J Korean Surg Soc 2010;78:133-139 □ 원 저 □ DOI: 10.4174/jkss.2010.78.3.133 133 Correspondence to: Yong Suk Cho, Department of General Surgery, Hangang Sacred Heart Hospital, Hallym University Medical Center, 94-200, Yeongdeungpo-dong 7-ga, Yeongdeungpo-gu, Seoul 150- 719, Korea. Tel: 02-2639-5442, Fax: 02-2678-4386, E-mail: maru- [email protected]Received October 5, 2009, Accepted December 18, 2009 A Clinical Study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Efficacy of Treatment in Burn Intensive Care Unit Departments of Surgery and 1 Plastic Surgery, Burn Center, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 2 Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea Haejun Yim, M.D., Jin Mo Park, M.D. 2 , Yong Suk Cho, M.D., Dohern Kim, M.D., Jun Hur, M.D., Wook Chun, M.D., Jong Hyun Kim, M.D., Dong Kook Seo, M.D. 1 Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), potentially life-threatening skin diseases with organ failures caused by drugs, require specialized intensive care. However, SJS and TEN have usually been managed in general wards and intensive care units by most doctors. This study describes the efficacy of treatment in the burn intensive care unit (BICU) compared to previous general treatments. Methods: To investigate the clinical features, outcomes and benefits of 11 patients with SJS and TEN treated in our burn intensive care unit. Data on 11 patients who were treated between January 2004 and December 2008 were collected via a retrospective chart review. Also, the data were reviewed with previous literatures on SJS and TEN treatments. Results: Patients were classified with overlap SJS/TEN (n=4, 36.36%) or TEN (n=7, 63.64%). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common causative agents. Hepatitis was the most common organ involvement in both overlap SJS/TEN (n=1, 9.1%) and TEN (n=4, 36.36%). Renal dysfunction (n=4, 36.36%) and respiratory disorders (n=3, 27.27%) were seen in some cases. Mean time of total reepithelization was 9 days and mean hospital day was 14.66 days. Two patients with TEN died from sepsis with multi-organ failure, and the mortality rate was 18.18%. Conclusion: Adequate treatment of SJS and TEN in the BICU supports efficacy with a low mortality rate, short healing time, short hospitalization and fewer complications. (J Korean Surg Soc 2010;78:133-139) Key Words: Burn intensive care unit, Stevens-Johnson syndrome, Toxic epidermal necrolysis INTRODUCTION Stevens-Johnson syndrome (SJS) and toxic epidermal ne- crolysis (TEN) are characterized by widespread epidermal necrosis and mucosal involvement secondary to keratino- cyte apoptosis mostly by drugs with high mortality. Though the pathophysiology has not yet been fully elucidated, both disorders are considered to be within the same spectrum, except the involved body areas.( 1-4) Several treatments with advanced dressing material and drug therapy were intro- duced. Some authors not by dermatologist but by surgeons suggested some advantages of burn intensive care unit (BICU) treatment in SJS and TEN. There were some reports of clinical studies of SJS and TEN in Korean dermatologic literature, however, only limited number of reports included treatment in the burn intensive care unit.(5-7) However, the BICU supports the patients with proper thermoregulations, intensive fluid replacement with electrolyte balance, enteral nutrition, infection control and wound management with specialized nursing. Those spe- cialized treatments of BICU provide the efficacy with a low mortality rate, short healing time, short hospitalization and
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J Korean Surg Soc 2010;78:133-139□ 원 저 □
DOI: 10.4174/jkss.2010.78.3.133
133
Correspondence to: Yong Suk Cho, Department of General Surgery,Hangang Sacred Heart Hospital, Hallym University Medical Center,94-200, Yeongdeungpo-dong 7-ga, Yeongdeungpo-gu, Seoul 150- 719, Korea. Tel: 02-2639-5442, Fax: 02-2678-4386, E-mail: [email protected]
Received October 5, 2009, Accepted December 18, 2009
A Clinical Study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Efficacy of Treatment in Burn Intensive Care Unit
Departments of Surgery and 1Plastic Surgery, Burn Center, Hangang Sacred Heart Hospital, College of Medicine, Hallym University, 2Department of Dermatology and Cutaneous Biology Research Institute,
Yonsei University College of Medicine, Seoul, Korea
Haejun Yim, M.D., Jin Mo Park, M.D.2, Yong Suk Cho, M.D., Dohern Kim, M.D.,
Jun Hur, M.D., Wook Chun, M.D., Jong Hyun Kim, M.D., Dong Kook Seo, M.D.1
Purpose: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), potentially life-threatening skin diseases with organ failures caused by drugs, require specialized intensive care. However, SJS and TEN have usually been managed in general wards and intensive care units by most doctors. This study describes the efficacy of treatment in the burn intensive care unit (BICU) compared to previous general treatments.Methods: To investigate the clinical features, outcomes and benefits of 11 patients with SJS and TEN treated in our burn intensive care unit. Data on 11 patients who were treated between January 2004 and December 2008 were collected via a retrospective chart review. Also, the data were reviewed with previous literatures on SJS and TEN treatments.Results: Patients were classified with overlap SJS/TEN (n=4, 36.36%) or TEN (n=7, 63.64%). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common causative agents. Hepatitis was the most common organ involvement in both overlap SJS/TEN (n=1, 9.1%) and TEN (n=4, 36.36%). Renal dysfunction (n=4, 36.36%) and respiratory disorders (n=3, 27.27%) were seen in some cases. Mean time of total reepithelization was 9 days and mean hospital day was 14.66 days. Two patients with TEN died from sepsis with multi-organ failure, and the mortality rate was 18.18%.Conclusion: Adequate treatment of SJS and TEN in the BICU supports efficacy with a low mortality rate, short healing time, short hospitalization and fewer complications. (J Korean Surg Soc 2010;78:133-139)
Key Words: Burn intensive care unit, Stevens-Johnson syndrome, Toxic epidermal necrolysis
INTRODUCTION
Stevens-Johnson syndrome (SJS) and toxic epidermal ne-
crolysis (TEN) are characterized by widespread epidermal
necrosis and mucosal involvement secondary to keratino-
cyte apoptosis mostly by drugs with high mortality. Though
the pathophysiology has not yet been fully elucidated, both
disorders are considered to be within the same spectrum,
except the involved body areas.(1-4) Several treatments with
advanced dressing material and drug therapy were intro-
duced. Some authors not by dermatologist but by surgeons
suggested some advantages of burn intensive care unit
(BICU) treatment in SJS and TEN. There were some
reports of clinical studies of SJS and TEN in Korean
dermatologic literature, however, only limited number of
reports included treatment in the burn intensive care
unit.(5-7) However, the BICU supports the patients with
proper thermoregulations, intensive fluid replacement with
electrolyte balance, enteral nutrition, infection control and
wound management with specialized nursing. Those spe-
cialized treatments of BICU provide the efficacy with a low
mortality rate, short healing time, short hospitalization and
134 J Korean Surg Soc. Vol. 78, No. 3
fewer complications. Therefore, the aim of the present
study is to present the efficacy of the burn intensive care
unit treatment with necessity in SJS and TEN.
Herein, we report our interesting retrospective study in
treating SJS and TEN in the burn intensive care unit with
literature reviews.
METHODS
1) Patients
A retrospective review was performed on all 11 patients
who visited our hospital burn center for SJS/TEN from
January 2004 to December 2008. All of them were ad-
mitted to the burn intensive care unit.
2) Diagnostic criteria
Diagnoses were made by dermatologists with histopa-
thological confirmation. The patients were divided into
three groups according to the following criteria of Bas-
tuji-Garin et al.(8,9). Bullous erythema multiforme (EM):
epidermal detachment involving <10% of the body sur-
face, coupled with localized typical targets or raised atypical
targets. SJS: epidermal detachment of <10% of the body
surface in association with widespread erythematous or
purpuric macules or flat atypical targets. SJS/TEN overlap:
epidermal detachment of 10% to 30% of the body surface
plus widespread purpuric macules or flat atypical targets.
TEN with spots: epidermal detachment of >30% of the
body surface coupled with wide spread purpuric macules
or flat atypical targets. TEN without spots: large sheets of
epidermal detachment involving >10% of the body surface
without purpuric macules or target lesions.
3) Evaluations
Data regarding demographics, causative agents, pattern
of involvement, underlying diseases, complications, mortali-
ty, and morbidity were obtained. As it is difficult to con-
firm which drugs are responsible for SJS/TEN, we checked
all drugs used within 3 weeks of onset.(5) Severity of illness
score for toxic epidermal necrolysis (SCORTEN) was eva-
luated during the first 24 hours of admission. From the
SCORTEN score, expected mortality and expected death
case were calculated. SCORTEN includes seven clinical
variables: 1) age above 40 years, 2) presence of malignancy,
3) tachycardia above 120/min, 4) involvement of >10%
of body surface area, 5) serum urea >28 mg/dl, 6) serum
glucose >252 mg/dl and 7) bicarbonate <20 mEq/L.(10)
4) Treatment
All patients received proper fluid and electrolyte resusci-
tation, pain management, nutritional support, wound care,
surgical debridement of dead tissue by intensive care unit
specialist. For the wound management, moisture retentive
dressings such as MedifoamⓇ (Hydrophilic polyurethane
foam dressing; Il Dong & Biopol, Korea), AQUACELⓇ
(ConvaTec, UK) or ActicoatTM (Smith & nephew, Canada)
were applied. Sulfonamide-containing topical agents were
avoided. Antibiotics were applied only to treat systemic
infections depending on the wound, urine, and blood
cultures, which were checked twice a week. Steroids were
prohibited and any steroid agents used prior to admission
were discontinued. Ten patients in the burn intensive care
unit were treated with intravenous immunoglobulin (IVIG)
at a dose of 1 g/kg/day for 3 to 7 days (mean 4.3 days).
RESULTS
1) Demographics
A total of 11 patients (9 males and 2 females, mean age
31.81 years, range 5∼83 years) were included in this study.
According to the criteria of Bastuji-Garin et al.,(8,9) four
patients were diagnosed with SJS/TEN (n=4, 36.36%) and
seven with TEN (n=7, 63.64%). Six (54.55%) of the pa-
tients had underlying diseases, including hypertension, con-
*Time of onset clinical disease following the institution of a new drug regimen; †TBSA = total body surface area; ‡NSAIDs = nonsteroidal anti-inflammatory drugs.
patient had taken the antiepileptic drug carbamazepine for
epilepsy. The average period between taking the relevant
drug to the appearance of symptoms was 9 days. Both
overlap SJS/TEN (100%) and TEN (71.4%) showed symp-
toms within 2 weeks. The mean percentage total body
surface area (TBSA) of skin involvement was 24.75% (18∼
30%) in overlap SJS/TEN and 68.7% (31∼100%) in TEN
(Table 1).
3) Clinical courses
The time from appearance of the first skin lesions to
the initiation of therapy varied from 1 to 10 days (mean
4.27 days). The mean period of hospital care to complete
skin healing time was 9 days (8∼12 days). The mean
period of hospitalization was 14.66 days (7∼22 days). All
patients showed involvement of the mucous membranes,
including the buccal, conjunctival, and genital mucosae.
4) Complications
During admission, coagulase negative staphylococcus, P.
aeruginosa, A. baumannii, and methicillin-resistant staphylo-
coccus aureus were cultured. On laboratory examination,
neutropenia was found in three cases and normocytic
anemia in six cases. The most common complication was
hepatitis, which was seen in one case in the overlap
SJS/TEN group and four cases in the TEN group. Acute
renal failure occurred in four cases in the TEN group.
Continuous renal replacement therapy (CRRT) was applied
in two patients. Two patients developed sepsis and three
patients had disseminated intravascular coagulation (DIC).
Conjunctivitis developed in six patients.
5) Mortality and SCORTEN evaluation
Two of eleven patients died of septic complications with
DIC due to TEN, resulting in a mortality rate of 18.18%
(Table 2). In two patients, acute renal failure and pneu-
monia were accompanied with a SCORTEN score of 5.
The mean SCORTEN score were 2.5 in the overlap SJS/
TEN group and 3.85 in the TEN group. Three patients
had a score of 5. One patient had a score of 4. Four
patients had as score of 3 and three patients had a score
of 2 (Table 3). The number of expected deaths was 5.058,
but the actual number of deaths was 2 (Table 4).
DISCUSSION
Drugs cause adverse reactions to the skin which can
occasionally be life threatening, such as SJS and TEN.
Although most adverse reactions are transient, SJS and
TEN can be persistent and are often accompanied with
multi-organ failure.(10) Cases with skin surface involve-
ment of <10% TBSA are diagnosed as SJS, while those
showing involvement of >30% TBSA are called TEN.
Epidermal detachment between 10% and 30% is classified
136 J Korean Surg Soc. Vol. 78, No. 3
as SJS/TEN overlap. SJS occurs predominantly in children
and adolescents, whereas TEN occurs in all ages regardless
of sex and race.(11) The incidence rates of SJS and TEN
are approximately 1∼7 cases and 0.4∼1.2 cases per 1
million people, respectively, per year.(11-15) The inciden-
ces of TEN and drug reactions are generally higher among
patients with HIV infection, SLE, and bone marrow trans-
plantation.(16) The most frequently implicated drugs are
sulfonamide antibiotics, aromatic anticonvulsants such as
phenytoin, phenobarbital, and carbamazepine, beta-lactam
2) Revuz J, Penso D, Roujeau JC, Guillaume JC, Payne CR, Wechsler J, et al. Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients. Arch Dermatol 1987;
Tabl
e 5.
A c
ompa
riso
n of
the
pre
viou
s st
udie
s on
SJS
and
TEN
tre
atm
ent
in g
ener
al w
ards
to
BIC
U t
reat
men
t
Rep
ort
No.
of
patie
nts
In
volv
emen
t of
ski
nar
ea (
TB
SA*,
%)
SCO
RT
EN†
(mea
n)
Re-
epith
eliz
atio
n tim
e (d
ays)
Le
ngth
of
hosp
ital
stay
s (d
ays)
Mor
talit
y ra
te (
%)
SJS
Ove
rlap
TEN
SJ
SO
verla
pT
ENSJ
SO
verl
apT
ENM
ean
SJ
SO
verla
pT
ENM
ean
SJS
Ove
rlap
TEN
Mea
n
Kim
et
al.(5
) 5
8 2
−
−−
3.5
10∼
1411
∼18
14∼
30 1
4.1
12
∼21
20∼
3014
∼30
20.6
00
50
6.
7K
im e
t al
.(6)
153
149.
119
.867
.3−
−−
−−
3∼
38
3∼38
3
∼38
16
.90
0 1
4.3
6.
25K
im e
t al
.(7)
80
12−
−−
−−
−−
−
7∼30
0 3
∼90
19
.70
0 4
225
Our
cas
e 0
4 7
0
24.
7568
.73.
70
8∼
14 8
∼14
9
010
∼20
7∼
22 1
4.66
00
29
18.1
8
*TB
SA =
tot
al b
ody
surf
ace
area
; †
SCO
RT
EN =
sco
re f
or t
oxic
epi
derm
al n
ecro
lysis
.
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