ofthe parent compound of these secondgeneration antihistamines, and, be-cause of this prolongation, place thepatient at risk for a ventricular arrhyth-mia. Cetirizine, fexofenadine, and lo-ratadine have not been shown to beassociated with QT interval changes orrhythm disturbances.28 Astemizoleshould not be prescribed at greater thanthe recommended dose, or with con-comitant medications that could inhibitastemizole metabolism by the cyto-chrome P450 3A4 isoenzyme systemof the liver. Drugs that should beavoided or approached with caution in-clude azole anti-fungals (fluconazole,itraconazole, miconazole), some mac-rolides (eg, erythromycin, clarithromy-cin) and ciprofloxacin. Patients usingastemizole (or existing supplies of ter-fenadine) should inform all physiciansthat they are taking these agents whenother medications are prescribed. Phy-sicians should avoid giving these anti-histamines to alcoholic patients or any-one suspected of significant liverdisease. The dose of the antihistaminesshould always be decreased to the low-est dose that controls the symptoms.Combined therapy with first and

second generation antihistamines. In astrategy intended to reduce costs of

antihistamine therapy while avoidingdaytime sedation and performance im-pairment, it has been advocated thatone may dose a non-sedating secondgeneration antihistamine (that wouldotherwise be dosed twice daily) onlyonce daily in the morning, followed bya first generation (and cheaper) antihis-tamine in the evening. The rationalefor this strategy assumes that daytimesedation and performance impairmentwill be avoided if a first generationantihistamine is administered only atbedtime. However, studies have dem-onstrated that first generation antihis-tamines dosed only at bedtime maycause significant daytime sedation, de-creased alertness and performance im-pairment,29–34 in part because antihis-tamines and their metabolites haveprolonged plasma half-lives and theirend-organ effects persist even longerthan plasma levels of the parent anti-histamine agent. Consequently, an“AM/PM” dosing regimen combining asecond generation agent in the AM withfirst generation agent in the PM is anineffective strategy for avoiding day-time sedation and performance impair-ment from antihistamine treatment.General principles of antihistamine

therapy. There are certain general prin-ciples of antihistamine use that shouldbe followed when treating patientswith allergic rhinitis. Since neither firstnor second generation oral antihista-mines are very effective in relievingnasal blockage, a decongestant agent(eg, pseudoephedrine, phenylpropa-nolamine) or a topical nasal corticoste-roid may need to be added to oralantihistamine therapy. Many combina-tion antihistamine-decongestant for-mulations are available in a fixed dosepreparation which allow the patient theease and convenience of taking justone tablet. The drawbacks of thesecombination agents are: (1) certain pa-tients are unable to tolerate the fixeddose of the decongestant (eg, causestimulation), and (2) the dose of oneingredient cannot be adjusted, if nec-essary, without changing the dose ofthe second ingredient which may notneed to be changed. For these reasons,using a separate antihistamine and sep-

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arate decongestant can have the advan-tage of permitting one medication to betitrated independently of the other.Patients need to be educated that for

optimal results, antihistamines shouldbe administered either prophylactically(2 to 5 hours before allergen exposure)or on a regular basis if needed chron-ically. Although antihistamines are ef-fective on a PRN basis, they work bestwhen taking them in a maintenancefashion.

References1. White MV, Kaliner MA. Mediators ofallergic rhinitis. J Allergy Clin Immu-nol 1992;90:699–704.

2. Simons FER. H1-receptor antagonists:clinical pharmacology and therapeu-tics. J Allergy Clin Immunol 1989;84:845–861.

3. Bousquet JB, Lebel B, Chanal I, et al.Antiallergic activity of H1-receptor an-tagonists assessed by nasal challenge. JAllergy Clin Immunol 1988;82:881–887.

4. Richards DM, Brogden RN, Heel RC,et al. Astemizole: a review of its phar-macodynamic properties and therapeu-tic efficacy. Drugs 1984;28:38–61.

5. Sue MA, Tamasky PR, Abernathy SB,Klaustermeyer WB. A comparison ofsix antihistamine drugs in the treat-ment of perennial allergic rhinitis. Im-munol Allergy Pract 1986;8:193–198.

6. Goetz DW, Jacobson JM, Murnane JE,et al. Prolongation of simple andchoice reaction times in a double-blindcomparison of twice daily hydroxyzineversus terfenadine. J Allergy Clin Im-munol 1990;186:1034–1039.

7. Gengo FM, Manning C. A review ofthe effects of antihistamines on mentalprocesses related to automobile driv-ing. J Allergy Clin Immunol 1990;186:1034–1039.

8. Simons FER, Reggin JD, Roberts JR,et al. Benefit/risk ratio of the antihis-tamines (H1 receptor antagonists) ter-fendaine and chlorpheniramine in chil-dren. J Pediatr 1994;124:979–983.

9. Vuurman EFPM, van Veggel LMA,Uiterwijk MM, et al. Seasonal allergicrhinitis and antihistamine effects onchildren’s learning. Ann Allergy 1993;71:121–126.

10. O’Hanlon JF, Ramaekers JG. Antihis-tamine effects on actual driving perfor-mance in a standard test. A summaryof the Dutch experience, 1989–1994.

Allergy 1995;50:234–242.11. O’Hanlon JF. Antihistamines and driv-

ing safely. In: Alcohol, drugs and traf-fic safety, vol 42. Institute for Drugs,Safety and Behavior: RyksunirersitietLimberg, Maastricht, The Netherlands,1998:10–12.

12. Ramaekers JG, Uiterwijk MMC,O’Hanlon JF. Effects of loratadine andcetirizine on actual driving and psy-chometric test performance and EEGduring driving. Eur J Clin Pharmacol1992;42:363–369.

13. Ray WA, Thapa PB, Shorr RI. Medi-cations and the older driver. Clin Geri-atr Med 1993;9:413–438.

14. Cimbura G, Lucas DM, Bennett RC, etal. Incidence and toxicological aspectsof drugs detected in 484 fatally injureddrivers and pedestrians in Ontario. JForensic Sci 1982;27:855–867.

15. Warren R, Simpson H, Hilchie J, et al.Drugs detected in fatally injured driv-ers in the province of Ontario. In:Goldberg L, ed. Alcohol, drugs andsafety, I. Stockholm: Almquist andWiksell, 1981:203–217.

16. US Dept of Transportation digest ofstate Alcohol-Highway Related Legis-lation. 147th ed. 1996.

17. Gilmore TM, Alexander BH, MuellerBA, Rivera FP. Occupational injuriesand medical use. Am J Ind Med 1996;30:234–349.

18. Walsh JK, Muehlbach MJ, SchweitzerPK. Simulated assembly line perfor-mance following ingestion of cetiriz-ine or hydroxyzine. Ann Allergy 1992;69:195–200.

19. Adelsberg BR, D’Amico-Beadone A.The effects of loratadine, diphenhydra-mine and placebo on worker produc-tivity. Results of a double blind trial. JAllergy Clin Immunol 1990;85:296.

20. Gaillard AWK, Grisen A, de Jong R.The influence of antihistamines on hu-man performance. Eur J Clin Pharma-col 1988;35:249–253.

21. Meltzer EO. Comparative safety of H1antihistamines. Ann Allergy 1991;67:625–633.

22. Kemp JP, Bahna SL, Chervinsky P, etal. A comparison of loratadine, a newnonsedating antihistamine, with clem-astine and placebo in patients with fallseasonal allergic rhinitis. Am J Rhinol1987;1:151–154.

23. Simons FER, Simons KJ. New nonse-dating antihistamines. Chapter 26 In:Settipane G, ed. Rhinitis. Providence:Oceanside Publications, 1991.

24. Siegel SC. Topical intranasal cortico-steroid therapy in rhinitis. J AllergyClin Immunol 1988;81:984–991.

25. Meltzer EO, Welch MJ. Adverse ef-fects of H1 receptor antagonists in thecentral nervous system. In: SimonsFER, ed. Histamine and H1 receptorantagonists in allergic disease. NewYork: Marcel Dekker, Inc., 1996:357–381.

26. Rafferty P, Jackson L, Smith R, Hol-gate ST. Terfenadine, a potent hista-mine H1-receptor antagonist in thetreatment of grass pollen sensitiveasthma. Br J Clin Pharmacol 1990;30:229–235.

27. Kemp JP. Antihistamines–is there any-thing safe to prescribe? Ann Allergy1992;69:276–280.

28. Woosley R, Darrow WR. Analysis ofpotential adverse drug reactions–a caseof mistaken identity. Am J Cardiology1994;74:208.

29. Hindmarch I, Parrot AC. A repeateddose comparison of the side effects offive antihistamines on objective as-sessments of psychomotor perfor-mance, central nervous system arousaland subjective appraisals of sleep andearly morning behavior. Arneim-Forsch/Drug Res 1978;28:484–486.

30. Goetz DW, Jacobson JM, Apaliski SJ,et al. Objective antihistamine side ef-fects are mitigated by evening dosingof hydroxyzine. Ann Allergy 1991;67:448–454.

31. Alford C, Rombaut N, Jones J, et al.Acute effects of hydroxyzine on noc-turnal sleep and sleep tendency the fol-lowing day: a C-EEG study. Hum Psy-chopharmacol 1992;7:25–35.

32. Klein GL, Littlejohn III T, LockhartEA, et al. Brompheniramine, terfena-dine and placebo in allergic rhinitis.Ann Allergy Asthma and Immunol1996;77:365–370.

33. Kay GG, Plotkin KE, Quig MB, et al.Sedating effects of AM/PM antihista-mine dosing with evening chlorphe-niramine and morning terfenadine.Am J Managed Care 1997;3:1843–1848.

34. Starbuck VN, Kay GG, Platenberg RC.Functional magnetic resonance imag-ing shows evidence of daytime sleep-iness following evening dosing withchlorpheniramine (CP). J Allergy ClinImmunol 1998;101 (no. 1, part 2): (ab-stract 408).

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Intranasal Antihistamines36. Intranasal antihistamines are ef-

fective for treatment of allergicrhinitis. These agents are appro-priate for use as first-line treat-ment for allergic rhinitis, and incontrast to most oral antihista-mines, may help reduce nasalcongestion. However, patientsmay perceive them as having abitter taste and because signifi-cant systemic absorption mayoccur, they may be associatedwith resultant sedation in somepatients.

Intranasal antihistamines have beenapproved for the treatment of thesymptoms of seasonal allergic rhinitissuch as rhinorrhea, sneezing and nasalpruritus. These agents are appropriatefor use as first line treatment for thesymptoms of allergic rhinitis, or as partof combination therapy with nasal cor-ticosteroids or oral antihistamines.Astelin (azelastine hydrochloride) is

the first intranasal antihistamine prep-aration approved for use in the US.1–3 Itis formulated as a 0.1% aqueous solu-tion in a metered spray delivery de-vice. Recommended dosing is 2 spraysin each nostril BID for patients �12years. An onset of action has beendemonstrated within 3 hours versusplacebo. Several studies have demon-strated efficacy that is at least equalto oral antihistamines. In clinical tri-als, 19.7% of patients complain of bit-ter taste, and 11.5% report somno-lence.4 In addition, azelastine nasal hasbeen reported to reduce nasal conges-tion.1–3

References1. Newson-Smith G, Powell M, et al. Aplacebo controlled study comparingthe efficacy of intranasal azelastineand beclomethasone in the treatmentof seasonal allergic rhinitis. Eur ArchOtorhinolaryngol 1997;254:236–241.

2. Ratner PH, et al. A double-blind, con-trolled trial to assess the safety andefficacy of azelastine nasal spray inseasonal allergic rhinitis. J AllergyClin Immunol 1994;94:818–825.

3. LaForce C, et al. Safety and efficacy ofazelastine nasal spray (Astelin NS) for

seasonal allergic rhinitis. Ann AllergyAsthma Clin Immunol 1996;76:181–188.

4. Anonymous. Astelin (azelastine hy-drochloride) nasal spray product insert(Rev. 10/96).

Oral and Nasal Decongestants37. Oral decongestants, such as

pseudoephedrine or phenylpro-panolamine, can effectively re-duce nasal congestion producedby rhinitis, but can cause insom-nia, loss of appetite or excessivenervousness. In addition, theseagents should be used with cau-tion in patients with certain con-ditions, eg, arrhythmias, anginapectoris, some patients with hy-pertension and hyperthyroid-ism. Topical sympathomimeticscan be useful for short-term (eg,2 to 3 days) therapy for nasalcongestion associated with rhi-nitis.

Oral alpha-adrenergic agents, such aspseudoephedrine, phenylephrine andphenyl-propanolamine, cause nasal va-soconstriction. These oral preparationsare useful in the management of vaso-motor rhinitis and relief of nasal con-gestion due to upper respiratory infec-tions. In addition, studies havedemonstrated that the efficacy of thesedrugs in combination with antihista-mines in the management of allergicrhinitis is superior to the efficacy ofeither drug alone.1 These combinationshave also been shown to be useful foreosinophilic nonallergic rhinitis and insome individuals with nasal hyperreac-tivity with diffuse rhinorrhea or postnasal discharge.2Some patients may experience sys-

temic side effects from oral alpha-ad-renergic agents which include elevatedblood pressure, palpitations, loss of ap-petite, tremor and sleep disturbance.2Pseudoephedrine is less likely to causeelevated blood pressure than phenyl-propanolamine.3,4 Oral alpha-adrener-gic agonists should be used with cau-tion in patients with certain conditions,eg, arrhythmia, coronary heart disease,hypertension, hyperthyroidism, glau-

coma, diabetes, and urinary dysfunc-tion.Topically applied sympathomimetic

decongestant alpha-adrenergic ago-nists can be catecholamines such asphenylephrine or imidazoline agentssuch as oxymetazoline or xylometazo-line. These medications cause nasalvasoconstriction and decreased nasaledema, decreased edema but have noeffect on the antigen provoked nasalresponse.2 Also, alpha-adrenergic va-soconstrictors reduce nasal obstructionbut do not alter itching, sneezing ornasal secretion. Topical decongestantscan decrease nasal airway resistanceand nasal blood flow5,6 but usually donot cause systemic sympathomimeticreactions.Topical sympathomimetics can lead

to rebound nasal congestion (rhinitismedicamentosa) with rhinitis medica-mentosa which usually occurs after 5to 10 days of treatment.7 This can oc-cur due to downregulation of alphaadrenoreceptors which makes themless sensitive to endogenously releasednoradrenalin and exogenously appliedvasoconstrictors. Topical sympathomi-metics can be useful for short-term (eg,2 to 3 days) therapy for nasal conges-tion associated with acute bacterial orviral infections, allergic rhinitis, andeustachion tube dysfunction.2

References1. Falliers CJ, Redding MA. Controlledcomparison of a new antihistamine-decongestant combination to its indi-vidual components. Ann Allergy 1980;45:75.

2. Druce HM. Allergic and nonallergicrhinitis. In: Middleton E, Reed CE,Ellis E, et al, eds. Allergy, principlesand practice, 5th edition. St. Louis:Mosby-Year Book, 1998:1005–1016.

3. Harowitz JD, Howes LG, Christophi-dis N, et al. Hypertensive responsesinduced by phenylpropanolamine inanorectic and decongestant prepara-tion. Lancet 1980;1:60.

4. Coates ML, Rembold CM, Farr BM.Does pseudoephedrine increase bloodpressure in patients with controlled hy-pertension. J Fam Prac 1995;40:22–26.

5. Anderson KE, Bende M. Adrenocep-tors in the control of human nasal mu-

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cosal blood flow. Ann Otol Rhinol La-ryngol 1984;93(2):179.

6. Malm L. Responses of resistance andcapacitance vessels in feline nasal mu-cosa to vasoactive agents. Acta Otolar-yngol (Stockh.) 1974;78:90.

7. Black MJ, Remsen KA. Rhinitis medi-camentosa. Can Med Assoc J 1980;122:881.

Nasal Corticosteroids38. Nasally inhaled corticosteroids

are the most effective medica-tion class in controlling symp-toms of allergic rhinitis. Theyare particularly useful for treat-ment of more severe allergic rhi-nitis and may be useful in someother forms of rhinitis. Exceptfor intranasal dexamethasone,these agents are generally notassociated with significant sys-temic side effects in adults. Al-though local side effects areminimal if the patient is care-fully instructed in the use of thisclass of drugs, nasal irritationand bleeding may occur, and na-sal septal perforations are rarelyreported. Intranasal corticoste-roids should be considered be-fore initiating treatment withsystemic corticosteroids for thetreatment of severe rhinitis.

Oral and Parenteral Corticosteroids39. A short (3 to 7 day) course of

oral corticosteroids may be ap-propriate for the treatment ofvery severe or intractable nasalsymptoms or to treat significantnasal polyposis. However, theuse of parenteral corticoste-roids, particularly if adminis-tered recurrently, is discouragedbecause of greater potential forlong-term corticosteroid side ef-fects.

The main mechanism by which corti-costeroids relieve the symptoms of al-lergic rhinitis is through their anti-in-flammatory activity.1 The concept ofdelivering steroids topically to the na-sal airway was developed in order tominimize potential steroid side effectsof using systemic corticosteroids. Na-sal steroids are variously available inpropellant metered dose inhalersand/or aqueous suspensions or glycolsolutions (Table 4).Nasal steroids are effective in con-

trolling the four major symptoms ofallergic rhinitis, including sneezing,itching, rhinorrhea and nasal blockage.In clinical trials nasal steroids are moreefficacious than nasal cromolyn sodi-um,2 or oral antihistamines.3–5 How-ever, one study has reported that atleast 50% of patients need to take both

nasal corticosteroids and oral antihis-tamines to adequately control symp-toms of seasonal allergic rhinitis.6 Na-sal steroids have also been shown to beeffective in the treatment of certaintypes of non allergic rhinitis, espe-cially NARES.7 Because a patent nasalairway is necessary for optimal intra-nasal delivery of nasal steroids, a top-ical decongestant spray may be neces-sary for several days when nasalsteroids are introduced.The most common side effects en-

countered using nasal steroids are dueto local irritation. This may presentwith burning or stinging and is morecommonly associated with glycol-con-taining solutions.Nasal bleeding is also seen with use

of intranasal steroids. This is usuallyapparent as blood-tinged blown secre-tions but nasal septal perforation hasalso been rarely reported with long-term use of intranasal steroids.8 Thismay occur secondary to local septaltrauma from the spray in combinationwith the vasoconstrictor activity of thesteroid. The use of aqueous prepara-tions, longer extension applicators, andlower velocity sprays should help re-duce local trauma to the nasal septum.Patients should always direct the sprayaway from the nasal septum to preventthe repetitive direct application to theseptum. The nasal septum should beperiodically examined to assure thatthere are no mucosal erosions that mayprecede development of nasal septalperforations that are rarely associatedwith intranasal corticosteroids. Nasalbiopsies in subjects with perennial al-lergic rhinitis suggest no signs of tissueatrophy or change after five years oftherapy.9 The judicious use of nasalsteroids in children is indicated withfrequent re-evaluation of the patient toassess further need for nasal steroiduse.Current studies in adults suggest

minimal systemic side effects with ad-ministration of nasal steroids in recom-mended doses (except dexamethasonewhich is capable of producing minorsystemic steroid effects). Studies ofnew steroid preparations even in rela-tively high doses demonstrate no sys-

Table 4. Nasal Corticosteroid Sprays

Agent Trade Name(s)Dose PerInhalation

Base Initial Adult Dosage*

Beclomethasone Beconase� 42 �g 1–2 sprays per nostril 2�/daydipropionate Beconase AQ�

Vancenase Pockethaler�Vancenase AQ 84 �g 1–2 sprays per nostril 1�/dayDouble Strength�

Budesonide Rhinocort� 32 �g 2 sprays per nostril 2�/day or4 sprays per nostril 1�/day

Flunisolide Nasarel� 25 �g 2 sprays per nostril 2�/dayNasalide�

Fluticasonepropionate

Flonase� 50 �g 2 sprays per nostril 1�/day or1 spray per nostril 2�/day

Mometasone Nasonex(AQ)� 50 �g 2 sprays per nostril 1�/dayTriamcinolone Nasacort� 55 �g 2 sprays per nostril 1�/dayacetonide Nasacort AQ�

Dexamethasonesodiumphosphate

Dexacort� 84 �g 2 sprays per nostril 2–3�/day

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temic steroid effect on hypothalamic-pituitary-adrenal axis as assessed bymorning cortisol concentrations, co-syntropin stimulation and 24-hour uri-nary-free cortisol excretion.10 Despitethe not uncommon occurrence of can-dida in the oropharynx in associationwith the use of inhaled steroids forasthma, candida overgrowth seems un-common with intranasal steroid admin-istration.There have been reports of a possi-

ble association between the develop-ment of posterior subcapsular cataractsand the use of intranasal or inhaledsteroids,11 but this association has notbeen confirmed by other studies.12Concomitant use of systemic steroidsin some subjects receiving intranasalsteroids confounds interpretation ofstudies that attempt to address thequestion of this possible association.Studies of newer intranasal steroids inprospective trials over 24 weeks oftreatment have not demonstrated thedevelopment of lenticular changesconsistent with posterior subcapsularcataracts.13 Based upon available stud-ies, patients receiving standard dosesof nasal steroids are not at increasedrisk for glaucoma.14 Although steroidsas a class of drugs are not thought to beteratogenic in humans, safety duringpregnancy has not been establishedand benefit/risk ratio should be care-fully considered. (See section on Rhi-nitis and Pregnancy under SummaryStatement #48) In children, concernsabout possible adverse effects ongrowth raise special considerations(see section on treatment of childrenunder Summary Statement #48).Although systemic steroids are not

appropriate for chronic rhinitis ther-apy, short courses of systemic steroidsmay be very effective in severe casesthat are unresponsive to other modali-ties of treatment, and especially thosecases associated with polyposis. Whensystemic steroids are necessary, it ispreferable to administer short (5 to 7day) bursts of short-acting oral steroidssuch as prednisone or methylpred-nisolone. At doses equivalent to 40mg/day of prednisone in adults, adre-nal suppression is avoided. Depot in-

jections of steroids may be effectivefor rhinitis symptoms but may be as-sociated with prolonged adrenal sup-pression and lack the flexibility of oraldosing. Consequently, parenteral corti-costeroid administration (particularlyif recurrent) is discouraged because ofgreater potential for long-term cortico-steroid side effects.Intraturbinate injection of cortico-

steroids is not recommended for treat-ment of rhinitis because the potentialbenefits do not outweigh the poten-tially serious side effects of cavernousvein thrombosis and blindness,15 andalternatives such as nasal and oral ste-roids are available.

References1. Pauwels R. Mode of action of cortico-steroids in asthma and rhinitis. ClinAllergy 1986;16:251–258.

2. Welsh PW, Stricker WE, Chu-Pin C, etal. Efficacy of beclomethasone nasalsolution, flunisolide and cromolyn inrelieving symptoms of ragweed al-lergy. Mayo Clin Proc 1987;62:125–134.

3. Storms WW. Treatment of seasonal al-lergic rhinitis with fluticasone propi-onate aqueous nasal spray: review ofcomparator studies. Allergy 1995;50:25–29.

4. Bronsky E, Dockhorn R, Meltzer E, etal. Intranasal fluticasone propionate ismore effective than terfenadine fortreatment of seasonal rhinitis [Ab-stract]. Ann Allergy 1994;72(1):86.

5. Jeal W, Faulds D. Triamcinolone ace-tonide. A review of its pharmacologi-cal properties and therapeutic efficacyin the management of allergic rhinitis.Drugs 1997;53:257–280.

6. Juniper EF, Guyatt GH, Ferrie PJ,Griffith LE. First-line treatment of sea-sonal (ragweed) rhinoconjunctivitis. Arandomized management trial compar-ing a nasal steroid spray and a nonse-dating antihistamine. CMAJ 1997;156:1123–1131.

7. Selner J, Banov C, Boltansky H, et al.Fluticasone propionate aqueous nasalspray effectively treats perennial non-allergic rhinitis. J Allergy Clin Immu-nol 1994;93:165.

8. La Force C, Davis V. Nasal septal per-foration with intranasal beclometha-sone. J Allergy Clin Immunol 1985;75:186.

9. Morrow Brown H, Storey G, JacksonFA. Beclomethasone dipropionateaerosol in treatment of perennial andseasonal rhinitis: a review of fiveyears’ experience. Br J Clin Pharmacol1977;4:2835.

10. van As A, Bronsky E, Grossman J, etal. Dose tolerance study of fluticasonepropionate aqueous nasal spray in pa-tients with seasonal allergic rhinitis.Ann Allergy 1991;67:156–162.

11. Fraunfelder FT, Meyer SM. Posteriorsubcapsular cataracts associated withnasal or inhalation corticosteroids.Am J Ophthalmol 1990;109:489–490.

12. Barenholtz H. Effect of inhaled ste-roids on the risk of cataract formationin patients with steroid-dependentasthma. Ann Pharmacother 1996;30:1324–1327.

13. van As A, Bronsky EA, Dockhorn RJ,et al. Once daily fluticasone propionateis as effective for perennial allergicrhinitis as twice daily beclomethasonedipropionate. J Allergy Clin Immunol1993;91:1146–1154.

14. Garbe E, LeLorier J, et al. Inhaled andnasal glucocorticoids and then risks ofocular hypertension or open-angleglaucoma. JAMA 1997;227:722–727.

15. Saunders WH. Surgery of the inferiornasal turbinates. Ann Oto Rhinol Lar-yngol 1982;91:445–457.

Intranasal Cromolyn40. Intranasal cromolyn sodium is

effective in some patients in con-trolling symptoms of allergicrhinitis and is associated withminimal side effects.

A 4% solution of cromolyn sodium,USP, was introduced into the US in1983 as Nasalcrom for topical intrana-sal treatment of allergic rhinitis. Cro-molyn sodium has been shown to in-hibit the degranulation of sensitizedmast cells thereby preventing the re-lease of mediators of the allergic re-sponse and of inflammation. Thus, itprevents the allergic event rather thanalleviate the symptoms once the reac-tion has begun.1–6 The protective effectof cromolyn against nasal antigen chal-lenge persists for 4 to 8 hours afterinsufflation.7Cromolyn sodium nasal spray is ad-

ministered as a metered aerosol via apump spray. Each spray contains ap-proximately 5.2 mg of cromolyn so-

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dium, and the starting dose is 1 sprayin each nostril every 4 hours when thepatient is awake until relief is evident;effect is normally noted within 4 to 7days. Severe or perennial cases mayrequire 2 weeks or more for maximumeffect. Thereafter, the treatment is con-tinued at whatever maintenance dose iseffective for the remainder of the ex-pected season or period of exposure.Since a patent nasal airway is a prereq-uisite, a decongestant may be neces-sary for a few days. The presence ofobstructing nasal polyps calls for theuse of measures other than cromolynsodium.Cromolyn sodium has no intrinsic

antihistamine effect. Although re-ported to be most effective in patientswith a high preseasonal serum IgElevel, it can be of benefit in both sea-sonal and perennial allergic rhinitis.The protective effect of cromolyn so-dium in preventing both the acute andlate-phase allergic reaction is notewor-thy, especially in treating individualswith predictable periods of exposure(eg, veterinarians). Pretreatment withcromolyn sodium before an allergenexposure will result in considerablediminution or ablation of the nasal al-lergic response. Patients who are givennasal cromolyn sodium must be in-structed to use it before an anticipatedallergen exposure and to use it on aregular basis during the season or pe-riod of exposure normally associatedwith allergic symptoms. In controlledstudies, cromolyn is generally less ef-fective than intranasal corticosteroids.Cromolyn appears to be useful for

the treatment of allergic rhinitis andbecause of its safety profile it shouldbe considered in very young childrenand pregnancy.Patient selection is critical. Its use

should be begun as early in an allergyseason as possible. The rationale forearly therapy is prevention of mediatorrelease from mast cells rather thantreatment of the pathologic sequelae ofsuch release. Because it is immediatelyeffective (provided that the nasal pas-sages are patent), it can be adminis-tered just before exposure in patientswith allergic rhinitis caused by occu-

pational allergens or animal danders,or in those who anticipate a limitedallergen exposure. When patients withhigh serum IgE levels and stronglypositive skin test reactions are begunon cromolyn prior to or early in theirseason, they are most likely to benefit.Patients who are already highly symp-tomatic may require the addition of anantihistamine-decongestant combina-tion during the first few days of cro-molyn treatment.Side effects are usually minor, in-

cluding sneezing (10%), nasal stingingor burning (4% to 5%), nasal irritation(less than 3%), and epistaxis (less than1%). No septal perforations or nasalcrusting have been reported with theuse of nasal cromolyn sodium. Terato-genicity of cromolyn sodium has notbeen demonstrated in animal studies,and nasal cromolyn sodium appears tobe one of the safest preparations foruse by the pregnant or pediatric patientwith nasal allergy. Therefore, an ad-vantage is its favorable safety profile.There is no evidence that intranasal

cromolyn will benefit patients with (1)vasomotor rhinitis; (2) NARES syn-drome (nonallergic rhinitis with eosin-ophilia); or (3) with nasal polyposis.8,9

References1. Altounyan REC. Review of clinical ac-tivity and mode of action of sodiumcromoglycate. Clin Allergy 1980;10:481–489.

2. Kay AB, Walsh GM, Moqbel R, et al.Disodium cromoglycate inhibits acti-vation of human inflammatory cells invitro. J Allergy Clin Immunol 1987;80:1–8.

3. Cox JSG, Beach JE, Blair AMJN, et al.Disodium cromoglycate (Intal). AdvDrug Res 1970;5:115–196.

4. Fisons Corporation. Cromolynsodium: clinical considerations.Princeton, NJ: Excerpta Medica, 1987:5–6.

5. Orie NGM, Booij-Noord H, Pelikan Z,et al. Protective effect of disodium cro-moglycate on nasal and bronchial re-actions after allergen challenge. In:Proc Symp Disodium Cromoglycate inAllergic Airways Disease, London:Butterworths, 1970:33–44.

6. Pelikan Z, Snoek WJ, Booij-Noord H,et al. Protective effect of disodium cro-

moglycate on the allergen provocationof the nasal mucosa. Ann Allergy1970;28:548–553.

7. Taylor G, Shivalkar PR. Disodiumcromoglycate: laboratory studies andclinical trial in allergic rhinitis. ClinAllergy 1971;1:189–198.

8. Nelson BL, Jacobs RL. Response ofthe nonallergic rhinitis with eosino-philia (NARES) syndrome to 4% cro-molyn sodium nasal solution. J AllergyClin Immunol 1982;70:125–128.

9. Donovan R, Kapadia R. The effect ofdisodium cromoglycate on nasal polypsymptoms. J Laryng Otol 1972;86:731–739.

Intranasal Anti-Cholinergics41. Intranasal anticholinergics may

effectively reduce rhinorrheabut have no effect on other nasalsymptoms. Although side effectsare minimal, dryness of the na-sal membranes may occur.

Increased cholinergic hyperreactivityhas been documented in nonallergicand allergic patients as well as in pa-tients with recent upper respiratorytract infections.1–4 A significant pro-portion of histamine- and antigen-in-duced secretion also appears to be cho-linergically-mediated as well.5,6 Inaddition to increased glandular secre-tion, parasympathetic stimulation alsocauses some vasodilation, particularlysinusoidal engorgement, which maycontribute to nasal congestion.Ipratropium bromide, oxitropium

bromide, tiotropium bromide and gly-copyrrolate are quaternary structuredammonium muscarinic receptor antag-onists which are poorly absorbedacross biological membranes. Ipratro-pium bromide, which has been mostextensively studied in rhinitic patients,is poorly absorbed into the systemiccirculation from the nasal mucosa; lessthan 20% of an 84 mcg per nostril doseis absorbed from the nasal mucosa ofnormal volunteers, induced-cold pa-tients or perennial rhinitis patients.7Controlled clinical trials have dem-

onstrated that a quaternary agent suchas intranasal fluorocarbon-propelledipratropium bromide, does not alterphysiologic nasal functions (eg, senseof smell, ciliary beat frequency, muco-

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cilliary clearance, or the air condition-ing capacity of the nose).8,9Ipratropium bromide has been the

most extensively studied intranasal an-ticholinergic agent. As a quaternaryamine that minimally crosses the nasaland gastrointestinal membrane and theblood-brain barrier, ipratropium bro-mide exerts its effect locally on thenasal mucosa resulting in a reductionof the systemic anticholinergic effects(eg, neurologic, ophthalmic, cardio-vascular, and gastrointestinal effects)that are seen with tertiary anticholin-ergic amines. Both a chlorofluorocar-bon based nasal formulation (AtroventMDI) developed in Europe and a newaqueous formulation (Atrovent NasalSpray) developed in the United Statesare available for use.The MDI formulation resulted in a

relatively high incidence of nasal ad-verse events (dryness, bleeding, irrita-tion and congestion) which may havebeen related to the concomitant admin-istration of a fluorocarbon (a physicaldrying agent) with ipratropium bro-mide (a pharmacological dryingagent). This has limited the clinical useof this formulation to those vasomotorpatients with refractory rhinorrhea.10Atrovent Nasal Spray sold in the

U.S.A. is an isotonic aqueous solutionwith a pH of 4.7 that is compatiblewith nasal mucosa. It is available intwo strengths, Atrovent (ipratropiumbromide) Nasal Spray 0.03% for thesymptomatic relief of rhinorrhea asso-ciated with allergic and nonallergic pe-rennial rhinitis and Atrovent NasalSpray 0.06%, for the symptomatic re-lief of rhinorrhea associated with thecommon cold.The most frequently reported ad-

verse events from ipratropium bromidenasal spray 0.03% compared to salinevehicle were mild, transient episodesof epistaxis (9% versus 5%) and nasaldryness (5% versus 1%). The dose ofipratropium bromide nasal spray0.03% is 2 sprays (42 mcg) per nostril2 or 3 times daily (total daily dose 168to 252 mcg).Ipratropium bromide has been dem-

onstrated to be effective in reducingrhinorrhea in adults and children with

perennial allergic and non-allergic rhi-nitis. Consequently, Atrovent (ipratro-pium bromide) Nasal Spray 0.03%alone or in combination with an anti-histamine or a nasal steroid is indicatedfor treatment of rhinorrhea associatedwith allergic and nonallergic perennialrhinitis.10–15 Ipratropium bromide is alsouseful in reducing rhinorrhea associatedwith eating, “gustatory rhinitis.”16Rhinorrhea associated with the com-

mon cold is due in part, to parasympa-thetic stimulation. Treatment with ananticholinergic agent such as ipratro-pium bromide (Atrovent nasal 0.06%)provides relief of rhinorrhea associatedwith the common cold.17–21

References1. Raphael GD, Baraniuk JN, KalinerMA. How and why the nose runs. JAllergy Clin Immunol 1991;87:457–467.

2. Drugs Acting at Synaptic and Neuroef-fector Junctional Sites. In: Goodmanand Gilman’s The pharmacological ba-sis of therapeutics, 9th Edition,McGraw-Hill, 1996;148–160.

3. White MV. Muscarinic receptors in thehuman airways. J Allergy Clin Immu-nol 1995;95:1065–1068.

4. Druce HM, Wright RH, Kossoff D, etal. Cholinergic nasal hyperreactivity inatopic subjects. J Allergy Clin Immu-nol 1985;76:445.

5. Baroody FM, Wagenmann M, Nacle-rio RM. A comparison of the secretoryresponse of the nasal mucosa to metha-choline and histamine. J Appl Physiol1993;74:2661–2671.

6. Baroody FM, Ford S, LichtensteinLM, et al. Physiologic responses andhistamine release after nasal antigenchallenge. Effect of atropine. Am JRespir Crit Care Med 1994;149:1457–1465.

7. Wood CC, Fireman P, Grossman J, etal. Product characteristics and pharma-cokinetics of intranasal ipratropiumbromide. J Allergy Clin Immunol1995;95:1111–1116.

8. Ohi M, Sakakura Y, Murai S, MiyoshiY. Effect of ipratropium bromide onnasal mucociliary transport. Rhinol-ogy. 1984;22:241–246.

9. Krumlien, Drettner. The effect of ipra-tropium bromide on the air condition-ing capacity of the nose. Clin Otolar-yngol 1985;10:165–168.

10. Meltzer EO. Intranasal anticholinergictherapy of rhinorrhea. J Allergy ClinImmunol 1992;90(6):1055–1070.

11. Meltzer E, Orgel A, Bronsky E, et al.Ipratropium bromide aqueousnasalspray for patients with perennial aller-gic rhinitis: a study of its effect on theirsymptoms, quality of life, and nasalcytology. J Allergy Clin Immunol1992;90:242–249.

12. Druce HM, Spector SL, Fireman P, etal. Double-blind study of intranasalipratropium bromide in nonallergic pe-rennial rhinitis. Ann Allergy 1992;69:53–60.

13. Bronsky EA, Druce H, Findlay SR, etal. A clinical trial of ipratropium bro-mide nasal spray in patients with pe-rennial rhinitis. J Allergy Clin Immu-nol 1995;95:1117–1122.

14. Georgitis JW, Banov C, Boggs PB, etal. Ipratropium bromide nasal spray innonallergic rhinitis: efficacy, nasal cy-tological response and patient evalua-tion on quality of life. Clin Exp Al-lergy 1993;24:1049–1055.

15. Grossman J, Banov C, Boggs P, et al.Use of ipratropium bromide nasalspray in chronic treatment of nonaller-gic perennial rhinitis, alone and incombination with other perennial rhi-nitis medications. J Allergy Clin Im-munol 1995;95:1123–1127.

16. Raphael G, Hauptschein-Raphael M,Kaliner M. Gustatory rhinitis: a syn-drome of food-induced rhinorrhea. JAllergy Clin Immunol 1989;83:110–115.

17. Borum P, Olsen L, Winther B, MygindN. Ipratropium nasal spray: a newtreatment for rhinorrhea in the com-mon cold. Am Rev Respir Dis 1981;123:418–420.

18. Gaffey MJ, Hayden FG, Boyd JC,Gwaltney J. Ipratropium bromidetreatment of experimental rhinovirusinfection. Antimicrob Agents Che-mother 1988;32:1644–1647.

19. Dockhorn R, Grossman J, Posner M, etal. A double-blind, placebo-controlledstudy of the safety and efficacy of ipra-tropium bromide nasal spray versusplacebo in patients with the commoncold. J Allergy Clin Immunol 1992;90:1076–1082.

20. Diamond L, Dockhorn R, Grossman J,et al. A dose-response study of theefficacy and safety of ipratropium bro-mide nasal spray in the treatment ofthe common cold. J Allergy Clin Im-munol 1995;95:1139–1146.

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21. Hayden FG, Diamond L, Wood PB, etal. Effectiveness and safety of intrana-sal ipratropium bromide in commoncolds. Ann Intern Med 1996;125:89–97.

Oral Anti-Leukotriene Agents42. Although there is evidence that

oral anti-leukotriene agents maybe of value in treatment of aller-gic rhinitis, their role in therapyfor this condition needs to bedefined by further study.

Data suggest that some oral anti-leu-kotriene agents are beneficial in aller-gic rhinitis. In one study, montelukast10 mg QD (a cysteinyl leukotriene an-tagonist) provided significant improve-ment in symptoms of seasonal rhino-conjunctivitis. The potential role ofanti-leukotriene agents in treatment ofallergic rhinitis needs to be defined byfurther study.

Reference1. Malmstrom K, Meltzer E, Prenner B,et al. Effects of montelukast (a leuko-triene receptor antagonist), loratadine,montelukast � loratadine and placeboin seasonal allergic rhinitis and con-junctivitis. J Allergy Clin Immunol1998;101(1 pt 2):S97.

Allergen Immunotherapy43. Allergen immunotherapy may

be highly effective in controllingsymptoms of allergic rhinitis.Patients with allergic rhinitisshould be considered candidatesfor immunotherapy based onthe severity of their symptoms,failure of other treatment mo-dalities, presence of comorbidconditions, and of preventingworsening or possibly the devel-opment of comorbid conditions.Selection of the patient’s immu-notherapy extract should bebased on a correlation betweenthe presence of specific IgE an-tibodies (demonstrated by al-lergy skin testing or in vitro test-ing) and the patient’s history.(See parameters on immuno-therapy and on diagnostic test-ing).

Individuals are appropriate candidatesfor immunotherapy if their rhinitis isallergic in origin, due to allergens forwhich potent extracts are available,and the exposure to those allergens issignificant and unavoidable. Also, thesymptom complex should be severeenough to warrant the time, expenseand relative risk of immunotherapy.Other factors such as age, duration ofillness, progression of illness, concur-rent illnesses, concurrent medications,response to pharmacotherapy and pa-tient acceptance should be consideredby the physician in the decision to rec-ommend allergen immunotherapy.With rare exceptions, immunotherapyis inappropriate in preschool childrenand senior citizens. Immunotherapymay be appropriate for those individu-als with yearly recurrent seasonalsymptoms, perennial symptoms due toallergic factors and/or significant pro-gression of symptoms. Immunotherapyis generally unnecessary for the treat-ment of an individual with sensitivityto only a single seasonal allergen whenthe seasonal exposure to that allergenis relatively short. Severe pulmonaryand cardiovascular disease may be arelative contraindication, as is the con-current use of beta blockers. Initiationof immunotherapy during pregnancy isto be avoided but continuation of ef-fective maintenance immunotherapyduring pregnancy is advisable.A most important shortcoming is the

lack of available standardized aller-genic extracts for all clinically impor-tant allergens. Ideally, patients shouldbe treated with only potent standard-ized extracts, but this is not yet possi-ble. Since standardized potent extractsare not available for all clinically im-portant allergens, nonstandardized butpotent extracts are used commonly inclinical practice. In the future, once astandardized potent extract becomesavailable for any given allergen, itshould be utilized and the nonstandard-ized extract abandoned. It is unaccept-able to routinely treat patients with al-lergenic extracts that are not potent.It is common clinical practice to

treat patients with more than one aller-gen. Often these allergens are com-

bined into a single mixture for admin-istration. When this is done, it isimportant to insure that the compo-nents are compatible and that the po-tency of each individual allergen is notdiminished by the presence of the othercomponents because of a chemical in-teraction or excessive dilution. Onceimmunotherapy is begun, every at-tempt should be made to administer thehighest possible tolerated dose. Immu-notherapy is most effective when a“high dose” is used. It should be rec-ognized that while safe, immunother-apy is not totally without risk. Immu-notherapy should only be administeredby professionals familiar with the pro-cedure, in a setting where they are pre-pared to deal with anaphylaxis. Pa-tients should wait at least 20 minutes insuch a setting since most cases of ana-phylaxis from immunotherapy occur inthis time frame. Periodic assessmentsof efficacy should be made. In general,if after one year the patient has notimproved, then immunotherapy shouldbe discontinued. In those patients ben-efiting from immunotherapy, treatmentshould not be indefinite. Generallythree to five years of treatment will beappropriate for most patients. Therewill be individual variability.The above discussion pertains to the

use of immunotherapy for the treat-ment of allergic rhinitis only. Manypatients have both allergic rhinitis andasthma. The presence of concomitantasthma may be the determining factorin whether or not a specific patient is agood candidate for immunotherapy.Presence of a comorbid condition suchas asthma that may benefit from im-munotherapy may be an additional in-dication for considering immunother-apy. However, severe, unstable asthmamay be associated with increased riskfor reactions and possibly mortalityfrom immunotherapy. Consequently,asthma should be well controlled whenimmunotherapy doses are given.In summary, immunotherapy is a

unique and effective treatment modal-ity for allergic rhinitis. The increasingcosts associated with excellent drugtherapy for allergic rhinitis place thisform of therapy in a position of relative

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cost-effectiveness as well. The properselection of patients and treatment al-lergens is key to the appropriate andsuccessful use of this therapy. The on-going supervision of a trained allergistis necessary. Both physician and pa-tient should have a clear understandingof the therapeutic goals.

References1. Creticos PS, Lockey RF, ed. Im-munotherapy: a practical guide to cur-rent procedures. American Academyof Allergy and Immunology. 1994.

2. Executive Committee, American Aca-demy of Allergy and Immunology.Personnel and equipment to treat sys-temic reactions caused by immuno-therapy with allergic extracts (Positionstatement). J Allergy Clin Immunol1986;77:271.

3. Executive Committee, American Aca-demy of Allergy and Immunology.The waiting period after allergen skintesting and immunotherapy [PositionStatement]. J Allergy Clin Immunol1990;85:526–527.

4. Greenberger PA, ed. Immunotherapyof IgE–mediated disorders. ImmunolAllergy Clin North Am 1992;12(1):1–203.

5. Lockey RF, Benedict LM, TurkeltaubPC, Bukantz SC. Fatalities from im-munotherapy (IT) and skin testing(ST). J Allergy Clin Immunol 1987;79:660–677.

6. Norman PS, Van Metre TE Jr. Thesafety of allergenic immunotherapy. JAllergy Clin Immunol 1990;85:522–525.

7. Nelson HS. Immunotherapy for inhal-ant allergens. In: Middleton E Jr, ReedCE, Ellis EE, et al, eds. Allergy prin-ciples and practice, 5th edition. St.Louis: CV Mosby, 1998:1050–1062.

8. Dykewicz MS. Allergen immunother-apy for the patient with asthma. Immu-nol Allergy Clin North Am 1992;12:125–144.

Surgical Approaches forCo-Morbid Conditions44. Although there is no surgical

treatment for allergic rhinitisper se, surgery may be indicatedin the management of co-morbidconditions, eg, nasal obstructionfrom severe nasal septal devia-tion or recurrent refractory si-nusitis.

There is no surgical treatment for al-lergic rhinitis. Surgery, however, playsa role in the management of nasal ob-struction and in the management ofproblems that are sequelae of rhinitis.In these situations, surgical consulta-tion should be considered.Sixty percent of patients with peren-

nial allergic rhinitis have x-ray evi-dence of sinus disease, which may sig-nificantly contribute to the patientssymptoms. (See “Practice Parameteron Sinusitis”). Patients with coexistingsinusitis will often require antibioticsand some will require surgical inter-vention. Even though they seldom oc-cur, complications of sinusitis maylead to permanent loss of vision or belife threatening. Complications can beclassified as local, orbital and intracra-nial or combinations of these threetypes.Allergic rhinitis causes swelling of

the nasal mucosa. The effect of swell-ing on nasal function depends on thestructure of the nasal cavity. For exam-ple a person with allergic rhinitis andan anterior septal deviation will be-come more obstructed compared toone without the septal deviation. Struc-tural improvements in the airway mayalso permit greater access for topicalmedications. Whether cauterization,cryosurgery or laser reduction of tur-binates helps the patient with allergicrhinitis by inducing submucosal fibro-sis is unproven. Turbinate surgery inpatients without allergic rhinitis pro-vides mixed clinical results and haspoor correlation with rhinomanometricchanges.In summary, although there is no

specific surgical treatment for allergicrhinitis, surgery may be indicated forco-morbid conditions eg, severe nasalseptal deviation or recurrent refractorysinusitis. Some patients with rhinitisbenefit optimally from a dual approachwhich includes both medical manage-ment as well as surgery to improvenasal obstruction or aid in the manage-ment of concomitant sinusitis.

Reference1. Druce HM. Allergic and nonallergicrhinitis. In: Middleton E Jr, Reed CE,

Ellis EE, et al, eds. Allergy principlesand practice, 5th edition, St. Louis:Mosby-Year Book, 1998:1005–1016.

Important Considerations inManagement45. Management of rhinitis should

be individualized, based on thespectrum and severity of symp-toms, with consideration of costeffectiveness and utilization ofboth step-up and step-down ap-proaches. More severe rhinitismay require multiple therapeu-tic interventions, including: (1)use of multiple medications, (2)evaluation for possible compli-cations, and (3) instruction inand/or modifications of the med-ication or immunotherapy pro-gram. Similar to other chronicdiseases, appropriate follow-upof patients with allergic rhinitison a periodic basis is recom-mended.

Education of Patients andCaregivers46. Education of the patient and/or

the patient’s caregiver in the re-gard to the management of rhi-nitis is essential. Such educationmaximizes compliance and thepossibility of optimizing treat-ment outcomes.

After initiation of therapy, appropriatefollow-up for patients with rhinitis isessential. This optimizes the chancesthat a patient will benefit from thebroad array of therapeutic approachesavailable, and that possible complica-tions from rhinitis or its treatment areidentified and addressed. At these vis-its, education and compliance are crit-ical elements.Maximum therapeutic responses re-

quire patients who are compliant withrecommendations. Patient compliancewith physicians’ recommendations fortherapy is more likely in patients whounderstand their disease, the variousavailable treatment options, and thelikelihood of success of each possibletreatment. This demands that the pa-tient establishes a relationship of trustwith, and confidence in their physi-

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cian. It is important to educate both thepatient and relevant family membersregarding the nature of the disease andavailable treatments. This should in-clude general information regardingthe symptoms, causes and mechanismsof rhinitis. In addition, education aboutmeans of avoidance, immunotherapy,and drug therapy must be provided. Itis vital that patients understand the po-tential side effects of therapy, espe-cially drug side effects, in order toinsure that patients do not abruptly dis-continue beneficial therapy but rathercommunicate adverse events to theirphysician so they can deal with them ina manner best for the patient. It is alsoimportant to provide education to pa-tients about complications of rhinitisincluding sinusitis, and otitis media,and about comorbid conditions such asnasal polyps. They should be aware ofhow such complications are recog-nized and how they are treated. Pa-tients need to be aware of the potentialnegative impact of rhinitis on qualityof life and potential benefits of com-plying with therapeutic recommenda-tions. Patients must also have realisticexpectations for the results of therapyand should understand that completecures do not usually occur in treatmentof any chronic disease, including rhi-nitis.Compliance is enhanced when: (1) a

fewer number of daily doses is re-quired; (2) the patient schedules whendoses are to be taken and selects anappropriate reminder mechanism, suchas mealtimes, daily rituals, etc; (3)there is a good doctor-patient relation-ship with a high level of physiciantrust; (4) the patient has written in-structions to follow; (5) rhinitis medi-cation is taken with the same dosingfrequency as other medications; (6)there is a well designed reminder chartfor times of dosing interval.1–5

References1. Horwitz RI, Horwitz SM. Adherenceto treatment and health outcomes.Arch Intern Med 1993;153:1863–1868.

2. Botelho RI, Dudrach II R. Home as-sessment of adherence to long-term

medication in the elderly. J Fam Prac1992;35:61–65.

3. Weinstein AG. Clinical managementstrategies to maintain drug compliancein asthmatic children. Ann Allergy1995;74:305–310.

4. Cramer JA. Optimizing long-term pa-tient compliance. Neurology 1995;45:825–828.

5. Raynor DK, Booth TG, BlenkinsoppA. Effects of computer generated re-minder charts on patients compliancewith drug regimens. Br Med J 1993;306:1158–1161.

Importance of RhinitisManagement for ConcomitantAsthma, Sinusitis, and Otitis Media47. Appropriate management of

rhinitis may be an importantcomponent in effective manage-ment of co-existing or compli-cating respiratory conditions,such as asthma, sinusitis, orchronic otitis media. Data sug-gest that failure to reduce in-flammation in the upper airwaymay lead to suboptimal resultsin asthma treatment.

Rhinitis and asthma frequently coexistin patients, and there is evidence thatrhinitis is a risk factor for asthma.Mechanisms that connect upper andlower airway dysfunction are under in-vestigation but include a nasal bron-chial reflex, mouth breathing causedby nasal obstruction, and pulmonaryaspiration of nasal contents.1 In a studyof patients with a history of allergicrhinitis symptoms that preceded or co-incided with exacerbations of asthma,controlled allergen challenge to the na-sal airways without delivery to thelungs significantly increased bronchialreactivity, suggesting that the nasal al-lergic response alters bronchial respon-siveness.2 Nasal obstruction has beenshown to lead to increased pulmonaryfunction decrements caused by exer-cise induced bronchospasm, presum-ably caused by mouth breathing thatfails to warm and humidify air as effi-ciently as does nasal breathing.3There is clinical evidence that treat-

ment of rhinitis can improve the status ofco-existing asthma. Nasal beclometha-

sone has been shown to prevent a sea-sonal increase in bronchial hyperrespon-siveness in patients with allergic rhinitisand asthma.4 Although systemic absorp-tion of nasal corticosteroids is minimal,the unlikely possibility has been raisedthat systemic absorption of corticoste-roids administered intranasally may havea direct effect on the lungs. However, ina large placebo-controlled study of pa-tients with asthma and allergic rhinitis,nasal cromolyn (an agent that has negli-gible systemic absorption) as well as in-tranasal steroids cause a significant re-duction in asthma symptoms.5 Althoughvery high doses of some antihistamineshave been required to achieve a modestbronchodilator effect in some studies,conventional doses of cetirizine, lorata-dine and oral decongestants have beenreported to improve asthma symptomsand pulmonary function in patients withconcomitant allergic rhinitis in placebocontrolled trials.6,7 Consequently, opti-mal control of asthma may require effec-tive control of concomitant rhinitis.

References1. Corren J. Allergic rhinitis and asthma:how important is the link? J AllergyClin Immunol 1997;99:S781–S786.

2. Corren J, Adinoff, Irvin C. Changes inbronchial responsiveness followingnasal provocation with allergen. J Al-lergy Clin Immunol 1992;89:611–618.

3. Shturman-Ellstein R, Zeballos RJ,Buckley JM, Souhrada JF. The bene-ficial effect on nasal breathing on ex-ercise-induced bronchoconstriction.Am Rev Respir Dis 1978;118:65–73.

4. Watson WTA, Becker AB, SimonsFER. Treatment of allergic rhinitiswith intranasal corticosteroids in pa-tients with mild asthma: effect onlower airway hyperresponsiveness. JAllergy Clin Immunol 1993;91:97–101.

5. Welsh PW, Stricker WE, Chu-Pin C, etal. Efficacy of beclomethasone nasalsolution, flunisolide and cromolyn inrelieving symptoms of ragweed al-lergy. Mayo Clin Proc 1987;62:125–134.

6. Grant JA, Nicodemus CF, Findlay SR,et al. Cetirizine in patients with sea-sonal rhinitis and concomitant asthma:prospective, randomized, placebo-controlled trial. J Allergy Clin Immu-nol 1995;95:923–932.

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7. Corren J, Harris A, Aaronson D, et al.Efficacy and safety of loratadine pluspseudoephedrine in patients with sea-sonal allergic rhinitis and mild asthma.J Allergy Clin Immunol 1997;100:781–788.

Special Considerations in Children,the Elderly, Pregnancy, Athletes,and Patients with RhinitisMedicamentosa48. Special diagnostic and therapeu-

tic considerations are warrantedin selected patient subsets, in-cluding in children, the elderly,pregnancy women, athletes, andin those with rhinitis medica-mentosa.

Rhinitis in ChildrenDisorders and prevalence. Rhinitis inchildren shares most of the pathophys-iologic, clinical, diagnostic, and thera-peutic characteristics observed inadults; however, the existence of somedifferences justify discussion.1,2Viral-induced rhinitis, which may

occur in the neonatal period, becomesmore common later in infancy withincreasing exposure of the infant toother children, averaging about 6 epi-sodes per year in children between 2 to6 years of age. The progression of viralto secondary bacterial rhinitis will pro-long infection and symptoms from sev-eral days to weeks unless shortened byappropriate antibiotics. Staphylococcalaureus infection secondary to other pri-mary rhinitis disorders, including aller-gic rhinitis, may manifest as impetigoof the anterior nares with characteristiccrusting and irritation. Secondary bac-terial rhinitis occurs with or withoutsinusitis in children with antibody,complement, and leukocyte deficiencydisorders, hyper-IgE syndrome, struc-tural defects (cleft palate, osteopetro-sis) and cystic fibrosis, and may alsooccur in normal children. Sinusitis iscommon in perennial allergic rhinitisin childhood, occurring in half of chil-dren referred to specialists. Purulentrhinorrhea, especially if unilateral, per-sistent, bloody, or fetorous may indi-cate an intranasal foreign body.3Chronic bacterial infectious rhinitis

(distinct from coexisting sinusitis and

pharyngitis) has been poorly docu-mented, but probably does occur inchildren in unusual cases. Characteris-tics include nasal obstruction and pu-rulent anterior and post-nasal dis-charge with erythematous turbinatesand neutrophilic and bacterial infiltra-tion of the nares. Primary bacterial rhi-nitis, though uncommon, may occur inthe newborn due to congenital syphiliswith characteristic rhinorrhea followedby ulceration. Localized bacterial rhi-nitis may also occur in during �-hemo-lytic Streptococcal infections, particu-larly scarlet fever (50% prevalence),diphtheria, yaws, gonorrhea, tubercu-losis, typhus, and scleroma.3Nasal symptoms, particularly con-

gestion and rhinorrhea, are common ininfants and children with pharyngona-sal reflux resulting from prematurity,neuromuscular disease, dysautonomia,velopharyngeal incoordination, or cleftpalate. Those affected experience fre-quent choking, apneic spells, recurrentpneumonia (due to concomitant gastro-esophageal reflux and/or tracheal aspi-ration), and aspiration of formula lead-ing to secondary chemical/infectiousrhinitis. Increasing age and thickenedfeedings improve the pharyngonasalreflux.3A critical period appears to exist

early in infancy in which the geneti-cally programmed atopic-prone orhigh-risk infant is at greater risk tobecome sensitized when exposed toboth food and aeroallergens. Food sen-sitization in infancy manifests as foodallergy, atopic dermatitis, urticaria/an-gioedema, and anaphylaxis which typ-ically develops in infancy and earlychildhood. Sneezing, nasal congestion,rhinorrhea, and ocular symptoms occurin about 30% of children during a foodallergic reaction. These upper respira-tory symptoms rarely occur in the ab-sence of gastrointestinal, dermatologic,or systemic manifestations. Althoughupper respiratory symptoms in infancyand early childhood are frequently at-tributed to foods, many studies haveconsistently failed to demonstratefoods as a trigger for chronic rhinitis.4On the other hand, aeroallergen sensi-tization which may begin in infancy

manifests typically in allergic rhinitisand atopic asthma beginning after thetoddler years.5 The natural history ofatopic disease characteristically beginswith atopic dermatitis, food allergy,and food sensitization in infancy andearly childhood followed by allergicrhinitis, atopic asthma, and aeroaller-gen sensitization after early childhood.In the general population, up to 10% ofchildren and about 20% of adolescentsmanifest allergic rhinitis. Studies sug-gest that allergic rhinitis tends not toremit during childhood.6 Atopic-proneinfants and young children comparedto their non-risk cohorts appear to ex-perience more otitis media and upperrespiratory infections which probablyderives from subtle immunologic dif-ferences rather than specific-IgEcauses, since sensitization is often notpresent yet. The child and adolescentwith allergic rhinitis manifests symp-toms indistinguishable from that seenin the adult, except for a greater fre-quency of the allergic salute and eyerubbing.Non-allergic, non-infectious rhinitis

with eosinophils (NARES) occurs ex-tremely infrequently in childhood andprobably accounts for less than 2% ofchildren with nasal eosinophilia. Anti-histamines/decongestants may provideadequate relief in some, but others mayrequire topical or oral corticosteroidsto control symptoms.7Nasal obstruction from structural

defects or adenoidal hypertrophy areoften seen in children with rhinitis. Na-sal polyps are rare in childhood, usu-ally occurring only in adults. Condi-tions associated with nasal polyps inchildhood include cystic fibrosis, cili-ary dyskinesia, chronic infections asseen in immunologic deficiency states,and occasionally allergic rhinitis,while aspirin intolerance may be re-sponsible in adolescents.Diagnosis in children. The evalua-

tion of children with chronic rhinitisdemands a systematic approach. Accu-rate diagnosis rests with careful histor-ical data collection and physical exam-ination supplemented by appropriatelaboratory studies. The history shouldinclude information pertaining to (1)

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the onset of symptoms (infancy vschildhood, post viral upper respiratoryinfection, trauma, or acquisition of anew pet or home), (2) frequency (daily,seasonal, episodic, or unremitting), du-ration (weeks, months, or years), se-verity (annoying, disabling, interferingwith sleep, or leading to emotional dis-turbance), symptoms (sneezing, ante-rior or posterior rhinorrhea, obstruc-tion, or anosmia), character (watery,mucoid, or purulent) and color (clear,yellow, green) of the secretions, pre-cipitating factors (allergens, irritants,climatic conditions), associated factors(atopic disorders, drugs, infections),and previous response to medication/treatment (efficacy and side effects).8,9The child with allergic rhinitis oftenmanifests characteristic facial featuresand mannerisms including the “allergicsalute,” the allergic crease, Dennie-Morgan’s lines (accentuated lines orfolds below the margin of the inferioreyelid), and infraorbital dark circles or“allergic shiners.”The physical exam of children with

rhinitis complaints should include, in ad-dition to the nasal exam described be-low, the ears (evaluating for infection,fluid, and eustachian tube dysfunction,with additional use of a pneumatic oto-scope or impedance tympanometer), theeyes (visualizing the palpebral infraor-bital area for Dennie-Morgan’s lines, theconjunctiva for infection, and the lids forblepharitis), the nasal pharynx for tonsil-lar and adenoid hypertrophy, and thechest for asthma or bronchitis. Class IImalocclusions due to chronic mouthbreathing may also be present. The nasalexam should describe the position of theseptum, appearance of the turbinates,quality and quantity of secretions, andthe presence of any abnormal growths.Should obstructing inferior turbinates bepresent in older children, topical vaso-constriction can be instilled to permitbetter visualization. Rhinopharyngos-copy may be necessary to evaluate struc-tural defects in the child with recalcitrantrhinitis or suspected abnormality.The laboratory work-up for children

with rhinitis is similar to adults andincludes the determination of specific-IgE by skin test or sensitive in vitro

testing when directed by history andsymptoms of allergic rhinitis. Othertests may also be indicated on an indi-vidual basis, including: (1) nasal cytol-ogy; and (2) specific diagnostic testssuch as quantitative immunoglobulins,complement studies, leukocyte assays,ciliary function and morphology, andsweat test when disorders such as im-munodeficiency, ciliary dyskinesia,and cystic fibrosis are suspected. As inadults, CT scans of the sinuses aremore sensitive than standard radio-graphs for detecting sinus disease inchildren. Nonetheless, a single Water’sview may be helpful in diagnosing si-nusitis in children, with mucosal thick-ening �6 mm, opacification, or airfluid levels strongly suggestive of in-fection. A lateral nasal pharynx x-raymay help to exclude adenoid hypertro-phy in those children with clinical his-tory and physical exam consistent withmouth breathing, snoring, sleep apneicepisodes, and nasal obstruction.Techniques for skin testing are sim-

ilar in children as for adults, exceptthat reactions may be smaller in in-fancy and early childhood due to lowerlevels of specific-IgE and reduced skinreactivity particularly in infants. Amulti-head puncture device may beuseful in uncooperative infants andyoung children. Topically-appliedEMLA� cream (lidocaine, prilocaine)has been advanced as a possible meansof reducing the discomfort associatedwith skin testing in children. Total se-rum IgE levels are not sensitiveenough (only about 50%) for routineclinical diagnosis of allergic rhinitis.The cellular pattern derived from the

nasal smear or tissue may help to dif-ferentiate eosinophilic from non-eosi-nophilic conditions. Eosinophil pre-dominance suggests allergic rhinitis,aspirin sensitivity, or NARES. The de-gree of nasal eosinophilia is related tothe severity of the condition. Baso-philic cells, either basophilic leuko-cytes or mast cells, are common inpediatric allergic rhinitis and NARES.Levels of nasal eosinophils and baso-philic cells correlate highly with eachother from ages 4 months to 7 years.Nasal eosinophils in nasal scrapings

possess a sensitivity, specificity, andpositive predictive value of about 90%for aeroallergen sensitization in high-risk children.9 (Also see SummaryStatement #28)Nasal allergen challenge in children

is reserved for research purposes.Therapeutic approach in children.

The therapeutic approach to rhinitis inchildren is based on principles used inadults, generally differing only in spe-cifics and dosages. Understanding thechild’s suffering and discomfort repre-sents the cornerstone of therapy. Theclinician must function as an advocatefor the infant and child who may beunable to express the extent of theirrhinitis problem.Allergen avoidance as described in

an earlier section represents the pri-mary treatment of allergic rhinitis andis especially relevant in early infancyand childhood in which allergen sensi-tization first occurs. Early effective al-lergen avoidance measures may func-tion during secondary prevention todown-regulate IgE production and turnoff allergic sensitization, if institutedearly enough in life. Controlled studiesare proceeding to determine whetherthe early treatment of the atopic childwith allergen avoidance, anti-inflam-matory allergic medication, or immu-notherapy will modify the natural his-tory of allergic rhinitis and asthma.Regurgitant rhinitis in infants should

be treated with thickened and uprightfeedings, avoiding lying with a bottle,discontinuing formula feeding by 1year, and prone resting at 30° follow-ing feeding.Nasal saline washes may be toler-

ated by the older child and adolescent.For the younger child and infant, com-mercial saline sprays followed by bulbsyringe suctioning of the nares may behelpful in reducing the tenacity of se-cretions often seen in bacterial rhinitis.Specific intervention for infectious

rhinitis of childhood include appropri-ate antibiotics in childhood dosages forproven bacterial rhinitis/sinusitis (Ta-ble 5).Surgery may be indicated for ade-

noid hypertrophy, nasal webs, pharma-cologically resistant nasal polyps,

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medically unresponsive sinusitis, andother structural defects. Correction ofseptal deviation should be delayed un-til late adolescent after cessation ofnasal growth. Multidimensional ther-apy is necessary for immune defi-ciency disorders, cystic fibrosis, andciliary dyskinesia.Pharmacotherapy is usually required

in the management of allergic rhinitiswhen supportive and avoidance mea-sures are inadequate in controllingsymptoms.Oral antihistamines (Table 6) or na-

sal cromolyn remain the first-line phar-macologic treatments of childhood al-lergic rhinitis.The second generation antihista-

mines astemizole, fexofenadine, andloratadine are labelled as non-sedating.The second-generation antihistaminecetririzine is significantly less sedatingthan its parent drug hydroxyzine. Notall of these second generation antihis-tamines have received approval by theUS Food and Drug Administration(FDA) for use in young children.These agents should provide a greaterbenefit risk ratio than the first genera-tion antihistamines, but generally donot provide any greater clinical effec-tiveness at ameliorating rhinitis symp-toms.Cromolyn nasal spray at dosages of

1 to 2 sprays TID to QID is effective inpreventing allergic rhinitis and may beused in very young children. It is welltolerated but the frequency of neededadministration may reduce its overallcompliance and effectiveness.Topical nasal corticosteroids in chil-

dren as in adults represent the mosteffective pharmacologic therapy of al-lergic rhinitis with the capacity to con-trol sneezing, pruritus, rhinorrhea, andcongestion but not ocular symptoms.Extensive clinical and toxicologicstudies have generally demonstratedthat nasal corticosteroids have an ex-cellent benefit/risk profile in long-termusage in children. In 1998, the FDApresented data that some nasal cortico-steroids may have a temporary adverseeffect on growth in children, but it isuncertain whether there may be a longterm effect on ultimate attained height.

Table 5. Antibiotics and Pediatric Dosages in the Treatment of Bacterial Rhinosinusitis

Antibiotic (generic name) Usual Pediatric Dosage

First line therapyAmoxicillin 20–50 mg/kg/24 hr divided TIDTrimethoprim(TMP)-sulfamethoxazole Dosage based on TMP component: 10

mg/kg/24 hr divided BIDPenicillin and sulfisoxazole in combinationbut each prescribed separately

Penicillin (25–50 mg/kg/24 hr dividedQID and sulfisoxazole (children �2months of age � 150 mg/kg/24 hrdivided QID)

Second line therapyErythromycin ethylsuccinate 50 mg/kg/24hr) and acetyl sulfisoxazole (150 mg/kg/24 hr)

Erythromycin (50 mg/kg/24 hr) andsulfisoxazole (150 mg/kg/24 hr)divided QID

Amoxicillin-clavulanic acid Children �40 kg: 20–40 mg/kg/24 hrdivided TID

Cefaclor 40 mg/kg/24 hr divided TIDCefixime 8 mg/kg/24 hr divided QD or BIDClarithromycin 15 mg/kg/24 hr divided BID

Table 6. Representative Oral Antihistamines and Their Pediatric Dosages

H1-antihistamine Usual Pediatric Dosage

First generationBrompheniramine 0.5 mg/kg/day in 4 divided doses (max. 6 mg/

24 hr for ages 2–6 yr; 12 mg/24 hr for ages6–12 yr)

Carbinoxamine 0.8 mg/kg/24 hr in 4 divided dosesChlorcyclizine 1.5 mg/kg/24 hr in 2–3 divided dosesChlorpheniramine 0.35 mg/kg/24 hr in 4 divided doses; over 7

years may use up to 8 mg q 12 hr timerelease form

Clemastine Children 6–12 yr: 0.5–1 mg BIDCyproheptadine 2–6 yr: 2 mg q 8–12 hr (max. 12 mg/24 hr);

7–14 yr: 4 mg q 8–12 hr (max. 16 mg/24 hr)Diphenhydramine 5 mg/kg/24 hr in 4 divided dosesHydroxyzine 2 mg/kg/24 hr in 3 divided doses or at

bedtime if toleratedPromethazine 0.5 mg/kg/dose q 6–8 hrTripelennamine 5 mg/kg/24 hr in 4 divided dosesTriprolidine hydrochloride �6 yrs: 0.3–0.6 mg q 6–8 hr

�6 yrs: 1.25 mg q 6–8 hrSecond generationAstemizole (Hismanal�) 6–12 yr: 5 mg/24 hr in single dose*Cetirizine (Zyrtec�) (tablet and syrup) �6 yr: 5–10 mg PO QD

2–5 yr: 2.5–5 mg in 24 hr (QD or BID)Fexofenadine (Allegra�) �12 yr: 60 mg PO BIDLoratadine (Claritin�) (tablet, syrup, �6 yr: 10 mg PO QDRediTab™) 2–6 yr: 5 mg PO QD for �30 kg body weight*

Terfenadine† (Seldane�) 3–6 yr: 15 mg BID†7–12 yr: 30–60 mg BID†

* As of August, 1998, not approved in the US for this age group. Information on pediatricdosages obtained from published medical literature or information supplied by pharmaceuticalmanufacturers about pediatric doses used in other countries.† Withdrawn from US market in 1998.

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It is also unclear whether all nasal cor-ticosteroids may have such an effect.Because of this concern, nasal cortico-steroids should be used in children atthe lowest possible effective dose, theFDA recommends that height be mon-itored routinely, and other therapeuticapproaches (environmental control,non-steroid pharmacologic agents, andif appropriate, allergen immunother-apy) should be used in conjunctionwith nasal corticosteroids so that nasalcorticosteroid doses may be mini-mized.Systemic corticosteroids are rarely

needed for uncomplicated rhinitis inchildhood. Rarely they may be neces-sary to control nasal polyps when top-ical corticosteroids prove ineffective.Topical vasoconstrictors are dangerousin infancy, due to the narrow marginbetween therapeutic and toxic dosewhich increases the risk for cardiovas-cular and CNS effects. Oral deconges-tants also should be used cautiouslyduring childhood owing to their stim-ulatory effects. Indications for institut-ing immunotherapy (noted in an earliersection) should be considered.Ipratropium nasal spray (Atrovent

0.03%) is approved for ages �6 yearsand may reduce rhinorrhea from aller-gic and non-allergic rhinitis, but has noeffect on other nasal symptoms (sum-mary statement #41).The treatment of the child with al-

lergic rhinitis should emphasize pre-ventive, non-pharmacologic measureswhenever possible before institutingmedication to control the disorder.Rhinitis in the elderly. Allergic rhi-

nitis is an uncommon cause of peren-nial rhinitis in individuals over 65years of age.10 More commonly, rhini-tis in the elderly is due to cholinergichyperreactivity (associated with pro-fuse watery rhinorrhea which may beaggravated after eating, “gustatory rhi-nitis”), alpha adrenergic hyperactivity(congestion associated with antihyper-tensive drug therapy) or sinusitis. Thewatery rhinorrhea syndrome frequentlyresponds to intranasal ipratropium.11Discontinuation of an antihypertensivemedication responsible for nasal con-gestion should be considered but maynot always be feasible. Although alpha

adrenergic agonists must be used withcaution in hypertensive patients, recentdata suggests that pseudoephedrinedoes not elevate the blood pressure inpatients with well controlled hyperten-sion.12 Other side effects from decon-gestants that are of concern in the el-derly include urinary retention inpatients with prostatic hypertrophy andcardiac and CNS stimulation.13In the elderly, certain adverse ef-

fects of medication for the treatment ofallergic rhinitis may be more commonor be of greater concern. The anticho-linergic effects of the first generationantihistamines may cause bladder dis-turbances or problems with visual ac-commodation, and sedation may alsobe bothersome. Second generation an-tihistamines (eg, fexofenadine and lo-ratadine), which do not cause signifi-cant anticholinergic effects, sedation,performance impairment or adversecardiac effects14 are better choices thansedating antihistamines for treatmentof the elderly. Elderly patients mayalso be more likely to be treated withbeta blockers, a relative contraindica-tion for immunotherapy.15Pregnancy. The most common

causes of nasal symptoms during preg-nancy are allergic rhinitis, sinusitis,rhinitis medicamentosa, and vasomo-tor rhinitis.16 Sinusitis has been re-ported to be six times more common inpregnant than non-pregnant women.17Preexisting allergic rhinitis mayworsen, improve or stay the same dur-ing pregnancy.16 Progesterone and es-trogen-induced glandular secretion18 aswell as nasal vascular pooling due tovasodilation and increased blood vol-ume may account for worsening aller-gic rhinitis, increased sinusitis and va-somotor rhinitis during pregnancy. Incontrast, increased serum free cortisolduring pregnancy could improve aller-gic rhinitis.Chlorpheniramine and tripelen-

namine have been the preferred anti-histamines for use during pregnancy,and pseudoephedrine is the preferreddecongestant.19 Case control studieshave linked first trimester use of oraldecongestants with infant gastroschisis(a defect in the abdominal wall).21,22Therefore, oral decongestants should

probably be avoided during the firsttrimester, if possible. For allergic rhi-nitis, nasal cromolyn is useful and maybe considered first in view of its topi-cal application and reassuring gesta-tional human and animal data.19 Intra-nasal beclomethasone may be used ifnasal cromolyn does not provide ade-quate control of daily symptoms, or asan alternative to oral therapy, althoughthere is no published experience on theuse of intranasal beclomethasone dur-ing pregnancy. Intranasal beclometha-sone may also be used to allow discon-tinuation of topical decongestants inpatients with rhinitis medicamentosa.If nasal beclomethasone is used, itshould be tapered to the lowest effec-tive dose. Vasomotor rhinitis often isadequately controlled by intranasal sa-line instillation, exercise appropriatefor pregnancy, and pseudoephedrine.16Appropriate antibiotics for use duringpregnancy for the treatment of sinusitisinclude amoxicillin with or withoutclavulanate, erythromycin, and cepha-losporins.19Immunotherapy for allergic rhinitis

may be continued during pregnancy, ifit is providing benefit without causingsystemic reactions.19,20 Doses shouldnot be increased and should be ad-justed in order to minimize the chanceof inducing a systemic reaction, whichcould be harmful to both mother andfetus. Benefit/risk considerations donot generally favor starting immuno-therapy during pregnancy.19Athletes. Physical exercise acts as a

potent vasoconstrictor, gradually de-creasing nasal resistance in proportionto increasing effort and pulse, owing torelease of noradrenaline. In most ath-letes, physical exercise will increasenasal due to vasodilatation, with theeffect frequently unobserved by the in-dividual. In normal exercise situations,no rebound occurs and the vasoconstric-tion persists for about one hour. Athletes,especially long-distance runners, cy-clists, or triathletes, may experience arebound nasal congestion after the initialimprovement in nasal patency whichmay affect peak performance.Prescription of medication for the

competitive athlete should be based on

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two important principles: (1) no med-ication given to the athlete should beon any list of doping products andshould be approved for use by the USOlympic Committee (USOC) and Inter-national Olympic committee (IOC) and(2) no medication should adversely af-fect the athlete’s performance.The USOC generally observes the

International Olympic Committee listof banned and allowed drugs. Before acompetitive athlete takes any medica-tion prior to competition, it should bedetermined if it is allowed (Table 7).The USOC has a toll-free hotline (1-800-233-0393) to answer any ques-tions a physician or athlete may have.Athletes and their physicians should beaware that all decongestants arebanned with the exception of topical(nasal or ophthalmological) phenyl-ephrine and imidazole preparations (ie,oxymetazoline and tetrahydrozoline).Antihistamines are allowed by the

USOC but may be banned by the in-ternational federation of certain sports.Substances allowed by the USOC forcompetitive athletes with asthma in-clude: (1) inhaled beta-2-agonists, butonly albuterol and terbutaline; (2) in-haled corticosteroids; and (3) theophyl-lines. Other allowed medications include(1) local anesthetics, (2) NSAIDs, (3)antacids, (4) antibiotics, antifungicidesand antiviricides, (5) contraceptives, (6)ulcer medications, (7) anti-diarrheals, (8)guaifenesin expectorants, (9) codeine/di-hydrocodeine/ and dextromethorphanantitussives, (10) laxatives, (11) anti-di-abetics, and (12) certain pain and fevermedications. Medications which are al-lowed by the USOC but may be bannedby International Federations of certainsports include: (1) anti-anxiolytics, (2)antinauseants, (3) beta-blockers, and (4)sedatives/sleep aids. All physicians treat-ing potential competitive athletes shouldhave the USOC booklet of allowed andbanned substances available for quickreference.An adverse influence on physical

performance may occur in the athletewith rhinitis treated with (1) first gen-eration antihistamines which may haveundesirable sedative and anticholin-ergic effects, or (2) immunotherapy, in

which local discomfort of an extremitymay rarely persist for several days af-ter a subcutaneous injection.After consideration of these issues,

the optimal therapy for the athlete withsymptomatic allergic rhinitis consistsof aggressive allergen avoidance, asecond generation H1-antihistamineand a topical nasal corticosteroid. In-tranasal cromolyn may be useful 30minutes prior to commencing a com-petition likely to be associated withhigh allergen exposure. Immunother-apy may provide help for those athleteswith seasonal allergic rhinitis not re-sponding adequately to avoidance andmedication.Rhinitis medicamentosa. Rhinitis

medicamentosa is a syndrome of re-bound nasal congestion which followsthe overuse of intranasal alpha-adren-ergic decongestants or cocaine and oc-casionally even systemic deconges-tants.23,24 Rhinitis medicamentosa maycomplicate a viral upper respiratory in-fection or be superimposed on anycause of chronic rhinitis. A presump-tive diagnosis may be made in a patient

with prominent nasal congestion whohas used intranasal decongestants orcocaine on a daily basis for more thanone week. Examination of the noseusually reveals a congested and red-dened mucous membrane, but a pale,edematous mucosa may occasionallybe observed. The mucosa in patientswith rhinitis medicamentosa is charac-teristically unresponsive to further ap-plication of decongestants.24Patients with rhinitis medicamen-

tosa should receive intranasal cortico-steroids and be advised to discontinuethe topical decongestants as soon asclinical symptoms abate. Occasionally,a short course of oral corticosteroids(eg, prednisone 30 mg daily for 5 to 7days) may be necessary in adults toallow for discontinuation of the topicaldecongestants. Underlying chronic rhi-nitis in patients with superimposed rhi-nitis medicamentosa must be appropri-ately evaluated and treated.25

References1. Siegel SC. Rhinitis in children. In:Mygind N, Naclerio RM, eds. Allergic

Table 7. Rhinitis Medications/Substances Banned by the USOC and Considered Doping

Class of substance Agents

Vasoconstrictors Desoxyephredrine (oral or nasal)These agents may be found in many Ephedrine (oral or nasal)single or combination agent OTC Ma Huang (herbal ephedrine)and prescriptions used for allergy Phenylephrine (oral)URIs, and cough, Phenylpropanolamine (oral or nasal)

Propylhexedrine (oral or nasal)Pseudoephedrine (oral or nasal)

Stimulants Equivalent to 6–8 cups of coffee, 4 vivarintablets, or 8 No Doz tablets 2–3 hr beforetesting

Caffeine in any form leading to urinarylevels of �12 mcg/mL

Corticosteroids The use of corticosteroids is banned exceptfor topical use (ear, eye, and skin),inhalation therapy (allergic rhinitis andasthma), and local or intra-articularinjections. Physicians prescribing topical,inhalational, and intraarticularcorticosteroids must send writtennotification of the indication to the USOC(USOC Drug Control Program, MedicalNotifications, One Olympic Plaza,Colorado Springs, CO 80909). Takingcorticosteroids (prednisoine,methylprednisolone, cortisone) orally orintravenously is banned.

Narcotic analgesics All narcotics except codeine anddihydrocodone

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and non-allergic rhinitis. Clinical as-pects. Copenhagen: Munksgaard,1993:174–183.

2. Van Cauwenberge P, ed. Immunologicand allergological items in pediatricotorhinolaryngology. Amsterdam: Ku-gler Publications; 1991.

3. Zeiger RS. Allergic and nonallergicrhinitis: classification and pathogene-sis. Part II. Non-allergic rhinitis. Am JRhinology 1989;3:113–139.

4. Bock SA, Sampson HA. Food hyper-sensitivity in infancy. In: Schatz M,Zeiger RS, ed. Asthma and allergy inpregnancy and early infancy, NewYork: Marcel Dekker, Inc, 1993;463–502.

5. Bjorksten BB, Kjellman NIM, ZeigerRS. Development and prevention ofallergic disease in childhood. In:Middleton E Jr, Reed CE, Ellis EE, etal, eds. Allergy principles and practice,5th edition. St. Louis: Mosby-YearBook, 1998;816–837.

6. Croner S, Kjellman NIM. Develop-ment of atopic disease in relation tofamily history and cord blood IgE lev-els. Eleven-year follow-up in 1654children. Pediatr Allergy Immunol1990;1:14–20.

7. Rupp GH, Friedman RA. Eosinophilicnon allergic rhinitis in children. Pedi-atrics 1982;70:437–439.

8. Meltzer EO, Zeiger RS, Schatz M,Jalowayski AA. Chronic rhinitis in in-fants and children: etiologic, diagnos-tic, and therapeutic considerations. Pe-diatr Clin North Am 1983;30:847–871.

9. Siegel CJ, Dockson RJ. An evaluationof childhood rhinorrhea. Ann Allergy1982;48:9.

10. Lund VJ, Aaronson D, Bousquet J, andThe International Rhinitis Manage-ment Working Group. Internationalconsensus report on the diagnosis andmanagement of rhinitis. Allergy 1994;49(Suppl 19):1–34.

11. Mygind N, Borum P. Anticholinergictreatment of watery rhinorrhea. Am JRhinology 1990;4:1–5.

12. Coates ML, Rembold CM, Farr BM.Does pseudoephedrine increase bloodpressure in patients with controlled hy-pertension. J Family Prac 1995;45:22–26.

13. Marin L, Anggard A. Vasoconstric-tors. In: Mygind N, Naclerio RM, eds.

Allergic and non-allergic rhinitis. Clin-ical Aspects. Copenhagen: Munks-gaard, 1993:95–100.

14. Simons FER. The therapeutic index ofnewer H, receptor antagonists. ClinExp Allergy 1994;24:707–723.

15. Van Metre TE, Adkinson NF. Immu-notherapy for aeroallergen disease. In:Middleton E Jr, Reed CE, Ellis EE, etal, eds. Allergy principles and practice,4th edition, St. Louis: CV Mosby,1993;1327–1344.

16. Schatz M, Zeiger RS. Diagnosis andmanagement of rhinitis during preg-nancy. Allergy Proc 1988;9:545–554.

17. Sorri M, Bortikanen-Sorri AI, Karja J.Rhinitis during pregnancy. Rhinology1980;18:83–86.

18. Toppozada H, Michaels L, ToppozadaM, et al. The human respiratory nasalmucosa in pregnancy. J Laryngol Otol1982;96:613–626.

19. National Asthma Education ProgramReport of the Working Group onAsthma and Pregnancy. Managementof Asthma During Pregnancy. NIHPublication No. 93-3279, September,1993.

20. Metzger WJ, Turner E, Patterson R.The safety of immunotherapy duringpregnancy. J Allergy Clin Immunol1978;61:268–271.

21. Werler MM, Mitchell AA, Shapiro S.First trimester maternal medication usein relation to gastroschisis. Teratology1992;45:361–367.

22. Torfs CP, Katz EA, Bateson TF, et al.Maternal medications and environ-mental exposures as risk factors forgastroschisis. Teratology 1996;54:84–92.

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25. Fischer TJ, Entis GN, Winant Jr JG,Bernstein IL. Basic principles of ther-apy for allergic disease. In: Lawlor JrGJ, Fischer TJ, eds. Manual of allergyand immunology: diagnosis and ther-apy, 2nd edition. Boston, MA: Little,Brown, and Company, 1988:46–95.

Consultation with an Allergist-Immunologist49. There are a variety of circum-

stances in which the special exper-

tise and training of an allergist-immunologist may offer benefitsto a patient with rhinitis. Reasonsfor consultation for rhinitis withan allergist/immunologist include,but are not limited to:

1. Clarification and identification ofallergic or other triggers for thepatient’s rhinitis condition.

2. When management of rhinitis isunsatisfactory due to inadequateefficacy or adverse reactions fromtreatment.

3. When allergen immunotherapymay be a consideration.

4. When there is impairment of pa-tient’s performance because ofrhinitis symptom manifestationsor medication side effects, eg, pa-tients involved in the transporta-tion industry, athletes, students,etc.

5. When the patient’s quality of lifeis significantly affected (eg, pa-tient comfort and well-being, sleepdisturbance, small, taste).

6. When complications of rhinitis de-velop, eg, sinusitis, otitis media,orofacial deformities.

7. In the presence of co-morbid con-ditions such as recurrent orchronic sinusitis, asthma or lowerairway disease, otitis media, nasalpolyps.

8. When patients require systemiccorticosteroids to control theirsymptoms.

9. When the duration of rhinitissymptoms is greater than 3months.

10. When there is a significant costfrom use of multiple medications.

11. When education in allergen avoid-ance techniques is needed.

Request for reprints should be addressed to:Joint Council on Allergy, Asthma, &Immunology

50 N Brockway St, Ste 3-3Palatine, IL 60067

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