560012

research-article2014
AOPXXX10.1177/1060028014560012Annals of PharmacotherapyLaw and Leung

Review Article
Annals of Pharmacotherapy

Steroids in Stevens-Johnson
1­–8
© The Author(s) 2014
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DOI: 10.1177/1060028014560012

Current Evidence and Implications for aop.sagepub.com

Future Research

Ernest H. Law, BSc (Pharm), ACPR, BCPS, PharmD1,

and May Leung, BSc (Pharm), PharmD, BCPS2

Abstract
Objective:To review the evidence for the use of steroids in adults presenting with Stevens-Johnson Syndrome (SJS),
toxic epidermal necrolysis (TEN), or overlap. Data Sources: EMBASE (1974 to April 2014), MEDLINE (1946 to April
2014), Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970 to January 2014) were
searched using the terms: prednisone, methylprednisolone, dexamethasone, prednisolone, steroids, glucocorticoids, corticosteroids,
Stevens-Johnson Syndrome, toxic epidermal necrolysis, and SJS/TEN overlap. Study Selection and Data Extraction: English-
language, full reports of experimental and observational studies were included. Bibliographies from pertinent publications
were reviewed for additional references. Prespecified outcomes included survival, survival to discharge, hospitalization
without intensive care, length of intensive care stay, duration of hospitalization, ophthalmological complications, infection
rates, and adverse events. Data Synthesis: Six studies that used steroids for SJS, TEN, and/or overlap were included. All
studies were retrospective cohort studies with no case-control or cross-sectional studies; 5 studies reported on steroid
doses, and 2 studies reported time from disease onset to steroid use (2-4 days). Only 1 out of 6 studies reported a statistically
significant impact on mortality with steroids use (odds ratio = 0.4; 95% CI = 0.2-0.9). Adverse event rates were not reported
in any of the studies. Conclusions: A review of the current evidence reveals a need for prospective, randomized controlled
studies to provide more definitive conclusions on steroid use in patients with SJS, TEN, and/or overlap.

Keywords
Stevens-Johnson, toxic epidermal necrolysis, steroids

Introduction lateral pressure on the skin surface—is universally present.

Stevens-Johnson Syndrome (SJS), toxic epidermal necroly-
sis (TEN), and SJS/TEN overlap are potentially fatal idio-
syncratic reactions, most commonly caused by medication
exposure.1 It can occur at any age and complicate the course
of 2% to 3% of hospital treatments, accounting for 1% of
consultations and 5% of hospitalizations in a dermatology
department.2 The diagnoses of SJS and TEN are based on
characteristic findings and a temporal association with drug
exposure or illness: a prodrome of fever, cough, sore throat,
and general malaise before the cutaneous signs and symp-
toms of SJS/TENS manifest.3 The acute phase, which typi-
cally occurs within the first 8 to 12 days, is characterized by
an acute macular exanthema with rapidly spreading necro-
sis of the mucous membranes, followed by similar manifes-
tations in the epidermis. At the time of skin involvement,
the Nikolsky sign—epidermal separation induced by gentle
Mucous membrane involvement, including conjunctival,
pharyngeal, tracheal, and esophageal, is a key finding.3
SJS, TEN, and SJS/TEN overlap are distinguished pri-
marily by severity and percentage of total body surface area
(TBSA) involved.4 SJS is the less-severe condition, in
which skin sloughing is limited to less than 10% of the
TBSA. Mucous membranes are affected in more than 90%
of patients, usually at 2 or more distinct sites (ocular, oral,
and genital). TEN involves sloughing of more than 30% of
1
University of Illinois at Chicago, Chicago, IL, USA
2
Surrey Memorial Hospital, Surrey, BC, Canada
Corresponding Author:
Ernest H. Law, Department of Pharmacy Systems, Outcomes and Policy,
College of Pharmacy, University of Illinois at Chicago, 833 South Wood
Street (MC 871), Chicago, IL 60612-7231, USA.
Email: elaw3@uic.edu

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2 Annals of Pharmacotherapy 
TBSA, whereas SJS/TEN overlap syndrome describes
patients with involvement of >10% but <30% of TBSA.
The leading cause of SJS and TEN is medication expo-
sure, with a wide range of associated drug classes, including
antibiotics, nonsteroidal anti-inflammatory drugs, psycho-
tropics (such as antipsychotics and antiepileptic drugs), and
antigout medications (such as allopurinol).5 However, there
are subsets of cases that are associated with infection or
where the definitive cause is unclear.
The prognosis differs greatly across the spectrum of SJS/
TEN. SJS is usually benign and associated with a mortality
rate of 1% to 3%, whereas in the case of TEN, this rate is as
high as 25% to 35%.6,7 Therefore, a validated prognostic
scoring system, SCORTEN, was developed based on 7 clin-
ical and laboratory variables to guide assessment of a
patient’s severity of illness, need for intensive care, and
prognosis (see Appendix).3
Management of SJS/TEN involves the early identifica-
tion of the trigger(s) followed by multidisciplinary sup-
portive measures to alleviate symptoms and prevent further
complications of the disease, including wound/burn care,
ocular care, pain control, and prevention/treatment of
infections. There are several pharmacological therapies
available, such as steroids, intravenous immunoglobulins
(IVIG), and cyclosporine.5 However, a universally accepted
drug treatment regimen has not been established, and much
controversy exists as to the role of each of these drugs indi-
vidually or in combination. In particular, a number of
issues have emerged with the use of steroids in acute man-
agement of these conditions. Much debate remains over the
role of steroids because they theoretically increase the risk
of sepsis, increase protein catabolism, and decrease the rate
of epithelialization; also, other studies have found that
administration of systemic steroids was associated with
increased morbidity and mortality.8 Moreover, if steroids
are to be used, the timing, dose, and duration of therapy
remain unclear.
Objectives
The objective of this article is to review the evidence for the
use of steroids in adults acutely presenting with SJS, TEN,
or SJS/TEN overlap.
Data Sources
The literature review process is summarized in Figure 1.
Published articles were systematically searched from
EMBASE (1974 to April 2014), MEDLINE (1946 to April
2014), Cochrane Database of Systematic Reviews, and
International Pharmaceutical Abstracts (1970 to April
2014). Combinations of the following search terms were
used: prednisone, methylprednisolone, dexamethasone,
prednisolone, steroids, glucocorticoids, corticosteroids,
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Stevens-Johnson Syndrome, toxic epidermal necrolysis, and
SJS/TEN overlap.
Study Selection and Data Extraction
This review included any randomized trials, cohort studies,
and case-control studies in English, with adult human par-
ticipants. Review articles, case reports or series, and cor-
respondence or letters to the editor were excluded.
Bibliographies from pertinent publications were reviewed
for additional references. A manual review of reference
lists from retrieved articles was performed to identify any
additional studies. The World Health Organization
International Clinical Trials Registry Platform (WHO
ICTRP [http://www.who.int/ictrp/]) was also searched for
relevant studies. Studies that evaluated administration of
steroids to adults with SJS, TENS, or overlap that provided
our defined primary outcome of interest with statistical
analysis were considered as meeting inclusion criteria for
this review. Measures of study quality, such as randomiza-
tion, blinding of assessors, prespecified outcomes, and
subgroup analyses were noted. The primary outcome of
interest was survival. Other prespecified outcomes of inter-
est were survival to discharge, hospitalization without
requiring intensive care, length of intensive care stay, dura-
tion of hospitalization, ophthalmological complications,
infection rates, and any adverse events.
Data Synthesis
The literature search yielded 814 citations. On screening
titles and abstracts, 799 citations were excluded, and 15
potentially relevant articles were retrieved for full-text
review. No additional potentially relevant reports were
identified through gray literature searching (ie, WHO
ICTRP and conference abstracts). Of the 15 potentially rel-
evant reports, 9 did not meet the inclusion criteria. Six pub-
lications were included in this review. No randomized
controlled trials (RCTs) or evidence-based clinical practice
guidelines were identified. All studies were retrospective in
nature (Table 1). The study selection process is outlined in a
flowchart (Figure 1).
In 2000, Schulz et al9 published the results of a retro-
spective cohort study evaluating the frequency and predic-
tors of mortality among patients admitted to a specialized
burn unit with a diagnosis of SJS, TEN, or erythema multi-
forme over an 11-year period (1987-1998). Patients included
had epidermal sloughing of greater than 20% TBSA. The
primary study objective was the identification of predictors
for in-hospital mortality. The study cohort consisted of 39
patients, with almost all cases associated with drug as the
etiological agent. Of the cohort, 87.1% received docu-
mented steroids (21 in those that survived and 13 in those
that died); 17 (43.6%) patients died while hospitalized.
Law and Leung 3
Figure 1.  Flow diagram of literature search.
Through univariate analysis, steroid use was not identi-
fied as a predictor of mortality among those who died and
those who survived. Instead, patients who survived were
typically younger (47.5 ± 4.2 vs 64.5 ± 5.3 years of age, P =
0.015), admitted earlier after onset of rash (3.5 ± 0.4 vs 5.9
± 1 days, P = 0.02), febrile on presentation (101.0 ± 0.5°F
vs 98.5 ± 0.5°F, P = 0.002), hospitalized for longer (38 ± 6
vs 18 ± 3 days, P = 0.012), less burdened with comorbidi-
ties (2.5 ± 0.4 vs 4.5 ± 0.8, P = 0.03), and less likely to
receive pre–burn unit admission antibiotics (43% vs 88%,
P = 0.005) or experience thrombocytopenia compared with
those who died. The authors concluded that their results
suggest poorer prognosis with regard to mortality in patients
with these characteristics.
A strength of this study was that it provided evidence of
the complexities and potential prognostic characteristics
that may influence the course of SJS/TEN. The greatest
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limitation of this study is the statistical method used by the
authors because a univariate analysis was likely inappropri-
ate to simultaneously adjust for the numerous potential
confounders.
In 2005, Kim et al10 published the results of a retrospec-
tive cohort study of patients hospitalized for the treatment
of TEN in a medical center in Korea from 1990 to 2003.
Patients hospitalized received monotherapy with either cor-
ticosteroids (IV methylprednisolone 250-1000 mg/d, later
stepped down to oral prednisolone) or IVIG (1.6-2.0 g/kg).
The primary outcome of mortality was reported as a stan-
dardized mortality ratio (SMR), which is calculated as the
observed frequency of deaths over the expected frequency
of death (based on the SCORTEN prognostic score). A total
of 38 patients (20 male, 18 female) were identified, with the
most common etiology of TEN being antibiotic exposure
(18 cases, 47.4%), followed by infection (14 cases, 36.8%).
4 Annals of Pharmacotherapy 

Table 1.  Characteristics of Included Studies.

Sample Size,
Classification, Suspected
Study Baseline Etiology of Adverse
Study (Year) Period Design Characteristics Disease Treatment Characteristics Outcome(s) Effects

Schulz et al9 1987- Retrospective, •• 39 Cases of TEN •• Univariate analysis of covariates

>90% drug- Steroid NR
(2000) 1998 cohort admitted to burn related
associated with mortality between exposure not
unit those who survived and those who associated
•• Mean 69% TBSA died with increase
involvement •• Steroid exposure (n = 34; 21 in mortality
patients in this group survived, and
13 patients died)
•• Dose of steroid, disease to onset
of treatment, and duration not
reported
Kim et al10 1990- Retrospective •• 38 Cases of TEN •• 47.4% •• Steroid only (n = 21) Steroids: NR
(2005) 2003 cohort •• Mean 47.7% TBSA drug- •• IVIG only (n = 14) SMR = 1.004
involvement related •• Treatment not described (95% CI =
•• 36.8% (n = 3) 0.369-2.187);
Infection •• Dose: IV methylprednisolone NS
250-1000 mg/d and stepped down
to oral prednisolone (dose not
reported)
•• Disease to onset of treatment, and
duration not reported
Schneck 1997- Retrospective, •• 110 Cases of SJS Drug-related, •• Supportive care (n = 87) Steroid use: NR
et al11 2001 cohort •• 104 Cases of SJS/ percentage •• Steroid only (n = 119) OR = 0.4
(2008) TEN overlap not reported •• IVIG (n = 35) (95% CI =
•• 67 Cases of TEN •• Steroid + IVIG (n = 40) 0.2-0.9) after
•• For analysis: 159 (56%) exposed to multivariate
any steroids analysis
•• Dose: 250 (100-500) mg
prednisone/d
•• Delay from disease onset to
treatment: 4 (2-5) days
•• Duration of treatment: 4 (2-12) days
Yang et al12 1993- Retrospective, •• 18 Cases of SJS Drug-related, •• Steroids only (n = 45) SMR = 1.16 NR
(2009) 2007 SCORTEN- •• 47 Cases of TEN percentage •• Steroids + IVIG (n = 20) (95% CI =
based •• Mean 41% TBSA not reported •• Dose: IV methylprednisolone: 1-1.5 0.56-2.13);
comparison involvement mg/kg/d (or GC at equivalent dose) NS
versus combination therapy (steroid
+ IVIG at 2 g/kg over 5 days)
•• Disease onset to treatment and
duration not reported
Kim et al13 2001- Retrospective •• 71 Cases of SJS 43 (52.4%) •• For analysis: IV steroids (n = 70) Steroid use NR
(2012) 2011 cohort •• 11 Cases of TEN drug-related •• PO steroids (n = 42) was not an
cases •• Overlapped or stepped down from independent
IV to PO not specified predictor of
•• Dose: dexamethasone IV 10 mg/d or survival
prednisolone PO 15 mg/d
•• Delay from disease onset to IV
steroid: 2.21 (1-15) days
•• Duration of treatment on IV and PO
steroids: 12.68 (1-65) days
Sekula et al14 2003- Retrospective •• 460 In cohort 305 (67%) •• Treatment analysis (n = 440) Corticosteroid NR
(2013) 2007 cohort •• 228 Cases of SJS “Probably •• Supportive care only (n = 97) use HR = 1.3
•• 161 Cases of SJS/ or very •• Any corticosteroids (n = 317) (95% CI =
TEN overlap probably” •• Any IVIG (n = 81) 0.9-2)
•• 71 Cases of TEN drug-related •• Other (n = 24)
cases •• Median dose: French cohort,
prednisone 75 mg/d; German
cohort, prednisone 250 mg/d
•• Disease to onset of treatment and
duration not reported

Abbreviations: GC, glucocorticoid; HR, hazard ratio; IVIG, intravenous immunoglobulins; NR, not reported; NS, not significant; SJS, Stevens-Johnson syndrome; SMR,
standardized mortality ratio; TBSA, total body surface area; TEN, toxic epidermal necrolysis.

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Law and Leung 5
The average TBSA involvement ranged between 15% and
70%, with the mean TBSA = 47.7% ± 17.1%. In all, 21
patients received corticosteroid treatment, and 14 patients
received IVIG. The remaining 3 patients’ treatments were
not described.
No statistically significant differences were noted with
respect to mortality in the overall cohort compared with the
SCORTEN-predicted rates of death (SMR = 0.928; 95% CI =
0.424-1.761). There was no statistical difference in mortality
in patients treated with steroids (SMR = 1.004; 95% CI =
0.369-2.187). In patients treated with IVIG, investigators did
note that the SCORTEN-predicted mortality rate was 16.8%
(2.53 deaths) compared with the observed rate (1 death,
7.1%); however, the number of patients was too small to draw
any final conclusions. The authors concluded that “further
large randomized, placebo-controlled trials” were required to
evaluate the consequences of treating TEN with IVIG.
This study adds to the knowledge of the effects of mono-
therapy steroids or IVIG in treating patients with TEN in
comparison with predicted mortality rates. Limitations of
this study include the retrospective design and nonrandom-
ized selection of patients, with an absence of adjustment for
potential confounders.
The largest study to evaluate the effect of treatments,
including steroids, was performed by Schneck et al.11 The
authors examined data procured from a case-control study
that evaluated the risk factors for SJS or TEN in 6 countries
in Europe (Austria, France, Germany, Israel, Italy, and the
Netherlands). The primary outcome was death during hos-
pitalization. Of a cohort of 379 patients with confirmed SJS
and TEN, 281 patients with information about treatment
were identified in 4 different treatment groups (supportive
care, n = 87; IVIG only, n = 35; IVIG + steroids, n = 40; and
steroids only, n = 119). Because of the small number of par-
ticipants in the combination group (IVIG + steroids), the
effects of this arm were not estimated. Logistic regression
was used in the comparisons to generate odds ratios (OR).
Of the 159 patients who received any steroids, 28
(17.6%) died during hospitalization. Compared with sup-
portive care, there was a statistically significant decrease in
the odds of death (OR = 0.4; 95% CI = 0.2-0.9) after multi-
variate adjustment for age group (<40, 40-70, >70 years),
disease severity (SJS, SJS/TEN, TEN), and country. Agents
used in the steroid-exposed patients were prednisone, meth-
ylprednisolone, and dexamethasone, started on admission
after a mean of 4 (2-5) days after disease onset at a mean
dose of 250 (100-500) mg/d of prednisone for a mean dura-
tion of 4 (2-12) days. The authors conclude that there was
inadequate evidence that any specific treatment is estab-
lished as effective for patients with SJS or TEN, with only
corticosteroids showing a “trend for possible benefit.” They
call for a prospective randomized trial to be conducted
before any conclusions can be drawn, recommending that
corticosteroids be trialed first.
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The strengths of this study are the large cohort study,
detailed description of treatments, and adjustment for
potential confounders. However, unmeasured confounders
may still exist given the retrospective, observational design.
This is further confounded with the addition of the 40
patients who received both IVIG and steroids into the treat-
ment arms.
In 2009, Yang et al12 published the results of a retrospec-
tive cohort study of patients hospitalized in an intensive
care unit for the treatment of SJS or TEN, in a tertiary care
center in China, from 1993 to 2007. Consecutive patients
hospitalized from 1993 to 2000 received corticosteroids,
whereas those hospitalized between 2001 and 2007 received
combination therapy with IVIG and steroids. The outcome
of interest was mortality, reported as the SMR based on
SCORTEN-predicted rates of death. Additional outcomes
included time to the arrest of progression, time to the taper-
ing of corticosteroids, time of hospitalization, side effects,
and complications. A total of 65 patients (18 cases of SJS
and 47 cases of TEN) were identified, with no statistically
significant differences between actual (13 deaths, 20%) and
SCORTEN-predicted (12.14 deaths, 18.7%) mortality rates.
The most common etiology for SJS or TEN was docu-
mented to be drug-related, and the average TBSA involve-
ment ranged between 15% and 70%, with the mean TBSA
= 41% ± 11%. In all, 45 patients received corticosteroid
treatment, and 20 patients received combination therapy.
No statistically significant differences were noted with
respect to mortality in the overall cohort (SMR = 1.16;
95% CI = 0.56-2.13). This non–statistically significant
difference in mortality was consistent in both SJS and
TEN subgroups. In patients with TEN, investigators did
find a statistically significant difference in mean time to
arrest of progression (P = 0.0188) and total hospitalization
time (P = 0.0034). In patients with SJS, a statistically sig-
nificant reduction in mean time to arrest of progression
(P = 0.019) and total hospitalization time (P = 0.0475)
were observed. No other statistically significant differ-
ences were seen in the other reported outcomes and sub-
groups. The authors concluded that combination therapy
with steroids and IVIG had a “tendency” to reduce mortal-
ity, and though this result was not statistically significant,
the positive results in the secondary outcomes support the
use of combination therapy.
This study adds to the knowledge of managing patients
with steroid therapy compared with combination treatment.
However, there are major limitations of this study such as
the retrospective design and nonrandomized selection of
patients, without adjustment for potential confounders. In
particular, the period of time for which the steroid group
was recruited (1993-2000) may differ significantly from the
combination therapy group (2001-2007) with respect to
supportive care measures and other therapies. Finally, the
authors report P values for impact of the treatments on
6 Annals of Pharmacotherapy 
mortality but do not provide event rates, point estimates, or
CIs to accompany these.
In a study of patient data collected from a South Korean
academic tertiary care hospital during the period 2001-
2011, Kim et al13 characterized risk factors for mortality
among patients with a diagnosis of SJS or TEN (n = 82).
Patient data and information related to treatment and out-
comes were collected from medical records and analyzed
by multivariate logistic regression to determine ORs for
mortality among several potential covariates for mortality.
Of the 82 cases, 52.4% were considered drug-related etiolo-
gies and predominantly single-drug causes. Most patients
(70/82, 85.4%) received IV steroids, and most of them were
given dexamethasone (52/70, 63.4%) at a dose of 10 mg/d,
started after a mean of 2.21 (1-15) days after admission ini-
tially. Oral steroids (predominantly prednisolone 15 mg/d)
were used in 42 (51.1%) patients during their hospitaliza-
tion. The mean duration for IV and PO corticosteroid use
was 12.68 days (1-68 days). In all, 8 patients died during
hospitalization (9.8%).
Through univariate analysis, steroid use was not identi-
fied as a predictor of mortality among those who died and
those who survived and, therefore, not included in the sub-
sequent multivariate analysis. The only statistically signifi-
cant predictor of mortality was the diagnosis of pneumonia
(OR = 25.79; 95% CI = 2.25-296.21; P = 0.009). The
authors concluded that the low mortality rate compared
with previous studies may be a result of the high rates of
steroid use, and therefore, suggested that steroid therapy
should be used early, with careful documentation of signs
and symptoms of upper-respiratory-tract infection.
The provision of detailed information characterizing ste-
roid use and other potential prognostic indicators strength-
ens the study. However, it would be premature to draw any
firm conclusions about the perceived benefit of early ste-
roid use, given that no statistically significant differences
were found. These results may have been a result of type II
error, based on the low mortality rate and the small size of
the study cohort.
In 2013, Sekula et al14 published the results of a retro-
spective cohort study based on patients with a diagnosis of
SJS, SJS/TEN overlap, and TEN enrolled in the multina-
tional, RegiSCAR study (2003-2007). The authors con-
ducted several analyses of the risk of mortality based on
age, severity of reaction, organ function, pertinent comor-
bidities/infections, and treatments received. The treatment
analysis included 442 cases, with 97 (22%) receiving sup-
portive care only; 317 (72%) were exposed to steroids, 81
(18%) exposed to IVIG, and 24 (5%) received another
immunomodulating drug (4.2% were given cyclosporine).
Also, 244 patients (55%) received corticosteroids only, but
this was not included in the statistical analysis for determin-
ing risk of mortality. Patients were admitted to hospital for
a median time of 2 days (range = 0-23 days) and received
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varying equivalent doses of prednisone depending on geo-
graphical location (France, 75 mg; Germany, 250 mg).
Time to start of therapy after disease onset and duration of
treatment was not reported. The statistical methods for
assessing treatment effect on survival were not clearly
reported by the authors, but survival was not changed by
steroid use (hazard ratio = 1.3; 95% CI = 0.8-1.9).
The large population-based cohort with time-adjusted
survival analysis is a strength of this study. However, the
lack of clarity regarding statistical methods and the “any
exposure” definition of corticosteroid use results in diffi-
culty in gaining insight into the incremental effect of ste-
roids in these patients.
Discussion
Corticosteroids are a class of medications that have been
long used for their immunosuppressive and anti-inflammatory
effects for treatment of a wide spectrum of disorders such as
rheumatoid arthritis and inflammatory bowel disease.15 It
has been suggested that the first known use of steroids for
the treatment of SJS was reported in 1951 by Bleier and
Schwartz16 in several cases of SJS with severe ocular mani-
festations. It was reported that these patients achieved sig-
nificant improvement in their symptoms with the
administration of cortisone or adrenocorticotropic hor-
mone.17 As more reports of success with corticosteroids
were published, the standard of treatment for children, ado-
lescents, and adults presenting with these conditions
included the use of corticosteroids. Controversy around this
practice first arose when 3 retrospective case review studies
were published.18-21 These studies challenged the established
standard of care that corticosteroids shorten the course of the
disease and improve survival rates. Instead, these authors
proposed that exposure to these agents increase the risk of
infectious complications and prolong hospitalization.
Our review of the data to date, which excluded low-quality
case reports, case-series, and reviews, but is limited to out-
come data from retrospective cohort studies, suggests that
the impact that steroids have on mortality among patients
presenting with SJS, SJS/TEN, and TEN is inconclusive.
Despite our attempts to include the highest-quality studies
possible, this review is still limited by several reoccurring
weaknesses of the included studies. All studies are limited
by their nonrandomized design, which increases their sus-
ceptibility to bias and confounding. There are also inconsis-
tencies in the reporting of disease severity and characteristics
of supportive care that create difficulty in applying the
study results to clinical practice. Furthermore, several out-
comes of interest were not reported in many of the studies,
particularly adverse events. Finally, the small study sizes
and differences in disease severity between those who
received steroids and those who did not introduces type II
error and confounding.
Law and Leung 7

To this point, the current body of evidence would benefit Conclusions

from studies with stronger internal validity, such as RCTs.
The lack of such studies likely exists for least 2 perceived A review of the highest-quality evidence available for ste-
reasons: (1) the disease is rare, and there are practical issues roid use in patients with SJS, SJS/TEN overlap, and TEN
around recruiting enough patients to adequately power a does not reveal an increase in mortality. It is common for
study; thus, an investigator would be left with a small or reviews to simply suggest that “more evidence” is required.
severely heterogeneous sample or both; and (2) there is a However, the results of this review and the precedence set
prevailing perception that conducting an RCT would be by a thalidomide RCT reveals a need to conduct a multi-
ethically inappropriate because SJS and TEN are life- centered trial to provide more definitive conclusions sur-
threatening conditions.22 rounding the role of steroids in adults in SJS, TEN, and SJS/
However, Wolkenstein et al23 challenged these per- TEN overlap.
ceived barriers by enrolling patients with SJS/TEN to
receive thalidomide or placebo in a randomized fashion, in
Appendix
the setting of best supportive care. The thalidomide arm
had 12 patients, and the placebo arm had 10 patients. Out SCORTEN scoring system
of 15 patients, 9 (60%) at 1 center died. This alerted the
local investigators to evaluate the data without breaking Risk Factor 0 1
protocol and unblinding participants. Across all centers
Age <40 Years >40 Years
included in the study, 13 of the 22 patients (59%) in the
Associated malignancy No Yes
treatment arms died. A decision was made to break blind-
Heart rate (beats/min) <120 >120
ing, and the mortality rate in the thalidomide group was
Serum BUN (mg/dL) <27 >27
observed to be higher than that in the placebo arm. The trial Detached or compromised <10% >10%
was subsequently terminated.23 This trial serves as an body surface
important example regarding the logistical and ethical Serum bicarbonate (mEq/L) >20 <20
implications of conducting a randomized experiment in Serum glucose (mg/dL) <250 >250
patients with SJS/TEN. First, it is possible to recruit ade-
quate numbers of participants into an RCT to obtain more
robust results, because of the high mortality rate in patients To calculate a SCORTEN score, assess patient with criteria
with SJS, TEN, and SJS/TEN. Second, through demonstra- in table to determine the total number of points.
tion of the feasibility of conducting an RCT in this popula-
tion, it provides credence to the fact that additional studies SCORTEN Score Expected Mortality
of similar methodology are needed to ensure that com- 0-1 3.2%
monly used medications such as corticosteroids are indeed 2 12.1%
providing the benefit that is assumed from less robust, non- 3 35.3%
randomized observational studies. 4 58.3%
Therefore, there is a need for carefully designed, multi- 5 or more >90%
center RCTs to evaluate the effects of corticosteroids com-
pared against best supportive care and other commonly
used agents (such as IVIG and cyclosporine) in the manage- Acknowledgments
ment of patients with SJS/TEN. These trials should take
We are indebted to Dr Michael Perlman for his assistance in
care to detail important characteristics of the patient, set- reviewing the article prior to submission.
ting, severity of disease, interventions, comparators, and the
timing of the outcomes to provide meaningful insight sur-
rounding the beneficial (or harmful) effects of these agents. Declaration of Conflicting Interests
The design of future studies should also consider several The author(s) declared no potential conflicts of interest with
key questions that remain regarding the optimal therapeutic respect to the research, authorship, and/or publication of this
regimen required for the safe and effective use of steroids. article.
First, does etiology influence responsiveness or adverse
effects of steroids? Second, do timing, dose, and duration of Funding
steroids have an effect on the course of the disease? Third, The author(s) received the following financial support for the
do different agents within the class (eg, prednisone vs meth- research, authorship, and/or publication of this article: At the
ylprednisolone) differ in effects? Finally, what is the role of time of revisions, Ernest Law was supported by 2014-2016
combination therapy and/or sequential therapy (stepwise UIC/Takeda Fellowship in Health Economics and Outcomes
add-on of agents rather than “upfront” multiple agents)? Research.

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8 Annals of Pharmacotherapy 

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