GRESIF: A Project for the Management of Severe Adverse Drug Reactions (SCARs). The Experience of Lombardy and Piedmont: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: In Lombardy and Piedmont (Northern Italy, about 14 million people) the GRESIF pharmacovigilance network project, aimed to collect, assess, treat and prevent severe systemic drug reactions was activated in 2021, supported by the Italian Medicines Agency (AIFA). GRESIF involves regional and hospital pharmacovigilance centers, and several hospital wards burn, dermatology, allergology, internal medicine, infectivology and intensive care departments. The registry collects in the National Pharmacovigilance Network all reports of suspected adverse drug reactions (ADRs) concerning Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), Drug reaction with eosinophilia and systemic symptoms (DRESS) and Acute Generalized Exanthematous Pustulosis (AGEP). Objective: The specific objectives of the study are to early detect severe systemic ADRs, evaluate their incidence, morbidity and mortality rates, focus on new generation drugs such as RNA antivirals and oncological drugs, implement and optimize guidelines, manage long-term sequelae by follow-up and create a consultable web-based database. Methods: We have drawn up the guidelines [1,2], through a multidisciplinary approach in order to improve the management of very complex patients even in facilities that are not habitually involved in the treatment of these pathologies. This document aims to support professionals in standardizing diagnostic criteria and methods of therapeutic approach. Its useful to inform the general practitioner about responsible drugs and give some information about risk /benefit on the riexposure. Results: In 2021, 27 cases of SJS/TEN, 18 cases of DRESS and no cases of AGEP were collected. There is a female prevalence (25 cases out 44);the age range is from 20 to 93 years. The median age of patients in Lombardy and in Piedmont is respectively 55 and 66 for females, 47 and 63 for males. The total mortality for cases of SJS/ TEN is about 19% and for DRESS we have no deaths. More frequent suspected drugs are antibiotics, followed by allopurinol and anticonvulsants. Noteworthy is the presence of 4 cases of severe ADR related to anti Covid19 RNA vaccines. In all cases, according to the guidelines, the timely discontinuation of the responsible drug was fundamental as the general management. Furthermore we started a study for the HLA typing of these patients. We enrolled 18 cases and the results showed that 6 patients who received allopurinol were all positive to HLA B 5801. Conclusion: Despite being extremely rare but serious reactions, the absolute need to implement shared diagnostic and therapeutic protocols to be applied promptly is highlighted, in order to reduce both patient mortality and long-term sequelae.