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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5200_Библиотеки_им_академика_М_И_Перельмана

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AlthoughTCSsareappliedtotheskin,systemiceffectsmayoccur,especiallywiththeuseofhigh-and very high-potency agents for a prolonged period of time. The main adverse effect is hypothalamic– pituitary–adrenalaxissuppression.
TCSs, or ingredients in their formulation, may also be a suspected allergen in CD and should be consideredasasourceofcontactsensitizationiflesionsfailtorespondorworsendespitetherapy.
TopicalCalcineurinInhibitors
TCIs inhibitcalcineurin-dependentT-cell activation,whichpreventsproductionofcytokinesandother mediators that play a role in inflammation. They also play a role in mast cell activation. TCIs are typicallyusedassecond-linetreatmentinADandmaybe usedinimmunocompetentpatientswithAD whocannottolerateTCSsandarenotresponsivetoothertreatmentsorusedwhenthereisaconcernfor topicalsteroid–inducedatrophy.Becausetheydonotcauseskinatrophy,thesemedicationsareespecially useful for thetreatmentof AD involvingtheface, including the periocular and perioral areas. Use of TCSsand TCIs together totreat ADmayalso be considered. EfficacyinACDandICDhas not been establishedyet.
Tacrolimusandpimecrolimusarethetwopreparationscurrentlyavailable.Tacrolimusisapprovedfor useinmoderatetosevereAD,andpimecrolimusisapprovedformildtomoderateAD.
Dosage
Tacrolimuscomesinointmentsof0.03%and0.1%concentrations,whereaspimecrolimuscomesina1% cream only. They are applied twice daily until the lesions and inflammation resolve. Prophylactic application2to3timesaweektoareasofrecurrentdiseasemayalsobeconsideredtopreventrelapse. Theskinisdriedbeforeapplication,butTCIsshouldnotbeusedwithocclusivedressings.
Contraindications
IfpatientsexperiencehypersensitivitytoTCIs,theagentshouldbediscontinued.Cautionisneededwith useduringacuteinfection,sincetheseagentsareimmunosuppressants.
AdverseEffects
TCIs can cause transientburningandpruritus, whichdisappear with continueduse or withshort-term applicationofTCSspriortouse.Moresevereadverseeffectsincludeimmunosuppressionand,inrare cases, malignancy. Duetoconcernsofmalignancy,thepatientshouldlimitsunexposureanduseofsun protectionisrecommended.
Crisaborole
Crisaboroleisatopicalphosphodiesterase-4(PDE-4)inhibitorthatmaybeusedinthetreatmentofmild tomoderateAD. Throughtheinhibitionof PDE-4, intracellular levels ofcAMP are elevated and this playsa roleinreducinginflammation.Theplaceintherapyisnotwellknownsincethis medicationis stillfairlynew,havingbeenapprovedin2016.It’savailableasa2% creamthatcanbeappliedtwice daily to the affected area. The most common side effects include application site reactions,
nasopharyngitis,andupperrespiratorytractinfections.
TopicalAntimicrobialsandAntiseptics
PatientswithAD are susceptibleto skin infectionsdueto a compromised skin barrier.Theprominent colonizeroftheskinisStaphylococcusaureus.Despitethisriskfactor,thereisnorecommendationfor theuseofanti-staphylococcaltreatmentinpatientswithAD.Ifsecondaryinfectionissuspected,bleach bathsandintranasalmupirocinmayhelpreducetheseverityofdisease.
Antihistamines
Antihistamines are used to relieve pruritus associated with CD, especially allergic CD. Topical antihistamines have not been shown to help with AD. Antihistamines come in oral and topical preparations.Thebesttimetousethem isbeforebedtopromotesleepbecausethemainsideeffectis drowsiness.AntihistaminesarediscussedfurtherinChapter46.
SystemicCorticosteroids
IfthedermatitisiswidespreadorrefractorytotreatmentwithTCSs,TCIs,orphototherapy,oralsystemic therapy may be used. The first oral therapy option is corticosteroids, which should be reserved for refractory CD. Oral corticosteroids inhibit cytokine and mediator release, attenuate mucus secretion, upregulate beta-adrenergic receptors, inhibit IgE synthesis, decrease microvascular permeability, and suppresstheinfluxofinflammatorycellsandtheinflammatoryprocess.
Dosing
Corticosteroidsshouldbeprescribedataninitialdoseof1mg/kg/dequivalenttoprednisoneandtapered down. The entire dose can be taken at the same time in the morning to minimize sleep disturbances. Takingcorticosteroidsforlessthan2weeksmaycauserebounddermatitis,especiallywithpoisonivy.If dermatitisflaresupduringthetapering,thedosagecanbeincreasedandtapereddownagain.
Contraindications
Becausetheysuppresstheimmuneresponse,systemiccorticosteroidsarecontraindicatedinpatientswith systemic fungal infections and in patients receiving a live or live attenuatedvaccination.These drugs shouldalsobeusedcautiouslyinpeoplewithtuberculosis,hypothyroidism,cirrhosis,renalinsufficiency, hypertension,osteoporosis,anddiabetesmellitus.
AdverseEffects
Systemiccorticosteroidsmaskinfection.Inshort-termuse,theymaycausegastrointestinalupset.Mood changes (hyperactivity, anxiety, depression) may be evident, and sleep disturbances may occur. The effects of systemic corticosteroids may be decreased if they are administered with barbiturates, hydantoins,orrifampin.Formoreinformationaboutsystemiccorticosteroids,refertoChapter25.
OtherSystemicTherapyOptions
Examples of other oral therapy options include cyclosporine, azathioprine, methotrexate, and mycophenolate.ThesefouragentsmaybeconsideredinrefractoryAD.
Cyclosporine is a calcineurin inhibitor. It inhibits production and release of interleukin II, which preventsactivationofT-cells. Dosingis150to300 mgdailyinadultsand3 to6mg/kg/dinchildren. Adverseeffectsincluderenalimpairment,hypertension,andinfection.Thisagentshouldnotbeusedin patientswithactivemalignancyorimpairedrenalfunction.
Azathioprineisanimmunosuppressantthatproducesmetabolitesthatincorporateintodeoxyribonucleic acid(DNA)andpreventreplication.Italsoplaysaroleininhibitingpurinesynthesis.Dosingis1 to3 mg/kg/dinadultsand1to4mg/kg/dinchildren.Ifthepatientispregnant,thismedicationshouldonlybe usedifthebenefitoutweighstherisk.
Methotrexateisafolateantimetabolitethatbindstodihydrofolatereductaseandthymidylatesynthetase, which play a role in DNA synthesis, repair, and cell replication. The mechanism in skin disease is unknown,butit isthoughttoaffectproliferationofepithelial cells.Dosingis7.5 to 25 mg a weekin adultsand0.2to0.7mg/kg/wkinchildren.Atestdoseof1.25to5mgshouldbeconsideredtoassessif thepatientcantoleratethemedication.Manyadverseeffectsareassociatedwithmethotrexate,including pulmonaryfibrosis,cytopenia,andulcerativestomatitis.Thisdrugshouldnotbeusedinpregnantpatients orpatientswithliverdisease.
Mycophenolateisanimmunosuppressantthatinhibitsguanosinenucleotidesynthesis,whichaffectsthe proliferationofT-andB-cells.Dosingis1to1.5gtwicedailyinadultsand1,200mg/m2daily(~30–50
mg/kg/d)inchildren.Gastrointestinalupsetismostcommonlyseenwiththisagent.Usecautioninpatients whoarepregnantandinpatientsreceivingalivevaccine.
SelectingtheMostAppropriateAgent
TherecommendedtreatmentorderislistedinTables12.2and12.3.
First-LineTherapy
NonpharmacologicoptionsshouldfirstbeconsideredinbothCDandAD.Thisincludesavoidanceofthe offending agent, use of skin protection, and use of moisturizers to maintain the skin barrier. If these approachesdonothelp,pharmacologictherapycanbeconsidered.
TCSsarethefirst-line topical medication foruse inCD andAD.Ifimprovement does not occur,a higher-potencyTCSmaybeconsidered.TCSscanbeappliedforbothtreatmentandpreventionoffuture flaresofAD.
OralantihistaminesareusedtorelievepruritusandshouldonlybeconsideredinCD.
Second-LineTherapy
IfthepatientdoesnotrespondtoTCSoriftheuseofasteroid-sparingagentiswarranted,aTCIcanbe considered as second-line therapyin AD.The use of both a TCSanda TCIcan be considered. One commonstrategyistheuseofaTCSduringanacuteflareofADandtheuseofaTCItopreventfuture flares as a steroid-sparing option.Crisaborole canalso be considered as an alternative to TCSs and TCIs.Phototherapymayalsobeconsiderediftopicalagentsdonotresolvethepatient’scondition.
TABLE12.2
RecommendedOrderofTreatmentforContact
Order Intervention Comments
First line
PreventionandavoidanceofoffendingagentMayconsider useofTCSOralantihistamineforreliefofpruritus
OcclusivedressingishelpfulApplytomoist skinsurface
Second line
Increasedpotencyoftopicalcorticosteroid Avoidusingmoderate-orhigh-potencytopical
corticosteroidonfaceorintertriginousareas
Third line
Oralcorticosteroids Commondosage:1mg/kgandtapereddown
ConsiderincreasingdoseifCDpersists
TCS,topicalcorticosteroids.
TABLE12.3
RecommendedOrderofTreatmentforAtopicDermatitis
Order Intervention Comments
First line
Nonpharmacologicapproaches;mayconsiderTCSin treatmentandpreventionofflares
Nonpharmacologictherapyincludestheuseof moisturizers,bathing,andWWT
Second line
TCI,crisaborole,orphototherapy MayconsiderTCIasasteroid-sparingagentor
useinconjunctionwithTCS Phototherapycanbeconsideredifpatientdoesnot respondtotopicaltherapy
Third line
Oralsystemictherapy ReservedforrefractoryAD
AD,atopicdermatitis;TCI,topicalcalcineurininhibitors;TCS,topicalcorticosteroids;WWT,wet-wraptherapy.
Third-LineTherapy
Systemictherapymaybeconsideredifthepatientdoesnotrespondtotopicaltherapyandphototherapy. Unfortunately,theadverseeffectprofilesofavailablesystemicoptionsarevast,andmonitoringofthese adverseeffectsiswarranted.
AproposedtreatmentalgorithmisprovidedinFigures12.1and12.2.
SpecialPopulations
Pediatric
Sincechildrenhavegreaterbodysurfacearea–weightratio,theycanabsorbmoreofaTCSthanadults. Therefore, the leastpotent TCSshould be used to minimize adverse effects when used for long-term disease.
Tacrolimus0.03%andpimecrolimus1%areapprovedforuseinpatientswhoare2yearsoldorolder, andtacrolimus1%isonlyapprovedforpatientswhoare15yearsoldorolder.Despitethis,theuseof tacrolimus0.03%orpimecrolimus1%maybeconsideredinpatientswhoarelessthan2yearsold.
Atopic
Dermatitis
Nonpharmacologic
Moisturizers
•
Bathing
•
-
wrap
therapy
•
Wet
options
1
Resolved
Yes
Stop
therapy
Consider
TCSs
prevent
Resolved
No
treat
to
flares
i
/
Yes
Stop
therapy
TCI
•
Crisaborote
•
Phototherapy
•
to
Yes
Stop
therapy
No
-
/
TCS
+
topical
therapy
1
Resolved
Cyclosporine
•
Azathioprine
•
Methotrexate
•
Mycophenolate
•
(
if
refractory
)
No
l
Key
Starting
decision
Clinical
I
(
assessing prescribing monitoring
Decision
for
point
-
making
actions
,
,
)
point
Yes
Stop
therapy
Resolved
No
Refer
to
pecialist
FIGURE12–1Proposedtreatmentalgorithmforatopicdermatitis.
TCIs,topicalcalcineurininhibitors;TCSs,topicalcorticosteroids.
Allergic
dermatitis
Prevention
.
1
Avoidance
•
Protective
•
googles
Mosturizers
•
Symptom
2
.
Cool
•
Colloidal
•
Calamine
•
Burow
•
contact
)
control
compresses
solution
Resolved
Instant
offending
of
equipment
oatmeal
lotion
i
dermatitis
agent
(
gloves
baths
contact
,
Yes
Stop
therapy
Yes
Stop
therapy
No
Topical
•
Oral
•
antihistamine
*
Resolved
Yes
corticosteroids
No
Increase
of
potency
TCS
I
Resolved
for
No
pruritus
Key
|
Starting
decision
j
Clinical
assessing
(
prescribing
monitoring
Decision
point
making
-
actions
,
,
)
point
Stop
therapy
for
Yes
Stop
therapy
Consider
oral
I
Resolved
,
TCS
No
Refer
to
specialist
FIGURE12–2Proposedtreatmentalgorithmforcontactdermatitis.TCSs,topicalcorticosteroids.
TCSs,topicalcorticosteroids
Geriatric
ThemostcommoncausesofCDinolder patientsaretopical medications(e.g.,neomycin[Myciguent]) andthebasesofothertopicalmedications.TheadhesivesonadhesivepatchesmayalsocauseCD.The rashofCDdoesnotpresentinaclassicpatternintheolderadult.Insteadofvesiclesorinflammation,the areaexposedtotheirritantmaysimplybecomescaly.TCSscancauseatrophyoftheskininolderadults, whichisaproblembecausetheirskinisalreadyfriable.
Women
Applycautionwhenusingvarioussystemictherapyoptionsinwomenwhoarepregnant.Mostsystemic therapyoptionsposearisktothefetus,andtherisksoftentimesoutweighthebenefits.Theonemedication toavoidinpregnancyismethotrexate.
MONITORINGPATIENTRESPONSE
Theresponsetotherapyismonitoredbyvisualexaminationoftheaffectedpartsoftheanatomyandthe reportedresolutionofsymptoms.Thepatientshouldreturnforfollow-upevaluationwithin2or3daysof initiationoftherapy. Ifa bacterial infectionrecurs secondarytoCD,itmaybe treated as discussed in
Chapter13,“Bacterial,Fungal,andViralInfectionsoftheSkin.”
PATIENTEDUCATION
Educationincludesteachingpatientstoavoidthecausativesubstance.Usingmildsoapswithoutperfume isanimportantpreventivemeasure.Asappropriate,thepractitionercandemonstratehowtoapplytopical preparationstomoistskinandapplyanocclusivedressingtoincreasetheefficacyofTCSs.Penetration ofTCSsisenhanced10-to100-foldbyhydrating(moistening)theareabeforeapplyingthemedication. Aneasy-to-makeocclusivedressingconsistsofplasticwrapappliedoverthemedicatedareaandheldin place by a sockortape.Onthehands, a glove can act as an occlusive dressing.Onthehead area, a showercapcanbeused.Occlusivedressingsshouldnotbeusedwithtopicalimmunosuppressants.The patientshouldavoidalcoholandshouldusesunscreen.
ThepractitionershouldalsoaddressanyfearsormisconceptionsabouttheuseofTCSssincepatients mayhaveafearofadverseeffectsfromTCSs.Thismayleadtoincorrectusageornoncompliancetothe TCSs.Ingeneral,TCSsarewelltoleratedaslongastheyarebeingappliedappropriately.
MostpatientswithADrequire hydrationthroughtheliberal useofblandemollients,whichserve to hydratethestratumcorneumandmaintainthelipidbarrier.Sufficientemollientsappliedliberallyseveral times a day may be enough to significantly reduce the disease activity of AD. Parents of infants and toddlersshouldapplyablandemollienttotheentirebodywitheachdiaperchange.Olderchildrenshould applyblandemollientsinthemorning,afterschool,andatbedtime.Bathingshouldbe limitedtobrief, coolshowersoncedaily.Soap,whichdriesandirritatestheskin,shouldbeavoided,butgentlelipid-free cleansersarebeneficial.
Skinhydrationisbestaccomplishedthroughdailysoakingbathsfor10to20minutes.Itisimportantto remindpatients andcaregivers toapplya topicalmedicationor moisturizerimmediatelyafter bathing. Thisis tosealinthewater thathasbeenabsorbedintotheskinandtopreventevaporation,whichcan leadtofurtherdryingoftheskin.
Foradditionalinformationthatispatientfriendly,thepractitionermayreferthepatienttotheWebsite of the American Academy of Dermatology (aad.org) and the National Eczema Association (nationaleczema.org).
Someadjunctiveandcomplementaryinterventionsarethoughttobe helpfulinAD,althoughthere is limitedor noevidencetoshowbenefit.Food allergiesmaycoexistwithAD,butthefrequencyofthat foodallergycausingaflareisprobablylow.VitaminDandEsupplementationmayhaveamildbenefit. Overall,thesestrategiesandotheralternativetherapiesshouldnotberoutinelyrecommended.
CASESTUDY1
J.F.,a15-year-oldboywhoweighs110pounds,isseekingtreatmentforaveryitchyrashconsistingof linearstreaksofpapules,vesicles,andblistersonhisarms,legs,andface.Hetellsyouhewashiking inthewoods2daysagoalongtrailslinedwithpatches ofshinyweedswiththree leaves.He tried using calamine lotion and over-the-counter diphenhydramine cream but the itching still persists (LearningObjectives1and3). 
1.WhatconditiondoesJ.F.presentwith?WhatsymptomsdoesJ.F.presentwithandwhatisthemost likelyoffendingagentthatsuggeststhiscondition?
Answer:J.F.presentswithcontactdermatitis,mostlikelyfrompoisonivy.ThesymptomsthatJ.F. presentswitharepruritus,papules,vesicles,andblistersontheareasofcontactwiththepoisonivy leaves.
2.Whatwouldbethefirst-lineoptionfordrugtherapy?
Answer: Prevention and avoidance of the offending agent is the best treatment. In terms of
pharmacotherapy, the first-line option is topical corticosteroids (TCSs). TCSs are best since contactdermatitisisoftenlocalizedontheskinandsystemictherapyisnotnecessary.
3.Whatwouldbethebestchoiceforsecond-linetherapy?
Answer: In the case of extensive contact dermatitis in poison ivy, oral corticosteroids may be
consideredifthepatientisrefractorytoTCSs.Topicalcalcineurininhibitors(TCIs)shouldnotbe consideredincontactdermatitis.Optimaldosingshouldbe1mg/kg,whichtranslatestoabout50 mg.Thisdosecanbetapereddownoverthecourseofafewdays.
4.WhatlifestylechangeswouldyourecommendtoJ.F.?
Answer:J.F.canconsiderwearingprotectiveclothingwhileatriskforcomingincontactwiththe
offendingagent.Inthissituation,wearingclothingthatcoversallareasofskincanpreventcoming incontactwithpoisonivyleaves.
CASESTUDY2
J.T.isa36-year-oldfemalewithapastmedicalhistoryofatopicdermatitisasachildwhopresentsto yourdermatologyclinicbecauseofrecurrentxerosisandpruritusonherarms.Shestatesthatshetried tomoisturizeherskinwithlotionandthatsheusedtouseasteroidcreamasachild.Ofnote,sheis25­weekpregnantandhasnonotabledrugallergies.
Diagnosis:flareofatopicdermatitis(LearningObjective3)
1.Whatwouldbethefirst-linetherapyforthispatient?
Answer:Theuseofmoisturizersisfirstline.Thepatienthasalreadyusedlotion,sothepatientcan
consider other nonpharmacologic options, such as bathing and wet-wrap therapy (WWT). Drug therapy can be considered if the patient does not respond to these options. First-line therapyis TCSs.
2.Listoneortwoadversereactionsfortheselectedagentthatwouldcauseyoutochangetherapy.
Answer:Mainexternaladverseeffectsincludepurpura,rosacea-likeeffects,andskinatrophy.The
systemicsideeffecttobeconsideredisadrenalsuppression.
3.Whatwouldbeexamplesofalternativetherapy?Whattherapyshouldbeavoided?
Answer:Topicalcalcineurininhibitors(TCIs)canbeconsideredasasecond-lineagent.TCIscan
be used if the patient does not respond to TCSs or if a steroid-sparing agent is necessary. Crisaborole or phototherapycanalsobeconsidered. Ofnote, systemic therapyoptions are risky sincetheymayposearisktothefetus.Methotrexateisanabsolutecontraindication,whereasthe otheroraloptionsshouldbeusedcautiouslyifnecessary.
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