DR SASKIA INGEN-HOUSZ-ORO (Orcid ID : 0000-0002-5383-7096)

DR NICOLAS DE PROST (Orcid ID : 0000-0002-4833-4320)

Accepted Article
Article type : Research Letter

Gastro-intestinal involvement in Stevens-Johnson syndrome and toxic

epidermal necrolysis : a retrospective case series

S. Gendreau1, A. Amiot2, Y. Le Baleur2, C Charpy3, P. Wolkenstein4, 5, O. Chosidow4,

5
, A. Mekontso Dessap1, 6, S. Ingen-Housz-Oro*4,5, N. de Prost*1, 5,6

* Contributed equally

1
Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor – Albert
Chenevier, Assistance Publique – Hôpitaux de Paris (AP-HP), Créteil, France ;
2
Service de Gastro-entérologie, Hôpitaux Universitaires Henri Mondor – Albert
Chenevier, Assistance Publique – Hôpitaux de Paris (AP-HP), Créteil, France ;
3
Département de pathologie, Hôpitaux Universitaires Henri Mondor – Albert
Chenevier, Assistance Publique – Hôpitaux de Paris (AP-HP), Créteil, France ;
4
Service de Dermatologie, Hôpitaux Universitaires Henri Mondor – Albert Chenevier,
Assistance Publique – Hôpitaux de Paris (AP-HP), Créteil, France ;
5
Reference Center for Toxic Bullous Diseases, Créteil, France ;
6
Groupe de Recherche Clinique CARMAS, Université Paris Est-Créteil, Créteil,
France ;

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/bjd.17428
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 Corresponding author:

Dr. De Prost Nicolas

Accepted Article
Service de Réanimation Médicale, Hôpital Henri Mondor, Créteil, France

E-mail : nicolas.de-prost@aphp.fr

Dear Editor,

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are

characterized by extensive skin and mucosal membrane detachment together with

specific visceral involvement1. While respiratory tract2 and ear, nose, and throat1

mucosal lesions have been comprehensively described, gastro-intestinal (GI)

involvement, although previously reported3, has been less investigated. Clinical

manifestations are non-specific, including ileus, emesis, diarrhea, hematemesis,

melena/rectal bleeding, abdominal pain, or dysphagia. We aimed to report

endoscopic findings amongst a cohort of SJS/TEN patients hospitalized in the

medical intensive care unit (ICU) of the French reference center for SJS/TEN.

Medical records were retrospectively reviewed for consecutive patients (age>18

years) admitted for SJS, TEN, or SJS/TEN overlap syndrome in the medical ICU of

Henri Mondor Hospital, Créteil, France, between January 2010 and April 2018, who

underwent at least one endoscopic procedure during hospital stay. Informed consent

was obtained from all included patients or their relatives. Patient management

followed a previously described standardized protocol4. Early nutritional support by

continuous enteral nutrition was routinely administered. Endoscopies (upper

gastrointestinal tract endoscopy and/or colonoscopy) were performed when upper or

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 lower digestive tract involvement was suspected (i.e., upper or lower gastro-intestinal

hemorrhage, enteral nutrition intolerance or bowel obstruction), or for routine mucosa

Accepted Article
assessment. Endoscopic findings were recorded as follows: normal investigation,

mucosa lining ulceration or detachment, inflammation, stricture, mucosal edema, and

polyps. According to endoscopic description and biopsy results, when available,

patients were categorized as having definite SJS/TEN-related lesions (i.e., mucosal

detachment or stricture), possible SJS/TEN-related lesions (i.e., inflammation) or

SJS/TEN-unrelated lesions.

During the study period, 145 patients with SJS/TEN were hospitalized. Amongst

them, 50 were admitted in the ICU, and 20/50 underwent at least one endoscopic

procedure (upper GI tract endoscopy, n=19; colonoscopy, n=7). Patients (median

age 45 years [35-58], 11 males) had a baseline detached body surface area (BSA)

of 18% [14-35], and were eventually categorized as TEN (n=14; 70%), SJS/TEN

overlap (n=5; 25%) and SJS (n=1; 5%). The SAPS II score upon admission, a

predictor of one-month mortality of ICU patients, was 37 [27-56] and the SCORTEN

2.5 [2-4]. Among the endoscopic procedures performed (Table 1), 18/20 (90%)

showed abnormal findings, including ulcerations in 50% of cases (esophageal, n=9;

gastroduodenal, n=4; and colonic, n=1), mucosal inflammation (45%, n=9/20), and

esophageal stricture (15%, n=3/20). Six GI biopsies were performed, three of which

were consistent with SJS/TEN-related lesions (i.e., necrotic epithelial detachment).

Definite SJS/TEN-related findings were evidenced in 11 (55%) patients, mainly

involving the esophagus (n=10/11, 91%) with nine patients presenting extensive

ulcerations/mucosal detachments, and two patients showing esophageal stricture.

SJS/TEN-related lesions were also recorded in the stomach, duodenum, and colon

(n=1). Enteral feeding discontinuation was required for 6 of 11 patients with definite

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 SJS/TEN-related lesions, eight of whom were treated with anti-acids. In-hospital

mortality when extensive mucosal detachments were evidenced was 36% (n=4/11)
Accepted Article
versus 33% (n=3/9) otherwise. Three patients (15%) died from intestinal ischemia.

There was no complication related to the endoscopic procedures performed. Of note,

the two patients who presented an SJS/TEN-related esophageal stenosis on the first

exam subsequently required endoscopic dilations.

The current study is, to our knowledge, the largest report of GI tract involvement in

an SJS/TEN cohort. Among the selected patients, 55% had definite SJS/TEN-related

lesions, including epithelial detachment, mucosal ulceration, and stricture. Such

lesions were mostly esophageal, and scarcely gastroduodenal, while the colon was

involved in only one of seven colonoscopies performed. Gastro-intestinal

involvement was described as the second most common visceral involvement in a

recent retrospective study5, with 12.5% patients presenting with GI symptoms

including diarrhea and gastrointestinal tract hemorrhage. Esophageal involvement is

now well documented during SJS/TEN and ranges from mild esophagitis to severe

epithelial necrosis and ulceration6,7. Whether a GI endoscopy should be routinely

performed in SJS/TEN patients remains debated; the finding of a severe GI

involvement is relevant for nutrition strategies, a crucial aspect of the supportive

management of SJS/TEN, as nasogastric tube for enteral nutrition could worsen

upper digestive tract lesions. Moreover, the rupture of the mucosal epithelium

possibly increases the risk of bacterial translocations, with a previously documented

high rate of bloodstream infections involving Enterobacteriaceae8. We acknowledge

that our study has a number of limitations, including its retrospective design, the

limited number of included patients, and the lack of standardization of endoscopic

procedures with only a small subset of patients who had biopsy-proven lesions.

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 Diagnosis of GI involvement was identified solely from endoscopy and biopsy; sub-

clinical involvement in asymptomatic patients might have been missed, especially in

Accepted Article
non-intubated patients, not fit enough to undergo endoscopic procedures. Yet, we

believe our article conveys an important message regarding esophageal

involvement, which will have to be confirmed by prospective studies.

SJS/TEN-related gastro-intestinal lesions frequently involve the esophagus and can

lead to esophageal stricture. Routine exploration of the upper digestive tract in

intubated SJS/TEN patients seems to be a safe procedure. Endoscopic findings can

help guide patients’ management during the early phase and allow for detecting

patients at risk of developing esophageal strictures.

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failure in patients with toxic epidermal necrolysis: clinical features and factors

associated with mechanical ventilation. Crit Care Med 2014; 42:118–28.

3. Chosidow O, Delchier JC, Chaumette MT, et al. Intestinal involvement in drug-

induced toxic epidermal necrolysis. Lancet Lond Engl 1991; 337:928.

4. Ingen-Housz-Oro S, Duong T-A, Bensaid B, et al. Epidermal necrolysis French

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 5. Wang L, Mei X-L. Retrospective Analysis of Stevens-Johnson Syndrome and

Toxic Epidermal Necrolysis in 88 Chinese Patients. Chin Med J (Engl) 2017;

Accepted Article
130:1062–8.

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 Table 1. Clinical features and endoscopic findings in Stevens-Johnson
syndrome/toxic epidermal necrolysis patients (n=20) who underwent ≥ 1 digestive
endoscopies during hospitalization.
Accepted Article
Variables All patients (n=20)
Population characteristics during ICU stay
Duration of hospital stay, days 42 (29 - 70)
Antibiotic treatment 19 (95)
Vasopressors 19 (90)
Mechanical ventilation 19 (95)
Bronchial epithelial lesions a 14 (74)
Bloodstream infection 11 (55)
Adjuvant therapy 11 (55)
Ciclosporin 10 (50)
Immunoglobulins 1 (5)
In-hospital death 7 (35%)

Endoscopy indication
Routine procedure 11 (55)
Enteral nutrition intolerance 4 (20)
Bowel obstruction 4 (20)
Hematemesis 1 (5)
Endoscopic findings Topography
Normal 2 (10)
Inflammation 9 (45)
Esophageal 8
Gastro-duodenal 6
Ulceration 10 (50)
Esophageal 9
Gastro-duodenal 4
Colonic 1
Stricture Esophageal b 3 (15)
Others 4 (20)
Polyp 2
Mucosal edema 2
Digestive biopsy findings 6 (30)
Localization Esophageal 3 (50)
Gastro-duodenal 3 (50)
Histological findings Specific pattern 3 (50)
Inflammation 2 (33)
Infection 1 (17)
Endoscopic lesions categorization
Definite SJS/TEN -related lesions c 11 (55)
Esophageal 10
Gastro-duodenal 4
Colic 1
Possible SJS/TEN-related lesions 1 (5)
Inflammation 1
SJS/TEN-unrelated lesions 6 (30)
Polyp 2
Colic edema 1
ischemia 1
Others 2

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 Therapeutic impact
Enteral nutrition discontinuation 7 (35)
In patients with definite SJS/TEN-related lesions 6
Anti-acids 9 (45)
Accepted Article
In patients with definite SJS/TEN-related lesions 8
Endoscopic dilation 2 (10)
Nominal variables are presented as n (%), and continuous variables are presented as
median (interquartile range, 25–75); a Evidenced by bronchoscopy; b one preexisting
stricture; c mucosal detachment or stricture

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