BRIEF SYSTEMATIC REVIEW OF LAMOTRIGINE-INDUCED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

Abstract

Aim: Since 2018 FDA has issued a warning concerning the risk of hemophagocytic lymphohistiocytosis
(HL) induced by lamotrigine. The aim of this article is to answer, through the study of such cases, whether
lamotrigine administration is related to HL.
Material-Method: We followed the PRISMA guidelines and we conducted a systematic search of
PubMed and Science Direct, with complementary search of Google Scholar, including case reports and
congress abstracts, using the terms («Lamotrigine» OR «Lamotrigine-induced») AND («Hemophagocytic
Lymphohistiocytosis» OR «Hemophagocytic Syndrome»). All titles and abstracts were screened, and the
full texts of relevant studies were obtained.
Results: We found 81 papers of which 49 were duplicate. Among the 32 papers, half were removed based on title and abstract (10) or full text reading (6). From the 16 papers which describe 16 case reports, 4
concerned children and adolescents and the remaining 12 concerned adult patients. Among children and
adolescents, the dose of lamotrigine was mentioned in 2 cases and was considered to be high. The time
interval between lamotrigine initiation and LH manifestation was 18.25 days. Among the adult patients,
the lamotrigine dose that induced HL was low (25-50 mg) and mentioned in only 3 cases. The time interval
between lamotrigine initiation and LH manifestation was on average 11.3 days.
Conclusions: Lamotrigine-induced HL is rare but timely diagnosis and proper treatment is essential,
otherwise it may even lead to death. The dose of the drug does not seem to play a role and the manifestation
of HL usually takes place within the first 3 weeks.