Hindawi Publishing Corporation

Dermatology Research and Practice

Volume 2014, Article ID 237821, 5
pages
http://dx.doi.org/10.1155/2014/237821

Research
Article
Retrospective Analysis of Corticosteroid Treatment in
Stevens-Johnson Syndrome and/or Toxic Epidermal Necrolysis
over a Period of 10 Years in Vajira Hospital, Navamindradhiraj
University, Bangkok
1

Wanjarus Roongpisuthipong, Sirikarn Prompongsa, and Theerawut Klangjareonchai

Division of Dermatology, Department of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok 10300,
Thailand
2
Research Center, Navamindradhiraj University, Bangkok 10300,
Thailand
3
Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400,
Thailand
Correspondence
should
[email protected]

be

addressed

to

Wanjarus

Roongpisuthipong;

rr

Received 19 March 2014; Revised 5 May 2014; Accepted 2 June 2014; Published 15 June
2014
Academic Editor: Jonathan L. Curry
Copyright 2014 Wanjarus Roongpisuthipong et al. This is an open access article distributed under the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.
Background. Stevens-Johnson syndrome (SJS) and/or toxic epidermal necrolysis (TEN) are uncommon and life-threatening
drug reaction associated with a high morbidity and mortality. Objective. We studied SJS and/or TEN by conducting a
retrospective analysis of 87 patients treated during a 10-year period. Methods. We conducted a retrospective review of the
records of all patients with a diagnosis of SJS and/or TEN based on clinical features and histological confirmation of SJS and/or
TEN was not available at the Department of Medicine, Vajira hospital, Bangkok, Thailand. The data were collected from two
groups from 2003 to 2007 and 2008 to 2012. Results. A total of 87 cases of SJS and/or TEN were found, comprising 44 males and
43 females whose mean age was 46.5 years. The average length of stay was 17 days. Antibiotics, anticonvulsants, and allopurinol
were the major culprit drugs in both groups. The mean SCORTEN on admission was 2.1 in first the group while 1.7 in second the
group. From 2008 to 2012, thirty- nine patients (76.5%) were treated with corticosteroids while only eight patients (22.2%) were
treated between 2003 and 2007. The mortality rate declined from 25% from the first group to 13.7% in the second group.
Complications between first and second groups had no significant differences. Conclusions. Short-term corticosteroids may
contribute to a reduced mortality rate in SJS and/or TEN without increasing secondary infection. Further well-designed
studies are required to compare the effect of corticosteroids treatment for SJS and/or TEN.

1. Introduction
Steven-Johnson syndrome (SJS) and/or toxic epidermal
necrolysis (TEN) are uncommon diseases with an incidence
about 1.9 cases per million per year [1]. SJS and/or
TEN are potentially mortal diseases, characterized by
extensive blistering exanthema and epithelial sloughing,
occurring with mucosal involvement (Figures 1 and 2) [2].
SJS and/or TEN are part of a spectrum, which is divided

into 3 groups: SJS when the total detachment is less

than 10% of the body surface area; TEN when it is
over 30%; SJS-TEN overlap when it is between 10% and
30% [3]. Differential

diagnoses of SJS and/or TEN are linear IgA bullous disease, paraneoplastic pemphigus, generalized bullous fixed
drug eruption, and staphylococcal scalded skin syndrome.
Even though many factors have been proposed as causes
of these diseases, hypersensitivity to medications reports
for the most of cases. -lactam antibiotics, sulfonamides,
anticonvulsants, and allopurinol were frequent triggers of
SJS and/or TEN [4]. The SCORTEN indicates a severity of
illness, which is strongly correlated with the risk of death
[5]. Aside from intensive supportive treatment, a normally
accepted regimen for specific therapy of SJS and/or TEN is
lacking.
Treatment
options
include
systemic
corticosteroids,

2
Dermatology
Research and Practice

Dermatology Research and Practice

2

2. Methods

Figure 1: Multiple denuded areas on diffuse dusky red patches at

forehead, neck, and right-sided trunk. Erosion on both upper and
lower lips.

A retrospective review was performed on patients admitted to Vajira Hospital, Navamindradhiraj University, with
the diagnosis of SJS and/or TEN based on clinical features
and histological confirmation of SJS and/or TEN was not
available. The data were collected into two groups from
2003 to 2007 and 2008 to 2012 (10-year study). The ethical
review board of the Faculty of Medicine Vajira Hospital,
Navamindradhiraj University, approved this study.
The electronic medical database and inpatient charts
were reviewed. The following data were collected:
demographic information, culprit drugs, extent of
mucocutaneous involve- ment, underlying diseases,
laboratory data, treatments, com- plications, and mortality.
Drugs that have been taken within
6 weeks before 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.

3. Statistical Analysis
Continuous variables are reported as mean SD and
data for categorical variables are reported as numbers
and percentages. Comparisons of categorical variables
2
among groups were performed using test or Fishers test.
Compar- isons of continuous variables among groups were
performed using unpaired Students -test or MannWhitney test. Statistical significance was set at
<
0.05 (two-tailed). Statistical analysis was performed with the
SPSS version 18.0 (SPSS Inc., Chicago, IL, USA).

4. Results

Figure 2: After 4 days, the patients developed progressive

denuded area on previous dusky red. Patches on trunk and
extremities. Erosion on both upper and lower lips, genitalia.

intravenous immunoglobulin therapy (IVIG), thalidomide,

and TNF- antagonist. Traditionally systemic corticosteroids
were advocated until early 1990s, although no benefit has
been demonstrated in case-controlled studies [6]. A retrospective single center study proposes that short-term dexamethasone therapy, given at an early stage of the disease,
may contribute to a reduced mortality rate [7].
Moreover, the study from a general hospital in Singapore
reports that the use of dexamethasone therapy may be a
benefit [8]. The argument over systemic corticosteroid
usage will still be continuously unresolved. The aim of
this study was to present the etiologies, treatment, and
clinical outcomes of SJS and/or TEN in Vajira Hospital,
Navamindradhiraj University in Bangkok, Thailand.

Eighty-seven patients (44 males and 43 females) were

admit- ted during this period. There were 36 cases (mean
age was
42.6) since the year of 2003 until 2007 and 51 cases (mean
age was 49.3) since the year of 2008 until 2012. In the first
group, 36 cases were classified as SJS 26 cases (70.6%), SJSTEN overlap 1 cases (2.8%), and TEN 9 cases (25.0%). In
the second group, 51 cases were classified as SJS 36 cases
(70.6%), SJS-TEN overlap 7 cases (13.7%), and TEN 8 cases
(15.7%). Cardiovascular disease, diabetes mellitus, and HIV
infection were not different between the first and second
groups. Malignancy was 7 cases (13.7%) in the second group,
while there was no case of malignancy in the first group.
Mucosal involvement involved mouth more than other sites
in both groups. Urethral involvement in the first group was
significantly higher than the second group, while genital
involvement in the second group was significantly higher
than the first group. The mean of SCORTEN on the day of
admission was 1.7 in the first group and 2.1 in the second
group. In the second group, thirty-nine patients (76.5%)
were treated with intravenous corticosteroids; the most
common agent was dexamethasone. Only eight patients
(22.2%) were treated with intravenous corticosteroid in the
first group. The duration and dose of corticosteroid did not
differ between the two groups. No patient received
intravenous immunoglobu- lin. Table 1 shows clinical
characteristics for the 87 patients.

Table 1: Clinical characteristics of Stevens-Johnson syndrome

and/or toxic epidermal necrolysis cases from 2003 to 2012 ( =
87).
20082012 20032007
(%)
Age (years)
Male
Underlying diseases
Cardiovascular disease
Diabetes mellitus
HIV infection

(%)

49.3 19.2 42.6 21.0

27 (52.9) 17 (47.2)

0.104
0.599

11 (21.5)
7 (13.7)
12 (23.5)

8 (22.2)
5 (13.8)
9 (25.0)

0.942
0.983
0.875

7 (13.7)

0 (0)

0.033

36 (70.6)

26 (72.2)

0.868

7 (13.7)
8 (15.7)

1 (2.8)
9 (25.0)

0.082
0.281

40 (78.4)
45 (88.2)

32 (88.8)
35 (97.2)

0.203
0.129

27 (52.9)

11 (30.5)

0.038

Urethra
Anus
SCORTEN
1
2
3
4
5
Causes of disease
Single drug-related
Multiple drug-related

2 (3.9)
3 (5.8)

7 (19.4)
1 (2.8)

0.019
0.496

16 (31.4)
19 (37.3)
12 (23.5)
1 (1.9)
3 (5.8)

13 (36.1)
19 (52.8)
3 (8.3)
1 (2.8)
0 (0)

0.664
0.151
0.065
0.802
0.139

44 (86.3)
7 (13.7)

30 (83.3)
6 (16.6)

0.705
0.705

Intravenous steroid use

39 (76.5)
8 (22.2)
Dexamethasone equivalent
13.2 6.1 14.5 6.3
doses (mg/day)
Steroid treatment duration
5.7 2.7 5.4 2.5
(day)
Steroid treatment duration of 13 (33.3)
4 (50.0)
7days

<0.001

Malignancy
Diagnosis

SCORTEN
1
2
3
4
5

( =51)

( =36)

87.5%
63.1%
83.3%
100%
66.7%

15.4%
13.0%
33.3%
0%

Table 3: Comparison of incidences of culprit drugs.

SJS
SJS-TEN overlap
TEN
Mucosal involvement
Ocular
Mouth
Genitalia

Table 2: Percentage of intravenous steroid usage in StevensJohnson syndrome and/or toxic epidermal necrolysis patients
stratified by
SCORTEN.

0.914
0.810
0.096

< 0.05, < 0.01.

SJS: Stevens-Johnson syndrome.
TEN: toxic epidermal
necrolysis.

20082012
( =58), (%)
Antibiotics
26 (44.8)
Penicillin
7 (12.1)
Cotrimoxazole
7 (12.1)
Cephalosporin
5 (8.6)
Quinolone
3 (5.2)
Carbapenem
2 (3.4)
Clindamycin
1 (1.7)
Tetracycline
1 (1.7)
Macrolide
0 (0)
Anticonvulsants
14 (24.1)
Phenytoin
8 (13.8)
Carbamazepine
4 (6.9)
Phenobarbital
1 (1.7)
Lamotrigine
1 (1.7)
Allopurinol
7 (12.1)
NSAIDs
5 (8.6)
Nevirapine
3 (5.2)
Antituberculosisa
3 (5.2)
Other drugs
0 (0)
TTM
0 (0)
Valacyclovir
0 (0)
Cetirizine
0 (0)
Chloroquine
0 (0)
Cinnarizine
0 (0)
Silymarin
0 (0)

20032007
( =42), (%)
14 (33.3)
4 (9.5)
4 (9.5)
2 (4.8)
2 (4.8)
0 (0)
0 (0)
0 (0)
2 (4.8)
4 (9.5)
3 (7.1)
1 (2.4)
0 (0)
0 (0)
8 (19.1)
4 (9.5)
4 (9.5)
0 (0)
8 (19.1)
2 (4.8)
2 (4.8)
1 (2.4)
1 (2.4)
1 (2.4)
1 (2.4)

value
0.265
0.718
0.718
0.473
0.949
0.229
0.398
0.398
0.089
0.064
0.309
0.317
0.398
0.398
0.301
0.844
0.377
0.139
0.089
0.089
0.231
0.231
0.231
0.231

Table 2 shows percentage of intravenous steroid usage in

SJS
and/or TEN patients stratified by SCORTEN.
All of the patients in this study were related to drug
administration.
Antibiotics,
anticonvulsants,
and
allopurinol were the major culprit drugs in both groups
(Table 3). The highest culprit drugs were allopurinol
(19.1%) in the first group and phenytoin (13.8%) in the
second group. Penicillin and cotrimoxazole were the most
frequent among antibiotics and phenytoin was the most
frequent among anticonvulsants in both groups.

Antituberculosis (isoniazid, rifampicin, pyrazinamide, and ethambutol).

NSAIDs: nonsteroidal anti-inflammatory drugs.
TTM: traditional Thai medicine.

Many patients showed organ involvement and other

com- plications (Table 4). Respiratory failure was the most
internal organ failure in both groups. Endotracheal
intubation and mechanical ventilation were needed for all
of these patients. Liver and renal dysfunctions were more
common in the first group than in the second group. Sepsis
was more in the first group than in the second group,
while skin infection and hospital-acquired pneumonia were
more in the second group

Table 4: Organ involvement and complications in patient

with Stevens-Johnson syndrome and/or toxic epidermal necrolysis
cases from 2003 to 2012 ( = 87).
20082012 20032007
( = 51), ( = 36),
(%)
(%)
Internal organ involvement
Liver failure
Renal failure
On hemodialysis
Respiratory failure
On ventilator
Infections
Skin infection
Hospital-acquired
pneumonia
Sepsis
Length
D
eath of stay

3 (5.9)
6 (11.8)
3 (5.9)

3 (8.3)
6 (16.6)
3 (8.3)

7 (13.7)

6 (16.6)

9 (17.3)

6 (16.6)

7 (13.7)

4 (11.1)

7 (13.7)
8 (22.2)
19.2
15.8 13.9
7 (13.7)
9 (29.6
5)

TEN in the same patient; therefore, drug having chemical

similarity to the initial causative compound should be
strictly avoided in management of SJS or TEN [15].

Management in SJS or TEN involves sequentially rapid

evaluation
of the severity and prognosis of disease by using
value
SCORTEN, prompting identification and discontinuation of
all causative drugs, and initiating supportive care (such as
fluid, electrolyte, wound, and nutritional management) and
0.657
eventual specific treatment. Up till now, a specific
0.514
treatment for SJS or TEN that has shown efficacy in controlled tri0.657
als does not exist. The use of systemic corticosteroids in
SJS or TEN is controversial. Although corticosteroids have
0.705
pleomorphic immunomodulating effect through inhibition
of various cytokines, the use of corticosteroids and prolong
0.905
use of corticosteroids increase the risk of secondary
and
masking early sign of sepsis. Therefore, the use of
infection
0.718
corticosteroids is usually limited in SJS or TEN. In the
0.301
present study, the use of systemic corticosteroids increased
0.287
from
22% in
group toepisodes
76% in of
thecephalosporin
second group.
0.181
a report
of the
twofirst
successive
and
carbapenem associated with

than in the first group. The admission duration was

average
13.9 days in the first group and 19.2 days in the second
group. The mortality rate declined from 25% from the first
group to
13.7% in the second group.

5. Discussion
In our study, incidence of SJS and/or TEN was 8-9 cases
per year which is similar to another report from Asia such
as Thailand and Korea [9, 10]. The mean age was
approximately
46 years which is as high as those reported from other
countries in Asia such as Japan, Singapore, and Korea
[2,
8, 10]. In contrast to earlier studies showing that
females are affected with SJS and/or TEN more than
males [2, 10], our series had equal numbers of males and
females, which was in agreement with the study done by
Tan and Tay [8]. The most common culprit drug group
in this study was antibiotics (penicillin group and
sulfonamide group) similar to other studies in Thailand [9,
11] and other Asian countries [2, 12]. Allopurinol showed a
higher risk in this study than in previous studies [2, 9,
10]. It was the most common culprit drugs similar to
EuroSCAR study [13]. The incidence of allopurinol
associated with SJS or TEN increased in the EuroSCAR
study because of increasing usages and dosages of this drug.
This study revealed that the incidence of allopurinol
associated with SJS or TEN declined from 19% in the first
group to 12% in the second group. It may be hypothesized
that the decreased rate is associated with physicians
caution use allopurinol to accepted guidelines and adjusted
dosage base on renal function. Carbapenems, a board
spectrum of antibiotics, are increasingly used in clinical
practice [14]. In this study, carbapenem-associated SJS or
TEN was reported to be 3.4% between 2008 and 2012. In
addition, Carbapenems are -lactam; therefore, they can
cross-react with penicillins or cephalosporins. There was

Moreover, corticosteroid treatment duration for more

than
7 days declined from 50% in the first group to 33% in
the second group. In the second group, mortality and
sepsis significantly declined when compared to the first
group, while rate of hospital-acquired pneumonia and skin
infection did not change. Additionally, the first group
had lower SCORTEN than the second group but the
mortality rate was higher in the first group than in the
second group. In interpreting these results, short-course
systemic corticos- teroids such as dexamethasone in SJS
or TEN reveals the benefit of decreasing the mortality rate
while not increasing secondary infection such as
septicemia, respiratory tract, and skin infection. In
addition, two monocenter retrospective studies suggested
that
short-course
high-dose
corticosteroids
(dexamethasone) might be of benefit [7, 8]. On the other
hand, a retrospective case-control study conducted in
France and Germany concluded that corticosteroids did not
show a significant effect on mortality in comparison with
supportive care only [6]. A retrospective analysis had
some pitfalls; therefore, multicentre, randomized, placebocontrolled trials using standardized design are required in
order to investigate further the use of corticosteroid in
SJS and/or TEN. In addition, such a system might be
useful for evaluation of genetic marker.

6. Conclusions
The most common drug-related SJS and/or TEN in
Vajira hospital was allopurinol and the most common
drug group was antibiotics. Short-term corticosteroids may
contribute to a reduced mortality rate in SJS and/or TEN
without increas- ing secondary infection. Further welldesigned studies are required to compare the effect of
corticosteroids treatment for SJS and/or TEN.

Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.

Acknowledgment
This work was supported by grant from Vajira
Hospital, Navamindradhiraj University.

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