Professional Documents
Culture Documents
Correspondence
Daniel Creamer.
E-mail: daniel.creamer@nhs.net
1.0 Purpose and scope
Accepted for publication
19 January 2016
The overall objective of the guidelines is to provide up-to-
date, evidence-based recommendations for the diagnosis and
Funding sources management of the full spectrum of Stevens–Johnson syn-
None. drome (SJS), toxic epidermal necrolysis (TEN) and SJS–TEN
overlap in adults during the acute phase of the disease.
Conflicts of interest
J.K.G.D. has received grant/research support from Dompe and SiFi. M.R.A.-J. has done The document aims to: (i) offer an appraisal of all relevant
commissioned work for Genus Pharmaceuticals; received sponsorship from AbbVie, Jans- literature up to February 2016, focusing on any key develop-
sen-Cilag, Pfizer, Galderma and Steifel to attend conferences; has performed clinical trials ments; (ii) address important, practical clinical questions relat-
for Zymogenetics, Pfizer, Genentech, Johnson & Johnson, Centocor and Novartis; has
received grant/research support from Emblation; and has developed a nonprofit website, ing to the primary guideline objective, i.e. accurate diagnosis
www.drugrash.co.uk, to assist clinicians in the management of drug allergy. None of and identification of cases and suitable treatment; (iii) provide
the authors has received commercial support from the manufacturers of any medication guideline recommendations; and (iv) discuss areas of uncer-
used in the management of Stevens–Johnson syndrome/toxic epidermal necrolysis.
tainty, potential developments and future directions
D.C., S.A.W., P.D., H.Y.L., J.K.G.D., J.S., C.B.B., M.R.A.-J., K.M.T.W., G.A.E.W.,
SJS/TEN is rare and few healthcare professionals are confi-
M.P., A.V., R.V.M., G.W., M.S., D.B., P.W. and C.H.S. are members of the guideline
development group with technical support provided by L.S.E. and M.F.M.M. dent in the recognition and management of the disorder.
This is a new set of guidelines prepared for the British Association of Dermatologists There is widely divergent practice among different specialities
(BAD) Clinical Standards Unit, which includes the Therapy & Guidelines (T&G) Sub- and healthcare settings, and limited information on outcomes.
committee. Members of the Clinical Standards Unit that have been involved are P.M. These guidelines aim to provide recommendations on the
McHenry (Chairman T&G), J.R. Hughes, M. Griffiths, K. Gibbon, A.J. McDonagh,
D.A. Buckley, I. Nasr, V.J. Swale, C.E. Duarte Williamson, N.J. Levell, T. Leslie, E. diagnosis and management of SJS/TEN, to inform clinical
Mallon, S. Wakelin, S. Ungureanu, P. Hunasehally, M. Cork, K. Towers [British decision-making and, when justified by evidence, to standard-
National Formulary (BNF)], J. Donnelly (BNF), C. Saunders (British Dermatological ize practice. The breadth of this document should be sufficient
Nursing Group), L.S. Exton (BAD Information Scientist), A.G. Brain (BAD Clinical
Standards Administrator) and M.F. Mohd Mustapa (BAD Clinical Standards Manager). to assist clinicians of all relevant specialities in the manage-
ment of patients with SJS/TEN. The recommendations will
DOI 10.1111/bjd.14530
also inform pathways of care to optimize healthcare delivery
Produced in 2016 by the British Association of Dermatologists. NICE and highlight key areas of uncertainty for future research.
has accredited the process used by the British Association of Dermatolo-
gists to produce guidelines. Accreditation is valid for 5 years from May In these guidelines, the term SJS/TEN encompasses the full
2010 and has been extended by agreement to May 2016. More informa-
tion on accreditation, and full details of our accreditation, can be viewed spectrum of the disease, i.e. SJS, TEN and SJS–TEN overlap
at www.nice.org.uk/accreditation.
(see section 7.2 for clinical definition of the separate entities).
The guideline is presented as a detailed review with
1194 British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1195
highlighted recommendations for practical use (see section specific targeted searches for hypersensitivity testing, causative
18.0), in addition to the development of a new patient infor- drugs, diagnostic and prognostic indicators, topical treatments,
mation leaflet [available on the British Association of Derma- oral/mouth, growth factors and granulocyte colony-stimulat-
tologists’ (BAD) website, www.bad.org.uk]. Unless otherwise ing factor (G-CSF), and analgesia. The lead authors screened
specified, recommendations apply to all forms of the disease. the identified titles, and those relevant for first-round inclu-
sion were selected for further scrutiny. All co-authors then
reviewed the abstracts for the shortlisted references and the
1.1 Exclusions
full papers of relevant material were obtained; disagreements
This guideline does not cover paediatric patients. An adden- in the final selections were resolved by discussion with the
dum to this guideline addressing the needs of paediatric entire GDG. In section 13.0, active interventions were assessed
patients with SJS/TEN is planned. The evidence for treatment only if studies recruited at least eight patients with SJS/TEN
of children differs from that of adult patients, and will be into the treatment group. The structure of the guidelines was
considered separately. then discussed, with headings and subheadings decided; dif-
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1196 Guidelines for SJS/TEN 2016, D. Creamer et al.
soluble factors induce keratinocyte apoptosis.10 Proapoptotic SJS/TEN, 97% developed erosive mucous membrane lesions;
molecules, including tumour necrosis factor (TNF)-a, inter- oral involvement was observed in 93% of patients, ocular in
feron (IFN)-c and inducible nitric oxide synthase, may link 78%, genital in 63% and all three sites in 66%.15 Respiratory
drug-induced immune responses to keratinocyte damage.11 tract epithelial necrolysis can occur, resulting in bronchial
Although soluble Fas ligand, perforin and granzyme have all obstruction and ventilatory compromise; necrolysis of gas-
been implicated in triggering keratinocyte programmed cell trointestinal epithelium leads to profuse diarrhoea. Owing to
death,12,13 current evidence favours granulysin as the key hypoperfusion and acute tubular necrosis, acute kidney injury
mediator of apoptosis in SJS/TEN.14 A study by Chung et al. may occur in the early phase of SJS/TEN. Mild elevation of
demonstrated the presence of high concentrations of secretory liver enzymes is common, but significant hepatic impairment
15-kDa granulysin in TEN blister fluid, while injection of 15- is rare.
kDa granulysin into mouse skin induces keratinocyte apopto- Despite the striking clinical presentation of SJS/TEN, a num-
sis, mimicking SJS/TEN.14 ber of disorders can present with blistering of the skin and
mucous membranes; the clinical differential diagnosis includes
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1197
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1198 Guidelines for SJS/TEN 2016, D. Creamer et al.
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Guidelines for SJS/TEN 2016, D. Creamer et al. 1199
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1200 Guidelines for SJS/TEN 2016, D. Creamer et al.
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Guidelines for SJS/TEN 2016, D. Creamer et al. 1201
causing significant dysuria or retention. A urinary catheter will symptoms. Use multiple sources [including patient, relatives,
also permit accurate output monitoring to assist fluid replace- general practitioner (GP), pharmacist] to obtain a full drug his-
ment. tory.
Delineate a timeline for each drug, identifying the date
the drug was commenced and, when appropriate, discontin-
7.5 Is there a clinical method of determining drug
ued. Tools to facilitate timeline analysis include web-based
causality in Stevens–Johnson syndrome/toxic epidermal
freeware such as www.drugrash.co.uk. A latent period
necrolysis?
between the initial drug intake and onset of SJS/TEN always
SJS/TEN is primarily a drug-induced phenomenon, with a cul- occurs; 5–28 days following drug initiation is the most
prit drug being demonstrated in approximately 85% of likely period, unless there is a history of a previous reaction
cases.21 Identification of the causative agent may be straight- to the same drug, in which case the latency may be
forward in cases where a single drug is implicated, but diffi- shorter.
culties are posed by a patient who has been exposed to Estimate the probability that the drug was present in the
NSAIDs, nonsteroidal anti-inflammatory drugs. SCORTEN should be calculated in all patients with SJS/TEN
within the first 24 h of admission.
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1202 Guidelines for SJS/TEN 2016, D. Creamer et al.
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1203
use of an appropriate dressing on exposed dermis will reduce prophylactic systemic antibiotics may increase skin coloniza-
fluid and protein loss, limit microbial colonization and help tion, particularly with Candida albicans; therefore, antimicrobial
pain control. Covering the denuded skin may also accelerate therapy should only be instituted if there are clinical signs of
re-epithelialization. Once active blistering and epidermal infection.7 The SJS/TEN disease process may be accompanied
detachment ceases, re-epithelialization commences. Healing by a fever, which complicates detection of secondary sepsis;
may occur within a few days or may be protracted and take a therefore, patients should be monitored carefully for other
number of weeks to attain completion. signs of systemic infection such as confusion, hypotension,
A surgical approach involves debridement of detached epi- reduced urine output and reduced oxygen saturation.48 Cuta-
dermis to remove potentially infected material followed by neous infection may be accompanied by an increase in skin
physiological wound closure using biosynthetic dressings, pain. The detection of sepsis may also be indicated by a rise
xenograft or allograft.40,47 This more aggressive approach can in C-reactive protein and neutrophilia. If a monoculture of
be considered following failure of conservative management, organisms is detected on culture of swabs taken from multi-
characterized by clinical deterioration, extension of epidermal ple sites, which had previously showed mixed growth, this
detachment, local sepsis/subepidermal pus, delayed healing sign indicates that one particular strain of organism is
and wound conversion (the spontaneous progression of super- becoming predominant and increases the likelihood of inva-
ficial skin loss into a deeper cutaneous defect). sive infection.48 Consider activation of HSV in eroded or
Denuded dermis in SJS/TEN exudes serum and becomes vesicular areas that are slow to heal, particularly in genital
coated with necrotic debris. The exposed dermis and haem- and oral sites.
orrhagic crust act as a substrate for microbial colonization,
initially by Staphylococcus aureus and later by Gram-negative rods
8.2.1 Recommendations [strength of recommendation D
from the digestive flora, especially Pseudomonas aeruginosa.7 Cuta-
(good practice point); level of evidence 4]
neous infection will impair re-epithelialization and may lead
to systemic sepsis, which is the most common cause of The following general principles are applicable to all
death in SJS/TEN. Indiscriminate administration of patients with SJS/TEN and in all settings: (i) employ strict
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1204 Guidelines for SJS/TEN 2016, D. Creamer et al.
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1205
peptic ulceration and limit translocation of gut bacteria. As be introduced, supplemented if required with oral opiate-
buccal mucositis in SJS/TEN often precludes normal oral based therapy such as codeine, or a synthetic opiate such as
intake, nasogastric feeding with a silicone tube should be tramadol. Nonsteroidal anti-inflammatory drugs should be
instituted when necessary. General principles of intensive care avoided because of the potential for renal and gastric injury.
nutrition are applicable and these are summarized in The If the pain score equates to moderate or severe pain then
European Society for Clinical Nutrition and Metabolism guide- prescribe regular opiate-based analgesia (e.g. morphine or fen-
lines.42,54 tanyl) delivered enterally, or by PCA, or via infusion. IV opi-
ates may be safely delivered in dedicated skin failure burn
centres or ICUs, with appropriate nursing levels. In patients
8.4.1 Recommendations (strength of recommendation C;
needing opiate-based analgesia, pain should be re-evaluated
level of evidence 3)
using the pain score on a 4-hourly basis and prior to any
Provide continuous enteral nutrition throughout the acute interventions. Involve the hospital acute pain team early.
phase of SJS/TEN, either by the oral route or via nasogastric Procedures such as dressing changes and bathing may
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1206 Guidelines for SJS/TEN 2016, D. Creamer et al.
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1207
at an unspecified time after the acute episode, were signifi- and should be used with caution in the presence of a corneal
cantly better in the group receiving topical corticosteroid com- epithelial defect.
pared with the lubricant group.66 Nonpreserved (as opposed to preserved) topical eye drops
are recommended; these are available in the U.K. for all the
preparations mentioned above.
9.1.1 Recommendations [strength of recommendation D
(good practice point); level of evidence 4]
9.2 Is systemic therapy effective in treating ocular
The eyes should be examined by an ophthalmologist as a part
involvement in Stevens–Johnson syndrome/toxic
of the initial assessment of a patient with SJS/TEN. Thereafter,
epidermal necrolysis?
daily ophthalmological review is necessary during the acute
illness. A direct ophthalmoscope to provide illumination, mag- Two studies have attempted to assess the efficacy of systemic
nification and a cobalt blue light source for fluorescein exami- therapy on ocular outcomes in SJS/TEN. A study by Araki et al.
nation is useful. Two-hourly application of a lubricant (e.g. reported five patients with acute ocular SJS/TEN receiving
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1208 Guidelines for SJS/TEN 2016, D. Creamer et al.
membrane transplantation (AMT) during the acute phase of symblepharon ring, and performed at the bedside is a new,
SJS/TEN.69–76 The suggested benefits of AMT include reduced promising, low-risk technique for delivering this therapy.
inflammation, enhanced re-epithelialization, reduction of scar-
ring and less symblepharon formation.69–72 One case report of
10.0 Treatment of mouth involvement in
bilateral AMT suggests that early AMT may provide better out-
Stevens–Johnson syndrome/toxic epidermal
comes than later application.77 Cryopreserved amniotic mem-
necrolysis
brane (obtained from the National Health Service Blood and
Transplant Tissue Services, Liverpool, U.K.) is now available in Oral involvement in SJS/TEN is characterized by painful
a large (5 9 5 cm) size, as well as smaller sizes. The large mucosal erythema with subsequent blistering and ulceration.
size is ideal for lining the entire ocular surface. AMT may be Similar involvement of the vermillion of the lips progresses to
sutured onto the ocular surface, usually under general anaes- haemorrhagic sloughing with the development of dark adher-
thetic or deep sedation. The technique is described both by ent crusts. The tongue and palate are frequently affected,
Muqit et al. (using a procedure also favoured by the authors, while in severe cases, mucosal involvement may extend to the
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Guidelines for SJS/TEN 2016, D. Creamer et al. 1209
a topical anaesthetic preparation, e.g. viscous lidocaine 2%, resolved, ultimately healing with scarring.85,86 In the long
15 mL per application, may be used as an alternative. Cocaine term, serious morbidity can ensue in the form of strictures
mouthwashes 2%–5% can be used for severe oral discomfort and stenosis of the urethra, phimosis in males and vaginal
three times daily. synechiae in females, with resultant urinary and sexual dys-
Use an antiseptic oral rinse twice daily to reduce bacterial function.87
colonization of the mucosa. Agents available include 1.5%
hydrogen peroxide mouthwash (e.g. Peroxylâ mouthwash,
11.1 Is topical therapy effective in treating urogenital
10 mL twice daily; Colgate, New York, NY, U.S.A.) or 0.2%
involvement in Stevens–Johnson syndrome/toxic
chlorhexidine digluconate mouthwash (e.g. Corsodylâ mouth-
epidermal necrolysis?
wash, 10 mL twice daily; GSK, Brentford, U.K.). Diluting
0.2% chlorhexidine mouthwash by up to 50% will reduce the Local measures for treating urogenital involvement in acute
soreness that can accompany this treatment. SJS/TEN are supportive and empirical. Along with regular
Oral and lip swabs should be taken regularly if bacterial or examination of the urogenital tract, attention should be given
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1210 Guidelines for SJS/TEN 2016, D. Creamer et al.
A single-centre, prospective study characterized airway trial has been conducted in TEN: the anti-TNF agent thalido-
involvement in SJS/TEN into three groups based on whether mide was compared with placebo; however, the study was
hypoxaemia and respiratory symptoms were present, and the discontinued prematurely because of an excess of deaths in
time course of the development of hypoxaemia.90 Patients the thalidomide treatment group.92
without hypoxaemia during the acute phase (group 1) suf- The immunological basis for SJS/TEN has led physicians to
fered no pulmonary complications or sequelae, and had low prescribe immunomodulating drugs, several of which have
mortality.90 One-quarter of patients presented with early pul- been studied in uncontrolled series. In this guideline, active
monary manifestations (group 2) characterized by dyspnoea interventions were assessed if studies recruited at least eight
and an increased respiratory rate – chest radiographs were typ- patients with SJS/TEN into the treatment group. Of all active
ically normal on admission, with later diffuse pulmonary infil- interventions (excluding thalidomide) only three drugs ful-
trates.90 Bronchial hypersecretion occurred in 70% of these filled the inclusion criteria: IVIg, systemic corticosteroid and
patients, and fibreoptic bronchoscopy revealed a pattern of ciclosporin.
diffuse loss of bronchial epithelium in the proximal airways,
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Table 7 Summary of intravenous immunoglobulin (IVIg) studies in Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)
Campione et al. Single Retrospective case TEN (10) 2 g kg 1 given over 1/10 (10%) SCORTEN-predicted Effective 3
(2003)97 dermatology unit series with 5 days mortality 3.5/10
SCORTEN-predicted (35%)
mortality as
comparator
Prins et al. Multiple centres Retrospective; case Overlap Mean 0.7 g kg 1 6/48 (12%) NA Effective 3 Duplicated cases
(2003)95 series SJS/TEN (7) daily for 4 days from Viard et al.
(including TEN (41) (1998),12 Campione
previously et al. (2003)97 and
reported cases, from Trent et al. (2003)94
three
other studies);
noncontrolled
Trent et al. Single Retrospective case SJS–TEN 1 g kg 1 daily for 1/16 (6%) SCORTEN-predicted Effective 3
(2003)94 dermatology unit series with overlap (6) 4 days (n = 15); mortality 5.81/16
SCORTEN-predicted TEN (10) 0.4 g kg 1 daily for (36%)
mortality as 4 days (n = 1)
comparator
1
Al-Mutairi et al. Single Retrospective, TEN (12) 0.5–1.0 g kg for 0/11 (0%) NA Effective 3
(2004)98 dermatology unit noncontrolled 4–5 days
(continued)
1
Gravante et al. Burns unit Retrospective; case SJS (1) 0.4 g kg daily for 7/17 (41%) No comparator group Effective 3
(2007)102 series TEN (16) 5 days or SCORTEN-
predicted mortality
given
Stella et al. Burns unit Retrospective case– IVIg group: 0.7 g kg 1 daily for 6/23 (26%) SCORTEN-predicted Effective 3 This series included
(2007)46 control SJS (2); 4 days + mortality 8.2/23 nine cases published
series; control SJS/TEN methylprednisolone (36%) in Stella et al.
group – supportive overlap 250 mg daily for (2001).93 Control
care only (16); TEN (5) 2 days group TBSA
involvement
significantly lower
in IVIg group
compared with
controls
Control
group:
TEN (8)
(continued)
Aihara et al. Multiple Prospective; case SJS (5) 400 mg kg 1 daily 0/8 (0%); 7/8 None Effective 3 Co-treatment of all
(2015)105 dermatology series; TEN (3) IVIg for 5 patients classed patients with
centres no comparator consecutive days in as ‘responders’ corticosteroid –
group conjunction with according to a variable dosing.
systemic severity-of-illness Only 8/41 cases
corticosteroid score designed included in the final
therapy (variable by the authors report – reporting
dose) bias
NA, not applicable; HDU, high-dependency unit; TBSA, total body surface area. aSee Appendix 1.
meta-analysis by Huang et al.,106 a further study by Firoz et al., This group was compared with six historical SJS/TEN con-
which included 23 patients with TEN treated with IVIg, trols treated with systemic corticosteroids.115 There was a
demonstrated no improved survival in patients receiving IVIg significantly enhanced speed of epithelialization and reduced
vs. supportive care alone.103 In 2013, Lee et al. published a length of hospital stay in the ciclosporin group.115 Compar-
retrospective analysis of 64 patients with SJS–TEN overlap or ison of SCORTEN-predicted mortality demonstrated a benefit
TEN treated with IVIg at a single specialized referral centre in of ciclosporin over corticosteroids.115 Kirchhof et al. pub-
Singapore.104 The mortality in their patients, when compared lished a retrospective review from a single centre of 64
with predicted outcome from SCORTEN, showed no benefit patients with SJS/TEN receiving either ciclosporin or IVIg
from IVIg.104 In addition, when stratified according to dosage, (doses of each varied).116 Analysis of predicted SCORTEN
there was no mortality difference between patients who mortality compared with actual mortality indicated a relative
received high-dose (> 3 g kg 1) vs. low-dose (< 3 g kg 1) mortality benefit for the use of ciclosporin [standardized
IVIg.104 mortality ratio (SMR) 0.43] vs. IVIg (SMR 1.43).116 Data
from the ciclosporin studies are summarized in Table 9.
British Journal of Dermatology (2016) 174, pp1194–1227 © 2016 British Association of Dermatologists
Table 8 Summary of corticosteroid studies in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
Reported Level of
Study Setting Design Patients (n) Intervention Outcome: mortality Comparator benefit evidencea Additional notes
Murphy Single burn Retrospective; TEN (12) Highly variable doses 8/12 NA No comment 3 Timing, duration
et al. centre case series; received, no details about made by and dose of
(1997)111 noncontrolled specific dosing authors corticosteroid
therapy highly
variable
Schulz Single burn Retrospective; TEN (34) No details about 13/34 NA Ineffective 3 No evidence of
et al. centre case series; corticosteroid dosing case validation;
(continued)
Reported Level of
Study Setting Design Patients (n) Intervention Outcome: mortality Comparator benefit evidencea Additional notes
Kardaun and Single Retrospective; SJS (1) First four patients: IV 1/12 SCORTEN- Effective 3 Case validation
Jonkman dermatology case series; SJS–TEN dexamethasome 100 mg predicted unclear. Change
(2007)107 centre noncontrolled overlap (4) once daily for 3 days + mortality: 4/12 of treatment
TEN (7) 500 mg protocol during
cyclophosphamide. series
Subsequent patients:
1.5 mg kg–1 IV
dexamethasone for 3 days
Schneck Multiple Retrospective; SJS (57) Maximum steroid dose 21/119 Mortality Ineffective (on 2 Robust case
et al. centres in case series; SJS–TEN 250 mg prednisolone expressed as multivariate validation.
(2008)28 Germany and noncontrolled overlap (44) equivalent (IQR 100– OR: corticosteroids analysis) Steroid group
France TEN (18) 500 mg). Given for compared with had less severe
1216 Guidelines for SJS/TEN 2016, D. Creamer et al.
Yang et al. Single Retrospective; SJS (10) and 1–1.5 mg kg 1 daily 10/45 (10 TEN) SCORTEN- Corticosteroid 2 Case validation
(2009)109 dermatology case series; TEN (35) in methylprednisolone or in corticosteroid predicted alone ineffective, unclear.
centre noncontrolled corticosteroid equivalent (details not group; 3/20 mortality 8.63 in IVIg/corticosteroid Insufficient
arm (n = 45) given); IVIg 0.4 g kg 1 (two TEN and corticosteroid may confer benefit detail on
SJS (8) and day for 5 days one SJS) in IVIg/ group; 3.51 in IVIg/ (nonsignificant corticosteroid
TEN (12) corticosteroid group corticosteroid difference) dosing
in IVIg/ group
corticosteroid
arm (n = 20)
(continued)
Results suggesting
Patients in IVIg/
varied according
of corticosteroid
Subsequent doses
Additional notes
reach statistical
benefit did not
involvement at
teroids or ciclosporin in the context of SJS/TEN. The GDG
corticosteroid
higher TBSA
significance.
to response
group had
considers that, ideally, such interventions should be practised
NA, not applicable; BSA, body surface area; IV, intravenous; IQR, interquartile range; OR, odds ratio; CI, confidence interval; IVIg, intravenous immunoglobulin; TBSA, total BSA. aSee Appendix 1.
baseline
under the supervision of a specialist skin failure MDT in the
context of a clinical study or a case registry.
evidencea
Level of
3
As the patient recovers from the mucocutaneous and systemic
manifestations of acute SJS/TEN, preparations can be made for
discharge. Before leaving the hospital, information on the cul-
prit drug should be relayed to the patient. The drug allergy
Reported
Effective
SCORTEN-predicted
corticosteroid group
TEN and specify the patient’s follow-up plan (see Appendix 2).
NICE guidance suggests that severe nonimmediate cutaneous
reactions are referred to a specialist drug allergy service for
expert review, which in the context of SJS/TEN is likely to be
0/8
corticosteroid
TEN (15) in
overlap (2)
SJS (9) and
SJS (43) and
TEN (15)
only arm
(n = 58)
(n = 24)
TEN (3)
in IVIg/
SJS–TEN
SJS (3)
noncontrolled
Retrospective;
Retrospective;
case series;
case series;
dermatology
centre
Setting
Single
Table 8 (continued)
drug(s).
At discharge, refer the patient to local social services, when
(2010)110
(2013)112
et al.
Study
Chen
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
Table 9 Summary of ciclosporin (CsA) studies in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
Singh et al. Dermatology Case–control study SJS (5) CsA 3 mg kg 1 daily 0/11 SCORTEN-predicted Yes 3 No evidence of case
(2013)115 unit (historical controls) SJS–TEN for 7 days, and mortality in control validation
overlap (3) tapered for 7 days group treated with
TEN (3) corticosteroid
Kirchhof et al. Dermatology Retrospective series: SJS–TEN Various doses of CsA CsA SMR CsA-treated group Yes 3 No evidence of case
(2014)116 unit CsA vs. IVIg overlap (64) and IVIg 0.43; IVIg compared with validation. No control
SMR 1.43 IVIg-treated group group
BSA, body surface area; ICU, intensive care unit; IVIg, intravenous immunoglobulin; SMR, standardized mortality ratio. aSee Appendix 1.
Encourage the patient to wear a MedicAlert bracelet or amu- this series patch testing showed positive reactions in 0%
let bearing the name of the culprit drug. (n = 0/5) of cases of carbamazepine-induced SJS/TEN.126
The drug allergy should be documented in the patient’s
notes. All doctors involved in the patient’s care, especially the
15.2 What is the evidence that in vitro tests can identify
GP, should be informed about the drug allergy episode and
a culprit drug in Stevens–Johnson syndrome/toxic
the culprit.
epidermal necrolysis?
Warn the patient to avoid OTC medications where precise
constituents are unclear. The method of isolation of peripheral blood mononuclear cells
Report episodes of drug-induced SJS/TEN to the national (PBMC) followed by in vitro challenge with the putative causal
pharmacovigilance authorities (the MHRA’s Yellow Card drug has been widely studied in the context of drug hypersen-
Scheme in the U.K., www.yellowcard.mhra.gov.uk). sitivity testing. Although these assays involve the culture of
If the patient had eye involvement during the acute phase, PBMC with the drug in question, it is generally accepted that
organize an outpatient clinic appointment with an ophthal- the responding cells are T lymphocytes.
© 2016 British Association of Dermatologists British Journal of Dermatology (2016) 174, pp1194–1227
1220 Guidelines for SJS/TEN 2016, D. Creamer et al.
Table 10 Summary
Initial assessment Take a detailed history from the patient and/or relatives
on presentation Perform a full physical examination, including baseline body weight, and record the vital signs, including oxygen
saturation
Order a set of investigations: FBC, U&E, LFT, glucose, magnesium, phosphate, bicarbonate, mycoplasma serology,
CXR, skin biopsy
Initiate a primary management plan: (i) establish peripheral venous access; (ii) if patient cannot maintain adequate
nutrition orally, insert a nasogastric tube and institute nasogastric feeding; (iii) insert a urinary catheter if
urogenital involvement is causing significant dysuria/retention
Strength of recommendation D (GPP)
Determination of Identify causative agent and withdraw immediately
drug causality Strength of recommendation D
Prognostic scoring Calculate SCORTEN within the first 24 h
Strength of recommendation C
(continued)
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Table 10 (continued)
Strength of recommendation C
Analgesia Use a patient-appropriate validated pain tool to assess pain in all conscious patients at least once daily
Patients should receive adequate analgesia to ensure comfort at rest, with the addition of supplementary opiates,
as required
Additional analgesia may be needed to address increased pain associated with patient handling, repositioning and
dressing changes
Strength of recommendation D (GPP)
Supportive Immobile patients should receive low molecular weight heparin
therapeutic Patients in whom enteral nutrition cannot be established should receive a proton pump inhibitor to reduce the risk
measures of stress-related gastrointestinal ulceration
Neutropenic patients may benefit from recombinant human G-CSF
Strength of recommendation C
Treatment of eye Daily ophthalmological review is necessary during the acute illness
FBC, full blood count; U&E, urea and electrolytes; LFT, liver function tests; CXR, chest X-ray; GPP, good practice point; BSA, body surface
area; ICU, intensive care unit; SJS/TEN, Stevens–Johnson syndrome/toxic epidermal necrolyis; MDT, multidisciplinary team; IV, intravenous;
G-CSF, granulocyte colony-stimulating factor.
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