J. Coloproctol. (Rio J.) vol.37 número3

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w w w . j c o l . o r g . b r

Journal

of

Coloproctology

Original

Article

A

prospective

study

on

tubercular

fistula

in

ano

and

its

management

Manoranjan

Sahu

a,∗

,

Jai

Krishna

Mishra

b

,

Ashish

Sharma

a

,

Uzma

Fatmi

a

a_Banaras_Hindu_University,_Institute_of_Medical_Sciences,_Faculty_of_Ayurveda,_Department_of_Shalya_Tantra,_Varanasi,_India

b_Banaras_Hindu_University,_Institute_of_Medical_Sciences,_Department_of_Respiratory_Diseases,_Varanasi,_India

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Articlehistory:

Received8January2017 Accepted21April2017 Availableonline19May2017

Keywords:

Tuberculosis Fistulainano

Antituberculartreatment

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b

s

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t

Objective:Tuberculosisfistulainano,thoughlessencountered,isanimportantclinicalentity indevelopingcountrieslikeIndia.DiagnosisofTBfistulaisachallengedespiteofadvances indiagnosticmodalitiesanditdependsuponbothlocalandsystemicclinicalpresentation. Thisprospectivestudyaimedattosubstantiatetheimportanceofclinicaldiagnosisaswell asmedicalmanagementoftubercularfistulabyantituberculardrugs.

Methodsandresults:25patientsoffistulainanosuspectedtobeoftubercularorigin under-wenthistopathologyoffistuloustracksandan8weektherapeutictrialofantitubercular treatmentaftergettinganinformedconsent.Thoughbiopsyshowedpositiveevidenceof tubercularpathologyonlyin52%cases,therapeutictrialshowedimprovementinlocaland systemicfeaturesin23(92%)cases.Ofthese23cases,3werecuredafter18monthsof antituberculartreatmentand18showedcureafter24monthsofantituberculartreatment while2caseswithdrewfromthestudyat12and14monthsrespectivelyduetoadversedrug reactionsthoughtheirfistuloussymptomswererelieved.

Conclusion: Meticulousclinicalevaluationplaysavitalroleindiagnosisoftubercularfistula inadditiontootherdiagnosticmethods.Antituberculartreatmentisthemainstayof treat-mentintubercularfistulawithaminimumdurationof18–24monthsowingtotherecurrent andrelapsingnatureofdisease.

Estudo

prospectivo

sobre

a

fístula

anal

tuberculosa

e

seu

tratamento

Palavras-chave:

Tuberculose Fístulaanal

Tratamentoantituberculose

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s

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m

o

Objetivo:Afístulaanaldatuberculose(TB),emboramenosobservada,constituientidade clínicaimportanteempaísesemdesenvolvimento,comoaÍndia.OdiagnósticodefístulaTB étarefadesafiadora,apesardosavançosnasmodalidadesdiagnósticas;seuestabelecimento dependetantodaapresentaçãoclínicalocal,comodaapresentaçãosistêmica.Esseestudo

∗ _{Corresponding}_author_.

E-mail:msahuvns@gmail.com(M.Sahu). http://dx.doi.org/10.1016/j.jcol.2017.04.005

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prospectivoteveporobjetivoconsubstanciaraimportânciadodiagnósticoclínicoetambém dotratamentoclínicodafístulaTBcommedicamentoscontratuberculose.

Métodoseresultados:Foirealizadoestudohistopatológicodetratosfistulososem25pacientes comfístulaanalcomsuspeitadeorigemtuberculosa;depoisdeobtidooconsentimentolivre einformado,essespacientesforamsubmetidosatratamentoanti-tuberculose(TAT)durante 8semanas.Emboraabiópsiatenhareveladoevidênciapositivadepatologiatuberculosa emapenas52%doscasos,ocursoterapêuticoresultouemmelhoranosaspectoslocale sistêmicoem23(92%)pacientes.Desses23casos,3e18casosestavamcuradosapós18e 24mesesdeTAT,respectivamente,enquantoque2pacientesdesistiramdoestudoapós12 e14meses,respectivamente,emdecorrênciadereac¸õesfarmacológicasadversas,mesmo diantedoalíviodeseussintomasfistulosos.

Conclusão: Juntamentecomoutrosmétodosdiagnósticos,umaavaliaçãoclínica meticu-losadesempenhapapelvitalnodiagnósticodafístulaTB.TATéoprincipalprocedimento terapêuticoempacientescomfístulaTB,comduraçãomínimade18-24mesesdevidoà naturezarecorrenteerecidivantedadoença.

Introduction

Tuberculosis(TB)isoneoftheleadingcausesofdeath world-wideparticularlyindevelopingcountries,rankingalongside HIV/AIDS. According toWHO Annual Report2016, 9.6 mil-lionpeople sufferedwith tuberculosisgloballyin2014and Indiasharedthe largestnumber ofcasesinthesouth-east Asian region withprevalence and incidenceof2.5 and 2.2 million respectively.1 _Tubercular _{manifestations} _can _be _of two types: pulmonary (PTB) and extra pulmonary (EPTB). Thoughpulmonaryinfectionsare morecommonly encoun-tered, extrapulmonary forms have also been a matter of concernsincelong.InIndia, 20%ofallTBcasesare extra-pulmonaryforms.2_Though_vascular_areas_like_lymph_nodes, meninges, kidney, spine and growing ends of bones are commonlyinvolvedsitesinEPTB;pleura,pericardium, peri-toneum,liver,gastrointestinaltract(GIT),genitourinarytract andskinmayalsobeinvolved.3_GI_tuberculosis_accounts_for 1–3%ofextrapulmonarycases,4_which_may_be_primary_due toingestionofM.bovisstrainormaybesecondaryduetoa primayfocus elsewherewhichisusuallypulmonary. Tuber-culosisofanoperinealregionisarelativelyrareformofEPTB whichmayoftenmanifestintheformofanorectalabscesses, fistulaandinsomecases,mayalsopresentwithanalstenosis. TBisoftena neglected cause ofanorectalsepsiswhich usuallyremainsunrecognizedleadingtorecurrenceofanal fistulae even after multiple surgeries. Although fistula in ano is a surgical disease,tubercular fistulae often present as an exception to this and can be managed effectively byproperantitubercularchemotherapeutic treatment. This paperdescribesaprospectiveseriesoftubercularfistulainano wherethepatientswereprimarilymanagedmedicallyandthe outcomeshavebeenreported.

Methods

Thisprospectivestudyincluded25patientsoftubercular fis-tulainanowhoattendedtheAno-rectalclinicatSirSunderLal

Hospital,BanarasHinduUniversity,Varanasi,IndiafromJune 2012toJuly2016.UnlikeallothertypesofEPTB,thereareno specificsymptomatologiesorinvestigativefindingsattributed totubercularfistulainanoandso,thediagnosiswasmade especiallyonthebasisofclinical grounds,bothonlocalas wellassystemicpresentation.Non-cryptoglandularoriginof fistulainano,recurrentnatureoffistulae,multiplefistulae notlinkedtoeachother(tracksnotcommunicatingtoeach other),fistulawithmultipleexternalopenings,thincaseous discharge, undermined edgesofexternalopening, progres-siveanorectalstenosisandinguinallymphadenopathyarouse suspicionoftubercularfistulainano(Fig.1).

Constitutionalsymptomslikelowgradefeverespeciallyin theeveninghours,anorexiaandweightlosswithfeaturesof anemiaaretheotherfeatureswhichfurtherstrengthenthe doubtofatubercularpathology,howeverallthesesymptoms werenotpresentinallcases.5,6 _All_patients_underwent rou-tinehematologicalinvestigationswhichincludedhemogram withESR,bloodsugarlevels,liverfunctiontests,serum urea-creatinine estimationalongwithserologicaltestingforHIV and HBsAg status. Digital chest radiography and Mantoux testingwasdone.Sigmoidoscopywasperformedtoruleout inflammatoryandotherbowelpathologies.Inadditiontothis, biopsyofthetissueexcisedfromthecoreofthefistuloustrack wassentforhistopathologicalexamination.Afterconfirming thediagnosisbyhistopathology,antituberculartreatmentwas startedaccordingtobodyweightondailydosagepattern.The regimeisshowninTable1.

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Fig.1–Clinicalphotographsshowingcaseatingdischargefrommultipleexternalopeningsoftubercularfistula(left)and recurrentfistulainanowithmultipleexternalopeningsandstenosisatanorectaljunction(right).

Table1–Regimeofantituberculartreatmentfor tubercularfistulainano.

Phase Duration

(months)

Drugs(dose)

Intensive(IP) 3 Isoniazid(H;5mg/kg), rifampicin(R;10mg/kg), pyrazinamide(Z;25mg/kg), ethambutol(E;15mg/kg), streptomycin(S,750mg), moxifloxacin(400mg)

3 HRZE+moxifloxacin

(400mg)

Continuation(CP) 12–18 HRE

wellasimprovementinsystemiccomplaintsandweightgain (Fig.2).

Results

Thestudyincluded23malesand2femaleswithmeanageof 36.8years(range18–72years).44%caseswereofrecurrent fis-tulaand20%ofthetotalcasespresentedwithanalstenosis atthelevelofanorectaljunction.Noanalcryptinvolvement couldbeelicitedinanyofthepatientonclinicalexamination. Sigmoidoscopydidnotrevealthepresenceofinflammatory

boweldisease(IBD)inanyofthecases.3(12%)patientshad a positive past history of antitubercular treatment for 6–9 months for pulmonary tuberculosis and their chest radio-graphs showed evidenceof previous pulmonarytubercular involvement.32%patientshadconstitutionalsymptomslike evening riseoftemperature, anorexiaand weightloss.ESR wasraisedinallcaseswithanaverageof54.5mm/1sthour byWestergrenmethod.Mantouxtestwaspositivein8(32%) patients with more than 15mm induration size measured after72hoftuberculininjection.Onhistopathological exam-inationofthetissuebiopsyobtainedfromthefistuloustrack, 13 (52%)cases showed presence ofgranulomatous pathol-ogywithcaseatingnecrosisandLanghansgiant cells,thus confirmingthediagnosisoftuberculosisandhence,ATTwas started in them. Among the biopsy negative cases, an 8 weektherapeutictrialofATTwasstarted.Twopatientsdid not respond to the therapeutictrial. Their anti tubercular chemotherapywasdiscontinuedandthecasesweremanaged by surgical intervention and medicated seton (ksharsutra) therapy. Theremainingten patientsrespondedtoATTand thus,atotalof23(92%)casesunderwentandcompletedthe6 monthsintensivephase(IP)schedule.Duringthecontinuation phase(CP),2patientsdiscontinuedthetreatmentthemselves attheendof6monthsand8monthsduetoadversereactions likearthralgia,lethargy,nausea,vomitingetc.anddidnotturn up forfurtherfollowup, howevertheirfistulous symptoms

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wererelieved.Intherest21(84%)cases,3patientsunderwent a12monthCPwhile18underwent an18 monthCP.Thus, 3patientscompletedacourseofATTfor18monthwhile18 patientsunderwenta24monthscourseofATT.

Discussion

Analtuberculosisisararelyencounteredformof extrapul-monarytubercularinvolvement.Astheincidenceofprimary GIT tuberculosishas declined due to the preferred use of pasteurizedmilk,tuberculosisofanalregionisusually sec-ondary to a primary focus elsewhere which is more often pulmonary.6_The_probable_method_of_infection_of_the anorec-talregionmaybeduetoswallowingofsputuminfectedwith tubercularbacilliwhichmayenterthe analor perianal tis-suethroughaminuteabrasionintheliningoftheanalcanal. Infectionmayalsooccurasadirectinoculationoftubercle bacilliduringanaltoiletontothe excoriationsorcracksin theanalorperianalskinfromthepatient’sfinger, contami-natedbycontactwithhisowninfectedsputum.Morerarely,a hematogenousorlymphaticspreadmayalsooccurleadingto thelodgingoftubercularbacillusintheperianalorischiorectal tissues.7_The_disease_may_have_varied_presentation_including theformationoffistulae,perianalormucosalulcerations,firm andannularstricturesorsubmucosalnodularformwith ulcer-ation.Itmayalsobepresentedinverrucousformwithsmooth wartyappearance.8_Suppurations_and_fistulae _are,_however, themostfrequentlyencounteredlesions.9

Though the recommendations are that EPTB should be diagnosedbacteriologically,histopathologicallyoronclinical judgmentoftreatingspecialistsbutinmostcases,diagnosis ofEPTBhasbeen foundtobemade onclinicalgrounds2,10 and itraises the difficulty amongtheclinicians with vary-ingdegreeofexperienceinfistulainanotreatment.So,the problemsofamissedoroverdiagnosisoftubercularfistulaare commoninpractice.IthasbeenobservedthatATTisadvised empiricallyincasesofrecurrentfistulainanoatseveral occa-sionsconsideringit tubercularin naturewhichis however notjustifiedbecauserecurrenceaftersurgicaltreatmentisnot uncommonspeciallyincomplexfistulainanoduetoseveral reasonslikemissedsepsis,inabilitytocorrectlyidentifythe internalopeningorthesiteofcryptoglandularinfectionetc. Ahighindexofclinicalunderstandingofbothlocalaswellas systemicfeaturesisrequiredformakingadiagnosisof tuber-cularfistulaasdescribedearlier.Constitutionalfeatureslike anorexia,fever,weightlossetc.however,maynotalwaysbe present6_as_only_32%_patients_presented_with_such_symptoms inthisstudyalso.Thediagnosiscanbeconfirmedby posi-tiveMycobacteriumtuberculosis(MTB)cultureinthepussample butbeingapaucibacillarydisease,theyieldandthe sensitiv-ityofthe testislow.Moreover,itgenerallytakesabout2–3 monthstoobtainthecultureresultswhichmaydelaythe com-mencementoftreatment.Also,MTBcultureisdifficultincases wherethemainpresentingfeatureisanorectalstenosiswith noorlittledischarge.So,thediagnosisdependsmainlyupon thehistopathologicalevidenceandhence,theexcisedtissue fromfistuloustractshouldalwaysbesentfor histopathologi-calexaminationinallsuspectedcases.Presenceofgiantcell (Langhanstype)granulomaswithepitheloidcellinfiltration,

caseatingnecrosisanddemonstrationofAFBarepositive his-tologicalevidencesbutthesemaynotbealwayspresentanda lowhostimmunitymayresultinmoreinflammatoryor sup-purativeresponseonhistologicalfindings.11 _Biopsy_may_be repeatedinsomecasesastuberculouslesionsmaybe submu-cosalinnatureandmaybemissedinthesectionstudied.12 Inthepresentstudyalso,histologicalevidencecouldnotbe foundin48%casesbutatherapeutictrialofATTbasedonthe clinicallysuspectedfeaturesshowedsuccessfulresultswhich approvedthediagnosisandthetreatmentwascontinued.The investigationslikeMantouxtestingandQuantiferonTBGold may aidtothediagnosisbut theirvalueisquestioned.The valueofMantouxtestislimitedinadultsinIndiaasabout40% oftheadultpopulationisinfectedwithTB.13_Since_there_have beennovalidatedhematologicalbiomarkerssuggestedthat candetectTB,theroleofbloodbasedantibodytestsor inter-ferongammareleaseassayssuchasTBGoldandTBplatinum isquestionable.14_Nucleic_acid_{amplification}_tests_(NAAT)_like polymerasechainreaction(PCR)testingusingpusandtissue specimenmaybeusefulinrapiddetectionofthediseasebut thesensitivityislowandvariableinEPTBcasesamplesand requireamultiplesampletesting.11_In_2013,_WHO_endorsed theuseofXpertMTB/RIFassay,acartridgebasedNAATfor extrapulmonary cases, which allowsfor rapiddetection of MTBDNAalongwithconfirmationofrifampicinresistance.15 Variousstudieshaveshownthateventissuebiopsiescanbe usedasasampleforthediagnosisoftuberculosisbythistest. MRIandTransrectalultrasonographymaybehelpfulin under-standingthecourseandextentofdiseasewhileMRIcanalso revealthefibrosisandstrictureformationwhichusuallyoccur within10cmfromanalvergebydetectingtheincreased pre-sacralspaceinsuchcases.16,17_Crohn’s_disease_is_an_important differentialdiagnosiswhereinanoncaseatinggranulomais foundinhistologyandalowerGIendoscopymaybehelpful insuspectedcases.

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inspecialsituations likeboneand jointTB,spinalTBwith neurologicalinvolvement,etc.21 _Tubercular_fistulae_are _also similar tothese special situations due tofactors like slow responsetotreatmentandtendencyforrelapseorrecurrence. Hence,anextensionofCPmaybedoneonthebasisof clin-icalassessment.Thehelpofradiologicalandotherrelevant investigationsmayalsobetaken.Inourexperience,total dura-tionoftreatmentfortubercularfistulashouldneverbeless than18months;ratherindifficultandcomplicatedcases,the durationmaybeincreasedupto24monthsortillsatisfactory clinicalresponseisachieved.Althoughthedailyand intermit-tentregimenshaveshownequalchemotherapeuticefficacy, thedailyregimenshouldbethechoiceintubercularfistula. Recentguidelinesunderrevisednationaltuberculosiscontrol programme(RNTCP)alsoadvocatesfordailyregimen.21_There arenoclearcutguidelinesforendpointoftreatmentinEPTB cases;however,incasesoftubercularfistula,improvementin systemicfeatures,weightgainandhealingoffistulamaybe takenastheendpointoftreatment.

Conclusion

Diagnosisoftubercularfistulaisstillabigchallengeanditis difficulttoestablishinafairnumberofcasesdespiteof avail-ablediagnostictools.Ameticulousclinicalobservationalong withnoncryptoglandularoriginoffistulaplaysanimportant roleincaseswherehistologicalevidencesare not support-ivefortuberculosis.Itisprimarilyamedicalconditionand surgicalinterventionisseldomrequired.ATTshouldnotbe initiatedmerelyonthebasisofrecurrentnatureofdisease andthereshouldbeadequateclinicalevidenceand/or inves-tigativesupporttostartantituberculartreatment. However, theregimeanddurationoftreatmentshouldbejudiciously decidedindividuallyonthebasisofresponsetothetreatment andpreferably,itshouldnotbelessthan18–24months.Ahigh indexofclinicalsuspicion,judicioususeofdiagnostic meth-odsforconfirmationofdiagnosisandproperregimeinterms ofdoseanddurationwithregularfollowupandassessment arethekeystosuccess.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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