severe bullous drug eruption and filgrastim

Conditions: Rare Diseases; Toxic Epidermal Necrolyses

Summary: 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

Keywords: toxic epidermal necrolysis (ten) stevens-johnson syndrome (sjs) lyell's syndrome ganulocyte-colony stimulating factor (g-csf) filgrastim randomized controlled trial (rct)