Description of the projectThe Project

RegiSCAR - objectives & summary

European Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs and Collection of Biological Samples
The aim of the consortium is to reduce the medical and economic burden of severe cutaneous adverse reactions (SCAR) on public health and to improve the safety of medication use. The practical objectives of this project are :
1) to build an European Registry of SCAR for continuous surveillance of new drugs with adequate pharmacoepidemiologic methodology and for providing reference information on SCAR
2) to organise a centralised collection of biological samples (plasma, lymphocytes, DNA and skin) to allow high quality studies on pharmacogenetics and investigations of the mechanisms of these reactions,
3) to constitute a cohort of patients in order to study the outcome, prognosis factors, sequelae and impact on quality of life of these severe side effects of medicine.

Brief description:

All cases of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS) requiring admission in one of the hospital participating to the network in 6 countries will be included in the study. Active case finding will be used through regular contact with all relevant facilities. In each country a trained investigator will interview each case patient and collect information on medication use in the 8 weeks preceding the onset of the disease, recent infections, demographic information and relevant medical history. A standardised case record form will be used to collect prospectively clinical information up to the date of discharge and one year later. As done in previous studies an international group of experts will ascertain all cases using a strict process of validation.
With informed consent, samples of skin biopsies (patients) and of blood (patients and controls) will be directed to a specialised bank for separation and conservation of plasma, lymphocytes and DNA.
The clinical database will provide estimates of the risks of medications using case-control and case cross-over analyses as well as linkage to databases on drug utilisation. It will also provide information on the outcome, allow the validation of prognosis indexes, and give insights on the effect of treatments.
Biological samples will be used for the following investigations: determination of the phenotype, functions and antigenic specificity of lymphocytes isolated at the time of the reaction from the blood and skin of patients; study of susceptibility genes by an association study directed first at candidate genes and second at the full genome by using 1000 single nucleotide polymorphisms (SNPs), determination of the serum level of a variety of cytokines that may have a prognostic value. Duplicates of biological samples and of the clinical database will be accessible to every scientist who has a project validated by an independent scientific board and the steering committee of the project.

Concerning the recruitement of cases, main emphasis is put on France and Germany, as the number of expected cases in smaller countries makes it very difficult to obtain national funding for the project. Still efforts are being made to support ,and if feasible, even expand the network to target a poulation as large as possible (necessary for such rare diseases). The analysis of drug risks (especially for newly markered drugs) and pathophysiological and pharmacogenetic studies on biologic samples have to be based on a large pool of patients with a thorough case validation and a detailed medication history.

At the moment our group is expanding to other countries. People interested in participating or potential sponsors are welcome to contact the study coordinator:

Prof.Dr. med Maja Mockenhaupt
Dokumentationszentrum schwerer Hautreaktionen (dZh)
Hauptstr. 7
D-79104 Freiburg
Tel. +49 761 270-6723
Fax +49 761 270-6834