To the editor:
It is a pleasure to see that sequential proteomic profiling of
Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis (SJS/TEN) patients
is gaining attention and we thank the authors of this commentary for
their interest in and reflections on our work. SJS and TEN are the
rarest types of delayed-type drug hypersensitivity reactions, with an
estimated incidence of about 1.53-6 cases per million in western Europe
[1, 2]. The aim of our study [3] was to perform the first
comparative study of sequential proteomic profiles of SJS/TEN patients
receiving different types of adjuvant therapies and thereby create a
rationale and basis for further investigations.
In their commentary, the authors emphasize the limitations of our study:
notably the number of patients (16 overall), the differences in baseline
characteristics (affected body surface area, SCORTEN, ethnicity), the
type of sampling (serum but not sequential skin biopsies) and type of
study (not a prospective, randomized controlled clinical trial). We
fully agree with all these points raised by the authors and consider
them important for interpreting our findings. Therefore, all of them are
mentioned and either discussed / thoroughly described in the methodology
of our paper and/or accounted for in proteomic sub-analyses that we
performed.
More specifically, we did a baseline analysis of the serum proteomic
profiles depending on the affected BSA (i.e. SJS vs TEN cases), which
was mentioned in our manuscript and, in addition, is shown in the Figure
1a. This analysis did not show significant differences between the
treatment groups. In the subgroup analysis of ethnicities, we found only
one differentially expressed protein (CNTNAP2), as displayed in Figure
1b. Although our study was not designed to primarily address the
question of ethnicity- or severity-related proteomic expression
differences, these analyses allowed us to exclude a baseline bias. As
addressed and shown in our manuscript (Table 1 of the original paper),
there were no significant differences in terms of other factors
(SCORTEN, age, gender) between the treatment groups.
On a clinical level, we agree that an ideal setting to further explore
and understand the efficacy of different adjuvant / supportive treatment
approaches of SJS/TEN is a randomized prospective clinical trial. Given
the rare incidence of SJS/TEN, there is, to the best of our knowledge,
so far no published prospective interventional randomized clinical
trials in the area and it was also for our setting not possible to
perform such a study. Our study was not designed to address this
question and we clearly did not draw any conclusions or claim the
preferential use of any SJS/TEN treatment. Of note, the ongoing CanadianNATIENS study (NCT02987257), a phase III randomized study
comparing cyclosporine versus etanercept versus supportive care, may
provide important answers regarding adjuvant treatments in the
management of SJS/TEN.
Finally, as also brought up by the authors, we discuss in our paper that
future studies should aim at consolidating and expanding our results
with concurrent analyses of skin and blood. We see our work as providing
a rationale for such investigations and look forward to further progress
in the field.