XEROSTOMIA: AN OVERVIEW

ISSN 0975-8437

INTERNATIONAL JOURNAL OF DENTAL CLINICS 2011:3(2):58-61

REVIEW ARTICLE

Xerostomia: An overview Nishat S ultana, M. Ehtaih S ham

Abstract Xerostomia is a subjective sensation of a dry mouth which is a co mmon co mplaint among older patients during period of anxiety, radiation therapy, immunological disorder which lead to increased frequency of caries, candida infection, dysarthria and dysphagia. This article presents an overview of the Xerostomia and its management. Key Words: Xerostomia; Sjogrens syndrome; Radiation therapy Received on: 13/08/2010 Accepted on: 13/11/2010 Xerostomia refers to a subjective sensation of dry mouth; it is frequently, but not always, associated with salivary gland hypo function.(1) Xerostomia is a co mmon co mplaint found often among older adults, affecting appro ximately 20 % of the elderly.(2-4) The dry mouth is common during periods of an xiety, mouth breathing and with advancing age. Very rarely, children are born with missing salivary glands so-called salivary gland aplasia or agenesis. The table 1 shows the common causes of dry mouth. Iatrogenic Drugs Local radiation Chemotherapy Chronic graft-versus-host disease Diseases of the salivary glands Sjo¨gren’s syndrome Sarcoidosis HIV disease Hepatitis C virus infection Primary biliary cirrhosis Cystic fibrosis Diabetes mellitus Rare causes Amyloidosis Hemochromatosis Wegener’s disease Salivary gland agenesis (with or without ectodermal dysplasia) T riple A syndrome Others T able 1:Common causes of Xerostomia (5)

Xerostomia is the most common adverse drug-related effect in the oral cavity. To date, xerostomia has been associated with more than 500 med ications. Medications cause xerostomia by interfering with the transmission of signals at the parasympathetic neuro effector junctions, interfering with act ions at the adrenergic neuro effector junctions, or causing the depression of the connections of the autonomic nervous system. Therapeutic doses of medications do not damage salivary gland anatomy and any damage is therefore reversible with discontinued use of

©I NTERNATIONAL JOURNAL OF DENTAL CLINICS VOLUME 3 ISSUE 2 APRIL-JUNE 2011

xerogenic drugs.(6) The drugs causing Xerostomia was tabulated in table 2. Drugs which directly damage the salivary glands Cytotoxic drugs Drugs with anticholinergic activity Anticholinergic agents: Atropine and Hyoscine Anti-reflux agents: Omeprazole Psychoactive agents: Amitriptyline, Dothiepin Selective serotonin re-uptake inhibitors Fluoxetine Others: Phenothiazines, Benzodiazepines, Opioids, Antihistamines Drugs acting on sympathetic system Drugs with sympathomimetic activity Ephedrine Anti-hypertensive: Alpha 1 antagonists: Terazosin, Prazosin Alpha 2 agonists: Clonidine Beta blockers: Atenolol, Propranolol Drugs which deplete fluid: Diuretics. T able 2: Drugs associated with dry mouth (5)

Xerostomia is a common side effect of radiation therapy, when emp loyed as primary, concomitant or ad juvant treatment for primary or recurrent tumors of head and neck. (5) The most radiosensitive salivary gland is parotid g land followed by submandibular, sublingual and minor salivary gland. A radiat ion dose as low as 20 Gy can cause permanent cessation of salivary flo w if given as a single dose. At doses above 52 Gy, salivary dysfunction is severe. Treatment of o ral carcino ma conventionally involves the administration of a dose of 60 Gy to 70 Gy, and this can lead to a rapid decrease in flow during the first week of rad iation, with an eventual reduction of 95%in the region. By 5 weeks of radiation, the flow virtually ceases and rarely recovers completely.(5) The degree of xerostomia depends on the degree of exposure of the salivary tissue to the radiation. To spare salivary function and improve quality of life, salivary gland exposure to radiation can be minimized by utilizing intensity modulated radiat ion therapy and three dimensional treatment planning and dose delivery techniques. A reduction in rad iation induce hypo salivation was

58

ISSN 0975-8437

noted with the use of the radio-protective agent amifostine wh ich provides cyto-protection to salivary glands.(7, 8) Xerostomia is a well-known comp licat ion of chronic graft-versus host disease (cGVHD). A prolonged significant reduction in parotid salivary flow rate correlates with the histopathology findings (ie, fibrosis of glands) and alterat ions in the chemical co mposition of saliva (i.e., a reduced sodium Na _ and raised K_ ion concentration). The squamous epithelium of the oral mucosa and the epitheliu m of salivary glands are affected early in the course of cGVHD but the major salivary functional injury in cGVHD occurs later, with the target of destruction possibly being the muscarinic receptor, water transporter or calcium ions.(9) Levels of diabetes associated xerostomia are reported in upwards of 40 to 80 percent of patients. Stimu lated parotid flow rates are observed to be the lowest in patients with poorly controlled d iabetes mellitus as compared to well controlled d iabetes mellitus. Approximately 24 to 48 pe rcent of diabetes mellitus patients have experienced parotid gland enlargement. Diabetic patients are also predisposed to develop oral candidiasis, med ian rhomboid glossitis, denture stomatitis and angular chelitis associated with denture use and poor glycemic control.it is believed that patient xerostomia is one possible cause for this predisposition.(10) Sjogren’s syndrome (SS) is a chronic mu ltisystem immune-mediated disorder characterized by inflammation of exocrine g lands leading to clinical sympto ms of dryness, particularly of the eyes and mouth, wh ich can be severe and disabling.(5, 11) Primary Sjogren’s syndrome presents in patients that do not suffer fro m another autoimmune disease, arthritic symptoms or degenerative connective tissue disease. Secondary Sjogren’s syndrome present alongside a second autoimmune disorder such as systemic lupus erythematosus (SLE), Rheumatoid Arthritis (RA), Scleroderma, mixed connective disease, relapsing polychronditis and polymyositis. Both primary and secondary forms are responsible for mouth dryness and eye dryness. Chronic Sarco idosis can give rise to xerostomia and salivary gland enlargement in up to 9% of affected patients, often occurring as part of Heerfordt’s syndrome.(12) In a study, the degree of xerostomia and xerophthalmia were similar among a group of patients with Sjogren’s syndrome and a group with Sarcoidosis, whereas parotid gland enlargement was more frequently found in those with Sarcoidosis.(13)



Salivary gland disease can arise in 4% to 8% of adults and children with HIV infection. The principal clinical features of salivary gland disease in HIV infection are as follow: a) associated xerostomia and salivary gland enlargement, b) Kaposi’s sarcoma causing salivary gland enlargement, c) nonHodgkin’s lympho ma and intra glandular ly mphadenopathy; and d) acute supportive sialadenitis.(14) A number of addit ional disease entities may contribute to the presence of xerostomia, either through pathophysiology of the disease process or due to the medications used in treating the disease and its symptoms.(15) Patients with the following disorders should be considered at risk for xerostomia Table 3. Risk factors for Xerostomia(5) 1. AIDS 2. Systemic Lupus Erythematosus 3. T hyroid Dysfunction 4. Parkinson’s Disease 5. Cerebral Palsy 6. Depression 7. Anxiety 8. Post-Traumatic Stress Disorder 9. Dehydration 10. Eaten-Lambert Syndrome 11. T rauma to Salivary Glands 12. Anorexia and Bulimia T able 3

The dental management of patients suffering fro m d ry mouth should begin with thorough patient education and the identification of the underlying cause. Treatment should include local and systemic stimulat ion of salivary glands, palliative treat ment for sympto matic relief, as well as preventing and treating oral co mp licat ions.(7) Patients with dry mouth may stop chewing and reactively modify their diet to a liquid or semi liquid diet rich in fermentable carbohydrates in order to compensate for oral dryness. Decreased mastication exacerbates the condition due to the fact that periodontal mechanoreceptors and mechanical stimulat ion of the oral mucosa and tongue are required stimu late salivation. Consequently, patients should be referred for nutritional counseling to educate them to min imize any negative effects from reactionary d iet alterations.(16) A non-specific mechanical and gustatory stimulant increases salivation; therefore, the use of sugar free gums, hard candies, and mints are highly recommended for the relief of sympto ms in patients with residual salivary capacity.(17) In studies it has been found that xylitol sweetened gums prevent caries develop ment due to limited ability of streptococcus mutants to ferment xy litol.(18) The use of citric acid or candies is

59

ISSN 0975-8437

discouraged due to accelerating caries development.(16) Lifestyle changes available to patients suffering fro m dry mouth to control and prevent dental caries include adhering to a rigorous oral hygiene regimen and non-cariogenic diet. The need for meticu lous plaque control via assiduous oral hygiene is necessary for xerostomic patients. Brushing twice a day with a soft bristle toothbrush and the use of a lo w abrasive, highly fluorinated toothpaste is reco mmended, acco mpanied by a sodium fluoride rinse.(19) Current interest involves the use of fluoride varnishes to prolong the exposure to fluoride an approach that may be beneficial to prevent xerostomia associated caries.(7) Medications are availab le to stimu late the salivation. Prescribing parasympathetic drugs like pilocarpine has been approved for xerostomia patients. Pilocarpine is a potent and naturally occurring nonspecific cholinergic agonist which stimulates muscarinic receptor lead ing to the secretion of water and electrolytes, if the patients has sufficient amount of functional salivary gland tissue. Pilocarpine has also shown to be effective in patients who have undergone radiation therapy or bone marrow transplantation. Initial dose of pilocarpine should be administered 30 minutes before meals, in 5 mg tablets 3 to 4 t imes a day, with the usual dose range being appro ximately 3 to 6 tablets a day, not to exceeds two tablets per dose. Side effects seen in rad iation induced xerostomia patients include sweating, chills, nausea, dizziness, rhinit is and asthenia 5. New modes of delivery are also being researched including loading nanoparticles with pilocarpine.(20) Cevimeline is another cholinergic agonist used to induce salivary function. Reco mmended dosage for Cev imeline is 30 mg, 3 times a day. It is capable of inducing salivation with minimal adverse cardiac and pulmonary effects due to the fact that Cevimeline has a high affin ity for the M3 muscarin ic receptor subtypes found on salivary and sweat gland. However its use in asthma patients or those suffering fro m narrow angle glauco ma is questionable. Animal studies have shown that Cevimeline has adverse effects on the fetus but its use during pregnancy is considered acceptable if the benefits are considered acceptable.(7, 21) Bethanecol found to increase the stimulated and unstimulated salivary flo w rates of patients with xerostomia secondary to radiation, but objective changes in salivary flow rates did not always correlate with symptomat ic improvement. It is given in a dose of 25 mg; 3 times daily orally.(20) Anethole trithione is specifically used to treat Sjogren’s associated xerostomia. It



increases the number of receptor sites on the salivary acinar cells. Patient’s benefits have been reported when Sjogren’s patients were administered 25mg doses 3 times a day. A synergistic effect on salivation has been observed when a co mbination of pilocarpine and anethole trithione has been administered.(22) When a patient complaints of xerostomia and is believed or diagnosed to be a side effect o f a med ication, an alternative medication that does not emp loy the same mode of action may be prescribed. The dentist should consult the patient’s physician and pharmacist if an eliminat ion or change of medicat ion is being contemplated. Patients are urged to coordinate the timing of the dose of necessary medications with meal times to allo w sufficient salivary flo w during the eating process, counteracting the drying effect of these med ications, due to the fact that salivary flow is lowest during sleep the patient should avoid taking medications before bedtime.(16) Patients affected with xerostomia should also increase their fluid intake due to the fact that most people do not drink enough water, contributing to the condition.(16) The patients should be encouraged to place ice chips in their mouth and sip water throughout the day to provide mo isture and possibly provide relief to dry mouth symptoms.(7). For patients with ext remely low salivary flow rates, the use of saliva substitute based on polyacrylic acid and Xanthan gum has been developed and are recommended.(17) Ideal characterizat ion of saliva substitute is that, it should be long lasting, provides lubrication to protect oral tissues as well as impedes the colonizat ion and action of cariogenic bacteria, has not been developed.(16) Salivary substitute tend to be short acting, providing relief for a limited period of time . They are most effective when applied before sleeping or speaking.(7) Acupuncture has been reported to increase parasympathetic activity, causing a release in neuropeptide, stimu lating salivary flo w and secretions. Three points are t reated in each ear, and one in the radial aspect of each index finger.(23) A regimen of three to four weekly treat ments followed by monthly sessions is now recommended, although some patients achieve lasting response without further therapy. Preliminary data revealed that many patients achieve relief, even for sympto ms refractory to pilocarpine therapy. (23) A wide range of systemic therapies have been advocated for the management of long-standing xerostomia . At present, the anticholinerg ic agents

60

ISSN 0975-8437


would seem to hold promise and are appropriate for the treat ment of xerostomia associated with radiation and Sjogren’s syndrome. Future treat ment for so me of the salivary gland disorders may require the use of gene therapy and tissue engineering, but at present there is a need to have a greater understanding of the causes and pathogenesis of salivary gland disease before specific therapies can be developed. Authors Affiliations: 1. Dr. Nishant. S, M DS, Assistant Professor, Dept. of Oral M edicine and Radiology, 2. Dr. M .E. Sham, M D, M DS Professor, Dept. Of Oral & M axillofacial Surgery, Videhi Institute of M edical and Dental Sciences, White Field, Bangalore, India. References: 1. Fox PC, Eversole R. Diseases of the salivary glands. Essentials of Oral M edicine. 2001:260–76. 2. Turner M , Jahangiri L, Ship JA. Hyposalivation, xerostomia and the complete denture: A systematic review. The Journal of the American Dental Association. 2008;139(2):146-50. 3. Astor F, Hanft K, Ciocon J. Xerostomia: a prevalent condition in the elderly. Ear, Nose, & Throat Journal. 1999;78(7):476-9. 4. Cathy L B, Pharm D. Helping patients with dry mouth. Available from: http://oralcancerfoundation.org/ dental/ xerostomia.htm. 5. Porter S, Scully C, Hegarty A. An update of the etiology and management of xerostomia. Oral Surgery, Oral M edicine, Oral Pathology, Oral Radiology & Endodontics. 2004;97(1):28-46. 6. Pajukoski H, M eurman JH, Odont D, Halonen P, Sulkava R. Prevalence of subjective dry mouth and burning mouth in hospitalized elderly patients and outpatients in relation to saliva, medication, and systemic diseases. Oral Surgery, Oral M edicine, Oral Pathology, Oral Radiology & Endodontics. 2001;92(6):641-9. 7. Guggenheimer J, M oore PA. Xerostomia: etiology, recognition and treatment. The Journal of the American Dental Association. 2003;134(1):61-9. 8. Antonadou D, Pepelassi M , Synodinou M , Puglisi M , Throuvalas N. Prophylactic use of amifostine to prevent radiochemotherapy -induced mucositis and xerostomia in head-and-neck cancer. International Journal of Radiation Oncology Biology Physics. 2002;52(3):739-47. 9. Nicolatou Galitis O, Kitra V, Vliet Constantinidou C, Peristeri J, Goussetis E, Petropoulos D, et al. The oral manifestations of chronic graft versus host disease (cGVHD) in paediatric allogeneic bone marrow transplant recipients. Journal of Oral Pathology & M edicine. 2001;30(3):148-53. 10. Chavez EM , Taylor GW, Borrell LN, Ship JA. Salivary function and glycemic control in older persons with diabetes. Oral Surgery, Oral M edicine,

Oral Pathology, Oral Radiology, and Endodontology. 2000;89(3):305-11. 11. Konttinen YT, Kasna-Ronkainen L. Sjögren's syndrome: viewpoint on pathogenesis. Scandinavian Journal of Rheumatology. 2002;31(2):15-27. 12. Drosos A, Voulgari P, Psychos D, Tsifetaki N, Bai M . Sicca syndrome in patients with sarcoidosis. Rheumatology International. 1999;18(5):177-80. 13. Ohtsuka S, Yanadori A, Tabata H, Yamakage A, Yamazaki S. Sarcoidosis with giant parotomegaly. Cutis; Cutaneous M edicine for the Practitioner. 2001;68(3):199-200. 14. Schiødt M . HIV-associated salivary gland disease: A review. Oral Surgery, Oral M edicine, Oral Pathology. 1992;73(2):164-7. 15. Gater L. Understanding xerostomia. Dental assistant. 2008;77(4): 22-3, 8-30. 16. Diaz-Arnold AM , M arek CA. The impact of saliva on patient care: A literature review. The Journal of Prosthetic Dentistry. 2002;88(3):337-43. 17. Anurag Gupta B, Epstein JB, Sroussi H. Hyposalivation in elderly patients. J Can Dent Assoc. 2006;72(9):841-6. 18. Burt BA. The use of sorbitol-and xylitol-sweetened chewing gum in caries control. The Journal of the American Dental Association. 2006;137(2):190-6. 19. Epstein JB, van der M eij EH, Lunn R, Le ND, Stevenson-M oore P. Effects of compliance with fluoride gel application on caries and caries risk in patients after radiation therapy for head and neck cancer. Oral Surgery, Oral M edicine, Oral Pathology, Oral Radiology, and Endodontology. 1996;82(3):268-75. 20. Gorsky M , Epstein J, Parry J, Epstein M . ND Le en S. Silverman. The efficacy of pilocarpine and bethanechol upon saliva production in cancer patients with hyposalivation following radiation therapy. Oral Surg Oral M ed Oral Pathol Oral Radiol Endod. 2004;97:190-5. 21. Suzuki K, M atsumoto M , Nakashima M , Takada K, Nakanishi T, Okada M , et al. Effect of cevimeline on salivary components in patients with Sjögren syndrome. Pharmacology. 2005;74(2):100-5. 22. Fox P. Systemic therapy of salivary gland hypofunction. Journal of Dental Research. 1987; 66: 689-92. 23. Blom M , Dawidson I, Angmar-M ånsson B. The effect of acupuncture on salivary flow rates in patients with xerostomia. Oral Surgery, Oral M edicine, Oral Pathology. 1992;73(3):293-8. Address for Correspondence Dr. Nishat.S, M DS, Asst. Prof., Dept. of Oral M edicine & Radiology , Vydehi Institute of Dental Sciences, White Field, Bangalore, India. Email:[email protected]

Source of Support: Nil, Conflict of Interest: None Declared


61

XEROSTOMIA: AN OVERVIEW

Recommend Documents