Community Dent Oral Epidemiol 2003; 31: 200±6

Printed in Denmark. All rights reserved

Reporting on adverse reactions

Gunvor Bentung Lygre1,2, Nils Roar
Gjerdet2, Arne Geir Grùnningsñter1
and Lars BjoÈrkman1

to dental materials ± intraoral

1
Dental Biomaterials Adverse Reaction Unit,
2
Department of Odontology ± Dental
Biomaterials, University of Bergen, Norway

observations at a clinical
follow-up
Lygre GB, Gjerdet NR, Grùnningsñter AG, BjoÈrkman L. Reporting on adverse
reactions to dental materials ± intraoral observations at a clinical follow-up.
Community Dent Oral Epidemiol. 2003; 31: 200±6. ß Blackwell Munksgaard, 2003

Abstract ± Objectives: A national reporting system designed to monitor adverse reactions

to dental materials was established in Norway in 1993. The activities have also included
clinical examination of patients with suspected reactions to dental materials. The
ongoing activities are coordinated by the Dental Biomaterials Adverse Reaction Unit at
the University of Bergen. The reporting procedure is based on voluntary spontaneous
reporting by dentists and physicians. The reports could be based on subjective
symptoms or objective ®ndings, or both. The aim of the present study was to compare
reported objective intraoral ®ndings with those found during examination at the unit.
Methods: Reported reactions were compared with clinical ®ndings obtained
following dental and medical examination at the unit. From 1993 to 1999, a total of 899
reports were received while 253 patients were referred and examined at the unit. Results:
The reports on patients who were examined at the unit involved mainly reactions
related to amalgam ®llings (84%), metals in ®xed dentures (11%), resin-based materials
and cements (4%), materials used in removable dentures (2%), and endodontic
materials (2%). Edema, lichenoid reactions, ulcers/vesicles, erythema, and atrophy were Key words: adverse reactions; dental materials;
intraoral; monitoring; objective ®ndings;
found in 80 patients during the examination at the unit. For 35 of these patients, reporting form
the intraoral ®ndings at the unit were also given in the reports. For another 45 patients,
objective intraoral signs of reactions were found upon examination at the unit, but
these ®ndings had not been reported. Conclusion: A spontaneous reporting system is a Gunvor Bentung Lygre, Dental Biomaterials
Adverse Reaction Unit, University of Bergen,
cost-effective method for monitoring intraoral reactions associated with dental Ê rstadveien 17, N-5009 Bergen, Norway
A
materials. Considering the increasing number and complexity of these materials, there Tel: ‡47 55 58 60 27
appears to be a need for continuous validation of reports by a speciality unit. In order to Fax: ‡47 55 58 98 62
receive more accurate information about the adverse reactions, it would be e-mail: Gunvor.Lygre@odont.uib.no
advisable that the reporting forms include more detailed guidance regarding signs of Submitted 4 January 2002;
reactions that practitioners should be on the look out for and consider. accepted 1 October 2002

Various types of adverse health effects have been
ascribed to the presence of dental materials. Such
effects are not always limited to the oral tissues, but
the body in general can also be affected. A large
number of people are exposed to dental materials.
Even though some individuals are sensitive to sub-
stances released from these materials, adverse reac-
tions are considered as rare (1±6).
To monitor adverse reactions from dental bioma-
terials, a national reporting system was established
in Norway in 1993, funded by the Ministry of Health
and Social Affairs. It was coordinated by the Dental
Biomaterials Adverse Reaction Unit at the Univer-
sity of Bergen (7). Similar reporting procedures were
started in Sweden in 1996 and in the UK in 1999.
The purpose of the unit was to establish an
adverse reaction registry as well as to serve as a
clinical unit for patients with suspected adverse
reactions to dental materials (i.e. undesirable side-
effects related to the presence of a dental material).

200
 Adverse reactions to dental material

Fig. 1. Localization and types of reac-

tions reported in association with den-
tal materials (adopted from (17)).

The reports could be based on subjective symptoms adverse reactions referred the patient to the Unit
or objective ®ndings, or both. The most common in Bergen. During 1993±99, a total of 253 patients
intraoral signs of reactions are lichenoid reactions in were examined at the unit (Fig. 2).
the oral mucosa (8±11). Signs or symptoms might
also be ulcers/vesicles, edema, erythema, or atrophy The reports
(12±16). The reporting procedure is based on voluntary, spon-
Many patients with suspected adverse reactions taneous reporting of suspected adverse reactions by
complain about symptoms including dry mouth,
disturbance of taste, burning sensation, pain from
muscles and joints, fatigue, dizziness, headache,
memory problems, as well as concentration pro-
blems, anxiety, restlessness and depression (Fig. 1;
11, 17±21). A large number of patients have general
subjective symptoms without observed objective
signs of reactions.
The aim of the present study was to compare the
reported objective intraoral signs of reactions with
®ndings during dental and medical examination
at the Adverse Reaction Unit. Thus, the reporting
system could be evaluated and re®ned.

Materials and methods

During 1993±99, a total of 899 adverse reaction
reports were received by the Dental Biomaterials
Adverse Reaction Unit in Bergen, Norway (Fig. 2).
Reporters who, in addition, wanted an assessment
and an examination of patients with suspected
Fig. 2. The Dental Biomaterials Adverse Reaction Unit serves
both as a registry and a clinical unit. Reporters of suspected
reactions who wanted a clinical examination of the patient
with an assessment of the suspected adverse reaction
referred patients (n ˆ 253) to the unit. Thus, the patients
examined at the unit constituted a subgroup of the total
number of reported cases (n ˆ 899).

201
Lygre et al.
dentists and physicians using a reporting form (22).
The clinicians were encouraged to submit reports
even if they were in doubt of the causality of the
reaction observed.
The reports included intraoral, orofacial or general
subjective symptoms and objective ®ndings.
Reported objective ®ndings were classi®ed into
intraoral ®ndings, observations related to surround-
ing tissue, and other ®ndings apart from oral cavity
and face. Subjective symptoms were reported by
using tick boxes for a range of symptoms. The
materials allegedly related to the adverse reaction
were checked off on a list including groups of dental
materials.
Clinical examination
Among the 899 patients with reported suspected
adverse reactions, 253 (69 men and 184 women)
were referred to the Dental Biomaterials Adverse
Reaction Unit for a detailed oral, orofacial, and
medical examination (Fig. 2). From 1993 to 1999,
the clinical team consisted of one general dental
practitioner, one specialist in oral surgery and oral
medicine, and one physician.
Before the examination, all patients completed a
questionnaire concerning health problems. Inform-
ed consent was obtained from all patients. Addi-
tional information from their own dentist and
physician, along with results from laboratory tests,
202
was obtained. The physician at the unit evaluated
the supplied medical information. An oral and oro-
facial examination including dental radiographs and
saliva sampling was conducted. Lesions in the oral
mucosa were documented by photography. Biopsies
of lesions were generally not taken at the examina-
tion. Patients with suspected allergy to dental mate-
rials were referred to a dermatologist and in most of
these cases patch-tested.
Results
There were no major differences regarding sex and
age between the total number of reported cases
(n ˆ 899) and the group of patients who were also
referred for clinical examination at the unit (n ˆ 253).
Both groups involved about twice as many
women as men, and the most prevalent age group
was 40±59 years with median age of 47 years for both
groups (Fig. 3). Dentists were the most frequent
reporters and also the most frequent referrers
(Table 1).
The types of material associated with the reported
adverse reactions were mainly related to dental
®llings. Amalgam was involved in 50% of the
reports. In the group of the 253 patients that were
also referred to and examined at the unit, 84%
ascribed the reactions to amalgam ®llings, metals
Fig. 3. Number of referred patients by
age and sex (n ˆ 253).
 Adverse reactions to dental material

Table 1. Distribution of reports and referrals from health Table 3. Number of intraoral objective findings in the
personnel subgroup of patients examined at the Adverse Reaction Unit
(n ˆ 253)
Total number Patients with reports
Reporter of reports, n (%) and referrals, n (%) Reported Clinical
Objective findings findings examination
Dentists 764 (85) 197 (78)
Physicians 99 (11) 52 (20) Lichenoid reaction 21 35
Unspecified in the 36 (4) 4 (2) Erythema 16 32
reporting form Wounds/vesicles 11 23
Edema 6 8
Total 899 (100) 253 (100)
Atrophy 0 4
Others 19 74
Total 73 176
Table 2. Number of patients with reactions allegedly related
to different dental materials One patient could present several objective findings.
Reports Examined
Material (n ˆ 899) patients (n ˆ 253)

Amalgam 453 213 19 observations were categorized as `others'. Liche-

Metals, fixed dentures 88 27 noid reactions in the oral mucosa (Fig. 4a) were the
Resin-based materials 164 9 most common ®nding, both in the reports and dur-
and cements ing the examination at the unit (Table 3).
Materials in removable 30 6
dentures
In 213 patients, the adverse reaction was ascribed
Endodontic materials 16 4 to amalgam; however, 24 of these patients claimed
Unspecified materials 254 19 other materials in addition to amalgam. In this
Others, including 85 5 group, the most common intraoral observation
temporary materials
was lichenoid reactions while 111 patients (52%)
Reports could involve more than one material. had no intraoral ®ndings at the clinical examination
at the unit (Table 4). Lichenoid reactions and
erythema were the most commonly observed reac-
in ®xed dentures (11%), resin-based materials and tions in patients referred for examination of possible
cements (4%), materials used in removable dentures reactions to metals in ®xed prosthesis. Seven of nine
(2%) and endodontic materials (2%) (Table 2). patients with suspected adverse reactions to resin-
In the 253 patients examined at the Adverse Reac- based materials and cements had no objective
tion Unit, 120 intraoral reactions were found in a intraoral signs of reactions (Table 4).
total of 80 patients and included lichenoid reactions For 35 of 46 patients (76%), the objective intraoral
(Fig. 4a), edema (Fig. 4b), erythema, ulcers/vesicles, ®ndings stated in the reports were con®rmed at the
and atrophy. Seventy-four intraoral ®ndings were examination at the unit. For patients referred for
grouped as `others' and included amalgam tattoo, amalgam-related complaints only (n ˆ 189), objec-
white lines in the level of the occlusal plane (linea tive intraoral ®ndings were con®rmed in 23 of 32
alba), impressions in tongue and cheek, Fordyce patients. For patients without amalgam-related
spots, and scars. In the reports, 54 intraoral ®ndings complaints (n ˆ 21), the ®ndings were con®rmed
were mentioned in a total of 46 patients; in addition, in seven of eight patients. For another 45 patients

Fig. 4. Signs of adverse reactions to dental materials. (a) Lichenoid reaction related to amalgam fillings, (b) edema related to
nickel-containing bridge, (c) acute reaction related to insertion of temporary crown and bridge materials. This case was reported
but not referred to the unit.

203
Lygre et al.
Table 4. Number of patients at the clinical examination with different intraoral findings related to dental amalgam, fixed
prosthesis, and resin-based materials and cements
Amalgam
Objective findings (213 patients)
Lichenoid reaction 26
Wounds/vesicles 19
Erythema 20
Edema 6 3
Atrophy 2 1
Others 58
No intraoral findings 111
Each patient could be referred for alleged reactions to more than one material, and each patient could exhibit several intraoral
signs of reaction.
objective intraoral signs of reactions were found at
the unit, but not reported.
In 36 of 80 patients with objective ®ndings, the unit
assessed that there was a probable relationship
between dental materials and the reactions. In 25
of these patients, the reactions were related to amal-
gam, seven to ®xed partial dentures, three to resin-
based materials and cements, and one to removable
dentures.
Discussion
The Norwegian Adverse Reaction Unit represents a
system including both a reporting system and a
clinical examination service. An external evaluation
of the unit revealed that the model was well received
among users (23). The large number of reports
permit the possibility to establish a general view
of suspected adverse reactions to different dental
materials.
In Europe, the use of dental materials is regulated
by the EU directive for Medical Devices (24). The
Medical Devices Vigilance reporting system deals
with actual or potentially serious and life-threaten-
ing reactions only and is not intended to handle
detailed information on other reactions. Further-
more, the reports should be supplied to the manu-
facturers of dental materials who in turn are obliged
to inform the appropriate competent authority. In
many cases, it is dif®cult to identify the speci®c
material which causes the reactions, particularly
in cases where a number of materials are used in
a single restoration.
The Norwegian reporting system constitutes an
opportunity to follow the frequency of reactions to
speci®c materials (25). The coordinated activities
make it possible to compare data from adverse
reaction reports with clinical ®ndings from exam-
204
Metals in fixed Resin-based materials
prosthesis (27 patients) and cements (9 patients)
6 1
0 0
7 1
0
0
10 1
7 7
ination of patients at the unit. Thus, there is a unique
opportunity to evaluate the reports.
A number of dentists reported adverse reactions
allegedly related to dental materials but did not refer
the patients to the unit. Figure 4(c) illustrates an
acute reaction related to insertion of temporary
crown and bridge materials. This case was reported
but not referred to the unit (Fig. 4c). These acute
cases are probably taken care of locally. It can be
assumed that dentists do not refer acute short-term
reactions and that some of these cases are not
reported at all (23). However, if patients with acute
reactions were referred, the reported reaction could
have disappeared at the time of examination at the
unit. The under-reporting can be due to lack of
information on how to report, not having enough
time to ®ll in the reporting form, or not feeling an
obligation to do so (26, 27).
Some of the intraoral objective observations in the
reports and results following the examination at the
unit were not identical. A possible reason for these
observed differences could be the time interval
between the registrations in the reporting form
and the examination at the Adverse Reaction Unit.
In some cases it could, for several reasons, have
taken months up to 1 year from the actual time of
reporting to the examination. During this period of
time, the intraoral conditions could have changed.
Findings initially reported could have disappeared
and new ones may well have appeared. Neverthe-
less, the objective intraoral ®ndings in the reports
were in good accordance with those found at the
examination at unit (76%).
Patients with amalgam-related complaints consti-
tuted a higher percentage among the examined
patients than in the total number of reports. In most
cases, patients with complaints related to amalgam
have general subjective symptoms as the main
complaints, and it could be assumed that intraoral

objective ®ndings for these patients were not
emphasized as much as for patients with objective
signs of reactions.
At the unit, the intraoral examination was done by
a specialist in oral surgery and oral medicine who
had obtained special experience of examination and
had expertise in evaluating which reactions were
relevant. The results of the present study do not
support previous data by Kallus and MjoÈr that
general dental practitioners with increased interest
of reporting adverse reactions could have a ten-
dency to over-report ®ndings (13).
In several cases, a causal relationship was far from
established and there was doubt regarding the asso-
ciation between material and the signs and symp-
toms. Thus, the reporter was encouraged to make a
causality assessment. In contrast to reactions to
dental materials, the association between drug
administration and the occurrence of adverse events
may be easier to identify (28). In the case of dental
materials, provocation and withdrawal of the sus-
pected adverse reaction agent are not simple to carry
out, especially when the nature of reactions are
general chronic subjective symptoms. Regarding
intraoral lesions, we have the opportunity to remove
the suspected material and observe a possible remis-
sion.
In Norway, as well in many other countries, the
use of resin-based materials has increased (29).
Despite this, there were far fewer patients referred
for reactions related to resin-based materials and
cements. This could indicate that these reactions
may be less frequent and short-term in nature.
Mainly, long-standing reactions were referred for
clinical examination at the unit. The low proportion
of intraoral ®ndings in patients with reactions alleg-
edly related to amalgam may be explained by the
fact that these patients mainly have subjective long-
standing symptoms. In referred cases with adverse
reactions addressed to metals in ®xed prostheses,
most of the reactions seemed to be local objective
reactions.
Conclusion
The number and complexity of dental materials is on
the increase. Thus, there is a need for monitoring
possible objective reactions associated with the use
of such materials. A spontaneous reporting system is
a cost-effective means of collecting data.
In order to receive more accurate information
about objective intraoral ®ndings using the adverse
Adverse reactions to dental material
reaction reporting system, it is suggested that report-
ing forms should include more detailed guidance
regarding intraoral signs the practitioners should
take into consideration.
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