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Therapeutic
Guidelines for the management of Stevens–Johnson
Guidelines -
IADVL syndrome/toxic epidermal necrolysis: An Indian
perspective
Lalit Kumar Gupta, Abhay Mani Martin1, Nidheesh Agarwal2,

Paschal D’Souza3, Sudip Das4, Rajesh Kumar5, Sushil Pande6,
Nilay Kanti Das4, Muthuvel Kumaresan7, Piyush Kumar8, Anubhav Garg9,
Saurabh Singh10
Department of Dermatology, ABSTRACT

RNT Medical College, Udaipur,
Rajasthan, 1Department of Background: Stevens–Johnson syndrome and toxic epidermal necrolysis are severe,
Dermatology, Baby Memorial
Hospital, Kozhikode, Kerala, life‑threatening mucocutaneous adverse drug reactions with a high morbidity and mortality
2
Department of Dermatology, that require immediate medical care. The various immunomodulatory treatments include
Geetanjali Medical College, systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide,
Udaipur, Rajasthan, plasmapheresis and tumor necrosis factor‑α inhibitors. Aim: The ideal therapy of Stevens–
3
Department of Dermatology,
ESI‑PGIMSR, New Delhi, Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are
4
Department of Dermatology, only a limited number of studies of good quality comparing the usefulness of different specific
Medical College, Kolkata, treatments. The aim of this article is to comprehensively review the published medical
West Bengal, 5Department literature and frame management guidelines suitable in the Indian perspective. Methods: The
of Dermatology, Grant
Medical College, Mumbai, Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned
6
Department of Dermatology, the task of preparing these guidelines to its special interest group on cutaneous adverse
NKP Salve Institute of drug reactions. The group performed a comprehensive English language literature search
Medical Sciences, Nagpur, for management options in Stevens–Johnson syndrome/toxic epidermal necrolysis across
Maharashtra, 7Department of
Dermatology, PSG Institute multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and
of Medical Sciences and in combination) and MeSH items such as “guidelines,” “Stevens–Johnson syndrome,” “toxic
Research, Coimbatore, epidermal necrolysis,” “corticosteroids,” “intravenous immunoglobulin,” “cyclosporine” and
Tamil Nadu, 8Department of “management.” The available evidence was evaluated using the strength of recommendation
Dermatology, Katihar Medical
College, Katihar, Bihar, taxonomy and graded using a three‑point scale. A draft of clinical recommendations was
9
Department of Dermatology, developed on the best available evidence which was also scrutinized and critically evaluated
Government Medical College, by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus
Gwalior, Madhya Pradesh, statement was prepared. Results: A total of 104 articles (meta‑analyses, prospective and
10
All India Institute of Medical retrospective studies, reviews [including chapters in books], previous guidelines [including
Sciences, Jodhpur, Rajasthan, Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus
India gathered was used in the preparation of these guidelines. Recommendations: This expert
group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and
Address for correspondence: judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or
Prof. Lalit Kumar Gupta, parenteral corticosteroids (prednisolone 1‑2 mg/kg/day or equivalent), tapered rapidly
RNT Medical College,
within 7‑10 days. Cyclosporine (3‑5 mg/kg/day) for 10‑14 days may also be used either
Udaipur, Rajasthan, India. alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a
E‑mail: lalitanj@yahoo.com multidisciplinary approach in the management of these patients is helpful.
This is an open access article distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows
Access this article online others to remix, tweak, and build upon the work non‑commercially, as long as the
author is credited and the new creations are licensed under the identical terms.
Quick Response Code: Website:
www.ijdvl.com For reprints contact: reprints@medknow.com
DOI: How to cite this article: Gupta LK, Martin AM, Agarwal N, D’Souza
10.4103/0378-6323.191134 P, Das S, Kumar R, et al. Guidelines for the management of Stevens–
Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.
PMID: Indian J Dermatol Venereol Leprol 2016;82:603-25.
*****
Received: January, 2016. Accepted: August, 2016.
© 2016 Indian Journal of Dermatology, Venereology, and Leprology | Published by Wolters Kluwer - Medknow 603
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Gupta, et al. Indian guidelines for management of Stevens–Johnson syndrome/toxic epidermal necrolysis
Key words: Biologicals, corticosteroids, cyclosporine, disease‑modifying therapy, drugs causing

Stevens–Johnson syndrome/toxic epidermal necrolysis, granulysin, human immunodeficiency
virus, intravenous immunoglobulin, management guidelines, plasmapheresis, prevention,
severe mucocutaneous adverse drug reactions, severity‑of‑illness score for toxic epidermal
necrolysis (SCORTEN), Stevens–Johnson syndrome, toxic epidermal necrolysis
INTRODUCTION both Asian and non‑Asian populations.10 Patients with

human immunodeficiency virus/acquired immune
Background deficiency syndrome have a significantly greater risk
Stevens–Johnson syndrome (SJS) and toxic epidermal of manifesting SJS/TEN.11
necrolysis (TEN) are rare, potentially life‑threatening,
severe mucocutaneous adverse reactions characterized The present understanding of epidermal necrolysis
by extensive epidermal detachment, erosion of is that it is an immune‑driven pathway mediated by
mucosae and severe constitutional symptoms. Based granulysin released by drug‑specific cytotoxic CD8 T
on the similar histologic findings, SJS and TEN were cells and natural killer cells.12 Tumor necrosis factor‑α,
synonymously associated with erythema multiforme perforin/granzyme B, Fas ligand, Tweak and tumor
major since 1983. However, Bastuji‑Garin et al.1 in necrosis factor‑related apoptosis‑inducing ligand
1993 and Roujeau2 in 1994 proposed the differentiation which were earlier considered key mediators, are now
of erythema multiforme from SJS and TEN based thought to have a lesser, accessory role.13
on clinical and etiologic information [Table 1] and
it remains the most acceptable classification till
Table 1: Classification of bullous erythema multiforme and
date. Stevens–Johnson syndrome, toxic epidermal epidermal necrolysis as proposed by Bastuji‑Garin et al.
necrolysis and overlap Stevens–Johnson syndrome/ Classification Type of lesions Distribution Percentage of
toxic epidermal necrolysis are considered to be variants BSA detached/
within a continuous spectrum of epidermal necrolysis. detachable
Bullous EM Typical targets Acral ‑
Most cases of SJS and TEN are drug‑induced. SJS Spots ± atypical Generalized <10
targets
Although any drug can cause SJS/TEN, the Overlap Spots ± atypical Generalized ≥10-<30
majority of reactions can be attributed to a group of SJS‑TEN targets
high‑risk drugs such as carbamazepine, phenytoin, TEN with Spots ± atypical Generalized ≥30
allopurinol, lamotrigine, oxicam and other spots targets
non-steroidal anti‑inflammatory drugs, sulfonamide TEN without Diffuse erythema, Generalized ≥10
spots no spot or target
antibiotics and nevirapine [Table 2].3,4 Mycoplasma SJS: Stevens-Johnson syndrome, TEN: Toxic epidermal necrolysis,
pneumoniae and Cytomegalovirus infections are the EM: Erythema multiforme, BSA: Body surface area
next most common triggers of SJS/TEN, particularly

in children.5,6 Table 2: Drugs most commonly implicated in toxic epidermal
necrolysis
People of specific ethnic groups with certain human Drug class Associated drugs
leukocyte antigen subtypes have an increased Sulfonamide Co‑trimoxazole, sulfadoxine, sulfadiazine,
incidence of SJS/TEN when exposed to specific sulfasalazine
drugs.6,7 An association between human leukocyte Anticonvulsant Carbamazepine, barbiturates, phenytoin,
lamotrigine, felbamate
antigen‑B*1502 and carbamazepine‑induced
Antiviral Nevirapine, abacavir
Stevens‑Johnson syndrome has been reported in
Antibiotics Cephalosporins, fluoroquinolones, vancomycin,
Indian patients.8 The usefulness of human leukocyte aminopenicillins, doxycycline, erythromycin,
antigen screening in preventing SJS/TEN due to ciprofloxacin
carbamazepine has been validated in Han Chinese Uric acid lowering Allopurinol
patients with human leukocyte antigen‑B*1502.9 Antitubercular Thiacetazone, rifampicin, isoniazid, ethambutol
A systematic review and meta‑analysis found a NSAID Piroxicam, diclofenac, sulindac, ibuprofen,
ketoprofen, naproxen, valdecoxib, celecoxib,
significant association between human leukocyte rofecoxib
antigen‑B*5801 and allopurinol‑induced SJS/TEN in NSAID: Non-steroidal anti‑inflammatory drug
604 Indian Journal of Dermatology, Venereology, and Leprology | November-December 2016 | Vol 82 | Issue 6
Clinical features Management

The clinical features of SJS/TEN are characteristic The management essentials include early recognition
and the diagnosis is primarily clinical.14,15 The of the condition, cessation of suspected drug(s) if any,
initial symptoms or prodrome include fever, upper prompt institution of supportive therapy, referral if
respiratory tract symptoms and conjunctivitis required, initiation of specific therapy, management
mimicking febrile illness of infective origin. of complications and prevention of future episodes.
This is followed by the detachment of mucous The various immunomodulatory treatments include
membranes (oropharyngeal, conjunctival, anogenital systemic corticosteroids, cyclosporine, intravenous
and nasal). Usually, more than two mucous immunoglobulin, cyclophosphamide, plasmapheresis
membranes are involved. Cutaneous lesions, in and tumor necrosis factor‑α inhibitors. The ideal
the form of dusky erythematous macules/purpura therapy still remains a matter of debate as there are only
and/or flat typical/atypical target lesions, erupt a limited number of studies of good quality comparing
in association with pain and burning sensation. the usefulness of different specific treatments. The
Typical raised target lesions, characteristic of management and overall prognosis depend on the
the erythema multiforme spectrum, are usually stage at which treatment is initiated, age of the
absent. The lesions extend symmetrically, patient, extent of necrolysis, associated comorbidities,
predominantly on the trunk and proximal limbs accompanying complications (electrolyte imbalance,
over a period of hours to 2–3 days. There is an renal or hepatic dysfunction, adult respiratory distress
appearance of flaccid blisters followed by sheet‑like syndrome and sepsis), the patient’s ability to pay,
detachment of epidermis. Shearing pressure on the drugs and resources available for patient care and the
involved erythematous skin may cause epidermal physician’s experience with their use.
detachment (pseudo‑Nikolsky’s sign). Peri‑lesional
erythema is a sign of disease activity and helps to Prognosis
monitor response to treatment.16 Systemic symptoms Prognostication is a complex exercise where the
are almost always associated with SJS/TEN overlap clinician has to take into account several parameters.
and toxic epidermal necrolysis. Involvement of the Several factors may influence the outcome of SJS/
mucosae can lead to impaired alimentation, painful TEN. Outcomes are based on several clinical and lab
micturition, photophobia, diarrhea and respiratory oratory parameters, age of the patient, co‑morbidities,
distress. Thermoregulation is impaired and energy co‑existing compromised disease states and
expenditure is increased. Re‑epithelialization begins physiologic states such as pregnancy. Table 4 lists the
in a few days after the cessation of disease activity poor prognostic indicators in a clinical setting.
and is usually complete in about 3 weeks, barring
mucosae and pressure sites which take longer. A validated mathematical tool named
"severity-of-illness score for toxic epidermal
Complications can cause both mortality and long‑term necrolysis (SCORTEN)” for the prognostication of
morbidity in SJS/TEN. There is an increased SJS/TEN patients has been developed.17 It should
risk of sepsis due to altered immune function. be computed within 24 h after admission and
Dyspigmentation and scarring may develop. Ocular again on the 3rd day. Some studies have suggested
sequelae such as sicca syndrome, synechiae, scarring that the SCORTEN should be assessed on day 5.
and blindness may develop. Hypopharyngeal stenosis It is useful to predict the mortality and severity of
combined with dysphagia, and esophageal strictures illness. The index identifies seven independent risk
are long‑term complications that are difficult to treat. factors for death [Box 1]. Each parameter is given
Synechiae in other mucosae such as mouth and a score of one and the total score is calculated by
genitalia (esophagus or vaginal stenosis) may require summing up the number of abnormal parameters.
surgery. Table 5 shows the mortality rate according to the
SCORTEN. These diseases are associated with a
Differential diagnosis high morbidity and mortality; mortality rates are
Although the clinical history and presentation of SJS/ 1–5% with Stevens‑Johnson syndrome, 10–15% with
TEN is quite characteristic at a fully evolved stage, transitional forms and 25–30% with toxic epidermal
early lesions can mimic several bullous dermatoses necrolysis. The most common causes of death are
and drug reactions [Table 3]. sepsis, pulmonary failure and multiple organ failure.
Indian Journal of Dermatology, Venereology, and Leprology | November-December 2016 | Vol 82 | Issue 6 605
Table 3: Differential diagnosis of Stevens–Johnson syndrome/toxic epidermal necrolysis

Disease Distinguishing features
EM major Acrally distributed, raised typical or atypical target lesions, more commonly caused by
infections, particularly herpes and mycoplasma. Mucosal affection is generally milder
with <2 sites involved. Systemic features, generally marked in SJS/TEN, are milder or
absent. Recurrences are more frequent
SSSS Affects infants and children, spares mucosa and has superficial epidermal peeling
Paraneoplastic pemphigus Presence of pleomorphic eruptions with flaccid blisters, erosions, EM‑like lesions with
severe mucosal involvement in patients with underlying malignancy
Pemphigus vulgaris Affects middle‑aged patients with flaccid blisters, erosions in scalp, trunk, flexures and
mucosal erosions
Bullous pemphigoid Affects elderly patients with prodrome of urticarial lesions and development of tense
blisters. Mucosal involvement is rare
Generalized bullous fixed drug eruption Presence of well‑demarcated round‑to‑oval erythematous dusky patches or plaques
which may develop bullae in the center
Drug‑induced linear IgA bullous dermatosis Commonly due to vancomycin. Annular configuration of bullae, rarity of mucosal
involvement and DIF showing linear deposits of IgA along the basement membrane
Acute GVHD Seen in bone marrow and allogeneic hematopoietic stem cell transplant patients. Has
a close clinical and histological resemblance to SJS/TEN but features such as acral
to proximal spread, folliculo‑centric distribution, voluminous diarrhea and jaundice are
useful for differentiation
AGEP Commonly due to aminopenicillins, typically presents with sterile pustules on an
erythematous background and lacks erosive mucosal lesions
DRESS The morbilliform rash and bullous lesions resemble SJS/TEN but it usually manifests
with facial edema, milder lip crusting without frank mucosal and epidermal detachment
Acute lupus erythematosus May closely mimic SJS/TEN but histology and DIF are characteristic
SSSS: Staphylococcal scalded skin syndrome, DIF: Direct immunofluorescence, DRESS: Drug eruption with eosinophilia and systemic symptoms, SJS: Stevens–
Johnson syndrome, TEN: Toxic epidermal necrolysis, AGEP: Acute generalized exanthematous pustulosis, GVHD: Graft versus host disease, EM: Erythema
multiforme
Table 4: Factors affecting prognosis in Stevens–Johnson syndrome/toxic epidermal necrolysis (noted by this expert group in
clinical practice)
Parameter Remarks
Age Elderly age is a high‑risk category as there is a high risk of
complications, higher incidence of comorbidities and delayed
wound healing
Sex No difference in outcomes was noted between the two sexes
Pre‑ or co‑existing diseases Diabetes (poorly controlled or uncontrolled), HIV, SLE, oncologic
disease.
Compromised cardiac, renal, hepatic, hematologic,
gastrointestinal, pulmonary, neurologic or vascular systems
Metabolic parameters Hypoglycemia, hyperglycemia, hyponatremia, hypo‑ and
hyper‑kalemia, hypomagnesemia are key metabolic disturbances
that could aggravate the disease condition
Sepsis Onset of sepsis in already compromised denuded skin is a
poor prognostic sign. Several factors contribute to this: altered
immunologic events, altered drug and metabolic profile and
altered hemodynamic profile
Nosocomial infections Catheter‑associated urinary tract infection, central line‑associated
blood stream infections and ventilator‑associated pneumonia are
common in SJS‑TEN patients due to prolonged use of invasive
lines
Extent of involvement Risk of morbidity and mortality is directly proportional to
Denudation of skin (TEN)/purpuric or hemorrhagic The percentage of skin involved
necrosis (SJS)
Mucosal damage (oral, genital, nasal, ocular and anal) The type, severity and number of mucosae involved
Time of reporting/detection of drug‑related illness Earlier detection of causative drug and its withdrawal improves
prognosis
Delayed detection increases the risk of complications arising
from complications of immunosuppressive drugs, opportunistic
infections, and compromised systemic functioning
SJS: Stevens–Johnson syndrome, TEN: Toxic epidermal necrolysis, SLE: Systemic lupus erythematosus, HIV: Human immunodeficiency virus
SCOPE AND VALIDITY OF THESE GUIDELINES “toxic epidermal necrolysis,” “corticosteroids,”

“intravenous immunoglobulin,” “IVIG,” “cyclosporine”
This document is a set of recommendations and “management.” The available evidence was
for evolving a standard of care in India for the evaluated using a unified system called the strength
management of patients with Stevens–Johnson of recommendation taxonomy (SORT) developed by
syndrome/toxic epidermal necrolysis. They are editors of the US Family Medicine and Primary Care
intended for all clinicians involved in the care of journals (i.e., American Family Physician, Family
suspected SJS/TEN patients at any level of health Medicine, Journal of Family Practice and British
care: primary, secondary or tertiary. The purpose Medical Journal USA).18
of these guidelines is to provide a framework for
clinicians for effective, evidence‑based management
Evidence was graded using a three‑point scale based
of patients of SJS/TEN, taking into consideration the
on the quality of methodology as follows:
minimum standard of care that may be provided in a
I. Good‑quality patient‑oriented evidence.
resource‑poor setting.
II. Limited‑quality patient‑oriented evidence.
III. Other evidence including consensus guidelines,
This consensus statement would be valid for 3 years
opinion or case studies.
from the date of publication when the document will
be reviewed for validity based on the current best
evidence at that time. Clinical recommendations were developed on the best
available evidence and ranked as follows:
METHODOLOGY OF PREPARATION OF GUIDELINES A. Recommendation based on consistent and good
quality patient‑oriented evidence.
The special interest group on cutaneous adverse B. Recommendation based on inconsistent or
drug reactions (SIG‑CADR) on behalf of the Indian limited‑quality patient‑oriented evidence.
Association of Dermatologists, Venereologists and C. Recommendation based on consensus, opinion or
Leprologists (IADVL) performed a comprehensive case studies.
English language literature search for management
options in SJS/TEN across multiple databases (PubMed, A draft was prepared which was then sent for review to
EMBASE, MEDLINE and Cochrane) for an expert panel appointed by the IADVL Academy of
keywords (alone and in combination) and MeSH items Dermatology. It was also circulated among members of
such as “guidelines,” “Stevens–Johnson syndrome,” the e‑groups of IADVL_Acad _IADVL for suggestions
and criticism. Based on the inputs received, the final
Box 1: Prognostic parameters in the severity‑of‑illness score consensus statement was prepared.
for toxic epidermal necrolysis (SCORTEN)
Age >40 years RESULTS
Presence of malignancy
Tachycardia (heart rate above 120 beats/min)
A total of 104 articles (meta‑analyses, prospective and
Initial percentage of epidermal detachment >10%
retrospective studies, reviews [including chapters in
Blood urea nitrogen >28 mg/dl
books], previous guidelines [including Indian guidelines
Serum glucose >252 mg/dl
of 2006 and UK guidelines of 2016] and case series) were
Bicarbonate level <20 mmol/L
critically evaluated and the evidence thus gathered was
used in the preparation of these guidelines.
Table 5: Mortality rates according to the severity‑of‑illness
score for toxic epidermal necrolysis level
Management of patients essentially consists of:
SCORTEN Mortality rate (%)
• Prompt withdrawal of drug
1 3.2
• Initial assessment
2 12.1
• Prompt referral, if required
3 35.3
4 58.3
• Supportive treatment and investigations
≥5 90 • Initiation of disease‑modifying therapy
SCORTEN: Severity‑of‑illness score for toxic epidermal necrolysis • Prevention of recurrences.
Withdrawal of drug (level of evidence II, grade of The extent of erythema and the epidermal detachment,
recommendation B) both detachable epidermis (i.e. Nikolsky‑positive), as
Instant cessation of the offending/suspected drug(s) is well as detached epidermis, should be recorded and
of supreme importance. Withdrawal of the offending depicted on a body map in the medical records. The same
drug will achieve the objective of aborting or slowing may also be documented with the help of photographs
the process of acute skin failure and allow skin taken at the time of admission and repeated during the
epithelialization in a shorter period of time. It has treatment at various stages. This helps to serve as an
been shown that the earlier the causative drug is important safeguard against any potential medicolegal
withdrawn, the better the prognosis and that patients litigation.
exposed to causative drugs with long half‑lives
have an increased risk of dying.19 It should be Unfortunately, a confirmatory laboratory test that
remembered that if the reaction has been caused by will allow the diagnosis of a drug reaction with some
drugs with longer half‑lives, the pathologic processes degree of certainty and identify the culprit drug is
may continue for quite some time even after drug presently not available and those mentioned in the
cessation. When the culprit drug is identified, it is current literature are in experimental stages and
easier to withdraw the offending drug. However, have been used for research purposes. Hence, the
when multiple drugs (polypharmacy) or multi‑drug recommended investigations for all the patients are
combination therapies are used, it is difficult to for the purpose of knowing the degree of underlying
ascertain the exact drug responsible for causing a damage to various organ systems, for prognosis and
drug reaction. Given the severity and life‑threatening to plan further management [Appendix 1]. It should
nature of SJS/TEN, it is generally logical to stop all be noted that the severity of systemic damage may not
drugs taken by the patient. However, if administration necessarily correlate with that of epidermal necrolysis.
of a drug is absolutely essential (especially relevant for The investigations include the following:
epileptics and also severe life‑threatening infections • Hemogram
such as septicemia), these drug(s) can be substituted • Liver and renal function tests
with structurally unrelated drug(s). The decision to • Blood electrolytes
continue/substitute essential drugs should be taken in • Blood sugar
consultation with the treating clinician by following • Blood culture
an interdisciplinary approach. It is important to • Urine routine and microscopy
restrict drug intake to the minimum possible. • Skin swab culture
• Chest radiograph.
Initial assessment
Patients with SJS/TEN should preferably be The patient and his/her relatives need to be taken into
hospitalized. A detailed history must encompass the confidence and the severity, prognosis and potential
list of all drugs (including herbal, indigenous and for complications during the course of the disease
other alternative system of medications) taken within need to be explained in language they understand.
a period of 2 months prior to the onset of the eruption.
Co‑morbidities (infections, immunosuppression, Referral
hepatic and renal disease, connective tissue disorders) Hospitalization in an intensive care setting or
and chronic diseases (such as diabetes mellitus and burns unit may be considered where such facilities
hypertension) should also be noted. The temporal are available. However, where there are limited
association with the drug intake and previous episodes resources, especially in rural or district hospitals,
of allergic reactions are important parameters to or where the patient may be unfit for transfer, they
incriminate a drug as an etiological agent. Personal or may need to be managed in the general/dermatology
family history of drug reactions may be contributory ward or high‑dependency units with strict infection
and this must be recorded. control with the help of nurses trained to deal
with such cases. If possible, the patient should be
An initial assessment should include evaluation of admitted to an isolation room to facilitate infection
airway, breathing and circulation, urinary output and any and temperature control. Owing to the multisystem
clinical evidence of septicemia. Percentage of body surface nature of disease, management should preferably
area involved and degree and the extent and number of be carried out by a team of experts including a
mucosae involved need to be assessed and documented. dermatologist, physician, ophthalmologist, plastic
surgeon, chest physician, dietician and any other Preventing infection

specialists required as needed. The following measures are important to prevent
sepsis in patients with SJS/TEN.
Supportive therapy (level of evidence II, grade of • Barrier nursing and sterile handling of the
recommendation B) patient
Supportive treatment is essentially the same as for • Regular hand hygiene with chlorhexidine
burn patients. For supportive treatment, this group hand rubs and hand washes to be practiced by
recommends most of the guidelines as suggested by health‑care workers and caregivers
the previous IADVL Consensus Guidelines 2006: • Avoid unnecessary insertion of urinary
Management of SJS/TEN.14 Table 6 enlists some of the catheters, intravenous lines or central lines
important components of supportive care. • If used, urinary catheters, intravenous lines and
central lines must be handled minimally and
Environmental temperature maintenance changed regularly
Environmental temperature maintenance at 30–32°C • Monitor for foci of sepsis in the body, features
helps to prevent a hypercatabolic state by reducing of septicemia and disseminated intravascular
caloric losses through the skin.20 Heated‑air body coagulation
warmers may also be used. • Environmental controls for dependency
units (air exchanges, humidity and temperature
Monitoring control) and intensive care unit
Frequent monitoring of vital signs is an essential • Activate sepsis protocols early
part of management as they offer the first sign of • Judicious use of antibiotics.
a worsening systemic condition. Monitoring (both
initially at baseline and subsequently at periodic In case barrier nursing is available, blood cultures are
intervals) includes parameters such as pulse rate, done at admission and then every 48 h. It is preferable
blood pressure, respiratory rate, fluid intake and urine to obtain the swab for culture and sensitivity from
output chart, blood glucose, serum electrolytes, serum three lesional sites, particularly sloughed or crusted
creatinine and specific cultures. areas on alternate days throughout the acute phase.21
Antibiotics can be initiated either when direct
When the patient is on immunosuppressives, one must proof of sepsis exists, i.e., when blood cultures are
monitor for foci of sepsis (dental, gastrointestinal and positive or as soon as indirect signs of sepsis occur,
urinary) that may flare up during the course of disease. i.e., general deterioration in the form of hypothermia,
Complications such as septicemia and disseminated fever or shivering after the 4th day, diminishing level
intravascular coagulation can be monitored by of consciousness, confused mental status, anxiety/
specialized tests such as coagulation assays, D‑dimer excitement, falling urine output, deterioration of
assay and fibrin degradation products, where facilities respiratory status/diabetic control, failure of gastric
are available. emptying and any sudden change in the condition.22
Table 6: Components of supportive care in toxic epidermal necrolysis/systemic lupus erythematosus

Component Parameter Remark
Environmental temperature 30-32°C To prevent hypercatabolic state
Monitoring Pulse rate, blood pressure, respiratory rate, body To watch for progression to complications such
temperature as DIC, sepsis, renal failure, ARDS and MODS
Fluid intake and urine output chart
Blood glucose
Serum electrolytes
Serum creatinine
Blood culture
Specific cultures*
D‑dimer assay*
FDP*
Prevention of infection Barrier nursing Helps to reduce the chances of sepsis
Minimal handling and regular changing of catheters
Monitor for foci of sepsis, features of septicemia and DIC
*To be used where resources are available. FDP: Fibrin degradation products, DIC: Disseminated intravascular coagulation, MODS: Multiple organ dysfunction
syndrome, ARDS: Acute respiratory distress syndrome
Staphylococcus aureus is the main bacterium present urine output decreases. Slowly, the serum urea
during the first few days; Gram‑negative strains appear and creatinine concentration increases and
later. It should be kept in mind that systemic steroids pre-renal failure may develop.
may mask the signs of sepsis. • The early fluid requirement of TEN patients is
two‑third to three‑fourth of that of a burn patient
Since most centers do not have the infrastructure with the same extent of skin involvement and
for barrier nursing, prophylactic antibiotic therapy should be fulfilled by macromolecules (Ringer
may be considered for widespread skin involvement lactate) or saline solutions.24 The fluid
and slightest clinical suspicion of sepsis. Empirical requirements of burn patients is calculated by
coverage should include one antibiotic each having the Parkland formula, as follows:
anti‑staphylococcal activity (amoxicillin + clavulanic Fluid requirement = 4 ml/kg body weight ×
acid/tetracyclines/vancomycin/clindamycin/ percentage of body surface area involved.
teicoplanin/linezolid), Gram-negative activity • For the first 24 h, half the calculated fluid is
(amikacin/piperacillin + tazobactam/cefoperazone + administered in the first 8 h and the other half
sulbactam/imipenem) and anaerobic activity in the next 16 h. Fluid requirements beyond the
(metronidazole/tinidazole). If there is even slight first 24 h should be managed according to the
suspicion that SJS/TEN has been caused by a particular patient’s condition. Input and output charting
antibiotic(s), it is important to strictly avoid that is useful to guide fluid administration. The
antibiotic group and use an alternative, structurally maintenance fluid is titrated so as to maintain a
unrelated agent. Box 2 lists the definite indications of urine output between 1000 and 1500 ml. It must
antibiotic use in SJS/TEN patients.22 be noted that overcorrection of hypovolemia may
also lead to pulmonary edema. Blood transfusion
Fluid and electrolyte balance may be useful in some cases and perhaps works
• Peripheral intravenous line can be left in place by the dilution of drug metabolites, cytokines,
for a long duration and should not be replaced cytotoxic T‑cells and autoantibodies, providing
before 96 h unless there is evidence of phlebitis, immunoglobulins and nutrition, besides
local infection or malfunction. Routine culture correcting anemia and hypovolemia.25
of vascular catheter tip is not recommended.23
• Patients of toxic epidermal necrolysis lose a Feeding
significant amount of fluid as blister fluid and After admission, an oral liquid diet, nasogastric tube
insensible fluid loss and should be assumed or total parenteral nutrition should be initiated. If
to be hypovolemic. Adult patients having feasible, oral feeding is always preferred though it
inolvement of 50% of body surface area lose is often difficult because of upper gastrointestinal
around 3–4 L of fluid every day. This is usually tract injury. In the early stages of disease when
accompanied by the loss of electrolytes such as
dysphagia and odynophagia are severe, a fluid/
sodium, potassium and chloride in blister fluid.
semisolid diet is preferable and better tolerated by
Hypophosphatemia is a common complication
the patient. Early and continuous enteral nutrition
in these patients aggravating insulin resistance
decreases the risk of stress ulcers, reduces bacterial
and altering the neurological status and
translocation and enterogenic infection and allows
diaphragmatic functions.22 If replacement is
early discontinuation of venous lines. Caloric
not given promptly, the patient may develop
requirements are calculated as 30–35 kcal/kg/day.
dehydration which may adversely affect the
Proteins (approximately 1.5 g/kg/day) are given to
outcome. Urine becomes hyperosmolar and
avoid a negative nitrogen balance.
Box 2: Indications of the use of antibiotics in patients with Topical antiseptics and dressing of denuded skin
Stevens-Johnson syndrome/toxic epidermal necrolysis
It is advisable to leave detached/detachable epidermis
High bacterial count (single strain) from skin/catheter sample of
urine in place to provide a natural dressing. Regular
Sudden hypothermia in a relatively stable patient cleaning of wounds with clean water or normal saline
Confused mental state, anxiety and excitement is important, whether the patient is bedridden or
Symptoms of infection pertaining to a particular system, for mobile, to remove the infected crusts as this reduces
example, pneumonia/urinary tract infection the chances of infection. Gentian violet paint in
dilution and silver nitrate (0.5%) are useful for treating body temperature >39°C should prompt measures
denuded areas. Silver sulfadiazine should be avoided to cool the patient (cooled intravenous fluids and
because of frequent implication of sulphonamides in cold sponges). Nonsteroidal anti‑inflammatory drugs
SJS/TEN.14 Dressing is useful to prevent heat losses, such as antipyretics/analgesics must not be used if
infection, adhesion of clothes to raw skin surfaces and suspected to be the causative agent of SJS/TEN.
to promote re‑epithelialization. For denuded areas,
dressing can be done with paraffin or petrolatum gauze, Anticoagulation
with or without antibiotic impregnation. Adhesive Thromboembolism and disseminated intravascular
dressings should be avoided. Frequent changes in coagulation are important causes of morbidity and
patient position and an air‑fluid bed/water bed help death and hence, anticoagulation with low‑molecular
in early healing of lesions, prevention of bed sores and weight heparin may be useful in some patients.19 Early
reduce patient discomfort. Burn cage is also useful in mobilization of the patient may also be helpful.
preventing adhesion of denuded areas to clothes in
cases of extensive involvement. Psychological care
Providing emotional support and maintaining a
Oral and ophthalmic care continual dialogue with the patient and his/her
Oral hygiene should be maintained with normal saline family is a vital part of supportive care and addresses
swishes or antiseptic or anesthetic mouth washes. the patient’s fears/anxieties, improves compliance
Saline compresses followed by the application of with daily nursing care and gives an opportunity for
lubricants can be advised for the lips. This also helps patient education about self‑care after discharge and
soften hemorrhagic lip crusts. Daily examination by prevention of future episodes.
an ophthalmologist and vigorous treatment reduce the
risk of long‑term ocular complications. Lubrication Investigations
and antibiotic eye drops/ointments with or without The role of investigations in SJS/TEN is primarily for
corticosteroids are needed frequently (every 2 h). Lid
the detection of systemic involvement, prognostication
globe adhesions should be cautiously removed with a
and guiding therapy rather than diagnosis, which is
glass rod daily. Recently, the application of amniotic
essentially clinical. There is no reliable and validated
membranes was reported to be effective in preserving
in vitro or in vivo diagnostic test for SJS/TEN. The
visual acuity and an intact ocular surface.26
laboratory changes commonly include anemia and
lymphopenia; neutropenia is seen in one‑third of
Respiratory care
the patients and is associated with a poor prognosis.
Lung involvement may be complicated by pulmonary
Hyperglycemia and glycosuria may occur due to stress,
edema during fluid replacement. Pulmonary care
infection and possibly pancreatitis and indicate a poor
includes normal saline aerosols, bronchial aspiration
and postural drainage by turning the patient to different prognosis. Liver enzymes are elevated in half of the
sides. Pooling of saliva and secretions may predispose patients and occasionally, frank hepatitis may develop,
to aspiration and therefore need to be cleared induced by drugs, sepsis or shock. Hematuria and
frequently. Hypostatic pneumonia should be prevented proteinuria may be seen indicating renal involvement.
by frequent change of posture and mobilization of the Blood urea nitrogen and serum creatinine levels may
patient as early as possible. The nose may require be raised because of dehydration. Serum electrolyte
attention in the form of moisturization with saline and levels may guide fluid and electrolyte administration.
removal of adherent crusts. Chest radiograph, blood and skin swab culture, human
immunodeficiency virus testing (enzyme‑linked
Antacids, analgesics, anxiolytics and antipyretics immunosorbent assay) and skin biopsy may be done if
Antacids (H2 receptor antagonists and proton pump indicated.
inhibitors) reduce the incidence of gastric bleeding.
Pain management has to be individualized taking The interest in investigations has now shifted to
into consideration the clinical needs of the patient, detect the early markers of SJS/TEN. Soluble Fas
viable route of administration, risk of respiratory ligand, perforin/granzyme B, soluble CD40 ligand
suppression and monitoring facilities. Opioids (such and granulysin have been studied with granulysin
as tramadol) and anxiolytics may be helpful. Core emerging to be the most useful of these markers.
A rapid immunochromatographic assay capable of “a review of the highest quality evidence available
detecting high levels of serum granulysin (>10 ng/ml) for steroid use in patients with Stevens‑Johnson
has been developed with a sensitivity of 80% and syndrome, SJS/TEN overlap and toxic epidermal
a specificity of 95.8% in detecting SJS/TEN when necrolysis does not reveal an increase in mortality.”
compared to ordinary cutaneous drug reactions.13 There have been several other international reports
The other emerging markers for the early detection supporting the role of corticosteroids in patients with
of SJS/TEN are serum lactate dehydrogenase, SJS/TEN.26,41‑49
thymus and activation‑regulated chemokine (TARC/
CCL17), glutathione‑S‑transferase‑pi (GSTpi) Among Indian studies, Pasricha et al., in multiple
and high‑mobility group protein B1 (HMGB1), reports, strongly recommended the use of high‑dose
alpha‑defensins 1–3 in blister fluid and Bcl‑2 short‑duration corticosteroids in the routine
expression in dermal infiltrate.13 management of SJS/TEN.16,50,51 The same has been
emphasized in other Indian publications.52‑55
Disease‑modifying therapy
Disease‑modifying therapy in SJS/TEN is aimed Ocular sequelae are one of the major complications
at halting the immunological processes leading to of Stevens‑Johnson syndrome and toxic epidermal
keratinocyte apoptosis. Various immunomodulating necrolysis. A few reports support the use of
agents such as systemic corticosteroids, cyclosporine, corticosteroids in preventing ocular sequelae also.26,41
intravenous immunoglobulin, plasmapheresis, These studies also emphasize that the early use
tumor necrosis factor‑α inhibitors, granulocyte of corticosteroids halts disease progression and
colony‑stimulating factor and N‑acetylcysteine have consequently complications.
been used with variable results across the globe.
When should steroids be given?
Systemic corticosteroids (level of evidence II, grade of Most authors agree that corticosteroids are useful
recommendation B) when given at an early stage.41‑47,52‑56 Dhar has very
Traditionally, systemic corticosteroids have remained aptly stated that “it is the lack of knowledge and
the mainstay of therapy of Stevens‑Johnson syndrome expertise about how to use it rather than the lack of its
and toxic epidermal necrolysis in most centers. efficacy which has made the role of corticosteroid(s)
The rationale is that both these consitions are a matter of debate.”52 Das et al. opined that systemic
immune‑mediated processes and corticosteroids corticosteroids are effective in controlling the disease
suppress the intensity of the reaction, prevent/decrease process as well as recovery if started preferably within
the necrolysis of skin, reduce fever and discomfort and 3 days (maximum up to 7 days) from the onset of toxic
prevent damage to internal organs when given at an epidermal necrolysis in resource‑poor settings.54
early stage and in sufficiently high dosage.27‑33 They also stated that systemic corticosteroids in the
initial phase of disease continue to be life‑saving
Evidence for the use of steroids drugs in developing countries such as ours. Kardaun
The largest study to evaluate the effect of treatments, and Jonkman concurred that the “general negative
including steroids, was performed by Schneck et al.34 opinion of corticosteroids is probably because they
The authors examined data from a case–control study are often given too late, in too low a dose and for too
that evaluated the risk factors for Stevens‑Johnson long a period” and admitted that during “the healing
syndrome or toxic epidermal necrolysis in six phase, corticosteroids may indeed impair wound
countries in Europe in a cohort of 379 patients with healing and promote sepsis.”46 They also challenged
confirmed disease. The authors concluded that there the general opinion that systemic corticosteroids
was inadequate evidence that any specific treatment are detrimental in Stevens‑Johnson syndrome and
is established as effective with only corticosteroids toxic epidermal necrolysis and felt that “short
showing a trend for possible benefit. They called courses of high‑dose corticosteroids in early SJS/
for “a prospective randomized trial to be conducted TEN have a good rationale, as immune mechanisms
before any conclusions can be drawn, recommending are directly responsible for the cascade of events
that corticosteroids be trialled first.” A recently leading to apoptosis.” A review by Kakourou et al.
published review identified six retrospective studies concluded that an early and short course of systemic
which analyzed the role of steroids in the survival corticosteroid therapy provides a favorable influence
of patients with SJS/TEN.34‑40 They concluded that on the outcome.47
How much and by what route? CD4+ and CD8+ (cytotoxic) T‑cells in the epidermis by
The dosing, duration and route of administration that suppressing interlekuin‑2 production from activated
is most effective in SJS/TEN patients is open to debate. T helper cells. Many case reports, case series, open
Tapering of corticosteroids over 7–10 days to as long as trials and retrospective studies have documented the
4 weeks has also been reported.43,57 efficacy of cyclosporine in SJS/TEN.58‑66 In fact, some
of these reports suggest the superiorty of cyclosporine
High/suprapharmacological doses of corticosteroids over other therapies including intravenous
as conventional therapy or pulse or a combination immunoglobulin, corticosteroids, cyclophosphamide
of both have been advocated.41,46,48,49,54 Das et al. and supportive care alone.
administered dexamethasone at a dose of 1 mg/kg to
18 patients with toxic epidermal necrolysis who had Cyclosporine is used in a dose of 3–5 mg/kg body weight,
had the eruption for 7 days or less. Corticosteroids as oral capsules or solution, in divided doses. However,
were tapered and withdrawn within 5 days after the there is apparently no consensus on the duration of
subsidence of erythema and there was no mortality therapy. Most authors have used it for 1 month, or till
in the group.54 Intravenous pulsed dose methyl resolution of skin lesions and re‑epithelization. It has
prednisolone (3 consecutive daily infusions of been suggested that long‑term treatment is probably
20–30 mg/kg to a maximum of 500 mg given over 2–3 h) unnecessary as the disease progression generally stops
has also been successfully given.49 In addition, before the 10th day of cyclosporine administration.
Hirahara et al. gave an infusion of methylprednisolone Hence, it appears that short duration treatment
at 1000 mg/day for 3 consecutive days, followed by (7–10 days) is equally useful and cost‑effective, an
oral prednisolone at 0.8–1 mg/kg/day in tapering important issue in a developing country like India.
doses in eight patients with no mortality.48 Kardaun
and Jonkman have recently proposed dexamethasone
In an Indian study, 11 patients treated with
pulse therapy (1.5 mg/kg intravenous over 30–60 min
cyclosporine at a dose of 3 mg/kg/day for 7 days (and
on 3 consecutive days) to avoid long‑term use of
then tapered for another 7 days) were retrospectively
systemic corticosteroids.46 The authors described
compared with nine patients treated with
the pleomorphic effects of dexamethasone on the
corticosteroids. Cyclosporine significantly reduced
immune system including the inhibition of epidermal
the time to the arrest of progression of SJS/TEN, the
apoptosis by several mechanisms. These mechanisms
total re‑epithelialization time and hospital stay in
include the suppression of various cytokines, such
comparison to corticosteroids.64 Cyclosporine in
as tumor necrosis factor‑α, interferon‑γ, interlekuin‑6
combination with suprapharmacological doses of
and interlekuin‑10; inhibition of interferon‑γ‑induced
intravenous dexamethasone has been successfully
apoptosis and inhibition of Fas‑mediated keratinocyte
used in the treatment of SJS/TEN.55 In another Indian
apoptosis. Rai and Srinivas have successfully used
report, cyclosporine was used to successfully treat toxic
suprapharmacological doses of dexamethasone along
epidermal necrolysis induced by cyclophosphamide.65
with cyclosporine in their patients.55
Advocates of systemic corticosteroids recommend In a recent comparative study between cyclosporine

the administration of a high dose (regardless of route) and intravenous immunoglobulin in SJS/TEN, the
early in the course of the disease for a short period expected mortality rate based on SCORTEN in
of time. Table 7 summarizes the various studies on 17 patients treated with cyclosporine was 14.1%;
corticosteroid usage in SJS/TEN. however, the observed mortality rate was 5.9%.67
Similar figures for 37 patients treated with intravenous
Cyclosporine (level of evidence II, grade of immunoglobulin were 20.8% (expected mortality rate)
recommendation B) and 29.7% (observed mortality rate). The calculated
In recent years, cyclosporine has gained popularity standardized mortality ratio also suggested a survival
in the treatment of SJS/TEN. The use of cyclosporine benefit to cyclosporine use.
in SJS/TEN was suggested based on the role of
T‑lymphocytes in the pathogenesis of toxic epidermal Most common side effects associated with long‑term
necrolysis and striking clinical and histologic similarity cyclosporin treatment such as hypertension and
of the disease to some cases of acute graft versus host renal toxicity are not seen in treatment with short
disease. Cyclosporine (CsA) inhibits the activation of duration of treatment. However, septic complications
Table 7: Summary of corticosteroid studies in Stevens-Johnson syndrome/toxic epidermal necrolysis

Author, Type of study Patients receiving Dose of corticosteroids Mortality Level of Remarks
year corticosteroids evidence
Schulz Retrospective TEN (34) Not clearly mentioned 13/34 II Steroid exposure not
et al., non‑controlled associated with an increase in
200036 case series mortality
Tripathi Retrospective SJS (67) Methylprednisolone 1/67 (mortality II All patients had a favorable
et al., non‑controlled 160-240 mg daily; was unrelated outcome and there was
200044 case series tapered when clinical to SJS) no mortality or permanent
response seen (no mean sequelae related to SJS
duration given)
Kim et al., Retrospective TEN (21) Methylprednisolone 6/21 III The authors concluded that the
200537 non‑controlled 250-1000 mg daily, low mortality rate compared
case series later switched to oral with previous studies may
prednisolone be a result of the high rates
of steroid use and therefore,
suggested that steroid therapy
should be used early
Kardaun Retrospective SJS (1), SJS‑TEN First four patients: 1/12 III Authors concluded that
and non‑controlled overlap (4), TEN (7) IV dexamethasone short‑term dexamethasone
Jonkman, case series 100 mg once daily pulse therapy, given at an
200746 for 3 days+500 mg early stage of the disease
cyclophosphamide may contribute to a reduced
Subsequent patients: mortality rate in SJS/TEN
1.5 mg/kg IV without increasing healing time
dexamethasone for 3 days
Schneck Retrospective SJS (57), SJS‑TEN Maximum steroid dose 21/119 II The authors concluded that
et al., multicenter overlap (44), TEN (18) 250 mg prednisolone there was inadequate evidence
200834 non‑controlled equivalent given for that any specific treatment is
case series a median of 4 days established as effective for
(2-12 days) patients with SJS or TEN with
only corticosteroids showing a
trend for possible benefit
Hirahara Retrospective SJS (3), SJS‑TEN 1000 mg IV 0/8 III There was no mortality in spite
et al., non‑controlled overlap (2), TEN (3) methylprednisolone for of the SCORTEN‑predicted
201348 case series 3 days mortality being 1.6. A decrease
in proinflammatory cytokines
was also noted
Pasricha Retrospective TEN (5) IV dexamethasone 0/5 III Authors concluded that
et al., non-controlled 16-24 mg/day, tapered corticosteroids used in
199650 case series and withdrawn within appropriate doses ensure early
7-10 days recovery
Das et al., Prospective, TEN (18) Injection 0/18 II Two other patients were
201354 non‑controlled dexamethasone (1 mg/ given (IVIG) in a total dose
case series kg/day till erythema of 2 g/kg (0.4 g/kg/day for
subsided) tapered and 5 consecutive days), both of
withdrawn within 5 days whom survived. Authors opined
after subsidence of that systemic corticosteroids
erythema in the initial phase of TEN are
life‑saving drugs
Rai and Retrospective TEN (3) Injection dexamethasone 0/3 III Authors concluded that the
Srinivas non‑controlled 100 mg for combination of initial high dose
200855 case series 2 days (2 patients) of steroids and subsequent
or 4 days (1 patient) cyclosporine is a safe
followed by cyclosporine alternative
2 mg/kg/day (tapered 50
mg every 3rd day and
stopped after 2 weeks)
SCORTEN: Severity‑of‑illness score for toxic epidermal necrolysis, SJS: Stevens-Johnson syndrome, TEN: Toxic epidermal necrolysis, IVIG: Intravenous
immunoglobulin, IV: Intravenous
and severe leukopenia (<1000 cells/mm3) should be Table 8 summarizes the various studies on cyclosporine
watched out for. usage in SJS/TEN.
Intravenous immunoglobulin (level of evidence II, grade treated with intravenous immunoglobulin concluded
of recommendation B) that the use of intravenous immunoglobulin in the
A perception that use of corticosteroids leads to treatment of SJS/TEN overlap and toxic epidermal
enhanced mortality in SJS/TEN led to the search for necrolysis does not yield survival benefits, even
alternative immunomodulatory agent(s). In 1998, when corrected for intravenous immunoglobulin
Viard et al. demonstrated the reversal of Fas‑mediated dosages, i.e., low dose (<3 g/kg) or high dose
keratinocyte apoptosis by human immunoglobulin (>3 g/kg) and prior exposure to corticosteroids.77 The
by in vitro studies.68 Since then, many studies have only meta‑analysis of intravenous immunoglobulin
investigated the role of intravenous immunoglobulin, studies in SJS/TEN has been done by Huang et al.
but the results have been conflicting. Several studies which indicated uncertainty regarding the efficacy of
have reported a decreased mortality in patients with intravenous immunoglobulin in TEN.78 They found
TEN treated with intravenous immunoglobulin. that the intravenous immunoglobulin dose, when
These studies found survival rates of 88%, 94% adjusted for age, total body surface area involvement
and 100% with total intravenous immunoglobulin and delay of treatment, did not correlate with
doses of 2.7, 4 and 3.4 g/kg, respectively.69‑73 On mortality benefits. This becomes more convincing
the contrary, studies have also found no mortality in the light of evidence negating the role of Fas‑Fas
benefit compared with supportive therapy alone ligand‑mediated necrosis of epidermal cells and the
or when compared with the mortality predicted by emergence of the role of granulysin as the primary
SCORTEN.34,74‑76 The largest study to date (EuroSCAR) pathogenetic mediator.12
on the treatment of SJS/TEN found that 75 patients
treated with an average total dose of 1.5–1.9 g/kg of There have been a few Indian studies on intravenous
intravenous immunoglobulin did not have improved immunoglobulin, used either alone or in combination,
mortality compared with the group that received in SJS/TEN.54,73,79 Two of these studies used extremely
supportive therapy alone.34 More recently, skepticism low doses of intravenous immunoglobulin (cumulative
surrounding the role of intravenous immunoglobulin dose of <0.5 g/kg) and had favorable results. This
has surfaced. A retrospective study of 64 patients might be a more feasible option in resource‑poor
Table 8: Summary of cyclosporine studies in Stevens-Johnson syndrome/toxic epidermal necrolysis

Authors, year Type of study Number of patients Dose of Mortality Level of Remarks
cyclosporine evidence
Arévalo et al., Retrospective, 17 patients of 3 mg/kg/day orally 0/11 (CsA group) II Authors concluded that
200058 non-controlled TEN (11 patients every 12 h for as compared to immunosuppressive treatment
case series CsA, 6 patients with 2 weeks and then 3/6 (steroids + with CsA is safe and is
cyclophosphamide tapered off (10 mg cyclophosphamide associated with a rapid
and steroid) a day reduction group) re‑epithelialization rate and a
every 48 h) low mortality rate in patients
with severe TEN
Valeyrie‑Allanore Retrospective, SJS (10), SJS/TEN 1.5 mg/kg BD 0/29 (as compared II Both the death rate and the
et al., 201066 non‑controlled overlap (12) and 1 mg/kg BD and to 2.8 deaths progression of detachment
case series TEN (7) 0.5 mg/kg BD for predicted by were lower than expected,
10 days each in a SCORTEN) suggesting usefulness of
tapering fashion cyclosporin in SJS and TEN
Singh et al., Retrospective, 11 patients CsA, 3 mg/kg/day for 0/11 (as compared II Authors concluded that
201364 non‑controlled 9 corticosteroids 7 days, then 2 mg/ to 1.1 deaths cyclosporine has an
case series kg/day for 7 days predicted by encouraging role in the
SCORTEN) management of SJS and TEN
Kirchhof et al., Retrospective, 64 patients (28 SJS, CsA 3-5 mg/kg/day The observed II The use of cyclosporine
201467 single‑center, 19 SJS/TEN overlap for an average of morality was over IVIG may offer a
non‑controlled and 17 TEN); 7 days. IVIG 1 g/ 29.7% (n=11) greater mortality benefit
case series 12 received only kg/day for 3 days for IVIG and in the treatment of SJS/
supportive treatment, 5.9% (n=1) for TEN, the study suggested a
35 received IVIG, cyclosporine‑treated potential therapeutic beneﬁt
15 CsA and 2 both patients of cyclosporine use in the
treatment of SJS/TEN and
questioned the purported
beneﬁts of IVIG
CsA: Cyclosporine A, SJS: Stevens-Johnson syndrome, TEN: Toxic epidermal necrolysis, IVIG: Intravenous immunoglobulin, SCORTEN: Severity‑of‑illness score
for toxic epidermal necrolysis
countries such as ours where the prohibitively high Prevention of recurrences, follow‑up and counseling
cost of intravenous immunoglobulin therapy is an Preventing the recurrence of reaction is an important
important constraint. It has been suggested that the aspect of management in any form of drug reaction,
addition of corticosteroids to low‑dose intravenous particularly in severe types like SJS/TEN. The episode
immunoglobulin might increase efficacy by a possible should be reported to the national pharmacovigilance
synergistic effect.79 authorities. Drug allergy should be documented in
the patient’s case sheet and the discharge ticket very
As outlined above, there has been a significant legibly, preferably in red ink. The patient or his/
lack of consistency in the efficacy of intravenous her attendant should be given written information
immunoglobulin in different reports. Any decisive about drug(s) to avoid. They should be issued a
conclusion is complicated by a lack of homogeneity drug reaction card mentioning the suspected drug(s)
in many key clinical areas such as disease severity, and encouraged to carry this card in their pocket
patient comorbidities, dose, duration and timing all the time and show it to the clinician every time
of intravenous immunoglobulin administration. they fall ill. The patient should also be advised to
The inconsistencies can also be attributed to the seek appropriate consultations for the management
variability in the potential to inhibit Fas‑mediated of complications/sequelae resulting from SJS/TEN,
cell death among intravenous immunoglobulin particularly ophthalmological complications. SJS/
batches. Knowledge of the possible adverse effects/ TEN patients and their first‑degree relatives have
complications of intravenous immunoglobulin been known to exhibit a defect in the detoxification
therapy is essential before the initiation of treatment. of reactive metabolites and hence, survivors and their
These include a risk of anaphylaxis in patients first‑degree relatives should avoid suspected offending
with IgA deficiency and that of acute renal failure agents and related compounds. For example, a patient
in patients with cryoglobulinemia. Therapy with developing SJS/TEN to carbamazepine should avoid
high‑dose intravenous immunoglobulin should be phenytoin and phenobarbital which can be substituted
used cautiously in patients with renal insufficiency with unrelated compounds such as sodium valproate
or impaired cardiac function because fluid overload or lamotrigine. In addition, β‑lactam antibiotics,
may occur. Table 9 summarizes the various studies on cephalosporins and carbapenems should be strictly
intravenous immunoglobulin usage in SJS/TEN. avoided in any patient with a history of SJS/TEN to
penicillin or any other β‑lactam antibiotic. Drugs of
Other therapies (level of evidence III, grade of the same pharmacologic class can be used, provided
recommendation C) they are structurally different from the culprit drug.
Plasmapheresis, pentoxifylline, N‑acetyl cysteine and For example, arylamine containing sulphonamides
cyclophosphamide have been reported to have some such as sulfamethoxazole, sulfadiazine, sulfapyridine
benefit in cases with SJS/TEN,80‑86 but other studies and sulfamethizole cross react, whereas sulphonamide
have not found any definite benefit.87,88 Granulocyte diuretics, hypoglycemics, sulfasalazine and
colony‑stimulating factor was previously given as an sulfisoxazole are unrelated compounds which can be
adjuvant therapy in SJS/TEN patients with severe given in these patients. Patients should be issued a drug
neutropenia, but of late, its efficacy in patients without card to be carried at all times and asked to produce
neutropenia has also been suggested.89‑91 it at the time of visiting any health‑care professional.
Provocation tests are not advisable routinely in SJS/
A trial involving tumor necrosis factor‑α inhibitor TEN; however, it is an established protocol in some
thalidomide was prematurely suspended due to higher centers such as the All India Institute of Medical
mortality in the thalidomide‑treated group and hence it Sciences, New Delhi. It helps patients, especially
is not recommended in SJS/TEN.92 However, subsequent with multiple comorbidities having alleged history of
case reports have shown favorable outcomes in patients drug reaction to multiple drugs. These patients greatly
treated with anti‑tumor necrosis factor‑α biologicals suffer due to unwillingness and apprehension on
such as infliximab and etanercept.93‑95 the part of physicians to prescribe them appropriate
medications for the fear of precipitating drug rash. In
The various aspects of the management of SJS/TEN with such cases, providing these patients a safe drug list by
their evidence levels and grade of recommendation are undertaking supervised drug administration may be
summarized in Table 10. highly gratifying.
Table 9: Summary of intravenous immunoglobulin studies in Stevens–Johnson syndrome/toxic epidermal necrolysis

Authors, Study design Number of Dose of IVIG/regimen Mortality (%) Level of Remarks
year patients evidence
Viard et al., Multiple centers; TEN (10) 0.2-0.75 g/kg daily for 4 days 0/10 (0) III Effective variable
199868 prospective; case IVIG dosing
series; non‑controlled
Stella et al., Single burns unit SJS (1) 0.6-0.7 g/kg daily for 4 days 1/9 (11.1) III Effective
200172 Prospective; case Overlap
series; non‑controlled SJS‑TEN (7)
TEN (1)
Bachot et al., Single dermatology SJS (9) 2 g/kg given over 2 days 11/34 (32.4) as II Ineffective
200376 HDU; prospective; SJS‑TEN compared to
case series; with Overlap (5) SCORTEN‑predicted
SCORTEN‑predicted TEN (20) mortality 8.2/34 (23)
mortality as comparator
Prins et al., Multiple centers; Overlap Mean 0.7 g/kg daily for 4 days 6/48 (12.5) II Effective
200369 retrospective; case SJS/TEN (7)
series (including TEN (41)
previously reported
cases, from three other
studies); non‑controlled
Trent et al., Single dermatology SJS‑TEN 1 g/kg daily for 4 days (n=15) 1/16 (6.3) as II Effective
200370 unit; retrospective; Overlap (6) 0.4 g/kg daily for 4 days (n=1) compared to
case series with TEN (10) SCORTEN‑predicted
SCORTEN‑predicted mortality 5.8/16 (36.3)
Al‑Mutairi Single dermatology TEN (12) 0.5-1.0 g/kg for 4-5 days 0/11 (0) III Effective
et al., 200471 unit retrospective,
non-controlled
Brown et al., Single burns unit; TEN (24) 0.4 g/kg for 4 days 10/24 (41.7) as II Ineffective
200474 retrospective; case- compared to
control 6/21 (28.6) mortality in
controls
Shortt et al., Single burns unit; SJS‑TEN Mean dose 0.7±0.2 g/kg 4/16 (25) as III Equivocal
200475 retrospective; case- Overlap (16) Daily for 4±1 days compared to
control 6/16 (37.5) mortality in
historic controls
Kim et al., Dermatology unit; TEN (14) IVIG: 1.6-2.0 g/kg 1/14 (7.1) as III Effective
200537 retrospective; compared to
case series with SCORTEN‑predicted
SCORTEN‑predicted mortality: 2.4/14 (17.1)
IVIG: Intravenous immunoglobulin, SCORTEN: Severity‑of‑illness score for toxic epidermal necrolysis, SJS: Stevens–Johnson syndrome, TEN: Toxic epidermal
necrolysis, HDU: High dependency unit
Table 10: Summary of management aspects of Stevens- In centers where provocation tests are not routinely
Johnson syndrome/toxic epidermal necrolysis undertaken, an algorithm for drug causality for
Recommendations Grade of Level of References epidermal necrolysis (ALDEN) developed by Sassolas
recommendation evidence et al. can be useful for ascertaining drug causality.96
Withdrawal of drug B II 19 ALDEN assigns each drug a score from ‑12 to +10
Supportive therapy B II 14,19,20,22‑25 based on six parameters: (1) the time delay from
Systemic B II 16,26,34‑56,79 initial drug intake to onset of reaction; (2) the
corticosteroids
probability of drug presence in the body on the index
Cyclosporine B II 55,64‑67
IVIG B II 12,34,54,68‑79
day; (3) a previous history of adverse reaction to the
Plasmapheresis, C III 80‑91 same drug; (4) the presence of the drug beyond the
pentoxifylline, progression phase of the disease; (5) the drug notoriety
N‑acetyl based on the previous results of the EuroSCAR study4
cysteine and
cyclophosphamide and (6) the presence or absence of other etiologic
IVIG: Intravenous immunoglobulin causes. The score is categorized as very probable (>6);
probable (4–5); possible (2–3); unlikely (0–1) and very in newborns.104 However, these adverse effects are
unlikely (0). usually seen with long‑term use of cyclosporine to
prevent rejection and toxic epidermal necrolysis does
Stevens–Johnson syndrome/toxic epidermal necrolysis not require long‑term treatment.
in pregnancy
Toxic epidermal necrolysis in pregnancy puts two Stevens–Johnson syndrome/toxic epidermal necrolysis
lives at risk and hence, it requires the immediate in children
attention of both dermatologist and gynecologist. Stevens–Johnson syndrome/toxic epidermal necrolysis
A large majority of patients who develop SJS/ in children does not differ significantly in its etiology,
TEN in pregnancy are human immunodeficiency clinical features and management strategies from adult
virus‑positive and nevirapine is the most common SJS/TEN. Some points, however, are worth mentioning.
drug incriminated.97 Drugs are the most common culprits in SJS/TEN (both
children and adults). However, the likelihood of
Effect on mother infections (Mycoplasma and Cytomegalovirus)
Pregnancy as such is not a risk factor for mortality in inducing SJS/TEN is relatively higher in children as
toxic epidermal necrolysis.90 A review of the literature compared to adults.5,6 Sulphonamides, penicillins
by Struck et al. supports a high survival rate of both and nonsteroidal anti‑inflammatory drugs are more
mother and child.98 Long‑term complications of genital commonly implicated in drug‑induced pediatric SJS/
involvement in SJS/TEN include vaginal stenosis and TEN owing to their more frequent use in children.105
adhesions, endometriosis and telangiectasia.99 To Anticonvulsants are another class of drugs commonly
prevent vaginal complications, a vaginal mold with implicated in SJS/TEN in children. Stevens–Johnson
local corticosteroids/lubricant gel can be inserted in syndrome and toxic epidermal necrolysis rarely
the vagina to prevent adhesions.100 cause mortality in children, but significant morbidity
is seen.105 In a study of 21 patients by Prendiville
Effect on fetus et al., there was an excellent response to supportive
Maternal toxic epidermal necrolysis is known to care alone which included reverse barrier isolation,
cause fetal stress and preterm labor.98 Hence, it is intravenous fluids and nutritional support, meticulous
prudent to keep a close watch on fetal parameters skin care, early detection and treatment of infection
during management. In most cases, the child is and daily ophthalmologic examination, with no
not affected by toxic epidermal necrolysis.97 In mortality.30 It has been seen that the energy needs of
fact, toxic epidermal necrolysis in neonates/early children with SJS/TEN are 22% less than the age and
infancy is very rare and only some cases have been wound size matched burn patients. The recommended
reported. Rodriguez et al. have reported a case of equation for the estimation of energy requirements in
toxic epidermal necrolysis in both a mother and her children with SJS/TEN is: (24.6 × weight in kg) + (%
stillborn child.101 wound × 4.1) + 940.106
Management Corticosteroids, intravenous immunoglobulin and

Management of toxic epidermal necrolysis in pregnant cyclosporine have been utilized for specific therapy of
women is not very different from that of non‑pregnant pediatric SJS/TEN in various studies. Kakourou et al.
patients. Systemic steroids should not be favored suggest a bolus infusion of methylprednisolone
in the first trimester, but may be useful in the third (4 mg/kg/day) for 3–7 days which showed a significant
trimester as they help to increase the lung maturity reduction of the period of fever and acute eruption
of fetus, more so in case of preterm labor. Intravenous and milder signs of prostration as compared to
immunoglobulin and cyclosporine (pregnancy category supportive therapy alone.47 No relapses occurred after
C) can also be used in individual cases.102 Intravenous treatment was discontinued. They concluded that an
immunoglobulin has been used safely in treating early and short course of intravenous corticosteroids
pregnant patients with toxic epidermal necrolysis.101,103 favorably influenced the course of SJS/TEN in
There is not much literature on the use of cyclosporine children. Intravenous immunoglobulin has been
in pregnant women with toxic epidermal necrolysis. used as a treatment with mixed results. An Indian
The use of cyclosporine in pregnant renal transplant study by Mangla et al. evaluated the role of low‑dose
recipients has been associated with adverse effects intravenous immunoglobulin (0.05–0.1 mg/kg/day
for 5 days) in pediatric toxic epidermal necrolysis by non‑dermatologists, mostly plastic surgeons.
and found it to be a safe and effective treatment.74 The important role of intensive care units in the
Cyclosporine has also shown promising results in management of SJS and TEN notwithstanding, it
the treatment of pediatric SJS and TEN.107 brought about a paradigm shift in the way these
diseases were perceived. Surgeons outrightly rejected
DISCUSSION the use of steroids and regarded them as the cause of
increased morbidity and complications (e.g., sepsis,
Some general questions relevant to a physician leukopenia, thromboembolism and gastrointestinal
managing SJS/TEN are as follows: ulcerations), prolonged recovery, worse prognosis
and reduced survival. Following widely cited
Should disease‑modifying therapy be administered or reports, there was a complete turnaround in the
not? management, to a non‑steroidal approach.109‑114
Due to ethical reasons, there is insufficient evidence These developments brought skepticism in the
comparing supportive therapy alone versus supportive usefulness of corticosteroids in SJS/TEN among
therapy combined with disease‑modifying agents. dermatologists who adopted defensive medicine.
Based on vast personal experience and clinical Fine, however, carefully scrutinized this literature
observations by the members of this group, members and revealed many methodological problems.56,108‑114
of the expert review committee, academicians and The report by Rasmussen did not specify the doses
senior practitioners across India, it is recommended of corticosteroids used.108 One widely cited paper
that systemic disease‑modifying therapy be used reported higher mortality in patients treated with
early in the disease to help prevent progression of the high‑dose corticosteroids as compared to those
disease. which were not.109 However, 73% of patients in the
group described as not having been treated with
What is an ideal disease‑modifying therapy? corticosteroids (with higher survival rate) had in
The special interest group on cutaneous adverse drug fact received corticosteroids for a mean of 3.5 days
reactions (SIG–CADR) acknowledges the lacunae which may have contributed to their higher survival
in knowledge in medical literature (both Indian and rate. Furthermore, patients with toxic epidermal
international). Lack of head‑to‑head, comparative, necrolysis were intermixed with patients with
clinical, double‑blinded trials to identify the efficacy Stevens‑Johnson syndrome and it was not clear
and safety of immunosuppressive drugs further whether the two entities were distributed equally in
makes it difficult to decide on the best therapy. No each treatment group, even though their mortality
single immunosuppressive drug can be considered rates differ greatly. In addition, too few details about
universally efficacious and superior to others in the corticosteroid therapy were provided to permit
arresting the immunologic damage caused by the any critical assessment of the treatment. This was
disease. Thus, the issue still remains unresolved. the case in other studies also, in which corticosteroid
However, a thorough scrutiny of the pros and cons of duration and dose had not been specified.108,115 These
different disease‑modifying drugs has been done later are crucial flaws because corticosteroid therapy given
in the text to arrive at a consensus. for too short a time, at too low a dose or too late in the
disease course may not have been of much benefit.
What is the dilemma regarding the use of Another interesting point has been made by Wolf and
corticosteroids in Stevens–Johnson syndrome/toxic Davidovici that plastic surgeons in‑charge of burn
epidermal necrolysis? care units view burn and toxic epidermal necrolysis
Prior to the 1970s, systemic corticosteroids were as similar entities and although there is an acute skin
used as a standard therapy for patients with failure in both conditions, they differ significantly
Stevens‑Johnson syndrome. A report by Rasmussen in terms of etiology and pathomechanism.116 Burn is
et al. presented the initial data challenging the role of a one‑time acute event which affects the skin from
systemic corticosteroids in treating Stevens‑Johnson outside whereas toxic epidermal necrolysis is a more
syndrome, pointing to longer hospital stays complex immune‑mediated process that reaches the
and higher complication rates in children who skin from within. Above all, unlike thermal burns,
received this treatment.108 In the 1980s, in Western toxic epidermal necrolysis continues to progress
countries, the management of SJS and TEN shifted and becomes more intensified over a period of days.
to specialized burn units and was taken over Therefore, it would make sense to turn to aggressive
disease‑modifying drugs that are capable of halting SUMMARY OF THE INDIAN GUIDELINES AND
disease progression, reduce the extent of skin RECOMMENDATIONS
detachment and decrease inflammatory cytokines,
organ damage and mortality. In addition, many of For the management of Stevens‑Johnson syndrome,
these studies from burn centers had some common SJS/TEN and toxic epidermal necrolysis, the Indian
authors and possibility of an investigator bias cannot Association of Dermatologists, Venereologists and
be excluded.109‑112 Leprologists’s special interest group on cutaneous
adverse drug reactions (SIG‑CADR) recommends:
When should disease‑modifying therapy be started? 1. Immediate withdrawal of all suspected/
The optimum time for starting disease‑modifying offending drug(s) and related compounds (grade
therapy has not been sufficiently scrutinized in the of recommendation B).
medical literature. However, most experts advocate 2. Initiation of supportive therapy as the primary
starting them early and tapering down quickly to measure to be undertaken in all patients
counter the risks involved with immunosuppressive of SJS/TEN presenting to a health‑care
therapy. The benefits of starting such medications professional (grade of recommendation B).
early in the disease include the following: 3. If the rash has been identified at a primary or
a. The progression of immunologic cellular secondary health‑care center, the treatment
damage is prevented should be initialized and thereafter referred to a
tertiary care center for care by a dermatologist.
b. The extent of denudation of skin is limited
4. If resources are available, the treatment
c. Relief of pain, burning, fever and pruritus
may be carried out in an intensive care setting
d. Systemic complications (lung, renal, cardiac,
or in an isolated room with maintenance of
hepatic, nervous and gastrointestinal) due to
sterile field. A multidisciplinary approach
immunologic damage are curtailed
involving dermatologist, physician/pediatrician,
e. Morbidity due to scarring and strictures is
ophthalmologist, respiratory physician,
limited.
intensivist, dietician and any other specialist as
per the need of the case should be adopted.
What if the patient reports late or the diagnosis is
5. Disease‑modifying treatment must be initiated
delayed
as early as possible.
No consensus could be reached on whether systemic
6. Systemic corticosteroids (preferably
immunosuppressives can be used when the drug
parenteral) are recommended as the
reaction has been detected late (more than 7 days
disease‑modifying treatment of choice (grade
duration). Some members were of the view that
of recommendation B). Prednisolone,
immunosuppressive therapy can be life‑saving in such
dexamethasone or methylprednisolone should
situations too, if sufficient monitoring mechanisms,
be given early (preferably within 72 h) in
nursing care requirements and appropriate antibiotic high dosage (1–2 mg/kg/day prednisolone or
coverage can be provided in an advanced care setting. 8–16 mg/day of dexamethasone intravenous
or intramuscular). A daily assessment of
The special interest group on cutaneous adverse drug disease activity (such as the appearance of
reactions (SIG‑CADR) of the IADVL is of the view new lesions, peri‑lesional erythema and skin
that therapy needs to be individualized taking into tenderness) should be done and steroids
consideration the following: should be maintained at the same dose till
• The stage at which the treatment is initiated disease activity ceases. Thereafter, dosage
• Age of the patient should be tapered quickly such that the total
• Extent of necrolysis duration of steroid therapy is around 7–10 days.
• Associated comorbidities Steroids can also be administered in pulse
• Accompanying complications (electrolyte form employing slow intravenous infusion
imbalance, renal or hepatic dysfunction, adult of methylprednisolone (500–1000 mg/day) or
respiratory distress syndrome and sepsis) dexamethasone (100 mg) for 3 days.
• Patient’s ability to afford interventions, drugs 7. Cyclosporine (grade of recommendation B)
and resources available for patient care and the can also be employed alone (3–5 mg/kg/day
physician’s experience with their use. for 10–14 days), especially in patients with
relative contraindications to corticosteroid not overrun the appropriateness of decisions

use (e.g., patients with tuberculosis and severe taken by the treating physician
hyperglycemia). • This document will serve as a guide to assess
8. If both steroids and cyclosporine are used, steroids and treat patients in a wise and informed
can be tapered even more quickly (2–3 days) manner, based on evidence from the current
and cyclosporine (3–5 mg/kg/day) can be medical literature and the experience of several
continued for 7–10 days. physicians across the country.
9. If a patient reports at a stage when the disease
activity has already ceased, there is no need of Acknowledgments
any disease‑modifying treatment. Such patients We appreciate the guidance received from
should be managed by supportive therapy Dr. Venkataram Mysore first as the Therapeutic
alone. Guidelines Committee Chairman 2012 and
10. Monitoring and management of subsequently as the president of IADVL (2015), for his
complications (vital signs, signs of sepsis and personal interest, academic inputs and coordination.
systemic involvement) and sequelae with the We also thank the other members such as Dr. Rajesh
help of a multidisciplinary team of specialists is M. Buddhadev, Dr. Satish Pai, Dr. Vinay Saraf and
important. Dr. Krupashankar of the Therapeutic Guidelines
11. In patients with human immunodeficiency Committee.
virus, children and pregnant women in
the first trimester, low‑dose of intravenous We gratefully acknowledge the chairperson and
immunoglobulin (cumulative dose convener of IADVL Academy Dr. Manas Chatterjee
0.2–0.5 mg/kg) may be considered (grade of and Dr. Ameet Valia, and Hon’ secretary of IADVL
recommendation B), given in the first 24–48 h. Dr. Rashmi Sarkar for entrusting the responsibility of
12. Strict avoidance of offending/suspected/related framing these guidelines to the special interest group
drug(s) is absolutely necessary. A drug card on cutaneous adverse drug reactions.
should be issued to facilitate this.
A large portion of “supportive care” in SJS/TEN
Disclaimer/legal standing of recommendations in the draft has been adopted from the previously
• The “Indian Association of Dermatologists, published guidelines on the management of SJS/TEN
Venereologists and Leprologists‑special interest by IADVL’sTherapeutic Guidelines Committee 2006.
group‑cutaneous adverse drug reactions We sincerely thank all the members of the committee
recommendations” is the consensus view of the including Dr. V. K. Sharma, Dr. H. R. Jerajani, Dr. C. R.
current working group and does not hold the Srinivas, Dr. Ameet Valia and Dr. Sujay Khandpur.
validity of a legal document in a court of law
or stand legal scrutiny. However, this statement We sincerely thank the members of Expert Review
may be admissible as “Recommendations for Committee appointed by IADVL: Dr. C. R. Srinivas,
reasonable standard of care in the management Dr. Murlidhar Rajgopalan, Dr. Sunil Dogra,
of SJS/TEN patients in India.” The members of Dr. V. K. Sharma and Dr. Sandipan Dhar who critically
the group cannot be held responsible for legal reviewed the document and provided their useful
consequences that may arise from following the suggestions.
recommendations mentioned in this document
• Adhering to these recommendations does not Several members including Dr. M. Ramam, Dr. Manas
ensure perfect outcomes or ensure complete Chatterjee, Dr. Suresh Talwar, Dr. Kiran Godse,
cure in all patients. The measures mentioned Dr. Abir Saraswat, Dr. Abhishek De, Dr. Nitin Walia,
are an aid to correctly diagnose, investigate, Dr. Rakesh Bharti, Dr. Manish Pahwa, Dr. Kingshuk
foresee and manage complications and treat Chatterjee, Dr. R. Manjunath, Dr. Vikas Yatagiri,
appropriately Dr. Vinay Kulkarni, Dr. Bela Shah, Dr. Asit Mittal and
• The group realizes that SJS and TEN are rare Dr. A. K. Khare provided their valuable inputs on the
and extremely complex diseases to manage and documents through the IADVL_Acad group and we
treat. The recommendations by this group do immensely thank all of them.
We deeply acknowledge the assistance of clinical features, systemic manifestations, etiology, and
immunopathogenesis. J Am Acad Dermatol 2013;69:173.e1‑13.
Dr. M. Ramam, Dr. Riti Bhatia, Dr. Akhilesh Shukla, 16. Pasricha JS. Management of toxic epidermal necrolysis. Indian
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Appendix 1
Algorithm for management of SJS/TEN
Prompt withdrawal of drug

Initial assessment drug or viral etiology
Airway, breathing, circulation Urine
output Evidence of septicemia Body
SURFACE area involvement and
mucous membrane involvement
Prompt referral if required (inadequate

facilities-lab/ICU/ventilator support,
Inadequately trained staff/physician, lack
Monitoring of 24 h monitoring, Non-availability of
Pulse rate, blood pressure, respiratory rate, expert consultations)
fluid intake and urine output chart, blood
glucose, serum electrolytes, serum
creatinine, blood culture
Specific cultures*D-dimer assay* fibrin
degradation products (FDP)* procalcitonin*
*If facilities are available
*to be used where resources are available
Investigations Specific Therapy

SUPPORTIVE Therapy
• Hemogram • Corticosteroids
• Temperature maintenance
• Liver and renal function tests • Cyclosporine
• Monitoring vital signs
• Urine routine and microscopy • IVIG
• Barrier nursing
• Blood culture
• Start antibiotic if evidence of sepsis
• Skin swab culture
• Fluid and electrolyte balance
• Topical antiseptics and dressing
of denuded skin
• Oral care
• Ophthalmic care
• Respiratory care OTHERS
• Antacids, analgesics • Pentoxifylline
• Anxiolytics and antipyretics • Plasmapheresis
• Anticoagulation Assess SCORTEN • N-acetyl cysteine
• Psychological care • Cyclophosphamide
• Etanercept
Special Situation
• Infliximab
Pregnancy Children
• Avoid steroid in first trimester • Early and short course of IV
• IVIG: Safe and effective steroids HIV
• Cyclosporine: Second line • Low dose IVIG • Low dose IVIG
(0.2–0.5 mg/kg) (0.2–0.5 mg/kg)
• Management of patients of SJS/TEN may preferably be carried out in an intensive care setting with
maintenance of sterile field and with a multidisciplinary approach involving dermatologist, physician/
pediatrician, ophthalmologist, respiratory physician, intensivist, dietician and any other specialist as
per need of the case.

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[Downloaded free from http://www.ijdvl.com on Monday, June 4, 2018, IP: 106.206.46.

Lalit Kumar Gupta, Abhay Mani Martin1, Nidheesh Agarwal2,

Department of Dermatology, ABSTRACT

Key words: Biologicals, corticosteroids, cyclosporine, disease‑modifying therapy, drugs causing

INTRODUCTION both Asian and non‑Asian populations.10 Patients with

next most common triggers of SJS/TEN, particularly

Clinical features Management

Table 3: Differential diagnosis of Stevens–Johnson syndrome/toxic epidermal necrolysis

SCOPE AND VALIDITY OF THESE GUIDELINES “toxic epidermal necrolysis,” “corticosteroids,”

surgeon, chest physician, dietician and any other Preventing infection

Table 6: Components of supportive care in toxic epidermal necrolysis/systemic lupus erythematosus

Advocates of systemic corticosteroids recommend In a recent comparative study between cyclosporine

Table 7: Summary of corticosteroid studies in Stevens-Johnson syndrome/toxic epidermal necrolysis

Table 8: Summary of cyclosporine studies in Stevens-Johnson syndrome/toxic epidermal necrolysis

Table 9: Summary of intravenous immunoglobulin studies in Stevens–Johnson syndrome/toxic epidermal necrolysis

Management Corticosteroids, intravenous immunoglobulin and

relative contraindications to corticosteroid not overrun the appropriateness of decisions

Prompt withdrawal of drug

Prompt referral if required (inadequate

*to be used where resources are available

Investigations Specific Therapy

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