The basis of knowledge for this article is to highlight the etiology, symptomatology, assessment and management of Xerostomia. Xerostomia, often described as mouth dryness, is a perceived sensation of a dry mouth or oral morbidity either subjectively or objectively depending on the etiology of the condition. Majority of Xerostomia patients have a significant measurable reduction in the amount of saliva in their mouths, a related condition known as Salivary gland hypo-function (SGH) or hypo-salivation, which is an objective evaluation of a reduction in the amount of saliva or rate of flow from salivary glands. Therefore, the two conditions are often used interchangeably or in tandem. However, not all patients with xerostomia will have hyposalivation, some patients have the feeling of a dry mouth (subjective xerostomia) without actual decrease in saliva. There are both primary causes, from local or systemic diseases, such as Sjögren’s syndrome, Diabetes, HIV/AIDS, or secondary causes from side effects from medication like anticholinergic, diuretic drugs and treatments from radiotherapy. The aim of the article is to present organized scientific and medical literature and studies based on accurate rules of evidence and relevant validity. Among the issues highlighted include the importance of saliva in oral healthcare and the implications of lack thereof; the etiology of xerostomia and the health repercussions of the condition; and the proposed treatment modalities for mouth dryness such as saliva stimulants and substitutes, with particular focus on NeutraSal treatment. The considerations for research literature was identified through the PubMed search engine and Medline medical literature database for journal articles, relevant textbooks and medical review articles and handbooks highlighting studies on xerostomia or clinical trials on xerostomia patients. From the literature review, it was established that there are differential established protocols for treatment depending on etiology and severity of xerostomia. The treatments are predominantly preventive and palliative (Villa et al, 2015).
Key words: Xerostomomia, Neutrasal, hyposalivation, etiology, saliva substitutes
Xeorostomia denotes the subjective or inherent feeling of mouth dryness with some patients describing the condition as a ‘parched-like’ feeling, roughness or lack of taste sensation. There is evidence of a relationship or correlation of the condition to quantitative or qualitative alteration in saliva in the mouth due to salivary secretion hypofuntion or reduction in flow rate. However, Xerostomia can still occur even when salivary glands are functioning normally. Regarding etiology of Xerotostomia, there is an association of the condition with systemic disorders such as Sjögren’s syndrome, diabetes, rheumatoid arthritis and HIV/AIDS. Individuals suffering from anxiety, stress and depression may also exhibit symptoms related to mouth dryness. Additionally, studies have shown that there is a likely occurrence of transient Xerostomia as a side effect of certain prescribed medications and treatments. Several studies highlighted radiation therapy of head and neck cancer malignancies as one of the major risk factors for Xerostomia. Based on severity, Xerostomia can be classified as either acute or chronic. An analysis of the epidemiology of Xerostomia revealed that it is a common condition primarily because it is often diagnosed as a symptom of underlying disorders. According to (Tanasiewicz, Hildebrandt, & Obersztyn, 2016), the reported prevalence of xerostomia in a particular population ranges from 10 to 47%, with increased prevalence in females and the elderly up to 35% and 50 % respectively. In addition, there is a common misconception that Xerostomia affects elderly people only when in reality it can affect individuals of any age.
2.0. Literature review
The literature review is a collective summary of articles, textbooks and studies that have accrued relevant knowledge on Xerostamia and the administration of NeutraSal for its treatment. The review begins with a brief analysis of normal physiological processes of salivary mechanism exploring the components and functions of saliva and salivary glands. Thereafter, focus will shift to presenting a practical, concise and evidence-based approach to identifying the etiology of Xerostomia and related hyposalivation, and the treatment and management of the condition.
2.1. Saliva, its components and functions for oral homeostasis
Saliva is a complex exocrine secretion composed of several components which altogether maintain normal oral homeostasis and facilitate oral, pharynx and esophageal health. There are three main pairs of salivary glands, which are sublingual, submandibular and parotid. There are additional minor glands all over the mouth. Saliva consists of 90% water and biochemical constituents that include, enzymes (salivary amylase), electrolytes, proteins and anti-microbial components such as lysozyme, mucin etc. Each constituent in saliva serves a specific function such as regulatory, digestive and protective functions. These include, facilitating speech; improving taste; food lubrication and irrigation for swallowing; protection through buffering the teeth or antimicrobial activity against potential oral infections. Owing to these important functions, it is clear that a dry mouth can result in severe effects which can be burdening for an individual. Some of the effects are, lack of or impaired taste sensation and speech, susceptibility to oral infections such as oral candidiasis, dental problems, chewing and swallowing (Epstein and Jensen, 2015).
2.1.1. Saliva flow rate and compositional change
It is important to consider change in production, flow rate or compositional change of saliva for the diagnosis of objective Xerostomia where all these oral mechanisms are hampered. There are differential measures in literature regarding assessment and diagnosis of Xerostomia. In most studies, the evaluation of saliva and salivary glands is one of the key methods for diagnosis. A deviation from normal function consequently leads to reduction in the amount of saliva in the body (hyposalivation) which is what causes the mouth dryness. Therefore, essentially, in the diagnosis of xerostomia, requires an investigation of saliva content except in cases where the sensation of mouth dryness is a perception without actual reduction in saliva or impairment of salivary glands. Under normal and healthy conditions, the average adult produces approximately 800mLto 1 liter of saliva a day, the excess of which is produced by the submandibular gland (65%), while the rest is produced by the parotid, sublingual and minor glands in the mouth. Salivary flow rate is used to provide information on the functioning of salivary glands. Even though flow rates vary for different individuals, Epstein and Jensen, (2015) classified salivary flow rate as either normal or stimulated where normal unstimulated salivary flow rate averages 0.2 to 0.4 mL/min while the stimulated flow rate averages 1 to 3 mL/min. According to Plemons et al., (2014), a stimulated flow rate of 0.4-0.8 mL/min and unstimulated flow rate of below 0.1 mL/min signifies a deviation from normal and implies a diagnosis for hyposalivation and potential xerostomia. Upon determination of objective hyposalivation, diagnosis of xerostomia is determined when the cumulative rate of fluid absorption and the rate of fluid evaporation across the oral mucosa undermines the rate of saliva flow from the salivary glands. In simple terms, this means that all the saliva produced is absorbed and evaporated from the mouth at a faster rate than the salivary glands can produce saliva. A study by (Villa, Connell, & Abati, 2014), found that both normal and stimulated saliva flow rates reduce with increase in age which explains the conception that xerostomia only occurs in the elderly. A similar finding, by Plemons et al. (2014), explains that there are histological evidence of salivary glandular changes due to increase in age which may hamper normal saliva flow rates. Therefore, there is a common consensus that salivary gland physiology is affected with increased age. Additionally, the study highlights that the submandibular gland is the most affected by age while the parotid gland maintains good functioning capacity because of its susceptibility to physiological permutations. Also, males have larger submandibular gland than female by up to 50% which corroborates the epidemiology statistics that Xerostomia is more prevalent in females than males. Coupled with the age related study on flow rates, Hahnel et al. (2014) found that a reduced salivary flow rate affects the biochemical composition of saliva regarding the output available. These components include, proteins, enzymes- lactate dehydrogenase and amylase, calcium, phosphorus, IgA, chloride, mucin, lysozyme among others.. However, without consideration of flow rate, xerostomia and hyposalivation can still occur a study between xerostomic patients and a corresponding control group of non-xerostomic individuals indicated that higher levels of these components were discovered in the salivary composition of patients with Xerostomia. Ultimately, the decrease in the available components of saliva leads to adverse consequences such as oral disorders which are usually indicative symptoms of Xerostomia.
As mentioned, hyposalivation is an objective measurement of salivary flow rate. Hyposalivation and Xerostomia are often used interchangeably because the diagnosis of hyposalivation in most literature significantly overlaps with that of Xeorstomia. The manifestation of signs and symptoms of Xerostomia result when salvia flow rate is reduced by 50% which in most cases a diagnosis of hyposalivation has already been established (Plemons et al., 2014)
2.2. Etiology of Xerostomia
There is wide variability in literature regarding the defining dimensions for Xerostomia and whether there exists a distinction between hyposalivation and xerostomia. Epstein and Jensen (2015), classifythe causes of xerostomia into three distinct causative categories; primary or direct causes, secondary or indirect causes and non-salivary causes.
2.2.1. Primary causes
These are systemic conditions or disorders which result in impairment of salivary glands either reversibly or irreversibly depending on histopathology findings, whichsubsequently alters the production of saliva. The most common disease associated with Xerostomia as a result of damage to salivary glands is Sjögren’s Syndrome, which is an autoimmune disease characterized by inflammation of exocrine and endocrine glands. The disease affects salivary glands through lymphocytic infiltration that impairs the secretory acinar cells of both major and minor salivary glands in the mouth. Additionally, glandular function can be destroyed by inhibition of nerve stimuli to facilitate production of saliva. In one study (Shannon and Dalonges, 2015), results showed a positive correlation between the duration of Sjögren’s syndrome and the development and severity of xerostomia. There is a variant of Sjögren’s syndrome (secondary) associated with degenerative connective tissue and autoimmune disorders such as Rheumatoid arthritis, Sleroderma or Systemic lupus erythematosus. Both variants of the disease lead to oral and mucosal surfaces-hyposalivation, which eventually develops into xerostomia.An evaluation of the prevalence of Sjögren’s syndrome reveals that 90 % of patients are females, in particular menopausal women.
There are other conditions associated with xerostomia such as endocrine disorders affecting the maintenance of normal body homeostasis like thyroid, adrenal, hepatic and renal disorders; type 1 and type 2 diabetes mellitus; chronic graft-versus host disease (cGVHD); and viral infections like HIV/AIDS and hepatitis C.
About 40 to 80 percent of diabetic patients have experienced diabetes-associated xerostomia, mainly caused by poorly stimulated parotid flow rates or enlargement due to poorly controlled diabetes mellitus. As that, these diabetic patients are susceptible to oral infections such as oral candidiasis, chelitis or denture stromatitis and predisposition to xerostomia is believed to be the reason for these conditions. Salivary compositional changes and gland disease in HIV positive patients with a study prevalence of about 10 to 30%. There are varied clinical features of salivary gland disease due to HIV as documented by Nittayanata et al. (2013), (Hopcraft & Tan, 2013), and (Villa et al., 2014), most of which are as a result of underlying diseases due to HIV infection, e.g. Kaposi sarcoma, intra-glandular lymphadenopathy, non-Hodgkin’s lymphoma, among others, all which have the potential of harming salivary glands.
2.2.2. Secondary causes
These are causative agents or conditions in which hyposalivation and mouth dryness are resulting consequences. These include medication and treatments whose side-effects result in xerostomia. Several studies, reflect the prevalence of radiation-induced xerostomia among cancer patients. It is a common side-effect due to radiotherapy for treatment of head and neck malignancies for radiation therapy administered as primary treatment or adjuvant or concurrent treatment modalities. Of all the salivary glands, the parotid gland is the most susceptible to radiation due to radio sensitivity. Radiation from cancer therapy causes irreversible damage of the acinar cells of salivary glands which could potentially lead to permanent xerostomia. However, the severity of xerostomia is dependent on the radiation dosage administered and degree of exposure of oral tissues to radiation. Practitioners have developed measures to mitigate impairment of salivary function by minimizing the intensity of radiation of therapy using radio-protective agents to provide cyto-protection or through dosage delivery planning and techniques where low dosage is administered systematically. Regarding the role of medication, there is wide consensus over the prevalence of xerostomia due to specific medications and polypharmacy (combinational drug use). According to (Villa et al., 2014), about 500 medications have the potential of causing xerogenic side-effects, that is, mouth dryness and eventual transient xerostomia. Longitudinal studies indicated that xerostomia as a result of side-effects of medication is 90% unstable or temporary with the chance of reversibility upon completion of dosage. This is because the majority of medications only hamper salivary flow rates by causing lack of stimulation of salivary glands by hampering the transmission of signals at the parasympathetic neuron effector junctions that stimulate secretion of saliva without necessarily causing damage to the glands. Several drug types and groups have been associated with xerostomia prevalence such as, anticholinergic, diuretics, cytotoxic, anti-depressants, drugs acting on the sympathetic transmission system such as antihypetensives, among others. In one study,(Hopcraft & Tan, 2013) analyzing the xerogenic effects of combinational drug use, it was discovered that combining different medications with the potential of causing xerogenic effects resulted in a higher prevalence of xerostomia than if the specific drugs were used alone. For example, the administration of thyroxine and a diuretic drug in tandem over a period of five years increased the incidence of patients developing xerostomia than if the drugs were prescribed separately proving that drug interactions can exacerbate the occurrence of xerostomia.
2.2.3. Non-salivary causes
These are psychogenic or psychological causes of xerostomia without the incidence of objective hyposalivation. They include cognitive and psychological disorders such as stress, depression; dehydration; oral dryness while sleeping; nasal problems which leads to mouth breathing or localized dryness of the mouth. Mouth dryness due to these causes are often rectifiable using through fluid intake.
2.3. Clinical Signs and symptoms
In the analysis of studies where afflicted patients documented their experience with the disease through interviews, most patients described xerostomia as a problematic condition with aggravated symptoms. These symptoms include, mouth dryness that leads to a rough or sensitive feeling in the mouth; dental carries or plaques that progress aggressively than usual; lips and tongue sticking together or to their teeth; and reduced saliva which appears frothy and sticky. Additionally, oral disorders may develop as a result, for example oral candidiasis, oral lesions and dental problems. In severe cases, patients may experience limited ability to speak; dysphagia, which difficulty in chewing or swallowing food due to decreased irrigation and lubrication from saliva; and dysgeusia which is alteration in taste sensation, such that patients experience a metallic-like taste.
2.4. Diagnosis and Treatment (NeutraSal)
Due to the rarity in the fact that xerostomia is a subjective symptom and is rarely a primary condition or complaint among patients, it diagnosis across different medical literature is predominantly taken at face value by assessment of clinical signs and symptoms. There is minimal correlation in the diagnosis of xerostomia with the administration of objective tests. However, there are several tests that can be administered to diagnose xerostomia and hyposalivation simultaneously. History and physical examination are the most basic methods for xerostomia diagnosis, where practitioners carry out comprehensive examination of a patient’s oral features, externally and internally, to identify irregularities such as swelling of glands or masses; quality of saliva; and absence of pooled saliva under the tongue and around the mouth. Diagnostic tests include saliva flow measurement referred to as sialometery where stimulated or unstimulated saliva flow is measured over a period of time. Stimulated flow measurement is done by prompting salivary glands to produce saliva through mastication or through stimulation with citric acid and thereafter saliva is collected into a collection tube with consideration of normal stimulated flow rates. Unstimulated saliva flow is analyzed by arching the patient forward to facilitate collection of saliva by draining or drooling. Blood tests as well as serological tests such as oral candida smears or cultures can also be administered especially when xerostomia is suspected to be the symptom of an underlying systemic disease such as the Sjögren syndrome. Finally, x-rays, magnetic resonance imaging and a minor salivary gland biopsy can be carried out to analyze the histological changes or pathology in the salivary glands function.
The treatment of xerostomia depends on the etiology and severity of damage to the salivary glands. As that practitioners use differential treatment modalities encompassing etiology, preventive, stimulative and palliative. The most common approaches are preventive and palliative. Preventive measures are those that eliminate or mitigate the developmentof xerostomia or alleviate its severity. These include treatment of the causes of xerostomia as in systemic disorders or by employing preventive measures such as habits that propagate the occurrence of xerostomia like smoking.Studies show that palliative treatment is often recommended when salivary function is irreversible. These include over-the counter medication such as oral patches, liquid rinses and gels, lozenges, chewing gum, among others. However, if salivary gland function is preserved, salivary substitutes and stimulants can be administered, of which salivary stimulants function better than salivary substitutes because they improve xerostomia symptoms as well as salivary gland function through stimulatory response. Salivary substitutes on the other hand, only relieve the effects of xerostomia symptoms without improving the problems of salivary gland damage. There are two methods of stimulation, local and systemic(Tanasiewicz et al., 2016), with variety of methods like, acupuncture, laser infrared light, electrical and drug stimulation.
NeutraSal is a supersaturated calcium and phosphate powdered medication for stimulating salivary function aimed at restoring ionic balance in saliva and stimulate salivary gland secretion. NeutraSal is dissolved in water and used as a mouth rinse(NeutraSal.com, 2016). Depending on the prescribed dosage NeutraSal can be used to treat xerostomia or hyposalivation as a result of side-effects to medication such as atropine and antihistamines; surgery near salivary glands; psychological or emotional factors like anxiety; obstruction of salivary ducts; and diagnosis of Sjögren’s syndrome. Additionally, (Anderson, 2014) proposes that NeutraSal can be used as an adjunct together with other medication in relieving xerostomia or oral discomfort during chemotherapy as a result of high dose radiation. An investigation of four research reviews that considered the administration of NeutraSal for patients with xerostomia revealed the prevalence of NeutraSal use for patients following radiation therapy for head and neck malignancies. Two of the reviews presented limited evidence on increased salivary function and relief of symptoms (Levin, 2014). The other reviews (Hamker, 2013) and (Shannon & Dalonges, 2015) analyzed treatment using NeutraSal for other causative factors for xerostomia such as medication side effects and systemic diseases. Research showed evidence of improved stimulation of saliva production reduction of xerostomia-related symptoms highlighting the efficacy of NeutraSal in managing xerostomia.
The diagnosis and treatment of xerostamia can be challenging for dentists and related medical practitioners because little attention is directed towards xerostomia as a disease majorly because it is not a primary condition. The conditions of the disease are however severely aggravating and devastating for patients with xerostomia. Therefore, comprehensive evaluation, assessment, diagnosis and treatment methods should be employed to prevent occurrence and severity of the disease. Future research considerations are currently geared towards gene therapy and transplantation to rectify irreversible salivary function.
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Hahnel, S., Schwarz, S., Zeman, F., Schäfer, L., & Behr, M. (2014). Prevalence of xerostomia and hyposalivation and their association with quality of life in elderly patients in dependence on dental status and prosthetic rehabilitation: A pilot study. Journal of dentistry, 42(6), 664-670. doi:10.1016/j.jdent.2014.03.003,
Hamker, J. (2013). Supersaturated Calcium Phosphate Rinse on Oral Mucositis in Head and Neck Patients Receiving Radiation and/or Chemotherapy. International Journal of Radiation Oncology• Biology• Physics, 87(2), S429.
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