A sparse number of studies have examined the bacteria in oral mucosal cultures of patients with SS. MacFarlane and Mason (1974) found significantly higher numbers of Staphylococcus aureus and coliform bacilli in SS patients without clinical signs of inflammation than in healthy subjects. Veillonella species, Neisseria pharyngis, Micrococcus mucilaginosus, S. salivarius and S. aureus have also been isolated in higher numbers from the tongue, palate, throat and dentures of patients than in healthy subjects (MacFarlane 1984). However, Almståhl and Wikström (1999) found no differences in the numbers of S. aureus and enterics between patients with pSS and healthy subjects, and the numbers of S. salivarius, Neisseria pharyngis and Veillonella species were lower in pSS patients. Regarding site specificity, a higher density of streptococci, S. salivarius, Fusobacterium nucleatum, Prevotella intermedia, Prevotella nigrescens and S. aureus has been demonstrated on the dorsal part of the tongue than on the buccal mucosa and in the vestibulum (Almståhl et al. 2001b). Species usually associated with gingivitis such as F. nucleatum, P. intermedia and P. nigrescens were found in slightly lower levels in the gingival crevice region of the patients with pSS, but in higher levels of the sSS patients, than in control subjects (Almståhl and Wikström 1999). In this regard, it is noteworthy that the susceptibility to gingivitis and periodontitis has not been found increased in patients with pSS compared to healthy controls (Boutsi et al. 2000; Kuru et al. 2002; Pedersen et al. 1999b; Schiødt et al. 2001; Tseng et al. 1990), which is supported by the rare detection of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in the gingival crevice region of patients with pSS (Almståhl et al. 2001b). However, increased levels of antibodies to A. actinomycetemcomitans and Porphyromonas gingivalis, but not to P. intermedia, in addition to an increased incidence of periodontal disease have been reported in patients with SS (Çelenligil et al 1998; Ergun et al. 2010), but they did not discriminate between pSS and sSS, and it is likely that patients with sSS display an increased risk of periodontal diseases due to its concomitant presence with rheumatoid arthritis (for further details on rheumatoid arthritis and periodontitis, see Chap. 4).

During cancer chemotherapy, there is a significantly increased risk of oral infections due to the immunosuppressive effect and the direct cytotoxic effect of the drugs on oral epithelial barrier function. Studies have shown that chemotherapy may induce temporary salivary gland hypofunction, although there is some controversy whether it is caused by the chemotherapy per se or by other factors, e.g. concomitant intake of xerogenic medication like antiemetics (Jensen et al. 2010). Salivary secretion may even be lower in individuals with cancer prior to the initiation of treatment (Harrison et al. 1998; Napeñas et al. 2013). Chemotherapy can induce compositional changes in saliva. Decreased saliva flow rates combined with the finding of slightly increased salivary sodium and chloride concentrations as well as decreased inorganic phosphate concentration suggest that salivary gland acinar secretion and duct modification mechanisms are impaired by cancer chemotherapy (Jensen et al. 2008a). The concentration and output of secretory IgA has been found to decrease both during and following chemotherapy (Harrison et al. 1998; Jensen et al. 2008a; Laine et al. 1992; Main et al. 1984; Meurman et al. 1997a) and the concentration of lysozyme to decrease after chemotherapy (Meurman et al. 1997a). The salivary peroxidase system is impaired during chemotherapy due to a lower concentration of thiocyanate and its oxidised form hypothiocyanite with antibacterial properties (Mansson-Rahemtulla et al. 1992). Findings on saliva pH and buffer capacity are inconsistent and have been shown to decrease, be unchanged or with regard to buffer capacity even be increased in response to cancer chemotherapy (Avsar et al. 2007; Jensen et al. 2008a; Nemeth et al. 2014; Pajari et al. 1989; Schum et al. 1979). Thus, salivary gland hypofunction, changed composition and reduced output of antimicrobial substances may impair the oral host defence against microorganisms, thus individuals in cancer chemotherapy may be more susceptible to oral infections.

Radiotherapy (RT) of tumours in the head and neck region often includes the major and minor salivary glands in the radiation field depending on the anatomical location and the extension of the tumour. RT can cause severe salivary gland hypofunction (Jensen et al. 2003, 2010). The severity of salivary gland hypofunction depends on the volume of salivary gland tissue included in the radiation field and on the total radiation dose (Vissink et al. 2010). RT targets cells with a rapid mitotic turnover like tumour cells and damages the DNA thereby leading to cell death. Acinar salivary gland cells are radiosensitive in spite of their slow mitotic turnover (Berthrong 1986), and the serous cells appear to be more sensitive to radiation than the mucous ones (Kashima et al. 1965). Radiation damage to the salivary glands may be seen as early as 1 week after initiation of RT (Dreizen et al. 1977) and results in both acute and long-term effects characterised by reduced saliva flow rates, high saliva viscosity and changes of saliva composition. During RT, saliva flow rates decrease and may even reach immeasurable levels (Vissink et al. 2010). With decreasing flow rates, the salivary pH drops and the buffer capacity decreases both during and after RT (Jensen et al. 2003; Valdez et al. 1993). RT also affects the salivary antimicrobial components. The salivary concentrations of IgA and IgG, lactoferrin, lysozyme and peroxidase have been shown to increase during RT due to acute tissue destruction, but after RT they decrease due to reduced functioning of the glands (Brown et al. 1976; Jensen et al. 2003; Makkonen et al. 1986). In the long term, recovery of salivary gland function is dependent on the total radiation dose that the tissue has received. Thus, saliva flow rates may remain severely decreased, and the compositional changes may persist in response to the decrease in saliva flow rates (Jensen et al. 2003, 2010). The standard therapeutic radiation dose for head and neck carcinoma amounts to a total dose of 60–70 Gy. The major salivary glands may have the potential to gradually recover within 1–2 years if gland-sparing radiation regimens have been applied, for example, intensity-modulated radiation therapy, and if it has been achievable to keep the radiation dose to the gland tissue below thresholds of ~26 Gy to the parotid gland and ~39 Gy to the submandibular gland (Murdoch-Kinch et al. 2008; Vissink et al. 2010). A compensatory increase in saliva flow rate from salivary glands not included in the radiation field may be seen (Eisbruch et al. 2001).

The most common cause of salivary gland dysfunction is the intake of prescribed medications (Handelman et al. 1986; Närhi et al. 1992; Smidt et al. 2010, 2011; Villa et al. 2015; Österberg et al. 1984). Xerostomia is a common complaint, especially in elderly people above the age of 65 years, and is often reported as an adverse effect of medications. The prevalence is ranging from 11 to 72 % (Smidt et al. 2011; Desoutter et al. 2012). Xerostomia is defined as the subjective feeling of oral dryness (Fox et al. 1987; Shetty et al. 2012), and salivary gland dysfunction denotes changes in the quantity and/or quality of saliva (Villa et al. 2015). More than 75 % of adults aged 65 and older take at least one prescription medication (Chrischilles et al. 1992; Smidt et al. 2010). Xerostomia has been associated with 80 % of the most commonly prescribed medications, and several of them have adverse effects directly on the mechanisms responsible for saliva secretion (Smith and Burtner 1994; Sreebny 2010; Smidt et al. 2011; Villa et al. 2015; Aliko et al. 2015). Regardless of the type of medication, saliva flow rates have been shown to decrease as the number of medications increases also known as polypharmacy (Thorselius et al. 1988; Närhi et al. 1992; Smidt et al. 2010). Xerostomia is not only associated with a decrease in the salivary flow rate, it may also be attributed to a change in quality of the saliva (Crogan 2011; Ekström et al. 2012; Tabak 1995). The duration of medication intake also affects the saliva flow rates and the prevalence of xerostomia (Navazesh et al. 1996; Thomson et al. 2006). Navazesh et al. (1996) found that unstimulated and stimulated whole saliva flow rates were significantly lower in adults who had been taking medication for more than 2 years as compared to those who had been taking medication for less than 2 years.

The mechanisms by which medications can influence salivary secretion and cause salivary gland dysfunction are complex, and this is also reflected in the variation and severity of oral complications. It is believed that medications can interact with the salivary secretory reflex at several sites (Ekström et al. 2012; Proctor 2015; Sreebny 2010; Villa et al. 2015). Thus some medications act at the level of the central nervous system such as antidepressants (both tricyclic and non-tricyclic), opioids, sedatives, anxiolytics and decongestants (pseudoephedrine). Also antihypertensives acting on central alpha-2 adrenergic receptors (e.g. clonidine) have been shown to reduce salivary secretion in humans (Proctor 2015; Sreebny 2010). Other medications like anticholinergics for overactive bladder, antiemetics, tricyclic antidepressants, serotonin reuptake inhibitors, certain neuroleptics, antihistamines and antihypertensives (alpha-1 adrenergic and beta-adrenergic blocking agents) are acting at the peripheral level of the neuro-glandular junction interfering with cholinergic muscarinic (M3), adrenergic, peptidergic and/or histaminergic receptor systems (for reviews Proctor 2015; Sreebny 2010). Antidepressants, i.e. inhibitors of serotonin and noradrenaline transporters responsible for reuptake, appear to cause salivary gland dysfunction through activation of alpha-2 adrenergic receptors by elevating endogenous levels of noradrenaline. Both centrally and peripherally acting medications include tricyclic antidepressants, the serotonin reuptake inhibitors, some neuroleptics and antihistamines (Clemmesen 1988; Del Vigna de Almeida et al. 2008; Hunter and Wilson 1995; Proctor 2015; Sreebny 2010). Furthermore, some medications like diuretics indirectly influence the salivary secretion by affecting the electrolytes and water homeostasis (Nederfors et al. 1989). Finally, a large number of factors influence the effect of medications on salivary secretion, such as the dose and the absorption and excretion rates of the drug as well as drug interactions (Del Vigna de Almeida et al. 2008).