IAA Consensus Document

Transcription

1 IAA Consensus Doument Orl retinois Isotretinoin (13-is-retinoi i) is erivtive of retinol (vitmin A). It is esily the most potent ntine gent ville toy, n the only one tht resses ll pthogeni mehnisms. [1] Isotretinoin represents the single most importnt vne in ne therpeutis. It ws linilly evlute in the 1970 s n the first seminl ppers were pulishe in the USA in 1979 [2] n in the UK the following yer. [3] Isotretinoin is potent seosuppressive. During isotretinoin therpy seum proution is reue y 90% or more (to prepuertl levels). [4] The mehnism of tion is ntinrogeni through ompetitive inhiition of 3-lph-hyroxysteroi oxition y retinol ehyrogense resulting in reue formtion of ihyrotestosterone n nrosteneione. [5] Isotretinoin lso normlizes utl hyperornifition, n generlly thins the epiermis to proue inrese light refletne retinoi glow tht is muh herishe y ptients. Isotretinoin is the most omeolyti of ll ntine gents. [6] It iniretly lowers P. nes ounts, n exerts n nti-inflmmtory effet. [1] Isotretinoin-inue linil improvement is ssoite with lowere levels of porphyrins in the seeous folliles [7] n reue onentrtions of MMPs in the seum. [8] lso n epte tretment for ne ssoite with psyhologi istress. [9] Isotretinoin is ville in Ini s 5, 10, 20, 30, n 40 mg sofgel psules. Isotretinoin is now generi in USA n EU. In Ini, it ws generi from the time of introution (2001). The ose of isotretinoin is mg/kg oy weight, in two ivie oses given fter mels. Isotretinoin sorption is only 20% in fste stte versus 40% in the fe stte. [10] In young hilren, sofgels n e issolve in wrm milk. The tretment is ontinue till umultive ose of mg/kg hs een hieve. [10] This typilly my tke 6 8 months. The linil response is generlly quik ut my vry from ptient to ptient [Figure 59 61]. Trunl ne is slow to respon. Initil flres re sometimes oserve Isotretinoin shoul only e use y experts those who know ne well n re well verse with ll spets of the rug. It is the first hoie therpy for severe forms of ne, espeilly nouloysti ne. It is lso inite in iffiult n refrtory ne. The ltter is efine s less thn 50% improvement with onventionl therpy onsisting of orl ntiiotis n topil omintions. [8] Diffiult ne inlues ne onglot, ne orporis, ult ne, nrogeni ne, severe infntile ne, ne fulminns, n SAPHO synrome. Isotretinoin is the most epenle ne tretment n my e justifie in mil to moerte ne where srring is imminent. Isotretinoin is ORAL ISOTRETINOIN: INDICATIONS Nouloysti ne Fulminnt ne Ane orporis Diffiult/relitrnt ne Moerte ne if srring is imminent Ane ssoite with psyhologi istress Figure 59: (,, n ) Gre II ne with ysts, suessfully trete with orl isotretinoin S39

2 not only in ptients with mroomeones ut lso in ptients with lose omeones n misse omeones. This n e prevente y uterizing or eletrofulgurting mroomeones n lose omeones prior to ommening therpy n lso y strting with lower ose, sy, 20 mg/y. Ane flre my still our in spite of ue preutions, n my require overge with low ose orl steroi [Figure 62]. It is esire tht the ptient hieve remission of 2 3 months efore the tretment is terminte. Tretments my exee prmeters etile ove where wrrnte n where the rug is well tolerte. Lower osges (0.1 mg/kg) re lso effetive ut relpse rte is muh higher. [12] Even with stnr ose/regimen, ORAL ISOTRETINOIN: DIFFERENT REGIMENS Stnr osing mg/kg ily in two ivie oses Pulse osing 0.5 mg/kg/y for seven ys eh month Low osing mg/kg ily for 6 12 months Eslting osing 20 mg o.. x 1 month introutory ose inrese in monthly steps to reh stnr osing Intermittent osing Fifteen ys tretment perio lternting with 15 ys of no tretment; not use in ne Tle 12: Isotetinoin verse effets Figure 60: ( n ) Ane orporis (onglot) efore n fter isotretinoin therpy ne relpses in 20 40% of ptients, typilly 6 12 months fter esstion of therpy. [11] There re other protools. Isotretinoin hs een suessfully given s pulse osing in ult ne. [12] Goulen et l. trete 80 ptients with isotretinoin 0.5 mg/kg for one week every four weeks for six months; ne resolve in 68 ptients; 26 ptients relpse fter one yer. [13] IAA memers hve use pulse osing n foun it effetive. An eslting ose protool is vise to prevent ne flres n ose tper is employe to exten the ourse of isotretinoin with view to minimize relpses. A mironize version of isotretinoin hs een introue (not s yet ville in Ini) whih n e given in fste onitions, s single ily ose of 0.4 mg/kg whih, reportely, is equivlent to 1.0 mg/kg of stnr isotretinoin. [10] Isotretinoin is viewe s equte monotherpy in most forms of ne. However, mny experts elet to opresrie ntiiotis. [4] Severl of us in the IAA frequently o Averse effet Cheilitis Dry nose Dry eyes Derese night vision Cornel ulers/opities Photosensitivity Hehes Hir loss Hyperostosis Elevte triglyeries Elevte holesterol Heptitis Infl mmtory owel isese Rhomyolysis Tertogeniity Depression, suiil ietion Comment My e severe, fi ssuring, leeing, impetiginiztion Osionl epistxis Prolemti for ontt-lens werers Very rre in Inins My inite pseuotumor ereri/overose Inites overose, ose-epenent Common, reversile, osionlly preipitte pnretitis Unommon, reversile, iiosynrti, oseinepenent Controversil the sme. We opresrie ntiiotis in the erly prt of the tretment for speeier result. Some of us lso opresrie ntinrogens (EE-CPA, spironoltone) with isotretinoin to ugment effiy [Figure 62]. Suh therpeuti mneuvers re justifie in ses of uner response. Often low ose isotretinoin (20 mg/y), or pulse osing (vie supr) uring the tlet-free perios of omintion ontreptive pill (EE-CPA), oes the trik. With isotretinoin ntiioti opresription, there is higher risk of intrrnil hypertension, n with S40

3 e f e f Figure 61: (-f) Gre III ne trete suessfully with isotretinoin n orl sterois Figure 62: (-f) Gre II ne trete suessfully with omintion of isotretinoin n Dine 35 isotretinoin ntinrogen menstrul isturnes re more frequent. It is sfe to repet isotretinoin ourse in the event of relpse, espeilly when the intervl etween the ourses is six months or greter. There is no limit on the numer of ourses given n the eision to o so is governe y linil nees n sfety issues tht re iniviulize. Isotretinoin shoul only e given to helthy iniviuls. It is solutely ontrinite in sexully tive women in the reproutive ge group unless stringent ontreption is seure n the nee for tretment S41

4 is ompelling. Mny ountries hve strit pregnny prevention progrms. Aientl use of isotretinoin uring pregnny is ssoite with high rte of spontneous ortion n mjor, potentilly lifethretening, ongenitl mlformtions. [13] Mle ne ptient on isotretinoin my fther hil without risk of tertogeniity. Isotretinoin shoul e voie in iniviuls with strong fmily history of oronry rtery isese n yslipiemis. Bloo levels of polipoproteins A re etter preitor thn triglyeries for isotretinoin-relte yslipiemi (onsensus of the IAA). Isotretinoin tretment in hypertriglyeriemi rries risk of ute pnretitis. Isotretinoin my e use for severe ne in the ontext of hroni meil onition suh s epilepsy ut with ue ution. Isotretinoin my e given for severe or iffiult ne in preolesents n olesents; most experts gree tht suh tretment in stnr osges n urtion oes not use premture losure of epiphyses or growth retrtion. On the rre osion when equte isotretinoin therpy fils, it is worthwhile exluing prtil/inomplete ongenitl renl hyperplsi y testing for serum 17- -hyroxyprogesterone (17-OHP). ADVERSE EFFECTS Isotretinoin omes pkge with wrnings n long list of possile/reporte verse effets [Tle 12]. While this serves the purpose of isourging selfmeition, it mkes the jo of the ermtologist fr more iffiult in onvining the ptient, the prents, n t times the extene fmily! It is very importnt to get the right perspetive on this issue n to e le to perform soun risk-enefit nlysis in eh se. The only verse effets tht re frequently enountere re muoutneous, n they re ose epenent. Cheilitis (hpping of lips) ours lmost in 100% of ses lthough severity vries; it persists through the ourse of tretment n fortuntely most ptients just to it n mke o with emollients. In severe ses, trolimus 0.3% n flutisone-mupiroin ointments provie relief. Dry eyes, ry nose with nose lees sometimes, n generl ryness, our less ommonly, often ontriute to y environmentl onitions, filure to just skin re, n onomitnt use of rying n peeling gents. All this n e juste n it is permitte to use moisturizers in n unlimite wy. Luriting eye rops re helpful. Contt-lens werers my hve to swith to soft lenses. ly, ryness is severe n requires ownwr ose justment. Conomitnt ministrtion of vitmin E 800 IU/y ws reporte to e effetive in iminishing muoutneous verse effets ut this ws refute y susequent stuy. [15] Suseptiility to impetigo n furunulosis inreses, [4] n is quite ommon mong our ptients here in Ini. Impetigo is ommonly seen in periorl lotion ut lso elsewhere [Figure 63]. Bteril pronyhis re oumente. Pyogeni grnuloms, reporte in the literture, re rrely seen in our ptients. Other verse effets inlue: skin frgility, one n joint pins, osteoporosis n osteophyte formtion, n visul isturnes. Persistent hehes n exessive hir sheing my e signs of overose. Depression n suiil ietion hve een reporte n usl ssoition with isotretinoin hs een ete. [15] It is vise tht isotretinoin e voie in ne ptients with oumente epression. It is lso knowlege tht negtive feelings ssoite with ne often meliorte fter tretment with isotretinoin. [16] Mil to moerte hypertriglyeriemi is note in 25% of ptients. [17] It is reversile. Biohemil monitoring osionlly throws up ytopeni or elevtion of trnsminses. While the former wrrnts isontinuing isotretinoin therpy, the ltter if moerte (less thn three times the upper limit) n e tolerte. Isotretinoin tretment of ysti ne in Greee ws foun to e ssoite with elevte levels of homoysteine t six weeks. [18] The explntion offere ws possile suppression of enzyme ystthionine-et-synthetse y the rug or euse of the ltere liver funtion. [18] High loo levels of homoysteine re risk ftor for premture olusive vsulr isese. [18] Pretretment pregnny testing, n pre, intr, n post-tretment lortory testing re hnle Figure 63: Impetigo following threing uring isotretinoin tretment of ne S42

5 ifferently in our ountry. Unlike EU n USA, it is not mntory for us to o two pretretment pregnny tests, n to hve to repet them every month. This will oviously not go own well with our ptients. We limit ourselves to verl enquiry to rule out pregnny, n rely upon ptient eution to prevent pregnny. It hs worke well thus fr n we re not wre of ny instnes of unwnte pregnnies, irth efets, or lw-suits with isotretinoin in use now for over five yers, thousns of femle ne ptients hving tken it. It my e pruent to reor in some wy tht pregnny prevention ws isusse with the ptient. It n e one through onsent forms (whih re time onsuming n evoke pprehension!), or imprinting stmps on presriptions tht sy Pregnny lert, Cution, or Informe onsent. The wshout perio for isotretinoin is 30 ys n this is lerly onveye uring pretretment isussions n reiterte uring follow-up visits. Lortory testing is lso envelope in isgreement. Mny t hve refute the usefulness of routine n frequent lortory testing in isotretinoin therpy of ne. Yet, from meiolegl stnpoint, n to ientify the rre se of hypertriglyeriemi, it is vise tht sreening tests inluing loo ounts, fsting lipis, n liver funtion e one, n repete t 4 n 8 weeks, n if norml n unhnge, n if the ose of isotretinoin is not inrese, no further tests nee e one. [17,19] ORAL ISOTRETINOIN: SOME DO S AND DON TS Isotretinoin shoul e tken fter proper mels. Isotretinoin shoul not e shre with friens. Threing, wxing, strenuous work-outs, n ontt sports shoul e voie in the ltter prt of the tretment. Exessive lohol onsumption n fttening foos shoul e voie. Bloo ontion shoul e voie while on tretment n for one month fter stopping therpy. REFERENCES 1. Hrper JC, Thiutot DM. Pthogenesis of ne: Reent reserh vnes. Av Dermtol 2003;19: Pek GL, Olsen TG, Yoer FW, Struss JS, Pny M, Butkus D, et l. Prolonge remissions of ysti n onglote ne with 13-is-retinoi i. N Engl J Me 1979;300: Jones DH, Bln D, Cunliffe WJ. 13-is-retinoi i n ne. Lnet 1980;2: Gollnik H, Cunliffe W, Berson D, Dreno B, Finly A, Leyen JJ, et l. Mngement of ne: A report from glol lline to improve outomes in ne. J Am A Dermtol 2003;49:S Krlsson T, Vhlquist A, Keishvili N, Torm H. 13-isretinoi i ompetitively inhiits 3-lph-hyroxysteroi oxition y retinl ehyrogense RoDH-4: A mehnism for its ntinrogeni effets in seeous glns? Biohem Biophys Res Commun 2003;303: Cunliffe WJ, Holln DB, Clrk SM, Stles GI. Comeogenesis: Some new etiologil linil n therpeuti strtegies. Br J Dermtol 2000;142: Boprelli C, Merk K, Jo K, Vogeser M, Weinl G, Berger U, et l. In vivo porphyrin proution y P. nes in untrete ne ptients n its moultion y ne tretment. At Derm Venereol (Stokh) 2006;86: Alests T, Gneviiene R, Fimmel S, Muller-Deker K, Zououlis CC. Enzymes involve in the iosynthesis of leukotriene B4 n prostglnin E2 re tive in seeous glns. J Mol Me 2006;84: Chivot M. Resiul ne lesions fter tretment. Ann Dermtol Venereol 1996;123: Struss JS, Leyen JJ, Luky AW, Lookingill DP, Drke LA, Hnifin JM, et l. A rnomize tril of the effiy of new mironize formultion versus stnr formultion of isotretinoin in ptients with severe relitrnt noulr ne. J Am A Dermtol 2001;45: Cunliffe WJ, Norris JFB. Isotretinoin: An explntion for its long-term enefit. Dermtologi 1987;175: Struss JS, Rpini RP, Shlit AR, Koneky E, Pohi PE, Comite H, et l. Isotretinoin therpy for ne: Results of multienter ose-response stuy. J Am A Dermtol 1984;10: Goulen V, Clrk SM, MGeown C, Cunliffe WJ. Tretment of ne with intermittent isotretinoin. Br J Dermtol 1998;137: Lmmer EF, Chen DT, Hor RM. Retinoi i emryopthy. N Eng J Me 1985;313: Struss JS, Gottlie AB, Jones T, Koo JY, Leyen JJ, Luky A, et l. Conomitnt ministrtion of vitmin E oes not hnge the sie effets of isotretinoin s use in ne vulgris: A rnomize tril. J Am A Dermtol 2000;43: Ferhs A, Turn MT, Esel E, Uts S, Kutlugun C, Kili CG. A pilot stuy evluting nxiety n epressive sores in ne ptients trete with isotretinoin. J Dermtol Tret 2004;15: Brown SK, Shlit AR. Ane vulgris. Lnet 1998;351: Shulpis KH, Kriks GA, Georgl S, Mihs T, Tskiris S. Elevte plsm homoysteine levels in ptients on isotretinoin therpy for ysti ne. Int J Dermtol 2001;40: Ally J, Lnu M, Zuker A. Anlysis of lortory t in ne ptients trete with isotretinoin: Is there relly nee to perform routine lortory tests? J Dermtol Tret 2001;12:9-12. S43