Oral Diseases (2016) doi:10.1111/odi.

12507
2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
All rights reserved
www.wiley.com

REVIEW ARTICLE

The spectrum of orofacial manifestations in systemic

sclerosis: a challenging management
S Jung1,2,3, T Martin4,5,6, M Schmittbuhl7, O Huck1,2,8
1
ole de Medecine et de Chirurgie Bucco-Dentaires, H^opitaux Universitaires de Strasbourg, France; 2Faculte de Chirurgie Dentaire,
P^
Universite de Strasbourg, France; 3Center of Chronic Immunodeciency (CCI), Medical Center, Faculty of Medicine, University of
Freiburg, Germany; 4Service dImmunologie Clinique, H^opitaux Universitaires de Strasbourg, France; 5Faculte de Medecine,
Universite de Strasbourg, France; 6CNRS UPR 3572 Immunopathologie et Chimie Therapeutique, Institut de Biologie Moleculaire et
Cellulaire (IBMC), Strasbourg, France; 7Faculte de Medecine Dentaire, Universite de Montreal, Centre de Recherche du Centre
Hospitalier de lUniversite de Montreal (CHUM), Montreal, QC, Canada; 8INSERM, UMR 1109 Osteoarticular and Dental
Regenerative Nanomedicine, Faculte de Medecine, Federation de Medecine Translationnelle de Strasbourg (FMTS), France

Systemic sclerosis (SSc) is a rare multisystem connec-
tive tissue disorder characterized by the triad fibrosis,
vasculopathy and immune dysregulation. This chronic
disease has a significant impact on the orofacial region
that is involved in more than two-thirds of the cases.
SSc patients can show a wide array of oral manifesta-
tions, which are usually associated with a severe impair-
ment of the quality of life. They often present a
decreased the salivary flow and a reduced mouth open-
ing that contribute substantially to the worsening of the
oral health status. Therefore, SSc patients require speci-
fic and multidisciplinary interventions that should be ini-
tiated as early as possible. The identification of specific
radiological and clinical signs at the early stage will
improve the management of such patients. This study
reviews the wide spectrum of orofacial manifestations
associated with SSc and suggests clues for the oral man-
agement that remains challenging.
Oral Diseases (2016) doi:10.1111/odi.12507
Keywords: systemic sclerosis; oral management; orofacial
manifestations; fibrosis
Introduction
Systemic sclerosis (SSc) is a rare multisystem connective
tissue disorder of unknown origin characterized by three
main pathological features: extended brosis, vasculopathy,
and immunological abnormalities. SSc patients have a
decreased quality of life (Almeida et al, 2015) and an
Correspondence: Sophie Jung, P^ole de M
edecine et de Chirurgie Bucco-
Dentaires, H^opitaux Universitaires de Strasbourg, 1 place de lH^opital,
67091 Strasbourg, France. Tel: +33 3 88 11 69 56, Fax: + 33 3 88 11 69
17, E-mail: s.jung@unistra.fr
Received 27 April 2016; revised 10 May 2016; accepted 16 May 2016
increased mortality with a 5-year survival rate estimated to
be around 85% (Ioannidis et al, 2005). The incidence of
SSc ranges from 0.6 to 2.4 per million per year in adult pop-
ulation (Chifot et al, 2008). There are geographic dispari-
ties in SSc prevalence, the latter being higher in the USA
than in Europe for instance (Mayes et al, 2003; Chifot
et al, 2008; Ranque and Mouthon, 2010). Differences are
also observed according to ethnicity, African Americans
having a higher prevalence in comparison with European
Americans (Mayes et al, 2003). SSc occurs most commonly
during the fth decade and preferentially affects women
with a mean sex ratio around 3 to 1 (Chifot et al, 2008).
Clinical manifestations and classications
Diagnosis of SSc is mainly based on medical history and
clinical examination. Patients can exhibit a wide range of
clinical features including skin thickening, calcinosis, lung
brosis, arthralgia, myocardial lesions and renal insuf-
ciency (Table 1). Raynauds phenomenon is almost
always the rst clinical manifestation of the disease
(Hachulla and Launay, 2011).
Despite the great phenotypic variability of the disease,
skin involvement is observed in the majority of SSc
patients (Krieg and Takehara, 2009). Pathological accumu-
lation of connective tissue components within the dermis
leads to the loss of cutaneous elasticity followed by
sclerosis i.e. thickening and hardening of the skin. The
skin becomes atrophic and is often tightly tethered to the
underlying tissue (Czirj
ak et al, 2008). Sclerosis usually
starts in the ngers, with progressive exion and retraction
(sclerodactyly) (Poole, 1994). The modied Rodnan skin
score (mRSS) is an approved tool that is widely used to
quantify skin involvement in SSc (Czirj
ak et al, 2008;
Krieg and Takehara, 2009). Cutaneous thickening is
assessed by palpation of the skin in 17 areas of the body,
which are scored from 0 to 3 (0 = normal, 1 = weak,
2 = intermediate and 3 = severe skin thickening), giving a
possible range from 0 to 51. Fibrotic manifestations have
 Orofacial manifestations in systemic sclerosis
S Jung et al

2
Table 1 Organ involvement in systemic sclerosis 2001 (LeRoy and Medsger, 2001). Internal organ involve-
ment can also be observed in the absence of skin thicken-
Organ/system ing in a rare form called SSc sine scleroderma (LeRoy and
involved Clinical manifestations
Medsger, 2001; Hachulla and Launay, 2011). The Ameri-
Skin and mucous Sclerosis (skin and mucosa) can College of Rheumatology/European League Against
membranes Atrophy (skin and mucosa) Rheumatism (ACR/EULAR) has developed a new set of
Pigmentation disorders (skin and mucosa) criteria that show high sensitivity and specicity, allowing
Calcinosis (subcutaneous calcications) an earlier diagnosis in particular of forms with very limited
Peripheral vascular Raynauds phenomenon or no skin brosis (Van den Hoogen et al, 2013).
system Telangiectasia
Ischemic ulcers (digital ulcers. . .)
Pathophysiology
Osteoarticular Polyarthralgia/arthritis
system Tenosynovitis, tendon retractions Fibrosis is the distinguishing hallmark of SSc (Ho et al,
Bone resorption 2014). Although the exact etiology is still unknown, accu-
Muscular system Myalgia mulation of extracellular matrix components is thought to
Myositis result from abnormal interactions between endothelial
Nervous system Trigeminal neuralgia cells, immune cells and broblasts leading to the produc-
Carpal tunnel syndrome tion of proinammatory and probrotic cytokines (e.g.,
Digestive system Esophagus: dysphagia, esophagitis, reduced TGF-b, IL-6, TNF-a) in a context of vascular hyper-reac-
peristalsis, gastroesophageal reux tivity and tissue hypoxia (Tamby et al, 2003; Scala et al,
(GERD). . . 2004; Lafyatis, 2014). Van Bon et al (2014) have shown
Stomach: gastroparesis. . . that CXCL4, an anti-angiogenic and probrotic chemo-
Small bowel: reduced peristalsis, bacterial
overgrowth. . .
kine, can be used as a predictive biomarker as high
Intestinal pseudo-obstruction syndrome, CXCL4 levels are correlated with severe complications
malabsorption. . . such as lung brosis and pulmonary hypertension.
Lungs Pulmonary arterial hypertension Autoimmunity plays an important role as evidenced by
Pulmonary brosis the presence of several SSc-specic autoantibodies (Steen,
Fibrosing alveolitis 2005). Anti-centromere antibodies are associated with lim-
Heart Pericarditis ited SSc while anti-topoisomerase I antibodies (anti-Scl
Pericardial brosis 70) and anti-RNA polymerase III are rather found in
Heart block patients with diffuse SSc (LeRoy and Medsger, 2001;
Myocardial brosis
Cardiac insufciency Chung and Utz, 2004; Steen, 2005; Dumoitier et al,
2014). The complexity of SSc pathogenesis and the diver-
Kidneys Scleroderma renal crisis (SRC) with kidney
failure sity of clinical features argue for a multifactorial process
Nephrosclerosis (Nikpour et al, 2010). The implication of genetic factors
Proteinuria is supported by an increased risk to develop the disease in
relatives of SSc patients. Although a higher incidence of
some genetic polymorphisms and HLA class II associa-
long been considered as untreatable, but this view has tions have been found (Arnett et al, 2010), only few cau-
changed over the past few years. Promising strategies sative variants have been identied yet (e.g., CD247,
include high-dose immunosuppression with autologous STAT4, IRF5) (Dieud
e et al, 2009, 2011; Rueda et al,
hematopoietic stem cell transplantation (Van Laar and Sul- 2009; Radstake et al, 2010; Dumoitier et al, 2014). The
livan, 2013) and a large number of disease-modifying combination of several single-nucleotide polymorphisms
therapies targeting proinammatory and probrotic cytoki- (SNPs) in different genes may therefore be required (Mar-
nes such as TGF-b (Antic et al, 2013). tin and Fonseca, 2011). Moreover, the low concordance
The gastrointestinal tract is the second most affected rate among monozygotic twins (4.2%) (Feghali-Bostwick
organ system and digestive manifestations can range from et al, 2003) highlights the important role played by envi-
abdominal bloating, gastroesophageal reux (GERD) to ronmental factors. Occupational exposure to silica and
severe weight loss due to malabsorption. The latter can be organic solvents has been reported to be implicated in SSc
the consequence of small bowel bacterial overgrowth that pathogenesis (Dospinescu et al, 2013; Marie et al, 2014).
is promoted by reduced peristaltism (Savarino et al, 2014). Different epigenetic changes have also been implicated in
Systemic sclerosis is usually classied into two major SSc pathophysiology (Broen et al, 2014).
subsets based on the extent of skin brosis. In limited cuta- As orofacial involvement in SSc is frequently under-
neous SSc (lcSSc), skin involvement is restricted to face, diagnosed, our aim was to describe the wide spectrum of
neck and area distal to elbows and knees whereas in dif- clinical manifestations that can be observed and to give an
fuse cutaneous SSc (dcSSc), skin brosis also involves the update on the oral management of SSc patients.
proximal limbs and/or the trunk (LeRoy et al, 1988).
dcSSc is associated with a more severe clinical course
characterized by internal organ involvement. Criteria for an Materials and methods
additional early or limited subset of SSc (lSSc)character- Search strategy
ized by Raynauds phenomenon and SSc-specic autoanti- A literature search was performed using PubMed without language and
bodies but without skin manifestationswere proposed in time restriction. The following search strategy was used: (systemic

Oral Diseases

sclerosis OR scleroderma, systemic) AND, respectively, orofacial,
oral, mouth, microstomia, oral mucosa, xerostomia, resorption, treatment challenging because of the limited access. A
temporomandibular joint, periodontal disease, periodontal ligament,
caries, dental treatment, implant.
Orofacial manifestations
Systemic sclerosis has a major impact on the orofacial
region that is affected in approximately 80% of SSc
patients. However, orofacial involvement remains under-
diagnosed and the corresponding symptoms are often
overshadowed by severe systemic manifestations (Del
Rosso and Maddali-Bongi, 2014).
Skin and mucosa
Facial appearance. Skin brosis affects rapidly the face,
leading to changes in personal appearance (Sticherling,
2012a). Subcutaneous collagen deposition in facial skin
results in a smooth, tight, expressionless mask-like facies
with disappearance of wrinkles, perioral furrows and atrophy
of nasal alae (pinched nose) (Figure 1) (Albilia et al, 2007;
Sticherling, 2012a). Hence, facial changes belong to the most
worrying aspects of the disease as they affect esthetics and
can lead to the loss of individual physiognomy (Amin et al,
2011; Del Rosso and Maddali-Bongi, 2014). SSc patients
frequently have a very similar appearance and one of the
most challenging aspect is the self-perception of their
modied appearance that may have a negative impact on
their social interactions (Amin et al, 2011). Other common
skin manifestations include hypo- and hyperpigmentation of
certain cutaneous areas, hypohidrosis, and modications of
the lip color (Krieg and Takehara, 2009).
Microstomia. Sclerosis of lips and of skin around the
mouth leads to reduced mouth opening (microstomia) and
width (microcheilia) (Figure 1). The decrease of the
interincisal distance was conrmed in a large cohort of
163 SSc patients compared with 231 controls (37.7 mm vs
44.3 mm, P < 0.0001) (Baron et al, 2014a). Microstomia
interferes considerably with oral functions, especially
Figure 1 Typical facial features in a patient with diffuse SSc. Mask-
like facies with disappearance of wrinkles and atrophy of nasal alae
(pinched nose) secondary to subcutaneous collagen deposition in facial
skin, reduced mouth opening (microstomia) and width (microcheilia) due
to sclerosis of the lips and telangiectases, especially on nose and cheeks
that are the consequence of the dilatation of small vessels in the skin
Orofacial manifestations in systemic sclerosis
S Jung et al
3
chewing, and also makes oral hygiene and dental
smaller interincisal distance was found to be signicantly
correlated with the overall disease activity, extent of
cutaneous involvement, and presence of anti-
topoisomerase I antibodies (Baron et al, 2014b).
Telangiectases. Telangiectases that are the consequence of
the dilatation of small vessels in the skin manifest as
small red macular areas and reect abnormal
neoangiogeneis. They represent a characteristic feature of
SSc as they frequently (7087.5%) affect facial skin,
especially cheeks, nose, and lips (Figure 1), but also the
oral mucosa (lateral border of tongue and buccal mucosa
of cheek) (Nagy et al, 1994; Vincent et al, 2009; Chu
et al, 2011).
Intra-oral mucosal manifestations. Submucous brosis
induces atrophy and subsequent fragility and sensitivity of
the oral mucosa (including gingiva and taste buds) that
becomes pale and sclerotic. Certain manifestations of the
disease such as denutrition, GERD, vitamins B9 and B12
deciencies, exocrine pancreatic insufciency, or small
bowel involvement associated with bacterial overgrowth
can worsen mucosal atrophy (Alantar et al, 2011). SSc
patients frequently complain of burning mouth syndrome
or dysesthesia. Flattening of the palate, shortening of the
uvula, mucosal crenations, and impaired tongue mobility
due to tongue brosis or to lingual frenum abnormalities
(reduced length and increased thickness) can also be
observed (Eversole et al, 1984; Vincent et al, 2009;
Sticherling, 2012a,b; Frech et al, 2016). Furthermore, the
tongue can be affected by Raynauds phenomenon (Casey
and Lawton, 1971; Bridges and Kelly, 2002).
Salivary gland involvement
Xerostomia that represents the subjective sensation of a
dry mouth (Nape~nas et al, 2009) is a common feature of
SSc with a prevalence varying from 25% to 71.2% (Wood
and Lee, 1988; Nagy et al, 1994; Avouac et al, 2006; Sal-
liot et al, 2007; Vincent et al, 2009; Chu et al, 2011;
Kobak et al, 2013). In SSc, xerostomia is not only a sub-
jective sensation, but it is usually the consequence of an
Figure 2 Xerostomia, mucosal atrophy of the tongue, and angular
cheilitis (candidiasis) in a patient with diffuse SSc
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 Orofacial manifestations in systemic sclerosis
S Jung et al
4
objective reduction in the quantity of the saliva produced.
SSc patients salivary ow was assessed in different stud-
ies (Andonopoulos et al, 1989; Nagy et al, 1994; Chu
et al, 2011; Kobak et al, 2013; Baron et al, 2014a,b). The
largest cohort study (163 SSc patients vs 231 controls),
performed recently by the Canadian Scleroderma Research
Group, revealed that the disease was associated with a
lesser saliva production (63.19 mg min 1 vs
1
147.52 mg min ) (Baron et al, 2014a). SSc patients have
lower stimulated and resting salivary ow rates than unaf-
fected individuals and also lower salivary pH values. This
might be responsible for an increased caries risk, difcul-
ties in wearing prostheses, altered taste sensation, and
pathological conditions such as burning mouth syndrome,
mucosal atrophy, or candidiasis (Figure 2) (Chu et al,
2011). However, decreased saliva production has not been
correlated with disease severity (Wangkaew et al, 2006;
Baron et al, 2014b). Xerostomia can be exacerbated by
GERD, severe microstomia, especially when patients are
unable to close their lips, and by certain medications (e.g.,
antidepressants).
Salivary defense system also seems to be affected (Kna
s
et al, 2014). Increased production of reactive oxygen spe-
cies can be responsible for the direct activation of brob-
lasts and the stimulation of TGF-b secretion. Moreover, it
can also worsen the development of brosis by altering
the balance between proteases and anti-proteases
(Zalewska et al, 2014). Mason et al have observed an
increased mast cell population in the salivary glands from
SSc patients. Their products are able to stimulate brob-
last proliferation and collagen synthesis. Changes in the
expression of TGF-b isoforms by glandular broblasts
were also found with a downregulation of TGF-b3 that
normally limits the deposition of brous tissue during
healing process (Shah et al, 1995; Mason et al, 2000).
Hebbar et al have shown that E-selectinan adhesion
molecule specic to activated endothelial cellswas
expressed in the salivary glands of patients with Ray-
nauds phenomenon before the onset of clinical skin
changes. TNF-a secretion by mast cells that also inltrate
the salivary tissues at the early onset of the disease con-
tributes to endothelial cell activation (Hebbar et al, 1995,
1996, 1998).
Xerostomia in SSc seems to be due to the brotic pro-
cess rather than to lymphocytic sialadenitis, the latter
being a typical feature of Sj ogrens syndrome. In SSc,
salivary gland brosis develops around capillaries and
excretory ducts. Capillary wall sclerosis induces functional
abnormalities by reducing vascular permeability whereas
periductal brosis impairs salivary excretion (Hebbar et al,
1994; Avouac et al, 2006). Sj ogrens syndrome is found
in only 14% to 33.9% of SSc patients, depending on the
diagnostic criteria (Cipoletti et al, 1977; Osial et al, 1983;
Coll et al, 1987; Drosos et al, 1988; Hebbar et al, 1994;
Avouac et al, 2006; Kobak et al, 2013). It is an autoim-
mune epithelitis (Skopouli and Moutsopoulos, 1994) that
can either occur alone (primary Sj ogrens syndrome) or
can be associated with other autoimmune disorders (sec-
ondary Sj ogrens syndrome). Salliot et al have demon-
strated that Sjogrens syndrome is not secondary to SSc
but can be associated with the disease (Salliot et al,
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2007). When it is associated with Sjogrens syndrome,
SSc seems to be less severe. Indeed, Sjogrens syndrome
is more frequently observed in patients with limited SSc
(Avouac et al, 2006; Salliot et al, 2007; Vincent et al,
2009). Lung brosisone of the most severe complica-
tions of limited SScaffects only 11% of the patients
with both SSc and Sjogrens syndrome (vs more than 30%
of patients with SSc alone) (Salliot et al, 2007). The asso-
ciation of Sjogren syndrome with SSc could reect a
spreading of autoimmunity as those patients are more
prone to develop a third autoimmune disease (e.g., pri-
mary biliary cirrhosis) (Salliot et al, 2007). Some studies
also report an enlargement of the parotid gland in about
20% SSc patients (Andonopoulos et al, 1989; Nagy et al,
1994).
Bone resorption and temporomandibular joint involvement
Involvement of bones and joints is common in SSc
patients but in the jaws, only the mandible is affected.
Mandibular osteolysis can be observed in 6.6 to 46.7% of
SSc patients (Seifert et al, 1975; Marmary et al, 1981;
Wood and Lee, 1988; Rout et al, 1996; Marcucci and
Abdala, 2009; Vincent et al, 2009; Leung et al, 2011;
Dagenais et al, 2015). There is no clear correlation
between the incidence of the mandibular resorption and
the severity or the progression of the disease (Marmary
et al, 1981; Wood and Lee, 1988; Baron et al, 2015a,b).
Although this condition tends to affect patients with a
longer disease mean time (7.29 years) (Marcucci and
Abdala, 2009), it can occur at any time during the course
of SSc (Seifert et al, 1975; Benitha et al, 2002). The
gonial angles are the most frequently affected sites
(37.6%), followed by the condylar heads (20.8%), the
coronoid processes (20.0%), and the posterior border of
the ramus (14.4%). Bilateral condylysis can be found in
713.7% of the cases (Haers and Sailer, 1995; Rout et al,
1996; Vincent et al, 2009; Doucet and Morrison, 2011).
Temporomandibular joint (TMJ) disorders are also fre-
quently associated with the disease (Vincent et al, 2009;
Matarese et al, 2016; Pischon et al, 2016) and can be the
consequence of mandibular resorption. The prevalence of
clinical signs of TMJ dysfunction (pain, TMJ sounds,
impairment of mandibular movements. . .) and characteris-
tic magnetic resonance imaging (MRI) ndings (disk,
articular surface and bone changes) is higher in SSc
patients compared to healthy controls (Matarese et al,
2016; Pischon et al, 2016).
The pathogenesis of bone resorption in SSc is not well
understood yet. The current hypothesis is that osteolysis
could be the consequence of a multifactorial process due
to the combination of microvasculopathy with pressure
ischemia secondary to skin thickening and muscular atro-
phy (Benitha et al, 2002; Auluck et al, 2005). Osteolytic
lesions coincide with the attachment zones of the facial
muscles such as condyles (lateral pterygoid insertion),
coronoid processes (temporal muscle insertion), and, espe-
cially, mandibular angles (masseter insertion) (Benitha
et al, 2002; Doucet and Morrison, 2011) that are usually
the last areas affected by the physiological resorption pro-
cess (Pogrel, 1988; Auluck et al, 2005). Ramon et al sug-
gested that SSc vasculopathy may preferentially affect the
 Orofacial manifestations in systemic sclerosis
S Jung et al

5
Table 2 Summary of the studies reporting tooth decay in SSc patients

Number of missing Number of decayed Caries experience Number of lled

Study Groups teeth teeth DMFT/S teeth

Wood and Lee (1988) SSc: n = 31 ND 3.2  4.3 DMFS: 95  37 ND

Controls: n = 30 1.8  2.6 DMFS: 77  35
SSc with xerostomia: n = 24 4.9  6.1 DMFS: 101  36
Nagy et al (1994) SSc: n = 25 ND ND DMFT: 21.9  6.5 ND
Controls: n = 15 DMFT: 18.7  6.1
Chu et al (2011) SSc: n = 40 4.1  5.5 (ns) 2.1  2.4 DMFT: 10.5  7.8 4.3  4.2
Controls: n = 40 4.9  5.5 1.5  2.5 DMFT: 11.6  7.0 5.2  4.2
Baron et al (2014a) SSc: n = 163 7.9  9.4 (ns) 0.9  1.8 ND 11.2  6.1
Controls: n = 261 5.7  7.0 0.6  1.8 11.8  5.8
Pischon et al (2016) SSc: n = 58 5.5 (2.010.0) (a) ND DMFT: 17.66  6.00 ND
Controls: n = 52 5.0 (0.58.5) DMFT: 18.12  6.85

Values are indicated as mean  standard deviation except for (a) where they are indicated as median (interquartile range). Statistically signicant results
are highlighted in bold.
ND: not determined; ns: not signicant.

small muscular branches of the internal maxillary artery
that provide vascularization of the sites commonly
involved by bone resorption. Those vascular abnormalities
could therefore account for the observed ischemic oste-
olytic lesions (Ramon et al, 1987). Muscles that often
become atrophic and bulkier secondary to increased bro-
sis exert a permanent pressure on the bone (Auluck et al,
2005). Skin hardening may also amplify pressure ischemia
with subsequent bone resorption, especially of the
mandibular angles (Pogrel, 1988; Auluck et al, 2005).
This hypothesis is supported by the recent work of Baron
et al that showed an inverse correlation between interden-
tal distance and the number of erosions (Baron et al,
2015a). Severe resorption can, in some cases, induce pain-
ful trigeminal neuropathy due to the compression of the
inferior alveolar nerve (Fischoff and Sirois, 2000). Ero-
sions of the condyles can also lead to degenerative disease
of the TMJ that is frequently associated with pain and
dysfunction (Haers and Sailer, 1995; Mugino and Ike-
mura, 2006; Doucet and Morrison, 2011; Delantoni and
Matziari, 2015; MacIntosh et al, 2015).
Calcinosis
Dystrophic calcinosis is a common nding in SSc.
Although it is usually associated with the limited form of
the disease, about 25% of all SSc patients are affected
(Boulman et al, 2005; Reiter et al, 2011). Calcinosis is
characterized by the deposition of hydroxyapatite and
amorphous calcium phosphate nodules in the skin, subcu-
taneous tissues, and periarticular regions (Boulman et al,
2005; Reiter et al, 2011). Calcications are also frequently
observed at sites that are exposed to recurrent microtrauma
and where tissue integrity has been compromised (Puga-
shetti et al, 2011; Reiter et al, 2011). To our knowledge,
only 4 SSc patients presenting with calcinosis in the facial
area have been reported so far (coronoid process of mand-
ible, along mandibular arch, nose, TMJ) (Temekonidis and
Drosos, 2001; Alp oz et al, 2007; Chikazu et al, 2008;
Nestal-Zibo et al, 2009). Calcications within the peri-
odontal ligament space (PDL) and the pulp chamber that
may also be related to the general spectrum of dystrophic
calcinosis have been evidenced by cone-beam computed
tomography (CBCT) approach in a patient with diffuse
SSc (Jung et al, 2013).
Dental involvement
Xerostomia and GERD are responsible for a decrease of
the salivary pH. Indeed, a low pH compromises the
buffering capacity of the saliva and can induce enamel
and dentin erosion. It also induces a modication of the
oral microora that becomes pathogenic, increasing caries
susceptibility (Albilia et al, 2007). The Canadian Systemic
Sclerosis Oral Health study, which describes the largest
SSc cohort, reveals that SSc patients had signicantly
more decayed teeth compared to healthy controls (0.88 vs
0.59, P = 0.0465) (Baron et al, 2014a). Two other studies
(Wood and Lee, 1988; Chu et al, 2011) also reported
more untreated decayed teeth in SSc patients than in con-
trols (respectively 3.2 vs 1.8 and 2.1 vs 1.5), but the dif-
ference was only signicant for patients with associated
xerostomia (4.9 vs 1.8; P < 0.05) (Wood and Lee, 1988)
(Table 2).
Regarding tooth loss, no study highlighted a statistical
difference between SSc patients and healthy controls (Chu
et al, 2011; Baron et al, 2014a; Pischon et al, 2016).
However, a trend toward an increased number of missing
teeth has been observed in recent studies (Baron et al,
2014a; Pischon et al, 2016). Interestingly, Baron et al
found a relationship between reduced manual dexterity
(sclerodactyly) and the number of missing teeth (Baron
et al, 2014a,b). Indeed, limitation in mouth opening, espe-
cially when it is associated with sclerodactyly, may impair
dental hygiene and result in a rapid deterioration of oral
health.
Periodontal involvement
Periodontal disease. SSc is associated with an impaired
periodontal health (Wood and Lee, 1988; Chu et al, 2011;
Leung et al, 2011; Mayer et al, 2013; Baron et al, 2014a;
Elimelech et al, 2015; Pischon et al, 2016). Most of the
studies showed that SSc patients have higher periodontal
indices (probing depth (PD), plaque index (PI), gingival
index (GI), and bleeding on probing (BOP)) than controls
(Leung et al, 2011; Mayer et al, 2013; Baron et al,

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Table 3 Summary of the studies reporting periodontal disease in SSc patients

Community
Gingival Clinical Attachment Periodontal Index
Study Groups Pocket Depth (PD) Bleeding Inammation Plaque Loss (CAL, mm) (CPI)

Wood and SSc: n = 29 PD score (a): Gingivitis score ND Plaque score (c): ND ND
Lee (1988) 10.1  8.9 mm (b): 8.8  4.2 13.2  8.5
Controls: n = 28 PD score: Gingivitis Plaque
3.9  5.3 mm score: 5.4  5.6 score: 12.3  9.0
Nagy et al SSc: n = 25 2.8  0.7 mm ND Gingivitis score PI% (d): 82  15 ND ND
(1994) Controls: n = 15 2.4  0.8 mm (%): 65  22 PI%: 68  25
Gingivitis score
(%): 58  27
Chu et al SSc: n = 40 % with >3 mm: 76 ND ND ND ND CPI 0: 0%, CPI 12:
(2011) Controls: n = 40 % with >3 mm: 55 23%, CPI 34: 77%
CPI 0: 0%, CPI 12:
45%, CPI 34: 55%
Leung et al SSc: n = 36 2.52  0.58 mm BOP%:78.4  19.6 ND PI% (d): 65  12.5 3.19  0.94 ND
(2011) Controls: n = 36 1.92  0.44 mm BOP%:49.3  22.6 PI%: 69.3  18.0 3.17  1.29
S Jung et al
Orofacial manifestations in systemic sclerosis

Mayer et al SSc: n = 12 3.74  0.36 mm FMBS%: 37.83  13.5% GI: 1.51  0.53 PI: 1.45  0.54 ND ND
(2013) Controls: n = 12 3.47  0.33 mm FMBS%: 30.08  16.9% GI: 1.21  0.67 PI: 1.41  0.82
Baron et al SSc: n = 163 Nb with PD>3 mm ND ND ND ND ND
(2014a) or
CAL 5.5 mm:
5.23  5.63
Controls: n = 231 Nb with PD>3 mm
or
CAL 5.5 mm:
2.94  4.11
Elimelech SSc: n = 20 3.74  0.32 mm BOP%: 37  14.8 GI: 1.53  0.34 PI: 1.47  0.40 ND ND
et al (2015) Controls: n = 20 3.35  0.31 mm BOP%: 27  90 GI: 1.12  0.54 PI: 1.24  0.61
Pischon et al SSc: n = 58 2.99  0.59 mm BOP: 0.29 (0.20.45) (e) GI: 0.16 (0.070.40) (e) PI: 0.88 (0.461.73) (e) 4.01  1.04 mm ND
(2016) Controls: n = 52 3.16  0.58 mm BOP: 0.41 (0.230.58) GI: 0.49 (0.260.73) PI: 0.35 (0.201.58) 3.4  0.89 mm

Values are indicated as mean  standard deviation unless stated otherwise. Statistically signicant results are highlighted in bold. (a) PD scores of 0, 1, or 2 were allocated for gingival sulcus depths of
less than 3 mm, 3 mm, or greater but less than 5 mm, and 5 mm or greater, and the scores were summed (b) sites were scored as 1 or 0 depending on gingival bleeding after periodontal probing and the
scores were summed; (c) sites were scored as 1 or 0 depending on the presence or absence of visible plaque and the scores were summed; (d) sites with detectable plaque (%); (e) values are indicated as
median (interquartile range). BOP: bleeding on probing (%); CAL: clinical attachment loss; CPI: Community Periodontal Index (CPI 0 = healthy, CPI 1 = gingivitis, CPI 2 = calculus, CPI 3 = pockets
45 mm, CPI 4 = pockets 6 mm); FMBS: Full-mouth bleeding score (%); GI: Gingival Index (GI); ND: not determined; ns: not signicant; PI: Plaque Index (02).
 Orofacial manifestations in systemic sclerosis
S Jung et al

7
Table 4 Summary of the studies reporting widening of the periodontal ligament space (PLS) in SSc patients

Number of patients Number/percentage of teeth

Study Groups PLS widening (mm) with PLS widening with PLS widening

White et al (1977) SSc=35 ND n = 13 (37%) ND

Rowell and Hopper SSc: n = 30 ND 30% ND
(1977) Controls: n = 30
Marmary et al (1981) SSc: n = 19 0.15 n = 19 (100%) ND
Objective Controls: n = 8 0.08
measurements
Alexandridis and SSc: n = 26 Maxilla: 65% SSc patients 32 to 35% of PLS around teeth in
White (1984) Controls: n = 26 0.295  0.053 have a mean PDL patients with progressive SSc are >
Objective 0.224  0.021 width > controls controls
measurements Mandibula:
0.290  0.043
0.219  0.020
Mean: 0.292  0.048
0.220  0.019
Janssens et al (1987) SSc: n = 47 ND 59.2% ND
Controls: n = 359 (SLE+RA patients) 0% (SLE)-4% (RA)
Wood and Lee (1988) SSc: n = 24 0.18  0.05 mm ND ND
Objective SSc with mandibular erosions: n = 6 0.22  0.22 mm
measurements Controls: n = 28 0.11  0.01 mm
Rout et al (1996) SSc: n = 21 ND 33% 14/214 teeth (7.5%)
Vincent et al (2009) Limited SSc: n = 20 ND n = 7 (35%)
Diffuse SSc: n = 10 n = 3 (30%)
Leung et al (2011) SSc: n = 36 (236 teeth) 0.360  0.057 ND ND
Objective Controls: n = 36 (240 teeth) 0.330  0.032
measurements
Jagadish et al (2012) SSC: n = 6 ND 66% ND
Dagenais et al (2015) SSc: n = 159 Mean: 0.16  0.06 n = 52 (37.96%) 1.08  2.57
Objective Controls: n = 222 0.15  0.04 n = 24 (11.11%) 0.16  0.49
measurements Periapical PLS: (1 tooth)
0.2  0.1
0.15  0.04

Values are indicated as mean  standard deviation. Statistically signicant results are highlighted in bold.
ns, not signicant; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.

2014a; Elimelech et al, 2015; Pischon et al, 2016)
(Table 3). Three recent studies found a positive
correlation between SSc and periodontitis (increased
number of teeth with PD >3 mm or clinical attachment
level 5.5 mm, increased PD, and increased periodontal
attachment loss, respectively) (Leung et al, 2011; Baron
et al, 2014b; Pischon et al, 2016). Periodontal disease
and SSc share many common features. They are
characterized by a comparable disease course (prominent
acute inammation during early stages and brosis,
atrophy, and tissue destruction during more advanced
stages) and by similar etiopathogenic pathways
(microvascular alterations, brosis, and inammation with
increased serum levels of proinammatory cytokines)
(Scala et al, 2004; Elimelech et al, 2015). The etiology
of periodontal disease in SSc is most likely multifactorial
but remains elusive (Baron et al, 2014b). Indeed, various
disease-related factors, such as xerostomia that promotes
the development of dental plaque, impaired oral hygiene
due to reduced manual dexterity and mouth opening or
microvascular alterations that can lead to tissue ischemia
could account for the higher prevalence of periodontal
disease in SSc patients (Yuen et al, 2014). According to
Yuen et al, a correlation between gingivitis and the
diffuse form of SSc and/or an impaired manual dexterity
has been observed (Yuen et al, 2014). In contrast, the
large casecontrol study of Baron et al did not found
any relationship between periodontal disease and global
disease severity, reduced saliva secretion or decreased
mouth opening, and sclerodactyly that could impede
oral hygiene (Baron et al, 2014b). Pischon et al
demonstrated very recently a higher periodontal clinical
attachment loss that remained statistically signicant
after adjustment for age, gender, education, smoking
status, and alcohol consumption but also after
adjustment for plaque accumulation (PI) (Pischon et al,
2016). This observation suggests that the impaired oral
hygiene may only partially account for the higher
prevalence of periodontal disease in SSc patients.
Despite the higher periodontal attachment loss, the other
clinical parameters (PD, BOP, and GI) were not
increased. Chronic brosis and microvascular alterations
that are hallmarks of the disease may mask the signs of
acute inammation, making the diagnosis of periodontal
disease more difcult in SSc patients (Pischon et al,
2016). Fibrosis, in particular when it involves the frena,
can promote gingival recession (Eversole et al, 1984;
Jagadish et al, 2012).

Oral Diseases
 Orofacial manifestations in systemic sclerosis
S Jung et al
8
Using capillaroscopy, Scardina et al reported microvas-
cular abnormalities in the gingival tissues of SSc
patients. Although the number of capillaries was reduced,
they were characterized by an increased diameter and
tortuosity (Scardina et al, 2005). Ozcelik et al have
shown that the histological inammatory inltrate is
more intense in gingival biopsy samples from SSc
patients than in controls whereas the expression of vascu-
lar endothelial growth factors (VEGF) is signicantly
lower (Ozcelik et al, 2008). Conversely, Matarese et al
(Matarese et al, 2012) observed an increased VEGF
expression in gingival tissue and periodontal samples
from SSc patients and suggested that this chronic overex-
pression could impair the formation of new vessels
(Koch and Distler, 2007; Matarese et al, 2012). Despite
being contradictory, these observations demonstrate that
the defective vascularization, which is characteristic of
the disease, also involves the periodontal tissues and can
therefore play a role in the pathogenesis of periodontal
diseases, impairing the inammatory response against
periodontal pathogens and decreasing the healing capaci-
ties. Higher TNF-a levels have been measured in gingi-
val crevicular uid from SSc patients (Mayer et al,
2013; Elimelech et al, 2015). The latter were not corre-
lated with periodontal parameters but with modied Rod-
nan skin score, suggesting the existence of similar
Figure 3 Cone-beam computed tomography (CBCT) of a patient with
diffuse SSc: mandibular axial (a) and cross-sectional (b) views showing
periodontal ligament space widening that affects particularly premolars
(black arrows) and molars
Oral Diseases
pathogenic pathways in the skin and in the periodontal
tissues (Elimelech et al, 2015).
The combination of those factors with impaired oral
hygiene, due to reduced mouth opening and manual dex-
terity, may lead to a more rapid progression of periodonti-
tis in SSc patients (Elimelech et al, 2015). Further studies
are needed to better characterize the association between
SSc and periodontal disease.
Periodontal ligament widening. Thickening of the
periodontal ligament (PDL) was rst described in SSc
patients by Stafne and Austin in 1944 (Stafne and Austin,
1944). Periodontal ligament space (PLS) widening is one
of the most common radiologic ndings in SSc
(Figures 3a,b and Table 4). Indeed, it can be observed in
more than one-third of the patients (Rowell and Hopper,
1977; White et al, 1977; Marmary et al, 1981; Janssens
et al, 1987; Wood and Lee, 1988; Rout et al, 1996;
Vincent et al, 2009; Leung et al, 2011; Jagadish et al,
2012; Dagenais et al, 2015). However, most of the
descriptions are based on case reports or on subjective
analysis of X-rays (Rowell and Hopper, 1977; White
et al, 1977; Janssens et al, 1987; Rout et al, 1996;
Vincent et al, 2009; Anbiaee and Tafakhori, 2011;
Jagadish et al, 2012; Bali et al, 2013). To our knowledge,
there are few studies presenting objective PLS
measurements in SSc patients (Marmary et al, 1981;
Alexandridis and White, 1984; Wood and Lee, 1988;
Leung et al, 2011; Dagenais et al, 2015). Leung et al
showed that SSc patients have a signicant widening of
the PLS compared to healthy controls (0.360  0.057 mm
in SSc patients vs 0.330  0.032 mm in controls;
P = 0.005). However, the main limitation of this study is
related to the measurements that have been performed on
panoramic radiographs, known to be prone to image
distortion (Leung et al, 2011). In the recent Canadian
study that assessed 159 SSc patients and 222 controls,
PLS widening affected at least one tooth in 38% of SSc
patients compared with 11.1% of controls. The difference
remains signicant after adjustment for age, gender,
ethnicity, education, and smoking status, in particular in
premolars and molars (Dagenais et al, 2015). PLS
thickening can be observed in every group of teeth but
posterior areas are more frequently involved (Stafne and
Austin, 1944; White et al, 1977; Marmary et al, 1981;
Alexandridis and White, 1984; Anbiaee and Tafakhori,
2011; Dagenais et al, 2015).
Although the exact mechanisms still remain unclear,
different hypotheses have been suggested. The width of
the roots is equivalent in SSc patients and control sub-
jects, suggesting that PLS widening occurs at the
expense of the alveolar bone (Wood and Lee, 1988).
According to Auluck et al, the masticatory muscles
become bulkier secondary to brosis leading to increased
occlusal forces (occlusal trauma), which may result in
PLS widening (Auluck, 2007). This hypothesis could
explain the increased prevalence of PLS widening around
posterior teeth. However, an opposite hypothesis has also
been proposed, suggesting that increased brosis of the
masticatory muscles and of the supplying vessels, that is
responsible for muscular atrophy, rather reduces the

mastication forces leading to PLS widening (Mehra,
2008). Indeed, occlusal traumatisms can induce angular
bone defects and tooth mobility that are usually not
observed in teeth affected by PLS enlargement during
SSc (Wood and Lee, 1988; Mehra, 2008; Jagadish et al,
2012). The lamina dura and the gingival attachment are
intact in most cases (Anbiaee and Tafakhori, 2011).
Baron et al (2015a) found a signicant correlation
between the number of teeth affected by PLS thickening
and the global disease severity. The enlargement of the
ligament may therefore reect the generalized overpro-
duction of collagen and the brotic process observed in
SSc (Baron et al, 2015a). The PDL contains mainly col-
lagen bers and also cells including broblasts. As in
the other connective tissues, broblast dysfunction can
lead to an excessive collagen production with subsequent
resorption of the alveolar bone around the roots, leading
to the enlargement of the PLS (Baron et al, 2015a).
PLS widening can be one of the rst radiographic signs
of SSc (Anbiaee and Tafakhori, 2011). Baron et al
(2015a) found a correlation between short disease duration
and enlarged PDL, suggesting that the increased width of
PLS could be more important during the early stages of
the disease. Further studies are needed to assess whether
this radiographic sign could be used as a potential diag-
nostic marker and in particular to determine a cutoff value.
In the absence of any other clinical manifestations, alterna-
tive aetiologies of PLS widening such as occlusal trauma,
recent orthodontic treatment, or periapical disease should
be of course considered (Prasad and Pai, 2012).
To our knowledge, there are no clinical consequences
of PLS widening and the affected teeth require no inter-
vention. Indeed, Baron et al (2015a) did not evidence any
correlation between thickening of the PLS and periodontal
disease or the number of missing teeth. However,
unawareness of this specic radiographic feature or confu-
sion with other pathological processes (endodontic infec-
tion, severe periodontal disease. . .) can lead to diagnosis
and treatment misconducts (unwarranted teeth extractions),
increasing the mouth handicap.
Neurologic involvement
Neurologic manifestations were previously considered as
rare events and rather as complications of other organs
damage. However, evidence of primary nervous system
involvement in SSc is currently increasing (Amaral et al,
2013). Moreover, neurologic manifestations may be under-
diagnosed as they can be easily confused with symptoms
related to skin hardening (Ribeiro et al, 2009).
Trigeminal neuropathy (TN), a chronic condition affect-
ing the fth cranial nerve, is the most frequently reported
peripheral nervous system manifestation. Indeed, the 73 TN
associated with SSc that have been documented in the litera-
ture account for more than 15% of all reported peripheral
nervous system events (Amaral et al, 2013). However, the
literature addressing TN during SSc principally consists of
case series and case reports (Teasdall et al, 1980; Jimenez-
Moreno et al, 1998; Fischoff and Sirois, 2000; Mohyuddin
et al, 2009; Ribeiro et al, 2009; Vincent et al, 2009), and
the link between the two conditions has only been investi-
gated in a small number of studies (Farrell and Medsger,
Orofacial manifestations in systemic sclerosis
S Jung et al
9
1982; Hagen et al, 1990; Amaral et al, 2013). In their retro-
spective analysis on 442 SSc patients, Farrel and Medsger
described an association with TN in 4% of cases (16
patients) (Farrell and Medsger, 1982). TN can be associated
with limited or with diffuse SSc (Jimenez-Moreno et al,
1998; Mohyuddin et al, 2009) and may occur prior to the
development of SSc clinical signs, as suggested by Scardina
et al (2002), who reported four cases with medical history
containing past TN preceding the onset of SSc by several
years.
Sensory involvement is predominant in TN that rarely
affects the muscles of mastication. It usually involves the
V2 (maxillary) and V3 (mandibulary) nerves (Farrell and
Medsger, 1982), but it can sometimes affect all three divi-
sions of the trigeminal nerve. TN can be uni- or bilateral
(Jimenez-Moreno et al, 1998; Mohyuddin et al, 2009) and
is frequently associated with pain, dysesthesia or even
anesthesia that can involve the oral cavity (Denton and
Ong, 2004).
Neuropathy may result from ischemic lesions of the
peripheral nerves. Some authors suggested that small arter-
ies providing blood supply to peripheral nerves can be
affected as microvascular lesions may alter nerves func-
tion (Lee et al, 1984; Denton and Ong, 2004). Autoimmu-
nity could also play a role with the production of specic
autoantibodies that may target the nervous system (Denton
and Ong, 2004). Moreover, autoimmune response against
basement membrane antigens could account for vascular
injury, leading to peripheral nerves dysfunction (Jimenez-
Moreno et al, 1998; Denton and Ong, 2004). Jimenez-
Moreno et al propose that TN could be regarded as an
entrapment neuropathy due to the inammatory response
with edema (Jimenez-Moreno et al, 1998; Ribeiro et al,
2009). Local compressive nerve damage should also be
considered in the pathogenesis of some TN cases as sug-
gested by Fischoff et al who described a case of severe
mandibular resorption resulting in a painful neuropathy
due to the compression of the inferior alveolar nerve
(Fischoff and Sirois, 2000). On the other side, Farrell and
Medsger found that the proportion of patients with severe
facial brosis is equivalent in both groups with TN or
without TN, suggesting that the neuropathy may not be
the consequence of direct extension of brosis to the
trigeminal nerve (Farrell and Medsger, 1982).
Oral cancer risk
Systemic sclerosis has been associated with an increased
risk of cancer, especially of the lung, liver, bladder, and
hematologic system (Derk et al, 2006; Kuo et al, 2012;
Szekanecz et al, 2012; Onishi et al, 2013). Men have a
higher risk than women (Onishi et al, 2013). Organs
affected by extensive brosis such as lungs may be prone
to cancer development whereas increased risk for lympho-
proliferative diseases (non-Hodgkins lymphomas) may
rather be the consequence of chronic B-cell activation
(Szekanecz et al, 2012). Derk et al (2006) demonstrated
elevated standardized incidence ratio (SIR) for oropharyn-
geal cancer in a cohort of 769 SSc patients (SIR 9.63
[95% CI 2.9716.29]). They found a highly signicant
increase in the incidence of tongue squamous cell carci-
noma associated with the diffuse form of the disease
Oral Diseases
 Orofacial manifestations in systemic sclerosis
S Jung et al
10
(Derk et al, 2005). A nationwide population study also
revealed increased SIR for cancer of the oral cavity and
pharynx (SIR 3.67 [95% CI 1.836.56]) (Kuo et al,
2012). Diagnosis of oral cancer is particularly challenging
in SSc patients as the symptoms of sclerosis can poten-
tially overshadow certain manifestations of malignant dis-
eases and as microstomia may limit access to the oral
 cek et al, 2015).
cavity (Co
Treatment-related adverse effects
Certain medications may be responsible for adverse
effects involving the oral cavity (Alantar et al, 2011). Cal-
cium-channel blockers, commonly used to treat Raynauds
phenomenon, can induce gingival hyperplasia (Shah and
Wigley, 2008). Different immunosuppressive drugs such
as cyclophosphamide or mycophenolate mofetil can be
prescribed to SSc patients. Corticosteroids are usually
used with caution and at low dosage as they are associ-
ated with an increased risk of scleroderma renal crisis
(Denton et al, 2009). Among the many adverse effects
that can be observed, such therapies are associated with
increased risk of infections (Alantar et al, 2011). All
patients should have a dental and radiographic examina-
tion prior to initiating immunosuppressive treatment in
order to remove potential sources of odontogenic infec-
tion, and a regular follow-up is recommended. Oral ulcer-
ations are frequent in patients receiving methotrexate
immunomodulator therapy, prescribed for muscular, joint,
and skin manifestations, and may appear at any time dur-
ing the treatment (Kalantzis et al, 2005). Folate supple-
mentation can help to reduce mucosal toxicity and may
avoid the need to discontinue methotrexate. Local treat-
ments (e.g., topical analgesics or steroids, covering agents,
chlorhexidine gluconate mouthwashes) can also be used
but they only provide symptomatic relief (Kalantzis et al,
2005). Penicillin should be avoided in combination with
methotrexate as it may increase the hematologic toxicity.
Baron et al also mentioned that 76.3% of SSc patients
use medications that are known to be associated with
mouth dryness (e.g., anticholinergic antidepressants for
psychiatric symptoms) and can enhance a preexisting
xerostomia (Baron et al, 2014a). Sicca syndrome should
be considered before the initiation of antibiotic treatment
to prevent the risk of associated oral candidiasis (Alantar
et al, 2011).
Oral health-related quality of life
Systemic sclerosis is associated with an impaired quality
of life. Outcome measurements are commonly used to
evaluate SSc patients (Pope, 2011). Global disability and
quality of life are usually measured by the Health Assess-
ment Questionnaire (HAQ) (Poole and Steen, 1991) or by
its modied version (sHAQ for scleroderma HAQ) (Steen
and Medsger, 1997) that has been specically developed
for SSc patients. HAQ and sHAQ are self-reported ques-
tionnaires, sHAQ also including visual analog scales (e.g.,
for pain or organ involvement evaluation) (Poole and
Steen, 1991; Steen and Medsger, 1997). SSc has a strong
impact on oral functions and therefore on oral health-
related quality of life, emphasizing the need for quantify-
ing the handicap related to mouth disability. The Oral
Oral Diseases
Health Impact Prole-49 (OHIP-49) is the most widely
used questionnaire to measure oral health-related quality
of life (HRQoL) in patients with oral diseases. Baron et al
have recently demonstrated, using OHIP-49 instrument,
that both global health-related quality of life (HRQoL)
and oral HRQoL of life are severely impaired in their
large cohort of 163 SSc when compared to the 231
healthy controls (Baron et al, 2014a). They found a statis-
tically signicant association between oral HRQoL and
global HRQoL (Baron et al, 2014b). In 2007, Mouthon
et al developed and validated a disease-specic question-
naire quantifying mouth disability in SSc: the Mouth
Handicap in Systemic Sclerosis Scale (MHISS) (Mouthon
et al, 2007). It contains a total of 12 items, with 5 levels
of answer per item (score 04) and a total score ranging
from 0 to 48. A higher value indicates a more important
functional impairment. This questionnaire is divided into
three parts that explore, respectively, the handicap related
to mouth-opening limitation, to xerostomia, and to esthetic
concerns (Mouthon et al, 2007). The MHISS has been
developed in French and validated in French, Italian, and
Dutch (Mouthon et al, 2007; Maddali-Bongi et al, 2012;
Schouffoer et al, 2013). Vitali et al created the Sclero-
derma Logopedic Scale (SLS) to assess the oropharyngeal
area disorders in SSc patients (Vitali et al, 2010). This 58-
items scale is divided into ve subscales (Impairment,
Swallow, Voice, Multield and Quality of life) but seems
more difcult to use in the daily practice.
Oral management
Systemic sclerosis requires a specic oral management that
involves a multidisciplinary team (dentist, oral surgeon,
physiotherapist. . .). However, SSc patients often encounter
some difculties in nding a dentist who agrees to treat them
(Leader et al, 2014).
Prevention measures and oral hygiene
A regular follow-up with appropriate preventive mea-
sures is essential to maintain adequate oral health in SSc
patients (Cazal et al, 2008). Prevention of dental caries,
gingival inammation, and tooth loss can only be
achieved by patient education (Poole et al, 2010) and by
the development of tailor-made oral hygiene techniques.
For example, in patients with impaired manual dexterity,
an electric toothbrush or a toothbrush with a foam ergo-
nomic handle can be proposed. Indeed, Balzer showed
that the use of adaptive oral hygiene devices (oscillat-
ingrotating toothbrush and osser with a toothbrush-like
handle) combined to exercises designed to increase
mouth opening and therefore facilitate oral hygiene
allows the improvement of gingival health in SSc
patients compared to the use of more traditional oral
hygiene devices (manual toothbrush and nger-held den-
tal oss) (Balzer, 2012). All kinds of preventive mea-
sures such as regular periodontal maintenance with
scaling or topical uorides applications (uoride tooth-
pastes, varnishes, etc) should be encouraged. The treat-
ment of GERD may also help in maintaining a normal
pH (Alantar et al, 2011).

Cessation of tobacco use is strongly recommended, as it
can worsen mucosal involvement (hyperkeratosis, xerosto-
mia. . .) and increase the risk of malignant transformation
(Alantar et al, 2011)
Dental treatment and prosthodontics
Teeth preservation is crucial as limited access to the oral
cavity can make the dental treatment challenging, espe-
cially when prosthetic rehabilitation is needed. Conven-
tional dental care can be performed in SSc patients but
short sessions with regular breaks should be favored
(Alantar et al, 2011). The use of sectional impression
techniques as well as of sectional or exible removable
prosthesis can be really helpful in patients with restricted
oral access. Midline hinges and stud attachment may facil-
itate insertion and removal of the fractionated denture
(Yenisey et al, 2005; Dikbas et al, 2007; Prithviraj et al,
2009). However, exible prostheses are often difcult to
adapt and show a reduced retention (Alantar et al, 2011).
To date, less than 20 reports and only one systematic
review on dental implant rehabilitation in SSc patients
have been published (Reichart et al, 2016). No evidence-
based recommendations are currently available and further
studies are strongly needed. Although data are only avail-
able for 28 patients and 165 implants, implant survival
rates seem to be comparable in patients with and without
SSc (Reichart et al, 2016). However, implantprosthetic
treatment in SSc patients is challenging. An interdisci-
plinary consultation with assessment of the individual
risk-benet balance is required. Several parameters need
to be considered such as the disease severity, microvascu-
lar impairment, ongoing medications (especially bisphos-
phonates), limitation in mouth opening, decreased salivary
production, and reduced ability to perform oral hygiene
that can favor the occurrence of peri-implantitis (Alantar
et al, 2011; Reichart et al, 2016).
Xerostomia
Spicy food and acidic products should be avoided.
Patients are encouraged to drink water regularly and eat
preferentially solid food that require more mastication
effort and provide a mechanical stimulation of the salivary
ow. A broad range of saliva substitute such as sprays,
gels, mouthwashes, or special toothpastes are also avail-
able. They help in maintaining moisture of the oral
mucosa, but they must be applied frequently during the
day. Oxygenated glycerol triester saliva substitute sprays
show evidence of effectiveness compared to electrolyte
sprays. Different saliva stimulants (e.g., sugar-free sweets,
chewing gums) can also be used during the day by
patients with residual secretion in order to increase sali-
vary production (Furness et al, 2011). The use of
parasympathicomimetic drugs such as pilocarpine that
stimulates saliva secretion was mainly studied for treat-
ment of dry mouth in patients with Sj ogrens syndrome
(Vivino et al, 1999) but it can also be tried for SSc asso-
ciated xerostomia (5 mg, 34 times a day) (Alantar et al,
2011). However, this cholinergic agonist is responsible for
several adverse affects (e.g., excessive sweating, vasodi-
latation) related to its non-selective action on muscarinic
Orofacial manifestations in systemic sclerosis
S Jung et al
11
receptors and may be contraindicated in patients with
chronic respiratory, cardiovascular, or renal disease.
Anetholtrithione (25 mg, 3 times a day) could be an alter-
native to pilocarpine chlorhydrate as it exhibits less side
effects (Vincent et al, 2009; Alantar et al, 2011).
Microstomia
Reports of surgical interventions to enlarge the oral orice
such as bilateral commissurotomy or commissuroplasty
have been described but represent very invasive proce-
dures (Johns et al, 1998; Mehra et al, 1998; TerzIo glu
et al, 2002; Koymen et al, 2009). Active (placing the
thumbs in opposite corners of the mouth and pulling out-
wards) or passive (using tongue depressors inserted
between the posterior teeth) mouth-stretching exercises,
facial grimacing, connective tissue massage, Kabats tech-
niques, or kinesitherapy can be proposed as an initial
non-surgical alternative to improve mouth opening, oral
functions, and skin elasticity (Pizzo et al, 2003; Maddali-
Bongi et al, 2011; Wada and Ram, 2013). Encouraging
SSc patient to perform exercises since the earliest phases
of the disease will help to limit the extension of skin
brosis. TheraBite Jaw Motion Rehabilitation System
(Atos Medical AB, Malmo, Sweden) that is based on
repetitive and passive stretching could also be used to
increase mouth width. It has been shown to be efcient in
patients with head and neck cancer suffering from trismus
and in case of myogenic temporomandibular disorder
(Kraaijenga et al, 2014; Pauli et al, 2015). Recently,
autologous fat transplantation and adipose-derived stromal
cells (ADSCs) injections have been performed in the peri-
oral region. Both therapeutic approaches appear to be
promising as they allowed the improvement of mouth
opening (Del Papa et al, 2015; Onesti et al, 2016). Del
Papa et al have even noticed the induction of a signicant
neovascularization (Del Papa et al, 2015).
Telangiectases
Telangiectases are usually not treated except in case of
bleeding or aesthetic concerns (Alantar et al, 2011). Both
intense pulse light and laser seem to be effective treat-
ments. Pulse dye laser has better outcomes in terms of
appearance, whereas intense pulsed light has fewer side
effects (Dinsdale et al, 2014).
Bone resorption and TMJ involvement
Resorption of the mandible is in most cases asymp-
tomatic and is therefore usually a fortuitous nding dur-
ing routine radiographic examination (Dagenais et al,
2015). A regular follow-up is still required, such lesions
being potentially associated with a signicant risk of
pathological fracture (Mugino and Ikemura, 2006). The
management of condylar resorption ranges from conser-
vative approaches with only functional appliances (Mug-
ino and Ikemura, 2006) to maxillary and mandibular
osteotomies (Haers and Sailer, 1995) or condylar resec-
tion (Doucet and Morrison, 2011) with genioplasty.
Recently, the replacement of destroyed temporomandibu-
lar condyles with costochondral grafts in two SSc
patients has been described with long-term functional
Oral Diseases
 Orofacial manifestations in systemic sclerosis
S Jung et al
12
improvement (MacIntosh et al, 2015). As TMJ involve-
ment is common in SSc patients, a careful examination
(including MRI exploration when necessary) should be
performed during rheumatologic assessment (Matarese
et al, 2016).
Trigeminal neuropathy
So far, the pharmacological treatment of Trigeminal neu-
ropathy (TN) has not been evaluated in randomised con-
trolled trials. Corticosteroids alone or associated with
other immunosuppressive drugs such as methotrexate are
frequently used. However, symptoms are rarely improved
by such therapies. Amitriptyline, nortryptiline, carba-
mazepine, oxcarbazepine, and gabapentin have been suc-
cessfully used (Amaral et al, 2013), but further studies are
required to establish guidelines.
Conclusion
Although rare, SSc is a complex disease characterized by
a wide range of clinical features. The orofacial region is
frequently involved and the multiple complications that
can be observed tend to enhance the degradation of the
quality of life. Dentists play a crucial role in the manage-
ment of this condition and should be integrated to the
pluridisciplinary team. They should also be involved in
the diagnostic process, and therefore, they have to know
the specic orofacial manifestations, specically PLS
widening. The reinforcement of oral hygiene and teaching
of facial exercises, along with a regular follow-up, are
essential measures to preserve oral health in SSc patients.
Acknowledgements
Authors would like to thank Fareeha Batool for her help in the
preparation of the manuscript. This work has been supported by
authors institutions, grant AAPJC 2014HUS no. 6026 and
EU-funded (ERDF) project INTERREG V RARENET.
Author contributions
All authors contributed to the development of the drafts, succes-
sive revision and renement of the manuscript. All authors
reviewed the nal version of the manuscript.
Conict of interest
The authors declared that they have no conict of interest.
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