Upload
derma202
View
2.494
Download
1
Embed Size (px)
Citation preview
General Dermatology 73
4 General DermatologyPriya Swamy Zeikus, MD
Bruce E. Strober, MD, PhD
Katherine L. White, MD
C o n t e n t s
4.1 Acne Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76
4.2 Rosacea. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .79
4.3 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4.4 Psoriatic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86
4.5 Reiter’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .86
4.6 SAPHO Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
4.7 Sneddon-Wilkinson Disease . . . . . . . . . . . . . . . . . . . . . .88
4.8 Lichen Planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .88
4.9 Atopic Dermatitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .92
4.10 Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95
4.11 Alopecia: Other Forms . . . . . . . . . . . . . . . . . . . . . . . . . . .96
4.12 Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98
4.13 Pityriasis Rubra Pilaris . . . . . . . . . . . . . . . . . . . . . . . . . . .99
4.14 Lichen Sclerosus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99
4.15 Granuloma Annulare . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
4.16 Hirsutism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.17 Amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
4.18 Calciphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.19 Angioedema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.20 Carcinoid Syndrome and Flushing Disorders . . . . . 106
4.21 Lupus Erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
4.22 Scleroderma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
(Continued on next page)
74 2011/2012 Dermatology In-Review l Committed to Your Future
4.23 Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .113
4.24 Sjogren’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . .115
4.25 Connective Tissue Disease: Serology . . . . . . . . . . . . .115
4.26 Relapsing Polychondritis . . . . . . . . . . . . . . . . . . . . . . . . .117
4.27 Behçet’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .118
4.28 Livedo Reticularis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
4.29 Leukocytoclastic Vasculitis. . . . . . . . . . . . . . . . . . . . . . .119
4.30 Cryoglobulinemia and Cryofibrinogenemia. . . . . . . 122
4.31 Acanthosis Nigricans . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
4.32 Lipodystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
4.33 Hyperlipoproteinemias. . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.34 Xanthomatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.35 Vitamin Deficiencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.36 Diabetes and Skin Disease . . . . . . . . . . . . . . . . . . . . . . 130
4.37 Langerhans Cell Histiocytosis . . . . . . . . . . . . . . . . . . . 132
4.38 Cutaneous T-cell Lymphoma . . . . . . . . . . . . . . . . . . . . 133
4.39 Pyoderma Gangrenosum . . . . . . . . . . . . . . . . . . . . . . . . 136
4.40 Sweet’s Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
4.41 Erythema Annulare Centrifugum . . . . . . . . . . . . . . . . 138
4.42 Erythema Elevatum Diutinum . . . . . . . . . . . . . . . . . . . 138
4.43 Erythema Nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
4.44 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.45 Cutaneous Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . 142
4.46 Perforating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
4.47 Elastosis Perforans Serpiginosa. . . . . . . . . . . . . . . . . . 144
4.48 Reactive Perforating Collagenosis . . . . . . . . . . . . . . . 145
4.49 Cutaneous Features and Disorders of Pregnancy . . 145
4.50 Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
4.51 Scleredema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
4.52 Nephrogenic Fibrosing Dermopathy/
Nephrogenic Systemic Fibrosis . . . . . . . . . . . . . . . . . . 149
For practice exam questions and interactive study tools, visit the Dermatology In-Review Online
Practice Exam and Study System at
DermatologyInReview.com/Galderma
Committed to Your Future
Sponsored by
76 2011/2012 Dermatology In-Review l Committed to Your Future
4.1 ACNE VULGARISKey Pathogenic Factors
• Abnormalkeratinization(follicularretentionhyperkeratosis)• Inflammation• PresenceofPropionibacterium Acnes (P. acnes)insebum• Sebumproduction,underhormonalcontrol,startingatadrenarche
Pathogenesis Overview• Precursorlesionofcomedonalandinflammatoryacneisthemicrocomedo• Humansebumisrichintriglycerides.1 P. acnes makesanenzymaticlipasewhichcleavestriglyceridesintofreefattyacids
• Inflammationistriggeredbyfollicularwallruptureandsubsequentimmuneresponse.P. acnes itselfispro-inflammatory;itcanactivatecomplement,andneutrophilchemotaxisandactivity
• IL-1,apro-inflammatorycytokine,maypromotefollicularpluggingandmicrocomedoformation2
• Toll-likereceptors(TLR’s)→alargegroupofreceptorsthatrecognizecertainbacterialpatterns.TLR-2activationbyP. acnes leadstointracellularsignaltransductionandupregulationoftheimmuneresponsebystimulatingpro-inflammatorycytokines.3 Certain topicalretinoidshavebeenshowntodownregulateTLR-2expression4
Clinical VariantsAcne Vulgaris• Noninflammatorylesionsarethemicrocomedoandthecomedo(openandclosed)• Inflammatorylesionsarepapules,pustulesandnodules
Acne Conglobata• Aseverevariantcharacterizedbylarge,oftenmultiplecomedones,abscesseswithsinusformation,andinflammatorynodules
• Seenmostfrequentlyinyoungmalepatients• Follicularocclusiontriadconsistsofacneconglobata,hidradenitissuppurativa,anddissectingcellulitisofthescalp.Treatmentiswithhighdoseisotretinoin
Acne Fulminans• Arare,explosiveformofseverecysticacneaffectingyoungmales• Markedbyacute,suppuratingnodulesandplaquesthatulcerateandformblackisheschar• Thetrunkisaffectedmoreseverelythantheface• Patientsmaybesystemicallyill,withleukocytosis,fever,arthralgias,andmyalgias.Lytic
changes, indicative of a sterile osteomyelitis, can be seen on x-ray and bone scans. The sternoclavicular joint and the chest wall are most frequently affected
• Treatmentiswithoralprednisone,intralesionalsteroids,antibiotics,andisotretinoinMiscellaneous Acne VariantsIndustrial Acne
• Chloracneisaformofindustrialacnetriggeredbyworkplaceexposuretochlorinated compounds
• Themalarcheeksandpostauricularscalp,aswellasthescrotum,areaffected.Thelesionsarecharacterized bylargecomedonesaswellasinflammatorypapules,pustules,andcysts
• Insolublecuttingoilsarethemostfrequentcauseofindustrialacne
General Dermatology 77
• Dioxin(2,3,7,8tetrachlorobenzodioxin)isawell-known,potenttriggerofacneiformeruptions5
Acneiform Eruptions • Numerousoralagentshavebeenassociatedwithacneiformeruptions,includingthehalogensbromideandiodide,androgenetichormonessuchastestosterone,ACTH,corticosteroids,isoniazid(INH),lithium,erbitux,phenytoin,cyclosporine,andVitaminsB2,B6,andB126
Treatment of Acne Vulgaris
Topical Retinoids • Tretinoin(alltrans-retinoicacid),adapalene,andtazaroteneareeffectivecomedolyticagentswhichnormalizefollicularepithelialdifferentiation
• Retinoidactivityismediatedbyretinoidreceptors.Twogroupsexist:RAreceptors(RAR)andRXreceptors(RXR).Eachhasthreereceptorsubtypes:α,β,γ.RAR-γisthemostimportantmediatorofretinoidactivityintheskin
• TretinoinandadapalenearepregnancycategoryCdrugs; tazarotene is category X.TretinionactivatesRARreceptorsα,β,γ.BexaroteneselectivelybindsretinoidXreceptors.AdapaleneactivatesRARβ and γ.TazoracbindsRARα,β,γbutshowsselectivelyforRARβ and RARγ
Topical Antibiotics (Erythromycinandclindamycin)• DecreasethepopulationofP. acnes ontheskin• Increasingantibioticresistancehasdiscouragedtheiruseasmonotherapy
Benzoyl Peroxide(BPO)• Bactericidalagentwithdirectoxidizingeffects,andthusnopotentialforresistance• Irritation,dryness,andbleachingofclothingorhairmayoccur
Combination Products (ClindamycinorErythromycinandBPO)• Synergisticefficacyanddecreasedpotentialforantibacterialresistance• Maycauseirritation
Azelaic Acid • DicarboxylicacidthathasweakactivityagainstP. acnes• Inhibitstyrosinase,andcanbehelpfulinreducingpost-inflammatorypigmentalteration.Itching,burningordrynessattheinitiationoftreatmentisnotuncommon
• PregnancycategoryB
Oral AntibioticsTetracyclines• Tetracycline,doxycycline,andminocycline• InhibitRNA-dependentproteinsynthesisbybindingthebacterial30sribosomalsubunit• Tetracyclineisbestabsorbedonanemptystomach,anditsabsorptionisinhibitedbychelationwithbi-andtrivalentcations(e.g.,calcium,bismuth,iron)
• Tetracyclinecancausepermanentbrowndiscolorationoftheteethinchildren,andisnotusedroutinelyforchildrenundertheageofeight
• RiskofphotosensitivityDemecycline>Doxycycline>Tetracycline>Minocyline• Photo-onycholysishasbeenreportedwithTetracycline• Unlikeothertetracyclines,doxycyclineisexcretedviatheGItractratherthanthekidneys,andthusisthetetracyclineofchoiceinrenallycompromisedpatients8
78 2011/2012 Dermatology In-Review l Committed to Your Future
• MinocyclinehasbeenassociatedwithCNSsymptoms,includingvertigoandheadache,autoimmunehepatitis,drug-inducedanti-histoneAbpositiveSLE-likesyndrome,andhyperpigmentation
• Minocyclinecancausehyperpigmentationoftheskin.Threetypesaregenerallydescribed:
-Blue-BlackDiscoloration:Appearinginareasofpriorskininjury,suchasacnescars -Blue-GrayDiscoloration:Oftenattheloweranteriorlegsandforearms -MuddyBrownDiscoloration:Foundonsun-exposedareas.Theleastcommontypeofhyperpigmentation
•Thefirsttwotypesshowstainingforbothironandmelanin[FontanaMassonstainsmelaninblack;Perlsstainstainsiron(hemosiderin)blue].Thethirdtypeshowsincreasedmelaninatthebasallayerandwithinmacrophages
• Dosesoftetracyclinesbelowtheminimuminhibitoryconcentration(MIC)caninhibitneutrophilchemotaxis,pro-inflammatorycytokinecascades,andreduceP. acnes productionoflipase
Macrolides• Includeerythromycinandazithromycin• InhibitRNA-dependentproteinsynthesisbybindingthe50sribosomalsubunit• Erythromycincancausegastrointestinaldistressandpotentiallysignificantdruginteractions
• ErythromycininhibitsthehepaticcytochromeP450systemandcanincreaseserumlevelsandpotentialtoxicitiesofcarbamazepine,theophylline,warfarin,digoxin,methylprednisolone
Trimethoprim-sulfamethoxazole (TMP-SMX) • Consideredsecond-linetherapyforacne,duetoincreasedriskofseriousadversereactions,includinghypersensitivityreactions
• TMP-SMXinhibitsbacterialfolicacidsynthesis• Drughypersensitivitysyndromeischaracterizedbyfever,skineruptionandinternalorgan
involvementIsotretinoin
• Goldstandardfortreatingnodularacneandrecalcitrantacne• Reducessebumproductionbyreducingsebaceousglandsize,normalizesfollicularkeratinization,andindirectlyreducesP. acnes anditsinflammatorysequelae
• Apotentteratogen• Half-lifeofisotretinoinis10-20hours13 • Dosesrangefrom0.5-2.0mg/kg/dayfor4to6months(or120-150mg/kgtotaldose)• Patientsaremonitoredmonthlyforchangesintheplasmalipids,liverfunctiontestsandcompletebloodcounts.Monthlypregnancytestsforwomenarealsorequired.Themostcommonlaboratoryabnormalitiesareincreasedtriglycerides,followedbyelevationofALTandAST;decreasedbloodcountsarerare;increasedexercisecancauseelevationofcreatininephosphokinase
• Almostallpatientsexperiencecheilitis,xerosis,drynasalmucosa,dryeyes• Other,lesscommonsideeffects:hairthinning(usuallyreversible),skininfection,petechiae,abdominalpain,cornealopacities,boneandjointpain,headache,diffuseidiopathicskeletalhyperostosis(DISH)
General Dermatology 79
• Screenforpapilledemaifheadache,nausea,andvomitingoccurs
• Recentreportsofseriouspsychiatriceventspossiblyrelatedtoisotretinoinhavedrawnconsiderableattention.Alargepopulationbasedstudywithcontrolgroupsfailedtoshowanincreasedriskofdepression,suicideattemptandsuicideamongisotretinointreatedpatients14
Hormonal Therapies • Maybeanimportantcomponentofacnetreatmentinthefemalepatient,especiallyforadultwomenwithapredominanceofacneatthelowerface
• Mostcommonendocrinopathyassociatedwithacneispolycysticovarysyndrome(PCOS),characterizedbyacne,obesity,hirsutism,amenorrheaandglucoseintolerance
• Congenitaladrenalhyperplasia(CAH)isalsoassociatedwithacne• Althoughrare,veryhighlevelsofDHEA-Smaysuggestanadrenalandrogen-secreting
tumor • Apatientwhoseacnefailstorespondtoconventionaltherapy,whoseacneflarescyclically,withhirsutism,alopeciaorirregularmenseswarrantsanendocrinework-up,includingfreeandtotaltestosterone,LH,FSH,andDHEA-S
• Benefitfromhormonally-basedtherapies,suchasoralcontraceptives(OCPs)• Usuallyethinylestradiol.OCP’sleadtoadecreaseinfreetestosteronelevelsbyincreasingtheadrenalproductionofsexhormonebindingglobulin(SHBG)
• Spironolactone,commonlydosedbetween50to200mg/day→blocksandrogenreceptorsandadrenalandrogensynthesis.Sideeffectsincludemenstrualirregularities,breasttenderness,andintestinalsymptoms,whichcanbemitigatedbyconcomitantOCPuse.Hyperkalemiaismorelikelyinthesettingofrenalfailure.SpironolactoneisnotFDA-approvedforthetreatmentofacne.ItispregnancycategoryX
4.2 RoSACEA• Papulesandpapulopustulesincentralregionoffaceagainstavividbackgroundoftelangiectases.Later,diffusehyperplasiaofconnectivetissuewithenlargedsebaceousglands
• Localizedtonose,cheeks,chin,forehead,glabella;lesscommonlyaffectedareasincludetheretroauricular,V-shapedchestarea,neck,back,scalp
• FlushingandblushingevokedbyUV,heat,cold,chemicalirritation,strongemotions,alcoholicbeverages,hotdrinks,andspices
Variants of RosaceaPersistent Edema of Rosacea (RosaceaLymphedemaorMorbihan’sDisease)• Hard,nonpittingedema• Oftenmisdiagnosedascellulitis
Ophthalmic Rosacea• Blepharitis,conjunctivitis,iritis,keratitis(inflammationofcornea)• Thetreatmentofchoiceforocularrosaceaisoralantibiotics
uTIPa�Pseudotumor cerebri occurs
more often with co-adminis-tration of a tetracycline
80 2011/2012 Dermatology In-Review l Committed to Your Future
Granulomatous Rosacea• Dozensofbrown-redpapulesornodulesondiffuselyreddenedskin,frequentlyinvolvinglowereyelids
• Histopathology:perifollicularandperivascularnoncaseatingepithelioidgranulomas• Chronicandunremitting
Steroid Rosacea• Rosacearesultingfromsteroiduse• Steroidatrophywithresultanttelangiectases• Flamingred,scaling,papule-coveredface• Severepain,discomfort• Withdrawalofsteroidaccompaniedbyexacerbationofdisease• Slowtaperingofsteroidovermonthsisrequired
Rosacea Fulminans (PyodermaFaciale)• Occursalmostexclusivelyinpost-adolescentwomen;lotsofflushingandblushing• Largecoalescentnodulesandconfluentdrainingsinusoccupymostoftheface• Prognosisisexcellent,andrecurrencesrare
Perioral Dermatitis• Maybetriggeredorexacerbatedbytopicalsteroiduse• Generallyrespondswelltotopicaland/ororalantibiotictreatment
TreatmentTopical• Antibiotics–ofteneffective– Topicalclindamycinanderythromycin– Topicalmetronidazoleactiveagainstpapulesandpustules,butnottelangiectasiaandflushing
– Topicalsulfur-basedpreparations• Azelaicacid• Sunscreens• Green-tintedmakeupconcealercanneutralizeredness
Systemic• Antibiotics–generallyrespondswell– Tetracyclines– Erythromycin
• Isotretinoin–indicatedinphymas;butrosaceaoftenrapidlyrecursafterdiscontinuationofisotretinoin
Treatment for Rosacea Fulminans • Oralglucocorticoids,1.0mg/kgperdayfor7-10days,addisotretinoin,withslowtaperingofsteroid,for3-4monthsuntilallinflammatorylesionsdisappear
• Donotincisedrainingabscesses• Topicalsteroids(potent)forfirsttwoweeks
General Dermatology 81
Phymas
Rhinophyma• Occursalmostexclusivelyinmen1.) Gnathophyma–chinswelling2.)Metophyma–foreheadandnosesaddle3.)Otophyma–earlobes4.)Blepharophyma–eyelids
4.3 PSoRIASISPsoriasisisanimmunedysregulatorydiseaseresultingfrompersistentT-cellactivationand
theresultantreleaseofTH1-basedcytokinessuchasTNF-αandIL-2.Thesecytokinescausekera-tinocyticproliferation(acanthosis),andincreasedrecruitmentofinflammatorycellsintothepsori-aticskin.
Epidemiology• Affectsapproximately2%ofpopulationofU.S.• Usuallybeginsin3rddecadeoflife.Bimodalincidence:peaksatages29and55• Anearlyonsetpredictsmoreseveredisease.Also,earlyonsetmorelikelywithpositivefamilyhistory
Inheritance• Increasedincidenceinoffspringofparentsinwhichoneorbothaffected• MonozygotictwinconcordanceHLAassociationwith• HLA-B13• HLA-B17(earlieronsetandmoreseriousdisease)• HLA-Bw57• HLA-Cw6(mostdefinitiveassociatedHLAtype)–relativerisk9-15timesnormal• PsoriaticarthritisindisequilibriumwithHLA-B27,especiallyifspondylitispresent
Clinical FeaturesSkin Lesions• Sharplydemarcatedpapulesandplaques• Non-coherentsilveryscales• Auspitzsign→bleedinguponremovalofscale• Koebnerizationseenin20%• WoronoffRing:Areaofblanchingaroundpsoriaticplaquessecondarytodecreaseinprostaglandin,PGE2
Clinical PatternsChronic Stationary/Psoriasis Vulgaris• Mostfrequent• Red,scalylesionspersistforyears• Littlealterationinshape/distributionofplaques• Areasofpredilection:elbows,knees,scalp,retroauricularregion,lumbar,umbilicus• Whenlocalizedinthemajorskinfolds,scalingisabsent
82 2011/2012 Dermatology In-Review l Committed to Your Future
Guttate (Eruptive) Psoriasis• Small(0.5to1.5cm)lesionsoveruppertrunkandproximalextremities• Earlyageofonset/youngadults
•StreptococcalthroatinfectionfrequentlyprecedeseruptionPsoriatic Erythroderma• Affectsallbodysites• Erythemaismostprominentfeature,scalinglessprominent
Generalized Pustular Psoriasis
•VonZumbuschtype;acutevariant• Usuallynootherformsonskinatsametime
•Fever,lastingseveraldays,witheruptionofsterilepustules2-3mmdiameterparalleling thefever
• Distribution:Trunk,extremitiesincludingnailbeds,palms,andsoles• Pustulesariseonhighlyerythematousskin• Fingertipsmaybecomeanonychicandatrophic
•Hypocalcemia,hypoalbuminemia,leukocytosisLocalized Pustular Psoriasis• Systemicsymptomsabsent• Twodistinctconditions1.)Pustulosispalmarisetplantaris2.)AcrodermatitiscontinuaofHallopeau
Psoriatic Nail Disease • Maybeofnailmatrixornailbedorigin• Fingernailsinvolvedin50%,toenailsin35%• Nailchangesmorefrequent(80-90%)inpatientswitharthritis
•Psoriaticnailchangesofmatrix→pits(themostcommonnailchangeofpsoriasisandrepresentingfocalpsoriasisoftheproximalmatrix)andleuconychia
• Pitsinpsoriasisaregenerallymorerandomlydistributedthantheregularrowsofpitsseeninalopeciaareata
• Psoriaticnailschangesofnailbedorigininclude:salmonspots,“oilspots,”onycholysis,subungualhyperkeratosis,andsplinterhemorrhages16
Psoriatic Arthritis• Asymmetricoligoarthritis,smalljointsofhands• Associatedonycholysis
Trigger Factors• Warmerweatherandsunlightreportedtobebeneficial
• Physicaltrauma–Koebnerreaction• Infection– 50%ofchildrenexacerbateexistingpsoriasisduring2-3weekintervalafterURI
– Acuteguttatepsoriasisfrequentlyfollowsanacutestreptococcalinfectionby1-2weeks(56-85%)andstreptococcalinfectionsmayplayaroleinexacerbatingotherformsofpsoriasis
uTIPa�Drugs
– Steroids – withdrawal of systemic and possibly topical) corticosteroids can result in severe flares
– Lithium – Beta-blockers – Interferons – ACE inhibitors – Granulocyte-colony stimulating factors17
a�Antimalarials and NSAIDS are not elieved to truly exacerbate psoriasis in most patients
General Dermatology 83
– InfectionwithHIVmayrepresentanothertriggerfactor• Stress–psoriasismadeworsebystressin30-40%ofcases
Systemic Associations• Psoriaticarthritis• Crohn’sdiseaseandulcerativecolitis• HTN,obesity,diabetes,andchronicoropharyngealinfectionsfoundmorefrequentlyinpsoriaticpatients
• PustularpsoriasisassociatedwithHLA-B27,andarthropathyiscommon• Increasedriskoflymphoma
Keratinocyte Proliferation• 8-foldshorteningofepidermalcellcycle(36hrsvs.311hrsfornormal)
TreatmentAnthralin (topical)• Advantage:lackslong-termsideeffects• Possessesantiproliferativeactivityonhumankeratinocytes• Also,stronganti-inflammatoryeffectsbyinhibitingPMNsandmonocytes• Irritantreactions,especiallyafterincreasingconcentrationtoofast• Canstainhairtopurple• Brownishdiscolorationofsurroundingskin—reversible
Vitamin D3 Analogues• Calcipotriol,tacalciol,calcitriol• Inhibitkeratinocyteproliferationandinduceterminaldifferentiation• Anti-inflammatory• Usedforplaque-typepsoriasisQDorBID• Calcipotriolinactivatedbysalicylicacidorlacticacid(Lac-hydrin)• ShouldbeusedafterUV-light(calcipotriolabsorbsUV)• Localirritation
Tazarotene• Retinoid• Reducesscalingandplaquethickness,withlittleeffectivenessonerythema• Maybebeneficialincombinationwithphototherapy
Tar• Unknownactivity• 2-5%tarinvariousbaseseffectiveinchronicplaque-typepsoriasis
Topical Glucocorticoids
PUVA• Oralingestionofapotentphotosensitizersuchas8-methoxypsoralen(8-MOP)ortrimethoxypsoralen(0.6mg/kg)andvariabledosesofUVA,2hoursafteringestion
• TreatmentsgivenTIWorQIW• Clearingusuallyoccursafter19to25treatments• Overdosingresultsinsunburn,24-48hourpost-treatment• Psoralens→intercalatewithDNA,withenergyofUVAcovalentlycross-linknucleicacidsbetweenopposingstrandsofduplexregions,leadstoirreversiblephoto-inhibitionofDNAsynthesisandmitosis
84 2011/2012 Dermatology In-Review l Committed to Your Future
• Nausea,dizziness,headache• Photosensitivityduringthe8-12hafteringestionofpsoralen,protectiveeyewearneeded• Higherfrequencyofsquamouscellcarcinomas,andperhapsmalignantmelanomarisk,increasesafter250treatments
Methotrexate• Syntheticanalogoffolicacidthatcompetitivelyinhibitsdihydrofolatereductase• InhibitsSphaseofcellcycle(likehydroxyurea)• 10-30mgonceperweekPOorIM• Nausea,anorexia,fatigue,headaches,alopecia,stomatitis• Leukopeniaandthrombocytopeniaindicateoverdose→leucovorinrescuerequired• Carefulinkidneydysfunction→renalexcretion• Acuteinterstitialpneumonitis(rare)• Hepatotoxicity;excludethosewithliverdiseaseoralcoholabuse;aboveacumulativedoseof1.5g,liverbiopsyisoftenrecommendedbeforecontinuingwiththerapy
• Alsoeffectiveintreatingpsoriaticarthritis
Cyclosporine• Inhibitsreleaseofcytokines,specificallyIL-2,bybindinganddeactivatingcalcineurin• Effectiveinerythrodermicandgeneralizedpustularpsoriasis• Startat2.5to4mg/kgperday,andcangoashighas5.5mg/kgperday• Renalimpairment(oftenreversible)→reducedosageby25%ifcreatinineincreasesto30%orgreaterofbaseline
• Hypertension(TreatwithACE-inhibitors)• Elevatedtriglycerides• Hyperkalemia• Hypomagnesemia• Hepatotoxicity• Hypertrichosis(common),gingivalhyperplasia,trichomegaly,nausea,vomiting,diarrhea,arthralgia,myalgia,tremor,acne,sebaceoushyperplasia,andfatiguemayoccur
• Long-termriskofmalignancy• MetabolizedbyP450,thuserythromycinorketoconazolewillincreasedruglevels
Retinoids → Acitretin• VitaminAderivatives• Effectiveinpustularandpalmoplantarformsofpsoriasis• Acitretinismostcommonlyused,givenat25mgperdayinitially• Restrictuseinwomenofchildbearingage• Regulategrowthandterminaldifferentiationofkeratinocytes;modulatetranscriptionofspecificgenesthroughretinoidresponseelements
• Showlowerresponseratesthanothersystemicmodalitiesfortreatmentofplaque-typepsoriasis→oftenineffectiveasmonotherapyforplaque-typepsoriasis
• Effectivewhencombinedwithultravioletphototherapy(eitherUVBorPUVA)• Treatmentover3-4monthsnecessary• Doserelatedadverseeffects:cheilitis,siccasymptomsofeyesandmouth,generalizedpruritus,dryskin,lossofstratumcorneumofpalmsandsoles,hairloss
• Muscleandjointpain• Elevationinserumlipids,andalsoLFTs• Monitorliverandkidneyfunction,bloodglucose,lipidprofile
General Dermatology 85
Biologic Agents (seeTable4.1)• Etanercept• Efalizumab• Alefacept• Infliximab• Adalimumab• Ustekinumab
Table4-1.BiologicsDrug Mechanism Labs Pregnancy
ClassOther
Etanercept RecombinantfusionproteintoTNFreceptor;bindssolubleTNF-alpha
50mgSCinjectionstwiceweekly
B
Efaluzimab HumanizedantibodythatbindsCD11acomponentofLFA1whichbindstoICAM1onAPCandendothelialcells
WeeklySCinjections
C
Adalumimab AntibodytowardshumanTNF-alpha SelfadministeredIMinjectionqoweek
B
Alefacept ProteinthatblockstheinteractionofLFA3andFchumanIgG,LFA3isthereceptorforCD2andincreasedin CD45RoTcells
IMinjectionsonceweeklyoronceweeklyIVbolus
CD4 counts
B
Infliximab MonoclonalantibodieswhichinhibitTNF-alpha
IVinjections,firstdosefollowedbydoseatweeks2,6,thendosed8weeks
B ContraindicatedinCHF,maycausedruginducedSLE
Ustekinumab HumanantibodythatblocksIL-12andIL-23
SCinjectionsonce,thenin4weeksthenin12weeks
PPD B
Systemic Glucocorticoids• Systemicsteroidsareveryrarelyusedinthetreatmentofpsoriasisasmanybetteralternativetherapiesexist
• Severereboundpsoriasiscanoccurafterdiscontinuation• Chronicuseleadstowell-characterizedsideeffectsofsystemiccorticosteroiduse
Combination Therapies• Oftendesirable,ascombinationscanlimitthetoxicitiesofindividualtherapies;examples:– TopicalsteroidswithUVBorPUVA– RetinoidswithPUVAornarrowbandUVB– VitaminDanalogueswithUVB– Ingrammethod:coaltarbaths,UVB,anthralin– MethotrexatewithUVB–Methotrexatewithcyclosporine– Etanerceptwithmethotrexate
Phototherapy,conventionalsystemicagents,andbiologicagentstreatingpsoriasisaredis-cussedelsewhereinthistext.
86 2011/2012 Dermatology In-Review l Committed to Your Future
4.4 PSoRIAtIC ARthRItISFeatures
• 20-40%ofpsoriaticpatients;higherfrequencyfoundinmoderatetoseverepsoriasispatients
• Ageofonset:18–50years• Usually(80%)rheumatoidfactornegative(seronegative)• Synovial,serumandlesionallevelsofTNF-αareincreasedinpsoriasisandpsoriaticarthritis18
Types of Psoriatic Arthritis • Asymmetricoligoarthritisorpolyarthritis(mostcommon)• Symmetricpolyarthritis(RA-like)• Spondylitis(axial)• Distalinterphalangealjoint(DIP)disease• Arthritismutilans(leastcommon)• Enthesopathy(inflammationofligamentsandtendonsatinsertionpointonbones)19
Clinical• Morningstiffnessofjointslastingmorethan60minutes• InflammationofDIPjoints→oftenwithnailinvolvement(~80%)• Dactylitis:“sausagedigits”• Enthesitis/Enthesopathy→Inflammationoftendonsorligamentsoratsitesoftendoninsertionintobone
• Spondylitis/sacroiliitisandaxialdisease• Reducedrangeofmotionofshoulders,neck,andlowerback• 80%ofpatientspresentwithskindiseasefirst
Radiographic Features of Psoriatic Arthritis• “Sausagedigits”• Largeeccentricerosions• Pencil-in-cupdeformities—erosivechangesofthejoint:phalangealdistraltipispencilonanerodedcuplikejointspace
• Tuftresorption:(acroostcolysis)• Periostitis:inflammationoftheperiosteum• Sacroileitis
Therapy for Psoriatic Arthritis• NSAIDs• Sulfasalazine• Methotrexate• Etanercept(FDA-approvedtherapy)• Ustekinumab(awaitingFDAapproval)
4.5 REItER’S SyNDRomEChronicinflammatorydiseasesimilartopsoriasiswithpsoriaticarthritis.•Urethritis• Conjunctivitis• Arthritis
General Dermatology 87
Fewpatientspresentwithclassictriad,thuscanbediagnosedwith• Peripheralarthritis>1monthduration• Associatedurethritis(orcervicitis)
OccursinyoungmenofHLA-B27genotype.Rarelyoccursinwomen.
Clinical• Anyoneoftriad• Fever,weakness,andweightloss• Nonbacterialurethritiswithpainfulandbloodyurinationandpyuria• Mayinvolvegastroenteritis• Cystitis,prostatitis,seminalvesiculitis• Keratitismayleadtocornealulceration• Iritiscommon• Arthritisisasymmetric• Endocarditis,pericarditis,myocarditis,aorticinsufficiency• Erythemanodosum
Skin Lesions• Multiplesmall,yellowishvesiclesthatbreak,becomeconfluent,andformsuperficialerosions→ frequentlyongenitalsandpalms
• Crusted,hyperkeratoticpapulesandplaquesonplantarsurfaces→keratodermablennorrhagicum• Penilelesions:Perimeatalbalanitis;circinatelesions;similarlesionsseenonvaginalmucosaofaffectedwomen
• Buccal,palatal,andlingualmucosamayshowpainless,shallow,rederosions,andseverestomatitis
• Nailsbecomethickandbrittlewithheavysubungualhyperkeratoticdeposits
Etiology• Chlamydia trachomatisassociatedwithcasesinvolvinginfectionofGUtract• HLA-B27in80%ofcases
Treatment• Topicalsteroids• NSAIDs• Methotrexate• Acitretin• Cyclosporine• TNF-inhibitingbiologicssuchasetanercept• Courseofdiseasemarkedbyexacerbationandremission.Achronicdeformingarthritisoccursin20%
4.6 SAPho SyNDRomE• Synovitis• Acne(Acnefulminansorconglobata)• Pustulosis(pustularpsoriasis)• Hyperostosis• Osteomyelitis
uTIPa�
Shigella flexneri (most common) of nonurethral form of Reiters, Salmonella spp., Yersinia spp., Ureaplasma urealyticum, Borrelia burgdorferi, Cryptosporidia, Campylobacter fetus
88 2011/2012 Dermatology In-Review l Committed to Your Future
4.7 SNEDDoN-WILkINSoN DISEASE• Subcornealpustulardermatosis• Middle-agedwomen• Superficialpustulesinannularandserpiginouspatterns• Abdomen,axillae,groin• Pustulesaresterile
Histology• Pustulesformbelowstratumcorneumwithoutacantholysis• Containsmanyneutrophils
Treatment• Dapsone• Acitretin• NarrowbandUVBChroniccondition,possiblyrelatedtopsoriasis,withremissionsofvariableduration.
4.8 LIChEN PLANUSInflammatorydisorderthataffectstheskin,mucousmembranes,nails,andhair.• Purple,polygonal,pruritic,papule,planar• Scalingisnotasprominentasotherpapulosquamousdiseases• Prevalence:<1%,noracialpreference• 2/3casesbetweenagesof30and60
Etiology and PathogenesisClassification Scheme• Idiopathic(classic)• Drugassociated• Associatedwithotherdiseases(UlcerativeColitis,AlopeciaAreata,Vitiligo,Dermatomyositis,MyastheniaGravis)
Role of Infection• HepatitisCimplicatedintriggeringLP• Associationwithsyphilis,HSV2,HIV,amebiasisandchronicbladderinfections
Clinical Manfiestations• Erythematoustoviolaceous,flat-topped,polygonalpapule,withoccasionalsmallcentralumbilication
• Thin,transparent,adherentscaleatopthelesion• Wickham’sstriae–fine,whitishreticulatednetworksonsurfaceofwell-developedplaques• LPbeginsaserythematousmaculesthatevolveoverweeks;initiallesionsalwaysappearontheextremities
• Generalizederuptiondevelopsoveronetofourmonths• Symmetricallyinvolvesflexuralareasofwrists,arms,legs;also,oralmucosaandgenitalia• InverseLP:Axillae,groin,inframammaryareas• LPisusuallypruritic;oralinvolvementgenerallyasymptomatic,unlesserosive→ extremely painful
• Koebnerization(isomorphicresponse)occurs
uTIPa AssociationwithIgAmonoclonal
gammopathy
General Dermatology 89
Clinical VariantsConfigurationAnnular LP• Blacksmorecommonlyaffected• Onpenisandscrotum• Also,largerlesionsreach2-3cmindiameterandbecomehyperpigmentedwithraised
outer rimLinear LP• Secondarytotrauma,often
Hypertrophic LP • Shins,interphalangealjoints• Mostpruritic• Healswithscarformationandhyper/hypopigmentation
Atrophic LP• Rare• White,bluishpapulesorplaqueswithcentralsuperficialatrophy• Mostcommonlowerextremitiesandtrunk• Resembleslichensclerosusetatrophicus
Vesiculobullous LP• Rare• VesiclesandbullaewithinlesionsofLP• BullaearisefrompapulesofLP,notnormalskin• Subepidermalseparation
Erosive Ulcerative LP• Chronicandpainfulbullaeandulcerationsonfeet• UsuallyassociatedwithmoretypicalLPlesionsofnails,mucosalsurfacesandskin• Lossoftoenailsandalopeciacommon• SCCmaydevelopinlesionsofulcerativeLP,thereforebiopsymaybeindicated
• InoralLP,oralmucosa,gingivaandtonguemaybeaffected.Desquamativegingivitismayoccur
• HistologyofmucosalLPdiffersfromLPoftheskininthatparakeratosisratherthanorthokeratosisisseen,secondarytothelackofgranularlayeronmucosalsurfaces21
Follicular LP (lichen planopilaris)• Individualkeratoticandfollicularpapulesandstuddedplaques• Trunkandmedialaspectsofproximalextremities• Affectsscalp–cicatricialalopecia• Graham-Little-Piccardi-Lassueur syndrome: triad of
1.) Follicular LP of skin and/or scalp2.) Multifocal cicatricial alopecia of scalp3.) Nonscarring alopecia of axillary and pubic areas
Lichen Planus Pigmentosus• Uncommon• Hyperpigmented,darkbrownmaculesinsun-exposedareasandflexuralfolds• Occursindarker-pigmentedpeople• Similartoerythemadyschromicumperstans
uTIPa
Erosive mucous membrane disease more common in patients with Hepatitis C infection
90 2011/2012 Dermatology In-Review l Committed to Your Future
Actinic LP• MorecommoninMiddleEasterncountriesinspring/summer• Affectssun-exposedareas• TypicalLPmaybeseenoverextremities• Pruritusandscalingminimal
Sites of InvolvementLP of the Scalp• LichenplanopilarisorfollicularLP:individualkeratoticpapulesthatcoalesceandmergetoformpatches
• Women>men• Uni-ormultifocalhairloss• End-stage:scarringalopecia• PseudopeladeofBrocq:scarringalopeciaandfibrosis;endstageoffollicularfibrosiscausedbyprimaryinflammatorydermatosissuchasLP,LE,pustularscarringformsoffolliculitis,favus,scleroderma,andsarcoidosis
Mucosal LP• Affectsmouth,vagina,esophagus,conjunctiva,urethra,anus,nose,andlarynx• 60-70%patientswithLP• OnlymanifestationofLPin20-30%• Forms:reticular,plaque-like,atrophic,papular,erosive-ulcerative,andbullousforms• Malegenitalia:25%ofcases,glanspenismostcommonsite(annularlesions,frequently)• Femalegenitalia:leukoplakia/erythroplakia,erosive,orgeneralizeddesquamativevaginitis• VulvarandgingivalLPcanexisttogether–erythemaanderosionsofgingivaeandtongueandwhitereticulatedplaques
• ConjunctivalLP:cicatricialconjunctivitis
LP of the Nails• 10-15%ofcases• UsuallyincombinationwithotherLPlesionsonskin• 20-naildystrophy(trachyonychia)canbeseen,buttrachyonychiaisnotdiagnosticofLP• Thinning,longitudinalridging,anddistalsplittingofnailplate(onychoschizia)• Also,oncholysis,longitudinalstriation(onychorrhexis),subungualhyperkeratosis,oranonychia
• Classicfinding:dorsalpterygiumorforwardgrowthoftheeponychiumwithadherenceofproximalnailplate;also“tenting”signasnailplateelevatedwithlongitudinalsplitting
• Pitscommon
Inverse LP• Rare• Occursinflexuralareassuchasaxilla,underbreast,groin• Reddish-brown,discretepapules
Palmoplantar LP• Yellowish,compactkeratoticpapulesandpapulonodulesonlateralmarginsoffingersandhandsurfaces
General Dermatology 91
Special Forms of LP/Lichenoid EruptionDrug-induced LP• MaybetypicaloratypicalforclassicLP,localizedorgeneralized• Typicallymanifestpostinflammatoryhyperpigmentation,alopecia,withoutWickham’sstriae
• Symmetriceruptionontrunkandextremities—photodistributioncommonwiththesedrugs:5-FU,carbamazepine,chlorpromazine,diazoxide,ethambutol,quinine/quinidine,tetracyclines,thiazidesandfurosemide
• Mucousmembraneinvolvementoftenassociatedwithspecificdrugsandchemicals—amalgamcontainingmercury;goldmorecommon
LP–Lupus Overlap• ClassiclesionsofLPnotusuallyseen• Photosensitivity,pruritus,follicularpluggingalsouncommon• Lesionsonextremities,commonly:atrophicplaquesandpatcheswithhypopigmentationandalividred-to-bluevioletcolorwithtelangiectasiaandminimalscaling;bullaemaydevelop
• MayprogresstoSLE• Prolongedcourse• Histo:LichenoidreactionandhistologicfeaturesofLEseeninsamebiopsy
Lichen Planus Pemphigoides• TenseblistersatoplesionsofLP,ordevelopmentofvesicledenovoonuninvolvedskin
• DifferentiatefrombullousLP,whereblistersinlesionsoflongstandingLPasaresultofintenselichenoidinflammationandextensiveliquefactiondegenerationofbasalkeratinocytes
• HistologicallylikeLP,withlineardepositionofIgGandC3atDEjunction
• CirculatingIgGautoantibodiesreactto180/200kDaantigenwithinBMzone
Keratosis Lichenoides Chronica (NekamDisease)• Violaceouspapularandnodularlesions;hyperpigmentedandhyperkeratotic,coveredwithgrayscales
• Often,linearandreticulatepatternonthedorsalhandsandfeet,extremitiesandbuttocks• Veryrefractorytotreatment
LP and Malignant Transformation• Riskisverylowtononeatall• Riskincreasedbylongstandingdisease,erosiveoratrophictypesofLP,andtobaccouse• Mostcommonsitesformalignanttransformationaretongue,gingivaandbuccalmucosa• MostpatientsdevelopingSCCincutaneousLPhadahistoryofeitherarsenicorX-rayexposure
Lichenoid Keratosis (LichenPlanus-likeKeratosis)• Browntoredscalingpapuleorplaquefoundonsun-exposedskinofextremities• HistologicalfeaturesofLPwithadditionalfindingofparakeratosis• Frequentlyoccurwithsolarlentigo,seborrheickeratosis,andactinickeratosis
uTIPa Lichenoid drug eruptions have
been associated with β-blockers, antimalarials, captopril, gold, peni-cillamine, HCTZ, NSAIDs
uTIPa Lichenoid contact dermatitis
– color film developers, dental restorative materials, musk ambrette, nickel, aminoglyco-sides, gold
92 2011/2012 Dermatology In-Review l Committed to Your Future
Associated Conditions• Autoimmunechronicactivehepatitis• Primarybiliarycirrhosis• Postviralchronicactivehepatitis• HCVinsomepopulations
Treatment• Spontaneousremissionsandexacerbations• Oral/MucosalLP–replacementofgoldoramalgamdentalrestorations• Topicalhighpotencysteroidsformucosalandlimitedcutaneousdisease• Topicalimmunomodulatorssuchastacrolimusointmentfororal/genitaldisease• Topicalanestheticsfororalpain• IntralesionalTAC• Systemicsteroidsforrefractorycases• PUVAphotochemotherapysuccessfulingeneralizedLP• Oralretinoids
Course and Prognosis• Typicallypersists1-2years• Mayfollowchronic,relapsingcourse• Spontaneousremissiononaverageafter15months• Lichenplanopilarismostchronicandprogressivewithlittlepotentialforhairregrowth• HypertrophicLPfollowsprotractedunremittingcourse• OralLPdoesnotusuallyspontaneouslyregress
4.9 AtoPIC DERmAtItISClinical Features
Major• Pruritus• Facialandextensorinvolvementininfantsandchildren• Flexurallichenificationinadults• Chronicorrelapsingdermatitis• Personal/familyhistoryofatopy
Associated Features• Xerosis• Cutaneousinfection• Nonspecificdermatitisofhands/feet• Ichthyosis,palmarhyperlinearity,keratosispilaris• Pityriasisalba• Nippleeczema• Whitedermatographismanddelayedblanchresponse• Anteriorsubcapsularcataracts,keratoconus• ElevatedserumIgElevels• Positiveimmediate-typeallergyskintests• Earlyageofonset• Dennie-Morganinfraorbitalfolds
General Dermatology 93
• Orbitaldarkening• Facialerythemaorpallor• Perifollicularaccentuation• Courseinfluencedbyenvironmentaland/oremotionalfactors
Genetics• Strongercorrelationbetweensiblingsthanbetweensiblingsandparents• Exposuretoenvironmentalfactorsduringchildhoodislikelytobethemajorfactor• Seeninfamilieswithatopicdermatitis,asthma,andallergicrhinitis•Filaggringenemutationsareknownriskfactor
Clinical Manifestations• Typicallybeginsininfancy→50%infirstyearoflife,andanadditional30%between1and5years
• MostchildrenwithADeventuallydevelopallergicrhinitisorasthmalaterinchildhood
Infancy • ADgenerallymoreacuteandprimarilyinvolvestheface,scalp,andtheextensorsurfacesoftheextremities
• Diaperareaspared
Older Children• PatientdevelopsthechronicformofADwithlichenificationandlocalizationoftherashtotheflexuralfoldsoftheextremities
• Subsidesaspatientgrowsolder,leavingadultwithskinthatispronetoitchingandinflammation
• ChronichandeczemamaybetheprimarymanifestationofadultswithAD
ComplicationsOcular Problems• Eyeliddermatitisandblepharitis• Atopickeratoconjunctivitis• Keratoconus:conicaldeformityofcornea• Cataracts
Infections• Frequentlycomplicatedbyrecurrentskininfections:– Kaposi’svaricelliformeruption→ herpessimplex→resultsineczemaherpeticum→ incubationof5-12days,multiple,itchy,vesiculopustularlesionseruptinadisseminatedpattern→ oftenbecomehemorrhagicandcrusted
–Molluscumcontagiosum– HPV– Superficialfungalinfections—Trichophyton rubrum and
Pityrosporum ovale– S. aureus–foundinover90%ofADskinlesions.Honeycoloredcrusting,folliculitis,andpyodermaareindicatorsofsecondarybacterialskininfection.Regionallymphadenopathycommon.Deep-seatedS. aureusinfectionsmayindicatehyper-IgEsyndrome
uTIPa Innate antimicrobial peptides
include human β-defensin (HBD) and cathelicidins, such as LL 37. Ong et al found a deficiency of HBD-2 and LL 37 in lesions from patients with atopic dermatitis com-pared to those with psoriasis. This decreased expression of innate antimicrobial peptides may explain the increased sus-ceptibility to colonization and skin infection with S. aureus in patients with atopic dermatitis4
94 2011/2012 Dermatology In-Review l Committed to Your Future
Foods• FoodallergensexacerbateskinrashesinatleastasubsetofpatientswithAD,particularlyinfantsandyoungchildren
• Eggs,milk,peanuts,soybeans,treenuts,fish,andwheatarethemostcommonallergensimplicatedinAD
• FollowingpositiveoralfoodchallengesinchildrenwithAD,histamineconcentrationincreasesintheplasma
• MostADpatientsdoNOThavefoodallergy
Immunohistochemistry• LymphocytesareCD3+,CD4+,andCD45RO+memoryThelpercells• LangerhanscellsandmacrophagesinfiltratingintoADskinlesionshavesurface-boundIgE• ActivatedeosinophilsarepresentinsignificantlygreaternumbersinchronicascomparedtoacuteADlesions
Immunologic Abnormalities in AD• IncreasedsynthesisofIgE• IncreasedexpressionofCD23(lowaffinityIgEreceptor)onBcellsandmonocytes• Increasedbasophilhistaminerelease• ImpairedDTHresponse• DecreasedCD8suppressor/cytotoxicT-cellnumberandfunction• IncreasedsecretionofIL-4andIL-5byTH2cells• DecreasedsecretionIFN-gammabyTH1cells
An Immunologic Aside• TH1cells→produceIL-2,IFN-γ,andTNF-β,associatedwithcell-mediatedimmunity• TH2cells→produceIL-4,IL-5,IL-6,IL-10,andIL-13,associatedwithantibodymediatedimmuneresponses
Management
Allergens• Dustmites,molds,animaldander,pollens• Avoidanceoftriggeringfoods• Infantsandyoungchildrenmorelikelytohavefoodallergies;olderchildrenandadultssensitivetoenvironmentalaeroallergens
Infectious Agents• Anti-staphylococcalantibioticshelpfulinthosecolonized• HSV:Antiviraltreatmentveryimportanttopreventdisseminateddisease;IVtreatmentmaybenecessaryfordisseminatedeczemaherpeticum
• Molluscumcontagiosum→topicalimiquimod,liquidnitrogen,topicalsalicylicacid,ornotherapy
Pruritus• Antihistamines→usesedatingantihistamineatnight
Systemic Glucocorticoids• Rarelyindicated,andriskofreboundflareafterdiscontinuation• Shortcoursescanbedonewhileothermodalitiesarestarted,andtaperingdosageiscritical
General Dermatology 95
UV Phototherapy• UVBusefuladjuncttotreatmentofchronicrecalcitrantAD• HighintensityUVAcanbefast-actingandeffectivewithacuteexacerbationsofAD
Systemic Cyclosporine or Tacrolimus• OralcyclosporineortacrolimuscanhelpsevereADthatisrefractorytotopicalsteroids• Discontinuationoftreatmentmayresultinrapidrelapseofskindisease
Probiotics• Theutilityofprobioticsinprimarypreventionofatopicdermatitishasbeenstudied• LactobacillusGGculturesweregiventopregnantwomenwithahistoryofatopytoassesstheeffectofpotentiallybeneficialgutfloraonthepreventionofatopicdiseaseintheirchildren
• Frequencyofatopicdermatitisintheprobioticgroupwashalfthatintheplacebogroupattwoyearsoflife
Prognosis• Diseasemoresevereandpersistentinyoungchildren• Periodsofremissiongrowlongeraspatientages• Milddiseaseatinfancy:Spontaneousresolutionoccursin40%ofpatientsafterage5• Poorprognosticfactors–WidespreadADinchildhood– Associatedallergicrhinitisorasthma– FamilyhistoryofAD– Earlyageofonset
4.10 ALoPECIA AREAtAGenetics
• Highfrequencyoffamilyhistory,especiallyinpatientswithearlyonset(37%)• Twinconcordance=55%(identicaltwins)
Immunologic Factors• Majorassociations:Vitiligoandthyroiddisease(10%),withincreasedprevalenceofantithyroidantibodiesandthyroidmicrosomalantibodiesinAA
• Otherautoimmunediseasesshowntobeassociated:perniciousanemia,diabetes,LE,myastheniagravis,RA,polymyalgiarheumatica,ulcerativecolitis
Emotional Stress• Maybeprecipitatingfactorinsomecases
Clinical Features• Prevalence:0.1-0.2%,withlifetimeriskof1.7%• Affectsmenandwomenequally• 60%presentbeforeage20• Pulltestmaybepositiveatmargins,indicatingearlydisease
• Usuallyasymptomatic,butsomepatientsperceivepruritus,tenderness,burning,orpainprecedinghairloss
• Areata–partiallossofscalphair
uTIPa PATTERNS of alopecia areata: patchy (most common);
reticulated; ophiasis (parietal/temporal/occipital); ophiasis inversus (sisapho – bandlike pattern in fronto parietotemporal scalp); diffuse
96 2011/2012 Dermatology In-Review l Committed to Your Future
• Totalis–totallossofscalphair• Universalis–100%lossonscalp,eyebrows,eyelashes,andrestofbody• Initialregrowthiswhite,followedbyrepigmentation• Naildystrophy(10-66%),seeninone,some,orallnails,preceding,coinciding,oroccurringafterhairdisease→ pittingwithirregularpatternorinorganizedrows;trachyonychia:longitudinalstriationsresultinginsandpaperappearance;Beau’slines;onychorrhexis;thinningorthickening;koilonychia;red-spottedlunula;punctateortransverseleukonychia
Prognosis• Unpredictablecourseandpattern• Mostpatientsseecompleteregrowthwithinoneyearwithouttreatment• 10%developseverechronicform• Predictorsforpoorprognosis:atopicdermatitis,childhoodonset,widespreadinvolvement,ophiasis,durationforlongerthanfiveyears,onychodystrophy
Treatment• Alllocaltreatmentshelptreatedareas,butdonotpreventfurtherspread• Spontaneousrecoveryisextremelycommon,withmostshowingregrowthwithin1year• Firstline:ILsteroidsconcentrationof5mg/ccmaximumof3ccpervisit→ 0.1ccpersite,approximately1cmapart;after6monthsandnoresponse,d/c
• Topicalsteroidsasmonotherapygenerallyineffective• Minoxidil5%:stimulatesfollicularDNAsynthesisandregulateshairphysiologyindependentlyofbloodflowinfluences;effectivewithalopeciaareatainvolving20-99%involvementin25-50%ofpatients→ initialhairregrowthin12weeks
• Anthralin0.25-1.0%• SquaricaciddibutylorDNCBorDPCP(diphenylcyclopropenone)–aimistomaintainlow-gradetolerableerythema,scaling,andpruritus,withweeklyapplications
• PUVA,witheithertopicalorsystemicpsoralentherapy;relapseafterdiscontinuationoccurs• Cyclosporineworks,butsystemicuseassociatedwithadverseeffectsandhighrecurrence
rate
4.11 ALoPECIA: othER FoRmSTrichotillomania
• Practiceofpluckingorbreakinghairfromthescalporeyelashes• Areasofalopeciacharacteristicallycontainhairsofvaryinglength• Girlsunderageof10• Treatwithpsychotherapyandantidepressant
Hot Comb Alopecia• AfricanAmericanwomenwhostraightenedtheirhairwithhotcombs• Characteristicallyonthecrownandspreadsperipherallytoformalargeovalareaofpartialhairloss
• Thermaldamagetofolliclebyhotpetrolatum,leadingtodestructionofhairfollicleandfollicularscar
• Maybesameasfolliculardegenerationsyndrome/centralcentrifugalscarringalopecia
uTIP a Biopsy shows high
number of catagen hairs, pigmentary defects and casts, trichomalacia, and hemorrhage
General Dermatology 97
Pseudopelade of Brocq• Scarringalopeciawheredestructionofthehairfollicleproducesmultipleround,oval,orirregularlyshapedcicatricialpatchesofvaryingsizes
• Nopustules,crusts,orbroken-offhairsarepresent• Onsetisinsidious• Female:male=3:1• Alopeciapermanent• Noinflammationwithdecreasedorabsentsebaceousglands,normaloratrophicepidermis
Traction Alopecia• Prolongedtensiononthehairfrombraiding,ponytails,rollingcurlers,twistingwithfingers
Pressure Alopecia• Occipitalareasofbabieslyingontheirbacks• Inadults,prolongedpressureonthescalpduringgeneralanesthesiaorafterprolongedbedrest
• Peoplewithchronicillnessafterprolongedbedrestinoneposition• Likelyrelatedtopressure-inducedischemia
Loose Anagen Syndrome• Anagenhairspulledfromthescalpwithlittleeffort• Blondegirls• Usuallyimproveswithage
Follicular Mucinosis• Depositionofmucinintheouterrootsheathandsebaceousglands• Mostcommonlyonscalpandbeardarea• SecondarytypeassociatedwithCTCLwithwidespreadandchroniclesions,andpatients
are older
Meralgia Paresthetica• Mayhavealopeciaoftheanestheticareaoftheouterthigh
Hypothyroidism• Haircoarse,dry,brittle,andsparse• Telogenhairs3xmoreprevalent
Hyperthyroidism• Hairbecomesextremelyfineandsparse
Alopecia Neoplastica• Hairlossfrommetastatictumors• Usuallybreastcarcinoma
98 2011/2012 Dermatology In-Review l Committed to Your Future
4.12 VItILIGo• Halfofallcasesbeginbeforeage20• Depigmentedwhitepatchessurroundedbynormalorhyperpigmentedborder• Trichromevitiligo:intermediatetanzoneshalfwaybetweenthenormalskincolorandthe
depigmentation• Hairsinvitiliginousareasbecomewhite
Four Types1.)Localizedorfocal(includessegmental)2.) Generalized(mostcommon)3.) Universal4.) Acrofacial
Generalized• Symmetrical• Face,upperchest,dorsalhands,axillae,groin• Skinaroundallorifices• Areasoftrauma(kneesandelbows)
Focal• Asymmetric• Treatmentresistant• 5%ofadult,20%ofchildhoodcasesofvitiligo
Universal• Entirebodysurfacedepigmented
Associations• Insulin-dependentdiabetes• Perniciousanemia• Hashimoto’sthyroiditis• Grave’sdisease• Addison’sdisease• Alopeciaareata
Genetics• Multifactorial• 30%ofvitiligopatientshaveanaffectedrelative
Treatment• Topicalcorticosteroids• Ultravioletphototherapy(NarrowbandUVBandPsoralenwithUVA)• Laser(308nmexcimer)• Topicaltacrolimus• Re-pigmentedsurgerywithpunchminigrafts,dermoscopicdermalgrafts
General Dermatology 99
4.13 PItyRIASIS RUbRA PILARIS • Smallfollicularpapules→ salmon-orangetoreddish-browncolor,pinheadsize,andtoppedwithscalyplug
• Yellowishpinkscalingpatches,oftenbeginsonscalp• Solidconfluentpalmoplantarhyperkeratosis
Progresses to: • Sidesoftheneckandtrunk• Extensorsurfacesoftheextremities• Anyportionofthebodycanbeaffected
Clinical Features• Involvementgenerallysymmetricalanddiffuse,withcharacteristicsmallislandsofnormalskinwithintheaffectedareas
• Palmsandsoleswillbehyperkeratoticwithfissuring• Nails:dull,rough,thickened,brittle,andstriated;maycrackandbreak;nopitting
Treatment• Topicalkeratolytics• Systemicretinoids• VitaminA500,000unitsdaily• Systemicsteroidsforshorttermmanagement• Methotrexate• Azathioprine• Cyclosporine
4.14 LIChEN SCLERoSUS• Presentsfromchildhoodtooldage,andoccursinallraces• Femalespredominateatallages
Clinical• White,polygonal,andflat-toppedpapulesorplaquessurroundedbyerythematoustoviolaceoushalo
• Later,lesionscoalesceintolargeatrophicpatches,becomingsmooth,slightlywrinkled,andwhite
• Bullaemayariseinpatches• Prurituscanbesevere,especiallyinanogenitalarea,whereerosionsandfissuringcanoccur• Inwomen,normalanatomicstructuresmaybeobliterated• Balanitisxeroticaobliterans→ maleinvolvementoftheglanspenis;hemorrhageiscommonintheglans
• Extragenitallesionsmostfrequentontheupperback,chest,andbreasts,andareusuallyasymptomatic
• +Koebnerization
Cancer Risk• IncreasedriskofgenitalSCCinbothmenandwomen• Lifetimeriskforwomenlessthan5%
100 2011/2012 Dermatology In-Review l Committed to Your Future
Etiology• Autoimmunephenomenon,likely• 20%ofbothmenandwomenhaveatleastoneautoimmunedisease(vitiligo,alopeciaareata,orthyroiddisease),andalargerproportionhavecirculatingantibodies
• Traumacaninducelesions,andboysdobetteraftercircumcision
Childhood LS• Onsetinchildhoodin10-15%ofcases• Girlsoutnumberboys10:1• Genitaldiseaserepresents90%ofchildhoodLS• Ingirls:Symptomsincludedifficultywithdefecation,dysuria,perinealpruritus,andperinealskinlesions
• Inboys:Phimosisismostcommonpresentingsign• Mayresolvespontaneously,especiallyaroundpuberty(50%ofgirls,aftercircumcisioninboys)
Treatment• Superpotenttopicalsteroidstwicedailytobetaperedineitherstrengthorfrequencyover
time• Topicaltacrolimusointmentorpimecrolimuscream,sometimeseffective• Oralretinoidsmayworkwithanogenitallichensclerosusinbothmenandwomen
4.15 GRANULomA ANNULARELocalized GA
• Youngadults• Lateralordorsalsurfacesoffingers,hands,elbows,feet,ankles• White,pink,flat-toppedpapulesthatspreadperipherally• Neverulcerateandhealwithoutscarring• 75%clearwithin2years
Generalized GA• Diabetesin20%• Diffusepapules• Maybepruriticorasymptomatic• Laststhreemonthstofouryears
Macular GA• Flatorslightlypalpablelesionsoverfeet,ankles,anduppermedialthighs• Smallpapulescanbefeltinsomecases
Subcutaneous GA• Mostcommoninchildren• Oftenahistoryoftraumatoarea• Multiplelesionsmaybepresent• Generallyasymptomatic
Perforating GA• Dorsumofhands
General Dermatology 101
• PapuleswithcentralkeratoticcorerepresentingtransepidermaleliminationofthedegeneratedmaterialinthecenterofGAlesions
4.16 hIRSUtISmAndrogens in Women
• Dehydroepiandrosterone(DHEA),adrenal• Androstenedione–adrenal,ovary• Testosterone–ovary,adrenal,extraglandularconversionof androstenedioneanddehydroepiandrosterone– Adrenalandrogenregulatedbyadrenocorticotropin– Ovarianandrogenregulatedbyluteinizinghormone– Thehairfolliclerequiresconversionoftestosteroneto dihydrotestosteroneforexpressionofandrogenaction
Tumors → Rapid Onset of Hair Growth with or without Accompanying Virilization• Adrenaladenomasandcarcinomas• Arrhenoblastoma• Kruckenbergtumorsofovary
Polycystic Ovarian Disease• Mostcommoncauseofovarianhyperandrogenism• Manifestations:Hirsutism,amenorrhea,virilization
Congenital Adrenal Hyperplasia Congenitaladrenalhyperplasia(defectsinadrenalsteroidogenesis)canoccuratanypoint
inlife.• 21-hydroxylasedeficiency• 11β-hydroxylasedeficiency• 3β-hydroxysteroiddehydrogenaseisomerasedeficiency(3β-hsd)
Idiopathic Hirsutism• Womenwithevidenceofandrogenexcessbutwithnormalmenses,normal-sizedovaries,noevidenceoftumorsofadrenalorovary,andnormaladrenalfunction
• Slightelevationsofplasmaandrostenedioneandtestosteronecommon
Signs of VirilizationSignsofvirilization→ correlateswithandrogenoverproduction• Deepeningofthevoice• Temporalbalding• Clitoromegaly• Increasedmusclemassinthelimbgirdles
Signs of Cortisol Excess• Plethora• Centralobesity• Striae• Dorsocervical/supraclavicularfatpads
uTIPa�Drugs → Hirsutism without
Virilization/Defeminization
• Phenytoin • Minoxidil • Diazoxide • Cyclosporine • Hexachlorobenzene
102 2011/2012 Dermatology In-Review l Committed to Your Future
Work-up• Pelvicexam:Searchforpalpableovarianmasses• Radiographicimagingofthepelvis/adrenalglands• Laboratoryexam:DHEA>8000ng/mlorserumtestosterone>2ng/mlsuggestneoplasm• Plasmatestosteronelevelsinthenormalrangearedifficulttointerpret→ doesnotnecessarilyreflectthefreeorunboundlevelsofhormoneunderconditionswhentestosterone-bindingglobulinlevelsareeitherincreasedordecreased
• Cushingsyndrome,ifsuspected,shouldbeevaluatedwithanovernightdexamethasonesuppressiontest
• Polycysticovariandisease:Diagnosisfromhistoryandphysicalexam• Delayedonsetadrenalhyperplasia:ShortACTHstimulationtestandmeasurementofplasma17-hydroxy-progesterone
4.17 AmyLoIDoSIS• Beta-pleatedsheetformsofvarioushost-synthesizedmolecules
Classification1.)Primary(oftenhasskinfindings)2.) Secondary(rareskinmanifestations)3.) Primarylocalized4.) Secondarycutaneousortumorassociated5.) Familialsyndromes
Pathology• PASpositiveanddiastaseresistant• Congo-redpositive• Purplewithcrystalviolet• PositivewiththioflavinT• Secondarysystemicamyloid(aa)losesitsbirefringenceaftertreatmentwithpotassiumpermanganate,butprimaryandlocalizedformsdonot
Primary Systemic Amyloidosis• Involvestongue,heart,GItract,andskin• Involvesskinin40%• Includesmyeloma-associatedamyloidosis
Clinical• Shiny,smooth,firm,flat-toppedpapulesofwaxycolorthatcoalesceintonodulesorplaques• Commonlyaroundnose,eyes,mouth,andmucocutaneousjunctions
• Purpuriclesionsresultfromamyloidinfiltrationofbloodvessels;occursaftertrauma(pinch purpura)
• Glossitis→ mayleadtodysphagia;lateralaspectsoftongueshowsindentationsfromteeth• Bullousamyloidosis→ subepidermalhemorrhagicbullaeatareasoftrauma
• Carpaltunnelsyndrome• RA-likearthropathy
• Shoulderpadsign → enlargeddeltoids
• CardiacarrythmiasandCHFcausedeath •Prognosispoor
uTIPa�Protein AL → derived from Ig
light chains (lambda subtype); AL also found in nodular amyloidosis produced by a plasmacytoma
General Dermatology 103
Secondary Systemic Amyloidosis• Amyloidintheadrenals,liver,spleen,andkidneyasaresultofsomechronicdisease,suchasTB,leprosy,Hodgkin’s,Behçet’s,rheumatoidarthritis,ulcerativecolitis,schistosomiasis,orsyphilis
• Skinnotinvolved
Primary Cutaneous Amyloidosis• Keratinistheproteincomponent• Noamyloidaroundthebloodvessels
Macular Amyloidosis• Moderatelypruritic,brown,rippledmaculesininterscapularregionoftheback
• Mayhaveassociatednotalgiaparesthetica
Lichen Amyloidosis• Bilateralshins• TypeIIaMEN• Small,brown,discrete,scalypapules• Treatbyreducingfriction,occlusion,ilsteroids
Nodular Amyloidosis• Singleormultiplenodulesonextremities,trunk,genitals,orface• Overlyingepidermismayappearatrophic• Numerousplasmacells• ALtype
Secondary Cutaneous Amyloidosis• SeenfollowingPUVAtherapyandinbenignandmalignantneoplasms:nonmelanomaskincancers,seborrheickeratoses,trichoepitheliomas
• Also,keratin-derivedamyloid
Familial Syndromes Associated with Amyloidosis• FamilialMediterraneanfeverandMuckel-Wellssyndrome→ showAAprotein• MENIIa→ keratin-derivedamyloid
Familial Amyloidotic Polyneuropathy (fap)• FapIandfapII→ mutationsintransthyretin• FapIII→ apolipoprotein a-1• FapIV→ gelsolinmutation
uTIPa�AA amyloid fibrils → derived from SAA protein, an
acute phase reactant
a�AA also seen in Muckle-Wells (renal amyloidosis, rti-caria, fevers, limb pains, and deafness) and familial Mediterranean fever
a�Dialysis-related amyloidosis: beta 2-microglobulin is the protein component altered by uremia → carpal tunnel syndrome, bone cysts, and spondyloarthropathy
104 2011/2012 Dermatology In-Review l Committed to Your Future
Table4-2.Amyloidosis
Types Fibril Protein Other Features
Systemic
Primary
AL(lambdaλchain) Involvestongue,heart,GItract,andskin.Petechiae,purpura,waxyskincoloredpapules,alopecia,car-paltunnelsyndrome,neuropathy,arthropath
Secondary AA Resultofchronicdisease:TB,leprosy,Hodgkin’s,RA,Reiter’s,syphilisNoSkininvolementAmyloidintheadrenals,liver,spleen,andkidney
Localized Cutaneous
Macular AlteredKeratin Rippledbrownmaculesininterscapularregiononback,notalgiaparesthetica
Lichen AlteredKeratin Brown,scalypapulesonbilateralshins
Nodular ALchains Singleormultiplenodulesonextremities,genitals,trunk,orface
Hereditary
Familial MediterraneanFever
AA AR,intermittentfevers,renalamyloidosis,peritonitis,pleurisyMEFVgene;marenostrin/pyrinprotein
MuckleWells AA AD,periodicattacksofurticaria,fever,deafness,renalamyloidosis
HemodialysisAssoication
β2microglobulin
Senile Bamyloidprotein Senileorneuriticplaques,Alzheimer’sdisease
4.18 CALCIPhyLAxIS• Painfulviolaceouseschar-likeplaquesassociatedwithsofttissuenecrosis• Metastaticcutaneouscalcificationfromincreasedparathyroidhormone(andincreasedcalciumphosphateproduct)secondarytorenalfailure
• Treatment:Phosphatebindingagents,parathyroidectomy
General Dermatology 105
4.19 ANGIoEDEmAReview of the Complement System
Classic Pathway• C1bindstoFcfragmentofIgMorIgGinimmunecomplexes• C1qdoesthebindingtoimmunoglobulin• C1sfragmentdigestsC4andC2,activatingthemintoaC4b,2acomplex,creatingC3convertase,thatactivatesC5convertase→ membraneattackcomplex
Alternative Aathway• Lessclear,butC3activatedbyaC3-convertasecomplexconsistingofC3b,bb• Duringinflammation,lowlevelsofC3bbindfactorb,thatundergoescleavagebyfactordtogenerateC3b,bb→ actsasaC3convertase
C1 Esterase Inhibitor• Proteaseinhibitor• Inhibitsthecatalyticsubunitsoffirstcomponentsofclassicalpathway(C1randC1s),kallikrein,plasmin
• InabsenceofC1esteraseinhibitor,activatedC1andplasmingenerateactivatedC2kinin• C2kininmediatesangioedema
AngioedemaTypeI:
•Occursinsettingoflymphoproliferativedisease(low-gradelymphoma,CLL,monoclonalgammopathyofundeterminedsignificance,systemicamyloidosis)orrheumatologicillness,whereidiotype/anti-idiotypeimmunecomplexesconsume availableC1q,andfunctionallyandquantitativelylowertheamountsofC1esteraseinhibitor• CanalsooccurinsettingofautoimmunitydirectedagainsttheC1esteraseprotein
• Importantpoint:inboththeinheritedandacquiredformslevelsofC2andC4aredecreasedbecauseoftheuncontrolledactionsofC1s
Clinical Presentation• Swellingofhead,neck,andextremities• Abdominalsymptoms• Upperairwaysymptoms• Recurrentsymptoms,withinterveningtimeofweekstomonths
Treatment• Androgentherapy:danazolorstanozolol→ bringaboutdramaticdecreasesinfrequencyandseverityofattacks
• Glucocorticoids,buttaperingresultsinrelapseofsymptoms• Therapyforunderlyingdisease• Pretreatmentwithandrogenspriortosurgicalprocedures
uTIPa Inherited (Quincke’s edema) (Normal C1q levels)
• Detectedinthefirstorseconddecadeof life • Autosomaldominantpatternofinheriance • SerumC1qnormalininheritedform • Defectinsynthesisand/orfunctionofC1
esterase inhibitor • TypeI:LowamountsofnormalC1sterase
inhibitor • TypeII:NormalamountsofdysfuncionalC1
esterase inhibor
aAcquired(LowC1q)
• Affectsadultorelderlywithnofamilyhistory
• SerumC1qdecreasedinacquiredform
106 2011/2012 Dermatology In-Review l Committed to Your Future
Diagnosis• ScreenwithC3andC4levels→ C4low,C3normalinangioedema• C1qlevellowinacquired,butnormalinhereditary
4.20 CARCINoID SyNDRomE AND FLUShING DISoRDERS
Menopausal Flushing • Perimenstrualflushingwhenestrogenlevelslow• Hotbeveragesandemotioncanexacerbate• Pharmocologicmenopausecausedbydrugs:danazol,tamoxifen,clomophenecitrate,decapeptyl,leuprolide,and4-hydroxyandrostenedione
• Tuballigationoranysurgicallossofovarianfunction• Clinicalmanifestationsincludedrenchingperspiration,wakingepisodesduringthenight,prodromalsensationofoverheatingbeforetheonsetofflushingandsweating
• Treatwithoralestrogenreplacementorclonidinehydrochloride0.05mgbid
Emotional Flushing• Cantreatwithbiofeedback,hypnosis,andnadolol(40-80mgqd)
Foods• Monosodiumglutamate• Scombroidgroupoffish(tunaandmackerel)• Spicyfoods
Mastocytosis•Seeseparatesectionlaterinthischapter
Medications• Nicotinamide,disulfiram,metronidazole
Carcinoid Syndrome• <4%withabdominalcarcinoidtumorshavethecarcinoidsyndrome• Presenceofsyndromeimplieshepaticmetastases,extraabdominalcarcinoidtumor,orlargeenoughtumorburdensuchthatthelivercannotdegradetheincreasedlevelofhormone
• Tumorsderivedfromenterochromaffin(Kulchitsky)cells• Appendixismostcommonsite,followedbytheileum• Ilealtumorsarethemostcommonsourceoftheclassiccarcinoidsyndrome,andthesetumorsmetastasizemostfrequently
Clinical• Pellagra-likelesionscausedbyexcessiveutilizationoftryptophan→ hyperkeratosis,xerosis,scalingoflegs,forearms,andtrunk,angularcheilitis,andglossitis
• Rosaceastigmata• Yellow-brownorbrown-graypatchesontheforehead,back,andwrists• Pruritus• Chronicwaterydiarrheain85%• Abdominalpain,constipation,nausea,vomiting,malabsorption,anorexia,weightloss,smallbowelobstruction,andrectalbleeding
• Respiratorysymptomsofwheezing,stridor,dyspnea,coughing,andbronchospasm
General Dermatology 107
• Arthritis,psychiatricsymptoms,osteoblasticbonelesions• Fibroticreactionsaffectingthevalvesoftheheart
Diagnosis• Serotoninoverproduction• Elevatedurinary5-HIAA• Foodsanddrugscanaffecttheurinaryexcretionof5-HIAA
4.21 LUPUS ERythEmAtoSUSClassification
Chronic Cutaneous LE• Discoid• Verrucous(hypertrophic)• LE-LPoverlap• Chilblain• LupusPanniculitis
Subacute Cutaneous LE• Papulosquamous• Annular• Neonatal• Complementdeficiencysyndromes
Acute Cutaneous LE• SystemicLEwithskinlesions→ localizedorgeneralizederythemawithbullae
Discoid Lupus• Youngadults,women:men2:1• Dullredmaculeswithadherentscalesextendingintopatulousfollicles• Pluggedfollicles• Patcheshealwithatrophy,scarring,dyspigmentation,andtelangiectasiaLocalized• Aboveneck:scalp,nose,malar,lips,ears• Pruritusandtendernesscommon• Mucosalinvolvementofmouth,nose,eyes,vulvacommon
Generalized• Lesscommonthanlocalized• Thoraxandupperextremities,inadditiontousualsitesabovetheneck• ElevatedESR,positiveANA,orleukopeniamorecommon
Course• 95%ofcasesconfinedtotheskinatoutsetwillremainso• AbnormallabssuchasANA,leukopenia,hematuria,oralbuminuriaidentifythosewhoprogress;also,rashaboveandbelowtheneck
• Relapsesarecommon• BCCorSCCoccurinscars,andafavoredsiteisthelowerlip
108 2011/2012 Dermatology In-Review l Committed to Your Future
Treatment• Sunavoidance• Avoidexposuretoheat,cold,trauma• Topicalcorticosteroids(potent)withorwithoutocclusion• ILsteroids
Antimalarials• Firsthydroxychloroquine(Plaquenil),thenchloroquine,oraddquinacrine• Sideeffects:erythemamultiforme,purpura,urticaria,ocularrisksareverysmall,nausea,vomiting,tinnitus,abducensnerveparalysis,toxicpsychoses,leukopenia,andthrombocytopenia
• ExacerbatePCT• Bleachhair• Quinacrineyellowshairandconjunctivaebecomeyellow
Other Forms of Cutaneous LEVerrucous LE (Hypertrophic)• Non-pruritic,papulo-nodularlesionsonarmsandhands• ResemblesKA’sorLP• TreatwithILTAC
LE-LP Overlap Syndrome• SeeLPsection
Chilblain Lupus Erythematosus• Chronic,unremittingformwithlesionsonfingertips,ears,calves,andheels• Lesionsareduetocold• TreatmentisthesameasLE
LE Panniculitis• Deepdermalandsubcutaneousnodules,rubbery-firm,sharplydefined,andnontender• Head,face,upperarms,chest,buttocks,thighs• Chronic,inwomen20-45yearsold• DLEatothersites,commonly• Healswithatrophyanddeepdepressions• Treatwithantimalarialsformanymonths
Subacute Cutaneous Lupus• Scalypapulesthatevolveintoeitherpsoriasiformorpolycyclicannularlesions(morecommonly)
• Telangiectasiaanddyspigmentationalwayspresent• Nofollicularinvolvement• Noscarring• Occursonsun-exposedsurfacesoffaceandneck,innerarms,axillaeandflanks• Sparesknuckles• Photosensitivityin40%• Hardpalateinvolvedin40%• ConcomitantDLEin20%• AtleasthalfofthepatientsmeetARAcriteriaofSLE (usuallyhavearthralgia,arthritis,leukopenia,positiveANA)
• Diseaserunsamildcourse
uTIPa Majority positive for anti-Ro
a Drugs that may induce: HCTZ, enicillamine, glyburide, griseofulvin, piroxicam, spironolactone, diltiazem, ACE inhibitors, terbinafine
General Dermatology 109
Neonatal LE• AnnularscalingerythematousmaculesandplaquesonheadandextremitieswithinthefirstfewmonthsoflifeinbabiesborntomotherswithLE,rheumaticdisease,orotherconnectivetissuedisorders
• 50%mothersasymptomaticatdelivery• Lesionsresolvespontaneouslyby6months,healingwithoutscarring• Photosensitivitymaybeprominent• 75%ofcasesinvolvegirls• Thrombocytopeniaandhepaticdiseaseasfrequentascardiacdisease
Complement Deficiency Syndromes• MostcommonlyC2andC4• Photosensitivity• AnnularSCLElesions• Roantibodyformation
Systemic LECriteria: 4 Needed• Malarerythema• DiscoidLE• Photosensitivity• Oralulcers• Nonerosivearthritis• Serositis(carditisorpleurisy)• Nephropathy• CNSdisorder(seizureorpsychosis)• Hematologicdisorder• Immunologicdisorder(positiveLEcellpreparation,anti-DNAorSm,false-positiveRPR)• PositiveANA
Cutaneousmanifestations •Butterflyfacialerythema,maybeassociatedwithedema→ lastsdaystoweeksandhealswithoutscarring
•Bullouslesions,sun-exposedareas→ histologicallylikeEBAwithantibodiesagainstcollagenTypeVII,butrespondstodapsone(EBAdoesnot)
•Fingertipsandtoetipsshowpuffyerythema,telangiectasias •Periungualtelangiectasias •Redlunulae •Erythematoustopurplishpalmsandsoles •Telangiectasiasonfaceorelsewhere •Diffusenonscarringhairlosswithshort,broken-offhairsinfrontalregion •Multiple(>15)dermatofibromas •Vasculitissecondarytoantiphospholipidantibody •Cryoglobulinemia,livedoreticularis,thrombophlebitis,cutaneousinfarction •Erythemamultiforme-likelesions(Rowell’ssyndrome) •Calcinosiscutis •Plaque-likedepositionsofmucin
uTIPa 50%havecongenitalheart
block,whichispermanent(thismaybetheonlymanifestationofdisease)
110 2011/2012 Dermatology In-Review l Committed to Your Future
Pregnancy and SLE• Miscarriagesoccurwithgreaterfrequency• LEmayworsen,orgointoremissionduringpregnancy• Fetaldeathriskincreasedwithanti-cardiolipinoranti-Roantibodies• Postpartumperiodshowsthehighestrisktothepatient
Drug-induced LE• Usuallybenigncourse• Hydralazine→ 14%,withslowacetylators(HLA-DR4)
more prone• Procainamide→ 50%oftreatedpatients• Anti-histoneantibodycloselyassociatedwithsymptomaticdisease
• Penicillamineinducesnativedisease,withanti-dsDNAAb’s• HCTZinducesSCLE
4.22 SCLERoDERmAChronicdiseaseofunknownetiologyaffectingthemicrovasculatureandlooseconnectivetissue.
ClassificationLocalized Scleroderma• Morphea→ mostcommontype• Generalizedmorphea→ morphea,symmetricandbilaterallesions;butabsenceofRaynaud’s,acrosclerosis,andorganinvolvementdifferentiatesfromSSc
• Guttatemorphea(LS&A)• Nodularmorphea• Subcutaneousmorphea(morpheaprofunda)• Linearscleroderma→ bandlikelesionsthatmayinvolvethedeeperlayersoftheskin
Systemic Sclerosis• Limited(lSSc):60%,includesCRESTsyndrome;70-80%haveanti-centromereantibodiesandsystemicinvolvementmaynotappearforyears;patientsareolderthandSScandmanyoutlivethedisease;bettersurvivalrate(50%at12years)
• Diffuse(dSSc):AbruptonsetofswellingofthehandsandfeetwithRaynaud’sandhideboundchangesintheskin;polyarticularsymmetricsynovitis,tenosynovitisandtendonfrictionrubsoftenpresent;nailfoldcapillarydilatationanddestruction
• Earlyonsetofinternalorganinvolvement;anti-topoisomerase1antibodies(SCL-70)in30%;worsesurvivalrate(15%at12years)
EpidemiologyLocalized Scleroderma• Women:men3:1• Morecommoninwhites
Systemic Sclerosis• Women:men4:1• Morecommoninblackwomen,withdiffusediseasemorelikelytoaffectblackwomen• 7-yearsurvival75%
uTIPa Hydralazine, procainamide, sulfon-
amides, penicillin, anticonvulsants, minocycline, and INH
a Drug-induced LE not usually associated with skin, renal, and CNS manifestations
General Dermatology 111
Scleroderma-like Disorders •Bleomycin:PulmonaryFibrosis,Raynaud’s,andcutaneous
changesindistinguishablefromSSc(reversibleupondiscontinuationofdrug)
•Scleroderma-likeskinchangesseeninscleromyxedema,PCT,GVHD
ClinicalLocalized Morphea• Circumscribedscleroticplaqueswithivory-coloredcentersandviolaceousborders(ifdiseaseactive)
• Plaquesmaybeelevatedordepressed,areinduratedbutnotboundtothedeeperstructures
• Mayoccurafterradiationtherapy• Allformsoflocalizedmorpheahavegoodprognosiswithdiseasebecominginactiveinthreetofiveyears
Generalized Morphea• Widespreadinvolvement• Multipleinduratedplaquesandhyperpigmentation• Uppertrunk,abdomen,buttocks,andlegs• Notassociatedwithsystemicdisease
Guttate Morphea (LS&A)• Multiplesmallchalk-whitelesionsthatlackthefirmcharacterofmorphea
Nodular Morphea• Lesionsresemblekeloids• Maycoexistwithmoretypicallesionsofmorphea
Morphea Profunda(SubcutaneousMorphea)• Deep,bound-down,scleroticplaques
Atrophoderma Pierini and Pasini• Idiopathicatrophyoftheskincharacterizedbysingleorseveraldepressedareasofskin• Lesionsarewell-definedwitha“cliffdrop”border
Linear Scleroderma• Single,unilaterallinearband• Lowerextremitiesaremostfrequentsite• Upperextremities,frontalhead(coup de sabre),thoraxalsoinvolved• Differentiatefrommorpheabyinvolvementofdeeperlayersofskinwithfixationtounderlyingstructures
• Maycauseseveredeformity• Maybeassociatedwithspinabifidaocculta
Melorheostosis• Linear,dense,corticalhyperostosis• Affectsaninvolvedlimbusually,butmaybewidespread
Parry-Romberg Syndrome• Facialhemiatrophy;maybeformoflinearscleroderma• Hyperpigmentationfollowedbyatrophyofthedermis,subcutaneousfat,muscle,andsometimesthebone
uTIPa Polyvinylchloride → scleroderma
withhepaticandpulmonaryfibrosis
112 2011/2012 Dermatology In-Review l Committed to Your Future
Systemic Sclerosis• InitialcomplaintsrelatedtoRaynauld’sorchronicnonpittingedemaofthehandsandfingers
• Painandstiffnessofthefingersandknees• Firstmanifestationmaybemigratorypolyarthritis• Usually,skinchangesprecedevisceralinvolvementbyseveralyears• Diseaseextendstoupperextremities,trunk,face,andfinallythelowerextremities• Periorbitaledemamayoccurintheearlyedematousphase• Facebecomesmask-like• Lipsthin,andopeningofthemouthbecomesconstricted(microstomia)• Painfulindurationofthegumsandtongue• Matliketelangiectases• Thinningorcompletelossofhairandanhidrosis• Generalizedhyperpigmentationwithoutadrenalinsufficiency• Focalhyper/hypopigmentation• PeriungualtelangiectasiaoccurslikeinSLEandDM;75%ofthosewithsschaveenlarged,dilatednailfoldcapillariesforminggiantloops
• Recurrentpainfululcerationofthefingertipsandslow-healingulcersoftheknuckles• Boneresorptioncausingdissolutionoftheterminalphalanges• Cutaneouscalcificationoverfingertipsandoverbonyprominences→ mayulcerate
Systemic Involvement in SSC• Esophagealdysfunctionismostcommon(>90%)• Dysphagiafromdecreasedperistalsis,andmayoccurbeforeskinfindingsseen• Heartburn• Smallintestineinvolvementgivesrisetoconstipation,diarrhea,bloating,andmalabsorption• PulmonaryFibrosis• Earlypulmonaryinvolvementwithlowereddiffusingcapacityofthealveolocapillarymembranecorrelateswithchangesofthenailfoldcapillaries
• Cardiacconductiondefects,heartfailure,pericarditiswitheffusion;myocardialfibrosisseenin50-70%ofSSc
• Renaldiseasewithslowlyprogressiveuremia
CREST Syndrome• Telangiectasiasonface,uppertrunk,hands• Developslaterinlife• Esophagealdysfunctionisidenticaltothatofthemoresevereformsofthedisease• Anti-centromereantibodiesin50-96%,butonly12-25%inthosewithdSSc• Mixedconnectivetissuedisease:combinedfeaturesofscleroderma,LE,andmyositis→ hightiterstoribonucleoprotein
PathogenesisThreeprocessesoccur• Damagetovascularendothelium• Immunologicandinflammatoryactivation• Dysregulatedextracellularmatrixmetabolism
Course• Morpheaandlinearscleroderma→ fewmonthstomanyyears• 50%ofpatientswithlesionsthatdisappearareleftwithareasofhypo-ordepigmentation
General Dermatology 113
• Coup de sabrelesionsmayremainunchangedorbecomemoreextensive• LimitedSScrarelyprogressestodSSc• VisceralinvolvementultimatelydevelopsindSSc• 5yearmortalityfordSScisabout50%→ pulmonaryfibrosisandrenalhypertensivecrisisindSSc;pulmonaryhypertensioninlSSc
ManagementLocalized Scleroderma• Generallyself-limited,sonotreatmentnecessary• HighpotencytopicalsteroidstolesionsaugmentedbyILsteroids• Antimalarials,phenytoin,colchicine,andsystemicsteroidshavelittlebenefitingeneralizedmorphea
• D-penicillaminemaysoftenskin,allowtheresumptionofskingrowth,andthecessationofnewlesions
• HighdoseUVA1(340-450nm)formorphea
Systemic Sclerosis• Azathioprine,chlorambucil,methotrexate,cyclophosphamidevariablysuccessful• Systemicsteroidsdonotaltertheoveralldiseasecourse• Cyclosporinemayresultindecreaseinskinthickness,butpulmonaryfunctionremainsunchangedandrenalfunctionmayworsen
• Extracorporealphotophoresisverycontroversial• D-penicillaminemaybeeffectiveifusedinearlydisease,withimprovedsurvivalcurvesinpatientsbecauseoflowerincidenceofrenaldisease;sideeffectslimitlong-termuse:autoimmunelupus/polymyositis,pemphigus,nephroticsyndrome,myastheniagravis,andGoodpasturesyndrome
• ACE-inhibitorsmarkedlyimprovesurvivalbytreatingrenaldisease• Peripheralvasospasmtreatedwithdiltiazem• Calcinosistreatedwithcalciumchannelblockers• Refluxesophagitiswithproton-pumpinhibitors• Physicaltherapy• CessationofsmokingdecreasesmorbidityinthosepatientswithdocumentedRaynaud’s
4.23 DERmAtomyoSItISWithorwithoutskinlesions,weaknessofproximalmusclegroupsistheprominentfeature.
Cutaneous Findings• Heliotroperash:Violaceouserythemaandswellingofperiorbitalskin• Gottron’spapules:Flat-topped,violaceouspapulesoverMCP,PIP,DIPjoints• Periungualtelangiectasiaswithfrayedcuticles• Erythematousorurticarialpatchesandplaquesonupperportionoffaceandextremities• Photosensitivity• Hyperkeratosis,scaling,fissuring,andhyperpigmentationoverthefingertips,sidesofthumb,andfingers
• “Mechanic’shands”• Raynaud’sphenomenon• Poikilodermaofchestorback(Shawlsing),Oronlateralthighs(Holstersign)• Calcinosiscutis:MoreofteninkidswithDermatomyositis
114 2011/2012 Dermatology In-Review l Committed to Your Future
Muscle Changes• Symmetricweaknesswithswellingandpain,involvingshoulder• Difficultyswallowing,talking,orbreathing• Cardiacdiseaselateindisease• Skineruptionprecedesmusclesymptomsbytwotothreemonths• Amyopathicdermatomyositis:lackofmuscleinflammationafterayearorlonger
Associated Diseases• Sclerodermatouschanges→ sclerodermatomyositis(anti-KUantibodies)• Othercollagenvasculardiseases• Presenceofanti-Jo-1antibody,aswellasanti-PL-7,anti-PL-12(anti-synthetaseantibodies)correlateswellwithpulmonarydisease
Neoplastic Risk• Cancercanprecede,occursimultaneouslyas,orfollowDM• Malignancyusuallyin5thor6thdecadeoflife,andmorecommoninwomen
Incidence• Twiceasprevalentinwomen• Bimodalpeak:Smallpeakinchildrenandlargepeakinadultsbetween40and65
Laboratory Findings• Creatininekinase,aldolase,LDH,andtransaminaseelevations(AST>ALT)
• PerformEMGandMRItofinddiseaseactivity• Pulmonaryfunctiontests• Bariumswallowforesophagealdysmotility
Myositis Specific Antibodies(MSAS)• PositiveANAin60-80%ofpatients• Anti-Mi-2• Anti-p-155(linkedtocancerassociatedmyositisandamyopathicdermatomyositis)• Anti-Jo-1• Anti-CADM-140(inpatientswithamyopathicDM)• Anti-Ku,Anti-Srp
Treatment• Systemiccorticosteroids• Azathioprine• Methotrexate• Sunscreens• Antimalarials• Mycophenolatemofehl• Cyclophosphamide• Treatcalcinosiswithaluminumhydroxide,diphosphonates,diltiazem,colchicine,lowdosewarfarin
uTIPaOvarian cancer is overrepresented
uTIpaChildhood DM
• BrunstingType:morecommon,slowcourse,progressiveweakness,calcinosis,teroidresponsive
• BankerType:vasculitisofmusclesandGItract,rapidonsetofsevereweakness,steroidunresponsive,anddeath
uTIpa�Anti-Mi-2 AB’s correlate with shawl
sign, cuticular changes, and good prognosis
a�Anti-Jo-1 AB’s correlate with pulmonary fibrosis, Raynaud’s, polyarthritis
a�Anti-SRP AB’s correlate with cardiac disease and poor rognosis
a�Anti-Ku AB’s correlate with sclerodermatomyositis
General Dermatology 115
Course• Majorcausesofdeatharecancer,ischemicheartdisease,andlungdisease
4.24 SjoGREN’S SyNDRomETriad
• Keratoconjunctivitissicca• Xerostomia• Rheumatoidarthritis• Morethan90%women• Vasculitis→ palpablepurpura• PatientsdeveloplymphoreticularmalignancysuchasNHL
Laboratory• Labialsalivaryglandbiopsy• SchirmerTestforxerostomiadetectsdiminishedglandularsecretion• RFpositive• Positivecryoglobulins• Anti-Ro• Anti-La• Antibodiestofodrin(93%specific)
4.25 CoNNECtIVE tISSUE DISEASE: SERoLoGy
Double-Stranded DNA Antibodies (dsDNA)• ELISAusedmorethanIF• PerformedonCrithidiaeLuciliae→ possessesgiantmitochondrionwithnossDNA• PositivityhighlycharacteristicofSLE→ highlycorrelativewithpositiveDIFinpatient’snormalskin(lupusband),lowcomplementlevels,renaldisease,andpoorprognosis
• HighlypositivelevelsconfirmdiagnosisofSLE;lowlevelsfoundinRA,Hashimoto’s,Grave’s,Waldenstrom’s,MCTD,SSc,Sjogren’s,autoimmuneliverdisease
• NegativetestdoesnotexcludeSLE(50-83%sensitive)
Single-stranded Antibodies• Verylowdiagnosticvalue→ detectedinLEandotherCTD’s(DM,morphea,Sjogren’s,andlinearmorpheaofchildren)
RNP Antibodies• Smallribonucleoproteins(SRNP)• SS-A(Ro),SS-B(La),SM,andU1RNP
Anti-Ro Antibodies• FoundinLE(varyingpercentagesbasedonsubsetofLE)andSjogren’s(50%)
• Stronglyassociatedwithphotosensitivity(especiallyinSCLE)
Anti-La Antibodies• Morethan90%withpositiveanti-Laalsopositiveforanti-Ro• Associateddiseasessimilartothoseassociatedwithanti-Ro
uTIPaHistoneAntibodies
• Characteristicofdrug-induced
SLE → >90%ofpatients • 30%ofpatientswithidiopathic
SLEhaveanti-histoneAb’s
uTIPa 100%ofpatientswithMCTD
116 2011/2012 Dermatology In-Review l Committed to Your Future
Ro and La Helpful in Workup of Photosensitivity• ConfirmclinicaldiagnosisofSCLE,Sjogren’s,orneonatalLE• Patientswithchronicidiopathicvasculitis• UsefulintestingANAnegativepatientswithclinicalmanifestationsofsleorscle
Anti-U1RNP • 30%ofpatientswithSLE;patientswithSLEandanti-U1RNPalsohaveotherpositiveserologies
• MajorityofpatientswithpositiveU1RNPhaveSLEratherthanMCTD• Presenceassociatedwithsclerodactyly,Raynaud’s,esophagealdysmotility
Anti-Sm• DiagnosticofSLE,andnotreportedinpatientswithotherCTD’s• Foundin15-40%ofpatientswithSLE• Mostpatientswithanti-SMalsohaveantibodiestoU1RNP(converseisnottrue)
ANAsubstrate → humanHep-2cells;aserumnegativeonanimalsubstratemaybepositiveonhumancellsTiter→ negative or low in young andhealthypersons;highinthosewithsystemicCTD;lessthan1:80hasnodiagnosticvalue.
Patterns– Peripheral→ SLE → stainingnativeDNA(mostspecificpatternforSLE)– Homogeneous→ SLE → stainingnativeDNA,histones– Nucleolar→ SSc,SLE → stainingnucleolarRNA– Centromere→ CREST → stainingkinetochore– Speckled→ MCTD,SLE,SSc,Sjogren’s→ stainingribonucleoproteins
• ANA-negativeSLE → determinedoftenonanimalsubstrates,yetlaterfoundtobepositiveonhumancells,orifpatientonlymakesantibodiestossDNA(notdetectedbymosttests)
• AlmostallpatientswithSLEhavepositiveANAs• ANA:highnegativepredictivevalue,lowpositivepredictivevalue
Antiphospholipid Antibodies• Alsocalledthelupusanticoagulantandanticardiolipinantibodies• Associatedwiththrombosis(notbleeding)• MostprevalentinSLEpatients• Seeninpatientstakingcertaindrugs(cocaine,IFN-α,procainamide,hydralazine,quinine,quinidine,phenytoin,fansidar,phenothiazines),chronicinfections
• Indicationsfortesting– Livedoreticularis– Purpuraandnecrosis– Ulcers– Internalorganthrombosis– Recurrentmiscarriages– ScreeninginpatientswithSLE
uTIPaOther Antibodies
• Scl-70 (anti-topoisomerase) → characteristic of SSc, and defines presence of systemic involvement
• Anti-centromere → marker for creSt syndrome • Anti–jO-1 (histidyl trnA synthetase) seen in minority
of patients with dm and polymyositis → associated with pulmonary involvement and mechanic’s hand skin lesions
General Dermatology 117
Table4-3.AntinuclearAntibodyPatterns
Pattern Associated Antibody Associated Disorder
Homogenous anti-histone SLEfalse+,DruginducedLE,SLE
Rim(peripheral) anti-dsDNA SLEnephritis
Speckled(finespeckled) anti-SmantiRoandLa(SSA/B)anti-U1RNPanti-Kuanti-topoisomerase(Scl-70)
SLESLE,SjogrenssyndromeSLE,MCTDSLE,scleroderma,myositisScleroderma,SLE
Centromere(discretespeckled) anti-kinetochore CREST
Nucleolaranti-RNApolymeraseanti-PM-Scl
anti-U1RNP Scleroderma,SLE
4.26 RELAPSING PoLyChoNDRItIS• Intermittentepisodesofinflammationofthearticularandnonarticularcartilage• Resultsinchondrolysis,dystrophy,andatrophyofthecartilage• Bothsexesequallyaffected• Onsetin4thto5thdecade
Clinical• Beefyredinvolvementoftheearsconfinedtothecartilaginousportion• Oftenunilateral• Acuteflareofinflammationlasts1-2weeks• 85-90%ofpatientsdevelopauricularchondritis• Conductivedeafnessbecauseofswollencartilage• Recurrentepisodesofchondritisresultindestructionofnormalcartilaginousstructuresandtheirfibroticreplacement→floppyorcauliflowerears
• Nasalseptalcartilageinflamed(50-70%)→rhinitis,crusting,bleeding,andsaddle-nosedeformity
• Involvementofbronchiresultsinhoarseness,coughing,anddyspnea• Migratoryarthralgiaseenin50-80%• Oculardisease:conjunctivitis,scleritis,iritis(anypartoftheeyemaybeaffected)• Cardiovascular:aorticregurgitationandaorticaneurysm• 1/3haveassociatedrheumaticorautoimmunediseaseandmanyhaveLCV
Laboratory• ElevatedESR
MAGIC Syndrome• Behçet’sandrelapsingpolychondritissimultaneously(mouthandgenitalulcerswithinflamedcartilage)
118 2011/2012 Dermatology In-Review l Committed to Your Future
Pathophysiology• Autoimmunity:IgGanti-typeIIcollagenantibodieswithtiterscorrespondingtodiseaseactivity→foundinupto50%ofpatientswithrelapsingpolychondritis(inonly15%inthosewithRA)
• AntibodiesdirectedagainstnativeandnotdenaturedcollagenII• TypeIIcollagenrestrictedtocartilage
Course• Unpredictable;chronicandvariablewithepisodicflares(usually1-4weeks)andspontaneousremissions
• Peripheralarthritispredictsaworsecourse• Causesdeathin1/3ofpatientssecondarytoairwaycollapse,cardiovascularcomplications,andinfection(secondarytosystemicsteroids)
Treatment• Dapsone100mgQDtoBIDwithmaintenancedosefor4-6months→butmaybeineffectiveincontrollingscleralinflammation
• Systemicsteroids• Cyclosporine• NSAIDs• TNF-alphainhibitors
4.27 bEhCEt’S DISEASERecurrent Oral Ulceration
• Recurredatleast3timesin12monthperiod
Plus 2 of the Following:• Recurrentgenitalulceration• Eyelesions(posterioruveitis)• Skinlesions(erythemanodosum,pseudofolliculitis,papulopustularlesions,oracneiformnodules)
• Positivepathergytest
Clinical Features• Lesionsarepainful• CNSlesionsoccurandgivepictureofmultiplesclerosis• Thrombophlebitis• Thrombosisofthesuperiorvenacava• Asymmetric,non-erosivepolyarthritis• AssociatedwithHLA-B51
Treatment• Sucralfate• Colchicine• Dapsone• Thalidomide• TNF-inhibitingagentssuchasinfliximabandetanercept
General Dermatology 119
4.28 LIVEDo REtICULARISPhysiologic
• Cutismarmorata
Intravascular Obstruction• Stasis• Cardiacfailure• Emboli• Cryoglobulinemia• Anticardiolipinsyndrome• Hyperoxaluria• Arteriosclerosis• Hyperparathyroidism• Arteritis(PAN,rheumatoidarteritis,LE,DM,syphilis,TB,pancreatitis)
Drugs• Amantadine,quinine,quinidine
4.29 LEUkoCytoCLAStIC VASCULItISDiversegroupofdisorders:combinesegmentalinflammationwithnecrosisofbloodvessels.
Maybeprimary,afeatureofasystemicdisorder,oridiopathic.
Pathogenesis• Postulatedthatcirculatingimmunecomplexesarelocallydeposited.Thecomplexesactivatecomplement,andthusattractneutrophils,whichreleaselysosomalenzymesanddamagetissue
• ANCAs,antineutrophilicautoantibodies– C-ANCAs(cytoplasmic)—specificforproteinase3– P-ANCAs(perinuclear)—specificformyeloperoxidase
• SeenwithhepatitisCinfection.ANCAsproducenecrotizingvasculitisbyactivatingcirculatingPMNsandmonocytes,whichthenadheretobloodvessels,degranulate,andreleasetoxicoxygenmetabolitestocausevascularinjury
Clinical Manifestations• Palpablepurpura–non-blanchingerythematouspapules• Papules,urticaria,angioedema,pustules,vesicles,ulcers,necrosis,andlivedoreticularis• Usuallyoccursonlowerextremitiesoroverdependentareassuchasthebackandglutealregions.Uncommononface,palms,soles,andmucousmembranes
• Palpablepurpurapersists1-4weeks,resolvingoftenwithtransienthyperpigmentationand/oratrophy
• Symptoms:pruritus,burning,andpainlesscommonly.Episodeassociatedwithfever,malaise,arthralgias,andmyalgias
Associated Chronic Disorders• Rheumatoidarthritis• Sjogren’ssyndrome• SLE
120 2011/2012 Dermatology In-Review l Committed to Your Future
• Dermatomyositis• Hypergammaglobulinemicpurpura• Mixedconnectivetissuedisease,relapsingpolychondritis,andscleroderma• Paraneoplasticvasculitis• AssociatedmalignanciessuchasHodgkin’s,lymphosarcoma,adultT-cellleukemia,mycosisfungoides,myelofibrosis,AML,CML,IgAmyeloma,diffuselargecellleukemia,hairycellleukemia,squamouscellbronchiogeniccarcinoma,prostatecancer,renalcellcarcinoma,andcoloncarcinoma
• Cryoglobulinemia• ParticularlymixedtypesIIandIII• OccurinidiopathicLCV• AssociatedwithhepatitisA,B,andC• Cysticfibrosis• IBDofthecolon• Behçet’sdisease
ANCA’s• SeenwithhepatitisCinfection• Palpablepurpura
Antiphospholipid Antibodies• Livedoreticularisismostcommonfinding
Precipitating Infections• GroupAβhemolyticstreptococci• Staphylococcus aureus• Mycobacterium leprae–erythemanodosumleprosum,cutaneousnodularlesionsofleprosy,involvescapillaries,venules,arterioles,veins,andsmalltomediumsizedarteries
• HepatitisB• HIV• N. meningitidis • RockyMountainspottedfever• Catheterinfections
Precipitating Drugs• Penicillin• Sulfonamides• Thiazides• Allopurinol• Phenytoins• NSAIDs• PTUandhydralazineinassociationwithancas• Streptokinase• Radiocontrastmedia• Monoclonalantibodies• G-CSF
General Dermatology 121
Idiopathic DisordersHenoch-Schonlein Syndrome• Mostwidelyrecognizedsubgroup• Mostlychildren• RecentURIin75%• Involvesskin,synovia,GItract,kidneys• Skinlesionsofadultsshowblistersandnecrosis• Long-termmorbidityfromkidneydisease,whichispredictedbythespreadofpurpuratotheuppertrunk
Acute Hemorrhagic Edema of Childhood• Affectschildrenandinfants<2yearsofage• Painful,edematouspetechiaeandecchymosesonheadanddistalextremities• Triggeringfactors:Infection,drugs,immunization• LackssystemicfeaturesofHSP,andresolveswithin1-3weekswithoutsequelae
Urticarial Vasculitis• Episodesofrecurrenturticariaandangioedema• Occurswithserumsickness,connectivetissuedisorders,infections(HepBandC,infectiousmononucleosis),physicalurticarias,coloncarcinoma,administrationofpotassiumiodide,fluoxetine,NSAIDs,andasanidiopathicdisorder
• Lesionsoftenpersistfrom3-5days,andusuallyhealwithoutresidua.Episodesarechronic,rangeindurationfrommonthstoyears
• 70%afflictedarewomen• Generalfeatures:Fever,malaise,andmyalgia,withpossiblelymphadenopathyandhepatosplenomegaly
• Episodicarthralgias• Renal:DiffuseGNorglomerulitis• GI:Diarrhea,nausea,vomiting• Pulm:Laryngealedema• Eye:Conjunctivitis,uveitis,episcleritis• CNS:Headaches,pseudotumorcerebri
Nodular Vasculitis• Recurrent,tender,red,subcutaneousnodulesoverlowerextremities,especiallythecalves;lesionscanoccuronthighs,buttocks,trunk,andarms
• Nosystemicmanifestations• Womenbetween30and40• Erythemainduratum:formofnodularvasculitisassociatedwithM. tuberculosis
Livedoid Vasculitis (AtrophieBlanche)• Recurrentpainfululcersoflowerextremitiesinassociationwithpersistentlivedoreticularis;oftendeeppurpleincolor
• Atrophieblanche:Healedlesionsresultinscleroticpaleareassurroundedbytelangiectases• Associatedwitharteriosclerosisorstasis• Pathogenesismaybesecondarytofibrinthrombiinlumensofsuperficialvessels• Sneddon’ssyndrome:Livedoreticularisandlivedoidvasculitisassociatedwithischemiccerebrovascularlesions,hypotension,andextracerebralarterialandvenousthromboses
uTIPa
Schnitzler’s syndrome: episodes of urticarial vasculitis that occur in association with monoclonal IgM M component. Fever, lymphadenopathy, hepatosplenomegaly, bone pain, and sensorimotor neuropathy
122 2011/2012 Dermatology In-Review l Committed to Your Future
Genetic Domplement Deficiencies• C2,C4aandC4bseeninsomepatients
Eosinophilic Vasculitis• Idiopathicsyndromewithrecurrentpruritic,purpuric,papularskinlesionswithangioedema• Also,urticarialplaquesandpalpablepurpurapresent• Infiltrateofeosinophils
LCV Treatment• H1antihistaminesusedwithpalpablepurpuratoalleviatelesionalsymptoms• H1blockerswithNSAIDs• Colchicineorhydroxychloroquinecanbeaddedtoorsubstitutedfortheseagents;nobenefit,thenusedapsone
• Systemicsteroids,azathioprine,cyclophosphamide,plasmapheresis,cyclosporine• IFN-alphaclearslesionsinHepC
Urticarial Vasculitis• H1blockers,indomethacin,colchicine• Systemicsteroidsalleviatesurticariaandsystemicproblems
Erythema Elevatum Diutinum• Dapsone
Nodular Vasculitis• NSAIDs,colchicine,systemicsteroids
Erythema Nodosum Leprosum• Thalidomide
Livedoid Vasculitis• Aspirin,dipyridamole,colchicine,low-doseheparin,systemicglucocorticoids,andlowmolecularweightdextran,nifedipine,pentoxyfylline
4.30 CRyoGLobULINEmIA AND CRyoFIbRINoGENEmIACryoglobulinemia
Circulatingimmunoglobulinscomplexedwithotherimmunoglobulinsorproteinsthatrevers-iblyprecipitateinthecold.
Type I• Singlemonoclonalimmunoglobulin,usuallyIgGorIgM• Usuallyanunderlyingβ-cellmalignancysuchasmyelomaorlymphoma• AssociatedalsowithCLLandWaldenstrom’smacroglobulinemia• Purpura,acrocyanosis,retinalhemorrhage,Raynaud’sphenomenon,andarterialthrombosis
Type II (MixedCryoglobulinemia)• MonoclonalIgMrheumatoidfactorcomplexedwithpolyclonalIgG• Multiplemyeloma,Waldenstrom’s,CLL,rheumatoidarthritis,Sjogren’s,HepatitisC• LCVwithpalpablepurpura,arthritis/arthralgias,andvascularpurpura
General Dermatology 123
Type III (MixedCryoglobulinemia)• RheumatoidfactorsthatarepolyclonalIgMandIgG,complexedwitheachotherorwithanotherprotein
• Oftencomplementactivatedandcomplementlevelsarelower• SLE,RA,Sjogren’s,infectiousmononucleosis,CMVinfection,primarybiliarycirrhosis,HepatitisB,HepatitisC
• LCVwithpalpablepurpura,arthritis/arthralgias,andvascularpurpura
Essential Mixed Cryoglobulinemia• Cryoglobulinsandthemanifestationofsymptomswithoutanidentifiableconnectivetissue,neoplastic,orinfectiousprocess
• OftenHCVinfectioncoincides
Clinical Features• Purpura,livedo,Raynaud’s,distalulcerations• Affectedorgansareskin,kidneys,liver,musculoskeletal,andnervoussystems
Cryofibrinogenemia• Cryoproteinsinanticoagulatedbloodorplasmathatreversiblyprecipitateinthecold• Composedoffibrinogen• Cutaneousmanifestations:purpura,ecchymoses,gangrene,ulcers• Associatedwithmalignancy,thromoembolicdisease,diabetes,pregnancy,oralcontraception,andpseudotumorcerebri
4.31 ACANthoSIS NIGRICANSCutaneousmarkerofeitherinsulinresistance,malignancyorobesity.
Clinical• Grayish-brown,velvetyplaques,hyperpigmentation,papillomatous• Mostcommontoleastcommonareas:axillae,neck,externalgenitalia,groin,face,innerthighs,antecubitalandpoplitealfossae,umbilicus,perianalarea
• Achrochordons• Tylosis:Palmoplantarhyperkeratosiswithacanthosispalmarisorpachydermatoglyphy(exaggerationoffingerprints,ortripepalms)
• Mucosalinvolvementconsistingofthickeningandpapillomatosiswithminimalhyperpigmentation
Associated Conditions• Insulinresistance,associatedwithobesity,withpositivecorrelationbetweendegreeofANandseverityofobesity
• Lipodystrophies(Lawrence-Seipsyndrome)• Leprechaunism–elfinappearanceofface,thickenedskin,absenceofsubcutaneousfat,andhirsutism
• TypeAsyndrome:Severeacanthosisnigricans,hirsutism,clitoromegaly,andmasculinehabitus• TypeBsyndrome:ANafterteenageyearswithlessextensiveinvolvement,withoftenunderlyingSLE(anti-insulinreceptorauto-antibodies)
• Malignancy:Moreextensiveandinvolvesmucosalsurfaces;usuallyadenocarcinomas(gastric)• Drugs:testosterone,nicotinicacid,diethylstilbestrol,oralcontraceptives,triazinate,glucocorticoids,topicalapplicationoffusidicacid
124 2011/2012 Dermatology In-Review l Committed to Your Future
4.32 LIPoDyStRoPhy
Partial Lipodystrophy• Etiologyunknown• Lossofsubcutaneousfatinclearlydemarcated,generallysymmetricareas• Beginsonface,spreadsdownward,stoppingatanylevel→facebecomecachectic,withdisappearanceofbuccalfatpads;prematureagedexpression;sunkeneyes;easyvisualizationofveins
• Lowerpartofbodymaybeaffectedwithoutupperpartbeingaffected• Excessfatdepositionoverhipsandthighsfrequentlyinwomen• 80%female,andusuallybeginsbeforeage15
Laboratory• Hypertriglyceridemiaandinsulinresistance• Clinicallyapparentdiabetesin20%• Decreasedserumcomplement(C3)• IncreasedC3nephriticfactor→immunoglobulinthatbindsFactorH,aninhibitorofC3,allowinguncontrolledC3activation
• Glomerulonephritis(unknownfrequency)
Treatment• Noeffectivetherapy
Generalized Lipodystrophy• Etiologyunknown• Lackbothsubcutaneousfatandextracutaneousadiposetissue• Congenital(Seip-Lawrencesyndrome)• Acquired(Berardinelli-Seipsyndrome)• Often,acanthosisnigricans,hypertrichosis,generalizedhyperpigmentation,andthick,curlyscalphair
• Patientshavevoraciousappetites,perspireexcessively,andmaybeheat-intolerantdespitenormalthyroidfunction(elevatedbasicmetabolicrate)
• Muscles,genitaliaappearhypertrophic• Mentalretardationiscommon
Laboratory and Internal Disease• Glucoseintolerance(lipoatrophicdiabetes);insulinresistancedetectedearlierthandiabetes• Hepatomegalyresultingfromincreasedfat;cirrhosismaydevelop• Renal,retinal,andneuropathicdiabeticchanges• CTandultrasoundshowreducedfataroundviscera• Eruptivexanthomasmayappear
Treatment• Noeffectivetreatment
General Dermatology 125
4.33 hyPERLIPoPRotEINEmIASType I
• Familiallipoproteinlipasedeficiency(AR)orapoproteinCIIdeficiency• Increasedchylomicrons• Eruptivexanthomas,lipemiaretinalis• Associatedwithhepatomegaly,pancreatitis,abdominalpain(“horrible,screamingpain”)
Type IIa• Familialhypercholesterolemia,commonhypercholesterolemia(AD)• IncreasedLDL• Tendinous,tuberous,xanthelasma,arcusjuvenilis,planar,eruptive• Secondarilycausedbyhepatoma,obstructivebiliarydisease,porphyria,hypothyroidism,anorexia,nephroticsyndrome,Cushing’s
• Atherosclerosis
Type IIb• Familialhypercholesterolemia(AD)• IncreasedLDLandVLDL• Tendinous,tuberous,xanthelasma,arcusjuvinilis,planar• SecondarilycausedbynephroticsyndromeandCushing’ssyndrome• Atherosclerosis
Type III• FamilialDysbetalipoproteinemia(AR)• IncreasedIDL• Palmar,planar,tendinous,tuberous,eruptive,intertriginousxanthomas• Secondarilycausedbyparaproteinemia• Atherosclerosis• Associatedwithdiabetes,gout,andobesity
Type IV• Familialhypertriglyceridemia(AD)• IncreasedVLDL• Eruptive,tendinous,tuberous• Secondarilycausedbydiabetes,uremia,paraproteinemia,alcoholism,lipodystrophy,obesity• Atherosclerosis
Type V• FamilialtypeVhyperlipoproteinemia,familiallipoproteinlipasedeficiency(AD)• IncreasedchylomicronsandVLDL• Eruptive,lipemiaretinalis• Secondarilycausedbydiabetes,obesity,andpancreatitis• Associatedwithhepatomegaly
126 2011/2012 Dermatology In-Review l Committed to Your Future
4.34 xANthomAtoSISClinical Types and Associations
Tuberous Xanthoma• Flatorelevated,rounded,grouped,yellowish,ororangenodulesoverjoints(particularlyelbowsandknees)
• TypesII,III,andIV• Biliarycirrhosis
Tendinous Xanthoma• Papulesornodulesovertendons(extensortendonsondorsumofhands,feet,andachilles)• TypesII,III
Eruptive Xanthoma• Smallyellow/orange/redpapulesappearingincropsoverentirebody→buttocks,flexorsurfaces,arms,thighs,knees,oralmucosaandmaykoebnerize
• Associatedwithmarkedlyelevatedorabruptincreaseintriglycerides(elevatedchylomicrons)
• TypesI,III,IV,andV• Diabetes,obesity,pancreatitis,chronicrenalfailure,hypothyroidism,estrogentherapy,corticosteroids,isotretinoin,acitretin
Planar Xanthoma• Flatmaculesorslightlyelevatedplaqueswithyellow/tancolor,spreaddiffuselyoverlargeareas
• Frequentlyassociatedwithbiliarycirrhosis,biliaryatresia,myeloma,HDL-deficiency,monoclonalgammopathy,lymphoma,leukemia,serumlipoproteindeficiency,xanthomasfollowingerythroderma,RA,acquired C1esterasedeficiency
• Characteristicallyaroundeyelids,neck,trunk,shoulders,oraxillae• TypesII,III
Palmar Xanthoma• Nodulesandirregularplaquesonpalmsandflexuralsurfacesoffingers• TypeIII
Xanthelasma• Mostcommontypeofxanthoma• Eyelids,2-30mminlength• Frequentsymmetry• Usuallypresentwithoutanyotherdisease,butmayoccurconcomitantlywithotherxanthomas;canoccurintypesIIandIII,particularly
• Commonamongwomenwithhepaticorbiliarydisorders,alsoseeninmyxedema,diabetes,andphytosterolemia
• Besttreatedwithsurgicalexcision
4.35 VItAmIN DEFICIENCIESAlcoholismisthemaincauseofnutritionaldiseaseindevelopednations.Otherconditions:• Postoperativepatients• Psychiatricpatients• Unusualdiets• Inflammatoryboweldisease
uTIPa�Xanthomastriatapalmaris:diagnosticoftypeIII
dysbetalipoprotinemia(broadbetadisease)
General Dermatology 127
• Cysticfibrosis• Surgicalboweldysfunction• Inbornerrorsofmetabolism
Vitamin APhrynoderma (HypovitaminosisA)• Diseasesoffatmalabsorption:Crohn’s,celiacdisease,CF,cholestaticliverdisease• Requiredfornormalkeratinization• Deficiencyleadstoinflammatorydiseaseofgutandlung• Supplementationrequiredinrubeola(200,000IU/dayfor2d)
Clinical• Phrynoderma→toadskin,keratoticpapulesoverextremitiesandshoulderssurroundingpilosebaceousfollicles
• Spreadstoinvolveabdomen,back,buttocks• Wholeskindrynessandfinescaling• Nightblindness• Xerophthalmia• Keratomalacia
Hypervitaminosis A• Similartosideeffectsofsyntheticretinoidtherapy• Proneindividuals:Children,hepaticdisease,dialysispatients• AllVitaminAsupplementationshouldbestoppedifpatienttakingaretinoid
ClinicalChildren
• Lossofhairandcoarsenessofremaininghair• Lossofeyebrows• Exfoliativecheilitis• Generalizedexfoliationandpigmentationofskin• Clubbingoffingers• Bonegrowthretardation• Pseudotumorcerebri(bulgingfontanellesininfants)
Adults• Drynessoflips• Anorexia• Jointandbonepains• Follicularhyperkeratosis• Desquamationofskin• Fissuringofcornersofmouthandnostrils• Lossofscalphairandeyebrows• Naildystrophy
Vitamin D• Deficiency:Alopeciaonlyskinmanifestation• Elderly:Resultsfromdecreasedsunexposureandpoorintake• Thosetakinganticonvulsants• Fatmalabsorption• ExtensivesunprotectionandsunscreendoesnotleadtoVitaminDdeficiency• Excess:Hypercalcemiaandgeneralizedcalcinosis
128 2011/2012 Dermatology In-Review l Committed to Your Future
Vitamin K• Doesnotoccurinadults(synthesizedbybacteriaingut)• Deficienciesoccurbecauseofmalabsorptioncausedbybiliarydisease,malabsorptionsyndromes,CF,anorexianervosa,liverdiseaseofallcauses
• Drugssuchascoumadin,salicylates,cholestyramine,cephalosporins• Cutaneousmanifestations:purpura,hemorrhage,ecchymosis
Vitamin B2 Deficiency (Riboflavin)• Mostofteninalcoholics• Oral-ocular-genitalsyndrome• Angularcheilitis• Atrophictonguethatismagenta• Seborrheic-likedermatitisaroundnose• Genitaldermatitis→scrotaldermatitissparingmidlineandextendingtothighs• Photophobiaandblepharitis
Vitamin B6 Deficiency (Pyridoxine)• Causedbyuremiaandcirrhosis;pharmacologicagents• Seborrheicdermatitis-likeeruption• Atrophicglossitiswithulceration• Angularcheilitis• Conjunctivitis• Intertrigo• Neurologicsymptoms:somnolence,confusion,neuropathy
Vitamin B12 Deficiency• Deficiencyofintrinsicfactor,achlorhydria,ilealdisease,congenitalabsenceoftranscobalaminII
• Occurs3-6yearsafterGIabnormalities• Glossitis→brightred,atrophictongue• Hyperpigmentation→resemblesAddison’sdisease• Canities• Neurologicfindings
Folic Acid Deficiency• Hyperpigmentation,glossitis,cheilitis,andmegaloblasticanemia,identicaltoVitaminB12deficiency
Vitamin C Deficiency (Scurvy)• Malealcoholicsandpsychiatricpatients• Hemorrhagicsigns,hyperkeratosisofthehairfollicles,hypochondriasis,andhematologicabnormalities
• Perifollicularpetechiae• Subperiostealhemorrhageleadingtopseudoparalysis• Subungual,subconjunctival,intramuscular,andintraarticularhemorrhage• Hemorrhagicgingivitis• Epistaxis• Delayedwoundhealing
General Dermatology 129
Niacin Deficiency (Pellagra)• Canresultfromdeficiencyinniacin(VitaminB3ornicotinicacid)oritsprecursortryptophan
• Alcoholics• Carcinoidtumors• Hartnupdisease(impairedabsorptionoftryptophan)• GIdisorders• ProlongedIVsupplementation• Anorexianervosa• Medications:INH,azathioprine,5-FU
Clinical• Photosensitiveeruptiononface,neck,andupperchest(Casal’snecklace);maybevesiculobullous
• Thickeningandpigmentationoverbonyprominences• Seborrheicdermatitis-likeeruptionontheface• Diarrhea,depression,abdominalpain,dementia,coma• Patientsdieinfourtofiveyearsifuntreated
Pathology• Mostcharacteristic→pallorandvacuolarchangesofkeratinocytesintheupperlayersofthestratummalphighii,justbelowthegranularlayer;acleftmaydevelopinupperepidermis
Biotin Deficiency• Patientswithshortgutormalabsorption• Ingestionofavidin(raweggwhites)bindsbiotincausingdeficiency• Multiplecarboxylasedeficiency• HolocarboxylasesynthetasedeficiencyClinical• Dermatitisissimilartozincdeficiency→periorificialandmarkedbypatchy,red,erodedlesionsoffaceandgroin
• Conjunctivitis• Alopecia
Zinc Deficiency• Inheritedabnormality,oracquired• Presentationininfancymostcommon→especiallyprematureinfants• Humanbreastmilkhasadequatezinc,andweaningprecipitatesdeficiencyinprematureinfantsandthosewithacrodermatitisenteropathica
• Lowmaternalbreastmilkzinclevelsorhigherinfantrequirementscanprecipitatedeficiencyinfull-terminfants
• Zincrequirementsincreaseduringmetabolicstress(infection)
Clinical• Pustularandbullouslesionsinanacralandperiorificialdistribution• Patchy,red,dryscalingwithexudationandcrusting• Angularcheilitisandstomatitis• Periungualerythema,scaling,andpustules• Patientsareirritableandemotionallylabile
130 2011/2012 Dermatology In-Review l Committed to Your Future
Labs• Lowserumzinclevels• Lowalkalinephosphatase(azinc-dependentenzyme)
Essential Fatty Acid Deficiency• Infantswithlowbirthweight• GIanomalies• Inflammatoryboweldisease• Intestinalsurgery• Parenteralnutrition(prolonged)
Clinical• Similardermatitistothatofzincandbiotindeficiency• Widespreaderythemaandintertriginousweepingeruption• Diffusealopecia• Ratioofeicosatrienoicacidtoarachidonicmorethan0.4diagnosticofEFAdeficiency
Iron Deficiency• Koilonychia,glossitis,angularcheilitis,pruritus,andtelogeneffluvium• Plummer-Vinson:Microcyticanemia,dysphagia,andglossitisseennearlyentirelyinmiddle-agedwomen;lipsarethinandopeningofmouthissmallandinelastic
Marasmus• Prolongeddeficiencyofbothproteinandcalories• Children60%oftheiridealbodyweight• Noedemaorhypoproteinemia• Skinisdry,wrinkled,andloose
Carotenemia• Excessiveingestionofcarrots,oranges,squash,spinach,yellowcornandbeans,butter,eggs,rutabagas,pumpkins,yellowturnips,sweetpotatoes,orpapayaleadingtoyellowishdiscolorationofskin
• Prominentonpalms,soles,andcentralface
Lycopenemia• Excessiveingestionofredfoodsliketomatoes,beets,chilibeans,andvariousfruitsleadstoreddishdiscolorationofskin
4.36 DIAbEtES AND SkIN DISEASEInfections
• Staphpyodermas• Candidiasis• Erythrasma• Epidermophytosis
Xanthomatosis• Chylomicronemiawithxanthomas• Regressionwhendiabetesbroughtundercontrol
uTIPaKwashiorkor
• Proteindeficiencybutadequatecaloricintake
• Edemaandpotbelly
• Hypopigmentedhair →reddish yellowtograyorwhite
• “Flagsign” → hairgrownduringperiodsofpoornutritionispale
General Dermatology 131
• Xanthelasma:Occursinhyperlipidemicstates(includingdiabetes)andmayoccurwithoutdemonstrableabnormalityofplasmalipids
Diabetic Dermopathy• Asymptomatic,irregularlyshapedpatchesoveranteriorlowerlegs• Depressedandbrownsurfaces• Oftenaccompaniedbysignificantmicroangiopathyelsewhereinbody
Bullous Lesions/Bullous Diabeticorum• Spontaneousbullaeonextremities,especiallyofthefeet• Healwithoutscarringwithinweeks• Bullaeoccurinplaneofbasementmembraneabovebasallamina
Thickened Skin and Stiff Joints• 1/3ofpatientshavetight,thickenedandwaxyskinoverdorsaofthehands• Multiple,minute,flesh-coloredpapulesondorsumoffingers,knucklepads,andperiungualareas
• Contracturesofhands• Scleredemaadultorum
Cutaneous Neuropathy• Autonomicdisturbancesthataccompanyneuropathyincludinganhidrosis
Necrobiosis Lipoidica• 0.3%ofdiabetics• 3:1female:male• OnlyaminorityofthosewithNLDactuallyhavediabetes• Anteriorandlateralsurfacesoflowerlegs,usually(alsoface,arms,andtrunk)• Beginsassmall,dusky-redelevatednodulewithsharplycircumscribedborder,enlargingtoanatrophicplaque
• Brownish-yellowcenter,redborder• Extremelychronicandindolent• Diabetesmayprecede(80%)oroccursubsequenttodevelopmentoflesions(10%);resthavenoglucoseintolerance;mosthaveabnormalglucosetoleranceinresponsetoglucocorticoids
Granuloma Annulare• GeneralizedformmorecommoninDM
Vitiligo• GreaterthanexpectedincidenceinpatientswithDMType1• Mayprecedeclinicallyevidentdiabetes
Acanthosis Nigricans• Seeseparatediscussion
132 2011/2012 Dermatology In-Review l Committed to Your Future
4.37 LANGERhANS CELL hIStIoCytoSISHistiocytosis X
• ProliferationofdendriticorLangerhanshistiocytes
Morphology• Rose-coloredpapules,somescaling,crusting,andulceration• Mergingoflesionsonscalpgivesseborrheicdermatitisappearance• Nailchanges:Paronychia,nailfolddestruction,onycholysis,subungualhyperkeratosis(poorprognosticsigns)
Systemic Manifestations• Extremelyvariable• Pulmonaryinvolvementin>50%→lungsshowhoneycombappearance;dyspnea,cyanosis,andpneumothorax
• Hepatosplenomegaly:Nevertheinitialsignofdisease• Bonelesions(60%)• Hematopoieticinvolvement(rare)• Fever
ClassificationLetterer-Siwe Disease• Acute,disseminatedLCH• Firstyearoflife• Cutaneousdiseasemorecommoninthisentity(80%),andusuallyinitialsign• Fever,anemia,thrombocytopenia,enlargementofliverandspleen(neverpresentingsign)• Potentiallyfatalvisceralinvolvement• Onlyosteolyticlesionisinmastoidbone(lookslikeotitismedia)
Hand-Schuller-Christian Disease• Earlychildhood• Lessextensivevisceralinvolvement• Chronic,multifocaldisease• Cutaneousdiseaseinonly30%• Osseouslesions,especiallyofcranium(80%)• Exophthalmos(10-30%)• Cancausediabetesinsipidus(50%),causedbygranulomatousinfiltrationofposterior
pituitary gland
Eosinophilic Granuloma• Olderchildrenandadults• Benign• Oneorafewbonelesions• Affectsskull,ribs,andvertebraemostfrequently• Canaffectmucosa
Hashimoto-Pritzker Disease (Congenital,Self-healingReticulohistiocytosis)• Presentatbirth,usually• Nomucousmembranelesions• Systemicsignsabsent• Rapidspontaneousregression
General Dermatology 133
Course and Prognosis• Skinandboneinvolvementgoodsigns,andorganinvolvementbad• 10%withmultifocaldiseasedie,60%havechroniccourse,30%showcompleteremission
ManagementTreatmentbasedonage,extentofdisease,andlocationoflesions
Children• Nonaggressivemanagement• Observation• Topicalnitrogenmustardforpersistentlesions
Adults• Topicalnitrogenmustard• PUVA• CO2laser• Thalidomide• Isotretinoin
Bone Involvement• Surgicalexcision• Glucocorticoidinjections• Radiotherapyinadults• Monochemotherapyformultiplebonelesions
4.38 CUtANEoUS t-CELL LymPhomA
Clinical TypesPatch and Plaque Stage• Flatlesionsassociatedwithinflammationandpruritus,thatcanpersistforyearsorresolvespontaneously
• Patchstagecanlastformonthstoyearsbeforeprogressing• Plaquescanarisede novo
Hypopigmented MF• Darker-skinnedpatients• Patientsrespondtotherapybyregainingpigment
Pigmented Purpura• Capillaritis
Granulomatous CTCL and Slack Skin• Primarilyinfemales• Largeregionsofslackskinaccompaniedbyfibroticbands
Pagetoid Reticulosis (Woringer-KoloppDiseaseorAcralMF)• Typicallypresentsasasolitaryplaque(localized)• Longduration,slowgrowing• Benign;longdurationwithoutprogression• Pronouncedepidermotropism• FollicularMF
134 2011/2012 Dermatology In-Review l Committed to Your Future
Alopecia Mucinosa• Follicularmucinosis• Groupedfollicularpapulesorred,raised,boggy,occasionallynodularplaques• Alopeciamaybepresentingsign• Histology:Sebaceousglandsandouterrootsheathsdisruptedwithincreasedmucindeposition
• CTCLmaybepresentbeforedevelopmentofalopeciamucinosa
Erythrodermas• De novo orasaprogressionfrompre-existingCTCLlesions• Mayleadtoleoninefacies• Alopecia,ectropion,naildystrophy,ankleedema• Sezarysyndromemaycause
Tumor Stage MF• Predilectionforfaceandbodyfolds• Mayoccurinpre-existingplaquesandpatchesofCTCL• Neoplasticcellsmoremalignantbiologically• Nodulesmayulcerate• Mayspontaneouslyresolve,butprognosisispoor• Infiltratedenserthanplaquestage,andextendstosubcutaneousfat• Epidermotropismisnotaprominentfeature,andgrenzzonemayappear
Diagnosis• Diagnosismadebybiopsy• Multiplepunchbiopsiesat3monthintervalsmaybeneeded• Anypatientwithchronic,refractorydermatosis(ACD,AD,psoriasis,PRP)shouldbebiopsiedtoruleoutCTCL
• Clonalityassistsindiagnosis,butisnotpathognomonic
Peripheral Blood• MalignantclonalT-cellpopulationsrecirculatefromskintolymphnodes,andthentoblood,eveninpatchstagedisease,CD4+/CD7-
• ElevatedCD4/CD8ratioindicatesdiseaseexpansionintoblood• Flowcytometrymustbeacomponentinthestagingprocess(CD4/CD8),CD3,CD45RO• MemorycellmarkerCD45ROiselevatedoftenincasesofperipheralbloodinvolvementbyCTCL
Sezary Cells• Hyperchromaticandhyperconvolutednuclei• RepresentanactivatedT-cell• Canbeseenininflammatorydermatoses,andinDilantin(phenytoin)hypersensitivitysyndrome• 100cellscountedtoassesspercentage,and>5%associatedwithpoorprognosis
Prognosis• Involvementof10%orlesswithpatchdisease:mediansurvivalof12years• Tumors,erythroderma,ornodeinvolvement:mediansurvival2-3years• Sezarysyndrome:2-3years
General Dermatology 135
Topical Chemotherapy• Nitrogenmustard(bis-chloronitrosurea,BCNU);mechlorethamine(10mgin50mltapwaterasinitialdose)
• Ointment-basedmechlorethaminehaslongershelflife• Sideeffects:Hypersensitivity,primaryirritation,secondcutaneousmalignancies,hypoandhyperpigmentation
• Dailywhole-bodyapplicationrequireduntilremission,afterwhichfrequentmaintenancetherapyused
Radiotherapy• Electronspenetrateonlytoupperdermis• Wholebodyirradiationinducescompleteremissionin>80%;withrelapseratehigherinlaterstagesofCTCL
• Mostrelapsesoccurwithinfirstyearaftercessationoftreatment• Localsideeffects:Alopecia,atrophyofsweatglandsandskin,radiodermatitis,andedema;fractionatingdosereducessideeffects
• SCCincidenceincreased• 2ndand3rdcoursesacceptableifneeded
Photochemotherapy• PUVA• Inducesremissionevenintumorstages
Extracorporeal Photochemotherapy• Photoinactivationofaportionofthepatient’slymphocytecompartmentwith8-methoxypsoralen+UVA,followedbyreinfusion
• Twoconsecutivedayseveryfourweeks• Effectiveforerythroderma• Requires4-12monthsforresponse
Alpha and Gamma Interferon• 10-27%completeresponsewithin6monthsusingmonotherapy• 3millionunits3x/week,andcanbeincreasedto20millionunitsperdayastolerated• Maintenancedoseof1millionunitsdaily• Toxicities:Flu-likesymptomsfirstweek.Sideeffects:chronicfatigue;long-termneurologictoxicitymayoccur,andautoimmunephenomenasuchasproteinuria,thrombocytopenia,and anemia
DAB-IL-2 Toxin/Denileukin Diftitox• DiphtheriatoxinfusedtoIL-2,bindingtoreceptor,killingcells• InfiltratesmustcontainhighlevelsofIL-2receptor-positivecells• Maycausefluidretention,diffuseerythema,andliverabnormalities,whichareallreversible
Systemic High-Dose Chemo• Palliative• Glucocorticoids,adriamycin,CHOPtherapy
136 2011/2012 Dermatology In-Review l Committed to Your Future
4.39 PyoDERmA GANGRENoSUmFour Types
Ulcerative• Inflammatorypustulewithsurroundinghalo• Enlargesoverdaysandulcerates• Manylesionsbeginatsitesoftrauma(pathergy)• Distinctrollededgesandshowsatelliteviolaceouspapulesthatbreakdownandfusewithcentralulcer
• Painful• Adults40-60yearsoldonlowerextremitiesandtrunk• Healwiththin,atrophicscars
Pustular• Describestheprimarypustularlesionsthatmayormaynotprogressontoulcerativelesions
• OftenseenassociatedwithIBD• Associatedwithpyostomatitisvegetansandsubcornealpustulardermatosis
Bullous• Lessdestructive,moresuperficial• OverlapwithatypicalSweet’s• Patientswithleukemiaorpolycythemiavera• Redinflammatoryplaquesthatbecomeduskyanddevelopsuperficialerosionoftheepidermis
• Lesspainfulthanulcerative
Vegetative• Leastaggressiveform• Cribiformchronicsuperficialulcerationsonthetrunk,usually• Notpainful• Notoftenassociatedwithsystemicdisease
Clinical Associations• 1.5-5%ofpatientswithIBDdevelopPG• Diseasesrunseparatecourses• Associatedwithleukemia,myeloma,monoclonalgammopathy(IgA),polycythemia,chronicactivehepatitis,HCV,HIV,SLE,pregnancy,andTakayasu’sArteritis
• AssociatedwithPAPAsyndrome→pyogenicarthritis,pyodermagangrenosum,severecysticacne
• 33%havearthritis→asymmetrical,seronegative,monoarticulararthritisofthelargejoints• Childrenwithcongenitaldeficiencyofleukocyte-adherenceglycoproteins
Histology• Massivedermaledemawithepidermalneutrophilicabscessesattheviolaceousunderminedborder
Treatment• Iflesionspustular,seekandtreatforunderlyingIBD• Aggressivenessoftreatmentdeterminedbyseverityofdisease
uTIPa50% have associated disease, most commonly is IBD (UC > Crohn’s)
General Dermatology 137
• Localtreatment:Compressesorwhirlpoolbathswithuseofointmentocclusivedressings• PotenttopicalsteroidsorILsteroids• Topicaltacrolimus• Systemicsteroids,andifnotresponding,pulsemethylprednisolone• Sulfapyridine,sulfasalzine,anddapsone• Clofazamine200-400mgqd• Cyclosporineisthenextchoice,with85%ofreportedcasesrespondingdramatically:startat5mg/kg
• Infliximab• Otheragents:thalidomide,SSKI,azathioprine,cyclophosphamide,chlorambucil
4.40 SWEEt’S SyNDRomEAcute Febrile Neutrophilic Dermatosis
• Recurrentpainfulplaque-forminginflammatorypapules,fever,peripheralleukocytosis,adiffusedermalinfiltrate,andpromptresolutionofsymptomsandlesionswithglucocorticoidtherapy
ClinicalSkin • Suddeneruptionoftenderredorbluishredpapulesornodulesoverface,neck,upperextremities
• Coalescetoformirregularsharplyborderedplaques(“reliefofamountainrange”)
• Transparentvesicularappearance,thoughsolid(“illusionofvesiculation”)• Eventuallyresolvewithoutscarringafterweeksormonths
Systemic• Fever,leukocytosis,withpatientsappearingdramaticallyill• Headache,arthralgia,myalgia,andgeneralmalaise,conjunctivitis,andepiscleritis• Bone:Sterileosteomyelitis• Neuro: Asepticmeningitis,neurologicandpsychiatricsymptoms,withneutrophilsintheCSF
• Renal:Proteinuria,hematuria,glomerulonephritis• Hepatic:InfiltrationofportaltriadandtractswithelevatedLFT’s• Pulmonary:Culture-negativeinfiltrates
Laboratory• ElevatedESR• Peripheralleukocytosiswithneutrophilia• Malignancy-associatedSweet’s:anemia,normalorlowneutrophilcountandabnormalplateletcount
• Proteinuriaifrenalinvolvement
Etiology• Noknowncause.Thoughttobeahypersensitivityreaction• Majorityofpatientshaveafebrileupperrespiratorytractinfection,tonsillitis,orinfluenza-likeillnessthatprecedestheirskinlesionsby1-3weeks
• CanbeassociatedwithintestinalinfectionwithYersiniaenterocolitica
uTIPa Face, upper extremities, and
neck, most commonly
uTIPaCan be drug-induced (GCSF)
138 2011/2012 Dermatology In-Review l Committed to Your Future
Pathology• Edemaofthedermalpapillaeanddenseinfiltratecomposedlargelyofneutrophils,withsomelymphocytesandhistiocytes,andoccasionaleosinophils
• Infiltrateisbandlikeinpapillarydermis(“Seaofneutrophils”)• Leukocytoclasiacommon
Associated DiseasesProbable Association• Infection:UsuallyupperrespiratorytractandGItract• Inflammatoryboweldisease• Medications:G-CSF–anemiacommonlyassociated,andTMP-SFX
• PregnancyTreatment• Corticosteroids• PotassiumIodide
4.41 ERythEmA ANNULARE CENtRIFUGUm• Polycyclicerythematouslesionsthatgroweccentricallyandslowly• Oftenrecurrent• Characteristictrailingscaleatinnerborder• Characteristiclymphocyticcoatsleevingofvascular/adnexaeonpathology
Associations• Idiopathic• Malignancy• Dermatophyte(feetandgroin) Butnoextensiveworkupnecessary
4.42 ERythEmA ELEVAtUm DIUtINUmClinical Features and Course
Morphology• Multiplelesions:Papulesplaquesornodules• Earlylesionsoftenpinkoryellow.Olderlesionsareredorpurpleandharder.Lesionsmayberoundoroval,andsurfaceissmoothwithoccasionalscale.Also,freelymovablefromunderlyingtissues
Distribution• Symmetriconextensorsurfaces,especiallyskinoverlyingjoints,especiallyonhandsandknees.Alsoinvolvethebuttocksandskinoverlyingtheachillestendon
Symptoms• Asymptomatictoverypainful
Associated Symptoms and Conditions• Arthralgia(mostcommon)• Recurrentpharyngealandsinopulmonaryinfection,usuallystreptococcal• Inflammatoryboweldisease
uTIPa
Malignancy, most commonly hematologic (AML); lesions may precede diagnosis of leukemia
General Dermatology 139
Course• Variable,butoftenprogressiveover5-10years,withlong-termremissionpossible• Periodsofwaxingandwaning
Laboratory Findings• ElevationinESR
Treatment• Dapsoneorsulfapyridine–withexacerbationafterthedrug’swithdrawal• Glucocorticoidsnoteffectivesystemically,butintralesionalandtopicalhighpotencysteroidsmaydecreasethesizeoflesions
4.43 ERythEmA NoDoSUmExtensorsurfaces,lowerextremities:inflammatory,spontaneously
regressing,tender,nodularlesions.
Clinical• Erythematous,tendernodulesonanteriorshins;alsoseenonthighs,lateralaspectsoflowerlegs,arms,andface
• Onsetofnewlesionsoftenaccompaniedbyfever,chills,malaise,andleukocytosis
• Oftenprogressesintoaviolaceousbluecolor• 70%haveassociatedarthropathythatmaypersistafterdisappearanceoferuption
• Occursatanyage,butmostprevalentbetween20and30yearsofage• Resultsfromimmunologicreactiontriggeredbydrugs,benignandmalignantsystemicillness,bacterial,viral,andfungalinfections
Infections• Streptococcal,betahemolytic:cutaneouslesionsdevelopwithinthreeweeksofinfection• Tuberculosis:Associatedwithprimaryinfection• Yersinia• Blastomycosis,coccidioidomycois,histoplasmosis;dermatophytes,particularlythosecausingtineacapitiswithkerionformation
• Oftenoccursafteracuterespiratoryillnessthatisnonstreptococcalforwhichnoagentidentified
• Viruses:paravaccinia,infectiousmononucleosis,lymphogranulomavenereum,cat-scratchdisease,psittacosis,HepatitisB
Sarcoidosis• Maybepresentingsignalongwithhilaradenopathy• Lofgren’ssyndrome:sarcoidosis,erythemanodosum(goodprognosis)
Drugs• Sulfonamides• Bromides• Oralcontraceptives
uTIPaIgA (mainly) or IgG or IgM monoclonal gammopathies or even myeloma
MNEMONIC Erythema Nodosum
SHOUT BCG
Sarcoid,Sulfa,Strep Histoplasmosis Oralcontraceptives Ulcerativecolitis TB
Bechet’s Crohns GI(Yersinia)
140 2011/2012 Dermatology In-Review l Committed to Your Future
Enteropathies• UlcerativecolitismorefrequentlythanCrohn’sdisease
Miscellaneous Causes• Behçet’ssyndrome• Malignancy:Lymphoma,leukemia,cervicalcancer• Onsetofradiationtherapyforcancer
Treatment• Spontaneousresolutionusuallyoccurswithinthreetosixweekswithoutscarring• NSAIDssuchasindomethacinornaproxen• Systemicsteroidseffectiveinseverecasesandcanbedangerousifinfectionisetiology• Potassiumiodide400to900mgdaily
4.44 mAStoCytoSIS• Mastcellhyperplasiainthebonemarrow,liver,spleen,lymphnodes,GItract,andskin• Clinical:Pruritus,flushing,urtication,abdominalpain,nausea,vomiting,diarrhea,bonepain,vascularinstability,headache,andneuropsychiatricdifficulties
Etiology and Pathogenesis• Originatefrompluripotent(CD34+)bonemarrowcells→circulatethroughblood→ mature intofullygranulatedcells
• Mutationsinc-kit→associatedwithenhancedreceptorfunction• Increasedproductionofmastcellmediators: –Histamine –Heparin –Tryptase –Leukotrienes –ProstaglandinD2 –Plateletactivatingfactor –Cytokines–growthenhancingandproinflammator
Clinical• Featuresareduetoexcessproductionofmastcell-dependentmediators• Patientsineverycategoryofmastocytosissometimesexperienceflushingorvascularcollapse→provokedbyalcohol,aspirin,narcotics,contrastagents(iodinated),insectstings,exercise,orinfections
Major Types of Mastocytosis •Urticariapigmentosa –Mostcommonskinmanifestationinchildrenandadults –90%ofthosewithindolentmastocytosis –Small,yellow-tantoreddish-brownmaculesorslightlyraisedpapules –Darier’ssign:Trauma/rubbingoflesionscausesurticationanderythema –Associatedwithpruritusexacerbatedbychangesintemperature,frictiononskin, ingestionofhotbeveragesorspicyfoods,ethanol,andcertaindrugs
•Diffusecutaneousmastocytosis –Diffusemastcellinfiltrationwithoutdiscretelesions
General Dermatology 141
–Usuallyoccursbeforeageofthree –Entireskininvolved –Skinnormaltoyellow-brownandthickened •Solitarymastocytomas –Rare –Onsetbeforesixmonthsofage –Involutespontaneously,usually •Bullouseruptionswithhemorrhage –Neonates –Blistersmayeruptspontaneously •Telangiectasiamaculariseruptivaperstans –<1%ofpatients –Tan-to-brownmaculesandpatchyerythema –Telangiectasiasobserved –Exclusivelyinadults
Systemic Features
Gastrointestinal Disease •Gastrichypersecretionsecondarytoelevatedhistamine→gastritiswithpepticulcerdisease •Diarrheaandabdominalpain •Malabsorption •LFT’sabnormalinhalfofpatients→alkalinephosphataseelevated
Splenomegaly •50%ofpatients •Mastcellinfiltrateswithfibrosis •Extramedullaryhematopoiesis
Bone Marrow •Radiographicallydetectablelesionsinmajorityofpatients→proximallongbonesmost oftenaffected;pathologicfracturesmayoccur
•Anemia,leukopenia,thrombocytopeniaandeosinophiliamayoccur
Neuropsychiatric •Decreasedattentionspan •Memoryimpairment •Irritability
Mastocytic Leukemia • Rarestformandhasmostfulminantbehavior;peripheralbloodshowsnumerousimmaturemastcells
Work Up 1.)Skinexam–grossandmicroscopic 2.)Bonemarrowbiopsy 3.)24hoururine• Suspicionshouldpromptabonemarrowbiopsyandaspiratefordiagnosisandcategorizationofthetypeofmastocytosis
• Obtain24hoururinefor5-hydroxyindoleaceticacid(5-HIAA)andurinarymetanephrinestoruleoutcarcinoidtumororpheochromocytoma
142 2011/2012 Dermatology In-Review l Committed to Your Future
Treatment •H1blockersreducepruritus,flushing,tachycardia •H2blockersadded •Cromolynsodium,particularlyforGIcomplaints •Ketotifenandazelastine,antihistaminesthatstabilizemastcells •Epinephrineforvascularcollapse(patientsshouldbepreparedtoself-administer) •PUVA(withmethoxsalen)relievespruritusandwhealingafter1-2months,butrecursafter 3-6months
•Topicalglucocorticoidsunderocclusionfor8hoursperdayover8-12weekscanbeused forextensiveUP;lesionsrecurafterdiscontinuation
•Radiotherapyforbonepain
Survival •50%ofchildrenwithUPresolvebyadulthood •AdultswithUPusuallyprogressgraduallytosystemicdiseaseandrarelydevelop hematologicdisease
•Diffusecutaneousmastocytosisisusuallyassociatedwithindolentsystemicdisease •Mastcellleukemia:survivallessthansixmonths •Lymphadenopathicmastocytosiswitheosinophilia:twotofouryearswithouttherapy
4.45 CUtANEoUS SARCoIDoSIS• Skinlesionsoccurin25%ofpatientswithsarcoidosis
Lupus Pernio• Middleagedfemales,increasedinAfricanAmericans• Chronic,violaceous,induratedplaques• Predilectionfornose,ears,lips,andface• Persistentsarcoidosischaracterizedbyextensivepulmonaryinfiltrationandfibrosis,chronicuveitis,andbonelesions
• Noselesionaccompaniedbygranulomatousinfiltrationofnasalmucosaandupperrespiratorytract,andbonynasalseptummaybedestroyed
• Bulbousorsausage-shapedfingerinapatientwithlupuspernioindicatespresenceofunderlyingbonelesion
Plaques• Violaceous,elevated,indurated• Limbs,face,back,andbuttocks• Distributionissymmetric• InAfricanAmericans,hypopigmentedappearance:“hypomelanoticumbrella”• Sarcoidlesionsmayappearpsoriatic
Papular Eruptions• MostcommonskinmanifestationsinAfricanAmericans• Waxy,translucent,flattop,2-6mm• Occuronface,lids,aroundorbits,neck,upperback
General Dermatology 143
Subcutaneous Nodules/Darier Roussy Sarcoidosis• Oval,firm,painless• Arisedeepindermisandsubcutis• Foundontrunkandextremities• Rarely,ulcerate
Erythema Nodosum• Mostcommonnonspecificcutaneousmanifestationofsarcoidosis(Lofgren’ssyndrome)• Hallmarkofacutesarcoidosis,predominantlyofwomenofchildbearingage• Maybeassociatedwithfever,malaise,polyarthralgia• Associatedwithgoodprognosisinsarcoidosis
Laboratory Investigations• Hypercalcemia:duetoincreasedintestinalabsorptionsecondarytoactiveformofVitaminD3overproduction(inlungs)
• ACElevel:raisedin60%,higherinpatientswithhilaradenopathyandpulmonaryinfiltration(stageII)andpositiveinpatientswithextrathoracicsarcoidosis;ACEderivedfromepithelioidcellsofgranulomasandthusreflectsgranulomaloadinthebody
• ACEusedformonitoringclinicalcourse,notfordiagnosis(60%sensitive,and90%specific)
ImmunologyCutaneous Anergy• DepressionofDTHreactions;negativePPDin66%• Anergydoesnotcorrelatewithdiseaseactivity—persistsevenduringrecovery
Humoral Responses• Exaggeratedcirculatingantibody• Hypergammaglobulinemiaoccursinhalfthepatients
Kveim Test• Intradermalinjectionofhomogenizedtissuefromsarcoidosispatient• Requiresfourtosixweeksfornoduletodevelop
TreatmentGlucocorticoids• Prednisone,20-40mgqd,istreatmentofchoice• Doseisreducedgraduallyto10mgdaily• After4-6weeksofdailytreatment,dosecanbereducedto10-20mgeveryotherday• ILtriamcinolonetodisfiguringlesions• Topicalglucocorticoidstoindividuallesions
Antimalarials• Chloroquine• Hydroxychloroquine
Immunosuppressive Drugs• Methotrexate• Infliximab
Surgery• Excisionofsmalllesions• Graftingofextensivesarcoidulcers
144 2011/2012 Dermatology In-Review l Committed to Your Future
4.46 PERFoRAtING DISoRDERS
Perforating Folliculitis
Pathogenesis• Lesionsmayberelatedtosuperficialtrauma
Clinical• Keratoticfollicularpapulesoverextensorsurfaces• Associationwithchronicrenalfailure
Reactive Perforating Collagenosis
Pathogenesis• Lesionsprecipitatedbysuperficialtraumaalteringcollageninthedermalpapillae
Clinical• Pinheadkeratoticpapulesthatgrowto6-10mmindiameter• Centeroflesionbecomesumbilicatedcontainingtightlyadherentplug• Firstlesionsusuallyappearininfancyafterminortraumaorarthropodbite
Kyrle’s Disease (Hyperkeratosisfolliculitis)
Pathogenesis• Absenceofcollagen• Follicularpluginanepidermalinvagination
Clinical• Scalyfolliculo-centricpapules
Elastosis Perforans Serpiginosum (EPS)
Pathogenesis• Alteredelasticfibersindermisandconcomitantalterationofcollagenfibers
• Elasticfibersactasaforeignbodyandareeliminatedthroughtransepidermalchannels
Clinical• PatientswithMADPORES:Marfans,Acrogeria,Downsyndrome,Penicillamine,OsteogenesisImperfecta,EhlersDanlos
• Fleshcoloredtoerythematousumbilicatedpapules2-3mmarrangedinarcuateserpiginousorgroundedfashion
• Napeandsidesofneck,upperextremities
Treatment• Cryotherapy
4.47 ELAStoSIS PERFoRANS SERPIGINoSA
Pathogenesis• Alteredelasticfibersindermisandconcomitantalterationsofcollagenfibers• Elasticfibersactasaforeignbodyandareeliminatedthroughtransepidermalchannels
MNEMONIC
MAD PORES Marfan’s Acrogeria Down’s
Penicillamine OsteogenesisImperfecta Rothmund-Thomson EhlersDanlos Scleroderma
General Dermatology 145
Patients• Idiopathic• PatientswithDown’ssyndrome,heritableconnectivetissuedisorders(Ehlers-DanlosTypeIV,osteogenesisimperfecta,Marfan’ssyndrome,Rothmund-Thomson,scleroderma,andacrogeria),penicillamine
Clinical• 2nddecadeoflife• Flesh-coloredtoerythematousumbilicatedpapule2-3mm,withcentral,tightlyadheringplugthatbleedswhenremoved
• Napeandsidesofneck,upperextremities• Arcuate,serpiginous,grouped,scattered,discrete• Regressionleavesatrophic,wrinkled,andhypopigmentedscars
Treatment• Cryotherapy• Avoidelectrocautery,dermabrasion,andsurgery
4.48 REACtIVE PERFoRAtING CoLLAGENoSIS
Pathogenesis• Perhapsgeneticpredisposition• Developmentoflesionslikelyprecipitatedbyminorsuperficialtraumaalteringcollageninthedermalpapillae
• Noassociatedmetabolicdisorders
Clinical• Lesionsstartaspinhead-sizedkeratoticpapulesandgrowto6-10mmindiameteroveronemonth
• Centeroflesionbecomesumbilicatedcontainingatightlyadherentleatheryplugthatifremovedleavesableedingcrater
• Healswithaminorscarofhypopigmentedmacule• Firstlesionsusuallyappearininfancyafterminortraumaorarthropodbite• Asymptomatic
Treatment• Noconsistentlysuccessfultherapy• Maybephototherapy
4.49 CUtANEoUS FEAtURES AND DISoRDERS oF PREGNANCy
Pemphigoid Gestationis• Seenonlyinpregnancyorwithtrophoblastictumors• Beginsin2ndor3rdtrimester• Urticarialorpapulovesicularlesionsontrunk;spreadsrapidlyandmayinvolvefaceandpalms/soles,evolvingintobulla
• Pruritusmayprecedelesions• Mayremitpriortodelivery,but75%flarepost-partum• Recurswithpregnancy,OCP’s,ormenses
146 2011/2012 Dermatology In-Review l Committed to Your Future
Laboratory• Severitymaycorrelatewitheosinophilia• Increasedanti-thyroidantibodies
Immunofluorescence• Direct:C3inhomogeneous,linearbandatBMZ(perilesionalandlesionalskin);IgGin30-40%
• Indirect:ComplementfixationatBMZ;HGfactor=complementfixingIgGantibody;almostallpatientsshowIgG1againstBMZ
Pathophysiology• IgGagainst180kdBPantigen;→extracellulardomain• Theory:CrossreactionofantibodiesdirectedagainstamnioticBMZ• Pregnanciescanskipdisease
Treatment and Course• Prednisone0.5mg/kg/day(topicalsteroidsoftenineffective)• Increasedriskforsmallforgestationalageinfantandprematurity• Mother:IncreasedlifetimeriskofGrave’sdisease
Cholestasis of Pregnancy• Thesameasprurigogravidarum+/-jaundice• Cholestaticjaundiceofpregnancy=abnormalLFT’s• Prurigogravidarum=pruritusandabnormalbileacidswithoutjaundiceClinical• Usually3rdtrimester• 50%associatedwithUTI• <50%developjaundice• Intenseprurituswithoutlesions• Resolveswithin2dayspost-partum
Laboratory• Bileacidselevated3-1000xnormal• Directbilirubinnotmorethan2-5mg/dl• Hepaticultrasoundisnormal
Course and Prognosis• Mother:LowVitaminK→post-partumhemorrhage• Mayrecurwithfuturepregnancy• Increasedriskofcholelithiasis
•Fetus:Prematurelabor(common),fetaldistress,perinataldeath
Treatment• UVBphototherapyforsymptoms• CholestyraminegivenwithVitaminK• Restandlowfatdiet• UrsodeoxycholicacidorUDCA(16mg/kg/day)→reducesriskofprematuredeliveryandpruritus
• Dexamethasone12mg/dayx7days→decreaseslababnormalitiesandpruritus,usedinconjunctionwithUDCA
• Deliverat38weeksorearlier
General Dermatology 147
Polymorphous Eruption of Pregnancy (orPUPPP)
Clinical• Papulesbegininstriaeandspreadtotrunkandextremities
• Usuallyin3rdtrimester• Resolves15dayspost-partum,sometimespriortodelivery
Laboratory• Normal
Treatment and Course• Topicalsteroids• Antihistamines• Systemicsteroids• Nomaternalorfetalmorbidity
Pustular Psoriasis of Pregnancy• Alsocalled“impetigoherpetiformis”
Clinical• Late1sttrimesterto3rdtrimester• Oftenbeginsinintertriginousregionsandspreadstotrunkandextremities• Sparesface,palms,andsoles• Erythematousplaquewithringofpustules,thatenlargesatperipheryanderodesorcrustsatperiphery
• Mucosacanbeinvolved• Onycholysis• Nopruritus• Malaise,anorexia,fever,chills,nausea,vomiting,diarrhea
Course• Remitsquicklypost-partum• Recurswithsubsequentpregnancies,mensesandOCP’s• Fetusatriskforplacentalinsufficiency
Laboratory• Hypocalcemia• Leukocytosis• ElevatedESR• Pustuleculturenegative
Treatment• Prednisolone80mg/d→decreasesmortalityriskformother• Treathypocalcemia• Mayrequireearlydelivery
4.50 PRURItUSPathophysiology
• Theonlyperipheraltissuefromwhichitchevokedisskin,withtheexceptionofthecornea• TheCandAdeltafibersintheuppermostskinuniqueintheirabilitytoproduceitch• HistamineproducesitchviatheH1receptor
uTIPa Primigravidas, increased with maternal
obesity and twin gestation
148 2011/2012 Dermatology In-Review l Committed to Your Future
• Othersubstancesthatproduceitch:papain,trypsin,serotonin,bradykinin,kallidin,kallikrein,substancePandVIP
• Prostaglandinsexaggerateexistingitch• Opiateshavebothcentralandperipheralitch-producingaction
Conditions that Cause PruritisChronic Renal Disease• Affects80%ofthoseondialysis• Dialysiscausestemporaryrelief• Emollients,antihistaminesineffective• Antihistaminesrarelywork• Secondaryhyperparathyroidismisanoccasionalcauseofuremicpruritus• Increasedpopulationofmastcellsinskin• UVphototherapymaybenefit
Cholestasis• Highlevelofbilesalts,andcholestyraminecausessymptomaticimprovement
Endocrine Disease• Thyrotoxicosis–oftenduetoincreasedskinbloodflowwhichraisesskintemperature• Hypothyroidism–pruritussecondarytothedryskinofmyxedema• Postmenopausalpruritusmaybegeneralizedorlocalized,usuallyinanogenitalarea
Malignancy• Mostcommonassociation:Hodgkin’sdiseaseandpolycythemiavera
Polycythemia Vera• 50%havewater-inducedpruritus;referredtoas“bathitch”oraquagenicpruritus
• MayprecededevelopmentofPVbyyears• Itchisindependentoftemperatureofwater
HIV Infection• Increaseditchingsecondarytoscabies,pediculosis,candidiasis,orseborrheicdermatitis,orrenal/hepaticdysfunction
• Eosinophilicfolliculitis• PruritusofHIV• MayrespondtoUVB,PUVA,ordapsone
Workup of Generalized Pruritus• Physicalexam,includingpelvicandrectal• CBC• StoolforO&P,occultblood• CXR• Thyroid,renal,andliverfunctiontests• Drughistory
4.51 SCLEREDEmAClinical Manifestations
• Skininvolvementmaybeprecededbyprodromeoflow-gradefever,malaise,myalgia,arthralgia
• 65%developinfectionusuallyofstreptococcaloriginafewdaysto6weeksbeforeonset
General Dermatology 149
• Marked,nonpitting,symmetricindurationoftheskin• Affectsposteriorandlateralaspectsofneck,spreadstoface,shoulders,back,arms,andthorax
• Indurationiswaxywhiteorshiny,anddiffusewithoutsharpdemarcationbetweeninvolvedanduninvolvedareas
Laboratory Findings• IncreaseinASOtiterinsomepatients• Glucosetolerancetestmaybewarranted• Hyperinsulinemiamaybepresent
Pathogenesis• Unknown• Syndromeoflongduration,obesity,adultonset,andlatentorovertdiabetesassociatedwithcardiovasculardiseasenoted
• Dermismarkedlyincreasedinsizewithincreaseinhydroxyprolineandhexosamines• Associationwithmonoclonalgammopathy,IgGtype
Treatment• None
Course and Prognosis• Spontaneouslyresolvesin6monthsto2years• 25%shownoresolution,especiallyinthosewithDM
Table4-4.MonoclonalGammopathyandDiseaseAssociations
Type Disease
IgA EED,pyodermaganrenosum,subcornealpustulardermatosis,IgApemphigus,POEMS,Sweet’ssyndrome
IgM Schnitzlersyndrome,Waldenstrommacroglobulinemia
IgG NXG(IgG κ),scleredema(IgG κ > λ),scleromyxedema(IgG λ > κ)
4.52 NEPhRoGENIC FIbRoSING DERmoPAthy (NFD)/ NEPhRoGENIC SyStEmIC FIbRoSIS (NSF)Pathogenesis
• OccursinpatientswithrenalinsufficiencywhohavehadimagingstudieswithgadoliniumClinical Manifestations
• Induration,thickening,hardeningofskinwithbrawnyhyperpigmenting• Flexioncontractures,stiffeningofthehands• Pain,prurituscommon• Extremitiesmostcommonlyinvolved,thentrunk• Affectedskinisshiny,withpeaud’orangeappearance
Treatment• Extracorporealpholophoresis• Limitedoptions• Increasedmorbidily/mortalitybecauseofcontractures,mobilityproblems,falls,andfractures• Prognosis
150 2011/2012 Dermatology In-Review l Committed to Your Future
REFERENCES1. FreedbergIM,EisenAZ,WolffK,etal.,eds.Fitzpatrick’s dermatology in general medicine.5thed.NewYork:
McGraw-Hill,HealthProfessionsDivision,1999.2. InghamEetal.Proinflammatorylevelsofinterleukin-1alpha-likebioactivityarepresentinthemajorityof
opencomedonesinacnevulgaris.J Invest Dermatol. 1992;98:895-901.3. KimJetal.Activationoftoll-likereceptor2inacnetriggersinflammatorycytokineresponses. J Immunol.
2002;169:1535-1541.4. WolfJE.Potentialanti-inflammatoryeffectsoftopicalretinoidsandretinoidanalogues. Adv Ther 2002;
19:109-118.5. Odom,RB.Andrews’diseasesoftheskin,9thed.Philadelphia:WBSaunders,2000;96.6. GoldsteinSMandWintroubBU,Adverse cutaneous reactions to medications. Baltimore:Williamsand
Wilkins,1996;55-57.7. Wolverton,SE.Comprehensive dermatologic drug therapy. Philadelphia:WBSaunders,2001;277.8. Wolverton,SE.Comprehensive dermatologic drug therapy. Philadelphia:WBSaunders,2001;41.9. ElderDetal.Lever’shistopathologyoftheskin,8thed.Philadelphia:LipincottRaven,2001;295.10. WebsterGFetal.Suppressionofpolymorphonuclearleukocytechemoacticfactorproductionin
Propionibacteriumacnesbysubminimalinhibitoryconcentrationsoftetracycline,ampicillin,minocyclineanderythromycin. Antimicrob agents chemother.1982;21:770-772.
11. Wolverton,SE.Comprehensive dermatologic drug therapy.Philadelphia:WBSaunders,2001;872.12. ArcherJS,ArcherDF.Oralcontraceptiveefficacyandantibioticinteraction:amythdebunked.J Amer Acad
Dermatol.2002June;46(6):917-23.13. Wolverton,SE.Comprehensive dermatologic drug therapy.Philadelphia:WBSaunders,2001;277.14. JickSSetal.Isotretinoinuseandriskofdepression,psychoticsymptomsandattemptedsuicide.Arch
Dermatol 2000;136:1231-1236.15. Wolverton,SE.Comprehensive dermatologic drug therapy.Philadelphia:WBSaunders,2001:396.16. BaranRandTostiA.Nails. Dermatology in General Medicine, 5thEdition.NewYork,McGraw-Hill,1999,p
757-759.17. KavanaughA.Flareofpsoriasisandpsoriaticarthritisfollowingtreatmentwithgranulocytecolonystimulat-
ingfactor.Am J Med1996;101(5):567-8.18. PartschGetal.Highlyincreasedlevelsoftumornecrosisfactoralphaandotherproinflammatorycytokines
inpsoriaticarthritissynovialfluid.J Rheumatol 1197;24(3):518-23.19. Odom,RB.Andrews’diseasesoftheskin,9thEdition.Philadelphia:WBSaunders,2000;220.20. RappSRetal.Psoriasiscausesasmuchdisabilityasothermajormedicaldiseases.J Am Acad Dermatol.
1999;41:401-407.21. ElderDetal.Lever’sHistopathologyoftheSkin,8thed.Philadelphia:LipincottRaven,1997;169.22. BachJF,Theeffectofinfectionsonsusceptibilitytoautoimmuneandallergicdiseases.N Engl J Med 2002;
347(12);911-920.23. BonerA,ValettaE,BellantiJA.Improvementofatopicdermatitisfollowingnaturemeaslesvirusinfection:
Fourcasereports.Ann Allerg1985;55:605-608.24. OngPYetal.Endogenousantimicrobialpeptidesandskininfectionsinatopicdermatitis.N Engl J Med2002;
347(15);1151-1159.25. KalliomakiMetal.Proboticsinprimarypreventionofatopicdisease:Arandomizedplacebocontrolledtrial.
Lancet.2001;357:1076-9.26. CerroniL,KerlH.Bcelllymphomasoftheskin.InBologniaJL,etal.,Eds.Dermatology.Mosby:London,
2003:1497.27. FairleyJ.Cacifyingandossifyingdiseasesoftheskin.InBologniaJL.etal.,Eds.Dermatology.Mosby:London.
2003:692-3.28. CallenJP,WortmanRL.Dermatomyositis.Clinical Dermatolo.Sept-Oct2006;24(5)363-73.29. CowperSE,KuoPH,BucalaR.Nephrogenicsystemicfibrosisandgadoliniumexposure:associationandles-
sonsforidiopathicfibrosingdisorders.Arthritis Rheun.Oct2007;56(10):3173-5.
General Dermatology 151
NOTES
152 2011/2012 Dermatology In-Review l Committed to Your Future
NOTES