Severe Bullous Drug Eruption and Filgrastim

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.


Eligibility Criteria:
Inclusion Criteria:

* Patient aged of 6 years old or more, presenting SJS/TEN, drug or infectious origin proofed and very strongly suspected (indirect certainty argument), confirmed by evaluator.
* SJS or TEN evolving since less than 7 days with a progression of the detachment or the eruption observed dating less than 48 hours.
* Patient and/or have right able to understand the objectives of the trial and having given their written consent to participate (parents for minors, have right for patients in immediate life-saving emergency).
* Patient registered with a social security scheme or benefiting from a similar scheme.
* Pregnancy test beta HCG negative for women of childbearing age

Exclusion Criteria:

* Patient weighing less than 20kg
* Chronic myeloid pathology such as myeloid leukemia or AML (acute myeloid leukemia)
* Thrombophilia or thrombotic pathology in progress
* PNN (polymorphonuclear neutrophils) \> 50.000/mm3 on the CBC (Complete Blood Count) during the inclusion visit
* Administration of G-CSF or GM-CSF within 5 days of inclusion
* Patient who received cyclosporine, anti-TNFalpha or intravenous immunoglobulins or lithium in the month prior the inclusion
* Pregnant or breastfeeding woman
* Patient under protective measure (safeguard measure, curatorship, guardianship) or deprived of liberty
* Patient in exclusion period after participation at other interventional clinical trial
* Known hypersensitivity to the active substance (FILGRASTIM) or to the one of the excipients (glutamine acid, sorbitol E420, Polysorbate 80)
* Patient presenting a known glucose intolerance or hereditary fructose intolerance
* Patient with a traumatic brain injury less than 24 hours
* Patient admitted with septic shock