Sjögren syndrome - Wikipedia

Sjögren syndrome or Sjögren's syndrome (SjS, SS) is a long-term autoimmune disease that affects the body's moisture-producing (lacrimal and salivary) glands ... Sjögrensyndrome FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch NottobeconfusedwithSjögren–LarssonsyndromenorMarinesco–Sjögrensyndrome. MedicalconditionSjögren'ssyndromeOthernamesSjögren'ssyndrome,siccasyndromeImagewithamicroscopeoffocallymphoidinfiltrationintheminorsalivaryglandassociatedwithSjögren'ssyndrome.PronunciationUK:/ˈʃɜːɡrɛn/,US:/ˈʃoʊɡrɛn/[1]Swedish: [ˈɧø̂ːɡreːn]SpecialtyImmunology,rheumatology SymptomsDrymouth,dryeyes,otherareasofdryness[2]ComplicationsLymphoma[2]UsualonsetMiddleage[2][3]DurationLongterm[4]CausesAutoimmunedisease(unknowncause)[4]DiagnosticmethodTissuebiopsy,bloodtests[2]DifferentialdiagnosisMedicationsideeffect,anxiety,sarcoidosis,amyloidosis[5]TreatmentArtificialtears,medicationstoreduceinflammation,surgery[4]PrognosisNormallifeexpectancy[6]Frequency~0.7%[7] SjögrensyndromeorSjögren'ssyndrome(SjS,SS)isalong-termautoimmunediseasethataffectsthebody'smoisture-producing(lacrimalandsalivary)glands,[4]andoftenseriouslyaffectsotherorgansystems,suchasthelungs,kidneys,andnervoussystem.[8]Primarysymptomsaredryness(drymouthanddryeyes[2]),painandfatigue.[9]Othersymptomscanincludedryskin,vaginaldryness,achroniccough,numbnessinthearmsandlegs,feelingtired,muscleandjointpains,andthyroidproblems.[4]Thoseaffectedarealsoatanincreasedrisk(15%)oflymphoma.[2][7] Whiletheexactcauseisunclear,itisbelievedtoinvolveacombinationofgeneticsandanenvironmentaltriggersuchasexposuretoavirusorbacterium.[4]Itcanoccurindependentlyofotherhealthproblems(primarySjögren'ssyndrome)orasaresultofanotherconnectivetissuedisorder(secondarySjögren'ssyndrome).[3]Sjögren'ssyndromemaybeassociatedwithotherautoimmunediseases,includingrheumatoidarthritis(RA),systemiclupuserythematosus(SLE)orsystemicsclerosis.Theinflammationthatresultsprogressivelydamagestheglands.[7]Diagnosisisbybiopsyofmoisture-producingglandsandbloodtestsforspecificantibodies.[2]Onbiopsytherearetypicallylymphocyteswithintheglands.[2] WhileSjögren'ssyndrome[10]isoneofthemostcommonauto-immunediseases,ithasnospecificandnon-invasivediagnostictestsandtreatmentisdirectedatmanagingtheperson'ssymptoms.[4]Fordryeyes,artificialtears,medicationstoreduceinflammation,punctalplugs,orsurgerytoshutthetearductsmaybetried.[4]Foradrymouth,chewinggum(preferablysugar-free),sippingwater,orasalivasubstitutemaybeused.[4]Inthosewithjointormusclepain,ibuprofenmaybeused.[4]Medicationsthatcancausedryness,suchasantihistamines,mayalsobestopped.[4]Themostspecificextantdiagnostictestrequireslipbiopsy. Thediseasewasdescribedin1933byHenrikSjögren,afterwhomitisnamed;however,anumberofearlierdescriptionsofpeoplewiththesymptomsexist.[3]Between0.2and1.2%ofthepopulationisaffected,withhalfhavingtheprimaryformandhalfthesecondaryform.[7]Femalesareaffectedabout10timesasoftenasaremales.[3]Thoughthediseasecommonlybeginsinmiddleage,anyonecanbeaffected.[2][3]Amongthosewithoutotherautoimmunedisorders,lifeexpectancyisunchanged.[6] Contents 1Signsandsymptoms 1.1Complications 1.2Associatedconditions 2Causes 2.1Genetics 2.2Hormones 2.3Microchimerism 2.4Environment 3Pathogenesis 3.1Geneticpredisposition 3.2Environmentaltriggers 3.3Inflammation 3.4Programmedcelldeath 3.5Hormonalfactors 4Diagnosis 5Prevention 6Treatment 6.1Eyecare 6.2Vaginaldryness 6.3Musculoskeletal 6.4Systemic 6.5Dentalcare 7Prognosis 8Epidemiology 9History 10Research 11Notablecases 12References 13Externallinks Signsandsymptoms[edit] Characteristicdrynessappearsatmultiplelocations,suchasthetongue,face,andeyes. ThehallmarksymptomofSjögrensyndromeisdrymouthandkeratoconjunctivitissicca(dryeyes).[11]Vaginaldryness,dryskin,anddrynosemayalsooccur.[11]Otherorgansofthebodymayalsobeaffected,[12]includingthekidneys,bloodvessels,lungs,liver,pancreas,andbrain.[11][13] SkindrynessinsomepeoplewithSSmaybetheresultoflymphocyticinfiltrationintoskinglands.Thesymptomsmaydevelopinsidiously,withthediagnosisoftennotconsideredforseveralyearsbecausesiccamaybeattributedtomedications,adryenvironment,oraging,ormayberegardedasnotofaseveritywarrantingthelevelofinvestigationnecessarytoestablishthepresenceoftheunderlyingautoimmunedisorder.[14] Sjögren'ssyndromecandamagevitalorgans,withsymptomsthatmayplateauorworsen,orgointoremission,aswithotherautoimmunediseases.Somepeoplemayexperienceonlythemildsymptomsofdryeyesandmouth,whileothershavesymptomsofseveredisease.Manypatientscantreatproblemssymptomatically.Othersexperienceblurredvision,constanteyediscomfort,recurrentmouthinfections,swollenparotidglands,dysphonia(vocaldisordersincludinghoarseness),anddifficultyinswallowingandeating.Debilitatingfatigueandjointpaincanseriouslyimpairqualityoflife.Somepatientscandevelopkidneyinvolvement(autoimmunetubulointerstitialnephritis)leadingtoproteinuria(excessproteininurine),urinaryconcentratingdefect,anddistalrenaltubularacidosis.[15] HypokalemicparalysisduetoprimarySjögrensyndromewasrarelyreportedintheliterature.[16] Complications[edit] Amongthecomplicationsdiscussedabove,womenwithanti-Ro/SS-Aandanti-La/SS-Bantibodieswhobecomepregnanthaveanincreasedrateofneonatallupuserythematosuswithcongenitalheartblockrequiringapacemaker.[17]TypeIcryoglobulinemiaisaknowncomplicationofSjögren'ssyndrome.[18] Sjögren'ssyndromecanaffectsuchorgansastheliver,pancreas,kidneys,lungs,andcentralnervoussystem.[19] Associatedconditions[edit] Sjögren'ssyndromeisassociatedwithanumberofothermedicalconditions,manyofwhichareautoimmuneorrheumaticdisorders,suchasceliacdisease,[20][21]fibromyalgia,SLE(lupus),autoimmunethyroiditis,multiplesclerosisandspondyloarthropathy,[22]andseveralmalignancies,principallynon-Hodgkinlymphoma.[22][23] Causes[edit] ThecauseofSjögren'ssyndromeisunknown,butitmaybetheinfluenceofacombinationofgenetic,environmental,andotherfactors,asisthecasewithmanyotherautoimmunedisorders.[24]Around20autoantibodiescouldbeinvolved.[25] Genetics[edit] TheobservationofhighratesofautoimmunedisordersinfamilieswithahistoryofSjögren'ssyndromeislinkedwithageneticpredispositiontothesyndrome.[26]Studiesonthepolymorphismsofhumanleukocyteantigen(HLA)-DRandHLA-DQgeneregionsinSjögren'spatientsshowdifferentialsusceptibilitytothesyndromeastheresultofdifferenttypesoftheresultingautoantibodyproduction.[26] Hormones[edit] SinceSjögren'ssyndromeisassociatedwithahighprevalenceinwomen,sexhormones,especiallyestrogen,arebelievedtoaffecthumoralandcell-mediatedimmuneresponsesaffectingsusceptibilitytothesyndrome.[26]Androgensaregenerallyconsideredtopreventautoimmunity.[27]Studiesonmicemodelssuggestestrogendeficiencystimulatespresentationofautoantigens,inducingSjögren's-likesymptoms.[26] Microchimerism[edit] Microchimerismoffetalcells(offspringlymphoidcellsinmaternalcirculation)maygenerateautoimmunityinwomenwhohavepreviouslybeenpregnant.[27][28]Generationofanautoimmunepotentialviamicrochimerismmayleadtoaswitchfromasilentformofautoimmunitywithage-dependentdecreaseinself-tolerance.[27] Environment[edit] Viralproteins,engulfedmolecules,ordegradedself-structuresmayinitiateautoimmunitybymolecularmimicryandincreasethechancesofSjögren'ssyndromedevelopment.[27]Epstein–Barrvirus,hepatitisC,andhumanT-cellleukemiavirus-1areamongthemoststudiedinfectiousagentsinSjögren'ssyndrome.[27]Todate,nodirectcausesandeffectrelationshiphasbeenidentifiedbetweenthesepathogensandthedevelopmentofSjögren'ssyndrome.Damagedself-structurestargetedforapoptosismaybemistakenlyexposedtotheimmunesystem,triggeringautoimmunityinexocrineglands,whichareoftenpronetoautoimmuneresponses.[27] Pathogenesis[edit] ThepathogeneticmechanismsofSjögren'ssyndromehavenotbeenfullyelucidated,resultinginthelackofpathophysiologyknowledgeofthemanagementofthisautoimmuneexocrinopathy.Althoughthenumerousfactorscontributingtotheprogressionofthisdiseasehavemadediscoveringtheexactoriginandcausedifficult,majoradvancesoverthepastdecadehavecontributedtoaproposedsetofpathogeniceventsthatoccurpriortothediagnosisofSjögren'ssyndrome.[26] Sjögren'ssyndromewasoriginallyproposedasaspecific,self-perpetuating,immunesystem-mediatedlossofexocrineglands,specificallyacinarandductalcells.Althoughthisexplainsthemoreobvioussymptoms(suchasthelackofsalivaandlacrimalfluid),itdoesnotexplainthemorewidespreadsystemiceffectsseenintheprogressionofthedisease.[citationneeded] Inthepresenceofasusceptiblegeneticbackground,bothenvironmentalandhormonalfactorsarethoughtcapableoftriggeringtheinfiltrationoflymphocytes,specificallyCD4+Tcells,Bcells,andplasmacells,causingglandulardysfunctioninthesalivaryandlacrimalglands.[26] Sjögren'ssyndromeisassociatedwithincreasedlevelsincerebrospinalfluid(CSF)ofIL-1RA,aninterleukin1antagonist.Thissuggeststhatthediseasebeginswithincreasedactivityintheinterleukin1system,followedbyanautoregulatoryupregulationofIL-1RAtoreducethesuccessfulbindingofinterleukin1toitsreceptors.Interleukin1likelyisthemarkerforfatigue,butincreasedIL-1RAisobservedintheCSFandisassociatedwithincreasedfatiguethroughcytokine-inducedsicknessbehavior.[29]However,Sjögren'ssyndromeischaracterizedbydecreasedlevelsofIL-1rainsaliva,whichcouldberesponsibleformouthinflammationanddryness.[30]PatientswithsecondarySjögren'ssyndromealsooftenexhibitsignsandsymptomsoftheirprimaryrheumaticdisorders,suchassystemiclupuserythematosus,rheumatoidarthritis,orsystemicsclerosis.[citationneeded] Geneticpredisposition[edit] ThegeneticlocusmostsignificantlyassociatedwithprimarySSisthemajorhistocompatibilitycomplex/humanleukocyteantigen(MHC/HLA)region,asdemonstratedbythepreliminaryresultsofthefirstgenome-wideassociationstudy.[31]Thisstudyincludeddatafromadiscoverycohortof395patientsofEuropeanancestrywithprimarySjögren'ssyndrome,and1,975healthycontrolindividuals,andfromareplicationstudythatcomprised1,234casesand4,779healthycontrols.Associationswithpolymorphismslocatedatsixindependentlociwerealsodetected;IRF5,STAT4,BLK,IL12A,TNIP1,andCXCR5.Thisalsosuggestedtheactivationoftheinnateimmunesystem,notablythroughtheIFNsystem,B-cellactivationthroughCXCR5-directedrecruitmenttolymphoidfolliclesandB-cellreceptor(BCR)activationinvolvingBLK,andT-cellactivationowingtoHLAsusceptibilityandtheIL-12-IFN-γ-axis.[32] PatientsofdifferentethnicorigincarrydifferentHLA-susceptibilityalleles,ofwhichHLA-DRandHLA-DQareinvolvedinthepathogenesisofSjögren'ssyndrome.Forexample,patientsfromNorthernandWesternEuropeandfromNorthAmericashowahighprevalenceofB8,DRw52,andDR3genes.[33]HLAclassIIallelesareassociatedwiththepresenceofspecificsubsetsofautoantibodies,ratherthanwiththediseaseitself.[34]AutoantibodiesrefertothelossofB-celltoleranceleadingtoproductionofantibodiesdirectedagainstdiverseorgan-specificandorgannonspecificantigens.[26]AssociationbetweenHLAandSSisrestrictedtopatientswithanti-SSA/Rooranti-SSB/Laantibodies.Seropositivityforanti-Roandanti-Laisassociatedwithgreaterseverityandlongerdurationofdisease,andfindingsoftheirhighabundancefromthesalivaryglandsofSjögren'spatientssuggeststheirimperativeroleinthepathogenesisofSS.[35] Beyondgenetics,epigeneticabnormalityrelatedtoDNAmethylation,histoneacetylation,ormicroRNAexpressionprobablyhasakeyroleinthepathogenesisofautoimmunediseases,includingSjögren'ssyndrome,thoughresearchinthisareaisverylimited.[36] Environmentaltriggers[edit] Environmentalfactors,suchasglandularviralinfection,couldpromptepithelialcellstoactivatetheHLA-independentinnateimmunesystemthroughtoll-likereceptors.[37]Althoughanumberofinfectious,exogenousagentshavebeenimplicatedinthepathogenesisofSjögren'ssyndrome,suchasEpstein-Barrvirus(EBV),humanT-lymphotropicvirus1,andhepatitisCvirus,theirassociationwithSjögren'ssyndromeappearsweak.WhileEBVispresentinthesalivaryglandsofnormalindividuals,ahighincidenceofEBVreactivationinSjögren'spatientshasbeenreportedwithincreasedlevelsofEBVDNA.ThisindicatesviralreactivationandinabilityoflymphoidinfiltratestocontrolEBVreplicationinSjögren'ssyndrome,leadingtotheinitiationorperpetuationofanimmuneresponseintargetorgans.Nonetheless,exactlyhowreactivationofEBVisinducedinlesionsofpatientswithSjögren'ssyndrome,andwhichspecificmolecularmechanismsareinvolvedintheprocessofviralreactivation,remaintobeclarified.[38] Inflammation[edit] EpithelialcellsinSjögren'ssyndromelesionsareactiveparticipantsintheinductionandperpetuationoftheinflammatoryprocess.Environmentalandhormonalfactors,inconcertwithanappropriategeneticbackground,arebelievedtotriggerSjögren'ssyndrome,whichdysregulatesepithelialcellsandallowsaberranthomingandactivationofdendriticcells(DCs),Tcells,andBcells.[39]Dendriticcellsareantigen-presentingcellsthatprocessantigenmaterialandpresentittootherTcells.Followingthemigrationoflymphocytesintotheglandsinresponsetochemokinesandspecificadhesionmolecules,Tcellsinteractwithepithelialcells.Epithelialcellsarefurtheractivatedbyproinflammatorycytokines(IL-1β,IFN-γ,andTNF),whichareproducedbyadjacentTcells.Theearlyaccumulationofplasmacytoiddendriticcellsinthetargettissues,whichproducehighlevelsoftype1IFNs,seemsimportant,asthesecellscanfurtherdysregulatetheimmuneresponsethroughabnormalretentionoflymphocytesinthetissuesandtheirsubsequentactivation.IFN-αstimulatestheproductionofB-cellactivatingfactor(BAFF)byepithelialcells,DCs,andTcells.BAFFstimulatesaberrantB-cellmaturation,leadingtotheemergenceofself-reactiveBcells,whichlocallyproduceautoantibodies,inagerminalcentre-likestructure(GC-like),whichisalsothelocationoflymphomagenesis(originoflymphoma).[26] Programmedcelldeath[edit] Dysregulationofapoptosis(programmedcelldeath)isbelievedtoplayaroleinthepathogenesisofavarietyofautoimmunediseases,thoughitsroleinSjögren'ssyndromeiscontroversial.BoththeFasandFasligandproteinsareoverexpressedinprimarySjögren'spatients,whileexpressionofBCL-1,whichisknowntodownregulateapoptosis,wasfoundsignificantlyreducedinacinarandductalepithelialcellsofSjögren'spatientscomparedtohealthypeople.[40][41]Insitustudiesdidnotshowincreasedapoptosisamongglandularepithelialcells,butdidshowreducedapoptosisamonginfiltratingmononuclearcells.ReducedapoptosiswasalsoimplicatedintheaccumulationofautoreactiveB-cellsfoundintheglands.TherelationshipofautoantibodiesexpressedinSjögren'ssyndromewithapoptosisisstillbeingresearched.[24] Hormonalfactors[edit] Sexhormonesseemtoinfluencehumoralandcell-mediatedimmuneresponse,withestrogenbeingconsideredoneofthebiggestfactorsresponsibleforsex-immunologicdimorphism.[42]EstrogendeficiencyappearstoplayaroleindevelopmentofSjögren'ssyndrome.[43]Ithasbeenhypothesizedthatandrogenadministrationtotheocularsurfacemayserveasaneffectivetherapyfordryeyes.[44] Diagnosis[edit] SpeckledimmunofluorescencestainingpatternofantinuclearantibodiesonHEp-20-10cells DiagnosingSjögren'ssyndrome(SS)iscomplicatedbytherangeofsymptomsthatapatientmaymanifest,andthesimilaritybetweensymptomsofSjögren'ssyndromeandthoseofotherconditions.Also,patientswithSSsymptomsapproachdifferentspecialitiesfortreatment,whichcanmakediagnosisdifficult.Sincedryeyesanddrymouthareverycommonsymptoms,andfrequentlyoccurinpeopleover40,affectedpeoplemaybelievethatthesymptomsareage-related,soignorethem.SomemedicationscancausesymptomssimilartothoseofSjögren'ssyndrome.Thecombinationofseveraltests,whichcanbedoneinaseries,caneventuallydiagnoseSjögren'ssyndrome.[28][45] Bloodtestscanbedonetodetermineifapatienthashighlevelsofantibodiesthatareindicativeofthecondition,suchasantinuclearantibody(ANA)andrheumatoidfactor(becauseSjögren'ssyndromefrequentlyoccurssecondarytorheumatoidarthritis),whichareassociatedwithautoimmunediseases.TypicalSSANApatternsareSSA/RoandSSB/La,ofwhichanti-SSB/Laisfarmorespecific;anti-SSA/Roisassociatedwithnumerousotherautoimmuneconditions,butisoftenpresentinSS,butaAnti-SSAandanti-SSBtestsarefrequentlynotpositiveinSS.[citationneeded] Therosebengaltestusesastainthatmeasuresstateandfunctionofthelacrimalglands.Thistestinvolvesplacingthenontoxicdyerosebengalontheeyes.Thedye'sdistinctivecolourhelpsindeterminingthestateandfunctioningoftearfilmandtherateoftearevaporation.AnydistinctivecolourchangecanindicateSS,butconfirmingtheconditionrequiresmanyrelateddiagnostictools.[45] Schirmer'stestmeasurestheproductionoftears:astripoffilterpaperisheldinsidethelowereyelidforfiveminutes,anditswetnessisthenmeasuredwitharuler.Producinglessthan5 mm(0.20 in)ofliquidisusuallyindicativeofSS.Thismeasurementanalysisvariesamongpeopledependingonothereye-relatedconditionsandmedicationsinusewhenthetestistaken.[45]Aslit-lampexaminationcanrevealdrynessonthesurfaceoftheeye.[citationneeded] Symptomsofdrymouthanddrynessintheoralcavityarecausedbythereducedproductionofsalivafromthesalivaryglands(parotidgland,submandibulargland,andsublingualgland).Tocheckthestatusofsalivaryglandsandtheproductionofsaliva,asalivaryflow-ratetestisperformed,inwhichthepersonisaskedtospitasmuchastheycanintoacup,andtheresultingsalivasampleiscollectedandweighed.Thistest'sresultscandeterminewhetherthesalivaryglandsarefunctioningadequately.NotenoughsalivaproducedcouldmeanthepersonhasSS.[45]Analternativetestisnonstimulatedwholesalivaflowcollection,inwhichthepersonspitsintoatesttubeeveryminutefor15minutes.Aresultantcollectionoflessthan1.5 ml(0.053 imp fl oz;0.051 US fl oz)isconsideredapositiveresult.[46] Chisholm-Masongrade[47] Grade Lymphocytes 1 Slightinfiltrate 2 Moderateinfiltrateorlessthanonefocus* 3 Onefocus* 4 Morethanonefocus* *Focus=anaggregrateof50lymphocytesormore. Alip/salivaryglandbiopsytakesatissuesamplethatcanreveallymphocytesclusteredaroundsalivaryglands,anddamagetotheseglandsfrominflammation.Thistestinvolvesremovingasampleoftissuefromaperson'sinnerlip/salivaryglandandexaminingitunderamicroscope.Onsuchbiopsies,thesinglemostimportanttestresultinthediagnosisoftheoralcomponentofSjögrensyndromeislikelythefocusscore,whichisthenumberofmononuclearcellinfiltratescontainingatleast50inflammatorycellsina4 mm2glandularsection.[48]TheChisholm-Masongradesarealsowidelyusedforsalivaryglandbiopsies(seetable).[49] AradiologicalprocedureisavailableasareliableandaccuratetestforSjögren'ssyndrome,intheformofasialogram.Acontrastagentisinjectedintotheparotidduct,whichopensfromthecheekintothevestibuleofthemouthoppositetheneckoftheuppersecondmolartooth.Thetestisintendedtodetectanyblockageinthesalivaryglandducts(i.e.parotidduct)andtheamountofsalivathatflowsintothemouth.[45] ForSjögren'ssyndrome,sudomotorfunctionthroughelectrochemicalskinconductancemayhelpinthediagnosisprocess.[50][51] Sjögren'ssyndromecanbeexcludedfrompeoplewithpastheadandneckradiationtherapy,acquiredimmunodeficiencysyndrome,pre-existinglymphoma,sarcoidosis,graft-versus-hostdisease,anduseofanticholinergicdrugs.[citationneeded] Prevention[edit] NopreventionmechanismexistsforSjögren'ssyndrome(SS)becauseofitscomplexityasanautoimmunedisorder,butlifestylechangescanreducetheriskfactorsrelatedtodevelopingSSorreducetheseverityoftheconditionforpatientswhohavealreadybeendiagnosed.Dietisstronglyassociatedwiththeinflammationseeninmanyautoimmunerelateddiseases,includingSS.AnexperimentalstudyconcludedthatSSpatientsoftenshowhighsensitivitytoglutenthatdirectlyrelatestoinflammation.[52]ModerateexerciseisalsohelpfulinSSpatients,mainlyreducingtheeffectoflunginflammation.[53][citationneeded] Treatment[edit] NeitheracurenoraspecifictreatmentforSjögren'ssyndromeisknowntopermanentlyrestoreglandsecretion.Instead,treatmentisgenerallysymptomaticandsupportive.[citationneeded] Eyecare[edit] Moisturereplacementtherapiessuchasartificialtearsmayeasethesymptomsofdryeyes.Somepatientswithmoresevereproblemsusegogglestoincreaselocalhumidityorhavepunctalplugsinsertedtohelpretaintearsontheocularsurfaceforalongertime.[citationneeded] Additionally,cyclosporine(Restasis)isavailablebyprescriptiontotreatchronicdryeyebysuppressingtheinflammationthatdisruptstearsecretion.Prescriptiondrugsarealsoavailablethathelptostimulatesalivaryflow,suchascevimeline(Evoxac)andpilocarpine.Salagen,amanufacturedformofpilocarpine,canbeusedtohelpproducetears,aswellassalivainthemouthandintestines.[54]Itisderivedfromthejaborandiplant.[55] Vaginaldryness[edit] InwomenwithSjögren'ssyndrome,vaginaldryness,vulvodyniaanddyspareunia(painfulsexualintercourse)areoftenreported;personallubricantsarerecommendedtohelplessenirritationorpainthatmayresultfromdrynessinthevaginalandvulvalareas.[45] Musculoskeletal[edit] Nonsteroidalanti-inflammatorydrugs(NSAIDs)maybeusedtotreatmusculoskeletalsymptoms.Forindividualswithseverecomplications,corticosteroidsorimmunosuppressivedrugsmaybeprescribed,andsometimesintravenousimmunoglobulins.Also,disease-modifyingantirheumaticdrugssuchasmethotrexatemaybehelpful.Hydroxychloroquine(Plaquenil)isanotheroptionandisgenerallyconsideredsaferthanmethotrexate.However,theseprescribeddrugshavearangeofsideeffectssuchasnausea,lossofappetite,dizziness,hairloss,stomachaches/cramps,headache,livertoxicityandincreasedriskofinfections.Also,thosewhotakedrugstosuppresstheimmunesystemaremorelikelytodevelopcancerlater.[45] Systemic[edit] Forsystemicsymptoms,includingfatigue,jointpain,myositisandneuropathy,biologicimmunosuppressantdrugssuchasrituximabandbelimumabthatworkviaB-cellpathologyareoftenusedandhavelesstoxicprofilesthantraditionalimmunosuppressiveregimens.[citationneeded] Dentalcare[edit] Preventivedentaltreatmentisalsonecessary(andoftenoverlookedbythepatient),asthelackofsalivaassociatedwithxerostomiacreatesanidealenvironmentfortheproliferationofbacteriathatcausecavities.[56]Treatmentsincludeat-hometopicalfluorideapplicationtostrengthentoothenamelandfrequentteethcleaningsbyadentalhygienist.Existingcavitiesmustalsobetreated,ascavitiesthatextendintothetoothcannotbeeffectivelytreatedbyteethcleaningalone,andareatahighriskofspreadingintothepulpofthetooth,leadingtothelossofvitalityandneedforextractionorrootcanaltherapy.Thistreatmentregimenisthesameasforallxerostomiapatients,suchasforthoseundergoingheadandneckradiationtherapy,whichoftendamagesthesalivaryglands;theseglandsaremoresusceptibletoradiationthanareotherbodytissues.[citationneeded] Prognosis[edit] PublishedstudiesonthesurvivalofSjögren'ssyndromepatientsarelimitedinvariedrespects,perhapsowingtotherelativelysmallsamplesizes,andthefactthatsecondarySjögren'ssyndromeisassociatedwithotherautoimmunediseases.Resultsfromanumberofstudiesindicatethat,comparedtootherautoimmunediseases,Sjögren'ssyndromeisassociatedwithanotablyhighincidenceofmalignantnon-Hodgkinlymphoma,acancerofwhitebloodcells.[26]About5%ofpatientswithSSdevelopsomeformoflymphoidmalignancy.[57]Patientswithseverecasesaremuchmorelikelytodeveloplymphomasthanpatientswithmildormoderatecases.[58]ThemostcommonlymphomasaresalivaryextranodalmarginalzoneBcelllymphomas(MALTlymphomasinthesalivaryglands)[59]anddiffuselargeB-celllymphoma.[58] LymphomagenesisinprimarySjögren'ssyndromepatientsisconsideredasamultistepprocess,withthefirststepbeingchronicstimulationofautoimmuneBcells,especiallyBcellsthatproducerheumatoidfactoratsitestargetedbythedisease.[60][61]Thisincreasesthefrequencyofoncogenicmutation,leadingtoanydysfunctionatcheckpointsofautoimmuneB-cellactivationtotransformintomalignancy.Astudy'sfindinghasconcludedthecontinuousstimulationofautoimmuneBcells,leadingtosubtlegerminalabnormalitiesingeneshavingspecificconsequencesinBcells,whichunderliesthesusceptibilitytolymphoma.[62] ApartfromthisnotablyhigherincidenceofmalignantNHL,Sjögren'spatientsshowonlymodestorclinicallyinsignificantdeteriorationinspecificorgan-relatedfunction,whichexplainstheonlyslightincreasesinmortalityratesofSjögren'spatientsincomparisonwiththeremainderofthepopulation.[26] Sjögren'ssyndromeisassociatedwithahighburdenofillness,[63]andhasbeenshowntomarkedlyreducequalityoflife(QoL),withasignificantimpactonabilitytoworkresultingfromincreasedratesofdisability.[64][65][66]ThereductioninQoLissimilartothatseeninotherchronicconditionssuchasrheumatoidarthritis,lupusandfibromyalgia.[65] Epidemiology[edit] Sjögren'ssyndrome(SS)isthesecond-mostcommonrheumaticautoimmunedisorder,behindrheumatoidarthritisandsystemiclupuserythematosus.[14]TherearenogeographicaldifferencesintheratesofSS.[67]Sjögren'ssyndromehasbeenreportedinallareasoftheworld,althoughregionalrateshavenotbeenwellstudied.[67][68]Dependingonthecriteriafordeterminingprevalence,studiesestimatetheprevalenceofSSatbetween500,000andtwomillionpeopleintheUnitedStates.BroaderstudiesofSSprevalencerangewidely,withsomereportsofuptoaprevalenceof3%ofthepopulation.[14]Afewstudieshavereportedthattheincidenceofthesyndromevariesbetweenthreeandsixper100,000peryear.[14][69] Nineoutof10SSpatientsarewomen.[24][68]Inadditiontoprevalenceinwomen,havingafirst-degreerelativewithanautoimmunediseaseandpreviouspregnancieshavebeenidentifiedasepidemiologicalriskfactors.[70]Despitethelowerriskformen,primarySSinmentendstorepresentamoresevereformofthedisease.[71]Theroleofraceandethnicityintheprevalenceofthediseaseisunknown.[citationneeded] AlthoughSjögren'ssyndromeoccursinallagegroups,theaverageageofonsetisbetweenages40and60,althoughasmanyashalfofallcasesmaybeleftundiagnosedorunreported.[24][14][72][73]TheprevalenceofSSgenerallyincreaseswithage.[14] Sjögren'ssyndromeisreportedin30-50%ofpeoplewithrheumatoidarthritisandin10-25%withsystemiclupuserythematosus.[24] History[edit] JanMikulicz-Radecki(1850–1905)isgenerallycreditedwiththefirstdescriptionofSS.In1892,hedescribeda42-year-oldmanwithenlargementoftheparotidandlacrimalglandsassociatedwitharound-cellinfiltrateandacinaratrophy.[45][74]However,thecriteriathatMikuliczestablishedfordiagnosisoftenledtomisdiagnosisofMikulicz'ssyndrome.Manyconditions,suchastuberculosis,infections,sarcoidosisandlymphomapresentwithsimilarconditionstothoseascribedtoMikulicz'ssyndrome.[45]Nevertheless,theterm"Mikulicz’ssyndrome"isstillusedoccasionallytodescribetheappearanceoflymphocyticinfiltratesonsalivary-glandbiopsies.[45] In1930,HenrikSjögren(1899–1986),anophthalmologistinJönköping,Sweden,observedapatientwithlowsecretionsfromthelacrimalandsalivaryglands.[75]Sjögrenintroducedthetermkeratoconjunctivitissiccaforthesymptomofdryeyes(keratoconjunctivitis).In1933,hepublishedhisdoctoralthesisdescribing19females,mostofwhomwerepostmenopausalandhadarthritis,showingclinicalandpathologicalmanifestationsofthesyndrome.[74]Sjögrenclarifiedthatkeratoconjunctivitissicca,resultingfromwaterdeficiency,hadnorelationtoxerophthalmia,resultingfromvitaminAdeficiency.[74]Sjögren'sthesiswasnotwellreceivedastheBoardofExaminerscriticizedsomeclinicalaspects.[75] Afterextensiveresearchanddatacollection,Sjögrenpublishedanessentialpaperin1951,describing80patientswithkeratoconjunctivitissicca,50ofwhomalsohadarthritis.[75]Hissubsequentfollow-upconferencetripspertainingtohispaperledtoaninternationalinterestinSjögren'ssyndrome.[75]Theterm"keratoconjunctivitissicca"wascoinedbySjögrenhimselfandbegantobeidentifiedasSjögren'ssyndromeinliterature,[75]althoughitcannowhavemoregeneralusage. Research[edit] Singer-actressCarrieAnnInabaisthenationalawarenessambassadorandspokespersonfortheSjögren'sSyndromeFoundation. ResearchintomultifactorialautoimmunediseasessuchasSSfocusesonexpandingtheknowledgesurroundingthedisorder,improvingdiagnostictoolsandfindingwaystoprevent,manageandcurethedisorder.TheUnitedKingdomPrimarySjögren'sSyndromeRegistry,atissuebiobankofsamplestakenforresearch,supportedbytheMedicalResearchCouncil,UK,wasestablishedin2010.ItsupportsclinicaltrialsandgeneticstudiesofSjögren'ssyndromeandisopentothosewishingtoparticipateinresearchstudiesandtoresearchersstudyingthedisease.[76] Aswithotherautoimmunediseases,susceptibilitytoSjögren'ssyndromeisgreatlyinfluencedbythehumanleukocyteantigen.[77]DQA1*05:01,DQB1*02:01,andDRB1*03:01alleleswereidentifiedasriskfactors,whileDQA1*02:01,DQA1*03:01andDQB1*05:01alleleswerefoundtobeprotectivefactorsforthedisease.[78]Therelationshipbetweenallelesandspecificracewasalsoestablished.[79]HLA-DQ2andHLA-B8aregenerallyfoundinCaucasianpatients,whileHLA-DR5isrelatedtoGreekandIsraelipatients.[79]Multiplegenome-wideassociationscansmaybeconductedinthefuturetoidentifykeyriskvariants.[77] VirusesthathavebeenassociatedwithSjögren'ssyndromeincludehumanT-lymphotropicvirustype1(HTLV-1),Epstein-Barrvirus(EBV),humanimmunodeficiencyvirus(HIV),hepatitisdeltavirus(HDV)andhepatitisCvirus(HCV).[79][80][81] SomeresearchhasshowedthatthelackofvitaminAandvitaminDareassociatedwiththedisease.[79]VitaminDdeficiencywasfoundtoberelatedtoneurologicalmanifestationsandthepresenceoflymphomaamongpatients,butvitaminAlevelswereinverselyassociatedwithextraglandularmanifestationsofthedisease.[79] SalivaisapotentialdiagnostictoolforSjögren'ssyndromebecausethesalivarycomponentischangedafteronsetofthedisease.[82]Withthenewminiaturizationtechnology,calledlabonachip,thediagnosiscanbemoreconvenient.[82] Withregardtotherapeutics,multiplemonoclonalantibodieswereunderinvestigationin2007.[83]Themostpromisingseemedtobetheanti-CD20rituximabandtheanti-CD22epratuzumab,whiletheanti-TNF-αandIFN-αseemedlesseffective.[83] In2014,theSjögren'sSyndromeFoundationannouncedafive-yeargoaltohalvethedisease'saveragetimetodiagnosis.[84] Notablecases[edit] ShannonBoxx(U.S.Olympicsoccerplayer)hasbothSjögren'ssyndromeandlupus.[85] 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SomeoftheoriginaltextforthisarticlewasobtainedfromapublicdomainresourceatNIH Externallinks[edit] WikimediaCommonshasmediarelatedtoSjögren'ssyndrome. SjögrensyndromeatNHSChoices Sjögrensyndrome–USNationalInstituteofArthritisandMusculoskeletalandSkinDiseases USSjögren‘sFoundation Price,EJ;Rauz,S;Tappuni,AR;Sutcliffe,N;Hackett,KL;Barone,F;Granata,G;Ng,WF;Fisher,BA;Bombardieri,M;Astorri,E;Empson,B;Larkin,G;Crampton,B;Bowman,SJ;BritishSocietyforRheumatologyStandards,GuidelineandAuditWorking,Group.(1October2017)."TheBritishSocietyforRheumatologyguidelineforthemanagementofadultswithprimarySjögren'sSyndrome".Rheumatology.56(10):e24–e48.doi:10.1093/rheumatology/kex166.PMID 28957550. ClassificationDICD-10:M35.0ICD-9-CM:710.2OMIM:270150MeSH:D012859DiseasesDB:12155ExternalresourcesMedlinePlus:000456eMedicine:med/2136emerg/537derm/846ped/2811oph/477oph/695PatientUK:Sjögrensyndrome vteSystemicconnectivetissuedisordersGeneralSystemiclupuserythematosus Drug-inducedSLE Libman–Sacksendocarditis Inflammatorymyopathy Myositis Dermatopolymyositis Dermatomyositis/Juveniledermatomyositis Polymyositis*Inclusionbodymyositis Scleroderma Systemicscleroderma Progressivesystemicsclerosis CRESTsyndrome Overlapsyndrome/Mixedconnectivetissuedisease Otherhypersensitivity/autoimmune Sjögrensyndrome Other Behçet'sdisease Polymyalgiarheumatica Eosinophilicfasciitis Eosinophilia–myalgiasyndrome Ehlers-Danlossyndrome fibrillin Marfansyndrome Congenitalcontracturalarachnodactyly vteHypersensitivityandautoimmunediseasesTypeI/allergy/atopy(IgE)Foreign Atopiceczema Allergicurticaria Allergicrhinitis(Hayfever) Allergicasthma Anaphylaxis Foodallergy commonallergiesinclude:Milk Egg Peanut Treenut Seafood Soy Wheat Penicillinallergy Autoimmune Eosinophilicesophagitis TypeII/ADCC IgM IgGForeign Hemolyticdiseaseofthenewborn AutoimmuneCytotoxic Autoimmunehemolyticanemia Immunethrombocytopenicpurpura Bullouspemphigoid Pemphigusvulgaris Rheumaticfever Goodpasturesyndrome Guillain–Barrésyndrome "TypeV"/receptor Graves'disease Myastheniagravis Perniciousanemia TypeIII(Immunecomplex)Foreign Henoch–Schönleinpurpura Hypersensitivityvasculitis Reactivearthritis Farmer'slung Post-streptococcalglomerulonephritis Serumsickness Arthusreaction Autoimmune Systemiclupuserythematosus Subacutebacterialendocarditis Rheumatoidarthritis TypeIV/cell-mediated(Tcells)Foreign Allergiccontactdermatitis Mantouxtest Autoimmune Diabetesmellitustype1 Hashimoto'sthyroiditis Multiplesclerosis Coeliacdisease Giant-cellarteritis Postorgasmicillnesssyndrome Reactivearthritis GVHD Transfusion-associatedgraftversushostdisease Unknown/multipleForeign Hypersensitivitypneumonitis Allergicbronchopulmonaryaspergillosis Transplantrejection Latexallergy(I+IV) Autoimmune Sjögrensyndrome Autoimmunehepatitis Autoimmunepolyendocrinesyndrome APS1 APS2 Autoimmuneadrenalitis Systemicautoimmunedisease vteOralandmaxillofacialpathologyLips Cheilitis Actinic Angular Plasmacell Cleftlip Congenitallippit Eclabium Herpeslabialis Macrocheilia Microcheilia Nasolabialcyst Sunpoisoning Trumpeter'swart Tongue Ankyloglossia Blackhairytongue Caviartongue Crenatedtongue Cunnilingustongue Fissuredtongue Foliatepapillitis Glossitis Geographictongue Medianrhomboidglossitis Transientlingualpapillitis Glossoptosis Hypoglossia Lingualthyroid Macroglossia Microglossia Rhabdomyoma Palate Bednar'saphthae Cleftpalate High-archedpalate Palatalcystsofthenewborn Inflammatorypapillaryhyperplasia Stomatitisnicotina Toruspalatinus Oralmucosa–Liningofmouth Amalgamtattoo Anginabullosahaemorrhagica Behçet'sdisease Bohn'snodules Burningmouthsyndrome Candidiasis Condylomaacuminatum Darier'sdisease Epulisfissuratum Erythemamultiforme Erythroplakia Fibroma Giant-cell Focalepithelialhyperplasia Fordycespots Hairyleukoplakia Hand,footandmouthdisease Hereditarybenignintraepithelialdyskeratosis Herpangina Herpeszoster Intraoraldentalsinus Leukoedema Leukoplakia Lichenplanus Lineaalba Lupuserythematosus Melanocyticnevus Melanocyticorallesion Molluscumcontagiosum Morsicatiobuccarum Oralcancer Benign:Squamouscellpapilloma Keratoacanthoma Malignant:Adenosquamouscarcinoma Basaloidsquamouscarcinoma Mucosalmelanoma Spindlecellcarcinoma Squamouscellcarcinoma Verrucouscarcinoma Oralfloridpapillomatosis Oralmelanosis Smoker'smelanosis Pemphigoid Benignmucousmembrane Pemphigus Plasmoacanthoma Stomatitis Aphthous Denture-related Herpetic Smokelesstobaccokeratosis Submucousfibrosis Ulceration Riga–Fededisease Verrucavulgaris Verruciformxanthoma Whitespongenevus Teeth(pulp,dentin,enamel) Amelogenesisimperfecta Ankylosis Anodontia Caries Earlychildhoodcaries Concrescence Failureoferuptionofteeth Densevaginatus Taloncusp Dentindysplasia Dentinhypersensitivity Dentinogenesisimperfecta Dilaceration Discoloration Ectopicenamel Enamelhypocalcification Enamelhypoplasia Turner'shypoplasia Enamelpearl Fluorosis Fusion Gemination Hyperdontia Hypodontia Maxillarylateralincisoragenesis Impaction Wisdomtoothimpaction Macrodontia Methmouth Microdontia Odontogenictumors Keratocysticodontogenictumour Odontoma Densindente Opencontact Prematureeruption Neonatalteeth Pulpcalcification Pulpstone Pulpcanalobliteration Pulpnecrosis Pulppolyp Pulpitis Regionalodontodysplasia Resorption Shovel-shapedincisors Supernumeraryroot Taurodontism Trauma Avulsion Crackedtoothsyndrome Verticalrootfracture Occlusal Toothloss Edentulism Toothwear Abrasion Abfraction Aciderosion Attrition Periodontium(gingiva,periodontalligament,cementum,alveolus)–Gumsandtooth-supportingstructures Cementicle Cementoblastoma Gigantiform Cementoma Eruptioncyst Epulis Pyogenicgranuloma Congenitalepulis Gingivalenlargement Gingivalcystoftheadult Gingivalcystofthenewborn Gingivitis Desquamative Granulomatous Plasmacell Hereditarygingivalfibromatosis Hypercementosis Hypocementosis Lineargingivalerythema Necrotizingperiodontaldiseases Acutenecrotizingulcerativegingivitis Pericoronitis Peri-implantitis Periodontalabscess Periodontaltrauma Periodontitis Aggressive Asamanifestationofsystemicdisease Chronic Perio-endolesion Teething Periapical,mandibularandmaxillaryhardtissues–Bonesofjaws Agnathia Alveolarosteitis Buccalexostosis Cherubism Idiopathicosteosclerosis Mandibularfracture Microgenia Micrognathia Intraosseouscysts Odontogenic:periapical Dentigerous Buccalbifurcation Lateralperiodontal Globulomaxillary Calcifyingodontogenic Glandularodontogenic Non-odontogenic:Nasopalatineduct Medianmandibular Medianpalatal Traumaticbone Osteoma Osteomyelitis Osteonecrosis Bisphosphonate-associated Neuralgia-inducingcavitationalosteonecrosis Osteoradionecrosis Osteoporoticbonemarrowdefect Paget'sdiseaseofbone Periapicalabscess Phoenixabscess Periapicalperiodontitis Stafnedefect Torusmandibularis Temporomandibularjoints,musclesofmasticationandmalocclusions–Jawjoints,chewingmusclesandbiteabnormalities Bruxism Condylarresorption Mandibulardislocation Malocclusion Crossbite Openbite Overbite Overeruption Overjet Prognathia Retrognathia Scissorbite Maxillaryhypoplasia Temporomandibularjointdysfunction Salivaryglands Benignlymphoepitheliallesion Ectopicsalivaryglandtissue Frey'ssyndrome HIVsalivaryglanddisease Necrotizingsialometaplasia Mucocele Ranula Pneumoparotitis Salivaryductstricture Salivaryglandaplasia Salivaryglandatresia Salivaryglanddiverticulum Salivaryglandfistula Salivaryglandhyperplasia Salivaryglandhypoplasia Salivaryglandneoplasms Benign:Basalcelladenoma Canalicularadenoma Ductalpapilloma Monomorphicadenoma Myoepithelioma Oncocytoma Papillarycystadenomalymphomatosum Pleomorphicadenoma Sebaceousadenoma Malignant:Aciniccellcarcinoma Adenocarcinoma Adenoidcysticcarcinoma Carcinomaexpleomorphicadenoma Lymphoma Mucoepidermoidcarcinoma Sclerosingpolycysticadenosis Sialadenitis Parotitis Chronicsclerosingsialadenitis Sialectasis Sialocele Sialodochitis Sialosis Sialolithiasis Sjögren'ssyndrome Stomatognathicsystem–Teeth,jaws,tongueandassociatedsofttissues Bruxism Mouthbreathing Sleepapnea Catathrenia Centralhypoventilationsyndrome Obesityhypoventilationsyndrome Obstructivesleepapnea Periodicbreathing Snoring Orofacialsofttissues–Softtissuesaroundthemouth Actinomycosis Angioedema Basalcellcarcinoma Cutaneoussinusofdentalorigin Cystichygroma Gnathophyma Ludwig'sangina Macrostomia Melkersson–Rosenthalsyndrome Microstomia Noma OralCrohn'sdisease Orofacialgranulomatosis Perioraldermatitis Pyostomatitisvegetans Other Eaglesyndrome Hemifacialhypertrophy Facialhemiatrophy Oralmanifestationsofsystemicdisease Authoritycontrol:Nationallibraries Japan Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Sjögren_syndrome&oldid=1109247046" 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