9/19/2015

ErythemaNodosumClinicalPresentation:History,Physical,Causes

ErythemaNodosumClinicalPresentation
Author:JeanetteLHebel,MDChiefEditor:WilliamDJames,MDmore...
Updated:Apr13,2015

History
Theeruptivephaseoferythemanodosumbeginswithflulikesymptomsoffeverand
generalizedaching.Arthralgiamayoccurandprecedestheeruptionorappears
duringtheeruptivephase.Mostlesionsininfectioninducederythemanodosumheal
within7weeks,butactivediseasemaylastupto18weeks.Incontrast,30%of
idiopathicerythemanodosumcasesmaylastmorethan6months.Febrileillness
withdermatologicfindingsincludesabruptonsetofillnesswithinitialfever,followed
byapainfulrashwithin12days.

Physical
Pertinentphysicalfindingsarelimitedtotheskinandjoints.

Primaryskinlesions
Lesionsbeginasredtendernodules(seetheimagebelow).Lesionbordersare
poorlydefined,andlesionsvaryfrom26cm.Duringthefirstweek,lesionsbecome
tense,hard,andpainfulduringthesecondweek,theymaybecomefluctuant,asin
anabscess,butdonotsuppurateorulcerate.Individuallesionslastapproximately2
weeks,butoccasionally,newlesionscontinuetoappearfor36weeks.Achinglegs
andswellinganklesmaypersistforweeks.

Classicpresentationoferythemanodosumwithnodularredswellingsovertheshins.

Distributionofskinlesions
Characteristically,lesionsappearontheanteriorleghowever,theymayappearon
anysurface.

Colorofskinlesions
Lesionschangecolorinthesecondweekfrombrightredtobluishorlivid.As
absorptionprogresses,thecolorgraduallyfadestoayellowishhue,resemblinga
bruise.Thisdisappearsin1or2weeksastheoverlyingskindesquamates.

Hilarlymphnodes
Hilaradenopathymaydevelopaspartofthehypersensitivityreactionoferythema
nodosum.Bilateralhilarlymphadenopathyisassociatedwithsarcoidosis,while
unilateralchangesmayoccurwithinfectionsandmalignancy.

Joints
Arthralgiaoccursinmorethan50%ofpatientsandbeginsduringtheeruptivephase
orprecedestheeruptionby24weeks.Erythema,swelling,andtendernessoccur
overthejoint,sometimeswitheffusions.Jointtendernessandmorningstiffness

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ErythemaNodosumClinicalPresentation:History,Physical,Causes

mayoccur.Anyjointmaybeinvolved,buttheankles,knees,andwristareaffected
mostcommonly.Synovitisresolveswithinafewweeks,butjointpainandstiffness
maylastupto6months.Nodestructivejointchangesoccur.Synovialfluidis
acellular,andtherheumatoidfactorisnegative.

Causes
Currently,themostcommoncauseoferythemanodosumisstreptococcalinfection
inchildrenandstreptococcalinfectionandsarcoidosisinadults. [3]Numerousother
causeshavebeenreported. [4]Thecausesreportedmostoftenintheliteratureare
asfollows:
Bacterialinfections:Streptococcalinfectionsareoneofthemostcommon
causesoferythemanodosum.Tuberculosiswasanimportantcauseinthe
past,butithasdecreaseddramaticallyasacauseforerythemanodosum
however,itstillmustbeexcluded,especiallyindevelopingcountries. [5,6]
Yersiniaenterocoliticaisagramnegativebacillusthatcausesacutediarrhea
andabdominalpainitisacommoncauseoferythemanodosuminFrance
andFinland. [7,8,9]Mycoplasmapneumoniaeinfectionmaycauseerythema
nodosum.Erythemanodosumleprosumclinicallyresembleserythema
nodosum,butthehistologicpictureisthatofleukocytoclasticvasculitis.
Lymphogranulomavenereummaycauseerythemanodosum.Salmonella
infectionmaycauseerythemanodosum.Campylobacterinfectionmaycause
erythemanodosum.
Fungalinfections:Coccidioidomycosis(SanJoaquinValleyfever)isthemost
commoncauseoferythemanodosumintheAmericanSouthwest.In
approximately4%ofmalesand10%offemales,theprimaryfungalinfection
(whichmaybeasymptomaticorinvolvesymptomsofupperrespiratory
infection)isfollowedbythedevelopmentoferythemanodosum.Lesions
appear3daysto3weeksaftertheendofthefevercausedbythefungal
infection.Histoplasmosismaycauseerythemanodosum.Blastomycosismay
causeerythemanodosum.
Drugs:Sulfonamidesandhalideagentsareanimportantcauseoferythema
nodosum.Drugsmorerecentlydescribedtocauseerythemanodosum
includegoldandsulfonylureas.Oralcontraceptivepillsareimplicatedinan
increasingnumberofreports.
Enteropathies:UlcerativecolitisandCrohndiseasemaytriggererythema
nodosum.Erythemanodosumassociatedwithenteropathiescorrelateswith
flaresofthedisease.Themeandurationofchroniculcerativecolitisbefore
theonsetoferythemanodosumis5years,anderythemanodosumis
controlledwithadequatetherapyofthecolitis.Erythemanodosumisthe
mostfrequentdermatologicsymptomininflammatoryboweldiseases,andit
isstronglyassociatedwithCrohndisease. [10]
Hodgkindiseaseandlymphoma:Erythemanodosumassociatedwithnon
Hodgkinlymphomamayprecedethediagnosisoflymphomabymonths.
Reportsoferythemanodosumprecedingtheonsetofacutemyelogenous
leukemiahavebeenpublished. [11]
Sarcoidosis:Themostcommoncutaneousmanifestationofsarcoidosisis
erythemanodosum.Acharacteristicformofacutesarcoidosisinvolvesthe
associationoferythemanodosum,hilarlymphadenopathy,fever,arthritis,
anduveitis,whichhasbeentermedLfgrensyndrome.Thispresentationhas
agoodprognosis,withcompleteresolutionwithinseveralmonthsinmost
patients.HLADRB1*03isassociatedwithLfgrensyndrome.Most
DRB1*03positivepatientshaveresolutionoftheirsymptomswithin2years
however,nearlyhalfofDRB1*03negativepatientshaveanunremitting
course. [12]
Behetdisease(associatedwitherythemanodosum)
Pregnancy:Somepatientsdeveloperythemanodosumduringpregnancy,
mostfrequentlyduringthesecondtrimester.Repeatedepisodesoccurwith
subsequentpregnanciesorwiththeuseoforalcontraceptives.
DifferentialDiagnoses

ContributorInformationandDisclosures
Author
JeanetteLHebel,MDDermatologist,DermatologyAssociatesofLancasterDermatologist,Departmentof
Dermatology,LancasterGeneralHospital
JeanetteLHebel,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatology,
AmericanCollegeofMohsSurgery
Disclosure:Nothingtodisclose.
SpecialtyEditorBoard
DavidFButler,MDSectionChiefofDermatology,CentralTexasVeteransHealthcareSystemProfessorof
Dermatology,TexasA&MUniversityCollegeofMedicineFoundingChair,DepartmentofDermatology,Scott
andWhiteClinic
DavidFButler,MDisamemberofthefollowingmedicalsocieties:AmericanMedicalAssociation,AlphaOmega
Alpha,AssociationofMilitaryDermatologists,AmericanAcademyofDermatology,AmericanSocietyfor
DermatologicSurgery,AmericanSocietyforMOHSSurgery,PhiBetaKappa
Disclosure:Nothingtodisclose.
EdwardFChan,MDClinicalAssistantProfessor,DepartmentofDermatology,UniversityofPennsylvania

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ErythemaNodosumClinicalPresentation:History,Physical,Causes

SchoolofMedicine
EdwardFChan,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatology,
AmericanSocietyofDermatopathology,SocietyforInvestigativeDermatology
Disclosure:Nothingtodisclose.
ChiefEditor
WilliamDJames,MDPaulRGrossProfessorofDermatology,ViceChairman,ResidencyProgramDirector,
DepartmentofDermatology,UniversityofPennsylvaniaSchoolofMedicine
WilliamDJames,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatology,
SocietyforInvestigativeDermatology
Disclosure:Nothingtodisclose.
AdditionalContributors
TimothyMcCalmont,MDDirector,UCSFDermatopathologyService,ProfessorofClinicalPathologyand
Dermatology,DepartmentsofPathologyandDermatology,UniversityofCaliforniaatSanFranciscoEditorin
Chief,JournalofCutaneousPathology
TimothyMcCalmont,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanMedical
Association,AmericanSocietyofDermatopathology,CaliforniaMedicalAssociation,CollegeofAmerican
Pathologists,UnitedStatesandCanadianAcademyofPathology
Disclosure:ReceivedconsultingfeefromApsaraforindependentcontractor.
Acknowledgements
ThomasHabif,MDAdjunctProfessor,DepartmentofInternalMedicine,SectionofDermatology,Dartmouth
MedicalSchool
ThomasHabif,MDisamemberofthefollowingmedicalsocieties:AmericanAcademyofDermatologyandNew
HampshireMedicalSociety
Disclosure:Nothingtodisclose.

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