Clinical Efficacy of Low Dose Intralesional 5-Fluorouracil (5-Fu) in the Treatment of Keloids

Jemds.comOriginal Article

CLINICAL EFFICACY OF LOW DOSE INTRALESIONAL 5-FLUOROURACIL (5-FU) IN THE TREATMENT OF KELOIDS

K. N. Shivaswamy1, A. L. Shyamprasad2, T. K. Sumathy3, M. Y. Suparna4

1Associate Professor, Department of Dermatology, M. S. Ramaiah Medical College.

2Professor, Department of Dermatology, M. S. Ramaiah Medical College.

3Senior Professorand HOD, Department of Dermatology, M. S. Ramaiah Medical College.

4Senior Resident, Department of Dermatology, M. S. Ramaiah Medical College.

ABSTRACT

Keloidisanareaofovergrowthoffibroustissuethatusuallydevelopsafterhealingofskininjuryandextendsbeyondtheoriginaldefect.Theexistingtreatmentmodalitiesincludeintralesionalsteroids,cryotherapy,siliconegelsheets,verapamiland5-fluorouracil(5-FU).1-6Butnonehaveshowntobeveryeffective.

OBJECTIVE

Toevaluatetheclinicalefficacyoflowdoseintralesional5-FUinthetreatmentofkeloids.

RESULTS

Atotalof30keloidsin15subjectswereassessedfortheefficacyoflowdoseintralesional5-FU.Outof30keloids,4showed<25%ofclinicalimprovementfrombaseline,8hadimprovementbetween26%-50%,16hadimprovementbetween51%-75%and2hadimprovementof>75%asassessedbyphotographicmethods.

CONCLUSION

Fromthisstudyithasbeenconcludedthatlowdoseintralesional5-FUissafeandeffectivemodalityofinthetreatmentofkeloids.

KEYWORDS

Keloids, Intralesional 5-FU, Low Dose.

HOW TO CITE THIS ARTICLE:K. N. Shivaswamy, A. L. Shyamprasad, T. K. Sumathy, M. Y. Suparna.“Clinical Efficacy of Low Dose Intralesional 5-Fluorouracil (5-FU) in the Treatment of Keloids.” Journal of Evolution of Medical and Dental Sciences 2015; Vol. 4, Issue 97, December 03; Page: 16229-16231, DOI: 10.14260/jemds/2015/2389

Journal of Evolution of Medical and Dental Sciences/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 97/ Dec.03, 2015 Page 1

Jemds.comOriginal Article

INTRODUCTION

Keloidisanareaofovergrowthoffibroustissuethatusuallydevelopsafterhealingofskininjuryandextendsbeyondtheoriginaldefect.Theyareprimarilyofcosmeticconcern,sometimescanbedisfiguring.Theexistingtreatmentmodalitiesincludeintralesionalsteroids,cryotherapy,siliconegelsheets,topicalretinoicacid,tacrolimus,imiquimod,colchicine,verapamiland5-fluorouracil(5-FU).1-6Butnonehaveshowntobeveryeffective.

Intralesionalinjectionofhighdoseof5-FUforkeloidsactsbynecrosisoffibroblastsandlowdosehasshowntoreducefibroblastproliferationandcauseapoptosis.Thereareonlyafewclinicalstudiesusinglowdose5-FUforkeloids.7,8

Needforthe Study

Theexistingtreatmentmodalitiesincludingintralesionalsteroids,cryotherapy,siliconegelsheets,imiquimod,verapamilandhighdose5-FUhavenotshowntobeveryeffectiveandthereareonlyafewclinicalstudiesusinglowdose5-FUforkeloids.Hence,thestudyisbeingundertaken.

OBJECTIVE

Toevaluatetheclinicalefficacyoflowdoseintralesional5-FUinthetreatmentofkeloids.

Financial or Other, Competing Interest: None.

Submission 17-11-2015, Peer Review 18-11-2015,

Acceptance 26-11-2015, Published 01-12-2015.

Corresponding Author:

K. N. Shivaswamy,

Associate Professor,

Department of Dermatology,

M. S. Ramaiah Medical College, Bengaluru.

E-mail:

DOI:10.14260/jemds/2015/2389

MATERIALAND METHODS

Study Design

Anopenlabelstudyon30keloidsin15subjectsattendingtheDepartmentofDermatologyinaTertiaryCareHospitalduringJune2012andNovember2012.

Inclusion Criteria

Patientswithkeloidsof10cmandlessalongthelongestdiameterintheagegroup18-75yearswereincludedinthestudy.

Exclusion Criteria

Keloidswithsignsofinfection.

Historyofhypersensitivityand/orintoleranceto5-FU.

Womenintheagegroup18to45yearswhohavenotcompletedthefamily.

Dosage Schedule

Atotaldoseofaround1mlof5-FU(10mg/ml)injectedintothelesiondependinguponthesizeofkeloidoncein2weeksforaperiodof3monthswithadoseofaround0.1mlateachinjectionsiteafterobtaininginformedconsent.Lignocaineisaddedinpatientswhoexperiencepainduringinjection.

Parameters Studied

Theinitialassessmentwasdonebysingleinvestigatoratbaselineregardingsite,size,extentandprogressionofkeloids.Clinicalassessmentwasdonebythesameinvestigatorateachvisitfollowingtheinjectionalongwithphotographicdocumentation.Theclinicalresponsesweregradedasgrade0,noimprovement (Noreductioninsizefrombaseline);gradeI,mildimprovement(<25%reductionfrombaseline);gradeII,moderate(25%-50%reductionfrombaseline);gradeIII,goodimprovement(50%-75%reduction

Journal of Evolution of Medical and Dental Sciences/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 97/ Dec.03, 2015 Page 1

Jemds.comOriginal Article

from baseline).Patientswerefollowedupatendof1,2,3and6monthsafterthelastinjectiontolookforfurtherreductioninsizeand/orifanyrecurrenceofkeloids.Sideeffectsofthedrugwererecordedateachvisit.Resultsweretabulatedandtheclinicalefficacywasassessedusingappropriatestatisticalmethods.

Statistical Analysis

ThedatawereanalyzedusingSPSSV19software.ThedescriptivestatisticsofreductioninsizeofkeloidswereanalyzedandexpressedintermsofmedianandInterquartileRange(IQR)sincethedatawasskewed.Wilcoxonsignedranktestwasusedtofindthestatisticalsignificanceinthereductioninsizeofkeloids.Pvalueoflessthan0.05wasconsideredforstatisticalsignificance.

RESULTS

Atotalof30keloidsin15subjectswereassessedfortheefficacyoflowdoseintralesional5-FU.Outof15patients,13weremalesand2werefemales.Theagerangewas19-63yrs.Thedurationofkeloidsvariedfrom10monthsto16years.

Theonsetwasspontaneousin10andin5followedbytrauma.In13patientstheprogressionwasgradual,butin2rapid.Ninepatientshadkeloidatsinglesiteandin6atmultiplesites.In4patientskeloidsizewaslessthan2cm,8hadsizebetween2-5cm,andin3itwasmorethan5cms.Fourpatientshadprevioushistoryoftakingtopicaltreatmentforkeloidsand11patientshadnotsoughttreatment.Familyhistoryofkeloidanddiabeteswasevidentin1patienteach.Lignocainewasaddedin3patientstoreducethepain.Sideeffectswerenotedintheformofpainin3,pustulesin2andnecrosisin1patient,whichwereself-limitingandnotwarrantdrugwithdrawal.

Outof30keloidsin15patients,themediankeloidareabeforethetreatmentwas4withaninterquartilerangeof1.5to7.8andthisiscomparedwithposttreatmentarea,median1.5andinterquartilerange0.6to4.Wilcoxonsignedranktestwasusedtoassessthereductioninthesizeofkeloidbeforeandaftertreatmentwhichwassignificant.(P<0.001).

Comparisonofareaofkeloid,preandpostvalues,

Keloid Area / Pre Treatment
Median (IQR) / Post Treatment
Median (IQR) / P - value
Score / 4.0(1.5–7.8) / 1.5(0.6–4.0) / 0.001

IQR–InterquartileRange

Outof30keloidsamong15patients,4showed<25%ofclinicalimprovementfrombaseline,8hadimprovementbetween26%-50%,16hadimprovementbetween51%-75%and2hadimprovementof>75%asassessedbyphotographicmethods.

DISCUSSION

Keloidisanareaofovergrowthoffibroustissuethatusuallydevelopsafterhealingofskininjuryandextendsbeyondtheoriginaldefect.Theyareprimarilyofcosmeticconcern,sometimescanbedisfiguring.Theexistingtreatmentmodalitiesincludeintralesionalsteroids,cryotherapy,siliconegelsheets,topicalretinoicacid,tacrolimus,imiquimod,colchicine,verapamiland5-fluorouracil(5-FU).1-6Butnonehaveshowntobeveryeffective.

Thepresentstudyhasbeenaimedatfindingtheclinicalefficacyoflowdose5-FUforkeloids.Theresultswerecomparabletootherstudiesinvolvinghigherdoseof5-FUandcombinationof % FUandtriamcinolone.2,4,9

Intralesionalinjectionofhighdoseof5-FUforkeloidsactsbynecrosisoffibroblastsandlowdosehasshowntoreducefibroblastproliferationandcauseapoptosis.

Thereareonlyafewclinicalstudiesusinglowdose5-FUforkeloids.7,8

Thesideeffectsnotedwerefewintheformofpain,pustulationsandnecrosiswhichdidnotwarrantdiscontinuationoftherapy.

CONCLUSION

Fromthisstudy,ithasbeenconcludedthatlowdoseintralesional5-FUissafeandeffectivemodalityinthetreatmentofkeloids.

REFERENCES

1. Boutli-KasapidouFetal.Hypertrophicandkeloidalscars:anapproachtopolytherapy.IntJDermatol2005;44:324.
2. NandaS,ReddyBS.Intralesional5-FUasatreatmentmodalityofkeloids.DermatolSurg2004;30(1):56-57.
3. GuptaS,KarlaA.Efficacyandsafetyofintralesional5-fluorouracilinthetreatmentofkeloids.Dermatology2002;204(2):130-2.
4. DavisonSP,DayanJH,ClementsMW,SonniS,WangA,CraneA.Efficacyofintralesional5-fluorouracilandTriamcinoloneinthetreatmentofkeloids.AesthetSurgJ2009;29:40-46.
5. KontochristopoulosG,StefanakiC,PanagiotopoulosA,etal.Intralesional5-fluorouracilinthetreatmentofkeloids:anopenclinicalandhistopathologicstudy.JAmAcadDermatol2005;52:474-79.
6. D’AndreaF,BrongoS,FerracoG,BaroniA.Preventionandtreatmentofkeloidswithintralesionalverapamil.Dermatology2002;204:60-62.
7. LHuang.Lowdose5-FUinducescellcycleG2arrestandapoptosisinkeloidfibroblasts.BJD2010;163:1181-85.
8. WuXL,LiuW,CaoYL.Clinicalstudyonkeloidtreatmentwithintralesionalinjectionoflowconcentration5-FU.ZhonghuaZhengXingWaikeZaZhi2006Jan;22:44-46.
9. Sharma S, Bassi R, Gupta A. Treatment of small keloids with intralesional 5-fluorouracil alone vs intralesional triamcinolone acetonide with 5-fluorouracil. Journal of Pakistan Association of Dermatologists 2012;22:35-40.

Fig. 1: Before Treatment

Fig. 2: After Treatment 2nd Visit

Fig. 3: After Treatment 3rd Visit

Journal of Evolution of Medical and Dental Sciences/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 97/ Dec.03, 2015 Page 1

Jemds.comOriginal Article

Journal of Evolution of Medical and Dental Sciences/ eISSN- 2278-4802, pISSN- 2278-4748/ Vol. 4/ Issue 97/ Dec.03, 2015 Page 1