Rhinitis 2020 Practice Parameter Update PDF

Practice parameter Rhinitis 2020: A practice parameter update Mark S. Dykewicz, MD,a Dana V. Wallace, MD,b David J. Amrol, MD,c Fuad M. Baroody, MD,d Jonathan A. Bernstein, MD,e Timothy J. Craig, DO,f Chitra Dinakar, MD,g Anne K. Ellis, MD,h Ira Finegold, MD,i David B. K. Golden, MD,j Matthew J. Gr...

Practice parameter Rhinitis 2020: A practice parameter update Mark S. Dykewicz, MD,a Dana V. Wallace, MD,b David J. Amrol, MD,c Fuad M. Baroody, MD,d Jonathan A. Bernstein, MD,e Timothy J. Craig, DO,f Chitra Dinakar, MD,g Anne K. Ellis, MD,h Ira Finegold, MD,i David B. K. Golden, MD,j Matthew J. Greenhawt, MD,k John B. Hagan, MD,l Caroline C. Horner, MD,m David A. Khan, MD,n David M. Lang, MD,o Desiree E. S. Larenas-Linnemann, MD,p Jay A. Lieberman, MD,q Eli O. Meltzer, MD,r,s John J. Oppenheimer, MD,t,u Matthew A. Rank, MD,v Marcus S. Shaker, MD,w Jeffrey L. Shaw, MD,x Gary C. Steven, MD,y David R. Stukus, MD,z,aa and Julie Wang, MDbb Chief Editor(s): Mark S. Dykewicz, and Dana V. Wallace Joint Task Force on Practice Parameters: Chitra Dinakar, Anne K. Ellis, David B. K. Golden, Matthew J. Greenhawt, Caroline C. Horner, David A. Khan, David M. Lang, Jay A. Lieberman, John J. Oppenheimer, Matthew A. Rank, Marcus S. Shaker, David R. Stukus, and Julie Wang Workgroup Contributors: Mark S. Dykewicz, Dana V. Wallace, David J. Amrol, Fuad M. Baroody, Jonathan A. Bernstein, Timothy J. Craig, Ira Finegold, John B. Hagan, Desiree E. S. Larenas-Linnemann, Eli O. Meltzer, Jeffrey L. Shaw, and Gary C. Steven St Louis, Mo; Fort Lauderdale, Fla; Columbia, SC; Chicago, Ill; Cincinnati, Cleveland, and Columbus, Ohio; Hershey, Pa; Stanford, and San Diego, Calif; Kingston, Ontario, Canada; New York, NY; Baltimore, Md; Aurora, Colo; Rochester, Minn; Dallas, Tex; Mexico City, Mexico; Memphis, Tenn; New Brunswick, and Morristown, NJ; Scottsdale, Ariz; Lebanon, NH; and Green Bay and Greenfield, Wis From athe Section of Allergy and Immunology, Division of Infectious Diseases, Allergy and Immunology, Department of Pediatrics, The Elliot and Roslyn Jaffe Food Allergy and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis Institute, Icahn School of Medicine at Mount Sinai, New York. University; bthe Department of Medicine, Nova Southeastern Allopathic Medical Disclosure of potential conflict of interest: The Joint Task Force on Practice Parameters School, Fort Lauderdale; cthe Department of Internal Medicine, School of Medicine, (JTFPP) members’ and work group members’ conflict of interest disclosure forms can University of South Carolina, Columbia; dthe Department of Otolaryngology–Head be found at www.allergyparameters.org. Mark S. Dykewicz has served as a committee and Neck Surgery, Pritzker School of Medicine, University of Chicago; ethe Allergy member for the American Academy of Allergy, Asthma, and Immunology (AAAAI) Section, Division of Immunology, Department of Internal Medicine, College of Med- Rhinitis, Rhino-sinusitis, and Ocular Allergy Interest Section and is also a member icine, University of Cincinnati; fthe Departments of Medicine and Pediatrics, Penn of the American College of Asthma, Allergy, and Immunology (ACAAI) Rhinitis/ State University, Hershey; gthe Division of Pulmonary, Allergy and Critical Care Med- Sinusitis Committee. Dana V. Wallace has received financial support from Mylan, Ka- icine, Department of Medicine, School of Medicine, Stanford University; hthe Division leo, Optinose, ALK-Abell
o, Bryan, and Sanofi. David J. Amrol has received financial of Allergy and Immunology, Department of Medicine, Queen’s University, Kingston; support from CSL Behring; and is a board member for the Southeastern Allergy, i the Division of Allergy and Immunology, Department of Medicine, Mount Sinai West, Asthma, and Immunology Society. Fuad M. Baroody is a member of the American New York; jthe Division of Allergy and Clinical Immunology, Department of Medi- Rhinologic Society and a member of the American Academy of Otolaryngology– cine, School of Medicine, John Hopkins University, Baltimore; kthe Section of Allergy Head and Neck Surgery. Jonathan A. Bernstein has received financial support from Sa- and Immunology, Department of Pediatrics, Children’s Hospital Colorado, School of nofi Regeneron, AstraZeneca, Merck, Optinose, Takeda, CSL Behring, Biocryst, Medicine, University of Colorado, Aurora; lthe Division of Allergic Diseases, Mayo Pharming, the National Institutes of Health, Taylor Francis, INEOS; is Editor-in- Clinic, Rochester; mthe Division of Allergy, Immunology and Pulmonary Medicine, Chief of the Journal of Asthma, INEOS medical immunosurveillance director, vice Department of Pediatrics, School of Medicine, Washington University, St Louis; chair, and lectureship chair of the AAAAI Foundation, chairman of AFI, ACAAI n the Division of Allergy and Immunology, Department of Internal Medicine, Univer- Asthma Chair, Scientific Chair, and Young Investigator Award Chair; and serves on sity of Texas Southwestern Medical Center, Dallas; othe Department of Allergy and the board of directors and scientific committee of Interasma. Timothy J. Craig has Clinical Immunology, Respiratory Institute, Cleveland Clinic Lerner College of Med- received financial support from CSL Behring, Dyax, Takeda, BioCryst, Pharming, Gri- icine at Case Western Reserve University, Cleveland; pthe Center of Excellence in fols, GlaxoSmithKline, Regeneron, and Novartis/Genentech; is on the medical advi- Asthma and Allergy, Hospital Medica Sur, Mexico City; qthe Division of Pulmonology sory board for Hereditary Angioedema Asssociation of America; serves of the board Allergy and Immunology, Department of Pediatrics, The University of Tennessee of directors for the AAAAI; and is a member of the American Lung Association Health Science Center, Memphis; rthe Division of Allergy and Immunology, Depart- Mid-Atlantic Board. Chitra Dinakar has received financial support from Propeller ment of Pediatrics, School of Medicine, University of California, San Diego; sthe Al- Health, ACAAI (stipend for Editorial Board of AllergyWatch), and the American As- lergy and Asthma Medical Group and Research Center, San Diego; tthe Division of sociation of Allergists of Indian Origin; serves on the board of directors of the AAAAI Pulmonary & Critical Care Medicine and Allergic & Immunologic Diseases, Depart- and on the medical advisory board of Food Equity Initiative; and is Assistant Editor of ment of Internal Medicine, University of Medicine and Dentistry of New Jersey– AllergyWatch. Anne K. Ellis has received financial support from ALK-Abell
o, Astra- Rutgers New Jersey Medical School, New Brunswick; and uthe Pulmonary and Allergy Zeneca, Green Cross, Merck, Novartis, Nuvo, Pediapharm, Pfizer, Kaleo, Novartis, Sa- Associates, Morristown; vthe Division of Allergy, Asthma, and Clinical Immunology, nofi, and Regerneron; and serves on the board of directors of the Canadian Allergy Mayo Clinic in Arizona, Scottsdale; wthe Department of Pediatrics, Dartmouth-Hitch- Society of Allergy and Clinical Immunology. Ira Finegold has no competing relation- cock Medical Center, Lebanon; xthe Prevea Health, Green Bay, Wis, ythe Allergy, ships, organizational interests, or conflicts to disclose. David B. K. Golden has received Asthma and Sinus Center, Greenfield; zthe Division of Allergy and Immunology, financial support from Aquestive, Sandoz, ALK-Abell
o, Sandoz, Genentech, Nationwide Children’s Hospital, Columbus; aathe Department of Pediatrics, College Stallergenes-Greer, and UpToDate. Matthew J. Greenhawt has received financial sup- of Medicine, The Ohio State University, Columbus; and bbthe Division of Allergy port from Aquestive, Merck, Allergenis, Allergy Therapeutics, Sanofi Genzyme, 721 722 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance Abbreviations used on diagnosis, assessment, selection of monotherapy and AH: Adenoidal hypertrophy combination pharmacologic options, and allergen AIT: Allergen immunotherapy immunotherapy for AR. Newer information about local AR is AR: Allergic rhinitis CBS: Consensus based statements reviewed. Cough is emphasized as a common symptom in both CHM: Chinese herbal medicine AR and NAR. Food allergy testing is not recommended in the CRS: Chronic rhinosinusitis routine evaluation of rhinitis. Intranasal corticosteroids (INCS) CT: Computed tomography remain the preferred monotherapy for persistent AR, but DBPC: Double-blind, placebo controlled additional studies support the additive benefit of combination DP: Dermatophagoides pteronyssinus treatment with INCS and intranasal antihistamines in both AR FDA: US Food and Drug Administration and NAR. Either intranasal antihistamines or INCS may be GRADE: Grading of Recommendations, Assessment, Development offered as first-line monotherapy for NAR. Montelukast should and Evaluation only be used for AR if there has been an inadequate response or INAH: Intranasal antihistamines intolerance to alternative therapies. Depot parenteral INCS: Intranasal corticosteroids JTFPP: Joint Task Force on Practice Parameters corticosteroids are not recommended for treatment of AR due LAR: Local allergic rhinitis to potential risks. While intranasal decongestants generally LTRA: Leukotriene receptor antagonist should be limited to short-term use to prevent rebound NAPT: Nasal allergen provocation test congestion, in limited circumstances, patients receiving NAR: Nonallergic rhinitis regimens that include an INCS may be offered, in addition, an NARES: Nonallergic rhinitis with eosinophilia syndrome intranasal decongestant for up to 4 weeks. Neither acupuncture NSAID: Nonsteroidal anti-inflammatory drug nor herbal products have adequate studies to support their use NSD: Nasal septal deviation for AR. Oral decongestants should be avoided during the first OAS: Oral allergy syndrome trimester of pregnancy. Recommendations for use of PAR: Perennial allergic rhinitis subcutaneous and sublingual tablet allergen immunotherapy in QOL: Quality of life SAR: Seasonal allergic rhinitis AR are provided. Algorithms based on a combination of SCIT: Subcutaneous allergy immunotherapy evidence and expert opinion are provided to guide in the sIgE: Serum-specific IgE selection of pharmacologic options for intermittent and SLIT: Sublingual immunotherapy persistent AR and NAR. (J Allergy Clin Immunol 2020;146:721- SLIT-D: Sublingual immunotherapy administered by liquid drops 67.) SLIT-T: Sublingual immunotherapy administered via tablets TRPV1: Transient receptor potential vanilloid 1 Key words: Allergic rhinitis, nonallergic rhinitis, vasomotor VAS: Visual analog scale rhinitis, local allergic rhinitis, food allergy antihistamines, cortico- VMR: Vasomotor rhinitis steroids, ipratropium, allergen immunotherapy, decongestants UACS: Upper airway cough syndrome Genentech, Aravax, Prota, Before Brands, the Institute for Clinical and Economic Re- Alliance of the MidSouth. Eli O. Meltzer has received support from Boehringer- view, ACAAI, DBV Technologies, and Intrommune; is supported by the Agency of Ingelheim, GlaxoSmithKline, Glenmark, GossamerBio, Merck, Mylan, Optinose, Healthcare Research and Quality; has served on the advisory board of International ALK-Abell
o, AstraZeneca, and Regeneron/Sanofi. John J. Oppenheimer has received Food Protein Induced Enterocolitis Syndrome Association, the Asthma and Allergy financial support from DBV Technologies, TEVA, GlaxoSmithKline adjudication/data Foundation of America, and the National Peanut Board; and is Associate Editor of safety monitoring board, AstraZeneca, Novartis, and Sanofi; is Associate Editor of the the Annals of Allergy, Asthma, and Immunology. John B. Hagan is member of the Qual- Annals of Allergy, Asthma, and Immunology and AllergyWatch, an American Board of ity, Adherence and Outcomes Committee at the AAAAI; and is chairman of the Internal Medicine Council Member and American Board of Allergy and Immunology Rhinitis/Sinusitis/Ocular Committee at the ACAAI. Caroline C. Horner has served Liaison to the American Board of Internal Medicine, UpToDate reviewer, American as committee chair for the AAAAI Asthma Diagnosis and Treatment Interest Section, College of Chest Physicians Cough Guideline Committee Member, and WebMD Ed- Interest Section Coordinating Committee, and In-Training Exam Coordinating Com- itor. Matthew A. Rank has received financial support from the ACAAI, National Insti- mittee. David A. Khan has received financial support from UpToDate and Aimmune; tutes of Health, and Levin Family Foundation; has served as chair of the AAAAI serves on the board of directors of the AAAAI, ACAAI Chair of Literature Review, co- Health Care Outcomes, Education Delivery and Quality Interest Section; and is chair of Conjoint Board Review, Texas Allergy, Asthma, and Immunology Society research director of the Phoenix Children’s Hospital Breathmobile. Marcus S. Shaker Chair of Meetings Committee; and is Associate Editor of the Journal of Allergy and has received financial support from the Eastern Allergy Conference; and has a family Clinical Immunology in Practice. David M. Lang is on the Editorial Board for Allergy member who is the chief executive officer of Altrix Medical. Jeffrey L. Shaw is a com- and Asthma Proceedings, topic editor for DynaMed, Associate Editor for the Journal mittee member for the Rhinitis, Sinusitis, and Ocular Committee of ACAAI. Gary C. of Asthma; and delegate to the National Quality Forum representing the AAAAI. De- Steven has received financial support from 3M, AstraZeneca, Attenua, Chiesi, Cipla, siree E. S. Larenas-Linnemann has received financial support from AstraZeneca, My- Glenmark5, GlaxoSmithKline, Lupin, Menlo, Merck, Novartis, Pearl, Sanofi, lan, GlaxoSmithKline, Sanofi, Novartis, DBV Technologies, SUMA/Circassia, and TEVA, Stallergenes, NeRRe, Watson, Westward, Aimmune, ALK-Abell
o, Regeneron, Thermo Fisher Scientific; is a board member of the Colegio Mexicano de Inmunologia American Academy of Neurology, Boehringer, and Optinose. David R. Stukus has Clinica y Alergia, member of Immunotherapy Committee of the AAAAI, chair of In- received financial support from Aimmune, Before Brands, Abbott Nutrition, the Amer- formation Technology Interest Group and Task Force of European Academy of Allergy ican Academy of Pediatrics, and ACAAI; has served as committee chair for AAAAI and Clinical Immunology (EAACI), and Chair of International Committee for the and ACAAI. Julie Wang has received financial support from ALK-Abell
o, Regeneron, Latin portfolio of the ACAAI. Jay A. Lieberman has received financial support from DBV Technologies, and Aimmune; is an UpToDate author; serves on the executive the ACAAI, Aquestive, Aimmune, DBV Technologies, Biotest Pharma, and Reger- committee of the American Academy of Pediatrics Section on Allergy and Immu- neron; is Associate Editor of the Annals of Allergy, Asthma, and Immunology, vice nology; and serves as vice chair of the AAAAI Anaphylaxis, Dermatitis, Drug Allergy chair for the ACAAI Food Allergy Committee, and medical director for Food Allergy Interest Section. J ALLERGY CLIN IMMUNOL DYKEWICZ ET AL 723 VOLUME 146, NUMBER 4 EXECUTIVE SUMMARY whether a patient has AR or NAR or another mimicking condition This comprehensive practice parameter for allergic and is important because management will differ. nonallergic rhinitis provides updated guidance on diagnosis, AR affects up to 60 million people in the United States assessment, selection of monotherapy and combination pharma- annually, can have a major impact on quality of life (QOL), and cotherapy options, and allergen immunotherapy. Food allergy poses a substantial economic burden on society. It also is often testing and parenteral corticosteroids are not recommended. Key associated with and can potentially impact asthma, allergic new and updated recommendations are emphasized (Table I). conjunctivitis, rhinosinusitis, and sleep disturbances. INTRODUCTION Prevalence The diagnosis of rhinitis is suggested by the presence of 1 or Self-reported rates of AR are 10% to 30% of adults and as many more of the following symptoms: nasal congestion, rhinorrhea as 40% of children in the United States.2 In recent surveys that (anterior and posterior), sneezing, and itching.1 Rhinitis can be required a physician-confirmed diagnosis of AR, the prevalence classified by pathogenic mechanisms, as allergic or nonallergic, rates were 14% of US adults and 13% of US children.3,4 Canadian and differentiated from conditions that have overlapping data support an even higher prevalence of up to 20% of the pop- symptoms of rhinitis. ulation having physician-diagnosed AR.5 Chronic NAR has been estimated to affect 17% to 52% of adults while up to 34% of pa- Rhinitis phenotypes tients with rhinitis in the United States may have a combination of Although the term rhinitis connotes inflammation, and allergic AR and NAR, often referred to as ‘‘mixed rhinitis.’’6-10 rhinitis (AR) and some types of nonallergic rhinitis (NAR) are associated with inflammation (eg, nonallergic rhinitis with eosinophilia syndrome [NARES], infectious rhinitis), some forms QOL in rhinitis of NAR such as vasomotor rhinitis (VMR) or atrophic rhinitis may Issues of QOL associated with rhinitis include disturbed sleep; not be associated with inflammation of the nasal mucosa. Rhinitis daytime somnolence and fatigue; irritability; depression; impair- frequently is accompanied by symptoms involving the eyes, ears, ment of physical and social functioning; and attention, learning, and throat. Conditions that have overlapping symptoms with and memory deficits. Thirty-five percent to 50% of adults reported rhinitis include rhinosinusitis with and without nasal polyps, that nasal allergies have at least a moderate effect on their daily cerebrospinal fluid rhinorrhea, ciliary dyskinesia syndrome, and life.3 Sleep disturbances associated with rhinitis include difficulty structural/mechanical factors, such as congenital anomalies, falling asleep, staying asleep, and awakening refreshed. Nearly 1 deviated septum, and pharyngonasal reflux. Recognition of in 4 of adult US respondents report they are unable to sleep or are Reprints: Joint Task Force on Practice Parameters Liaison: Rebecca Brandt (American Disclaimer: The AAAAI and the ACAAI have jointly accepted responsibility for Academy of Allergy, Asthma, and Immunology, 555 E. Wells Street, Suite 1100, Mil- developing ‘‘Rhinitis 2020: a practice parameter update.’’ The medical environment is waukee, WI 53202. E-mail: [email protected]); [email protected]. rapidly changing, and not all recommendations will be appropriate or applicable to all Previously published practice parameters and guidelines of the JTFPP are available at patients and may change over time. Because this document incorporates the efforts of http://www.allergyparameters.org. http://www.AAAAI.org, and http://www.ACAAI. many participants, no single individual, including members serving on the JTFPP, is org. authorized to provide an official AAAAI or ACAAI interpretation of this guideline. Resolving conflict of interest: The JTFPP is committed to ensuring that all guidelines are Any request for information or interpretation of this practice parameter by the AAAAI based on the best scientific evidence at the time of publication, and that such evidence or ACAAI should be directed to the executive offices of the AAAAI and the ACAAI. is free of commercial bias to the greatest extent possible. Before confirming the Practice parameters and guidelines are not designed for use by the pharmaceutical selection of the work group chairperson and members, the JTFPP discusses and industry in drug development or promotion. The JTFPP understands that the cost of resolves all relevant potential conflicts of interest (COIs) of each work group member. diagnostic tests and therapeutic interventions is an important concern that may The JTFPP recognizes that experts in a field are likely to have interests that could come appropriately influence the evaluation and treatment selected for a given patient. The into conflict with the development of a completely unbiased and objective guideline. JTFPP recognizes that the emphasis of our primary recommendations regarding a Therefore, a process has been developed to acknowledge potential COIs when making medication may vary, for example, depending on third-party payer issues and product specific recommendations. To preserve the greatest transparency regarding potential patent expiration dates. However, because a given test or a therapeutic intervention’s COIs, all members of the JTFPP and work group complete a COI form prior to the cost is so widely variable, and there is a relative paucity of pharmacoeconomic data, the development of each document and again prior to the guideline submission for JTFPP is not always able to consider cost when formulating recommendations. In publication. extraordinary circumstances, when the cost benefit of an intervention is prohibitive as During the review process there are additional measures to avoid bias. At the work group supported by pharmacoeconomic data, commentary may be provided. level, all the recommendations and discussion sections are reviewed by all work group Contributors: The JTFPP has made a concerted effort to acknowledge all contributors to members to ensure that content is appropriate and without apparent bias. If any this parameter. If any contributors have been excluded inadvertently, the JTFPP will recommendation or section is deemed to have apparent bias, it is appropriately revised, ensure that appropriate recognition is provided. without the section author’s involvement, in an attempt to remove potential bias. In Received for publication February 6, 2020; revised June 22, 2020; accepted for publica- addition, the entire document is also reviewed by the JTFPP and any apparent bias is tion July 1, 2020. acknowledged and removed at that level. For each and every recommendation, a vote is Available online July 22, 2020. required by the work group and JTFPP, and any member with any perceived COI is Corresponding author: Mark S. Dykewicz, MD, Saint Louis University School of Med- recused from that vote (and so explained in the document). Any dissenting votes that icine, Section of Allergy and Immunology, Department of Internal Medicine, 1402 cannot be resolved are described and explained in the document. S. Grand Boulevard, M157, St Louis, MO 63104. E-mail: mark.dykewicz@health. In a final stage of review, the practice parameter is sent to invited expert reviewers for slu.edu. review, selected by the AAAAI and the ACAAI. The document is also posted on the The CrossMark symbol notifies online readers when updates have been made to the AAAAI and ACAAI websites for general membership and the public-at-large to article such as errata or minor corrections review and offer comment. All reviewers must provide statements of potential COIs. 0091-6749/$36.00 Although the JTFPP has the final responsibility for the content of the documents Ó 2020 American Academy of Allergy, Asthma & Immunology submitted for publication, each reviewer’s comments will be discussed and reviewers https://doi.org/10.1016/j.jaci.2020.07.007 will receive written responses to comments when appropriate. The JTFPP members’ and work group members’ COI disclosure forms can be found at www.allergyparameters.org. 724 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 TABLE I. What is new or newly emphasized in Rhinitis 2020? Four new algorithms based on a combination of evidence and expert opinion can guide the clinician in the treatment of intermittent and persistent AR and NAR. New tables assist in making (1) the differential diagnosis for rhinitis based on patient history and (2) the diagnosis and treatment for rhinitis-associated conditions or conditions that mimic rhinitis. Cough is emphasized as a common symptom present in both AR and NAR. New information is presented about LAR, possibly present in up to 25% of patients with rhinitis, and its response to both SCIT and SLIT, although more research is needed. We recommend that food allergy testing not be performed in the routine evaluation of possible AR (Recommendation 4). We recommend that the oral LTRA montelukast should only be used for AR in patients who have an inadequate response or intolerance to alternative therapies. Serious neuropsychiatric events that may include suicidal thoughts or actions have been reported in patients taking montelukast (Receommendation 7). Either INAH or INCS may be offered as first-line monotherapy for NAR (Recommendations 12, 32). Since the 2008 rhinitis update, additional studies support the use of combination INCS and INAH in AR and NAR (Recommendations 22-24). Oral decongestants should be avoided during the first trimester of pregnancy (Recommendation 19). Additional information is presented as to why first-generation antihistamines should not be used in AR, especially on a chronic basis, due to potential sedation, performance impairment, poor sleep quality, anticholinergic-medicated symptoms, and increased risk of dementia (Receommendation 6). We continue to suggest that the use of intranasal decongestants generally be limited to short-term use to prevent rebound congestion that may occur with longer use. However, in limited circumstances discussed in the document, patients on regimens that include an INCS may be offered combination therapy with addition of an intranasal decongestant for up to 4 wk (Receommendations 16, 26). SCIT and SLIT tablets are both effective for the treatment of AR and may help prevent and/or treat allergic asthma (Receommendation 34). Neither acupuncture nor herbal medications have adequate studies to support a recommendation to use them in the treatment of AR (Receommendations 36, 37). awakened most days or every day, and up to 45% of children expe- Classification of AR: severity, frequency, and rience sleep disruption because of nasal allergy symptoms.3,11 environmental exposure Most studies indicate associations between nasal allergies and Assessment of rhinitis by severity, frequency, and exposure can anxiety/mood syndromes.12 assist the clinician in developing the most appropriate treatment Limited available data report that health-related QOL is strategies for an individual patient. Mild rhinitis severity is reduced in patients with NAR, with greatest reductions in patients present when symptoms are not interfering with QOL such as with NARES.13 A decreased sense of smell, present in both AR impairment of daily activities, work or school performance, and NAR, can lead to a significant decrease in QOL, including leisure activities, and sleep. Moderate/severe rhinitis is present disturbing a patient’s ability to appreciate flavors, losing the plea- when symptoms are troublesome or there is negative impact on sures of eating, and increasing health risks such as not appreci- any of these QOL parameters.1,20 Other groups have proposed a ating spoiled food or leaking gas and adding larger quantities of division into mild, moderate, and severe,21 but as this division sugar and salt to highlight flavors, thus worsening general does not clearly translate into a change in therapy, the most health.14 accepted division is still the dual one, which is also used in the majority of clinical trials. Symptom frequency has been divided by some into intermittent Economic and societal burden of rhinitis ( _4 consecutive weeks/year).20,22 This strict defini- dous,15,16 rhinitis is also a significant cause of lost work and tion has some limitations; for example, a patient who has school days and decreased work productivity/presenteeism symptoms 3 days/week year-round would be classified as ‘‘inter- (work interference) and school performance. Up to 10% of mittent’’ although they might more closely resemble a ‘‘persis- workers reported absenteeism because of their nasal allergies, tent’’ patient. and up to 25% reported presenteeism, with an estimated 23% to The preceding definitions of severity and frequency may be 33% decrease in productivity on days when allergies were at their applied to AR, NAR, or mixed rhinitis (when both allergic and worst compared with days when the respondent experienced no nonallergic components contribute to rhinitis symptoms). symptoms.3 Increased symptom severity, decreased sleep quality AR may also be classified by the temporal pattern of and quantity, adverse effects on mental function, and treatment environmental exposure to a triggering allergen: seasonal (Inter- with soporific antihistamines negatively impact work productivi- national Classification of Diseases, 10th Revision, J30.2, eg, from ty.17Appropriate therapy can substantially reduce both societal pollens, J30.1), perennial (year-round, eg, dust mites, J30.89 and employer costs. Lack of treatment, undertreatment, or nonad- ‘‘other allergic rhinitis’’ and J30.9 ‘‘allergic rhinitis, unspeci- herence to treatment have been shown to increase direct and indi- fied’’), or from episodic allergen exposures not normally encoun- rect costs.18 AR can, by itself, introduce significant inattention, tered in the patient’s environment, such as visiting a home with impairment of cognition, and decreased daytime school pets.1 AR from animals (J30.81) therefore may be perennial with performance.19 ongoing exposure, or occur only with episodic exposure. AR, notably present in about 75% to 80% of all patients with In the United States, AR has traditionally been viewed as either asthma and in nearly 100% with allergic asthma, is associated seasonal (SAR) or perennial (PAR), and it is this classification with increased asthma-related hospitalizations and higher total system that the US Food and Drug Administration (FDA)23 uses annual medical costs. when approving new medications for AR. The reality is that a J ALLERGY CLIN IMMUNOL DYKEWICZ ET AL 725 VOLUME 146, NUMBER 4 patient may have both SAR and PAR, SAR or PAR with NAR (In- perennial LAR and SAR (skin prick test–positive) has also been ternational Classification of Diseases, 10th Revision, J30 ‘‘vaso- described.50,51 However, prevalence rates of LAR in China have motor and allergic rhinitis’’), intermittent symptoms with PAR, been reported to be much lower (eg, 7.7%).52 LAR is reported or persistent symptoms with SAR. It is also recognized that the to be more prevalent in women, to be associated with a family his- distinction between SAR and PAR has limitations; in different cli- tory of atopy equal to or greater than that of AR, and to have a matic regions, the same aeroallergen can be either seasonal or mean onset of 21 years; however, LAR may start in childhood perennial. Nonetheless, the recognition that an individual has 36% of the time.49,53,54 Local occupational rhinitis, diagnosed SAR and is allergic to particular pollen allergens of known sea- by nasal provocation studies, should be considered in workers sonality in a region may help guide administration of medications with a convincing history but with negative immunological concurrent with (or in anticipation of) that defined seasonal expo- tests.55 sure. That said, one must be mindful that nasal inflammation and The most frequently reported symptoms in patients with LAR thereby need for treatment may persist for weeks after a pollen are watery rhinorrhea, sneezing and itching, compared with season is over. The majority of patients are polysensitized to congestion and mucoid rhinorrhea for patients with NAR.49,56 both pollens and perennial allergens. In a population of 6000 pa- While most patients with LAR are monosensitized, most tients with AR, it was shown that 55% of patients with seasonal commonly to dust mite, up to 37% are polysensitized to seasonal symptoms and 45% of those with perennial symptoms had inter- and/or perennial allergens.46,49,57 Of particular interest is a signif- mittent AR; thus, the SAR-PAR classification is independent from icantly lower incidence (2.7%) of animal dander sensitization in the intermittent-persistent one.24 Since then, numerous studies patients with LAR compared with in patients with AR (31%).49 have duplicated these findings in other regions.25,26 The majority of adult patients with LAR have moderate/severe, persistent, and perennial symptoms, with common comorbidities of conjunctivitis (50%-65%) and asthma (18%-47%). These Local AR studies show that the severity of LAR and associated comorbid- In local allergic rhinitis (LAR), also referred to as entopy, there ities increase with disease duration.39,49,58-60 is (1) a clinical history of perennial and/or seasonal symptoms The mainstay of current LAR treatment has consisted of following allergen exposure, with (2) negative skin prick tests avoidance and pharmacotherapy. However, recent well- (and intradermal tests, when performed) and absence of serum- controlled trials suggest that if the specific triggering allergen specific IgE (sIgE) antibodies but (3) a positive nasal allergen can be accurately identified, subcutaneous allergy immuno- provocation test (NAPT) to aeroallergens.27-30 therapy (SCIT) or sublingual immunotherapy (SLIT) might be a While a major study center in Europe has contributed the bulk reasonable consideration. SCIT has been successfully used to of the research on LAR as discussed above, additional small treat dust mite–, grass-, and birch-induced LAR in 2 different studies from Australia,31 Sweden,32 Egypt,33 and China34,35 have European centers.40,60-62 A randomized, double-blind, placebo supported their findings. There have been limited US studies, not controlled (DBPC) parallel group study demonstrated that SCIT all confirming these findings.36,37 with DP in patients with LAR who are DP-sensitized produced A dual (immediate and late) response to NAPT had been noted significant improvement with reduction in total symptom score in 37% to 70% of LAR.38,39 Although it would be expected that (47%), reduction in total medication scores (51%), and reduced local sIgE would be detected in all patients with NAPT responses to NAPT-DP (with total suppression in 50% of patients) challenge-diagnosed LAR, some studies of LAR from pollens over a 24-month treatment period.62 Significant symptom detect local sIgE in as few as 30% of patients.39,40 When present improvement and nasal tolerance to NAPT-DP was noted as early in patients with SAR, an increase in nasal sIgE is noted both dur- as 6 months into treatment.60 A small randomized DBPC 24- ing NAPT challenge and during pollen season.40 Likewise, in 1 month trial of birch SCIT to patients with SAR produced a signif- dust mite LAR study of patients who had a positive NAPT-dust icant reduction in symptom medication score, a decrease in local mite challenge, only 22% had nasal sIgE to dust mites.38 sIgE, and an increase in IgG4 levels.40 In this study, local sIgE A recent method of detecting nasal sIgE by the direct application levels significantly increased during birch season in all patients, of the solid phase of a commercial ImmunoCAP test showed a but a blunted seasonal increase was noted at 24 months in the sensitivity of 43% and high specificity and offers promise for active treatment group.40 An observational study using preseaso- future clinical use.41 Making the diagnosis can be challenging nal grass SCIT demonstrated significant clinical improvement given the current low sensitivity of assays for the local sIgE and and increased NAPT nasal tolerance in all patients.61 However, the need to conduct an in-office NAPT procedure.42,43 Studies in this early study, 40% of the SCIT group developed positive have suggested that the basophil activation test might serve as a skin prick tests after 6 months of treatment followed by sIgE surrogate marker of LAR, although currently this is available and sIgG antibodies to grass after 12 months of treatment.61 only as a research tool. It has been shown that using the basophil The same group completed a randomized DBPC study involving activation test with Dermatophagoides pteronyssinus (DP) 56 patients with LAR to grass, established by either a positive extract and olive tree identifies 50% to 66%, respectively, of pa- NAPT or nasal sIgE > _ 0.35 kU/L.63 There was significant tients with NAPT-established LAR with a specificity of 93% improvement in combined symptoms medication score and Rhi- and showing identical specificity for both LAR and AR.44 noconjunctivitis Quality of Life Questionnaire after 6 months of In some studies, using NAPT, up to 26% of all patients with preseasonal treatment. The effect was sustained during the second rhinitis and up to 100% of patients with NAR have year when year-round SCIT was used. There was a significant in- LAR.31,32,35,36,45-48 In a population-based observational study crease in serum IgG4 levels and allergen tolerance with 83% of that categorized all patients with rhinitis, over 25% and 63% patients completing at least 6 months of treatment tolerating were diagnosed to have LAR and AR, respectively, indicating over 50 times higher concentration of grass pollen during that 1 hour but 20% but with the guideline updates ‘‘The diagnosis and management of rhinitis: an absence of sIgE by skin and blood testing in all but 3 of 52 updated practice parameter’’ published in 2008.1 This guideline subjects. The original cohort included no patients with clinical was not intended to be a Grading of Recommendations, Assess- evidence of CRS with nasal polyps. Oral aspirin and inhaled ment, Development and Evaluation (GRADE) document such methacholine challenges performed on limited numbers of sub- as we published in 2017 to update for a limited number of ques- jects were negative.162 Onset of symptoms ranged from the first to tions for SAR.174 Because GRADE documents require a compre- fifth decades. hensive literature search, systematic review, and meta-analysis However, other systematic evaluations of nonallergic subjects for each question, they require substantial resources, making it with eosinophilic NAR showed significant associations with cost prohibitive to attempt to conduct a GRADE analysis for all rhinosinusitis with nasal polyps, sinus mucosal thickening, and of the questions for which clinicians would like an answer. In asthma leading to speculation that NARES may be a prelude to addition, for many questions, there is very limited evidence and the onset of CRS, asthma, or perhaps NSAID-exacerbated the work group/Joint Task Force on Practice Parameters (JTFPP) respiratory disease.7,163 must rely on expert evidence and opinion. Therefore, in this Blood eosinophilia is occasionally present in patients with guideline, the only GRADE recommendations are those that NARES and the term ‘‘blood eosinophilic NAR’’ had been were previously published in the 2017 rhinitis guideline update. proposed but not routinely used to represent this possible condi- The remainder of the recommendations are consensus-based tion.164 The prevalence of NARES is unknown but is suspected to statements (CBS), which are based, at best, on a recent literature represent 1% to 5% of children and from 5% to 15% of adults with search of PubMed to update or add to the 2012 rhinitis document. rhinitis.7,165,166 One cluster analysis from a single center in We have changed our method of grading our recommendations to Beijing characterized NARES in 23.6% of predominately adult be more transparent, choosing words that are used in a formal subjects with chronic rhinitis.167 Nasal eosinophilia persisted in GRADE document, (eg, strong and conditional), to be consistent children without allergies who were followed throughout the in terminology and to maintain a common thread. However, the year including the winter season when not exposed to use of these words do not imply that we are equating our recom- allergens.166 Total nasal resistance and mucociliary transport mendations to the rigor required by a GRADE document. time is increased in patients with NARES versus in healthy The strength of the CBSs is determined to be either strong or controls.168 conditional as defined below. The certainty of evidence for each The differential diagnosis of persistent nasal eosinophilia recommendation is determined to be high, moderate, low, or very includes PAR with positive allergy skin or IgE blood tests, low as defined below. When the JTFPP did not have adequate LAR, rhinosinusitis with nasal polyps, CRS without polyps, published evidence with which to determine the certainty of eosinophilic granuloma, allergic fungal rhinosinusitis, and evidence but recognized, nonetheless, the need to provide NSAID-exacerbated respiratory disease.169 guidance to the clinician, the CBSs were based on the collective NARES is particularly responsive to corticosteroids.7 In 1 un- expert opinion and experience of the work group and JTFPP. We controlled study, montelukast 10 mg daily reduced nasal obstruc- have provided the tabulated vote for and against each such tion, rhinorrhea, sneezing, and nasal pruritus in subjects with statement. NARES and asthma.170 Intranasal cromolyn was studied and The guideline development process involves several stages. found to have no benefit in NARES.171 The work group begins the process by developing a list of key To date there has not been consensus regarding the specific clinical questions and topics to be addressed. At least 2 work clinical criteria for diagnosis of NARES. The lower limits of nasal group members are assigned to write and review each section. eosinophilia required for diagnosis have been variable, ranging A PubMed literature search is completed to determine the most from 5% to 25% and the percentage may vary depending on updated information for each CBS and discussion. The draft specimen type.172,173 Current clinical guidelines have not sections are reviewed by the work group chair and co-chair with recommended routine assessments of nasal eosinophils.1 The subsequent revision by the authors. Subsequently, all sections diagnosis of NARES should be considered in patients who are are reviewed and revised by the entire work group through nonallergic and presenting with prominent symptoms of several rounds of electronic and teleconference reviews. The perennial rhinorrhea and sneezing in the absence of facial pain, guideline is reviewed in detail by the JTFPP and revisions, nasal obstruction, rhinosinusitis with nasal polyps on rhinoscopy, when needed, are made in conjunction with the work group. and sinus mucosal thickening in individuals with notable response The external review follows as described above under to nasal steroids or with eosinophilia in blood or if assessed in ‘‘resolving conflict of interest’’ in the preface (Tables II, III, nasal secretions. and IV). 730 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 TABLE II. Grading the strength of the Consensus Based Statements (CBSs) Strong CBS The work group and JTFPP are confident that the desirable effects of adherence to the statement outweigh the undesirable effects. This CBS may be appropriate to be used as a practice standard indicator. When making a strong CBS, the wording is ‘‘We recommend,’’ implying that the clinician ‘‘should’’ follow the recommendation. The implications of a strong CBS are d For patients—most people in your situation would want the recommended course of action and only a small proportion would not; request discussion if the intervention is not offered. d For clinicians—most patients should receive the recommended course of action. d For policy makers—the recommendation can be adopted as a policy in most situations. Conditional CBS The work group and JTFPP reach a decision that the desirable effects of adherence to a CBS probably outweigh the undesirable effect. When making a conditional CBS, the wording is ‘‘We suggest,’’ implying that the clinician ‘‘may’’ follow the recommendation. The implications of a conditional CBS are d For patients—most people in your situation would want the recommended course of action, but many would not. d For clinicians—you should recognize that different choices will be appropriate for different patients and that you must help each patient to arrive at a man- agement decision consistent with her or his values and preferences. It is likely that shared decision making will play a major role in arriving at the management decision. d For policy makers—policy making will require substantial debate and involvement of many stakeholders. TABLE III. Grading the certainty of evidence for each CBS High 5 Further research is very unlikely to change our confidence in the estimate of effect. The recommendation is based on high-quality evidence, such as multiple highly rated randomized controlled trials, systematic reviews, or meta-analyses. Moderate 5 Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. The recommendation would likely be based on somewhat limited evidence, such as reduced number or quality of randomized controlled trials or controlled trials without randomization. Low 5 Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. The recommendation would likely be based on very weak evidence, such as nonexperimental studies, registries, or comparative studies. Very low 5 Any estimate of effect is very uncertain. The recommendation is based largely on very low quality studies and/or on expert opinion. CBS without determination of certainty: When there are either no published studies, or very limited and/or very weak evidence, a consensus statement without any category of certainty of evidence was developed. The degree of agreement by all JTFPP and work group members is indicated, with voting details provided if there were dissenting votes. Clinical history and physical examination CRS) should be discussed. Because patients may not recognize Recommendation 1. CBS: We recommend that the clinician symptoms of asthma, a history of symptoms suggestive of asthma complete a detailed history and a physical examination in a pa- (eg, wheezing, shortness of breath, chest tightness, and cough) tient presenting with symptoms of rhinitis. should be sought, and if appropriate from symptoms, spirometry Strength of recommendation: Strong obtained. As noted earlier, AR coexists in about 75% to 80% of all Certainty of evidence: Low patients with asthma, in nearly 100% of those with allergic Recommendation 2. CBS: We recommend that for patients asthma, and is a marker for more difficult-to-control or severe presenting with rhinitis symptoms, a review of all current medica- asthma. The overall medical, social, and psychiatric history; tions should be completed to assess whether drug-induced rhinitis medication history (current and past); environmental exposures may be present. in the home or workplace; and family views on disease state Strength of recommendation: Strong and health care should be included in the patient history. As the Certainty of evidence: Ungraded due to lack of studies address- final therapeutic decisions will involve shared decision making, ing this specific issue. the history should explore the wishes and desires of both the pa- Note: Unanimous vote in favor by work group and JTFPP. tient and family in selecting diagnostic procedures and therapeu- Clinical history in patients with rhinitis. The most tic interventions, including their willingness to adhere to these important single element for establishing the diagnosis of rhinitis, therapies. allergic or nonallergic, and differentiating it from other conditions In clinical practice, especially in primary care, the diagnosis of with overlapping symptoms, is the clinical history.1,20,175 The age AR is often made solely by history.176 The use of validated ques- of onset, duration, frequency, severity, timing during the year, sus- tionnaires is more beneficial for excluding than for confirming pected triggers, pattern of presentation, and progression of each AR. The use of a validated 4-question screening tool has been patient-specific symptom should be obtained and recorded. The shown to have a high negative predictive value for positive skin history should include the success or failure of past therapeutic in- prick tests to common aeroallergens.177 Furthermore, if a patient terventions, including self-prescribed over-the-counter medica- has a late onset of symptoms (age >45 years); no family history of tions, homeopathic agents, or physician-prescribed treatments. allergies; no seasonality of symptoms or symptoms around cats, The family history and personal history of comorbid respiratory dogs, or other furry pets; and has trouble with nonallergic triggers conditions (eg, asthma and chronic rhinitis with or without such as deodorants/fragrances, the likelihood of having a J ALLERGY CLIN IMMUNOL DYKEWICZ ET AL 731 VOLUME 146, NUMBER 4 TABLE IV. JTFPP practice parameter CBSs and GRADE recommendations on the diagnosis and management of rhinitis Recommendation Strength of Certainty of no. CBS or GRADE recommendation recommendation evidence 1 CBS: We recommend that the clinician complete a detailed history and a physical examination in Strong Low a patient presenting with symptoms of rhinitis. 2 CBS: We recommend that for patients presenting with rhinitis symptoms, a review of all current Strong Ungraded medications should be completed to assess whether drug-induced rhinitis may be present. 3 CBS: We recommend that aeroallergen skin prick testing or sIgE testing be completed to confirm Strong High the diagnosis of AR in a patient with a history consistent with AR. 4 CBS: We recommend that the clinician not perform food skin prick testing or sIgE for foods in Strong Ungraded their routine evaluation of a patient presenting with the signs and symptoms compatible with the diagnosis of AR. 5 CBS: We suggest that the use of a validated instrument (eg, scoring system, scale, or Conditional Low questionnaire) be considered to help determine the severity of rhinitis and to monitor the degree of disease control. 6 CBS: We recommend against prescribing a first-generation antihistamine and are in favor of a Strong High second-generation antihistamine when prescribing an oral antihistamine for the treatment of AR. 7 CBS: We suggest that the clinician not select the oral LTRA montelukast for the initial treatment Conditional Very low of AR due to reduced efficacy when compared with that of other agents. Furthermore, serious neuropsychiatric events that may include suicidal thoughts or actions have been reported in some patients taking montelukast. As advised by the FDA, montelukast should be used to treat AR only in patients who are not treated effectively with or cannot tolerate other alternative therapies. 8 CBS: We recommend that the clinician not select an oral LTRA for the treatment of NAR. Conditional Ungraded 9 CBS: We suggest that for the treatment of very severe or intractable AR, the clinician may Conditional Very low consider a short course (5-7 d) of oral corticosteroids. 10 CBS: We suggest that for the treatment of very severe or intractable AR, the clinician not Conditional Low prescribe a depot parenteral corticosteroid for AR due to the potential risks of systemic and local corticosteroid side effects. 11 CBS: We recommend that the clinician offer INAH as an initial treatment option for patients with Strong High SAR. 12 CBS: We recommend that the clinician offer INAH as a first-line monotherapy option for patients Strong High with NAR. 13 CBS: We recommend that the clinician offer INAH as a first-line option for patients with Conditional Ungraded intermittent AR. 14 CBS: We recommend that when choosing monotherapy for persistent AR, INCS be the preferred Strong High medication. 15 GRADE: We recommend that for the initial treatment of moderate/severe SAR in patients > _15 y Strong High of age, the clinician use an INCS over an LTRA. (Also see Recomendation 7.) 16 CBS: We suggest that the use of intranasal decongestants be short term and used for intermittent Conditional Low or episodic therapy of nasal congestion. (However, see also Recommendation 26.) 17 CBS: We suggest that in patients having severe mucosal edema, which impairs the delivery of Conditional Ungraded other intranasal agents, an intranasal decongestant be considered for up to 5 d of use. 18 CBS: We suggest that oral decongestant agents be used with caution in older adults and children Conditional Low younger than 4 y old, and in patients of any age who have a history of cardiac arrhythmia, angina pectoris, cerebrovascular disease, uncontrolled hypertension, bladder outlet obstruction, glaucoma, hyperthyroidism, or Tourette syndrome. 19 CBS: We recommend that oral decongestants be avoided during the first trimester of pregnancy. Strong Low 20 CBS: We suggest that in patients with PAR and NAR who have rhinorrhea as their main nasal Conditional Low for PAR; symptom be offered intranasal ipratropium. moderate for NAR 21 CBS: We suggest that intranasal cromolyn be offered as an option to be taken just prior to Conditional Very low allergen exposure to reduce symptoms of AR from episodic allergen exposures. 22 GRADE: We suggest that the clinician consider the combination of an INCS and an INAH for the Conditional High initial treatment of moderate/severe nasal symptoms of SAR in patients > _12 y old. 23 CBS: We suggest that the clinician consider the combination of an INCS and an INAH for Conditional Moderate moderate/severe SAR and PAR that is resistant to pharmacologic monotherapy.* 24 CBS: We suggest that the clinician consider the combination of an INCS and an INAH for Conditional Low moderate/severe NAR that is resistant to pharmacologic monotherapy.* 25 CBS: We suggest that for patients taking an INCS who have persistent rhinorrhea, the clinician Conditional Moderate may consider the addition of intranasal ipratropium. 26 CBS: We suggest that patients with persistent nasal congestion unresponsive to an INCS or to an Conditional Low INCS-INAH combination be offered combination therapy with addition of an intranasal decongestant for up to 4 wk. (Continued) 732 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 TABLE IV. (Continued) Recommendation Strength of Certainty of no. CBS or GRADE recommendation recommendation evidence 27 CBS: We suggest that for patients with AR and nasal congestion uncontrolled with an oral Conditional Moderate antihistamine, the clinician consider the addition of pseudoephedrine, when tolerated. (See Recommendation 18.) 28 CBS: We suggest that for SAR the clinician not combine the oral LTRA montelukast with an oral Conditional Moderate antihistamine for symptoms not controlled with an oral antihistamine. (See Recommendation 7.) 29 GRADE: We recommend that the clinician not prescribe, as initial treatment, a combination of an Strong Moderate oral antihistamine and an intranasal steroid in preference to monotherapy with an intranasal steroid in patients > _12 y of age with symptoms of SAR. 30 CBS: We suggest that the clinician not prescribe the combination of an oral antihistamine and an Conditional Very low INCS in preference to monotherapy with an intranasal steroid in all patients with SAR and PAR. 31 CBS: We suggest against the addition of the oral LTRA montelukast to an INCS for AR, due to Conditional Very low the lack of adequate evidence of improved efficacy and concerns for serious neuropsychiatric events from montelukast. (See Recommendation 7.) 32 CBS: We suggest that the clinician offer an INCS as a first-line therapy for NAR. Conditional Low 33 CBS: We suggest that the clinician offer an INAH as a first-line therapy for NAR. Conditional Very low 34 CBS: We suggest that AIT (subcutaneous or sublingual tablets) be offered through shared Conditional Moderate decision making to patients with moderate/severe AR who (1) are not controlled with allergen avoidance and/or pharmacotherapy or (2) choose immunotherapy as the preferred method of treatment (eg, due to the desire to avoid the adverse effects, costs, or long-term use of pharmacotherapy) and/or (3) desire the potential benefit of immunotherapy to prevent or reduce the severity of comorbid conditions, such as asthma. 35 CBS: We suggest that AIT (subcutaneous or sublingual tablets) be considered for patients with Conditional Moderate controlled mild/moderate asthma with coexisting AR. 36 CBS: We cannot make a recommendation for or against the use of acupuncture for the treatment N/A Very low of AR. 37 CBS: We cannot make a recommendation for or against the use of specific herbal products for the N/A Very low treatment of AR. N/A, Not applicable. *‘‘Resistant to pharmacologic monotherapy’’ assumes that the patient has been compliant and taken medication for adequate duration. component of NAR before diagnostic skin or serologic testing is large multinational observational study, 47% of patients with 98% predictive.178 While the history has greater reliability and AR frequently reported cough as a symptom, although only predictive value than solely relying on the physical exam, 11% had cough as the main reason for seeking medical atten- the combination of history and physical exam is still advised tion.192 In a prospective study, cough as a symptom increased (Table V).179 from mild intermittent to moderate/severe persistent AR.193 Cough sensitivity has been described to be heightened in patients with AR, both during and outside of pollen season.194,195 With up Cough and rhinitis to 23% of patients with chronic cough having at least 2 Chronic cough, often defined as cough persisting for >4 weeks contributing comorbidities (eg, AR with postnasal drip and (children)180 or >8 weeks (adults),181 in patients who are immu- gastroesophageal reflux disease), the complexity of managing nocompetent and nonsmoking is usually due to upper airway chronic cough becomes magnified.196 cough syndrome (UACS), formerly referred to as postnasal drip The mechanism of cough in AR has often been explained both syndrome; asthma; and/or gastrointestinal reflux disease, with as a rhinobronchial reflex and as part of the UACS. In nasal UACS being the most common cause.182-186 While the challenge studies of patients with AR, cough was described most pathogenesis of chronic cough has often been attributed to frequently in patients with PAR.197 Patients with persistent AR some combination of upper airway inflammation, nasobronchial report more postnasal drip along with more cough.198 The mech- reflex, cold dry air stimulation, inflammatory mediators from anisms of cough from UACS in children may differ from adults the systemic circulation, or central and peripheral neuroplasticity, and may differ among children of different age groups. In 1 Chi- a clear pathway has not been shown experimentally.187-189 nese study, rhinitis was the major pathogenesis in the school-age Cough as a consequence of rhinitis, especially AR, is often children, whereas it was adenoid hypertrophy in a group of pre- underappreciated, due in large part to a lack of high-level school children, indicating that mechanical obstruction may be evidence. Overall, guidelines minimize or conclude that there is a major cause of UACS in some children.199 low-level evidence associating AR with cough without the Frequently, cough in a patient with AR is related to concom- presence of concurrent asthma.179,190 Cough is often considered itant asthma or nonspecific bronchial hyperreactivity, often to be a comorbidity of AR rather than viewed as a direct symptom undiagnosed. Furthermore, bronchial biopsy studies in patients of AR. In 1 study, rhinitis was found to be an independent risk fac- with AR and without asthma have shown inflammatory cell tor for the development of cough in adults.191 Furthermore, in 1 infiltrate and active structural remodeling of the lower airways J ALLERGY CLIN IMMUNOL DYKEWICZ ET AL 733 VOLUME 146, NUMBER 4 TABLE V. Patient-reported symptoms and likely diagnosis Acute upper respiratory CRS without CRS with Symptom AR NAR tract infection nasal polyps nasal polyps Rhinorrhea, sniffing Very common, can be Common, but less than Common clear Common, Common, clear intermittent AR or AR overall, but some to purulent, watery clear to to mucoid persistent AR, most subtypes have to mucoid, associated mucoid common symptom, rhinorrhea as a major with crust formation clear watery symptom Sneezing Very common, Common, intermittent, Common Very uncommon Very uncommon intermittent and less common than in persistent AR, almost AR, rarely persistent universal Hyposmia/anosmia Occasional Occasional Common Common Very common Nasal congestion/blocked Very common, persistent Very common, usually Common Very common Very common, nose, mouth breathing AR more than persistent chronic, almost intermittent AR universal Mouth breathing Common Common Common Occasional Common Ocular pruritus, watery Very common Uncommon Uncommon Very uncommon Very uncommon discharge, red eyes Postnasal drip Uncommon, persistent Very common Common Common Occasional more than intermittent AR Nasal/palate/ear itching Common Very uncommon Very uncommon Very uncommon Very uncommon Sore throat Occasional, persistent Uncommon Common Occasional Uncommon more than intermittent Constant clearing of Uncommon Common Common Common Uncommon throat Chronic cough Common, persistent more Common, unless Common Occasional Uncommon than intermittent postnasal drip treated (persistent more than intermittent) Bleeding of nose Very uncommon Uncommon Very uncommon Very uncommon Very uncommon Facial or sinus pain/ Very uncommon, Common Common Common Uncommon pressure persistent more than intermittent Eustachian tube Occasional Occasional Common Uncommon Uncommon dysfunction Snoring Uncommon, persistent Common Common Common Common more than intermittent AR Sleep disturbance/sleep Common, persistent more Common Common Common Common apnea than intermittent AR Headache as part of Occasional Common Common Common Common symptomology This table is developed based predominantly on expert opinion. Frequencies—very common, common, occasional, uncommon, very uncommon—are based on expert evidence and opinion. similar to that of patients with asthma, thereby potentially conjunctivitis, otitis, eustachian tube dysfunction, CRS with and contributing to cough in these patients.200,201 without nasal polyps, asthma, and/or atopic dermatitis.1,204-206 While intranasal corticosteroids (INCS) are often used to treat Documentation of normal findings (eg, no septal perforation) UACS, high-quality evidence is lacking. INCS have been shown is important to establish baseline exam findings prior to the pre- to reduce cough sensitization in patients with AR.202 Nasal- scribing of medications that might lead to adverse events. While pharyngeal saline irrigation, compared with INCS, was shown specific nasal and oropharyngeal physical exam findings (eg, to be more effective at reducing daytime and nighttime cough pale, boggy nasal mucosa, allergic shiners, and pharyngeal hy- score and in lowering nasal lavage histamine and LTC4.203 perplasia) may support the diagnosis of AR, there are no patho- gnomonic findings that distinguish allergic versus nonallergic versus infectious rhinitis.1,179,207,208 Furthermore, a patient Physical examination with a history of rhinitis who is asymptomatic or minimally For a patient with rhinitis symptoms, a physical exam should symptomatic at the time of the physical exam, may have mini- be completed that encompasses not only the upper airway but mal or no abnormal findings.209 While conducting a physical also the lower airway, eyes, ears, and skin to identify findings exam is recommended by all major rhinitis guidelines to that may suggest the presence of a comorbid allergic or make the diagnosis of AR,1,20,175 the very limited, low-quality nonallergic condition (see Table VI for more details).1,20,179 research evidence that is available demonstrates a much lower These comorbid conditions may include accompanying allergic sensitivity and specificity and high interpreter variability for 734 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 TABLE VI. Physical examination of patient presenting with symptoms compatible with rhinitis Vital signs (including weight and height): Record on all patients. General observations: facial pallor, elongated facies, preferred mouth breathing, and any evidence of systemic disease. Eyes: Excessive lacrimation, erythema, and swelling of the bulbar and/or palpebral conjunctiva, cobblestoning of the tarsal conjunctiva, swelling or dermatitis of outer eyelids, Dennie-Morgan lines, or venous stasis below the lower eyelids (‘‘allergic shiners,’’ which may occur in AR or NAR). Nose: Reduced patency of nasal valve; alar collapse; transverse external crease; external deformity such as saddle nose (loss of nasal bridge that may occur from nasal trauma or systemic disorders such as relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, or some systemic infections); septal deviation or perforation, spurs, ulcers, perforation, prominent vessels, or excoriation; nasal turbinate hypertrophy, edema, pallor or erythema, and crusting; discharge (amount, color, consistency), and nasal polyps. The presence of tumors or foreign bodies should be noted. Ears: Tympanic membrane dullness, erythema, retraction, perforation, reduced or increased mobility, and air-fluid levels. Oropharynx: Halitosis, dental malocclusion or high arched palate associated with chronic mouth breathing, tonsillar or AH, cobblestoning of the oropharyngeal wall, pharyngeal postnasal discharge, temporomandibular joint pain or clicking with occlusion, furrowing, coating, or ulceration of tongue or buccal mucosa. Neck: Lymphadenopathy, or tenderness, thyroid enlargement or nodule. Chest: Signs of asthma such as wheezing or other abnormal or diminished sounds by auscultation. Skin: Rashes, especially eczematous or urticarial (distribution and description), or dermatographism. Other organ systems: When history or general observation indicate these should be included. This list is not intended to be totally inclusive. Elements of the examination that will assist in the differential diagnosis of rhinitis or that may indicate complications of treatment are included. Documentation of presence or absence of these elements should be considered. This table is modified from Table V in the 2008 rhinitis practice parameter.1 the physical exam when compared with the patient’s history for symptoms can be present concurrently and contribute to the making a diagnosis of AR, suggesting that both are essential to rhinitis-induced morbidity. increase diagnostic accuracy.179,209,210 Considering both the high prevalence of AR and NAR and the large number of differ- ential diagnoses for rhinitis, perhaps the greatest benefit of completing the physical exam is to exclude the rare, but poten- Selected conditions that may mimic rhinitis tially life-threating diagnosis, intranasal tumor), which may Nasal septal deviation. NSD is a common cause of fixed even co-exist with AR. nasal obstruction leading to nasal congestion.211 It appears to be The nasal-pharyngeal exam can usually be accomplished as common an anatomical cause of congestion as nasal valve with the use of a nasal speculum with appropriate lighting or an collapse and turbinate hypertrophy.212 It may cause bilateral or otoscope with a nasal adapter,1 although these provide a more unilateral congestion and is often associated with nasal valve limited view of the nasal cavity than a nasopharyngolaryngo- collapse and compensatory turbinate hypertrophy.212-214 The scope does. For mucosal edema that prohibits an adequate importance and effectiveness of septoplasty for NSD does not exam, the use of a topic nasal decongestant may reduce turbi- appear to be universally accepted.215,216 nate mucosal edema, allowing for better visibility and delinea- Nasal valve collapse. The internal nasal valve is the tion of abnormal findings (eg, distinguishing nasal polyps from narrowest portion of the nasal cavity and is the anatomical area polypoidal mucosal hypertrophy). A pneumatic otoscope al- bounded medially by the nasal septum and laterally by the inferior lows for the assessment of tympanic membrane mobility and edge of the upper lateral cartilage and the anterior aspect of the presence of transudative fluid. At times, an impedance tympan- inferior turbinate. As such the nasal valve is the area most ometer may also be of benefit to assess tympanic membrane commonly associated with the subjective perception of obstruc- mobility and the presence/absence of middle ear fluid. tion and is responsible for more than two-thirds of the airflow A nasopharyngolaryngoscope exam should be completed resistance produced by the nose.217 Nasal valve collapse refers to when a more extensive nasal/pharyngeal/laryngeal exam is any weakness or further narrowing of the nasal valve and can required due to suspected structural or functional abnormal- result in change of airflow that is perceived as nasal congestion. ities, inadequate therapeutic response, or a suspected complica- The nasal examination should note the patency of the nasal valve tion (eg, deviated septum, rhinosinusitis with or without nasal and any alar collapse. If there is improvement in breathing when polyps, foreign body, nasal septal perforation, or vocal cord performing the Cottle maneuver—pulling the patient’s cheek dysfunction). laterally to open the nasal valve angle—this may suggest nasal valve pathology. Turbinate hypertrophy. Hypertrophy, with or without Differential diagnosis of rhinitis concha bullosa, can account for severe unilateral or bilateral The differential diagnosis of chronic rhinitis symptoms in- obstruction and accounts for severe congestion equally as cludes AR, NAR, mixed rhinitis, including the rhinitis-specific commonly as nasal valve collapse and septal deviation do.212 Hy- subtypes discussed in previous sections; common conditions that pertrophy can be primary (eg, from AR and NAR) or compensa- mimic rhinitis such as rhinosinusitis with or without nasal polyps tory, often being associated with congenital or traumatic septal and nasal septal deviation (NSD); and more uncommon condi- deviation.213 While medical treatment for some causes of turbi- tions (Table VII). A comprehensive history, physical examina- nate hypertrophy (eg, AR) can be very effective, not infrequently tion, and appropriate testing is important to ascertain the correct a surgical approach will be required for other causes. The diagnosis as this will help direct the therapeutic approach recog- consensus for treatment in refractory cases can include turbinate nizing that some diseases mimicking rhinitis can lead to substan- reduction.218-220 When performing septoplasty for unilateral tial morbidity and even mortality. Furthermore, >1 cause of nasal NSD, it is often necessary to also perform turbinate reduction J ALLERGY CLIN IMMUNOL DYKEWICZ ET AL 735 VOLUME 146, NUMBER 4 TABLE VII. Diagnosis and treatment of rhinitis-associated conditions or conditions that mimic rhinitis History that may differen- Condition tiate from rhinitis Physical exam findings Diagnostic studies Treatment CRS with nasal polyps May have reduced sense of Mucosal polypoidal changes Fiberoptic Saline irrigation, consider smell/taste; chronic that will not shrink with nasopharyngoscopy, sinus short course oral congestion, nocturnal topical decongestant, CT corticosteroids, INCS, mouth breathing, NSAID- nonpainful growths LTRAs, surgery, anti-IL-4/ induced respiratory 13 (dupilumab). symptoms Aspirin desensitization in aspirin/NSAID- exacerbated respiratory disease Research ongoing: anti-IL-5, IL-5 receptor antagonist, anti-IgE. CRS without nasal polyps Facial pain/pressure, Mucopurulent discharge, Fiberoptic Evidence for treatment headache, mucopurulent facial tenderness, nasopharyngoscopy, sinus effectiveness may differ discharge, decreased sense cobblestoning posterior CT, consider immune between CRS with and of smell, postnasal drip, pharyngeal wall system evaluation CRS without nasal polyps. fatigue, poor sleep quality, Options include INCS, depression saline irrigation, chronic macrolide antibiotics (conflicting evidence), acute antibiotics for superimposed infection, surgery Septal wall abnormalities, Severity worse unilateral Septal deviation noted, septal Fiberoptic Surgery, such as septoplasty such as deviated septum, side, previous surgery, erosion and/or nasopharyngoscopy, sinus or surgical correction of septal erosion, nasal septal trauma, history of abuse of perforations, septal spurs, CT perforations, septal button perforation cocaine (perforation) asymmetrical nasal vault (for septal perforation) openings Nasal valve collapse Nasal congestion as main Improvement in breathing Fiberoptic Adhesive spring-like symptom, poor response to when performing the nasopharyngoscopy and externally applied nasal medication Cottle maneuver (ie, anterior rhinoscopy strips, nasal cones, surgery pulling the patient’s cheek laterally to open the nasal valve angle) Turbinate hypertrophy: with Severe unilateral or bilateral Turbinate hypertrophy Fiberoptic INCS, surgery or without concha bullosa obstruction. nasopharyngoscopy, Sinus Hypertrophy can be primary CT or compensatory and often associated with congenital or traumatic septal deviation Adenoidal hypertrophy Child with recurrent ear Posterior nasal, pharyngeal Tympanogram, fiberoptic INCS, LTRAs, infections and/or snoring, fullness may be noted, nasopharyngoscopy, lateral Consider short-course oral congestion as main or only adenoids may not be neck radiological studies, steroids, surgery symptom, possible sleep visualized on regular exam CT scan disturbance Foreign body History of possible foreign Unilateral halitosis, May require otolaryngologist Removal of foreign body body placement by child or mucopurulent discharge, referral for rigid impaired adult (with or use topical decongestant rhinoscopy for both without direct during exam for diagnosis and treatment observation), visualization and possible (possibly under sedation mucopurulent discharge dislodgment for child) Nasal tumors (benign or Progressive unilateral Unilateral mass incompatible Consider fiberoptic Surgery usually required, malignant) congestion, bloody with normal mucosal nasopharyngoscopy, CT variable depending on discharge, nasal or ear pain edema or polyps scan, and/or referral to diagnosis otolaryngologist for examination, possible biopsy, and treatment Cerebral spinal fluid leak Unilateral clear discharge, Clear discharge unilateral Test nasal discharge for beta- Otolaryngologist to evaluate intermittent, increased with —may or may not be noted 2 transferrin and if positive whether there is need for dependent head position, on exam refer to otolaryngologist surgical leak closure recent surgery or trauma (Continued) 736 DYKEWICZ ET AL J ALLERGY CLIN IMMUNOL OCTOBER 2020 TABLE VII. (Continued) History that may differen- Condition tiate from rhinitis Physical exam findings Diagnostic studies Treatment Primary ciliary dyskinesia Recurrent rhinosinusitis, Findings compatible with Nasal nitric oxide; nasal No effective medical syndrome otitis, sinus surgeries, CRS with or CRS without brush biopsy and electron treatment other than diagnosis of rhinosinusitis nasal polyps microscopic exam are infection intervention with with nasal polyps, atypical definitive tests; consider antibiotics,