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JOURNAL OF DENTAL SCIENCES


Volume 2 Issue 1
BIOCOMPATIBILITY OF NICKEL CONTAINING
DENTAL ALLOYS : A REVIEW OF LITERATURE
Address for Correspondence :
Dr. Rakesh G. Makwana
Department of Prosthodontics, Faculty of Dental Science,
Dharmsinh Desai University, NADIAD-387001. GUJARAT
Mobile : 9825395427
E-mail : drrakesh_77@yahoo.com
Dr. Rakesh G. Makwana
Reader
Department of Prosthodontics, Faculty of Dental Science,
Dharmsinh Desai University, NADIAD-387001. GUJARAT
Introduction
Nickel is with you and does things for you from the time you
get up in the morning until you go to sleep at night. This
phrase from the brochure The Romance of Nickel clearly
shows that this metal is present in a large variety of products,
1,2
and therefore is almost impossible to avoid.
Nickel is an important cause of allergic contact dermatitis in
the general population, both among children and adults, with
3
a worldwide prevalence of around 8.6%. The prevalence
4
among young females is even higher, around 17%.
Sensitization to nickel can occur from skin contact with
jewelry and consumer products, from occupational exposure
and experimentally. It can occur either by exogenous (skin
contact) or endogenous exposure (oral, inhalation).
Nickel-containing dental alloys continue to be used
successfully in the provision of various forms of dental care.
Many of these alloys have applications in the construction of
restorations designed to remain in clinical service for many
years, including crowns, fixed bridgework, and removable
partial dentures. Furthermore, nickel-containing alloys find
extensive application in orthodontics, including metallic
brackets, arch wires, bands, springs and ligature wires. Many
instruments and devices, for example, endodontic
instruments also contain nickel.
An international workshop was held in Michigan, USA in 1985
on the biocompatibility, toxicity and hypersensitivity to alloy
systems used in dentistry. The workshop summary
concluded that despite the apparent lack of data on the
biocompatibility of many cast and wrought dental alloys, their
clinical efficacy is established.
Given the importance of nickel in the development of optimal
qualities of alloys used in dentistry, it is considered important
to periodically provide a comprehensive, evidence based
review of the existing knowledge and understanding of the
biological reactions to and the biocompatibility of nickel
containing dental alloys as the possible adverse effects have
concerned both the people who have these alloys intraorally
and the clinicians and dental technologists who work with
them.
Immune response to nickel
a) Allergy to nickel-containing dental alloys
Although many common allergens are found in dental
materials, few allergic reactions are associated with the use
of them.
Mucosal allergy to metals may be rare for several reasons:
saliva is constantly washing away potential allergens,
which are swallowed;
the vascularity of the oral mucosa allows for rapid
dispersion of potential allergens;
particulate metals may have a suppressive effect on
chemotaxis, phagocytosis and immune response in
5
6
Abstract
Nickel is very widely used in various applications in dentistry i.e. crown and bridge, cast partial dentures and orthodontic
appliances to name a few. However, nickel is an important cause of allergic contact dermatitis in general population and as
a result there have been a concern about the safety of both the people who have these alloys intraorally and the clinicians
and dental technologists who work with them.
The purpose of this article is to review the information regarding the biologic reactions to nickel in dentistry.
Nickel is an allergen, but there is no evidence that individual patients are at a significant risk of developing sensitivity solely
due to contact with nickel-containing dental appliances and restorations. Hypersensitivity reactions to nickel are only likely
to occur with prior sensitization from non-dental contacts and even these are rare. Clinical evidence has been presented to
show that small doses of nickel, e.g. from dental appliances,may induce tolerance to this allergen. The papers reviewed
report low rates of release of nickel from dental alloys. Some nickel compounds, which are mildly cytotoxic, have been
implicated as carcinogens by inhalation in industrial settings, but these compounds are not present in dentistry-related
operations, including dental technology procedures. Nickel-containing alloys and compounds have not been associated
with increased cancer risk by oral or dermal routes of exposure. It is concluded that, subject to use according to established
techniques, nickel-containing dental alloys do not pose a risk to patients or members of the dental team.
Key words - Nickel, Alloys, Dental appliances, Biomaterials, Toxicology, Allergy, Oral Lichen Planus, Hyposensitization
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JOURNAL OF DENTAL SCIENCES
Volume 2 Issue 1
some systems and the paucity of the stratum corneum
on mucous membranes may reduce the availability of
carrier proteins to combine with metallic haptens to form

complete antigens.
Case reports of allergic reactions to intraoral nickel have
8,9,10,11
occasionally been reported in the literature. The reports
are generally of patients with presensitisation to nickel who
then, post-insertion of a nickel-containing orthodontic device,
developed a form of dermatitis. The clinical signs and
symptoms seen included oral oedema, perioral stomatitis,
gingivitis, and extraoral manifestations such as eczematous
rashes. The time taken for the dermatitis to resolve was from
8,9,10,11
two days to several months, after removal of the device.
With these reports in mind, it has been suggested that high
content nickeltitanium wires should be avoided in nickel-
sensitive patients, nickel-free alternatives being available for
12
use in such cases.
Renewed interest in nickel allergy occurred when it was
shown that a low incidence of both hypersensitivity and partial
13
tolerance followed oral exposure to nickel.
b) Toxic reactions to nickel-containing dental alloys
An investigation of the effect on human epithelial cells of non-
precious dental casting alloys containing up to 84% nickel
showed that the concentration of nickel liberated from the
14
metals did not reach cytotoxic levels. Orthodontic arch wires
15
that contained up to 54% nickel caused no cytotoxic effect.
Similarly, it has been determined that the maximum amount
of nickel released from orthodontic arch wires was 700 times
lower than the amount necessary to elicit cytotoxic reaction in
16
a human peripheral blood mononuclear cell culture. These
findings are important as the use of high level nickel-
containing 'shape-memory' wires is increasing in
orthodontics.
c) Oral lichen planus & lichenoid reactions to nickel-
containing dental alloys
Metals like nickel, gold, palladium, cobalt or copper released
from certain dental cast alloys are thought to be the cause of
reactions such as lichenoid reactions and gingival
inflammation. The most common reported metal is nickel.
Dental materials in direct contact with the oral mucosa may
directly alter the antigenicity of basal keratinocytes by the
release of corrosion products. Contact allergy to dental
materials (presented as lichenoid reactions) mostly involved
17
type IV /delayed hypersensitivity reaction. Type IV
hypersensitivity involved cell mediated immunity primarily
macrophages and T lymphocytes which are sensitized to
antigen (haptens), but it is unknown how metallic haptens
released from dental materials are capable of triggering
immune reactions.
d) Carcinogenic reactions to nickel and nickel-
containing dental alloys
Laboratory investigations into the carcinogenicity of dental
and orthopaedic alloys were undertaken decades ago, when
it was noticed that workers in nickel and chromate refining
18
had higher risks of nasal and lung tumors. These findings
raised questions as to whether there may be risks to industrial
and laboratory personnel exposed to forms of nickel in dust or
7
vapors during casting and grinding procedures. Since
exposure is to nickel alloys, which are not carcinogens, these
risks are not considered to exist in the dental laboratory. This
is ensured when nickel-containing alloys are cast according
to manufacturer's directions and the grinding and polishing of
nickel-containing castings is accomplished using ducted air
evacuation at the workbench. No reports of carcinogenicity
associated with the intraoral use of dental alloys have been
found.
Diagnosis
The diagnosis of a response to nickel in the oral mucosa is
more difficult than on the skin. A known allergy to nickel
should be determined when the patient completes the
medical history. The patient should then be forewarned of a
possible response to the nickel in dental appliances or
prosthesis. If a nickel allergy is still in question, a diagnosis
can be confirmed by a dermatologist by conducting a
cutaneous sensitivity test called a patch test using 5% nickel
19
sulphate in petroleum jelly.
Oral clinical signs and symptoms of nickel allergy can include
20
the following: a burning sensation, gingival hyperplasia ,
labial desquamation, angular chelitis, erythema multiforme,
periodontitis, stomatitis with mild to sever erythema, papular
peri-oral rash, loss of taste or metallic taste, numbness,
21,22,23,24,25,26
soreness at side of the tongue. It should be noted
that symptoms can occur without signs. Extraoral
27
manifestations of nickel allergy may have an intraoral origin.
Before the diagnosis of nickel hypersensitivity can be made,
other lesions should be eliminated including candidiasis,
herpetic stomatitis, ulcers due to mechanical irritation and
28
allergies to other materials including acrylic.
The nickel leachability test consists of solutions of 1%
dimethylglyoxime and 10% ammonium hydroxide solutions
which are mixed just prior to use. A moistened Q-tip with the
combined solution is used for swabbing the appliance in vitro
or samples can be immersed in the mixed solution. A positive
test for nickel leachability is a colour change to red. While a
positive result can be supportive of nickel leachability from
the suspected dental material, a negative test is always
29
overriden by the clinical response to removal of the material.
Treatment
If intra- oral signs and symptoms are present and a diagnosis
of nickel hypersensitivity is established, the fixed or
removable prosthesis should be replaced with another nickel
free alloy. The nickel titanium archwire should be removed
and replaced with a stainless steel archwire which is low in
nickel content or preferably a titanium molybdenum alloy
(TMA), hereafter known as TMA, which does not contain
30
nickel.
Most patients who develop a reaction to Ni-Ti archwires
31
subsequently tolerate stainless steel without a reaction.
This is believed to be a result of the nickel being tightly bound
to the crystal lattice of the alloy, rendering them unable to be
leached into the oral cavity. Stainless steel has been shown to
release low amount of nickel in artificial saliva or sweat which
32
could help account for its low allerginicity. In the rare event
that the patient continues to manifest an allergic reaction, all
stainless steel archwires and brackets should be removed. If
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JOURNAL OF DENTAL SCIENCES
Volume 2 Issue 1
any severe allergic reaction develops, the patient should be
referred to a physician to be treated with antihistamines,
33
anesthetics or topical corticosteriods. Attempts should be
made to complete orthodontic treatment with TMA, fibre
reinforced composite, pure Ti or gold-plate wires.
The most commonly used orthodontic brackets that do not
contain nickel include ceramic brackets, products using
polycrystalline alumna, single crystal sapphire and zirconia.
Other nickel-free alternative brackets include polycarbonate
brackets made from plastic polymers, titanium brackets and
29
gold brackets.
Nickel hyposensitization
Since nickel sensitization is a hapten-specific immunological
process, it is possible to induce immune tolerance to this
metal. It had been shown that oral exposure to nickel through
dental braces prior to ear piercing reduces the risk of
34, 35
developing nickel allergy.
Oral administration of nickel sulfate 5.0mg once a week for 6
weeks in nickel-allergy patients significantly reduced the
degree of contact allergy, as measured by patch test
36
reactions before and after nickel administration.
Although nickel vaccination using oral hyposensitizing
treatment is commercially available in some countries its
37
efficacy is still to be definitely proven.
Discussion

The current classification systemfor dental casting alloys is

broken down into Types I through IV based on the alloy's

mechanical and physical properties. Before an alloy can be

classified according to its mechanical and physical

properties, however, it first must be evaluatedfor its reactivity

in the oral cavity, which is governed by thermodynamic

principles and electrochemical reaction kinetics. The

potential for corrosion is important in the bio-compatibility of
an alloy. Corrosion can produce ionized elements that

interact with biological tissues. Therefore, corrosion

increases the risk of toxicity, making it desirable to balance

corrosion against clinical performance when choosing an

alloy.

Alloys used in dentistry usually contain at least four metals
and often more, making the issue of bio-compatibility

complex. Elements making up an alloy are not necessarily

released in proportion to their percent weight; other factors
38
can influencehow much of a particular element is released.

For example, the structure of an alloy may be single-phase

(homogeneous) or multiphase (heterogeneous). This phase

structure can be important to the corrosive properties of an

alloy. Other factors found to affect corrosion are pH and the

presence of proteins. For example, nickel is released from

nickel-chromium alloys to a much greater extent in an acidic
39
environment, and the presence of proteins in saline was

found to enhance the release of silver, copper, palladium and

zinc compared with a saline solution alone(the opposite was
40
found for nickel).
The objectives of this report are to present a review of the
literature to cutaneous and mucosal nickel allergy arising
after the placement of dental appliances.
Oral nickel contact allergy is rare. An extensive literature
search found only a few reports. 15 patients with lichenoid
oral manifestations showed positive reactions when patch
tested and the positivity to Ni represented the 12.9% of all
positive reactions. The substitution of the fixed replacements
of white metal and crowns and dental bridges improved the
41 42
healing of the disease. Er and colleagues reported a case
of localized gingival recession thought to be related to oral
piercing of the lower lip. Oral allergic contact dermatitis from
nickel has been associated with oral lichenoid eruptions.
43
Scalf and colleagues reported on a series of 51 patients with
oral lichen planus, 15.7% of whom reacted positively to
44
nickel. Temesvari and Racz reported three adolescent girls
who developed chelitis and edema of the face and lips 1 to 12
weeks after exposure to dental appliances. All three girls had
+++ patch-test reactions to 5% nickel sulfate, and their
symptoms resolved after they ceased wearing the dental
45
appliances. Trombelli and colleagues reported the case of a
woman who developed eczema on her hands and feet 6
months after having had dental braces placed. The patient
had no signs of stomatitis and had a ++ patch-test reaction to
nickel. Her dermatitis clinically improved after the removal of
46
all dental braces. Wilson and Gould reported the case of an
adolescent girl who had a history of patch-test-positive
contact dermatitis from nickel and who moreover had a recall
reaction of her dermatitis on her hips, forearms, and
abdomen 2 weeks after having had dental braces placed.
There was no oral involvement. The dermatitis resolved after
47
the removal of the dental braces. Veien and colleagues
reported on five girls with dermatitis or stomatitis related to
orthodontic appliances. Four of the five girls developed
extraoral dermatitis after the placement of dental appliances.
The four girls had negative reactions on patch tests for nickel
but tested positively to nickel on oral challenge. One of the
five girls had developed pruritic oral discomfort after the
placement of an orthodontic appliance. She had a ++ patch-
test reaction to nickel; however, she had a negative reaction
to nickel on oral challenge. After her dental appliance was
48
removed, her discomfort resolved. Counts and colleagues
reported a case of gingival hypertrophy secondary to a nickel-
containing transpalatal arch appliance in an adolescent. The
patient also had a positive patch-test reaction to 5% nickel
sulfate.
In general, nickel-sensitive patients are not at an increased
risk of developing an oral eruption after dental work when
49
compared with patients who are not sensitive to nickel. It has
been proposed that oral nickel exposure may actually protect
50
patients from cutaneous nickel allergy. Van Hoogstraten
51
and colleagues suggested that oral exposure to nickel
induces a specific T-cell tolerance, preventing subsequent
52
cutaneous hypersensitivity. Marigo and colleagues reported
that continuous oral exposure to nickel might modulate nickel
sensitivity through oral tolerance, which they demonstrated
through in vitro cell proliferation assays. Working with 132
49
nickel-sensitive adolescents, Kerosuo and colleagues
found that dental braces may reduce nickel sensitivity and
that there may be a protective threshold for oral tolerance to
53
nickel. Haudrechy and colleagues reported that previous
oral nickel exposure through dental appliances prevented 51
patients from developing allergic contact dermatitis from
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JOURNAL OF DENTAL SCIENCES
Volume 2 Issue 1
52
nickel after ear piercing. Marigo and colleagues suggested
that continuous oral exposure to nickel may lead to oral
tolerance and may modulate nickel sensitivity.
Conclusion
Nickel is found in many alloys used in the practice of dentistry.
These alloys have a long-standing history of successful use
in dentistry, with no significant reports of biological effects.
Nickel is a moderate allergen, as detected by patch testing for
contact allergies, but there is no evidence that individual
patients are at a significant risk of developing nickel
sensitivity solely attributable to contact with nickel-containing
dental appliances and restorations. There is no evidence of
carcinogenicity associated with the intraoral use of nickel-
containing dental alloys.
On the contrary, the frequency of Prosthodontic and
Orthodontic treatment and the common use of nickel
containing dental materials raise the interesting question of
whether dental treatment may act to increase or decrease the
burden of nickel hypersensitivity in the population. There is
evidence that oral exposure to nickel may induce
immunologic tolerance to nickel and thereby reduce the
incidence of nickel allergies. Nevertheless when clinical signs
or symptoms presumed to be due to nickel hypersensitivity
are distressing to patients there are many choices of
materials available to the dentist as alternatives.
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