1. Marilene B. Wang, MD, FACS Professor UCLA Division of Head Neck Surgery Chief of Otolaryngology VA Greater Los Angeles Healthcare System

4.  From Anterior Nasal Spine ◦ To Sphenoid Ostium7 cm ◦ To Pituitary Fossa8.5 cm

5.  Middle turbinate  Lamina papyracea  Ethmoid fovea  Cribriform plate  Sphenoid

6.  Facial pain/pressure  Nasal obstruction/blockage  Nasal discharge/purulence/discolo red postnasal drip

7.  Hyposmia/anosmia  Purulence in nasal cavity on examination  Fever (acute rhinosinusitis only)

8.  Headache  Fever  Halitosis  Fatigue

9.  Dental pain  Cough  Ear pain/pressure/fullness

10.  Acute  Subacute  Chronic  Recurrent, acute  Acute exacerbations of chronic

11.  Duration up to 4 weeks  > 2 major factors  1 major factor + 2 minor factors  Nasal purulence on exam

12.  Duration 4-12 weeks  >2 major factors  1 major factor + 2 minor factors, or nasal purulence on exam  Complete resolution after effective medical therapy

13.  Duration > 12 weeks  History same as for subacute  Facial pain does not constitute suggestive history in absence of other nasal symptoms or signs

14.  >4 episodes/year + each episode last >7-10 days.  Absence of intervening signs of chronic rhinosinusitis

15.  Sudden worsening of chronic rhinosinusitis  Return to baseline after treatment

16.  Allergies  Immunodeficiency  Genetic/congenital

17.  Endocrine  Neuromechanism

18.  Anatomic  Neoplastic  Acquired mucociliary dysfunction

19. Microorganisms—viral, bacterial, fungal Noxious chemicals, pollutants, smoke Medications Trauma Surgery

20. S. pneum (20-43%) H. influenzae (22-35%) Strep spp. (3-9%) Anaerobes (0-9%) M. catarrhalis (2-10%) S. aureus (0-8%) Other (4%)

21.  S. pneum (25-30%)  H. influenzae (15-20%)  M. catarrhalis (15-20%)  S. pyogenes (2-5%)  Anaerobes (2-5%)  Sterile (20-35%)

22.  Mild disease with no recent antimicrobial use  Augmentin, Amoxicillin  Vantin  Ceclor  Omnicef

23.  Tequin, Levaquin, Avelox  Augmentin  Combination (Amox or clinda + Suprax)

24.  Bactrim  Doxycycline  Zithromax, Biaxin, Erythromycin  Switch to quinolone if no improvement in 72 hours

25.  Quinolone  Augmentin  Clindamcin + rifampin  Consider IV abx

26.  Augmentin, Amoxicillin  Vantin  Ceclor  Omnicef  Switch if no improvement after 72 hours

27.  Bactrim  Macrolide

28.  Augmentin  Rocephin  Bactrim, macrolide  Consider IV abx if no improvement

29.  Afrin for 3 days  Normal saline sprays  Decongestants  Antihistamines  ?Steroids

30.  Periorbital cellulitis  Preseptal cellulitis/abscess  Orbital cellulitis  Orbital abscess  Cavernous sinus thrombosis

31. Widespread affliction—the most common allergic disease Affects 10-30% of American adults— >20 million people, adults and children Results in missed work and school days, poor quality of life

32.  Allergic salute  Shiners  Itchy, red conjunctiva  Sneezing  Post-nasal drip, rhinorrhea, congestion

33.  Dust  Mold, mildew  Plants  Animal dander  Feathers/down

34.  Pollen  Smog  Trees, grasses, weeds  Dust, fertilizer, chemicals

35. Asthma Allergic fungal sinusitis Cystic fibrosis Mucociliary dysfunction Connective tissue disorders (Wegener’s granulomatosis, sarcoid)

36.  Nasal polyposis  Samter’s triad (aspirin sensitivity, nasal polyps, asthma)  Cocaine use

37.  Antibiotics  Antihistamines  Nasal steroids  Normal saline irrigations  Allergy evaluation +/- immunotherapy

38.  Sinus CT scan  Consider anatomic factors— septal deviation, nasal polyps, concha bullosa, ostio-meatal blockage

39.  Nasal polyposis  Anatomic blockage—deviated septum, enlarged turbinate, concha bullosa  Mucocele  Orbital abscess

40.  Fungal sinusitis—allergic vs. invasive (mucor)  Tumor of nasal cavity or sinus

41.  Chronic, recurrent sinusitis  Failure to respond to maximal medical therapy  Obtain cultures

42.  Nasal congestion  Headache/sinus pain  Fatigue  Prolonged bleeding/crusting

43.  Breach of lamina papyracea— damage to extraocular muscles, periorbital ecchymoses  Damage to optic nerve— blindness  Breach of cribriform—CSF leak  Meningitis

44.  May be a lifelong disease  Allergy control— antiihistamines, nasal steroids, immunotherapy  Oral steroids—judiciously  Antibiotics for acute exacerbations

45.  Environmental control—avoid carpet, damp, mold, older homes, smog  Saline irrigations

46.  Alternative therapies— acupuncture, stress management, herbal remedies  Pain management  Multi-disciplinary effort—work with allergy, infectious disease, neurology/pain management services

47.  4 types of allergic reactions (Gell and Coombs)  Type 1 – IgE  Type 2 - IgG--antigen  Type 3 – Immune complex  Type 4 – Delayed hypersensitivity

48. Mast cells bind IgE via their Fc(ε) receptors Mast cell degranulates and releases mediators--produce allergic reactions Hypersensitivity usually appears on repeated contact with the allergen. Examples of type I allergic reactions – Anaphylaxis, atopic asthma, atopic eczema, drug allergy, hay fever

49. Antibody (IgG or IgM) directed against antigen on an individual's own cells, or against foreign antibody (after blood transfusion) Cytotoxic action by killer cells, or to lysis mediated by the complement system. – Autoimmune hemolytic anemia, Goodpasture's syndrome, hemolytic disese of the newborn, myasthenia gravis, pemphigus

50. Immune complexes (antigen and usually IgG or IgM) deposited in the tissue Complement is activated and polymorphonuclear cells are attracted, causing local tissue damage and inflammation. – Polyarteritis nodosa, post-streptococcal glomerulonephritis, systemic lupus erythematosus

51. T cells, sensitized to antigen, release lymphokines following secondary contact with the antigen Cytokines induce an inflammatory response, activate and attract macrophages, release inflammatory mediators. Antibodies produced against fixed cellular or tissue antigens are usually autoantibodies – Crohn's disease, leprosy, tuberculosis, sarcoidosis, schistosomiasis

52.  Parents with allergy greater likelihood of producing allergic children  Food allergies  Environment— air pollution  Smoking

53.  History—environmental exposure, smoking, seasonal occurrence, pets, foods  Examination ◦ Allergic shiners ◦ Allergic salute ◦ Supratip crease ◦ Dennie’s lines (skin fold under eyes) ◦ Adenoid facies

54.  Skin testing ◦ Prick/puncture (scratch or patch) ◦ Intradermal ◦ Dilutional intradermal (skin end-point titration-SET)  In vitro testing ◦ RAST (radioactive marker) ◦ ELISA (enzymatic marker)

55.  Prick—few drops of purified allergen pricked onto skin surface (dust, dander, pollen)  Patch—large patch with different allergens (latex, medications, metal, fragrances, preservatives)  Histamine or glycerin used as positive controls

56. Intradermal injection of allergens at increasing concentrations to measure allergic response Start with a very dilute solution If 2mm of growth noted, then second injection at a higher concentration is given to confirm the response End point is concentration of antigen that causes an increase in the size of the wheal followed by confirmatory whealing Stop at 13 mm

57.  Avoid medications which may interfere ◦ Antihistamines ◦ Antidepressants ◦ Antacids

58.  Anaphylaxis ◦ Low-grade fever ◦ Lightheadedness or dizziness ◦ Wheezing or Shortness of breath ◦ Extensive skin rash ◦ Swelling of face, lips or mouth ◦ Difficulty swallowing or speaking

59.  RAST -radioallergosorbent test—detect specific IgE antibodies to allergens  Improved sensitivity without loss of specificity  Excellent reproducibility across the full measuring range of the calibration curve  Not always necessary to remove patient from an anthihistamine medication regimen  If skin conditions (such as eczema) are so widespread that allergy skin testing can not be done

60.  ELISA – enzyme linked immunosorbent assay  Used more for food allergies  Not as sensitive as skin tests

61.  Environmental control ◦ Stop smoking, clean house, avoid mold, indoor plants, pets, HEPA filter  Pharmacotherapy ◦ Antihistamines, anti-leukotrienes, mast-cell stabilizers, topical and systemic steroids

62.  Specific allergens  Vial test ◦ Intradermal test ◦ Smallest measurable dose  Once or twice weekly injections  Dose escalated  Continue treatment 3-5 years

63.  Invasive ◦ Acute fulminant ◦ Chronic invasive ◦ Granulomatous invasive

64.  Noninvasive ◦ Saprophytic fungal infestation ◦ Fungal ball, “mycetoma” ◦ Allergic fungal rhinosinusitis

65.  Corollary to allergic bronchopulmonary aspergillosis (ABPA)  AFRS cycle ◦ Immune and eosinophilic response to protein components of fungi ◦ Sinonasal inflammation, viscid allergic fungal mucin, obstruction, stasis

66.  Bony remodeling  Inflammatory mediators ◦ Major basic protein ◦ Eosinophilic peroxidase ◦ Tumor necrosis factor ◦ Interleukins ◦ Interferons

67.  Evidence of Type I hypersensitivity (IgE mediated)  Nasal polyposis  Characteristic CT findings  Eosinophilic mucous  Positive fungal smear Kuhn and Javer: Otolaryngol Clin North Am 2000,33:2;419-432

68.  Asthma  Unilateral predominance  Radiographic bone erosion  Fungal culture  Charcot-Leyden crystals  Serum eosinophilia Kuhn and Javer: Otolaryngol Clin North Am 2000,33:2;419-432

69.  Not all 5 criteria for diagnosis  Gradual nasal airway obstruction  Thick nasal mucous/crusts  May take years to manifest  AFS-like syndrome

70.  Immunocompetent  Normal ESR, WBC  Atopic ◦ Asthma, hay fever, inhalant allergy Nasal polyposis

71.  Hyperactive allergic inflammatory response  Possible fungal toxin  Inflammatory mediators  Recurrent bacterial sinusitis

72.  Role of IgE  Not consistently elevated in serum  Local IgE-mediated immune response in nasal mucosa  IgE as cause of inflammation or merely a marker

73.  Allergic response to fungus by skin testing and in vitro (radioallergosorbent) methodology  Variable culture results (64-100%) from sinus contents

74.  Allergic fungal mucin ◦ Sheets of eosinophils ◦ Charcot-Leyden crystals ◦ Extramucosal fungal elements

76.  CT ◦ Unilateral or asymmetric ◦ Sinuses Expanded--Bony attenuation or erosion ◦ Displacement of adjacent structures ◦ Signal heterogeneity Manning S et al. Laryngoscope 1997;107:170-176

79.  MRI-T1 weighted ◦ Variable signal intensity in involved sinuses ◦ Signal void at periphery (mucosal edema)  MRI-T2 weighted  Hypointensity of signal in sinus (dehydrated allergic fungal mucin)  Enhancement of periphery of sinus (mucosal edema)

83.  Medical  Surgical  Break the Allergic Fungal Rhinosinusitis Cycle

84.  Functional endoscopic sinus surgery  Complete ventilation of the sinuses  Wide maxillary antrostomies  Complete ethmoidectomies  Sphenoid sinusotomies  Frontal sinusotomies

85.  Complete removal of allergic fungal mucin and fungal debris  Mucosal sparing  Save middle turbinate  Frontal sinus obliteration not advised

86.  PREOPERATIVE REGIMEN ◦ Antibiotics ◦ Steroids

87.  POSTOPERATIVE REGIMEN ◦ Steroid taper ◦ Intranasal steroids ◦ Antibiotics ◦ Clinic endoscopy and debridement

88.  Long-term systemic steroids ◦ Effective ◦ Multiple potential complications ◦ Screen for DM, cataracts, glaucoma, + PPD, active hepatitis

89.  Systemic antifungal agents  Amphotericin B, itraconazole, voriconazole  Mixed results  Expensive  Hepatotoxic  Need regular evaluation of liver function tests

90.  83 patients managed with ESS, itraconazole, low dose oral steroids, topical steroids  36,000 doses of itraconazole—no adverse effects  Reoperation required in only 20% Rains et al. AJR 2003;17:1-8

91. Intranasal Amphotericin irrigation—chronic rhinosinusitis patients Ponikau et al. J Allergy Clin Immunol 2002:110:862-866 Reduced mucosal inflammation on CT scan Improvement in symptoms and endoscopic staging in 75% Ricchetti et al. J Laryngol Otol 2002;116:261-263 Disappearance of polyps in 62% of mild and 42% of moderate chronic rhinosinusitis

92.  Beneficial ◦ Mabry, Marple et al. (1997 and 1998) ◦ Prospective study, immunotherapy after surgery, patients improved, did not require systemic steroids, recurrences decreased ◦ Retrospective study, 11 patients matched with controls, immunotherapy patients had improved quality of life and objective endoscopic measures of mucosal edema

93.  Both fungal and nonfungal antigens, administered in separate vials  Weekly immunotherapy, dosage advancement as tolerated  Include wide variety of mold antigens  Continue for 3-5 years  Regular endoscopy and cleaning

94.  Caveats  Ferguson (1993) reported patients who received immunotherapy prior to surgery had worsening of symptoms-ongoing antigenic load  local reactions, immune complex deposits  Patients who received immunotherapy after surgery improved  Caution with concomitant ABPA, unable to surgically remove fungi in lower respiratory tract

95.  Recurrence of disease common  Surgical treatment mandatory  Multidisciplinary management ◦ Steroids, antifungals—systemic vs. topical ◦ Immunotherapy

96.  Better control with prolonged postoperative medical therapy  Probably immunological disease, not infectious  Therapy evolving as understanding of disease process improves  Prolonged, close follow-up needed