Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe mucocutaneous reaction with few large cohorts reported. This multicenter retrospective study included patients with SJS/TEN seen by inpatient consultative dermatologists at 18 academic medical centers in the United States. A total of 377 adult patients with SJS/TEN between January 1, 2000 and June 1, 2015 were entered, including 260 of 377 (69%) from 2010 onward. The most frequent cause of SJS/TEN was medication reaction in 338 of 377 (89.7%), most often to trimethoprim/sulfamethoxazole (89/338; 26.3%). Most patients were managed in an intensive care (100/368; 27.2%) or burn unit (151/368; 41.0%). Most received pharmacologic therapy (266/376; 70.7%) versus supportive care alone (110/376; 29.3%)—typically corticosteroids (113/266; 42.5%), intravenous immunoglobulin (94/266; 35.3%), or both therapies (54/266; 20.3%). Based on day 1 SCORTEN predicted mortality, approximately 78 in-hospital deaths were expected (77.7/368; 21%), but the observed mortality of 54 patients (54/368; 14.7%) was significantly lower (standardized mortality ratio = 0.70; 95% confidence interval = 0.58–0.79). Stratified by therapy received, the standardized mortality ratio was lowest among those receiving both steroids and intravenous immunoglobulin (standardized mortality ratio = 0.52; 95% confidence interval 0.21–0.79). This large cohort provides contemporary information regarding US patients with SJS/TEN. Mortality, although substantial, was significantly lower than predicted. Although the precise role of pharmacotherapy remains unclear, co-administration of corticosteroids and intravenous immunoglobulin, among other therapies, may warrant further study.
Abbreviations:BSA (body surface area), CI (confidence interval), IVIG (intravenous immunoglobulin), SCORTEN (SCORe of Toxic Epidermal Necrolysis), SD (standard deviation), SJS (Stevens-Johnson syndrome), TEN (toxic epidermal necrolysis)
Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a spectrum of severe mucocutaneous adverse reaction characterized by blistering and erosions of skin and mucous membranes. The disease is rare, with an incidence estimated between 2 and 13 per million patients per year (
Hsu et al., 2016,
Strom et al., 1991), but it is a significant source of morbidity and mortality for those affected. SJS is defined as detachment of less than 10% of cutaneous body surface area (BSA), whereas TEN involves more than 30%, and SJS/TEN overlap between 10% and 30% BSA (
Bastuji-Garin et al., 1993). Potential complications of SJS/TEN are numerous, including multiorgan failure and significant long-term sequelae (
Dodiuk-Gad et al., 2016,
Haber et al., 2005,
Schwartz et al., 2013a,
Schwartz et al., 2013b). The published overall mortality is 20%–25%, based primarily on European cohorts from the 1990s and early 2000s (
Mockenhaupt et al., 2008,
Sekula et al., 2013). No large cohort of patients from the United States has been reported. A prognostic score (SCORe of Toxic Epidermal Necrolysis [SCORTEN]) was introduced in 2000 to help predict in-hospital mortality (
Bastuji-Garin et al., 2000,
Cartotto et al., 2008,
Trent et al., 2004).
Despite the significant morbidity and mortality of the disease, knowledge of its causes, natural history, treatments, and outcomes is limited by small size and heterogeneity of published cohorts. Although prompt cessation of the causative agent and transfer to an appropriate specialized unit are associated with improved outcomes (
Garcia-Doval et al., 2000,
McGee and Munster, 1998,
Oplatek et al., 2006,
Palmieri et al., 2002), no literature has convincingly shown benefit from the use of any systemic pharmacotherapy. Although providers in the United States frequently use intravenous immunoglobulin (IVIG), especially in more severe cases (
Curtis et al., 2016), no clear benefit from this approach has been shown (
Creamer et al., 2016). The appropriate management of SJS/TEN remains controversial (
Creamer et al., 2016).
This multicenter retrospective study was a collaborative effort of members of the Society of Dermatology Hospitalists (a US-based organization of dermatologists specializing in the care of hospitalized patients) to collect a large, contemporary cohort of SJS/TEN patients with the goal of describing important disease-associated factors, management, and outcomes.
A total of 377 adult patients from 18 academic medical centers across the United States were included in this study (see Supplementary Table S1 online). All patients were diagnosed and treated for SJS/TEN between January 1, 2000 and June 1, 2015, most from 2010 onward (260/377; 69.0%). Patients had a mean age of 49.0 years (standard deviation [SD] = 19.2), and the majority (198/377; 52.5%) were female. One hundred seventy-five (46.4%) of the 377 patients were white, 112 (29.7%) were black, 39 were Asian (10.3%), and 15 (4.0%) were described as Hispanic or Latino (Table 1). Comorbid medical conditions at the time of hospital admission included active infection (92/377; 24.4%), diabetes mellitus (69/377; 18.3%), tobacco use (52/377; 13.8%), active malignancy (41/377; 10.9%), mood disorder (40/377; 10.6%), chronic kidney disease (39/377; 10.3%), connective tissue disease (39/377; 10.3%), chronic liver disease (35/377; 9.3%), coronary artery disease (34/377; 9.0%), chronic obstructive pulmonary disease (33/377; 8.8%), seizure disorder (30/377; 8.0%), and HIV (22/377; 5.8%).
Table 1Patient Demographics and Comorbidities (N = 377)
|Year of diagnosis, n (%)|
|Age in years, mean (SD)||49.0 (19.2)|
|Sex, n (%)|
|Race, n (%)|
|Hispanic or Latino||15 (4.0)|
|Medical comorbidities, n (%)|
|Active infection||92 (24.4)|
|Diabetes mellitus||69 (18.3)|
|Tobacco use||52 (13.8)|
|Active malignancy||41 (10.9)|
|Mood disorder||40 (10.6)|
|Chronic kidney disease||39 (10.3)|
|Connective tissue disease||39 (10.3)|
|Chronic liver disease||35 (9.3)|
|Coronary artery disease||34 (9.0)|
|Chronic obstructive pulmonary disease||33 (8.8)|
|Seizure disorder||30 (8.0)|
|HIV infection||22 (5.8)|
Abbreviation: SD, standard deviation.
SJS/TEN was most frequently attributed to medication reaction (338/377; 89.7%), most commonly to trimethoprim/sulfamethoxazole (89/338; 26.3%), β-lactam antibiotics (42/338; 12.4%), phenytoin (32/338; 9.5%), lamotrigine (30/338; 8.9%), allopurinol (29/338; 8.6%), and nonsteroidal anti-inflammatory drugs (18/338; 5.3%) (Table 2). Infections, mainly Mycoplasma pneumoniae (n = 7) and herpes simplex virus (n = 3), accounted for a small minority (13/377; 3.4%) of SJS/TEN cases, and in 26 of 377 patients (6.9%), the cause was unknown. (See Supplementary Table S2 online for a complete list of attributed causes of SJS/TEN).
Table 2Most Common Causes of Drug-Induced SJS/TEN (N = 338)
|Class of Medication||n (%)|
|β-lactam antibiotics||42 (12.4)|
|Antiepileptics/mood stabilizers||83 (23.7)|
Median percentage of BSA denuded at the time of admission was 15% (interquartile range = 6%–30%), and median maximal BSA skin loss during the disease course was 25% (interquartile range = 10%–50%). A total of 110 of 347 patients (31.7%) met criteria for SJS (<10% BSA) at the time of admission, 158 of 347 patients (45.5%) for SJS/TEN overlap (10%–30% BSA), and 79 of 347 patients (22.8%) for TEN (>30% BSA). With a mean SCORTEN score of 2.0 (SD = 1.3) on day 1 of admission, the overall predicted mortality for the cohort was 21.1% (77.7/368) (Table 3).
Table 3SJS/TEN Disease Severity and Management (N = 377)
|Disease Severity and Management||Value|
|Body surface area involvement, median % (IQR)|
|BSA involved at admission||15 (6–30)|
|BSA maximum during hospitalization||25 (10–50)|
|Disease classification at admission, n (%)|
|SJS/TEN overlap||158 (45.5)|
|SCORTEN on admission, mean (SD)||2.0 (1.3)|
|SCORTEN predicted mortality, %||21.1|
|Primary management site, n (%)|
|Intensive care unit||100 (27.2)|
|Burn unit||151 (41.0)|
|Nonspecialized medical ward||117 (31.8)|
|Supportive care alone, n (%)||110 (29.3)|
|Systemic pharmacotherapy, n (%)|
|Steroids only||113 (42.5)|
|IVIG only||94 (35.3)|
|Both IVIG and steroids||54 (20.3)|
Abbreviations: BSA, body surface area; IQR, interquartile range; IVIG, intravenous immunoglobulin; SJS/TEN, Stevens-Johnson syndrome; toxic epidermal necrolysis.
1 Four patients received cyclosporine and one patient etanercept.
Most patients were managed in an intensive care unit (100/368; 27.2%) or a burn unit (151/368; 41.0%), and they were followed by inpatient consultative dermatologists. Most received some form of pharmacologic therapy (266/376; 70.7%) versus supportive care alone (110/376; 29.3%), usually corticosteroids (113/266; 42.5%), IVIG (94/266; 35.3%), or both therapies (54/266; 20.3%), and less commonly cyclosporine (n = 4) or a tumor necrosis factor inhibitor (n = 1).
Among those receiving IVIG alone, the mean daily dose was 1.0 g/kg (SD = 0.4), given daily for 3.1 days (SD = 0.9), with a total dose of 3.2 g of IVIG (SD = 1.5). Those receiving corticosteroids alone received a mean daily dose of 148.0 mg (SD = 182.8) prednisone equivalent daily for 9.8 days (SD = 15.1). There was no significant difference in dose between those who received one of these agents only and those who received both.
Patients who were prescribed IVIG tended to have more severe SJS/TEN at the time of admission than those receiving other treatments, including higher median BSA involvement (30% vs. 12%, P < .01); a higher percentage of patients meeting the definition of TEN (28.0% vs. 18.7%, P = 0.01); and higher rates of severe ocular, oral, and genitourinary involvement (all P < .05) compared with other treatment groups.
Based on day 1 SCORTEN predicted mortality, approximately 78 in-hospital deaths were expected for the cohort (77.7/368; 21.1%), but the observed mortality in 54 of 368 patients (14.7%) was less than predicted (standardized mortality ratio = 0.70; 95% confidence interval [CI] = 0.58–0.79). Stratified by the therapy received, the standardized mortality ratio compared with SCORTEN predicted mortality was 0.52 (95% CI = 0.21–0.79) among patients receiving both corticosteroids and IVIG, 0.72 (95% CI = 0.48–0.89) among those receiving corticosteroids only, 0.79 (95% CI = 0.55–0.92) among those receiving IVIG only, and 0.70 (95% CI = 0.47–0.87) among those treated with supportive care alone (Table 4). There was no apparent difference in mortality between patients receiving low- and high-dose (>2 g/kg total) IVIG (P > 0.99); however, the number of patients receiving low-dose IVIG was small (n = 12).
Table 4SJS/TEN Disease Outcome
N = 368
n = 92
n = 116
|IVIG + Steroid|
n = 54
n = 117
|SCORTEN predicted mortality, n (%)||77.7 (21.1)||21.6 (23.5)||20.8 (17.8)||11.6 (20.9)||22.7 (19.4)|
|Observed mortality, n (%)||54 (14.7)||17 (18.5)||15 (12.9)||6 (10.7)||16 (13.7)|
|Standardized mortality ratio (95% CI)||0.70 (0.58–0.79)||0.79 (0.55–0.92)||0.72 (0.48–0.89)||0.52 (0.21–0.79)||0.70 (0.47–0.87)|
Abbreviations: CI, confidence interval; IVIG, intravenous immunoglobulin; SCORTEN, SCORe of Toxic Epidermal Necrolysis; SJS/TEN, Stevens-Johnson syndrome/toxic epidermal necrolysis.
Important in-hospital complications of SJS/TEN included acute renal insufficiency (130/377; 34.5%), intubation (89/377; 23.6%), pneumonia (57/377; 15.1%), urinary tract infection (55/377; 14.6%), bacteremia (50/377; 13.3%), sepsis (48/377; 12.7%), major thromboembolic event/diffuse intravascular coagulation (31/377; 8.2%), and cutaneous infection (30/377; 8.0%). Average length of hospital stay for those surviving to discharge was 16.2 days (SD = 16.1). Overall length of hospital stay (including those who died) was 21.9 days (SD = 79.9).
This study represents one of the largest existing SJS/TEN cohorts to date and describes the US dermatology hospitalist experience with SJS/TEN. Although not necessarily representative of the experience of all such patients in the United States, the cohort is geographically diverse and drawn from a broad array of tertiary referral centers around the country. Unlike cohorts derived from insurance claims data, all included cases of SJS/TEN were diagnosed and later confirmed by experienced providers specializing in inpatient dermatology.
Frequent disease triggers in this cohort, including trimethoprim/sulfamethoxazole, β-lactam antibiotics, antiepileptics, allopurinol, and (among infections) Mycoplasma pneumoniae, were similar to those previously reported in the literature (
Canavan et al., 2015,
Halevy et al., 2008). In contrast with a large European cohort in which allopurinol was the drug most commonly associated with SJS/TEN (accounting for 17.4% of cases), in this cohort trimethoprim/sulfamethoxazole (26.3%) was the most common cause (
Halevy et al., 2008). Differences in physician prescribing habits and medication use rates in the patient populations may at least partially account for these differences.
Medications are responsible for the vast majority of SJS/TEN cases, and this cohort was no exception, but prior work has shown that a substantial minority of cases can be attributed to other exposures (
Heng et al., 2015,
Sassolas et al., 2010). We included such cases with presumed infectious triggers as long as they satisfied the consensus criteria for SJS/TEN, but there are ongoing efforts to reclassify such cases to reflect differences in their clinical presentations and severity (
Canavan et al., 2015). Among the 13 cases of SJS/TEN in this cohort attributed to infection, there was one in-hospital mortality (7.7%).
A higher-than-expected percentage of black and Asian patients in this cohort compared with the background US population suggests that these individuals may be at increased risk of SJS/TEN (
Frey et al., 2017,
Hsu et al., 2016). However, further work is needed to quantify any increased risk more accurately and to explore reasons for possible racial disparities, including genetic variations, patterns of medication use, and access to care, as well as disease outcomes.
Disease severity and medical complexity—as measured by the area of involved skin, SCORTEN predicted mortality, and medical comorbidities—were high in this group, reflecting the makeup of the cohort drawn from tertiary care academic medical centers. Most patients were managed in an intensive care unit or burn unit (depending on local institutional practice), a surrogate for careful fluid and electrolyte management, temperature regulation, nutritional support, airway maintenance, wound care, infection surveillance, and other specialized care associated with improved outcomes (
Palmieri et al., 2002,
Schwartz et al., 2013a,
Schwartz et al., 2013b). This percentage (68.2%) was greater than that reported in the RegiSCAR cohort (55%) (
Sekula et al., 2013). Still, almost one third of patients were managed primarily in a nonspecialized medical ward. Because SJS/TEN can progress rapidly, previously published guidelines recommend initial management in a specialized unit (
Creamer et al., 2016,
Lim et al., 2016).
Besides intensive supportive care, published literature has not consistently shown benefit from the use of any particular systemic therapy (
Creamer et al., 2016,
Roujeau and Bastuji-Garin, 2011). Treatment with corticosteroids has shown mixed results for SJS/TEN, with some studies showing either no benefit or increased infection, duration of hospital stay, and mortality (
Halebian et al., 1986,
Kelemen et al., 1995,
Kim et al., 2005), and others showing a possible mortality reduction, including the results of a recent meta-analysis (
Hirahara et al., 2013,
Kardaun and Jonkman, 2007,
Liu et al., 2016,
Schneck et al., 2008,
Zimmermann et al., 2017). The efficacy of IVIG in the treatment of SJS/TEN is similarly uncertain. Case series and a systematic review suggest that IVIG, particularly high-dose IVIG (>2 g/kg total dose), improves survival (
Campione et al., 2003,
Huang et al., 2012,
Prins et al., 2003,
Trent et al., 2003,
Viard et al., 1998), but other reviews, and the 281-patient EuroSCAR cohort, showed no mortality benefit (
Faye and Roujeau, 2005,
Firoz et al., 2012,
Lee et al., 2013,
Schneck et al., 2008,
Zimmermann et al., 2017). Some studies have suggested improved outcomes in those receiving both corticosteroids and IVIG (
Chen et al., 2010,
Yang et al., 2009,
Ye et al., 2016). Although the ability to draw definitive conclusions from our data is limited, those receiving both agents in this cohort had the lowest standardized mortality ratio (0.52; 95% CI = 0.21–0.79) of any treatment group, suggesting a reason for further study of combination corticosteroids and IVIG as a therapeutic option for SJS/TEN.
The choice of pharmacotherapies for SJS/TEN in this cohort mirrored what is known of US practice. Providers who care for patients with SJS/TEN more frequently are more likely to prescribe IVIG (
Curtis et al., 2016), and in this cohort managed by inpatient consultative dermatologists, IVIG was used extensively (55.6% of patients). Patients receiving IVIG had more severe disease at presentation, as measured by higher median BSA involvement (30% vs. 12%, P < 0.01) and higher rates of TEN (28.0% vs. 18.7%, P = 0.01) on admission, consistent with survey responses from US providers, who are more likely to use IVIG when they perceive SJS/TEN to be more severe (
Curtis et al., 2016). Such differences in disease severity may not be completely accounted for by adjusting for SCORTEN-predicted mortality, and this must be considered when determining the efficacy of IVIG versus other therapies.
Emerging data from Europe, including a meta-analysis and systematic review, report a mortality benefit from treatment with cyclosporine (
Arévalo et al., 2000,
Gonzalez-Herrada et al., 2017,
Kirchhof et al., 2014,
Lee et al., 2017,
Reese et al., 2011,
Valeyrie-Allanore et al., 2010,
Zimmermann et al., 2017), whereas a more recent retrospective cohort study showed no benefit (
Poizeau et al., 2018). Etanercept has also been reported beneficial in a small case series (
Paradisi et al., 2014) and, recently, in a randomized trial (
Wang et al., 2018). Only five patients in this cohort were treated with these agents, so no conclusions can be drawn about their efficacy from these data. The high rate of acute renal insufficiency among those with SJS/TEN, as observed in this cohort, could complicate the dosing and administration of cyclosporine and other systemic SJS/TEN therapies to some patients. In general, a lack of consensus regarding the appropriate pharmacologic management of SJS/TEN persists (
Curtis et al., 2016), even among this group of experienced providers.
The overall survival rate in this cohort was better than reported in the literature and significantly better than predicted by SCORTEN. Published SJS/TEN mortality rates are roughly 20%–25% (
Schneck et al., 2008). In this cohort, mortality was 14.7%, compared with 21.1% predicted by SCORTEN. The standardized mortality ratio was 0.70 (95% CI = 0.58–0.79), compared with a standardized mortality ratio of 0.82–0.92 reported in a large systematic review (
Roujeau and Bastuji-Garin, 2011). The improved survival of these patients likely reflects a combination of factors, perhaps including excellent supportive care in tertiary centers, increased use of ICUs or burn units, the presence of experienced consulting dermatologists, inaccuracy of SCORTEN as a predictive tool, or other factors.
Although mortality in each treatment subgroup (IVIG, corticosteroids, IVIG + corticosteroids, and supportive care alone) was significantly lower than predicted by SCORTEN, outcomes in individual subgroups may not be directly comparable to one another because SCORTEN-predicted mortality may not fully account for mortality risk. Without adjusting for additional confounding variables beyond SCORTEN-predicted mortality, these results must be interpreted with caution, and no definitive conclusions regarding optimal treatment choice should be drawn at this time. Further work attempting to account for medical comorbidities, timing of diagnosis, provider decision-making, and other potential confounding factors is necessary to adjust for differences in treatment groups that might offset any relative benefit (or harm) caused by a particular therapeutic agent.
Despite its large size, limitations of this study include the heterogeneity of patients, supportive care, and pharmacotherapeutic treatment decisions and the difficulty of accounting for all relevant confounders. Although involvement of an expert specializing in inpatient dermatology at all stages of diagnosis and management, case selection, and data entry may be a source of reliability compared with some cohorts, the limitations and biases inherent in retrospective study design must be acknowledged. In particular, we note the potential for bias in diagnosis and selection of cases and nonstandardized determination of SJS/TEN causality by treating providers. In addition, disease severity assessment based on clinical estimation of epidermal detachment may be inaccurate. Prospective data collection with centralized case review and standardized assessment and management protocols might improve diagnostic accuracy, causality determination, and homogeneity of data.
Future work includes revising the SCORTEN mortality prediction model, which was developed in 2000 at a single center in France and remains the standard for predicting mortality in patients with SJS/TEN (
Bastuji-Garin et al., 2000,
Cartotto et al., 2008,
Trent et al., 2004). Further analysis should attempt to identify risk factors for mortality in this multi-institutional US cohort and develop additional models to help explore the relationship between choice of treatment and mortality outcome. Prospective multicenter studies with standardized treatment and supportive care regimens and, ultimately, well-planned randomized controlled trials are necessary next steps to bring additional clarity to questions of management, mortality, and long-term sequelae. This study has created a research network of inpatient consultative dermatologists within the Society of Dermatology Hospitalists, which is well-positioned for the conduct of future studies in SJS/TEN and other rare diseases.
This study represents one of the largest SJS/TEN cohorts to date and provides additional, contemporary information regarding disease causes, severity, management, and outcomes among validated cases managed at tertiary care centers in the United States.
Trimethoprim/sulfamethoxazole was the most common disease trigger. Mortality was lower than reported in the literature and significantly less than predicted by SCORTEN among all subgroups, including those receiving supportive care only. Despite these better-than-predicted outcomes, mortality, in-hospital complications, and length of hospital stay remain high, and the optimal approach to management of SJS/TEN remains unclear. Further research is necessary to develop evidence-based treatment guidelines, including supportive care protocols and recommendations for use of effective pharmacotherapies. Based on the results of this study, co-administration of corticosteroids and IVIG could be considered among the regimens deserving further study in future prospective trials. Finally, care in a specialized center, preferably with access to an experienced consulting dermatologist, may be beneficial.
Materials and Methods
Patients age 18 years and older with SJS/TEN hospitalized at the participating institutions between January 1, 2000 and June 1, 2015 were identified from inpatient consult databases and electronic medical record systems. Not all centers had data available from the earliest part of the study period; consequently, most cases were derived from the latter part of the study period. Initial diagnoses of SJS/TEN were made at the time of presentation by expert consultants specializing in inpatient dermatology (dermatology hospitalists) using all available clinical, laboratory, and histologic features. All diagnoses were subsequently confirmed before study entry by the dermatology hospitalist principal investigator at each site via detailed chart review, based on predefined clinical and histologic parameters (e.g., presence of epidermal detachment, erosion of >2 mucous membranes, dusky/atypical target lesions, exclusion of alternate diagnoses, and histologic findings of epidermal necrosis). Histology results were available for review and showed findings characteristic of SJS/TEN in 73% of cases. Cases with insufficient information to support the diagnosis of SJS/TEN were discarded. Equivocal cases were adjudicated by a centralized reviewer to make final determination of inclusion/exclusion. To minimize the risk of possible misclassification, only cases meeting the consensus definition of SJS/TEN proposed by
Bastuji-Garin et al. (1993)were included.
Because of the difficulty of uniformly applying causality assessment tools retrospectively (as well as the overall poor reliability of available tools compared with expert opinion) (
Goldman et al., 2017), determination of the cause or trigger of SJS/TEN in this study was based on the expert opinion of the treating inpatient dermatology specialist at the time of diagnosis, based on all available clinical data.
Detailed medical information, including timing of disease onset (defined as the onset of mucocutaneous symptoms), relevant demographics, medications received (including dates of initiation and discontinuation), medical comorbidities and other potential mortality risk factors, laboratory data, physical examination, treatment regimen and timing, and outcome (morbidity and mortality), was extracted from the medical record using a standardized form and managed in a secure database using Research Electronic Data Capture (i.e., REDCap) tools hosted by the University of Pennsylvania (
Harris et al., 2009). The cohort was analyzed collectively, and participants were also grouped into one of four large subgroups for comparative analysis based on systemic treatment received (IVIG vs. corticosteroids vs. IVIG + corticosteroids vs. supportive care only).
Descriptive statistics were used to examine the frequency and distribution of covariates of interest. Comparisons between groups were made using chi-square analysis or Fisher exact test for dichotomous variables and the Student t test or the Mann-Whitney rank sum test for continuous variables. Standardized mortality ratios and 95% CIs were calculated to quantify the difference between observed and SCORTEN-predicted mortality in the entire cohort and among treatment subgroups. All statistical analyses were performed using STATA 13 (Stata Corporation, College Station, TX).
The study was approved by the institutional review boards at the participating institutions. The requirement for informed consent was waived because all collected data were deidentified.
Conflict of Interest
The authors state no conflict of interest.
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Published online: May 11, 2018
Accepted: April 5, 2018
Received in revised form: March 14, 2018
Received: December 19, 2017
© 2018 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
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