Multiple calcifications within the parotid gland of patients with Sjögren’s syndrome
Masahiro Izumi
∗, Yoshiaki Kise, Keiko Murata, Atsushi Murata, Miwa Nakayama, Yoshiko Ariji, Munetaka Naitoh, Eiichiro Ariji
DepartmentofOralandMaxillofacialRadiology,Aichi-GakuinUniversitySchoolofDentistry,Nagoya,Japan
a r t i c l e i n f o
Articlehistory:
Received21March2012
Receivedinrevisedform24May2012 Accepted1June2012
Keywords:
Sjögren’ssyndrome Calcinosis Parotidgland
Multidetectorcomputedtomography
a b s t r a c t
Purpose:Thepurposeofthisstudywastoinvestigatecomputedtomography(CT)andclinicalfeatures relatingtocalcificationswithintheparotidglandofpatientswithSjögren’ssyndrome(SS).
Methods:Datafrom30patientswithSSwhohadbeenexaminedbyCTwereextractedfromourradiolog- icalinformationdatabaseaccumulatedfrom2001to2011,andtheirCTimageswererereadcarefully.Of thesepatients,14(allfemale;agerange20–95years;meanage61.4years)withcalcificationswithinthe parotidglandwereretrospectivelyinvestigatedwithCTfindings.Therelationshipbetweencalcification occurrenceandclinicalsymptomsincludingparotidswellingand/orsalivacolicwasinvestigated.The degreeofdestructionoftheparotidglandonCTimageswasalsoevaluated.
Results:Allcalcificationsof14patientswerelocatedwithintheparotidgland,notintheparotidduct.CT imagesofallcalcificationsshowedsmallandregularroundshapes.Multipleoccurrencesofcalcifications wererecognizedin10patients,andasolitaryoccurrencewasseenin4patients.Sevenpatientshad bilateralcalcifications.Therewaslittlerelationshipbetweentheoccurrenceofcalcificationsandclinical symptoms,andtheseverityofdestructionoftheparotidgland.
Conclusion:ThepresentedCTandclinicalfeatureswouldbepeculiartoSSbecausetoomanypatients lackedthetypicalfeaturesofsialolithswithintheparotidgland.
© 2012 Japanese Stomatological Society. Published by Elsevier Ltd. All rights reserved.
1. Introduction
Sjögren’ssyndrome(SS)isamulti-systemautoimmunedisor- dermainlytargetingthesalivaryandlacrimalglands[1–4].Clinical symptomsarecharacterizedbyprogressivedrymouthanddryeyes [2–4].Inrecentyears,bilateralandmultiplesmallcalcificationsin theparotidparenchymahavebeenreportedasanewfeatureofSS [5–8].Theoccurrenceofsmallcalcificationswasconsideredtobe intheseverelydestructedparotidparenchymaofSS[8]andtobe extremelyrareinthewholeSSpopulation[6,7].Toourknowledge, therehadbeenlessthan20casesinthepreviousnumerousstudies ofSS[5–8].Therefore,characteristicsofsmallcalcificationswere notsufficientlyinvestigated.
Severalimagingmodalities, suchasplainX-rayexamination [8,9], sialography, ultrasound, and computed tomography (CT) [5,10],areavailablefordetectionofcalcifications intheparotid gland.CTisthemostusefultoolindetectionandevaluationofsmall calcificationsbecauseofitshighspatialresolution[11,12].CTcan
∗ Correspondingauthorat:DepartmentofOralandMaxillofacialRadiology,Aichi- GakuinUniversitySchoolofDentistry,2-11Suemori-Dori,Chikusa-Ku,Nagoya464- 8651,Japan.Tel.:+81527592165;fax:+81527592165.
E-mailaddress:izumim@dpc.agu.ac.jp(M.Izumi).
alsodepictthedestructedparotidparenchyma,whichwasreplaced byfat,duetoautoimmunereactionsofSS[8,13].Weplannedaret- rospectiveCTinvestigationtoclarifysomecharacteristicsofsmall calcifications.ThepurposeofthisstudywastoinvestigateCTand clinicalfeaturesrelatingtocalcificationswithintheparotidgland ofpatientswithSS.
2. Patientsandmethods
WesurveyedpatientswithSS,whohadbeenexaminedbyCT, fromaradiologicalinformationdatabaseaccumulatedfrom2001to 2011.Datafrom38patientswithSSwereextracted.Thepurposesof CTexaminationwerefordiagnosisofinflammation,cysts,tumors, andtrigeminalneuralgia.PatientshadconsentedtoCTexamina- tionanditsstudyapplication.CTimageswererereadcarefullyto confirmthepresenceofcalcificationsintheparotidglandbythree radiologists.Clinicalinformationwassimultaneouslyinvestigated frommedicalrecordsandlettersofintroductionfrompreviousdoc- tors,inparticularpastexaminationsfordefinitediagnosisofSS, complicationsofotherautoimmunediseases,ahistoryofparotid swelling,and/orsalivacolic.Ifclinicalinformationwasnotenough, we interviewed the patientsagain if possible. Allpatients sat- isfiedtherevisedJapanese diagnosticcriteriaforSSof 1999.Of 1348-8643/$–seefrontmatter © 2012 Japanese Stomatological Society. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/S1348-8643(12)00052-3
Fig.1.TheseverityofdestructionoftheparotidglandparenchymainpatientswithSjögren’ssyndrome.(A)Slightdestruction;Slightfatdepositsareseenwithintheparotid gland,andmostparenchymaremain.(B)Moderatedestruction;Moderatefatdepositsareseenwithintheparotidgland,andparenchymaremaintoadegreebetweenslight andsevere.(C)Severedestruction;Severefatdepositsareseenwithintheparotidgland,andmostparenchymadisappear.
38patients,8patientswereexcludedbecause5hadsialographic examinationbeforeCTexaminationand3patientshadinsufficient clinicalinformationforthisstudy.Oftheremaining30patients, 14(allfemale;agerange20–95years;meanage61.4years)had calcificationsintheparotidglandonCTimages.
CT examination was performed with a single slice scanner (Somatom ART:Siemens Medical Systems, Erlangen,Germany), a 2-detectorscanner (HiSpeedNX/I Pro:GEYokogawa Medical Systems,Tokyo,Japan),ora4-detectorscanner(Asteion:Toshiba MedicalSystemsCorporation,Tokyo,Japan).Scanconditionswere 120kVand100mA.Transverseimageswith3mmor2mmthick- nesswerecontinuouslyacquiredwithascandirectionparallelto theocclusalormandibularplane.
CTimagesof14patientswithcalcificationswereinvestigated forlocation,distribution,size,andshapeofcalcifications.Thesever- ityofthedestructedparotidparenchymaonCTimageswasalso evaluatedbasedonaconsensusoftwoexperiencedradiologists.
Wepresumedthedestructedparotidparenchyma,whichresults fromautoimmunereactionsofSS,fromtheextentoffatdeposition
intheparotidgland(Fig.1).WhethertheseCTfindingsandclinical featureshadanycharacteristicsin14patientswereinvestigated.
3. Results
CTfindingsandclinicalfeaturesofthe14patientsaresumma- rizedinTable1.Thereweremanycharacteristicsdifferingfromthe typicalfeaturesofsialoliths.
Allcalcifications of the 14 patientswerelocated withinthe parotidgland,notintheparotidduct.CTimagesofallcalcifications showedthatthesizedidnotexceed2mmandtheshapewasregu- larandround.Multipleoccurrencesofcalcificationswereobserved in10patients,andbilateraloccurrencewasseenin7patients.
As to the relationship between the occurrence of calcifica- tionsandtheseverityofthedestructedparotidparenchyma,slight destructionamountedtoabout60%.Therewereafewpatientswith ahistoryofparotidswellingand/orsalivacolic(21%,3/14)andwith complicationsofotherautoimmunediseases(14%,2/14).
4 80 WithinBil.PG Multiple <2mm Regularround Severe – RA
5 58 WithinBil.PG Multiple <2mm Regularround Slight – –
6 20 WithinLt.PG Multiple <2mm Regularround Slight – –
7 42 WithinRt.PG Multiple <2mm Regularround Slight – –
8 68 WithinBil.PG Multiple <2mm Regularround Slight – –
9 71 WithinBil.PG Multiple <2mm Regularround Slight + –
10 41 WithinBil.PG Multiple <2mm Regularround Slight + –
11 95 WithinLt.PG Solitary <2mm Regularround Moderate – RA
12 40 WithinRt.PG Solitary <2mm Regularround Moderate – –
13 55 WithinRt.PG Solitary <2mm Regularround Slight – –
14 64 WithinRt.PG Solitary <2mm Regularround Severe + –
Rt,right;Lt,left;Bil,bilateral;PG,parotidgland;–,None;RA,rheumatoidarthritis.
Fig.2showstypicalmultiplecalcificationswithinthebilateral parotidgland.Manysmallcalcificationswerescatteredthroughout thewholeoftheparotidgland.Fig.3shows anatypicalcaseof calcificationswhereisolatedcalcificationwasobservedwithinthe rightparotidgland.
4. Discussion
SSisamulti-systemautoimmunedisorderthatcausesabnor- malitiesinmanyorgansandtissues.Theoccurrenceofcalcifications inSShasbeencomparativelyknownasoneoftheextra-glandular
Fig.2. Computedtomography(CT)imagesofa55-year-oldwomanwithSjögren’ssyndrome(CaseNo.3).(A)AxialCTimageforsofttissuewindowshowsatypicalfinding ofbilateralmultiplecalcificationsintheparotidgland.(B)AxialCTimageforbonewindowofthesameslice.(C)ThreedimensionallyreconstructedCTimageclearlyshows scatteredcalcificationsintherightparotidgland.
Fig.3. Computedtomography(CT)imagesofa40-year-oldwomanwithSjögren’s syndrome(CaseNo.12).AxialCTimageforsofttissuewindowshowsanatypical findingofsolitarycalcificationintherightparotidgland(arrow).
manifestations,suchasnephrolithiasisand urolithiasis[14–16].
Distalrenaltubularacidosisisconsideredasariskfactorfordevel- opmentofcalcifications[14–16].
Incontrast,thecalcificationswithinthebilateralparotidgland ofSS werenotwellknownbecauseof theirrareoccurrence in SS[6,7].However,consideringtheincidenceofourinvestigation, calcificationswithinthebilateralparotidglandappeartobeafre- quent occurrence (23%,7/30). Sun etal. also reportedthat the incidenceofcalcificationswithinthebilateralparotidglandofSS was29.4–35.2%intheirCTinvestigation[8].Areasonforthecon- tradictionbetweenrareandfrequentoccurrencemaybethatCT examinationisseldomdoneinpatientswithSS.Mostradiological examinationstoSSarescintigraphyand/orsialography,whichare inferiortodetectsmallcalcifications,fordefinitediagnosisofSS.
IfCTexaminationisperformedinhigherfrequency,thepotential existenceofcalcificationswithintheparotidglandmayberevealed inmanypatientswithSS.
Mostpreviousreportsdealtwiththesecalcificationsassialoliths [5–7]. However, in this investigation,a lack of CT and clinical features possibly relating to sialolith occurrence wasobserved.
Ordinarysialolithsoccuratanincidencerateofabout1%inthe population[17],and 6–20%of thewholesialolithsoccurinthe parotidgland[10].InourSSseries,theincidencerateofcalcifi- cationswithintheparotidglandwas46%(14/30).Furthermore, althoughsialolithsarepredominantly foundintheduct,allcal- cificationsinourcaseswerefoundwithinthegland.Theshape of ordinary sialolithsis oblong and is often pointed and sharp [17]. Thesecalcifications were regularand roundshapes. Com- monly,sialolithiasispresentswithpainfulswelling(59%),painless swelling(29%),andpainonly(12%)[10].Clinicalsymptomsinour calcificationcaseswerefew(21%,3/14).Althoughlowersalivary flow rate is considered to be associated with sialolith occur- rence [10], the severity of the destructed parotid parenchyma was not related to the occurrence of calcifications in our SSseries.
RauchandGorlindescribedinthetextbook[17]oforalpathol- ogythat“The“calculus”ofthesalivaryglandisetiologicallyand clinicallyasarelativelyheterogeneousterm.Apartfromsialolith, therearedysplasticcalcificationsininflammatorysalivarygland tissues and calcified venousthrombi.” Asthey described, some calcificationsinthisinvestigationmaybedysplasticcalcifications ofthesalivaryglandtissuessecondarytochronicinflammation of SS. And CT findings of these calcifications were very simi- lartothecharacteristicsofangioliths[18]in theparotidgland.
Regardingthecalculusofthesalivarygland,we shouldkeep in mind the existence of calcifications except for sialolith in the duct.
Wedonot negateanotionofpreviousreportsthat allcalci- ficationsinSScasesaresialoliths,becauseofnoclearorenough evidencetonegatethisnotionatpresent.Andthisinvestigation hasthefollowinglimitations:asmallnumberofcases,casebias, andnon-analysisofthecomponentsofcalcifications.Somecontra- dictionsbetweenordinarysialolithsandthesecalcificationsmaybe astudyerror.Butitisdifficulttoconsiderfromouroverallresults thatthesecalcificationsoccurredfromjustthesamemechanismas ordinalsialolithsintheducts.Furtherresearchbypathophysiolog- icalandbiochemicalapproachesisexpectedtorevealthisissuein thefuture.
Fig.4. Computedtomography(CT)imagesofa57-year-oldmanwithSjögren’ssyndrome.Hehad7yearshistoryofsialographicexaminationoftherightparotidglandbefore CTexamination.(A)High-densitystructuresintheductsareconsideredtobetheresidueofcontrastmedium(arrow).(B)Ontheinferiorslice,high-densityspotscannotbe distinguishedfromcalcifications(arrow).
differ fromordinary sialoliths in the mechanism of occurrence because too many cases lacked typical features of ordinary sialoliths.
Conflictofintereststatement
Noneoftheauthorshasanyconflictofinterestregardingthis research.
References
[1]Delaleu N, Jonsson R, Koller MM. Sjögren’s syndrome. Eur J Oral Sci 2005;113:101–13.
[2]Gannot G, Lancaster HE, Fox PC. Clinical course of primary Sjögren’s syndrome: salivary, oral, and serologic aspects. J Rheumatol 2000;27:
1905–9.
[3] KruizeAA,HenéRJ,vanderHeideA,etal.Long-termfollowupofpatientswith Sjögren’ssyndrome.ArthritisRheum1996;39:297–303.
[4]PijpeJ,KalkWW,BootsmaH,etal.Progressionofsalivaryglanddysfunctionin patientswithSjögren’ssyndrome.AnnRheumDis2007;66:107–12.
[9] SuleimanSI,HobsleyM.Radiologicalappearancesofparotidductcalculi.BrJ Surg1980;67:879–80.
[10] WilliamsMF.Sialolithiasis.OtolaryngolClinNorthAm1999;32:819–34.
[11]BryanRN,MillerRH,FerreyroRI,etal.Computedtomographyofthemajor salivaryglands.AmJRoentgenol1982;139:547–54.
[12]MandelL,HatzisG.Theroleofcomputerizedtomographyinthediagnosisand therapyofparotidstones:acasereport.JAmDentAssoc2000;131:479–82.
[13] IzumiM,EguchiK,NakamuraH,etal.Prematurefatdepositioninsalivary glandsaffectedbySjögren’ssyndrome:evidencebyMRandCT.AmJNeuroradiol 1997;18:951–8.
[14]Moutsopoulos HM,Cledes J, SkopouliFN,et al. Nephrocalcinosis inSjö- gren’s syndrome: a late sequela of renal tubular acidosis.J Intern Med 1991;230:187–91.
[15]ErikssonP,DennebergT,TiseliusHG.Riskfactorsofcalciumstoneformation inpatientswithprimarySjögren’ssyndrome.UrolRes1996;24:39–43.
[16]ErikssonP,DennebergT,LarssonL,etal.Biochemicalmarkersofrenaldisease inprimarySjögren’ssyndrome.ScandJUrolNephrol1995;29:383–92.
[17]RauchS,GorlinRJ.Diseasesofthesalivaryglands.In:GorlinRJ,GoldmanHM, editors.Thoma’soralpathologysixthedition,vol.2.Missouri:C.V.MosbyCo;
1970.p.996–1003.
[18]RaymondAK,BatsakisJG.Angiolithiasisandsialolithiasisintheheadandneck.
AnnOtolRhinolLaryngol1992;101:455–7.
[19] SchortinghuisJ,PijpeJ,SpijkervetFK,etal.Retentionoflipiodolafterparotid glandsialography.IntJOralMaxillofacSurg2009;38:346–9.