Core Curriculum: Impact of HIV on Gastroenterology/Hepatology AshutoshAshutosh Barve,Barve, M.D.,M.D., Ph.D.Ph.D. Gastroenterology/HepatologyGastroenterology/Hepatology FellowFellow UniversityUniversityUniversity ofofof LouisvilleLouisville Louisville Case 4848 yearyear oldold manman presentspresents withwith aa historyhistory ofof :: dysphagiadysphagia odynophagiaodynophagia weightweight lossloss EGDEGD waswas donedone toto evaluateevaluate thethe problemproblem University of Louisville Case – EGD Report ExtensivelyExtensively scarredscarred esophagealesophageal mucosamucosa withwith mucosalmucosal bridging.bridging. DistalDistal esophagealesophageal nodulesnodules withwithUniversity superficialsuperficial ulcerationulceration of Louisville Case – Esophageal Nodule Biopsy InflammatoryInflammatory lesionlesion withwith ulceratedulcerated mucosamucosa SpecialSpecial stainsstains forfor fungifungi revealreveal nonnon-- septateseptate branchingbranching hyphaehyphae consistentconsistent withwith MUCORMUCOR University of Louisville Case TheThe patientpatient waswas HIVHIV positivepositive !!!! University of Louisville HAART (Highly Active Anti Retroviral Therapy) HIV/AIDS Before HAART After HAART University of Louisville HIV/AIDS BeforeBefore HAARTHAART AfterAfter HAARTHAART ImmuneImmune dysfunctiondysfunction ImmuneImmune reconstitutionreconstitution OpportunisticOpportunistic InfectionsInfections ManagementManagement ofof chronicchronic ¾ Prevention diseasesdiseases e.g.e.g. HepatitisHepatitis CC ¾ Management CirrhosisCirrhosis NeoplasmsNeoplasms ManagementManagement ofof drugdrug ¾ Management sideside effectseffects University of Louisville General Considerations for GI symptoms in AIDS ClinicalClinical signssigns andand symptomssymptoms seldomseldom correlatecorrelate withwith specificspecific diagnosisdiagnosis IfIf patientpatient isis onon HAARTHAART –– etiologyetiology isis usuallyusually nonnon--opportunisticopportunistic oror drugdrug inducedinduced LikelyLikely diagnosesdiagnoses basedbased inin extentextent ofof immunocompromiseimmunocompromise ÆÆ CD4CD4 << 100100 favorsfavors CMV,CMV, fungi,fungi, mycobacteriummycobacterium aviumavium complexcomplex (MAC)(MAC) whilewhile CD4CD4 >> 200200 favorsfavors commoncommon bacteriabacteriaUniversity andand otherother nonnon -of-opportunisticopportunistic Louisville infectionsinfections General Considerations for GI symptoms in AIDS InIn AIDS,AIDS, GIGI pathogenspathogens areare aa partpart ofof aa systemicsystemic infectionsinfections EarlyEarly endoscopyendoscopy isis keykey inin certaincertain settingssettings MultipleMultiple infectionsinfections areare commoncommon EvidenceEvidence ofof tissuetissue invasioninvasion ÆÆ hallmarkhallmark ofof pathogenicitypathogenicity University of Louisville General Considerations for GI symptoms in AIDS RecurrenceRecurrence ofof opportunisticopportunistic infectionsinfections isis commoncommon ÆÆ maintenancemaintenance antimicrobialantimicrobial maymay bebe neededneeded unlessunless HAARTHAART isis initiatedinitiated TreatmentTreatment ofof allall opportunisticopportunistic disordersdisorders shouldshould includeinclude HAARTHAART University of Louisville HIV/AIDS in Gastroenterology OdynophagiaOdynophagia andand DysphagiaDysphagia AbdominalAbdominal PainPain DiarrheaDiarrhea AnorectalAnorectal DiseaseDisease AbnormalAbnormal LFTLFT ViralViral HepatitidesHepatitides andand HIVHIV University of Louisville Differential Diagnosis of Dysphagia and Odynophagia in AIDS AIDS related esophageal disease Candida albicans* Cytomegalovirus* Idiopathic ulcerations* Herpes simplex Histoplasma capsulatum Mycobacterium avium complex Cryptosporidium spp. Neoplasm: Kaposi's sarcoma, lymphoma, squamous cell carcinoma, adenocarcinoma Non-AIDS esophageal disease Gastroesophageal reflux UniversityPill-induced esophagitis of Louisville ** More common Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. Candida albicans MostMost frequentfrequent esophagealesophageal infectioninfection inin AIDSAIDS MayMay occuroccur duringduring primaryprimary HIVHIV infectioninfection (transient(transient immunosupression)immunosupression) OralOral thrushthrush ÆÆ PPVPPV forfor esophagitisesophagitis == 90%90% NPVNPV forfor esophagitisesophagitis == 82%82% FrequentlyFrequently coexistscoexists withwith otherother disordersdisorders University of Louisville Candida albicans ClinicalClinical presentationpresentation:: SubsternalSubsternal dysphagiadysphagia OdynophagiaOdynophagia –– usuallyusually notnot veryvery severesevere DiagnosisDiagnosis –– byby EGDEGD FocalFocal oror diffusediffuse plaquesplaques inin associationassociation withwith mucosalmucosal hyperemiahyperemia andand friabilityfriability University of Louisville Candida esophagitis University of Louisville Candida albicans Histopathology:Histopathology: DesquamatedDesquamated epithelialepithelial cellscells withwith yeastyeast formsforms presentpresent onlyonly inin thethe superficialsuperficial epitheliumepithelium Esophageal squamous mucosa with numerous pseudohyphae admixed within an acute Universityinflammatory exudate of Louisville Candida albicans Treatment:Treatment: FluconazoleFluconazole ¾¾ 200200 mgmg loadingloading dosedose ¾¾100100 mgmg everyevery dayday NarcoticsNarcotics forfor painpain CaspofunginCaspofungin maymay bebe usedused inin resistantresistant casescases RelapseRelapse cancan bebe preventedprevented byby HAARTHAART University of Louisville CMV esophagitis ClinicalClinical Presentation:Presentation: OdynophagiaOdynophagia oror substernalsubsternal chestchest painpain –– usuallyusually severesevere DysphagiaDysphagia isis lessless commoncommon comparedcompared toto CandidaCandida FeverFever –– reportedreported occasionallyoccasionally AssociatedAssociated CandidaCandida infectioninfection -- commoncommon University of Louisville CMV esophagitis DiagnosisDiagnosis –– EGD:EGD: ExtensiveExtensive largelarge andand deepdeep ulcersulcers BiopsyBiopsy –– basebase ofof ulcerulcer providesprovides thethe highesthighest yieldyield BiopsyBiopsy moremore sensitivesensitive thanthan cultureculture University of Louisville CMV Esophagitis Cytomegalovirus and herpes simplex virus esophagitis. Multiple pathogens are frequently found in patients with AIDS.University of Louisville From Wilcox CM: Atlas of Clinical Gastrointestinal Endoscopy. Philadelphia, WB Saunders, 1995, p 28. CMV esophagitis HistopathologyHistopathology –– ViralViral cytopathiccytopathic effectseffects inin mesenchymalmesenchymal and/orand/or endothelialendothelial cellscells inin granulationgranulation tissue.tissue. IntranuclearIntranuclear inclusioninclusion bodiesbodies (Owls(Owls--eye)eye) maymay bebe absentabsent ÆÆ confirmationconfirmation byby immunohistochemistryimmunohistochemistryUniversity of Louisville CMV esophagitis Treatment:Treatment: GanciclovirGanciclovir –– 1414--2828 daysdays FoscarnetFoscarnet –– 1414--2828 daysdays CidofovirCidofovir –– 1414--2828 daysdays HAARTHAART University of Louisville HIV associated - Idiopathic ulcers ClinicalClinical PresentationPresentation andand EGDEGD findingsfindings:: IdenticalIdentical toto CMVCMV esophagitisesophagitis OdynophagiaOdynophagia worseworse thanthan dysphagiadysphagia MultipleMultiple largelarge deepdeep raisedraised ulcersulcers onon endoscopyendoscopy –– punchedpunched--outout appearance,appearance, normalnormal interveningintervening mucosamucosa University of Louisville HIV associated - Idiopathic ulcers University of Louisville From Wilcox CM: Atlas of Clinical Gastrointestinal Endoscopy. Philadelphia, WB Saunders, 1995, p 75. HIV associated - Idiopathic ulcers DiagnosticDiagnostic criteria:criteria: EndoscopicEndoscopic andand histopathologichistopathologic ulcerulcer NoNo viralviral cytopathiccytopathic effect,effect, negativenegative immunohistochemistryimmunohistochemistry forfor CMVCMV NoNo clinicalclinical oror endoscopicendoscopic evidenceevidence ofof refluxreflux diseasedisease oror pillpill--inducedinduced esophagitisesophagitis University of Louisville HIV associated - Idiopathic ulcers Treatment:Treatment: PrednisonePrednisone 4040 mg/daymg/day taperedtapered overover 44 weeksweeks isis moremore thanthan 90%90% effectiveeffective ThalidomideThalidomide ¾¾ whenwhen PrednisonePrednisone failsfails ¾¾ alsoalso veryvery highlyhighly effectiveeffective University of Louisville Herpes simplex esophagitis NotNot commoncommon inin AIDSAIDS –– alsoalso seenseen inin immunocompetentimmunocompetent patientspatients HSVHSV typetype II asas wellwell asas HSVHSV typetype IIII cancan causecause ShallowShallow ulcersulcers asas opposedopposed toto CMVCMV DiscreteDiscrete vesiclesvesicles ÆÆ shallowshallow ulcersulcers ÆÆ coalescecoalesce intointo regionsregions ofof diffusediffuse shallowshallow ulcerationsulcerations University of Louisville Herpes simplex esophagitis ShallowShallow ulcerationulceration withwith islandsislands ofof normalnormal--appearingappearing esophagealesophagealUniversity mucosamucosa of Louisville Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. Herpes simplex esophagitis Diagnosis:Diagnosis: BiopsiesBiopsies areare takentaken fromfrom ulcerulcer edgeedge BiopsiesBiopsies ,, cytologiccytologic brushingsbrushings (also(also fromfrom ulcerulcer edge)edge) asas wellwell asas cultureculture ofof biopsybiopsy specimenspecimen areare sensitivesensitive HistopathologyHistopathology –– nuclearnuclear changeschanges typicaltypical forfor HerpesHerpes virusvirus infectioninfection inin epithelialepithelial