Research

Original Investigation

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Ear, Nose, and Throat Description at Acute Stage
and After Remission
Emilie Bequignon, MD; Tu Anh Duong, MD; Emilie Sbidian, MD, PhD; Laurence Valeyrie-Allanore, MD;
Saskia Ingen-Housz-Oro, MD; Veronique Chatelin, MD; Andr Coste, MD, PhD; Pierre Wolkenstein, MD, PhD;
Olivier Chosidow, MD, PhD; Jean Franois Papon, MD, PhD

IMPORTANCE Ear, nose, and throat (ENT) lesions are frequently involved in Stevens-Johnson

Video at
jamadermatology.com

syndrome and toxic epidermal necrolysis (SJS/TEN), although a detailed description is lacking
in the literature.
OBJECTIVES To describe ENT lesions at the acute stage and follow-up in a large series of
patients with SJS/TEN and identify factors associated with the severe ENT form.
DESIGN, SETTING, AND PARTICIPANTS Retrospective study of 49 patients with SJS/TEN
hospitalized in a referral care center from 2005 to 2010. Patients who underwent a full ENT
workup including examination and a nasal fiberoptic endoscopy by an otorhinolaryngologist
in the acute phase and during follow-up at 2 and 12 months were included in the study.
MAIN OUTCOMES AND MEASURES Recorded variables included maximal body surface area
(BSA) detachment, SCORTEN (Score of Toxic Epidermal Necrosis [a severity of illness score]),
sites and type of ENT mucosal lesions, intensive care unit transfer, pulmonary infection, and
mortality. Severe ENT form was defined by the occurrence of laryngeal lesions with the risk
of airways obstruction. Clinical characteristics associated with severe ENT form were
analyzed in univariate and multivariable analysis.
RESULTS Of the 49 patients who underwent a full ENT workup (female to male ratio, 1.1:1),
ENT symptoms (eg, odynophagia, dysphagia, dysphonia, dyspnea, earache, nasal
obstruction) occurred in 48 (98%). Dyspnea or dysphonia were significantly associated with
severe ENT form (21% [P = .03] and 50% [P<.001], respectively). Topographic frequencies of
lesions were as followed: lips and oral cavity (n = 46 [93%]) and pharynx and vestibule of the
nose (n = 26 [53%]). Fourteen patients (29%) had severe ENT form. Findings for other
recorded variables for those with vs without ENT examination are as follows: maximal BSA
detachment (20% [0%-95%] vs 5.5% [0%-95%]; P = .004), SCORTEN (1 [0-5] vs 1 [0-5];
P = .54), intensive care unit transfer (10 [20%] vs 9 [19%]; P = .80), pulmonary infection
(9 [18%] vs 6 [13%]; P = .10), and mortality (3 [6%] vs 5 [10%]; P = .70). In multivariable
analysis, pulmonary infection was significantly associated with severe ENT form (odds ratio,
5.9 [95% CI, 1.1-32.8] [P = .04]). After remission of SJS/TEN, a complete ENT mucosal healing
occurred in 36 patients (74%) at 2 months and in nearly all patients (n = 48 [98%]) at 1 year
of follow-up.
CONCLUSIONS AND RELEVANCE Severe ENT form is associated with pulmonary infection and
is easily detected by nasal fiberoptic endoscopy. ENT evaluation should be suggested when
dysphonia or dyspnea is observed at the acute stage of SJS/TEN.
Author Affiliations: Author
affiliations are listed at the end of this
article.

JAMA Dermatol. 2015;151(3):302-307. doi:10.1001/jamadermatol.2014.4844

Published online February 11, 2015.
302

Corresponding Author: Tu Anh

Duong, MD, Department of
Dermatology, Hpitaux Universitaires
Henri-Mondor, AP-HP, 51, Avenue du
Marechal de Lattre de Tassigny,
94010 Creteil CEDEX, France
(tu-anh.duong@hmn.aphp.fr).
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Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

tevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening severe cutaneous adverse reactions, with associated blistering, detachment of large epidermal sheets, and the involvement of at least
2 mucous membranes (eg, ocular, nasal, oral, genital, anal).1
Their annual incidence is estimated to be 1 to 2 persons per 1
million, and mortality at the acute stage reaches up to 22% (10%
for SJS to 39% for TEN).2 The onset of SJS/TEN occurs 4 to 28
days after drug exposure, and no causative drug is yet identified in 30% of the patients.3 General symptoms such as influenza-like syndrome and fever, ocular pain, and ear, nose, and
throat (ENT) pain often precede skin lesions.4,5 Mucous membrane lesions (ie, erythema, blisters, and/or erosions) precede skin detachment in 80% of the patients.5 Oral mucosa and
ENT are frequently involved in small series in the literature.6
The aim of this study was to precisely describe ENT symptoms and lesions in a large series of patients with SJS/TEN.

Methods

Original Investigation Research

follow-up at 2 and 12 months. The ENT workup included the

following at each consultation: ENT clinical data collection;
examination of the oral cavity and ears; and a nasal fiberoptic endoscopy to evaluate nasal cavities and pharyngolarynx. Data were retrospectively collected and analyzed by 1
investigator (E.B.). The clinical ENT data recorded included
symptoms (ie, odynophagia, dysphagia, dyspnea, dysphonia, nasal obstruction, epistaxis, earache, conductive deafness, otorrhea) initial type of lesions (ie, enanthema, erosions, ulcerations, edema, scabs, pseudomembranes),
topography of mucosal involvement (ie, oral cavity, pharynx, larynx, external ear, nose), and natural course of
lesions.

Classification of Patients
Considering the prior literature about SJS/TEN, otolaryngologic manifestation, and the potential risk of upper airway obstruction, supraglottic and laryngeal lesions were considered
to define a severe ENT form.9 Patients were subgrouped as
with severe ENT form or without severe ENT form.

Population

Statistical Analysis

This retrospective study was approved by the CPP Paris IX local

ethics committee. The study population included 49 patients
with SJS/TEN who had a full ENT workup (ie, examination and
nasal fiberoptic endoscopy by an otorhinolaryngologist). These
patients were consecutively admitted in a national referral center from January 2005 to January 2010. The diagnosis of SJS/TEN
was established according to the European Registry of Severe Cutaneous Reactions (RegisSCAR) criterion7 and confirmed by a skin
biopsy result showing epidermal necrosis with a negative finding for immunoglobulin deposit along the dermoepidermal junction on direct immunofluorescence.
During this period, the characteristics of all patients admitted in the referral center were collected. Only patients who
underwent ENT examination under routine care in the acute
phase and during follow-up at 2 and 12 months were retrospectively considered.

Quantitative variables were expressed as mean (SD) or median (range) when appropriate and qualitative variables as number (percentage). All tests were 2 tailed, and P < .05 was considered statistically significant. The characteristics of the
patients who were not included (without a standardized ENT
physician examination) were compared with those included
in the study sample. Table 1 gives the characteristics of the
study population. Then, the characteristics of patients with and
without severe ENT form were compared in univariate analyses. Odds ratios (ORs) were estimated with their 95% CIs using
logistic regression models. Potential interactions were assessed by pairwise analyses, and confounding by fitting multiplicative models. Variables yielding P values smaller than 0.15
in the univariate analyses were entered into a multiple logistic regression model. The final model included the variables
independently associated with severe ENT form. We conducted all statistical analysis using STATA Statistical Software (version 11.0, StataCorp LP).

Data Collection
Patients were classified as having SJS, TEN, or overlap syndrome according to their maximal body surface area (BSA) detachment (ie, SJS, <10%; TEN, 30%; and overlap syndrome,
10%-29%). For each patient the following variables were recorded: demographic data (age and sex), delay between disease onset and admission, duration of hospital stay, causative drug, associated immunosuppression factors (eg, cancer,
human immunodeficiency virus seropositivity), initial and
maximal BSA detachment, SCORTEN (Score of Toxic Epidermal Necrosis [a prognosis score including 7 independent clinical and biological variables]) at the day of admission,8 pulmonary infection, intensive care unit (ICU) transfer, tracheal
intubation, and death. When assessed by bronchoscopy, bronchial detachment was described.

Standardized ENT Evaluation

The ENT workup was performed by 3 senior investigators
(V.C., A.C., and J.F.P.) in the acute phase and during
jamadermatology.com

Results
Study Population
During the study period, 49 of the 97 patients in the SJS/TEN
cohort who were admitted consecutively in our department underwent a complete ENT workup (ie, examination and nasal fiberoptic endoscopy) and were considered the study population. The mean (SD) delay between disease onset and admission
was 5 (3.8) (range, 1-20) days. The mean (SD) length of hospital
stay was 21.5 (12.5) (range, 2-62) days. Causative drugs were identified in 41 patients (84%) and listed in Table 2. The initial onset presentation of SJS/TEN was cutaneous exanthema in 22 patients (45%), exclusively mucosal in 13 patients (26%), and
concomitant cutaneous and mucosal in 14 patients (29%). The
mean (SD) time interval between cutaneous and mucosal exanthema was 1.8 (3.0) (range, 0-18) days. ENT examination was
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Research Original Investigation

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Table 1. Demographic Data of 49 Patients With SJS/TEN

Patients
With ENT Examination
(n = 49)
Variable

No. (%)

Age

Without ENT Examination

(n = 48)

Median (Range)

No. (%)

37 (17-89)

.86
.51

26 (53)

NA

22 (46)

NA

Immunosuppression factor

15 (30)

NA

15 (31)

NA

4 (8)

NA

10 (21)

NA

14 (7)

NA

6 (3)

NA

8 (4)

NA

10 (5)

NA

BSA detachment, %

NA

20 (0-95)

NA

5.5 (0-95)

.004

SCORTEN

NA

1 (0-5)

NA

1 (0-5)

.54

HIV
Renal insufficiency

Pulmonary Infection
ICU transfer

.80

9 (18)

NA

6 (13)

NA

.10

10 (20)

NA

9 (19)

NA

.80
<.001

Tracheal intubation

8 (16)

NA

3 (6)

NA

Death

3 (6)

NA

5 (10)

NA

.70

38 (78)

NA

22 (46)

NA

<.001

Treatment with cyclosporin

Table 2. Causal Drug Identified in 41 Patientsa

Drugs

Abbreviations: BSA, maximal body

surface area; ENT, ear, nose, and
throat; HIV, human
immunodeficiency virus;
ICU, intensive care unit; NA, not
applicable; SCORTEN, Score of Toxic
Epidermal Necrosis;
SJS/TEN, Stevens-Johnson syndrome
and toxic epidermal necrolysis.

Table 3. ENT Symptoms in 49 Patients With SJS/TEN

Patients,
No. (%)

ENT Clinical Symptoms

Patients,
No. (%)

Allopurinol

7 (17)

Odynophagia

48 (98)

Amifostine

2 (5)

Dysphagia

45 (92)

Antibacterial sulfonamides

4 (10)

Dyspnea

Others antibiotics

5 (12)

Dysphonia

Carbamazepine

1 (2)

Nasal obstruction

Lamotrigine

3 (7)

Epistaxis

4 (8)

Nevirapine

3 (7)

Ear ache

16 (32)

2 (5)

Conductive deafness

Piroxicam
Others

14 (34)

Drug causality assessment was determined using the 6 ALDEN (Algorithm of

Drug Causality for Epidermal Necrolysis) scoring criteria, which included the
following: time to toxic epidermal necrolysis onset; drug present in the body at
the time of the reaction onset; drug prechallenge or rechallenge; dechallenge,
drug discontinued, or continued without harm; drug role, known for causality;
other causes possible.

performed with a mean (SD) delay of 6 (7.5) (range, 0-34) days

after admission and 9 (9.8) (range, 1-50) days after disease onset. Because of secondary transfer of patients to our referral care
center, there was a delayed ENT examination for 8 patients.
Death was reported for 3 patients (6%) during hospital stay (cardiogenic shock, septic shock, and renal failure). Because of an
open ongoing clinical trial, 38 patients (78%) were treated with
cyclosporin during this period.10 The characteristics of patients with a full ENT workup were compared with those of patients with SJS/TEN without ENT workup (Table 1). Patients with
SJS/TEN and a full ENT workup did not significantly differ from
the cohort without an ENT workup for age, sex, immunosuppression factor, SCORTEN, pulmonary infection, ICU transfer,
and death (Table 1). However, the study population had significantly higher median (range) BSA detachment (20% [0%-95%]
vs 5.5% [0%-95%]) (P = .004), and was significantly more treated
by cyclosporin (78% vs 46%) or mechanical ventilation (16% vs
6%) (P < .001) (Table 1).
304

P Value

45.5 (17-91)

Female sex

Cancer

Median (Range)

Otorrhea

3 (6)
7 (14)
23 (47)

4 (8)
10 (20)

Abbreviations: ENT, ear, nose, and throat; SJS/TEN, Stevens-Johnson syndrome

and toxic epidermal necrolysis.

ENT Presentation
ENT symptoms (ie, odynophagia, dysphagia, breathing difficulties, dysphonia, nasal obstruction, earache) were found in 48 patients (98%), with odynophagia being the most frequent symptom (n = 48 [98%]), and their frequencies are listed in Table 3.
ENT lesions were mostly located in the oral cavity (n = 46 [94%]),
mainly the lips, the buccal mucosa, and the gum. Lesions included erythematous maculae (n = 45 [92%]), superficial erosions
(n = 39 [80%]), oral ulcerations (n = 7 [14%]), and bullous (n = 5
[10%]). Most of the severe lesions were hemorrhagic bullous (n
= 5 [10%]) on the palate (Figure). Nasal lesions were observed in
26 patients (53%), mainly in the vestibule. The nasal pits and the
cavum were mostly intact. For 1 patient, the head of the middle
turbinates was involved. Nasal lesions were scabs (n = 20 [41%]),
enanthema (n = 19 [39%]), and erosions (n = 8 [16%]). Pharyngeal lesions were observed in 26 patients (53%) and consisted in
enanthema (n = 26 [53%]), erosion (n = 15 [31%]), and edema of
the epiglottis (n = 8 [16%]). Ulceration was reported for 1 patient.
Laryngeal lesions that defined severe ENT form were found in
14 patients (29%) including enanthema (n = 14 [29%]), erosions
(n = 2 [14%]), edema (n = 8 [16%]), and pseudomembranes (n = 3
[6%]) (Video). Diffuse pharyngolaryngeal lesions were found in

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Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Original Investigation Research

Figure. Patient Oral Mucosa Lesion in a Patient With Stevens-Johnson Syndrome

B Labial blisters, erosions, and crust 48 hours later

A Early stage of labial vesicles and erosion

Table 4. Univariate Analysis of Characteristics Associated With Severe ENT Involvement in 49 Patients
Patients
Without Severe
ENT Form
(n = 35)

With Severe
ENT Form
(n = 14)

OR (95% CI)a

Age, median (range), y

40 (17-89)

36.5 (20-79)

0.99 (0.96-1.02)

.55

Men, sex, No. (%)

15 (43)

8 (57)

1.8 (0.5-6.2)

.37

Variables

Cancer, No. (%)

P Valuea

6 (2)

14 (2)

2 .3 (0.3-18.6)

.42

17 (6)

7 (1)

0.4 (0.04-3.4)

.38

Pulmonary infection, No. (%)

3 (8)

43 (6)

7.3 (1.5-35.8)

.008

SCORTEN, median (range)

1 (0-5)

1 (0-3)

1.1 (0.6-1.8)

.87

6 (0-70)

11 (1-80)

1.0 (0.98-1.04)

.48

20 (0-95)

22.5 (1-80)

HIV, No. (%)

BSA detachment, median (range), %

Initial
Maximal
Death, No. (%)
Bronchial detachment, No. (%)
Reanimation stay (ICU transfer), No. (%)

1.0 (0.98-1.03)

.95

8 (3)

NA

.55

3 (1)

14 (2)

5.1 (0.4-62.0)

.20

14 (5)

36 (5)

3.2 (0.8-13.7)

.11

79% of the patients (11 of 14). Ear lesions were epidermolysis of

the ear canal (n = 22 [45%]) and major chondritis (n = 2 [2%]). The
ENT symptoms dysphonia or dyspnea were significantly more
frequent in patients with severe ENT form vs those without severe ENT form (50% [P < .001] and 21% [P = .03], respectively).

Characteristics Associated With Severe ENT Form

The clinical characteristics of the patients with and without severe ENT are compared in Table 4. By univariate analysis, pulmonary infection was significantly associated with severe ENT
form (OR, 7.3; 95% CI, 1.5-35.8) (P = .008). By multivariable analysis, pulmonary infection remained significantly associated with
severe ENT form (OR, 5.9; 95% CI, 1.1-32.8) (P = .04).

Natural Course of ENT Disease

Twenty-nine patients (59%) required nasogastric feeding tube
with a mean (SD) length of 11 (10.2) (range, 2-34) days. Placement of a nasogastric feeding tube over 10 days was necesjamadermatology.com

Abbreviations: BSA, body surface

area; ENT, ear, nose, and throat;
HIV, human immunodeficiency virus;
ICU, intensive care unit; NA, not
applicable; OR, odds ratio;
SCORTEN, Score of Toxic Epidermal
Necrosis.
a

Determined by logistic regression.

sary for 13 patients (27%).Twelve otitis externa (n = 12 [24%])

(ie, otorrhea and erythema in the ear canal) were secondarily
reported at a mean (SD) delay of 17 (9.7) (range, 10-30) days after admission. At 2 months of follow-up, most patients (n = 36
[74%]) had a complete mucosal healing without sequelae. Persistent lesions were mostly located on the tongue (n = 10
[20%]). At the first year of follow-up, complete ENT mucosal
healing without sequelae was confirmed in 48 patients (98%).
For 1 patient, a persistent bullous lesion was located on the palate 7 months after disease onset, which displayed a congestive mucosa without alteration of the epithelium on histopathological examination (Figure).

Discussion
To our knowledge, this is the largest series to first describe
acute-stage ENT manifestations in patients with SJS/TEN. All
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Research Original Investigation

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

patients included in this study underwent an otorhinolaryngologist examination and a nasal fiberoptic endoscopy. Comparison of the characteristics of the study population with those
of the nonincluded patients admitted in the referral center
(without a standardized ENT physician examination) did not
display any significant difference for sex, age, immunosuppression factor, disease severity criteria (SCORTEN), pulmonary infection, ICU transfer, or death. However, the management of the study population might have differed from the rest
of cohort without a full ENT workup because they had higher
BSA detachment or were notably receiving more mechanical
ventilation or cyclosporin treatment. These factors might explain why these patients had received a full ENT workup under routine care.
Interestingly, despite potential selection bias, our main results are as follows: (1) Almost all patients (n = 48 [98%]) had
ENT symptoms from disease onset. (2) The oral cavity had the
highest topographic frequency (94%). (3) Fourteen patients
with SJS/TEN (29%) had severe ENT form defined by the occurrence of laryngeal lesions with the risk of airways obstruction. (4) Patients with severe ENT form had significantly more
dysphonia or dyspnea. (5) Complete ENT mucosal healing at
2 months was observed in 36 of 49 patients with SJS/TEN (74%)
and in 48 (98%) at 1 year. (6) In multivariable analysis, severe
ENT form was only significantly associated with pulmonary
infection.
Our patients demographic and clinical characteristics are
consistent with previously described series.11-15 Causal drugs
used by patients included high-risk drugs identified in a prior
case-control study (ie, allopurinol, antibacterial sulfonamides, lamotrigine, carbamazepine, nevirapine, and
piroxicam).16 Our series mortality rate at the acute stage was
6%, which is lower than previously described in the literature
(22%-35%)13; however, median (range) maximal BSA detachment was 20% (0%-95%) and most of the patients were managed in the department of dermatology and not the ICU, potentially minimizing the disease severity.
To our knowledge, ENT manifestations and follow-up in
patients with SJS/TEN have not been described in detail in the
literature. In prior studies, head and neck manifestations occurred in up to 95% of patients17,18 and in 93% in a pediatric
series of 28 cases.19 In accordance with our study, the oral cavity was reported as the first topographic site of ENT manifestation and oral cavity or lip blisters as the first SJS/TEN sign.14
The lesions could also be located to gingiva, tongue, pharynx, nasal cavity, and larynx.6 Interestingly, laryngeal involvement was common in our series and more frequent than previously reported in the pediatric population (1 of 28 cases in
the series reported by Stewart et al19). With the support of our
results in comparing the study population characteristics with
that of the entire cohort with SJS/TEN, particularly the lack of
a significant difference in pulmonary infection, we suggest that
laryngeal lesions are underreported. To add, our results possibly highlight that pulmonary infection associated with severe ENT form is more severe, requiring oral intubation.
After acute stage, SJS/TEN is significantly associated with
long-term sequelae such as pigmentation or skin disorders, ocular synechia, symblepharon, blindness, chronic sialadenitis, den306

tal abnormalities, or psychiatric disorders.17,20,21 Complete ENT

mucous healing was observed in nearly in 74% of the patients
after 2 months of follow-up and in 98% of the patients after 1
year of follow-up. In the literature, oral lesions usually heal without scarring complications6; in accordance with our series, their
kinetic mechanism of healing is unknown.
In our series, severe ENT form was significantly associated with pulmonary infections. Dysphonia or dyspnea were
also significantly associated with severe ENT form. Respiratory tract infection may be linked to bacterial colonization of
pharyngolaryngeal mucosal lesions. Sepsis is described as the
main cause of death at the acute stage of SJS/TEN. In a 5-year
retrospective study, septicemia and pulmonary infections were
associated with higher mortality.22 In a prospective series assessing pulmonary complications in 41 patients with SJS/
TEN, all patients had oral cavity involvement, even those without pulmonary symptoms. Patients with pulmonary
complications were classified into 2 groups with early (<48
hours) pulmonary manifestations or delayed pulmonary manifestations (pulmonary edema, atelectasis, and bacterial
pneumonia).23 Specific bronchial necrosis was found in 10 patients (27%), but unfortunately laryngeal tract was not described. More recently, in a study of 221 patients with SJS/
TEN pulmonary infiltrate was significantly associated with
mechanical ventilation, while oral lesion was not significantly associated with either specific bronchial erosion or mechanical ventilation.18 Because of our small sample of patients, a significant association between severe ENT
manifestation and specific bronchial lesions was not displayed (P = .10); this may be linked to a lack of power.
Treatment for SJS/TEN mainly relies on early drug withdrawal; compared with supportive care, no specific treatment seems beneficial.2,24 Most of the patients in this series
received cyclosporin because its use and effectiveness were
evaluated in an open phase 2 trial from March 2005 to September 2007.25 In this trial, death rate and the progression of
skin detachment were lower than expected, but its effect on
severe ENT form was not evaluated. ENT manifestations largely
respond to local care, and the routine use of prophylactic antibiotics or systemic steroids is not recommended.19 Our patients received mucosal supportive care including hygienic
mouthwashes and oral topical anesthetics.26 At the acute stage,
half of the patients were fed using a nasogastric tube because
of oral mucosa pain or swallowing disorders or to limit aspirations. Scabs were softened by regular isotonic saline irrigation. Preventive aspiration of desquamating epidermis could
also be suggested to limit external otitis.

Conclusions
Despite some bias linked to their management, patients with
ENT workup did not differ from the rest of the population with
SJS/TEN, especially regarding their severity factors. Complete ENT workup with nasal fiberoptic endoscopy led us to
identify severe ENT form, which was associated to pulmonary infection. Nasal fiberoptic endoscopy at a patients bedside is simple, noninvasive, and helpful to detect severe ENT,

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Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Original Investigation Research

especially in the case of dysphonia or dyspnea. Because infection is the main cause of death in SJS/TEN, monitoring ENT
symptoms or detecting laryngeal lesions may be relevant. Clinical perspectives include complete ENT examination when

ARTICLE INFORMATION
Accepted for Publication: November 5, 2014.
Published Online: February 11, 2015.
doi:10.1001/jamadermatol.2014.4844.
Author Affiliations: Hpital Intercommunal,
Service dORL et de Chirurgie Cervico-Faciale,
Crteil, France (Bequignon, Coste); UPEC Universit
Paris Est Crteil, Facult de Mdecine, Crteil,
France (Bequignon, Sbidian, Coste, Wolkenstein,
Chosidow); Service de Dermatologie, Assistance
PubliqueHpitaux de Paris (AP-HP), Hpitaux
Universitaires Henri-Mondor, Crteil, France
(Duong, Sbidian, Valeyrie-Allanore,
Ingen-Housz-Oro, Wolkenstein, Chosidow);
Laboratoire dInvestigation CliniqueEA439, France
(Sbidian, Valeyrie-Allanore, Wolkenstein); INSERM,
Centre dInvestigation Clinique 006, Crteil, France
(Sbidian, Chosidow); Service dORL et de Chirurgie
Cervico-Faciale, AP-HP, Hpitaux Universitaires
Henri-Mondor, Crteil, France (Chatelin, Coste);
INSERM, U955, Crteil, France (Papon); Service
dORL et de Chirurgie Cervico-Faciale, AP-HP,
Groupe Hospitalier Bictre, Kremlin-Bictre, France
(Papon).
Author Contributions: Drs Bequignon and Duong
had full access to all of the data in the study and
take responsibility for the integrity of the data and
the accuracy of the data analysis. Drs Bequignon,
Duong, Wolkenstein, Chosidow, and Papon
contributed equally to the study.
Study concept and design: Bequignon, Duong,
Wolkenstein, Chosidow, Papon.
Acquisition, analysis, or interpretation of data:
Bequignon, Duong, Sbidian, Valeyrie-Allanore,
Ingen-Housz-Oro, Chatelin, Coste, Papon.
Drafting of the manuscript: Bequignon, Duong,
Papon.
Critical revision of the manuscript for important
intellectual content: Bequignon, Sbidian,
Valeyrie-Allanore, Ingen-Housz-Oro, Chatelin,
Coste, Wolkenstein, Chosidow, Papon.
Statistical analysis: Bequignon, Duong, Sbidian.
Administrative, technical, or material support:
Bequignon, Duong, Coste, Papon.
Study supervision: Wolkenstein, Chosidow, Papon.
Conflict of Interest Disclosures: None reported.
Additional Contributions: Jean-Claude Roujeau,
MD, Department of Dermatology, Hpitaux
Universitaires Henri-Mondor (retired), assisted in
contributing his knowledge on the study subject.
Financial compensation was not provided.
REFERENCES
1. Bastuji-Garin S, Rzany B, Stern RS, Shear NH,
Naldi L, Roujeau JC. Clinical classification of cases of
toxic epidermal necrolysis, Stevens-Johnson
syndrome, and erythema multiforme. Arch Dermatol.
1993;129(1):92-96.

jamadermatology.com

pulmonary infections are present to detect a potential relationship between bronchial detachment and severe ENT form
or to determine the role of ENT standardized therapeutic protocols to limit pulmonary infections.

2. Schneck J, Fagot JP, Sekula P, Sassolas B,

Roujeau JC, Mockenhaupt M. Effects of treatments
on the mortality of Stevens-Johnson syndrome and
toxic epidermal necrolysis: a retrospective study on
patients included in the prospective EuroSCAR
Study. J Am Acad Dermatol. 2008;58(1):33-40.
3. Sassolas B, Haddad C, Mockenhaupt M, et al.
ALDEN, an algorithm for assessment of drug
causality in Stevens-Johnson Syndrome and toxic
epidermal necrolysis: comparison with case-control
analysis. Clin Pharmacol Ther. 2010;88(1):60-68.
4. Auquier-Dunant A, Mockenhaupt M, Naldi L,
Correia O, Schrder W, Roujeau JC; SCAR Study
Group. Correlations between clinical patterns and
causes of erythema multiforme majus,
Stevens-Johnson syndrome, and toxic epidermal
necrolysis: results of an international prospective
study. Arch Dermatol. 2002;138(8):1019-1024.

Stevens-Johnson syndrome and toxic epidermal

necrolysis: analysis of mortality risk for causative
agents. Burns. 2013;39(7):1449-1455.
15. Tan SK, Tay YK. Profile and pattern of
Stevens-Johnson syndrome and toxic epidermal
necrolysis in a general hospital in Singapore:
treatment outcomes. Acta Derm Venereol. 2012;92
(1):62-66.
16. Mockenhaupt M, Viboud C, Dunant A, et al.
Stevens-Johnson syndrome and toxic epidermal
necrolysis: assessment of medication risks with
emphasis on recently marketed drugs: the
EuroSCAR-study. J Invest Dermatol. 2008;128(1):
35-44.
17. Fellahi A, Zouhair K, Amraoui A, Benchikhi H.
Stevens-Johnson and Lyell syndromes:
mucocutaneous and ocular sequels in 43 cases [in
French]. Ann Dermatol Venereol. 2011;138(2):88-92.

5. Assier H, Bastuji-Garin S, Revuz J, Roujeau JC.

Erythema multiforme with mucous membrane
involvement and Stevens-Johnson syndrome are
clinically different disorders with distinct causes.
Arch Dermatol. 1995;131(5):539-543.

18. de Prost N, Mekontso-Dessap A,

Valeyrie-Allanore L, et al. Acute respiratory failure in
patients with toxic epidermal necrolysis: clinical
features and factors associated with mechanical
ventilation. Crit Care Med. 2014;42(1):118-128.

6. Ayangco L, Rogers RS III. Oral manifestations of

erythema multiforme. Dermatol Clin. 2003;21(1):
195-205.

19. Stewart MG, Duncan NO III, Franklin DJ,

Friedman EM, Sulek M. Head and neck
manifestations of erythema multiforme in children.
Otolaryngol Head Neck Surg. 1994;111(3 Pt 1):236-242.

7. Sekula P, Dunant A, Mockenhaupt M, et al;

RegiSCAR Study Group. Comprehensive survival
analysis of a cohort of patients with
Stevens-Johnson syndrome and toxic epidermal
necrolysis. J Invest Dermatol. 2013;133(5):1197-1204.
8. Bastuji-Garin S, Fouchard N, Bertocchi M,
Roujeau JC, Revuz J, Wolkenstein P. SCORTEN:
a severity-of-illness score for toxic epidermal
necrolysis. J Invest Dermatol. 2000;115(2):149-153.
9. Koch WM, McDonald GA. Stevens-Johnson
syndrome with supraglottic laryngeal obstruction.
Arch Otolaryngol Head Neck Surg. 1989;115(11):13811383.
10. Valeyrie-Allanore L, Wolkenstein P, Brochard L,
et al. Open trial of ciclosporin treatment for
Stevens-Johnson syndrome and toxic epidermal
necrolysis. Br J Dermatol. 2010;163(4):847-853.
11. Rajaratnam R, Mann C, Balasubramaniam P,
et al. Toxic epidermal necrolysis: retrospective
analysis of 21 consecutive cases managed at a
tertiary centre. Clin Exp Dermatol. 2010;35(8):853862.
12. Zajicek R, Pintar D, Broz L, Suca H, Knigova R.
Toxic epidermal necrolysis and Stevens-Johnson
syndrome at the Prague Burn Centre 1998-2008.
J Eur Acad Dermatol Venereol. 2012;26(5):639-643.
13. Firoz BF, Henning JS, Zarzabal LA, Pollock BH.
Toxic epidermal necrolysis: five years of treatment
experience from a burn unit. J Am Acad Dermatol.
2012;67(4):630-635.

20. Gueudry J, Roujeau JC, Binaghi M, Soubrane G,

Muraine M. Risk factors for the development of
ocular complications of Stevens-Johnson syndrome
and toxic epidermal necrolysis. Arch Dermatol.
2009;145(2):157-162.
21. Gaultier F, Rochefort J, Landru MM, et al. Severe
and unrecognized dental abnormalities after
drug-induced epidermal necrolysis. Arch Dermatol.
2009;145(11):1332-1333.
22. Thammakumpee J, Yongsiri S. Characteristics
of toxic epidermal necrolysis and Stevens-Johnson
syndrome: a 5-year retrospective study. J Med
Assoc Thai. 2013;96(4):399-406.
23. Lebargy F, Wolkenstein P, Gisselbrecht M, et al.
Pulmonary complications in toxic epidermal
necrolysis: a prospective clinical study. Intensive
Care Med. 1997;23(12):1237-1244.
24. Garcia-Doval I, LeCleach L, Bocquet H, Otero
XL, Roujeau JC. Toxic epidermal necrolysis and
Stevens-Johnson syndrome: does early withdrawal
of causative drugs decrease the risk of death? Arch
Dermatol. 2000;136(3):323-327.
25. Valeyrie-Allanore L, Wolkenstein P, Brochard L,
et al. Open trial of ciclosporin treatment for
Stevens-Johnson syndrome and toxic epidermal
necrolysis. Br J Dermatol. 2010;163(4):847-853.
26. Fernando SL. The management of toxic
epidermal necrolysis. Australas J Dermatol. 2012;53
(3):165-171.

14. Weinand C, Xu W, Perbix W, et al. 27 years of a

single burn centre experience with

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