Autoimmune Hepatitis/ Autoimmune Pancreatitis

Autoimmune Hepatitis/ Autoimmune Pancreatitis

EdmundEdmund Krasinski,Krasinski, JrJr.,., D.O.D.O. F.A.C.G.F.A.C.G. Assessment of Liver Function

„ WhichWhich ofof thethe followingfollowing isis notnot aa goodgood biochemicalbiochemical assessorassessor ofof hepatichepatic function?function? „ A)A) SerumSerum bilirubinbilirubin „ B)B) SerumSerum lactatelactate dehydrogenasedehydrogenase „ C)C) SerumSerum aspartateaspartate aminotransferaseaminotransferase (AST)(AST) „ D)D) SerumSerum alaninealanine aminotransferaseaminotransferase (ALT)(ALT) „ E)E) SerumSerum alkalinealkaline phosphatasephosphatase Assessment of Liver Function

„ CorrectCorrect answeranswer :: BB „ MeasurementMeasurement ofof LDHLDH andand eveneven moremore specificspecific LDHLDH--55 addsadds littlelittle toto evaluationevaluation ofof suspectedsuspected hepatichepatic dysfunctiondysfunction „ HighHigh levelslevels ofof LDHLDH seenseen in:in: „ HepatocellularHepatocellular necrosis,necrosis, IschemicIschemic hepatopathyhepatopathy ““shockshock liverliver””,, Cancer,Cancer, HemolysisHemolysis Case Presentation AA 3535 yr.yr. OldOld femalefemale presentspresents forfor evaluation.evaluation. SheShe hashas notednoted jaundicejaundice manifestmanifest byby scleralscleral icterusicterus,, acholicacholic stools,stools,choluriacholuria.. SheShe alsoalso complainscomplains ofof undueundue fatigue.fatigue. SheShe tooktook aa recentrecent triptrip toto NewNew OrleansOrleans wherewhere sheshe ateate rawraw oysters.oysters. Case Presentation

Meds:Meds: MacrodantinMacrodantin PhysicalPhysical examination:examination: GeneralizedGeneralized icterusicterus,,ScleralScleral icterusicterus,, TenderTender hepatomegalyhepatomegaly,, NoNo stigmatastigmata ofof chronicchronic liverliver diseasedisease Case presentation

Labs:Labs: SerumSerum bilirubinbilirubin 15.015.0 SerumSerum ASTAST 15001500 SerumSerum ALTALT 17001700 SerumSerum AlkAlk phosphos 120120 Case Presentation

„ WhichWhich ofof thethe followingfollowing diseasesdiseases areare consistentconsistent withwith thisthis clinicalclinical presentation?presentation? „ A)A) AutoimmuneAutoimmune hepatitishepatitis „ B)B) ViralViral hepatitishepatitis „ C)C) WilsonWilson’’ss DiseaseDisease „ D)D) DrugDrug--inducedinduced liverliver diseasedisease „ E)E) AllAll ofof thethe aboveabove Case Presentation

CorrectCorrect answer:answer: E)E) AllAll ofof thethe above.above. AllAll ofof thethe diseasesdiseases inin thethe differentialdifferential diagnosisdiagnosis cancan presentpresent asas such.such. AllAll cancan presentpresent withwith acuteacute decompensationdecompensation withwith primarilyprimarily hepatocellularhepatocellular dysdysfunctionfunction Case Presentation

„ AutoimmuneAutoimmune hepatitishepatitis-- ToTo bebe discusseddiscussed atat length.length. „ ViralViral hepatitis:hepatitis: HBsAgHBsAg,Anti,Anti--HBC,HBC,IgMIgM antianti-- HAV,HAV, AntiAnti--HCV.HCV. „ WilsonWilson’’ss Disease:Disease: SerumSerum ceruloplasminceruloplasmin,, 2424 hrhr urinaryurinary copper,copper, OpthoOptho evaleval forfor KayserKayser-- FleisherFleisher ringsrings „ DrugDrug inducedinduced liverliver dzdz..-- historyhistory ofof drugdrug POPO Autoimmune Hepatitis

Definition:Definition: AA selfself--perpetuatingperpetuating hepatichepatic inflammationinflammation ofof unknownunknown cause,cause, characterizedcharacterized byby interfaceinterface hepatitis,hepatitis, hypergammaglobulinemiahypergammaglobulinemia,and,and liverliver associatedassociated antibodies.antibodies. Exclusion of other conditions

„ WilsonWilson’’ss diseasedisease „ ChronicChronic viralviral hepatitishepatitis „ AlphaAlpha 11 antitrypsinantitrypsin deficiencydeficiency „ HereditaryHereditary hemochromotosishemochromotosis „ DrugDrug inducedinduced liverliver diseasedisease „ NonNon--alcoholicalcoholic steatohepatitissteatohepatitis „ ImmuneImmune cholangiopathiescholangiopathies:: PBC/PSCPBC/PSC Autoimmune Hepatitis

Nomenclature:Nomenclature: AIHAIH replacesreplaces termsterms ofof lupoidlupoid hepatitis,hepatitis, autoimmuneautoimmune liverliver disease,disease, andand autoimmuneautoimmune chronicchronic activeactive hepatitis.hepatitis. Autoimmune Hepatitis

„ NoNo subtypessubtypes formallyformally recognized,recognized, butbut descriptivedescriptive terms:terms: „ TypeType 11 „ TypeType 22 „ TypeType 33 Basic Diagnostic Tests

„ AST,AST, ALT,ALT, BilirubinBilirubin,, alkalk phosphos,, gammagamma globulinglobulin levelslevels (( AssessAssess severityseverity ofof liverliver injuryinjury andand characterizecharacterize thethe patternpattern ofof injury)injury) „ SerumSerum albumin,albumin, PT/INRPT/INR (( EstimateEstimate levellevel ofof impairmentimpairment ofof hepatichepatic syntheticsynthetic function)function) „ ANAANA (( AntinuclearAntinuclear antibody)antibody) „ ASMAASMA (( AntiAnti-- smoothsmooth musclemuscle antibody)antibody) „ AntiAnti-- LKMLKM 11 (Anti(Anti--liverliver kidneykidney microsomalmicrosomal antibodyantibody „ SLASLA (( SolubleSoluble liverliver antigen)antigen) Autoimmune Hepatitis

„ LiverLiver tissuetissue examinationexamination „ HistologicHistologic changeschanges confirmconfirm diagnosisdiagnosis „ InterfaceInterface hepatitishepatitis „ LobularLobular panacinarpanacinar hepatitishepatitis withwith interfaceinterface hepatitishepatitis Autoimmune Hepatitis

„ ViralViral hepatitishepatitis exclusion:exclusion: HBsAgHBsAg// AntiAnti-- HBcHBc//IgMIgM AntiAnti--HAV/HAV/ AntiAnti--HCVHCV „ WilsonWilson’’ss diseasedisease exclusion:exclusion: SerumSerum ceruloplasminceruloplasmin „ HHCHHC exclusion:exclusion: SerumSerum Fe,Fe, TIBC/TIBC/ %% sat/sat/ FerritinFerritin// HFEHFE analysis(ifanalysis(if needed)needed) International Criteria for Diagnosis

„ DiagnosticDiagnostic FeaturesFeatures „ DefinitiveDefinitive DiagnosisDiagnosis „ ExclusionExclusion ofof riskrisk „ DailyDaily ETOHETOH << 2525 factorsfactors forfor otherother gm/dgm/d diseasesdiseases „ NoNo hepatotoxichepatotoxic drugsdrugs „ NN AlphaAlpha 11 ATAT phenotypephenotype „ NormalNormal ceruloplasminceruloplasmin „ NormalNormal Fe/Fe/ ferritinferritin „ NoNo HAV/HBV/HCVHAV/HBV/HCV International Criteria for Diagnosis

„ DiagnosticDiagnostic FeaturesFeatures „ Probable Diagnosis „ Daily ETOH < 50 gm/ d „ ExclusionExclusion ofof riskrisk „ No Hepatotoxic drugs factorsfactors forfor otherother „ Partial A1 AT deficiency diseasesdiseases „ Abnormal cu/ ceruloplasmin but Wilson’s excluded „ Non-specific Fe/ Ferritin abnls „ No HAV/HBV/HCV International Criteria for Diagnosis Diagnostic Features Definitive Diagnosis Probable Diagnosis

Inflammatory Indices Serum AST/ALT elev Serum AST/ALT elev Min chol. chng Min Chol. Chng Auotantibodies ANA/ASMA/ALKM ANA/ASMA/ALKM ≥ 1: 80 (adults) ≥ 1: 40 ≥ 1: 20 (peds) Immunoglobulins Glob, IgG ≥1.5 N Inc. IgG any degree

Histologic features Interface hep. Mod- Same severe, no bile lesions, gran., other dz ∆ International Scoring System for Diagnosis

„ Factor „ Score „ + AMA „ -4 „ Viral Markers „ + „ -3 „ - „ +3 „ Hepatotoxic drugs „ Yes „ -4 „ No „ +1 „ Pretreatment score „ > 15 „ Definite diagnosis „ 10-15 „ Probable Diagnosis International Scoring System for Diagnosis „ Factors „ Score „ ETOH < 25 gm „ +2 „ ETOH > 60 gm „ -2 „ HLA DR3 or DR4 „ +1 „ Concurrent AI Dz „ +2 „ Other liver Ab „ +2 „ Interface Hepatitis „ +3 „ Plasmacytic inflitrate „ +1 „ Rosettes „ +1 „ No Charact. Features „ -5 „ Biliary changes „ -3 „ Fat/ granulomas „ -3 International Scoring System for Diagnosis

„ FactorsFactors „ ScoreScore „ TreatmentTreatment responseresponse „ +2+2 completecomplete

„ RelapseRelapse „ +3+3 „ PostPost treatmenttreatment scorescore

„ DefiniteDefinite DiagnosisDiagnosis „ >17>17 ProbableProbable diagnosisdiagnosis „ 1212--1717 Pathogenesis

„ PrincipalPrincipal HypothesisHypothesis „ AutoantigenAutoantigen DrivenDriven cellcell--mediatedmediated „ AutoantibodyAutoantibody DependentDependent cellcell-- mediatedmediated cytotoxicitycytotoxicity Subclassifications

„ TypeType 11-- ++ ANA/ASMAANA/ASMA „ MostMost commoncommon USAUSA „ FemaleFemale gendergender 78%78% „ ConcurrentConcurrent autoimmuneautoimmune diseasesdiseases 38%38% „ AutoimmuneAutoimmune thyroiditisthyroiditis 12%12% „ GravesGraves diseasedisease 6%6% „ UlcerativeUlcerative colitiscolitis 6%6% „ RheumatoidRheumatoid arthritisarthritis 11 %% „ PerniciousPernicious anemiaanemia 1%1% „ PSSPSS 1%1% Subclassifications

„ TypeType 11 „ CoombCoomb’’ss positivepositive hemolytichemolytic anemiaanemia 1%1% „ ITPITP 1%1% „ LeucocytoclasticLeucocytoclastic vasculitisvasculitis 1%1% „ NephritisNephritis 1%1% „ ErythemaErythema nodosumnodosum 1%1% „ PyodermaPyoderma gangrenosagangrenosa (( II havehave seenseen oneone case)case) „ FibrosingFibrosing alveolitisalveolitis 1%1% Subclassifications

„ TypeType 11 „ HLAHLA DR3DR3 andand DR4DR4 areare independentindependent riskrisk factorsfactors forfor susceptibilitysusceptibility andand suggestssuggests aa polygenicpolygenic disorder.disorder. Subclassifications

„ TypeType 22 „ ++ AntiAnti LKMLKM antibodyantibody „ AffectsAffects mainlymainly childrenchildren (2(2--1414 yrs)yrs) „ AffectsAffects 20%20% EuropeanEuropean adultsadults „ AffectsAffects 44 %% USAUSA patientspatients „ CommonlyCommonly associatedassociated with:with: „ VitiligoVitiligo „ DMDM--11 „ AutoimmuneAutoimmune thyroiditisthyroiditis Subclassifications

„ TypeType 33 „ ++ SolubleSoluble liverliver antigenantigen (SLA)(SLA) „ Newest,Newest, LeastLeast establishedestablished „ MaybeMaybe aa variantvariant ofof typetype 11 Variants

„ OverlapOverlap withwith PBCPBC „ ++ AMAAMA „ ++ bilebile ductduct injuryinjury onon histologyhistology „ ++ responseresponse toto steroidssteroids ifif alkalk phosphos ≤≤ 22 XX NormalNormal Variants

„ OverlapOverlap withwith PSCPSC „ +IBD+IBD „ ++ CholestaticCholestatic changeschanges „ ++ injuryinjury pattern:pattern: CholestasisCholestasis,, DuctopeniaDuctopenia,, portalportal fibrosis,fibrosis, portalportal edemaedema „ AbnormalAbnormal CholangiogramCholangiogram „ RefractoryRefractory toto corticosteroidscorticosteroids Variants

„ AutoimmuneAutoimmune CholangitisCholangitis „ ++ ANAANA oror ASMAASMA „ -- AMAAMA „ ++ CholestaticCholestatic changeschanges „ DuctopeniaDuctopenia// CholangitisCholangitis onon histologyhistology „ -- IBDIBD „ NormalNormal cholangiogramcholangiogram Variants

„ ConcurrentConcurrent HCVHCV „ ++ HCVRNAHCVRNA serumserum „ ANAANA oror ASMAASMA ≥≥ 1:1: 320320 „ HistologyHistology „ InterfaceInterface HepatitisHepatitis „ AbsenceAbsence ofof viralviral featuresfeatures Variants

„ Cryptogenic/Cryptogenic/ AutoantibodyAutoantibody negativenegative hepatitishepatitis „ ClassicClassic featuresfeatures ofof AIHAIH withoutwithout autoantibodiesautoantibodies „ ++ ResponseResponse toto conventionalconventional corticosteroidcorticosteroid regimensregimens Prevalence

„ TypeType 11-- 1.91.9 cases/cases/ 100,000100,000 perper yearyear „ TypeType 22-- 33 cases/cases/ 1,000,0001,000,000 perper yearyear (rare)(rare) „ 1111--23%23% ofof chronicchronic hepatitishepatitis inin USAUSA „ 5.9%5.9% OLTOLT inin USAUSA „ DiverseDiverse populations:populations: Caucasians,Caucasians, AfricanAfrican Americans,Americans, AlaskanAlaskan Natives,Natives, Japanese,Japanese, Hispanics,Hispanics, SubcontinentalSubcontinental Indians,Indians, Asians,Asians, Arabs.Arabs. Treatment

„ IndicationsIndications „ BasisBasis onon thethe severityseverity ofof hepatichepatic inflammationinflammation ratherrather thanthan thethe degreedegree ofof ofof hepatichepatic dysfunctiondysfunction „ Regimens:Regimens: „ PrednisonePrednisone alonealone „ Prednisone/Prednisone/ AzathioprineAzathioprine (AZA)(AZA) combinationcombination Treatment

„ PrednisonePrednisone alonealone „ WeaningWeaning scheduleschedule „ RelativeRelative contraindications:contraindications: Obesity,Obesity, OsteopeniaOsteopenia,, EmotionalEmotional labilitylability,, BrittleBrittle Diabetes,Diabetes, LabileLabile hypertension,hypertension, PostPost-- menopausalmenopausal state,state, AcneAcne Treatment

„ Prednisone/Prednisone/ AZAAZA „ WeaningWeaning scheduleschedule forfor PrednisonePrednisone „ AZAAZA 5050 mgmg oror (1.5(1.5--2.52.5 mg/kg/d)mg/kg/d) ifif neededneeded „ RelativeRelative contraindications:contraindications: SevereSevere cytopeniascytopenias,, ThiopurineThiopurine methyltransferasemethyltransferase deficiency,deficiency, Pregnancy,Pregnancy, ActiveActive NeoplasmNeoplasm Treatment Results

„ RemissionRemission „ 65%65% withinwithin 22 yearsyears „ FailureFailure „ 9%9% „ IncompleteIncomplete remissionremission „ 13%13% „ DrugDrug toxicitytoxicity „ 13%13% Promising Alternative Drugs

„ CyACyA-- CyclosporineCyclosporine „ TacrolimusTacrolimus „ MycophenolateMycophenolate MofetilMofetil „ 66--MercaptopurineMercaptopurine „ BudesonideBudesonide „ DeflazacortDeflazacort „ UrsodeoxycholicUrsodeoxycholic acidacid Conclusions

„ CriteriaCriteria forfor diagnosisdiagnosis havehave beenbeen quantifiedquantified andand aa quantitativequantitative scoringscoring systemsystem existsexists „ SubtypesSubtypes areare basedbased onon distinctivedistinctive serologicserologic markers,markers, butbut theirtheir validityvalidity notnot yetyet establishedestablished „ GeneticGenetic factorsfactors influenceinfluence susceptibility,susceptibility, clinicalclinical expression,expression, andand treatmenttreatment outcomesoutcomes Conclusions

„ EvolvingEvolving antibodyantibody discoveriesdiscoveries maymay havehave diagnosticdiagnostic andand prognosticprognostic valuevalue inin futurefuture „ VariantVariant formsforms areare commoncommon andand treatmenttreatment isis directeddirected atat thethe predominantpredominant featuresfeatures „ NovelNovel drugsdrugs areare emergingemerging Autoimmune Pancreatitis

„ HistoryHistory „ 19611961-- SarlesSarles,, etet al.,al., describeddescribed aa casecase ofof pancreatitispancreatitis associatedassociated withwith hypergammaglobulinemiahypergammaglobulinemia „ 19821982--84:84: PancreatitisPancreatitis withwith otherother AIDAID described:described: SjogrenSjogren’’ss syndrome,syndrome, PSC,PSC, PBCPBC Autoimmune Pancreatitis

„ 1992:1992: Toki,Toki, etet al.,al., ReportedReported fourfour casecase withwith unusualunusual narrowingnarrowing ofof pancreaticpancreatic ductduct withwith diffusediffuse enlargementenlargement ofof thethe pancreaspancreas withwith lymphocyticlymphocytic infiltrationinfiltration „ 1995:1995: JapaneseJapanese firstfirst reportreport thethe conceptconcept ofof AutoimmuneAutoimmune PancreatitisPancreatitis (AIP)(AIP) Autoimmune Pancreatitis

„ 1995:1995: TermsTerms used:used: DiffuselyDiffusely enlargedenlarged pancreas,pancreas, narrowednarrowed pancreatogrampancreatogram,, presencepresence ofof autoantibodiesautoantibodies (ANA),(ANA), fibroticfibrotic changeschanges withwith lymphocyticlymphocytic infiltration,infiltration, steroidalsteroidal efficacyefficacy „ 20032003--2007:2007: AcceptedAccepted asas newnew clinicalclinical entityentity Clinicopathologic Features of AIP „ Age/sex:Age/sex: MoreMore commonlycommonly elderlyelderly malesmales „ ClinicalClinical Symptoms:Symptoms: „ MildMild abdominalabdominal symptoms,symptoms, usuallyusually withoutwithout acuteacute attacksattacks ofof pancreatitispancreatitis „ OccasionalOccasional presencepresence ofof obstructiveobstructive jaundicejaundice Laboratory Data

„ IncreasedIncreased levelslevels ofof IgGIgG,, IgG4IgG4 „ PresencePresence ofof autoantibodiesautoantibodies „ IncreasedIncreased hepatobiliaryhepatobiliary// pancreaticpancreatic enzymesenzymes „ ImpairedImpaired exocrine/exocrine/ endocrineendocrine functionfunction Clinicopathologic Features

„ ImagingImaging ofof thethe pancreaticobiliarypancreaticobiliary systemsystem „ EnlargementEnlargement ofof thethe pancreaspancreas „ IrregularIrregular narrowingnarrowing ofof PDPD „ StenosisStenosis ofof intrapancreaticintrapancreatic bilebile ductduct „ SclerosingSclerosing cholangitischolangitis similarsimilar toto PSCPSC Histopathologic Findings

„ InterlobularInterlobular fibrosis,fibrosis, occasionallyoccasionally intralobularintralobular fibrosisfibrosis „ AtrophyAtrophy ofof aciniacini „ InfiltrationInfiltration ofof lymphocyteslymphocytes andand IgG4IgG4 positivepositive plasmaplasma cellscells „ ObliterativeObliterative phlebitisphlebitis Clinicopathologic Features

„ SclerosingSclerosing cholangitischolangitis similarsimilar toto PSCPSC „ SclerosingSclerosing SialadenitisSialadenitis „ RetroperitonealRetroperitoneal fibrosisfibrosis „ InterstitialInterstitial nephritisnephritis „ ChronicChronic thyroiditisthyroiditis „ InterstitialInterstitial pneumoniapneumonia „ LymphadenopathyLymphadenopathy ((MediastinalMediastinal/peritoneal/peritoneal „ PseudotumorPseudotumor:: pancreas/liver/lungpancreas/liver/lung „ IBDIBD Clinicopathologic Features

„ OccasionalOccasional associationassociation withwith otherother autoimmuneautoimmune diseasesdiseases „ EffectiveEffective steroidsteroid therapytherapy „ Prognosis:Prognosis: „ UnclearUnclear longlong termterm „ PancreaticPancreatic stonesstones inin somesome Epidemiology

„ RareRare „ RecentRecent reviewreview ofof 521521 casescases ofof chronicchronic pancreatitispancreatitis „ 6%6% AIPAIP Mayo Clinic Diagnostic Criteria

„ HistologyHistology „ LymphoplasmacyticLymphoplasmacytic infiltrateinfiltrate withwith storiformstoriform fibrosisfibrosis „ +/+/-- AbundantAbundant (>10(>10 cells/HPF)cells/HPF) IgG4IgG4-- positivepositive cellscells Mayo Clinic Diagnostic Criteria

„ ImagingImaging „ Typical: Diffusely enlarged pancreas w/ delayed rim enhancement and diffusely irregular, attenuated MPD „ Other: Focal pancreatic mass/ enlargement, focal PD stricture, Panc Atrophy, Panc Ca++,or pancreatitis Mayo Clinic Diagnostic Criteria

„ SerologySerology „ ElevatedElevated serumserum IgG4IgG4 levelslevels (8(8--140140 mg/dl)mg/dl) „ HilarHilar/IHD/IHD „ Other organ Other organ strictures,distalstrictures,distal CBDCBD involvementinvolvement strictures,strictures, parotid/parotid/ lacrimallacrimal ductsducts involvement,involvement, MediastinalMediastinal adenopathyadenopathy,, retroperitonealretroperitoneal fibrosisfibrosis Mayo Clinic Diagnostic Criteria

„ ResponseResponse toto steroidsteroid „ Resolution/Resolution/ MarkedMarked therapytherapy improvementimprovement ofof pancreatic/pancreatic/ extrapancreatcextrapancreatc manifestastionsmanifestastions w/w/ steroidsteroid therapytherapy Mayo Clinic Criteria/ Define AIP

„ GroupGroup A(PancreaticA(Pancreatic „ 1.1. AndAnd // oror 22 histology)histology) „ 1.1. TypicalTypical LPSPLPSP byby resectionresection oror corecore biopsybiopsy „ 2.2. IgG4IgG4 ++ cellscells >> 1010 HPFHPF Mayo Clinic Criteria / Define AIP

„ GroupGroup BB „ 1 + 2 +3 „ 1) CT or MRI with diffuse „ TypicalTypical ImagingImaging 1) CT or MRI with diffuse enlargement of pancreas „ AndAnd ElevatedElevated IgG4IgG4 or delayed rim enhancement „ 2) Diffusely irregular MPD on pancreatogram „ 3) Elevated IgG4 levels Mayo Clinic Criteria/ Define AIP

„ GroupGroup CC „ 11 +2+2 ++ 33 „ ResponseResponse toto steroidssteroids „ 1)1) UnexplainedUnexplained pancreaticpancreatic diseasedisease „ 2)2) ElevatedElevated IgG4IgG4 oror IgG4IgG4 inin otherother organsorgans „ 3)3) Resolution/Resolution/ ImprovementImprovement ofof manifestationsmanifestations w/w/ steroidssteroids Pathophysiology

„ HumoralHumoral ImmunityImmunity andand TargetTarget AntigensAntigens „ CellularCellular ImmunityImmunity andand EffectorEffector CellsCells Differential Diagnosis

„ PancreaticPancreatic carcinomacarcinoma „ MalignantMalignant LymphomaLymphoma „ PlasmacytomaPlasmacytoma „ MetastaticMetastatic carcinomacarcinoma „ DiffuselyDiffusely infiltrativeinfiltrative pancreaticpancreatic cancercancer „ BiliaryBiliary CarcinomaCarcinoma „ CholangiocarcinomaCholangiocarcinoma „ MetastaticMetastatic CarcinomaCarcinoma Treatment

„ Jaundice:Jaundice: BiliaryBiliary DecompressionDecompression „ SteroidSteroid therapy:therapy: ExtrapancreaticExtrapancreatic lesions,lesions, BileBile duct/duct/ PancreaticPancreatic lesionslesions „ SpontaneousSpontaneous improvementimprovement „ Surgery:Surgery: MayMay bebe neededneeded toto excludeexclude malignancymalignancy Prognosis

„ LongLong termterm prognosisprognosis unknownunknown „ Clinical/Clinical/ LaboratoryLaboratory findingsfindings usuallyusually reversereverse withwith steroidssteroids „ SeveritySeverity maymay dependdepend onon coexistingcoexisting autoimmuneautoimmune diseasesdiseases oror DMDM Conclusions

„ RecentRecent studiesstudies suggestsuggest conceptconcept ofof AIPAIP asas aa uniqueunique clinicalclinical entityentity „ FutureFuture studiesstudies areare neededneeded toto clarifyclarify pathogenesispathogenesis andand longlong termterm prognosisprognosis Conclusions

„ ““DonDon’’tt alwaysalways saysay nono toto steroids.steroids.””