From Volume 49, Issue 10, November 2022 | Pages 840-846
Xerostomia is the subjective sensation of a dry mouth. It can negatively impact oral health and quality of life. The underlying aetiology consists of both local and systemic factors. This two-part series aims to comprehensively review the aetiology and oral manifestations involved with xerostomia.
Xerostomia is the subjective sensation of a dry mouth, a common complaint with a variety of causes. Dry mouth is most frequently associated with salivary gland hypofunction, where either the quantity or quality of saliva is altered. In some cases, the perception of dryness can also occur in the presence of normal salivary gland function.
The prevalence of a persistent dry mouth ranges from 1% to 68% of the population,1,2,3 with an increased prevalence in women (~30%) and the elderly (~50%).1 This great variability is due to a lack of global consensus regarding the definition of xerostomia, a lack of standardized assessment tools and outcome measures used in research, as well as the different populations investigated.4
Daily salivary output in a healthy adult is approximately 1.5 litres, of which 90% is contributed from the parotid, sublingual and submandibular glands. The remaining 10% is produced by minor salivary glands.5 At rest, secretion can range between 0.25 ml/min and 0.35 ml/min, which is mostly contributed by the submandibular and sublingual glands.6 When there has been mechanical, electrical and/or sensory stimuli, the secretion rate can increase to 1.5 ml/min.6 The highest volume produced is usually around mealtimes and will reach a maximum peak at around midday, reducing considerably during sleep, following a circadian rhythm.6,7 Studies have suggested that the salivary glands may contain a circadian clock that regulates the amount, type and content of saliva.7,8 Research has shown that clock genes regulate circadian gene expression and, in turn, daily physiological function.8 Abnormalities of clock genes have been found in patients with reduced salivary flow; however, more research is needed to support these claims.8
Saliva plays an important role in maintaining the health of the oral cavity and, while the quantity is important, so is the quality. Each component of saliva has a specific function. The major purposes of saliva include protection of the oral and peri-oral tissues, and the facilitation of eating and speech (Figure 1).6 Therefore, salivary gland hypofunction can have a deleterious effect on a patient's oral health and quality of life.9
There are many causes of xerostomia including disorders of the salivary glands, association with systemic disease and as a medication-related side-effect. As life expectancy is increasing, there will be more people who will be affected by chronic illness and the side-effects that arise from their pharmacological management. The more common causes of xerostomia and salivary gland hypofunction are described below.
Diabetes mellitus (DM) types I and II can result in a reduction of salivary flow rate, particularly when the condition is poorly controlled.10,11,12 Xerostomia caused by DM has been attributed to damage to the gland parenchyma, disturbances in glycaemic control, dehydration and alterations in the microcirculation to the salivary glands.13 Reduced salivary flow rate among patients with DM is one factor that may lead to increased susceptibility to caries and oral infections, especially in cases where the blood glucose is not controlled.13
In the era before effective antiretroviral therapy, decreased salivary flow rates and xerostomia were observed among individuals living with HIV,14 with the prevalence of dry mouth ranging between 7% and 63% depending on the geographic location and populations studied.15,16 Studies demonstrated that the degree of xerostomia was affected by both the immune status of the patient and the presence of other systemic disease.15 Viral loads greater than 10,000 copies/ml correlated with a higher prevalence of xerostomia17 and Navazesh et al18 proposed that CD4+ cell counts also played a role as a risk factor in salivary gland hypofunction. Antiretroviral therapy has also been suggested as a probable risk for decreased salivary flow and hyposalivation, dependent on the number of years of use by the patient.19 Additionally, individuals living with HIV have been shown to have an altered salivary composition as well as enlargement of the major salivary glands.20,21
Xerostomia is a common finding in patients who present with chronic hepatitis C (HCV), with a prevalence ranging between 10% and 35%.22 There have been several studies that suggest an association between HCV and Sjögren's syndrome (SS) supported by more than 250 reported cases.23 A study carried out by Garcia-Carrasco et al indicated a prevalence of 14% of HCV in patients previously diagnosed with primary SS.24 Cross-reactivity between the HCV envelope and host salivary tissue or an immune-mediated stimulation against salivary glands are proposed mechanisms.25 Although salivary gland disorders have been reported as an extra-hepatic manifestation of the infection, further investigations and research is warranted.26
Sjögren's syndrome (SS) is a chronic autoimmune multisystem disease with a range of glandular and extra-glandular manifestations (Table 1).27 It is characterized by lymphocytic infiltration and destruction of the exocrine glands, primarily the salivary and lacrimal glands, which results in the hallmark symptoms of dry eye and dry mouth.28 Dysfunction of the exocrine glands can be encountered alone (primary SS) or in association with a connective tissue disorder (secondary SS), most commonly rheumatoid arthritis or systemic lupus erythematosus.29 There is a well-recognized female predilection with a F:M ratio of 9:1 and patients typically presenting in their fourth to sixth decade of life.30
| Glandular involvement | Salivary | Dry mouth |
| Lacrimal | Dry eyes | |
| Skin | Dry skin | |
| Reproductive system | Vaginal dryness | |
| Respiratory tract | Nasal dryness, dry trachea | |
| Extra glandular involvement | Constitutional symptoms | Fatigue, fever, lymphadenopathy |
| Musculoskeletal | Arthralgia, arthritis, myalgia, fibromyalgia | |
| Dermatological | Raynaud's phenomenon, purpura | |
| Endocrine | Thyroiditis | |
| Pulmonary | Cough, interstitial pneumonitis | |
| Neurological | Cranial neuropathies, peripheral neuropathies | |
| Psychological | Anxiety, depression | |
| Haematological | Anaemia, leukopenia, thrombocytopenia, lymphoproliferative disease |
In addition to dry mouth, salivary gland enlargement is a common feature of SS. This enlargement is generally due to the autoimmune inflammatory process occurring within the gland, or episodes of acute suppurative sialadenitis.31,32 Such swellings can follow a chronic or episodic pattern.29 Gland enlargements, however, may be due to the development of B cell non-Hodgkin's lymphoma, predominantly mucosa-associated lymphoid tissue (MALT) lymphoma.33 It is estimated to occur in approximately 5% of SS patients and therefore, close monitoring with regular head and neck examinations in primary care is essential.33
Systemic lupus erythematosus (SLE) is a systemic autoimmune and inflammatory disease and 75% of patients experience oral complaints, including xerostomia.34 The reduction in salivary flow seen in SLE can be either as a result of the multisystem nature of the disease or secondary to SS.35 The medical management of SLE, in addition to the systemic nature of the disease have been suggested to contribute to the decline in salivary gland function.34
Chronic graft-versus-host disease (GVHD) is a complication of allogenic haematopoietic stem cell transplant. In such patients, 90% have oral manifestations including salivary gland dysfunction.36 The severity of the oral manifestations is associated with the severity of the disease.37 One of the distinctive oral features of GVHD is xerostomia.37 Salivary gland dysfunction and reduced salivary flow rates related to GVHD are important as early diagnosis can lead to more effective management of the dry mouth complications.38 Complications, such as higher susceptibility to secondary infections, are essential to overcome early in such patients in order to maintain oral homeostasis.38
IgG4-related disease is a fibro-inflammatory condition. It can affect organs such as the salivary glands, pancreas, lymph nodes and retroperitoneum, as well as orbital and peri-orbital tissues.39 Localized or diffuse swelling presenting in various organs as well as an elevated serum IgG4 concentration are characteristic of the disease.39 Although the underlying mechanism is not fully established, it is believed to be a reactive rather than primary disease.39 The salivary glands are involved in 27–53% of patients and often present clinically as bilateral and painless swelling of the salivary glands, which can persist for more than 3 months.40,41
Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology that frequently involves the salivary glands, leading to xerostomia and bilateral parotid swelling in one-third of patients.42,43 There is a limited number of documented cases, and oral involvement usually presents in patients who have chronic multisystemic sarcoidosis.44
Xerostomia is one of the most common oral manifestations in Parkinson's disease (PD) affecting approximately 55% of patients.45 Clifford and Finnerty carried out a survey that showed patients with PD experienced xerostomia twice as often as the general population.46 Xerostomia can occur as a result of an early autonomic manifestation, or as a result of xerogenic medications.47 This is particularly important for dentists as PD's detrimental impact on oral health means that patients are at an increased risk of developing caries, periodontitis and tooth loss, especially as they experience more difficulty with performing routine oral hygiene manoeuvres.48
Oral dysaesthesia (burning mouth syndrome) is a chronic pain disorder that is characterized by burning, stinging, itching and altered/phantom taste in the oral cavity.49 Often, oral dysaesthesia is accompanied by symptoms of xerostomia.50 It occurs in the absence of any organic disease. Although the exact aetiology has not been confirmed, oral dysaesthesia has been shown to have a clear predisposition to peri-/post-menopausal women, and can be secondary to thyroid disease, psychiatric illness, oral infection, medication intake and vitamin/mineral deficiencies.51,52
End-stage renal disease (ESRD) affects 1.8 million patients worldwide and includes those on treatments such as haemodialysis, peritoneal dialysis or who have had a transplant.53 The dialysis treatment that these patients receive can lead to systemic changes and oral complications, including changes in salivary flow rate and composition, causing xerostomia.54 Mansourian et al found that xerostomia (4.3%) was the most prevalent oral manifestation in kidney transplant and haemodialysis patients.55 It is important to be mindful of precipitating oral manifestations in haemodialysis patients, as every effort should be taken to prevent bacteraemia and consequent complications.54
The most common causes of dry mouth can be attributed to medication-related xerostomia. Medication-induced salivary gland dysfunction may be a result of medications acting either on the central nervous system and/or at the neuroglandular junction.56 There are several mechanisms that can lead to drug-induced xerostomia with anticholinergic and sympathomimetic actions being the two principal mechanisms. Several types of receptors, including muscarinic acetylcholine receptors, exist in salivary glands, which may be affected by many anticholinergic drugs.57,58 Medication may also affect adrenoceptors in the frontal cortex of the brain. This can, in turn, produce an inhibitory effect on salivary nuclei resulting in xerostomia.59
A wide range of medications can give rise to xerostomia. Table 2 outlines a list of medications to aid practitioners when taking a medical history to anticipate that patient may be experiencing a dry mouth.
| Antidepressants | TCA | Amitriptyline |
| SSRI | Citalopram, fluoxetine, sertraline | |
| SNRI | Venlafaxine | |
| Antihistamines | Loratadine | |
| Antihypertensives | ACE inhibitor | Ramipril |
| Beta blocker | Atenolol | |
| Calcium-channel blocker | Verapamil | |
| Diuretics | Furosemide, spironolactone (bendroflumethiazide) | |
| Anti-cholinergic | Atropine/oxybutynin | |
| Benzodiazepines | Diazepam | |
| Opiate analgesics | Codeine, morphine | |
| Antipsychotics | Typical and atypical | Quetiapine, chlorpromazine, lithium, risperidone |
| Anti-epileptics | Narrow- and broad-spectrum AEDs | Sodium valproate, gabapentin, pregabalin |
SSRI: selective serotonin re-uptake inhibitor; SNRI: serotonin–norepinephrine re-uptake inhibitor; TCA: tricyclic antidepressant; ACE inhibitor: angiotensin-converting enzyme inhibitor; AED: anti-epileptic drug.
The types of medications that have been shown to be most commonly implicated in salivary gland dysfunction are those that act on the respiratory, musculoskeletal, genitourinary, cardiovascular and nervous systems.59 It is important to note that certain medications, for example lithium, which is used commonly in the treatment of bipolar disorder, can have side effects including excessive thirst (polydipsia) in 70% of patients. This can be mistaken for xerostomia.60 There can be a late onset of the symptoms after starting the medication, which are often dose dependent.59 A dry mouth is likely to resolve once the medication is stopped; however, it has been shown to persist in some patients.59 Polypharmacy and the synergistic effects of combinations of medications have shown to increase the risk of drug-induced xerostomia, which as a result is increasingly common in the elderly.61 In some circumstances, substituting medications may help to reduce the adverse effects leading to xerostomia if similar medication is available.58
The effects of head and neck irradiation for the treatment of cancer are dose, time and field dependent. Radiation exposures equal to or exceeding 52 Gy, can lead to permanent salivary gland damage and dysfunction.62 Radiotherapy for cancers of the oral cavity often involve doses up to 70 Gy and are typically given alongside chemotherapy treatment, which can have damaging effects on saliva production.63 Owing to the impact this can have on patients, the application of 3D conformal radiation therapy (D-CRT) and intensity-modulated radiotherapy (IMRT) has been introduced to improve organ preservation and maintain the patient's quality of life.64 The use of IMRT has meant that a higher dose can be delivered to specified target volumes while reducing the dose to adjacent tissues and structures, and thus lowering the risk of potential side effects.64
Stress, anxiety and depression are physiological causes of dry mouth with no functional loss of saliva. Salivary cortisol levels have been shown to increase during stress, which can lead to changes in saliva composition.65 A similar study conducted by Hugo et al showed that stress could result in salivary gland hypofunction.66 Borahan et al also showed that depression plays a significant role in the reduction in salivary flow rate and xerostomia.65 It may be common that patients, especially those who are anxious about attending for their appointments report this, or it may be noticed during a clinical examination.
Patients who breathe primarily from their mouths can cause the oral mucosa to dry out. This is particularly true for those complaining that their dryness is worst on waking.67 These patients are unlikely to report problems during eating or speaking as there will be no loss of salivary gland function.68
Patients with xerostomia may present with a number of clinical features in practice, of which dentists are the first-line health professionals to be confronted with the problem. It is important to recognize and intervene early to prevent further complications, and reduce the impact on the patient's quality of life.
An important consequence of hypo-salivation is an increase in the risk of caries owing to higher levels of cariogenic bacteria (Streptococcus mutans and Lactobacilli), which may be present as a result of poorer buffering capacity. Secondary root caries is most commonly associated with severe xerostomia.68 In one study, 70% of patients who reported having a dry mouth had at least one carious lesion compared with only 56% of those who did not report a dry mouth.68
There is an inverse relationship between salivary flow rates and Candida albicans counts in saliva that can result in clinical signs of candidiasis, including acute pseudomembranous candidiasis, median rhomboid glossitis, denture-associated stomatitis and angular cheilitis.68 Therefore, patients presenting with xerostomia are at a higher risk of developing candidal infections (Figures 2 and 3).68
Furthermore, patient's who wear dentures may present with a higher number of Candida and Staphylococci species that can result in denture-related stomatitis appearing as redness of the mucosa beneath the limitations of the denture.68
Kleinberg demonstrated that over a longer term, a reduction in salivary flow and overall lower pH could potentially result in a shift in oral microflora leading to a higher proportion of acidogenic microbial composition.69 This is in line with the belief that the presence of xerostomia can aggravate a pre-existing malodour, when in some circumstances, there would have been little or no malodour present.69 According to Yaegaki and Coil's classification, this would place such patients in the ‘pseudo-halitosis’ category.69 However, the reduction in salivary flow can lead to a higher accumulation of bacteria on mucosal surfaces, which can in turn increase the likelihood halitosis in some patients.69
Patients who wear dentures may experience an increase in food or debris building around their dentures or difficulty with controlling their dentures as a result of limited or poor suction caused by the absence or reduction of saliva.
Patients who have very sparse or thick saliva may experience or complain of difficulty with swallowing certain dry foods, speaking due to the tongue adhering to the palate or the lips sticking together as a result of poor lubrication, and alteration in taste as a result of altered salivary flow and concentration.
When the production of saliva is reduced to approximately half its normal levels, especially that of resting saliva, a sensation of dry mouth will ensue.5 Burning, tingling, soreness and redness of the tongue are all signs alongside the sensation of dry mouth, which are evident in patients with xerostomia. As well as the deterioration in oral health, xerostomia can affect nutrition and therefore have subsequent negative effects on general health.
Patients who experience a chronic dry mouth can be at an increased risk of psychological distress and depression.70
Patients with xerostomia have complained of feeling embarrassed, self-conscious and having difficulty with carrying out daily activities, which, if left unmanaged, can have an adverse impact on their quality of life.70,71,72
Therefore, early diagnosis, effective management as well as patient education and awareness, are crucial to prevent and/or minimize the associated detrimental consequences of the condition.
Understanding the aetiology of xerostomia is a crucial first step towards diagnosis and early intervention in dental patients. Xerostomia has an impact not only on the patient's oral health, but also on their psychological wellbeing and over-all oral health-related quality of life. The implications of dry mouth can lead to a higher risk of potential failures in their restorative management and their motivation to care for their dentition. Therefore, it is important that we both educate and inform our patient's should this become a primary concern.
