**4. Causes of xerostomia**

The most severe conditions with effect on the salivary flow are SS and radiotherapy in the head and neck area, with the prevalence of xerostomia in almost 100% in these cases. These conditions are characterized by a progressive loss of secretory cells, and thus a progressive decline in saliva production [36, 37]. Less severe conditions may be dehydration, smoking, and inflammation or infection of the salivary glands [12]. In older people, the most common cause of xerostomia is the use of medications because the vast majority of the elderly are being treated with at least one drug that causes salivary hypofunction [32]. A summary of the main causes of xerostomia can be seen in **Table 2**.

## **4.1. Aging**

**3. Diagnosis of xerostomia**

18 Salivary Glands - New Approaches in Diagnostics and Treatment

and burning sensation, and others [26].

diseases of the salivary glands.

The objective of the diagnosis is to provide treatment as early as possible, thus minimizing side effects in patients suffering from xerostomia. In order to establish a diagnosis of xerostomia, a clinical history is essential to identify the possible etiological factors [24]. It is necessary to investigate its causes. Thus, three orders of factors need to be known: the occurrence of systemic diseases, medication, and the history of radiation therapy. Questions are asked to the patient, trying to find out if he feels the dry mouth sensation, whether he needs to wet his mouth, if he can eat a wafer without drinking water, if the tongue chews the food and clings to the teeth, and the daily water intake daily among other issues [24, 25]. The qualitative clinical diagnosis of xerostomia is made through the observation of clinical signs such as palpation of the salivary glands, observation of the oral mucosa and its hydration, cracked lips, saliva under the tongue, appearance and texture of saliva, the identification of caries, candidiasis

Several methods have been developed to evaluate the level of dryness of the mouth, the discomfort being the most used: sialography, sialochemistry, sialometry and scintigraphy, salivary gland biopsy, ultrasound, magnetic resonance, and computed tomography [19]. Sialography is a technique of imaging that involves the injection of a retrograde form of radiopaque material into the salivary duct system in order to define the anatomy of the glands. This test is very important to demonstrate the presence of nodules or sialectasis, but it has its disadvantages, such as: the difficulty of the technique, since it is invasive and the patient can react acutely or chronically with the contrast material. The biopsy of the major or minor salivary glands allows the detection of inflammatory infiltrations, acinar destruction and dilation of salivary channels with thick mucus, and sometimes fibrosis [27]. Ultrasound, magnetic resonance, and computed tomography are tests that may also contribute to the diagnosis of

To establish the condition of the symptom or to evaluate a possible salivary glandular dysfunction, the most used mechanisms are the questionnaire of xerostomia developed by Fox et al. [11, 28] and the determination of salivary flow rate. Sialometry and scintigraphy (an imaging diagnostic method of nuclear medicine that allows the study of the physiology of the various organs) are complementary tests that must be performed in order to evaluate the involvement of the salivary glands in patients with xerostomia. Sialometry is a relatively common procedure in normal clinical practice and include determination of stimulated salivary flow rate (s-SFR), unstimulated salivary flow rate (u-SFR), palatal secretion (PAL), and parotid secretion (PAR). These measurements are the simplest methods of evaluating the salivary glandular function. It is essential to measure the salivary flow, that is, the amount of saliva produced per unit of time. Very low unstimulated and stimulated salivary flow rates or hyposalivation are defined as <0.1 and <0.7 mL/min, respectively [7]. At rest, secretion ranges from 0.25 to 0.35 mL/min and is mostly produced by the submandibular and sublingual glands [29]. Under stimulation, the parotids account for 50% of salivary volume [30]. Determining the stimulated and unstimulated salivary flow is a procedure to measure the amount of saliva it produces a person at a given time. Generally, the stimulated salivary flow is measured for 5 min and unstimulated salivary flow is measured for 15 min [31]. This The reduced salivary flow is commonly seen in the aging populations. This can be attributed to either age-related localized degeneration of salivary glands or systemic diseases [38, 39]. As the patient ages, the organs atrophy and often result in a decrease in salivary production. It was described that in older people the loss was about 30% of acinar cells, with substitution of secretory components by fibrous and adipose tissue [40]. Besides, there are changes in salivary levels of potassium, sodium, IgA, proline-rich protein, lactoferrin, and lysozyme in elderly [28, 40]. A reduction in salivary flow of older people was identified, even in those not using systemic drugs, suggesting a relation between salivary dysfunction and aging [41]. Smith determined that a stimulated salivary flow in healthy adults older than age 70 is lower than in adults under 50 [42].


**Table 2.** Systemic diseases and other causes of xerostomia.

#### **4.2. Drugs**

The most common cause of xerostomia is the use of some systemic medications [43]. Several drugs are able to induce hyposalivation and xerostomia, but they rarely cause irreversible damage to the salivary glands. Over 400 medicines, many of them in common use, induce salivary gland hypofunction [44]. Some examples are: anxiolytics, anticonvulsants, antidepressants, antiemetics, antihistamines, antiparkinsonian, antipsychotics, bronchodilators, decongestants, diuretics, muscle relaxants, analgesics, sedatives and anti-hypertensives, and others (**Table 3**) [29]. The exact mechanisms whereby some drugs determine xerostomia or hyposalivation are still unknown. Salivary dysfunction associated to drugs may occur through anticholinergic, cytotoxic action, sympathomimetic, or by damaged ion transport pathways in the acinar cells [39, 45, 46]. Patients who consume a higher number of daily medications have been associated with complaints of xerostomia [47, 48]. The therapeutic and controlled doses of medications do not damage the salivary gland structure. For that reason, drug-induced xerostomia is reversible. The discontinued use of these drugs can restore salivary flow [49].

treatment of cancer [11, 50]. The effects of radiation are dose, time, and field dependent. When the damage of salivary glands by radiation happens is severe [39] permanent gland damage can be expected if the radiation exposure exceeds 50 Gy [50, 51]. Other systemic conditions that also affect the salivary flow are autoimmune diseases (SS, rheumatoid arthritis, AIDS, systemic lupus erythematosis, and scleroderma), neurological disorders (Parkinson's), psychogenic illness such as depression and hormonal disorders (thyroid dysfunction and diabetes mellitus) [9]. Regarding diabetes, we will refer more deeply about it since it is the most frequent metabolic disease in the world and the trend demonstrates that it continues to grow. Both diabetes mellitus (DM) type 1, as type 2 have been associated with xerostomia. In diabetic subjects were shown that salivary flow was significantly lower than in nondiabetic subjects [49]. The causes of low salivary flow may be due to direct injury in the gland parenchyma, changes in the microcirculation to the salivary glands, glycemic control disorders, and dehydration. Some studies consider that this decrease in salivary flow in diabetic subjects is related to an increased diuresis or polyuria, involving a decrease in extracellular fluid and consequently in saliva production [10]. Others explain this as a consequence of dehydration from glycosuria that would be more evident in cases of metabolic decompensation [52]. Regarding neurological diseases, studies have demonstrated that the salivary flow is lower in Parkinson's disease patients. This phenomenon could contribute to dysphagia, which affects up to 75% of patients with this disease [53]. Autonomic dysfunction could explain the decrease in salivary flow in subjects with this disease and the drugs used to their treatment could increase the problem [54]. One of the diseases most associated with a xerostomia is SS, a condition that involves dry mouth and dry eyes and that may be accompanied by rheumatoid arthritis or a related connective tissue disease. The oral manifestations observed in this disease are attributed to the involvement of the salivary glands, which leads to a decrease in salivary secretion [31, 39]. Patients with depression can have hyposalivation medication-induced. However, xerostomia may be of psychological origin. A study observed that subjects with a subjective sensation of dry mouth were significantly more depressive than non-depressive subjects [55]. Another study indicates the

Xerostomia: An Update of Causes and Treatments http://dx.doi.org/10.5772/intechopen.72307 21

possibility of depression as an underlying factor of the sensation of dry mouth [56].

Patients with xerostomia may have oral and dental consequences. Xerostomia can seriously impact quality of life and may alter speech, eating, and swallowing [13]. The most common complaints of patients with xerostomia include oral discomfort, difficulty speaking, dysphagia, dysgeusia (decreased taste), feeling of thick saliva, and generally, chewing issues, dental caries, dental demineralization, periodontal disease, salivary gland infection (sialodenitis), oral microflora alterations, burning sensation, mucosal inflammation, sore throats, hoarseness, ulcerations, halitosis, mucosal dehydration, reduced lubrication, painful tongue (glossodynia), enlarged parotid gland, oral mucosal fracture, inflammation and fissures of the lips (cheilitis). The reduction of rates of elimination of substances can affect the palate and be associated with changes in the mouth microbiota. The reduction of rates of elimination of substances can affect the palate and be associated with changes in the mouth microbiota. From the mouth, alterations of taste and intolerance to acidic or spicy foods, dry foodstuffs like biscuits can be very uncomfortable for them, and oral cavity examination may exhibit signs such as fissures on the tongue and

**5. Consequences of xerostomia**

#### **4.3. Systemic conditions**

Xerostomia or hyposalivation may be caused by local factors, including salivary gland disease (sialadenitis) or salivary gland destruction associated with head and neck irradiation for the


**Table 3.** Medicines and drugs with side effects on salivary secretion.

treatment of cancer [11, 50]. The effects of radiation are dose, time, and field dependent. When the damage of salivary glands by radiation happens is severe [39] permanent gland damage can be expected if the radiation exposure exceeds 50 Gy [50, 51]. Other systemic conditions that also affect the salivary flow are autoimmune diseases (SS, rheumatoid arthritis, AIDS, systemic lupus erythematosis, and scleroderma), neurological disorders (Parkinson's), psychogenic illness such as depression and hormonal disorders (thyroid dysfunction and diabetes mellitus) [9]. Regarding diabetes, we will refer more deeply about it since it is the most frequent metabolic disease in the world and the trend demonstrates that it continues to grow. Both diabetes mellitus (DM) type 1, as type 2 have been associated with xerostomia. In diabetic subjects were shown that salivary flow was significantly lower than in nondiabetic subjects [49]. The causes of low salivary flow may be due to direct injury in the gland parenchyma, changes in the microcirculation to the salivary glands, glycemic control disorders, and dehydration. Some studies consider that this decrease in salivary flow in diabetic subjects is related to an increased diuresis or polyuria, involving a decrease in extracellular fluid and consequently in saliva production [10]. Others explain this as a consequence of dehydration from glycosuria that would be more evident in cases of metabolic decompensation [52]. Regarding neurological diseases, studies have demonstrated that the salivary flow is lower in Parkinson's disease patients. This phenomenon could contribute to dysphagia, which affects up to 75% of patients with this disease [53]. Autonomic dysfunction could explain the decrease in salivary flow in subjects with this disease and the drugs used to their treatment could increase the problem [54]. One of the diseases most associated with a xerostomia is SS, a condition that involves dry mouth and dry eyes and that may be accompanied by rheumatoid arthritis or a related connective tissue disease. The oral manifestations observed in this disease are attributed to the involvement of the salivary glands, which leads to a decrease in salivary secretion [31, 39]. Patients with depression can have hyposalivation medication-induced. However, xerostomia may be of psychological origin. A study observed that subjects with a subjective sensation of dry mouth were significantly more depressive than non-depressive subjects [55]. Another study indicates the possibility of depression as an underlying factor of the sensation of dry mouth [56].
