Introduction

Systemic sclerosis (SSc) is a multisystem disease of unknown aetiology characterised by microangiopathy, dysregulated immune function and tissue remodelling. Evidence of each of these three heavily inter-dependent pathological hallmarks can be identified within the diverse anatomical tissues that comprise the oral cavity; the accessibility of which makes this area an attractive site to study the pathogenesis of this heterogeneous and poorly understood disease. Moreover, orofacial manifestations of SSc are common, contributing greatly to overall disease burden and yet are regularly overlooked and potentially under-treated. This perhaps reflects a pre-occupation amongst treating clinicians on potentially life-threatening internal organ involvement, but is also a consequence of insufficient engagement between rheumatologists and dental professionals. Surveys have identified a high proportion of SSc patients who have had difficulty accessing a dentist with knowledge of the disease and there is recognition amongst dentists that this could impact negatively on patient care.1 This review shall describe the clinical features and burden of orofacial manifestations of SSc, the methods available to assess oral pathology and a practical approach to managing such problems.

Background and clinical features

SSc is rare with an estimated prevalence of approximately 250 per million and an annual incidence of 26/million/person years2 with a strong propensity for women (7:1).3 Previously, clinical descriptions of SSc focused heavily on the presence of excessive cutaneous fibrosis - hence the synonym, scleroderma. However, it was gradually acknowledged that a combination of vasculopathy, fibrotic disease, and dysregulated immune function were responsible for pathology in a number of internal organs including the heart, lungs and gastrointestinal (GI) tract (Table 1).4

Table 1 SSc classification criteria adapted from American college of rheumatology/European league against rheumatism (2013). Adapted with permission from Arth Rheum 65 (11), 2737–2747, ©2016 BMJ & EULAR7
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Fibrosis

Classification of SSc according to the extent of cutaneous fibrosis was proposed in the 1980s owing to its value in predicting internal organ involvement and survival, with two main types described: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc).5 Diffuse cutaneous SSc with skin thickening affecting proximal regions such as the upper arms, thighs and trunk, generally predicts a more 'fibrotic' phenotype with significant morbidity and mortality secondary to fibrosis and loss of internal organ function. Meanwhile, lcSSc involves skin changes restricted to the face, distal arms and feet, and predicts a more 'vascular' phenotype with lower morbidity and mortality.

Dysregulated immune function

Altered vascular permeability and extravasation of leukocytes is thought to represent a key driver of tissue remodelling, resulting in inflammatory conditions such as arthritis and myositis. An early clinical presentation of this disease process is the appearance of puffy fingers. Immunosuppression remains the mainstay of treatments to arrest the progression of organ fibrosis.

Microvascular angiopathy

Endothelial injury at the microvascular level is considered an important early pathological driver.6 Episodic vasoconstriction of the digital microvasculature in response to cold exposure or emotional stress (Raynaud's phenomenon [RP]) is typically the earliest manifestation of the disease. In addition to functional vascular disturbance, structural microvascular abnormalities occur in SSc including disorganised neoangiogenesis and capillary loss; both of which can be directly visualised using nail-fold capillaroscopy which is an important diagnostic tool.7 This microangiopathy can result in significant tissue hypoxia that threatens tissue viability leading to digital ulceration and occasionally gangrene. Microvascular injury occurs in other vascular beds and can result in potentially life-threatening organ manifestations such as scleroderma renal crisis and pulmonary arterial hypertension (PAH). Increased vascular permeability, tissue hypoxia and oxidative stress are thought to contribute to the excessive collagen synthesis and fibrosis.

The gastrointestinal tract in SSc

Gastrointestinal (GI) tract manifestations are a major cause of morbidity in SSc but have not attracted the same attention to therapeutics as manifestations of the skin, lung and kidneys perhaps owing to the limited contribution to mortality and the unique challenges associated with evaluating the GI tract. The GI tract has three major functions: digestion, the excretion of waste products, and the transit of food and waste. The architecture of the GI tract wall constantly evolves throughout its course to achieve these goals and each segment can be affected in SSc. There is a high burden of GI symptoms in SSc with cross-sectional studies identifying GI symptoms in more than 90% of patients with approximately 10% of patients experiencing symptoms on a daily basis.8

Motility is achieved by smooth muscle within the GI tract wall, as well as striated muscle in the oropharynx. A combination of neural dysfunction and fibrotic replacement of muscle significantly impairs GI motility, resulting in dysphagia, gastro-oesophageal reflux and gastroparesis within the proximal GI tract. Mucosal abnormalities and bacterial overgrowth within the distal GI tract may affect its absorptive capacity, leading to malnourishment, weight loss, and deficiencies of important vitamins and minerals. Mucosal vascular malformations such as gastric antral vascular ectasia (GAVE) in the stomach wall, can occur leading to potentially life-threatening haemorrhage or chronic iron deficiency.9

Clinical orofacial features

Similar to GI manifestations, there is a very high prevalence of abnormalities of the oral cavity and surrounding tissues with one or more features evident in virtually all patients with SSc (Table 2). Reports of oral manifestations predate recognition of a number of major organ manifestations of SSc such as PAH.10 Patients with early or limited forms of SSc may present to their dentist with detectable clinical features before a formal diagnosis has been established. Dentists are encouraged to enquire about symptoms of RP and changes in the quality of their skin elsewhere should they identify one or more of the following features in the correct clinical context.

Table 2 Summary of orofacial features of systemic sclerosis
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Orofacial fibrosis and microstomia

Cutaneous involvement of the orofacial region causes reduction of the oral aperture, with the characteristic circumoral furrows or perioral 'whistle lines' seen in approximately 70% of patients (Figs 1 and 2), as well as a 'wide-eyed' appearance caused by periorbital fibrosis.11 Mouth opening can be impaired by tissue remodelling of the TMJ capsule12 demonstrated by a significantly reduced mean interincisal distance compared with the general population.13 Microstomia complicates maintenance of oral hygiene, dental treatment and prosthetic rehabilitation, and can also lead to difficulty with mastication and deglutition.12 Reduced lip and facial strength may cause difficulty with speech, facial expressions and saliva control. Fibrosis of the lingual fraenum (Fig. 3) has the potential to affect speech, saliva control and bolus manipulation.14,15

Figure 1
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Circumoral furrows

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Figure 2: Reduced oral aperture with restricted mouth opening.
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Also note the telangiectasese present on the tongue and lips

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Figure 3
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Thickening and shortening of the lingual fraenum secondary to SSc

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A large patient survey examining features of SSc which cause greatest aesthetic concern, found that the presence of circumoral furrows (80%), tighter mouth (77%), thin lips (73%) and loss of facial lines (68%) all featured most prominently, and were significantly more common than non-facial SSc appearances.16 From an aesthetic perspective, attempts have been made to manage circumoral furrowing using pulsed CO2 laser treatment.17 The use of dermal fillers and botulinum injections are also sometimes used with good results but have not been reported.

Functionally, daily exercises that aim to stretch the tissues of the face and neck have been shown to be effective in improving mouth opening but long-term outcomes are influenced by low exercise continuation rate, with secondary loss of efficacy linked with deterioration in compliance.12,18,19,20,21 A number of 'microstomia orthoses' have been developed and tested for a number of indications including post-radiotherapy22 and burns23,24,25,26,27 but such devices have not been as extensively investigated in SSc.28 Other non-surgical approaches have been described for microstomia including intense pulsed light therapy but require further study.29 Successful surgical interventions to increase the oral aperture such as commissuroplasty and autologous fat grafting have also been reported in SSc, and should be reserved for the more severe cases.30,31

Telangiectasia

Telangiectasiae are cuttaneous vascular malformations that are commonly found in SSc and are thought to occur secondary to disordered neoangiogenesis in ischaemic tissue.32 Telangiectasiae mostly develop in exposed cutaneous regions of the hands and face which has marked aesthetic implications, and can also be found on oral mucosal surfaces, typically the labial mucosa (Fig. 4). Telangiectasia may bleed following trauma but generally do not present a significant clinical risk when found intra-orally. Many patients consider them unsightly and efforts can be made to conceal extra-oral telangiectases using camouflage creams and make-up. Light-based treatments such as pulsed dye laser and intense pulsed light have been shown to have short term efficacy in SSc but long-term recurrence rates are not known.33

Figure 4
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Prominent mucosal telangiectasia visible on the labial mucosa and face

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Oral mucosal atrophy and ulceration

Atrophy and ulceration of the oral mucosa can occur in SSc secondary to poor nutritional intake and vitamin deficiencies.12 Oral ulceration may also be an adverse consequence of the pharmacological management of SSc, involving methotrexate, azathioprine and cyclophosphamide.34 Management will involve correction of any nutritional deficiencies, topical treatment of the ulcers such as covering agents, and substitution of immunosuppressant medication as required. Persistent, non-healing ulcers should still be managed with caution, and biopsy may be indicated to rule out more sinister pathology.

Xerostomia

Xerostomia is reported in approximately two thirds of SSc patients and the impact is considered moderate to severe in over half of these patients.35,36,37 Studies involving minor salivary gland biopsies indicate that xerostomia may occur by two distinct mechanisms: immune-mediated destruction of the acinar tissues (as is typically found in Sjögren's syndrome), or fibrosis of the salivary glands themselves reducing their exocrine capacity.36,38,39,40 The presence of Sjögren's syndrome in patients with SSc appears to have a greater association with the lcSSc phenotype.36,39

Initial management should include specific advice on maintaining adequate oral hydration, minimising the frequency of sugar-containing food and drink, and stimulating saliva flow with sugar-free gum.41 Patients should have appropriate dental recall intervals and be provided with appropriate preventative care such as topical fluoride application, appropriate fluoride toothpaste and mouthwash prescription. A large number of artificial saliva replacement products are available in gel, spray, and pastille preparations, and can be helpful in patients with symptoms of xerostomia which are not managed effectively through routine advice. Referral to oral medicine departments might be necessary for those not responding to simple local measures. Pilocarpine hydrochloride may be prescribed in a hospital setting to stimulate saliva production but is only effective in those with some residual gland function.

Radiographic features

Periodontal ligament widening

Periodontal ligament (PDL) widening (Fig. 5) is a reported radiographic feature of SSc, but should be considered as an incidental finding rather than a diagnostic feature. Studies have reported the PDL width to be significantly increased, on average, in comparison to the general population, with posterior teeth affected to a greater degree.42,43,44,45 The precise cause and mechanisms of this PDL widening in the absence of an infective pathological cause have yet to be elucidated; however, it has been proposed that PDL volume is increased due to excessive collagen synthesis, as seen in other features of SSc.46

Figure 5
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Periodontal ligament widening in absence of dental and periodontal pathology, affecting the canine and second molar in the lower left quadrant

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Mandibular resorption

Mandibular resorption has been reported in 10-33% of SSc patients and most commonly involves the angles of the mandible, followed by the condyle, coronoid process and the ascending ramus,47 with bilateral condylysis occurring in 13.7% of cases of resorption. Resorption of the zygomatic arch has also been reported.48 The underlying mechanisms are poorly understood but are thought to be primarily of vascular origin,12,47,49 and resorption patterns suggest sites of muscle insertions are particularly vulnerable to ischaemic injury of this nature.

Resorption may be visible on OPT radiographs (Fig. 6) and the degree and distribution of resorption can extend from minor blunting of the angles, to more pronounced concavity of the posterior ramus and eventually to more extensive resorption.11 Mandibular resorption can result in facial asymmetry, malocclusion, osteomyelitis and pathological fractures.50,51 Trigeminal neuralgia has been reported in SSc,52 with mandibular resorption proposed as a potential contributing factor in such cases.53 Resorption is usually managed conservatively, but total TMJ reconstruction has been used in the management of significant condylar resorption.12,54,55

Figure 6
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Resorption of the posterior rami and angles, as well as coronoid processes.

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Impact on dental and perio disease

Patients can be at greater risk of caries, periodontal conditions, and infections due to a number of factors including xerostomia, impaired oral hygiene practices and immunosuppressive drug use.13 Microvascular abnormalities within the gingival tissues have been observed, with a suggestion that the disease process itself may be a contributory factor in the emergence of periodontal disease.56 Gingival biopsies have identified higher levels of inflammatory infiltrate and lower expression of vascular endothelial growth factors in SSc compared with healthy controls.57 In addition, patients who are prescribed calcium channel blockers for Raynaud's phenomenon or ciclosporin as a part of immunosuppressant therapy may experience gingival overgrowth as a side-effect.58

Oral hygiene maintenance can be physically challenging for patients with SSc due to microstomia and reduced manual dexterity (Fig. 7), each of which can compromise the ability to use toothbrushes and inter-dental cleaning aids. Digital cutaneous fibrosis and ulceration, as well as ectopic calcinosis can significantly affect dexterity. Poor oral hygiene has been found to be closely associated with a reduced oral aperture, increased skin thickness, and reduced hand dexterity and finger flexion.59 Appropriate advice on the importance of maintaining oral hygiene should be provided to all patients with SSc and management of caries and periodontal disease does not differ from that of the general population. Other groups have demonstrated the value of a combined intervention program comprising orofacial exercises, education on oral hygiene techniques and adapted dental appliances on improving oral hygiene in SSc.60

Figure 7: Site of recent exfoliation of calcific mass from nail-bed.
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Note the taut skin due to cutaneous fibrosis and scarring which can significantly affect manual dexterity.

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Oral cancer

There has been a long-standing interest in the association between SSc and malignancy. A recent systematic review of cohort studies identified cancer as a contributing factor to mortality in up to 30% of patients.61 A recent large retrospective study identified a history of cancer in 7.1% of patients with SSc.62 The most commonly occurring cancers were breast (42.2%) followed by haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%) cancers.62 Oral and oropharyngeal cancers are not commonly associated with SSc,63 but some studies have shown an association.64,65,66

It has been reported that there is a greater risk of cancer within the first 12 months following SSc diagnosis,63 with 69% of cancers detected after SSc diagnosis.65 This is likely to be influenced by detection bias due to the closer monitoring and investigations following a diagnosis of SSc; however, it has been suggested that the disease process itself or the treatment of SSc (for example, immunosuppressant therapy) may be a role in cancer pathogenesis.65

Impact on quality of life

Overall oral health-related quality of life is significantly reduced in SSc compared with the general population, and independently associated with global health-related quality of life.13,67 The Mouth Handicap in Systemic Sclerosis (MHISS) has been developed to provide a disease-specific tool for evaluating mouth-related disability in SSc,68 and can be used to assess the patients concerns and the impact of SSc on day-to-day life.

Conclusions

Oral manifestations of SSc are common and often overlooked despite representing a significant cause of co-morbidity and reduced health-related quality of life in SSc. Dental professionals have the potential to identify some of the common early manifestations of this condition, which could result in earlier diagnosis. Appropriate education on orofacial exercises and oral hygiene can be delivered by dental professionals and may significantly lessen the burden of oral manifestations in SSc. Better collaboration between rheumatologists and the dental team is required to improve access to dental care and oral health outcomes for patients with SSc.