Philippe Gevaert , MD, PhD Michael A. Kaliner, MD Paul Van Cauwenberge, MD, PhD Reviewers: Kamal Hanna, Richard F. Lock

1. Chronic Rhinosinusitis and Nasal Polyposis Philippe Gevaert , MD, PhD Michael A. Kaliner, MD Paul Van Cauwenberge, MD, PhD Reviewers: Kamal Hanna, Richard F. Lockey, Todor Popov Updated: June 2011

3. Global Resources in Allergy (GLORIA™) Global Resources In Allergy (GLORIA™) is the flagship program of the World Allergy Organization (WAO). Its curriculum educates medical professionals worldwide through regional and national presentations. GLORIA modules are created from established guidelines and recommendations to address different aspects of allergy-related patient care.

4. World Allergy Organization (WAO) The World Allergy Organization is an international coalition of 89 regional and national allergy and clinical immunology societies.

5. WAO’s Mission WAO’s mission is to be a global resource and advocate in the field of allergy, advancing excellence in clinical care, education, research and training through a world-wide alliance of allergy and clinical immunology societies

6. Module 10: Chronic Rhinosinusitis and Nasal Polyposis

7. Lecture objectives At the end of this presentation, participants will be able to: Discuss the underlying pathology of acute and chronic rhinosinusitis and nasal polyposis Describe the management of acute and chronic rhinosinusitis and nasal polyposis

8. Rhinosinusitis Facts: • 14.7% incidence in US population: 31,000,000 cases per year • Incidence increased by 18% over the past 11 years • 26 million office visits for sinusitis in 1997 • >21 million antibiotic prescriptions in 1997 • Third most common diagnosis for antibiotics • >70 restricted activity days in 1992 • 250,000 surgeries per year

9. Survey IMS Health 2001 USA, 1997 Germany, 7/2000-6/2001 Prevalence of sinusitis: 14.7% Prescriptions of antibiotics for sinusitis 985 5.8 million 1992 13 million Work loss (days) 1986 50 million 1992 73 million Acute sinusitis Diagnosis: 6.3 million Prescriptions: 8.5 million Chronic sinusitis Diagnosis: 2.6 million Prescriptions: 3.4 million Nasal polyposis: Diagnosis: 221 000

10. Maxillary sinus • Ethmoidal bulla • Ethmoidal cells • Frontal sinus • Uncinate process • Middle turbinate • Inferior turbinate • Nasal septum • Ostiomeatal complex

11. Infections induce changes in sinus mucosa The ostiomeatal complex Key B: bulla ethmoidalis IT: inferior turbinate MT: middle turbinate MS: maxillary sinus Ventilation and Drainage B MT MS IT Inflammation and Remodeling

12. Anterior Posterior Posterior ethmoid Anterior ethmoid Sphenoid sinus Anatomy & physiology RADIOGRAPHIC ANATOMY OF THE PARANASAL SINUSES Coronal Axial Frontal sinuses Sphenoid sinus Ethmoid sinus Maxillary sinus

13. Anatomical and mechanical factors:Epithelial barrier Mucus/mucociliary clearance Mucosal immune system: Innate immunity: Antimicrobial peptides: Defensins Receptors: Toll-like receptors Cells: Macrophages, neutrophils, dendritic cells, NK cells, mast cells Adaptive immunity: Antigen-presenting cells T-lymphocytes B-lymphocytes => IgA Rapid, non-specific Specific, memory Anatomy and physiology MUCOSAL IMMUNITY

14. Aetiology of rhinosinusitis • Others • Dental, periapical abcess • Underlying diseases, cystic fibrosis • Occupational irritants and allergens • Drug induced, rhinitis medicmentosa • Irritants induced rhinitis • Atrophic rhinitis • Allergy • Seasonal • Perennial • Infection • Acute • Chronic: specific e.g. Bacterial, fungal or nonspecific • Possible host defense deficency • Structural • Ostiomeatal complex: • Deviated nasal septum • Hypertrophic turbinates After International Consensus Report on the diagnosis and management of rhinitis. Allergy Suppl 19,49,1994

15. COMMON COLD BACTERIAL SUPERINFECTION Strep pneu./Haemo inf./Morax catar. Increasing symptoms after 5 DAYS No resolution after 10 DAYS ACUTE rhinosinusitis MULTIFACTORIAL ETIOLOGY CHRONIC rhinosinusitis Anatomy and physiology EAACI Position Paper on Rhinosinusitis and Nasal Polyps, Allergy 2005: 60: 583-601

16. Underlying conditions • Sinusitis and Immunodeficiencies • Sinusitis and cystic fibrosis Humoral immunodeficencies frequently associated with sinusitis Congenital immunodeficencies Selective IgA deficency, Common variable IgG immunodeficency, Agammaglobulinemia, specific antibody deficency, (rarely IgG Subclass deficency) Acquired immunodeficencies Immunosupressive agents, HIV

17. Classification: chronic rhinosinusitis with and without nasal polyps 2 OR MOREMAJOR SYMPTOMS • nasal blockage • anosmia/hyposmia • purulent nasal discharge/post-nasal drip • facial pain/pressure AND EITHER • endoscopic findings of polyps • mucopurulent discharge • edema or obstruction OR • CT scan abnormality: mucosal changes within ostiomeatal complex or sinus cavity EAACI Position Paper on Rhinosinusitis and Nasal Polyps, Allergy 2005: 60: 583-601

18. Classification: chronic rhinosinusitis with and without nasal polyps DURATION ACUTE/intermittent < 12 weeks complete resolution of symptoms CHRONIC / persistent > 12 weeks incomplete resolution of symptoms EAACI Position Paper on Rhinosinusitis and Nasal Polyps, Allergy 2005: 60: 583-601

19. Symptoms associated with rhinosinusitis Major symptoms:Minor symptoms: Facial pain/pressure Headache Facial congestion/fullness Fever Nasal obstruction/blockage Halitosis Nasal discharge/purulence/postnasal drip Fatigue Hyposmia/Anosmia Dental pain Fever Cough Ear pain/fullness

20. Microbiology Normal sinuses: Free of growth Acute rhinosinusitis: Viral Bacterial (Strept. Pneumoniae,H. Influenzae, M. Catharralis) Chronic rhinosinusitis: Anaerobes: Propionibacterium, Bacteriodes, Peptococcus Aerobes: Staphylococcus, Corynebacterium, Pseudomonas Fungi (Aspergillus fumigatus, Curvularia, Dreschelaria) Dental sinusitis:Microaerophilic strept. species

21. Nasal polyps

22. Imaging of sinsuses MRI: only recommended in tumor diagnosis CT sinuses: current standard imaging - Acute rhinosinusitis: only for possible complications - Chronic sinusitis: only after 4+ weeks of treatment!

23. Septal deviation Chronic Sinusitis Dental sinusitis Nasal polyps

24. The signs and symptoms of acute sinusitis(>10 days and < 12 weeks): • Prerequisite symptoms • Persistent upper respiratory infection (>10 days) • Persistent muco-purulent nasal or posterior pharyngeal discharge • Cough • Supporting symptoms • Congestion • Facial pain/pressure • Post-nasal drip • Fever • Headache • Anosmia, hyposmia • Facial tenderness • Periorbital edema • Ear pain, pressure • Halitosis • Upper dental pain • Fatigue • Sore throat

25. or Have not improved after 10 days Have worsened after 5 to 7 days Diagnosis of acute bacterial sinusitis (ABS) A diagnosis of ABS is suggested when Symptoms of a viral URI International Rhinosinusitis Advisory Board. ENT J 1997;76(suppl):1; Lanza and Kennedy. Otolaryngol Head Neck Surg 1997;117:S1.

26. Association between viral and bacterial sinusitis infections • Viral infections • Self-limiting • 2 to 3 acute viral respiratory infections per year (6-8 in children) • >80% symptoms resolve in 7-8 days • Often inciting event for development of sinusitis and other respiratory tract infections • 0.5%–2% of cases complicated by acute bacterial infection (>20 million cases) Brook. Primary Care 1998;25:633; Gwaltney. Clin Infect Dis 1996;23:1209; Gwaltney et al. N Engl J Med 1994;330:25.

27. Acute bacterial rhinosinusitis (ABRS) Copyright permission for reproduction pending Sinus and Allergy Health Partnership, 2000

28. acute chronic Therapy • Decongestives/pain • Saline washes • Antibiotics (oral, IV) • Corticosteroids (local, oral) • Surgery: Adenoidectomy (child) Endoscopic sinus surgery (adult)

29. Strength of evidence for treatment of acute rhinosinusitis EAACI Position Paper on Rhinosinusitis and Nasal Polyps, Allergy 2005: 60: 583-601

30. An update on acute rhinosinusitis management: antibiotics in adults Cochrane Review Antibiotics for acute maxillary sinusitis • 7330 subjects in 32 studies (10 double blind) • antibiotic vs. control (n=5) • newer, non-penicillin antibiotic vs. penicillin class (n=10) • amoxicillin-clavulanate vs. other extended spectrum antibiotics (n=10) • Confirmed radiographically or by aspiration, current evidence is limited but supports penicillin or amoxicillin for 7 to 14 days. Clinicians should weight the moderate benefits of antibiotic treatment against the potential for adverse effects • Williams Jr JW, The Cochrane Library2003

31. Evidence for treatment of rhinosinusitis with topical corticosteroids plus antibiotics - 1

32. Evidence for treatment of rhinosinusitis with topical corticosteroids plus antibiotics - 2

33. Evidence for treatment of rhinosinusitis with topical corticosteroids plus antibiotics - 3

34. Copyright permission for reproduction pending J Allergy Clin Immunol. 2005 Dec;116(6):1289-95.

35. Inflammatory component: Topical corticosteroids Symptomatic treatment Community-acquired acute sinusitis If unsuccessful, prolonged, or primary signs Infectious bacterial component: Antibiotic treatment Primary signs of bacterial infection: Localized severe headache Pus in the middle meatus Complications (orbital, skin, etc.) If unsuccessful on several trials, or complications Surgical intervention

36. Considerations in antibiotic selection Pharmacokinetics (PK)/ Pharmacodynamics (PD) Activity Against Likely Pathogen Ease of Dosing Medication Allergy Considerations in Antibiotic Selection Cost/ Formulary Status Adverse Effects Resistance Patterns Adapted from Kennedy et al. Ann Otol Rhinol Laryngol Suppl 1995;167:22; Sinus & Allergy Health Partnership. Otolaryngol Head Neck Surg. 2000;123:S1.

37. Conditions for effective antibiotic treatment • Appropriate spectrum • Appropriate penetrance and local activity • Minor side-effects • Good tolerance • Liklihood of no resistence • Affordable • Available

38. Erythromycin/sulfisoxazole Clarithromycin Azithromycin Amoxicillin Amoxicillin/clavulanate Cephalosporin Miscellaneous Cefuroxime Cefopodoxime Cefixime Cefprozil Cefdinir Ketolides Quinalones Metronidazole Trimethoprin/sulfamethoxazole Clindamycin Antibiotic therapy for sinusitis 2007 Macrolide Penicillin

39. Recommended antibiotic choices - 2007 First choice: Amoxicillin/clavulante or cephalosporin Good second choice: Clarithromycin Back-ups: Quinalones Use metronidazole plus one of the above or clindamycin when gram negative is suspected Topical mupiricin very useful in select cases

40. An update on acute rhinosinusitis management: Antibiotics in acute rhinosinusitis? • Don’t treat viral common cold with antibiotics • Use symptomatic treatment in mild acute rhinosinusitis • saline • decongestant • NSAID • Use topical steroids in acute and chronic sinusitis (evidence) • Reserve antibiotics for severe acute presumably bacterial rhinosinusitis • Prescribe antibiotics based on local resistance patterns

41. Sinusitis - conclusions • Sinusitis is common and over-looked • Causes are complex • Treatment requires appreciation of causes and careful follow-up • Medical management is effective in most cases • Functional endoscopic surgery is helpful in resistant sinusitis after adequate medical management

42. Definitions and classification CLINICAL DEFINITION OF RHINOSINUSITIS/NASAL POLYPS 2 OR MORE MAJOR SYMPTOMS • nasal blockage • smell dysfunction • nasal discharge/post-nasal drip • facial pain/pressure AND EITHER • endoscopic findings of polyps • mucopurulent discharge • edema or obstruction OR • CT scan abnormality: mucosal changes within ostiomeatal complex or sinus cavity EAACI Position Paper on Rhinosinusitis and Nasal Polyps, Allergy 2005: 60: 583-601

43. The signs and symptomsof chronic sinusitis(symptoms persisting >12 weeks): Prerequisite symptoms • Purulent nasal and posterior pharyngeal discharge • Plus: • Facial pain/pressure • Persistent nasal obstruction • Cough/post-nasal drip/throat clearing Supporting symptoms • Hyposmia, anosmia • Sore throat • Malaise • Fever • Headache, facial pressure, dental pain • Halitosis • Sleep disturbance • Fatigue

44. Diagnosis of chronic rhinosinusitis Symptoms suggestive of chronic rhinosinusitis Initial evaluation: • Medical history: major, minor symptoms • General examination • Evaluation of underlying disease and co-morbidities • Anterior rhinoscopy, • Nasal endoscopy • CT scan (not in an acute episode)

45. Allergy tests Microbiology (eventually sinus puncture) Challenge test for aspirin sensitivity Nasal cytology (eosinophils, neutrophils) MRI (if tumor or fungus suspected) Ciliary function studies Biopsy Biopsy Blood examinations (Wegener’s, immunodeficencies) Sweat chloride test Electron microscopy of cilia Genetic analyses Consultations of other specialities (ophthalmologist, neurologist etc.) Special indications (differential diagnosis and underlying disease)

46. Differential diagnosis of chronic rhinosinusitis - 1 • Infectious rhinitis: viral upper respiratory tract infection • Allergic rhinitis: seasonal, perennial, occupational • Nonallergic rhinitis: “Vasomotor rhinitis”, NARES, aspirin- exacerbated respiratory disease • Rhinitis medicamentosa • Rhinitis secondary to pregnancy, hypothyroidism • Anatomical abnormalities: severe septal deviation, foreign body • Nasal polyps • Inverted papilloma, benign and malignant tumors Claus Bachert, Allergy: principles and practice.

47. Differential diagnosis of chronic rhinosinusitis - 2 • Cerebrospinal fluid leak, meningoencephaloceles • Mucoceles • Wegener‘s granulomatosis • Cocaine abuse • Atrophic rhinitis • Specific or tropic infections • Fungal sinus disease • Ophthalmologic or neurologic diseases Claus Bachert, Allergy: principles and practice.

48. Chronic rhinosinusitis: why? • Chronic inflamed (eosinophilic) mucosa • Possible superimposed infections • Bacteria • Fungi • Superantigens • Biofilms • Osteitis

49. Chronic Rhinosinusitis Nasal Polyps The spectrum of sinus disease Nasal Polyps Chronic rhinosinusitiswith and without nasal polyps Rhinosinusitis - Eosinophils +

50. Chronic rhinosinusitiswith and without nasal polyps