Cutaneous Vasculitis with Gut Involvement During Secukinumab Treatment for Psoriatic C Chelli, J Loget, C Vanhaecke, A Durlach, L Gagneux-Lemoussu, C Soriano, M Viguier

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C Chelli, J Loget, C Vanhaecke, A Durlach, L Gagneux-Lemoussu, et al.. Cutaneous Vasculitis with Gut Involvement During Secukinumab Treatment for Psoriatic Arthritis. Acta Dermato-Venereologica Supplementum, Society for Publication of Acta Dermato-Venereologica, 2020, 100 (6), pp.adv00077-2. ￿10.2340/00015555-3435￿. ￿hal-03049051￿

HAL Id: hal-03049051 https://hal.archives-ouvertes.fr/hal-03049051 Submitted on 7 Jan 2021

HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV This isan open access article under the CC BY-NC license.www.medicaljournals.se/acta C-reactive protein level, and negative serology for HIV or hepa showed normal plateletcount, renal andliver function, elevated necrotic on the lower limbs (Fig. 1). Biological analyses the patientpresentedsub-acutefebrilediarrhoeawithpersisting Secukinumab wasstopped2monthsafteronset.Onemonthlater, purpuraonthelowerlimbs.vulva, withnodularandpustular secukinumab, the patient developed psoriasiform lesions on the , withrapid control ofPsA.Onemonthafterstarting adalimumab wasswitchedtosecukinumab,inassociationwith and controlled longer no PsAwas her later,Two years steroids. pustular palmoplantarpsoriasis,whichwascontrolledbytopical with adalimumabandmethotrexate,shehaddevelopedparadoxical then methotrexateplusadalimumab. After oneyearoftreatment hoea. PrevioustreatmentsforPsA includedmethotrexatealone, progressing for3months,recentlyassociatedwithfebrilediarr years wasreferredtoourdermatologyunitforcutaneouspurpura A 54-year-old womanwhohadaxialandperipheralPsA for6 CASE REPORT involvement aftertreatmentwithsecukinumabforPsA. report here a case of severe cutaneous vasculitis with gut tis hasrarelybeenreportedduringIL-17blockage. We vasculi cutaneous anti-TNFα, with reported previously cutaneousAEs.Although specific other about known is of cutaneousandmucosalCandidainfections(3),butlittle duced for and PsA. They placed patients at risk well identified (2). Recently, IL-17 inhibitors were intro (1) and,inparticular, cutaneousadverseevents(AEs)are profile of TNFα and anti-IL-12/IL-23 is now well known safety The IL-23. or IL-17 (IL)-12/IL-23, interleukin of biotherapies targeting tumour necrosis factor α (TNFα), treatment hasundergone a revolution, withtheapproval In the past few years, psoriasis and psoriatic arthritis (PsA) Accepted Feb 19,2020;EpubaheadofprintFeb 28,2020 Departments of Clara Cutaneous Vasculitiswith GutInvolvement DuringSecukinumab Treatment forPsoriaticArthritis and and ManuelleVIGUIER Journal Compilation ©2020ActaDermato-Venereologica. Fig. 1.Lower-limbpurpura3months afteronsetofsymptoms. 3 Department of , Maison-Blanche Hospital, Reims University Hospital, Reims, France. *E-mail: [email protected] CHELLI 1 , 1 Dermatology-Venereology and Jeffrey LOGET 1 * 1 , Clélia VANHAECKE 4 Gastrology, Robert-Debré Hospital, AvenueduGénéralKoenig,FR-51092Reims, Gastrology, Robert-DebréHospital, SHORT COMMUNICATION 1 , Anne DURLACH - - - - recurrence ofcutaneous,digestiveorjointsymptoms. 15 mg/week. At 2monthsaftersteroidwithdrawal,therewasno blockers werecontra-indicatedandmethotrexatewasre-startedat while colchicine was maintained. Regarding PsA treatment, IL-17 1 month,allowingaslowtaperingofsteroidswithin6months, remission, withonlyresidualskinerosions,wasobtainedafter kg/day, associatedwithcolchicine,1mg/day, wasstarted.Partial withdrawal ofsteroids. A newregimenofprednisone,0.5mg/ after week 1 within occurred purpura cutaneous of flare new A were normal.Corticosteroidsgraduallytaperedover7weeks. erythematous congestiverectocolicmucosa.Iterativebiopsies Digestive pan-endoscopy, performed onemonthlater, revealed The diarrhoea stopped rapidly and the lesions were attenuated. vasculitis wassuspected,andprednisone1mg/kg/daystarted. fraction was low. No proteinuria was detected. A faecal micro faecal Adetected. was proteinuria No low. was fraction at 1:100titres,withnuclearspeckledpattern;C4complement antibodies wasnegative. Anti-nuclear antibodieswerepositive, factor, anti-double-stranded DNA and anti- cytoplasmic titis B or C viruses. Search for cryoglobulinaemia, rheumatoid arrows pancolitis (white tomography showing 2. Abdominalcomputed Fig. 1 pathogenesis (5),andnew therapies targeting IL-17or matory factors, as TNFα and IL-17, are Inflam implicated (4). in their life of quality on impact high potentially a Psoriasis and PsA are chronic inflammatory diseases, with DISCUSSION vessel walls,withnoIgA deposits(Fig.S1 blood in deposits C3 showed samples skin of munofluorescence blood vesselswalls,leukocytoclasiaandthrombosis.Directim in necrosis fibrinoid infiltrates, dermal perivascular polynuclear Skin biopsyrevealedparakeratosis,acanthosis,lymphocyticand . epithelioid non-specific unique a with ischaemia, with aphthoidulcerations.Digestivebiopsiessuggestedchronic only. A short colonoscopy revealed purpuric inflammatory mucous (Fig.2).Magneticresonanceimagingrevealedpancolitis fistula diffuse recto-pancolitiswith terminalileitis,withoutabscessor revealed tomography computed Abdominal µg/l). (118 specific bial searchwasnegativeandthefaecalcalprotectinratenot https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3435 Diagnosis ofsecukinumab-inducedcutaneousanddigestive 2 , Laurence ), andterminalileitis GAGNEUX-LEMOUSSU Acta DermVenereol 2020;100: adv00077 (yellow arrow). doi: 10.2340/00015555-3435 3 , 1 Clothilde ). 2 Biopathology Biopathology SORIANO 1/2 - - - 4

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV www.medicaljournals.se/acta guselkumab maybeaninteresting alternativetherapy,guselkumab or ustekinumab with IL-23 of vasculitis. blockade Thus, immunological contextthat isconduciveto AEs suchas duction of IL-22 (14). This situation creates a favourable 17 (Th17) numbers, leading to increased pro T-helperenhance may drugs (13). Anti-TNFα vasculitis mune complexes, as hypothesized in anti-TNFα-induced is unclear, andcouldimplicate cytokineimbalanceorim ankylosing spondylitisassociatedwithCDratherthanPsA. hout cutaneouspsoriasislesions;thus,shemayhavehad wit and axial mainly was PsA, as identified , patient’s inflammatory the lines, same the disease. Along have controlledthesymptomsofanunderlyingdigestive history of CD, the previous treatment with anti-TNFα could mab oflatentCD.Indeed,anddespitetheabsence a would havebeentheinductionorunveilingbysecukinu is 27 days. The major digestive differential diagnosis here explained by the long mean half-life of secukinumab, which be can evolution paradoxical apparently This period. this related togutinvolvementbyvasculitis,appearedduring discontinuation. Moreover, digestivesymptoms,eventually mab onset,itdidnotinitiallyimproveafter4weeksofdrug Although cutaneouspurpuradevelopedsoonaftersecukinu induced cutaneousanddigestivevasculitis was suspected. after onemonthoftreatment. PsA with woman 62-year-old a in findings pathological riasis, andonecaseoflower-limb purpurawithunclear purpura afteronemonthina42-year-old manwithpso of treatment respectively), one case of Henoch- Schönlein 58-year-old woman with PsA (after 2 months and 34 days leukocytoclastic vasculitisina47-year-old mananda all in patients receiving secukinumab: 2 cases of cutaneous found4similarcasesofcutaneousvasculitis, database, we the vasculitis and PsA. In the French pharmacovigilance stopped, andprednisonecyclosporinecontrolledboth secukinumab treatment for PsA (12). Secukinumab was of months 8 after vasculitis leukocytoclastic cutaneous presenting woman 28-year-old a in recently described secukinumab orixekizumab(9–11). induced lupuserythematosushavebeenreportedwith psoriasiform eruption,granulomaannulareanddrug- have beendescribed. Atopic-like andeyeliddermatitis, toid nodes)(1),andsimilarcaseswithIL-17blockage cutaneous vasculitis,granulomatousdermatitis,rheuma lesions, (psoriasiform anti-TNFα with described widely are reactions cutaneous been reported.Dysimmunological (3).MucocutaneousCandidahave are rhinopharyngitis,,andupperrespiratorytract (CD), whichshowedpotentialworsening(8). diseases (6,7),thiswasnotthecaseinCrohn’s disease both for efficacy high-sustained shown has it Although first anti-IL-17A therapy approved for psoriasis and PsA. their receptorshavebeendeveloped.Secukinumabwasthe 2/2 The pathophysiology of vasculitis after secukinumab after vasculitis of pathophysiology The In thecurrentcase,diagnosisofsecukinumab- A caseofvasculitistriggeredbysecukinumabwas secukinumab with reported frequently most AEs The Short communication ------14. 13. 12. 11. 10. REFERENCES authors havenoconflictofinteresttodeclare. Lilly, Arrow,Pfizer, Medac.MSD, or Janssen, other Abbvie, All has received fees from Amgen, Boehringer, Novartis, Leo Pharma, fees from Abbvie. MV has been an investigator, a board member or Conflicts of interest: CC received a grant from Sanofi. JL received partment, University Hospital of Reims) for radiological analysis. De (Radiology Hoeffel Christine Professor to indebted Weare ACKNOWLEDGEMENTS vasculitis withcutaneousandgutinvolvement. siology ofanti-IL-17 AEs. whether similarpathwaysareinvolvedinthepathophy Th17 differentiation. Further studies are needed to assess as IL-23 is known to be the main driver and sustainer of 8. 7. 6. 5. 4. 3. 2. 9. 1. We report here the first case of secukinumab-induced of case first the Wehere report Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Rei Mease PJ, Kavanaugh A, Reimold A, Tahir H, Rech J, Hall S, Abrouk M, Gandy J, Nakamura M, Lee K, Brodsky M, Singh R, Barnas JL, Ritchlin CT. 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