Identification of inflammatory mediator profiles associated with dental devices in order to provide leads in detecting an oral allergic reaction.

Skin and oral mucosa (e.g. gingiva, buccal mucosa, palatum) are both fully
immunologically competent tissues involved in the induction and effector phase
of the immune response. They both function by forming a barrier to harmful
environmental factors with the capacity to maintain homeostasis and regulate
immune responses when dealing with pathogens. However, clinical observations
suggest that these tissues react differently to insults arising from the
environment. For example, differences were observed in immune reactions to
nickel when comparing skin to oral mucosa. Whereas first nickel exposure via
the skin can result in sensitization, a first oral exposure to nickel e.g. in
the form of dental braces has been shown to induce specific tolerance1 where an
oral exposure to a person that became allergic to nickel by skin contact can
result in an oral and systemic allergic reaction. This would indicate that skin
is immune-stimulatory and oral mucosa is tolerogenic at first exposure and
suggests a differential role for residential cells (e.g. keratinocytes,
fibroblasts and DC) and their cross-talk with immune cells within skin and oral
tissue.
However many allergies within the oral cavity have also been reported e.g.
nickel and palladium allergy caused by dental restorative materials2,3. An
allergic reaction due to an oral exposure to allergens can also often result in
systemic reactions, e.g face or foot eczema. This raises the question whether
oral or another skin exposure is the cause of those symptoms.
Currently, measurements for diagnostic purposes are indirectly made by patch
testing the skin of patients suspected of an allergy towards their metal dental
devices. Recently a new method became available (Meso Scale) that opens the
possibility to analyze the extremely low concentrations of cytokines within the
crevicular fluid within the gingival pocket around de tooth or oral dental
device. This will give the opportunity to compare cytokine profiles of skin and
mucosal exudate in patients with (systemic) symptoms of oral metal allergy.
With this study we will evaluate the immunological reaction of oral mucosa
(gingiva) directly in contact with palladium or nickel based dental devices and
compare this to healthy mucosa not directly in contact with palladium or
nickel. Furthermore, we aim to compare the oral mucosa immunological reaction
with a *gold standard*, the skin patch test (routine diagnostic). This study
will identify potential diagnostic cytokine profiles which will provide leads
to identifying an oral allergic reaction. The knowledge obtained might in the
future lead to the development of a totally new diagnostic approach for the
determination of *oral allergy* with systemic symptoms.

Primary: To identify potential diagnostic cytokine profiles for an allergic
reaction towards a dental device in patients with symptoms of oral metal
allergy. Which might lead to a better understanding of allergic based systemic
reaction of oral exposure to metals in sensitized patients.

Secondary: To compare the immunological reaction of mucosa in contact with
palladium or nickel based dental devices with the cytokine profile obtained
from tape stripping of the routine diagnostic skin patch test site. And to
re-evaluate the peripheral blood lymphocyte assay as a diagnostic assay for
metal allergy.

This study will eventually lead to the development of a new diagnostic approach
for the determination of *oral allergy* with systemic symptoms.

Multi- center observational cross-sectional study.

Participants could benefit from the additional advice they receive about their
allergy. They could gain more information about their allergy. Also, if
possible, safe implant material alternatives can be proposed. Both methods
(crevicular washes and sequential adhesive tape stripping) are very low risk
procedures. Tape stripping can cause minor discomfort on removal and moderate
erythema resulting from application and removal. The collection of blood by
venipuncture is a routine clinical procedure and does not contain any specific
risk.