# The role of dental professionals in identifying patients with a suspected primary Sjögren's syndrome and suggestions for prevention and treatment of oral complications: a narrative review

Franck Decup, Boughanmi Rihab, Gaetane Nocturne, Marjolaine Gosset

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Franck Decup, Boughanmi Rihab, Gaetane Nocturne, Marjolaine Gosset. The role of dental professionals in identifying patients with a suspected primary Sjögren's syndrome and suggestions for prevention and treatment of oral complications: a narrative review. Heliyon, 2025, 11 (13), pp.e43564. 10.1016/j.heliyon.2025.e43564. hal-05381456

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# The role of dental professionals in identifying patients with a suspected primary Sjögren's syndrome and suggestions for prevention and treatment of oral complications: a narrative review

Franck Decup<sup>a,b,c</sup>, Boughanmi Rihab<sup>d</sup>, Gaetane Nocturne<sup>e,f</sup>, Marjolaine Gosset<sup>a,b,c,*</sup>

ARTICLE INFO

Keywords:

Sjögren's syndrome

Oral health

Salivary

Identification

Treatment

A B S T R A C T

**Objectives:** To improve the identification and management of undiagnosed primary Sjögren Syndrome (pSS) in daily practice.

**Data, sources, study selection:** We conducted a literature search in PubMed on the etiology, medical diagnosis, oral characteristics, oral health-related quality of life, treatment of oral diseases, and oral rehabilitation of patients with pSS, with a special focus on those who experience dry mouth. Observational studies, clinical trials, and systematic reviews in English, without limitation as to year of publication, were retrieved and reviewed.

**Results:** pSS is an auto-immune disease characterized by the association of a triad of symptoms (dryness, pain, and fatigue), with systemic involvement in approximately 30% of patients. Dry mouth, especially if associated with a severe clinical picture (severe caries, tooth wear, gingival inflammation, candidiasis), should be a red flag for dentists and dental hygienists, prompting them to apply a specific diagnostic procedure, as we proposed according to our clinical experience, and to refer the patient to the appropriate medical team. In addition, the implementation of appropriate preventive strategies (mainly hydration, fluoridation) and the treatment of oral diseases aim to increase salivary flow, restore oral health, prevent the recurrence of oral diseases, and improve the comfort of these patients. Together, early detection, prevention and appropriate treatment are essential to improve patients' quality of life, which is severely impaired in primary Sjögren syndrome.

**Conclusion and clinical significance:** Dentists and dental hygienists have a key role to play in identifying patients with undiagnosed primary Sjögren's syndrome by being alert to the oral characteristics of patients with dry mouth and analyzing them as part of the patients' overall clinical picture. Early detection of pSS is crucial, given the negative impact of this syndrome on patients' health and quality of life.

<footnote><sup>a</sup> UMR1333 - Santé Orale, Université Paris Cité and Sorbonne Paris Nord, Inserm, Santé Orale, F-92120, Montrouge, France</footnote>

<footnote><sup>b</sup> inIDEx INFIBREX. Service de médecine bucco-dentaire, AP-HP, Hôpital Charles Foix, F-94205, Ivry-sur-Seine, France</footnote>

<footnote><sup>c</sup> Centre de Compétence des maladies rares orales et dentaires, CCMR-O-Rares, Filière Santé Maladies rares TETE COU, Hôpital Charles Foix, Ivry Sur Seine, France</footnote>

<footnote><sup>d</sup> Faculté de Médecine Dentaire, Université de Monastir, Monastir, 5000, Tunisia</footnote>

<footnote><sup>e</sup> Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Inserm UMR 1184, Le Kremlin-Bicêtre, France</footnote>

<footnote><sup>f</sup> Department of immuno-rhumatology, FHU CARE 2, AP-HP, GHU Paris Saclay, Hôpital Bicêtre, Le Kremlin-Bicêtre, France</footnote>

<footnote>* Corresponding author. UMR1333 - Santé Orale, Université Paris Cité and Sorbonne Paris Nord, Inserm, Santé Orale, F-92120, Montrouge, France.</footnote>

<footnote>E-mail addresses: franck.decup@u-paris.fr (F. Decup), rihab.boughanmi@hotmail.com (B. Rihab), gaetane.nocturne@aphp.fr (G. Nocturne), marjolaine.gosset@u-paris.fr (M. Gosset).</footnote>
# 1. Introduction

Primary Sjögren's syndrome or Sjögren's disease (pSS) is a disease that mainly affects the exocrine glands, in particular, the salivary glands. It is often characterized by a dry mouth and, consequently, poor oral health. This disease highlights the critical role of both the quantity and quality of saliva in the physiology of the mouth [1]. Dentists and dental hygienists could be at the forefront of helping to identify undiagnosed patients, as pSS is associated with numerous oral manifestations, of which dry mouth is the first sign. This narrative review based on the literature and our clinical experience of around 5 years in the diagnosis and treatment of oral diseases in patients with Sjögren's syndrome aims to improve the identification and management of pSS patients by dentists and dental hygienists in daily practice.

# 2. Material and methods

For this literature review, we selected articles and accepted preprints in English indexed in PubMed (MEDLINE) and supported by other research on Web of Science (ISI) or Google Scholar databases to avoid missing papers. The search terms used were "primary Sjögren's Syndrome", "Sjögren's Syndrome", "Dental", "Diagnosis", "Caries", "Dental Wear", "Periodontal Disease", "Candidiasis", "Oral mucosal lesions", "Burning Mouth Syndrome", "Denture", and "Dental Implants". All abstracts or articles, if directly available, published over the last 24 years (from January 2000 until November 2024) were retrieved and selected observational studies, clinical trials, and systematic reviews with high-quality methodology were reviewed (inclusion criteria). The articles that only mentioned the above-mentioned themes without in-depth analyses were excluded, as well as duplicated publications or those dealing with juvenile forms (exclusion criteria).

This review is also based on our clinical experience within the dental department of the Charles Foix Hospital (AP-HP, Ivry/Seine, France), combining practitioners specialized in periodontology and pathology of the oral mucosa with practitioners specialized in restorative dentistry and endodontics. For over 4 years, we have been running a specialist dental consultation for patients suffering from dry mouth, especially patients with primary or associated Sjögren's disease. We work closely with the medical team (rheumatologist, ophthalmologist, ENT specialist, nutritionist) at the Rare Autoimmune Disease Reference Centre at Bicêtre Hospital (AP-HP, Le Kremlin-Bicêtre, France), which looks after these patients and refers them to us for prevention and dental care. For our part, we refer patients whom we suspect of having Sjögren's syndrome, after applying the diagnostic approach proposed in this article. More than 125 patients have been screened in this consultation.

# 3. Primary Sjögren's syndrome

Primary Sjogren's syndrome (pSS) is typically characterized by the triad of dry mouth, dry eyes and fatigue [2,3]. It should be distinguished from secondary or associated Sjogren's syndrome (sSS), which occurs with an underlying autoimmune connective tissue disorder, such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. Patients may also present permanent or recurrent enlargement of the major salivary glands, in particular, the parotid gland. These glandular symptoms lead to the diagnosis of pSS in almost 1/4 of the patients [4] and highly impact on the quality of life and psychological balance of patients. Recently, in a French survey on 1,458 patients with Sjögren syndrome, 86.97% of respondents reported experiencing frequent or constant dry mouth and which highly alter their quality of life [5]. In another study published in 2020 on 2,961 patients with pSS, dry syndrome ranked second among the factors that negatively affect the quality of life, far ahead of systemic complications or the use of immunosuppressants [6]. It is therefore a warning sign for dentists and dental hygienists, who could be at the forefront of identifying undiagnosed patients.

In this study, we will first summarize the basic knowledge of primary Sjögren's syndrome, before going on to discuss in detail the clinical features of these patients' mouths and their management.

## 3.1. Epidemiology

The exact prevalence of pSS is still being determined, as most published studies applied out-of-date classification criteria and used different methodologies. According to a 2014 systematic review of the literature, the prevalence of pSS is estimated to be 60.82/100,000 individuals per year and the incidence rate 6.92/100,000 individuals in the general population. There is a female predominance (female to male ratio of 9:1). The mean age at diagnosis varies between 50 and 60 years of age, with the typical profile being defined as perimenopausal women [7]. In the most recent estimates, pSS may be underestimated, as many of its symptoms are non-specific. Indeed, in a population of patients with pSS in Taiwan, the median time between the onset of sicca symptoms and the subsequent diagnosis of pSS was 115 weeks [8].

## 3.2. Physiopathology

### 3.2.1. Immunological and environmental mechanisms

pSS is multifactorial in origin, involving a genetic predisposition and environmental triggers. A role for an infectious trigger (bacterial and/or viral, such as HIV, hepatitis C, or Epstein-Barr virus) has long been suspected, but no specific infectious agent has been found as an unequivocal explanation [9]. More recently, it has been suspected that abnormal expression of endogenous retroviral
sequences may lead to the activation of epithelial cells and the innate and adaptive immune system. The importance of hormonal factors in pSS, in particular, estrogen deficiency, is strongly suggested by the female preponderance and the peak of onset after menopause. The existence of polymorphisms, particularly in genes involved in the interferon (IFN) response, could promote this excessive response of the immune system [10].

### 3.2.2. IFN signature and B cell activation

All these factors increase the production of IFN, called the IFN signature (type I or II), which is present in more than 50 % of patients in the blood and target tissues (especially salivary glands) [11]. Such an increase in IFN leads to excessive production of the cytokine B-cell activating factor (BAFF), which stimulates the survival, proliferation, and maturation of B lymphocytes. B lymphocytes are the principal inflammatory cells in glandular infiltrates and their hyperactivation is a characteristic feature of pSS. This is reflected by the presence of the autoantibodies anti-Sjögren's syndrome-related antigen A (anti-SSA), anti-SSB, and rheumatoid factor, as well as hypergammaglobulinemia and ectopic germinal centers in the salivary glands. However, these antibodies do not have a clear role in glandular destruction.

### 3.2.3. Role of epithelial cells and lymphocytes

The presence of plasma cells infiltrating the salivary glands is part of the cellular signature of pSS, which also includes the presence of activated CD4⁺ and CD8⁺ T cells, which have been suggested to be responsible for glandular damage. Such B-cell over-activation is largely regulated by epithelial cells, which are not only the target of the disease but also play an active role. Notably, epithelial cells, the main target of the disease, produce BAFF upon stimulation by IFN. BAFF in turn, activates B cells [12]. The IFN signature and B and T lymphocyte hyperactivation, as well as epithelial cell modification, are therefore therapeutic targets currently being explored in this disease [11,13].

## 3.3. Clinical features

### 3.3.1. Glandular symptoms

#### 3.3.1.1. Dry mouth: xerostomia and hyposalivation.
The experience of oral dryness is called xerostomia, and must be distinguished from hyposalivation, a measurable decrease in salivary flow rates. A decrease of the unstimulated whole saliva flow (UWSF) rate below 0.1 mL/min is one of the criteria for Sjögren's EULAR classification (the normal UWSF rate is 0.2–0.3 mL/min) (Table 1). Clinically, a frothy and thick saliva, when it is not absent, leading to a dental mirror that sticks to the tongue or oral mucosa is often observed by the dentist or the dental hygienist [14]. This may also be explained by qualitative changes in the saliva as it has been reported an altered glycosylation profile of salivary proteins [15,16] and an enrichment in lipid components. This could explain the dry mouth and related oral complications more than the reduction of the unstimulated salivary flow [15]. Occasionally, patients may experience xerostomia without clinical evidence of hyposalivation. Dry mouth, which is largely experienced by patients with pSS [17], can lead to dysphagia, adherence of the food bolus to the palate, dysgeusia, but also affects the ability to speak and impairs the quality of sleep. Complications of dry mouth syndrome include an increased incidence and number of carious lesions, increased risk of oral candidiasis, and chronic esophagitis [18–20]. All these oral clinical features are described below.

#### 3.3.1.2. Dry eyes.
The other dry feature is the presence of xerophtalmia, a sensation of dryness of the eyes. It can be measured objectively using the Schirmer test (assessment of tear production) and the ocular staining score of at least one eye (measure of damage to the ocular surface due to dryness), which are also criteria of the EULAR ACR 2016 Sjögren classification (Table 1) [21,22]. Eye dryness affects 13–36 % of the general population and over 93 % of patients diagnosed with pSS [23]. It results in functional symptoms related to inflammation of the ocular surface (burning, stinging, sensation of a foreign body or sand, pruritus) and visual symptoms related to lacrimal instability and keratitis sicca (visual blurring, photophobia). The presence of dry eyes for more than three months, the sensation of a foreign body, and the use of tear substitutes more than three times a day are symptoms that can be easily asked for by dentist or the dental hygienist to investigate the presence of pSS [24]. Dry eye is managed by compensating hyposecretion with tear

**Table 1**

Classification criteria of the American-European Consensus - European League Against Rheumatism (ACR-EULAR) Group (2016).

<table><thead><tr><th>Sjögren classification criteria: ACR/EULAR 2016</th><th>Score</th></tr></thead><tbody><tr><td>Lymphocytic sialadenitis with a focus score ≥1 on accessory salivary gland biopsy and a focus score ≥1 foci/4 mm²</td><td>3</td></tr><tr><td>Anti-SSA/Ro-positive antibodies</td><td>3</td></tr><tr><td>Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) for at least one eye</td><td>1</td></tr><tr><td>Schirmer's test ≤5 mm/5 min for at least one eye</td><td>1</td></tr><tr><td>Salivary flow without stimulation ≤0.1 mL/min</td><td>1</td></tr><tr><td colspan="2"><strong>Exclusion criteria:</strong> History of cervical irradiation, active HCV infection, HIV infection, sarcoidosis, amyloidosis, graft versus host disease, IgG4 associated disease</td></tr></tbody></table>

The 2016 EULAR/ACR classification criteria emphasize objective evidence of disease, focusing on serological, histological, and clinical findings. In this classification, each diagnostic criterion is assigned a specific score. The total score is used to determine whether a patient meets the classification for primary Sjögren's syndrome. A total score of ≥4 is required for a classification of primary Sjögren's syndrome. The 2016 EULAR/ACR classification criteria are primarily classification criteria to aid in recruitment for clinical trials. These criteria can be used to guide clinical diagnosis, with incorporation of other features, without the use of the score.
substitutes to decrease tear film instability and reduce inflammation of the ocular surface [3,25].

Finally, other glands can also be affected, leading to various clinical symptoms, such as vaginal dryness, dry skin, itchiness, pur-pura, pulmonary infection, and dry nose.

### 3.3.2. Extra-glandular manifestations

Systemic or extra-glandular symptoms affect 20-40% of patients, with diverse clinical signs. They are divided between visceral (e. g., articular, pulmonary, cardiovascular, renal, gastrointestinal, endocrinological, and neurological) and non-visceral (cutaneous and musculoskeletal) symptoms. The main systemic complication is the occurrence of B-cell lymphoma, which occurs 10 to 15 times more frequently than in the general population. It affects 5% of patients with pSS, in particular, those with extra-glandular symptoms [26]. The most common subtype is MALT (mucosa-associated lymphoid tissue) lymphoma, often seen in the parotid glands, with a pre-dominance of extra-nodal localization [12,26]. Other systemic manifestations can include articular involvement with arthralgia and arthritis, lung involvement, such as interstitial lung disease associated with dry cough and dyspnea, renal involvement, of which interstitial nephritis is the most common, or neurological involvement, such as motor or sensitivity deficits up to cognitive dysfunction, all leading to a lower quality of life [27]. Faced with such a diversity of clinical signs in a patient with a dry mouth, the dentist or the dental hygienist must consider referring the patient to search for the presence of a possible systemic pathology.

## 3.4. Diagnosis

Given the diversity of symptoms and the fact that they may be present in other diseases, diagnosis of primary Sjögren's syndrome will be optimized if carried out by a multidisciplinary medical team, including an oral health professional. The diagnostic criteria used to establish the clinical diagnosis of pSS for a patient are those of the most recent classification criteria developed in 2016 by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [22], but without weighting and with a comprehensive assessment of the patient's clinical presentation, symptoms, and test results. Of note, the classification criteria are used to classify patients into groups for research and epidemiological analysis and imply the weighting of five criteria.

1. the presence of an objective immunological abnormality (anti-SSA antibodies)

2. a biopsy of the accessory salivary glands with a lymphocytic infiltrate evaluated by a focus score $\ge$1 (a focus score of 1 corresponds to the presence of a cluster consisting of 50 lymphocytes over $4 \text{ mm}^2$ of the glands examined; a Chisholm score $\ge$3 is equivalent to a focus score greater than or equal to 1)

3. an unstimulated whole salivary flow rate <0.1 mL/min

4. a Schirmer's test result $\le$5 mm/5 min in at least one eye

5. an ocular Staining Score $\ge$5 (or a Van Bijsterveld score $\ge$4) in at least one eye.

The threshold is 4 (the maximum score is 10). These criteria are applicable only if the patient has at least one symptom of oral or ocular dryness assessable with simple questions and in the absence of another medical reason or treatment associated with dryness (Table 1).

These criteria are now complemented by two scores validated by the EULAR [28].

- the EULAR Sjögren's syndrome disease activity index (ESSDAI), which measures systemic features of the disease;

- and the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), which measures fatigue, pain, and dryness symptoms and the feelings of the patient. A complete assessment of dryness may involve objective measurement of tear and saliva flow, histological evaluation of the salivary glands, and possible imaging using salivary gland ultrasonography [29].

It is evident that a pSS diagnosis must be made by a medical team. Dry mouth and dry eyes are very common with age, and are not specific symptoms. They are insufficient to diagnose pSS on their own [30,31].

## 3.5. Perspectives for the diagnosis of pSS

Today, the challenge is to reduce the delay in diagnosis of primary Sjögren's syndrome, estimated at between 2 and 6 years [8,32], in order to reduce the impact on the patient, particularly in terms of quality of life. Research in the field of the diagnosis of pSS is very active, and aims to identify subcategories of patients to better adjust treatment and follow-up [33]. Ultrasonography of the salivary glands is increasingly used and can help to better identify patients who require a minor salivary gland biopsy [34]. Some authors have also been interested in salivary biomarkers and, recently, the expression of salivary proteases (cathepsin G, neutrophil elastase, myeloblastin, matrix metalloproteinase 9) has been found in the saliva of pSS and sSS patients, compared to healthy controls, with interestingly increased activity of the serine protease dipeptidyl peptidase-4/CD26 (DPP4/CD26), only in the pSS group [35].

## 4. Characteristics of the mouth of a patient with pSS

Knowing the characteristics of a patient with dry mouth (Fig. 1) will enable the oral health professional, dentist or dental hygienist, to be more alert to suspect an undiagnosed patient with pSS and optimize its management.
## 4.1. Hyposalivation

Dry mouth can be easily screened by any dentist or dental hygienist using the two questions of the 2002 American-European consensus classification criteria for SS: (1) the presence of dry mouth for more than three months and (2) the need to drink liquids to aid in swallowing [36]. Moreover, the observation of frothy and viscous saliva with a tendency to form "bubbles", associated with a severe clinical picture of gingival inflammation, loss of papillae on the tongue or a fissured tongue, and atypical caries or severe erosion, should suggest dry mouth and lead to an objective assessment of hyposalivation by measuring the UWSF rate [37]. Measurement of the UWSF rate can be performed as follows: in the morning, 1 h after drinking, smoking, eating, and in the absence of stress, the patient spits every minute for 5-15 min into a tube that is weighed empty with an analytical balance and then after it is filled with saliva. The volume is determined according to the formula: $V = \frac{m}{\rho} \times 1000$, where $m$ is the mass of the saliva and $\rho$ is the density of the saliva. The result is expressed in mL/min, with an alert threshold of less than 0.3 mL/min. Note that a flow rate less than or equal to 0.1 mL/min is a severity criterion, which highlights the impact of the syndrome on the salivary glands, in accordance with the criterion-based classification of Sjögren's syndrome [36].

The lack of saliva is often associated with xerostomia. In daily practice, its assessment can be performed using a number of tools [28], such as the Xerostomia-Related Quality of Life Scale (XeQOLS) [38] or the Xerostomia Inventory [39] even if none of these questionnaires have been specifically designed for pSS patients. The XeQOLS was initially designed for patients undergoing salivary gland irradiation for orofacial cancer. It includes 15 items that explore four domains (physical functioning, pain/discomfort, personal/psychological functioning, and social functioning) [38]. The Xerostomia Inventory has been designed for old people (≥65

<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Oral health characteristics of patients with primary Sjögren's syndrome and their impact on oral health-related quality of life. Sjögren's syndrome leads to dry mouth, which increases the prevalence of dental caries and oral candidiasis (full-line arrows). Moreover, this dryness is often associated with increased gastro-oesophageal reflux: dryness and acidity may increase the risk of dental and periodontal wear lesions (recessions), as well as alterations in taste and smell. The autoimmune component of the disease could also explain a number of features found in these patients (dotted arrows): an increase in stomatodynia and alterations in taste and smell due to damage to nerve fibers, and a protective effect against periodontitis despite a higher plaque index, through modulation of the immune response. Prevalence rates and confidence intervals are provided where applicable, based on referenced studies (noted in brackets). Taken together, these oral health problems account for a poorer quality of oral life, due in particular to discomfort, chewing difficulties, night-time awakenings, pain and the frequency of dental care.</figcaption></figure>
years). It includes 11 items that cover both the experiential and behavioral aspects of dryness and four items are dedicated for the assessment of extra-oral tissue dryness (eyes, nose, face, lips) [39]. As saliva is crucial in oral cavity homeostasis [40] (Fig. 2), hyposalivation can lead to numerous clinical manifestations for the mucosa and periodontal and dental tissues, which should alert the dentist or the dental hygienist.

## 4.2. Dental diseases

### 4.2.1. Dental caries

Carious disease is caused by an imbalance between the host and specific cariogenic bacteria, the most common of which is *Streptococcus Mutans*. Poor oral health, dental structural abnormalities (enamel hypoplasia [41], malposition [42], inadequate restoration [43]), and carbohydrate-based foods are aggravating factors, whereas a normal saliva flow rate and good dental hygiene are protective factors. Given the lack of saliva, as well as an altered oral microbiota [44,45], pSS patients are considered to have a very high risk of caries [46]. Their DMFT (decayed, missing, and filled teeth) index is significantly higher than that of the non-SS population and they have up to four times more tooth loss due to caries [47–50]. A large retrospective population-based cohort study conducted on 709 patients with pSS showed a significantly higher incidence rate (adjusted incidence rate ratio equal to 1.64) and prevalence (74.6 % vs. 63.0 %) of dental caries [20]. Carious lesions have atypical characteristics: they evolve rapidly and are mainly found on the smooth surfaces, tips of the cusps, and free edges (normally little affected), as well as in the cervical areas. In addition, recurrences are numerous, despite good oral health behaviors, i.e. good oral hygiene, fluoride use and regular dental check-ups (on average every 6 months) [40,51].

### 4.2.2. Tooth wear

Saliva lubricating capacity prevents the mechanical wear of surfaces (dental attrition and dental abrasion) and its buffering capacity neutralizes acids and maintains hydroxyapatite saturation to chemically limit the wear of the dental tissues (dental erosion). These protective mechanisms are altered in patients with hyposalivation [52,53]. The assessment of tooth wear has been standardized with the creation of the Basic Erosive Wear Examination (BEWE) score in 2008. The BEWE index is calculated based on the record of the most severely affected surface in each sextant (score 0–3), allowing the calculation of a cumulative score (0-18), classified in four risk levels (none to high) [54]. In 2011, a higher percentage of tooth surface wear in patients with SS compared to controls was reported [55]. In addition, many SS patients suffer from gastro-oesophageal reflux [19], which has been reported to be a major risk factor

<figure><img src="image_5.png" /><figcaption>**Fig. 2. Saliva roles.** Saliva allows maintenance of the homeostasis of the oral cavity through several functions: (i) physical, through the self-cleaning of surfaces and the healing and lubrication of mucous membranes by its continuous flow; (ii) chemical, through digestion and taste, buffering against extrinsic or intrinsic acidic aggression, and remineralization of dental tissues; and (iii) biological, through its anti-bacterial, antiviral, and antifungal properties.</figcaption></figure>
<figure><img src="image_6.png" /><figcaption>**Fig. 3.** Decision tree for the diagnosis of Sjögren's syndrome by the dentist or the dental hygienist.</figcaption></figure>
for tooth wear. Recently it has been shown that a higher proportion of people with xerostomia have a BEWE score ≥2 (surface with dentin exposure >50 %) and a significantly higher cumulative BEWE score than that of the general population [56], which could be explained by higher consumption of acidic beverages to promote salivation.

### 4.3. Periodontal diseases

Periodontal diseases, e.g., gingivitis and periodontitis, are highly prevalent chronic inflammatory diseases [57]. Severe periodontitis concerns 11.2 % of the global population and leads to esthetic and functional disorders due to the loss of healthy teeth, as well as chronic bacteremia and systemic inflammation [58]. They are recognized as a risk factor for chronic inflammatory diseases, such as cardiovascular disease or diabetes, whereas the systemic inflammation or autoimmunity disturbances may have an impact on the pathogenesis of periodontitis [59,60]. The association of periodontitis and rheumatoid arthritis has been studied for the last 20 years, and a recent meta-analysis concluded a higher prevalence of rheumatoid arthritis in patients with periodontitis than healthy controls [61]. In addition, hyposalivation and/or dry mouth (due to medical conditions, drug treatments, as well as malocclusions and lip incompetence) are also associated with gingival inflammation [62]. In this context, an association between periodontitis and SS has been sought, and data from the literature has long been conflicting. Today, three recent systematic reviews and meta-analyses concluded that SS is not a risk factor for periodontitis. Clinical loss of attachment and pocket probing depths, the two main markers of periodontal destruction in periodontitis, were comparable between SS patients and controls [49,63], although pSS and sSS patients showed more gingival inflammation than control patients [49,64]. However, these results should be interpreted with caution, as it was noted that the included studies had a risk of bias and showed significant heterogeneity.

### 4.4. Candidiasis

In pSS patients, reduced unstimulated salivary flow is associated with decreased mucosal lubrication and changes in the concentration of immunoglobulins (salivary IgA) and the antibacterial proteins lysozyme and lactoferrin. This increases the risk for oral microbiota dysbiosis and *Candida* infections, which can show different clinical aspects: erythematous (especially on the palate and tongue), pseudomembranous, or angular cheilitis. In angular cheilitis, bacteria present on the skin or mucous membranes, mainly *Staphylococcus aureus* or Streptococcus pyogenes, can superinfect candidiasis [65]. Recently, an observational cross-sectional study conducted on 61 pSS patients showed that 13.1 % presented oral signs of candidiasis, mainly consisting of denture stomatitis and angular cheilitis [18]. The risk of developing candidiasis may be higher if topical steroids are used, in particular, for patients with oral mucosal lesions.

### 4.5. Oral mucosal lesions

The prevalence of oral mucosal lesions of autoimmune etiology (e.g., lichen planus, recurrent aphthous stomatitis, pemphigus vulgaris) in patients with pSS has been studied. In a systematic review conducted in 2017, the analysis of 18 studies showed that patients with SS (primary and secondary) presented with more oral mucosal lesions than non-SS patients. The most frequent were atrophic glossitis, recurrent oral ulcerations, and grooves or fissures on the tongue. However, the authors noted that the studies were performed on small samples using heterogeneous protocols including the failure to systematically assess confounding factors such as smoking, alcohol consumption, salivary flow measurements, the presence of removable prosthesis, associated systemic diseases, and drug intake [66]. In 2013, Likar-Manookin et al. reported that 12 % of patients in a multi-center retrospective cohort study on 155 patients with pSS had oral mucosal lesions of immune-mediated etiology, mainly lichen planus and aphthous stomatitis, and, rarely, chronic ulcerative stomatitis [67]. In 2019, Belkacem Chebil et al. evaluated 30 patients diagnosed with SS (24 with primary SS) and found that eight had erosive oral lichen planus and one oral lichenoid lesions [68]. In addition, although it had never been described before, we recently reported a case of plasma cell gingivitis in a woman with pSS [69]. Further studies are needed to evaluate whether pSS patients present with specific oral mucosal lesions, which may help in better understanding the pathogenesis of this disease and help oral health professionals to better identify these patients. Indeed, many immune-mediated diseases have oral manifestations that may be the first signs of the disease [70].

### 4.6. Neuropathic pain

Burning mouth syndrome, or stomatodynia, is an idiopathic burning sensation of the oral mucosa, with no apparent underlying cause. The etiology and pathogenesis of this syndrome is still unknown, appears to be multifactorial, and may be due to small fiber neuropathy. It has been reported that 45 % of pSS patients experience burning mouth syndrome, whereas only 7–8 % of the general population are affected [71]. Recently, neuropathic pain of the eyes, body, and mouth was extensively studied in the Sjogren's International Collaborative Clinical Alliance, composed of 3,541 patients, of whom 52.9 % met the ACR/EULAR classification criteria. Neuropathic oral pain was defined as a burning sensation of the tongue or other parts of the mouth in the absence of oral mucosal abnormalities or oral candidiasis. Surprisingly, neuropathic oral pain was negatively associated with the presence of SS [72]. Because neuropathic pain is a rare and poorly defined condition, it is still difficult and highly challenging to evaluate it in patients with pSS.
4.7. Alterations of smell and taste

Quantitative or qualitative alterations of taste and smell can have an impact on quality of life, self-esteem, appetite, psychological balance, and even nutritional status and are associated with comorbidities [73]. Alterations of smell and taste have been investigated in several studies using questionnaires, as well as tests [73]. A decreased olfactory ability (olfactory detection threshold, identification, and memory) in pSS patients, with a higher proportion of anosmic (absence of smell) and hyposmic (decreased smell) patients were found in patients with pSS compared to healthy controls. Similar results were found with regard to taste with a higher proportion of agueusic (complete loss of taste), hypogueusic (decrease of taste sensitivity for sweet, sour, salty, bitter), and dysgeusic (distorted sense of taste) patients with pSS compared to healthy controls [73–75]. For example, Singh et al. compared 58 pSS patients, 22 patients without SS but with dry mouth, and 57 healthy controls and found a higher proportion of patients with ageusia and dysgeusia among patients with dryness (pSS or non-SS) than controls. In addition, these patients had significantly lower gustatory scores in taste strip-based tests assessing the four basic tastes (sweet, sour, salty, bitter), as well as in participants’ self-assessment of taste by Visual

<figure><img src="image_7.png" /><figcaption>Fig. 4. Prescription and advice for dry mouth care depending on the severity of hyposalivation.</figcaption></figure>
Analogue Scale (VAS) [74].

## 4.8. Oral health-related quality of life

The Oral Health Impact Profile (OHIP)-14 is a short form of the original OHIP-49, which was developed in 1994 by Slade and Spencer to assess the impact of oral symptoms and disorders on the quality of life [76]. The OHIP-14 consists of 14 questions organized into seven dimensions (functional limitations, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap). The higher the score (with a maximum of 56), the more "oral distress" the patient has.

In 2020, Azuma et al. found that OHIP-14 scores were higher for 35 patients with SS (22 of whom had pSS) than 23 control patients, specifically for the following domains: functional limitation ("trouble pronouncing words"), physical pain ("uncomfortable eating foods"), psychological discomfort ("self-conscious"), and physical disability ("unsatisfactory diet"). The authors reassessed 22 patients with SS (13 of whom had pSS) and investigated the possible correlation with stimulatory salivary flow three years later. They observed an inverse correlation between a decrease in the stimulatory salivary flow rate (even though it remained greater than 0.7 mL/min) and an increase in the OHIP-14 scores of SS patients. Scores for the social disability domain ("irritable with other people" and "difficulty doing usual job"), as well as for disability ("felt like less satisfying" and "unable to function"), increased significantly in only three years for the SS patients with a decrease in saliva production over time. This highlights that the burden of disease of SS patients is due, in part, to dry mouth [77]. In addition, a higher OHIP-14 score appears to correlate with a higher prevalence of oral diseases in patients with pSS. Indeed, in a study of 163 women with pSS, Enger et al. found that recurrent oral fungal infections, taste alterations, oral pain, eating problems, increased dental caries, and recurrent salivary gland swelling were more common among those that had a high OHIP-14 score than those that had a low OHIP-14 score [78]. Similarly, a moderate positive correlation between the mean OHIP-14 sum score (16.2 ± 10.8 vs. 2.7 ± 3.1) and the presence of self-reported halitosis, dysgeusia, and burning mouth syndrome was found for 31 patients with pSS with hyposalivation [79].

The development of qualitative research to explore the thoughts, beliefs, attitudes, and behaviors of patients with pSS has recently provided new insights concerning the pathway to a diagnosis of pSS, acceptance of the disease, and the patient's day-to-day experience with the disease, including oral dryness [80]. Through semi-structured interviews or focus groups and specific analysis techniques (thematic analysis, grounded theory, and the framework approach), these studies have highlighted: (i) the mechanisms associated with the delay in diagnosis (e.g., the symptoms described by the patient appear to be minor and are not investigated by the practitioner), as well as the distress felt by the patient at the same time; (ii) the fear felt by the patient when diagnosed with a disease often unknown to their close family or friends, for which the evolution and prognosis are uncertain; (iii) the impact on daily life, especially during meals, with a loss of pleasure; (iv) fatalism regarding the evolution of oral problems and the financial stress associated with their treatment; and (v) the weight of intense fatigue, from which one does not recover and which is unpredictable [81-83]. In addition, these studies have also made possible to understand and propose models concerning the acceptance, or not, of the illness by the patient and its effect on maintaining their social integration. These studies are important for clinicians because they allow an understanding of the psycho-affective impact, as well as the experience, of the disease. This makes it possible to adapt the management of the patient and to promote compliance with any treatment. For example, a patient reminds us of the importance of listening to them: "It's so important that you can talk to them [implying health professionals], I know right now that you can't do anything for me! It doesn't matter, but you were listening." [80].

## 5. Identification and multidisciplinary management of undiagnosed primary Sjogrens's syndrome

pSS may be a serious systemic disease, not only due to the large impact on the health-related quality of life of the predominant symptoms (dryness, fatigue, and pain), but also the systemic involvement and excess mortality caused by cancer (lymphoma). The low prevalence of pSS in the general population, associated with its heterogeneous clinical expression, makes it difficult to diagnose and manage all aspects of the disease in a non-specialized clinical setting. Thus, dentists and dental hygienists, whom every patient should normally consult at least once a year as a preventive measure, play a very important role as health professionals in the detection of pSS. The main situations for which pSS should be investigated are the following (Fig. 3).

- The patient reports xerostomia of more than three months, characterized by the need to drink liquids to facilitate swallowing or the existence of nocturnal awakening to drink in which the patient does not take any medication nor have any disease that could explain the oral dryness (Table 1). However, the dental professional must be attentive to the complaints of a patient who is taking a drug with a side effect of reducing salivary flow, and who may express xerostomia problems that worsen over time.

- The clinical examination reveals a combination of some or all of the following characteristics: frothy and thick saliva, severe dental caries on smooth tooth surfaces, severe tooth wear (often reported as "my teeth are crumbling"), gingival inflammation, and loss of papillae on the tongue or a fissured tongue, as well as candidiasis or oral cheilitis. The fact that oral mucosa sticks to the mirror during clinical examination is often found.

- The patient suffers from parotitis that cannot be explained by the existence of a salivary calculus.

The combination of these factors should prompt a further detailed medical interview to gather further arguments to support the hypothesis of the presence of pSS, especially if the patient is a woman of approximately 50 years of age. At the time of taking the history, the dentist or the dental hygienist must particularly look for (i) pain in the limbs and, more precisely, in the joints and muscles; (ii) disabling dryness of the eyes, obliging the patient to often put lubricating drops in the eyes; (iii) intense fatigue (asthenia); and (iv)
a history of autoimmune disease in the patient or family (especially in first-degree relatives), such as Hashimoto's disease or rheumatoid arthritis. If the oral health professional is equipped with salivary tests, a measurement of the unstimulated salivary flow rate (threshold of 0.1 mL/min), which is more sensitive and specific, and stimulated salivary flow rate (threshold of 0.7 mL/min) can be performed to objectively measure hyposalivation.

The coexistence of several of these factors should lead to an investigation of pSS by a specialized multidisciplinary team in centers of expertise for patients with SS. These experts perform clinical and biological examinations (including blood tests for anti-SSA and anti-SSB antibodies, salivary gland biopsy, and ophthalmological examination) to diagnose pSS, excluding non-autoimmune etiologies, as well as assess the extent of organ damage and propose an adapted follow-up tailored to the patient. The salivary gland biopsy can be performed by the dentists if they have sufficient experience. Indeed, an insufficient biopsy can lead to a wrong interpretation of the examination and a second sampling, which is painful for the patient. Management of the disease is coordinated by autoimmune disease experts with local practitioners, including the oral health professional.

Improving the identification of suspected SS patients with primary Sjogren's syndrome is an important area of research, particularly with the development of innovative technologies for the analysis of serum, lacrimal, salivary or tissue biomarkers (particularly within salivary gland biposies). For example, a salivary molecular signature using metabolomic analysis that would be associated with disease status [84], or the existence of an association of combined salivary (TRIM29 upregulated) and serum (anti-SSA/Ro+) biomarkers [85] represent interesting prospects. With regard to imaging, recent studies point to the improved diagnostic accuracy of salivary gland ultrasonography instead of assayed salivary gland biopsy [86]. Ultimately, the development of artificial intelligence (AI) tools based on biomarkers, salivary gland ultrasound and/or biopsy could exploit large datasets to predict, stratify and monitor disease and treatment outcomes [87-89].

However, these approaches cannot yet be implemented by every dentist or dental hygienist in a general practice. To improve the identification of undiagnosed patients by oral health professionals, it would be useful to have tools to better discriminate between patients to be referred to these teams. In 2022, Yu and collaborators proposed a 5-question SS Screening Questionnaire (SSSQ) based on the patient's symptomatology and tobacco smoking habits. It was found that a SSSQ score superior or equal to 7 distinguishes SS from non-SS patients with 64 % sensitivity and 58 % specificity [82], which is not sufficient to be discriminating. A similar study should be carried out to assess the validity of our proposed approach. Continuing to model and test new identification or screening tools for dental practice, which could be composite by integrating symptomatic and oral data, such as DMFT, is an important prospect.

# 6. Consideration for oral treatment of patients with primary Sjogren syndrome

Dental professionals have an important role to play in implementing a preventive oral health strategy, as well as providing dental care tailored to the specific conditions of dry mouth, guaranteeing stable results over time. These approaches are described in detail below.

## 6.1. Treatment of dry mouth

In 2020, a task force including specialists in rheumatology, internal medicine, and oral health and patient representatives from 30 countries of the five continents proposed EULAR recommendations for the management of SS. They concluded that the therapeutic approach to oral dryness should be driven by the baseline measurement of salivary glandular function and not by the patient's subjective feelings. Thus, measurements of both unstimulated and stimulated salivary flow should always be performed before starting any therapeutic intervention, as they are very easy to perform in daily practice in all clinical settings [90]. When hyposalivation is observed based on unstimulated salivary flow (UWSF <0.1 mL/min), the measurement of stimulated salivary flow (SWF) is performed and guides the management of the oral dryness (Fig. 4).

- if it is > 0.7 mL/min, non-pharmacological stimulation is preferred because glandular function can be stimulated. Patients are advised to consume taste stimulants, such as sugar-free candies, lozenges, or discs of xylitol sticking to oral tissues or dentures, or to chew (mechanical stimulation) sugar-free chewing gum. Massaging the salivary glands can also be suggested. On the other hand, the consumption of acidic drinks should be avoided, as they increase the risk of tooth wear.

- if it is between 0.1 and 0.7 mL/min, the patient has moderate glandular dysfunction. Pharmacological stimulation of the residual glands is proposed through the use of muscarinic agonists (pilocarpine and cevimeline). To note, these pharmacological treatments can be combined with the use of both saliva-stimulating and saliva-substituting products.

- if it is < 0.1 mL/min, the gland is no longer functional: only salivary substitutes (e.g gel, spray, mouthwash) are proposed to alleviate the symptoms of patients.

Of note, these are expert recommendations, with a high level of agreement between experts, but which are not based on the literature. Moreover, experts do not agree on the use of salivary substitutes, as certain experts believe that they should be used for all patients who experience oral dryness, irrespective of glandular function. Of course, prescribers will need to take the patient's opinion into account when prescribing and renewing these treatments.

In 2019, a systematic review of the literature and subsequent meta-analyses aimed to assess the interventions that lead to decreased xerostomia symptoms, as well as changes in the salivary flow and quality of life of pSS patients [91]. The meta-analyses showed that patients using pilocarpine were significantly more likely to experience a large reduction in xerostomia and increased unstimulated salivary flow relative to placebo, although the effect size, clinical significance, and duration of the effect remained unclear. Similar
<caption>**Table 2**</caption>

Recommendations for maintaining or restoring good oral health in patients with pSS and hyposalivation.

<table><thead><tr><th>Clinical Features</th><th>Recommendations</th></tr></thead><tbody><tr><td>Dry mouth</td><td><strong>Depending on patient feedback and saliva flow measurements:</strong><ul><li>Pharmacological stimulation: muscarinic agonists (pilocarpine and cevimeline).</li><li>Non-pharmacological stimulation: taste stimulants (sugar-free candies, lozenges, xylitol, sugar-free chewing gum, salivary glands massage)</li><li>Artificial salivary substitutes</li></ul><strong>For all patients</strong><ul><li>Regular hydration (at least 1.5 L of water per day)</li><li>Reduction or cessation in consumption of caffeine, alcohol, tobacco, and certain medications</li></ul></td></tr><tr><td>Basic recommendation for all patients</td><td><strong>Prevention</strong><ul><li>Good oral hygiene techniques:<ul><li>Two brushings/day for 2 min with a soft toothbrush and an appropriate technique; if electric toothbrush: model with pressure controller</li><li>Daily use of interdental brushes. If the use of interdental brushes is too complex, use an alternative interdental brushing technique such as dental floss or hydropulsators (e.g. Waterpick®).</li><li>Daily cleaning of dentures with a hard toothbrush, household soap and tap water</li></ul></li><li>Toothpaste prescription:<ul><li>With fluoride (a highly fluoridated toothpaste ≥2500 ppm is recommended in cases of hyposialia)</li><li>Mild-tasting (e.g. not strong mint)</li><li>In case of dentine hypersensitivity: desensitizing and/or occluding toothpastes</li><li>In case of oral mucosal lesion: SLS-free toothpaste</li></ul></li><li>Oral examination every 6 months</li><li>Dietary advices:<ul><li>Avoid acidic foods and sodas and eat dairy products, or water rich in bicarbonate, after eating acidic foods, such as fruit</li><li>Limit the consumption of fermentable carbohydrates</li><li>No snacking, meals at regular times</li></ul></li></ul></td></tr><tr><td>Dental Caries &amp; Tooth Wear</td><td><strong>Prevention</strong><ul><li>Personal use of topical fluoride: adjust the concentration of fluoride in toothpaste; use of fluoride trays (5–30 min min/day) and/or fluoride rinse (30sec - 1min after toothbrushing)</li><li>If the patient does not wish to use fluoride or cannot tolerate fluoride gel in trays, use CPP-ACP, CPP-ACPF gel in the trays (5–30 min/week).</li><li>Professional use of topical remineralizing agents in the dental chair:<ul><li>fluoride varnish (2/year)</li><li>Silver Diamine Fluor (one-off treatment for initial dentine caries lesions)</li></ul></li><li>Carious lesion excavation under specific control (e.g. magnification, rubberdam ...)</li><li>Selective removal excavation</li><li>Pulp preservation</li><li>Cavity restoration with glass ionomer and composite fillings</li></ul></td></tr><tr><td>Periodontal disease (gingivitis, periodontitis)<br>Periodontal lesions (gingival recession)</td><td><strong>Periodontal disease treatment:</strong><ul><li>No treatment specificity: follow the recommendations for the treatment of gingivitis and stage 1–4 periodontitis according to the European Federation of Periodontology [98].</li><li>Note that:<ul><li>residual gingival inflammation may persist over time due to hyposalivation, but pSS is not a risk factor for periodontitis.</li><li>if there is active inflammatory/autoimmune disease of the oral mucosa, treatment of periodontal disease will contribute to its remission.</li></ul></li><li>Mucogingival surgery:<ul><li>Mucogingival surgery is possible and successful</li></ul></li></ul></td></tr><tr><td>Candidiasis</td><td><strong>Prevention</strong><ul><li>Recommendation for the patient: 1 % Sodium bicarbonate mouthwash (approximately 1 teaspoon in a glass of warm water, 2 mouthwashes/day for 30 s to 1 min, without rinsing).<strong>Recommendation for the dentist:</strong> Oral rehabilitation to the correct vertical occlusal dimension</li></ul><strong>Treatment</strong><ul><li>To note: smear of lesion for microscopy and antifungiogram is recommended to prescribe the right treatment.</li></ul></td></tr></tbody></table>

(continued on next page)
<table><caption>**Table 2 (continued)**</caption><thead><tr><th>Clinical Features</th><th>Recommendations</th></tr></thead><tbody><tr><td></td><td><ul><li><strong>Oropharyngeal candidiasis</strong><ul><li>Local: 10% amphotericin B mouthwash for 5 min for 21 days, 2% miconazole in the intrados of prosthesis for 21 days</li><li>Systemic: fluconazole 200 mg - Loading dose: 800 mg on the first day; subsequent dose: 400 mg once daily for 21 days in total.</li></ul></li><li><strong>Angular cheilitis</strong><ul><li>Topical antifungals (e.g., nystatin 100.000 U/mL ointment; ketoconazole 2% cream, miconazole 2% cream) - 2 to 3 times daily for two weeks</li></ul></li></ul></td></tr><tr><td>Prosthodontic treatment</td><td>Dental Implants or Removable Prostheses are possible options.</td></tr></tbody></table>

results with similar limitations were found for cevimeline [91]. In 2017, the tolerability and side effect profile of these drugs were compared among 118 pSS patients. Cevimeline was associated with a lower failure rate than pilocarpine among users. Severe sweating, as well as hot flushes and tachycardia, were the most frequent side effects leading to the cessation of therapy and occurred more frequently among pilocarpine than cevimeline users [92]. To limit the cessation of therapy, in daily practice, it is recommended to progressively introduce pilocarpine up to 15–20 mg/day, a process that is facilitated by prescribing it as a magistral preparation [90]. Of note, pilocarpine is the only drug licensed worldwide.

Topical saliva substitutes and topical saliva stimulants can be proposed as an adjunct to, or in addition to, systemic therapies. The ideal preparation of a salivary substitute has a neutral pH and contains fluoride and other electrolytes, mimicking the composition of natural saliva. They are available commercially in the form of oral sprays, gels, and rinses. To date, publications on their effect on xerostomia, salivation, and quality of life are lacking or have a high risk of bias [91]. In a recent study, Purdie et al. (2023) evaluated the effects of different xerostomia products and found that participants with normal salivary flow rate had significantly better responses to lozenges and parasympathomimetic prescriptions [93]. However, it appears that the use of artificial saliva, as oral lubricants, provides temporary comfort that can be appreciated by the patient based on a decrease in xerostomia symptoms found in certain studies. Despite their short duration of action and a certain financial cost, they can be proposed for temporary patient comfort [90]. If saliva substitutes bring comfort to the patient, he or she can continue to use them. Finally, the patient should be advised to frequently hydrate (every 30 min) to lubricate the mucous membranes and assure clearance of the mouth and avoid, if possible, drugs responsible for atropine syndrome (e.g., atropine antiparkinsonians, such as tropatepine, and imipraminic antidepressants, such as clomipramine or imipramine).

According to the EULAR recommendations, the use of systemic SS drugs, e.g., synthetic and biological disease-modifying anti-rheumatic drugs (DMARDs), should not be prescribed for the treatment of dry mouth [90]. However, it is true that certain patients treated for pSS are on these drugs and that these systemic treatments can modify the dryness of the mouth and thus affect oral health. Of note, none of the conventional DMARDs (i.e., hydroxychloroquine) used in pSS have been shown to be associated with an increased UWSF rate [93,94]. Among the biological DMARDs used for pSS [94,95], there is some evidence for a significantly positive effect on dry mouth syndrome for rituximab [96,97].

## 6.2. Prevention of oral diseases

A preventive approach should be implemented (Table 2), with the teaching of good oral hygiene techniques (two brushings/day with a soft toothbrush and a fluoridated toothpaste and interdental brushes; daily cleaning of removable dentures when present, with a hard toothbrush, household soap and tap water), the use of topical fluoride, dietary advice (e.g., limit consumption of easily fermentable carbohydrates, avoid acidic foods and sodas and eat dairy products after eating acidic foods, such as fruit), and consultation with the dentist or the dental hygienist every six months. The quality of oral hygiene is crucial for the prevention of periodontal and peri-implant diseases [98]. Moreover, the patient should be informed of the substances that may aggravate dry mouth to adapt their lifestyle (e.g., the consumption of caffeine, alcohol, tobacco, and certain medications) and hydration throughout the day is recommended (at least, 1.5 L of water/day) [98]. According to experts, mouthwashes with sodium can be proposed to reduce the risk of oral candidiasis [99].

The use of topical fluoride is recommended to decrease the incidence of carious lesions [100] (Table 2): the higher the fluoride concentration in toothpaste (2500 ppm/Fluocaril® 250 ppm, 5000 ppm/Duraphat®, or 13500 ppm/Fluodontyl®), the lower the risk of caries. To reinforce this effect, it can be advisable not to rinse the mouth after brushing and to boost topical fluoride intake by using a fluoride mouthwash at another time-point during the day [101]. Depending on the patient (severity of dry mouth, dietary behavior, etc.), topical application of fluorides is achieved through the use of fluoride trays containing a 20,000-ppm fluoride gel, worn daily (5–30 min) by the patient, and possibly the application of a 5 % sodium fluoride varnish by the dentist or the dental hygienist. Finally, the oral health professional may use CPP-ACP (amorphous casein phosphopeptide) and CPP-ACPF (casein phosphopeptide - amorphous calcium fluoride phosphate) remineralization agents as fluoride adjuvants, either in addition to toothpaste or placed in the fluoridation tray. It is important to emphasize that many patients with low salivation cannot tolerate strongly flavored toothpastes or mouthwashes that contain alcohol or phenolic compounds. In addition, many toothpastes contain a foaming agent called sodium lauryl
sulfate (SLS), which has been described as potentially damaging to oral mucosa [102,103]. Toothpastes containing SLS should therefore be avoided by patients suffering from dry mouth and/or sensitive oral mucosa. This information should guide the dentist and the dental hygienist in the choice of toothpaste (e.g., aniseed flavor instead of mint flavor, no SLS). However, although these prevention strategies have been described for many years [99], it should be noted that there are no studies to base them according to the presence of Sjogren's disease, nor to validate their effectiveness.

### 6.3. Treatment of tooth decay and tooth wear

Because carious lesions develop in atypical sites, careful observation is necessary. As soon as carious or wear lesions are diagnosed, intervention is necessary to treat the lesions and/or protect the remaining tooth structure with appropriate dental materials (Table 2). The main challenge is to cope with an acidic oral environment (caused by the loss of the buffering effect of saliva). The ideal material should be resistant to mechanical and chemical wear, easy to handle, provide fluoride release, and help re-mineralize caries in their early stages.

Despite the lack of studies in the literature on the ideal material for patients with dry mouth, a study by Alghilan et al. provides some guidance. It appears that glass ionomer fillings (FUJI II LC, GC©) and composite fillings (Filtekk Z250) from 3M© are resistant to acid attack and could be used for patients with little or no saliva [53]. However, each material has its own disadvantages: glass ionomer shows high biocompatibility, with resistance to acid attack, but its mechanical and esthetic characteristics are poor; composite fillings have better mechanical and esthetic characteristics, but do not release fluoride, require sealing (which can be difficult to achieve), and do not attach well to the dentinal lesion. Neither of these biomaterials are sufficiently effective for large-scale dental rehabilitation. In addition, there are no data in the literature on the use of ceramic restoration in acidic conditions or a saliva-free environment.

In conclusion, there is no ideal material. The choice of material is based on the clinical situation and the cost-benefit-risk balance analysis for the patient. We currently lack data from large prospective cohort studies to evaluate the long-term success of complex oral rehabilitation in pSS patients with hyposalivation and assess the most appropriate restoration material to be used in this context [104].

### 6.4. Treatment of oral candidiasis

Patients typically require treatment with prophylactic anti-fungal medications when topical steroids are prescribed, in particular, when oral mucosal lesions are present. Special consideration should also be made when choosing an antifungal agent, because the high sugar content of most can greatly increase the risk of dental caries for SS patients. In addition, several commonly prescribed topical antifungal medications come in the form of lozenges. These formulations depend on saliva for dissolution and the medications will likely be ineffective if the patient has SS [18] (Table 2).

In cases of oropharyngeal candidiasis (Table 2), as the diagnosis of oral candidiasis is essentially clinical [105], local (amphotericin B, miconazole) or systemic (fluconazole) antifungals should be prescribed. Amphotericin B should be used as a mouthwash for 5 min before swallowing (topical action) for 21 days. In situations of removable prosthesis, miconazole is applied to the intrados of the prosthesis. If failure is observed at the re-evaluation at 21 days, superficial smear of lesion for microscopy and antifungigram are performed to identify the *Candida* species and determine its sensitivity to antifungal agents. In case of confirmed infection with *C. albicans* infection, fluconazole is indicated; as its action is systemic, it is not necessary to carry out a mouthwash with the product. If another species is identified, the choice of antifungal agent should be adapted as described in the literature [105,106]. In these cases, microbiological testing for opportunistic bacteria is also advisable. Indeed, the frequent presence of bacteria such as *Staphylococcus aureus*, Pseudomonas spp or Enterococcus has been described in patients suffering from oral mucosal affections [107], making it necessary to adapt medical treatment by prescribing the appropriate antibiotic (local or per os).

### 6.5. Treatment of angular cheilitis

Although there is little data to support antifungal use [64], topical antifungals (e.g., nystatin 100.000 U/mL ointment; ketoconazole 2 % cream, miconazole 2 % cream) are indicated for the treatment of angular cheilitis, with local application generally 2 to 3 times daily for two weeks [105] (Table 2). Recently, Federico et al. reported the antifungal 1 % isoconazole nitrate and the anti-inflammatory 0.1 % diflucortolone valerate ointment to be the most effective treatment based on their clinical experience [108]. In addition, the dentist must ensure a good fit (as well as daily cleaning of dentures, reservoirs of *C. albicans*) to regain the vertical dimension of occlusion, avoiding a depression of the commissures, where *C. albicans* proliferates [108].

### 6.6. Treatment of parotitis

In cases of parotitis with painful parotid swelling and after the exclusion of differential diagnoses, systemic treatment with glucocorticoids (with a dose <20 mg per day) for 5-7 days is prescribed. Re-evaluation is necessary and repeated episodes should be reported to the treating medical team. Sustained enlargement of one or more glands for more than 2-3 months should raise suspicions of an intervening lymphoma.

### 6.7. Dental implants

Oral rehabilitation of edentulism, with a partial or total removable prosthesis, is always a challenge for patients with pSS with
hyposalivation (Table 2). Therefore, the use of dental implants is a very attractive treatment option for these patients (Table 2). Several authors have reported positive experiences with implant treatment in real-life experience, characterized by a good survival rate and greatly improved quality of life for the patient [104,109,110]. Indeed, in a recent systematic review, the probability of implant failure was estimated equal to 2.5 % of implants in patients with pSS [109].

After osseointegration, a major issue in peri-implantology is the development of peri-implant bacterial diseases with bone destruction, called peri-implantitis. These diseases are highly prevalent and are a public health issue [111,112]. Thus, when studying implant health, a distinction is made between the implant success rate (notably healthy peri-implant tissue, loaded implants) and survival rate. Clinical researchers have been interested in these rates in pSS patients, whose immune component of the disease (and immunomodulatory treatment) and oral dryness could represent factors of early or late failure. In 2015, a prevalence of peri-implantitis of 14 % was found in a retrospective study on 50 SS patients, mainly primary, and was comparable to that for matched healthy controls, with an equal survival rate of 97 % (2 patients lost implants) [113]. In 2016, a survival rate of 95.2 % was found in a large retrospective study of 205 SS patients (mainly primary) versus 87 for control patients, leading the authors to conclude that dental implants should be considered for SS patients. In addition, they highlighted the improvement in the quality of life of patients with dental implant rehabilitation [111]. Finally, a 2017 systematic review and meta-analysis of six studies also showed a good survival rate, with an average of 93.7 % for a mean period of 3.97 years, as well as a low late complication rate [114]. Dental implants are therefore very well suited for pSS patients.

## 7. Conclusion

Here we have proposed an approach based on the literature and on our experience to guide dentists and dental hygienists in the identification of as yet undiagnosed patients with pSS. In the future, the development of composite scores based on all or part of clinical or interview data could open up new prospects for the early screening of these patients, and referral for molecular (serum, salivary, tears, tissular biomarkers) and imaging (e.g. ultrasonography, MRI) diagnosis. Today, the combination of biomarker, imaging and AI technologies and knowledge offers exciting prospects as sensitive, minimally invasive tools for diagnosis, stratification, prognosis and personalized treatment of pSS patients. To conclude, early diagnosis of pSS is essential and allows us to offer chemical treatments (e.g. cholinergic agonist, DMARDs, bDMARDs), increased preventive measures using local fluorides and lifestyle advice to prevent the development of oral symptoms, preserve the mouth and thus avoid distress for the patient.

### CRediT authorship contribution statement

**Franck Decup:** Writing – review & editing, Writing – original draft, Validation, Project administration.
**Boughanmi Rihab:** Writing – review & editing, Writing – original draft.
**Gaetane Nocturne:** Writing – review & editing, Writing – original draft, Supervision.
**Marjolaine Gosset:** Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Conceptualization.

### Data and Code availability statement

No new data was generated for the research described in the article.

### Ethics declaration

Nothing to declare.

### Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marjolaine Gosset reports was provided by Paris Cité University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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