<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_1905-7415.0902.386_s_005_w2aab3b7b9b1b6b1aab1c17b1Aa"><h3>Background</h3><p>Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin conditions with an etiology of drug exposure or infections.</p></sec><sec id="j_1905-7415.0902.386_s_006_w2aab3b7b9b1b6b1aab1c17b2Aa"><h3>Objectives</h3><p>To determine the cause, treatments, complications, and outcomes of SJS/TEN in children admitted to Srinagrind Hospital during 1992–2012.</p></sec><sec id="j_1905-7415.0902.386_s_007_w2aab3b7b9b1b6b1aab1c17b3Aa"><h3>Methods</h3><p>Retrospective chart review. A diagnosis of SJS and TEN was confirmed by pediatric dermatologists.</p></sec><sec id="j_1905-7415.0902.386_s_008_w2aab3b7b9b1b6b1aab1c17b4Aa"><h3>Results</h3><p>A total of 38 patients was recorded. They consisted 31 (82%) SJS patients and 7 (18%) TEN patients. Mean age 6.6 years (range 1 to 14 years). Male to female was 1.1:1. Most cases (30 or 79%) were caused by drug exposure. Three cases (8%) by infection, and 5 cases (13%) were of unknown cause. The antiepileptic drug group was the most common cause. Systemic corticosteroids were used in 33 cases (87%). Intravenous immunoglobulin was used in one TEN patient (3%). There were 18 cases (47%) with acute complications. Ocular complications (7 cases, 39%), septicemia (4 cases, 22%), and secondary skin infections (3 cases, 17%) were the most common. Mean difference in length of hospital stay between those with and without acute complications was 12.3 days (<italic>P</italic> &lt; 0.01, 95% CI 5.9–18.6). Ocular complications were the only long-term complications at 1-year follow up, and included symblepharon, corneal pannus, and dry eyes. Two patients (5%), both having cases of TEN, died.</p></sec><sec id="j_1905-7415.0902.386_s_009_w2aab3b7b9b1b6b1aab1c17b5Aa"><h3>Conclusions</h3><p>Antiepileptic drugs were the most common causes of SJS/TEN in our study. Good ophthalmologic care of the prevalent acute eye complications in these patients is needed to prevent long-term ophthalmic complications.</p></sec></abstract>

BackgroundStevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin conditions with an etiology of drug exposure or infections.ObjectivesTo determine the cause, treatments, complications, and outcomes of SJS/TEN in children admitted to Srinagrind Hospital during 1992–2012.MethodsRetrospective chart review. A diagnosis of SJS and TEN was confirmed by pediatric dermatologists.ResultsA total of 38 patients was recorded. They consisted 31 (82%) SJS patients and 7 (18%) TEN patients. Mean age 6.6 years (range 1 to 14 years). Male to female was 1.1:1. Most cases (30 or 79%) were caused by drug exposure. Three cases (8%) by infection, and 5 cases (13%) were of unknown cause. The antiepileptic drug group was the most common cause. Systemic corticosteroids were used in 33 cases (87%). Intravenous immunoglobulin was used in one TEN patient (3%). There were 18 cases (47%) with acute complications. Ocular complications (7 cases, 39%), septicemia (4 cases, 22%), and secondary skin infections (3 cases, 17%) were the most common. Mean difference in length of hospital stay between those with and without acute complications was 12.3 days (P < 0.01, 95% CI 5.9–18.6). Ocular complications were the only long-term complications at 1-year follow up, and included symblepharon, corneal pannus, and dry eyes. Two patients (5%), both having cases of TEN, died.ConclusionsAntiepileptic drugs were the most common causes of SJS/TEN in our study. Good ophthalmologic care of the prevalent acute eye complications in these patients is needed to prevent long-term ophthalmic complications.

<div xmlns="http://www.w3.org/1999/xhtml"><p>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 &lt;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 [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_001_w2aab3b7b9b1b6b1ab1b5b1Aa">1</a>]. The other causative agents are infections, especially by <italic>Mycoplasma pneumonia</italic> among pediatric populations [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_002_w2aab3b7b9b1b6b1ab1b5b2Aa">2</a>]. Treatments that have been proven to decrease morbidity and mortality are rapid withdrawal of the suspected drug [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_002_w2aab3b7b9b1b6b1ab1b5b2Aa">2</a>] with good nursing and supportive care to prevent complications. The use of systemic corticosteroids is controversial because some cases are caused from severe infection and may this increase mortality. However, some case reports have shown the benefit of corticosteroids in reducing epidermal loss when given early in the course of the disease [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_003_w2aab3b7b9b1b6b1ab1b5b3Aa">3</a>, <a ref-type="bibr" href="#j_1905-7415.0902.386_ref_004_w2aab3b7b9b1b6b1ab1b5b4Aa">4</a>]. Other treatments have been used include intravenous immunoglobulin (IVIG), tumor necrosis factor-a inhibitors, cyclosporin, cyclophosphamide, plasmapheresis, and hemodialysis [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_003_w2aab3b7b9b1b6b1ab1b5b3Aa">3</a>]. Acute complications frequently found in SJS/TEN are secondary skin infections because of the detachment of skin, pneumonia, septicemia, hepatitis, and ocular complications. SJS has less mortality than TEN in both adult and pediatric populations [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_001_w2aab3b7b9b1b6b1ab1b5b1Aa">1</a>, <a ref-type="bibr" href="#j_1905-7415.0902.386_ref_003_w2aab3b7b9b1b6b1ab1b5b3Aa">3</a>-<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_005_w2aab3b7b9b1b6b1ab1b5b5Aa">5</a>]. The long-term complications are varied, mainly focusing on mucosal involvement during the acute phase, postinflammatory hypo or hyperpigmentation of skin and scaring [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_003_w2aab3b7b9b1b6b1ab1b5b3Aa">3</a>].</p><sec id="j_1905-7415.0902.386_s_001_w2aab3b7b9b1b6b1ab1b1Aa"><div>Methods</div><p>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.</p><p>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. <italic>P</italic> &lt; 0.05 was considered significant.</p></sec><sec id="j_1905-7415.0902.386_s_002_w2aab3b7b9b1b6b1ab1b2Aa"><div>Results</div><sec id="j_1905-7415.0902.386_s_002_s_001_w2aab3b7b9b1b6b1ab1b2b1Aa"><div>Demographic data</div><p>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 (<bold><a ref-type="table" href="#j_1905-7415.0902.386_tab_001_w2aab3b7b9b1b6b1ab1b2b1b2aAa">Table 1</a></bold>).</p><p><table-wrap id="j_1905-7415.0902.386_tab_001_w2aab3b7b9b1b6b1ab1b2b1b2aAa" position="float" orientation="portrait"><label>Table 1</label><caption><p>Etiology of SJS/TEN</p></caption><table rules="groups"><thead><tr><th align="left">Causative etiology</th><th align="center">No. of cases</th></tr></thead><tbody><tr><td align="left"><bold>Drug–induced</bold></td><td align="center">30 (79%)</td></tr><tr><td align="left"><bold>Antiepileptic drugs</bold></td><td align="center"></td></tr><tr><td align="left">   Carbamazepine</td><td align="center">8</td></tr><tr><td align="left">   Phenobarbital</td><td align="center">7</td></tr><tr><td align="left">   Phenytoin</td><td align="center">2</td></tr><tr><td align="left">   Levetiracetam</td><td align="center">1</td></tr><tr><td align="left"><bold>Antibiotics</bold></td><td align="center"></td></tr><tr><td align="left">   Erythromycin</td><td align="center">3</td></tr><tr><td align="left">Trimethoprim-sulfamethoxazole</td><td align="center">2</td></tr><tr><td align="left">   Cefotaxime</td><td align="center">1</td></tr><tr><td align="left">   Cloxacillin</td><td align="center">1</td></tr><tr><td align="left">   Amoxicillin</td><td align="center">1</td></tr><tr><td align="left"><bold>Others</bold></td><td align="center"></td></tr><tr><td align="left">   Aspirin</td><td align="center">1</td></tr><tr><td align="left">   Ibuprofen</td><td align="center">1</td></tr><tr><td align="left">   Methotrexate</td><td align="center">1</td></tr><tr><td align="left">   Paracetamol</td><td align="center">1</td></tr><tr><td align="left"><bold>Infection</bold></td><td align="center"></td></tr><tr><td align="left">   <italic>Mycoplasma pneumonia</italic></td><td align="center">3 (8%)</td></tr><tr><td align="left"><bold>Unknown</bold></td><td align="center">5 (13%)</td></tr></tbody></table></table-wrap></p></sec><sec id="j_1905-7415.0902.386_s_002_s_002_w2aab3b7b9b1b6b1ab1b2b2Aa"><div>Treatments</div><p>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.</p></sec><sec id="j_1905-7415.0902.386_s_002_s_003_w2aab3b7b9b1b6b1ab1b2b3Aa"><div>Complications and outcomes</div><p>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%).</p><p>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 <italic>P</italic> &lt; 0.01, [95% CI 5.9–18.6]. Ocular involvement, pneumonia, septicemia, and secondary skin infections had significant mean differences in the length of hospital stay by multivariate analysis (<bold><a ref-type="table" href="#j_1905-7415.0902.386_tab_002_w2aab3b7b9b1b6b1ab1b2b3b3aAa">Table 2</a></bold>).</p><p><table-wrap id="j_1905-7415.0902.386_tab_002_w2aab3b7b9b1b6b1ab1b2b3b3aAa" position="float" orientation="portrait"><label>Table 2</label><caption><p>Multivariate analysis of each complication and length of hospital stay</p></caption><table rules="groups"><thead><tr><th align="left">Complications</th><th align="left">Mean difference of hospital stay (days)</th><th align="left"><italic>P</italic></th><th align="left">95% CI</th></tr></thead><tbody><tr><td align="left">Urinary tract infection</td><td align="left">1.17</td><td align="left">0.82</td><td align="left">9.6–11.9</td></tr><tr><td align="left">Ocular involvement</td><td align="left">11.04</td><td align="left">&lt;0.01</td><td align="left">3.5–18.5</td></tr><tr><td align="left">Pneumonia</td><td align="left">11.82</td><td align="left">0.03</td><td align="left">0.8–22.8</td></tr><tr><td align="left">Septicemia</td><td align="left">14.72</td><td align="left">&lt;0.01</td><td align="left">5.8–23.6</td></tr><tr><td align="left">Secondary skin infection</td><td align="left">10.00</td><td align="left">0.03</td><td align="left">0.9–19.0</td></tr></tbody></table></table-wrap></p><p>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%).</p></sec></sec><sec id="j_1905-7415.0902.386_s_003_w2aab3b7b9b1b6b1ab1b3Aa"><div>Discussion</div><p>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 [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_004_w2aab3b7b9b1b6b1ab1b5b4Aa">4</a>-<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_008_w2aab3b7b9b1b6b1ab1b5b8Aa">8</a>]. However, the most prevalent drug group found in this study was antiepileptics, rather than antibiotics, in contrasts with a previous study in Thai children [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_004_w2aab3b7b9b1b6b1ab1b5b4Aa">4</a>].</p><p>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</p><p>high when compared with other general hospitals.</p><p>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 [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_004_w2aab3b7b9b1b6b1ab1b5b4Aa">4</a>]. One TEN patient in our study was treated with IVIG.</p><p>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 [<a ref-type="bibr" href="#j_1905-7415.0902.386_ref_009_w2aab3b7b9b1b6b1ab1b5b9Aa">9</a>]. 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.</p></sec><sec id="j_1905-7415.0902.386_s_004_w2aab3b7b9b1b6b1ab1b4Aa"><div>Conclusion</div><p>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.</p><p>The authors have no conflict of interest to report.</p></sec></div>

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

BackgroundStevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin conditions with an etiology of drug exposure or...

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Article Category: Brief communication (Original)

Published Online: Jan 31, 2017

Page range: 193 - 196

DOI: https://doi.org/10.5372/1905-7415.0902.386

Keywords
Stevens-Johnson Syndrome, toxic epidermal necrolysis

© 2017 Watuhatai Paipool, Leelawadee Sriboonnark

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Multivariate analysis of each complication and length of hospital stay

Etiology of SJS/TEN

Complications	Mean difference of hospital stay (days)	P	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

Causative etiology	No. of cases
Drug–induced	30 (79%)
Antiepileptic drugs
Carbamazepine	8
Phenobarbital	7
Phenytoin	2
Levetiracetam	1
Antibiotics
Erythromycin	3
Trimethoprim-sulfamethoxazole	2
Cefotaxime	1
Cloxacillin	1
Amoxicillin	1
Others
Aspirin	1
Ibuprofen	1
Methotrexate	1
Paracetamol	1
Infection
Mycoplasma pneumonia	3 (8%)
Unknown	5 (13%)

Stevens-Johnson Syndrome and toxic epidermal necrolysis in children: a retrospective study at Srinagarind Hospital, Khon Kaen, Thailand 1992–2012

Article Category: Brief communication (Original)

Published Online: Jan 31, 2017

Page range: 193 - 196

DOI: https://doi.org/10.5372/1905-7415.0902.386

KeywordsStevens-Johnson Syndrome, toxic epidermal necrolysis

© 2017 Watuhatai Paipool, Leelawadee Sriboonnark

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Multivariate analysis of each complication and length of hospital stay

Etiology of SJS/TEN

Keywords
Stevens-Johnson Syndrome, toxic epidermal necrolysis