Causes of hyposalivation and xerostomia
The salivary glands derive their fluid from the circulating blood. This fluid, with its electrolytes and small organic molecules, is modified by the glands and, together with the macromolecules synthesized by the gland cells, secreted into the oral cavity (see Figs 80 and 81). Secretion occurs in response to neural stimulation. Disturbances of the blood supply to the gland, of its secretory apparatus, or of the stimuli that elicit secretion may lead to a decrease in the production of saliva.
As mentioned earlier, a person experiences oral dryness when the volume of saliva decreases to about half the normal flow rate; in xerostomia, the most extreme form of dry mouth, the decrease is significantly greater. For the resting flow of saliva to fall to such a level, more than one gland must be affected. The loss of activity of a single gland, observed in patients with salivary gland tumors and of sialoliths, does not result in oral dryness. Thus, xerostomia is the result of multiglandular salivary hypofunction, frequently as a result of the intake of xerogenic drugs, therapeutic irradiation, or certain systemic conditions. Age and decreased mastication may also contribute to the feeling of oral dryness. The most common causes of salivary gland hypofuction and xerostomia are listed in Box 9.
Medicines. The most common cause of hyposalivation and xerostomia is the use of xerogenic drugs. It is estimated that more than 400 drugs, some commonly used, can cause oral dryness and induce salivary gland hypofunction. These include anticholinergics, anorectics, antihistamines, antidepressants, antipsychotics, antihypertensives, diuretics, and antiparkinsonian drugs (Box 10). Many physicians are still unaware of these side effects, and patients are not informed about the increased risk of caries.
The dentist should therefore always ask for detailed information about the patient’s medication. When the medication has a known saliva-inhibiting effect, the physician should be consulted: Although management of systemic disease has first priority, and medication should not be changed for dental reasons alone, the physician may be able to suggest an alternative drug or modify the dose.
Irradiation. Patients irradiated for the treatment of oral, head, and neck carcinomas frequently experience severe hyposalivation (and even the absence of salivation), xerostomia, mucositis, and dysgeusia. The effects of the radiation are dose, time, and gland dependent. As far as possible, radiation oncologists shield the glands from the full dose of radiation, but, when bilateral exposure of the salivary glands is unavoidable, xerostomia may be permanent.
Patients often experience oral dryness at an early stage of treatment, and this is exacerbated as the therapy proceeds. In one study, a 50% reduction in the resting flow rate of parotid saliva was recorded 24 hours after the administration of only 2.25 Gy; after 6 weeks of treatment (60.00 Gy/fraction), the flow rate had declined by more than 75% (Sreebny et al, 1992). In most patients, the disturbance of salivary gland function and the associated xerostomia are irreversible. A more than 95% reduction in salivary secretion has been found to persist 3 years after treatment.
The mechanisms underlying the acute effects of radiation on salivary function are not known; the early effects may result from damage to the blood supply or interference with transmission of nerve impulses. The later effects are due to destruction of the secretory apparatus and its subsequent replacement by fibrous connective tissue and to specific vascular damage (endarteritis). The secretory cells, the blood supply and the nerves may all be affected by ionizing radiation. Serous cells are more sensitive to radiation than are mucous cells: the parotid gland, which contributes the bulk of the serous component of saliva, is therefore most vulnerable to damage, while the minor salivary glands may still function normally. Thus there is not only a pronounced reduction in salivary flow rate but also a change in salivary composition. The saliva
becomes a viscous, white, yellow, or brownish fluid with a reduced pH, reduced buffering capacity, and altered electrolyte and protein content (see Fig 94).
Among the irradiation-induced changes in the mouth is also a pronounced increase in
the numbers of acidogenic, cariogenic microorganisms at the expense of
noncariogenic bacteria. Clinically, the most significant changes are increases in
mutans streptococci, lactobacilli, and Candida species. The quantitative and
qualitative salivary changes predispose the irradiated patient to a variety of oral
problems, such as extreme xerostomia and all its symptoms, listed in Box 7, and rapid
and extensive dental caries (see Fig 96), unless intensive caries-preventive measures
are stringently followed. In addition to having rapid onset and progression, radiation
caries characteristically occurs at sites normally relatively resistant to dental caries
(lingual and incisal surfaces). The areas just below the contact points, usually the sites
most susceptible to caries, are often the last to be affected.
Because therapeutic doses of radiation cause no direct damage to the tooth structure,
the associated enormous increase in the cariogenic challenge is attributable to
hyposalivation-related alterations in microbial, chemical, immunologic, and dietary
variables. The salivary glands are usually located within the treatment portals for head
and neck cancer, and, at present, there is no proper clinically acceptable
radioprotection. Treatment of the resulting severe hyposalivation is therefore partly
palliative and partly directed toward caries prevention: mechanical plaque control, use
of antimicrobial and slow-release fluoride agents, stimulation of residual salivary
gland tissue by masticatory and gustatory stimuli, such as fluoride chewing gums, and
symptomatic relief of oral dryness with artificial saliva that contains fluoride. These
measures are not limited to irradiated patients but are appropriate for all patients with
severe hyposalivation and xerostomia.
Systemic diseases. Systemic diseases, and the drugs used in their management,
frequently cause a marked reduction in salivary secretion. Xerostomia and salivary
gland hypofunction are intimately associated with a number of systemic diseases and
conditions, some of which cause progressive destruction, usually irreversible, of the
gland parenchyma. Others may have vascular or neural effects that are transient and
reversible. Included among the diseases are rheumatoid conditions (sometimes
referred to as collagen-vascular, connective tissue, or autoimmune disorders);
hyposecretory states; certain common diseases (eg, hypertension and diabetes
mellitus); cystic fibrosis; certain neurologic conditions; depression and dehydration,
anorexia nervosa, and hormonal changes (see Box 9).
The classic example of the rheumatoid conditions is Sjogren’s syndrome. The primary
form is characterized by salivary and lacrimal gland involvement, usually presenting
as dry mouth and dry eyes. The secondary form involves at least one of these organs
and, in addition, is an associated collagen disorder, most commonly rheumatoid
arthritis. Systemic lupus erythematosus, scleroderma, dermatomyositis, and primary
biliary cirrhosis may also be associated with secondary Sjogren’s syndrome.
In the early stages, there may be little change in the SSR; as the disease progresses,
there is a corresponding decrease in SSR, resulting from the gradual destruction of the
gland parenchyma by a lymphoreticular cell infiltrate. There is massive irreversible
acinar cell degeneration and atrophy. Changes resulting from Sjogren’s syndrome are
not restricted to the mouth and eyes; there may be extraglandular manifestations in the
gastrointestinal, renal, genitourinary, and pulmonary systems. The condition is
associated with increased risk of pseudolymphoma and malignant lymphoreticular
disease.
The diagnosis of Sjogren’s syndrome is usually made several years after onset, and, in
many patients, the dentition is severely damaged before the definitive diagnosis is
made. Meticulous assessment of salivary secretion rate by the dentist is an aid to early
identification of these patients. The presence of Sjogren’s syndrome is often
confirmed by biopsy of the minor salivary glands of the lower lip.
Sjogren’s syndrome is believed to occur in about 1% of the population. It affects eight
times as many women as men, most above the age of 45 years. Although it is the
cause of profound distress in older women, it is a condition that has been largely
overlooked, and surprisingly little information is available in the medical and dental
literature.
There is increasing evidence that xerostomia is associated with a number of common
disorders and diseases such as hypertension and diabetes mellitus. The evidence for
the link between diabetes mellitus and xerostomia is of two types. First, there is a
greater incidence of diabetes mellitus in xerostomic subjects than in nonxerostomic
controls. Second, diabetic subjects with no other diseases and taking no drugs other
than insulin have a far greater prevalence of xerostomia than do matched nondiabetic
controls (Sreebny et al, 1992). However, insulin-dependent (type 1) diabetes mellitus,
as such, does not damage salivary glands to such an extent that hyposalivation can be
regarded as a common complication. Reduced salivary secretion is typical only during
periods of diabetic instability or during the onset of the disease: During these periods,
increased glucose levels in salivary secretions are common, heightening caries risk.
This is one reason why such diabetic patients are at least as caries susceptible as
nondiabetic patients.
Other conditions associated with reduced SSR. The changes in SSR associated with
chronic depression are generally persistent. When oral dryness cannot be attributed to
organic change, the patient should be advised to consult a psychologist or psychiatrist
to explore possible psychogenic factors. Although psychic states can induce oral
dryness, the underlying mechanisms are not well understood. Depression is frequently
treated with tricyclic antidepressants, which tend to aggravate the severity of oral
dryness.
In patients suffering from severe or prolonged malnutrition or anorexia nervosa,
deterioration in SSR and the quality of the saliva may lead to oral symptoms, for
example, increased susceptibility to dental caries, erosion, and dry mouth. Although
short-term fasting also reduces the SSR significantly, it does not lead to true
hyposalivation, and the flow rate is restored to normal values soon after the fasting
period ends.
Hormonal changes may also affect the SSR and the composition of human saliva. The
most profound changes are postmenopausal, many studies confirming that the salivary
secretion rate is lower in postmenopausal women than in younger women. However,
there is a widely varying individual response: Some postmenopausal women
experience no detectable change in SSR, while others experience distressing oral
dryness (with a number of symptoms, such as “burning mouth,” sore tongue,
difficulties with speech and swallowing, and fungal infections). Estrogen
supplementation therapy has little, if any, effect on SSR after menopause.
Age as such does not have a clinically obvious effect on SSR: In healthy individuals,
the stimulated whole SSR does not decline. Age-related decreases in secretions from
both minor and submandibular glands have been observed, similar decreases in SSR
from the parotid glands have not been found. [au: Reference?]Comparative studies of
stimulated minor gland secretion in older and younger adults have reported an agerelated
decline of more than 50% in secretion, a functional decrease consistent with
morphologic studies showing a 40% to 50% reduction in acinar volume with age
(Percival et al, 1994).
These physiologic changes may explain why many old people experience discomfort
from dry mouth, even though the secretion rate for paraffin-stimulated whole saliva is
normal. Alterations in submandibular and sublingual gland functions have the greatest
impact on the sensation of oral dryness. These changes will also increase the risk for
development of denture stomatitis and reduced denture retention in edentulous
elderly.
Both human and animal studies (Dawes, 1987) have shown salivary gland atrophy to
be associated with decreased masticatory activity. In humans, this has been reported
in subjects on liquid diets and in patients whose jaws were wired together after
orthognathic surgery. The extent to which varying degrees of decreased masticatory
activity contribute to salivary gland hypofunction and xerostomia in humans is not
known. On the other hand, as will be discussed later in this chapter, studies have
shown that introduction of agents to stimulate chewing may increase the SSR in
patients with hyposalivation (Axelsson et al, 1997a).
