w w w . r e u m a t o l o g i a . c o m . b r
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
Review
article
What
rheumatologists
should
know
about
orofacial
manifestations
of
autoimmune
rheumatic
diseases
Aline
Lauria
Pires
Abrão
a,∗,
Caroline
Menezes
Santana
b,
Ana
Cristina
Barreto
Bezerra
a,
Rivadávio
Fernandes
Batista
de
Amorim
b,
Mariana
Branco
da
Silva
c,
Licia
Maria
Henrique
da
Mota
d,
Denise
Pinheiro
Falcão
baProgramadePós-Graduac¸ãoemCiênciasdaSaúde,FaculdadedeCiênciasdaSaúde,UniversidadedeBrasília(UnB),Brasília,DF,Brazil bProgramadePós-Graduac¸ãoemCiênciasMédicas,FaculdadedeMedicina,UniversidadedeBrasília(UnB),Brasília,DF,Brazil
cFaculdadedeCiênciasdaSaúde,UniversidadedeBrasília(UnB),Brasília,DF,Brazil dServic¸odeReumatologia,HospitalUniversitáriodeBrasília(UnB),Brasília,DF,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received4February2015 Accepted28August2015 Availableonline16March2016
Keywords:
Autoimmunerheumaticdiseases Orofacialmanifestations Saliva
Orallesions Periodontaldisease
a
b
s
t
r
a
c
t
Orofacial manifestationsoccur frequently inrheumatic diseases andusually represent earlysignsofdiseaseorofitsactivitythatarestillneglectedinclinicalpractice.Among theautoimmunerheumaticdiseaseswithpotentialfororalmanifestations,rheumatoid arthritis(RA),inflammatorymyopathies(IM),systemicsclerosis(SSc),systemiclupus ery-thematosus(SLE),relapsingpolychondritis(RP)andSjögren’ssyndrome(SS)canbecited. Signsandsymptomssuchasoralhyposalivation,xerostomia,temporomandibularjoint dis-orders,lesionsoftheoralmucosa,periodontaldisease,dysphagia,anddysphoniamaybe thefirstexpressionoftheserheumaticdiseases.Thisarticlereviewsthemainorofacial man-ifestationsofrheumaticdiseasesthatmaybeofinteresttotherheumatologistfordiagnosis andmonitoringofautoimmunerheumaticdiseases.
©2016ElsevierEditoraLtda.ThisisanopenaccessarticleundertheCCBY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).
O
que
o
reumatologista
deve
saber
sobre
as
manifestac¸ões
orofaciais
das
doenc¸as
reumáticas
autoimunes
Palavras-chave:
Doenc¸asreumáticasautoimunes Manifestac¸õesorofaciais Saliva
Lesõesbucais Doenc¸aperiodontal
r
e
s
u
m
o
Manifestac¸õesorofaciaisocorremcomfrequêncianasdoenc¸asreumáticase,comumente, representamsinaisiniciais oude atividadeda doenc¸aqueaindasãonegligenciadosna práticaclínica.Entreasdoenc¸asreumáticasautoimunescompossíveismanifestac¸õesorais, incluem-se a artrite reumatoide(AR),miopatiasinflamatórias (MI), esclerosesistêmica (ES), lúpuseritematososistêmico(LES), policondriterecidivante(PR)esíndromede Sjö-gren (SS). Sinais e sintomas orofaciais como hipossalivac¸ão, xerostomia, disfunc¸ões
∗ Correspondingauthor.
E-mail:alinelauria@hotmail.com(A.L.Abrão).
http://dx.doi.org/10.1016/j.rbre.2016.02.006
temporomandibulares, lesões na mucosa bucal, doenc¸a periodontal, disfagia e disfo-nia podem ser a primeira expressão dessasdoenc¸as reumáticas.Esse artigo revisaas principais manifestac¸ões orofaciais das doenc¸as reumáticasque podem ser de inter-esse doreumatologista, para diagnóstico e acompanhamentodas doenc¸as reumáticas autoimunes.
©2016ElsevierEditoraLtda.Este ´eumartigoOpenAccesssobumalicenc¸aCC BY-NC-ND(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Autoimmunerheumaticdiseasesconstituteaheterogeneous group of conditions characterized by immune tolerance breakdownandproductionofautoantibodiesandofa num-ber of substances responsible for lesions in several body structures.Inthiscategory,rheumatoidarthritis(RA), inflam-matory myopathies (IM), systemic sclerosis (SSc), systemic lupuserythematosus(SLE)andSjögren’ssyndrome(SS)can beincluded.1
Somerheumaticdiseasesshowmucocutaneous manifes-tations.Generally,thechangesareconsequencesofsystemic disordersandmanifestthemselvesinsidiously,showingsigns andsymptomsintheoralcavity(Table1).However,inthe con-textofautoimmune diseases,the oralapproachappearsto havenotyetarousedscientificinterest.Inthispaper,some dentalclinicalfindingsoftenfoundinpatientstreatedatthe RheumatologyOutpatientClinicofBrasília,Hospital Univer-sitáriodeBrasilia (HUB)–UNBwillbediscussed,basedon a narrativeliteraturereview.Forthisreview,thefollowingterms wereenteredinPubMeddatabase(AutoimmuneRheumatic Disease[allfields])AND“dentistry”[allfields],limitedtothose studiesconductedonhumansubjects.Itwasfoundthatare onlysixty-eightstudieswere publisheduntilJune21,2015. Somestudiespointtoepidemiologicaldata ofmedicaland dentalinterest.Inthiscontext,clearlyonerealizesthelimited approachtothesubject.However,thepaperschosen demon-stratethatthedentistcanandshouldactintheearlydiagnosis andmanagementofthesedisorders,sincethesepatientshave specificneeds.
Thus,thisnarrativereviewaimstoaddressthemain orof-acialmanifestationsinautoimmunerheumaticdiseasesthat maybeofinterest totherheumatologist fordiagnosis and clinicalfollow-up.
Literature
review
Rheumatoidarthritis
Rheumatoidarthritis(RA)isachronicautoimmune inflam-matorydiseaseofunknownetiology.2Theclassicfeaturesof
thisdiseasearechronic,bilateralandsymmetric polyarthri-tis,jointpainandinflammationthatcanresultindeformity, instability and destruction of synovial joints.3,4 RA affects
more often the synovial membrane of small joints of the extremities,resultinginswelling,edemaandpain,andcan leadtoboneandcartilagedestruction,severedisabilityand untimelymortality.3
ThemostcommonoralmanifestationsinpatientswithRA are:
Temporomandibulardisorder(TMD)
The temporomandibularjoint (TMJ) isasynovial joint and can be affected bydisorders innon-articular tissues, with manifestationsofmusclespasm,fibromyalgia,andmyotonic dystrophy,amongothers.However,TMJjointtissuesmayalso beaffectedbymechanicaltrauma,infection,iatrogenic disor-ders,andgout,aswellasbyautoimmunerheumaticdiseases suchasRAandpsoriasis.5Onecanobservethepresenceof
typical inflammatorymediators ofosteoarthritis, including tumornecrosisfactor(TNF)-␣,interleukin(IL)-1,IL-6and IL-8.Thesefindingsmaintaincorrelationwiththeextentofthe disease,i.e.,clinicalsymptoms,numberofjointeffusionsor morphologicalchanges.6,7
TMDsareconsideredtobethemostcommonconditions causingorofacialpainofnon-dentalorigin,and thedentist isthe professional responsibleforthe clinicalexamination ofTMJ andforrequestingimagingexams ofthis anatomi-calregion.ATMDcanmanifestsymptomssuchasearpain, headache,non-specificnervepain,andtoothache.Its diagno-sisrequiresamedicalanddentalapproach,whichmakesthe evaluationoftheprevalenceofTMDacomplexissue,andits studyisoftenoverlookedintheclinicalpracticeofrheumatic autoimmunediseases.8,9
TMD can occur bothin adultsand –more commonly– in children with RA. A study that evaluated 223 children with juvenile idiopathic arthritis revealed that 38.6% had some TMJinvolvement (pain, swelling and/orlimitation in range of motion).10 When TMJ involvement is manifested
during a child’s development, there may be a mandibu-lar growth restriction, resulting in micrognatia and/or ankylosis.11
Inadults,studiesontheprevalenceofTMDinRApatients resultedinextremelyvariedvalues(5–86%),dependingonthe populationstudied,diagnosticcriteriaused,andassessment methods.4,5TMDisthemostcommonorofacialmanifestation
inRApatients.Thepatientmayshowabilateral,profound and pervasiveacute pain, which isexacerbated duringthe function.Theclinicalexaminationmayreveal:malocclusion, sensitivity andinflammationofpre-auricular regions, joint stiffnessuponwaking,limitationofjawmovement, intracap-sularcrepitusorclickingandpaininmasticatoryand/orneck muscles.4,12Imagingstudiesmayshowbonestructurelossat
Table1–Oralmanifestationsofautoimmunerheumaticdiseasesandtheirclinicalimplications.
Oralevents Autoimmunerheumaticdiseases
RA IM SSc SLE SS Clinicalimplications
PM DM
Periodontaldisease X X X •Worseningfactorfordiabetesandrheumatic
andheartdiseases
Dentalcaries X X X •Dependingontheextentoftheinjury,pain,
chewinginvolvement,andfociofinfectioncan occur,likelyworseningdiabetesandrheumatic andheartdiseases
Candidiasis X X •Itchingand/orburninginthemucosa
•Riskofesophagealinfection •Inappetence
Hyposalivation X X X X •Dysphonia
•Dysphagia
•Thrushandulcersintheoralmucosa •Greatertendencytooralandoropharyngeal
infections30
•Recurrentesophagitis
•Sleepinterruptedforwaterintakeand urination
Xerostomia X X X X X •Decreaseinqualityoflife
Halitosis X •Decreaseinqualityoflife
Mouthburning X X X X •Dysgeusia
•Eatingdifficulty •Cancerphobia
Oralulcers X X X •Pain
•Difficultyinfeedingandoralhygiene
TMD X X X X •Headache
•Otalgiaand/ortinnitus •Afeelingofeartamponade •Anirradiatingcervicalpain •Chronicheadache •Limitedmouthopening •Difficultytochewandspeak12
Microstomia X •Limitedmouthopening
•Difficultyineatingandtohaveagoodoral hygiene46
Regionalresorptionof jawbone/TMJ
X •Limitedmouthopening
Dysphagia X X X •Dehydration
•Malnutrition
Aspirationofsecretionsand/orfoodtothe lung–aspirationpneumonia
Dysphonia X X X X •Decreaseinqualityoflife
Changesinlanguage X X X •Difficultytoperceivefood,speechand
swallowing.
Anglecheilitis X •Painandlimitedmouthopening
Alterationsintooth morphology
X •Facialestheticsandmasticatoryfunction
changes
Pathologicalchangesin salivaryglands
X X •Hyposalivation
Changesinmimicand chewingmusclesand inthepharynx
X •Dysphagia
•Dysphonia •Difficultytochew
Trigeminalneuralgia •Episodesofintensepainintheeyes,lips,nose,
scalp,foreheadand/orjaw
Fig.1–Computedtomographyoftemporomandibularjointofapatientwithrheumatoidarthritisandcomplaintofclicking whilechewing.Presenceofsubchondralcystintheupperportionoftherightmandibularhead(a),erosionoflateralportion oftheleftmandibularhead(b)andflatteningofarticulareminences(c).
Periodontaldisease(PD)
PDisachronicinfectiousdiseasecausedbyGram-negative anaerobic bacteria, affectingthe tissues of protection and supportof the tooth, suchas gums, periodontal ligament, cementum and alveolar bone. Under PD designation, both reversible(gingivitis)andirreversible(periodontitis)processes areincluded.Whenundiagnosedanduntreated,PDcancause progressivedestructionofalveolarbone,causingtooth mobil-ity and subsequent dental loss.14 According to the World
Health Organization, periodontal disease affects approxi-mately10–15% ofthe world population.14 Brazilian official
datashowthat19.4%ofadultsaged35–44yearsarecarriers ofthisdisease.15
Somerecentstudiesalsosuggestasignificantassociation betweenRAandPD.13,16–18TherelationshipbetweenRAand
progressionofinflammatoryconditions(p.ex.,periodontitis) isnotclear.Themainreasonforthisscenarioisthelackof uniformityintheclassificationofthevariousformsofboth diseases.19ItisestimatedthattheprevalenceofPDincreases
twiceinRApatientscomparedtothegeneralpopulation.17
Thus,thepresenceofamoderate-to-severeRAalsoincreases morethan twicetheriskofdevelopingformsof moderate-to-severeperiodontitiscomparedtoindividualswithoutthe disease.17–19
Furthermore,thereisevidenceofsimilarityinthe patho-genesisofRAandPD.MicroorganismssuchasPorphyromonas gingivalismayplayaroleinbothconditions,16beingableto
invadeisolatedhumanchondrocytesinthekneejoint, inter-feringwithcellcycle andinducingthesecells’apoptosis.20
AnotherimportantfactorwouldbethatP.gingivalisexpresses the peptide argininedeiminase (PAD),which converts argi-nine to citrulline by a citrullination process. Thisprocess, which is common to some human proteins, is associated withthepathophysiologyofRA.Ithasalowimmune toler-ancetocitrullinatedproteinsinsynovialfluid,whichtriggers thedevelopmentofimmunoglobulinsagainsttheseproteins, presentinjointsandtendons.21,22 Inaddition,studieshave
demonstratedthepresenceofantibodiesinresponsetooral anaerobicbacteriainthesynovialtissueandserum.Others authorsalsofoundthepresenceoforalbacterialDNAinthe synovialfluidofRApatients.18Infact,RAandPDhavea
vari-etyofmarkedlysimilarclinicalandpathophysiologicfeatures (Table2).23,24
Table2–Pathophysiologicalsimilaritiesinthe characteristicsofrheumatoidarthritisandperiodontal disease.23,24
Pathophysiological characteristics
RA PD
Cellinfiltrate Macrophages,T lymphocytes, plasmacellsand PMN
Equivalent
Immune phenomenon
Immunecomplex deposition, complement fixation
Equivalent
Cytokines IL-1␣,IL-1,IL-6, IL-8,TNF-␣and TGF-
Equivalent
Localcellsaffected Chondrocytesand synoviocytes
Gingival fibroblast, osteoblast,and keratinocytes
Inductionofbone resorption
PGE2,TNF-␣,IL-1 LPS,PGE2, TNF-␣,IL-1
TissueDestruction Metalloproteinase, phospholipase andelastase
Equivalent
Granulationtissue Presentin cartilage/bone interface
Presentinthe cement/bone interface
IL-1␣, interleukin-1 alpha; IL-1, interleukin-1 beta; IL-6, interleukin-6; IL-8, interleukin-8; LPS, lipopolysaccharide; PD, periodontaldisease;PGE2,prostaglandinE2;PMN, polymorphonu-clearleukocytes;RA,rheumatoidarthritis;TNF-␣,tumornecrosis factoralpha;TGF-,growthtransformingfactorbeta.
improvementinendothelialfunction,withadecreaseinlocal andsystemicinflammatoryprocesses.25
Hyposalivation/xerostomia
Amongoral changes,it turns out that hyposalivation (low salivaryflow) and xerostomia (dry mouth) are common in autoimmunerheumaticdiseases,andxerostomiaaffects1% ofRApatients.26 About one thirdofRApatientshave
sec-ondary SS.27 A study including 604 RA patients showed a
decrease in salivary flow in43% ofsubjects.28 The risk of
developinghyposalivationincreaseswiththeseverityofthe disease.Itisworthmentioningthatanotherstudyconducted in483hospitalizedpatientsduetocomplicationsofarthritis foundthatonly17.7%ofxerostomia-positivepatientswere treatedforxerostomia.Incontrast,84.8%ofpatientstreated forxerophthalmiaweretreatedforthiscondition.Itwasalso observed that the therapeutic modalities administered for xerostomia were not effectiveand alsowere notin accor-dancewithcurrentrecommendationsfoundinthemedical literature.29
Therefore,atimelydiagnosisandpropermonitoringofSS associatedwithRAareimportantstepstopromotegainsin thequalityoflifeofthesepatients(aswillbediscussedinthe
SSsection),takingintoaccountthatsalivaperformsfunctions ofsystemicinterest,forinstance,thesenseoftaste, epithe-lialrepairoforopharynxandesophagus,andesophagealacid contentbuffering,amongotherfunctions.30
Inflammatorymyopathies
Polymyositis(PM)anddermatomyositis(DM)areautoimmune diseases classified as idiopathic inflammatory myopathies, beingcharacterizedbymusculoskeletalinflammation.31
PMisasystemicconnectivetissuedisease,characterizedby bilateral,symmetrical,proximalmuscleweakness.Itaffects muscles of the shoulder and pelvic girdle and progresses towardproximalmusclesofthelimbs.Itsonsetisfrequently gradualandprogressive.PMexhibitsageographicallyvariable incidence,withaboutonecaseforevery100,000inhabitants, predominantlyaffectingfemales.32
Impairment of skeletal muscles ofposterior pharyngeal wall and proximal third of the esophagus can lead to oropharyngeal dysphagia, with aspiration and dysphonia. Consequently, thepatient cancomplain ofhypersalivation. Thiscomplication,however,willbeduetoanimpaired func-tionalactivityofswallowingmusclesinassociationwiththe salivary reflexcaused byreflux.Two thirds ofthe patients present involvementoftheneckflexormuscles, whichcan cause difficulty in neck support. Constitutional symptoms includefatigue,low-gradefever,weightloss,andarthralgia orarthritisofsmallandmediumjoints.33
Somerarecasereportsrelatepresenceofulcerationsonthe entiretongue,ofalinearaspectandwithawhitesecretionon theedges,andalsotongueatrophy,inwhichonecanobserve areddenedmucosa.34
DMisanautoimmunediseaseofunknownetiologythat is characterized by a systemic small-vessel vasculopathy predominantlyinvolvingmusclesandskin.Besidesthe cuta-neousinvolvement,thecharacterizationofDMisbasedinthe patternofmuscleinvolvement,presenceofassociatedclinical manifestations,andhistopathologicalchanges.35
The prevalenceoforal involvementinDM is unknown. Mostoftheinformationavailablecomesfromindividualcase reportsorsmallcaseseries,andsomeearlyreportsofcases didnotclearlyseparateMSfromPM.36
Aninvolvementofmimicmusclesmayoccur,whichleads toadecreaseinfacialexpression.Similarly,theinvolvement ofthemasticatoryandpharyngealmusclesmayresultin dys-phagia,dysphonia,andhypersalivation.Theinvolvementof striatedmuscleofthepharynxoresophagusalsocontributes totheoccurrenceofdysphagia.Inpatientswithdysphagia, DM reaches18–50%ofpatientsand correlateswithdisease severity.36,37Inaddition,thepresenceofdysphagiaincreases
theriskofaspirationpneumonia.Mortalityratesrangefrom1 to5years,reaching31%ofpatientswithDManddysphagia.37
However, the occurrence of hypersalivation is not always attributable toan excess insaliva production, but may be causedbyaninabilitytoretainsalivaandswallowingit,dueto theweaknessofperioralmuscletone,orbecauseofdysphagia. Theinvolvementoftonguemuscle resultsinmacroglossia, inadditionofhypotonia,whichcanalsomakeitmore diffi-cult chewing,swallowingand speech.38 Involvementofthe
Mucosaledema, erythemaand telangiectasia are the com-monestoralchanges.38
Although27.5%ofpatientswithDMalsosufferarthritis, TMJinvolvementisrare,withonlyonecasereportedinthe literature.Insomereports,thepresenceofprominentblood vesselsthroughouttheoralmucosaandaphthousstomatitis/ ulcer-likelesionsweredescribed.40About10–46%ofpatients
developpainfuloralandgingivalulcers.41Theteethhaveshort
andbulgingroots,withobliterationofrootcanalsaswellas pulpchambercalcification.Xerostomiaisalsoseenasa com-moncomplaint.42
Systemicsclerosis
Systemic sclerosis (SSc)isan autoimmune disease charac-terizedbyinflammationandhyper-reactivity ofmicro-and macrovascularcirculationassociatedwithexcessivecollagen deposition intissues, withsubsequent fibrosis ofthe skin and/orinternalorgans.43SSchasapredilectionforfemales,
withanincidenceof2–10/onemillioninhabitantsinthe gen-eralpopulation.44Inaddition,thereisaconsensusaboutan
increaseinmorbidityandmortality,withanestimated66% survivalat10years.45
The oral manifestationsare scarcely studied and often neglectedbyclinicians,althoughleadingtomajorfunctional disability.Microstomiaisthemostcommonoralfindingand developsduetocollagendepositioninperioraltissues, caus-inglimitation ofmouth opening,perioralgroovewrinkling, and soft palate, larynx and oral mucosa stiffness.46
Fur-thermore, hyposalivation and/or dry mouth are secondary manifestationsofthedisease.TMDcanalsooccur,with vary-ingdegreesofsubsequentresorptionofmandibularbranch, coronoidprocess,menton and condyle.5 Itisbelieved that
these areas are reabsorbed due to the chronic collagen deposition.Tonguecancerhasasignificantlyincreased fre-quencyinpatientswithSScthat presentamouth opening <30mm.47
Theresorptionofsometeethhasalsobeenreportedwith somefrequencyinthesepatients.There maybean abnor-malincrease in the frequency ofdecayed teethand of an
atypical tooth eruption. Apparently there is also a predis-position forthe occurrenceofPD,due toincreasedplaque buildup.Thisproblemarisesfromthedifficultyofcleaningthe mouth(causedbyasmallermouthopening)andintheuse ofthedentalbrush.Thislattercomplicationisdueto scle-roticchangesinfingersandhands.Furthermore,theuseof systemiccorticosteroidsforlongperiodsinfluencein reduc-ingtheperiodontalinflammatoryresponse,thusmakingthis processaprogressiveandofteninsidiousone.48
Systemiclupuserythematous
SLE isan autoimmune disease ofunknown etiology, influ-enced by environmental and genetic factors, and which mainly affects women inthe second and thirddecades of life.49 The prevalence of oral lesions in patients with SLE
variesbetween6.5%and21%.SLEaffects primarilytongue, oralmucosa,lipsandpalate.Forthisreason,oralulcersare considered primaryevents,thatare includedinthe follow-ingactivityindexesofthisdisease:BILAG(BritishIslesLupus AssessmentGroup),50SLEDAI(SystemicLupusErythematosus
Disease Activity Index),51 SELENA-SLEDAI (Safety of
Estro-gens in LupusErythematosus National Assessment),SLAM (SystemicLupusActivityMeasure),52 andECLAM(European
ConsensusLupusActivityMeasurement).53
Thelesionsappearindifferentways,suchasblemishes and plaques on the mucosa. The lesions may be erythe-matous, ulcerated,ofa recurrentaphthousstomatitis, and lichenplanus-orleukoplakia-likelesions(Fig.2).Thesizeof these lesionsisalsovariable,from asmall surface erosion to ulcers covering a wide and extensive area.54,55 The few
studiesonorallesionsinpatientswithSLEshow, microscop-ically,parakeratosisororthokeratosis,acanthosis,epithelial atrophy,vacuolardegenerationofthebasalmembranewith necrosisofbasalkeratinocytes,basementmembrane thick-ening,lichenoidmononuclearinfiltrate,anddeepconnective tissuevasculitis.Injuriesinthevermilionborderoflips (espe-cially in the lower lip), deserve special attention,as these lesions may be related to lupus cheilitis, with or without epithelialdysplasia.54,56
Othersecondaryorofacialsigns/symptomsinclude:mouth burning,hyposalivation,xerostomia, salivary glanddisease (suchasfocal necrosisofthe parotidgland),TMD, desqua-mative gingivitis and PD.54 Hyposalivation can lead to an
increasedoccurrenceofdentalcariesandtoapredisposition tocandidiasis,especiallyifimmunosuppressiveagentssuch ascorticosteroidsarebeingused.56
Sjögren’ssyndrome(SS)
SSisaninflammatoryautoimmunediseasepresentinga fre-quentchroniccourse,inwhich thelymphocyticinfiltration ofexocrineglands,particularlylacrimalandsalivaryglands, impairs its secretory function.55 Simultaneously, systemic
manifestationsofcutaneous,respiratory,renal,hepatic, neu-rologicand vascular naturecan occur. SS hastwo distinct forms:primarySS–notassociatedwithanotherdisorder;and secondarySS–inwhichthepatientexpressesthissyndrome inassociationwithotherautoimmunediseases.57,58
ItisestimatedthatSSaffects0.2%oftheworld popula-tion,mainlywomen,inaratioof9:1.57,58InBrazil,duetothe
absenceofofficialestimatesorscientificallyconfirmeddata onitsincidence,nooneknowstheexactnumberofpatients withthissyndrome.However,itwasstatedthatthemajorityof diagnosedcasesarerelatedtomenopausal,orolder,women.59
SSfollowsavariablecourseandexhibitsawidespectrum ofclinicalmanifestations.Inaddition,manyofitssymptoms arenon-specific,makingdifficultanddelayingthediagnosis. EightypercentofpatientswithSSexhibitaninsidiousonsetof symptomsofdrynessthatdevelopoveraperiodfromseveral monthstoyears.58
TheoralmanifestationsobservedinpatientswithSSare attributedtotheinvolvementofsalivaryglands,whichleads tolesssalivarysecretion.Inconsequence,theworse lubrica-tionandlossofbufferingandantimicrobialactionofsalivary secretion increase the incidence of oral/dental infections, mucosal friability, and symptomsof irritationand burning mouth(Fig.3).57Ontheotherhand,somepatientscomplain
ofxerostomia,whichmaynotbeaccompaniedbyadecrease insalivary secretion.30 However,in the initialstage ofthe
disease, when the diagnosis has not yet been well estab-lished,patientsmaycomplainofxerostomiaduetochangesin
salivarycomposition,ortoareductionofsalivarysecretion fromthesmallersalivaryglands(fromlipmucosaandpalate). Thus,sialometrymay revealthatthe patienthasanormal salivaryflow;however,salivarycompositiontestswillindicate qualitativechanges.60
Usually,dentalcariesandfungalinfectionsareobservedin mucousmembranes(especiallycandidiasis)thatcanmanifest aspseudomembranousorerythematouslesions.Thefriability of the mucosa in patients with SS often leads tosoft tis-sueinjuries.Suchsignsincludedryandcrackedlips,median rhomboidglossitisorafissuredtongue,lossoflingual papil-lae,stomatitis,angularcheilitis,aphthousinjury,lipmucosal ulcers,difficultyinswallowingsolids,andodynophagia.57
SS patients oftendisplay voice disorders andcorrelated symptomsthatareassociatedwithadecreaseintheirquality oflife.Itisknownthatthelubricationofthevocalcordsis carriedoutbysaliva.61Thus,thisbiologicalfluidisimportant
foraproperphonation.
Another relevantpoint referstothe drop inthe quality oflifeofpatientswithSS,becauseoftheirchangingeating habits,causedbydrymouth.62ThereisaStrongcorrelation
amongoraldrynessandfatigue,pain,psychologicaldistress, andaworsequalityofsleep;andthatitisconsideredasa car-diovascularriskfactor.63Inthisstudy,theauthorsconcluded
thatamultidisciplinarytherapeuticapproachmaybethebest waytominimizedrymouthanditsconsequencesinpatients withprimarySS.63
Finally,anothercommonoralmanifestationisan asymp-tomaticandself-limitingincreasesofparotidglandsorother majorsalivaryglands,55whichmaybepointingtotheearly
stageofSS.
Therefore,theestablishmentofanearlydiagnosisofSSis essentialforthechoiceofthecorrecttreatment,which con-sistsinrelievingthesignsandsymptomsinordertominimize oravoidsequelsthatcanimpactonthehealthandqualityof lifeofpatients.64
Gustatory,mechanicalandchemicalsialogogueshavebeen usedtostimulatesalivaproduction.However,the effective-ness of these resources is low, because they provide only temporaryrelief,requiringfrequentapplications.65Many
top-icaltreatmentssuchassprays,lozenges,mouthwashes,gels, oilsortoothpasteshavebeenevaluated,butthereisnostrong
evidencethatanyofthesetopicaltreatmentsiseffectiveto alleviatethepatientwithdrymouth.66 Oxygenatedtri-ester
glycerol-basedlubricantsaremoreeffectivethanwater-based electrolytesprays.Chewinggumincreasessalivaproduction, butthereisnoevidencethattheseproductsarebetterorworse than saliva substitutes. However, acidic secretagogues and those containingsugar shouldbe avoided,66 because these
productsloweroralpH,promotegreatertooth demineraliza-tionandirritateamucousalreadyverysensitive.Oneshould optfortheuseofsugar-freechewinggum,butcontaining flu-orideandbicarbonateinitscomposition.Thesecomponents increasesalivarypHandassistinpreventingtoothdecay.67,68
Chemical sialagogues, such as pilocarpine and cevime-line,areeffectiveinrelievinghyposalivation,butmaycause adverseeffects.65Electricalstimulationappliedtothe
affer-entpathways(throughtheoralmucosaorskin)inareasof salivaryglands,showedincreasedsalivaproductionandrelief ofdrymouthinpatientswithSS65andinpatientsundergoing
cervical-brainradiotherapy.69
Asystematicreviewofrandomizedcontrolledtrialswas conductedtogatherevidenceondrugtherapyinprimarySS. Theauthorssuggestedthatsalivasubstitutesandsugar-free chewinggumsmaybeeffectiveincasesofmild-to-moderate drymouth.Consumptionofalcoholandsmokingshouldbe avoided, and it is a critical factor the establishment of a thoroughoralhygiene.Thetreatmentofchoiceforpatients withresidual functionofsalivaryglandsiscevimelineand oralpilocarpine. However,nostudywas published compar-ing theefficacy ofthese twodrugs. Thedoses which have shown better effects in terms ofefficacy and safety were: pilocarpine5mgevery 6h; andcevimeline 30mgevery 8h. N-acetylcysteinecouldbeanalternativeinpatientswith con-traindicationsorintolerancetomuscarinicagonists.70
Conclusion
Orofacial manifestations in patients with autoimmune rheumaticdiseasesarecommonproblems,butstillsparsely addressed by rheumatologists in their everyday clinical practice.Thisarticleproducedasummaryofthemain mani-festationsobserved,inordertofamiliarizetheseprofessionals withtheirdiagnoses,underlyingthepossibleneedforanearly referraltothedentist.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgements
TheauthorswouldliketoacknowledgeNathalyaLopesSilva, RafaellyStavale,TalithaGiovannadaSilvaandFrancisca Ires-daniaAlvesMacedofortheircollaboration.Thesecondand seventhauthorsarealsogratefulforthefinancialsupportof CAPES–Coordenac¸ãodeAperfeic¸oamentodePessoaldeNível Superior.
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