Abstract
Background: Since the 2002 SCAR study, erythema multiforme(EM), a
post-infectious disease, has been distinguished from Stevens-Johnson
syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported
in the French pharmacovigilance database (FPDB). Objectives: To describe
EM reported in the FPDB and to compare the characteristics of the
reports. Methods: This retrospective observational study selected all EM
cases reported in the FPDB over two periods: period 1 (P1, 2008-2009)
and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of
clinically typical EM and/or one validated by a dermatologist; 2) a
reported date of onset of the reaction; and 3) a precise chronology of
drug exposure. Cases were classified confirmed EM (typical acral target
lesions and/or validation by a dermatologist) and possible EM
(not-otherwise-specified target lesions, isolated mucosal involvement,
doubtful with SJS). We concluded possible drug-induced EM when EM was
confirmed, with onset ranging from 5 to 28 days without an alternative
cause. Results: Among 182 selected reports, 140(77%) were analyzed. Of
these, 67(48%) presented a more likely alternative diagnosis than EM.
Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32),
36(49%) had a probable non-drug cause and 28(38%) were associated with
only drugs with an onset time ≤4 days and/or ≥ 29 days. Possible
drug-induced EM was retained in 9 cases (6% of evaluable reports).
Conclusions: This study suggests that possible drug-induced EM is rare.
Many reports describe “polymorphic” rashes inappropriately concluded
as EM or post-infectious EM with unsuitable drug accountability subject
to protopathic bias.