The Medication Risk of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label

Abstract

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Chemotherapy‐induced skin toxicity and capillary leak syndrome

“…Many medications including antibiotics can cause TEN . In this cohort, Scorten risk was high (>90%) due to the multi‐organ damage.…”

Defining Regional Differences in Drug‐Induced Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis: A Tool to Improve Drug Safety?

“…In an attempt to define the risk of medication‐related SJS/TEN more broadly across Asian populations, Wang et al . analyzed registration databases in eight Asian countries, including seven in Southeast Asia and Japan, and compared them with medications labeled by the FDA as having a high risk for SJS/TEN.…”

“…Despite the limitations, the study by Wang et al . has provided important insights into regional differences of medication‐induced SJS/TEN across Asia, and highlights key differences between Asia and Europe.…”

“…4 In 2004, a strong association between HLA-B*15:02, an HLA class I allele prevalent in those of Southeast Asian ancestry but uncommon (<1% prevalence) in those of European and African ancestry, was reported that again provided an explanation for the initial epidemiological observation. 4 In an attempt to define the risk of medication-related SJS/TEN more broadly across Asian populations, Wang et al 5 analyzed registration databases in eight Asian countries, including seven in Southeast Asia and Japan, and compared them with medications labeled by the FDA as having a high risk for SJS/TEN. From patients treated between 1998 and 2017, they identified 1,028 cases of SJS/TEN that met a minimum of a probable score on the algorithm of drug causality for epidermal necrolysis causality assessment scoring system for SJS/TEN, and in 98%, a single drug was implicated as having a probable or definite causality.…”

Severe TEN Management in a Patient with Schizophrenia

“…Surface involvement in TEN is more than 30% with 20% to 60% mortality, and 10% to 30% of the patient's skin are overlap of SJS/TEN. The annual rate of TEN is 0.4 to 1.3 cases per million population (1,2). Several causes can lead to this reaction, the most important of which are medicines, but HLA differences in ethnic populations can lead to these syndromes with different medicines in different countries (3).…”