真菌性鼻竇炎課件

1、FUNGAL SINUSITISDavid Gleinser, MDPatricia Maeso, MDThe University of Texas Medical Branch (utmb health)Department of OtolaryngologyGrand Rounds PresentationJanuary 30, 2012FUNGAL SINUSITISDavid GleinserIntroductionFungi are ubiquitousImmune system keeps organisms suppressedMost infections are benig

2、n, non-invasiveImmunocompromised higher risk of invasive diseaseNon-invasive vs. invasiveIntroductionFungi are ubiquitoBasic Mycology20,000 1.5 million fungal speciesFew dozen species cause human infectionForms: yeast or moldYeastUnicellularReproduce asexually by buddingPseudohyphae when bud doesnt

3、detach from yeastMoldMulticellularGrow by branching hyphaeBasic Mycology20,000 1.5 milPseudohyphae vs. HyphaePseudohyphae vs. HyphaeBasic MycologySporeReproductive structure produced in unfavorable conditionsWithstand many adverse conditionsFavorable environment growthInhalation of spores most commo

4、n way fungi infiltrate sinuses to cause diseaseBasic MycologySporeBasic MycologyMicroscopic Appearance of Specific FungiAspergillusSeptated hyphae with branching at 45MucromycosisNonseptated hyphae with branching at 90Basic MycologyMicroscopic AppeAspergillusNote septations (yellow arrows) and 45 de

5、gree branching (red arrows)AspergillusNote septations (yeNote the 90 degree branching and lack of septationsNote the 90 degree branching aClassification of InfectionNon-invasiveSaprophytic fungal infestationSinus fungal ball (mycetoma)Allergic fungal sinusitisInvasiveAcute fulminant invasive fungal

6、sinusitisChronic invasive fungal sinusitisGranulomatous invasive fungal sinusitisClassification of InfectionNonSaprophytic Fungal InfestationVisible growth of fungus on mucus crusts without invasionMinimal to no sinonasal symptomsDiagnosisEndoscopic visualization of crusts with fungiTreatmentRemoval

7、 of crustsNasal saline irrigationsWeekly nasal endoscopy with removal of crusts until disease process resolvesSaprophytic Fungal InfestationSinus Fungal Ball (Mycetoma)Sequestration of fungal elements within a sinus without invasion or granulomatous changesInhaled spores grow while evading host immu

8、ne system (no invasion)Aspergillus most common speciesMaxillary sinus most often involved (70-80% of cases)Sinus Fungal Ball (Mycetoma)SeSinus Fungal Ball (Mycetoma)ClinicallySymptoms due to mass effect and sinus obstructionPresents similar to rhinosinusitisCongestion, facial pain, headache, rhinorr

9、heaPhysical examinationMild to minimal mucosal inflammationPolyps in 10% of casesSinus Fungal Ball (Mycetoma)ClSinus Fungal Ball (Mycetoma)DiagnosisCT ScanSingle sinus in 59-94% of cases (maxillary)Complete or subtotal opacification of sinusRadiodensities within the opacificationsDue to increased he

10、avy metal contentBony sclerosis; destruction is rare (3.6-17% of cases)Biopsy = fungal elementsSinus Fungal Ball (Mycetoma)DiFungal BallImages show thickening of bony walls (short arrows) and heterodense material within the sinus with calcifications (long arrows) Fungal BallImages show thickenSinus

11、Fungal Ball (Mycetoma)TreatmentComplete surgical removal of fungal ballIrrigation of involved sinusesAntifungal therapyOnly if patient is high risk for invasive disease (very rare)Severely immunocompromisedContinued recurrence of disease despite proper medical/surgical managementConsider topical ant

12、ifungal irrigation first and then systemic therapy if no improvementSinus Fungal Ball (Mycetoma)TrFungal BallFungal BallAllergic Fungal SinusitisFungal colonization resulting in allergic inflammation without invasionIgE mediated response to fungal proteinSymptoms:Nasal obstruction (gradual)Rhinorrhe

13、aFacial pressure/painSneezing, watery/itchy eyesPeriorbital edemaAllergic Fungal SinusitisFungaAllergic Fungal SinusitisDiagnostic CriteriaEosinophlic mucinNasal polyposisRadiographic findingsImmunocompetanceAllergy to fungiAllergic Fungal SinusitisDiagnAllergic Fungal SinusitisEosinophilic MucinPat

14、hognemonicThick, tenacious and highly viscousTan to brown or dark green in appearanceMicroscopic examinationBranching fungal hyphaeSheets of eosinophilsCharcot-Leyden crystalsBreakdown of cells by enzymes produced by eosinophilsSlender and pointed at each endPair of hexagonal pyramids joined at base

15、sAllergic Fungal SinusitisEosinEosinophilic MucinEosinophilic MucinAllergic Fungal SinusitisRadiographic findingsCTUnilateral (78% of cases)Sinus expansionBone destruction in 20% of casesMore often in advanced or bilateral disease“Double Densities”Heterogeneity of signal increased heavy metal conten

16、t (iron and manganese) and calcium saltsAllergic Fungal SinusitisRadioAllergic Fungal SinusitisArrows show double densities. Note sinus expansionAllergic Fungal SinusitisArrowAllergic Fungal SinusitisDouble densities (arrows). Expansion of sinus with extension of disease into the nasal cavity (star)

17、Allergic Fungal SinusitisDoublAllergic Fungal SinusitisRadiographic findingsMRIVariable signal intensity on T1 (usually hyperintense)T2 hypointense central portion (low water content of mucin) with peripheral enhancement due to edemaAllergic Fungal SinusitisRadioAllergic Fungal SinusitisT1 MRI high

18、signal intensity of debris T2 MRI central area of low intensity surrounded by high intense signalAllergic Fungal SinusitisT1 MRAllergic Fungal SinusitisT1 MRI high signal intensity of debris T2 MRI central area of low intensity surrounded by high intense signalAllergic Fungal SinusitisT1 MRAllergic

19、Fungal SinusitisAllergy to FungiMost patient with AFS will have allergy to fungus causing diseaseManning et alProspective studyCompared8 patients with AFS and (+)culture with Bipolaris10 controls with chronic rhinosinusitisAll 8 patients showed (+) skin testing, RAST, and ELISA to Bipolaris8 of 10 c

20、ontrols (-) for all testsIgE levels 1000 IU/mLAllergic Fungal SinusitisAllerAllergic Fungal SinusitisTreatmentSurgicalRemove all mucinProvide permanent drainage and ventilation of affected sinusesSystemic +/- topical steroidsSystemic steroids decrease rate of recurrenceCourse can range from 2-12 mon

21、thsSchubert showed that longer courses had better results, but more side effects0.5mg/kg Prednisone starting dose and taper over 2-3 monthsAllergic Fungal SinusitisTreatAllergic Fungal SinusitisImmunotherapyDecrease recurrenceAlleviate need for steroidsProspective reviewAll patients had surgery and

22、systemic steroidsOne group got immunotherapy, the other did notConsisted of fungal and non-fungal antigens to which patients were sensitiveAfter 1 year:No requirement for systemic or topical steroids by patients in immunotherapy groupRecurrence of disease significantly less in immunotherapy groupAll

23、ergic Fungal SinusitisImmunAllergic Fungal SinusitisImmunotherapyFolker et alRetrospective studyCompared 11 patients who received immunotherapy post-operatively vs. 11 who did notRecurrence rates did NOT decreaseHowever:Quality of life scores and mucosal edema were much better in those who received

24、immunotherapyAllergic Fungal SinusitisImmunAcute Fulminant Invasive Fungal SinusitisPatient populationMost often compromised immune systemDM, AIDS, hematologic malignancies, organ transplant, iatrogenic (chemotherapy and steroids)Most common fungiAspergillusMucormycosisMucor, Rhizopus, AbsidiaLess c

25、ommon fungiCandidaBipolarisFusariumAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisPathogenesisSpores inhaled fungus grows in warm, humid sinonasal cavityFungi invade neural and vascular structures with thrombosis of feeding vesselsNecrosis and loss of sensation acidic environ

26、ment further fungal growthExtrasinus extension occurs via bony destruction, perineural and perivascular invasionNasal and palate mucosa destroyedFacial anesthesiaProptosisCranial nerve deficitsMental status changesAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisOther signs/sym

27、ptomsFever (most common 90% of cases)Loss of sensation over face or oral cavityUlceration of face and sinonasal/palatal mucosaRhinorrhea, facial pain/anesthesia, headachesSeizures, CN deficitsFast progressing symptomsIn some cases, hours to days till death!Acute Fulminant Invasive FungaAcute Fulmina

28、nt Invasive Fungal SinusitisEndoscopic findingsLoss of sensation and change in appearance of mucosa (pale or black)Most consistent findingUlcerations and black mucosa are late findingsSerial examinations are requiredAcute Fulminant Invasive Funga真菌性鼻竇炎課件Acute Fulminant Invasive Fungal SinusitisBiops

29、y + CultureShould always be performed when:Suspect fungal diseaseChange in sensation or color of mucosaAny immunocompromised patient with signs of sinusitis who fails to improve after 72 hours of IV antibioticsWhere?Diseased mucosa (pale, insensate, ulcerative, black)Normal appearance/sensationMiddl

30、e turbinate most common spot for AFIFS (67%)Septum 24% of casesMust request silver stainingCultureVery difficult to get (+) result, especially with MucormycosisAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisRadiographic studiesCT sinusMRI to assess tissue invasion, and orbita

31、l, intracranial, or neural involvementFindingsCTBone erosion and extrasinus extension classic findingSevere, unilateral mucosal thickeningThickening of periantral fat planesAcute Fulminant Invasive FungaCT scans; Left image: Destruction of medial wall of orbit with extension of disease into the orbi

32、t. Right image: Destruction of medial and inferior walls of the orbit with extension of disease into the orbitCT scans; Left image: DestructAxial CT scans. Left image: invasion through lateral wall of the sphenoid sinus and into the cavernous sinus. Right image: lack of enhancement of the cavernous

33、sinus due to fungal thrombosisAxial CT scans. Left image: iAcute Fulminant Invasive Fungal SinusitisMRIObliteration of the periantral fatLeptomeningeal enhancement (intracranial extension)Granuloma formationHypointense on T1 and T2Extrasinus extensionCavernous sinus involvementAbsent flow void of ca

34、rotidSoft tissue thickening of the involved sinusAcute Fulminant Invasive FungaAxial MRI, T2 left sphenoid sinus with central hypointense region with surrounding hyperintensity. Flow void in left cavernous sinus absent (arrow)Axial MRI, T2 Acute infarction of the left temporal lobe in same patientAx

35、ial MRI, T2 left sphenoid Acute Fulminant Invasive Fungal SinusitisCombination of medical and surgical treatmentMedicalCorrect the underlying compromised stateReverse DKA and improve hydration80% survival if done promptlyAbsolute neutrophil count 1000 = poor prognosisWBC transfusion and granulocyte

36、colony stimulating factor to increase ANCAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisMedical treatmentSystemic antifungalsAmphotericin B infusion1mg/kg/daySerious side effectsototoxicity, nephrotoxicity (occurs in 80% of cases)Lipid-based form of Amphotericin BMore expensi

37、veLess toxicCan achieve higher concentrations of drugVoriconazole or itraconazoleUsed most often when Aspergillus involvedMuch less toxic than Amphotericin BMucormycosis are resistant to theseAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisTopical Amphotericin B rinsesHave sho

38、wn some success, but mixed resultsSurgical treatmentGoalsDecrease pathogen loadRemove devitalized tissueEstablish pathways for sinus drainageDebride until clear, bleeding marginsAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisEndoscopic vs. Open proceduresRecommend endoscopic

39、in early course of diseaseDecreased morbiditySimilar survival rates as open proceduresAdvanced disease (orbit, palatal, skin)Open approach requiredOnce disease has gone intracranial, prognosis is very poorMust be considered prior to partaking in extensive surgical resectionAcute Fulminant Invasive F

40、ungaAcute Fulminant Invasive Fungal SinusitisRetrospective review out of TurkeyExamined treatment of AFIFS26 patient19 endoscopic resection7 open resection5 orbital exenteration (2 survived)All patients with skull base/intracranial extension diedOverall mortality rate 50%Survival ratesEndoscopic 90%

41、 (less severe disease)Open 57%In those who died, Mucormycosis were involved in 62% of casesMore aggressive with early orbital and intracranial invasionAcute Fulminant Invasive FungaAcute Fulminant Invasive Fungal SinusitisPrognosisMortality rate: 18-80%Early detection and treatment = much better cha

42、nce of survivalIntracranial involvementMost predictive indicator for mortality70%+ mortality rateAbsolute Neutrophil Count (ANC) 80% of cases)BipolarisCandidaMucormycosisChronic Invasive Fungal SinusiChronic Invasive Fungal SinusitisSigns/SymptomsSimilar to symptoms of chronic rhinosinusitisNasal co

43、ngestion, rhinorrhea, facial pressure, headaches, polyposisProptosis, visual changes, anesthesia of skin, epistaxisMore concerningDoes not respond to antibioticsWorsens with steroidsChronic Invasive Fungal SinusiChronic Invasive Fungal SinusitisDiagnosisFull H&N examination with nasal endoscopyNasal

44、 polyps, thick mucusRarely find ulcerationsBiopsy if suspect fungal disease or note any changesCT & MRISimilar findings to AFIFS bony destruction, extrasinus extension, unilateralChronic Invasive Fungal SinusiCT showing destruction of right lateral maxillary sinus and zygomatic archCT showing opacif

45、ication of left maxillary sinus with extrasinus extension of disease into the periantral tissues (arrows)CT showing destruction of righChronic Invasive Fungal SinusitisDiagnosisPathologyInvasion of blood vessels, neural structures, and surrounding mucosaFew if any inflammatory cellsMajor difference

46、between acute and chronic invasive diseaseNo Granuloma formationMain difference between chronic invasive fungal disease and granulomatous invasive fungal diseaseChronic Invasive Fungal SinusiChronic Invasive Fungal SinusitisTreatmentSimilar to AFIFS surgical + medicalSurgeryresect all involved tissu

47、e to expose bleeding marginsSystemic antifungalsStart with Amphotericin B until can rule out MucormycosisBest length of treatment not well studied Most recommend 3-6 months of therapyTopical Amphotericin B sinus rinsesClose F/U and debridement requiredBiopsy anything that is suspicious as asymptomatic recurrence is not uncommonChronic Invasive Fungal SinusiGranulomatous Invasive Fungal SinusitisAppears exactly like CIFSVery rarePresen