Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV consented toskinbiopsies.Histopathologicalexamina (Fig. S1 the meannumberofnaeviwas549.7(range212–1,756) of radotinibtherapywas16.7(range7–48)months,and with slightlyelongatedandclubbedreteridges(Fig.S2 melanocytes ornestsatthedermoepidermaljunction tion ofthepigmentedlesionsdemonstrateddiscrete years) aresummarizedin and 5females,meanage43.4years,range24–74 The characteristics of the 10patients with CML (5males RESULTS University ofKorea. The studywasapprovedbytheethicscommitteeofCatholic was givenwritteninformationregardingtheaimofstudy. examination wasdocumentedforallpatients.Eachparticipant January 2012 and May 2015. Past medical history and clinical administration ofradotinibwerereferredtoourclinicbetween developed multiple eruptivepigmented lesions duringoral Ten patientswithCML intheDepartmentofHematologywho MATERIALS ANDMETHODS development ofEMN. between radotinibtherapyinpatientswithCML andthe association an of report first the is this knowledge, our the treatment of CML with intolerance of other TKIs. To selective BCR/ABL tyrosinekinaseinhibitor(TKI)for developed whilereceivingradotinib.Radotinibisanovel with chronicmyeloidleukaemia(CML),allofwhich role (6). We describehere10casesofEMNinpatients that animmunosuppressedstatemayplayimportant mechanism leading to EMNisunclear, butitisthought administration ofimmunosuppressivedrugs(1–5). The have beendescribedafterseverebullousdiseasesand sudden onsetofhundredsmelanocyticnaevi. EMN is anuncommonphenomenoncharacterizedbythe Development oferuptivemelanocyticnaevi(EMN) wanted toremovemultiple naeviforcosmeticreasons during radotinibtherapy. We treated4patientswho diagnosed melanocyticnaeviwithEMNthatdeveloped Based on the clinical and histopatho­ 1 Journal Compilation ©2017ActaDermato-Venereologica. ISSN 0001-5555 This isan open access article under the CC BY-NC license.www.medicaljournals.se/acta Youngdeunpo-gu, Seoul, 150-713, Korea.*E-mail: [email protected] Accepted May 30,2016;EpubaheadofprintJun8,2016 Departments of Miri KIM 10 CasesandaLiterature Review Eruptive MelanocyticNaeviCausedbyRadotinibTherapyinPatientswithChronicMyeloidLeukaemia: https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2475 Skin samples were taken from 2 enrolled patients who 1 1 , ). Young Hoon YOON 1 Dermatology, and Table SI 1 , 2 Ji HyunLEE Hematology, StMary’s Hospital,Collegeof Medicine,TheCatholicUniversityof Korea, 62Youido-dong, 1 . The meanduration logical findings, we SHORT COMMUNICATION 1 , Dong Wook KIM 1 ). ). - 2 and Hyun Jeong PARK and thecolourofmaculesfaded. for 2 The weeks (right). number of eruptive melanocytic naevi decreased treatment with radiotinib andafterstoppingradotinib during (left) and neck on the face 1. CaseMultiple macules Fig. pigmented EMN inpatientswithCML. no reporthasbeenpublishedaboutradotinib-induced radotinib inCML patients. To thebestofourknowledge, only afewreportsofcutaneousadverseeventscausedby CML patientstreatedwithradotinib. There havebeen In thisreport,wepresent10casesofEMNoccurringin DISCUSSION for manypigmentedmacules. was reduced(Fig.1).Hedidnotreceiveanytreatment EMN decreasedtoapproximately300andtheircolour 2 weeksduetoelevatedliverenzymes,thenumberof Interestingly, afterthepatienthadstoppedradotinib for more than 500 naevi with diameters of 2–5 mm (Fig. 1). exposed tothesun.Onphysicalexamination,wefound and spreadacrosshisentirebody, including areas not the number of pigmented macules and papules increased papules onhisfaceandextremities.Overthenextyear, months, hedevelopedmultiplepigmentedmaculesand on 800mgradotinibtwiceadayin2013. After several old man(case1)was diagnosed with CML andstarted administration ofradotinib.Inourcaseseries,a32-year- 2 and7)developedlocalrecurrenceduetocontinuous Among the4patientstreatedwithlasertherapy, 2(cases with along-pulse755-nmalexandritelaser(GentleMax cm Syreron Candela,EastCoast)withsettingsof300J/ 2 , using a 1.5-mm spot size, and a 10-ms pulse width. 1 * Acta DermVenereol 2017;97: 115–116 doi: 10.2340/00015555-2475 115 ® , Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta EMN associatedwithsorafenib,aFDA-approvedmul been reported(7–9).Kongetal.(7)2casesof patient’s appearance and create significant psychological important toconsiderthatEMNcanadverselyaffect the dations forthe proper management ofmultiple naevi. It is aware ofthis potential association and make recommen of theincreasingusemulti-TKIs,cliniciansshouldbe dered asapotentialsecondarycauseofEMN.Because melanocytic naevi. are responsible for the abrupt appearance of multiple iatrogenic immunesuppressionproducedbyradotinib in ourpatients,itislikelythatvariouscytokinesand we couldnotdetermine the factors thattriggeredEMN nocyte proliferationandsurvival.Inaddition,although other enzymesinthepathway, thusstimulatingmela similar potentialtoparadoxicallyup-regulateMAPKor BCR-ABL1, notc-KIT (12).Perhapsradotinibhasa melanocytes wascausedbyselectivelyinhibitingonly stimulated. The authorssuggestedthattheactivationof this suggestedthatmelanocyteproliferationhadbeen of basalmelanocyteswasobservedintheirpatient,and ginosis afterradotinibtreatment. An increasednumber elucidated. Won etal.(12)reportedonecaseoflenti pathogenesis ofradotinib-inducedEMNhasnotbeen naevi mayhaveresultedfromeffects ofradotinib. The the treatmentleadustospeculatethatthesemultiple starting radotinib, as well as the regression afterstopping the multiplicityandabruptonsetofappearanceafter treatment forCML (11). However, inthepresentstudy, associated withwide­ study reportedthataCML-relatedimmunestatuswas drugs oraneffect ofimmunosuppressiveaction.One the proliferationofmelanocytesisadirecteffect of senescence inducedbyBRAF(10).Itisunclearwhether triggered theproliferationofmelanocytesduetoloss MAP/ERK pathwaybysorafenibandsunitinib,this was probablyduetoexceptionalinhibitionoftheBRAF/ the authorshypothesizedthatdevelopmentofEMN a 53-year-old manwithmetastaticrenalcellcarcinoma; action similartothat of sorafenib also caused EMNin Sunitinib, amultikinaseinhibitorwithmechanismof cases of eruptive naevi in patients treated with sorafenib. cellular carcinoma.Bennani-Lahlouetal. 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