Cases from the Cornfields! F027 - Wanat... · Cases from the Cornfields! NkanyeziFerguson, MD John...
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Cases from the Cornfields! Nkanyezi Ferguson, MD John Selby, MD, PhD Brian Swick, MD Karolyn Wanat, MD Departments of Dermatology and Pathology University of Iowa Hospitals and Clinics Iowa City VA Health Care System
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Transcript of Cases from the Cornfields! F027 - Wanat... · Cases from the Cornfields! NkanyeziFerguson, MD John...
CasesfromtheCornfields!Nkanyezi Ferguson,MDJohnSelby,MD,PhDBrianSwick,MD
KarolynWanat,MDDepartmentsofDermatologyandPathology
UniversityofIowaHospitalsandClinicsIowaCityVAHealthCareSystem
Cases#2and#3• DermatitisHerpetiformis– New diagnosis?• CheckG6PD• GastroenterologyConsultifnoknowndiagnosisofCeliac• Startdapsone• DietitianConsultforinstitutionofagluten-freediet
dapsone
monoacetyldapsone
glucuronides
N-acetyltransferase acrylacetamidedeacetylase
renalexcretion
dapsone
dapsonehydroxylamine
N-hydroxylase
hemolyticanemiamethemoglobinemia
G6PD
reducedmetabolites
hepaticglucuronidation
enterohepatic circulation
Cases#2and#3
J Am Acad Dermatol 2001;45:420-34Arch Dermatol Res2014;306:103-24
• Dapsone- MechanismofAction– Anti-inflammatoryeffects• Interferencewithneutrophilchemotaxis• Scavengingofextracellularreactiveoxygenspecies• Inhibitionofmyeloperoxidase-mediatedcytotoxicity• Inhibitionofeosinophilperoxidase• SuppressionofleukotrieneB4-stimulatedinflammation
Cases#2and#3
J Am Acad Dermatol 2001;45:420-34Arch Dermatol Res2014;306:103-24
• Dapsone- AdverseEffects– Hemolyticanemia–Methemoglobinemia– Agranulocytosis– Hypersensitivitysyndrome– Gastrointestinaleffects– Photosensitivity– Carcinogenesis
Edhegard,k.,andR.P.HallIII.“Dapsone.”ComprehensiveDermatologicDrugTherapy,ThirdEdition.Ed.Wolverton,S.E.Edinburgh:ElsevierSaunders,2013.228-240.Print.
Cases#2and#3
HemoglobinA1Clevelsfalselylow
Labmonitoringforweeks1-12
• Dapsone- AdverseEffects– Psychiatriceffects?
• JAmAcad Dermatol 1983;9(2):274-5– Irritability– Insomnia
– Psychiatriceffectsappeartobe...• Dose-independent• Occurearlyorlateinthetreatmentcourse• Independentofapre-existingmoodorpsychoticdisorder
Cases#2and#3
– Irrationalspeech– Psychosis
• Dapsone- AdverseEffects– Peripheralneuropathy• Primarilydistalmotor,butsensoryinvolvementcanoccur• Reportedforvariabledoses/exposures
– highdose/shortterm– lowdose/longterm
• Recoverycanbeobservedupto2yearsafterdiscontinuationofdapsone• Mechanismuncertain
Cases#2and#3
• Stopdapsone?– Yes;neuropathyisthoughttobereversible
• Dietitianconsult?– Important,but...– Youcan’tteachanolddognewtricks
Cases#2and#3
• Sulfapyridine?– CasereportsofDHpatientssuccessfullytreatedwithsulfapyridine after developmentofdapsoneneuropathy• Int JDermatol 1986;25:314-6• ArchDermatol 1984;120:356-9
– Jacobus Pharmaceuticalshaltedproductionanddistributionofsulfapyridine circa1/2011
– NolongeravailableintheU.S.
Cases#2and#3
• Topicaldapsone?– CasereportsofDHpatientssuccessfullytreatedwithtopicaldapsone• JCutan MedSurg 2016;20(6):600-1• JDermatol CaseRep2012;6(4):132-3
– Systemicabsorption?• Acutemethemoglobinemia reportedinanacnepatientNEnglJMed 2015;372(5):491-2• No reports of neuropathy
Cases#2and#3
-Yes!
• Cimetidine?– 400mgTIDdecreases methemoglobinemia byinhibiting formation of hydroxylaxmine metabolites
– Effect(s)onneuropathy prevention/treatment uncertain
Cases#2and#3
• Sulfasalazine(SS)?– NumerouscasereportssuggestingefficacyofsulfasalazineforthetreatmentofDH• JAmAcad Dermatol1990;22(4):697• Australas JDermatol 2005;46:101-3• Dermatol Clin 2011;29:631-5• Int JDermatol 2017;56:e89-e105
Cases#2and#3
• Sulfasalazine(SS)- Pharmacokinetics– Enteric-coatedSSpoorlyabsorbedinsmallintestine
– Gutflorainlargeintestineconvertenteric-coatedSSinto5-aminosalicylicacid(5ASA)andsulfapyridine
Cases#2and#3
• Sulfasalazine(SS)- Pharmacokinetics– Sulfapyridine isvariablyabsorbed,dependentonguttransittime
– 5ASAconcentrateslocallyinthelargebowel;excretedinfeces
– Metabolismofsulfapyridine similartodapsone(acetylation,hydroxylation,glucuronidation)
Cases#2and#3
• Sulfasalazine(SS)- Mechanismofaction
– Sulfapyridine effectslikelysimilartodapsone• Inhibitionofneutrophilchemotaxis• Modulationofpolymorphonuclear leukocytefunction• Inhibitionofhistaminereleasefrommastcells
Cases#2and#3
• Sulfasalazine(SS)- AdverseEffects– Common• Nausea,anorexia,dyspepsia,vomiting
– Minimizedbyenteric-coatedformulation• Headache
– Rare• Hepatitis• Pneumonitis• Hypersensitivity
Cases#2and#3
• Aplasticanemia• Agranulocytosis
• Sulfasalazine(SS)- AdverseEffects
–Veryrareassociations• Granulomatosiswithpolyangiitis• Encephalopathy• EBVhypersensitivitysyndrome• Hemophagocyticsyndrome
Cases#2and#3
• Sulfasalazine(SS)- AdverseEffects– DoesSScauseorexacerbateaperipheralneuropathy?• ReportsofSS-associatedneuropathyarescarce
– Practitioner 1970;204:850-1– Postgrad MedJ1985;61:147-8– RevueNeurologique1992;148:154-6– ClinExp Rheumatol 2008;26:671-2
Cases#2and#3
• CaseOutcomes– Bothpatientsstartedonenteric-coatedsulfasalazine1gtwicedaily(G6PDnormal)
–MonitoredCBCwithdifferential,ALT,ASTeveryotherweekfor2months,thenevery3-4months
–Markedimprovementinflaresofpruritusandrashwithin1-3months
– Nochangesinneuropathy-relatedsymptoms>2years
Cases#2and#3
PharmacologyPearls#1• HbA1Clevelsarefalselylow inpatientstakingdapsone
• Dapsonecanhavepsychiatriceffects
• SulfapyridineisnolongeravailableintheU.S.
• Topicaldapsonecanhavesystemicabsorption
PharmacologyPearls#1• Consider enteric-coatedsulfasalazineforthetreatmentofDHinpatientswhoareintolerantofdapsoneorwhenthereisconcernforevolvingneuropathy
• Dapsoneorsulfasalazine– Continuevigilantmonitoringforsigns/symptomsofneworworseningneuropathy
• Methemoglobinemiainpatientstakingdapsone?– Asymptomatic(3-15%)– Cyanosis(>15%)• Slate-bluecolorofskinandmucousmembranes
Cases#2and#3
• Methemoglobinemiainpatientstakingdapsone?– Asymptomatic(3%<MetHb<15%)– Cyanosis(MetHb>15%)
• Slate-bluecolorofskinandmucousmembranes• Differentialdiagnosis
– Methemoglobin >1.5g/dL or8to12%oftotalhemoglobin– Deoxygenatedhemoglobin>4to5g/dL– Sulfhemoglobin >0.5g/dL
– Signs&symptomsofhypoxia• Lightheadedness,headache,tachycardia(15%<MetHb<30%)• Fatigue,confusion,lethargy,tachypnea(30%<MetHb<50%)• Coma,seizures,death(MetHb>50%)
Cases#2and#3
ClevClinJMed2015;82(3):156-60
Cases#2and#3
• Whenmethemoglobinpresent...• Leftshiftinoxygendissociationcurve• Decreasedoxygenunloading• Increasedtissuehypoxia
Clin Chem 2005;51(2):434-44
• Methemoglobinemiainpatientstakingdapsone?– Whataboutanasymptomatic patienttakingdapsonewhohasno cyanosisandno signs&symptomsofhypoxia?
• Methemoglobinemia (3-15%)shouldbeexpected
• Bereadytoexplain abnormalpulseoximetry readingsanddiscrepancieswitharterialbloodgasmeasurements!
Cases#2and#3
Cases#2and#3
• SaO2 (%)=percentageofhemoglobinthatissaturatedwithoxygen
• IndirectlymeasuredwithaninvasiveABG
• SpO2 (%)=estimateofSaO2measuredbynon-invasivepulseoximetry
• Standardtwo-wavelengthpulseoximetry• 660nm– deoxyhemoglobin• 940nm– oxyhemoglobin• SpO2 =SaO2 +/- 3%
Cases#2and#3• Standardtwo-wavelengthpulseoximetry
doesnotyieldaccuratereadingsinthepresenceofmethemoglobinemia
• SpO2 underestimates SaO2formethemoglobin <20%
• SpO2 overestimates SaO2formethemoglobin>20%
• “Saturationgap”SaO2 - SpO2 >5%>10%clinicallysignificant
Anesthesiology 1989;70(1):112-7
• Methemoglobinemiainpatientstakingdapsone?– Normalvaluesforarterialoxygensaturation(SaO2,SpO2)arenotdefined
– Manypractitionersunfamiliarwithdapsonepharmacologywillgetnervousfor90%<SpO2 <95%
– YoushouldbenervousforSpO2 <89%
– SignificanceofabnormalpulseoximetryandABGmeasurementsdependsontheclinicalcontext• Cyanosisandsigns&symptomsofhypoxia?• Totalhemoglobin?• Functionalcardiopulmonarystatus?
Cases#2and#3
• Methemoglobinemiainpatientstakingdapsone?– Considertwoasymptomatic patientstakingdapsone
• PulseoximetryshowsSpO2 =92%• OrderHbandMetHb
– PatientA(Healthy):• Hb12.0g/dL;MetHb15%
– PatientB(CADstatuspoststentplacement):• Hb10.0g/dL;MetHb15%
Cases#2and#3
Edhegard,k.,andR.P.HallIII.“Dapsone.”ComprehensiveDermatologicDrugTherapy,ThirdEdition.Ed.Wolverton,S.E.Edinburgh:ElsevierSaunders,2013.228-240.Print.
EffectiveHb10.2g/dL
EffectiveHb8.5g/dL
PharmacologyPearls#2• Methemoglobinemiawilloccurinallpatientsondapsone
• Standardpulseoximetrymeasurementsareinaccurate forpatientstakingdapsone
• SpO2 >90%may ormaynotbeacauseforconcern– Dependsontheclinicalcontext
• SpO2 <89%arecauseforconcern,eveninanasymptomaticpatient(MetHb~20%)
Case#4• OralCandidiasis– Pseudomembranous(whitenon-adherent plaques)• Thrush
– Erythematous(redwithout plaques)• Medianrhomboidglossitis• Antibioticsoremouth• Angularcheilitis
– Hyperplastic(white/yellowadherent plaques)• Chronichyperplasticcandidiasis
Case#4• Chronichyperplasticcandidiasis– Adherent keratotic plaques– Buccal mucosa,dorsaltongue,palate– Riskfactors• Immunosuppression• Diabetes• Tobaccouse• Reducedsalivaryglandfunction• Steroiduse
Case#4• Chronichyperplasticcandidiasis– Treatment
• Minimizationofriskfactors• Systemics
– Azoles» fluconazole,itraconazole
• Topicals– Azoles
» clotrimazole troche,miconazole solution– Nystatin suspension
– Questionableroleinpromotingdysplasia&malignancy
PharmacologyPearls#3
• Shouldyoueverworryaboutmedicationinteractionswithclotrimazoletroches?– Yes!
PharmacologyPearls#3• Clotrimazole trochescommonlyadministeredasroutineprophylaxisoforalthrushinpost-transplantpatients
– Multiplecasereportsandcaseseriesinliverandkidneytransplantpopulationsdemonstratingincreasedtacrolimuslevelsinpatientsusingclotrimazole troches
• Transplantation 1991;56(6):1086-1087• ClinicalTransplantation2001;15(2):95–99• Therapeutic DrugMonitoring2005;27:587–591• Pharmacy and Therapeutics 2010;35(10):568-569
PharmacologyPearls#3
Clin Transplant 2001;15(2):95–99
PharmacologyPearls#3• Recommendclosemonitoringoftacrolimuslevelswhenstarting orstopping clotrimazoletrochesinatransplantpatient
• Nystatin swish/swallowandswish/spitareprobablysaferalternatives
Blastomycosis-likecandidiasis• “Moniliasisaspossibleetiologicfactorforpseudoepitheliomatoushyperplasia”– Verruciformlesionsinthemouthunderorthodontics
– ArchDerm1967;96:598
• “InductionofepithelialhyperplasiabyCandidaalbicans”– Comparisonofhumanmucousmembranelesionstoinoculatedchorio-allantoicmembraneofembryonatedchickeneggs
– BrJDermatol1973;89:497
Blastomycosis-likepyoderma• Singleormultipleverrucousplaquesonfaceordistalextremities– Pseudoepitheliomatoushyperplasiawithabscessesand/orgranulomatousinflammation• Resemblingblastomycosisortubeculosisverrucosacutis
• Usuallybacterial– S.aureus>ß-streptococcus,Pseudomonas,Proteus,E.coli
• RarelyCandida– ArchDerm 1979;115:170
Blastomycosis-likepyoderma.ArchDerm 1979;115:170
Blastomycosis-likepyoderma• Exaggeratedtissuereactionpatientsw/lowresistancetoinfection
– ArchDerm 1979;115:170– IndianJDermatol Venereol Leprol 1985;51:226– PedDermatol 2017;34:201
– Iatrogenicimmunosuppression– Diabetesmellitus– Leukemia– Alcoholism– Genodermatosesw/cutaneousinfx(KIDsyndrome)
VegetatingCandidiasis:AMimickerofSquamousCellCarcinomainKeratitisIchthyosisDeafnessSyndrome
PediatricDermatologyVolume34,Issue2,pages201-203,23JAN2017
VegetatingCandidiasis:AMimickerofSquamousCellCarcinomainKeratitisIchthyosisDeafnessSyndrome
PediatricDermatologyVolume34,Issue2,pages201-203,23JAN2017
Fusionofmyogeniccellstonewmyofibersindamagedskeletalmuscle• Skeletalmuscleregenerationafterinjury(undergraftinthiscase)– Inflammation,phagocytosis,&– Activation,proliferation,fusionmuscleprecursors• Sarcoplasmicextensionscontainingmultipleclumpednucleicalled“buds”or”stumps”atendsofmyofibers– Neuropathology&appliedneurobiology1993;19:350– Diagnosticcytopathology1985;2:91
Reactivechangesinskeletalmuscle• Canmimicrhabdomyosarcoma
• Histopathology1998;33:136• Recognitionasskeletalmuscle
(notcarcinomaormyofibroblastic)– Occurringunderflap/graft– Striations– Desminexpression
PTAH
Hypertrophiclupuserythematosus• Discoidlupuserythematosusvariant
– Extensorextremities&face(earlyonfewlesionspresent)– Difficulttotreat
• Clinicalresemblance– Hypertrophicactinickeratosis– Squamouscellcarcinoma– Keratoacanthoma– Hypertrophiclichenplanus– Prurigo nodularis– Verrucavulgaris
• BothcutaneousLE&atypicalsquamouslesionsonsunexposedskin
• FrederickMohsinadvertentlyperformedsurgeryonDLEmasqueradingasSCC
DermatolSurg 1995;21:255
Hypertrophiclupuserythematosus• HyperLP-likeorSCC(KA)-like
– Squamousatypia(reactive)– Pseudo-invasivegrowth– Lichenoidtissuerxn
• Follicularplugging• Superficial&deepperivascular
infiltrate• BMZthickening• Dermalmucin
Clinicalinformation&Adequatetissueveryhelpful!
JCutan Pathol 2003;30:443JCutan Pathol 2011;38:889
Plasmacytoid dendriticcellsinhypertrophicdiscoidlupuserythematosus:anobjectiveevaluationoftheir
diagnosticvalue
JournalofCutaneousPathologyVolume42,Issue1,pages32-38,15DEC2014
• IncreasedCD123expressingplasmayctoiddendriticcells(pDCs) inlupusinfiltrate
• LackinginSCC/HAK• Nothelpfulindistinguishing
hypertrophicLPvshypertrophicLE• pDCs secretetypeIIFN&playamajor
roleinpathogenesisoflichenoid/interfacedermatoses
JInvestDermatol2009;129:1088
Squamouscellcarcinomaarisinginhypertrophiclupus
JournalofCutaneousPathologyVolume42,Issue1,pages32-38,15DEC2014
• LesionsofdiscoidLEmaydevelopSCC(3.3%longstandingcases)
• Mostcommoninfacialdiscoidlesions• Heavilyscarredareas• Activelesionsonthelip!
• MeandelayfromLEtoSCC30.8yrs(range26-41yrs)
• Clin Exp Derm 1978;3:161
Surgicalpearl• Importanttolookattheentireclinicalpicture
• Avoidsurgicalblinders• Delaysurgeryiffurtherwork-upisneeded– Importantasmorepatientsareseenassame-dayMohsevaluationandsurgery
Surgicalpearl• Haveahighindexofsuspicion• DonotperformMohssurgeryorexcisiononhypertrophiclupus
Reviewingexternalpathologyslides• ConsideredstandardofcaretoreviewoutsidebiopsyslidespriortoMohs
• Ratesofdiscrepancybetweenpathologyreportsintheliteraturerangewidely (0.5%to43%)
• StudywithinMohs– Diagnosisof74(2.2%)outof3,345tumorswaschangedonreviewofpathology
– 45(61%)resultedinachangeinmanagement
ButlerST,etal.DermatolSurg.2009Mar;35(3):407-12
Desmoplasticmelanoma• Desmoplasticmelanomasmayhaveanoverlyinglentigomalignaoratypicalintraepidermalmelanocyticproliferation
• ?progressionfromthelentiginouscomponentorarises"denovo“
EgbertB,etal.Cancer.1988Nov1;62(9):2033-41DeSouzaBastos,etal.AnBrasDermatol.2013May-Jun;88(3):408–412
Desmoplasticmelanoma• Desmoplasticmelanomarepresentsaminority(4%)ofcutaneousmelanomas
• “UnrecognizedDesmoplasticMelanoma”areresponsibleformalpracticeclaimsrelatedtomelanoma– Shavebiopsiesorsuperficialpunchbiopsiesmayonlycapturetheatypicallentiginousproliferation
Troxel DB,Etal.AmJSurg Pathol.2003Sep;27(9):1278-83
MohsPathologyPearl• Importanttolookfordesmoplasticmelanomainallbiopsiesoflentigomaligna
• ForthelayMohssurgeon/dermatologist:– “Actinicdamagedskin+scarordesmoplasia=ruleoutdesmoplasticmelanoma”
Troxel DB,Etal.AmJSurg Pathol.2003Sep;27(9):1278-83
Mohsdebulkspecimen• CriticaltosubmitMohsdebulkforLM,MISormelanoma
forpermanenthistology– LM/MISmaybeupstagedonreviewofMohsresectionmargins
(range5– 8%)• Importanceofverticalpermanenthistology
– Necessaryforaccuratetumorstaging– Mohsmicrographicsurgeryexaminesonlytheperipheryand
baseofthecentralportionofthetumortodeterminewhetherthemarginisclear
– HorizontalsectionsprecludemeasurementofBreslow
Iorizzo L,etal.DermatolSurg 2013;39:365–371
Mohsdebulkspecimen• Detectionofhigh-riskhistologicfeaturesandtumor
upstagingofnon-melanomaskincancers– Aggressivehistologicsubtypemaydirectlyaffectstaging,
treatment,andoutcomes– Potentialforsamplingerrorininitialbiopsy– MMScentraltumorisoftencurettedorscalpeldebulked– SinghB,etal:
• BCC:30%reclassifiedfromlow-risktohigh-riskhistology• SCC:9.1%perAJCC-7and11.1%perBWHwereupstaged• Biopsyspecimensfailedtodetect89%ofcasesofPNI
SinghB,etal.DermatolSurg.2017Aug;43(8):1003-1011
Surgerypearl• BillingforMMS(17311-17315)
– Reservedforthesurgeonwhoremovesthelesionandpreparesandinterpretsthepathologyslides
• Medicarerecoveryauditcontractors– MayassertthatMMSwasnotbeingperformedifpermanent-
sectionpathologycodesareusedonthesamedayasMohs• Documentationmustbeexplicitregardingreasonsfor
sendingdebulkforpermanentsections– Tumorstaging
Iorizzo L,etal.DermatolSurg 2013;39:365–371
Epidermalnevus– syndromes?• Heterogeneousgroupofsyndromes• EpidermalandadnexalhamartomasPLUSotherorganinvolvement– CNS– clinicalorstructural– Ocular– Skeletal– includingfacialdysmorphism
• SomaticmutationsincludeFGFR3,RAS,PIK3CABMCMedGenet.2011Jun5;12:79AmJMedGenetA.2008Sep1;146A(17):2275-9 .BrJDermatol.2007Jun;156(6):1353-6.Epub 2007Apr17.
Orallinearepidermalnevus?• Fewcasereportswithbothassociatedcutaneousepidermalneviandasisolatedfinding
Reportsofepidermalneviandmucosalneuromas?
• Onecasereportfrom2009• TeenagegirlinItaly– Leftsidedepidermalnevus– Leftsidedfacialhypertrophyandtonguepapules
Castelli,etal.Kosmetiche Medizin.Dec2009.31(6):298-305
PIK3CAMutations
AmJMedGenetA.2015Feb;0(2):287–295.
AmJMedGenetA.2015Feb;0(2):287–295.
PIK3CAPearls• PIK3CAsomaticmutationscanresultinovergrowthinanynormalunderlyingtissue
Managementofepidermalnevus• Cryotherapy• Shave• Excisionaldebulking• AblativeCO2laser
Managementofmucosalneuroma• Shaveorexcisionaldebulking• AblativeCO2laser– Goodlocalhemostasis– Reducededema– Reducedpostoperativediscomfort–Minimaltonowoundcontractionandscarring
GamaSKC,etal.LasersMedSci 2008;23:459-465
Oralsofttissuebiopsypearls• Stabilizetissue– Gauze,chalazionclamp
• Anesthesia– Localinfiltration
• Hemostasis– Pressure,silvernitrate,electrocautery
– Suture*AvonS,etal.JCanDentAssoc 2012;78:c75Davari P,etal.ClinicsinDermatology(2016)34,440–448
Oralsofttissuebiopsypearls• Suture– Silk:Soft,goodtensilestrengthandlesslikelytocutthroughmucosaltissue
– Chromicgut:Eliminatesneedforsutureremoval
– Suturemaybecomelooseonthetongueinthishighlymobileregionwithriskforaspiration
AvonS,etal.JCanDentAssoc 2012;78:c75Davari P,etal.ClinicsinDermatology(2016)34,440–448
LaserLightEffectsonTissue• SelectivePhotothermolysis–Wavelengthmustpenetratetheskintoreachitsdepth
–Wavelengthoflightisabsorbedbythetargetchromophore
– Lightisabsorbedandconvertedintothermalenergy
NouriK.HandbookofLasersinDermatology
AblativeCO2Laser• Wavelengthsthatarehighlyabsorbedbywateraretermed‘ablative’
• Variouswater-containingstructuresatdifferingdepths:– Epidermalkeratinocytes,collagen,bloodvessels
• Fullfieldablativelaserresurfacingremovestheentireepidermalskin/mucosalsurface
Hruza G,etal.LasersandLightsNouriK.HandbookofLasersinDermatology
AblativeCO2Laser• Vaporization– Watervaporizesandgasifiesandvolumeexpands
– Targetisremovedbyfragmentation,vaporization,andablation
• Coagulation– Residualthermaldamageoccursinsurroundingzoneviathermocoagulation
Omi,T,etal.LaserTher.2014Mar27;23(1):49–60
