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Chapter14:DermatologicUrgenciesandEmergencies
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DermatologicUrgenciesandEmergencies

RetiformPurpura
Purpuraischaracterizedbynonblanchable,redpurplemaculesorpapulesthatresultfromthe
leakageoferythrocytesintotheskin.Thetermretiformdescribestheangulatedornetlike
configurationthatreflectsthevascularstructureintheskin.Thecolorisoftenadarkbrickredor
purple(Figure115).Itisimportanttorecognizethesecolorsastheymayindicatelocalskin
ischemiaduetoocclusionorbreakdownofvascularintegritythatmayleadtonecrosis,whichmay
becomelifethreateningifnotaggressivelytreated.Variousconditionscancauseretiformpurpura,
manyofwhichdisruptarterialbloodflow(Table28).Thromboticandemboliccausesshouldbe
consideredfirst.Thromboticcausesincludealterationstothecoagulationcascadesuchas
disseminatedintravascularcoagulation,thromboticthrombocytopenicpurpura,anddruginduced
thrombosis(warfarinorheparin).Emboliccausesincludecardiacsourcesofemboli(bacterialor
maranticendocarditis,atrialmyxoma),aswellascholesterolembolithatmaybedislodgedafteran
intravascularprocedure.Cholesterolembolimaycausemultisystemchangessuchaseosinophilia,
acutekidneyinjury,stroke,intestinalischemia,andamaurosisfugax.Ecthymagangrenosumand
pyodermagangrenosumareotherdiseasesthatcancausedark,dusky,orpurplelesionsbutdonot
havearetiformconfiguration.
Figure115.OpeninNewWindow

Retiformpurpuraonthelowerlegsduetovasculitis.

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Table28.OpeninNewWindowCausesofRetiformPurpuraandAssociatedFindings
Etiology

AssociatedFindingsandCauses
InfectioncausedbyMucorales,Aspergillus,Fusarium,Pseudallescheria

Angioinvasive
fungalinfection

Neutropenic,solidorgantransplantrecipients,burnvictims
Infectslocallybutcanbecomesystemic
Painoutofproportiontoexamination

Necrotizing
fasciitis

Historyofprecedingtrauma
CanbeamixedinfectionorduetoStreptococcus
Surgicalemergencyimagingcanbesupportivebutshouldnotdelaysurgical
exploration
Polyarteritisnodosa
ANCAassociatedvasculitides:
Eosinophilicgranulomatosiswithpolyangiitis

Granulomatosiswithpolyangiitis
Immunemediated
vasculitis
Microscopicpolyangiitis
Connectivetissuediseaseassociated(systemiclupuserythematosus,
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rheumatoidarthritis,dermatomyositis)
EvaluateforANCA,signsofconnectivetissuedisease,otherendorgan
damage(kidney,lung,eye,gastrointestinal,musculoskeletal)
Associatedwithadvancedkidneydisease
Calciphylaxis

Extremelypainful
Extensiveformsoccuroncentral,adiposesites(breast,abdomen,hips)
Limitedformsoftenoccurdistally
DIC,purpurafulminans

Thromboembolism Systemicinflammationduetoinfectionorotherinsult
Evidenceoforganischemiaanduncontrolledbleedingfrommultiplesites
Levamisoleadulteratedcocaine:tenderpurpuraontheearsisprominent

Drugs

Warfarinskinnecrosis:rare,occursinfirstweekoftherapy,commonly
involvesadiposeareassuchasthebreasts,abdomen,andhips
Heparinnecrosis:rare,onsetinthefirst5to10daysoftherapy,canoccuratthe
sitesofinjectionorelsewhere,mayormaynotbeassociatedwith
thrombocytopenia

ANCA=antineutrophilcytoplasmicantibodyDIC=disseminatedintravascularcoagulation.
Thehistorycanyieldimportantcluestothecausesuchasinfection,thromboticdisease,recent
intravascularprocedures,spontaneousabortion,solidorganorhematologicmalignancy,or
prescribedmedicationorillicitdrugreactions.Laboratorytests,directedbythehistoryandphysical
examination,areindicatedtoinvestigatethecauseandassessforendorgandamage.Inselect
patients,skinbiopsymaybehelpfulinestablishingthediagnosis.Largeincisionalbiopsies,which
includethedermisandsubcutis,arepreferredoverpunchbiopsies.Anadditionalspecimenissent
fortissuecultureifinfectionissuspected.

KeyPoint
Retiformpurpuraoftenindicatesinfection,thromboticdisease,recentintravascular
procedures,spontaneousabortion,solidorganorhematologicmalignancy,orprescribed
medicationorillicitdrugreactions.

ErythemaMultiforme,StevensJohnsonSyndrome,andToxic
EpidermalNecrolysis
Erythemamultiforme(EM)canberecognizedbythetargetlesionsonthepalmsandsolesaswellas
mucosalerosions,mostfrequentlyinthemouth(Figure116).Incontrast,typicaltargetlesionsare
rareinStevensJohnsonsyndrome(SJS)andtoxicepidermalnecrolysis(TEN).SJSandTENare
distinguishedbytheamountofskininvolvedbyblistersorerosions(Table29).SJSisdefinedas
affectinglessthan10%bodysurfacearea(BSA),andTENaffectsmorethan30%BSA.When10%
to30%BSAisinvolved,itisconsideredSJSTENoverlapwithamortalityratebetweenthetwo.
SJSandTENarerare,withaprevalenceof1:100,000forSJSand1:1,000,000forTEN.The
conditionsontheSJSTENspectrumcancausesignificantpainandscarringofinvolvedmucosal
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surfaces,althoughthemortalityriskisassociatedwiththemoresevereendofthespectrum.The
causesofSJSandTENarenotdefinitelyknownhowever,severalcellsandsignalingpathways
havebeenimplicatedintriggeringkeratinocytedeath.Someofthepossibleapoptoticmechanisms
includeFasFasligand,damagebyperforinorgranzymeB,andgranulysin.Cytokinesandreactive
oxygenspecieshavealsobeenlinkedtokeratinocyteinjury.
Figure116.OpeninNewWindow

Erythemamultiformecancausetargetlesionsonthepalmsandsolesthatcanvaryinsizeandmay
haveacentralerosion.

Table29.OpeninNewWindowComparisonofErythemaMultiforme,StevensJohnsonSyndrome,
andToxicEpidermalNecrolysis
Erythema
Multiforme
(EM)

StevensJohnsonSyndrome
(SJS)

ToxicEpidermalNecrolysis
(TEN)

Morphology

Typical3
zonedtarget

Atypicaltargetsandconfluent
erythemawithsloughing

Extensive,confluenterythema
withsloughing

Distribution

Favors
extremities

Trunkandextremitiesatleast
Trunkandextremitiesupto10%
30%bodysurfacearea
bodysurfaceareainvolvementa
involvementa

1or2sites

2ormoresites

Mucosal
disease
(oral,eye,

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genitourinary)
Constitutional
+
symptoms

++/+++

+++

Infection(%) 50

26

Drugs
implicatedin 50
(%)

74

94

Mortalityrate
0
(%)

513

2539

Etiology:

aSJSTENOverlap:10%to30%bodysurfaceareainvolvement,remainingfeaturesthesame

asSJS.
AdrugoraninfectioncantriggerEM.EMerupts1to3weeksfollowinganinfectionsuchasherpes
simplexvirusorMycoplasmapneumoniae.Childrenareaffectedequallybydrugsandinfections
however,drugsareamorefrequentcauseinadults.MostpatientswithEMarebetween20and40
yearsofage.Targetlesionsonthepalmsandsolesareoften1to6cminsize.Acentralpurpuricor
duskyzone,surroundedbyapaleringandaperipheralredring,formsthetarget.Thecenteroften
becomesvesicularoreroded.Targetlesionsareprominentonthepalmsandsoles,whereasred
maculesandpapulesoccurelsewhereonthebodybutfavortheextremities.Mucosalerosionsare
painful,andintactvesiclesorbullaeonmucosaarerare.
SJSandTENarepotentiallylethalbecauseofwidespreadskininflammation,necrosis,anderosion
(Figure117andFigure118).TENisalmostexclusivelycausedbymedications(Table30),whereas
SJSisnormallytriggeredbymedicationsbutmayoccasionallybecausedbyvaccinesorinfection.
PatientfactorssuchasHIVinfection,kidneydisease,activeautoimmunedisease,andhuman
leukocyteantigentype(HLAB*1502andHLAB*5801)alsocontributetoincreasedrisk.Patients
ofAsianandSouthAsianancestrywhoarepositiveforHLAB*1502haveuptoa10%riskforSJS
TENwhenexposedtoaromaticanticonvulsants(carbamazepine,phenytoin,andphenobarbital).
ThesepatientsshouldbetestedforthepresenceofHLAB*1502antigenbeforethesedrugsare
initiated.HLAB*5801positivitypredictsriskofSJSTENuponexposuretoallopurinol.
Figure117.OpeninNewWindow

HemorrhagiccrustsanderosionsofthelipsandmoutharecommoninStevensJohnsonsyndrome
andtoxicepidermalnecrolysis.

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Figure118.OpeninNewWindow

Toxicepidermalnecrolysiscanresultinlargeareasofskindetachment,suchasthoseseenhereon
thetrunk.

Table30.OpeninNewWindowMedicationClassesReportedtoCauseStevensJohnsonSyndrome
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andToxicEpidermalNecrolysis
MedicationClass

Examples

Aromaticantiepileptic Carbamazepine,fosphenytoin,lamotrigine,oxcarbazepine,phenobarbital,
drugs
phenytoin
OxicamNSAIDs

Meloxicam,piroxicam,tenoxicam

AceticacidNSAIDs

Diclofenac,indomethacin,lonazolac,etodolac,aceclofenac,sulindac,
ketorolac

Antibiotics

Sulfonamidesfluoroquinoloneaminopenicillins,cephalosporins,
macrolides,minocycline

Antiviralagents

Nevirapine,abacavir

Miscellaneous

Pantoprazole,sertraline,allopurinol

Whenduetodrugs,SJSandTENoccurwithin8weeksofdruginitiation,oftenbetween4and28
days.Patientsmayreportflulikesymptomsfor1to3dayspriortotheskineruption.Initially,red
purplemaculesorpapulesdeveloponthetrunkandextremities,whichenlargeandcoalesce.Skin
painisprominent.Vesicles,bullae,anderosionsreflecttheepidermalnecrosisseenonbiopsy.
Nikolskysign(theshearingoffoftheepidermiswithlateralpressure,asbytheexaminer'sthumbon
theskin)ispresent.Twoormoremucosalsurfaces,suchastheeyes,nasopharynx,mouth,and
genitals,areinvolvedinmorethan80%ofpatients(Figure119).Systemicinflammationcanresult
inpneumonia,hepatitis,nephritis,arthralgia,andmyocarditis.
Figure119.OpeninNewWindow

StevensJohnsonsyndromecausingerosionsonthetongue,lips,andredbrownpatchesonthe
surroundingfacialskin.

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DiagnosisandTreatment
RelatedQuestion
Question25
DiagnosisofEMisusuallymadeclinically.AbiopsyisoftenperformedwhenSJSorTENis
suspected.Frozensectionsoffreshtissuecanprovidediagnosticinformationmorerapidlythan
routinehistology.Thebiopsydemonstratesacantholysisandepidermalnecrosis,thedegreeofwhich
dependsontheageofthelesion.Thebiopsycanhelptodistinguishthespectrumofdermatoses
fromurticaria,urticarialvasculitis,drughypersensitivityreaction,graftversushostdisease,or
autoimmunebullousdiseases,buthistopathologycannotdistinguishamongtheentitiesintheSJS
TENspectrum.
SCORTENisaseverityofillnessscorevalidatedforTEN.ItincorporatesbloodSugar(plasma
glucose252mg/dL),presenceofCancer,Olderage(40years),heartRate(120/min),Tenpercentor
moreBSAinvolvementonday1,Electrolytes(serumbicarbonate20mEq/L),andbloodurea
Nitrogen(28mg/dL)(Table31).IfthediagnosisofTENismade,theSCORTENscaleisa
validated,severityofillnesstoolforTENandSJS.Themortalityrateisdirectlycorrelatedwiththe
numberofSCORTENvariablesthatarefulfilled.
Table31.OpeninNewWindowSCORTENSeverityofIllness
Scale
Plasmaglucose

>252mg/dL(14.0mmol/L)

Cancerorassociatedmalignancy

Yes

Olderage

>40years

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Heartrate

>120/min

Detachedorcompromisedbodysurface >10%
Bloodureanitrogen

>28mg/dL(10.0mmol/L)

Electrolyte(serumbicarbonate)

<20mEq/L(20mmol/L)

IfM.pneumoniaeisthetriggerofEMorSJS,thenantimicrobialtherapyishelpful.Systemic
glucocorticoidsarehighlyeffectivefordecreasinginflammationandpainevenwhenpatientshave
aninfectioustriggerforEM.ForEM,shortcourses(3to4weeks)ofsystemicglucocorticoidsearly
inthecourseshouldbeconsidered.EMcanrecur,andinapproximately70%ofpatientsthisis
associatedwithherpessimplexvirusinfection.Thesepatientsmaybenefitfromsuppressiveantiviral
therapy.
Ifamedicationisimplicated,thefirststepiscessationoftheoffendingdrug.Supportivetherapy,
suchasavoidingdehydrationandtheuseoftopicalanalgesicsfororaldisease,isimportantforall
patients.Skinfindingscommonlywillworsenevenifthetriggerisremoved.Moreaggressive
supportivecare,suchasthatreceivedinaburncenterorICU,hasconsistentlybeenshownto
improvesurvival.Fluid,electrolyte,andnutritionalsupportarecritical.Theroleofglucocorticoids
orintravenousimmuneglobuliniscontroversial.Earlyinterventionisessential,andmanyexperts
believethatintravenousimmuneglobulindosedappropriatelymayhelparresttheprocesshowever,
firmdataarelacking.Decisionsregardingtherapyshouldbemultidisciplinaryandinclude
consultationwithadermatologist.Infectionisasignificantcauseofmortality.Alowthresholdis
recommendedforperformingculturesandinitiationofempiricantibiotics.Useofprophylactic
antibioticsisnotrecommended.Scarringisacomplication,especiallyformucosalsurfacessuchas
theeyesandgenitourinarytract.Ophthalmologicorurologicconsultationshouldbeobtainedwhen
involvementofthesesitesissuspected.

KeyPoints
Erythemamultiforme(EM)canberecognizedbythetargetlesionsadrugorinfection(herpes
simplexvirusorMycoplasmapneumoniae)cantriggerEM.
StevensJohnsonsyndromeandtoxicepidermalnecrolysisarepotentiallylethalbecauseof
widespreadskininflammation,necrosis,anderosionthetwosyndromesaredistinguishedby
theamountofskininvolved.

DHS(orDRESSSyndrome)
RelatedQuestions
Question38
Question68
Drughypersensitivitysyndrome(DHS)ordrugreactionwitheosinophiliaandsystemicsymptoms
(DRESS)isasevere,lifethreatening,idiosyncraticmedicationreaction.Thepathophysiologymay
involvedrugtriggeredviralreplicationandanexuberanthostantiviralresponsewithwidespread
inflammation.Themostcommonculpritmedicationsincludesulfonamideantibiotics,allopurinol,
andanticonvulsants,butmanymoremedicationshavebeenimplicated.DHSisuniqueinthatthe
onsetisusually2to6weeksafterstartingthecausativemedication.Becauseofthisdelayedonset,it
isoftenunderrecognizedormisdiagnosed.Theeruptionisusuallyanexuberantmorbilliform
eruptionwithprominentfacialedema,lymphadenopathy,fever,and,inseverecases,hypotension
(Figure120).DHScanbeconfusedwithlymphoma,viraleruptions,orhemophagocytic
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lymphohistiocytosis.Rarely,hemophagocyticlymphohistiocytosiscanbeduetoadrug.Patients
withsuspectedDHSshouldhaveacompletebloodcountwithdifferentialtoevaluatefor
eosinophiliaoratypicallymphocytosis.Liverchemistrytests,serumcreatininelevel,andurinalysis
shouldbeperformed.GiventheseverityofDRESSassociatedmyocarditis,someexpertssuggest
thatbaselineechocardiographyshouldbeperformedoneverypatient.Becauseofthefeverand
lymphadenopathy,therapyforDHSistostopthecausativemedicationimmediately.Systemic
glucocorticoidsaretypicallyneeded(often12mg/kg,taperedslowlyovermultipleweeksto
months).Becausethereisa10%mortalityrate,anypatientstartedonahighriskmedicationwho
developsfeverandarashshouldbeevaluatedforDHS.Therearereportsofthewidespread
inflammationofDHScausingdelayedautoimmunereactions,includingthyroiddiseaseanddiabetes
mellitus,whichrequiresregularfollowuplongaftertheeruptionresolves.
Figure120.OpeninNewWindow

Generalizedpapulareruptioninapatientwithdrugreactionwitheosinophiliaandsystemic
symptoms(DRESS).

DHSisoftenanunderrecognizedcauseoffeverofunknownorigin,andifnotproperlydiagnosed,
canbefatal.ThepossibilityofDHSmustbekeptinmindinpatientsintheICUswhoareonmany
medications.DHScausedbyanaromaticantiepilepticagentcanalsoposeaseriousthreatdueto
crossreactionwithotherantiepileptics.Forexample,ifphenytoincausesDHSbutisappropriately
stopped,neitherphenobarbitalnorcarbamazepineshouldbesubstitutedbecauseoftheriskofcross
reaction.

Erythroderma
RelatedQuestion
Question36
Erythrodermaischaracterizedbyerythema,indicatinginflammation,ofatleast80%to90%ofthe
skinsurface(Figure121).Peripheraledema,skinerosions,scaling,andlymphadenopathyare
commonfindings.Dehydration,heatloss,andskininfectionsarepotentialcomplicationsandcan
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compromisetheskinbarrierandleadtosystemicinfectionsandtissuedamage.Erythrodermais
morecommoninmenthanwomentheaverageageofonsetis55years.Erythrodermaisareaction
pattern,andthespecificcausecanbeelusive.Themostcommoncausesaremedicationreactionsor
anexistingskinconditionthathasflared,mostcommonlyatopicdermatitisorpsoriasisfollowingan
abruptdiscontinuationofsystemicglucocorticoids.Thecauseisidiopathicin25%to40%of
patientsevenafterarigorousevaluation.Historyandphysicalexaminationprovidecriticalcluesto
thecause(Table32).Alopecia,naildystrophy,andthickeningofthepalmsandsolesareindicative
ofalongstandingcausesuchascutaneousTcelllymphoma,graftversushostdisease,psoriasis,or
pityriasisrubrapilaris.Pityriasisrubrapilarisisachronicpapulosquamousdermatosisthatoften
beginsonthescalpandwithtimebecomesgeneralized.Itcanbedistinguishedfrompsoriasisbythe
prominent,firm,orangered,folliclebasedpapulesthatcoalescewithinterveningislandsof
normalskin.Drugreactions,staphylococcalscaldedskinsyndrome,andautoimmunebullous
diseasesoftenhaveamoreacuteonsetwithoutalongstandinghistoryofprecedingdermatosis.
Becauseerythrodermaisacute,thickscalingofthepalmsandsolesornailchangesdonotoccur.
Figure121.OpeninNewWindow

Erythrodermaofthetrunkandarmscausedbymycosisfungoides,aformofcutaneouslymphoma.

Table32.OpeninNewWindowCausesofErythroderma
Existingdermatosis
Psoriasis,atopiceczema,allergiccontactdermatitis,lichenplanus,pityriasisrubrapilaris
Drugreaction
Exanthem,drughypersensitivitysyndrome/drugrashwitheosinophiliaandsystemicsymptoms,
acutegeneralizedexanthematouspustulosis,TEN
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Infection
Staphylococcalscaldedskinsyndrome,tineacorporis,scabies,viralinfection
Autoimmunedisease
Pemphigusfoliaceus,pemphigusvulgaris,bullouspemphigoid,linearIgAdisease,lupus
erythematosus,dermatomyositis
Malignancy
CutaneousTcelllymphoma(mycosisfungoides),paraneoplasticsyndromewithinternal
malignancy
Sarcoidosis,graftversushostdisease
Idiopathic
TEN=toxicepidermalnecrolysis.

DiagnosisandManagement
Severaldiagnosticstudies,guidedbytheclinicalhistoryandexamination,arepotentiallyhelpful.A
completebloodcountwithdifferentialcanassessforleukocytosis,whichcanbereactiveordueto
anocculthematologicmalignancy.Eosinophiliacanbeasignofadrughypersensitivityreaction,
scabiesinfestation,orcutaneousTcelllymphoma.Imagingstudiessuchasachestradiographcan
assessforlymphadenopathy(reactiveorfromlymphoma)oroccultmalignancyinotherorgans.A
skinscrapingcandemonstratedermatophytosisortheSarcoptesscabieimitesthatcausescabies.
Immunofluorescencestudiescandistinguishpossibleautoimmunedisease,andpatchtestingisdone
forasuspectedcontactallergycausinggeneralizedeczema.Biopsycanbehelpfulinerythroderma,
butnonspecificchangesarecommon(30%to40%ofbiopsies).Itisnotuncommonforpatientsto
havemultiplebiopsiesovertimebeforeadefinitivediagnosisismade.
Managementinconjunctionwithadermatologistisfrequentlynecessary.Treatmentofinfection,as
wellasmanagementoffluidandelectrolyteimbalance,iscritical.Thickemollientshelptorestore
skinbarrierfunction.Topicalglucocorticoidsandsystemicantihistaminescanimprovepruritus.
Sincedrughypersensitivityisacommoncause,drugcessationisafrequentmaneuver.Systemic
therapydependsonthesuspectedcauseandseverityofsymptoms.Additionaltherapiesmayinclude
ultravioletlighttherapy,systemicglucocorticoids,oralretinoids,andsystemicimmunosuppressants
suchasmethotrexate,azathioprine,andmycophenolatemofetil.

KeyPoints
Erythrodermaischaracterizedbyerythemaof80%to90%ofskinsurfacewithperipheral
edema,erosionsoftheskin,scaling,andlymphadenopathy.
Treatmentofinfection,aswellasmanagementoffluidandelectrolyteimbalance,iscriticalin
managingerythrodermathickemollientshelptorestoreskinbarrierfunction,andtopical
glucocorticoidsandsystemicantihistaminescanimprovepruritus.

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