www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Diagnosing
acquired
syphilis
through
oral
lesions:
the
12
year
experience
of
an
Oral
Medicine
Center
夽
Michelle
Danielle
Porto
Matias
a,
Alessandro
Oliveira
de
Jesus
a,
Renata
Gonc
¸alves
Resende
b,
Patrícia
Carlos
Caldeira
a,
Maria
Cássia
Ferreira
de
Aguiar
a,∗aUniversidadeFederaldeMinasGerais(UFMG),FaculdadedeOdontologia,DepartamentodeCirurgiaOralePatologiaOral,Belo Horizonte,MG,Brazil
bHospitalMetropolitanoOdilonBehrens,MedicinaOral,BeloHorizonte,MG,Brazil
Received28May2018;accepted19December2018 Availableonline23February2019
KEYWORDS Syphilisinfection; Orallesions; Diagnosis; Epidemiology Abstract
Introduction:AresurgenceofsyphilisinBrazilhasbeenreportedinrecentyears.
Objective:With thisinmind,thepresentstudy soughtto investigatethe frequency, demo-graphics,andclinicalcharacteristicsofpatientswithacquiredsyphiliswithoralinvolvement whoreceivedmedicalcareatanOralMedicineReferenceCenterinaBrazilianPublicHospital.
Methods:Aretrospectivestudy,spanningaperiodof12years,wasperformedtoidentify chang-ing trendsinsyphilis overtime.Medical records from all patients diagnosedwithacquired syphiliswhoreceivedmedicalcareattheHospital’s OralMedicineClinicfrom2005to2016 werereviewed,andthedemographicandclinicaldatawerecollected.
Results:A totalof85 patientshadbeendiagnosedwithacquiredsyphilis,withasignificant increaseinthenumberofcasesoverthepast5years.Patientsrangedfrom16to76yearsof age,withapeakinthethirdandfourthdecades.Forty-eightcasesaffected males(56.5%), while37casesaffectedfemales(43.5%).Mostoftheorallesionsappearedasuniqueulcersor plaques,withthelipsandtonguerepresentingthemostaffectedsites.Allcaseswerepositive forVenerealDiseaseResearchLaboratoryorFluorescentTreponemalAntibodyAbsorption,and treatmentwasperformedwithPenicillinGbenzathineinmostcases(84.7%).
Conclusion:Thefrequencyoforalsyphilishasbeenrisingovertimeandorallesionsmaywell representadiagnosticclue;therefore,oralhealthprofessionalsmustbemadeawareand prop-erlytrainedinanattempttodevelopahighdegreeofclinicalsuspicioninthediagnosisof syphilis.
© 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
夽 Pleasecitethisarticleas:MatiasMD,JesusAO,ResendeRG,CaldeiraPC,AguiarMC.Diagnosingacquiredsyphilisthroughorallesions: the12yearexperienceofanOralMedicineCenter.BrazJOtorhinolaryngol.2020;86:358---63.
∗Correspondingauthor.
E-mail:cassiafa@ufmg.br(M.C.Aguiar).
PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial. https://doi.org/10.1016/j.bjorl.2018.12.010
1808-8694/©2019Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
PALAVRAS-CHAVE Infecc¸ãoporsífilis; Lesõesorais; Diagnóstico; Epidemiologia
Diagnosticandosífilisadquiridaatravésdelesõesorais:aexperiênciade12anosde umCentrodeMedicinaOral
Resumo
Introduc¸ão: UmressurgimentodasífilisnoBrasiltemsidorelatadonosúltimosanos.
Objetivo: Investigarfrequência,ascaracterísticasdemográficaseclínicasdospacientescom sífilisadquiridacomenvolvimentooralquereceberamatendimentomédicoemumcentrode referênciaemmedicinaoralemumhospitalpúblicobrasileiro.
Método: Estudoretrospectivo,abrangeu12anos,feitoparaidentificartendênciasdemudanc¸a nasífilis.Registrosmédicosdetodosospacientesdiagnosticadoscomsífilisadquiridaque rece-beram atendimento médico na clínica de medicinaoral do hospital de 2005 a2016 foram revisadoseosdadosdemográficoseclínicosforamcoletados.
Resultados: Foramdiagnosticas85pacientescomsífilisadquirida,comumaumento significa-tivononúmerodecasosnosúltimos5anos.Aidadedospacientesvarioude16a76anos,com piconaterceiraequartadécadas.48casoseramdosexomasculino(56,5%)e37dosexo fem-inino(43,5%).Amaioriadaslesõesoraisapareceucomoúlcerasouplacasúnicas,oslábiosea línguarepresentaramoslocaismaisafetados.TodososcasosforampositivosparaVenereal Dis-easeResearchLaboratoryeFluorescentTreponemalAntibodyAbsorptionTesteotratamento foifeitocompenicilinaGbenzatinanamaioriadoscasos(84,7%).
Conclusão:A frequênciadasífilisoraltemaumentadocomotempoeaslesõesoraispodem representar umapistadiagnóstica;portanto,osprofissionaisdesaúdebucaldevemser con-scientizadosedevidamentetreinadosnatentativadedesenvolverumaltograudesuspeic¸ão clínicanodiagnósticodasífilis.
© 2019 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
Syphilisisasexuallytransmitteddiseasecausedbythe spiro-chete‘‘Treponemapallidum’’, includinginfectionthrough orogenital contact. Another infective route is congeni-tal syphilis, in which the disease is transmitted during pregnancy.1Inbothforms,whethercongenitaloracquired,
the oral cavityis the most frequent siteof the extragen-italmanifestation ofsyphilis.2The mostaffected sitesfor
secondarysyphiliticlesionsaretongue,gingiva,softpalate, andlips.Orallesionscommonlyappearasulcersandmucous plaques.3
Inthe1950s,syphiliswaseradicatedindeveloped coun-tries, and due tothe discovery of penicillin,a significant declineintheincidenceofthediseasewasobserved.4
How-ever, a resurgence of the disease has been reported in recent years.5 Many studies describe this increasing
bur-deninFrance,theNetherlands,Sweden,Germany,Ireland, Norway, and Great Britain.6---9 These studies support the
factthattheincreasingnumberofsyphiliscasesis associ-atedwithhigh-risksexualbehavior,coincidingwiththenew eraofHumanImmunodeficiencyVirus(HIV)infection.10 In
this sense,syphilis continues tobe amajor publichealth problemin Brazil. The detectionrate of acquired syphilis was 43.7 cases per 100 million habitants in 2015. From 2010to2016,227,663caseswerediagnosed.11---13This
sce-nariopointstotheneedfor broadinformativecampaigns, coupledwithpreventiveactionsbythegovernmentand non-governmentalorganizations.11
The current study sought to describe the frequency, demographics, and clinical characteristics of acquired syphilis diagnosed through oral manifestations at an Oral Medicine reference center at a public hospital. Improve-ments in knowledge regarding epidemiological and oral manifestationsofsyphilisareessentialinordertoguide den-tistsandhealthprofessionalstowardacorrectandprompt diagnosisandpreventionofthedisease.
Methods
The study protocol was approved by the Institu-tional Committee of Ethics on Research (protocol no. 55609516.1.0000.5149).
AretrospectivestudywasperformedattheOralMedicine ServiceoftheHospitalMetropolitanoOdilonBehrens,inthe city of Belo Horizonte, Brazil. This hospital is a regional reference center in oral medicine. None of the patients sought medical treatment before being treated at the OralMedicineService. Themedicalrecordsofallpatients diagnosedwithoralmanifestationsofacquiredsyphilis (ICD-10-A53.9)betweenJanuary2005andDecember2016were retrieved.Caseslackingserologicalconfirmation(Venereal Disease Research Laboratory --- VDRL) or Fluorescent Tre-ponemalAntibodyAbsorption(FTA-ABS)wereexcluded.The
20 18 16 14 12 10 8 6 4 2 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Figure1 Numberofcasesdiagnosedasacquiredsyphiliswith oralmanifestationsbetween2005and2016attheOralMedicine Service---HMOB.
following data were collected from the medical records: age,sex, description oforal lesion,affected site,disease stage,serologicaltests,andtreatment.
Data were organized into a database and descriptive analyses were conducted. The Pearson chi-square and
t-testtestwereusedtoevaluatetheassociationbetweenthe variablessex,age,site,clinicalpresentation,andstage.The levelofsignificancewassetat5%.Analyseswereperformed usingSPSS® version19.0forWindows.
Results
Atotalof85diagnosesofacquiredsyphiliswereregistered from2005to2016,withamarkedincreaseinthenumberof diagnosesperyearinthelast5years(Fig.1).
Forty-eight patients were males (56.5%), while 37 werefemales(43.5%).The traditionalmalepredominance changed over the past 2 years, in which female patients havebegun tooutnumber malepatients(Fig.2). Patients ranged from 16 to 76 years of age, with a mean age of 29.58 years.Females had a lower meanage (26.46) than males (31.98) (p<0.05) at diagnosis. Most patients were diagnosedin thethird decadeof life(40%---47%), followed bythefourthdecade(21%---24.7%),howeverthenumberof womenaffected in the second decade (n=14)washigher thanmen(n=4)(p<0.05).Therefore,thetotalofpatients from21to40yearsofagewas61cases,representing71.7%. Agesbeloworabovethisrangerepresented24cases(28.3%). Acquiredsyphiliswasmorefrequentinmenthaninwomen inalmost allage groups,except inthe second andfourth decadesoflife(p<0.05)(Fig.3).
12 10 8 6 4 2 0 2005 2006 2007 2008 2009 2010 Male Female 2011 2012 2013 2014 2015 2016
Figure2 Annualfrequencydistributionofacquiredsyphilis withoralmanifestationsaccordingtopatient’ssex.
71 to 80 years 61 to 70 years 51 to 60 years 41 to 50 years 31 to 40 years 21 to 30 years 10 to 20 years 0 5 10 15 20 MEN WOMEN 25 30 35 40 45
Figure3 Frequencydistributionofacquiredsyphiliswithoral manifestations between 2005and2016 accordingto sex and age.
Mostpatients(72%---84.7%)livedinthecityofBelo Hor-izonte (the state capital where the hospital is based), although 13 individuals (15.3%) were from neighboring cities.
PatientssoughttheOralMedicineServicebecauseoforal lesions.Someof themhave reportedpainfulsymptomsor difficulty inswallowing.Mostnoticed thepresence of the lesionstwoweeksbeforeconsultation.
Oral lesions were mainly described as single (96.5%) ulcerations(78.8%).Themostaffectedsiteswerethetongue andlips(23%---27.1%each)(Fig.4).Whenthelesionswere inmultiplesitestheywereusuallyrepresentedbymucosal plaques(p<0.05).Comparisonsbetweentheothervariables didnotshowstatisticalassociation.
Adiagnosisofthesecondarystageofsyphiliswas estab-lished in 94.1% of the cases, and all patients had tested positive for VDRLandFTA-ABS. Allthe 5cases ofprimary syphilis were diagnosed in men (p<0.05). Thirty patients (35.3%)underwentadditionalserologicaltests,suchasblood countandanti-HIV.Itisimportanttonotethatallofthe28 patientstestedforanti-HIVpresentedapositiveresult.
PenicillinGbenzathine(84.7%)anddoxycycline(15.3%) were the drugs used for treatment. The summary of our study’sresultscanbeseeninTable1.
Discussion
Acquired syphilis is a sexually transmitted disease that develops through three stages. In the primary stage, the syphilitic complexis themain characteristic.This encom-passes the ‘‘cancrum’’, which appears at the inoculation siteofT.pallidum,alongwithlymphadenopathy.Nomatter whatthetreatment,theseinitiallesionscanresolve natu-rally,whileT.pallidumfurtherdisseminates.Thesecondary stage is characterized by multiple mucous and cutaneous lesions, along with lymphadenopathy. Once again, these lesionscanresolvespontaneously,andT.pallidumremains as a latent infection, however, about one third of all patientswithuntreatedsecondarysyphilisdevelopthe ter-tiaryform.2
A patient’s oral mucosa can be affected in all three stages,butit ismostcommonlyaffectedinthesecondary stage,whichwasconfirmedinthepresentstudy.Secondary syphiliticorallesionsareusuallymultipleandmore diversi-fiedthanthesingleulceroftheprimarystage.Nevertheless, asinglelesionmaybetheonlymanifestationthatappearsin
Figure4 Oralsyphilisrepresentedbymultiple(A)andsingle(B)ulcerandmucousplaque.
Table 1 Clinical features of 85 patients diagnosed with acquiredsyphilisduetooralmanifestations.
Variables n % Sex Male 48 56.5 Female 37 43.5 Age(years-old) <20 12 14.2 21---30 40 47.0 31---40 21 24.7 41---60 9 10.6 61---80 3 3.5
Numberoforallesions
Single 82 96.5 Multiple 3 3.53 Site Lips 23 27.1 Tongue 23 27.1 Cheek 14 16.5 Softpalate 8 9.4 Palatinetonsil 6 7.0 Oropharynx 6 7.0 Labialcomissure 1 1.2 Mouthfloor 1 1.2 Missing 3 3.5 Clinicalpresentation Ulcers 67 78.8 Mucosalplaque 17 20.0 Verrucous 1 1.2 Syphilisstage Secondary 80 94.1 Primary 5 5.9 Treatment PenicillinGbenzathine 72 84.7 Doxycycline 13 15.3
thesecondarystage.Orallesionsincludemucouspatches, macule, papule,andanodular/ulcerative form.The pres-enceofmaculopapularskinlesions,lymphadenopathy,and medicalhistorymost oftenguide thecliniciantoward the properdiagnosisofsecondarysyphilis.3
Syphilitic lesions in the oral mucosa are known to be quite variable, simulating diverse diseases,14 such as
HIV, lichen planus, eosinophilic ulcers, traumatic ulcers,
lymphomas, leukoplakia, gonorrhea, squamouscell carci-noma, and necrotizing sialometaplasia. Accordingly, the clinicalpresentationfoundhereinincludedulcers,mucous plaques, and verrucous lesions. Since a histopathological routineexamis nonspecific,serologicaltestsareessential toreachingthefinaldiagnosis.
Theserologicaltestsusedtodiagnosesyphilisare classi-fiedasnontreponemalandtreponemal.4Thenontreponemal
tests(VDRLandRapidPlasmaRegain---RPR)arenonspecific, althoughtheyarefasterandcheaper,6andarewidelyused
forscreeninganddiseasedetection.Thesetestsarereactive inthesecondaryandlatentphasesandarelesssensitivein patientswithprimarysyphilis.VDRLandRPRmaybe reac-tiveinotherdiseases,suchassystemiclupuserythematosus, ulcerativecolitis,andRickettsialdisease.15Thetreponemal
tests(FTA-ABS,T.pallidumHaemagglutination---TPHA),and Microhemagglutination Assay--- MHA-TP)aremore specific andsensitive,andthusbecomepositiveintheearlystagesof thedisease.However,theyaremoreexpensive.Despitethe limitationspointedout above,theserologicaltests,along witha well-conductedclinicalexamination, playacrucial roleinthe diagnosis of syphilis.3All patients investigated
inthecurrentstudypresentedaserologicalconfirmationby VDRLandFTA-ABS.
The occurrence of syphilis used to be a great health problem before the discovery of penicillin.16 After the
antibioticsera,syphilisremainedacontrolledinfectionfor some decades. Nevertheless, a new burden is now being reportedworldwide.5,8Itisimportanttonotethatthis
resur-genceofsyphilisalsocoincideswitharesurgenceofHIVin society.6,10
Thepresentstudyconfirmedthisresurgenceofsyphilis, ascanbeseeninthealarmingincreaseofthediseaseover thepastfiveyears.Socialandbehavioralaspectsseem to playimportantrolesinthisscenarioandhavebeenpointed out as major reasons for this reemergence. A decrease in safe sex practices, the optimism with antiretroviral treatment,recreationaldruguse,anderectiledysfunction medication use aresome examplesof behavioral changes thatincurhigherrisks.6
Casesweresearchedinthepresentstudythough a ret-rospectivestudybasedonthediagnosisofacquiredsyphilis (ICD-10-A53.9).Allnotifiedcaseswereofpatientswithoral lesions,stressingtheimportanceoftrainingoralhealth pro-fessionalsinidentificationofacquiredsyphilis.
Thepresentstudyidentifiedthemostaffectedagerange to be from 20 to 39 years of age, which is exactly the reproductiveage.5Moreover,theincreasedfrequencyofthe
forcongenitalsyphilis.Therefore,itispivotal toofferthe populationpreventiveandeducationalactionstoavoidthe verticaltransmissionofsyphilis.11,14Patientsabove60years
ofagerepresentedonly 3.5%,whileyoung peopleintheir early 20srepresented 14.2%. Although the most frequent casesarebetween20and39yearsofage,thereare stud-iesshowingariseincasesamongtheelderly(60---76years ofage).7,17 This couldbeexplainedbythe increaseinthe
elderlypopulation, thedevelopment ofmedicine totreat erectiledysfunction, aswell asother possibilities of sex-ual contact.18 The involvementof theseextremes in ages
highlightstheneedforbroaderpublichealthactions. Reportsintheliteratureshowan importantassociation betweensyphilis andHIV infection.19,20 It isbelieved that
syphilitic lesionsrepresent a potential gateway toHIV, in turnfacilitatinginfection.Inaddition,both diseasesshare thesexualrouteofinfection.10,21Otherstudieshavepointed
outthat itis essential for all patientssuspected of being infectedwithsyphilistoundergoHIVtesting.18InBrazil,the
anti-HIVtesthasbeenrecommendedincasesofsuspected sexually transmitteddisease since2016, following recom-mendation of the Federal Medical Council. This explains whyonly afew patientsunderwentthis test.Likewise, in thepresentstudy,allpatientsscreened forHIV presented apositiveserology.Hence,informativeactionsforsafesex maybeefficientin reducingsyphilis,HIV, andother sexu-allytransmitteddiseases.Moreover,itisimportantthatall sexualpartnersofsyphilispatientsbescreenedaswell.
Penicillin remains the treatment of choice for syphilis,22,23andmostpatientsweretreatedwithpenicillin
G benzathine. Interestingly, a single or double dose pro-tocol of azithromycin is also beingadvocated toimprove treatmentadherence.24,25
Retrospective studies using medical records have the advantageofprovidinginformationatalowcost;however, datacollectedaredependent onhowcompletethe infor-mationis.Moreover,inthepresentstudy,casesofacquired syphilis in patients not presenting oral lesions could not bediagnosed andthe accurate numbers maybe underes-timated.Despitetheselimitations,theresultsdescribedin thispaperareinconsonancewiththeliterature.
Conclusion
Inconclusion,thepresentstudycorroborateswithreportson thenewsyphilisburdeninrecentyears.Thestudyreported on 85 cases of acquired syphilis diagnosed through oral lesions,highlightingtheneedforthecontinuouseducation andtrainingoforalhealthprofessionals.Patientsofallages and sexes were affected, reinforcing the need for more widespreadpreventiveactions.
Funding
ThisworkwassupportedbyFAPEMIG(StateofMinasGerais ResearchFoundation),CAPES(Coordinationforthe Improve-mentofHigherLevelEducationPersonnel),andPRPq/UFMG grantnumber #05/2016 (Pró Reitoria de Pesquisa UFMG). MichelleDaniellePortoMatiasisaFAPEMIGscholarship.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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