r e v b r a s r e u m a t o l . 2 0 1 6;5 6(5):441–450

REVISTA BRASILEIRA DEREUMATOLOGIA

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eview article

hat rheumatologists should know about orofacialanifestations of autoimmune rheumatic diseases

line Lauria Pires Abrãoa,∗, Caroline Menezes Santanab, Ana Cristina Barreto Bezerraa,ivadávio Fernandes Batista de Amorimb, Mariana Branco da Silvac,icia Maria Henrique da Motad, Denise Pinheiro Falcãob

Programa de Pós-Graduacão em Ciências da Saúde, Faculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, DF, BrazilPrograma de Pós-Graduacão em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, BrazilFaculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, DF, BrazilServico de Reumatologia, Hospital Universitário de Brasília (UnB), Brasília, DF, Brazil

r t i c l e i n f o

rticle history:

eceived 4 February 2015

ccepted 28 August 2015

vailable online 16 March 2016

eywords:

utoimmune rheumatic diseases

rofacial manifestations

aliva

ral lesions

eriodontal disease

a b s t r a c t

Orofacial manifestations occur frequently in rheumatic diseases and usually represent

early signs of disease or of its activity that are still neglected in clinical practice. Among

the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid

arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus ery-

thematosus (SLE), relapsing polychondritis (RP) and Sjögren’s syndrome (SS) can be cited.

Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint dis-

orders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be

the first expression of these rheumatic diseases. This article reviews the main orofacial man-

ifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis

and monitoring of autoimmune rheumatic diseases.

© 2016 Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

O que o reumatologista deve saber sobre as manifestacões orofaciaisdas doencas reumáticas autoimunes

alavras-chave:

r e s u m o

Manifestacões orofaciais ocorrem com frequência nas doencas reumáticas e, comumente,

iniciais ou de atividade da doenca que ainda são negligenciados na

oencas reumáticas autoimunes representam sinais

anifestacões orofaciais

aliva

esões bucais

oenca periodontal

prática clínica. Entre as doencas reumáticas autoimunes com possíveis manifestacões orais,

incluem-se a artrite reumatoide (AR), miopatias inflamatórias (MI), esclerose sistêmica

(ES), lúpus eritematoso sistêmico (LES), policondrite recidivante (PR) e síndrome de Sjö-

gren (SS). Sinais e sintomas orofaciais como hipossalivacão, xerostomia, disfuncões

∗ Corresponding author.E-mail: alinelauria@hotmail.com (A.L. Abrão).

ttp://dx.doi.org/10.1016/j.rbre.2016.02.006255-5021/© 2016 Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/icenses/by-nc-nd/4.0/).

442 r e v b r a s r e u m a t o l . 2 0 1 6;5 6(5):441–450

temporomandibulares, lesões na mucosa bucal, doenca periodontal, disfagia e disfo-

nia podem ser a primeira expressão dessas doencas reumáticas. Esse artigo revisa as

principais manifestacões orofaciais das doencas reumáticas que podem ser de inter-

esse do reumatologista, para diagnóstico e acompanhamento das doencas reumáticas

autoimunes.© 2016 Elsevier Editora Ltda. Este e um artigo Open Access sob uma licenca CC

muscles. Imaging studies may show bone structure loss at

Introduction

Autoimmune rheumatic diseases constitute a heterogeneousgroup of conditions characterized by immune tolerancebreakdown and production of autoantibodies and of a num-ber of substances responsible for lesions in several bodystructures. In this category, rheumatoid arthritis (RA), inflam-matory myopathies (IM), systemic sclerosis (SSc), systemiclupus erythematosus (SLE) and Sjögren’s syndrome (SS) canbe included.1

Some rheumatic diseases show mucocutaneous manifes-tations. Generally, the changes are consequences of systemicdisorders and manifest themselves insidiously, showing signsand symptoms in the oral cavity (Table 1). However, in the con-text of autoimmune diseases, the oral approach appears tohave not yet aroused scientific interest. In this paper, somedental clinical findings often found in patients treated at theRheumatology Outpatient Clinic of Brasília, Hospital Univer-sitário de Brasilia (HUB)–UNB will be discussed, based on anarrative literature review. For this review, the following termswere entered in PubMed database (Autoimmune RheumaticDisease [all fields]) AND “dentistry” [all fields], limited to thosestudies conducted on human subjects. It was found that areonly sixty-eight studies were published until June 21, 2015.Some studies point to epidemiological data of medical anddental interest. In this context, clearly one realizes the limitedapproach to the subject. However, the papers chosen demon-strate that the dentist can and should act in the early diagnosisand management of these disorders, since these patients havespecific needs.

Thus, this narrative review aims to address the main orof-acial manifestations in autoimmune rheumatic diseases thatmay be of interest to the rheumatologist for diagnosis andclinical follow-up.

Literature review

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflam-matory disease of unknown etiology.2 The classic features ofthis disease are chronic, bilateral and symmetric polyarthri-tis, joint pain and inflammation that can result in deformity,instability and destruction of synovial joints.3,4 RA affectsmore often the synovial membrane of small joints of the

extremities, resulting in swelling, edema and pain, and canlead to bone and cartilage destruction, severe disability anduntimely mortality.3

BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The most common oral manifestations in patients with RAare:

Temporomandibular disorder (TMD)

The temporomandibular joint (TMJ) is a synovial joint andcan be affected by disorders in non-articular tissues, withmanifestations of muscle spasm, fibromyalgia, and myotonicdystrophy, among others. However, TMJ joint tissues may alsobe affected by mechanical trauma, infection, iatrogenic disor-ders, and gout, as well as by autoimmune rheumatic diseasessuch as RA and psoriasis.5 One can observe the presence oftypical inflammatory mediators of osteoarthritis, includingtumor necrosis factor (TNF)-�, interleukin (IL)-1�, IL-6 and IL-8. These findings maintain correlation with the extent of thedisease, i.e., clinical symptoms, number of joint effusions ormorphological changes.6,7

TMDs are considered to be the most common conditionscausing orofacial pain of non-dental origin, and the dentistis the professional responsible for the clinical examinationof TMJ and for requesting imaging exams of this anatomi-cal region. A TMD can manifest symptoms such as ear pain,headache, non-specific nerve pain, and toothache. Its diagno-sis requires a medical and dental approach, which makes theevaluation of the prevalence of TMD a complex issue, and itsstudy is often overlooked in the clinical practice of rheumaticautoimmune diseases.8,9

TMD can occur both in adults and – more commonly –in children with RA. A study that evaluated 223 childrenwith juvenile idiopathic arthritis revealed that 38.6% hadsome TMJ involvement (pain, swelling and/or limitation inrange of motion).10 When TMJ involvement is manifestedduring a child’s development, there may be a mandibu-lar growth restriction, resulting in micrognatia and/orankylosis.11

In adults, studies on the prevalence of TMD in RA patientsresulted in extremely varied values (5–86%), depending on thepopulation studied, diagnostic criteria used, and assessmentmethods.4,5 TMD is the most common orofacial manifestationin RA patients. The patient may show a bilateral, profoundand pervasive acute pain, which is exacerbated during thefunction. The clinical examination may reveal: malocclusion,sensitivity and inflammation of pre-auricular regions, jointstiffness upon waking, limitation of jaw movement, intracap-sular crepitus or clicking and pain in masticatory and/or neck

4,12

the condylar head (Fig. 1). The occurrence of TMJ ankylosis isquite unusual, becomes evident only at a late stage, and maybe bilateral.4,13

r e v b r a s r e u m a t o l . 2 0 1 6;5 6(5):441–450 443

Table 1 – Oral manifestations of autoimmune rheumatic diseases and their clinical implications.

Oral events Autoimmune rheumatic diseases

RA IM SSc SLE SS Clinical implications

PM DM

Periodontal disease X X X • Worsening factor for diabetes and rheumaticand heart diseases

Dental caries X X X • Depending on the extent of the injury, pain,chewing involvement, and foci of infection canoccur, likely worsening diabetes and rheumaticand heart diseases

Candidiasis X X • Itching and/or burning in the mucosa• Risk of esophageal infection• Inappetence

Hyposalivation X X X X • Dysphonia• Dysphagia• Thrush and ulcers in the oral mucosa• Greater tendency to oral and oropharyngealinfections30

• Recurrent esophagitis• Sleep interrupted for water intake andurination

Xerostomia X X X X X • Decrease in quality of life

Halitosis X • Decrease in quality of life

Mouth burning X X X X • Dysgeusia• Eating difficulty• Cancer phobia

Oral ulcers X X X • Pain• Difficulty in feeding and oral hygiene

TMD X X X X • Headache• Otalgia and/or tinnitus• A feeling of ear tamponade• An irradiating cervical pain• Chronic headache• Limited mouth opening• Difficulty to chew and speak12

Microstomia X • Limited mouth opening• Difficulty in eating and to have a good oralhygiene46

Regional resorption ofjaw bone/TMJ

X • Limited mouth opening

Dysphagia X X X • Dehydration• MalnutritionAspiration of secretions and/or food to thelung–aspiration pneumonia

Dysphonia X X X X • Decrease in quality of life

Changes in language X X X • Difficulty to perceive food, speech andswallowing.

Angle cheilitis X • Pain and limited mouth opening

Alterations in toothmorphology

X • Facial esthetics and masticatory functionchanges

Pathological changes insalivary glands

X X • Hyposalivation

Changes in mimic andchewing muscles andin the pharynx

X • Dysphagia• Dysphonia• Difficulty to chew

Trigeminal neuralgia • Episodes of intense pain in the eyes, lips, nose,scalp, forehead and/or jaw

DM, dermatomyositis; IM, inflammatory myopathies; PM, polymyositis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus;; SSc,systemic sclerosis; SS, Sjögren’s syndrome; TMD, temporomandibular dysfunction.

444 r e v b r a s r e u m a t o l . 2 0 1 6;5 6(5):441–450

Fig. 1 – Computed tomography of temporomandibular joint of a patient with rheumatoid arthritis and complaint of clickingrtioinen

while chewing. Presence of subchondral cyst in the upper poof the left mandibular head (b) and flattening of articular em

Periodontal disease (PD)

PD is a chronic infectious disease caused by Gram-negativeanaerobic bacteria, affecting the tissues of protection andsupport of the tooth, such as gums, periodontal ligament,cementum and alveolar bone. Under PD designation, bothreversible (gingivitis) and irreversible (periodontitis) processesare included. When undiagnosed and untreated, PD can causeprogressive destruction of alveolar bone, causing tooth mobil-ity and subsequent dental loss.14 According to the WorldHealth Organization, periodontal disease affects approxi-mately 10–15% of the world population.14 Brazilian officialdata show that 19.4% of adults aged 35–44 years are carriersof this disease.15

Some recent studies also suggest a significant associationbetween RA and PD.13,16–18 The relationship between RA andprogression of inflammatory conditions (p.ex., periodontitis)is not clear. The main reason for this scenario is the lack ofuniformity in the classification of the various forms of bothdiseases.19 It is estimated that the prevalence of PD increasestwice in RA patients compared to the general population.17

Thus, the presence of a moderate-to-severe RA also increasesmore than twice the risk of developing forms of moderate-to-severe periodontitis compared to individuals without thedisease.17–19

Furthermore, there is evidence of similarity in the patho-

genesis of RA and PD. Microorganisms such as Porphyromonasgingivalis may play a role in both conditions,16 being able toinvade isolated human chondrocytes in the knee joint, inter-fering with cell cycle and inducing these cells’ apoptosis.20

n of the right mandibular head (a), erosion of lateral portionces (c).

Another important factor would be that P. gingivalis expressesthe peptide arginine deiminase (PAD), which converts argi-nine to citrulline by a citrullination process. This process,which is common to some human proteins, is associatedwith the pathophysiology of RA. It has a low immune toler-ance to citrullinated proteins in synovial fluid, which triggersthe development of immunoglobulins against these proteins,present in joints and tendons.21,22 In addition, studies havedemonstrated the presence of antibodies in response to oralanaerobic bacteria in the synovial tissue and serum. Othersauthors also found the presence of oral bacterial DNA in thesynovial fluid of RA patients.18 In fact, RA and PD have a vari-ety of markedly similar clinical and pathophysiologic features(Table 2).23,24

Although periodontal disease has local clinical manifes-tations, its chronic inflammatory nature can contribute tochange – and even worsen – the course of RA and of otherrheumatic diseases. A recent systematic review by Kaur et al.(2013) demonstrated a good level of evidence to support anassociation between RA and PD, taking into account tooth loss,the clinical attachment level, and erythrocyte sedimentationrates. Moderate evidence was noted in C-reactive protein andinterleukin-1 values. A positive outcome of periodontal treat-ment was observed, with respect to the clinical features ofRA. However, more studies are needed to fully explore thebiochemical processes and the relationship between these

chronic inflammatory diseases, despite the similarity in thepathophysiologic characteristics of RA and PD. It is found thatsix months after the completion of periodontal therapy, theimprovement of oral health is strongly associated with an

r e v b r a s r e u m a t o l . 2 0 1

Table 2 – Pathophysiological similarities in thecharacteristics of rheumatoid arthritis and periodontaldisease.23,24

Pathophysiologicalcharacteristics

RA PD

Cell infiltrate Macrophages, Tlymphocytes,plasma cells andPMN

Equivalent

Immunephenomenon

Immune complexdeposition,complementfixation

Equivalent

Cytokines IL-1�, IL-1�, IL-6,IL-8, TNF-� andTGF-�

Equivalent

Local cells affected Chondrocytes andsynoviocytes

Gingivalfibroblast,osteoblast, andkeratinocytes

Induction of boneresorption

PGE2, TNF-�, IL-1� LPS, PGE 2,TNF-�, IL-1�

Tissue Destruction Metalloproteinase,phospholipaseand elastase

Equivalent

Granulation tissue Present incartilage/boneinterface

Present in thecement/boneinterface

IL-1�, interleukin-1 alpha; IL-1�, interleukin-1 beta; IL-6,interleukin-6; IL-8, interleukin-8; LPS, lipopolysaccharide; PD,periodontal disease; PGE2, prostaglandin E2; PMN, polymorphonu-

ia

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clear leukocytes; RA, rheumatoid arthritis;TNF-�, tumor necrosisfactor alpha; TGF-�, growth transforming factor beta.

mprovement in endothelial function, with a decrease in localnd systemic inflammatory processes.25

yposalivation/xerostomia

mong oral changes, it turns out that hyposalivation (lowalivary flow) and xerostomia (dry mouth) are common inutoimmune rheumatic diseases, and xerostomia affects 1%f RA patients.26 About one third of RA patients have sec-ndary SS.27 A study including 604 RA patients showed aecrease in salivary flow in 43% of subjects.28 The risk ofeveloping hyposalivation increases with the severity of theisease. It is worth mentioning that another study conducted

n 483 hospitalized patients due to complications of arthritisound that only 17.7% of xerostomia-positive patients werereated for xerostomia. In contrast, 84.8% of patients treatedor xerophthalmia were treated for this condition. It was alsobserved that the therapeutic modalities administered forerostomia were not effective and also were not in accor-ance with current recommendations found in the medical

29

iterature.Therefore, a timely diagnosis and proper monitoring of SS

ssociated with RA are important steps to promote gains inhe quality of life of these patients (as will be discussed in the

6;5 6(5):441–450 445

SS section), taking into account that saliva performs functionsof systemic interest, for instance, the sense of taste, epithe-lial repair of oropharynx and esophagus, and esophageal acidcontent buffering, among other functions.30

Inflammatory myopathies

Polymyositis (PM) and dermatomyositis (DM) are autoimmunediseases classified as idiopathic inflammatory myopathies,being characterized by musculoskeletal inflammation.31

PM is a systemic connective tissue disease, characterized bybilateral, symmetrical, proximal muscle weakness. It affectsmuscles of the shoulder and pelvic girdle and progressestoward proximal muscles of the limbs. Its onset is frequentlygradual and progressive. PM exhibits a geographically variableincidence, with about one case for every 100,000 inhabitants,predominantly affecting females.32

Impairment of skeletal muscles of posterior pharyngealwall and proximal third of the esophagus can lead tooropharyngeal dysphagia, with aspiration and dysphonia.Consequently, the patient can complain of hypersalivation.This complication, however, will be due to an impaired func-tional activity of swallowing muscles in association with thesalivary reflex caused by reflux. Two thirds of the patientspresent involvement of the neck flexor muscles, which cancause difficulty in neck support. Constitutional symptomsinclude fatigue, low-grade fever, weight loss, and arthralgiaor arthritis of small and medium joints.33

Some rare case reports relate presence of ulcerations on theentire tongue, of a linear aspect and with a white secretion onthe edges, and also tongue atrophy, in which one can observea reddened mucosa.34

DM is an autoimmune disease of unknown etiology thatis characterized by a systemic small-vessel vasculopathypredominantly involving muscles and skin. Besides the cuta-neous involvement, the characterization of DM is based in thepattern of muscle involvement, presence of associated clinicalmanifestations, and histopathological changes.35

The prevalence of oral involvement in DM is unknown.Most of the information available comes from individual casereports or small case series, and some early reports of casesdid not clearly separate MS from PM.36

An involvement of mimic muscles may occur, which leadsto a decrease in facial expression. Similarly, the involvementof the masticatory and pharyngeal muscles may result in dys-phagia, dysphonia, and hypersalivation. The involvement ofstriated muscle of the pharynx or esophagus also contributesto the occurrence of dysphagia. In patients with dysphagia,DM reaches 18–50% of patients and correlates with diseaseseverity.36,37 In addition, the presence of dysphagia increasesthe risk of aspiration pneumonia. Mortality rates range from 1to 5 years, reaching 31% of patients with DM and dysphagia.37

However, the occurrence of hypersalivation is not alwaysattributable to an excess in saliva production, but may becaused by an inability to retain saliva and swallowing it, due tothe weakness of perioral muscle tone, or because of dysphagia.

The involvement of tongue muscle results in macroglossia,in addition of hypotonia, which can also make it more diffi-cult chewing, swallowing and speech.38 Involvement of themucous membrane is reported in about 10–20% of cases.39

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Mucosal edema, erythema and telangiectasia are the com-monest oral changes.38

Although 27.5% of patients with DM also suffer arthritis,TMJ involvement is rare, with only one case reported in theliterature. In some reports, the presence of prominent bloodvessels throughout the oral mucosa and aphthous stomatitis/ulcer-like lesions were described.40 About 10–46% of patientsdevelop painful oral and gingival ulcers.41 The teeth have shortand bulging roots, with obliteration of root canals as well aspulp chamber calcification. Xerostomia is also seen as a com-mon complaint.42

Systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease charac-terized by inflammation and hyper-reactivity of micro- andmacrovascular circulation associated with excessive collagendeposition in tissues, with subsequent fibrosis of the skinand/or internal organs.43 SSc has a predilection for females,with an incidence of 2–10/one million inhabitants in the gen-eral population.44 In addition, there is a consensus about anincrease in morbidity and mortality, with an estimated 66%survival at 10 years.45

The oral manifestations are scarcely studied and oftenneglected by clinicians, although leading to major functionaldisability. Microstomia is the most common oral finding anddevelops due to collagen deposition in perioral tissues, caus-ing limitation of mouth opening, perioral groove wrinkling,and soft palate, larynx and oral mucosa stiffness.46 Fur-thermore, hyposalivation and/or dry mouth are secondarymanifestations of the disease. TMD can also occur, with vary-ing degrees of subsequent resorption of mandibular branch,coronoid process, menton and condyle.5 It is believed thatthese areas are reabsorbed due to the chronic collagendeposition. Tongue cancer has a significantly increased fre-quency in patients with SSc that present a mouth opening

<30 mm.47

The resorption of some teeth has also been reported withsome frequency in these patients. There may be an abnor-mal increase in the frequency of decayed teeth and of an

Fig. 2 – Patient with systemic lupus erythematosus with gingivadisease with extensive loss of attached gingiva (a) and regions wlichen planus reticular with gingival (c) and mucosal (d) Wickhamrheumatologist, suspecting that the lupus was active; this suspic

0 1 6;5 6(5):441–450

atypical tooth eruption. Apparently there is also a predis-position for the occurrence of PD, due to increased plaquebuildup. This problem arises from the difficulty of cleaning themouth (caused by a smaller mouth opening) and in the useof the dental brush. This latter complication is due to scle-rotic changes in fingers and hands. Furthermore, the use ofsystemic corticosteroids for long periods influence in reduc-ing the periodontal inflammatory response, thus making thisprocess a progressive and often insidious one.48

Systemic lupus erythematous

SLE is an autoimmune disease of unknown etiology, influ-enced by environmental and genetic factors, and whichmainly affects women in the second and third decades oflife.49 The prevalence of oral lesions in patients with SLEvaries between 6.5% and 21%. SLE affects primarily tongue,oral mucosa, lips and palate. For this reason, oral ulcers areconsidered primary events, that are included in the follow-ing activity indexes of this disease: BILAG (British Isles LupusAssessment Group),50 SLEDAI (Systemic Lupus ErythematosusDisease Activity Index),51 SELENA-SLEDAI (Safety of Estro-gens in Lupus Erythematosus National Assessment), SLAM(Systemic Lupus Activity Measure),52 and ECLAM (EuropeanConsensus Lupus Activity Measurement).53

The lesions appear in different ways, such as blemishesand plaques on the mucosa. The lesions may be erythe-matous, ulcerated, of a recurrent aphthous stomatitis, andlichen planus- or leukoplakia-like lesions (Fig. 2). The size ofthese lesions is also variable, from a small surface erosionto ulcers covering a wide and extensive area.54,55 The fewstudies on oral lesions in patients with SLE show, microscop-ically, parakeratosis or orthokeratosis, acanthosis, epithelialatrophy, vacuolar degeneration of the basal membrane withnecrosis of basal keratinocytes, basement membrane thick-ening, lichenoid mononuclear infiltrate, and deep connective

tissue vasculitis. Injuries in the vermilion border of lips (espe-cially in the lower lip), deserve special attention, as theselesions may be related to lupus cheilitis, with or withoutepithelial dysplasia.54,56

l and tooth sensitivity complaint. Presence of periodontalith a purulent exudate (b). There is a manifestation of

striae. The dentist referred this patient to theion was subsequently confirmed.

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Other secondary orofacial signs/symptoms include: mouthurning, hyposalivation, xerostomia, salivary gland disease

such as focal necrosis of the parotid gland), TMD, desqua-ative gingivitis and PD.54 Hyposalivation can lead to an

ncreased occurrence of dental caries and to a predispositiono candidiasis, especially if immunosuppressive agents suchs corticosteroids are being used.56

jögren’s syndrome (SS)

S is an inflammatory autoimmune disease presenting a fre-uent chronic course, in which the lymphocytic infiltrationf exocrine glands, particularly lacrimal and salivary glands,

mpairs its secretory function.55 Simultaneously, systemicanifestations of cutaneous, respiratory, renal, hepatic, neu-

ologic and vascular nature can occur. SS has two distinctorms: primary SS – not associated with another disorder; andecondary SS – in which the patient expresses this syndromen association with other autoimmune diseases.57,58

It is estimated that SS affects 0.2% of the world popula-ion, mainly women, in a ratio of 9:1.57,58 In Brazil, due to thebsence of official estimates or scientifically confirmed datan its incidence, no one knows the exact number of patientsith this syndrome. However, it was stated that the majority ofiagnosed cases are related to menopausal, or older, women.59

SS follows a variable course and exhibits a wide spectrumf clinical manifestations. In addition, many of its symptomsre non-specific, making difficult and delaying the diagnosis.ighty percent of patients with SS exhibit an insidious onset ofymptoms of dryness that develop over a period from severalonths to years.58

The oral manifestations observed in patients with SS arettributed to the involvement of salivary glands, which leadso less salivary secretion. In consequence, the worse lubrica-ion and loss of buffering and antimicrobial action of salivaryecretion increase the incidence of oral/dental infections,ucosal friability, and symptoms of irritation and burningouth (Fig. 3).57 On the other hand, some patients complain

f xerostomia, which may not be accompanied by a decreasen salivary secretion.30 However, in the initial stage of theisease, when the diagnosis has not yet been well estab-

ished, patients may complain of xerostomia due to changes in

ig. 3 – Loss of papillae of the tongue(a) and candidiasis (b) in a pomplaints of a burning mouth, feeling of “something stuck in thalivary patterns showed severe hyposalivation (unstimulated sand an acidic pH (6.3). Loss of mineral structure with clefts formaromote great discomfort to the patient, because of the greater a

6;5 6(5):441–450 447

salivary composition, or to a reduction of salivary secretionfrom the smaller salivary glands (from lip mucosa and palate).Thus, sialometry may reveal that the patient has a normalsalivary flow; however, salivary composition tests will indicatequalitative changes.60

Usually, dental caries and fungal infections are observed inmucous membranes (especially candidiasis) that can manifestas pseudomembranous or erythematous lesions. The friabilityof the mucosa in patients with SS often leads to soft tis-sue injuries. Such signs include dry and cracked lips, medianrhomboid glossitis or a fissured tongue, loss of lingual papil-lae, stomatitis, angular cheilitis, aphthous injury, lip mucosalulcers, difficulty in swallowing solids, and odynophagia.57

SS patients often display voice disorders and correlatedsymptoms that are associated with a decrease in their qualityof life. It is known that the lubrication of the vocal cords iscarried out by saliva.61 Thus, this biological fluid is importantfor a proper phonation.

Another relevant point refers to the drop in the qualityof life of patients with SS, because of their changing eatinghabits, caused by dry mouth.62 There is a Strong correlationamong oral dryness and fatigue, pain, psychological distress,and a worse quality of sleep; and that it is considered as a car-diovascular risk factor.63 In this study, the authors concludedthat a multidisciplinary therapeutic approach may be the bestway to minimize dry mouth and its consequences in patientswith primary SS.63

Finally, another common oral manifestation is an asymp-tomatic and self-limiting increases of parotid glands or othermajor salivary glands,55 which may be pointing to the earlystage of SS.

Therefore, the establishment of an early diagnosis of SS isessential for the choice of the correct treatment, which con-sists in relieving the signs and symptoms in order to minimizeor avoid sequels that can impact on the health and quality oflife of patients.64

Gustatory, mechanical and chemical sialogogues have beenused to stimulate saliva production. However, the effective-

ness of these resources is low, because they provide onlytemporary relief, requiring frequent applications.65 Many top-ical treatments such as sprays, lozenges, mouthwashes, gels,oils or toothpastes have been evaluated, but there is no strong

atient with Sjögren’s syndrome who presented withe throat” and reduced sense of taste. Examinations oflivary flow rate: 0 ml/min; flow with stimulus: 0.1 ml/min)tion in teeth (c) and resin porosity (d), conditions that

ttrition with the dried up mucosa.

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448 r e v b r a s r e u m a t

evidence that any of these topical treatments is effective toalleviate the patient with dry mouth.66 Oxygenated tri-esterglycerol-based lubricants are more effective than water-basedelectrolyte sprays. Chewing gum increases saliva production,but there is no evidence that these products are better or worsethan saliva substitutes. However, acidic secretagogues andthose containing sugar should be avoided,66 because theseproducts lower oral pH, promote greater tooth demineraliza-tion and irritate a mucous already very sensitive. One shouldopt for the use of sugar-free chewing gum, but containing flu-oride and bicarbonate in its composition. These componentsincrease salivary pH and assist in preventing tooth decay.67,68

Chemical sialagogues, such as pilocarpine and cevime-line, are effective in relieving hyposalivation, but may causeadverse effects.65 Electrical stimulation applied to the affer-ent pathways (through the oral mucosa or skin) in areas ofsalivary glands, showed increased saliva production and reliefof dry mouth in patients with SS65 and in patients undergoingcervical-brain radiotherapy.69

A systematic review of randomized controlled trials wasconducted to gather evidence on drug therapy in primary SS.The authors suggested that saliva substitutes and sugar-freechewing gums may be effective in cases of mild-to-moderatedry mouth. Consumption of alcohol and smoking should beavoided, and it is a critical factor the establishment of athorough oral hygiene. The treatment of choice for patientswith residual function of salivary glands is cevimeline andoral pilocarpine. However, no study was published compar-ing the efficacy of these two drugs. The doses which haveshown better effects in terms of efficacy and safety were:pilocarpine 5 mg every 6 h; and cevimeline 30 mg every 8 h.N-acetylcysteine could be an alternative in patients with con-traindications or intolerance to muscarinic agonists.70

Conclusion

Orofacial manifestations in patients with autoimmunerheumatic diseases are common problems, but still sparselyaddressed by rheumatologists in their everyday clinicalpractice. This article produced a summary of the main mani-festations observed, in order to familiarize these professionalswith their diagnoses, underlying the possible need for an earlyreferral to the dentist.

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgements

The authors would like to acknowledge Nathalya Lopes Silva,Rafaelly Stavale, Talitha Giovanna da Silva and Francisca Ires-

dania Alves Macedo for their collaboration. The second andseventh authors are also grateful for the financial support ofCAPES – Coordenacão de Aperfeicoamento de Pessoal de NívelSuperior.

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