Rev. Bras. Reumatol. vol.56 número2

r e v b r a s r e u m a t o l . 2016;56(2):101–104

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Original

article

Retroperitoneal

fibrosis:

case

series

of

five

patients

and

review

of

the

literature

Shacahf

Shiber

,

Noa

Eliakim-Raz

,

Molad

Yair

a_{RheumatologyUnit,RabinMedicalCenter,PetachTikva,Israel}

b_{SacklerFacultyofMedicine,TelAvivUniversity,TelAviv,Israel}

c_{DepartmentofMedicine,RabinMedicalCenter,BeilinsonHospital,PetahTikva,Israel}

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Articlehistory:

Received5April2014 Accepted14September2014 Availableonline6January2015

Keywords:

Retroperitonealfibrosis Prednisone

Renalfailure Tamoxifen IgG4

a

b

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Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologi-callyalliedconditionsthatincludeidiopathicretroperitonealfibrosis(Ormond’sdisease), inflammatory abdominalaorticaneurysm, andperianeurysmal retroperitonealfibrosis. Retroperitonealfibrosisencompassesarangeofdiseasescharacterizedbythepresenceof a fibro-inflammatorytissue,whichusuallysurroundstheabdominalaortaandtheiliac arteriesandextendsintotheretroperitoneumtoenvelopneighboringstructures-ureters. Retroperitonealfibrosisisgenerallyidiopathic,butcanalsobesecondarytotheuseof cer-taindrugs,malignantdiseases,infections,andsurgery.Herewedescribea5yearsfollow-up (2006–2011)of5patientsadmittedtoourhospitalwithsymptoms,laboratory,imagingand pathologicfindingcompatiblewithretroperitonealfibrosis.Wereviewourclinicalcourseof ourpatientwithrespecttotheliterature.

©2014ElsevierEditoraLtda.Allrightsreserved.

Fibrose

retroperitoneal:

série

de

cinco

casos

e

revisão

da

literatura

Palavras-chave:

Fibroseretroperitoneal Prednisona

Insuficiênciarenal Tamoxifeno IgG4

r

e

s

u

m

o

Periaortitecrônica(PC)éumtermogenéricousadoparadescreverumgrupodecondic¸ões nosologicamente ligadas que incluem a fibrose idiopática retroperitoneal (doenc¸a de Ormond),oaneurismadaaortaabdominalinflamatórioeafibroseretroperitoneal peri-aneurismática. Otermo fibrose retroperitonealengloba uma gama de doenc¸as quese caracterizam pela presenc¸a de um tecido fibroinflamatório que geralmente envolve a aortaabdominaleasartériasilíacas,seestendeaoretroperitôneoeenvolveestruturas ureteraisvizinhas.Afibroseretroperitonealgeralmenteéidiopática,maspodetambémser secundáriaaousodedeterminadosfármacos,doenc¸asmalignas,infecc¸õesecirurgia.Este

∗ _{Correspondingauthor.}

E-mail:[email protected](S.Shiber).

http://dx.doi.org/10.1016/j.rbre.2014.09.006

102

estudodescreveoseguimentoporcincoanos(2006–2011)decincopacientesinternadosem nossohospitalqueapresentavamsintomaseachadoslaboratoriais,deimageme patológi-coscompatíveiscomafibroseretroperitoneal.Revisou-seaevoluc¸ãoclínicadospacientes, quefoicomparadacomosachadosdaliteratura.

©2014ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Chronic periaortitis encompasses a group of rare abdom-inal aorta diseases, including idiopathic (nonaneurysmal) retroperitoneal fibrosis, inflammatory abdominal aortic aneurysm (IAAA), and perianeurysmal retroperitoneal fibrosis.1 _{Some cases involve the thoracic aorta, leading}

to mediastinal fibrosis. The idiopathic form accounts for over 70% of cases of retroperitoneal fibrosis.2 _According

to a Finnish study, the estimated incidence of idiopathic retroperitonealfibrosisis0.1per100,000person-years.3_Men

areaffectedtwicetothreetimesmoreoftenthanwomen,the meanageatpresentationis50–60years,althoughreportsof theconditioninchildrenandolderadultsarenotuncommon. Thisreportreviewstheliteratureanddescribesclinicaland laboratorycharacteristics,treatment,andoutcomeofaseries ofpatientswithretroperitonealfibrosis.

Results

Five patients with retroperitoneal fibrosis were identi-fied reviewing all rheumatology clinic inpatients records (2006–2011). The mean (±SD) age was 62.6±5.7 years and mean (±SD)duration ofdisease atdiagnosis was3.2±2.16 years.Abdominalandgroinpainwerethemostcommon clin-icalmanifestations(allpatients).

AllpatientshadnormocyticanemiaandahighC-reactive protein(CRP)and ESRlevels. Threepatients were foundto haverenalfailure.Treatmentinallcasesconsistedofsteroids andtamoxifen.Onepatientdidnotimproveaftertreatment, twopatientshadpartialresponse,andtwopatientshadfull response(completeremission).

Case

reports

Patient1

A64-year-oldmanwithahistoryofdyslipidemiapresented with chief complaint of groin pain during the preceding two months. Physical examination was normal, labora-tory tests revealed elevated ESR (101mm/h), mild anemia withhemoglobinof11.6g/dL,andmildlyelevatedcreatinine (1.29mg/dL).Anti-nuclearantibody(ANA)titerwasnegative. Imagingincludedacomputedtomography(CT)scan,which showedbilateralmoderatehydronephrosisandamass sur-rounding the abdominal aorta from the level of the renal arteriesthroughtheiliacbifurcation.Thepatientunderwent bilateralureterolysisandomentopexy.Biopsyofthe retroperi-tonealmassdisclosedcollagenoustissuewithinflammatory

cells,compatiblewithretroperitonealfibrosis.Thepatientwas firstprescribedprednisone1mg/kg/daywithtaperingtherapy downforthreemonthsthenmaintenancetherapywith aza-thioprine2mg/kg/dayandtamoxifen20mgbid.Ata6-month follow-up, anincrementinthe retroperitonealprocess was notedandthedoseofazathioprinewasincreased.Repeated CTscanoneyearlaterrevealedastableretroperitoneallesion. Thepatientcontinuedtamoxifenandazathioprine.

Patient2

A55-year-oldman,asmokerandwithahistoryofdiabetes mellitustype2,presentedwithabdominalpainandweight loss during the preceding 6 months. Physicalexamination was remarkableforabdominaltenderness.Laboratorytests revealedelevatedinflammatorymarkers(CRP138mg/L,ESR 77mm/h), mild anemiaand normal creatinine.A CT scan, revealed hardtissuesurroundingthe abdominalaortawith hydronephrosis,andsignsofatherosclerosiswithinthelarge arteries.Thebiopsyrevealedfibroustissueandinflammatory cells.

Treatmentwithhigh-dosesteroids(1gmethylprednisolone for 3 days) and cyclophosphamide (500–1000mg/m2 _IV

monthlyfor6doses)ledtoresolutionofthesymptoms. There-after,thepatientwasprescribedtamoxifenandazathioprine 2mg/kg/day.Undertreatment,repeatedimagingofmagnetic resonance(MR)angiographystudy,oneyearlateratfollowup, disclosedminortissuesurroundingtheaortaand inflamma-torymarkersnormalized.Treatmentwithcyclophosphamide wasstoppedafter6monthsandthepatientcontinued tamox-ifenandazathioprine.

Patient3

rev bras reumatol.2016;56(2):101–104

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Patient4

A 59 year-old woman with history of hypothyroidism was hospitalized for abdominal pain and evidence of bilateral hydronephrosis on abdominal ultrasound study. Physical examinationwasremarkablefordiffuseabdominal tender-nesswithno reboundor peritoneal signs.Laboratorytests revealed elevated creatinine level of 2.4mg/dL with ele-vatedinflammatorymarkers(CRP57mg/L),andanemiawith hemoglobinlevelof9.5g/dL.Imagingduringhospitalization includedpositronemissiontomographyPET-CTscan,which revealedfibrotictissuesurroundingtheabdominalaortaatthe levelofL3totheiliacbifurcation.Thepatientunderwent bilat-eralroboticureterolysisfollowedbyadministrationof pred-nisone60mg/day.Nobiopsyofthelesionwasperformed,and treatmentwasinitiatedonclinicalandradiologicalgrounds. Creatininelevelatthelastfollow-up(2yearslater)wasgreatly improved(1.26mg/dL).Prednisonewastapereddownand cur-rentlythepatientisundernotreatment,duetouncontrolled glucoselevelunderprednisonetreatment.RepeatedPET-CT imagingshowednoevidenceoftheretroperitonealmass.

Patient5

A57-year-oldwomanwithahistoryofdyslipidemiapresented withthechiefcomplaintofgroinpainandgeneralweakness. Physicaltestwasnormal,laboratorytestsrevealedelevated inflammatorymarkers(ESR105mm/h,CRP57mg/L),normal renal functionwith creatinine of 0.9mg/dL. ANA titerwas positive(1:160) withHomogenous(diffuse)pattern.Imaging includedPET-CTuptake,whichshowedamasssurrounding theabdominalaortafromthelevelofthesuperiormesenteric arterythroughtheiliacbifurcationwithouthydronephrosis. Thepatientwasdiagnosedwithretroperitonealfibrosisand treatedwithprednisone60mg/dayandtamoxifen20mgbid. At one-year follow-up, symptoms resolved, inflammatory markersnormalized and repeated PET-CT imaging2 years latershowednoevidenceoftheretroperitonealmass. Pred-nisonewastapereddownto5mg/dandtamoxifencontinued.

Discussion

Retroperitonealfibrosiscaninvolveany organproximate to the retroperitoneum. Ureteral obstruction occurs in up to 80–100% of cases.3 _{Intestinal or biliary-pancreatic}

involve-ment,lower-extremityvenous obstruction,aorticor branch arterial compression, and other pelvic organ and periph-eralnerveinvolvementhaveallbeenreported,ashavemore distantinflammatoryandfibroticcomplicationsofthe medi-astinum,pericardiumorpleura,andeventhethyroid,sinuses, ororbit,thoughtheseareuncommon.4,5 _{Infourofourfive}

patientshydronephrosiswasapresentingmanifestation,in resemblancetotheliterature.

Patients 4and 5 diagnosedwith retroperitoneal fibrosis basedonlyonPET-CT imagingwithoutbiopsy.Afew stud-iesshowedthatretroperitonealfibrosiscanbediagnosedbase onlyonPET-CTalone.In2010,Jansenetal.6_{evaluatedweather}

PET-CTwasusefulforthediagnosisofretroperitoneal fibro-sis. At baseline, the test was positive in20/26 ofpatients

withpositivepredictivevalueof0.63.Systematicreview pub-lishedin2013,7_{evaluatedtheroleofPET-CTinthediagnosisof}

retroperitonealfibrosis.Theauthorsconcludedthatthetestis usefulinthediagnosisandinevaluatingtreatmentresponse. Theresultsofroutinelaboratorytestsareconsistentwith inflammatorydiseases.Inalargecohortof58patientswith retroperitonealfibrosis,8_{Elevationsinacute-phasereactants,}

suchasESRandCRPwasfoundin66.7%andin64.9%, respec-tivelyandinallofourpatients.Positiveantinuclearantibodies detectedinupto27%ofthecohortandinonepatientofthis caseseries.

IgG4antibodiesaredynamicmoleculesthatcanexchange Fabarmsbyswappingaheavychainandattachedlightchain, IgG4canformbispecificantibodies,aswellasfunctioningas amonovalentmolecule.9

IgG4predominanceinmalepatientswithretroperitoneal fibrosis wasreportedrecently,likepatient3ofourseries.10

IgG4-relateddisease(IgG4RD)isanovelclinicaldiseaseentity characterized by elevated serum IgG4 concentration tissue infiltrationbyIgG4-positiveplasmacells.

In the absence of randomized trials, the treatment of idiopathicretroperitonealfibrosisisempirical.Spontaneous resolutionhasbeenreportedinsomecases,11_{and patients}

withindolentdiseasenotaffectingadjacentstructuresmight needonlymonitoring.However,patientswithactivedisease usually require medication. Glucocorticoids are the main-stayoftherapyandallourpatientsreceivedthistreatment, otherimmunosuppressivedrugs(e.g.,mycophenolatemofetil, azathioprine)12 _{have been used successfully together with}

glucocorticoids, but the superiority of these combinations overglucocorticoidsaloneisstillunproven.13_Tamoxifenhas

becomean attractivetherapeuticoption. However,in2011, Vaglioetal.14_{enrolled40patientswithnewlydiagnosed}

idio-pathic retroperitoneal fibrosis in a treatment trial. The 36 patientswhoachievedremissionafterinductiontherapywith 1mg/kgprednisonedailywererandomlyassignedtoreceive either tapering prednisone (initial dose 0.5mg/kg daily) or tamoxifen(fixeddose0.5mg/kgdaily)for8months.Evaluation atterminationoftreatmentrevealedrelapseratesof6%inthe prednisonegroupand39%inthetamoxifengroup,suggesting anadvantageofprednisone.

Conclusion

Wepresentedaseriesof5patientswithretroperitoneal fibro-sis. Weemphasizethat anabdominal and groinpain with elevatedacutephasereactantsshouldpromptanevaluation forretroperitonealfibrosis.

OnepatientinourserieswithelevatedserumIgG4level developed this syndrome after being treated with Etaner-cept. Thisis the second report15 _{published concerned the}

developmentofretroperitonealfibrosis afterTNFinhibitors treatment,andfurtherstudiesareneeded.

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2. GilkesonGS,AllenNB.Retroperitonealfibrosis:atrue connectivetissuedisease.RheumDisClinNorthAm. 1996;22:23–38.

3. vanBommelEF.Retroperitonealfibrosis.NethJMed. 2002;60:231–42.

4. VaglioA,CorradiD,ManentiL,FerrettiS,GariniG,BuzioC. Evidenceofautoimmunityinchronicperiaortitis:a prospectivestudy.AmJMed.2003;114:454–62.

5. DemkoTM,DiamondJR,GroffJ.Obstructivenephropathyasa resultofretroperitonealfibrosis:areviewofitspathogenesis andassociations.JAmSocNephrol.1997;8:684–8.

6. JansenI,HendrikszTR,HanSH,HuiskesAW,vanBommelEF. (18)F-fluorodeoxyglucosepositionemissiontomography (FDG-PET)formonitoringdiseaseactivityandtreatment responseinidiopathicretroperitonealfibrosis.EurJIntern Med.2010;21:216–21.

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Anti-inflammatoryactivityofhumanIgG4antibodiesby dynamicFabarmexchange.Science.2007;317:1554–7.

10.StoneJH,ZenY,DeshpandeV.IgG4-relateddisease.NEnglJ Med.2012;366:539–51.

11.PierreS,CordyPE,RazviH.Retroperitonealfibrosis:acase reportofspontaneousresolution.ClinNephrol.2002;57:314–9.

12.vanBommelEF,SiemesC,HakLE,VanderVeerSJ,Hendriksz TR.Long-termrenalandpatientoutcomeinidiopathic retroperitonealfibrosistreatedwithprednisone.AmJKidney Dis.2007;49:615–25.

13.ScheelPJJr,FeeleyN,SozioSM.Combinedprednisoneand mycophenolatemofetiltreatmentforretroperitonealfibrosis: acaseseries.AnnInternMed.2011;154:31–6.

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