Determining the possible association of skin irritation threshold and hypertrophic scar formation

Preliminary data show that the inflammatory response in wounds which give rise
to hypertrophic scars (HTSs) is reduced compared to wounds which result in
normal scars. In the general population some individuals have severe
inflammatory responses to skin irritants (low skin irritation threshold (IT)),
while others react with mild responses or no response at all (high IT).
Our study aims to examine the possible association between high IT (low skin
irritation) and HTS formation. We will also examine the possibility to use high
IT as a non-invasive prognostic tool for HTS formation.

The main objective of our study is to examine whether there is an association
between IT (as determined by visual irritation grading scale after SLS patch
test) and HTS formation and whether IT is a good predictor for HTS formation.
If so then this may be used as a non-invasive tool to predict scar outcome in
terms of HTS formation.
The secondary objectives consist of examining the association of HTS formation
with IL1a/IL1Ra ratios in the stratum corneum (SC), PBMC stimulation,
peripheral blood leukocyte and cytokine concentrations, trans-epidermal water
loss (TEWL) and DermaSpectrometer® erythema measurements after SLS patch
testing. The secondary parameters can support our findings with respect to the
primary objective.

We will conduct an observational study with reduction mammoplasty patients. A
total of 30 subjects with HTS and 30 subjects with normal scars will be
included.
At the first out-patient visit, the scars resulting from the reduction
mammoplasties will be scored either hypertrophic or normal by a scar
specialist. Peripheral blood will be collected via venipuncture. The SLS patch
test will be applied on the upper arm and will be removed 2 days later by the
participant.
4 days after the first visit, skin irritation at the patch test site will be
scored by means of a visual grading system, erythema is measured with a
DermaSpectrometer® and TEWL is measured with a TEWAmeter TM300®. Perifeer bloed
wordt afgenomen met een venapunctie. In order to determine the IL1a/IL1Ra ratio
at the patch test site, SC fluids will be collected via sebutapes. Null
measurements of TEWL, erythema and IL1a/IL1Ra ratio are performed on skin of
the opposite upper arm to the patch test. The scars as well as the skin to
which the patch has been attached will be photographed in a standardized
manner.

Participants will be subjected to a completely non-invasive ambulant skin
irritation patch test, where a patch with 4 different concentrations of SLS and
1 water control will be applied to the upper arm at time point zero and removed
after 2 days, followed by readout of primary and secondary parameters at day 4.
Participation in this study will require 2 hospital visits.
The patch test is a well established method of determining skin irritation that
can cause minor discomfort e.g. transient erythema.
SC cytokines are collected using sebutape. There are no known risks for the
IL1a/IL1Ra collection from SC by using sebutape.
Peripheral blood is collected by venipuncture, which is a very low risk
procedure.
If the IT determined by patch testing proves to be a good predictive tool for
HTS formation, future surgical patients will benefit from this test, since
clinicians will be able to predict HTS formation and possibly interfere early
in the process of HTS formation, before it becomes clinically visible.