Distinguishing between erythema multiforme major and Stevens-Johnson syndrome/toxic epidermal necrolysis immunopathologically

The early clinical presentations of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are similar to that of erythema multiforme major (EMM). Cytotoxic molecules, especially granulysin, are expressed in the skin lesions of SJS/TEN and cause extensive keratinocyte death. It is postulated that the function of regulatory T cells (Treg) in SJS/TEN is inadequate. This study examined whether an immunohistological examination of cytotoxic molecules and the immunophenotype of Treg is useful for discriminating SJS from EMM in the early period. Over the past 9 years, the lesional skin of 14 patients with SJS/TEN and 16 patients with EMM was biopsied. Double immunofluorescence labeling of CD8 and granulysin, perforin, or granzyme B was performed, and immunohistochemical analyses of granulysin, perforin, granzyme B, CD1a, CD3, CD4, CD8, CD68 and Foxp3 were conducted using a highly sensitive indirect immunoperoxidase technique. The number of cells positive for each antibody per five high‐power fields was counted. The proportions of granulysin⁺ cells/CD8⁺ cells (P = 0.012) and perforin⁺ cells/CD8⁺ cells (P = 0.037) in SJS/TEN were significantly higher than in EMM. The number of Foxp3⁺ cells/five high‐power fields in SJS/TEN was significantly lower than in EMM (P = 0.004). Similarly, the number of CD4⁺ cells/five high‐power fields in SJS/TEN was significantly lower than in EMM (P = 0.0017). These data suggest that these panels of antibodies for labeling cytotoxic molecules, CD4 and Treg are useful for discriminating early SJS/TEN and EMM with a skin biopsy.     

High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases

Stevens-Johnson Syndrome (SJS) and Toxic epidermal necrolysis (TEN) are drug-induced diseases with a low incidence but high mortality. While there is no standard treatment, corticosteroids and intravenous immunoglobulin (IVIG) therapy have been widely used, with controversy. Our objective was to summarize the etiology and therapeutic regimen of SJS or TEN in 82 hospitalized patients in China. A retrospective study was performed on 82 patients who were diagnosed with SJS or TEN and hospitalized in Peking Union Medical College Hospital from July 1994 to August 2009. Of them, 24 were treated with IVIG plus corticosteroids (IVIG group) and the other 58 were treated with corticosteroids only (corticosteroids group). SCORTEN was used to evaluate the severity and prognosis of the patients. The efficacy of therapeutic modalities was assessed by the following parameters: starting and the maximum dose of corticosteroids, cumulative dose of corticosteroids before tapering, cumulative dose of IVIG, days of corticosteroid application before its tapering and the hospitalization days. The common agents triggering SJS/TEN in these patients were non-steroidal anti-inflammatory drugs (31 cases), anti-epileptics (18 cases), antibiotics (14 cases), antipodagrics (4 cases), sulfanilamides (4 cases) and others (11 cases), respectively. Carbamazepine was the most common drug, and induced 15 cases of SJS/TEN. The SCORTEN was significantly higher in the IVIG group than that in the corticosteroid group (2.0 ± 1.7 vs 0.8 ± 1.0, P = 0.001). Whereas no differences were observed between the two groups in the parameters including starting and maximum dose of corticosteroids, cumulative dose and the number of application days of corticosteroids before tapering and hospitalization days. However, in patients whose SCORTEN scores were 2, application of IVIG and corticosteroids shortened the duration of hospitalization from 26.4 ± 9.5 d to 18.1 ± 5.3 d (P < 0.05). No significant difference was observed in the incidence of complications between the two groups (54.2% vs 39.7%, P > 0.05). The actual mortalities were 12.5% in the IVIG group and 3.4% in corticosteroid group respectively, which were significantly lower than the predicted values (22.0% and 7.2%, respectively). Standardized mortality ratio (SMR) analysis showed a trend to a lower actual mortality (not significant) with corticosteroid treatment than the predicted mortality (SMR = 0.480; 95% CI: 0.075-1.923) and combination therapy had a tendency to reduce the mortality (not significant) rate of TEN (SMR = 0.569; 95% CI: 0.318-1.910). No significant difference in SMR was found between the two groups (P = 0.1474). Survival analysis showed that a favorable overall survival was associated with younger age (P = 0.0405). Our data indicated that early application of corticosteroids presented beneficial effects on SJS/TEN, and that combination therapy of corticosteroids and IVIG achieved a better therapeutic effect than the administration of corticosteroids alone. We recommend early treatment with IVIG at total doses of more than 2 g/kg in SJS/TEN patients whose SCORTEN are higher than 0.     

重症多形红斑与中毒性表皮坏死松解症患者的临床对比研究

目的探讨重症多形红斑(SJS)与中毒性表皮坏死松解症(TEN)的临床特点与临床治疗。方法对9例SJS和4例TEN住院患者的临床资料进行回顾性分析。结果 SJS组和TEN组患者中药物为最常见病因。TEN组的皮损范围、损害程度、粘膜病变均较SJS组更广泛、更严重。TEN患者主要表现为全身表皮松解,而SJS患者以靶形红斑为特征。TEN患者较SJS患者更易出现并发症。TEN患者病程急性期和恢复期时间均长于SJS患者。9例SJS和4例TEN患者早期均予以足量糖皮质激素治疗,TEN患者同时联用免疫球蛋白,13例患者均获痊愈。结论药物是SJS和TEN发病最主要的原因。TEN患者较SJS患者病变广泛且严重。药物诱发的SJS和TEN患者早期使用足量激素十分必要,TEN患者尚需静脉联用免疫球蛋白,提高抢救成功率。     

Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis

Background Generalized bullous fixed drug eruption (GBFDE) is a rare cutaneous adverse reaction to drugs, and may resemble Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), but is usually considered less severe. Objectives To compare the severity and mortality rate in cases of GBFDE and control cases of SJS or TEN of similar extent of skin detachment. Methods This was a case–control analysis of 58 patients with GBFDE matched by age and extent of skin detachment to 170 control patients with a validated diagnosis of SJS or SJS/TEN overlap. Data for cases and controls were extracted from the EuroSCAR and RegiSCAR databases resulting from two population‐based studies of severe cutaneous adverse reactions conducted in Europe. Preselected outcome criteria were death (primary), and fever, duration of hospitalization and transfer to an intensive care or burn unit (secondary). Results GBFDE affected mainly older patients (median age 78 years, interquartile range 68–84 years); 13 of 58 cases died (22%). The mortality rate was slightly but not significantly lower for patients with GBFDE than controls [28%, multivariate odds ratio 0·6 (95% confidence interval 0·30–1·4)]. Patients with GBFDE and controls did not differ in other preselected criteria for severity. Conclusions Although our study featured limited statistical power, we were not able to confirm that GBFDE had better prognosis than SJS or SJS/TEN of similar disease extent in older patients. Severe cases of GBFDE deserve the attention and active management given to patients with SJS or TEN.     

Profile and pattern of Stevens-Johnson syndrome and toxic epidermal necrolysis in a general hospital in Singapore: treatment outcomes

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but potentially life-threatening, reactions to medications. Both conditions have significant morbidity and mortality. The aim of this study was to document the epidemiological features, aetiologies, treatment and clinical outcomes of retrospectively reviewed data of all patients with SJS or TEN treated from January 2004 to November 2010 in a general hospital. There were 18 cases of SJS, seven cases of SJS/TEN overlap and three cases of TEN. Mean age was 50.6 years, with a range of 13-85 years. The male/female ratio was 1. Drugs accounted for 26 cases; one case was caused by Neisseria gonorrhoea infection. Anti-convulsants (35.7%) were the most common implicated drugs followed by antibiotics (28.5%), non-steroidal anti-inflammatory drugs (NSAIDS) (14.3%), allopurinol (7.1%) and traditional Chinese medication (7.1%). In seven cases, multiple drugs were implicated. Most SJS cases (88%) were treated with corticosteroids, of which 61% were given high-dose systemic corticosteroids. No infective complications were observed. Six out of the seven SJS/TEN overlap syndrome and all three TEN cases were given intravenous immunoglobulins. One patient with TEN died. In conclusion, anti-convulsants, especially carbamazepine, were the most frequently implicated drugs, followed by antibiotics and NSAIDS. High-dose corticosteroids were effective in SJS, whereas intra-venous immunoglobulin were useful in TEN and SJS/TEN overlap syndrome.     

Role of nanocrystalline silver dressings in the management of toxic epidermal necrolysis (TEN) and TEN/Stevens–Johnson syndrome overlap

Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are severe mucocutaneous eruptions. There is currently no defined optimal approach to wound care. The objective of this study was to evaluate silver dressings in the wound‐care management of TEN and SJS/TEN syndrome overlap with a retrospective case review of nine patients with TEN and SJS/TEN overlap presenting to our institution. Nanocrystalline silver dressings appear to be useful in the rapid commencement of healing in these patients. TEN and SJS/TEN overlap are rare conditions. This contributed to a relatively small number of cases included in the study. The ease of application, antimicrobial properties and low frequency of change make nanocrystalline silver dressings ideal in TEN/SJS.     

A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions

Background Drug patch tests (PTs) can reproduce delayed hypersensitivity to drugs and entail a moderate re‐exposure of patients to offending drugs. Objectives To determine the value of PTs for identifying the responsible drug in severe cutaneous adverse drug reactions (SCARs) such as acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods In a multicentre study, PTs were conducted on patients referred for DRESS, AGEP or SJS/TEN within 1 year of their SCAR. All drugs administered in the 2 months prior to and the week following the onset of the SCAR were tested. Results Among the 134 patients included (48 male, 86 female; mean age 51·7 years), positive drug PTs were obtained for 24 different drugs. These included positive tests for 64% (46/72) of patients with DRESS, 58% (26/45) of those with AGEP and 24% (4/17) of those with SJS/TEN, with only one relapse of AGEP. The value of PTs depended on the type of drug and the type of SCAR (e.g. carbamazepine was positive in 11/13 DRESS cases but none of the five SJS/TEN cases). PTs were frequently positive for beta lactams (22 cases), pristinamycin (11 cases) and in DRESS with pump proton inhibitors (five cases), but were usually negative for allopurinol and salazopyrin. Of 18 patients with DRESS, eight had virus reactivation and positive PTs. In DRESS, multiple drug reactivity was frequent (18% of cases), with patients remaining sensitized many years later. Conclusions PTs are useful and safe for identifying agents inducing SCAR.     

Epidemiology of Ophthalmologic Disease Associated with Erythema Multiforme,Stevens‐Johnson Syndrome,and Toxic Epidermal Necrolysis in Hospitalized Children in the United States

The objective of the current study was to characterize the epidemiology and resource use of U.S. children hospitalized with ophthalmologic disease secondary to erythema multiforme (EM), Stevens‐Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). We studied children ages 5 to 19 years hospitalized in 2005 in 11 states, encompassing 38% of the U.S. pediatric population. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified admissions of children with EM, SJS, or TEN and the presence of concurrent ophthalmologic disease, analyzed patient and hospitalization characteristics, and generated age‐ and sex‐adjusted national estimates. We identified 460 children admitted with EM, SJS, or TEN, corresponding to 1,229 U.S. hospitalizations in 2005. Of the children with EM, SJS, or TEN, 60 (13.0%) had ophthalmologic disease, primarily (90.0%) disorders of the conjunctiva. Children with the highest proportions of ophthalmologic disease included those with mycoplasma pneumonia (26.7%), herpes simplex virus (15.6%), upper respiratory infection (13.9%), and lower respiratory infection (13.7%). Individuals with EM, SJS, or TEN and ophthalmologic disease were more likely than those without ophthalmologic disease to receive intensive care unit care (28.3% vs 17.0%, p = 0.03) and to be admitted to a children's hospital (63.3% vs 48.8%, p = 0.03). Ophthalmologic disease was also associated with a significantly longer median length of stay (6.0 days, interquartile range [IQR] 3–9 days vs 3.0 days, IQR 2–6 days, p < 0.001) and median hospital cost ($7,868, IQR $3,539–$17,440 vs $2,969, IQR $1,603–$8,656, p < 0.001). In children with EM, SJS, or TEN, ophthalmologic disease was most common in those with concurrent Mycoplasma pneumoniae and herpes simplex virus infections. Ophthalmologic disease was associated with considerably higher inpatient resource use in this population. Children with EM, SJS, or TEN should be screened and treated early for ophthalmologic disease to prevent morbidity and minimize long‐term sequellae.     

Retrospective analysis of stevens-johnson syndrome and toxic epidermal necrolysis over a period of 10 years

Background:

Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), are the acute emergencies in dermatology practice. Prompt diagnosis and management may reduce the morbidity and mortality in SJS/TEN patients. Early identification of the offending drug is necessary for early withdrawal and to prevent the recurrences of such a devastating illness.

Aims

To study the demography, offending agents, clinical and laboratory features, treatment, complications, morbidity and mortality of SJS/TEN in our hospital.

Materials and Methods:

In this retrospective study, we reviewed the medical records of SJS, TEN, SJS/TEN overlap of inpatients over a period of 10 years

Results:

Maximum number of SJS/TEN cases were in the age group of 11-30 years. Males predominated in the SJS group with a ratio of 1.63:1, whereas females predominated the TEN group with a ratio of 1:2.57.Nonsteroidal anti-inflammatory drugs (NSAIDs) were the commonest group of drugs among the SJS group in 5/21 patients (23.8%). Antimicrobials were the commonest group of drugs causing TEN in 11/25 patients (44%). Mucosal lesions preceded the onset of skin lesions in nearly 50%. Our study had one patient each of SJS/TEN due to amlodipine and Phyllanthus amarus, an Indian herb. The most common morbidity noted in our study was due to ocular sequelae and sepsis leading to acute renal failure respectively. Kaposi''s varicelliform eruption was found in three of our patients.

Conclusion:

Antimicrobials and NSAIDS are the common offending agents of SJS/TEN in our study.     

Causative Drugs and Clinical Outcome in Stevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and SJS-TEN Overlap in Children

Background:

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe adverse drug reactions in children.

Objectives:

The objective was to study the causative drugs and outcome in children with SJS, SJS-TEN overlap, and TEN.

Materials and Methods:

Retrospective analysis of all the in-patient records of children below 18 years of age with the diagnosis of SJS, SJS-TEN overlap, and TEN was carried out.

Results and Conclusions:

Twenty children were identified, eight patients each were diagnosed as SJS and TEN and four as SJS-TEN overlap. Multiple drugs were implicated in 15 cases while single drug was responsible in 5 cases. Antibiotics (40.7%) were implicated as the commonest cause followed by NSAIDS (25.9%) and anticonvulsants (7.4%). Seventeen patients recovered completely and three patients died.     

Epidermal necrolysis: 60 years of errors and advances

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions characterized by extensive epidermal detachment and mucositis. Both are associated with a high mortality rate and significant long‐term morbidity. Since the initial report introducing the term TEN in 1956, diagnosis of the condition has been fraught with difficulties that continue to exist today. The terms ‘erythema multiforme major’ (EMM) and SJS, and their relationship to TEN have also been confusing to clinicians. It is now recognized that EMM is a different entity from SJS and TEN in terms of demographics, causality and severity. SJS and TEN represent a continuum of disease, and differ only by the extent of epidermal detachment and therefore severity. The term ‘epidermal necrolysis’ (EN) is used in this article to describe the spectrum of disease that includes SJS and TEN. Important advances in understanding the pathomechanism and treatment of EN have been made over the years. These include the recognition of human leucocyte antigen (HLA) associations (e.g. HLA‐B*1502 with carbamazepine‐induced TEN) and understanding of the pathogenic roles of drug‐specific cytotoxic T cells and granulysin. It was previously believed that widespread keratinocyte death in EN is predominantly mediated by soluble Fas‐ligand and that intravenous immunoglobulin therapy is useful in blocking this mechanism with resultant survival benefits. Further studies have since proven these theories to be incorrect. This short review describes the key advances in the terminology, classification, causality and treatment of EN, and identifies future priorities and challenges in the understanding and management of this condition.     

Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens–Johnson syndrome/toxic epidermal necrolysis

Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, skin blistering conditions in which areas of skin die and detach. They actually represent a single disease with a spectrum of severity: less than 10% body surface area detachment in SJS and more than 30% in TEN. It affects around 500 people in the UK each year and is most commonly caused by a reaction to a wide-range of commonly prescribed drugs. This study brought together researchers and patients from the U.K., Spain, Taiwan and the U.S.A. and aimed to determine levels of a protein called high mobility group box 1 (HMGB1) in the serum (part of the blood), blister fluid and skin biopsy tissue of SJS/TEN patients. HMGB1 is a protein which is known to be a marker (biological sign) of a) tissue/cell injury and b) activation of the immune response, both of which occur in SJS/TEN. The authors detected elevated serum HMGB1 levels in SJS/TEN patients at the time of reaction in three independent patient populations, and also extremely high levels in patients’ blister fluid. Levels of HMGB1 in the epidermal (upper) layer of the skin were considerably decreased in SJS/TEN patients but not healthy control or drug-induced rash skin. The decrease in HMGB1 levels in the epidermis of the skin appears to occur prior to blistering and may represent an early indicator. In addition, levels of HMGB1 appear to be retained at the junction between the epidermis and the next layer of skin, called the dermis, which may suggest a potential role for HMGB1 in the mechanism by which the layers become detached in SJS/TEN patients. The authors conclude that serum HMGB1 may not represent a good clinical marker of SJS/TEN, but that decreased levels of it in the skin may be a sign of the early onset of skin blistering, and could have a key role in the mechanism by which this occurs.     

Toxic epidermal necrolysis and Stevens-Johnson syndrome after COVID-19 infection and vaccination

Stevens-Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes; toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID-19 have been limited. We present a review of TEN/SJS after COVID-19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty-eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS-TEN overlap after COVID-19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID-19 vaccines can activate T-cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID-19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug-induced TEN/SJS. Treatments for post-infection and post-vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication.     

Erythema multiforme,Stevens–Johnson syndrome and toxic epidermal necrolysis: Frozen‐section diagnosis

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)‐like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM‐like lesions, we performed frozen‐section diagnosis. Thirty‐five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial‐visit day. Half of a histological section taken from a lesion was snap‐frozen and immediately cryostat‐sectioned, acetone‐fixed and stained with hematoxylin–eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft‐versus‐host reaction (GVHR)‐like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS‐TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS–TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR‐like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS–TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN).     

Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany

Little work has been carried out on the epidemiology of the two serious skin reactions--toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, beta-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs.     

Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality. Some expressions of lupus erythematosus (LE) may cause enormous difficulties in differentiating them from SJS and TEN by showing large areas of sheet‐like epidermal necrosis. Objective To evaluate clinically and histopathologically probable or definite cases of SJS/TEN with a history of systemic or other LE [(S)LE]. Methods This was a retrospective analysis of validated cases of SJS/TEN with a history of (S)LE, based on a large population‐based national registry. Results Among 1366 patients with SJS/TEN, 17 with a sufficiently documented history of (S)LE and representative histological material could be identified, suggesting a considerable over‐representation of LE in patients with SJS/TEN. Eight of these showed clinically and/or histopathologically some LE‐characteristic features interfering with the diagnosis of SJS/TEN. Differentiation could be elaborated on clinical and histopathological grounds: four patients were classified as SJS/TEN with a preceding (S)LE exacerbation and/or LE‐typical histopathological features, and four as ‘TEN‐like’ (S)LE. Conclusion Most patients with SJS/TEN and a history of (S)LE demonstrate clinical and histopathological properties allowing clear differentiation. However, occasionally acute cutaneous manifestations of (S)LE and SJS/TEN can be phenotypically similar, caused by extensive epidermal necrosis. Although no feature by itself is conclusive, a combination of recent (S)LE exacerbation, evident photodistribution, annular lesions and absent or only mild focal erosive mucosal involvement may favour LE over SJS/TEN clinically. Histopathologically, in particular, junctional vacuolar alteration, and the presence of solitary necrotic keratinocytes at lower epidermal levels, combined with moderate to dense periadnexal and perivascular lymphocytic infiltrates with a variable presence of melanophages, and mucin point to a LE‐related origin.     

Association of Early Systemic Corticosteroid Therapy with Mortality in Patients with Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis: A Retrospective Cohort Study Using a Nationwide Claims Database

Background

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatologic disorders with high mortality. The role of systemic corticosteroids as an adjunctive therapy for SJS or TEN remains controversial.

Objective

The aim of this study was to determine whether treatment with early systemic corticosteroids impacts the in-hospital mortality of patients hospitalized with SJS or TEN.

Methods

Using the Japanese Diagnosis Procedure Combination Database, a large nationwide inpatient administrative claims database, we identified inpatients aged ≥ 18 years who were admitted with SJS or TEN. Treatment with early systemic corticosteroids was defined as starting treatment with systemic corticosteroids within 2 days (day 0 or day 1) of admission. The primary outcome was in-hospital mortality. We examined the association between early systemic corticosteroids and in-hospital mortality using propensity score (PS) analyses.

Results

We identified 1846 eligible patients with SJS or TEN, including 793 patients with early systemic corticosteroid use at ≤ 2 mg/kg/day, 558 patients with early systemic corticosteroid use at > 2 mg/kg/day, and 495 patients without early corticosteroid use. PS matching created 235 pairs (> 2 mg/kg/day vs. controls) and 332 pairs (≤ 2 mg/kg/day vs. controls). Early systemic corticosteroid use was not significantly associated with lower in-hospital mortality by PS matching (> 2 mg/kg/day vs. controls: relative risk [RR] 0.83, 95% confidence interval [CI] 0.37–1.85; ≤ 2 mg/kg/day vs. controls: RR 0.61, 95% CI 0.28–1.36) and by inverse probability of treatment weighting (> 2 mg/kg/day vs. controls: RR 0.99, 95% CI 0.45–2.19; ≤ 2 mg/kg/day vs. controls: RR 0.65, 95% CI 0.29–1.47).

Conclusion

Early systemic corticosteroid therapy for patients with SJS or TEN was not associated with lower in-hospital mortality. Further studies are needed to define the effect of corticosteroids for patients with SJS or TEN.

     

The role of prior corticosteroid use on the clinical course of Stevens-Johnson syndrome and toxic epidermal necrolysis: a case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologically mediated, severe cutaneous adverse reactions involving cytotoxic T cells, natural killer cells and various mediators. In large studies, up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is unclear if this prior exposure to corticosteroids modified the disease course. Objectives To evaluate whether systemic corticosteroid usage prior to the onset of SJS/TEN modified the clinical course and outcome. If a disease‐modifying effect is present, information from such an analysis may have implications on the therapeutic use of corticosteroids in SJS/TEN. Methods This is a case–control study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety‐two cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease, and 321 randomly selected SJS/TEN patients without prior exposure were included. Primary outcomes included progression of disease, disease severity and mortality. A secondary analysis of latency between the beginning of drug use and the onset of disease, based on exposure to a single high‐risk drug, was also performed. Results On multivariate analysis, cases with prior exposure to corticosteroids had a longer progression of disease by 2·2 days [95% confidence interval (CI) 1·1–3·2]. The disease severity and mortality outcome were unaffected. In addition, there is evidence that corticosteroids delayed the onset of SJS/TEN in patients with exposure to high‐risk drugs by 7·1 days (CI ?0·2 to 14·5). Conclusions The prior use of corticosteroids prolonged the period of disease progression without influencing the disease severity or mortality. In addition, when SJS/TEN is preceded by use of a single high‐risk drug, the latency between the drug intake and the onset of SJS/TEN may also be increased. These findings suggest that corticosteroids have a mild impact on the course of SJS/TEN, and further studies are required to clarify any potential therapeutic effects.     

The psychological impact of Stevens-Johnson syndrome and toxic epidermal necrolysis on patients’ lives

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions (affecting 1-2 people per million per year) usually caused by a severe immune reaction to certain medications and, in some cases, the cause may be linked to particular infections. Those affected are likely to have a loss of skin and mucous membranes. People who get these conditions become very ill quickly and experience severe pain. SJS and TEN can have long-term physical effects such as skin, eye, breathing and stomach problems. Little is known about the psychological effects on patients’ lives. This research was inspired by a man diagnosed with TEN. Because he appeared anxious and fearful, the authors questioned how SJS/TEN affected patients’ lives. The authors systematically searched for research papers regarding SJS and TEN, to help understand the psychological impact of these conditions on patients’ lives, and they found six relevant studies. The findings highlight that some healthcare practitioners lacked information about the conditions, leading to fear and anxiety in patients. Some patients had symptoms of post-traumatic stress disorder (PTSD), anxiety and depression. The findings conclude that SJS/TEN impacts psychologically on patients’ lives. The authors suggest that, if healthcare practitioners are educated about SJS/TEN, this should assist them to provide patients with the information and support which they need in order to be less anxious. In addition, on discharge, patients should have a follow up appointment with a relevant healthcare practitioner to reduce the possibility of PTSD occurring. Linked Article:   O’Reilly et al. Br J Dermatol 2020; 183 :452–461 .