Disclosure. Learning Objectives

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1 Chronic Rhinosinusitis Subcategories and unusual manifestations of systemic disorders. BJ Ferguson MD Director Division of Sino nasal Disorders and Allergy University of Pittsburgh Disclosure Teva: Advisory Board Meda: Advisory Board Integrity: CME speaker Sanofi Aventis: Research Industry sponsored Phase III trial Learning Objectives Describe Chronic Rhinosinusitis and its subcategories, discussing diagnosis and management. Identify the role and evaluation of eosinophilic disease in Chronic Rhinosinusitis. Recognize the unusual manifestations of systemic disease in the nose such as Wegener s and narcotic abuse. 1

2 Categorizing CRS No Nasal polys Odontogenic Pyogenic Anatomic With Nasal Polyps With Eosinophilia AFS AERD Food Hypersensitivity Without Eosinophilia Cystic Fibrosis Antral Choanal Polyp Boring through the alveolus after excavation of a tooth (Cowper method) After extraction of the offending tooth, (usually second premolar or first molar) Pledglet of cotton saturated with a 20% solution of cocaine packed into the cavity for 10 minutes A large dental drill or a guarded Hartmann borer is now used to make an opening into the sinus. Skillern, 3 rd ed 1920 Must be recognized in order to be treated effectively I recommended extraction Rt. Rear molar Repeat Dental consult: no dental pathology Patient and I insist on dental extraction Tooth extracted No recurrence x 1 year 2

3 July 2010: telephone consult advice on patient with sinus CT showing right max, frontal sinusitis. She is on MTX for RA and has been sx x 7 months, failed course of augmentin Microbiology of intracranial abscesses associated with sinusitis of odontogenic origin. Brook I. Ann Otol Rhinol Laryngol Dec;115(12): Management of OMS Resolve dental infection Root canal or extraction Can try office irrigation and antibiotics Culture frequently negative If no subsequent resolution, ESS with irrigation If anticipate Oral Antral fistula with extraction then concomitant ESS and repair Between 1995 and 2010: 11 of 85 (13%) sinus guidelines specifically mentioned odontogenic maxillary sinusitis (OMS) Longhini A, Ferguson BJ: Clinical Aspects of OMS: a case series, IFAR

4 OMC obstruction Unusual from orbital decompression for Graves Anatomic causes Maxillary sinus tap Same patient, 3 days preop, decompressed with inferior meataltap Video of antral tap Mimics and Comorbidities of CRS Migraine CFS/fibromyalgia Allergic rhinitis OSA GERD 4

5 CRS + (n=75) and CRS neg (n=50) CRS + CT sx > CRS nl CT.01 CRS nl CT sx> CRS + CT Ferguson et al: CID 2012 Prospective observational study of CRS Ferguson et al: CID 2012 Prospective observational study of CRS 30% of CT+CRS had endoscopic purulence 0% of CT CRS had endoscopic purulence Both groups reported similar antibiotic use and response to therapy 50% PPI therapy Improves symptoms of PND Vaezi M; gastroenterology 2010 BRPCT Nl sinus CT Negative allergy testing PPI x 16 weeks vs placebo Significant improvement in PND sx at 8 weeks and 16 weeks No GI/reflux test predictive of response 5

6 OSA, recumbent nasal blockage, GERD and the ANS a unifying hypothesis Normal Sleep GERD VMR (nasal congestion) OSA Parasympathetic same same Same or Sympathetic same Para/sympathetic > 1 >1 >1 >1 Jaradeh, Smith et al Laryngoscope 2000 Theory: ANS impacts multiple disorders which may in turn influence comorbidities Parasympathetic > Sympathetic ANS dysfunction Treatment VMR and Recumbinant congestion oxymetazolin with NSS Turbinate reduction Ipratrobium nasal spray OSA positive pressure, IX nerve stimulation GERD Proximal Vagotomy Baseball in style at Miller Park 6

7 Allergies and Sinusitis: the Rational Patient Experiment a practical method for best treatment of nasal symptoms regardless of cause. Sitska, Alaska 8/2012 Learning Objectives Formulate a logical management plan for patients with allergic rhinitis (AR) or Chronic Rhinosinusitis (CRS) according to available evidence based clinical guidelines MAKE ALLERGY /NASAL CARE EASY Recognize the symptoms of AR and CRS and understand impact upper airway can have have on the lower airway unified airway Asthma and CRS / AR coexist Describe the characteristics of available therapeutic options for patients with AR and CRS Implement strategies to improve treatment adherence while considering patient preferences for therapy 20 Diagnosing by Symptoms Allergic rhinitis Non allergic rhinitis CRS congestion Drainage PND Facial pain and pressure rhinorrhea cough sneezing + + Nasal itch + +/ Upper teeth pain 40% dental infections Rotten odor 50% of dental sinusitis Decreased smell +/ +/ Majority of nasal polyp 7

8 Medications approved by Indication Allergic rhinitis (SAR, PAR): antihistamines (oral and topical), antihistamines/decongestants, nasal steroid sprays, leukotriene modulators (montelukast) Nonallergic Rhinitis: none for > 10 years, FDA changed criteria for indication. Some steroid sprays and azelastine Chronic Rhinosinusitis: nasal steroid sprays for nasal polyps How often is CRS substantiated by an abnormal sinus CT scan? Up to 30% of asymptomatic patients have some abnormality of sinuses on CT 40% of patients with strong litany of CRS symptoms x 3 months have normal sinus CT Sinus CT is a picture in time and is abnormal in 80% of patients with a cold, however in 2 weeks these changes are much improved Allergic Rhinitis: Targeted Symptom Relief Nasal congestion Sneezing Nasal itching Eye Sx Rhinnorrhea Nasal Steroid Antihistamines 1 st 2 nd +/- +/- * Decongestants Ipratropium /- + Mast Cell Stablizer LTR * Azelastine has +++ decongestive properties

9 What is the Rational Patient Experiment? In an experiment, one variable is changed to observe whether it changes the out come of the experiment The outcome is: How do your nose/sinus symptoms feel; how do you feel? The Variable is the Medication or Intervention Each pharmacologic intervention is tried one at a time Snow fall in Pride s Crossing, MA Jan 2009 Rational Patient Experiment RPE: Instructions Our goal is to relieve your nose and sinus problems with the fewest number of medications. People respond differently to medicines and we will not know which medicine works best for you, or even causes a side effect, without doing an experiment. The RATIONAL PATIENT EXPERIMENT: Try each checked medicine ONE AT A TIME. If the medicine does NOT make you feel better in 3 to 4 days then STOP the medicine and try the next medicine listed. If the medicine makes you feel PARTIALLY better, but not completely symptom free, then ADD the next medicine listed to the medicine that was partially helping you. If the medicine RELIEVES your symptoms, then CONTINUE it for at least several days or weeks. If you are feeling back to normal, then stop the medicine, but restart it if your symptoms start to return. 9

10 EMRS (n=69) vs. AFS (n=431) * AGE Male (%) Polyps (%) Unilateral Dz(%) # EMRS AFS *P<.001 # P< Eosinophilic CRS multiple often overlapping causes Eosinophilic CRS Super antigen IGE mediated Fungus AFS AERD Nasal Polyposis? + food allergies Churg Strauss Asthma. Spector SL. J Allergy Clin Immunol. 1997;99:S773 S780. Categorization of Eosinophilic CRS 1. Fungus allergic fungal sinusitis a. TLR4 Independent(classic) b. TLR4 Dependent triggered by coagulation byproducts induced by fungal or other proteases Science 2013; NEJM 11/ Bacteria Superantigen 3. Food Hypersensitivity 4. Aspirin Exacerbated Respiratory Disease 5. Eosinophilic Vasculitis (Churg Strauss Syndrome) 10

11 Spectrum of Fungal Sinusitis Immunologic Spectrum compromised competent? Allergic Invasive-acute Mucor Aspergillus Fusarium Pseudallescherii Chronic invasive Fungus Balls Aspergillus NA EFRS AFS Bipolaris Aspergillus Curvularia Alternaria Saprophytic fungus N.P. A 42 year old woman with a 6 month history of worsening headaches and scant discolored drainage is admitted through the ER multiple courses of antibiotics over last 6 months no improvement IDDM in moderate control Renal transplant 2 years earlier ESS to remove fungus ball 10 years earlier PE: in moderate distress because of pain Temp: 37.9 C Without cranial neuropathy Sinus CT on Admision 11

12 What do you do next? A. IV Clindamycin, Rifampin and Gentamicin B. MRI C. urgent ESS with debridement D. Amphotericin B Mimics of AFS EMRS AFS: fungi present in eosinophilic mucin with IgE mediated allergy to cultured fungus No fungal allergy, no fungus on path just eosinophilic mucin Allergic Fungal Sinusitis versus Eosinophilic Mucin Rhinosinusitis without Fungus (AFS Like) Ferguson, BJ; Laryngoscope AFS total cases 418 literature 13 personal series 69 EMRS total cases 40 from literature 29 personal series Toulouse ARS

13 Therapeutic Implications AFS vs AFS like or EMRS AFS EMRS Surgery + + Steroids + + Nasal lavage + + Antifungals + - Immunotherapy + - Omaluzumab? Superantigen Ponikau and the Anti fungal controversies 98% of CRS patients with fungus 70% improved with amphotericin irrigations, non randomized trial Wechta DBRCT: no difference between saline lavage and amphotericin, excluded AFS, but 3 patients had 50% improvement on CT in Amp arm and none on Placebo Ebbens DBRCT: definitive study, NO difference amphotericin irrigations or placebo But study has not been done in just AFS patients, especially post op Antifungal washes cure most CRS, because fungus is everywhere and so are eosinophils; 1999 Ponikau Balloons cure sinus disease because they atraumatically enlarge the sinus ostia 13

14 The obstacle to discovery is not ignorance,it is the illusion of knowledge Dan Boorstin Best Evidenced Based Review is EPOS 2012 For CRS only saline irrigations and topical steroids show efficacy. No evidence for antibiotics, antifungals Future: targeted agents like duplizumab (anti IL4 receptor) Hana no hana nose flowers Colorized TEM of nasal epithelium and cilia Can Elimination Challenge Food Diets Help? Prospective collection of data on CRS patients undergoing ECFD 43 Adults with CRS: 21 without nasal polyps, 22 without Intervention: Completion of QoL surveys, nasal endoscopy, allergy testing, ECFD 49% reported improvement in sinonasal symptoms 22% reported increased energy, decreased abdominal symptoms Elimination Challenge Food Diet Take food out of diet x 5 to 10 days, then ingest and monitor for symptoms for next 24 hours. 14

15 Can Elimination Challenge Diets Help? Most commonly reported food was wheat (43%) followed by dairy (28%), or both 14% Endoscopic improvement in 24% 33% of responders had positive allergy testing Only 9% aware of food allergies prior to office visit UNUSUAL CAUSES OF CHRONIC RHINOSINUSITIS (CRS) VASCULITIC CHURG STRAUSS (EOSINOPHILIC VASCULITIS) LUPUS Granulomatosis with polyangiitis (GPA) formerly known as WEGENER S GRANULOMATOSIS GRANULOMATOUS SARCOID RHINOSCLEROMA Other Intranasal abuse with oxycontin or acetomenophin Vasculitic Causes of CRS Granulomatosis with polyangiitis (GPA) used to be known as Wegener;s Granulomatosis Renal, Pulmonary and Upper Airway Nasal bleeding and septal perforation Elevated canca, WSR, Path: granulomas and vasculitis 15

16 Early: submucosal masses along septum Later: sticky mucus crusting with bacterial colonization Occasionally perforation Dx: usually bx with noncaseating granulomas Sarcoid Eosinophilic Vasculitis Churg strauss syndrome 1. Allergic stage: 90% have asthma 3 to 5 years prior to dx 2. Eosinophilic stage: hypereosinophilia; 3. Vasculitic Stage: GI, cardiac (1/2 of deaths) Diagnosis 4/6 criteria panca Asthma >10% Eosinophilia Neuropathy Pulmonary infiltrates CRS Extravascular E s Conclusion and a few additional pearls CRS symptoms x 12 weeks, sx are nonspecific Decreased smell Drainage Congestion Facial pressure Initially Rational Patient Experiment Saline nasal washes Nasal Steroid Spray If purulent culture, nasopharyngeal swab surrogate for sinus CT scan if impending complication Cone Beam CT less radiation Only get CT if it will change therapy or if ESS planned Usually after endoscopic evaluation and management and persistence 16

17 Summary Only Level 1 evidence for topical steroids and saline washes No good evidence for antibiotics (culture directed studies not done) Dental cause (maxillary), rotten smell, sometimes tooth pain May require CT for diagnosis Thank you 17