[Federal Register Volume 59, Number 98 (Monday, May 23, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-12457]
[[Page Unknown]]
[Federal Register: May 23, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Health Care Financing Administration
[BPD-782-PN]
RIN 0938-AG45
Medicare Program; Noncoverage of Electrostimulation of Salivary
Glands for the Treatment of Xerostomia (Dry Mouth)
AGENCY: Health Care Financing Administration (HCFA), HHS.
ACTION: Proposed notice.
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SUMMARY: This notice announces the Medicare program's proposal not to
cover electrostimulation of the salivary glands for the treatment of
xerostomia secondary to Sjogren's syndrome, and electrostimulation
devices, such as the Salitron System. Public Health Service (PHS)
studies show that there are insufficient data to establish the clinical
utility of electrostimulation, to evaluate its long-term effectiveness,
and to identify those xerostomia patients who would benefit from this
procedure. Also, PHS reports that electrostimulation is not widely
accepted as a treatment for xerostomia secondary to Sjogren's syndrome.
Therefore, it does not meet HCFA's criteria for effectiveness.
DATES: Comments will be considered if we receive them at the
appropriate address, as provided below, no later than 5 p.m. on July
22, 1994.
ADDRESSES: Mail written comments (1 original and 3 copies) to the
following address: Health Care Financing Administration, Department of
Health and Human Services, Attention: BPD-782-PN, P.O. Box 26688,
Baltimore, Maryland 21207.
If you prefer, you may deliver your written comments (1 original
and 3 copies) to one of the following addresses:
Room 309-G, Hubert H. Humphrey Building, 200 Independence Avenue, SW.,
Washington, DC 20201, or
Room 132, East High Rise Building, 6325 Security Boulevard, Baltimore,
MD 21207.
Because of staffing and resource limitations, we cannot accept
comments by facsimile (FAX) transmission. In commenting, please refer
to file code BPD-782-PN. Comments received timely will be available for
public inspection as they are received, generally beginning
approximately 3 weeks after publication of a document, in room 309-G of
the Department's offices at 200 Independence Avenue, SW., Washington,
DC, on Monday through Friday of each week from 8:30 a.m. to 5 p.m.
(phone: (202) 690-7890).
FOR FURTHER INFORMATION CONTACT: Francina C. Spencer (410) 966-4614.
SUPPLEMENTARY INFORMATION:
I. Background
A. Program Description
Section 1862(a)(1)(A) of the Social Security Act (the Act)
generally prohibits payment for any expenses incurred for items or
services ``which, * * * are not reasonable and necessary for the
diagnosis or treatment of illness or injury or to improve the
functioning of a malformed body member.'' We have interpreted this
statutory provision to exclude from Medicare coverage medical and
health care services and items that are not demonstrated to be safe and
effective by acceptable clinical evidence. This prohibition applies to
items for which claims are submitted under Medicare's durable medical
equipment (DME) benefit.
B. Medicare Coverage of Electrostimulation of Salivary Glands for the
Treatment of Xerostomia (Dry Mouth) Secondary to Sjogren's Syndrome
Patients with chronic xerostomia complain of a continual feeling of
oral dryness, have difficulty eating dry foods, and are susceptible to
increased tooth decay, oral pain, tongue fissures, and infection.
Saliva contains proteins and enzymes that aid digestion, conduct
electrolytes necessary to maintain hard tooth enamel, and produce
antibacterial agents to control oral bacteria. Salivary gland
dysfunction leads to difficulty in speaking, chewing, swallowing, and
tasting. A decrease in salivary secretion may result from damage to the
salivary glands caused by chronic infection, irradiation, or systemic
diseases such as hypertension, diabetes, or Sjogren's syndrome.
Sjogren's syndrome is a chronic, inflammatory, and autoimmune disease
in which the salivary and tear glands undergo progressive destruction
by lymphocytes and plasma cells resulting in decreased production of
saliva and tears.
Treatment for xerostomia varies considerably. If Vitamin C tablets,
gum, and hard candy do not stimulate salivation in patients with some
salivary gland function, artificial saliva using either an atomizer or
an intraoral reservoir are used. While these methods relieve the
symptoms of chronic xerostomia, they usually offer only temporary
relief. Oral drugs such as pilocarpine and pyridostigmine are effective
in increasing salivation if there are some functioning salivary gland
tissues. However, because of side effects and contraindications, the
usefulness of these drugs is limited.
On March 27, 1987, Biosonics, Inc. requested marketing approval by
the FDA of the Salitron System. This device is a battery-powered, hand-
held electrostimulation device for stimulating salivation from existing
glandular tissue by delivering a small electrical stimulus to the mouth
using a probe with two metal electrodes. It is used for patients with
xerostomia secondary to Sjogren's syndrome with residual salivary
tissue in the oral and pharyngeal regions. Physicians use the device to
screen patients to determine a response to electrostimulation before
prescribing the system. After reviewing the recommendation of the
Dental Devices Panel, FDA's Center for Devices and Radiological Health,
the FDA granted premarket approval for the Salitron System on May 18,
1988. The approval was announced in the July 14, 1988, notice entitled
``Biosonics; Premarket Approval of the Salitron System'' (53 FR 26673).
At this time, the Salitron System is the only device approved for
marketing by the FDA for electrostimulation of salivary glands.
Currently, Medicare does not have a national policy for covering
electrostimulation of salivary production for treating xerostomia
secondary to Sjogren's syndrome. Without a national policy, Medicare
carriers have authority under section 1842(a) of the Act to make
coverage decisions within the parameters set by the statute,
regulations, and program instructions. Some carriers are paying for
electrostimulation of the salivary glands using the Salitron System and
others are not because they question the medical efficacy of the
treatment. This has resulted in inconsistent coverage policies among
carriers.
C. Recommendation Not to Cover Electrostimulation of Salivary
Production in the Treatment of Xerostomia Secondary to Sjogren's
Syndrome
On May 26, 1988, Biosonics requested that Medicare issue a national
policy decision that would provide for coverage of the Salitron System.
Based on our evaluation of their request, we consulted the HCFA
Physicians Panel. The Panel recommended that OHTA evaluate the safety
and effectiveness of the Salitron System as well as the criteria used
to identify xerostomia patients who would benefit from the device.
On October 4, 1988, we asked OHTA to conduct a full assessment of
the safety and effectiveness of the Salitron System and to develop
patient selection criteria. To conduct this assessment, OHTA solicited
information from clinicians, appropriate private organizations,
researchers, other government agencies, other components of PHS, and
the National Institutes of Health (NIH). OHTA evaluated studies, data
provided to the FDA, published articles, and information from
respondents to the March 2, 1989, notice entitled ``National Center for
Health Services Research and Health Care Technology Assessment;
Assessment of Medical Technology'' (54 FR 8829). In that notice, OHTA
announced that it was assessing the patient criteria for
electrostimulation of salivary glands for the treatment of xerostomia
secondary to Sjogren's syndrome and an electrostimulation device's
acceptability, cost, and effectiveness relative to other therapies.
On July 30, 1990, we received OHTA's assessment ``Salivary
Electrostimulation in Sjogren's Syndrome'' with a bibliography of
literature and investigations evaluating electrostimulation of salivary
glands. (A copy of this assessment is included as an addendum to this
proposed notice.)
According to OHTA, from the limited studies as well as data
provided to the FDA, it appears that electrostimulation of salivary
glands may be useful in managing xerostomia in certain patients. OHTA,
however, states that there are insufficient data to determine the
clinical utility of electrostimulation, to evaluate its long-term
clinical effectiveness, and to identify xerostomia patients who would
benefit from this procedure. Also, OHTA has determined that
electrostimulation is not widely accepted as an effective method for
treating xerostomia secondary to Sjogren's syndrome and that other
treatments, such as the use of Vitamin C tablets, gum, hard candy, and
artificial saliva, are available.
NIH advised OHTA that guidelines specifying the types and
conditions of xerostomia patients who would benefit from
electrostimulation cannot be developed without further clinical studies
of well-characterized patient populations. Given the single published
study showing that only patients with residual salivary flow in an
unstimulated state will respond to electrostimulation, NIH suspects
that those individuals are likely to respond as well to other means of
salivary stimulation.
OHTA reviewed the published study, the preliminary investigation,
and the study presented to the FDA. The 1988 study by M. Steller and
associates (``Electrostimulation of Salivary Flow in Patients with
Sjogren's Syndrome'' Journal of Dental Research 1988; 67(60): 1334
through 1337) revealed that only 3 of 13 patients using an active
device showed a significant response in salivary production when
compared to the response of the placebo device group. The 1986
preliminary investigation conducted by W. W. Weiss and associates
(``Clinical Trial of an Electronic Stimulatory Device in the Management
of Xerostomia'' Journal of Oral and Maxillo-facial Surgery November
1986: M10) did not include a control group or any quantitative
assessment of salivary response, duration of response, or long-term
assessment of efficacy. Moreover, 7 of the 9 patients tested had
residual saliva production before treatment and may have been
exhibiting a tactile response to the probe. The 1988 study by N. Talal
and associates (``The Clinical Effects of Electrostimulation on
Salivary Function of Sjogren's Syndrome Patients'' Rheumatology
International June 1992; 12(12) 43 through 45), upon which the FDA
based its approval, describes the clinical effects of
electrostimulation in 77 patients. Salivary production was measured at
the start of the study, at 2 weeks, and at 4 weeks. The researchers
reported that salivation was higher among the group using an active
device than the placebo device group. However, because of a
misunderstanding about the length of the study, about half of the
subjects dropped out of the study by the fourth week.
Thus, OHTA concluded that additional, long-term studies with larger
patient populations are needed to define the specific degrees of
salivary dysfunction that would respond to electrostimulation and to
determine how long it takes to determine if salivary glands have been
regenerated. These studies could help determine whether a single
salivary response to electrostimulation or some other test, such as a
lip biopsy, should be used to help identify those patients who may
benefit from electrostimulation. In addition, OHTA stated that to
determine the effectiveness of electrostimulation, studies should
include information regarding concomitant therapy and the duration of
the salivary response to compare the device to other therapies. Studies
and subsequent management should include quantitative assessment of
salivary function, assessment of oral conditions, and subjective
patient evaluations.
The comments OHTA received from knowledgeable clinicians were
inconsistent. Some clinicians state that electrostimulation is safe and
effective while others suggest that the method has been inadequately
tested and are not convinced that it is more effective than other
simple, less costly stimulation techniques.
After OHTA's published report, Biosonics requested review of
additional data on the use of the Salitron System. On September 21,
1990, we submitted the data to OHTA. OHTA reported on October 26, 1990,
that this data had been presented to the FDA and was included in the
OHTA assessment of July 30, 1990. OHTA concluded that the treatment
could be reassessed when additional data from a larger patient
population is available to evaluate the long-term clinical
effectiveness of electrostimulation and identify those xerostomia
patients who would benefit from an electrostimulation device.
On November 2, 1990, we submitted to OHTA another request for a
review of data from Biosonics. On November 14, 1990, OHTA informed us
that it had previously reviewed this data and referred us to its
October 26, 1990, recommendation.
On October 9, 1992, Biosonics requested a reassessment and
submitted two new articles on electrostimulation for xerostomia
published in ``Geriatric Consultant'' and ``Rheumatology
International.'' One article reported a physician's experience in
treating 33 patients for 6 months. The other article reported on the
unpublished clinical study evaluated by the FDA in 1988. We have
determined that the medical evidence and conclusions upon which OHTA's
assessment is based are still accurate based on our own medical
expertise and a thorough review of all the medical literature on the
subject since the 1990 assessment.
II. Provisions of This Proposed Notice
OHTA concluded that there are insufficient data to determine the
clinical utility of electrostimulation, to evaluate its long-term
clinical effectiveness, and to identify xerostomia patients who would
benefit from this procedure and that electrostimulation is not widely
accepted as an effective treatment for xerostomia. Based on these
conclusions, we have determined that electrostimulation of salivary
glands and the electrostimulation device, the Salitron System, do not
meet our criteria for effectiveness. Therefore, we propose to publish a
final notice announcing a national coverage decision that Medicare does
not cover electrostimulation of salivary glands for treating xerostomia
secondary to Sjogren's syndrome.
The provisions of this notice would not affect any existing
Medicare regulations. However, they would be incorporated in the
Medicare Coverage Issues Manual (HCFA Pub. 6).
III. Response to Comments
Because of the large number of items of correspondence we normally
receive on proposed notices, we are not able to acknowledge or respond
to them individually. We will consider all comments that we receive by
the date and time specified in the DATES section of this preamble, and
if we proceed with a subsequent document, we will respond to the
comments in the preamble to that document.
IV. Collection of Information Requirements
This document does not impose information collection and
recordkeeping requirements. Consequently, it need not be reviewed by
the Office of Management and Budget under the authority of the
Paperwork Reduction Act of 1980 (44 U.S.C. 3501 et seq.).
V. Regulatory Impact Statement
A. Introduction
Currently, Medicare does not have a national policy for covering
electrostimulation of salivary production for treating xerostomia
secondary to Sjogren's syndrome. Medicare carriers have authority to
make coverage decisions within the parameters set by the statute,
regulations, and program instructions. Because this service is not
ordered often and because of the low total allowed charges by Medicare
Part B for this service, less than $26,000 in calendar year (CY) 1991,
and no reported payments in CY 1992, we believe this proposed notice
would result in negligible savings during calendar years 1994 through
1998.
B. Regulatory Flexibility Act
We generally prepare a regulatory flexibility analysis that is
consistent with the Regulatory Flexibility Act (RFA) (5 U.S.C. 601
through 612) unless the Secretary certifies that a notice would not
have a significant economic impact on a substantial number of small
entities. For purposes of the RFA, all physicians prescribing and
suppliers distributing a device to stimulate salivary production from
existing glandular tissue are considered to be small entities.
In addition, section 1102(b) of the Act requires the Secretary to
prepare a regulatory impact analysis if a notice may have a significant
impact on the operations of a substantial number of small rural
hospitals. This analysis must conform to the provisions of section 603
of the RFA. For purposes of section 1102(b) of the Act, we define a
small rural hospital as a hospital that is located outside of a
Metropolitan Statistical Area and has fewer than 50 beds.
The Medicare program paid for 41 electrostimulation devices during
CY 1991 totaling an estimated $26,000 at an average cost of
approximately $630 each. It appears that carriers are no longer paying
for this electrostimulation device, thereby explaining why no invoices
for this device were processed in CY 1992. In the absence of this
notice, it is possible that the number of devices prescribed by
physicians would increase and carriers would resume payment. Physicians
have at least two alternate methods for treating xerostomia. One method
is to rely on the use of artificial saliva in conjunction with the
sipping of liquids for moisture. The second alternative is the use of
gums and candies to induce saliva. Since there are alternative
treatment methods, we believe this proposed notice would affect
physicians and beneficiaries minimally.
Therefore, we are not preparing analyses for either the RFA or
section 1102(b) of the Act since we have determined, and the Secretary
certifies, that this proposed notice would not result in a significant
economic impact on a substantial number of small entities and would not
have a significant impact on the operations of a substantial number of
small rural hospitals.
In accordance with the provisions of Executive Order 12866, this
proposed notice was not reviewed by the Office of Management and
Budget.
(Secs. 1861 and 1862 of the Social Security Act (42 U.S.C. 1395x and
1395y))
(Catalog of Federal Domestic Assistance Program No 93.774,
Medicare--Supplementary Medical Insurance)
Dated: March 3, 1994.
Bruce C. Vladeck,
Administrator, Health Care Financing Administration.
Dated: April 7, 1994.
Donna E. Shalala,
Secretary.
Salivary Electrostimulation in Sjogren's Syndrome
Number 8
Patient Selection Criteria for Electrostimulation of Salivary
Production in the Treatment of Xerostomia Secondary to Sjogren's
Syndrome
Prepared by: Martin Erlichman
Introduction
Electrostimulation has been introduced as a technique for
increasing salivary output in the treatment of patients with
xerostomia (dry mouth) secondary to Sjogren's syndrome. The
procedure uses an electrostimulation device (salivation
electrostimulator) to increase salivary production from existing
glandular tissue. The device delivers a small electrical stimulus to
the mouth via a probe. The electrostimulation device consists of an
electric control module, a connecting cord, and a hand-held stimulus
probe with two metal electrodes. The device may be battery-powered.
Patients with residual salivary tissue in the oral and pharyngeal
regions who demonstrate a decrease in the flow rate of saliva are
potential candidates for this procedure.
Xerostomia may be the result of Sjogren's syndrome, other
diseases, medications, or radiation therapy to the head and neck. To
determine that the xerostomia has resulted from Sjogren's syndrome,
clinicians also confirm the presence of keratoconjunctivitis sicca
(dry eye) and a positive lip biopsy with or without the presence of
a connective tissue disease. It is estimated that more than one
million people, mostly women, suffer from Sjogren's syndrome in the
United States.1
Xerostomia is usually defined as a symptom that exists when
saliva production is less than 0.1 mL/min (or 0.1 g/min). However,
the symptom of xerostomia has been reported to appear when normal
salivary output declines by approximately 50%, regardless of the
starting value. Normal saliva production has been estimated to be
600 mL/24h.2 Patients with chronic xerostomia complain of a
continual feeling of oral dryness and find it difficult to eat dry
foods.3 In addition to the subjective complaints, the patient
with salivary gland dysfunction is susceptible to increased dental
caries, oral pain, frequent infections, and difficulties in
speaking, chewing, and swallowing.4 Several tests are available
for measuring salivary function. According to Fox et al,5
evaluation of salivary gland function can be assessed by stimulated
saliva collection and analysis. The biopsy of the salivary glands,
usually obtained from the lower lip, is used to differentiate true
Sjogren's syndrome from other forms of salivary gland dysfunction.
The approach to the treatment of this condition varies
considerably. In some patients, xerostomia may be managed by sipping
water frequently. Other patients stimulate salivary flow with
sugarless mints or gum.6 Salivary substitutes such as a
carboxymethylcellulose-based artificial saliva have been used by
some patients to supplement low quantities of salivary flow.
Pharmacologic agents have been introduced to treat the oral dryness
of salivary gland dysfunction in patients where unstimulated
salivary flow was low or nonexistent but where some functional
salivary gland tissue existed. Fox et al4 reported that
pilocarpine was effective for relieving xerostomia by increasing
natural salivary function. The production of endogenous saliva is of
greatest benefit to the patient both for its convenience and the
importance of natural saliva to oral functions. Recently, attempts
to increase saliva production have utilized electrical stimulation.
Preliminary investigations were reported by Weiss et al7 in
1986.
This report will examine the published literature and other
available evidence to evaluate the electrostimulation of salivary
production and determine if there are xerostomic patients who would
benefit from this procedure.
Background
Sjogren's syndrome is a chronic inflammatory and autoimmune
disease in which the salivary and lacrimal glands undergo
progressive destruction by lymphocytes and plasma cells resulting in
decreased production of tears and saliva.8 Sjogren's syndrome
is seen predominantly in middle-aged elderly women.9 Females
are involved 10 times more commonly than males. Secondary effects of
xerostomia include impairment in the normal movement of lips and
tongue, thereby hampering speech, mastication, and
swallowing.10 Additional signs include oral soreness, adherence
of food to buccal surfaces, fissuring of the tongue, an altered
sense of taste, and a marked increase in dental caries and
infection. Soreness and redness of the mucosa are usually the result
of candidal infection, which is found in approximately 70% of the
Sjogren's syndrome patients.11
Complaints resulting from dryness of the mouth are varied and
often describe the difficulties encountered in trying to eat dry
foods without sufficient lubrication.11 Many subjects require
frequent ingestion of liquids. They may resort to carrying water
bottles or hard candy.
The parotid gland enlarges in many patients secondary to
cellular infiltration and ductal obstruction. Usually asymptomatic
and self-limited, the enlargement can be recurrent and associated
with pain or erythema. Focal infiltrates of lymphocytes are also
found in the minor salivary glands of the lower lip. Biopsy provides
histologic confirmation and quantification of the degree of
infiltration.
The subjective imprsssion of xerostomia, or oral dryness, may
not reflect actual salivary gland capabilities.\12\ Salivary flow
rate estimation is a sensitive indicator of salivary gland function.
A suction cup is used to obtain parotid saliva from the gland after
the tongue is stimulated with citric acid. Although the parotid
glands make the major contribution to the total salivary flow, the
submandibular glands are the most consistently affected glands in
patients with Sjogren's syndrome. Measurement of parotid function
may result in false-normal valuse. In Sjogren's syndrome,
measurement of the submandibular/sublingual secretions are a
sensitive indicator of salivary gland hypofunction. According to Fox
et al\12\ alterations in submandibular/sublingual function have the
greatest impact on the sensation of oral dryness.
Another useful technique for studying the salivary glands is lip
biopsy. The technique is a sensitive and specific diagnostic
procedure for Sjogren's syndrome. It is well tolerated and causes no
disfigurement. The changes in the minor glands of the lower lip show
a close correlation with those in the major salivary glands.\11\ In
addition to confirming the diagnosis, biopsy allows quantification
of the degree of lymphocytic infiltration and tissue damage.
Aggregates of lymphocytes within the acinar tissue are scored. An
aggregate of 50 or more cells represents a focus. The number of foci
within 4mm\2\ of glandular tissue is determined and constitutes the
focus score. A focus score of more than 1 is characteristic of
Sjogren's syndrome.\8\
Salivary scintigraphy, which measures the uptake, concentration,
and excretion of technetium pertechnetate by the major salivary
glands, is also a sensitive index of glandular function. However, it
is expensive, requires exposure to a radionuclide, and has little
advantage over the other two procedures.\8\
The symptoms of dry eyes and dry mouth in the absence of any
drug treatment or other disorder likely to be causal suggest a
diagnosis of Sjogren's syndrome.\11\ According to Talal\8\ the
diagnosis of Sjogren's syndrome is based upon the confirmed presence
of two of the following three criteria: (1) a focus score of more
than 1 in the labial salivary gland biopsy, (2) dry eye
(keratoconjunctivitis sicca), and (3) an associated connective
tissue or lymphoproliferative disorder. The triad of dry eyes, dry
mouth, and a connective tissue or collagen disease, usually
rheumatoid arthritis, is termed secondary Sjogren's syndrome.\11\
Dry eyes and dry mouth in the absence of a collagen disease is
referred to as primary Sjogren's syndrome. The use of diuretics,
anti-hypertensive drugs, antihistamines, antipsychotic, and
antidepressants may diminish lacrimal and salivary gland
function.\13\ Because the use of anticholinergic drugs as well as a
number of other medications may be the single most frequent cause of
xerostomia, it is essential to estsblish the presence of focal
lymphoid infiltrates and autoimmunity in a patient suspected of
having Sjogren's syndrome. Supportive serologic data would include
the presence of antinuclear antibodies, an elevated erythrocyte
sedimenation rate, and the presence of anti-SS-A and anti-SS-B
antibodies.
Treatment of xerostomia is difficult and includes preventing
caries, treating and retreating oral candidiasis, and attempting to
relieve the symptoms of dry mouth by increasing fluid intake,
replacing absent saliva with saliva substitutes, or stimulating the
remaining glandular tissue to secrete. Patients presenting with
milder stages of xerostomia may benefit from frequent small sips of
water or other fluids such as fruit nectars, and this may be as
effective as any other means of alleviating symptoms. Sialagogues
such as vitamin C tablets, sugarless chewing gum, mints, or hard
candies may offer temporary relief through masticatory or gustatory
stimulation. For other patients, saliva substitutes may ameliorate
symptoms and possibly increase salivary flow. Efforts at relieving
the symptoms of chronic xerostomia through the use of salivary
substitutes and by stimulating salivary flow usually offer only
temporary relief from dryness. Nevertheless, appropriate management
of patients with xerostomia requires that those patients whose
salivary flow can be increased by means of sialagogues be
distinguished from those patients whose salivary flow cannot be
stimulated, or whose flow is insufficiently stimulated.\14\ Patient
response can be tested with the use of a mechanical (paraffin
chewing) or a gustatory (citric acid) stimulant.\15\ The placement
of citric acid crystals or a 2% citric acid solution in the mouth
will stimulate demonstrable salivary flow within a few minutes in
responsive patients.\12\,\14\
Where stimulation of salivary flow by sialagogues has been
ineffective, saliva substitutes have been applied symptomatically to
alleviate mucosal discomfort and to air oral functioning.\10\
Artifical saliva substitutes usually contain carboxymethylcellulose
with or without the presence of natural mucins.
Carboxymethylcellulose is used to impart lubrication and viscosity.
Saliva substitutes that contain natural mucins maintain a surface
tension similar to that of natural salival. Salts are added to
artifical saliva to mimic the electrolyte content of natural
saliva.\15\ According to Brastings,\16\mucin-containing salivas are
preferred by patients because carboxy-methylcellulose compounds seem
to be uncomfortably sticky. Preparations containing mucin are
considered to provide formualtions that most closely resemble human
saliva.\17\ When applied using an atomizer, saliva substitutes wet
the oral cavity for about 30 minutes.\18\ In addition, intraoral
reserviors have been designed to allow continuous wetting of the
oral surfaces. Recently, a denture with a palatal reservoir for
artificial saliva has been constructed. The reservoir holds 2-3 cc
of substitute and needs to be refilled every 2-5 hours.\16\ Several
saliva substitutes are available and appear to be most successful
when used at night.\3\
Parasympathomimetic drugs have been used as pharmacologic
sialagogues in the treatment of xerostomia. Fox et al\4\
demonstrated that in persons with documented salivary gland disease
who have some functional salivary gland tissue, an orally
administered systemic agent is effective in relieving xerostomia and
increasing silivary output. Orally administered pilocarpine
increases the production of saliva by parotid and submandibular or
sublingual glands and relieves the sensation of oral dryness. The
investigators suggest that a sustained-release form of the drug may
offer increased therapeutic benefit. Scully\11\ recommends
pyridostigmine because it is longer acting with fewer side effects
than other pharmacologic agents. According to Vissink et at\14\ the
usefulness of pharmacologic sialagogues is limited because of their
side effects and contraindications.
By application of the concept of electrically stimulating nerves
to elicit a response, electrostimulation was developed for use in
the oral cavity to stimulate the salivary reflex. Investigators have
reported that electro-stimualtion increases salivary output and
should be used to treat patients with xerostomia secondary to
Sjogren's syndrome.\37\ The cost of a battery-operated, hand-held
stimulus probe that can provide electrical stimulation to the tongue
and hard palate is approximately $1,500.
Rationale
Proponents of electrostimulation as a method to increase
salivary production suggest that this procedure enhances the
patient's ability to generate saliva by augmenting normal
physiologic salivary reflexes. Salivary secretion is normally
controlled by reflex stimulation with effector nerve impulses
traveling along sympathetic as well as parasympathetic nerves to the
glands. Sympathetic nerve stimualtion produces a sparse viscous
secretion, whereas the parasympathetic nerve stimualtion produces a
voluminous watery secretion.\19\ The dual secretion (saliva) is a
flued mixture produced from paired major salivary glands (parotid,
submandibular, and sublingulal) and many smaller aggregations of
minor salivary glands imbedded in the submucosa of the cheeks, lips,
hard and soft palates, and tongue.
Proponents believe that xerostomia secondary to Sjogren's
syndrome can be caused by interruption of the stimulus that elicits
salivation at the effector site; such interruption results from loss
of glandular tissue with replacement by round cell infiltration,
scar, or fatty tissue. They postulate that an electronic device that
touches the tongue and roof of the mouth simultaneously will
stimulate tactile receptors, taste receptors, and intrinsic muscle
mechanoreceptors within the mucosa of the dorsum of the tongue and
the roof of the mouth. This produces electrical stimuation to the
oral and pharyngeal afferent nervous system resulting in a reflex
volley of efferent impulses to all residual salivary tissue, major
and minor, in the oral and pharyngeal regions causing salivation.
Review of Available Literature
It has long been known that the nerves to salivary glands
control the secretion of saliva. According to Garrett\19\ an
experiment in 1850 by Ludwig demonstraed that electrical stimulation
of the chordalingual nerve in the dog caused a copious secretion of
submandibular saliva.
In 1986 Weiss et al\7\ reported on the use of an electronic
stimulator as a mothod for increasing salivary production. In this
prelimianry investigation, 9 of the 24 patients with a primary
complaint of xerostomia had Sjogren's syndrome (diagnosed on the
basis of mdical history only). Following a visual examination of the
oral cavity as well as a gloved finger test to determine the
presence of moisture (any reflection was considered a sign of
wetness), patients were administered a 3-minute stimulus to the
tongue and roof of the mouth with the probe (electrodes) of the
hand-held stimulator. The maximum voltage delivered by the device is
6V with a current of 9 A. Patient tolerance controls and
determines the level of stimulation. Two subsequent stimulations of
3 minutes each were conducted at the same sitting by most of the
patients (actual numbers not reported). Each stimulation procedure
was followed by a subjective patient evaluation of improvement and a
repeat clinical examination.
According to the investigators, prior to stimulation, seven of
the nine patients with Sjogren's syndrome were considered to have
slight amounts of moisture present, and the remaining two patients
had ``no moisture'' present. Following stimulation, all nine
patients reported subjective impressions of increased salivation as
compared with prestimulation conditions. Clinical assessment was in
agreement with the subjective patient evaluations. Weiss et al.\7\
reported that the electronic device stimulates residual salivary
tissue in the oral and pharyngeal regions, producing increased
salivation.
In 1988, Steller et al.\3\ conducted a study of electrical
stimulation of salivary flow in patients with biopsy-proven
Sjogren's syndrome. The response to an electrical stimulus applied
to the tongue and hard palate was observed in a randomized, double-
blind, 4-week study of 29 subjects with xerostomia secondary to
Sjogren's syndrome. To be eligible to participate in the study,
subjects had to have an unstimulated whole (total gland secretions)
salivary flow rate of less than 0.2 g/min. Patients were randomly
assigned to active or placebo devices, which they used for 3
minutes, three times a day for 4 weeks. Response to stimulation was
assessed as whole saliva flow rates, which were measured at weeks 0,
2, and 4, both before and after stimulation with the device.
According to the investigators, there were no statistically
significant differences between changes in prestimulation whole
saliva flow rates or differences between the net changes in mean
whole saliva flow rate (poststimulation minus prestimulation flow)
of the active and placebo groups at each visit. The investigators
did find the changes in mean poststimulation whole saliva flow rates
between subjects using active and placebo devices from weeks 0 to 4
of the study to be statistically significant. However, analysis of
the results showed that the mean increase in the poststimulation
flow rate of the active device group (13 subjects) was due mainly to
the responses of three subjects who showed marked increases in their
whole saliva flow rates during the study. The investigators noted
that the initial salivary flow rates of these subjects were the
highest in that group, and their labial salivary gland focus scores
were among the lowest.
The investigators concluded that some Sjogren's syndrome
patients with residual salivary flow show significant responses to
electrical stimulation, but others with low or absent whole saliva
flow rates do not respond. During the 4-week study period no change
in the appearance of the oral mucosa was observed at the site of
electrode placement, and no marked changes or patterns of variation
in subjects' pulse and blood pressure were observed before or after
the device was used.
Discussion
Xerostomia is a complaint of elderly individuals, particularly
women.\6\ Decreases in both quantity of saliva as well as
composition cause a multitude of problems. In a healthy mouth,
copious saliva containing essential electrolytes, glycoproteins, and
antimicrobial enzymes continually lubricates and protects the oral
mucosa, thus cleaning the mouth, regulating acidity, maintaining the
integrity of the teeth, and destroying bacteria.
Currently, xerostomia is managed on the basis of subjective
symptoms, evidence of reduction in salivary flow, and complications
that result from dry mouth. To alleviate some of the problems
resulting from salivary dysfunction, pharmacologic sialagogues such
as pilocarpine and pyridostigmine as well as sialagogues that
include sugarless chewing gum, mints, or candy are prescribed in
order to stimulate more salivary flow.\18\ Sialagogues are effective
only if salivary gland function is present.
The preliminary investigation by Weiss et al.\7\ in 1986
demonstrated that a probe providing electrical stimulation applied
to the tongue and hard palate of patients with xerostomia presumed
secondary of Sjogren's syndrome produces a salivary response. The
salivary response was obtained in the nine patients following a
single session of one to three electrical stimulations of 3 minutes
each. As a preliminary investigation, this study did not include a
control group or any quantitative assessment of salivary response,
duration of response, or long-term assessment of efficacy. Moreover,
seven of the nine patients tested exhibited residual saliva
production prior to treatment and may have been exhibiting a tactile
response to the probe.
The only other published report determining whether an
electrical stimulus applied to the tongue and hard palate could
stimulate salivary flow in subjects with xerostomia secondary to
Sjogren's syndrome is the randomized, double-blind, 4-week study
reported by Steller et al. in 1988.\3\ The results of this short-
term study indicate that some Sjogren's patients with residual
salivary flow in an unstimulated state (<0.11-0.20 g/2 min) show a
significant response to electrical stimulation, but others with low
(less than 0.11 g/2 min) or absent whole saliva rates do not respond
or respond to a clinically insignificant degree. Only 3 of 13
patients using the active device showed a significant response
(about 0.6-1.0 g/2 min) in salivary production when compared with
the responses of the placebo group. The whole saliva flow rates of
the remaining 10 subjects in the active group remained below 0.25 g/
2 min throughout the study and were not of the order of magnitude
necessary to indicate a significant salivary response. Whole saliva
flow rates of 10 subjects in the placebo group remained below 0.20
g/2 min throughout the study. It appears that additional studies
with larger patient populations are needed to define specific
degrees of salivary function or dysfunction that would respond to
electrical stimulation. These studies could help to determine
whether a single salivary response to electro-stimulation or some
other test such as lip biopsy focus score should be used to help
identify those patients who may benefit from the technique.
Guidelines that would specify which types of Sjogren's patients
with what degree of xerostomia and at what points in their clinical
evaluation or management would benefit from electrostimulation
cannot be developed without further clinical investigation. Long-
term studies of well-characterized patient groups will also help to
determine how long it takes to achieve a response. According to some
investigators, this should allow sufficient time to determine if any
regeneration of the salivary gland parenchyma is achieved. In order
to determine the effectiveness of electrical stimulation of salivary
flow in Sjogren's patients, studies should include information
regarding concomitant therapy (continued frequent water sipping or
use of other sialagogues) and the duration of the salivary response
so that it can be compared with the use of other therapies. Studies
and subsequent management of Sjogren's patients with dry mouth
should include quantitative assessment of salivary function
(unstimulated and stimulated, whole and individual gland salivas),
assessment of oral conditions for signs of salivary hypofunction,
and subjective patient evaluations.
Salivary glands in patients who suffer from rheumatoid diseases
show varying degrees of destruction. This damage is progressive and
considered irreversible by some investigators.\17\ The ability to
induce secretion in individuals with these conditions will be
inversely related to the glandular damage. The study by Stellar et
al\3\ shows that a device providing electrical stimulation to treat
dry mouth in patients with Sjogren's syndrome appears to be
effective after 4 weeks of study in only a small percentage of
patients. These patients may represent a group with less advanced
disease (lesser degree of lymphocytic infiltration) and a greater
amount of functional salivary parenchyma. These individuals would
likely respond equally well to mechanical, chemical, tactile, and
pharmacologic means of salivary stimulation. Anything that enhances
mastication will induce secretion. So, too, will salts and citric
acid solutions. While all of these techniques are effective, their
effects are transient; however, there have been no studies to
demonstrate that electrical stimulation provides any advantage or is
more effective than other existing techniques.
Successful treatment for dry mouth is recorded as both
subjective and objective increases in saliva output. According to
Fox et al,\5\ patient complaints of xerostomia or oral dryness may
not reflect actual salivary gland capabilities or function.
Subjective assessments alone are not adequate for diagnostic or
therapeutic purposes. Although there is no fixed salivary level for
intervention, xerostomia is generally associated with whole saliva
flow rates of less than 0.1 mL/min. For some patients, a 50%
reduction in salivary output leads to the subjective impression of
dry mouth. However, the level of diminished salivary output where a
patient becomes subject to increased risk of oral disease or
dysfunction is not known. Moreover, there is a wide variability of
``normal'' salivary output. A 50% decline for one individual might
still result in a flow rate greater than another individual's normal
output. Some investigators feel that if the minor salivary glands
can be stimulated to coat the mucosa with a thin layer of mucous,
the sensation of dryness will be relieved. Even very small increases
in saliva output may be beneficial in preventing or minimizing the
oral effects of salivary dysfunction. Long-term clinical studies are
needed to examine these issues.
Consultations
According to the National Institutes of Health (NIH),
electrostimulation may be useful in management of salivary
hypofunction, but adequate data for definitive conclusions are not
available. Electrostimulation is not widely accepted as an effective
method of treating xerostomia secondary to Sjogren's syndrome. In
addition, the number of published studies is limited.
NIH has informed OHTA that guidelines that specify which types
of xerostomic patients with which conditions and at what points in
their clinical evaluation and/or management would benefit from
electrostimulation cannot be developed without further clinical
studies utilizing well-characterized patient populations. Given the
single published study showing that only patients with residual
salivary flow in an unstimulated state will respond to
electrostimulation, NIH suspects that those individuals would likely
respond as well to other means of salivary stimulation, including
gustatory or masticatory stimuli. NIH has expressed doubt as to
whether electrostimulation using a limited stimulus time (3 minutes,
three times a day) could provide sufficient duration of increased
salivary output to have a significant impact on the oral health or
symptoms of the patient.
The Food and Drug Administration (FDA) has informed OHTA that in
May 1988 a manufacturer received premarket approval for a salivation
electrostimulator device based upon submission\20\ of engineering,
preclinical, and clinical studies and the recommendation of the
Dental Devices Panel, FDA's Center for Devices and Radiological
Health. The short-term double-blind clinical study of the device was
conducted at three institutions and included 40 patients using an
active device and 37 patients assigned a placebo. The work by
Steller et al\3\ discussed in the literature review section is part
of this submission. Based on the data submitted, the FDA found an
increase in saliva production from the patient group using the
active device compared with the patient group using the placebo
device. Subjective improvement of a burning sensation of the tongue
was noted by 12 of 22 patients treated with the active device, and
an improvement in the ability to swallow was reported by 13 of these
patients.
The manufacturer provided the FDA with a long-term clinical
study of 34 patients with Sjogren's syndrome and xerostomia that was
intended to follow patients for up to 12 months. Patients were
assessed by the physician for moisture (oral examination) prior to
the study and at visits on 1, 3, 6, and 12 months following
stimulation. Eleven of 12 patients who completed 12 months of
electrical stimulation were found on the last visit to have a
discernible improvement in salivary status when compared with the
initial assessment. As a followup to this study, a group of 23
patients was surveyed by the manufacturer via telephone to assess
changes in quality of life after using electrical stimulation for 6-
18 months. Patients indicated improvement that included increased
ease of swallowing and improved dental checkups as well as education
in burning tongue sensation, sleep interruptions, and water intake.
This device is indicated for use in patients with xerostomia
secondary to Sjogren's syndrome and intended to stimulate salivary
production from existing glandular tissue. Patients who show an
initial response to electrostimulation are considered to be
candidates for this therapy. According to the FDA there are no
contraindications associated with the use of this device.
Medical Specialty and Clinician Responses
Medical specialty groups such as The American Dental Association
were unable to provide any information regarding the
electrostimulation of salivary glands.
Comments from clinicians with knowledge of or experience with
electrical stimulation of salivary production are equivocal. Some
expressed the opinion that electrostimulation is a safe and
effective method for the treatment of xerostomia secondary to
Sjogren's syndrome. Others suggested that the method has been
inadequately tested. Some clinicians recommended beginning
electrical stimulation of the salivary glands in patients with
Sjogren's syndrome and dry mouth early in the course of the disease
in order to possibly prevent, modify, or even reverse the
progression of a salivary gland atrophy. Other clinicians are not
convinced that electrostimulation is more effective than other
simple, less costly stimulation techniques such as gustatory
stimulation or intraoral tactile stimulation.
Summary
Electrostimulation has been introduced as a technique for
increasing salivary output in the treatment of patients with
xerostomia (dry mouth) secondary to Sjogren's syndrome. The
procedure uses an electrostimulation device (salivation
electrostimulator) to increase salivary production from existing
glandular tissue. The device delivers a low-voltage electrical
stimulus to the mouth via a probe. Patients with residual salivary
tissue in the oral and pharyngeal regions who demonstrate a decrease
in the flow rate of saliva are potential candidates for this
procedure.
It is estimated that more than one million people in the United
States, predominantly middle-aged and elderly women, suffer from
Sjogren's syndrome. Patients with chronic xerostomia complain of a
continual feeling of oral dryness and have difficulty eating dry
foods. These patients are susceptible to increased caries, oral
pain, infection, and have difficulty speaking, chewing, and
swallowing.
The approach to the treatment of xerostomia in Sjogren's
patients is usually determined by the level of severity of the
symptoms. Appropriate management of patients with xerostomia
requires that those patients whose salivary flow can be increased by
means of sialagogues be distinguished from those patients whose
salivary flow is either unaffected or insufficiently stimulated. To
alleviate some of the complications due to salivary dysfunction in
those patients who respond to stimuli, pharmocologic sialagogues as
well as sialagogues that include sugarless gums, mints and candies
are prescribed in order to increase salivary flow.
Recently, electrostimulation via a hand-held stimulus probe has
been introduced as a method of treatment in xerostomia secondary to
Sjogren's syndrome. From the single published study as well as data
provided to the FDA, it appears that an electrical stimulus applied
to the tongue and hard palate (by a battery-operated device) may be
useful in the management of salivary hypofunction in certain
patients. It appears, however, that there are insufficient data at
the present time to determine the clinical utility of
electrostimulation, to evaluate the long-term clinical effectiveness
of this modality of salivary production, or to identify those
xerostomic patients who would benefit from this procedure. Also,
electrostimulation is not widely accepted as an effective method of
treatment for xerostomia secondary to Sjogren's syndrome. The number
of published studies is limited and other less expensive treatments
are available. Further research of electrical stimulation of
salivary flow is required to determine its role in the treatment of
Sjogren's patients with xerostomia.
References
1. Arthritis Medical Information Series: Sjogren's Syndrome.
Atlanta: Arthritis Foundation, 1988.
2. Peterson JK. Xerostomia. Scand J. Rheumatol 1986;61(suppl):185--
189.
3. Steller M, Chou L, Daniels TE. Electrical stimulation of salivary
flow in patients with Sjogren's syndrome. J Dent Res.
1988;67(60):1334--1337.
4. Fox PC, Baum BJ, Mandel ID. Pilocarpine for the treatmnt of
xerostomia associated with salivary gland dysfunction. Oral Surg
1986;61(3):243--248.
5. Fox PC, van der Ven PF, Sonies BC, et al. Xerostomia: Evaluation
of a symptom with increasing significance. J Am Dent Assoc.
1985;110:519--525.
6. Rhodus NL. Xerostomia: An increasingly significant dental
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for the treatment of dry mouth, J Oral Maxilo-fac Surg 1986;41:845--
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8. Talal N. Sjogren's syndrome, in Wyngaarden JB, Smith LH (Eds):
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Ruddy s, et al(Eds): Textbook of Rheumatology (vol 1). Philadelphia:
Saunders, 1985, pp. 956--973.
10. Weerkamp AH, Wagner K, Vissinic A, et al. Effect of the
application of a mucin-based saliva substitute on the oral
microflora of xerostomic patients. Oral Pathol 1987;16(9):474--478.
11. Scully C. Sjogren's syndrome: Clinical and laboratory features,
immunopathogenesis, and management. Oral surg 1986;62(5):510--523.
12. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomic and
objective measures of salivary gland performance. J Am Dent Assoc
1987;115:581--584.
13. Talal N. Overview of Sjogren's syndrome. J Dent Res
1987;66(special issue): 672--674.
14. Vissink A, Johannes's-Gravenmade E, Panders AK, et al. Treatment
of Hyposalivation. Ear Nose Throat J 1988;67:179--185.
15. Levine MJ, Aquirre A, Hatton MN, et al. Artificial salivas:
Present and future. J Dent Res 1987;66:693--698.
16. Brastings ED. Saliva, xerostomia, and salivary substitutes. Pa
Dent J 1987;54(5):23--24.
17. Duxbury AJH, Thakker NS, Wastell DG. A double-blind cross-over
trial of a mucin-containing artificial saliva. Br Dent J
1989;166:115--120.
18. Vissink KA, Panders AK,'sGravenmade EJ, et al. Treatment of oral
symptoms in Sjogren's syndrome. Scand J Rheumatol
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19. Garrett JR. The proper role of nerves in salivary secretion: A
review. J Dent Res 1987;66(2):387--397.
20. Food and Drug Administration. Summary of Safety and
Effectiveness Data: Salivation Electro-Stimulation Device,
(unpublished report), 1988.
[FR Doc. 94-12457 Filed 5-20-94; 8:45 am]
BILLING CODE 4121-01-P