A 50-year old woman presents with 3 months history of dry mouth. On further questioning, she also complains of difficulties in swallowing and speaking.
Introduction: Xerostomia is a common symptom among patients referred to ENT clinics. We present an evidence-based approach in a patient complaining of xerostomia who has not been exposed to radiotherapy.
Method (search strategy): This review was based on a literature search last performed on 1 July 2008. MEDLINE and EMBASE databases and the Cochrane Library were searched using the subject headings dry mouth, hyposalivation and xerostomia in combination with diagnosis, therapy and surgery. Results were limited to English language articles including clinical trials, randomised controlled trials, meta-analyses, systematic reviews, review articles and human studies. Relevant references from selected articles were reviewed.
Results: Xerostomia is not synonymous with hyposalivation. Effective management covers symptomatic relief with selected saliva substitutes, sialogogic agents, addressing underlying dental complications and oral infections, and review of prescribed medication.
Conclusion: Xerostomia is a common symptom for a wide range of triggering factors, but the treatment is largely palliative and preventative in nature.
What you should cover in the history
Xerostomia refers to the subjective experience of mouth dryness, whilst salivary gland hypofunction refers to alterations in the quality or quantity of saliva. Usually, when salivary secretion has decreased to half of an individual’s normal rate, that individual will begin to experience xerostomia.1 However, this symptom can be experienced even in the presence of normal salivary flow. Conversely some patients with objective hyposalivation may not have a complaint of xerostomia. Therefore, the terms hyposalivation and xerostomia should not be used interchangeably.2
- • Ask about the dryness. An affirmative response to at least one of the five following questions has been shown to correlate with a decrease in saliva3,4: Does your mouth usually feel dry? Does your mouth feel dry when eating a meal? Do you have difficulty swallowing dry foods? Do you sip liquids to aid in swallowing dry foods? Is the amount of saliva in your mouth too little most of the time? Ask whether the dryness is constant or simply present at night time which may indicate whether the problem is simply related to a mouth breathing or snoring problem. Some patients may report xerostomia more subtly by complaining that ‘the tongue sticks to the top of the mouth’ or ‘they need to drink sips of water when eating/swallowing dry food’.
- • Oral functions. Saliva is necessary to lubricate oral tissues for speech, lubricate food and help deglutition and is essential for taste perception. Reflex salivation is critical for the chewing and swallowing of food. In addition a smaller amount of resting saliva is secreted which covers the oral and resting mucosa and is essential in the maintenance of oral health. Hyposalivation causes difficulties in eating, tasting and speaking. Chewing and swallowing also become a problem.5 It is especially difficult to eat dry foods, which stick to the oral mucosa. The patient may suffer from taste disturbances, bad breath, a greater awareness of the oral structures, frequent biting of the lips, cheeks or tongue and also complain of salivary gland swelling.
- • Ask about the dental history. Hyposalivation leads to a reduction in salivary proteins that inhibit cariogenic microorganisms and electrolytes that buffer oral acids. This has catastrophic implications on the teeth causing atypical dental caries such as caries along the cervical or incisal margin of teeth, erosion, abrasion and eventual teeth loss. New and recurrent dental caries is the second most frequent infection in patients with hyposalivation. Saliva is also essential for both the retention and comfort in wearing removable prostheses. Lack of saliva in the denture-mucosa interface can produce denture sores owing to lack of lubrication. This can lead to social embarrassment if prostheses dislodge when eating or speaking in public.6
- • Recurrent infections. Reduced secretion of saliva predisposes to oral candidiasis.7,8 Individuals with Sjögren’s syndrome (SS) acquire candidal infection more frequently than the general population.8
Other systems and symptoms
- • Ageing. Natural ageing significantly changes the composition of saliva, but not the quantity. In elderly people, the amount of ptyalin decreases and mucin increases, causing the saliva to become thicker and more viscous. Xerostomia in the elderly population is more likely to be drug induced.
- • Associated symptoms of dry, gritty eyes, arthralgia, arthritis, rash, fatigue and Raynaud’s phenomenon are important as they can point to a diagnosis of primary or secondary SS. Patients should also be asked regarding dryness involving nasal and genital mucosae which can be troublesome in some patients with SS.
- • A comprehensive medical history is mandatory in patients presenting with xerostomia. The condensed list of systemic diseases causing dry mouth in Table 1 emphasises the importance of looking for concurrent medical problems.
- • Drug history. Did the onset coincide with the commencement of new medication? More than 400 medications cause dry mouth symptom. These are medications with antimuscarinic side effects such as tricyclic antidepressants, antihistamines and antispasmodics.5 Other common drug groups that cause dry mouth in more than 10% of users include diuretics, antihypertensives, anxiolytics, non-steroidal anti-inflammatory drugs and opioid analgesics. The prevailing cause of xerostomia in elderly persons is the use of medication and the risk for xerostomia increases with the number of drugs being taken.9,10
- • Past history of radiation. Xerostomia starts early during treatment and salivary function continues to decline for up to several months after radiotherapy.11 Parotid glands exposed to doses of greater than 60 Gy sustain damage with no recovery in salivary hypofunction with time.12 Radiation-induced damage to the salivary glands alters the volume, consistency and pH of secreted saliva.
- • Autoimmune diseases. SS is characterised by dry mouth, dry eyes, arthralgia and fatigue. The most widely accepted classification criteria for SS is that of the American-European Consensus Group criteria, which includes both subjective and objective assessment of oral and ocular function, as well as either histological or serological evidence of immune-mediated processes. The diagnosis is established by identifying objective evidence of poor tear secretion (Schirmer’s test), hyposalivation, lymphocytic infiltration of salivary gland tissue and the presence of autoantibodies in blood. Secondary SS occurs with other autoimmune diseases. It is estimated that 15% of patients with rheumatoid arthritis, 25% with systemic sclerosis and 30% with systemic lupus erythematosus may develop SS.13 Thus, a previous diagnosis or symptoms of these underlying diseases can point to the cause of dry mouth.
- • Other illnesses. Significant hyposalivation is reported after bone marrow transplantation (especially in those who develop chronic graft versus host disease) and in patients undergoing haemodialysis for end-stage renal disease. Viral infections such as HIV, HTLV and hepatitis C are associated with dry mouth. Patients with sarcoidosis may develop symptoms of xerostomia with an overall clinical picture similar to SS and may also develop swelling of the major salivary glands.14,15 Psychosocial factors such as anxiety may also influence salivary secretion and composition probably owing to pre-dominantly sympathetic stimulation during such periods.
- • Social history. Smoking, chewing tobacco and alcohol are linked to xerostomia. Also of importance is the profession of patient. Those whose jobs involve speaking, e.g. teachers, lecturers, switchboard operators can be affected.
|Short term drug use (e.g. antihistamines)|
|Viral infection (e.g. mumps)|
|Psychological conditions (e.g. anxiety)|
|Chronically administered drugs|
|Primary biliary cirrhosis|
|Human immunodeficiency virus|
|Head and neck radiation|
|Graft versus host disease|
|Bone marrow transplant|
What you should cover on examination
Oral cavity and salivary glands
- • Dry, cracked and peeling lips which may stick to each other.
- • Absence of a pool of saliva in the floor of mouth. The consistency of saliva may appear frothy.
- • Dry and sticky oral mucosa. Palpation of the oral mucosa may result in the finger adhering to the mucosal surfaces.
- • Erythematous, fissured and dry tongue with atrophy of the filiform papillae and a pebbled, cobblestone appearance.
- • Expression of saliva from the parotid ducts may not be possible.
- • Bad breath.
- • Characteristic, atypical pattern of dental caries, particularly cervical caries16, where decay appears on the tooth surface at the level of the gingival margins and then progresses to surround the tooth at that level.
- • Oral candidiasis; this may not be the classical white plaque of pseudomembranous candidiasis and it may present in denture wearers as chronic erythematous candidiasis (denture stomatitis) which appears clinically as erythema and may be patchy or continuous confined to the denture bearing area. Angular cheilitis may also be evident.
- • Major salivary glands: check for salivary gland enlargement or tenderness. Bilateral ill-defined parotid enlargement is commonly seen in SS, diabetes, alcoholism and HIV infection. Firm or hard salivary gland masses should raise the suspicion of malignant transformation; SS patients are 44 times more prone to developing B cell lymphomas of the salivary gland.17
- • Nutritional status and systemic signs of dehydration.
- • The systemic signs that can be identified when dry mouth presents secondary to the autoimmune or infectious diseases mentioned above are numerous to be summarised here. If suspected, prompt specialised medical consultation, as appropriate, should be obtained.
What management should you offer?
- • By now the history and examination should provide a clue to the probable underlying mechanism of xerostomia; for instance if an autoimmune disease is suspected, a full relevant work up should be arranged to confirm the clinical suspicion.
- • Blood counts. In the presence of active autoimmune diseases, anaemia, leukopenia and a high erythrocyte sedimentation rate may be seen.
- • Biochemistry. A high total protein level can be an indicator of polyclonal gammopathy, often seen in SS. A high alkaline phosphatase level may indicate primary biliary cirrhosis, presenting with dry mouth. With elevated transaminase levels chronic active hepatitis, which is associated with sicca symptoms, should be considered. There is an increased frequency of autoimmune hypothyroidism (10–15%) in SS and thyroid-stimulating hormone measurement is recommended.
- • Immunological tests. Autoantibodies (rheumatoid factor, antinuclear antibody, and SS-A/Ro and SS-B/La) are typically seen in SS. Autoantibodies to the Ro and La antigens occur in about 50% of affected individuals and along with salivary gland histology form one of the two essential criteria for diagnosing primary SS on the American-European Consensus Group guidelines.
- • Salivary flow rate measurement. The measurement of saliva flow is known as sialometry. A healthy adult produces about 1.5 L of saliva every 24 h, or 0.4 mL of saliva per min.18 The unstimulated saliva flow rate should exceed 0.1 mL/min. Interpretation of the results is difficult and not disease-specific. Whole mixed saliva can be collected by the methods of spitting, suction or cotton wool/absorbent devices.19 Saliva can also be collected selectively from each major gland by using a suction cup, such as the Lashley cup in the case of the parotid gland. Salivary flow can be measured when stimulated, e.g., with 2% citric acid or by chewing or unstimulated during which the patient should be fasting for a minimum of 1 h, including not drinking, chewing gum or brushing the teeth. Where the above mentioned equipment is not available, it is possible to obtain an approximate unstimulated salivary flow reading by asking the patient, who should be sitting in a quiet environment, to dribble in a measuring container over 15 min.
- • Imaging studies. Radioisotope salivary function test and sequential salivary scintigraphy using intravenous sodium pertechnetate99mTc can be used to objectively document reduced salivary flow, but the findings are not disease-specific and not widely used. More recently the value of MR sialography and diffusion-weighted MRI have been assessed, especially in radiation-induced xerostomia, but wider clinical applications await further research. Ultrasound examination of the salivary glands is increasingly utilised as an investigational tool. It allows the exclusion of masses and may also help indicate a diagnosis of SS with high specificity. Characteristically gland damage in SS patients is visualised as multiple hypoechoic areas with parenchymal inhomogenicity.20,21
- • Histopathology. The presence of ‘focal lymphocytic sialadenitis’ on labial salivary gland biopsy is one of two essential criteria for diagnosing primary SS.16 Otolaryngologists are often called upon to perform this procedure in patients who satisfy clinical criteria for SS but are seronegative. Care should be taken to harvest five to ten gland lobules 2–4 mm in diameter through an incision on the mucosal surface of the lip. The presence of periductal infiltrates of at least 50 lymphocytes and/or plasma /4 mm2 is necessary to make a diagnosis. It should be noted that past and present smokers can have a lower focus score. Unilateral discrete enlargement of the salivary gland should prompt other work up as appropriate for neck lumps.
- • Infection screen. HIV and hepatitis C virus infections should be ruled out. They cause dry eyes and mouth, swelling of salivary glands, and biopsy changes very similar to that of primary SS and can be clinically indistinguishable. All can be associated with hypergammaglobulinaemia, a raised erythrocyte sedimentation rate, and autoantibodies.
Whenever possible, treatment should be directed to any underlying causes and exacerbating factors should be identified and managed. However, as no cure exists for the majority of the underlying causes, treatment is therefore palliative and preventative in nature. The cornerstones of treatment are the prevention and treatment of complications, control of the underlying problems that may cause or contribute to xerostomia and symptom control. Some patients will require multidisciplinary care and referral to oral medicine specialists should be considered early on to ensure that an oral and dental dimension to their care is put in place.1
- • Prevention. This applies specifically to patients who are about to start radiotherapy to the mouth and salivary glands.
- • Cytoprotectants. A meta-analysis of 14 randomised controlled studies of amifostine as a cytoprotectant during radiotherapy found it effective in preventing acute and late xerostomia.22 It is not licensed for use in the UK currently.
- • Salivary gland-sparing radiotherapy. Several reports have demonstrated the efficacy of intensity modulated radiotherapy in objective and subjective reduction of xerostomia by sparing parts of the salivary glands without compromising tumour control rates.11
- • Salivary gland transfer. This involves the transfer of one submandibular gland to the submental space where it can be shielded during radiation and long term results show reduction in xerostomia.11,23
Prevention/management of adverse effects of xerostomia
- • Dental measures. Complications should be anticipated, especially in patients who are about to start radiotherapy. Preventative advice includes meticulous oral hygiene and strict avoidance of a cariogenic diet. Dental management options involve use of fissure sealants and daily use of topical fluorides. A patient who suffers from hyposalivation needs to be seen by the dental hygienist and dentist more often. Patients who have had radiation and with chronic xerostomia will need lifelong dental follow-up.
- • Dry mouth and dentures. Many patients with xerostomia will have full or partial dentures. Partial dentures allow increased contact with the dental tissues and further scope for debris and plaque to accumulate without the clearing effects of saliva and may result in accelerated dental caries and periodontal disease in the dentate patient. Simple advice such as moistening the dentures, even with salivary substitutes and possibly combining this with a denture adhesive can prevent dislodgement.6 Other considerations would include the provision of implant retained dentures although previous irradiation to the area would limit this option.
- • Diagnosis and rigorous treatment of oral candidiasis using topical oral rinses with antifungal medications help in preventing worsening symptoms.5
Optimising underlying condition
- • Optimal management of systemic illnesses may improve xerostomia complaints, e.g. in the case of poorly controlled diabetes.
- • If medication-induced xerostomia is suspected, a review of the current drugs and reduction of dosage or substituting the offending drug should be done if possible.
- • Smoking and alcoholic drinks are best avoided because they will worsen symptoms.
- • Patients may find some relief from having sips of cool drinks, sucking on ice chips, artificial saliva or saliva substitutes which have the scope of providing prolonged wetness of the oral mucosa. Although there is a wide range of commercial products in the market, only one (LuborantTM, Goldshield, Croydon, England) is licensed for any condition causing dry mouth. The others are licensed for SS and post-radiation xerostomia; however their use on an off label basis is widespread within the relevant medical and dental specialties. In dentate patients care must be taken as some preparations such as Glandosane artificial saliva sprayTM Glandosane (Fresenius Kabi, Runcorn, England) have an acidic pH and repeated use can result in non-carious tooth surface loss. Saliva Orthana spray TM is not acidic and contains fluoride and is safe for use in dentate patients as long as there are no religious objections to its use as it contains porcine mucin. Other products such as Biotene OralBalance are gel based. Patient preference varies and will dictate the most effective preparation. These products have been shown to improve patient reported symptoms of xerostomia and quality of life.24,25
- • Chewing sugar-free gums, especially those containing xylitol (which has antibacterial properties), will prevent caries by stimulating salivary flow.
- • Pilocarpine is a non-selective muscarinic agonist which stimulates the secretions of salivary and lacrimal glands. There is strong evidence supporting its use for the treatment of xerostomia in SS and after radiation.26 It is contraindicated in patients with uncontrolled asthma, acute iritis and hepatic impairment. The recommended dose of pilocarpine is 5 mg orally three times daily up to 10 mg.27
- • Cevimeline is a selective muscarinic agonist (acts on the M3 receptor) with similar mechanisms of action and side effects to pilocarpine. It is not licensed for use in the UK. The US Food and Drug Administration approved its use in SS.28,29 but not for radiation-induced xerostomia. The recommended dose of cevimeline is 30 mg three times daily.
- • Topical sialogogues are available, such as Salivix pastilles TM (Galen, Craigavon, Northern Ireland) or SSTTM (Medac, Stirling, Scotland), which are sugar-free but acidic and hence a similar cautious note applies to their repeated use in dentate patients.
This review was based on a literature search last performed in July 2008. The MEDLINE, EMBASE and COCHRANE databases were searched using the subject headings dry mouth and xerostomia in combination with diagnosis, therapy and surgery. Results were limited to English language articles including clinical trials, randomised controlled trials, meta-analyses, systematic reviews and review articles. Relevant references from selected articles were reviewed.
The authors are grateful to Dr Fai Ng, Clinical Senior Lecturer in Rheumatology, University of Newcastle upon Tyne, for critically reviewing the manuscript.
Conflict of interest
None to declare.