Systemic Corticosteroid Therapy for Steven Johnson Syndrome

(SJS): Toxic Epidermal Necrolysis (TEN) Inhospitalized

Patients of Dr. Moewardigeneral Hospital Surakarta

January 2016-December 2017

Rakhma Tri Irfanti, Ummi Rinandari, Harijono Kariosentono

Dermatovenereology Departement Dr. Moewardi General Hospital/Faculty of Medicine Sebelas Maret University,

Surakarta

Keywords: Systemic corticosteroid, SJS – TEN

Abstract: This retrospective descriptive study was conducted in hospitalized patients ofDr. Moewardi General

HospitalSurakarta between January 2016 and December 2017. The secondary data were taken from medical

record.The total number of patients was 26 people with the most age affected was 46 - 55 years and 56 - 65

years (23%). Male (57%) tended to be more affected than female (42%). The most common diagnosis was

SJS(61%) followed by SJS overlap TEN (19%) andTEN (19%).Hypertension was the most comorbid

disease (15%), mucosal involvement mostly affected mouth (88%) and the causes of SJS – TEN

mostlyinvolved more than one drug (53%). Most suspected causative drugs were cephalosporin and

paracetamol (23%). The average duration of systemic corticosteroid therapy was 10 days with an average

dose 25 mg per day (1.5 mg / kg body weight / day). Treatment of systemic corticosteroids in cases of SSJ -

NET in Dr. Moewardi General Hospital Surakarta showed clinical improvement with an average of 10 days

treatment and an average dose of 25 mg per day, tappering dose.

1 INTRODUCTION

Epidermal Necrolysis (EN) is an acute

mucocutaneous syndrome with symptoms of

necrosis and scalling inepidermal leading to

mortality.

Epidermal Necrolysis is classified into

several types of severity based on the area of the

body involved,below 10% is SJS, 10% - 29% is SJS

overlap TEN and 30% is TEN.

The incidence rates

of SJS and TEN are 1,2 – 6 and 0,4–1,2 per million

people annually, respectively (Valeyrie-Allanore,

2012; Gupta et al., 2016).

Most cases of SJS – TEN are induced by drugs

(Kariosentono, 2015). Although all drugs can be the

etiology but most of the reactions are associated

with several high-risk drugs such as carbamazepine,

phenytoin,allopurinol, lamotrigine, oxycam, Non

Steroid Anti Inflamasi, sulphonamides,

cephalosporin and nevirapin (Maciejewska et al.,

2014; Gupta et al., 2016).

The success rate of SJS – TENtreatment depends

on the stage at which treatment begins, the age of the

patient, the degree of necrolysis, comorbidity,

complications (electrolyte imbalance, renal or

hepatic dysfunction, Adult Respiratory Distress

Syndrome - ARDS and sepsis), availability of drugs

and clinicians (Gupta et al., 2016). One of the

treatments for SJS – TENissystemic corticosteroids

because both of these diseases aremediated by the

immune system and corticosteroids have the effect

of suppressing the intensity of the reaction,

preventing or decreasing skin necrolysis, reducing

fever and discomfort as well as breaking down

internal organs when given in the early stages and

high doses (Gupta et al., 2016).

Due to the lack of data on SJS – TEN and the use

of systemic corticosteroid in Indonesia in general

and Dr. Moewardi General Hospital in particular,

therefore we conducted this study to provide an

overview of SJS – TEN patients as well as systemic

corticosteroid therapy, in order to improve the

therapeutic quality and management of SJS – TEN.

Irfanti, R., Rinandari, U. and Kariosentono, H.

Systemic Corticosteroid Therapy for Steven Johnson Syndrome (SJS): Toxic Epidermal Necrolysis (TEN) Inhospitalized Patients of Dr. Moewardigeneral Hospital Surakarta January

2016-December 2017.

DOI: 10.5220/0008149800180022

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 18-22

ISBN: 978-989-758-494-7

2 METHODS

This retrospective descriptive study was conducted

in hospitalized patients ofDr. Moewardi General

Hospital Surakarta between January 2016 and

December 2017. The secondary data were taken

from medical record.Datastudy includes the number

of SJS - TEN patients, sex, age, comorbid disease,

mucosal involvement, culprit drugs, systemic

corticosteroid therapy, organ involvement and

complications. The data obtained were then

analyzed.

3 RESULTS

Table 1. Clinical characteristics and suspected causative agents of cases SJS – TEN January 2016 - December 2017.

Total

(n = 26)

Percentage

(%)

Age (year)

0 – 5

5 – 11

12 – 16

17 – 25

26 – 35

36 – 45

46 – 55

56 – 65

>65

Gender

Male

Female

Diagnosis

SJS

SJS overlap NET

NET

Comorbid Disease

Epilepsy

Diabetes Mellitus

Stroke

TBC

Malignancy

HIV/AIDS

CKD

Hypertension

Cardiovascular

Mucosal involvement

Eye

Mouth

Genitalia

Culprit Drug

One type

More than 1 drug

Not known

Internal organs involvement

Hepar

Kidney

Antibiotics

Penicillin

Cephalosporins

Clindamycin

Quinolones

Anticonvulsants

Systemic Corticosteroid Therapy for Steven Johnson Syndrome (SJS): Toxic Epidermal Necrolysis (TEN) Inhospitalized Patients of Dr.

Moewardigeneral Hospital Surakarta January 2016-December 2017

Carbamazepine

Phenytoin

Valproic Acid

Non Steroid Anti Inflammatory

Potassium Diklofenak

Diclofenac Sodium

Methampiron

Mefenamic acid

Paracetamol

Ibuprofen

Antituberculosis drug 2 7

Other drug (benzodiazepines) 1 3

Table 2: The use of systemic steroids in SJS - TENin hospitalized patients of dr. Moewardi General Hospital, January 2016

- December 2017

Research result

Average treatment duration (days) 10

Number of patients with systemic

corticosteroid therapy

The average dose of corticosteroid equivalent

dexamethasone (mg / day)

Average duration of systemic corticosteroid use (days) 10

Total use of corticosteroid therapy over 7 days 12

The averages length of stay (LOS) of SJS -

TENpatients was 10 days. All patients received

systemic corticosteroid therapy with an average dose

of 25 mg per day for 10 days (1.5 mg / kg body

weight / day) (Table 2).

4 DISCUSSION

Both SSJ and TEN are rare diseases, with the

incidence for SJS 1-6 cases per million inhabitants

annually, while TEN 0.4 - 1.2 cases / million / year

(Kariosentono, 2015). In this study, during the

period of January 2016 - December 2017, 26

patients were hospitalized due to SJS - TEN with the

average number of patients was 13 annually. Study

by Wanjarus et al reported the average age was 46

years old and women were more affected than men

(Roongpisuthipong et al., 2014). These findings are

in contrast with our findings in which men were

more likely to be affected do than women with the

average age of 45 years old. One of the factors that

influence the number of SJS -TEN events is genetic

factor (Stocka-Łabno et al., 2016).

Research conducted by Stocka-Łabno et al. the

most common culprit drug are sulfonamides and

anticonvulsants (lamotrigine). In our study the most

common culprit drug is antibiotic group

cephalosporin and NonSteroid AntiInflammatory

paracetamol.

In this study the most involved lesion was in the

oral mucosa (88%) followed by eye mucosa (65%)

andgenital mucosa (11%). In addition, the

manifestation of allergic conditions is not only on

the skin and mucosa but also involves internal

organs (Venkateshwarlu and Radhika, 2011). Organ

involvement in the occurrence of SJS andTEN are

8,1% - 61,5% and 53,8%, respectively (Huang et al.,

2009). We found the internal organs involved were

liver (57%) and kidney (43%). This occurs because

drug mediated hepatitis istoxic whereas abnormal

metabolism and hepatocyte damage are the major

pathogenic mechanisms. Increased transaminase

enzyme is affected by several factors such as

inflammatory reactions, fatty liver and viral hepatitis

(Huang et al., 2009).

In addition, SJS -TEN patients also partially have

comorbid disease. Research conducted by Stocka-

Łabno et al. reported that patients with SJS - TEN

have comorbid disease such as hypertension. It is the

same as our finding that hypertension is the most

comorbid disease too.

In SJS -TENpatients require hospitalization to

improve the condition (Stocka-Łabno et al., 2016).

The length of stay is different depending on the

severity of the illness and the accompanying

infection (Huang et al., 2009). The average LOS in

this study is 10 days, not much different from the

research done by Stocka-Łabno et al. 7 days. While

research by Haejun et al. has a LOS for 14 days

(Yim et al., 2010).

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

There are no standard guidelines for management

SJS-TEN patients. Recognizing and stopping the

causative agent are primary (Venkateshwarlu and

Radhika, 2011). A retrospective control study

conducted in Paris and Germany concluded that

corticosteroids did not show any significant effect on

mortality but only provided supportive care alone

(Kardaun and Jonkman, 2007; Stat et al., 2008).

Corticosteroids prevent disease prolongation when

administered during the first 72 hours of the initial

symptom occurrence. The dose of intravenous

dexamethasone (iv) was 1.5 mg / kg / day for 3

consecutive days (Prins, 2012; Valeyrie-Allanore,

2012; Kariosentono, 2015). The use of

methylprednisolone iv 500 mg daily (2 days) and

250 mg daily (in the next 3 days) (Kariosentono,

2015). Kim et al. and Hirahara et al. administered

methyl prednisolone therapy 250 - 1000 mg / day in

NET patients and tapering dose was done gradually

with oral prednisone. In our study all SJS -TEN

received systemic corticosteroid therapy with a

mean duration of corticosteroid tapering dose for 10

days with an average dose equivalent to

dexamethasone 25 mg / day or 1.5 mg / kg / body

weight.Doses of corticosteroids in SJS -TENpatients

at Inpatient Installation of Dr. Moewardi General

Hospital is in accordance with therapeutic

guidelines. By administering these systemic

corticosteroids the patients improved because the

mechanism of action is by inhibition of epidermal

apoptosis by several mechanisms like IFN-ɣ

inhibition that may induce apoptosis and

inhibitionapoptosis of Fas.-mediated keratinocyte

(Del et al., 2009).

5 CONCLUSION

This retrospective descriptive study was conducted

in hospitalized patients of Dr. Moewardi General

Hospital Surakarta between January 2016 and

December 2017. Treatment of systemic

corticosteroids in cases of SSJ-NET in Dr.

Moewardi General Hospital Surakarta showed

clinical improvement with an average of 10 days

treatment and an average dose of 25 mg per day,

tappering dose.

REFERENCES

Del, J.Q., Michaels, B., Rosso, J.Q. 2009., The Role of

Systemic Corticosteroid Therapy in Erythema

Multiforme Major and Stevens-Johnson Syndrome A

Review of Past and Current Opinions. The Journal of

clinical and aesthetic dermatology 2(3) ,pp. 51-55.

Gupta, L.K., Martin, A.M., Agarwal, N., D'Souza, P., Das,

S., Kumar, R., Pande, S., Das, N.K., Kumaresan,

M., Kumar, P., Garg, A., Singh, S., 2016. Guidelines

for the management of Stevens–Johnson

syndrome/toxic epidermal necrolysis: An Indian

perspective. Indian Journal of Dermatology,

Venereology, and Leprology, 82(6), pp. 603-625.

Hirahara, K., Kano, Y., Sato, Y., 2013.

Methylprednisolone pulse therapy for Stevens-

Johnson syndrome/toxic epidermal necrolysis: Clinical

evaluation and analysis of biomarkers. Journal of the

American Academy of Dermatology, 69(3), pp. 496-

498.

Huang, C.-H., Ho, J.-C., Cheng, Y.-W., Wu, W.-M.,

Huang, S.-L., Wang, C.-Y., 2009. Epidemiological

Study of Stevens-Johnson Syndrome and Toxic

Epidermal Necrolysis: Retrospective Analysis of

Southern Taiwanese Population During 2002 to 2007.

DERMATOLOGICA SINICA 27, pp. 15–26.

Kardaun, S.H., Jonkman, M.F. 2007. Dexamethasone

Pulse Therapy for Stevens-Johnson Syndrome/Toxic

Epidermal Necrolysis. Acta dermato-venereologica,

87(2), pp. 144-148.

Kariosentono, H., 2015. Sindroma Stevens Johnson dan

Nekrolisis Epidermal Toksika (NET). In: Mochtar, M.,

Penyakit Kulit Gawat Darurat. 1st ed. Surakarta:

UPT. Penerbitan dan Percetakan UNS,pp. 1-31.

Kim, K., Lee, D., Suh, H., 2005. Toxic Epidermal

Necrolysis: Analysis of Clinical Course and

SCORTEN-Based Comparison of Mortality Rate and

Treatment Modalities in Korean Patient. Acta

Dermato-Venereology, 85(6), pp.497-502.

Maciejewska, J., Jankowski, M., Zegarska, B.,

Czajkowski, R., 2014. Stevens-Johnson

syndrome/toxic epidermal necrolysis presumably

induced by norfloxacin. Advances in Dermatology

and Allergology/Postȩpy Dermatologii i

Alergologii, 31(3), 194-197.

Prins, C.F.L.E., 2012. Erythem multiforme, Steven

Johnson syndrome and toxic epidermal necrolysis. In:

Jean L Bolognia JLR, ed. Dermatology. 3rd ed. Spain,

pp. 323–333.

Roongpisuthipong, W., Prompongsa, S., Klangjareonchai,

T., 2014. 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. Dermatology Research Practice, pp.1-5.

Stat, D., Fagot, J., Sekula, P., 2008. Effects of treatments

on the mortality of Stevens- Johnson syndrome and

toxic epidermal necrolysis: A retrospective study on

patients included in the prospective EuroSCAR Study.

Journal of the American Academy of

Dermatology, 58(1), pp. 33-40.

Stocka-Łabno, E., Gabzdyl, N., Misiak-Gałązka, M.,

Pawłowska-Kisiel, M., Łazowski, T., Rudnicka, L.,

2016. Stevens–Johnson syndrome and toxic epidermal

necrolysis in an academic hospital setting: a 5-year

Systemic Corticosteroid Therapy for Steven Johnson Syndrome (SJS): Toxic Epidermal Necrolysis (TEN) Inhospitalized Patients of Dr.

Moewardigeneral Hospital Surakarta January 2016-December 2017

retrospective study. Our Dermatology Online 8, pp.

381–384. doi:10.7241/ourd.20164.104.

Valeyrie-Allanore, L., Roujeau, J.C., 2012. Chapter 40.

Epidermal Necrolysis (Stevens–Johnson Syndrome

and Toxic Epidermal Necrolysis). In: Goldsmith LA,

Katz SI, Gilchrest BA, Paller AS, Leffell DJ, W.K.

(Ed. 8), Fitzpatrick’s Dermatology in General

Medicine. McGraw Hill, New York Chicago, pp. 814.

Venkateshwarlu, M., Radhika, B. 2011. Diagnosis and

Management of Drug-induced Stevens-Johnson

Syndrome: Report of Two Cases. Journal of Indian

Academy of Oral Medicine and Radiology, 23(5), pp.

429-433.

Yim, H., Park, J.M., Cho, Y.S., Kim, D., Hur, J., Chun,

W., Kim, J.H., Seo, D.K., 2010. A Clinical Study of

Stevens-Johnson Syndrome and Toxic Epidermal

Necrolysis: Efficacy of Treatment in Burn Intensive

Care Unit. Journal of the Korean Surgical

Society, 78(3), pp. 133-139.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018