Toxic epidermal necrolysis (TEN) including Stevens Johnson (SJS) and Lyell syndromes
represent the most severe drug eruptions. It is an allergic disorder caused by cytotoxic T
lymphocytes, specific of drugs, responsible for the destruction of keratinocytes by
apoptosis. Regulatory T cell (CD25 high CD4+), normally responsible for controlling the
activation of cytotoxic T lymphocytes, have altered function. Despite the progress made in
the pathophysiological understanding of TEN, there is currently no effective treatment.
The main symptom is bullous and skin peeling > 10% giving the appearance of great burns. The
death rate is estimated between 30 and 40% due to visceral inflammatory injuries and
bacterial superinfection. The risk of mortality is estimated during the initial treatment by
calculating the SCORTEN (mortality>10% if SCORTEN>2, mortality>90% if SCORTEN>5). The
morbidity is also very important (92% at 1 year), especially ophthalmologic with high risk of
blindness...
The therapeutic potential of G-CSF (Granulocyte-Colony Stimulating Factor) in TEN is
supported by several observations.
The G-CSF promotes skin healing. This has been shown in human burns, with a significant
reduction in healing time under G-CSF. The mechanisms associate the growth factor effect on
keratinocytes, macrophages stimulation and metalloprotease activity allowing tissue
remodeling limiting sequels onset. Otherwise, healing altered in deficient G-CSF mice is
corrected by the growth factor injection.
The G-CSF is an immunomodulator whose activities appear to justify use in TEN :
- Polarization of immune response to Th2 non-cytotoxic (anti Th1),
- Preferential differentiation of naive LT (T lymphocytes) in regulator LT (CD25 high
CD4+) and mobilization of regulator LT of the spinal cord to altered tissues.
The G-CSF was used in a few cases of TEN with great efficacy. No data is available concerning
sequels of SJS/TEN in treated patients.
This clinical trial program, by providing proof of the efficacy of filgrastim in SJS/TEN,
should allow progress in care of this serious toxics diseases. In the future, it could thus
reduce the significant morbidity of these syndromes with a high rate of sequelae.