Current Evidence in Allergic Rhinitis Brought to you by the ARS/AAOA Education Committees Chair Education Committee ARS: Jeremiah A. Alt MD PhD FARS FACS Project Co-Director AAOA: Kristin Seiberling MD Project Co-Director: Elina Toskala MD PhD MBA Contributing Authors American Rhinologic Society: Garret Choby MD, Anthony Del Signore MD, Carrie Flanagan MD, Wayne Hsueh MD, Ian Humphreys MD, Chris Ito MD, Sandra Lin MD, Mike Marino MD, Edward McCoul MD, Bobby Tajudeen MD, Arthur Wu MD, Mike Yim MD American Academy of Otolaryngic Allergy: Douglas Anderson MD, Dole Baker MD, Chris Brook MD, Melissa Hertler MD, Mona Patadia MD, Christopher Vickery MD Manuscript ▶ There is a wide variety in the type and quality of the growing literature on allergic rhinitis (AR) ▶ The International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) was developed to summarize the best evidence relating to AR. ▶ More than 100 international authors evaluated the evidence using a structured review process. Section I pg. 113 Introduction ▶ There is a wide variety in the type and quality of the growing literature on allergic rhinitis (AR) ▶ The International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR) was developed to summarize the best evidence relating to AR. ▶ More than 100 international authors evaluated the evidence using a structured review process. Introduction ▶ This document summarizes findings of meta-analyses and other systematic reviews to provide recommendations based on the best AR evidence ▶ High value placed on strength of evidence ▶ Similar to the 2016 International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS), this is not a clinical practice guideline or meta-analysis ▶ Practitioners are able to use this evidence-based knowledge to provide support for treatment Section II Methods II.A. pg. 114 Topic development ▶ The 2011 Rudmik and Smith evidence-based review with recommendations (EBRR) method was utilized as the foundation for ICAR:AR ▶ AR was divided into 103 topics/content areas ▶ Section topics were assigned to senior authors who reviewed the literature using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standardized guidelines Topic development ▶ An aggregate level of evidence was produced for each topic guidelines from the American Academy of Pediatrics Steering Committee on Quality Improvement and Management (AAP SCQIM) ▶ A recommendation using the AAP SCQIM guidelines was then produced Topic development Section II Methods II.B. pg. 115 Iterative review ▶ Each section underwent a two-stage online iterative review process using two independent reviewers ▶ The purpose was to evaluate the completeness of the identified literature and ensure any EBRR recommendations were appropriate ▶ The first draft was reviewed by a first reviewer and changes were agreed upon by the author and first reviewer ▶ The same process was employed with the revised section and a second reviewer ▶ All changes were then agreed upon by the initial authors and both assigned reviewers Iterative review Section II Methods II.C. pg. 115 ICAR statement development ▶ After each topic’s content was reviewed and consensus was reached amongst the author and two iterative reviewers, the principal editor compiled all topics into one ICAR:AR statement ▶ The first draft underwent additional reviews by 6-8 authors ICAR statement development Section II Methods II.D. pg. 116 Limitations of methods and data presentation ▶ Search results by each individual author may demonstrate some variability despite specific and detailed search instructions ▶ This document may not present every study published on every topic ▶ Only high quality studies or systematic reviews are listed, especially for topics with extensive literature Section III Definition and differential diagnosis: III.A. pg. 117 Allergic rhinitis definition ▶ AR is an immunoglobulin E (IgE)-mediated inflammatory nasal condition resulting from allergen introduction in sensitized individuals ▶ AR includes the following 3 cardinal symptoms defined in 1929: sneezing, nasal obstruction, and mucus drainage ▶ AR results from an overactive response of T helper (Th) 2 lymphocytes which may initiate a systemic, IgE-driven reaction Section III Definition and differential diagnosis: III.A. pg. 117 Allergic rhinitis definition ▶ In atopic individuals, exposure to allergens may prompt antigen-specific IgE production ▶ Re-introduction of the allergen triggers early and late- stage reactions ▶ Early stage àwithin minutes. nasal itching, nasal congestion, and rhinorrhea ▶ Late stage à 4-8 hours later; nasal blockage, hyposmia, increased secretions, and nasal hyper-responsiveness Section III. Definition and Differential Diagnosis III.B pg. 117 Allergic rhinitis classification ▶ Allergic Rhinitis Classification ▶ ARIA proposed classification - can be confusing ▶ Seasonal Allergic Rhinitis (SAR) ▶ Perennial Allergic Rhinitis (PAR) ▶ Recommended Update: ▶ Intermittent Allergic Rhinitis (IAR) (<4 days/week or <4 consecutive weeks) ▶ Persistent Allergic Rhinitis (PER) (>4 days/week or >4 consecutive weeks) ▶ Severity ▶ Based on disturbances in quality of life (QOL), sleep, exercise tolerance, productivity, and social functioning ▶ Mild or Moderate-Severe Sensitization vs clinical allergy u Monosensitization31 u Polysensitization u Sensitization to 1 allergen u Sensitization to 2 or more allergens u Monoallergy u Polyallergy u Single sensitizing agent causing clinical u Affirmed clinical symptoms to 2 or allergy symptoms more sensitizing allergens u In vivo and in vitro results must be carefully interpreted in the context of patient symptoms u Component-resolved diagnosis testing (in vitro) u More objective means of identifying clinically relevant allergens u Better distinguishes true co-sensitization from polysensitization due to cross-reactivity Section III Definition and Differential Diagnosis III.C. pg. 118 Allergic rhinitis differential diagnosis ▶ Drug-induced rhinitis ▶ NARES ▶ Rhinitis medicamentosa ▶ Vasomotor rhinitis (nonallergic ▶ Occupational rhinitis rhinopathy) ▶ Chemical rhinitis ▶ Age-related rhinitis (ie, elderly) ▶ Smoke-induced rhinitis ▶ Empty nose syndrome ▶ Infectious rhinitis ▶ Atrophic rhinitis ▶ Rhinitis of pregnancy and hormonally- ▶ Autoimmune, granulomatous, and induced rhinitis vasculitic rhinitis ▶ Food- and alcohol-induced rhinitis ▶ Rhinosinusitis Section III. Definition and Differential Diagnosis III.C.1 pg. 118 Drug-induced rhinitis Neurogenic/ Neuromodulator Local Inflammatory Idiopathic ► � antagonists ► Psychotropics ► α-1: doxazosin, silodosin, prazosin, ► NSAIDs, ASA, Ketorolac ► Chlorpromazine, tamsulosin, alfuzosin, indoramin; thioridazine, amitriptyline, ► α-1, α-2: phentolamine Illicit intranasal drug use alprazolam, reserpine, ► Presynaptic �-2 agonists risperidone, mianserin ► Clonidine, methyldopa, guanfacine, piribedil ► Cocaine, narcotics, ► Immunomodulators ► �-antagonists ► Cyclosporine ► β-1: metoprolol, atenolol, bisoprolol; antidepressants, ► - β-1, β-2: pindolol; ► Hormones ► - β-1, β-2, α-1: carvedilol, labetalol anticholinergics, ► Estrogen, oral ► Presynaptic depletion psychostimulants contraceptives norepinphrine stores ► Antihypertensives ► Guanethidine ► Amiloride, chlorothiazide, ► Phosphodiesterase Inhibitors hydralazine, ► PDE-3 - Cilostazol hydrochlorothiazide ► PDE-5 - Sildenafil, tadalafil, ► Other vardenafil ► Gabapentin, gingko biloba ► Non-specific - Pentoxyfylline ► ACE inhibitors Section III. Definition and Differential Diagnosis III.C.2 pg. 120 Rhinitis medicamentosa Rhinitis Medicamentosa (RM) ▶ Induced by prolonged use of topical intranasal decongestant (IND) - exact mechanism unknown ▶ Triad ▶ Prolonged IND use ▶ Constant nasal obstruction ▶ Poor shrinkage of nasal mucosa ▶ Physical exam ▶ Mucosal edema, erythema and hyperemia ▶ Studies suggest IND use should be discontinued after 3 days to avoid RM ▶ Intranasal corticosteroids - only treatment with demonstrable improvement in rebound symptoms62,76,77 Section III. Definition and Differential Diagnosis III.C.3 pg. 121 Occupational rhinitis Occupational Rhinitis (OR) ▶ Inflammatory condition of the nasal mucosa ▶ Intermittent or persistent nasal congestion, sneezing, rhinorrhea, itching, and/or hypersecretion ▶ Attributable to a particular work environment ▶ not encountered outside the workplace ▶ typically involves occupational exposure to high molecular weight (HMW) (more common) or low molecular weight (LMW) agents ▶ HMW-associated occupational rhinitis ▶ 3x more prevalent than occupational asthma ▶ often precedes asthma onset Occupational rhinitis ▶ Diagnosis ▶ Clinical and occupational history, identify high risk occupational exposures ▶ Examination, including anterior rhinoscopy and nasal endoscopy ▶ SPT and/or in vitro sIgE assessment for suspected HMW agent if available ▶ Nasal provocation test (NPT) with suspected agent in lab setting = gold standard ▶ Suggestive history + exposure to HMW agent(s) + negative immunologic tests + positive NPT may suggest local allergic rhinitis (LAR) ▶ Unified airway theory - testing including spirometry, measurement of nonspecific airway hyperresponsiveness, and measurement of bronchial inflammation by exhaled NO Occupational rhinitis ▶ Treatment ▶ Early identification and prevention reduces risk of development of occupational asthma ▶ Avoidance or reduction of exposure ▶ Nonspecific allergic/nonallergic rhinitis pharmacotherapy ▶ Specific immunotherapy may be available