Protocol for the clinical management of dry mouth

SILVESTRE-DONAT FJ, MIRALLES-JORDÁ L, MARTINEZ-MIHI V. PROTOCOL FOR THE CLINICAL MANAGEMENT OF DRY MOUTH. MED ORAL 2004;9:273-9.

SUMMARY

Dry mouth is a very common condition in dental practice, and the causes underlying this alteration in salivary secretion are diverse. The problem is particularly common in polymedicated elderly people. Treatment should aim to eliminate the background cause; however, when this is not possible, management should focus on the stimulation of salivation or the provision of a saliva substitute. The present study provides a systematic account of the management protocol for patients with dry mouth.

Key words: Dry mouth, xerostomia, treatment.

INTRODUCTION

Although many dental patients complain of dry mouth, physical exploration often fails to find objective evidence to account for the situation. Much has been published about patients with dry mouth, though progress in recent years in the management of the problem have been rather modest. Such patients should be correctly evaluated, due to the relationship between hyposialia and certain systemic disorders.

Subjective dry mouth sensation is known as xerostomia, though the term hyposialia or salivary hyposecretion is used when objective sialometric determinations establish a resting or unstimulated whole saliva flow of < 0.1-0.2 ml/min. and a stimulated whole saliva flow of < 0.4-0.7 ml/min. These values are equivalent to the secretion of < 500 ml a day (1,2).

Persistently reduced salivary output leads to changes in the environment of the oral cavity and induces the appearance of hard and soft oral tissue lesions (3).

Hyposialia can develop as a result of many different factors capable of inhibiting secretion - from alterations of the peripheral nerve receptors, structures of the central nervous system and vegetative system innervating the salivary glands, to disorders of the gland parenchyma. One of the most frequent causes of hyposialia is the administration of so-called xerostomizing drugs which affect salivary gland innervation at either central or peripheral level (4). These drugs include substances as common as analgesics, antihypertensive agents, anticholinergic drugs, antidepressive medication, anxiolytics, antipsychotics, antihistamines and opiate derivatives. Different psychopathological conditions such as stress or anxiety can also cause xerostomia as a result of action at central level (5).

On the other hand, a deficient supply of elements needed for the production of saliva can also cause hyposialia, including a chronic lack of proteins, deficient water intake or excessive loss (as in intensely dehydrated patients), very low-salt diets,prolonged diuretic treatment, or diabetes (6).

However, the clinically more serious situations of dry mouth typically correspond to patients with acute or chronic salivary gland parenchyma destruction. Specifically, two clinical models exist in which salivary hyposecretion can reach maximum intensity: long-evolving Sjögren's syndrome, and patients subjected to large-dose radiotherapy for head and neck cancer. Less serious situations of hyposialia are in turn observed in patients with chronic infection or inflammation of the salivary glands (4).

Dry mouth, together with dryness of other mucosal membranes can often be seen in the general population, though the maximum incidence corresponds to elderly subjects (i.e., over 60 years of age), particularly in association to increased drug use for the treatment of systemic disorders typically found in older people (7).The first clinical manifestations of hyposialia are of a functional nature and include speech, chewing or swallowing difficulties. In addition, taste sensation may be diminished. Patients characteristically refer a dry mucosa sensation, and the saliva feels thick or filamentous. Burning mouth can also be reported (8). Examination of the oral mucosa shows the latter to be dry and poorly lubricated. Gingiva-supported dentures can irritate the oral mucosa, while adherence proves lacking in the case of complete removable dentures (9). The dorsal surface of the tongue is particularly vulnerable to cracking when oral dryness is intense and sustained over time, and the lips tend to suffer desquamation.

When hyposialia persists for a long period of time, the risk of oral infection increases, due to alterations in the ecological balance afforded by normal saliva output in the oral cavity. The oral defenses are lowered as a result, with changes in the resident saprophytic population (10). One of the most common infectious processes in such situations is chronic erythematous candidiasis, with lesions affecting different parts of the oral mucosa. Commissural or angle cheilitis can also develop, particularly in elderly patients presenting a reduction in vertical dimension and atrophic lesions on the back of the tongue (11,12).

In cases of very severe acute hyposialia, such as patients in the postoperative period after general surgery, acute sialoadenitis may develop. This disorder tends to affect the parotid gland, and is of bacterial origin. Sialoadenitis is characterized by gland swelling, with the emergence of pus from the orifice of the parotid gland duct (Stenson's duct) - either spontaneously or in response to squeezing of the gland (13). In cases of chronic hyposecretion and in susceptible patients, the incidence of dental caries is seen to increase. The latter are usually rapidly evolving and affect the dental neck (14). The absence of salivary cleansing action in these situations favors the accumulation of bacterial plaque, which in turn facilitates gingival tissue inflammation and bad breath (halitosis)(1).

The diagnosis of dry mouth should begin with an exhaustive anamnesis to identify the factors directly implicated (2). Three main factors should be taken into account: the systemic disorders present, pharmacological prescription, and possible antecedents of radiotherapy. The oral mucosa should be explored in search of clinical signs (which are sometimes very little evident), such as increased cracking or fissures of the lingual mucosa, lip desquamation, or a dry gingival or cheek mucosa, as well as the possible existence of irritative lesions (15).

Likewise, the major salivary glands should be palpated in search of swellings, with the examination of salivary outlet following massage and drainage of the major glands. The complementary evaluations indicated include whole salivary drainage sialometry under both resting and stimulated conditions. Stimulation can be achieved by mechanical means, e.g., by chewing paraffin tablets in dentate patients, or by chemical stimulation with 10% citric acid in edentulous individuals. Imaging techniques can also be used, including sialography with the administration of contrast, which can assess slowed secretion or the presence of sialectasias - though the technique is scantly accurate (in the same way as gammagraphy).

In cases where an autoimmune mechanism is suspected, as in patients with Sjögren's syndrome, minor salivary gland biopsies are indicated (normally of the lower lip) in order to evaluate the existence of a focal inflammatory infiltrate (16). In these patients blood tests should be requested, including the determination of specific antibodies - e.g., anti-SSA (anti-Ro) and anti-SSB (anti-La) - and nonspecific antibodies such as antinuclear antibodies (ANA) and rheumatoid factor (RF)(17).

A series of European criteria have been defined for assessing the possible existence of autoimmune disease in such patients (see Table 1).

MANAGEMENT OF DRY MOUTH

When planning treatment for dry mouth, a prognosis should be established, with knowledge of a series of key factors for the correct management of each individual patient. A first consideration is whether the cause underlying dry mouth is reversible or irreversible, i.e., whether the alteration affecting the salivary reflex is functional (as when administering xerostomizing drugs that inhibit afferent innervation of the salivary glands) or involves permanent gland parenchymal destruction (as occurs over time in patients with Sjögren's syndrome, or in head and neck cancer patients subjected to large-dose radiotherapy). In this way it is possible to know whether the causal factor can be corrected, and whether residual gland tissue amenable to stimulation remains (18).

Although there have been no major advances in recent years in this field, therapeutic measures do exit for planning the management of dry mouth (Table 2).

 

1.- General measures (etiological treatment)

Among the general measures to be taken into account when treating patients with dry mouth, consideration should first focus on the control of any systemic disorders that may be responsible for the oral problem. The most important examples in this case are Sjögren's syndrome and the side effects of high-dose radiotherapy in head and neck cancer patients (19).

Aminofostine, a selective cytoprotector that acts upon the salivary glands, kidneys, liver, heart or bone marrow can be used to limit the undesirable effects of radiotherapy for head and neck cancer (20). This drug is an organic thiophosphate that undergoes dephosphorylation mediated by alkaline phosphatase to yield the active thiol metabolite, which eliminates free radicals in healthy cells. In addition, uptake is faster in healthy cells than in tumor cells. Aminofostine is usually administered as an infusion (200 mg/min.) approximately 15 or 30 minutes before each radiotherapy session. The drug has side effects such as nausea, vomiting and hypotension, and hypocalcemia may also result. Attempts have been made to inject the agent via the subcutaneous route, with the purpose of reducing these systemic side effects.

In these patients with dry mouth it is essential to substitute, reduce or suppress any xerostomizing medication. The physician controlling the patient should be consulted on this point (21,22). Likewise, some patients may be on diets that induce a degree of dehydration, such as low-salt diets in hypertensive individuals, while others may be using antidiuretic drugs. In these cases adequate patient hydration must be ensured, with the ingestion of at least two liters of liquid daily. It is also important to avoid irritants such as coffee, alcohol or tobacco smoking.

Psychopathological factors are increasingly frequent causes of xerostomia, particularly chronic anxiety and stress (23). These disorders must be evaluated and treated. In this sense, benzodiazepines can be prescribed, such as ketazolam 15-30 mg after dinner, followed by gradual (not sudden) dose reduction.

2.- Salivary stimulation (sialogogues)

In patients with dry mouth it is important to determine whether functional salivary gland parenchyma remains that can be stimulated mechanically or chemically. Stimulation can be achieved through simple measures such as more frequent meals, the ingestion of lemonade or acid drinks, the dissolving of sugar-free essence candies in the mouth, or the prescription of xylitol chewing gum.

It is also possible to administer sialogogues that directly stimulate the salivary glands, such as anetoltritione, pilocarpine and cevimeline, among others (24,25).

In this context, anetoltritione is not a muscarinic receptor agonist, and its mechanism of action remains unclear - though the drug seems to favor parasympathetic neurotransmitter action. Efficacy is improved by combining anetoltritione and pilocarpine. The drug is supplied in 50-mg tablet form, and the recommended posology is three tablets a day for one week, followed by a reduction to two daily tablets. Urine discoloration and diarrhea are known side effects of the drug (26).

Pilocarpine, a tertiary amine extracted from the South American plant, Pilocarpus jaborandi, is a potent muscarinic receptor stimulator with important effects upon exocrine gland secretion. It is administered as 5-mg tablets three times a day via the oral route. It is also available as a 0.04% solution that can be instilled in the floor of the mouth several times a day. Pilocarpine has undesirable effects in the form of perspiration, flushing, urinary incontinence and digestive effects; caution is thus required in patients with digestive ulcers. It is also contraindicated in patients with hyperthyroidism, asthma, heart disease, epilepsy and Parkinson's disease (27,28).

Cevimeline has been introduced in recent years. This drug acts as a cholinergic agonist with effects upon the muscarinic receptors. It exhibits increased specificity for the M3 receptors, and consequently exhibits greater potency than pilocarpine (29). Cevimeline is generally well tolerated, though it can cause alterations in heart rate and conduction. The drug is administered in the form of 30-mg tablets three times a day via the oral route. Treatment should be maintained for 6-12 weeks. This agent is presently not marketed in Spain. The potential side effects of cevimeline are perspiration, polyuria, nausea and diarrhea (29). It is counterindicated in patients with asthma, allergy to the compound, and angle-closure glaucoma and iritis. The clinical trials conducted to date do not show cevimeline to cause fewer undesirable effects than pilocarpine.

Bethanechol is a choline esterase-resistant acetylcholine analog with muscarinic activity and also a degree of nicotinic action (30). The recommended dosage is one 20 mg tablet every 8 hours (31). However, this drug has a number of side effects such as headache, nausea, diarrhea, abdominal discomfort, urinary incontinence, flushing, perspiration, bronchiolar constriction and tearing.

Pyridostigmine is another muscarinic and nicotinic receptor agonist with prolonged action via choline esterase inhibition (32). The latter two drugs are not commonly used in clinical practice, due to their side effects and the risks associated to prolonged muscarinic action.

3.- Saliva substitutes

In patients with extreme or prolonged dry mouth, substances that replace lost salivary function and components can be used (33). These options include artificial saliva, which humidifies the oral cavity, particularly protecting it from irritative mechanical or chemical factors and infections. Such preparations consist of aqueous solutions containing glycoproteins or mucins, and salivary enzymes such as peroxidase, glucose oxidase or lysozyme (34). Polymers such as carboxymethylcellulose have also been used with the aim of protecting the soft tissues, or ions such as calcium and phosphates or fluorides for protecting the hard structures of the teeth (35).

Finally, antimicrobial agents and antiseptics have also been used, such as chlorhexidine, triclosan or hexetidine for the chemical control of bacterial plaque (36). Likewise, saliva or water solution reservoirs added to or forming part of dental prostheses have been proposed, though they do not seem to improve patient sensation, and are not much used in practice.

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