Stevens-Johnson syndrome/toxic epidermal necrolysis in Jewish and Arab populations.

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We have recently reported on antiepileptic drug (AED-) and non–AED-related cases of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Israel.1, 2 A subanalysis of the cases in which SJS/TEN was associated with AEDs (mostly phenytoin, lamotrigine, and carbamazepine) now reveals a relatively high percentage of Arabs and Jews of North African and Middle Eastern origin (combined) in this cohort. Of the 16 Israeli patients, 4 were Arab. The other 12 were Jews, among whom the country of origin was recorded for 7, including 2 patients from Morocco and one from each of the following countries: Iraq, Lebanon, former USSR, and Ethiopia (total 8 Middle Eastern Jews, North African Jews and Arabs vs 2 others). A patient from France was not included in the group analysis due to uncertainty regarding her ethnic origin, although the majority of French Jews originate from Algeria, Tunisia, and Morocco.3 An additional patient, an Arab from the Gaza strip, was also excluded to allow comparisons to Israeli population databases. By the end 2016, Arabs (excluding Druze) and Jews of Moroccan, Iraqi, and Lebanese origin comprised 19.1%, 5.6%, 2.6%, and 0.4% of the Israeli population, respectively (total 27.8%).4 If these populations were similarly represented in the SJS/TEN cohort of 10 AED-exposed patients, this would have translated to 3 AED-associated SJS/TEN cases (P < .001; Fisher's exact test). For comparison, among the 9 patients who developed SJS/TEN following consumption of drugs other than AEDs, one was Bedouin, one a Lebanese Jew, 4 Ashkenazi Jews, one Bulgarian Jew, one Ethiopian Jew (P = .054 versus the AED group), and one of mixed Jewish origin. The numbers are small, and bias may be introduced by different prevalence of AED indications and hospitalization rates among subpopulations in the studied hospitals. Yet, our finding may also suggest that genetic variability exists among Jewish and Arab populations in terms of their propensity to develop SJS/TEN following exposure to AEDs. Recently, HLA-A*24:02 was reported to be a common genetic risk factor for cutaneous adverse reactions induced in Han Chinese by carbamazepine, lamotrigine, and phenytoin.5 The newly published data of the Ezer Mizion Bone Marrow Donor Registry,6 which includes 275 699 individuals of 19 subethnic Jewish and Arab populations, reveals that the distribution of this allele in Israeli populations is unique: 10.13% in Israeli Arabs and 9%-15% in Jews from the Caucasus (15.0%), Tunisia (12.0%), Morocco (11.4%), Poland (9.0%), and Iraq (8.8%) carry HLA-A*24:02. Among all the other published Israeli subpopulations, including Ashkenazi (other than Polish), Yemen, and Libya Jews, as well as the Druze, the allele frequency is 3% or less (Figure 1). These figures suggest that some Jewish and Arab ethnic groups might be at greater risk of severe cutaneous adverse reactions when treated with aromatic AEDs compared to other subpopulations. Clearly, carrying this allele might not be sufficient for developing these reactions, even in populations in which the allele frequency is high. Until data from pharmacogenetic studies are available, Arabs and Jews of certain North African and Middle Eastern origins require greater attention upon initiation of treatment with aromatic AEDs. The authors declare no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.