1、DaviD Gleinser,MDPatricia Maeso,MDthe University of texas MeDical Branch (UtMB health)DePartMent of otolarynGoloGyGranD roUnDs PresentationJanUary 30,2012introDUctionFungi are ubiquitousImmune system keeps organisms suppressedMost infections are benign,non-invasiveImmunocompromised higher risk of in
2、vasive diseaseNon-invasive vs.invasiveBasic MycoloGy20,000 1.5 million fungal speciesFew dozen species cause human infectionForms:yeast or moldYeastUnicellularReproduce asexually by buddingPseudohyphae when bud doesnt detach from yeastMoldMulticellularGrow by branching hyphaePseUDohyPhae vs.hyPhaeBa
3、sic MycoloGySporeReproductive structure produced in unfavorable conditionsWithstand many adverse conditionsFavorable environment growthInhalation of spores most common way fungi infiltrate sinuses to cause diseaseBasic MycoloGyMicroscopic Appearance of Specific FungiAspergillusSeptated hyphae with b
4、ranching at 45MucromycosisNonseptated hyphae with branching at 90asPerGillUsNote septations(yellow arrows)and 45 degree branching(red arrows)Note the 90 degree branching and lack of septationsclassification of infectionNon-invasiveSaprophytic fungal infestationSinus fungal ball(mycetoma)Allergic fun
5、gal sinusitisInvasiveAcute fulminant invasive fungal sinusitisChronic invasive fungal sinusitisGranulomatous invasive fungal sinusitissaProPhytic fUnGal infestationVisible growth of fungus on mucus crusts without invasionMinimal to no sinonasal symptomsDiagnosisEndoscopic visualization of crusts wit
6、h fungiTreatmentRemoval of crustsNasal saline irrigationsWeekly nasal endoscopy with removal of crusts until disease process resolvessinUs fUnGal Ball(MycetoMa)Sequestration of fungal elements within a sinus without invasion or granulomatous changesInhaled spores grow while evading host immune syste
7、m(no invasion)Aspergillus most common speciesMaxillary sinus most often involved(70-80%of cases)sinUs fUnGal Ball(MycetoMa)ClinicallySymptoms due to mass effect and sinus obstructionPresents similar to rhinosinusitisCongestion,facial pain,headache,rhinorrheaPhysical examinationMild to minimal mucosa
8、l inflammationPolyps in 10%of casessinUs fUnGal Ball(MycetoMa)DiagnosisCT ScanSingle sinus in 59-94%of cases(maxillary)Complete or subtotal opacification of sinusRadiodensities within the opacificationsDue to increased heavy metal contentBony sclerosis;destruction is rare(3.6-17%of cases)Biopsy=fung
9、al elementsfUnGal BallImages show thickening of bony walls(short arrows)and heterodense material within the sinus with calcifications(long arrows)sinUs fUnGal Ball(MycetoMa)TreatmentComplete surgical removal of fungal ballIrrigation of involved sinusesAntifungal therapyOnly if patient is high risk f
10、or invasive disease(very rare)Severely immunocompromisedContinued recurrence of disease despite proper medical/surgical managementConsider topical antifungal irrigation first and then systemic therapy if no improvementfUnGal BallallerGic fUnGal sinUsitisFungal colonization resulting in allergic infl
11、ammation without invasionIgE mediated response to fungal proteinSymptoms:Nasal obstruction(gradual)RhinorrheaFacial pressure/painSneezing,watery/itchy eyesPeriorbital edemaallerGic fUnGal sinUsitisDiagnostic Criteria1.Eosinophlic mucin2.Nasal polyposis3.Radiographic findings4.Immunocompetance5.Aller
12、gy to fungiallerGic fUnGal sinUsitisEosinophilic MucinPathognemonicThick,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 poin
13、ted at each endPair of hexagonal pyramids joined at baseseosinoPhilic 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 c
14、ontent(iron and manganese)and calcium saltsallerGic fUnGal sinUsitisArrows show double densities.Note sinus expansionallerGic fUnGal sinUsitisDouble densities(arrows).Expansion of sinus with extension of disease into the nasal cavity(star)allerGic fUnGal sinUsitisRadiographic findingsMRIVariable sig
15、nal intensity on T1(usually hyperintense)T2 hypointense central portion(low water content of mucin)with peripheral enhancement due to edemaallerGic fUnGal sinUsitisT1 MRI high signal intensity of debris T2 MRI central area of low intensity surrounded by high intense signalallerGic fUnGal sinUsitisT1
16、 MRI high signal intensity of debris T2 MRI central area of low intensity surrounded by high intense signalallerGic fUnGal sinUsitisAllergy to FungiMost patient with AFS will have allergy to fungus causing diseaseManning et alProspective studyCompared8 patients with AFS and(+)culture with Bipolaris1
17、0 controls with chronic rhinosinusitisAll 8 patients showed(+)skin testing,RAST,and ELISA to Bipolaris8 of 10 controls(-)for all testsIgE levels 1000 IU/mLallerGic fUnGal sinUsitisTreatmentSurgicalRemove all mucinProvide permanent drainage and ventilation of affected sinusesSystemic+/-topical steroi
18、dsSystemic steroids decrease rate of recurrenceCourse can range from 2-12 months-Schubert showed that longer courses had better results,but more side effects0.5mg/kg Prednisone starting dose and taper over 2-3 monthsallerGic fUnGal sinUsitisImmunotherapyDecrease recurrenceAlleviate need for steroids
19、Prospective reviewAll patients had surgery and 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 diseas
20、e significantly less in immunotherapy groupallerGic 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 thos
21、e who received immunotherapyacUte fUlMinant invasive fUnGal sinUsitisPatient populationMost often compromised immune systemDM,AIDS,hematologic malignancies,organ transplant,iatrogenic(chemotherapy and steroids)Most common fungiAspergillusMucormycosisMucor,Rhizopus,AbsidiaLess common fungiCandidaBipo
22、larisFusariumacUte 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 environment further fungal growthExtrasinus extension occurs
23、 via bony destruction,perineural and perivascular invasionNasal and palate mucosa destroyedFacial anesthesiaProptosisCranial nerve deficitsMental status changesacUte fUlMinant invasive fUnGal sinUsitisOther signs/symptomsFever(most common 90%of cases)Loss of sensation over face or oral cavityUlcerat
24、ion of face and sinonasal/palatal mucosaRhinorrhea,facial pain/anesthesia,headachesSeizures,CN deficitsFast progressing symptomsIn some cases,hours to days till death!acUte fUlMinant invasive fUnGal sinUsitisEndoscopic findingsLoss of sensation and change in appearance of mucosa(pale or black)Most c
25、onsistent findingUlcerations and black mucosa are late findingsSerial examinations are requiredacUte fUlMinant invasive fUnGal sinUsitisBiopsy+CultureShould always be performed when:Suspect fungal diseaseChange in sensation or color of mucosaAny immunocompromised patient with signs of sinusitis who
26、fails to improve after 72 hours of IV antibioticsWhere?Diseased mucosa(pale,insensate,ulcerative,black)Normal appearance/sensation-Middle turbinate most common spot for AFIFS(67%)-Septum 24%of casesMust request silver stainingCultureVery difficult to get(+)result,especially with MucormycosisacUte fU
27、lMinant invasive fUnGal sinUsitisRadiographic studiesCT sinusMRI to assess tissue invasion,and orbital,intracranial,or neural involvementFindingsCTBone erosion and extrasinus extension classic findingSevere,unilateral mucosal thickeningThickening of periantral fat planesCT scans;Left image:Destructi
28、on of medial wall of orbit with extension of disease into the orbit.Right image:Destruction of medial and inferior walls of the orbit with extension of disease into the orbitAxial CT scans.Left image:invasion through lateral wall of the sphenoid sinus and into the cavernous sinus.Right image:lack of
29、 enhancement of the cavernous sinus due to fungal thrombosisacUte fUlMinant invasive fUnGal sinUsitisMRIObliteration of the periantral fatLeptomeningeal enhancement(intracranial extension)Granuloma formationHypointense on T1 and T2Extrasinus extensionCavernous sinus involvementAbsent flow void of ca
30、rotidSoft tissue thickening of the involved sinusAxial 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 patientacUte fUlMinant invasive fUnGal sinU
31、sitisCombination of medical and surgical treatmentMedicalCorrect the underlying compromised stateReverse DKA and improve hydration-80%survival if done promptlyAbsolute neutrophil count-1000=poor prognosis-WBC transfusion and granulocyte colony stimulating factor to increase ANCacUte fUlMinant invasi
32、ve fUnGal sinUsitisMedical treatmentSystemic antifungalsAmphotericin B infusion1mg/kg/daySerious side effects-ototoxicity,nephrotoxicity(occurs in 80%of cases)Lipid-based form of Amphotericin BMore expensiveLess toxicCan achieve higher concentrations of drugVoriconazole or itraconazoleUsed most ofte
33、n when Aspergillus involvedMuch less toxic than Amphotericin BMucormycosis are resistant to theseacUte fUlMinant invasive fUnGal sinUsitisTopical Amphotericin B rinsesHave shown some success,but mixed resultsSurgical treatmentGoalsDecrease pathogen loadRemove devitalized tissueEstablish pathways for
34、 sinus drainageDebride until clear,bleeding marginsacUte fUlMinant invasive fUnGal sinUsitisEndoscopic vs.Open proceduresRecommend endoscopic in early course of diseaseDecreased morbiditySimilar survival rates as open proceduresAdvanced disease(orbit,palatal,skin)Open approach requiredOnce disease h
35、as gone intracranial,prognosis is very poorMust be considered prior to partaking in extensive surgical resectionacUte fUlMinant invasive fUnGal sinUsitisRetrospective review out of TurkeyExamined treatment of AFIFS26 patient19 endoscopic resection7 open resection5 orbital exenteration(2 survived)All
36、 patients with skull base/intracranial extension diedOverall mortality rate 50%Survival ratesEndoscopic 90%(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 fUnGal sinUsitisProg
37、nosisMortality rate:18-80%Early detection and treatment=much better chance of survivalIntracranial involvementMost predictive indicator for mortality70%+mortality rateAbsolute Neutrophil Count(ANC)80%of cases)BipolarisCandidaMucormycosischronic invasive fUnGal sinUsitisSigns/SymptomsSimilar to sympt
38、oms of chronic rhinosinusitisNasal congestion,rhinorrhea,facial pressure,headaches,polyposisProptosis,visual changes,anesthesia of skin,epistaxisMore concerningDoes not respond to antibioticsWorsens with steroidschronic invasive fUnGal sinUsitisDiagnosisFull H&N examination with nasal endoscopyNasal
39、 polyps,thick mucusRarely find ulcerationsBiopsy if suspect fungal disease or note any changesCT&MRISimilar findings to AFIFS bony destruction,extrasinus extension,unilateralCT showing destruction of right lateral maxillary sinus and zygomatic archCT showing opacification of left maxillary sinus wit
40、h extrasinus extension of disease into the periantral tissues(arrows)chronic invasive fUnGal sinUsitisDiagnosisPathologyInvasion of blood vessels,neural structures,and surrounding mucosaFew if any inflammatory cellsMajor difference between acute and chronic invasive diseaseNo Granuloma formationMain
41、 difference between chronic invasive fungal disease and granulomatous invasive fungal diseasechronic invasive fUnGal sinUsitisTreatmentSimilar to AFIFS surgical+medicalSurgeryresect all involved tissue to expose bleeding marginsSystemic antifungalsStart with Amphotericin B until can rule out Mucormy
42、cosisBest 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 uncommonGranUloMatoUs invasive fUnGal sinUsitisAppears exactly like CIFSVery ra
43、rePresence of multinucleated giant cell granulomasMost important difference between Chronic and Granulomatous diseaseAspergillus flavusMost often seen in North Africa and Southeast AsiaGranUloMatoUs invasive fUnGal sinUsitisPresentation and work-up are exactly the same as CIFSTreatmentSurgical resec
44、tion to bleeding marginsTopical antifungal rinsesSystemic antifungalsOral voriconazole or itraconazoleMinority of authors believe systemic antifungals not requiredClose F/U and debridement requiredBiopsy anything that is suspicious as asymptomatic recurrence is not uncommonconclUsionFungi are ubiqui
45、tousDisease in immunocompetent is nearly always benign,but must consider invasive diseaseInvasive fungal disease must be considered in all immunocompromised patientsLow threshold for biopsyconclUsionSurgical debridementMainstay of treatment of fungal sinus diseaseInvasive disease debride until clear
46、,bleeding marginsWeigh extent of surgery with prognosisSkull base/intracranial involvement very poor prognosis even with aggressive therapySystemic antifungals required for invasive diseaseMonitor for severe side effectsClose follow-up with debridement and biopsy of any suspicious lesions58写在最后写在最后成功的基础在于好的学习习惯成功的基础在于好的学习习惯The foundation of success lies in good habits谢谢聆听 学习就是为了达到一定目的而努力去干,是为一个目标去战胜各种困难的过程,这个过程会充满压力、痛苦和挫折Learning Is To Achieve A Certain Goal And Work Hard,Is A Process To Overcome Various Difficulties For A Goal
