CHAPTER 216 Topical Corticosteroids ‘sabel C. Valencia Francioco A. Kerdel Hi weotenasat oF acon Comicenteraids have specie and noo: specie effects that are related to differ (ene mechaniems of action, incloding: anchinflammatory, immunosupprestive, ancproliferative, and vacoconstrictive effects, Most of the effects of coreico- sseroids on cell are mediated by bind- ing of the corticomeraid to its seceptor in the cyeoeol,fllenved by tranlcation ‘of the drug receptor complex ta a region ofthe nuclear DNA known as the cni- cover responsive element, where © is then able 29 stimulate or inkit eran tiption of the adjacent genes, thus rep- ulating che inflammatory process” Anti-Inflammatory Effects (Comicosteroids are thought co exer their patent antiinflammatory effects by in- hibiing the release of phospholipase A,, |anerzyme responsible forthe format of prectaplanalins leukotriene, and other ervasves of the amchidonic ace path way: Cartcncrecide ale inte ane cription factors, such as arvana proein 1 and nuclear far hae are iraied tthe activation of prodndlammatary penes, Genes known ta be upregulated by cortcanteros and that play a mle ia the reschition of ‘nlamemtson incude lipocemin ane pllcalpactn-binding. pro suing, toh involved im the lease of archidonic acd Lipocorcin T inhabits phospholipase Ay reducing the reese of Irnchidonie acid from phospholipids? Conscontraids also decrease the zelease of iseroukin Ie (ta), 29 soporare preanlammatory cytokine, from ker Docytes!® Otier proposed mechanisms fox the anh inflarmarony effeers of co conteroide inclu inhibition of phapecy tosis ane tablbzation of lyzasomal mem: branes of phagaeyrisirg celle” Immunosuppressive Effects The effectverass of coriccetera i, in part, alto due t their immunosuppressive properties. Comicostemids suppress the production and effects of humoral factors ‘nwolved in the inlamenatory response, in: Fiber leukocyte mipmion to star of in: Samenstice, and icserfere with the func Son of endothe alk, pranuacyies, mace cells, and fbmblaes 1 Several smudies have shown shat comicostercies TOPICAL CORTICO- STEROIDS AT AGLANCE T can cause matt cell depletion in the skin Experimenes also shew thar topéal cor comteroide cats local inhibition of cheeo- ‘ms of reuerophule!* in vm, and deceaseHBL 211 Potency Rirking of Soc Tonal Cartatened Pronerasonst (en me Cas 1—Suprpoiet Betawehasane eiproplenate i 06% eptirize wri Satta septa 0.05% (stone dace 05% Flsetoriss 0:15 pine venice Flarancenalie, 4 mpian? Flaockine score 000% Cass 7—Least oat Topics ih decane, fumethaane onacne Neshyteedhicokne, pecnbakna peters geonanermeent (cba ontevepy ‘ux fea Tova esac xe? getonnent Feoroon cherand Veit ern Conde ape Lewin craarvoketnt jot meat Cetera 4 ream Dicsene chien Topic creaaveurent Tagine get Pavone chetrent sito ote Lies cram yevttmert aby emarnekusentment Bacon onaneat (psoet rear oton Cree eres Velonre often Pavene tes | Mor eam asoan € cam Lex € crea Cutetacirand unig tam (seem eres Talos LP cream Syrae hetrent| (oat earner Panda cream Westar cetoent Bacon eramfaton Deore cranent ong oktrent Dice ion Velore crea eten Syer cream | Coat eam, aon Cute cream Loon Hpccteam the number of lat Langerhans cls in vivo. Cominstemids reduce eosinophilia inpwrienss wich asthma: They also reduce “Tall profleration and induce cll apo ‘oxi, In par from inhibition ofthe Teal growth facor 1.2." Ta addition, sever Cytokines ae direc affected by corico- smerids, including Ti, tumor necrosis freee, ganulacyemacrophage eolory: stimulating facto, and 118. These effec ray ao be a ru of the stemid action onansigen presensing ce. © Antipraliferative Effects. “The antiproliferacive effece of sapical com ‘Sconteroids is mediated by inhibition af DNA syehesis ancl entosis, party ex plaining che therapeutic action of these dng in scaling dermatoses. Fibroblast activity and collagen formation are also inhibited by topical corticosteroids” \Vasaconstriction ‘The mechanism by which conicosen ods induce vasoconstriction is noe yet completely cleat I i thoughe © be re lined to inhibition of natural vasodilators such a hiscamsine, bradykinin, and pros: taglandins 4" Topical stemids cause capillaries in the superiial dermis © consict, dus reducing erythema, The abiliey of a given comicomercd agent © cause vasosonatiction tually correlates with i anbinflammatary potency) and thus, vazscenstricson amays are oiten cused to predict dhe clinical activity of an agent. These assays, in combination with double-blind clinical wale, have been used to separate the topical comicomter oi into seven clases based. on potency. (Glass inchuces the most potent, while class 7 contains the least potent Table 26-1 fees many of the available topical coniconteroids arcording to this clazc cation. Noeice that the same drug can be found in different potency elasibications depending on the debivery vehicle used. BB seanacoxnencs Comicostercids have a basic skeletal stracure comprising 17 carbon azoms ar. ‘Reged tee incre spy and sey i eter! py and Seanad (2101 Oy addon or ‘eration of functional’ groups at certain penton, hive led tn compounds wit Stale ansinBarmony poser, se covericomteid venus mntrlocorr activity, and adveme affects. (I Tplal cicourcid reese has fo camel on amg © optiine poseyALFIGURE 216-1 Sasic steroid mobo, ‘while minimizing side effec. One sat sey develop compounds with en. Barcel sotvrinmatey efecs and micimal unwacted stophogenic and a+ renal suppreative affezs. In this tena, progtess as been nade withthe devel Spenentofglancoracaal molecule tat, ‘hie raling high acide in ohe akin fllewing pea apaation, ae quickly ‘omen Sowa in maccve tetabeties, ‘herby maging tyre and pomebly Some eal a ccs de pacocore, oie. Some ofthe newest ofthese corn peurds inlet dveens 1721 hyos Eontrone aceponate and Pydoeortane [Pinay] propiomes, prechicxbate, ‘cortisone aceponare, precnicarbate, and methyiprednisalone aceponate have induce skin atrophy; ‘therefore, they can be used to treat areas such as the face, the serofum, and large ‘body surface areas in children, with mini mal adverse effec! Ruticarone propi- conate i dacified asa potent comtcnster ‘oid with lower potential to cause akin satophy and adrenal suppression Ie offers ‘he avaneage of once daily application and infrequere local allepic reactions Momeeasone furoate alo has hightyanci= inflammatory effects wh low inadence ‘of adzeral suppressson! [if hoicanones ‘Topical contcoeceoids ame recor treed for their ancandlameatory a ‘thee in inlamrmatny sin diseases, ba ‘they can alto be ued for their ancimi- feck fleas and their capacity to des ‘crease the synthesis of connective tissue molecules! Certain variables must be ‘onsidered when eating din disorders ‘with copa! placocorsaide For exams ple che responsiveness of dszases 10 fopical glucocomicoids varies. In thi setting, Ghveazes can be divided into the three categories shown in Table 216-2 highly responsive, moderately respon: ive, ad lene responsive. Pediatrie Uses “Topical glucacomienids are highly effec: th andi eee ae oboe ‘when.a low-potency preparation is used for brief periods of time without occlu: sion in chuldren. Flower, children and, fn particular, infants, are at an increased rick of absorbing topical coricameroids for several earons, Because they have a higher ratio of skin surface area to body swefghe, application to a given area = cule: in a greater potensally systemic doce of steroid. Infanss may alto be lest able to metabolize potent lucocorti- ‘ois rapdly.®* Premature infants are e5- pecially ae rick because their skin is chin: nerand the penetration rate af topically applied drugs is greatly increased.” Ap plication of tpicalsceroide tothe diaper ara results in ocelusion of the steroid bay the diaper, and increased penetration foncurs. Excess asarpsion of tapical glu: cocorticoids can suppress endogenoxs corézal production. Consequently, sub: sequent cessation nf tnpical steroid ther. apy afer an excended treatment period can, albeit rarely, eeu in an addsonian crisis. Deaths from addiconian crisis have been zeported with the use of ropi- cal steroid and the risk ofthis occur- ring is greater in children. Chronic sup: prison of cried procion can alo to growth retardation. A monin ied poweh apt mami fp screen for adrenal suppression. [Esup: pression is present, the child should be slowly weaned from the steroids to pre- ‘vent these complicatbans, Geriatric Uses Elderly patints similarly can have thin stein, which allows for inereared pene tation of topical plucoconicoids. They fre also more ikely to have pre-erissing, skin atrophy secondary to aging and may be diapendependens, 20 the same precautions used in che seatmens oi fants should be used when teasing el dlesly patents. Uses in Pregnancy ‘Appropsate human studies using topical flucocomicnids in pregnancy have never been undertaken, Studies in animals, hhowevey, chow that topical steroids are systemically aboorbed and may cause fe: ‘al abnemalisc, expecially whan used in excessive amoures, under cechusive clresings, for pmlonged periods of ime, corwhen the more potent agents are ured. oweres, numerous soudies of pregnant paienss taking systemic plucocontcaie throughout perganey shew no ins creases inthe incidence offer! abnaemal ies, Most topical seroide ae rated by the US, Food and Drug. Administration a catagory C drugs, which imply that caurion must be exerczed when used in pregnancy. Tc is cumentiy unknown whether topical glacoconicoids are: creted in breast milk; however, they should be used. with caucion in breaso feeding, mothers and should never be used on the beasts before reas feecing. I oosnic pecinaen The frequency of sopical pplication af conicnsteroids was developed in an em- pial manner, with most textbooks and physicians recommending maliple daily Use. Lagos and Maibach observed ina re cent review of the lieranure thar for su: ‘assieaienonte of Dantatvane ta Topied Mopiestan af Carbenetarcice ‘cay Reson Movesaren sre Least Resronare -ePontac dwg} = Poids Fad plat pis -eAiupccdematts hiker) © Aug demas (tit + Pacis -eSebornek denna, sMunmusrecser Dahil acem vekrmtron Pom ism daserts + Lup erfherate, + Pagal wats + ergnis = Papen -llcen rus sUinmsipecdinins +Grankmasruse ‘Nbr gi dsbeeonun Saraki “+e coma vans, seeps ‘encesperpotent coricostercids, once-daily ap- jn was as beneficial as ewice- daily application. Likewise, there was no life ference or only 3 sight difference with ‘once or ewice daily application of potent or moderately potent comicomercids. ‘The auchom concluded thac once-daily application af enpical eorbensteroide may be preferable, may decrease the risks of side effeces and tachyphydarix, decrease the cost of therapy, and improve the pa- ‘ents complianes?? Tachyyphylaxis has ‘been demonstrated in experimental con isons by diminished vacoconstricson, rebound of DNA synthesis, and reooveny of histamine wheals afer application af ‘topical steroids in patients with s history of long-term topical roi usage Asa working rule, nat mare than. 45 sfweek of potent or 100 giweek of ‘weak or modemicly potent topical oor: ‘icameroid should be applied (without ‘occlusion if systemic altsorgcion is to beawoided HB conical Forvuranons wag BB baratine tHerary Before choasing a topical glucocomicoid aration, oa must consider the area fof the body that isto be treated because regional differences. greatly affecr the accviry of the topical agent Penetration of the plucocorticnid varies according to the shin ste, whic in rar, is related to the thickness of che sxrasum comeum and the vascular supply to the area. For ‘example, penetration of topical steroids ‘through the eyelids and scrocum ia four ‘imes greaeer than for the forehead and 836 times greater than for the palms and soles Inflared, moist, and denuded skin also shows increased penetration. ‘Areas of the body winere the skin tine erently thin not only allaw for in- creased penesation of the drug bue ar more susceptible to develop side effoccs than other areas where che skin ie chick. Potent topical steroids (classes 1 and 2) should rarely, if ever, be used in the ar as with the highest level of pence tion, such a che eyelids. Some general rules shauld be remembered when initi- ating topical eortcomteroile!™ + Highly responsive discus wail usualy respond ts wesk steroid preparations, whereas leserespensive diseares re sue meu a igh pots tp + Low:potene preparasions should be used on the fice and ineerepiccas ‘+ Very potent contcesteroids frequently Under occlusion are usually required on hypetkeratotc of bzherified der rmarnaes and for disease of the pals and sales Hi wonrrorine tHerapy Api of corticosteroids to large surface areas, occlusion, higher concens trations, or more poten: derivatives di- recy increate the risk of hypothalamic: piuitary-axis (HEA) suppression. If the Lotter is suspected, laboratory analyzes that include a complete blood cell count, chemistry panel, and a baseline moming conse! level should be per Formed. th a patiene urith confirmed HPA suppression, the simultaneous ine ssnution of oma steroid supplementation aad a reduction of poteney and amount of topical eroid is needed ™ Hil asks 00 precaumons Leal as well as systemic side effects have been documented with the use of topical conicosteroids. Under normal conditions, up to #9 percent of the ap pied topical eorticostemid ic removed From the skin, and only 1 percent is therapeutically active. Cutancous ad- tere elles fan wale fm the tall percentage of percutaneously absorbed sonicasterid oF may also resulc from ie transient presence onto che skin Continued use of topical costicosten ‘ide may also lead to tachyphy/anis.* ‘Consideration for prescribing sopi- cal comicosternide th prevent side ffect! 0.8, ++ Highly potent formulations should be used for short periods (2 tm 3 weeks) of intermictendy. Once dit- ase contol is partially achieved, he tue of a less potent compound should be initiated, s+ Reduce frequency af application (esp, applicarion ony in the morning, alrer nane-day therapy, weekend use) once disease comtrl is paral achieved. Topical cortcosterids should. be avoided on ulcerated or atrophic skin, and on skin with co-existent ine Fecsious dermatoses + Sudden discontinuation should be avoided after prolonged use ta pre: vent rebound phenomena. Special guidelines should be. fal. lowed when treating cemain bedy ar fas (eg, interciginous areas) or cen tain populations (eg. children or the elderly) to prevene the occurrence of local or systemic adverse effecs ‘Laboratory tests should be consid cred if systemic absorption of cons: costernids is suspected ++ Use combination therapy when clin cally indicated (eg. addition af top cal wetinoin or keratolytics) Hi coveucanons Toeal adverse effects of topical comico: smeroid uee are mote prevalent than sys ‘Atrophic Changes Skintoply i the mont common acherse fect of cortcortercid therapy. Desmal Srophy develope from the dace antipno: ifeereve effects of epical comeanerds ‘on Bibroblazcs, with inhibition of collagen nd rxcopolyaccharide eythesi, eit ing in lows of dermal support. Fragmerea: tion and thinning of ela bers ‘onthe upper layers, whereas decper fibers form a compact and dense netuvotk.™ As areal of these atrophic changes, cher is waccular dibraton, tlargiecacias, pur pore, easy bruising, stcllce pecusoears (pumpune, regularly shaped, and hypo: Pipmenced smsphic eam), and uleeroons ‘Athough atrophy b,c cme eens, re ‘versible, fomnation of striae, visiole linear feats that form in arear of deal damage prcsurnably during mechanical ress are pemnanen. Acneitorm Reactions. ‘The development ar exacerbation of desmaroses ofthe face, including steroid ronacea, acne, and perioral dermatitis a welldknawn effece of topical cortico: steroids, Although steroids initially lead to the suppression of inflammarory papules and purtules, pationss become addicted because they notice that the lesions Haze when treatment is with: denn, This frequently leads tn the oor sinued use of preater potency tmpical corticosteroids, For these reasons, ster cid use should be discouraged in the tueatment of rosacea and perioral and pesinculardermacii Prolonged corticosteroid cearment can alsa result in fteroid acne,” which is characterized by crops of dence, ins flamed pustules in the same develop: mental stage. These lesions occur on the face, chest, and back (sce Chap. 78}. Hypertrichasis Hiypertichosis occurs rarely in wremen and children who apply potent corticoseroids to the face, The mechanism is sll unknown! Pigmentary Changes Decreased pigmensaton 3 2 common sie effect of topical steroid tse, The pigment generally retums ater discone Finuation of therapy Development of infections ‘Topical corticosteroids are resporsibie for exacesbating andior masking cutane cout infectious diseares, The incidence ff skin infection during corticosteroid therapy varies but is probably berween $6 percent and 44 percent” Tinea versi- color, disseminated Alemaria infection, and dermanphytosis, including. snes incognito (masked dermatapinyse infec- fiom), can develop. Graruioma gluteale infareum, characterized by reddish purplish granulomazous lesions on che caper area ix a well-known complica: tion of diaper demain that is being treated with comtcnscemids, Candida al Ihcawe i commonly recovered in these patents. Topical coricosterails have alsa an effect on prolongation or mitiga- ‘om of herpes simplex, molluscur cone ‘agiomum, and scabies infection Alergie Reactions ersistence or worsening of skin dis- jeter occur ar a resale of conmact hypersensitivity to topical comicoater ods, The prevalence ta topical cortca- seroid sensitization ranges between 0.2 escent and 6.0 percent, and in- creates with prolonged exposure and the selection of certain drugs ?***"! The allergen may be the vehile, the preset tative, orthe steroid itself. Alot topical steroid ointments are fez of presecva- tives and am les Likely than her top cal agents an steroid creama to eatte an allergic ot iritanc contact dermatcs. The most common preservatives that cause allergic contact denmatiie Induce parabens, polyethylene glycol, and ben: Eyl alc (Table 216.3) Peapance and local anesthetics are also scasitizers that may be inchaded in the topical preparers, Systemic Adverse Effects OCULAR EFFECTS The development of glsucoma from the use of topical corti- centers around the eye has been de- sented" Prolonged comicsateroid Ue has alo led to wision loss SUPPRESSION OF THE iNYPOTHALAMIC- PITUTARY-ADRENAL AXIS Suppression of the HEA axis has been described with the use of patene tnpical corticosteroids. larogenic Cushing syndrome, camico- sterosdtelated Addison cries, and re: tarded growth of children have all been described afer prolonged use of pocent topical corticoseroid preparations. A doze of 1d gfweek of labecaso! propio: nate or 49 p/vreek of betamethasone di propionate ir sufficient to supprese plasma como! levels” METABOUC SIDE EFFECTS: Increased gu: cote production and decreased glucose ‘use induce hyperglycernin and may lead so diaberes melitus. KEY REFERENCES The full reference list forall chapters ‘s available at wivws.digm7.com, 1. Bears B, Pimplnelli N: New and establihed comicbnetoka in demmaec- ig Dea 4,2 17, Siath EW! Do we eed new and dif {fa Pasgeomcaie Cer Pa Dea 29, Lapin BR, Mastach Hi: Feoqueney of spplicatcn, of topical conicemercide: Ae overview: Br'} Dermal 138268, ‘wie 81. Hughes |, Rustin Me Cortasercids. ‘Gis Deena 15-715, 1297 22, Sapa A Cl BG Tepe aaa me AML New" York, Raven, 6 Heghe URceal Adveneeiec aftp- eal ead] At tad Do 541, 2008 4. Goosen A, Manan Mi, Degeel HE Resthors © oonicusrotis Some new Soa aoe sey Cee secs 2000