Causative Drugs and Clinical Outcome in Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and SJS-TEN Overlap in Children

Abstract

Background:

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe adverse drug reactions in children.

Objectives:

The objective was to study the causative drugs and outcome in children with SJS, SJS-TEN overlap, and TEN.

Materials and Methods:

Retrospective analysis of all the in-patient records of children below 18 years of age with the diagnosis of SJS, SJS-TEN overlap, and TEN was carried out.

Results and Conclusions:

Twenty children were identified, eight patients each were diagnosed as SJS and TEN and four as SJS-TEN overlap. Multiple drugs were implicated in 15 cases while single drug was responsible in 5 cases. Antibiotics (40.7%) were implicated as the commonest cause followed by NSAIDS (25.9%) and anticonvulsants (7.4%). Seventeen patients recovered completely and three patients died.

Introduction

Cutaneous adverse drug reactions can be caused by a wide variety of drugs.[1–2] The incidence of adverse drug reactions in hospitalized children is 9.5%.[3] Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered as the most severe cutaneous reactions that occur in pediatric population.[4] There are several reports on these serious adverse reactions in adults. However, not much data are available in children. Hence the present study was conducted to evaluate the causative drugs and outcome in SJS and TEN in children below 18 years.

Materials and Methods

In-patient records of all children below 18 years of age with the diagnosis of SJS, TEN, and SJS-TEN overlap, between January 2007 and July 2010, were analyzed. Following details were recorded: the duration of the rash, drug intake, the time period between the drug intake, and the appearance of the rash, systemic symptoms, extent of epidermal necrosis or detachment, mucosal involvement, and systemic evaluation.

The diagnosis of SJS, TEN, and the SJS-TEN overlap was made as per the criteria laid down by Bastuji et al.[5] Drug(s) that have been taken within 4 weeks preceding the onset of symptoms were considered as “culprit drugs.” If the patient had taken more than one drug, all of them were considered as culprit drugs.

Results

A total of 20 children with the diagnosis of SJS-TEN spectrum were seen. Eight patients (40%) each had SJS and TEN, four (20%) had SJS-TEN overlap. There were 10 males (50%) and 10 females (50%) with an age range of 5-18 years (mean 11.9±3.42). The duration of illness varied from 2 to 27 days (mean 9.4±6.09). The time period between the intake of drug and the start of eruption ranged from 0.5 to 30 days (mean 9.55±9.10). All patients had prodromal symptoms in the form of fever, sore throat, and headache. Seven patients had pre-existing systemic illness in the form of seizure disorder (2), neurocysticercosis (2), cerebral palsy with epilepsy (1), cerebral abscess (1), and HIV (1) for which the implicated drug was given. The detailed list of drugs causing adverse reactions is shown in Table 1.

Table 1.

List of drugs implicated in the reaction

The following systemic complications were seen: anemia in 15 patients (75%), leucocytosis in 3 (15%), leucopenia in 1 (5%), thrombocytopenia in 2 (10%), thrombocytosis in 5 (25%), transaminitis, and/or increased bilirubin in 7 (35%), hypoalbuminemia in 3 (15%), septicemia in 3 (15%).

All the children were given barrier nursing care, which included fluid and electrolyte balance, strict asepsis, nutrition, and monitoring of vitals. Prophylactic antibiotics were administered. Ten patients received short (1-8 days) course of tapering doses of systemic steroid-inj. dexamethasone, doses ranging from 3 mg to 8 mg or oral prednisolone in doses ranging from 30 mg to 40 mg. One patient of TEN who recovered had been treated with oral cyclosporine for 2 weeks.

Outcome

Seventeen patients recovered completely while three patients died (all three had TEN and had received steroids). Two patients died of septicemia and another died of disseminated intravascular coagulation and septicemia.

Discussion

We observed an equal sex ratio, as has already been reported.[6] Kob and Tay in their recent series of SJS-TEN in Asian children observed a higher incidence in boys.[7] Male predominance was also observed in a large 10-year series in Canada.[8] The average age in our study was 11.35 years which is higher than the past reports.[7,8] There was no correlation between age and sex and the diagnosis.

Contrary to the reports of a higher number of SJS (13/15),[7] our series had an equal number of SJS and TEN. In Lam et al.'s[9] series of EM, SJS, and TEN in Taiwanies children, 19 had EM, eight had SJS, two had SJS/TEN, and one patient had TEN. In a recent pooled analysis by using data from two multicenter international case control studies in children <15 years of age, 32 had SJS-TEN overlap, 27 had TEN, and 21 had SJS.[6]

Antibiotics were the most common drugs implicated in our study as in earlier series.[8] Penicillins, cephalosporins, and fluoroquinolones were the most common drugs. Sulphonamides and penicillins were the commonest drugs causing SJS and TEN in several of the earlier published reports.[6,8]

Anticonvulsants are the commonest group of drugs causing SJS and TEN in several earlier reports.[4,7,9] In our five cases in whom single drug was responsible for the reaction, anticonvulsants were the commonest drugs. Phenytoin was the commonest drug, whereas phenobarbitol and valproic acid were the two common anticonvulsant drugs in a pooled analysis of the two multicenter international case-controlled studies.[6]

Mortality rate in our series was 15% (3/20), of these all were TEN patients. In other reports the mortality rate was 3.6%-60%. Sepsis was the overwhelming cause of death in other published reports as seen in our series.[10]

The treatment of SJS/TEN includes supportive care, monitoring of fluids and electrolytes, barrier nursing care, and control of infection. The use of steroids and other immunosuppressive therapy still remains controversial. We have used steroid in 10 cases. There was no mortality in the SJS group. The maximum mortality was seen in three patients in the TEN group. This may be due to the fact that most of the TEN patients had extensive skin necrosis and hence had more complications.

In conclusion serious adverse drug reactions such as SJS, TEN, and SJS-TEN overlap in children are caused by antibiotics, NSAIDs, and anticonvulsants. The mortality rate is higher in the TEN groups.