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MedicineToday 2014; 15(4): 30-37

PEER REVIEWED FEATURE 2 CPD POINTS

An approach to the patient with a dry mouth Key points • The subjective complaint of ELHAM AFLAKI MD; TAHEREH ERFANI MD; NICHOLAS MANOLIOS MB BS(Hons), PhD, MD, FRACP, FRCPA; needs to be MARK SCHIFTER FFD, RCSI(Oral Med), FRACDS(Oral Med) differentiated from true salivary hypofunction. Dry mouth is a common and disabling problem. After exclusion of treatable • Salivary hypofunction can significantly reduce quality causes, treatment is symptomatic to prevent the consequences of salivary of life through its adverse hypofunction, such as and infection of the . effects on taste, mastication, swallowing, cleansing of the erostomia, or the subjective feeling of ­neuropathic-induced orofacial dysaesthesia) mouth, killing of microbes a dry mouth, is a common complaint. and psychological and psychiatric disorders, and speech. It is often a consequence of salivary such as anxiety and depression. • Salivary hypofunction is a hypofunction (hyposalivation), in substantive risk factor for X which there is objective evidence of reduced NORMAL PRODUCTION dental caries, oral mucosal salivary output or qualitative changes in saliva. Under normal physiological conditions, the disease and infection, Typically, patients complain of oral dryness ­salivary glands produce 1000 to 1500 mL of particularly . only when salivary secretion is reduced by more saliva daily as an ultrafiltrate from the circu- • Patients should be than half.1 As saliva has a crucial role in taste lating plasma. Therefore, simple dehydration investigated for contributory perception, mastication, swallowing, cleansing reduces saliva production. The parotid glands and underlying causes, of the mouth, killing of microbes and speech, are the major source of serous saliva (60 to 65% which include drugs and abnormalities in saliva production can signif- of total saliva volume), producing the stimu- rheumatological diseases. icantly affect quality of life. lated salivary flow seen with mastication. • Patients with salivary Xerostomia also occurs in patients with no Serous saliva is also produced during rest by hypofunction can be treated measurable decrease in saliva production. the ­submandibular glands. This unstimulated with artificial saliva, Causes of this ‘subjective’ xerostomia include ­salivary flow is essential for maintenance of moisturising gels, sugar-free (better termed oral and dental health. Mucinous saliva is lozenges or and muscarinic drugs Dr Aflaki was a Visiting Academic of the University of Sydney (currently Assistant Professor of Rheumatology, Shiraz (, ). University of Medical Sciences, Shiraz, Iran) and Dr Erfani was a Basic Physician Trainee Registrar in the Department • Attention to maintaining and of Rheumatology, Westmead Hospital, Sydney (currently a Clinical Research Fellow in the Department of Rheumatology, improving oral health is Royal North Shore Hospital, Sydney). Professor Manolios is Head of the Department of Rheumatology, Westmead important, and treatment of Hospital, Sydney. Dr Schifter is Head of the Department of Oral Medicine, Oral Pathology and Special Needs consequent dental Copyrightcaries is _LayoutDentistry, 1 17/01/12 Westmead 1:43 Hospital, PM Page Sydney; 4 Clinical Associate Professor in the Faculty of Dentistry, the University of

essential. Sydney; and a Consultant in Oral Medicine at the Skin and Cancer Foundation Australia, Sydney, NSW. © JACKIE HEDA

30 MedicineToday x APRIL 2014, VOLUME 15, NUMBER 4 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2014. ­produced ­primarily by minor salivary of the tongue glands. The ­quality of saliva depends on • a feeling of xerostomia or more 1. CAUSES OF XEROSTOMIA5 the rate of flow. Resting saliva is viscous ­commonly a sense of an unpleasant and acidic, whereas stimulated saliva is alteration in the texture and quality Psychological and psychiatric hypotonic and alkaline. of the saliva disorders • frequently, . • Anxiety SYMPTOMS OF A DRY MOUTH Best described as an orofacial dysaes- • Depression Several studies have reported discordance thesia, with an element of neuropathic-­ Burning mouth syndrome between patients’ complaints of xerostomia induced sensory disturbance and associated Hyposalivation and hyposalivation, with a limited associ- psychogenic factors, burning mouth syn- • Medications and other drugs ation observed between perceived dry drome warrants specialist evaluation, for • Rheumatological diseases mouth and decreased salivary flow.2,3 A example by a specialist in oral medicine. −− Sjögren’s syndrome South Australian study reported that −− Rheumatoid arthritis although dry mouth and hyposalivation Hyposalivation −− Systemic lupus erythematosus had similar prevalence estimates (about Drugs −− Scleroderma 20%), the two conditions occurred together Hyposalivation is a common side effect of • Immune-mediated conditions in only 6% of participants.4 many medications (see Box 2).6 Most of −− Sarcoidosis Symptoms and signs that may accom- these medications affect the neural regu- −− Primary biliary cirrhosis pany hyposalivation include: lation of the saliva, which is controlled by • Endocrine disorders • increased thirst and the need to the autonomic nervous system. The sym- −− Diabetes mellitus ­constantly sip or drink water pathetic arm with adrenergic receptors −− Diabetes insipidus • difficulty in eating and swallowing inhibits saliva production, and the para- • Radiotherapy (> 50 Gy) encompassing dry foods sympathetic arm with (specif- one or more major salivary glands, • difficulty in wearing dentures ically muscarinic) receptors stimulates especially the parotid glands • an increased rate of dental caries saliva production. Many drugs are innately • Metabolic and nutritional disorders • halitosis , thereby limiting or reduc- −− Dehydration • a hoarse voice or the inability to ing saliva production. Some drugs and • Infections (viral) speak continuously common beverages such as caffeine and −− HIV infection • a constantly sore mouth or throat also have a diuretic effect, depleting −− Hepatitis C • oral candidiasis. the body’s water reserves and so reducing −− Cytomegalovirus (and other herpes Other symptoms that suggest ­sub­jective saliva production. infections) xerostomia in the absence of hyposalivation • Renal disease (end-stage) include: Sjögren’s syndrome • Congenital • a burning sensation of the tongue Sjögren’s syndrome (autoimmune exocrin- −− Prader–Willi syndrome • a feeling of altered quality and opathy) is a chronic autoimmune disorder −− Congenital rubella ­viscosity of the saliva characterised by lymphocytic infiltration −− Lacrimo-auriculo-dento-digital • altered sense of taste (dysgeusia). of all exocrine glands, with destruction of (LADD) syndrome the acini. It is more common in middle-­ −− Complete agenesis of salivary glands CAUSES OF A DRY MOUTH aged women, ­particularly those of north- Causes of xerostomia are summarised in ern European ancestry. Sjögren’s syndrome Box 1.5 was previously classified as primary or as seen in two-thirds of patients with primary secondary to other autoimmune diseases, Sjögren’s syndrome but is not common Burning mouth syndrome particularly the mixed connective t­issue when the syndrome is associated with other A proportion of patients with subjective diseases, rheumatoid arthritis, systemic immune-mediated conditions. Systemic xerostomia have burning mouth syn- lupus erythematosus (SLE) and manifestations are seen in one-third of drome. This poorly understood syndrome scleroderma. patients and include arthralgia, arthritis, presents in the absence of any identifiable The major presenting complaint is Raynaud’s phenomenon and vasculitis. pathology of the oral mucosa or of saliva increasing dryness of the eyes and mouth, Lymphoma (particularly extranodal, production and quantity. It has a typical but the nose, throat, trachea and vagina ­low-grade marginal zone B cell lymphoma) triad of symptoms:Copyright _Layout 1 17/01/12may 1:43 also PM be Pageaffected. 4 Enlargement of the is a known complication of Sjögren’s • a burning sensation, particularly parotid or other major salivary glands is syndrome.7

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Endocrine disorders with a history of radiotherapy or systemic 2. DRUGS THAT COMMONLY The most common endocrine disorders conditions associated with hyposalivation CAUSE SALIVARY HYPOFUNCTION6 that can cause dry mouth include diabetes may indicate progression of the underlying ­mellitus, hypothyroidism and diabetes disease and the need for more aggressive • Alpha blockers: , prazosin insipidus. Diabetes mellitus can have two intervention or treatment of the conse- • Angiotensin–converting enzyme major adverse effects on saliva production: quences of salivary hypofunction. inhibitors: captopril, lisinopril diabetes-induced neuropathy of the para- • : , hyoscine, sympathetic nervous supply results in Physical examination reduced saliva and, indirectly, the diuresis Before specifically examining the mouth • Antihistamines: loratadine, fexofenadine, associated with diabetes (also seen with for signs of hyposalivation, assess the diabetes insipidus) can also impair saliva patient’s skin for xeroderma and eyes for • Antiparksonian agents: levodopa–­ production. Reduced saliva production signs of xerophthalmia, such as a reduced carbidopa combined with the immunosuppression tear meniscus. Palpate the major salivary • Antipsychotics: , risperidone associated with diabetes mellitus can result glands for enlargement. Examine also • Benzodiazepines: alprazolam in persistent oral Candida infection, which for any extrastomal signs associated • Beta blockers: atenolol, propranolol can present with treatment-refractory with rheumatoid arthritis, SLE or • Calcium channel blockers: nifedipine, ­fissuring of the corners of the (angular scleroderma. verapamil ), atrophic candidiasis or severe On intra-oral examination, check the • Central analgesics: hydromorphone, denture-related­ . state of the dentition and the oral mucosa. methadone, morphine Frank dental decay of the smooth surfaces • Decongestants: pseudoephedrine Metabolic and nutritional causes or exposed root surfaces of the teeth is • Diuretics: frusemide, hydrochlorothi- A variety of diseases and conditions asso- generally a sure sign of severe salivary azide ciated with metabolic or nutritional hypofunction. The presence of dry, erythe­

• H2 receptor antagonists: cimetidine, changes are associated with hyposalivation, matous and ulcerated lips, dry ‘tacky’ or ranitidine including simple dehydration (caused by ‘sticky’ oral mucosa or denudation or atro- • Monoamine oxidase inhibitors: inadequate fluid intake, excessive exercise phy of the normal filiform and fungiform moclobemide, phenelzine or overheating), eating disorders such as papillae of the dorsal tongue are also highly • Muscle relaxants: baclofen anorexia and bulimia, and malnutrition. indicative of hyposalivation (Figure 1). • Nonbenzodiazepine hypnotics: The quantity and quality of the saliva zopiclone Radiation should also be assessed, with decreased or • Selective noradrenaline reuptake Profound, often permanent, salivary absent pooling of saliva on the floor of the inhibitors: reboxetine hypofunction is seen in almost all patients mouth or saliva that appears ‘frothy’ and • Tricyclic antidepressants: , after radiotherapy for malignant head strings easily being a clear indication of 9 and neck tumours. Radiation at dosages hyposalivation. higher than 50 Gy directed at any of the The presence of Candida infection also major salivary glands damages the serous suggests there is insufficient saliva to Sarcoidosis acini, leading to a reduction in output maintain the health of the oral mucosa. Sarcoidosis is a chronic granulomatous and an increase in viscosity of the saliva Candida infection may present as fissuring multi s­ ystem disease of unknown aetiology within a week. The loss of saliva produc- of the corners of the lips (), that involves the lungs and lymph nodes. tion is temporary and improves after pseudomembranous candidiasis (thrush), Sarcoidosis can, albeit rarely, present with several months in 8% of patients, but is markedly erythematous atrophic candid- xerostomia associated with true hypo­s­­ al­ irreversible in the remaining 92%. iasis of the or dorsal tongue or an ivation, and investigation for this condi- unusually red, hyperplastic appearance tion is warranted in patients presenting ASSESSMENT OF PATIENTS WITH A of the mucosa supporting the dentures. with xerostomia or reduced saliva. The DRY MOUTH minor salivary glands can also be involved History taking INVESTIGATIONS in ­sarcoidosis.8 Heerfordt’s syndrome is a Leading and open questions regarding After careful history taking and physical very infrequent presentation of systemic symptoms and signs can help distinguish examination, the focus is on objective sarcoidosis characterised by swelling of xerostomia from salivary hypofunction. assessment of salivary flow followed by the parotid glands, uveitisCopyright and _Layout facial nerve 1 17/01/12 Progression 1:43 PM in Page the symptoms4 of xerostomia investigation of the causes and complica- palsy. or features of hyposalivation in patients tions of dry mouth.

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Complications of this method include 3. ACR CLASSIFICATION CRITERIA allergic reaction and rarely . FOR SJÖGREN’S SYNDROME11 scintigraphy. Dynamic evaluation of the function of the major Proposed criteria salivary glands is possible by quantitative The classification of Sjögren’s syndrome assessment of the uptake of 99m-technetium applies to individuals with signs or pertechnetate. This test is relatively insen- symptoms suggestive of Sjögren’s sitive but highly specific for the diagnosis syndrome that meet at least two of the of Sjögren’s syndrome. following three objective features. Ultrasound and CT scans. These forms of 1. Laboratory investigations imaging are indicated if there is enlargement Positive serum anti-SSA/Ro and/or or a mass within any of the major salivary anti-SSB/La antibodies or positive glands that cannot be explained. Ultrasound rheumatoid factor plus ANA titre 1:320 currently has a limited role in the diagnosis  of Sjögren’s syndrome but is useful as an 2. Histopathological findings of labial minor salivary glands adjunctive investigation, in addition to its Labial salivary gland biopsy exhibiting role in assessing salivary gland masses.10 focal lymphocytic with a Figure 1. Atrophy of the dorsal tongue focus score 1 focus/4 mm2 caused by salivary hypofunction. Laboratory investigations All patients with a dry mouth should have 3. Ocular findings a full blood count, thyroid function study Keratoconjunctivitis sicca with an Assessment of salivary flow rates and measurement of blood glucose, ocular staining score  3 (assuming The first step is to evaluate the extent of oral ­erythrocyte sedimentation rate, C-reactive that the individual is not currently using dryness and the amount of resting (unstim- protein level, rheumatoid factor, antinu- daily eye drops for and has ulated) and stimulated saliva produced. clear antibody, anti-SSA (anti-Ro) and anti- not had corneal surgery or cosmetic Assessment of salivary flow is a simple SSB (anti-La) antibodies and serum eyelid surgery in the previous five years) bedside examination. For measurement of angiotensin-converting enzyme (ACE) Exclusions unstimulated salivary flow, ask the patient levels. If the diagnosis of Sjögren’s syn- Prior diagnosis of any of the following to expectorate their saliva into a container drome is strongly suspected or already conditions would exclude a diagnosis every 30 seconds for 15 minutes. An established then supplementary investiga- of Sjögren’s syndrome because of unstimulated saliva flow of less than 1.5 mL tions should be considered. These include overlapping clinical features or in 15 minutes indicates hyposalivation. For measurement of serum total immunoglob- interference with criteria tests: measurement of stimulated saliva ulin and specific IgA, IgM and IgG levels, • history of head and neck radiation ­production, ask the patient to chew some together with a serum electrophoresis gel • hepatitis C infection paraffin wax or chewing gum and again (EPG) and immunoelectrophoresis gel • AIDS expectorate every 30 seconds, for 5 minutes. (IEPG) to identify any peaks in expression • sarcoidosis A stimulated saliva flow of less than 5 mL of monoclonal immunoglobulins that may • amyloidosis indicates salivary hypofunction, and ­further indicate lymphoma. Serological tests for • graft versus host disease investigations of the cause is warranted. hepatitis C virus and HIV should be per- • IgG4-related disease

formed to exclude these infections. ABBREVIATIONS: ACR = American College of Imaging Rheumatology; ANA = antinuclear antibody. The following imaging tests may help Biopsy of a minor salivary gland evaluate the function of the salivary glands Diagnosis of Sjögren’s syndrome is based and diagnose underlying diseases. on the finding of dryness of oral and eye guidance on the approach to a patient with Sialography. This invasive procedure was mucosa in addition to positive serology for suspected Sjögren’s syndrome (Box 3).11 often used before the development of CT anti-Ro and anti-La antibodies. If the diag- scanning. It involves injecting contrast nosis is uncertain then biopsy and histo- Fine-needle aspiration biopsy material into the opening of the parotid pathological examination of a labial minor Patients with established Sjögren’s syndrome duct(s) followed by radiography. The salivary gland is indicated. The revised who present with unilateral major salivary changes seen are usuallyCopyright nonspecific _Layout 1 and 17/01/12 American 1:43 PM College Page of4 Rheumatology criteria gland enlargement, masses within any sal- include ductal destruction and sialectasis. for Sjögren’s syndrome provide excellent ivary gland or lymphadenopathy associated

34 MedicineToday x APRIL 2014, VOLUME 15, NUMBER 4 Downloaded for personal use only. No other uses permitted without permission. © MedicineToday 2014. and beverages, regular and frequent 4. MANAGEMENT OF SALIVARY HYPOFUNCTION ­consumption of fluoridated water, home use of specific high-dose topical fluoride • Artificial saliva dentifrices and mouthwashes, and main- tenance of adequate hydration. • Oral moisturising gels • Sugar-free lozenges or gums Dentist and specialist referral • Secretagogue drugs (cevimeline, Hyposalivation has a significant impact pilocarpine) on the dentition, warranting regular check- • Candida prevention (chlorhexidine) ups by the patient’s dentist and, in severe cases, assessment by a specialist in oral Figure 2. Dental caries exacerbated by • Candida treatment (nystatin, medicine. Three- to six-monthly dental severe salivary hypofunction. ­clotrimazole) check-ups, depending on the severity of • Referral to a dentist for prevention the salivary hypofunction, are essential Prevention of dental caries and management of dental caries for monitoring dental decay, professional Dental caries is a significant complication cleaning and provision of high-dose topical of hyposalivation, caused by decreased fluoride treatments. An oral medicine oral irrigation and the inability to rapidly with the major salivary glands merit inves- specialist can evaluate the cause of the clear foods from the oral cavity (Figure 2). tigation for non-Hodgkin’s lymphoma. Fine- xerostomia or salivary hypofunction, Caries is accelerated by sugar-containing needle aspiration biopsy is readily available. monitor for complications affecting the or acidic foods. Patients with a dry mouth Referral for such investigations should dentition, oral mucosa and salivary glands, tend to drink soft drinks to moisturise the include a direction to consider sending fresh and provide interventions such as prescrip- mouth, further increasing their risk of biopsy material for flow cytometry. tion of sialagogues to stimulate saliva tooth decay because of the high sugar and production. acid content of these drinks. Low-sugar MANAGEMENT and diet soft drinks also carry a risk of For patients with xerostomia alone and no Artificial saliva, moisturising gels tooth erosion because of their low pH. objective findings of salivary hypofunction Various artificial saliva preparations are fluoride supplements and good or disorders of the salivary glands, effective available in the form of sprays, liquids and oral hygiene can reduce the risk of dental treatment remains a dilemma. Patients with lozenges. These products contain glycerine caries.1 suspected burning mouth syndrome, which or carboxymethylcellulose, hydroxypro- has an element of neuropathic-induced sen- pylcellulose or hydroxyethylcellulose, Management of oral candidiasis sory disturbance and associated psychogenic which approximate but do not replicate Dentures should be removed for a pro- factors, warrant referral for evaluation by the physical and rheological characteristics longed period (more than two hours) at an appropriate specialist (such as a specialist of saliva. They also lack digestive and least once during the day, and ideally over- in oral medicine or oral surgeon). ­antibacterial enzymes. Artificial saliva night, and soaked in chlorhexidine to help For patients with hyposalivation, the preparations have a limited duration of prevent candidiasis. Amphotericin lozenges following strategies are currently recom- action, and some are mildly acidic, poten- (requiring a prescription) and miconazole mended to improve quality of life (sum- tially demineralising with oral gels can be used to treat oral candidi- marised in Box 4).1 prolonged use. asis. These medications should be used four An alternative is a sodium bicarbonate times daily after meals and at bedtime. Patient education rinse, which patients can easily make them- Miconazole gel can also be used to line Patients must be warned of the dental con- selves, consisting of a tablespoon of baking dentures before the patient places them in sequences of inadequate saliva. They should soda dissolved in a litre of water. Patients the mouth. Nystatin, although a popular be encouraged to sip water frequently and need to be strongly advised to use this as a treatment for oral candidiasis, contains up to be meticulous about dental hygiene to rinse only and to spit it out after use to avoid to 33% sucrose and therefore is not suitable prevent severe dental decay. They should the side effects of ingestion. These include for use in dentate patients with salivary avoid excessive air-conditioning and con- renal impairment and in large doses, met- hypofunction. sider using a room air-humidifier. Patients abolic alkalosis, oedema due to sodium If patients dislike or are unable to use also need advice on dietary modifications, overload, hypervolaemic hypernatraemia miconazole or amphotericin lozenges then with use of noncalorificCopyright sugar _Layout replace 1 17/01/12- with 1:43 hypertension PM Page 4 and worsening of con- chlorhexidine mouthwashes (preferably ments, avoidance of highly acidic foods gestive heart failure. alcohol-free formulations) can also be used

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for prevention and treatment of Candida CONCLUSION 8. Baughman RP, Teirstein AS, Judson MA, et al. infection. Patients should rinse the mouth Dry mouth is a common and disabling Clinical characteristics of patients in a case control or gargle with the mouthwash for one minute problem often seen in general practice. study of sarcoidosis. Am J Respir Crit Care Med after meals. Xerostomia, or the subjective complaint of 2001; 164: 1885-1889. Hydrocortisone–clotrimazole cream is oral dryness, needs to be differentiated 9. Epstein JB, Thariat J, Bensadoun RJ, et al. Oral the agent of choice for angular cheilitis. from salivary hypofunction, an objectively complications of cancer and cancer therapy: from Systemic azole agents such as fluconazole assessed decrease in saliva production or cancer treatment to survivorship. CA Cancer J Clin may be indicated for intractable oral can- change in saliva quality. Salivary hypo- 2012; 62: 400-422. didiasis. However, all azole agents, both function substantially increases the risk of 10. Cornec D, Jousse-Joulin S, Pers JO, et al. systemic and topical, are contraindicated dental disease and infections such as oral Contribution of salivary gland ultrasonography to in patients taking warfarin. candidiasis, and also impairs phonation, the diagnosis of Sjögren’s syndrome: toward taste perception, chewing and swallowing new diagnostic criteria? Arthritis Rheum 2013; Salivary stimulants and reduces oral comfort. 65: ­2­16-225. Chewing gums, hard lollies and mints are The most common cause of salivary 11. Shiboski SC, Shiboski CH, Criswell L, et al. helpful in stimulating salivation, providing hypofunction is medication use. Auto­ American College of Rheumatology classification patients with some relief particularly over immune diseases such as Sjögren’s syn- criteria for Sjögren’s syndrome: a data-driven, expert the course of the day. These should be drome and head and neck radiotherapy consensus approach in the Sjögren’s International ­artificially sweetened and/or sugar-free for malignancy are rare causes but can lead Collaborative Clinical Alliance cohort. Arthritis Care (i.e. free of noncalorific/nonfermentable to profound salivary hypofunction. Once Res 2012; 64: 475-487. simple carbohydrate). treatable causes of salivary hypofunction 12. Fox R, Creamer P. Treatment of dry mouth and have been excluded then treatment is con- other non-ocular sicca symptoms in Sjögren’s Secretagogue drugs servative, with attention to preventing the ­syndrome. Available online at: www.uptodate.com/ The muscarinic agonists pilocarpine and sequelae of a dry mouth. Management contents/treatment-of-dry-mouth-and-other-non- cevimeline directly increase exocrine includes liaison with the patient’s dentist ocular-sicca-symptoms-in-sjogrens-syndrome gland secretion. These medications are and, in severe cases, referral to an oral (accessed April 2014). relatively contraindicated in patients with medicine specialist. MT closed- a­ ngle glaucoma, congestive heart COMPETING INTERESTS: None. failure or . Patients require educa- REFERENCES tion about these drugs and warnings about Online CPD Journal Program their cholinergic side effects (flushing, 1. Guggenheimer J, Moore PA. Xerostomia: etiology, , excessive sweating, diarrhoea recognition and treatment. J Am Dent Assoc 2003; and urinary frequency). These drugs 134: 61-69. should be started at lower doses and then 2. Sreebny LM, Valdini A. Xerostomia. A neglected titrated to symptoms. Pilocarpine is avail- symptom. Arch Intern Med 1987; 147: 1333-1337. able on prescription in Australia but only 3. Narhi TO, Meurman JH, Ainamo A. Xerostomia in the topical form for the treatment of and hyposalivation: causes, consequences and glaucoma. Cevimeline is available from treatment in the elderly. 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