Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.br
INVESTIGATION
Atypical
manifestations
of
recent
syphilis:
study
of
19
cases
夽,夽夽
José
Carlos
Sardinha
a,
Livia
Lima
de
Lima
a,
Marcel
Heibel
b,
Antonio
Schettini
c,
Sinesio
Talhari
a,
Carolina
Talhari
a,d,∗aDepartmentofSexuallyTransmittedInfections,Fundac¸ãoAlfredodaMattadeDermatologiaeVenereologia,Manaus,AM,Brazil bDepartmentofUrology,UniversidadedoEstadodoAmazonas,Manaus,AM,Brazil
cDepartmentofDermatopathology,Fundac¸ãoAlfredodaMattadeDermatologiaeVenereologia,Manaus,AM,Brazil dDepartmentofDermatology,UniversidadedoEstadodoAmazonas,Manaus,AM,Brazil
Received8December2019;accepted5March2020
Availableonline15July2020
KEYWORDS Syphilis; Syphilis,cutaneous; Treponemapallidum; Treponemal infections Abstract
Background: Syphilisisoneofthemostcommondiseasesthatstartwithgenitalulcers.Aside
fromtheinitial,classiculcerativelesionofsyphilis,calledhardchancre,atypicalpresentations
arecommon,witherosions,erythema,edema,balanitis,andotherdermatologicalconditions.
Associatedwithinitialgenitallesions,thepresenceofinguinaladenopathiesisfrequent,and
thepresenceofhardenedandpainlesslymphangitisonthedorsumofthepenisisrare.
Objectives: Todescribeatypicalpenilemanifestationsinpatientswithearlysyphilis.
Methods: Thepresentstudyreportspatientswhodevelopedcord-likelesionsonthepenis.
Results: Thestudyincluded25patientswithcord-likelesionsonthepenis;in19ofthose,the
diagnosisofsyphiliswasconfirmed.
Studylimitations: Smallnumberofpatientsincluded.
Conclusions: In view ofthefindings ofthepresent investigation,itisimportantto
empha-sizethatall patients whopresentwith cord-like lesionsonthe penismustundergoarapid
test for syphilis, VDRL,serologies for HIV viral hepatitis B and Cand, whenever possible,
histopathologicalandDopplerexams.
©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan
openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
夽 Howtocitethisarticle:SardinhaJC,LimaLL,HeibelM,SchettiniA,TalhariS,TalhariC.Atypicalmanifestationsofrecentsyphilis:study of19cases.AnBrasDermatol.2020;95:589---93.
夽夽StudyconductedattheFundac¸ãoAlfredodaMattadeDermatologiaeVenereologia,Manaus,AM,Brazil. ∗Correspondingauthor.
E-mail:[email protected](C.Talhari). https://doi.org/10.1016/j.abd.2020.03.008
0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
withgenitalulcers.Asidefromtheinitial,classiculcerative lesion of syphilis, called hard chancre, atypical presen-tations are common, with erosions, erythema, edema, balanitis, and other dermatological manifestations.1,3,4
Associated with initial genital lesions, the presence of inguinaladenopathiesisfrequent,andthepresenceof hard-enedandpainlesslymphangitisonthedorsumofthepenis israre.5
Amongthevariousclinicalmanifestationsofsyphilis,the authors of the present study have observed, in patients withrecentsyphilis,painlesscord-likelesions,hardenedon palpation,located mainly in the balanopreputial groove.6
Similarlesionshavealsobeenobservedinpatientsforwhom adefinitiveconclusionabout theetiologyofthe dermato-logicalmanifestationcannotbeobtained.
The present study reports 25 patients with cord-like lesionsonthepenis;in19ofthose,thediagnosisofsyphilis wasconfirmed.
Methods
Inthisretrospectivestudy,25patientswithclinicalsuspicion ofrecentsyphilis,presentinglesionswithacord-likeaspect in the balanopreputial groove, had their medical records evaluated. These patientswere treated at an STI diagno-sisand treatment center, from January 2015 to February 2018.Demographic data,historyofsexualactivities, clini-calevolutionofthemanifestationsobserved,andresultsof laboratorytestsweresurveyed.
All 25 patients underwent rapid test (treponemic), immunochromatographic testing (SD 65, Korea), and the venereal disease researchlaboratory panel (VDRL, Labor-clin----Brazil), asanon-treponemic test.Furthermore, as routine exams, a rapid immunochromatographic test for HIV(Quibasa---BH/MG,Brazil)andserologyforhepatitisB (BioMerieux----France)andC(SD65,Korea)wereperformed. Insixpatients,biopsieswereperformed(with3or4mm punches)for histopathological,immunohistochemical,and polymerase chain reaction (PCR) assessments. The sec-tions for histopathological examination werestained with hematoxylin-eosin.Immunohistochemistryexaminationwas performedintwopatients,usinganti-Treponemapallidum monoclonal antibodies (Dako ---- Santa Clara, CA, United States).PCRwasperformedinfourpatients.Toperformthe PCR,probes andprimersdevelopedinthe molecular biol-ogylaboratoryofthecenterwherethestudywasdeveloped wereused,targetingthepolAgeneofT.pallidum,adapted fromLeslieetal.7
ThisstudywasapprovedbytheEthicsCommitteeofthe STI diagnosis and treatment center where the data were collected(CAAE:13217519.0.0000.0002).Allpatientssigned aninformedconsentformtoparticipateinthestudy.
All patients had lesions with arciform disposition, of cartilaginous consistency on palpation, of variable sizes, located around the balanopreputial groove (Figs. 1A and 1B, 2A and 2B and 3). In some patients, mild ulcerations and scars were observed in the vicinity of the hardened areas (Figs. 1A and 1B, and 3). Two (8%) patients presented inguinal lymphadenomegaly and syphilitic roseola, associated with penile lesions (Figs. 2 and3).
TheVDRLwaspositivein19patients(76%),withvariable titrationsfrom1:4to1:512(mode:1:32).Inallpatientswith reagentVDRL,therapidtreponemictestwasalsopositive. No pattern was identified between the time of evolution andthepositivityfortherapidtest,orbetweenthetimeof evolutionandVDRLtitration.
HIVserologywaspositiveintwopatients(8%);one(4%) of them wasonregular antiretroviraltreatment. Serolog-ical tests for viral hepatitis Band C were negative in all patients.
Thesixpatients(24%)withnegativecomplementarytests for syphiliswereclinicallysimilartothosewithconfirmed treponematosis.Theprobablecauses,intwocases(33.3%), werebalanitisassociatedwithpsoriasisandseborrheic der-matitis.Intheotherfourpatients(66.6%),noinflammatory processes were observed in the glans or balanopreputial groove.
Histopathologicalexamination of thesixpatients (31%) whosepenilelesionswerebiopsiedshowedalterations usu-ally observed in recent syphilis lesions: epidermis with hyperkeratosisandacanthosis;inthedermis,theinfiltrate varied from mild to moderate, arranged around the ves-sels,withtumefiedendothelialcells(Fig.4).Twopatients (10.5%) presented ill defined granulomas, formed by his-tiocytes, lymphocytes, and rare epithelioid cells. In five cases (26.3%) numerous plasma cells werefound andtwo (10.5%)patients presentedneutrophils intheinfiltrate. In thesesix cases(31.5%), thediagnosis of syphilis was con-firmed.
PCR for T. pallidum was positive in all four cases in whichthistestwasperformed.Thepresenceoftreponema was demonstrated in the two patients who underwent immunohistochemistry(Fig.5).Inallofthesecases,there was agreement with the positive serological results for syphilis.
The 19patients diagnosed withsyphiliswere classified ashaving recent infection andtreated witha singledose of 2,400,000 IU of penicillin G benzathine, according to the recommendation of the Brazilian Ministry of Health.3
All patients presented clinical cure, withcomplete lesion resolution within 30 days; they continue to be regularly followed-up, withclinical evaluation andcontrol serology forsyphiliseverythreemonths.
Figure1 (A)Recentsyphilis.Cord-likelesion(VDRL1:128).(B),Noticethelarge-volumepainlessadenomegaly.
Figure2 Recentsyphilis.Cord-likelesionandshallow,clean ulcer.
Figure3 Cord-likelesionandunderlyingshallowulceralong
almosttheentireinduratedarea.Noticethesecondarylesions
inthehandandglans.
Discussion
STIs,andparticularlysyphilis,areanimportantglobalpublic healthissue.Theincreaseinthenumberofsyphiliscaseshas beensignificantinrecentyears,affectingpopulationsofall socioeconomiclevels.3InBrazil,therewasanincreasefrom
2.0 cases/100,000 inhabitants, in 2010, to 42.5/100,000 inhabitants,in2016.Itisimportanttonotethatsyphilis
noti-Figure4 Hyperkeratosisandregularacanthosisofthe
epithe-lium.Inthechorion,lymphoplasmacyticinfiltratesurrounding
superficialvessels(Hematoxylin&eosin,×100).
Figure 5 Immunohistochemistry−Patient # 1. Positive for
Treponemapallidum.
ficationbecamemandatoryinBrazilin2010.Therefore,this increaseincasesmayalsoberelatedtothebetterrecords.3
Over the last four decades, the professionals at the referencecenterwhere thestudywascarriedout metan important demand for STI treatment in the state capital wherethecenterislocated.From2010to2018,4,373new casesofsyphiliswereobservedinthiscenter.
Theclinical presentationsofsyphilis,inallphases, are varied,anditisconsideredtobe‘‘thegreatimitator’’by mostscholarsinthisarea.Intheearlyphase,mainlyinthe genitalregion,theinitiallesionsofsyphiliscanpresentthe typical,classiculcerativeaspect,calledhardchancre.
How-andpositiveafteroneweek. Theliterature indicatesthat treponemaltestscanbenegativein30%ofcasesatthefirst consultationofpatientswithlesionssuggestiveof primary syphilis.10
Inthesixcasesinwhichthehistopathological examina-tionwasperformed, an inflammatory infiltrate suggestive of recent infection was found; all of these patients had laboratoryconfirmationforsyphilis.
Among the references consulted, current and classic, only Fournier, in 1889,17 described recent syphilis with a
cord-likeaspect.1,2,11---17
Accordingtooneoftheauthorsofthisarticle,nocases ofpenilecord-likelesioninrecentsyphiliswerediagnosed inthecenterwherethestudywasconductedintheperiod priorto2015. Itispossiblethat theincreasednumbersof patientswithSTIs, inthecenter where thepatientswere included, and, consequently, of the cases of syphilis and atypicalpenilelesions,arerelatedtotherestrictive mea-suresforthepurchaseofantibiotics,establishedinBrazilas of2010(ResolutionRDC44,ofOctober26,2010,fromthe BrazilianNationalHealthSurveillanceAgency[ANVISA]).
In the differential diagnosis of penile lesions withthe clinicalaspectspresentedinthisstudy,mainlyMDand scle-rosinglymphangitis(SL)shouldbeconsidered.8,9,18---22
The MD described in 1939, is secondary to superficial thrombophlebitis,withatypicallocationonthechestwall.20
PenileMDissecondarytosuperficialthrombophlebitisofthe dorsalveinofthepenis; itispainfulonpalpationandthe diagnosis is relatively easy through Doppler ultrasonogra-phy.Vascularimpairmentmaybeassociatedwithexcessive sexual activity, intense physical exercise, or malignant neoplasias.Dependingonthetimeofevolution, histopatho-logicalexaminationmaybenecessary;itusuallyevidences thrombusformation,recanalization,fibrosis,andthickening ofthevenouswall.8,9,18---21In2009,acaseofMDassociated
withprimarysyphiliswasreported.8
For most authors, SL is not of venereal etiology as well beingpractically indistinguishable fromMD.21 Itmay
beassociatedwithintense sexualpractice,and thereare referencesofitsassociationwithcircumcision.Thereis dis-agreementregardingthepathogenesisofSL;impairmentof lymphatic and venous vesselshas already been reported. Inthehistopathological examination ofSL, thereis thick-eningofthelymphvesselwall,withpartialortotallumen occlusionand,occasionally,chronicinflammatoryprocess.22
Although penile SL and MD are rarely of venereal etiol-ogy,routineSTIexamsaresuggested inallcaseswiththis topography.8,9,18---22Inallpatientsinthepresentstudy,there
wasno involvement of the dorsal vein of the penis. The lesionswerearciform,aroundthebalanopreputialgroove.
Some patientsin thiscase serieshad lesionssimilarto ‘‘giantsyphiliticchancre’’, characterizedbythepresence ofulcers,associatedwithcord-likelesions,locatedinthe
Inamorerecentpublication,underthename‘‘Indurative edema of the foreskin simulating phimosis, an atypical manifestation ofprimarysyphilis,’’twocases withlesions similarto theones described in thepresent investigation aredescribed,called‘‘necklacelesions.’’8Inthisstudy,the
authorsdrawattentiontothedifferentialdiagnosisbetween syphilitic phimosis, characterized by fibrosis of the fore-skin,andhardenededema,acomplicationofhardchancre located in the coronal sulcus or internal surface of the foreskin. Despite the hardened,necklace-like appearance observed in the 19 cases in the present study, none pro-gressedtosyphiliticphimosis.
Aclinicalpicturesimilartothatofthe19syphiliscases describedinthepresentstudyisshowninaphotooftheSTI chapterofaclassictextbook,beingdescribedasSL.11The
authorhoweverdoesnotpresentdiagnosticevidence. Itis noteworthythatcord-like lesions,similartothose observedinpatientswithsyphilisinthepresentstudy,may berelatedtootherinflammatoryprocessesoftheglans.In sixofthe25patientsstudied,serologyforsyphiliswas nega-tive,anditisreasonabletoconsideraprobableassociation withbalanitissecondarytopsoriasis,seborrheicdermatitis, chroniculcerationoftheglans,andunidentifiedcauses.To date,thereisnoexplanationforthepathophysiologyofthe manifestationsobservedinthesepatients.
Conclusions
In light of the findings of the present investigation, it is importanttoemphasizethatallpatientswhopresentwith cord-likelesionsinthepenismustundergoarapidtestfor syphilis,VDRL,serologiesforHIV andviralhepatitisBand C and, whenever possible, histopathological and Doppler exams.
Financial
support
Nonedeclared.
Authors’
contributions
José Carlos Sardinha: Approvalof the final version of the manuscript; conception andplanning of the study; elabo-rationandwritingofthemanuscript;obtaining,analyzing, andinterpretingthedata;criticalreviewofthemanuscript. Livia Lima de Lima: Elaboration and writing of the manuscript;criticalreviewoftheliterature;criticalreview ofthemanuscript.
Marcel Heibel: Conception and planning of the study; elaborationandwritingofthemanuscript;obtaining, ana-lyzing,andinterpretingthedata;intellectualparticipation
in propaedeutic and/or therapeutic conduct of studied cases.
Antonio Schettini: Approval of the final version of the manuscript;obtaining,analyzing,andinterpretingthedata; effectiveparticipationinresearchorientation;intellectual participationinpropaedeuticand/ortherapeuticconductof studiedcases;criticalreviewofthemanuscript.
Sinesio Talhari: Approval of the final version of the manuscript;conceptionandplanningofthestudy; elabora-tionandwritingofthemanuscript;obtaining,analyzing,and interpreting the data; effective participation in research orientation;criticalreviewofthemanuscript.
Carolina Talhari: Approval of the final version of the manuscript;conceptionandplanningofthestudy; elabora-tionandwritingofthemanuscript;obtaining,analyzing,and interpretingthedata;effectiveparticipationinresearch ori-entation;intellectualparticipationinpropaedeuticand/or therapeuticconductofstudiedcases;criticalreviewofthe literature;criticalreviewofthemanuscript.
Conflicts
of
interest
Nonedeclared.
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