Findings such as an increase in caries activity, mucosal alterations, oral infections, and salivary gland enlargement may indicate salivary dysfunction. The dental team needs to explain the oral consequences of dry mouth in the patientsÕ daily lives. Thus, patient education plays a central role. Early recognition will minimize damage and dysfunction and allow appropriate management to begin [25].

Dental caries is a multifactorial disease in which the simultaneous presence/occurrence of four main factors is detrimental: (1) host (teeth),

(2) microorganisms (cariogenic bacteria), (3) substrate (fermentable carbohydrates), and (4) time [64]. In addition to these strictly biological factors, education, social class, income, knowledge, attitude and behavior, ßuoride, and saliva will inßuence the development of carious lesions [65].

Caries lesions develop in so-called predilection sites where bacteria in bioÞlm are protected or difÞcult to remove, such as the occlusal surface, the approximal area between teeth, and cervically along the gingival border of the tooth. Important factors in the progression of caries are diet, ßuorides, oral hygiene, and saliva [64]. In patients exhibiting alterations in saliva secretion capacity and saliva composition due to SS or other causes such as radiation to the head and neck region or xerogenic medication, atypical caries lesions such as incisal, cervical, buccal and lingual caries lesions, and rapidly progressing caries lesions are frequently observed [25]. In healthy individuals, caries on such Òeasy to cleanÓ surfaces are uncommon and indicate a high caries activity [64], and studies have shown that unstimulated whole saliva composition was more important for caries development than stimulated whole saliva composition [66, 67].

Despite more thorough oral hygiene, patients with SS often present with more caries and Þllings [15] and Candida infections [16]. Patients with SS and low stimulated salivary secretion were associated with Candida infection [68]. Fungal infections may be manifested as pseudomembranous or erythematous lesions in the mucosa, as median rhomboid glossitis and tongue Þssuration, denture-associated stomatitis, or angular cheilitis, reviewed in Ref. [69].

14.3.2 Caries Preventive Measures

Caries preventive measures should aim to disrupt the four previously mentioned factors required for the formation and progression of caries. Early, non-cavitated caries lesions can be remineralized and, in theory, stopped from progressing by non-operative treatment. Manifest, cavitated lesions must be operatively treated, and further progression of the disease prevented to avoid secondary/recurrent caries and/or loss of restorations. Intensive caries preventive measures including an individually tailored prophylactic dental program are often needed [70]. The relation of saliva and dental caries is best documented in patients who have lost salivary function following tumoricidal radiation, and it is assumed that the same relationship exists in SS, reviewed in Ref. [71].

In a patient with dry mouth, key concepts of preventive dental care include measures to (1) increase the host factor resistance and quality,

(2) modify the bioÞlm, (3) modify the substrate factor, and (4) affect the time factor. By this approach, individually adapted prophylaxis home programs including ßuorides, hygiene measures, dietary advice, and salivary stimulation or substitution can be made for each patient, addressing each individualsÕ special needs.

14.3.2.1 Host Factors—Teeth and Saliva

Fluorides

All patients with xerostomia should use some sort of supplemental ßuoride in addition to ßuoride toothpaste. The use of topical ßuoride should be based on the severity of the patientsÕ conditions as well as individual caries risk. The ßour program should be made in collaboration with the dental team and the patient. A combination of in-ofÞce applied and at-home-based ßuoride program is considered optimal.

Topical ßuoridation may be effective for both prevention and possible remineralization of enamel. Supplements that contain sodium ßuoride, acidulated phosphate ßuoride, and sodium monoßuorphosphate are present in different vehicles including gels, rinses, lozenges, and chewable tablets. Commercial ßuoride varnish or lacquers, such as Duraphat R (2.26% F) or Fluor

Protector R (0.1% F), contain high levels of ßuorides and are usually applied at intervals of 3Ð6 months in patients with hyposalivation/dry mouth.

For teeth, use of a ßuoride-containing toothpaste with at least 1,500 parts per million (ppm) ßuorides (F) is recommended. For high caries active patients recently introduced Duraphat R toothpaste from Colgate with 5,000 ppm F can be used either as an ordinary toothpaste or in an individually Þtted tray. Non-foaming toothpaste with enzymes is seemingly milder to the dry oral mucosa and may be used instead of the conventional sodium lauryl sulfate (SLS)-containing toothpaste. SLS may disrupt the protective Þlm of saliva on mucosa and, in an experimental model of oral mucosa, SLS induced epithelial shedding [72]. Available products are Salutem R , Sensodyne Proenamel R , and various Zendium R and Biot•ne R toothpastes.

In high caries active individuals, additional ßuorides are warranted, for instance, provided by an individually Þtted soft acrylic tray/spoon (Fig. 14.3) with 1% NaF gel used for 5 min/day [73]; custom-made ßuoride carriers. This forces the ßuoride into the interproximal areas and around the cervical margins. The combination of gels with 0.2% chlorhexidine and 0.05% ßuoride may be beneÞcial by both suppressing oral bacteria and remineralizing the teeth [70].

Alternatively, in cases where gel treatment is not tolerated, patients can rinse their mouth with

a 0.05 or 0.2% NaF solution for 1Ð2 min/day. Additional topical application of ßuorides (see above) is then recommended. Patients with dry mouth should also be advised to avoid astringent products such as alcohol-containing or strong mint-ßavored mouthwashes and strongly ßavored toothpastes. It is also advised to use oral care products that have a neutral and alkaline pH, containing no sugar and with added lubricants.

In patients with low salivary ßow, retention of ßuoride is prolonged because of reduced oral clearance [4]. Systemic consequences of highdose ßuorides are critically discussed, but only very few randomized clinical trials on topical ßuoride application are available, and a Cochrane review failed to present conclusive results regarding adverse effects of topical ßuorides [74].

Stimulation

Local Salivary Stimulation

PatientÕs medication should always be checked for anti-cholinergic effects, and, if possible, changed to medication with fewer adverse effects. However, the systemic disease has a higher treatment priority compared to treatment of an oral condition and the necessary medication should not be changed for oral health reasons alone.

Gustatory and/or masticatory stimulation such as chewing food that requires more mastication, or regular use of sugar-free sweets or sugar-free chewing gum [75] are stimulants to increase the

secretion of saliva. Although patients may get the sensation that their mouth is drier following gum chewing, studies indicate that unstimulated salivary ßow rate is not reduced even after prolonged gum chewing [76], and it was suggested that the sensation of dryness in such cases may be due to the excess of saliva during chewing.

Sucking on sugar-free saliva stimulating lozenges/tablets will increase salivary secretion through physiological stimulation of the taste buds. Ideally, tablets also contain low-dose ßuorides; Xerodent R contains 0.25 mg F, malic acid, xylitol, and ßuoride. According to the producer, this composition provides stimulation of saliva both by sucking on the tablet and by the buffered malic acid. Xylitol ÒprotectsÓ against caries and ßuoride strengthens the tooth enamel. Such tablets can be ingested up to 12 times a day by patients with high caries activity. Sucking on regular ßuoride tablets with concentration from 0.25 up to 1 mg F is also beneÞcial. In addition to ßuorides, such tablets contain sorbitol and xylitol. However, it is important to remember that the use of tablet/lozenges will only be beneÞciary if there is enough saliva to dissolve them. Another disadvantage of local saliva stimulants is limited effectiveness at nighttime when the symptoms are most severe.

Electrical stimulation of the salivary glands has been attempted. However, application is challenging and at best the results have been modest [77].

Systemic Salivary Stimulation

The Food and Drug Administration has approved two parasympathicomimetic medications, pilocarpine (Salagen R ) and cevimeline (Evoxac R ), for the relief of dry mouth symptoms [78Ð80]. Pilocarpine and cevimeline act via activation of muscarinic cholinergic receptors in the salivary gland tissue and may in patients with remaining functional salivary gland tissue lead to increased salivary secretion and ultimately improved subjective and objective symptoms. Common side effects of such systemic stimulants include extreme sweating, increased urinary frequency, ßushing, and headache, reviewed in Ref. [34], and need to be prescribed in

collaboration with the patientÕs physician to avoid possible unexpected side effects such as aggravation of heart disease or interactions with other medication. Parasympathicomimetics are contraindicated in patients with uncontrolled asthma, narrow angle glaucoma, and acute iritis and should be used with caution in patients with signiÞcant cardiovascular disease, ParkinsonÕs disease, asthma, and chronic obstructive pulmonary disease, reviewed in Ref. [25].

The recommended dose of pilocarpine with minimal side effects is 5 mg four times a day (total 20 mg/day). An open, uncontrolled study evaluated the efÞcacy of a hydrogel polymer buccal insert as a controlled release delivery vehicle for pilocarpine in eight patients with SS [81]. The authors found that the insert delivered more than 85% of a 5-mg dose of pilocarpine hydrochloride with minimal side effects. The primary endpoint for the therapeutic efÞcacy is increased salivary ßow. However, increased salivary ßow does not necessarily give an improvement in subjective symptoms of dryness. In some cases it may require up to 4 weeks before the peak effect of pilocarpine is evident on salivary ßow. Careful and frequent follow-up of the patient is important in order to assess clinical parameters as well as to determine adverse side effects and adjust dosage quantities and intervals. As long as the salivary ßow continues to be stimulated and the patient does not suffer severe side effects, pilocarpine may be administered indeÞnitely. Pilocarpine may also be discontinued immediately and completely without adverse effects [78].

The recommended dose for cevimeline is 30 mg/day, given in three oral doses [79, 80]. Oral cevimeline was generally well tolerated in patients with SS [82]. Compared with pilocarpine, cevimeline has a 40-fold higher relative afÞnity for M3 receptors than for the M2 receptors found in cardiac muscle and a longer half-life in serum [83].

When saliva secretion can still be stimulated, a special type of acupuncture has been reported to provide some relief [84, 85], a possible alternative for patients who respond well to muscarinic agonists.

Systemic treatment with high doses of expectorant bromhexine have suggested a modest beneÞcial response in both tear and saliva ßow, but controlled trials have failed to improve salivary output [86, 87].

Salivary Substitutes

Salivary substitutes and oral moisturizers intend to mimic the inorganic composition of natural saliva by containing calcium, phosphate, magnesium, and potassium and are the primary choices in initial, local treatment of xerostomia [88]. Depending on the degree of reduced salivary ßow and xerostomia, artiÞcial saliva can moisten and lubricate the mouth, but water may have the same beneÞcial effect. These agents attempt to replace essential salivary components with ingredients such as animal mucins, carboxymethylcellulose, polyglycerylmethacrylate, lactoperoxidase, glucose oxidase, lactoferrin, and lysozyme [19]. The substitute agents are formulated as solutions, sprays, or gels. However, viscosity, surface tension, and adsorption/desorption of saliva substitutes are different from the properties of whole saliva and may limit the duration and extent of their effects [89]. Preferentially, the pH is ≥6. Products containing anti-microbial proteins, such as peroxidase, lysozyme, and lactoferrins, are also available, with intent to compensate for the shortcomings of the host saliva. These products are most useful when used immediately before bedtime or speaking, but clinical studies on the efÞcacy of these products are still limited [70].

Small studies of over-the-counter oral moisturizers, e.g., Saliva Orthana R , Biot•ne R , and Oral Balance R , indicate that these agents can relieve oral discomfort [90Ð93]. There are few data to indicate superiority of any of the substitute products. Selection should therefore be based on availability and personal preference.

For instance, Saliva Orthana R contains natural mucin, namely, porcine gastric mucin and bovine mandibular mucin to simulate the viscoelastic properties of human saliva [94, 95]. At present, research is directed to saliva substitutes, which, besides wetting and puriÞcation, provide protection against microorganisms. Biot•ne R and Oral Balance R primarily contain three

enzymes, namely, lactoperoxidase, lysozyme, and glucose oxidase, and the protein lactoferrin. The enzyme system penetrates the cell wall of plaque-forming bacteria, helping to maintain a healthy balance of oral ßora [92].

Oral Balance R is a moisturizing gel that is applied toward the inside of the cheeks, lips, and on the tongue. The manufacturer claims that the gel quickly relieves dry mouth, protects against irritations and burning sensations for several hours, as well as promotes healing of inßammation. It is also recommended for use under dentures, reviewed in Ref. [96].

Biot•ne R is naturally sweetened with xylitol and provides a range of dry mouth products such as toothpaste, alcohol-free gentle mouthwash, and dry mouth chewing gum. The producer claims that Biot•ne R products are beneÞcial for patients with dry mouth. For the best results it is recommended to use Biot•ne R mouthwash in conjunction with Biot•ne R toothpaste, especially at bedtime [96].

Biot•ne R and Oral Balance R work by different mechanisms, and, therefore, using them in combination may be more effective [92].

Zendium R contains a composition of enzymes [97, 98]. According to the fabricant, the spray and saliva gel with ßuoride can help patients with dry mouth by providing moisture. Both the gel and the spray can be used to supplement brushing.

Saliva substitutes based on polyacrylic acid and xanthan gum have also been developed and some studies have shown that they are effective for patients with extremely low salivary production rates [99]. Relief of symptoms may also be achieved by coating the lips and buccal mucosa with Vaseline R , oil, or glycerin swabs [70]. When at home the patient can hold ice chips in his or her mouth to provide moisture and hopefully relieve symptoms. For dry lips, a hydrating cream or ointment may reduce symptoms. Use of products with aloe vera or vitamin E may also be advised. In addition, several pseudopharmaceutical products and herbal supplements are available [25].

Smoking may be drying and irritating to the oral mucosa and should be avoided. An increase