Full text of DOI:10.1038/sj.bdj.4800392a

PRACTICE
case study
Delayed and immediate hypersensitivity
reactions associated with the use of
amalgam
1
2
2
3
4
B.McGivern, M.Pemberton, E.D. Theaker, J.A.G.Buchanan, and M.H.Thornhill,
Hypersensitivity to the constituents of dental amalgam is
In brief
uncommon. When it occurs it typically manifests itself as a
lichenoid reaction involving a delayed, type IV, cell-mediated
hypersensitivity response. Rarely, a more acute and generalised
response can occur involving both the oral mucosa and skin. We
describe two cases that illustrate the presentation and
management of these two types of reaction.
ꢀ Despite the widespread use of dental
amalgam as a restorative material,
hypersensitivity reactions to amalgam are
relatively uncommon.
ꢀ When hypersensitivity reactions occur,
they most commonly take the form of
delayed lichenoid reactions affecting oral
mucosa in direct contact with amalgam
fillings.
here is an increasing awareness that Department of Oral Medicine by his general
ꢀ Much more rarely a more acute
generalised mucocutaneous response
can occur.
ꢀ Dental practitioners should be aware of
the possibility of such hypersensitivity
reactions so that they may institute
appropriate management.
T
materials routinely used in dentistry dental practitioner for investigation of pos-
can give rise to hypersensitivity reactions in sible lichen planus (LP). He complained of
both sensitised patients and members of the soreness affecting the left buccal mucosa
dental team. Well-recognised allergenic and right side of his tongue that was made
substances encountered in the dental envi- worse by consuming spicy foods and acidic
1
ronment include local anaesthetic agents,
drinks. He had first noticed symptoms 12
2
3
antibiotics, restorative materials and months before presentation and they had
latex. Hypersensitivity to mercury associ- become progressively worse with time. His
4
ated with amalgam restorations may also medical history was unremarkable, he was Materials Series (Trolab Biodiagnostics Ltd,
occur and present in one of two different taking no medication and had no known Worcestershire, UK) patch test allergens. A
ways. Most commonly it presents as an oral allergies. Intra-oral examination revealed a strongly positive response to mercury (Tro-
lichenoid reaction affecting oral mucosa in heavily restored dentition with asymmetri- lab allergen E0602, 1% ammoniated mer-
direct contact with an amalgam restoration cally distributed white striated and red, cury in petrolatum) and a slightly weaker
and represents a delayed, type IV, cell medi- atrophic lesions affecting the left buccal response to amalgam (Trolab allergen
ated immune response to mercury or one of mucosa and right and left lateral borders of E2509, 5% amalgam in petrolatum) were
the other constituents of the dental amal- the tongue. The lesions were in direct con- obtained after 72 hours (Fig. 2). These
gam. Much more rarely an acute more gen- tact with the buccal and palatal surfaces of results were conveyed to the patient’s dentist
5–7
eralised or systemic reaction can occur.
an old corroding amalgam restoration in 7 who placed a bonded porcelain crown over 7
In both cases the diagnosis may not be (Fig. 1) and the lingual surface of an amal- ensuring complete coverage of the amalgam
immediately obvious. To illustrate these dif- gam restoration in 6 . core. The smaller amalgam restoration in the
ferent responses and their management, we
present 2 cases here.
Given the close association of the lesions lower right 6 was replaced with glass
with the amalgam restorations, a provisional ionomer cement. Other amalgam restora-
diagnosis of a lichenoid reaction to amalgam tions not in contact with the oral mucosa
was made and the patient was patch tested were left alone. Within 2 months of replace-
Case 1
A 50 year old man was referred to the using the European Standard and Dental ment of these restorations the patient was
1
2
Senior House Officer, Clinical Lecturer in Oral
Medicine, Clinical Academic Group of Oral Medicine
and Dental Diagnostic Science, The University
Dental Hospital of Manchester, Higher Cambridge
3
Street, Manchester M15 6FH, Clinical Lecturer in
Oral Medicine, Department of Oral Medicine,
4
Professor of Clinical Oral Science, The Oral Disease
Research Centre, St. Bartholomew’s and the Royal
London School of Medicine and Dentistry,Turner
Street, London E1 2AD
Correspondence to Professor M. H. Thornhill.
REFEREED PAPER
Fig. 1 Buccal lichenoid
reaction to a large
amalgam restoration
of 7 (case 1).
Received 05.07.99; ACCEPTED 03.08.99
© British Dental Journal 2000; 188: 73–76
BRITISH DENTAL JOURNAL VOLUME 188X. NO.2 JANUARY 22 2000
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PRACTICE
case study
Fig. 2 A strong positive
skin patch test
response to
ammoniated mercury
and a weaker response
to amalgam after 72
hours exposure (case
1).
consistent with a local anaesthetic or latex
allergy, no local anaesthetic had been given
on this occasion and it transpired that the
patient’s dentist did not wear gloves for rou-
asymptomatic and at follow-up 12 months resolve over 2–3 days and be completely tine dental procedures.
later the lichenoid lesions had completely gone within one week. In general the reac- Patch testing to various allergens includ-
tions had become progressively worse and ing the European Standard Series, the Den-
resolved (Fig. 3).
the intraoral signs and symptoms were a rel- tal Material Series (Trolab Biodiagnostics)
atively new feature. To date the patient had and various brands of latex glove was per-
Case 2
A 57 year old woman was referred to the not noticed any difficulty breathing or any formed. The patient was reviewed after 2, 24
Department of Oral Medicine by her gen-
eral dental practitioner for investigation of
episodes of intra-oral blistering and a facial
rash provoked by dental treatment. At her
last visit to the dentist an amalgam restora-
tion in a tooth on the left side of her mouth
had been repaired with a small amount of
amalgam without the need for local anaes-
thetic. The procedure was atraumatic but
within three hours bullae had developed on
the oral mucosa adjacent to the tooth and a
pruritic rash had developed on the left side
of her face extending into her scalp and
neck.
Fig. 3 Resolution of the
lichenoid reaction
following crowning
of 7 (case 1).
On direct questioning the woman gave a
long history of recurrent episodes of other systemic manifestations.
and 72 hours. She reported itching soon
urticarial rash affecting the skin of her face,
Routine dental examination alone did not after application of the test allergens and
scalp and neck precipitated by restorative elicit a reaction and for some years the after 2 hours slight erythema was noted at
dental treatment. Within three hours of the patient had thought that she might be ‘aller- the ammoniated mercury test site. On
visit the patient would notice an itchy sensa- gic’ to local anaesthetic but had not examination at 24 hours there was a very
tion affecting the skin of the face, neck and informed her dentist. The patient gave a his- strong positive reaction to ammoniated
on one occasion her scalp. This was rapidly tory of allergy to penicillin, fish and straw- mercury with vesiculation, spreading ery-
followed by the development of an urticarial berries but there was no personal or family thema and oedema. All other allergens were
rash consisting of numerous pinhead-sized history of eczema or asthma. The patient negative (Fig. 4). The mercury patch was left
wheals and erythema normally confined to was taking no medication and there was off and the others re-applied. The response
the side on which the restorative procedure no history suggestive of exposure to to ammoniated mercury was only slightly
had been carried out. The reaction was fully mercury other than from amalgam restora- reduced in intensity at 72 hours with no
established within 12 hours and would tions. Whilst the reaction could have been response to any of the other materials tested.
These results were consistent with an
acute hypersensitivity response to mercury.
The patient and her dental and medical
practitioners were advised that alternative
restorative materials should be used in
future. Furthermore, they were advised that
should the removal of any existing amalgam
restoration be required, then it should be
Fig. 4 Strong positive
skin patch test response,
with vesiculation,
spreading erythema
and oedema, following
24 hours exposure to
ammoniated mercury in
case 2.
performed under rubber dam with high
speed suction to reduce exposure to any free
mercury that might be released.
Discussion
In spite of the widespread use of amalgam as
a posterior restorative material, reported
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BRITISH DENTAL JOURNAL, VOLUME 188, NO. 2, JANUARY 22 2000

PRACTICE
case study
cases of hypersensitivity to amalgam are rel-
atively infrequent. By far the most common
type is the delayed oral lichenoid reaction
6,8
(OLR). Essentially this involves a cell-
mediated, type IV hypersensitivity response
to a constituent of the amalgam restoration
and as such is the oral equivalent of skin
allergic contact dermatitis. Most often the
allergen is mercury but occasionally the
response is to one of the other components
of amalgam alloy such as copper, tin or zinc.
The lesions of OLR are similar to those of
LP. However, they can be distinguished
from the lesions of LP by their close rela-
tionship with amalgam restorations, and time of 2 months. Providing that there is no correct interpretation.
their tendency to be localised and asymmet- amalgam in physical contact with the
rically distributed. In contrast the lesions mucosa there is no need to replace all the tivity reactions to the components of amal-
of classical LP tend to be more widespread, amalgam restorations in the mouth and, as gam are far less common. In a recent review,
More acute and generalised hypersensi-
9
16
bilateral and symmetrical in distribution. in case 1, amalgam can even be left in situ as Veron et al. found that of 41 cases of amal-
As with LP, OLRs may have reticular, a core for a crown. gam allergy with systemic features reported
plaque-like, atrophic and erosive compo- It is not known why particular individuals between 1905–1986, 37 were due to mer-
nents (Table 1). A positive patch test to mer- should develop lichenoid reactions to amal- cury hypersensitivity. Of the remainder, 2
cury or another component of amalgam gam. Many patients have had amalgam were due to copper and 2 due to silver. In
may help to confirm the diagnosis. Final restorations in their mouths without prob- contrast to the more delayed amalgam-
confirmation, however, may have to await lems for many years before becoming sensi- associated OLRs, inhalation or absorption
resolution of the lesion following removal of tised. Once sensitised they then consistently of mercury vapour leads to the development
the offending amalgam restoration.
OLRs may also occur in response to a longed contact with the mucosa.
number of other allergens including drugs To become sensitised, patients require their flexural aspect. Often, as in case 2,
develop lesions wherever amalgam is in pro- of a cutaneous, erythematous, urticarial
rash affecting the face and limbs, usually on
17
such as antimalarials, antihypertensive prior exposure to the antigen. In the case of the rash is on the same side of the body as
agents, oral hypoglycaemics and non mercury this commonly occurs through the dental intervention. Acute oral manifes-
10
steroidal anti-inflammatory agents, as exposure to dental amalgam but may also tations of exposure to mercury or amalgam
11
well as palladium-based crowns and com- involve other sources of mercury notably are much less common than cutaneous
12
18,19
posite resins. It is, therefore, not surpris- disinfectants, cosmetics, dyes, foods and lesions
and may present as a burning
7
ing that reports of mercury sensitivity on vaccine preservatives. Sensitising allergens sensation associated with the formation of
patch-testing in OLR have varied between are usually highly reactive molecules of rela- vesicles which rupture to leave areas of ero-
12–62%. Patients in whom the OLR is inti- tively low molecular weight (<1 kDa) which sion. Frykholm found that only one in
mately associated with an amalgam restora- bind covalently to skin or tissue proteins seven patients with mercury allergy devel-
tion are much more likely to have a positive prior to becoming immunogenic. In the oped oral signs and symptoms whereas all
3
19
20
3
mercury sensitivity response than those case of mercury it is believed that sensitised had a cutaneous reaction. Reports have
with more extensive or non contacting mercury specific T cells react with, and often been imprecise on the time course of
13
lesions. Similarly, the reported benefit of damage, basal keratinocytes within the the reaction but they tend to occur relatively
replacing amalgam restorations in patients epithelium that present mercury-peptide rapidly in comparison to OLRs, usually
14
21–26
with LP or OLRs has been variable but has complexes, or mercury alone, bound to within hours
of placement or removal
7
been most effective in those patients with MHC molecules on their surface. Skin of an amalgam filling. As with patient 2
OLR lesions in direct contact with amalgam patch testing is a useful way of identifying these reactions are usually self-limiting and
15
fillings. Bratel et al.
demonstrated the allergen responsible for such cell medi- completely resolve over a period of a few
25
improvement in 95% of such patients ated, delayed, type IV hypersensitivity days, presumably as the release of free
treated. The time course of resolution is also responses and typically results in a positive mercury from the amalgam restoration
14
variable. Ibbotson et al. found that the response after 72–96 hours. Although it is a diminishes.
lesions resolved in 16 out of 17 patients with relatively straightforward procedure, it
The precise nature of these acute allergic
patch test positive OLR to amalgam within needs to be performed at a specialist derma- responses is not clear. However, the rapid
12 months of replacement, with a mean tology, allergy or oral medicine centre for onset, urticarial rash and more widespread
BRITISH DENTAL JOURNAL, VOLUME 188, NO. 2, JANUARY 22 2000
75

PRACTICE
case study
nature of the response, suggest that a type I sensitivity reactions to mercury are gener-
hypersensitivity response may be involved. ally self-limiting and resolve after a few days,
Type I immediate hypersensitivity reactions existing sound amalgam restorations may
tend to occur rapidly and are caused by anti- be left in situ. However, alternative materials
gen binding to, and cross linking, allergen should be used for new restorations. When
10 McCarten B E, McCreary C E. Oral lichenoid
drug reactions. Oral Diseases 1997; 3: 58-63.
11 Downey D. Contact mucositis due to palla-
dium. Contact Dermatitis 1989; 21: 54.
12 Lind P O. Oral lichenoid reactions related to
composite restorations. Acta Odontol Scand
1988; 46: 63-65.
13 Finne K, Goransson K, Winckler L. Oral lichen
planus and contact allergy to mercury. Int J Oral
Surg 1982; 11: 236-239.
specific IgE or IgG on the surface of mast removal of amalgam restorations is neces-
4
cells. This causes the mast cells to degranu- sary, it should be performed using rubber
late releasing histamine and other acute dam, water-spray, and high-volume suction
inflammatory mediators. If localised, this to minimise exposure to any mercury that
14 Ibbotson S H, Speight E L, Macleod R I, Smart E
R, Lawrence C M. The relevance and effect of
amalgam replacement in subjects with oral
lichenoid reactions. Br J Dermatol 1996; 134:
420-423.
17,27
results in an urticarial rash and other local may be liberated.
Antihistamine cover
changes. However, if more severe, the effects may also be beneficial during amalgam
may be more widespread with oedema, removal in those where the response is
15 Bratel J, Hakeberg M, Jontell M. Effect of
replacement of dental amalgam on oral
lichenoid reactions. J Dent 1996; 24: 41-45.
16 Veron C, Hildebrand H F, Martin P. Amalgames
dentaires et allergie. J Biol Buccale 1986; 14: 83-
100.
17 Holmstrup P. Oral mucosa and skin reactions
related to amalgam. Adv Dent Res 1992; 6: 120-124.
18 Gaul L E. Immunity of the oral mucosa in epi-
dermal sensitization to mercury. Arch Dermatol
1966; 93: 45-46.
19 Eversole L R. Allergic stomatitides. J Oral Med
1979; 34: 93-102.
20 Frykholm K O. On mercury from dental amal-
gam, its toxic and allergic effects and some com-
ments on occupational hygiene. Acta Odontol
Scand 1957; 15 (suppl. 22): 1-108.
21 Wiltshire W A, Ferreira M R, Ligthelm A J.
Allergies to dental materials. Quintessence Int
1996; 27: 513-520.
22 White I R, Smith B G. Dental amalgam dermati-
tis. Br Dent J 1984; 156: 259-260.
23 Thomson J, Russell J A. Dermatitis due to mer-
cury following amalgam dental restorations. Br
J Dermatol 1970; 82: 292-297.
24 Wright F A. Allergic reaction to mercury after
dental treatment. N Z Dent J 1971; 67: 251-252.
25 Nakayama H, Niki F, Shono M, Hada S. Mer-
cury exanthem. Contact Dermatitis 1983; 9:
411-417.
tachycardia and respiratory difficulty.
thought to be due to type I hypersensitivity.
Skin patch testing is not designed
for investigating type I hypersensitivity
responses, although reactions within the
first 24 hours of applying skin patch test
allergens may occur in sensitised individu-
1
2
3
Wildsmith J A, Mason A, McKinnon R P, Rae S
M. Alleged allergy to local anaesthetic drugs. Br
Dent J 1998; 184: 507-510.
Norris L H, Papageorge M B. The poisoned
patient. Toxicologic emergencies. Dent Clin
North Am 1995; 39: 595-619.
als. Normally, type
I hypersensitivity
Kaaber S. Allergy to dental materials with spe-
cial reference to the use of amalgam and poly-
responses are detected using the in-vitro
radioallergosorbent test (RAST) for anti-
gen-specific IgE antibodies or by skin prick
testing. However, the small size of the mer-
cury molecule, the lack of its conjugate and
its toxicity, precludes performing these
assays and to our knowledge no center cur-
rently offers a RAST for mercury. This
makes it difficult to confirm that acute
reponses to mercury in amalgam are the
result of a type I hypersensitivity response.
Indeed, it is possible that some cases, partic-
ularly those that are very localised or have a
more prolonged time course, represent a
mixed or more acute type IV response. In
general, however, the clinical features help
to clearly distinguish between acute
responses to mercury and chronic lichenoid
reactions (Table 1).
methylmethacrylate. Int Dent
J 1990; 40:
359-365.
4
Shah M, Lewis F M, Gawkrodger D J. Delayed
and immediate orofacial reactions following
contact with rubber gloves during dental treat-
ment. Br Dent J 1996; 181: 137-139.
5
6
Duxbury A J, Ead R D, McMurrough S, Watts D
C. Allergy to mercury in dental amalgam. Br
Dent J 1982; 152: 47-48.
Eley B M. The future of dental amalgam: a
review of the literature. Part 6: Possible harmful
effects of mercury from dental amalgam. Br
Dent J 1997; 182: 455-459.
7
8
9
Enestrom S, Hultman P. Does amalgam affect
the immune system? A controversial issue. Int
Arch Allergy Immunol 1995; 106: 180-203.
Jolly M, Moule A J, Bryant R W, Freeman S.
Amalgam-related chronic ulceration of oral
mucosa. Br Dent J 1986; 160: 434-437.
Lamey P J, McCartan B E, MacDonald D G,
MacKie R M. Basal cell cytoplasmic autoanti-
bodies in oral lichenoid reactions. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 1995;
79: 44-49.
26 Duxbury A J, Watts D C, Ead R D. Allergy to
dental amalgam. Br Dent J 1982; 152: 344-346.
27 Bauer J G, First H A. The toxicity of mercury in
dental amalgam. Cda J 1982; 10: 47-61.
Since lesions associated with acute hyper-
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