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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5200_Библиотеки_им_академика_М_И_Перельмана
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1.Whatinformationwouldbediscussedregardingnewdiagnosisandexpectationsfordiseasecourse
andsuccessfultherapy?
Answer:Psoriasisisachroniccondition,sorealisticexpectationsoftherapyratherthancureneed
tobeaddressed.Anytreatmentwillneedtimeforefficacy.Ifconsiderationofabiologicagentis
undertaken,baselinelabsmustbeobtained.
2.Whichclassofdrugtherapywouldyouprescribe?Why?
Answer: Consider beginning with topical agents both corticosteroids and vitamin D analog to
decreasesymptomsofpruritus,inflammation,andscale.Theonlyoraloptionwherebloodtestsare
notrequiredpriortoinitiationwouldbeApremilast.
3.Whichnecessarylaboratoryresultsareneededpriortoinitiatingbiologictherapy?
Answer: Prior to most oral agents and biologics, the required and suggested labs include
tuberculosis testing (PPD placement, Quantiferon Gold, or chest X-ray if warranted), complete
bloodcount,CMP,Lipidpanel,andHepatitisBpanel.
4.Whatwouldbethechoiceforsecond-linetherapy?
Answer: Second-line therapy will take into consideration lab results, coexisting medical
conditions,age,insurancecoverage,andwillingnessforconsistenttreatmentandfollow-up.Most
ofthebiologicagentsrequireselfadministration.Forsomethisisamajordeterrent.Infliximabis
administered ataninfusion center everyfewmonths.Ifmethotrexate,Soriatane, or cyclosporine
follow-uplabsarerequiredinearlytherapy.
5.Whenwouldbethetimetodiscussmedicationchangesfromtopicaltosystemicoptionsorreferral
tospecialist?
Answer: This chronic condition waxes and wanes. Daily application of topical agents can be
messyandtimeconsuming.Topicalagentsdonothingtocontrolinflammationoccurringinsidethe
bodywhichcanleadtolong-termchronic disease.Atleast4 weeksshouldbegivenfortopical
agentsto showeffectiveness.Biologicagentsneedatleasta 3-monthtrialbefore consideringto
changedrugorclass.Ifuncomfortableintreatingwithinjectableagents,feelfreetoconsultwitha
localspecialist.
Bibliography
Busard, C., Zweegers, J., Limpens, J., et al. (2014). Combined use of systemic agents for psoriasis: A systematic review. JAMA
Dermatology,150(11),1213–1220.
Egeberg,A.,Byrd,L.,&Skov,L.(2019).DrugsurvivalofSecukinumabandIxekizumabformoderatetosevereplaquepsoriasis.Journalof
AmericanAcademyofDermatology,81(1),173–178.
Elmets,C., Lim, H., etal. (2019). Jointacademyof dermatology-nationalpsoriasis foundationguidelines of care for the managementand
treatmentofpsoriasiswithphototherapy.JournalofAmericanAcademyofDermatology,81(3),778–804.
Feldman,S.(2014).Fivefactorsforchoosingtherightbiologictreatment.TheDermatologist,22(9),26–29.
Fu, Y., Lee, C. et al. (2018). Association of psoriasis with inflammatory bowel disease: A systemic review and meta-analysis. JAMA
Dermatology,154(12),1417–1423.
Green,L.,Yamauchi,P., & Kircik,L.(2019).Comparisonofthesafetyandefficacyoftumornecrosisfactor inhibitors andinterleukin-17
inhibitorsinpatientswithpsoriasis.JournalofDrugsinDermatology,18(8),776–789.
Habif,T.,Diunlos,J.,Chapman,M.S.etal.(2018).Skindisease:Diagnosis andtreatment. NewYork: Elsevier.Han,G.(2019).What’s
newintopicaltreatmentsforpsoriasis.Cutis,103(2),65–66.
Lebwohl, M., Sugarman, J., et al. (2018). Long term safety results from a phase 3 open-label study of a fixed combination halobetasol
proprionate0.01%andtazarotene0.045%lotioninmoderatetosevereplaquepsoriasis.JournalofAmericanAcademyofDermatology,
80(1),282–285.
Menter, A., Korman, N., Elmets,C.,et al. (2010). Guidelines of care for managementof psoriasis andpsoriaticarthritis. Journal of the
AmericanAcademyofDermatology,62(1),114–135.
Murphy,E.,Nussbaum,D.,etal. (2019).Use of complementaryandalternativemedicine bypatientswithpsoriasis.Journal ofAmerican
AcademyofDermatology,81(1),281–283.
Stein-Gold,L.,Lain,E.,et al.(2019). Halobetasol0.01%/tazarotene 0.045% lotioninthe treatmentofmoderate-to-severeplaquepsoriasis:
Maintenanceoftherapeuticeffectaftercessationoftherapy.JournalofDrugsinDermatology,18(8),815–820.
Yamauchi,P.S.,&Bagel,J.(2015).Nextgenerationbiologicsinthemanagementofplaquepsoriasis:AliteraturereviewofIL-17inhibition.
JournalofDrugsinDermatology,14(3),244–250.
15
AcneVulgarisandRosacea
ShellyR.Schneider
LearningObjectives
1.Thelearnerwillidentifyagentsusedtotreatmildtomoderateacnelesions.
2. The learner will distinguish the need for topical therapy, understand when to add oral agents if
appropriate,andunderstandwhentorefertodermatology.
3.Thelearnerwilldiscussthevariedtopicalagentsavailabletotreatbothtelangectaticandpapulopustularrosacea.
ACNEVULGARIS
Acne vulgaris isviewed bysomeas a riteof passage duringtheadolescent years. Upto90% of all
teenagersreporthavingsomeformofacne.Adultssufferfromtheeffectsofacneaswell:between30%
and50% of adult womenreport experiencingacne. Consumers spend millions ofdollars annuallyon
prescription and over-the-counter (OTC) acne preparations. The psychosocial costs of acne are high.
Adolescentsareparticularlyaffectedbyphysicaldefects,nomatterhowminortheyappeartoothers.The
healthcarepractitionermustbeparticularlysensitivetotheperceivedseriousnessoftheacneinaddition
to the clinical picture. What may seem inconsequential to the practitioner may be devastating to the
patient.Nomatterhowminortheacnemayappeartotheprovider,itisimportanttoaskpatientsifthey
areconcernedabouttheiracneandwhethertheywouldliketreatment.
CAUSES
Historically, numerous theoriesof the cause ofacnevulgaris havebeenproposed, yettheexactcause
remains unknown. Foods, stress, and hormones, although not causative, mayexacerbate existing acne,
whichiswhyitisimportantto obtaina completehealthhistoryto ascertainprecipitatingfactors. For
example,avarietyofdrugs,topicalagents,andmedicalconditionsmayexacerbateacne.Certaindrugs
usedtotreattuberculosis,seizuredisorders,chronicillness,ordepressionandsteroiddependencymay
bethecauseofdrug-inducedacneiformrash(Table15.1).Drug-inducedacneshouldbesuspectedwhen
alllesions are in the samestage(e.g.,the lesions are uniformly all pustules or allopencomedones),
coveringtheface,chest,trunk,arms,andlegs.
Acnemaybeexacerbatedinteenagersandadultswhoseskinisexposedtooilyagents,suchasmakeup,
oil-based sunscreen,andoil-based hair products that come incontactwith the foreheadandtemporal
regionsoftheface(referredtoaspomadeacne).Frictionacnefrom tight-fittingclothes(sportsbrasin
females),footballhelmets(chinstraps),andhatbandsmaybefoundovertheskinrubbedbytheclothes.
Exposuretoanimalvegetableandpetroleum-basedoilsusedinworkplacessuchasfast-foodrestaurants
andautomotivegaragesmayalsoexacerbateacne.Emotionalstressmaycontributetoacneexacerbations
inpersonspronetobreakouts,butstudies havenotconsistentlyproventhis correlation.Womenwitha
history of menstrual irregularities, hirsutism, and treatment-resistant acne should be evaluated for
androgenexcessassociatedwithpolycysticovariansyndrome.
TABLE15.1
MedicationsThatCauseAcneiformRash
Medication UnderlyingCondition
Corticosteroids Chronicinflammatoryconditions
Isoniazid Tuberculosis
Lithium Depression
Phenytoin Seizuredisorder
Trimethadione Seizuredisorder
PATHOPHYSIOLOGY
Acneusuallybegins1to2yearsbeforetheonsetofpuberty,whenandrogenproductionincreases.Excess
androgen causes increased sebum production. For unknown reasons, abnormal keratinization causes
retentionofsebuminthepilosebaceousfollicle.Thisproducesopencomedones(blackheads)andclosed
comedones (whiteheads). When closed comedones continue to produce keratin and sebum, the
pilosebaceousfollicle ruptures andinflamesthesurrounding tissue.Iftheinflammationis closetothe
surface, a papuleforms.Ifitisdeeper inthedermis, a larger papule or nodule forms. These deeper,
nodularacnecystscancausepermanentscars.
AlthoughCutibacteriumacnes(C.acnes)formerlyknownasPropionibacteriumacnes,ananaerobic
gram-positivebacterium,ispresentasnormalflorainthepilosebaceousfollicle,acneisnotaninfectious
entity.Rather,itis believedthatC.acnes produces lipolyticenzymes thatinturnproducebiologically
activeextracellularproducts.Theseinturnattractpolymorphonuclearleukocytesandmonocytes,which
increaseinflammation.
DIAGNOSTICCRITERIA
Acne vulgaris is diagnosed from the clinical presentation of the patient’s skin. It is classified and
subsequentlytreateddependingonitsseverity. Themildest formofacneiscomedonal.Bothopenand
closed comedones may be present. Mild inflammatory acne is manifested by papules. Moderate
inflammatoryacneconsistsofpustulesandsomecysts.Severecysticacneconsistsofcysts,nodules,and
scarring(Table15.2).
TABLE15.2
ClassificationofAcneVulgaris
Classification PhysicalFindings
Comedonalacne Opencomedones(blackheads),
closedcomedones(whiteheads)
Mildinflammatoryacne Papules
Moderateinflammatoryacne Pustules,cysts
Severecysticacne Cysts,nodules,“ice-pick”scarring
INITIATINGDRUGTHERAPY
Skincareis themostimportantnonpharmacologictoolinthemanagementofacnevulgaris. Thepatient
shouldbeinstructedtowashthefacegentlytwiceadaywithamildagent.Acleanserislessdryingand
harsh than soap, and multiple preparations are available OTC. Washing should be gentle because
scrubbing the skin may exacerbate the acne. Comedonal removal, although therapeutic, should be
undertakenonlybysomeoneskilled inthe proper technique.Pickingorpoppingpimplesmayincrease
tissuedamage,leadingtoscarringandinfection.The healthcareprovider shouldadvisethe patientto
avoidmanipulatingtheacnewiththefingers.
Ingeneral,moisturizersandcosmeticsshouldbewaterbased,non-comedogenic,andfragrancefree.If
hairpreparationsareused,theyshouldalsobewaterbased.Thepatientshouldbeinstructedtoapplyhair
productssothattheyavoidcontactwithsidesofface,shoulders,andtrunk.
The practitioner also needs to stress that ingestion of specific foods, suchas sugar and dairy, may
contributetoinflammatoryfactors thatpredispose oneto acne.Hereditymayalso be a precipitatinga
factorforseverescarringacne.
GoalsofDrugTherapy
Thegoalofpharmacotherapyistominimizethenumberandseverityofnewlesions,preventscarring,and
improvethepatient’sappearance.Thepatientmustbecounseledthatimprovementofacnevulgaristakes
time—usually 4 to 6 weeks. Some form of therapy will probably need to be continued throughout
adolescenceandevenintoyoungadulthood.
Pharmacotherapychoices are based ontheseverityoftheacne.Currently,successfultherapyusually
reliesonacombinationofmedications.Thesynergisticeffectoftwoormoredrugsfromdifferentclasses
producesthebestresults.SeeTable15.3forasummaryofacnemedications.
Comedolytics
Tretinoin
MechanismofAction
Whenappliedtopically,retinoicacid(RetinA,RetinAMicro,Altreno)actsontheepidermiswithlittle
systemicabsorptiontodecreasecohesionbetweenepidermalcellsandincreaseepidermalcellturnover.
Theresultisexpulsionofopencomedonesandtheconversionofclosedcomedonestoopenones.
Dosage
Retinoicacidisavailableincreams(0.025%,0.05%,0.06%,0.08%,and0.1%),gels(0.01%,0.025%,
and0.05%),andmicrosphere(0.04%and0.1%)formulations.Themicrosphereformulationencapsulates
theactiveingredientinmicrospheres,whichactasareservoirthatslowlyreleasestheretinoicacidinto
theskin.
TABLE15.3
OverviewofTopicalandOralAcnePreparations
BPO,benzylperoxide;CBC,completebloodcount;PABA,para-aminobenzoicacid.
Contraindications
All retinoids are considered teratogenic, and women should ensure that they do not become pregnant
whileusingtheseagents.
SideEffects
Erythema,dryness,andpeelingoftheskinmayresultifoverused.Somepatientscannottoleratedailyuse
orprolongedcontactattheinitiationoftherapy.
SpecialConsiderations
Fair-skinned and sensitive patients should be advised to start out using the product every other day.
Alternatively,thepatientmaybeinstructedtoapplyretinoicacid tothefacefor15 to30minuteseach
nightandthenwashoffthemedication.Gradually,thelengthoftimethemedicationremainsonthefaceis
increaseduntilitcanbetoleratedovernight.Itis besttoapplythemedicationonclean,thoroughlydry
skintoavoidexcessiveirritation.Patientsshouldbeadvisedtoavoidprolongedexposuretothesunorto
wearanon-comedogenicsunscreenformulatedspecificallyforuseontheface.
Informing individuals to stop the topical preparation for at least 3 days before facial waxing is
recommendedduetosensitivityandsloughing.Inaddition,avoidanceofcornersofeyes,nose,andmouth
duetoincreasedsensitivityandirritationinsuchsensitiveareasisrecommended.
Adapalene
MechanismofAction
Adapalene(Differin)0.1%and0.3%gel,a topical medicationfor treatingnoninflammatoryacne,isa
derivativeofnaphthoicacid,whichbindstoretinoidreceptors.
Dosage
Itisappliedoncedailyineveningtoavoidsunsensitivity.Contraindications
Thedrugisconsideredteratogenic,sofemalesofchildbearingpotentialshouldbecautionedtoavoid
pregnancywhileusingtheseagents.
SideEffects
Erythema,dryness,andpeelingoftheskinmayresultifoverused.Somepatientscannottoleratedailyuse
orprolongedcontactattheinitiationoftherapy.
SpecialConsiderations
Itisconsideredlessirritatingthanretinoicacid. Upto40%ofpatientsreportirritation,butitsubsides
duringthefirstmonthoftreatment.Adapaleneisappliedinthesamewayasretinoicacid.Thelowerdose
isnowavailableOTC.
Tazarotene
MechanismofAction
Aretinoidprodrug,tazarotene(Tazorac)0.05%gel,0.1%gel,cream,andfoampreparationiseffective
againstbothcomedonalandinflammatoryacne.
Dosage
Itisappliedoncedailyinevening.Theusermayalternateeveryotherdaywhenfirstintroduced.
Contraindications
All retinoids are considered teratogenic, andwomenshould be cautionedto use contraceptionand/or
preventpregnancy.
SideEffects
Redness, dryness, burning, and peeling of the skin may result when initiating therapy. Some patients
toleratealternatedailyuseorlessprolongedcontactattheinitiationoftherapy.
SpecialConsiderations
Alternatingdaysofapplication,aswellasusingapea-sizeddosefortheentireface,canreduceirritation.
Use of a moisturizer prior to application is helpful. Address the use of a gentle cleanser if dryness
continuesorseekalesspotentformoftherapy.
ComedolyticBactericidals
BenzylPeroxide
MethodofAction
Benzylperoxide(BPO)isbothcomedolyticandbactericidaltoC.acnes.Ithasa roleininflammatory
acnebecauseofitsantibacterialqualities.DecreasingC.acneslevelsdecreasestheinflammationcaused
by leukocytic andmonocytic attractionto the pilosebaceous follicle. Themajor side effect of BPOis
irritation.
Dosage
BPOisavailable invariousstrengthsandformsinOTCpreparations.Gelformulationsareconsidered
moreeffective,butallareavailableinmanydifferentstrengths.Itisalsoavailableaswashesorleave-on
lotionandcreams.Thisproductcanbeusedonceortwicedaily,inadditiontouseonalternatedays.
Contraindications
Hypersensitivityreactionsmayoccurinthosewithmoresensitiveskintypes.
SideEffects
Irritation,erythema,anddrynessmayallbeexperiencedwiththeuseofBPOproducts.
SpecialConsiderations
Similartoallcomedolytics, BPOisappliedinitiallyinalow-percentageformulationinanonirritating
base.Thepatientincreasesthedosagestrengthandfrequencyastolerated.SinceBPOmaybleachcolored
items,thepatientshouldbeinstructedtonotlettheproductcomeincontactwithbrightlycoloredtowels,
pillowcases,orclothing.
AzelaicAcid
MechanismofAction
Azelaicacid(Azelex)20%creamisbelieved to interfere withthedeoxyribonucleic acid synthesis of
acne-causingbacteria.Usedto treatmild tomoderate acne,the drugisalso available in15% gel and
foamformulationsforuseinrosacea.
Dosage
Azelaicacidisappliedoncedailytocleanskininitially;dosingmaybeincreasedtotwicedaily.
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