Marilene B. Wang, MD, FACSProfessor

UCLA Division of Head Neck SurgeryChief of Otolaryngology

VA Greater Los Angeles Healthcare System

From Anterior Nasal Spine◦To Sphenoid Ostium 7 cm

◦To Pituitary Fossa 8.5 cm

Middle turbinateLamina papyraceaEthmoid foveaCribriform plateSphenoid

Facial pain/pressureNasal obstruction/blockage

Nasal discharge/purulence/discolored postnasal drip

Hyposmia/anosmiaPurulence in nasal cavity on examination

Fever (acute rhinosinusitis only)

HeadacheFeverHalitosisFatigue

Dental painCoughEar pain/pressure/fullness

AcuteSubacuteChronicRecurrent, acuteAcute exacerbations of chronic

Duration up to 4 weeks> 2 major factors1 major factor + 2 minor factors

Nasal purulence on exam

Duration 4-12 weeks>2 major factors1 major factor + 2 minor factors, or nasal purulence on exam

Complete resolution after effective medical therapy

Duration > 12 weeksHistory same as for subacuteFacial pain does not constitute suggestive history in absence of other nasal symptoms or signs

>4 episodes/year + each episode last >7-10 days.

Absence of intervening signs of chronic rhinosinusitis

Sudden worsening of chronic rhinosinusitis

Return to baseline after treatment

AllergiesImmunodeficiencyGenetic/congenital

EndocrineNeuromechanism

AnatomicNeoplasticAcquired mucociliary dysfunction

• Microorganisms—viral, bacterial, fungal

• Noxious chemicals, pollutants, smoke

• Medications• Trauma• Surgery

• 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%)

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

Mild disease with no recent antimicrobial use

Augmentin, AmoxicillinVantinCeclorOmnicef

Tequin, Levaquin, AveloxAugmentinCombination (Amox or clinda + Suprax)

BactrimDoxycyclineZithromax, Biaxin, Erythromycin

Switch to quinolone if no improvement in 72 hours

QuinoloneAugmentinClindamcin + rifampinConsider IV abx

Augmentin, AmoxicillinVantinCeclorOmnicefSwitch if no improvement after 72 hours

BactrimMacrolide

AugmentinRocephinBactrim, macrolideConsider IV abx if no improvement

Afrin for 3 daysNormal saline spraysDecongestantsAntihistamines?Steroids

Periorbital cellulitisPreseptal cellulitis/abscess

Orbital cellulitisOrbital abscessCavernous sinus thrombosis

• 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

Allergic saluteShinersItchy, red conjunctivaSneezingPost-nasal drip, rhinorrhea, congestion

DustMold, mildewPlantsAnimal danderFeathers/down

PollenSmogTrees, grasses, weedsDust, fertilizer, chemicals

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

Nasal polyposisSamter’s triad (aspirin sensitivity, nasal polyps, asthma)

Cocaine use

AntibioticsAntihistaminesNasal steroidsNormal saline irrigationsAllergy evaluation +/- immunotherapy

Sinus CT scanConsider anatomic factors—septal deviation, nasal polyps, concha bullosa, ostio-meatal blockage

Nasal polyposisAnatomic blockage—deviated septum, enlarged turbinate, concha bullosa

MucoceleOrbital abscess

Fungal sinusitis—allergic vs. invasive (mucor)

Tumor of nasal cavity or sinus

Chronic, recurrent sinusitis

Failure to respond to maximal medical therapy

Obtain cultures

Nasal congestionHeadache/sinus painFatigueProlonged bleeding/crusting

Breach of lamina papyracea—damage to extraocular muscles, periorbital ecchymoses

Damage to optic nerve—blindness

Breach of cribriform—CSF leakMeningitis

May be a lifelong diseaseAllergy control—antiihistamines, nasal steroids, immunotherapy

Oral steroids—judiciouslyAntibiotics for acute exacerbations

Environmental control—avoid carpet, damp, mold, older homes, smog

Saline irrigations

Alternative therapies—acupuncture, stress management, herbal remedies

Pain managementMulti-disciplinary effort—work with allergy, infectious disease, neurology/pain management services

4 types of allergic reactions (Gell and Coombs)

Type 1 – IgEType 2 - IgG--antigenType 3 – Immune complexType 4 – Delayed hypersensitivity

• 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

• 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

• 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

• 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

Parents with allergy greater likelihood of producing allergic children

Food allergies Environment— air pollution Smoking

History—environmental exposure, smoking, seasonal occurrence, pets, foods

Examination ◦ Allergic shiners◦ Allergic salute◦ Supratip crease◦ Dennie’s lines (skin fold under eyes)◦ Adenoid facies

Skin testing◦ Prick/puncture (scratch or patch)◦ Intradermal◦ Dilutional intradermal (skin end-point

titration-SET) In vitro testing

◦ RAST (radioactive marker)◦ ELISA (enzymatic marker)

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

• 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

Avoid medications which may interfere◦Antihistamines◦Antidepressants◦Antacids

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

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

ELISA – enzyme linked immunosorbent assay

Used more for food allergies Not as sensitive as skin tests

Environmental control◦ Stop smoking, clean house, avoid mold,

indoor plants, pets, HEPA filter Pharmacotherapy

◦ Antihistamines, anti-leukotrienes, mast-cell stabilizers, topical and systemic steroids

Specific allergens Vial test

◦ Intradermal test◦ Smallest measurable dose

Once or twice weekly injections Dose escalated Continue treatment 3-5 years

Invasive◦Acute fulminant ◦Chronic invasive◦Granulomatous invasive

Noninvasive◦Saprophytic fungal infestation

◦Fungal ball, “mycetoma”◦Allergic fungal rhinosinusitis

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

Bony remodeling Inflammatory mediators

◦Major basic protein◦Eosinophilic peroxidase◦Tumor necrosis factor◦Interleukins◦Interferons

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

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

Not all 5 criteria for diagnosis

Gradual nasal airway obstruction

Thick nasal mucous/crustsMay take years to manifest

AFS-like syndrome

ImmunocompetentNormal ESR, WBCAtopic◦Asthma, hay fever, inhalant allergy

•Nasal polyposis

Hyperactive allergic inflammatory response

Possible fungal toxinInflammatory mediatorsRecurrent bacterial sinusitis

Role of IgENot consistently elevated in serum

Local IgE-mediated immune response in nasal mucosa

IgE as cause of inflammation or merely a marker

Allergic response to fungus by skin testing and in vitro (radioallergosorbent) methodology

Variable culture results (64-100%) from sinus contents

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

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

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)

MedicalSurgicalBreak the Allergic Fungal Rhinosinusitis Cycle

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

Complete removal of allergic fungal mucin and fungal debris

Mucosal sparingSave middle turbinateFrontal sinus obliteration not advised

PREOPERATIVE REGIMEN◦Antibiotics◦Steroids

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

Long-term systemic steroids◦Effective ◦Multiple potential complications

◦Screen for DM, cataracts, glaucoma, + PPD, active hepatitis

Systemic antifungal agents Amphotericin B, itraconazole,

voriconazole Mixed results Expensive Hepatotoxic Need regular evaluation of liver

function tests

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

• Intranasal Amphotericin irrigation—chronic rhinosinusitis patients

Ponikau et al. J Allergy Clin Immunol 2002:110:862-866

Reduced mucosal inflammation on CT scanImprovement in symptoms and endoscopic staging in 75%

Ricchetti et al. J Laryngol Otol 2002;116:261-

263Disappearance of polyps in 62% of

mild and 42% of moderate chronic rhinosinusitis

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

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

Caveats Ferguson (1993) reported patients

who received immunotherapy prior to surgery had worsening of symptoms-ongoing antigenic loadlocal reactions, immune complex deposits

Patients who received immunotherapy after surgery improved

Caution with concomitant ABPA, unable to surgically remove fungi in lower respiratory tract

Recurrence of disease commonSurgical treatment mandatoryMultidisciplinary management

◦Steroids, antifungals—systemic vs. topical

◦Immunotherapy

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