第四軍醫(yī)大學(xué)第一附屬醫(yī)院老年病科高建苑

臨床病例報告Churg-StraussSyndrome(CSS)

FirstDescription

Churg-StraussSyndrome(CSS)isasystemicvasculitis.Thisdiseasewasfirstdescribedin1951byDr.JacobChurgandDr.LotteStraussasasyndromeconsistingof“asthma,eosinophilia[anexcessivenumberofeosinophilsintheblood],fever,andaccompanyingvasculitisofvariousorgansystems”.CSSsharesmanyoftheclinicalandpathologicalfeaturesofpolyarteritisnodosa(“PAN”,anothertypeofvasculitis).ChurgandStraussdiscoveredthatthepresenceofgranulomasaswellastheabundanceofeosinophilsdistinguishedthisdiseasefromPAN.AnothernameforChurg-StraussSyndromeisAllergicgranulomatosis.WhogetsChurg-StraussSyndrome(the“typical”patient)?

ThetypicalpatientwithCSSisamiddleagedindividualwithahistoryofnew-onsetornewly-worsenedasthma.

Thedistributionofthediseaseamongmalesandfemalesisapproximatelyequal.ClassicsymptomsandsignsofChurg-StraussSyndrome

AsthmaisoneofthecardinalfeaturesofCSS.Asthmasymptomsmaybeginlongbeforetheonsetofvasculitis–e.g.,manyyearsbeforeanyothersymptomsofCSSarise,andlongbeforethediagnosisofCSSismade.Otherearlysymptoms/signsincludenasalpolypsandallergicrhinitis.Thenextphaseofthediseaseisoftenmarkedbyeosinophilia,thefindingofanexcessivenumberofeosinophilsinthebloodorintissues.

Aneosinophilisonesubtypesofwhitebloodcell.Normally,eosinophilscomprise5%orlessofthetotalwhitebloodcellcount.InCSS,thepercentageofeosinophilsmayreachashighas60%.Inthepicturebelow,theeosinophilsareshownbythedarkpinkstain.Thethirdphaseoftheillnessisavasculitis,whichinvolvestheskin,lungs,nerves,kidneys,andotherorgans.Particularmentionshouldbemadeofthefrequentdevastatinginvolvementofthenerves(calledmononeuritismultiplex),whichproducesseveretingling,numbess,shootingpains,andseveremusclewasting/powerlossinthehandsorfeet.ThelistbelowcontainstheorganscommonlyinvolvedbyCSSandthespecificdiseasemanifestation(s)ineachorgan.Nose

Sinusitis,includingallergicrhinitisNasalpolypsLungPulmonaryinfiltrates(onlyone-thirdofallpatients)Bleedingintothelungs(occasionally)Diffuseinterstitiallungdisease(rarely)RashesPalpablepurpuraNodules(aboveorbelowtheskin),oftenatsitesofpressure,suchastheelbows

Nerve

Peripheralnerveinvolvementincludingpain,numbness,ortinglinginextremities(neuropathy/mononeuritismultiplex)

Churg-Strausssyndrome(CSS),orallergicgranulomatousangiitis,isararesyndromethataffectssmall-tomedium-sizedarteriesandveins.Wegenergranulomatosis,Churg-Strausssyndrome,andthemicroscopicformofperiarteritis(ie,microscopicpolyangiitis)arethreecloselyrelatedvasculiticsyndromesthataffectmedium-andsmall-sizedvesselsandareassociatedwithantibodiestoneutrophilcytoplasmicantigens(ANCAs).Diagnosticmarkersincludeeosinophilgranulocytesandgranulomas

inaffectedtissueandanti-neutrophilcytoplasmicantibodies(ANCA)againstneutrophilgranulocytes.DifferentiationfromWegener'sgranulomatosisisnotdifficult.Wegener'siscloselyassociatedwithc-ANCA,whileChurg-Straussshowselevationsofp-ANCA.Peoplecanliveformanyyearsinthefirsttwostagesbeforeprogressingtostagethree.

TheFrenchVasculitisStudyGrouphasdevelopedafive-pointscore("five-factorscore"orFFS)thatpredictstheriskofdeathinChurg–Strausssyndrome.Theseare(1)reducedrenalfunction(creatinine>1.58

mg/dLor140μmol/l),(2)proteinuria(>1g/24h),(3)gastrointestinalhemorrhage,infarctionorpancreatitis,(4)involvementofthecentralnervoussystemor(5)cardiomyopathy.Presenceof1oftheseindicatesseveredisease(5-yearmortality26%)and2ormoreveryseveredisease(mortality46%),whileabsenceofanyofthese5indicatesamildercase(mortality11.9%).4

WhatcausesChurg-StraussSyndrome?

ThecauseofCSSisunknownbutisprobablymulti-factorial.Geneticsmayplayasmallroleinthedisease,butCSSisalmostneverseenintwomembersofthesamefamily.Environmentalfactorssuchasexposuretoindustrialsolventsmayplayaroleinsusceptibilitytothisdisease,butthisislargelyspeculative.

Infectionsmaybetheincitingevent(s),buttodatethereisnodefinitiveevidenceofthis.HowisChurg-StraussSyndromeDiagnosed?

Amongallofthevasculitides,asthmaisadistinctivefeatureofCSSalone.However,notallpatientswithasthmahavevasculitis–onlyatinyminoritydo,infact.Itisthespecificcombinationofsymptomsandsigns,thepatternoforganinvolvement,andthepresenceofcertainabnormalbloodtests(eosinophilia,inparticular)thathelpthedoctormakethediagnosis.Inadditiontoadetailedhistoryandphysicalexamination,bloodtests,chestX-raysandothertypesofimagingstudies,nerveconductiontests,andtissuebiopsies(e.g.,oflung,skin,ornerve)maybeperformedtohelpdiagnoseCSS.asthmaeosinophilia[>10%ondifferentialWBCcount]mononeuropathytransientpulmonaryinfiltratesonchestX-raysparanasalsinusabnormalities

biopsycontainingabloodvesselwithextravasculareosinophils.

TheAmericanCollegeofRheumatology(ACR)hasproposed6criteriaforthediagnosisofChurg-Strausssyndrome

Thepresenceof4ormorecriteriayieldsasensitivityof85%andaspecificityof99.7%.

(1)asthma(wheezing,expiratoryrhonchi),(2)eosinophiliaofmorethan10%inperipheralblood,(3)paranasalsinusitis,(4)pulmonaryinfiltrates(maybetransient),(5)histologicalproofofvasculitiswithextravasculareosinophils,and(6)mononeuritismultiplexorpolyneuropathy.TreatmentandCourseofChurg-StraussSyndromeCSSusuallyrespondstoprednisone.Initially,highdosesoforalprednisoneareusedinanattempttogetthediseaseintoremissionasquicklyaspossibly(e.g.,usingoralprednisone40-60mg/day).Afterthefirstmonthorso,thishighdoseofprednisoneisgraduallytapereddownovertheensuingmonths.Otherimmunosuppressivedrugs,suchasazathioprine,cellcept,methotrexate,orcyclophosphamidemaybeusedinadditiontoprednisone.Highdosesofintravenoussteroids(usuallymethylprednisolone)maybeusefulforthosepatientswithseverediseaseorforthosewhoareunresponsivetothecombinationoforalprednisoneusedwithotherimmunosuppressivemedications.Priortotheadventofprednisone,CSSwasoftenafataldisease.Themajorityofpatientsdiedfromrampant,uncontrolleddisease.Withpresenttherapy,constitutionalsymptomsbegintoresolvequitequickly,withgradualimprovementincardiacandrenalfunction,aswellasimprovementinthepainthatresultsfromperipheralnerveinvolvement.Thecourseoftherapycanlastfor1to2years,althoughthelengthandtypeoftreatmentdependontheseverityofdiseaseandtheorgansinvolved.Thepatient’sresponsetotreatmentandthecontinuationofdiseasecontrolduringloweringoftheprednisonedosearetheprimarydeterminantsofhowlongtherapyiscontinued.

Laboratorymonitoringofbloodtestsisveryhelpfulingaugingtheactivityofdisease.Someofthemostusefull