80 Indian Journal of Pharmacology | February 2013 | Vol 45 | Issue 1

Retrospective analysis of Steven Johnson syndrome and toxic

epidermal necrolysis over a period of 5 years from northern
Karnataka, India
Kikkeri Narayanasetty Naveen, Varadraj V. Pai, Vijetha Rai, Sharatchandra B. Athanikar
Research Article
Department of Dermatology,
Sri Dharmasthala
Manjunatheshwara College of
Medical Sciences and Hospital
(SDMCMS and H), Dharwad,
Karnataka, India
Received: 20-04-2012
Revised: 28-09-2012
Accepted: 29-10-2012
Correspondence to:
Dr. Kikkeri Narayanasetty Naveen,
E-mail: naveenkn80@yahoo.com
ABSTRACT
Objective: Cutaneous drug reactions are the most common type of adverse drug
reactions. Adverse cutaneous drug reactions form 2-3% of the hospitalized patients. 2%
of these are potentially serious. This study aims to detect the drugs commonly implicated
in Steven Johnson Syndrome-Toxic Epidermal Necrosis (SJS-TEN).
Materials and Methods: A retrospective analysis was done in all patients admitted in
the last ve years in SDM hospital with the diagnosis of SJS-TEN.
Results: A total of 22 patients with SJS-TEN were studied. In 11 patients anti-epileptics
was the causal drug and in 7, anti-microbials was the causal drug. Recovery was
much faster in case of anti epileptics induced SJS-TEN as compared to that induced
by ooxacin.
Conclusion: SJS-TEN induced by ooxacin has a higher morbidity and mortality
compared to anti convulsants.
KEY WORDS: Anti-epileptics, ooxacin, Stevens Johnson syndrome, toxic epidermal
necrosis
Introduction
Cutaneous drug reactions are the most common type of
adverse drug reactions.
[1]
Adverse cutaneous drug reactions
form 2-3% of the hospitalized patients.
[2]
The percentage of
potentially serious reactions is around 2%.
[2]
Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN) are
potentially serious cutaneous reactions, characterized by high
fever, wide-spread blistering exanthema of macules and atypical
target-like lesions, accompanied by mucosal involvement.
[3,4]
In
SJS, detachment of the epidermis is less than 10% of the body
surface area; the detachment is >30 in TEN.
[3]
In addition to
the severe skin symptoms, both diseases are accompanied by
complications in numerous organs, such as the liver, kidney,
and lung.
[5]
Historically, SJS was first described in 1922 by
two American physicians named Stevens and Johnson They
described an acute mucocutaneous syndrome in two young
boys characterized by severe purulent conjunctivitis , severe
stomatitis with extensive mucosal necrosis.
[3]
TEN, also
called Lyells syndrome was first described by the scottish
dermatologist Alan Lyell in 1956. He reported four patients
with an eruption resembling scalding of the skin objectively
and subjectively, which he called toxic epidermal necrolysis or
TEN.
[4]
Incidence of SJS and TEN is 0.05 to 2 persons per million
populations per year.
[6,7]
Incidence is higher in HIV patients than
general population.
[8]
The reported mortality varies from 3 to
10% for SJS and from 20 to 40% for TEN.
[9]

This retrospective study was done to detect the drugs
implicated in SJS-TEN in our hospital and their clinical outcome.
SJS-TEN is seen to occur among most commonly prescribed
drugs. Early identification of the drug will help in prompt
withdrawal of the drug thus reducing mortality and morbidity
among the patients with SJS TEN. This study aims to create
awareness among the treating physicians about the drugs
implicated in life threatening reactions to facilitate judicious
use of these drugs in future.
Materials and Methods
A retrospective analysis was carried out in all patients
admitted in the last five years in SDM hospital with the diagnosis
of SJS, TEN. Bastujis criterion was used to classify the reactions
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DOI: 10.4103/0253-7613.106441
Naveen, et al.: An analysis of Stevens Johnson syndrome
81 Indian Journal of Pharmacology | February 2013 | Vol 45 | Issue 1
25 and 63 in SJS and TEN respectively in a study in Germany
[10]

In Indian studies like Sharma et al
[1]
mean age was 22.3.
Devi et al
[11]
observed 68% of the patients were in 20-50 group.
Yamane et al
[14]
reported a mean age of 45.7 yrs.
In our study the most common drugs implicated were
antiepileptics (50%) followed by antibiotics (31%). Of the
antiepileptics, carbamazepine was the most often implicated
drug (27%) followed by phenytoin (13.6%). Carbamazepine
was given to the patients mainly for seizure episodes and
occasionally for post herpetic neuralgia. Anticonvulsants were
the drugs most commonly implicated in SJS-TEN in a six year
study conducted on 500 patients in Chandigarh.
[15]
Kamaliah
et al in their report of EM, SJS TEN in North East Malaysia
also confirmed that carbamazepine was the most commonly
implicated drug in SJS.
[16]
One of our patients developed reaction
to sodium valproate which has been rarely reported in literature
and the same has been reported from us.
[17]
into SJS, TEN and SJS-TEN. We recorded the duration of the
rash, drug intake, time period between the drug and reaction,
complications, associated comorbidities.
Drug that have been taken within four weeks preceding the
onset of symptoms were taken as causal drugs. All patients
were treated with barrier nursing with regular monitoring of
vitals, fluid and electrolyte balance, strict asepsis and nutrition.
Prophylactic antibiotics were given. All patients were given
short courses of systemic steroids which were gradually
tapered. Institutional ethical committee clearance has been
taken for the study.
Results
A total of 22 patients were analysed. Of the 22 cases that
were scrutinized we found 13 cases of SJS and 9 cases of TEN.
Of the 22 cases 14 were men and eight were women. The mean
age of the patients was 32.27 years with the youngest being one
year old and the oldest 65 years old. 13 of the 22 patients were
in the age group of 20-40 years followed by 0-20 years (five
patients). [Figure 1] four patients were suffering from HIV, three
of who were on antiretroviral therapy and one was diagnosed on
admission. 20 patients recovered completely without any major
sequelae, one patient died and another was lost to follow up. Of
the 20 patients who recovered, two developed symblepheron. In
the patient who died, the drug implicated was ofloxacin. Patient
presented with seven days history of rashes and fever. She was
admitted in Intensive care unit for eight days after which she
died of septicaemia. Patient had no history of any systemic
illness before the onset of SJS.
In 50% (11 of 22) of the patients antiepileptics were
implicated as the cause of SJS/TEN, followed by antibiotics
(7 of 22) [Table 1]. Analgsics, antipsychotics and antiretrovirals
were the other offending drugs. The patient who had developed
TEN for antiretroviral was on combination therapy with
zidovudine, nevirapine and lamivudine. Probably the reaction
was due to Nevirapine. In one case the causative drug was
unknown. Among the anticonvulsants carbamazepine was
responsible for most reactions (27%) followed by phenytoin
(13.6%). Ofloxacin was the most common antibiotic causing
SJS (18%). One patient developed reaction to sodium valproate
which has been rarely reported in literature.
Mean time taken for recovery in SJS induced by ofloxacin
was 9.6 days whereas carbemazepine and phenytoin took
six days and 6.6 days for recovery respectively. None of the
patients on antiepileptics died whereas one patient on ofloxacin
succumbed.
All patients were given adequate supportive therapy and
nursing care. All patients were given systemic steroids for a few
days and then tapered. One baby was given IV Immunoglobulins
for the treatment and it responded well in five days.
Discussion
In contrast to other studies we noticed a male preponderance
(14 males v/s 8 females) with a ratio of 1.75.
[1,10,11]
This was
in agreement with the study done by Barvaliya et al which
also reported a male preponderance.
[12]
Maximum number of
patients were in the age group of 20-40 yrs unlike in a study
by Roujeau et al
[13]
where most of the patients were in the
5th decade. Mean age in our study was 32.27 as compared to
Fi gure 1: Age distribution of the patients with Steven Johnson
Syndrome and Toxic Epidermal Necrolysis (SJS-TEN)
Table 1:
Drugs causing SJS-TEN
No. of patients
Antiepileptics 11
Carbamazepine 5
Phenytoin 3
Phenobarbitone 1
Risperidone 1
Sodium valproate 1
Antibiotics 7
Ooxacin 4
Levooxacin 1
Ceftriaxone 1
Cotrimoxazole 1
Antipsychotics 1
Olanzapine 1
Analgesics 1
Antiretrovirals Zidovudine, Lamivudine and
Nevirapine, probably Nevirapine
1
Unknown 1
Naveen, et al.: An analysis of Stevens Johnson syndrome
82 Indian Journal of Pharmacology | February 2013 | Vol 45 | Issue 1
Cite this article as: Naveen KN, Pai VV, Rai V, Athanikar SB. Retrospective
analysis of Steven Johnson syndrome and toxic epidermal necrolysis over
a period of 5 years from northern Karnataka, India. Indian J Pharmacol
2013;45:80-2.
Source of Support: Nil. Conict of Interest: No.
In contrast to the Indian studies in many of the reports from
developed countries antimicrobials were the most common
offending drugs.
[18-20]
In a French survey, NSAIDS were found
to be the culprit drugs.
[13]
Among the antibiotics ofloxacin was
most common offending drug (18%) in our study whereas in a
study by Yamane et al
[14]
in Japan the most common offending
antibiotics were the cephalosporins. Beta lactams were
the most common antibiotics causing SJS-TEN in a study by
Wong et al.
[20]
18% of patients were HIV positive in our study. Whereas in a
study by Barvaliya M,
[12]
37.5% of the patient were HIV positive.
And in study by European group 7.3% patients had AIDS.
[21]
In
a study by Sharma V,
[1]
mortality was 26 in SJS and nine in TEN.
In our study, all cases were treated with systemic
steroids. Though the role of steroids in treatment of SJS
and TEN is controversial, beneficial effect may be there if
steroids are started early in treatment with proper dose.
[22]

IV Immunoglobulin was given in one patient and recovery was
seen within five days. We could not make any conclusion about
the use of IV Immunoglobulin in treatment of SJS and TEN as
it was used only in one patient in our study.
We noticed that recovery time associated with ofloxacin
was 9.6 days which was much longer than recovery time with
anticonvulsants (six days). No deaths were reported with
anticonvulsants while one patient on ofloxacin died. Thus though
the adverse reactions with anticonvulsants were more severe,
the recovery was much faster than in patients who developed
these reactions with antibiotics. Besides, the recovery was
uneventful with no major sequelae in case of antiepileptic
induced reactions.
Conclusion
Oflaxacin, a commonly used antibiotic in India, has a risk
of inducing SJS-TEN, which may be fatal. SJS-TEN induced by
ofloxacin has a higher morbidity and mortality compared to anti
convulsants. Anti epileptics also have a potential for causing this
serious adverse reaction. Since the number of cases studied is
less, it warrants further research.
References
1. Sharma VK, Sethuraman G, Minz A. Stevens Johnson syndrome, toxic epidermal
necrolysis and SJS-TEN overlap: A retrospective study of causative drugs and
clinical outcome. Indian J Dermatol Venereol Leprol 2008;74:238-40.
2. Sharma VK, Sethuraman G. Adverse cutaneous reactions to drugs: An overview.
J Postgrad Med 1996;42:15-22.
3. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical
classication of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome,
and erythema multiforme. Arch Dermatol 1993;129:92-6.
4. Lyell A. Toxic epidermal necrolysis: An eruption resembling scalding of the skin.
Br J Dermatol 1956;68:355-61.
5. Roujeau JC. The spectrum of Stevens-Johnson syndrome and toxic epidermal
necrolysis: A clinical classication. J Invest Dermatol 1994;102:28S-30.
6. Li LF, Ma C. Epidemiological study of severe cutaneous adverse drug reactions
in a city district in China. Clin Exp Dermatol 2006;31:642-7.
7. Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME. Stevens-Johnson
syndrome and toxic epidermal necrolysis. Autoimmun Rev 2008;7:598-605.
8. Khambaty MM, Hsu SS. Dermatology of the patient with HIV. Emerg Med Clin
North Am 2010;28:355-68.
9. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. Toxic epidermal
necrolysis and Stevens-Johnson syndrome: Does early withdrawal of causative
drugs decreasethe risk of death? Arch Dermatol 2000;136:323-7.
10. Schopf E, Stuhmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. Toxic epidermal
necrolysis and Stevens-Johnson syndrome: An epidemiologic study from West
Germany. Arch Dermatol 1991;127:839-42.
11. Devi K, George S, Criton S, Suja V, Sridevi PK. Carbamazepine--the commonest
cause of toxic epidermal necrolysis and Stevens-Johnson syndrome: A study of
7 years. Indian J Dermatol Venereol Leprol 2005;71:325-8.
12. Barvaliya M, Sanmukhani J, Patel T, Paliwal N, Shah H, Tripathi C. Drug-induced
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-
TEN overlap: A multicentric retrospective study. J Postgrad Med 2011;57:115-9.
13. Roujeau JC, Guillaume JC, Fabre JP, Penso DP, Fletchet ML, Girre JP. Toxic
epidermal necrolysis(Lyells syndrome). Arch Dermatol 1990;126:37-42.
14. Yamane Y, Aihara M, Ikezawa Z. Analysis of Stevens-Johnson Syndrome and
Toxic Epidermal Necrolysis in Japan from 2000 to 2006 Allergol Int 2007;56:
419-25.
15. Sharma VK, Sethuraman G, Kumar B. Cutaneous adverse drug reactions:
Clinical pattern and causative agents - a 6 year series from Chandigarh, India.
J Postgrad Med 2001;47:95-9.
16. Kamaliah MD, Zaimal D, Mokhtar N, Nazmi N. Erythema multiforme, Steven
Johnson Syndrome, Toxic Epidermal Necrolysis in North East Malaysia. Int J
Dermatol 1998;37:520-3.
17. Naveen KN, Arunkumar JS, Hanumanthayya K, Pai VV. Stevens-Johnson
syndrome induced by sodium valproate monotherapy. Int J Crit Illn Inj Sci
2012;2:44-5.
18. Alanko K, Stubb S, Kaupinen K. Cutaneous drug reactions. Clinical types and
causative agents. Acts Derm Venerol 1989;69:223-6.
19. Kauppinen K, Stubb S. Drug reactions. Causative agents and Clinical types. Acts
Derm Venerol 1984;64:320-4.
20. Wong KC, Kennedy JP, Lee S. Clinical manifestations and outcome in 17 patients
of Steven Johnson Syndrome and Toxic Epidermal Necrolysis. Australas J
Dermatol 1999;40:131-4.
21. Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN, Naldi L, Viboud C, Roujeau
JC. Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal
necrolysis. AIDS 2001;15:1843-8.
22. Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens-Johnson
syndrome/toxic epidermal necrolysis. Acta Derm Venereol 2007;87:144-8.
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