TEN/SJS are severe mucocutaneous reactions triggered mainly by exposure to medications. In up to a third of the cases, no causative agent can be identified [1, 2]. Factors that increase the risk of this reaction include HIV infection, genetic factors, malignancy, high doses of medications, systemic lupus erythematosus, and some physical stimuli [13]. However, studies from Saudi are relatively few. In this retrospective study, we reviewed all TEN/SJS cases admitted to our hospital during the last 10 years. Antibiotics were confirmed to be the causative agents in four cases (ciprofloxacin in two, trimethoprim/sulfamethoxazole in one, and levofloxacin or amoxicillin/ clavulanic acid in one case) and were suspected but not confirmed in another two cases. Tegretol and allopurinol were implicated in one case each. For the remaining four cases, the causative agents were not identified (one of them was suspected to be allopurinol or empagliflozin). These findings are consistent with those of two previous studies from Saudi implicating antibiotics (including trimethoprim/sulphamethoxazole (TMP/SMZ), amoxicillin/clavulanate, and ciprofloxacin) as the most common cause of TEN/SJS [3, 4]. A previous study from Japan on 52 cases of SJS and 65 cases of TEN reported medications to be the causative agents in all the TEN cases and most SJS cases [14]. These included antibiotics, NSAIDs, anticonvulsants, and others. Mycoplasma pneumoniae and the antibiotics used to treat it are also known to cause TEN/SJS. A study involving a cohort of cancer patients found antibiotics (most frequently, trimethoprim/sulfamethoxazole), followed by anticonvulsants and antineoplastics agents, to be the most common inducers of TEN/SJS [15]. On the other hand, a study from China found anticonvulsants to be the most common causative agent followed by antibiotics [16]. A study by the Food and Drug Administration from the USA between July 2014 and December 2017 reported that antiepileptic medications were the most reported cause of TEN/SJS [17].
The first large case-control study (SCAR study) to assess TEN/SJS risk associated with exposure to medications was conducted in four European countries from 1989 to 1993. This study confirmed the high relative risk associated with antibiotics (especially cotrimoxazole, aminopenicillins, cephalosporins, quinolones, and cycline antibiotics), carbamazepine, phenytoin, phenobarbital, NSAIDs of the oxicam type, allopurinol, and chlormezanone [18]. A later case-control study (EuroSCAR study), which included 379 patients with SJS or TEN, and 1505 matched hospitalized controls [19], added more medications to the list of causative agents (lamotrigine and sulfasalazine, among others). Another study, including 66 patients and 28 control subjects, found allopurinol to be the most frequently associated drug with SJS or TEN [20].
Consistent with previous studies that have reported a 30% mortality rate associated with TEN/SJS [21, 22], our study had a mortality rate of 25% (3 out of 12 patients died). All patients who died were diagnosed with TEN.
Supportive care is the most universally accepted strategy for the management of TEN/SJS [23]. Pharmacological therapy includes systemic corticosteroids, IVIG, cyclosporine [24, 25], and new inhibitors of tumor necrosis factor with varied effects. The use of plasmapheresis is equivocal, and thalidomide increases mortality [23]. A study from China comparing treatments based on the clinical outcomes in 39 cases of SJS and 48 cases of TEN found that increasing doses of corticosteroids did not influence the time taken to control SJS lesions but decreased the time taken to control TEN lesions. IVIG shortened the hospital stay for TEN and SJS and the time taken to control TEN [16]. A recent meta-analysis of 67 studies involving 2079 patients who received TEN treatment with immunomodulators concluded that IVIG in combination with corticosteroids could reduce the mortality in patients with TEN and SJS/TEN overlap. Thalidomide was found to be associated with a higher mortality rate [26]. Cyclosporine and etanercept emerged as promising therapies, but more studies are required to provide clearer evidence [26].
Our study has some limitations. First, it was restricted to a single center. The second is the small sample size. Finally, because of different coding, we might have missed on some TEN/SJS patients.