Introduction

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, mucocutaneous drug reactions associated with high mortality and morbidity. Both are part of a disease continuum and are distinguished from each other based on severity and the percentage of body surface area (BSA) involvement [1]. Patients with SJS typically develop a deeply erythematous exanthematous eruption, mucosal and cutaneous bullae, and desquamation, with less than 10% BSA involvement. Patients with TEN have more widespread, rapidly evolving skin sloughing, with greater than 30% BSA involvement. Those with cutaneous involvement between10 and 30% BSA involvement are considered to have SJS/TEN overlap. Although in practice, our approach to SJS may be slightly different from our approach to TEN, for the purpose of this review, the term “SJS/TEN” includes all three disease states.

Patients with SJS/TEN may experience fever and flu-like symptoms early in the course of their disease. Initial skin findings may include an exanthematous eruption, deep red macules and purpura, atypical targetoid lesions, and/or generalized erythema. Patients may also complain of skin tenderness. These are followed by a painful, generalized vesiculobullous eruption and desquamation (Fig. 1). Full-thickness epidermal necrosis leads to splitting of the sub-epidermal layers [2]. Application of shear forces on seemingly intact skin induces epidermal separation and sloughing—a phenomenon known as Nikolsky sign [3]. Mucosal involvement (oral, ocular, and/or genital) occurs in 90% of cases and can precede the generalized eruption [4]. SJS/TEN is associated with significant morbidity and mortality. Extensive skin detachment may lead to insensible fluid loss and a high risk of infections, often resulting in severe multi-systemic derangements.

Fig. 1
figure 1

Coalescing deep red erythematous targetoid macules and papules with blister formation and desquamation in a patient with Stevens-Johnson syndrome/toxic epidermal necrolysis overlap

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The pathogenesis of SJS/TEN is still unclear, but several HLA subtypes have been associated with a predisposition for developing SJS/TEN to specific medications [5•, 6]. Keratinocyte cell death in SJS/TEN is caused by a type IV delayed hypersensitivity reaction, mediated in part by cytotoxic T cells and natural killer cells that release granulysin and activate transmembrane death receptors [7, 8]. Engagement of the programmed cell death surface receptor Fas by its ligand induces keratinocyte apoptosis [8, 9]. More recent studies also point to human leukocyte antigen (HLA) class 1 restricted cytotoxic T cell activity against the offending drug [10,11,12]. Histopathology typically demonstrates epidermal necrosis and keratinocyte apoptosis with basket weave stratum corneum and separation of the dermis and epidermis, and a perivascular lymphocytic infiltrate within the dermis [13]. Our current understanding of the pathogenesis of SJS/TEN is central in the development of therapeutic approaches to this rare but potentially fatal condition.

The relatively rare occurrence of SJS and TEN presents challenges for conducting prospective, randomized, controlled clinical trials to investigate therapies. While SJS is more common than TEN, the pooled incidence is thought to be between one to ten cases per million people per year [14,15,16,17,18]. The most recent studies from the UK, Germany, and Korea point to an incidence of 5.7 or fewer per million people per year [19•, 20•, 21•]. Studies from the USA found an incidence of 5.3 cases (SJS) and 0.4 cases (TEN) per million children per year [22]. The average age of patients with SJS/ TEN varies, but the median age of adult patients in a recent retrospective, multicenter study from the USA was estimated at 49 years (SD 19.2). [2, 23•] Many of these patients have associated co-morbidities, including active infection, diabetes mellitus, active malignancy, kidney, pulmonary and heart disease, seizure disorder, and HIV infection. The natural history of SJS/TEN among pediatric patients is different from that of adults [24]. Pediatric patients with SJS/TEN tend to have better outcomes and lower mortality compared with adults. Although there are similarities in how we approach SJS/TEN in adults and children, the treatment of pediatric SJS/TEN requires a separate discussion.

Medications remain the major cause of SJS/TEN, with infections such as mycoplasma pneumonia and herpes simplex comprising a smaller population [23•]. Antibiotics (especially trimethoprim-sulfamethoxazole), antiepileptic medications, allopurinol, and NSAIDs remain commonly implicated causes of drug-induced SJS/TEN [23•].

Mortality ranges from about 24% in SJS to about 49% in TEN after 1 year [25]. A 2017 study using data from the US Health Care Utilization Project (HCUP) National Inpatient Sample (NIS) from 2009 to 2012 estimates inpatient mortality rates to be 4.8% for SJS, 14.8% for TEN, and 19.4% for SJS/TEN overlap [22•]. Recent findings point to a reduced mortality, likely due to improved SJS/TEN management, overall improvements in health care, and/or other patient factors [23•].

The SCORTEN is a validated, prognostic scoring system that estimates mortality based upon clinical features and laboratory values on days 1 and 3 of hospitalization [26] (Table 1). New evidence suggests that the SCORTEN may overestimate mortality in contemporary patients [23•, 29,30,31]. An updated model, the ABCD-10, has been proposed, based on a retrospective, multicenter study conducted in the USA (Table 1) [27•]. Further research is required to determine the generalizability of this updated model. These scoring systems are important not only for guiding management but also in the conduct of both retrospective and prospective studies on SJS/TEN. Due to the relative rarity of these severe drug reactions, and inherent challenges in designing comparative trials, studies investigating the efficacy of therapies for SJS/TEN typically utilize differences in standardized mortality ratio as a primary outcome measure. That is, the efficacy of a treatment modality for SJS/TEN is assessed by comparing the observed, vs the SCORTEN-predicted mortality, among who received that treatment.

Table 1 Comparison of SCORTEN and ABCD-10 model with predicted mortality values
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Management of SJS/TEN is divided into two arms: supportive care and adjuvant medication therapies. There remains an unmet need for good quality, prospectively collected data that informs us about the appropriate treatment for SJS/TEN. National societies have developed consensus guidelines, but also highlight this knowledge gap [32•, 33•, 34•]. This review serves to provide an update on the literature for the management of SJS/TEN.

Supportive Care

Supportive care remains the mainstay of treatment for SJS/TEN. Supportive management of SJS/TEN should include removal of inciting drug, transfer to appropriate level of care, and multidisciplinary management medical co-morbidities, fluid and electrolyte balance, airway, nutrition, and temperature (Fig. 2). Wound care, pain control, and prevention of infection are also essential [35•].

Fig. 2
figure 2

A potential step-wise approach to SJS/TEN supportive care [32, 35]

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Initial Management

The first and most crucial step in a patient presenting with SJS/TEN is discontinuation of the culprit drug. Prompt withdrawal has been shown to lead to better outcomes and a reduced risk of death [36•]. Patients should be admitted to the hospital if SJS/TEN is suspected, and prognosis evaluated using SCORTEN. The SCORTEN score can be helpful in determining whether a patient’s disease is severe enough to require a specialized intensive therapy or burn unit, or whether a nonspecialized ward is sufficient. Any pre-existing or associated co-morbidities need to be identified and addressed. The need for expertise and resources for advanced wound care, fluid and electrolyte resuscitation, and advanced medical care should be considered in deciding where to admit the patient. Generally, patients with involvement of large areas of epidermal loss (> 10% body surface area) or a high SCORTEN score should be transferred to a specialized intensive care or burn unit [32•]. Patients with SJS/TEN are also more likely to have underlying co-morbidities that are risk factors for both developing severe cutaneous drug reactions and poorer outcomes—HIV, malignancies, autoimmune disease, viral infections, renal, pulmonary and cardiac disease, among others. Patients may also develop involvement of other organ systems as part of their SJS/TEN [37•]. Access to expertise and appropriate medical monitoring and support depending on medical risk factors is equally crucial in the care of patients with SJS/TEN.

Wound Care

Wound care is an essential part of caring for patients with SJS/TEN. It helps preserve the epidermis, prevent infection, and minimize water loss [31]. An optimal approach to wound care in these patients has yet to be determined, and strategies, choice of dressings, can differ among various medical centers.

Our overall approach to wound care in SJS/TEN is the same as our approach to other immune-mediated conditions of epidermal separation. We prefer the use of simple dressings composed of bland ointments such as white petrolatum and nonstick dressings. Other authors prefer the use of advanced dressings, such as fiber, biologic, and synthetic dressings, and note that patients treated with advanced dressings may require fewer dressing changes. There does not appear to be a significant difference, however, in the healing time among SJS/TEN patients treated with simple vs advanced dressings [38•, 39•]. In our hands, the frequency and choice of dressings depend on the extent and characteristics of the wounds (i.e., how exudative the wounds are, whether or not there are signs of superimposed infection).

Certain medical centers or burn units follow an aggressive debridement policy, in which wounds are actively debrided and necrotic epidermis removed either surgically or through whirlpool therapy [40•]. This kind of aggressive surgical approach can facilitate adherence of modern dressings such as allografts, xenografts, or BIOBRANE to the underlying dermis, but is also associated with an increased risk of infection and hyperpigmentation [30•, 41•]. Our preferred approach, on the other hand, is a conservative strategy of leaving the detached skin in situ to act as a biologic dressing unless there are clear signs of infection or necrosis [41•]. In a recent observational study in a burn unit setting, a more conservative wound care program that minimizes or avoids shear stress on wounds, and leaves skin intact, was associated with better than expected rates of survival and re-epithelialization [42]. In addition, the patients required fewer dressing changes, and there was a reduced need for operating room time. The cost of care was also reduced. Wound management must therefore be tailored to the patient’s requirements, including the wound extent and characteristics as well as the patient’s medical status.

Fluids, Electrolytes, and Environment

Patients with SJS/TEN should have careful management of their intake and environment. Patients can have imbalances in fluids and electrolytes due to dermal exfoliation, similar to burn victims. However, replacement volumes are approximately one-third lower than those needed for burn victims [43]. The environment should be kept at an optimal temperature, generally at 30–32 °C to prevent excess caloric expenditure [2]. SJS/TEN patients should be given oral nutrition as soon as possible and continued throughout the acute phase, via nasogastric tube if necessary, in order to maintain caloric needs [17, 32•].

Infection Control and Management of Co-morbidities

Patients with SJS/TEN can develop other organ co-morbidities. The development of associated infection and sepsis, however, remains the most prominent causes of morbidity and mortality in patients with SJS/TEN [2, 17]. In a recent retrospective study, a low hemoglobin (< 10 g/dL) on admission, pre-existing cardiovascular disease, and > 10% BSA involvement on admission were predictors of the development of bacteremia [44•]. Nonetheless, prophylactic antibiotics are not regularly used and have not been shown to improve outcomes [45]. Management primarily revolves around careful clinical assessment and appropriate wound care and sterile handling. Antiseptic solutions can also be used for disinfection, in conjunction with wound care materials [32•], as long as one is mindful of the risk of systemic absorption when used in large, denuded areas. Cultures of the skin, blood, catheters, and gastric or urinary tubes should be obtained as medically indicated, with other authors recommending that this be done at 48-h intervals [2, 46]. Signs of infection include visible superinfection of skin lesions, increase in quantity of bacteria on culture, a sudden decrease in temperature, or deterioration of patients’ condition [2]. Hypothermia and a pro-calcitonin > 1 μg/L at the time of blood culture was found to be predictive of bacteremia [44•]. Other more subtle signs of infection including neutrophilia or increased C reactive protein can indicate the need for systemic antibiotic therapy [32•].

Prevention of Sequelae

Special care must be given to avoid ophthalmologic and urogenital complications. A careful history and physical examination should include evaluation of these organ systems, as regular monitoring and early detection is very important to prevent severe irreversible consequences [35•]. A 1997 retrospective study on SJS/TEN found that 12.5% of its 40 participants had chronic gynecological sequelae, and that these cases often could be successfully corrected with appropriate intervention. [47] Women with vaginal involvement of SJS/TEN can develop introital stenosis and labial agglutination with histological findings of vulvovaginal adenosis [48]. These changes commonly lead to functional impairments such as dyspareunia, bleeding, and urinary obstruction, and tissue metaplasia carries a risk of malignant transformation [49]. Strategies to prevent these long-term sequelae include topical glucocorticoids as first-line therapy, vaginal molds to disrupt adhesion formation, and menstrual suppression [48]. Urology specialists may also be consulted to check for urogenital involvement.

Ocular involvement occurs in about 80% of patients with SJS/TEN is varied and can range from a mild acute conjunctivitis to severe pseudomembranous ulcers [50]. The conjunctiva, cornea, and anterior chamber may be affected causing symptoms of pain and photophobia. The SCORTEN score used to predict mortality in SJS/TEN patients does not appear to correlate with the development of ocular complications in several studies, and so it is important to monitor closely for ocular involvement regardless of SCORTEN value. [51, 52] Long-term sequela occurs in 50–90% of patients and includes pain, dry eye, trichiasis, neovascularization of the cornea, keratitis, and scarring and formation of synechiae between the conjunctiva and eyelid [53, 54]. To prevent or reduce these sequelae, patients should be referred to an ophthalmologist for a comprehensive evaluation and aggressive, early treatment. Ocular involvement is typically graded from none to severe (grades 0–3) in effort to both assess the severity of involvement and guide therapy [55]. Lubrication drops and close monitoring are recommended for patients with no initial eye involvement (grade 0), as these patients can still have long-term complications [53]. Patients with conjunctival hyperemia (grade 1) require topical corticosteroid and antibiotic preparations. For patients with involvement of the bulbar conjunctiva or pseudomembrane formation (grades 2 and 3), amniotic membrane transplantation is added to the treatment armament and is shown to reduce sequelae in case studies and a randomized control trial [56, 57]. In all patients, saline rinses can also be initiated as a supportive measure to clear inflammatory debris from the eye [58]. To prevent scarring and loss of visual acuity, it is critical that these measures are taken early in the disease course.

Pain Control and Emotional Support

Many patients have significant pain, especially at sites of epidermal detachment. Mild pain can be controlled with acetaminophen, supplemented with opiate-based therapy for more severe pain [32•]. Additionally, patients with SJS/TEN can have psychological sequelae and reduction in quality of life [59]. Clinicians should keep this in mind and provide appropriate emotional support and information for patients and their families.

Adjuvant Therapy

In addition to supportive therapies, there is an increasing interest in adjuvant medical therapies that may speed re-epithelialization and reduce mortality in patients with SJS/TEN. In spite of the lack of conclusive data on the benefit of adjuvant pharmacologic therapy for SJS/TEN, a recent multicenter retrospective study demonstrated that the majority of patients are treated with pharmacologic therapy (70.7%) vs supportive care alone (29.3%) [23•]. Therapies such as cyclosporine, corticosteroids, IVIG, anti-TNF-alpha antibodies, and plasmapheresis, used alone and in combination, have shown mixed results in various studies (Tables 2 and 3). Most of the data addressing the use of adjuvant therapy for SJS/TEN is derived from case reports/series and retrospective studies, or non-comparative, small, prospective clinical trials. An exception is a recent open-label, randomized clinical trial comparing the use of etanercept with systemic corticosteroids in the treatment of SJS/TEN [68•]. Analysis of outcomes in most of these studies relies on differences between the observed mortality rate and the predicted mortality by SCORTEN. As a result of these limitations, there continues to be little consensus among experts on the ideal adjunctive therapy for SJS/TEN. In one of the rare, prospective, randomized clinical trials performed, the use of thalidomide for SJS/TEN was associated with increased mortality. It is therefore firmly contraindicated for use in SJS/TEN.

Table 2 Review of adjuvant therapies
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Table 3 Trials, systematic reviews, and observational studies of adjuvant therapies
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Corticosteroids

The use of systemic corticosteroids in patients with SJS/TEN remains controversial. In our practice, we may consider the use systemic corticosteroids for certain SJS patients who have milder disease. Although some retrospective studies have shown lower than expected mortality rates among patients with SJS/TEN who were treated with systemic corticosteroids, other studies have shown no significant benefit (Table 3). More recent retrospective data suggests that corticosteroids may be more useful in combination with other pharmacologic therapies (Table 3). There is also evidence that short-term, high-dose pulse corticosteroids may improve outcomes [63, 77]. Potential adverse effects of steroid use include sepsis, skin infection, slowed epithelialization, and increased protein catabolism. Systemic corticosteroids are relatively contraindicated for patients with widespread skin detachment [78].

In a systematic review published in 2011, 20 of 128 children in their included studies received a short duration of prednisolone, prednisone or methylprednisone. There were no deaths reported among these 20 patients, although 5 of the 20 had mild skin infections [77]. The 2013 RegiSCAR examined a registry of 442 patients and did not find a survival advantage for systemic corticosteroids, or any other adjuvant therapies for that matter [25]. This was a departure from the 2008 retrospective EuroSCAR study, which showed a potential benefit for corticosteroid use in 281 patients [79]. In another 2011 systematic review, mortality was similar to those predicted by SCORTEN in corticosteroid and supportive measures group [66]. More recently, a 2017 meta-analysis of data including 1209 patients demonstrated a decreased risk of death in patients treated with corticosteroids and supportive therapy compared with supportive therapy alone [64•]. There is also support for use of a short duration (3 days) of high-dose pulsed corticosteroids early in the disease course to decrease mortality, slow disease progression, and speed healing [63, 77].

Cyclosporine

As a stand-alone therapy, cyclosporine has more robust evidence for improved outcomes for SJS/TEN among adjuvant therapies. Cyclosporine inhibits interleukin-2 mediated T cell activation, and may also inhibit apoptosis by repressing NF-kB activation [65]. Adverse side effects from cyclosporine may include leukoencephalopathy, neutropenia, pneumonia, and nephropathy.

A 2018 meta-analysis of nine retrospective and prospective observational studies found that the observed mortality among SJS/TEN patients who received cyclosporine was approximately 70% less that predicted by SCORTEN [80•]. A 2017 systematic review and meta-analysis also found decreased mortality in patients who were treated with cyclosporine compared with IVIG, consistent with findings from a 2014 retrospective review [81•, 82]. Other recent studies also show benefits for patients treated with cyclosporine [83•, 84]. In a review of data from 93 patients who received either cyclosporine or systemic corticosteroid therapy, investigators found that patients who received cyclosporine had complete re-epithelialization of their skin compared with those treated with systemic steroids (9.6 vs 14.1 days, respectively) [69]. Hospital stay of patients in the cyclosporine group was 7 days shorter than those in the corticosteroid group, although this was not statistically significant. In a case series, three pediatric patients who had rapid improvement and near complete resolution 10–15 days after being given 3 mg/kg/day for 7–21 days [85•]. Not all data is supportive, however, as one recent retrospective cohort did not demonstrate a benefit for patients treated with cyclosporine [86•].

An open-label, uncontrolled, phase II trial of 3 mg/kg/day of oral cyclosporine for 10 days given to 29 patients with SJS, TEN, or overlap SJS/TEN showed a modest reduction in observed mortality compared with the SCORTEN prediction, and re-epithelialization within 12.4 ± 7.7 days [72]. In another uncontrolled open-label study, 11 patients with SJS, TEN, or overlap SJS/TEN were given oral cyclosporine, 3 mg/kg per day for 7 days and then tapered over another 7 days. Patients had improved time to re-epithelialization, reduced hospital stay, and lower mortality when compared with historical data from corticosteroid-treated patients at the same institution [87].

Human Intravenous Immune Globulin

Human intravenous immune globulin (IVIg) is used for treatment of a variety of autoimmune conditions. Autoantibodies against Fas are thought to interfere with Fas-FasL-mediated apoptosis thereby slowing progression of SJS/TEN [9]. In the USA, this treatment modality is commonly used for patient with a more severe disease with higher median BSA involvement [88•]. Risks of this therapy include acute renal failure, thrombotic complications and hemolysis. Caution should be used with elderly patients and patients with cardiovascular or renal disorders.

Studies that address the efficacy of IVIg monotherapy for SJS/TEN have had mixed results. In the early 2000s, there were several studies that had showed improved survival among SJS/TEN patients who were treated with high-dose (2 g/kg or more) IVIg significantly improved survival with high doses [9, 71, 89,90,91]. A 2011 systematic review of treatments for SJS and TEN demonstrated 24% mortality rate for patients treated with IVIg compared with 27% for those treated with supportive therapy only [66]. The observed mortality in the IVIG group, however, was still lower than mortality as predicted by SCORTEN [66]. A 2012 systematic review that included 17 studies showed that adults who received high-dose IVIg had a decreased mortality compared with those who received low-dose IVIg [24]. This association with IVIg and mortality benefit, however, did not hold when this was subjected to a multivariate regression model. In that same systematic review, none of the pediatric patients who received IVIg died, but pediatric patients with SJS/TEN may have better outcomes overall compared with adults. A 2015 meta-analysis that included data from 391 patients, however, found no difference in mortality for the IVIG group compared with the supportive care group [76]. However, the authors did find a significant association between increasing doses of IVIg and improved mortality when they subjected their data to further analysis. Zimmerman et al. found no reduction in mortality compared with supportive therapy alone in a 2017 meta-analysis of 215 patients treated with IVIg [64•]. More recent retrospective data suggests that patients treated with a combination of IVIg and corticosteroids may have better outcomes that those treated with either therapy by itself. In a 2018 multicenter study of 377 patients from the USA, patients who received a combination of IVIG and corticosteroids had a greater reduction in their observed vs SCORTEN-predicted mortality, when compared with patients who received either IVIG or corticosteroids alone [23•]. Prior studies support these findings of reduced mortality and enhanced disease resolution in patients treated with a combination therapy IVIg therapy [79, 92, 93]. A 2016 meta-analysis for IVIG and corticosteroid combination therapy found benefits in hospital stay but not mortality [94•]. Dosing and duration of combination therapy was different for each study.

TNF-α Inhibitors

TNF-α is potentially upregulated in TEN and thought to promote apoptosis. TNF-α monoclonal antibody (infliximab) and TNF-α decoy receptor (etanercept) that target TNFα are being actively explored as potential therapies for SJS/TEN. Potential adverse effects include sepsis and respiratory failure. In case reports, 5 mg/kg of infliximab immediately halted the progression of skin detachment and induced re-epithelization within 2–10 days [28, 60,61,62, 95]. Other case reports have shown a benefit from a single 50-mg subcutaneous injection of etanercept [67]. In a landmark randomized, unblinded, comparative, clinical trial, 96 patients with SJS/TEN received either etanercept 25 mg (or 50 mg if their body weight was > 65 kg) by subcutaneous injection twice a week or 1–1.5 mg/kg/day IV prednisolone until their skin lesions were healed [68•] . Patients treated with etanercept had improved mortality compared with patients treated with corticosteroids. In addition, patients who had > 10 BSA involvement had a shorter median time to complete healing when they were treated with etanercept vs corticosteroids (14 vs 19 days, respectively).

Other Therapies

Other therapies such as plasmapheresis, granulocytic-colony stimulating factor (G-CSF), and thalidomide have been tried for the treatment of SJS/TEN.

Plasmapheresis was proposed as a mechanism for removal of cytotoxic mediators and drug metabolites. Complications from this procedure depend largely on the medical status of the patient and the type of fluids and plasma replacement used, along with infection risk from venous access. A prospective study including 28 patients with SJS/TEN demonstrated that patients who received plasmapheresis had more rapid improvement in their severity of illness score over 20 days compared with the non-plasmapheresis group [70•]. In addition, investigators did not observe any significant difference in their outcome measures among patients who received plasmapheresis as monotherapy vs those who received concomitant IVIg or corticosteroids. An earlier case series, on the other hand, suggested no improvement in mortality, length of hospital stay, or time to re-epithelialization [73]. Plasmapheresis may nevertheless be an option, however, among patients with refractory SJS/TEN [74, 75].

G-CSF is thought to have bioregenerative and immunomodulating properties and currently under investigation. Thalidomide is a potent TNF-α inhibitor. Unlike infliximab and etanercept, it is firmly contraindicated for the treatment of SJS/TEN, as it was shown to increase mortality in a randomized placebo-controlled trial in patients with TEN [96, 97, 98•, 99•, 100, 101•, 102•].

Ongoing and Future Clinical Trials

There is a critical need for interventional studies that can determine the true effect of adjuvant therapies on mortality, length of hospital stay, time to re-epithelialization, and other important outcomes. Several studies are on the horizon. Ottawa Hospital Research Institute is planning a multicenter, phase III clinical trial to determine if either cyclosporine or etanercept therapy improves short-term outcomes in SJS/TEN compared with supportive care alone (ClinicalTrials.gov Identifier: NCT02987257). Massachusetts General Hospital is sponsoring an upcoming multicenter, prospective, observational study to investigate the efficacy of cyclosporine, IVIG, etanercept, and corticosteroids for patients with SJS/TEN (ClinicalTrials.gov Identifier: NCT03585946). A phase 4 trial to determine the efficacy of four days of 5 μg/kg of recombinant granulocyte-colony stimulating factor (G-CSF) vs placebo, among patients with TEN, is in the recruiting phase (ClinicalTrials.gov Identifier: NCT02739295) as is a pilot, comparative, trial to investigate the efficacy of oral isotretinoin (ClinicalTrials.gov Identifier NCT02795143).

Conclusion

SJS/TEN is a rare but life-threatening condition with a potentially high morbidity and mortality. Tools such as the SCORTEN and ABCD-10 may be used to predict mortality. Management of SJS/TEN remains a challenge and there continues to be a limited consensus due to a lack of prospective studies for this serious but rare entity. A multidisciplinary approach, early recognition of the condition, and removal of the offending agent, along with aggressive supportive therapy, significantly improve outcomes. There may be benefits to using adjuvants alone or in combination, but they must be used cautiously, with consideration of the individual patient’s medical status and potential adverse effects. Majority of the data addressing the use of adjuvant therapy in SJS/TEN is retrospective. Recent, open-label, prospective non-comparative studies investigating the use of cyclosporine, and a randomized, unblinded clinical trial comparing etanercept with corticosteroids have demonstrated a possible benefit of these treatments in SJS/TEN.