Dermatomyositis - Practice Essentials, Background, Pathophysiology

23/10/2015
Dermatomyositis:PracticeEssentials,Background,Pathophysiology
Dermatomyositis
Author:AlisaNFemia,MDChiefEditor:HerbertSDiamond,MDmore...
Updated:Sep30,2014
PracticeEssentials
Dermatomyositisisanidiopathicinflammatorymyopathywithcharacteristic
cutaneousfindingsthatoccurinchildrenandadults(seetheimagebelow).This
systemicdisordermostfrequentlyaffectstheskinandmusclesbutmayalsoaffect
thejointstheesophagusthelungsand,lesscommonly,theheart. [1,2]Dystrophic
calcinosismaycomplicatedermatomyositisandismostoftenobservedinchildren
andadolescents.
Theselesionsondorsalhandsdemonstratephotodistributionofdermatomyositis.Notesparing
ofinterdigitalwebspaces.
Signsandsymptoms
Personswithdermatomyositisoftenpresentwithskindiseaseasoneoftheinitial
manifestations,anditmaybethesolemanifestationatonsetinperhapsasmany
as40%ofindividualswiththiscondition.Cutaneousinvolvementmaymanifestas
follows:
Eruptionpredominantlyonphotoexposedsurfaces
Pruritusofskinlesions,sometimesintenseenoughtodisturbsleep
Erythemaofthemidface
Eruptionalongtheeyelidmargins,withorwithoutperiorbitaledema
Eruptiononthedorsalhands,particularlyovertheknuckles
Changesinthenailfoldsofthefingers
Eruptionoftheupperouterthighs
Scalyscalpordiffusehairloss [3]
Musclediseasemayoccurconcurrently,mayprecedetheskindisease,ormay
followtheskindiseasebyweekstoyears.Muscleinvolvementmanifestsasthe
following:
Proximalmuscleweakness
Musclefatigue/weaknesswhenclimbingstairs,walking,risingfromaseated
position,combinghair,orreachingforitemsaboveshoulders
Muscletenderness:Mayoccur,butnotatypicalfeatureofdermatomyositis
Systemicmanifestationsthatmayoccurincludethefollowing:
Generalsystemicdisturbances,fever,arthralgia,malaise,weightloss,
Raynaudphenomenon
Dysphagiaduetoesophagealskeletalmuscleinvolvement
Gastroesophagealrefluxduetoesophagealsmoothmuscleinvolvement
Dysphonia
Atrioventriculardefects,tachyarrhythmias,dilatedcardiomyopathies
Gastrointestinalulcersandinfections,morecommoninchildren
Pulmonaryinvolvementduetoweaknessofthoracicmuscles,interstitiallung
disease
Subcutaneouscalcification, [4]whichmayresultincontractureofjointsmore
commoninchildren
Childrenmayalsodevelopatiptoegaitsecondarytoflexioncontractureof
theanklesinearlychildhood
Malignancyinadultpatients
SeeClinicalPresentationformoredetail.
Diagnosis
http://emedicine.medscape.com/article/332783overview#a1
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Examinationforcutaneousdermatomyositismayrevealthefollowingfindings:
Characteristic,possiblypathognomoniccutaneousfeatures:Heliotrope,
Gottronpapules
Characteristicbutnotpathognomonicfeatures:Malarerythema,violaceous
erythemaorpoikilodermainaphotosensitivedistribution,violaceous
erythemaontheextensorsurfaces,andperiungualandcuticularchanges
Violaceouserythemaorpoikilodermainvolvingtheanteriorchestis
referredtoastheVnecksignwhereasinvolvementoftheupper
backandshouldersisreferredtoastheshawlsign
Rarecutaneousmanifestationsincludevesiculobullouserosivelesionsand
anexfoliativeerythroderma,whichmaybemorecommoninpatientswithan
associatedmalignancythaninthosewithoutamalignancybiopsysamples
ofthesemanifestationsrevealaninterfacedermatitissimilartothatseenin
biopsysamplesofheliotroperash,Gottronpapules,poikiloderma,orscalp
lesions
Examinationformusclediseaseindermatomyositismaydemonstratethefollowing:
Quadriparesisinvolvingproximalmusculature
Difficultyrisingfromaseatedorsupinepositionwithoutsupport
Extensormusclesoftenmoreaffectedthantheflexormuscles
Neckflexormuscleweakness
Distalstrength,sensation,andtendonreflexesmaintained(unlessthe
patienthasseverelyweakandatrophicmuscle)
Testing
Laboratoryandotherstudiesthatmaybehelpfulincludethefollowing:
Muscleenzymelevels(eg,creatinekinase,aldolase,aspartate
aminotransferase,lacticdehydrogenase)
Myositisspecificantibodies
Antinuclearantibodylevels
Pulmonaryfunctionstudieswithdiffusioncapacity
Electrocardiography
Esophagealmanometry
Colonoscopytoscreenforunderlyingmalignancy
Papanicolaousmearinwomenformalignancyscreening
CA125andCA199formalignancyscreening
Imagingstudies
Thefollowingimagingstudiesmaybeusedintheevaluationofdermatomyositis:
MRIorultrasonographyofthemuscles
Chestradiography
Bariumswallow
Electromyography
Imagingtoscreenforunderlyingmalignancy,includingCTscanningofthe
chest,abdomen,andpelvis,aswellastransvaginalultrasoundand
mammographyforwomen
Procedures
Thefollowingproceduresmaybehelpfulintheevaluationofdermatomyositis:
Skinbiopsy
Musclebiopsy(openorviaaneedle):Findingscanbediagnostic
(perivascularandinterfascicularinflammatoryinfiltrateswithadjoininggroups
ofmusclefiberdegeneration/regeneration)
SeeWorkupformoredetail.
Management
Therapyforthemusclecomponentofdermatomyositisinvolvestheuseof
corticosteroids,typicallywithanimmunosuppressiveagent.Therapyfortheskin
diseaseincludesthefollowing,amongotheroptions:
Sunavoidance
Sunscreensandphotoprotectiveclothing
Topicalcorticosteroids
Antimalarialagents
Methotrexate
Mycophenolatemofetil
Immuneglobulins
Pharmacotherapy
Medicationsusedinthemanagementofdermatomyositisincludethefollowing:
Corticosteroids(eg,prednisone):Prednisoneisafirstlinetherapyformuscle
involvementindermatomyositis
Immunosuppressiveagents(eg,methotrexate,mycophenolatemofetil,
azathioprine,rituximab,sirolimus)
Immuneglobulins(eg,intravenousorsubcutaneousimmunoglobulin)
Antimalarialagents(eg,hydroxychloroquine,chloroquine)
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Inadditiontothemedicationslistedabove,diltiazem,colchicine,alendronate,and
warfarinareamongthemedicationsthathaveshownpotentialbenefitintreating
calcinosis.Surgicalexcisionoffocal,tendercalcinoticlesionsisalsoconsidereda
therapeuticoption.
Nonpharmacotherapy
Generaltherapeuticmeasuresmayincludethefollowing:
Physicaltherapyandrehabilitativemeasures
Sunavoidance
Sunprotection(eg,broadspectrumsunscreens,sunprotectiveclothing)
Elevationofheadofbed
Avoidanceofeatingbeforebedtime
Surgery
Surgicalcareisusuallyunnecessaryinthemanagementofdermatomyositis.
However,somepatientsmaybenefitfromsurgicalremovaloflocalizedareasof
calcinosis,particularlythosethatarepainful.
SeeTreatmentandMedicationformoredetail.
Background
Dermatomyositisisanidiopathicinflammatorymyopathy(IIM)withcharacteristic
cutaneousfindings.Itisasystemicdisorderthatmostfrequentlyaffectstheskin
andmuscles,butmayalsoaffectthejointstheesophagusthelungsand,less
commonly,theheart. [1,2]Calcinosisisacomplicationofdermatomyositisthatis
observedmostofteninchildrenandadolescents.Anassociationbetween
dermatomyositisandcancerhaslongbeenrecognizedinadultpatients. [5,6,7,8,9,
10]
In1975,BohanandPeterfirstsuggestedasetoffivecriteriatoaidinthediagnosis
andclassificationofdermatomyositis. [11,12]Fourofthefivecriteriaarerelatedto
themuscledisease,asfollows:
Progressiveproximalsymmetricalweakness
Elevatedlevelsofmuscleenzymes
Anabnormalfindingonelectromyography
Anabnormalfindingonmusclebiopsy
Thefifthcriterioniscompatiblecutaneousdisease.
Inadditiontodermatomyositis,BohanandPetersuggestedthefollowingfour
subsetsofmyositis[12]:
Polymyositis
Myositiswithmalignancy
Childhooddermatomyositis/polymyositis
Myositisoverlappingwithanothercollagenvasculardisorder
Inasubsequentpublication,Bohanetal.notedthatcutaneousdiseasemay
precedethedevelopmentofthemyopathyinpatientswithdermatomyositis. [11]In
addition,theexistenceofanothersubsetofpatientswithdermatomyositisthat
affectsonlytheskin(ie,amyopathicdermatomyositis[ADM],ordermatomyositis
sinemyositis)hasbeenrecognized.Finally,anothersubsetofpatientswith
dermatomyositisarethosewithcontrolledmyopathywhocontinuetohavesevere
andsometimesdebilitatingskindisease(ie,postmyopathicdermatomyositis).
ADMisdiagnosedinpatientswithtypicalcutaneousdiseasewhoshownoevidence
ofmuscleweaknessandinwhomserummuscleenzymelevelsarerepeatedly
normalovera2yearperiodintheabsenceoftheuseofdiseasemodifying
therapiessuchascorticosteroids,immunosuppressiveagents,orbothfor2months
orlonger.
Whenstudied,someADMpatientsmayhaveabnormalfindingson
ultrasonography,electromyography,magneticresonanceimaging(MRI),magnetic
resonancespectroscopy,ormusclebiopsy.Thesepatientsarebetterclassifiedas
havinghypomyopathicdermatomyositis.ADMorhypomyopathicDMmayalsobe
relatedtoanunderlyingmalignancy.
Thetermclinicallyamyopathicdermatomyositis(CADM)isoftenusedto
encompasspatientswithbothamyopathicandhypomyopathicdermatomyositis. [13]
CADMisestimatedtoaccountforabout20%ofpatientswithdermatomyositis, [14]
andonelargereviewsuggeststhatCADMisassociatedwithmalignancyandlung
diseaseasfrequentlyasclassicdermatomyositis. [15]Inaddition,somepatientswith
CADMdevelopseverepulmonarydisease,particularlypersonsfromAsian
countries. [16]
Patientsexistinwhommyositisresolvesaftertherapybutskindiseaseremainsan
activeandimportantfeatureofthedisorder.Thesepatientsarenotclassifiedas
havingADM,eventhoughbythispoint,theskinisthemajorandoftenonly
manifestationofthedisease.Germaniandcolleagueshavesuggestedtheterm
postmyopathicdermatomyositisforthesepatients. [17]
Therapyforthemusclecomponentofdermatomyositisinvolvestheuseofsystemic
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corticosteroids,withorwithoutanimmunomodulatoryagent.Theskindiseaseis
treatedwithsunavoidance,sunscreens,photoprotectiveclothing,topical
corticosteroids,antimalarialagents,methotrexate,mycophenolatemofetil,or
intravenous(IV)immunoglobulin.Systemiccorticosteroidsaregenerallynot
administeredforcutaneousinvolvement.Rituximabmaybeusefulinthetreatment
ofmusclediseaseindermatomyositis,andhashadmixedresultsintreatmentof
skindisease. [18,19]
Physicaltherapyandrehabilitativemeasuresarenecessaryinselectedpatients.
Sunprotectivemeasuresarenecessaryforpatientswithskindisease.Patientsmay
visitTheMyositisAssociationWebsiteformoreinformation.
Theprognosisofdermatomyositisdependsontheseverityofthemyopathy,the
presenceofmalignancy,and/orthepresenceofesophagealand/orcardiopulmonary
involvement.Residualweaknessiscommon,eveninpatientswhofullyrecover.
Fordiscussionofdermatomyositisinpediatricpatients,seeJuvenile
Dermatomyositis.
Pathophysiology
Dermatomyositisisconsideredtobetheresultofahumoralattackagainstthe
musclecapillariesandsmallarterioles(endotheliumoftheendomysialblood
vessels).Since1966,therehasbeenevidencesupportinganongoing
microangiopathy. [20]
ThediseasestartswhenputativeantibodiesorotherfactorsactivateC3,forming
C3bandC4bfragmentsthatleadtoformationofC3bNEOandmembraneattack
complex(MAC),whicharedepositedintheendomysialvasculature.Complement
C5b9MACisdepositedandisneededinpreparingthecellfordestructionin
antibodymediateddisease.BcellsandCD4(helper)cellsarealsopresentin
abundanceintheinflammatoryreactionassociatedwiththebloodvessels.
Asthediseaseprogresses,thecapillariesaredestroyed,andthemusclesundergo
microinfarction.Perifascicularatrophyoccursinthebeginninghowever,asthe
diseaseadvances,necroticanddegenerativefibersarepresentthroughoutthe
muscle.
Thepathogenesisofthecutaneouscomponentofdermatomyositisispoorly
understood,butisthoughttobesimilartothatofmuscleinvolvement.
Studiesonthepathogenesisofthemusclecomponenthavebeencontroversial.
Somesuggestthatthemyopathyindermatomyositisispathogeneticallydifferent
fromthatinpolymyositis.Theformerisprobablycausedbycomplementmediated
(terminalattackcomplex)vascularinflammation,thelatterbythedirectcytotoxic
effectofCD8+lymphocytesonmuscle.However,othercytokinestudiessuggest
thatsomeoftheinflammatoryprocessesmaybesimilar.Onereporthaslinked
tumornecrosisfactor(TNF)abnormalitieswithdermatomyositis. [21]
Etiology
Thecauseofdermatomyositisisunknown.However,genetic,immunologic,
infectious,andenvironmentalfactorshavebeenimplicated.
Ageneticcomponentmaypredisposetodermatomyositis.Dermatomyositisrarely
occursinmultiplefamilymembers,butalinktocertainhumanleukocyteantigen
(HLA)types(eg,DR3,DR5,DR7)mayexist.
Polymorphismsoftumornecrosisfactor(TNF)maybeinvolvedspecifically,the
presenceofthe308Aalleleislinkedtophotosensitivityinadultsandcalcinosisin
children. [21,22,23]AmetaanalysisdemonstratedthattheTNF308A/G
polymorphismmightcontributetodermatomyositissusceptibility,especiallyina
Europeanpopulation. [24]
Immunologicabnormalitiesarecommoninpatientswithdermatomyositis.Patients
frequentlyhavecirculatingautoantibodies.AbnormalTcellactivitymaybeinvolved
inthepathogenesisofboththeskindiseaseandthemuscledisease.Inaddition,
familymembersmaymanifestotherdiseasesassociatedwithautoimmunity.
Antinuclearantibodies(ANAs)andantibodiestocytoplasmicantigens(ie,
antitransferRNAsynthetases)maybepresent.Althoughtheirpresencemayhelpto
definesubtypesofdermatomyositisandpolymyositis,theirroleinpathogenesisis
uncertain.
Infectiousagents,includingviruses(eg,coxsackievirus,parvovirus,echovirus,
humanTcelllymphotropicvirustype1[HTLV1],HIV)andToxoplasmaand
Borreliaspecies,havebeensuggestedaspossibletriggersofdermatomyositis.
Severalcasesofdruginduceddermatomyositishavebeenreported.
Dermatomyositislikeskinchangeshavebeenreportedwithhydroxyureainpatients
withchronicmyelogenousleukemiaoressentialthrombocytosis. [25,26]Otheragents
thatmaytriggerthediseaseincludethefollowing:
Statins
Penicillamine
Antitumornecrosisfactordrugs
Interferon
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Cyclophosphamide
BacillusCalmetteGurin(BCG)vaccine
Quinidine
Phenylbutazone
Dermatomyositismaybeinitiatedorexacerbatedbysiliconebreastimplantsor
collageninjections,buttheevidenceforthisisanecdotalandhasnotbeenverified
incasecontrolstudies.OnereportdetailedHLAdifferencesamongwomenin
whominflammatorymyopathydevelopedaftersiliconeimplants. [27]
Epidemiology
Theestimatedincidenceofdermatomyositisis9.63casespermillionpopulation.
TheestimatedincidenceofAMDis2.08casespermillion. [14]
Dermatomyositiscanoccurinpeopleofanyage.Twopeakagesofonsetexist:in
adults,thepeakageofonsetisapproximately50years,whereasinchildren,the
peakageisapproximately510years.Dermatomyositisandpolymyositisaretwice
ascommoninwomenasinmen.Neitherconditionshowsanyracialpredilection.
Prognosis
Mostpatientswithdermatomyositissurvive,inwhichcasetheymaydevelop
residualweaknessanddisability.Childrenwithseveredermatomyositismaydevelop
contractures.Thediseasemayspontaneouslyremitinasmanyas20%ofaffected
patients.About5%ofpatientshaveafulminantprogressivecoursewitheventual
death.Therefore,manypatientsrequirelongtermtherapy.
Patientswithdermatomyositiswhohaveanassociatedmalignancythosewith
cardiac,pulmonary,oresophagealinvolvementandthosewhoareelderly(ie,>60
years)haveapoorerprognosis.Dermatomyositismaycausedeathbecauseof
muscleweaknessorcardiopulmonaryinvolvement.Patientswithanassociated
cancermaydieofthemalignancy.
Theassociationbetweenmalignancyanddermatomyositishaslongbeen
recognized.Anestimated25%ofpatientswithdermatomyositishaveorwilldevelop
anassociatedmalignancy,andtheriskappearstoremainelevatedfor35years. [28,
29,30]StrongdatafromScandinavia,Australia,NorthAmerica,andAsiacontinue
toconfirmthisassociationwithmalignancy,andexistingdatasupportsthatpatients
withCADMhaveasimilarmalignancyrisktothosewithclassicdermatomyositis. [29,
30,31,32,33,34,35]
Ovariancancerisclearlyoverrepresentedinpatientswithdermatomyositis
however,anymalignancymayoccur.Reportedmaliganciesincludelung,colon,
prostate,breast,pancreatic,cervical,andhematologicmalignancies. [36]Predilection
forcertaintypesofmalignancymaybemorecommoninspecificpopulations.For
example,nasopharyngealcarcinomaappearstobeoverrepresentedincertain
Asianpopulations. [37,38,39]
Inarecentlypublished,approximately10yearretrospectivestudyfromsouthern
China,60of246dermatomyositispatientsdevelopedmalignancies.Theriskof
malignancywashighestinthefirstyearafterdiagnosisofdermatomyositis,and
nasopharyngealcarcinomaandovariancarcinomawerethemostcommon
malignancies.Malegender,dysphagiaandelevatederythrocytesedimentationrate
wereriskfactorsformalignancy,whereasthepresenceofinterstitiallungdisease
appearedtoreducetheriskofmalignancy. [40]Olderageappearstobethe
strongestpredictorofmalignancyinpatientswithdermatomyositis.
Calcinosismayalsocomplicatedermatomyositis.Itisrareinadultsbutismore
commoninchildrenandhasbeenlinkedtodelayindiagnosisandtoless
aggressivetherapy. [41]Contracturescanoccurifthepatientisimmobile.
AfricanAmericansandpatientsinlowersocioeconomicgroupsaremorelikelyto
experienceadelayindiagnosis.Theprognosisinchildrenwithdermatomyositisis
worseinthoseinwhomdiagnosisisdelayed.
ClinicalPresentation
ContributorInformationandDisclosures
Author
AlisaNFemia,MDAssistantProfessor,RonaldOPerelmanDepartmentofDermatology,NewYorkUniversity
MedicalCenter
AlisaNFemia,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanAcademyof
Dermatology,SocietyforInvestigativeDermatology,MedicalDermatologySociety,RheumatologicDermatology
Society
Disclosure:Nothingtodisclose.
Coauthor(s)
JeffreyPCallen,MDProfessorofMedicine(Dermatology),Chief,DivisionofDermatology,Universityof
LouisvilleSchoolofMedicine
JeffreyPCallen,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanAcademyof
Dermatology,AmericanCollegeofPhysicians,AmericanCollegeofRheumatology
5/10
23/10/2015
Disclosure:Receivedincomeinanamountequaltoorgreaterthan$250from:EliLillyXOMABiogen/IDEC
NovartisCelgene<br/>ReceivedhonorariafromUpToDateforauthor/editorReceivedhonorariafromJAMA
DermatologyforassociateeditorandintermittentauthorReceivedroyaltyfromElsevierforbookauthor/editor
Receivedidonotcontroltheseaccounts,buthavedirectedourmanagerstodivestpharmaceuticalstocksasis
fiscallyprudentfromStockholdingsinvarioustrustaccountsincludesomepharmaceuticalcompaniesanddevice
makersforiinheritedthesetrustaccounts.
RuthAnnVleugels,MD,MPHAssistantProfessorofDermatology,HarvardMedicalSchoolAssociate
Physician,DepartmentofDermatology,BrighamandWomen'sHospitalAssociatePhysician,Departmentof
ImmunologyandAllergy,Children'sHospitalBoston
RuthAnnVleugels,MD,MPHisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,American
AcademyofDermatology,AmericanCollegeofRheumatology,AmericanMedicalAssociation,Societyfor
InvestigativeDermatology,MedicalDermatologySociety,DermatologyFoundation
ChiefEditor
HerbertSDiamond,MDVisitingProfessorofMedicine,DivisionofRheumatology,StateUniversityofNewYork
DownstateMedicalCenterChairmanEmeritus,DepartmentofInternalMedicine,WesternPennsylvaniaHospital
HerbertSDiamond,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanCollege
ofPhysicians,AmericanCollegeofRheumatology,AmericanMedicalAssociation,PhiBetaKappa
Acknowledgements
LawrenceHBrent,MDAssociateProfessorofMedicine,JeffersonMedicalCollegeofThomasJefferson
UniversityChair,ProgramDirector,DepartmentofMedicine,DivisionofRheumatology,AlbertEinsteinMedical
Center
LawrenceHBrent,MDisamemberofthefollowingmedicalsocieties:AmericanAssociationforthe
AdvancementofScience,AmericanAssociationofImmunologists,AmericanCollegeofPhysicians,and
AmericanCollegeofRheumatology
Disclosure:AbbottHonorariaSpeakingandteachingCentocorConsultingfeeConsultingGenentech
Grant/researchfundsOtherHGS/GSKHonorariaSpeakingandteachingOmnicareConsultingfeeConsulting
PfizerHonorariaSpeakingandteachingRocheSpeakingandteachingSavientHonorariaSpeakingand
teachingUCBHonorariaSpeakingandteaching
WilliamDJames,MDPaulRGrossProfessorofDermatology,ViceChairman,ResidencyProgramDirector,
DepartmentofDermatology,UniversityofPennsylvaniaSchoolofMedicine
WilliamDJames,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatologyand
SocietyforInvestigativeDermatology
KristineMLohr,MD,MSProfessor,DepartmentofInternalMedicine,CenterfortheAdvancementofWomen's
HealthandDivisionofRheumatology,Director,RheumatologyTrainingProgram,UniversityofKentuckyCollege
ofMedicine
KristineMLohr,MD,MSisamemberofthefollowingmedicalsocieties:AmericanCollegeofPhysiciansand
AmericanCollegeofRheumatology
JeffreyMeffert,MDAssistantClinicalProfessorofDermatology,UniversityofTexasSchoolofMedicineatSan
Antonio
JeffreyMeffert,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatology,
AmericanMedicalAssociation,AssociationofMilitaryDermatologists,andTexasDermatologicalSociety
FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollege
ofPharmacyEditorinChief,MedscapeDrugReference
Disclosure:MedscapeSalaryEmployment
RichardPVinson,MDAssistantClinicalProfessor,DepartmentofDermatology,TexasTechUniversityHealth
SciencesCenter,PaulLFosterSchoolofMedicineConsultingStaff,MountainViewDermatology,PA
RichardPVinson,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatology,
AssociationofMilitaryDermatologists,TexasDermatologicalSociety,andTexasMedicalAssociation
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