Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin conditions with high morbidity and mortality. The clinical manifestations are a combination of typical skin findings or denuded skin with at least 2 or more mucosal involvements. The difference between SJS and TEN is the extension of skin involvement in which skin detachment for SJS is <10 percent of the body surface, while TEN involves detachment of >30 percent of the body surface area. The range of 10%–30% of cutaneous involvement is defined as SJS–TEN overlap. The etiology of SJS/TEN is often unclear; however, it has been shown to be associated with drug exposure or infections. Many studies showed similar causative agents for SJS/TEN as the result of a hypersensitivity reaction to a drug [1]. The other causative agents are infections, especially by
Medical records of SJS/TEN patients aged less than 15 years, admitted at Srinagarind Hospital of Khon Kaen University, Thailand from 1992 to 2012 were retrospectively reviewed after the study was approved by the Institutional Review Board (approval No. HE561346). The diagnosis of SJS and TEN were confirmed by pediatric dermatologists.
Statistical analysis was performed using STATA software, version 10. Descriptive statistical methods (mean, standard deviation, median, and frequency) were applied to analyze the demographic data. The continuous variables (length of hospitalization) were compared using a one-way ANOVA with multiple comparisons of the complications.
A total of 38 patients was recorded. There were 31 (82%) SJS patients and 7 (18%) TEN patients. The age range was from 1 year to 14 years with an average age of 6.6 years. Male to female ratio was 1.1:1. The most common causes were drug exposure which was found in 30 cases (79%), infections were found in 3 cases (8%), and unknown was found in 5 cases (13%). Among the causative drugs, the most common were antiepileptic drugs including carbamazepine, phenytoin, phenobarbital, and levetiracetam. These were followed by antibiobics, which included erythromycin, cefotaxime, trimenthoprim, cloxacillin, and amoxycillin. The other causative drugs found in our study were aspirin, ibuprofen, methotrexate, and paracetamol (
Etiology of SJS/TENCausative etiology No. of cases 30 (79%) Carbamazepine 8 Phenobarbital 7 Phenytoin 2 Levetiracetam 1 Erythromycin 3 Trimethoprim-sulfamethoxazole 2 Cefotaxime 1 Cloxacillin 1 Amoxicillin 1 Aspirin 1 Ibuprofen 1 Methotrexate 1 Paracetamol 1 3 (8%) 5 (13%)
All patients were admitted. Thirty-six patients were admitted to regular pediatric wards. Two were admitted to intensive care units because of the severe degree of skin detachments presented and need for intensive monitoring. Standard nursing care included sterile wound care, intravenous fluid replacement, adequate analgesic drugs, and adequate nutritional support. The use of sterile gauze with normal saline and Vaseline gauze were commonly used in the area of skin detachment. Pain during wound dressing was controlled by intravenous analgesic drugs before the dressing process. Two patients with severe TEN received total parenteral nutrition during the hospital stay. Systemic corticosteroids were used in 33 cases (87%). IVIG was used in one TEN patient. Opthalmologist consultation was obtained in most cases within the first day of admission.
There were 18 cases (47%) with acute complications during their stay in hospital. Ocular complications were found in 7 cases (38%), septicemia was found in 4 cases (22%), and secondary skin infections were found in 3 cases (17%), and were the first 3 most common manifestations. Two patients developed pneumonia and one patient had a urinary tract infection. Ocular complications were the only long term complication at 1-year follow up. They included symblepharon, corneal pannus, and dry eyes which were found in 6 cases (16%).
Mean length of hospital stay was 14.1 (SD 11.3) days. Mean difference in length of hospital stay between with and without acute complications was 12.3 days with
Multivariate analysis of each complication and length of hospital stayComplications Mean difference of hospital stay (days) 95% CI Urinary tract infection 1.17 0.82 9.6–11.9 Ocular involvement 11.04 <0.01 3.5–18.5 Pneumonia 11.82 0.03 0.8–22.8 Septicemia 14.72 <0.01 5.8–23.6 Secondary skin infection 10.00 0.03 0.9–19.0
Most patients (30, 79%) had a complete recovery with no long-term complications. Ocular complications were the only long term complications at 1-year follow up. They included symblepharon, corneal pannus, and dry eyes, which were found in 6 patients (16%). Two patients with TEN died (5%).
Our study reviewed data regarding SJS/TEN during the past 20 years from Srinagarind hospital, of Khon Kaen university, a tertiary care center for the North East of Thailand. A majority etiology of this study was drug-induced causes, which is consistent with most other earlier studies [4-8]. However, the most prevalent drug group found in this study was antiepileptics, rather than antibiotics, in contrasts with a previous study in Thai children [4].
This may be because our facility is a referral center for neurological diseases in the north east of Thailand. The prevalence of antiepileptic drug use is therefore
high when compared with other general hospitals.
In our study, the prevalence of SJS was higher than TEN. Boys were slightly more frequently involved than girls. Most cases were treated with systemic corticosteroids, which was consistent with the most prevalent treatment options in SJS/TEN in Thai children [4]. One TEN patient in our study was treated with IVIG.
Acute complications during hospital stay varied and included septicemia, pneumonia, and local complications such as ocular involvements and secondary skin infections. The mean difference in the length of hospital stay between the group with and without complications was 12.3 days. By using multivariate analysis, every complication including ocular involvement, was found to significantly increased the length of hospital stay. A previous study showed that prolonged hospital stay was because of systemic complications [9]. The overall outcomes in our institute resulted in complete recovery (30 patients, 79%). Ocular complications were the only long-term complications found at one year follow up. They included symblepharon, corneal pannus, and dry eyes, which were found in 6 cases. Two patients with TEN died.
Antiepileptic drugs were the most common cause of SJS/TEN in our study. Systemic corticosteroids remain treatment options in SJS/TEN in children. SJS patients had more favorable outcomes when compared with TEN patients. Complications occurred during the acute phase and resulted in prolonged length of hospital stay in SJS/TEN. Eye complications were the most prevalent as acute and long-term events in SJS/TEN. We recommend good ophthalmologic care should be routine.
The authors have no conflict of interest to report.