CASE
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InternationalJournalofSurgeryCaseReports4 (2013) 11–14
ContentslistsavailableatSciVerseScienceDirect
International
Journal
of
Surgery
Case
Reports
jo u r n al h om ep a g e :w w w . e l s e v i e r . c o m / l o c a t e / i j s c r
Gouty
arthritis
at
interphalangeal
joint
of
foot
after
sildenafil
use:
A
case
report
Tugrul
Alici
a,1,
Yunus
Imren
b,∗,
Mehmet
Erdil
b,2,
Hakan
Gundes
c,3aDepartmentofOrthopaedicsandTraumatology,MaltepeUniversity,Istanbul,Turkey bDepartmentofOrthopaedicsandTraumatology,BezmialemVakifUniversity,Istanbul,Turkey cDepartmentofOrthopaedicsandTraumatology,MedipolUniversity,Istanbul,Turkey
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t
i
c
l
e
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n
f
o
Articlehistory: Received9May2012
Receivedinrevisedform8August2012 Accepted24August2012
Available online 28 September 2012 Keywords: Arthritis Gouty/chemicallyinduced Interphalengealjoint Sildenafil
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INTRODUCTION:Interphalangealjointoffootisaveryunusuallocationforgoutyarthritisandsildenafil usemaycausethisphenomenon.
PRESENTATIONOFCASE:A58-year-oldhypertensivemanwasadmittedtohospitalwithpainandswelling overinterphalengealjointofhisrightgreattoe.Hishealthhistoryincludedtheuseofdiureticsforalong timeandhislastgoutattackwastwoyearsagoatfirstmetatarsophalengealjointofrightfoot.Sildenafil, aselectiveinhibitorofphosphodiesterasetype5(PDE5),wasadministeredincaseoferectiledysfunction fortwomonths.Subsequently,hehadseveralepisodesofpainandswellingatfirstinterphalangealjoint ofrightgreattoe.Boththeonsetandrecurrenceofsymptomswerejustseenthedayaftersildenafiluse. Thepatientwasfreeofsymptomsafterdiscontinuationofthedrug.Afteraninitialevaluation,goutwas diagnosedonthebasisofsynovialfluidanalysis.
DISCUSSION:Thiscasedemonstratesararelocationofgoutyarthritiswithanuncommonetiology: sil-denafil.Regardingtheclinicaldata,thediscussionwasmadetoexpandthehorizonfordiagnosisof patientswithsimilarsymptoms,toidentifyriskfactorsforgoutrelevanttoelderliness,andtoreviewthe managementofgout.
CONCLUSION:Sildenafilusemaycausegoutyarthritis,andsurgicaldecompressionmaybehelpfulfor definitivediagnosisandsymptomreliefinatypicalpresentationofgout.
© 2012 Surgical Associates Ltd. Published by Elsevier Ltd.
1. Introduction
Goutisaclinicalconditionaffecting1%ofadultmalesin devel-opedcountries.1Itisthemostcommoncauseofinflammatoryjoint
diseaseinmenagedover40years.1 Depositionofmonosodium
uratemonohydratecrystalsintojointandsofttissueisthe under-lying pathology and there is a causative relationship between elevatedblooduricacidlevelanduratecrystalformation.Although theexacttriggermechanismofanacuteattackispoorly under-stood,predictorsfor thedevelopmentofgoutin hyperuricemic individuals have beenidentified.2 These include increased uric
acidlevel,alcoholconsumption,hypertension,useofdrugs espe-ciallyantihypertensives, increasedbody massindex,and family historyofgout.2–4Sildenafil,aselectiveinhibitorofcyclic
guano-sine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5),mayrarelycausegoutyarthritis.5 Goutcaneither
mani-festasacutearthritisorchronicarthropathy,whichisalsocalled
∗ Corresponding authorat: Department ofOrthopaedics and Traumatology, BezmialemVakifUniversity,AdnanMenderesBulvarı,VatanCaddesi,34093Fatih, Istanbul,Turkey.Tel.:+905423661038;fax:+902126217580.
E-mailaddresses:tugrulalici@yahoo.com(T.Alici),yunusimren@yahoo.com
(Y.Imren),drmehmeterdil@gmail.com(M.Erdil),gundesh@yahoo.com(H.Gundes). 1 Tel.:+905326841119;fax:+902166261070.
2 Tel.:+905324249732;fax:+902126217580. 3 Tel.:+905326841119;fax:+902166261070.
tophaceous gout.1,6 Gouty arthritis is most commonly seen at
metatarsophalangealjoint.Weherereportanuncommoncaseof tophusformationatfirstinterphalengealjointoffoot,probablydue tosildenafiluse.
2. Casepresentation
A58-year-oldmalepatientwasadmittedtohospitalwith two-monthhistoryofmoderatepainandswellingoverinterphalangeal jointofhisrightgreattoe,whichwasaffectingshoewear.Thepain wasoutofproportionwithswellingandworseatnightsafterusing medicationfor erectiledysfunction.Hehadvisitedtwoprimary carephysiciansbeforeadmissionandwasprescribedpainkillers for hisacutesymptoms. Hishealth history includedtwo previ-ousepisodesofgoutinboth firstmetatarsophalangealjoints (2 and4yearsprior),hypertensionandcoronaryarterydiseasefor 8years.Hismedicationswereperindopril(4mg), hydrochloroth-iazide (25mg),salicylicacid(100mg),allopurinol (800mg)and colchicine(0.5mg).Hedeniedsmoking,butoccasionalalcoholuse wasnotedoneveryweekend.Hewasnotonanyparticulardiet. Dueto erectiledysfunction,hehastaken 100mgsildenafil p.o. weeklyfor2monthsandwasstillonmedicationjustbeforethe dayofadmission.Anycontributoryfamilyhistoryorallergyhistory werenotnoted.Physicalexaminationrevealed3cm×2cmtender swellingwithoutcellulitisorulcerationoverdorsomedialaspectof firstinterphalengealjointofrightfoot(Picture1).Jointmotionwas 2210-2612 © 2012 Surgical Associates Ltd. Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.ijscr.2012.08.014
Open access under CC BY-NC-ND license.
Open access under CC BY-NC-ND license.
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12 T.Alicietal./InternationalJournalofSurgeryCaseReports4 (2013) 11–14
Picture1. Swellingoverdorsomedialaspectoffirstinterphalengealjointofright foot.
extremelylimitedduetopainandswelling.Therewerenoother swellingsortophinotedespeciallyonearsorotherjoints.Hehad anaveragebuiltwithbodymassindex(BMI)of27.4.
Plainradiographyofrightfootshowedjointeffusion,andsoft tissueswellingaroundfirstinterphalengealjoint(Fig.1). Labora-torydata werewithinnormallimits (Table1).In theoperating room,surgicaldecompressionoffirstinterphalangealjointofhis rightfootwasperformedwithadorsomedialincisionoverswelling (Pictures2and3).Debrisconsistedofthick,chalky,whitematerial correspondingtogoutytophus(Picture2).Thesurgicalapproach wasadequatetoexposethearticularsurfaces.Afterdebridement andvigorousirrigationwithsterilesalinesolution,intraarticular methyprednisolone20mgwasinjectedtotheaffectedsite.Incision wasgentlysuturedwithouttightening.Additionalindomethacin 50mgwasprescribedthreetimesdailyfor10days.Hispainscale was7/10and 3/10beforeand aftersurgery, respectively. Syno-vialfluidanalysiswasconfirmatory(Table2).Lightmicroscopyof debrisdemonstratedgoutytophiconsistingofmonosodiumurate
Table1
Laboratorydataatadmission.
Test Value Valuerange
WBC 8200mm3 4–10 Hemoglobin 12.1g/dl 12.5–16.5 Sodium 141meq/l 135–145 Potassium 3.9meq/l 3.5–4.9 Chloride 105meq/l 96–110 BUN 19mg/dl 6.0–23.0 Creatinine 0.8mg/dl 0.6–1.4 Totalprotein 5.4g/dl 6.0–8.0 Albumin 3.7g/dl 3.6–5.0 Calcium 8.2mg/dl 8.0–10.5 Hemoglobin 11.6g/dl 12.6–16.5 Plateletcount 236,000mm3 150–400 Uricacid 6.4mg/dl 3.4–7.0
Fig.1. Plainradiographyofrightfootshowingjointeffusion,andsofttissueswelling
aroundfirstinterphalengealjoint.
Picture2.Debrisconsistingofthick,chalky,whitematerialcorrespondingtogouty tophus.
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T.Alicietal./InternationalJournalofSurgeryCaseReports4 (2013) 11–14 13
Picture3. Closureofdorsomedialincisionafterdecompression.
crystals(Fig.2).Microscopicexaminationofthespecimenrevealed polynuclear giant cells and histiocytes around needle-like void spacesandgranularnoduleformationwasseen(Fig.3).Wound healingwasobservedonday18withoutcomplication.Thepatient wasfreeofsymptomsat2months,postoperatively.
3. Discussion
Goutisametabolicdiseasethatcanmanifestasacuteorchronic arthritiswithdepositionofuratecrystalsinconnectivetissueand kidneys.Goutytophiarecommonlyfoundinarticularandother cartilages;in synovium,tendonsheaths,and otherperiarticular structures;inepiphyses,and insubcutaneouslayersoftheskin intheextremities.Tophiaremostoftenseenintissuesthathavea poorbloodsupplyandlowtemperature,suchastheearhelixand firstmetatarsophalengealjoint.7Thenodulesareyellowish-white,
andnon-tender,andrangeinsizefrom1mmto7cm.Aspiration yieldsachalky-likematerialthatappearsasneedle-likecrystals underlightmicroscopy.Allpatientshavehyperuricemiaatsome pointoftheirdisease.Hyperuricemiaresultsfromeitherdecreased renalexcretion(whichoccursin90%ofgoutpatients)or hyperpro-ductionofuricacid.8Drugsthatmaycausehyperuricemiaandgout
Table2
Synovialfluidanalysis.
Test Value Normal
Clarity Translucent Transparent
Color WhitishYellow Clear
WBC(permm3) 2000 <200
PMNs(%) 55 <25
Gramstain Noorganisms Noorganisms
Culture Negative Negative
Totalprotein(g/dl) 1.9 3.1
LDH(IU/l) 494 105–330
Glucose(mg/dl) 44 70–110
Crystal Monosodiumuratecrystals None
Fig. 2.Light microscopy of debris demonstrating gouty tophi consisting of
monosodiumuratecrystals.
Fig.3.Microscopicexaminationofthespecimenrevealingpolynucleargiantcells
andhistiocytesaroundneedle-likevoidspacesandgranularnoduleformation.
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14 T.Alicietal./InternationalJournalofSurgeryCaseReports4 (2013) 11–14
include diuretics, cyclosporine, low-dose aspirin, ethambuthol, pyrzinamide,andnicotinicacid.9 Sildenafil,a selectiveinhibitor
ofcyclicguanosinemonophosphate(cGMP)-specific phosphodie-sterasetype 5 (PDE5),may alsoplaya role in theetiology.5 In
pre-marketingclinicaltrialsover3700patients,rareadverseevents reportedwithsildenafil inadults (all <2%)include arrhythmias, cerebralthrombosis,hypertonia,paresthesias,priapism,migraine, tremor,photosensitivity, colitis, vomiting, abnormal liver func-tiontests,anemia,leukopenia,gout,arthritis,dyspnea,andallergic reactions.5Exactmechanismofsildenafiltotriggeragoutattack
isnot known,butPDE5 is alsofoundinplatelets, vascular and visceralsmoothmuscle,andskeletal musclein additionto cor-puscavernosum.InhibitionofPDE5inthesetissuesbysildenafil mayincreaseantiaggregatoryactivityofnitricoxideand periph-eralarterial-venousdilatation.5Chenetal.reportedacaseofacute
goutyarthritisatfirstmetatarsophalengealjointaftertaking sil-denafil.Thepatienthadseveralattacksonlyafteradministration ofsildenafil,implyingacausalrelationbetweensildenafilandgout episodes.10Sinceourpatient’slastattackwastwoyearsago,and
boththeonsetand recurrenceofsymptomswerejust seenthe dayaftersildenafiluse,itwasconsideredthattherewasacausal relationwithdetoriationofsymptomsandthemedication. Fur-thermore,ourcase had goutattacksat interphalengeal jointof rightgreattoewhichisveryuncommonlocationforgouty arthri-tis.Literaturereviewyielded onlyonecaseof goutyarthritis at interphalangealjointofbigtoethatisreportedasanatypical pre-sentationofgoutbyDobsonetal.11
As some are commonly prescribed, it is important that physiciansdealingwithmusculoskeletaldiseasesanderectile dys-functionmustbeawareofthemedicationsthattheirpatientsare taking.So far,increasing attentionhasbeen drawn tothe role playedbydiureticsinthepathogenesisofgout,particularlyinthe elderly,however,theuseofphosphodiesteraseinhibitorsmayalso contributetotheprogressionofdisease.Goutyarthritisiscaused byintenseinflammationsecondarytomonosodiumuratecrystal depositionin joints.Tophusis oftenfoundintheauricular car-tilageormetatarsophalengealjointofgreattoe.Wepresenteda patientwithgoutytophusformationatthefirstinterphalengeal jointofhisrightfoot.Localfactorsthatcontributetotophus forma-tionarechangesinperioperativepHlevel,lowerbodytemperature, explainingnocturnalattacks;andthelevelofarticulardehydration duetodiuretics.8Thegoalsofgouttreatmentaresymptomcontrol
foracuteattacks,riskfactormodification,pharmacotherapyto pre-ventrecurrenceandchronicsequelaeinthelongrun,andsurgical decompressionoftophiforpainmanagement.
Tophaceous gout may lead to significant morbidity and, if untreated,cancausejointerosionanddestruction.9 Tophaceous
materialmaypresentinaliquid,pasty,orchalky/granularstate. Treatmentmaybeassimple asaspiratingtheliquidor squeez-ingoutpastytophaceousmaterial.Surgeryisoftenindicatedfor thepatientwithsignificanttendonandjointcompromiseaswell asskinbreakdown.Surgicaldecompressionfollowedby optimiza-tionofpharmacologictreatmentandlifestylemodificationprovide goodrecovery.
Conclusion
Sildenafilusemayrarelycausegoutyarthritis.Interphalengeal jointinvolvement of great toe is atypical for goutand surgical decompressionmaybehelpfulfordefinitivediagnosisand symp-tomrelief.
Competinginterests
Theauthorsdeclarethattheyhavenocompetinginterests.
Funding
None.
Consent
Writteninformedconsentwasobtainedfromthepatientforthe publicationofthiscasereportandaccompanyingimages.Acopy ofthewrittenconsentisavailableforreviewbytheEditor-in-Chief ofthisjournalonrequest.
Authors’contributions
TA,YI, ME,and HGwereinvolvedin conception,design and interpretation.TAandYIwrotethemanuscript.TA,YI,andME col-lecteddata,reviewedtheliterature,andprovidedtheimages.All authorsreadandapprovedthefinalversionsubmitted.
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