Life-threatening dermatologic adverse events in oncology

Abstract

Background: The incidence of life-threatening toxicities such as Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are inconsistently reported. The potential association of anticancer agents with SJS or TEN has not been systematically investigated. Methods: We searched the literature (Ovid:1950-June 2013 and PubMed:1948-June 2013) using terms for SJS/TEN and anticancer therapy. Primary case reports, case series, and clinical trials were included. Additionally, MedWatch, Food and Drug Administration Adverse Event Reporting System (FAERS), was searched (1968-August 2012) for SJS/TEN reports associated with anticancer therapies. Proportional reporting ratios (PRR>2, N>3) and empirical Bayes geometric mean (EBGM>2, N>3, lower 95% confidence interval (EBGM0.05 >2) were used as thresholds to constitute a signal of association between SJS/TEN and anticancer drugs. Results: There were 45 SJS and 37 TEN cases associated with 17 and 22 anticancer drugs in the literature, respectively. Among cases in FAERS, significant signals were associated with SJS for bendamustine and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine, and procarbazine . Conclusion: Several drugs reported in published literature to be associated with SJS/TEN were not found to have significant signals in FAERS. Proactive pharmacovigilance to detect and define safety signals serves to assist oncology practitioners in the recognition of possible, yet uncommon, serious and/or life-threatening skin reactions.

Crizotinib-associated toxic epidermal necrolysis in an ALK-positive advanced NSCLC patient

“…If the skin involvement ranges between 10 to 30%, it is defined as overlapping syndrome (7). The most well-known causes for the above syndromes are certain medications, but in very rare cases, the coexistence of cancer can also have an impact on the incidence of SJS and TEN (7). Several cutaneous adverse cases have also recently been reported while more and more immune checkpoint inhibition were used in cancer treatment (8,9).…”

“…SJS and TEN are two overlapping syndromes of burning-like severe skin lesions and characterized by skin detachment. Both syndromes are life-threatening skin conditions, with mortality rates of 1-10% for SJS and 20-40% for TEN (7). The only differentiate criterion for the two syndromes is the quantitative evaluation of the range of affected skin.…”

Dermatologic adverse events associated with chemotherapy and targeted anticancer therapy

“…Według danych statystycznych umieralność dla SJS wynosi 1-10%, dla TEN 20-40%, a według innych źródeł nawet 70%. Związek pomię-dzy obu powikłaniami a stosowaniem leków przeciwnowotworowych jest oparty na danych z literatury z lat 1968-2012 [51].…”

“…sulfonamidy, antybiotyki. W wielu doniesieniach dokładna analiza wskazywała na taki prawdopodobny związek z lekiem przeciwnowotworowym [51,54].…”

Érythème toxique à la chimiothérapie

“…Enfin, des toxidermies sévères sont toujours possibles dans ce contexte, incluant la nécrolyse épidermique toxique, la pustulose exanthématique aiguë généralisée ou encore le DRESS [10]. Le dermatologue doit garder ses réflexes et rechercher de façon systématique les signes cliniques évocateurs d'une origine immunoallergique, ainsi que les critères de gravité associés.…”