0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Ear, Nose, and Throat Description at Acute Stage and After Remission FREE

Emilie Bequignon, MD1,2; Tu Anh Duong, MD3; Emilie Sbidian, MD, PhD2,3,4,5; Laurence Valeyrie-Allanore, MD3,4; Saskia Ingen-Housz-Oro, MD3; Veronique Chatelin, MD6; André Coste, MD, PhD1,2,6; Pierre Wolkenstein, MD, PhD2,3,4; Olivier Chosidow, MD, PhD2,3,5; Jean François Papon, MD, PhD7,8
[+] Author Affiliations
1Hôpital Intercommunal, Service d’ORL et de Chirurgie Cervico-Faciale, Créteil, France
2UPEC Université Paris Est Créteil, Faculté de Médecine, Créteil, France
3Service de Dermatologie, Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri-Mondor, Créteil, France
4Laboratoire d’Investigation Clinique–EA439, France
5INSERM, Centre d’Investigation Clinique 006, Créteil, France
6Service d’ORL et de Chirurgie Cervico-Faciale, AP-HP, Hôpitaux Universitaires Henri-Mondor, Créteil, France
7INSERM, U955, Créteil, France
8Service d’ORL et de Chirurgie Cervico-Faciale, AP-HP, Groupe Hospitalier Bicêtre, Kremlin-Bicêtre, France
JAMA Dermatol. 2015;151(3):302-307. doi:10.1001/jamadermatol.2014.4844.
Text Size: A A A
Published online

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

Figures in this Article

Stevens-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.

Population

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.

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 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.”

Statistical Analysis

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).

Table Graphic Jump LocationTable 1.  Demographic Data of 49 Patients With SJS/TEN
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 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).

Table Graphic Jump LocationTable 2.  Causal Drug Identified in 41 Patientsa
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 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).

Table Graphic Jump LocationTable 3.  ENT Symptoms in 49 Patients With SJS/TEN
Place holder to copy figure label and caption
Figure.
Patient Oral Mucosa Lesion in a Patient With Stevens-Johnson Syndrome
Graphic Jump Location

Video.

Nasal Fiberoptic Endoscopy of the Larynx and Pharynx at Day 4 in a Patient With Stevens-Johnson Syndrome

Findings include enanthema, edema and pseudomembranes of the epiglottis, and laryngeal vestibule enanthema without involvement of the vocal cords.

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).

Table Graphic Jump LocationTable 4.  Univariate Analysis of Characteristics Associated With Severe ENT Involvement in 49 Patients
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 necessary 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).

To our knowledge, this is the largest series to first describe acute-stage ENT manifestations in patients with SJS/TEN. All 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.1115 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, dental 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.

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 patient’s bedside is simple, noninvasive, and helpful to detect severe ENT, 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 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.

Accepted for Publication: November 5, 2014.

Corresponding Author: Tu Anh Duong, MD, Department of Dermatology, Hôpitaux Universitaires Henri-Mondor, AP-HP, 51, Avenue du Marechal de Lattre de Tassigny, 94010 Creteil CEDEX, France (tu-anh.duong@hmn.aphp.fr).

Published Online: February 11, 2015. doi:10.1001/jamadermatol.2014.4844.

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, Hôpitaux Universitaires Henri-Mondor (retired), assisted in contributing his knowledge on the study subject. Financial compensation was not provided.

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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Auquier-Dunant  A, Mockenhaupt  M, Naldi  L, Correia  O, Schröder  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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Ayangco  L, Rogers  RS  III.  Oral manifestations of erythema multiforme. Dermatol Clin. 2003;21(1):195-205.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Koch  WM, McDonald  GA.  Stevens-Johnson syndrome with supraglottic laryngeal obstruction. Arch Otolaryngol Head Neck Surg. 1989;115(11):1381-1383.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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):853-862.
PubMed   |  Link to Article
Zajicek  R, Pintar  D, Broz  L, Suca  H, Königova  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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Weinand  C, Xu  W, Perbix  W,  et al.  27 years of a single burn centre experience with Stevens-Johnson syndrome and toxic epidermal necrolysis: analysis of mortality risk for causative agents. Burns. 2013;39(7):1449-1455.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Fernando  SL.  The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53(3):165-171.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Patient Oral Mucosa Lesion in a Patient With Stevens-Johnson Syndrome
Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1.  Demographic Data of 49 Patients With SJS/TEN
Table Graphic Jump LocationTable 2.  Causal Drug Identified in 41 Patientsa
Table Graphic Jump LocationTable 3.  ENT Symptoms in 49 Patients With SJS/TEN
Table Graphic Jump LocationTable 4.  Univariate Analysis of Characteristics Associated With Severe ENT Involvement in 49 Patients

References

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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Auquier-Dunant  A, Mockenhaupt  M, Naldi  L, Correia  O, Schröder  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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Ayangco  L, Rogers  RS  III.  Oral manifestations of erythema multiforme. Dermatol Clin. 2003;21(1):195-205.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Koch  WM, McDonald  GA.  Stevens-Johnson syndrome with supraglottic laryngeal obstruction. Arch Otolaryngol Head Neck Surg. 1989;115(11):1381-1383.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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):853-862.
PubMed   |  Link to Article
Zajicek  R, Pintar  D, Broz  L, Suca  H, Königova  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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Weinand  C, Xu  W, Perbix  W,  et al.  27 years of a single burn centre experience with Stevens-Johnson syndrome and toxic epidermal necrolysis: analysis of mortality risk for causative agents. Burns. 2013;39(7):1449-1455.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
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.
PubMed   |  Link to Article
Fernando  SL.  The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53(3):165-171.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Video.

Nasal Fiberoptic Endoscopy of the Larynx and Pharynx at Day 4 in a Patient With Stevens-Johnson Syndrome

Findings include enanthema, edema and pseudomembranes of the epiglottis, and laryngeal vestibule enanthema without involvement of the vocal cords.

Some tools below are only available to our subscribers or users with an online account.

2,210 Views
1 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Original Article: Does This Child Have Acute Otitis Media?

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Quick Reference

brightcove.createExperiences();