A Four Years Retrospective Study of Stevens Johnson Syndrome:

Toxic Epidermal Necrolysis Treatments in a National Tertiary

Referral Hospital

Sarah Mahri, Teffy Nuary, Fadhli A. Mughni, and Windy Keumala B.

Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia / Dr. Cipto Mangunkusumo

National General Hospital, Jakarta

Keywords: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Treatments

Abstract: Stevens-Johnson syndrome (SJS) and/or toxic epidermal necrolysis (TEN) are drug reactions associated to

high morbidity and mortality. Prompt diagnosis and management may reduce the mortality rate. The research

aims to evaluate the consistency of current treatments for SJS/TEN with the clinical pathway by Dr. Cipto

Mangunkusumo National General Hospital and Indonesian Society of Dermatology And Venereology

(ISDV). A retrospective review was conducted on patients with SJS/TEN admitted to Dr. Cipto

Mangunkusumo National General Hospital, Jakarta during January 2014 to December 2017. The data were

collected from paper-based and electronic health medical record database. A total of 34 cases of SJS/TEN

were admitted, but only 30 cases with complete data was included, comprising of 20 males and 10 females

with the mean age were 37.5 (15-70) years. Carbamazepin was the most common culprit drug. All patients

were treated with intravenous methylprednisolone. The average length of stay were 6 days (3-20) in SJS, 8

(3-18) in SJS-TEN, and 11 (4-18) in TEN, while the mortality rate were 18.2% in SJS, 8.3% in SJS-TEN, and

14.3% in TEN. As conclusion, corticosteroids may contribute to reduced mortality rate in SJS/TEN without

increasing secondary infection and serious sequele. The current treatments for SJS/TEN in our hospital is

consistent with the clinical pathway by Dr. Cipto Mangunkusumo National General Hospital and Indonesian

Society of Dermatology And Venereology (ISDV). Further well-designed studies are required to compare the

effect of corticosteroids treatment for SJS/TEN to other medications.

1 INTRODUCTION

Stevens-Johnson syndrome (SJS) and toxic epidermal

necrolysis (TEN) are life-threatening diseases

characterized by widespread red rash, blisters, and

shedding of dead skin, with mucosal involvement.

The incidence of SJS/TEN has been reported to be

1.5–1.8/per million persons per year. SJS and TEN,

based on clinical manifestations, are generally

considered as different spectrum of the disease.

Bastuji-Garin et al. proposed

that disease

classification should be based on the percentage

of the

total body surface area (BSA) of the epidermolysis or

epidermal detachment. Epidermal detachment <10%

of the BSA is classed as SJS, detachment above 30%

as TEN, and detachment between 10% and 30% as

intermediate (SJS/TEN overlap). SJS/TEN usually

caused by medications (Wang & Mei, 2017; Bastuji

et al., 1993).

In addition to the damage to the skin,

gastrointestinal tract, and respiratory tract mucosa,

SJS/TEN can also associated with visceral

involvement (e.g liver, kidneys, lungs, and

hematopoietic system), leading to organ dysfunction

or even failure. The mortality rates of SJS and TEN

are 10% and 34%, respectively (Kim et al., 2012; Lee

et al., 2011).

SCORTEN, a severity-of illness scoring system

for TEN was used to evaluate prognosis. The

SCORTEN criteria are: serum blood urea nitrogen

>10 mmol/L, serum bicarbonate <20 mmol/L, serum

glucose >14 mmol/L, age >40 years, malignancy

present, heart rate >120 bpm, and percentage of BSA

with epidermal detachment >10%. The mortality rate

was predicted according to the SCORTEN total score

as follow: 1 point, 3.2%; 2 points, 12.1%; 3 points,

35.3%; 4 points, 58.3%; and 5 or more points, 90%

(Fouchard et al., 2000).

Mahri, S., Nuary, T., Mughni, F. and B., W.

A Four Years Retrospective Study of Stevens Johnson Syndrome: Toxic Epidermal Necrolysis Treatments in a National Tertiary Referral Hospital.

DOI: 10.5220/0008151300830087

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 83-87

ISBN: 978-989-758-494-7

The treatment for these diseases is not well

established all over the world. Clinical pathway 2017

for SJS/TEN treatments by Indonesian Society of

Dermatology And Venereology (ISDV) include

discontinue potential offending drugs,

hospitalization, ophthalmologist consultation,

systemic corticosteroids: intravenous dexamethasone

prednisone equivalent dose 1-4 mg/kg/day for SJS, 3-

4 mg/kg/day for SJS-TEN, and 4-6 mg/kg/day

intravenous; IVIG high dose 1 g/kg/day for 3 days in

TEN; cyclosporine; and combination IVIG and

systemic corticosteroids, and topical treatment

include petrolatum gel with parafin liquid or

debridement. In addition to clinical pathway by

ISDV, clinical pathway by Dr. Cipto Mangunkusumo

National General Hospital for the treatment of

SJS/TEN include identify and discontinue potential

offending medications/drugs and other drugs that can

cross react, hospitalization, intravenous fluid drug,

systemic corticosteroids: intravenous

methylprednisolone (prednisone equivalent dose) 1-2

mg/kg/day for SJS; 2-3 mg/kg/day for SJS-TEN; and

3-4 mg/kg/day for TEN, topical treatment for erosion

with 1% salicylic acid in cream or vaselin album or

fucidic acid cream 2%, Nacl 0.9% for crusts lesions,

and consultations to ophthalmologist; dentists,

internist; and otolaryngologist.

We conducted a retrospective review on patients

admitted to Dr. Cipto Mangunkusumo National

General Hospital, Jakarta with a diagnosis of SJS,

SJS-TEN overlap and TEN based on clinical features

during four years. The aim of this study is to evaluate

the consistency of SJS/TEN current treatments with

the clinical pathway by Dr. Cipto Mangunkusumo

National General Hospital and Indonesian Society of

Dermatology And Venereology (ISDV).

2 METHODS

A retrospective review was performed on patients

admitted to Dr. Cipto Mangunkusumo National

General Hospital, Jakarta, with the diagnosis of

SJS/TEN based on clinical features. The data were

collected from paper-based and electronic health

medical record database from January 2014 to

December 2017. Diagnostic criteria were based on

those proposed by Bastuji-Garin et al (Bastuji et al.,

1993). Prognostic were assessed using the

SCORTEN standard system. (Bastuji et al., 1993;

Kim et al., 2012). The following datas were collected:

demographic information, time from onset to

admission, culprit drugs, underlying diseases,

SCORTEN, extent of mucocutaneous involvement,

laboratory data, treatments, complications, and

mortality.

Institutional ethical committee clearance was

obtained. All drugs that have been taken within six

weeks before the onset of symptoms were considered

as the culprit drugs (Yamane et al., 2007).

3 RESULTS

Of the total 34 medical records, 30 with complete data

were selected and four with uncomplete data were

excluded. The clinical characteristics of patients are

available in table 1.

In our study, drug hypersensitivity was the causes

in all SJS/TEN patients. The causative drugs are

shown in figure 1. The most common culprit drug was

anticonvulsants (carbamazepine, fenobarbital,

haloperidol, gabapentin, pregabalin, lamotrigin,

fenitoin, valproic acid), followed by antibiotics

(cefixime, cotrimoksazole, ciprofloxacin, cefadroxil,

meropenem levofloxacin, clindamicyn, amoxicillin),

NSAIDs (paracetamole, mefenamic acid, ibuprofen,

metamphyron), antituberculosis (rifampicin,

isoniazide, pirazinamide, ethambutol), antiretroviral

(tenofovir, nevirapine, stavudine, lamivudine),

antiulcerative (ranitidin, omeprazole, lansoprazole),

cough and flu medicines (ephedrine,

phenylpropanolamine, phenylephrine, bromhexine,

N-acetylcysteine), tramadol, antigout (allopurinol),

antihistamine (cetirizine), anticancer (5-fu, cisplatin),

antihypertension (captopril) , anticoagulant

(transamin, aspilet), furosemide, antiparasites

(pirimetamine, rescovulin), antiemetics (ondansetron,

metoclopramide) and other drugs (activated

attapulgite, loperamide, eperisone, fructus

schizandrae extract).

Laboratory abnormalities showed increased

amino transferase (AST, ALT), hiponatremia,

anemia, leucocytosis, azotemia, hypoalbuminemia,

thrombocytopenia, hyperglycemia, and increased

procalcitonin. Patch test was performed in two

patients, one patient had positive patch test for

carbamazepine, and the other patient showed negative

result.

All 30 cases (100%) were treated with intravenous

methylprednisolone and fast tappering to oral

methylprednisolone. Corticosteroids usage, length of

stay, and mortality rate are shown in table 2.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

Table 1. Clinical characteristics of SJS/TEN patients (n=30)

n (%)

Age (years) 37.50 (15-70)

Gender

Male

Female

20 (66.7)

10 (33.3)

Time from onset to

admission (days)

3 (1-9)

Diagnosis

SJS

SJS-TEN

TEN

11 (36.7)

12 (40.0)

7 (23.3)

Underlying diseases

Epilepsi

Gastrointestinal

problem

HIV infection

Chronic Kidney

Disease

Hyperuricemia

Cardiovascular

Disease

Respiratory Tract

Infections

Stroke

Tuberculosis

Malignancy

Diabetes mellitus

Systemic Lupus

Erythematosus

Hepatitis

9 (30.0)

7 (23.3)

6 (20.0)

5 (16.7)

4 (13.3)

3 (10.0)

2 (6.7)

1 (3.3)

Mucosal involvement

Oral

Ocular

Genitalia

28 (93.3)

21 (70.0)

11 (36.7)

SCORTEN

≤1

≥5

3 (10.0)

8 (26.7)

11 (36.7)

5 (16.7)

1 (3.0)

Organ involvement and

complications

Liver dysfunction

Renal

dysfunction

Pulmonary

infections

Sepsis

Electrolyte

imbalance

9 (30)

6 (20)

3 (10)

6 (20)

8 (26)

Figure 1. The causative drugs of SJS/TEN

A Four Years Retrospective Study of Stevens Johnson Syndrome: Toxic Epidermal Necrolysis Treatments in a National Tertiary Referral

Hospital

Table. 2 Corticosteroids doses, length of stay and mortality in 30 patients

SJS (n=11)

n (%)

SJS-TEN overlap

(n=12)

n (%)

TEN (n=7)

n (%)

Corticosteroids

1 mg/kg/day

1.5 mg/kg/day

2 mg/kg/day

9 (81.8)

2 (18.2)

0 (0)

9 (75)

3 (25)

0 (0)

2 (28.6)

5 (71.4)

Length of stay (days) 6 (3-20) 8 (3-18) 11 (4-18)

Mortality rate 2 (18.2) 1 (8.3) 1 (14.3)

4 DISCUSSION

The median age was 37.5 years, which is lower than

those reported from other countries in Asia such as

Bangkok, Japan, Singapore, and Korea (Tan & Tay,

2012; Kim et al., 2012).

Our study shows that females

are affected with SJS/TEN more than males with a

male-to-female ratio of 2:1, which was in agreement

with earlier studies (Yamane et al., 2007; Kim et al.,

2012). The causes of SJS/TEN were considered to be

caused by an adverse reaction to drugs. The most

common culprit drug was anticonvulsants, especially

carbamazepine, followed by antibiotics, and

NSAIDs, this is in agreement with study by Yamane

et al

. The results may be because antibiotics and

NSAIDs were available without prescription in

Indonesia, and thus many patients with fever,

headache, or other symptoms of infection purchased

such drugs over the counter instead of consulting a

doctor.

All 30 cases (100%) in our study were treated with

intravenous corticosteroids, methylprednisolone.

Methylprednisolone for SJS was 1-1.5 mg/kg/day

prednisone equivalent dose. In SJS-TEN overlap and

TEN group, the dose was increased to 1.5-2

mg/kg/day prednisone equivalent dose. These

treatment is consistent with clinical guidelines for

SJS/TEN treatment by Dr. Cipto Mangunkusumo

National General Hospital and Indonesian Society of

Dermatology And Venereology (ISDV) that

recommends application of systemic corticosteroids

1-4 mg/kg/day. The differences between clinical

guidelines from ISDV and our hospital is the

preferences to use methylprednisolone rather than

dexamethasone, because of the minimal adverse

reactions. The corticosteroids doses were in

agreement with guidelines by Gupta LK that

recommends prompt withdrawal of the culprit drug,

meticulous supportive care, and early (preferably

within 72 hours) initiation of moderate to high dose

of oral or parenteral corticosteroid (prednisolone 1-2

mg/kg/day or equivalent), tapered rapidly within 7-10

days (Gupta et al., 2016).

Additional therapies include supportive care with

intravenous fluid drug, systemic antibiotics for

prophylaxis, skin and wound care with 1% salicylic

acid in cream or petrolatum and topical antibiotics for

the secondary infections. No patient received other

immunosuppressant or intravenous immunoglobulin.

All patients were consulted to ophtamologist, dentist,

otolaryngologist, and internist, consistent ith clinical

pathway.

The length of stay in TEN group is higher than

SJS and SJS-TEN overlap group. A total four cases

died, two cases in SJS group, one case in SJS-TEN

overlap, and one case in TEN group. Among SJS

group, one patient both of patients who died had a

severe underlying disease, one patient with end stage

renal failure had complications such as septic shock

and pneumonia, the other patient had a carcinoma

sinonasal. The actual mortality rate in SJS group was

higher (18.2%) compared to the predicted mortality

rate (12.1%). The differences underlying diseases and

infectious morbidity mainly influenced the mortality

rate. In the SJS-TEN overlap group, one case with

SCORTEN 4 died due to septic shock. The actual

mortality rate in SJS-TEN overlap is lower (8.3%)

than the predicted mortality rate (35.3%). One patient

who died in TEN group was a 18 years old female

with systemic lupus erythematosus, end stage renal

failure, epilepsi, hypertension, ischemic heart disease

and complications such us pneumonia and pleural

efusion. The actual mortality rate in TEN group

(14.3%) was lower than the predicted mortality score

(35.3%).

5 CONCLUSIONS

Corticosteroids moderate or high doses and short

period may contribute to reduced mortality rate in

SJS/TEN without increasing secondary infection and

serious sequele. The current treatments for SJS/TEN

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

in our hospital is consistent with the clinical pathway

an clinical guidelines by Dr. Cipto Mangunkusumo

National General Hospital and Indonesian Society of

Dermatology and Venereology (ISDV). Further well-

designed studies are required to compare the effect of

corticosteroids treatment for SJS and/or TEN.

ACKNOWLEDGEMENTS

We express our gratitude to Dr. Cipto

Mangunkusumo National General Hospital medical

record staff for data collection.

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A Four Years Retrospective Study of Stevens Johnson Syndrome: Toxic Epidermal Necrolysis Treatments in a National Tertiary Referral

Hospital