Serum IL-17 in patients with erythema multiforme or Stevens-Johnson syndrome/toxic epidermal necrolysis drug reaction, and correlation with disease severity.

BACKGROUND: There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. AIM: To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity. METHODS: In total, 32 patients (13 with EM and 19 with SJS/TEN) and 15 age- and sex-matched healthy controls (HCs) were enrolled. Patients with SJS/TEN were assessed clinically using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Serum IL-17 levels were determined by ELISA. RESULTS: Serum IL-17 levels were significantly higher compared with HCs (16.46 ± 5.21 pg/mL) in the EM (35.1 ± 23.89 pg/mL, P < 0.02) and SJS/TEN (68.19 ± 35.42 pg/mL, P = 0.001) groups. IL-17 levels were also significantly higher in the SJS/TEN group than in the EM group (P = 0.004). Mean affected body surface area percentage was 0.9 ± 0.21 in the EM group and 22.8 ± 10.67 in the SJS/TEN group. The SJS/TEN SCORTEN ranged from 1 to 5, with a mean of 2.5 ± 1. Serum IL-17 level correlated positively with both percentage surface area of detached skin and SCORTEN. CONCLUSIONS: Serum IL-17 levels may have prognostic and diagnostic value in patients with EM or SJS/TEN reactions, and can provide a valuable approach in managment.

New Grading System and Treatment Guidelines for the Acute Ocular Manifestations of Stevens-Johnson Syndrome.

PURPOSE: To describe a new grading system and associated treatment guidelines for the acute ocular manifestations of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). DESIGN: Prospective case series. PARTICIPANTS: Seventy-nine consecutive patients (158 eyes) evaluated and treated for acute ocular involvement in SJS or TEN during hospitalization. METHODS: Photographic and chart review of acute ocular findings, interventions received, and outcomes with regard to visual acuity, dry eye symptoms, and scarring sequelae at least 3 months after the acute illness. MAIN OUTCOME MEASURES: Visual acuity, dry eye severity, and scarring of the ocular surface and eyelids were assessed after follow-up of at least 3 months. RESULTS: Cases graded as mild or moderate were managed medically. All had best-corrected visual acuity (BCVA) of 20/20, no dry eye symptoms, and no scarring sequelae. Cases graded as severe or extremely severe were treated with urgent amniotic membrane transplantation (AMT) in addition to medical management. Severe cases all had BCVA of 20/20 and mild or no dry eye problems. Five of 28 patients had mild tarsal conjunctival scarring. No other scarring sequelae occurred. Nine of the 10 extremely severe cases had BCVA of 20/20 (1 was 20/30). Three of 10 had moderate scarring of the tarsal conjunctiva and lid margins and also moderate dry eyes with severe photophobia. Seven of 10 had only mild or no dry eye symptoms and scarring sequelae. CONCLUSIONS: This grading system facilitates decision making in the evaluation and management of the acute ocular manifestations of SJS and TEN. Mild and moderate cases have a low risk of significant scarring or visual sequelae and may be monitored and treated medically if not worsening. Severe and extremely severe cases should receive urgent AMT to decrease the risk of scarring and visual sequelae.

[Stevens-Johnson Syndrom and Toxic Epidermal Necrolysis--based on literature]. / Zespól Stevensa-Johnsona oraz zespól toksycznej nekrolizy naskórka--na podstawie pismiennictwa.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis syndrome (TEN) also known as Lyell's syndrome, are acute autoimmune dermatoses, which are potentially life threatening. They are both forms of necrotic skin reactions which causes epidermis to separate from dermis as a result of abnormal process induced by drugs or infections. Historically they were classified as a form of exudative erythema multiforme, but nowadays they are categorized as different disease entities. The reason is more severe clinical course in case of SJS and TEN, and known causes (medicines, infections). The criterion for distinguishing the two forms is based on the quantitative evaluation of the surface of affected skin. In case of SJS the affected area comprise up to 10% of body surface area, while in Lyell's syndrome it is over 30%. If affected skin surface ranges from 10% to 30%, it is defined as overlapping syndrome.

Severity of acute ocular involvement is independently associated with time to resolution of ocular disease in toxic epidermal necrolysis patients.

PURPOSE: Toxic epidermal necrolysis (TEN) is a severe, life-threatening mucocutaneous disorder that frequently involves the ocular surface. This study aims to investigate the natural history and resolution of acute ocular involvement in patients with TEN admitted to the intensive care unit (ICU). METHODS: Case notes of patients admitted to ICU with TEN at a tertiary referral centre in a 9-year period were retrospectively reviewed. Patients' characteristics, severity of ocular involvement, SCORTEN systemic severity score and treatment were correlated with resolution of ocular involvement and time to resolution. RESULTS: Nine out of 10 (90%) patients had ocular involvement with 4 graded as mild, 2 as moderate and 3 as severe. All had bilateral ocular disease. The median length of hospital stay was 28 days and the median time to resolution of ocular involvement was 19 days. Four out of 9 (44%) patients still had active ocular disease at the time of discharge. Only older age (p=0.032) and a milder grade of ocular disease (p=0.001) were significantly associated with resolution of ocular disease. In a multivariable Cox-regression model, only a milder grade of ocular disease remained independently associated with time to resolution of ocular disease (p=0.006). CONCLUSIONS: Grading of acute ocular disease severity does not reflect systemic disease severity and is significantly associated with resolution and time to resolution of ocular involvement in TEN. The high rate of ocular involvement in patients with TEN and relatively large proportion of patients with active disease on discharge reiterates the need for constant ophthalmological monitoring of these patients.

Mycoplasma pneumonia--associated mucocutaneous disease in children: dilemmas in classification.

There is controversy regarding precise definitions for Stevens-Johnson syndrome (SJS) and erythema multiforme (EM) major because of overlap in clinical presentations. SJS and EM major associated with Mycoplasma pneumoniae have been reported to occur in children, but Mycoplasma is more commonly reported with SJS. We sought to further characterize Mycoplasma-associated mucocutaneous disease. Through retrospective chart review over 10 years, six children hospitalized with a diagnosis of SJS who also tested positive for Mycoplasma infection were reviewed. Using documented physical examinations and photographs, diagnoses of SJS or EM major were retrospectively made based upon cutaneous lesional morphology employing the classification system proposed by Bastuji-Garin et al. The majority of patients were boys, with limited acral cutaneous lesions. All patients required prolonged hospitalization because of mucosal involvement and had good short-term outcomes. When the classification system was retrospectively applied, five of the six patients were reclassified with a diagnosis of EM major instead of SJS. Children with Mycoplasma-associated EM major and SJS in our small retrospective series appeared to have significant mucosal involvement but more limited cutaneous involvement with lesional morphology, which is more characteristic of EM major.

Toxic epidermal necrolysis (TEN): the Chelsea and Westminster Hospital wound management algorithm.

Toxic epidermal necrolysis syndrome (TEN) is a potentially catastrophic exfoliative muco-cutaneous disorder first described by Lyell in 1956. It represents the most extensive form of Steven-Johnson syndrome. TEN is defined varyingly around the globe, but in the United Kingdom the consensus opinion describes the process as involving >30% of the total body surface area. It can rapidly become more extensive and threatens life. The estimated annual incidence is approximately 1-2 cases per million population. The risk of mortality increases with surface area involved and meta-analysis of the literature shows this risk to be between 16% and 55%. Over a six month period the Chelsea and Westminster Hospital Burns Service treated five consecutive patients with more than 80% total body surface area involvement or a more than 80% mortality risk, using the severity-of-illness score for toxic epidermal necrolysis (SCORTEN). All patients were treated according to the Chelsea and Westminster Hospital wound management algorithm with excellent outcome and no mortalities. The aim of this paper is to propose a generic TEN wound management algorithm according to the severity of skin lesions, using a simple wound grading system.

From erythema multiforme to toxic epidermal necrolysis. Same spectrum or different diseases?

Erythema multiforme (EM), Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute bullous disorders associated to different prognosis, mainly due to infections and drugs. More in particular EM in more than 90% is caused by infections (especially Herpes virus infection), while, on the other hand SJS and TEN are referable in more than 95% of cases to drugs. Distinction among these three forms is often controversal and still debated. An attempt to distinguish these forms has been possible mainly according to anamnesis, clinical presentation (morphology, involved sites, extension of lesions) and pathogenetic mechanisms, being on the contrary more difficult from an histopathological point of view. Nowadays a clear diagnosis and a distinction from other life-threatening diseases is possible with the integration of all the mentioned aspects. Moreover, this recognition should be as early as possible in order to perform a prognostic evaluation of the case and to start supportive cares and therapies as soon as possible.

Indications and outcomes of amniotic membrane transplantation in the management of acute stevens-johnson syndrome and toxic epidermal necrolysis: a case-control study.

PURPOSE: To evaluate the indications and outcomes of amniotic membrane transplantation (AMT) performed within the first 2 weeks of presentation in the management of patients with acute Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: A retrospective chart review from January 1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University Medical Center Burn intensive care unit. The degree of initial ocular surface inflammation was graded as mild, moderate, or severe within the first 2 weeks of admission. Patients were managed either medically or with amniotic membrane (AM). Outcomes were graded as good [best-corrected visual acuity (BCVA)>20/40], fair (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens or reconstructive surgeries), or poor (BCVA<20/200). RESULTS: Of the 182 eyes (91 patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1 month of follow-up, 17 patients (33 eyes) were treated with medical management and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with moderate or severe presentation treated with early AMT (4.3%) resulted in a poor outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically managed (P=0.022). CONCLUSIONS: We present the first case-control study of the use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe vision loss in SJS/TEN patients with initial moderate or severe ocular surface inflammation.

Ophthalmic Manifestations of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis and Relation to SCORTEN.

PURPOSE: To evaluate the severity of ocular involvement of patients with Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap, and to investigate the relationship of the SCORTEN (a severity-of-illness score for SJS and TEN based on a minimal set of well-defined variables calculated within 24 hours of admission) with eye disease in this patient population. DESIGN: Retrospective observational case series. METHODS: Charts of all patients admitted to the Parkland Memorial Hospital Burn Center with a preliminary diagnosis of SJS, SJS/TEN overlap, or TEN between 1998 and 2008 were reviewed. Patients were included for study if they met clinical criteria, had positive diagnostic skin biopsy, and had dermatologic and ophthalmologic consultations. Eighty-two patients with a diagnosis of SJS, SJS/TEN overlap, or TEN met inclusion criteria. Ocular manifestations were classified as mild, moderate, or severe. Admission data were used to calculate the SCORTEN. Main outcome measure was the severity of ocular involvement with respect to diagnosis and SCORTEN. RESULTS: Overall, 84% of patients had ocular involvement (71% SJS, 90% TEN, 100% SJS/TEN overlap). There was no difference in the severity of acute ocular complications among groups. While the SCORTEN value did correlate well with mortality rate (correlation coefficient 0.97, P = .005), there was no correlation between the SCORTEN value and severity of eye involvement in the acute setting. There was also no association of any individual diagnosis of SJS/overlap/TEN with the severity of eye involvement, although eye findings are more common in TEN (P = .03). CONCLUSIONS: Ocular damage in the acute setting was more frequent in patients with epidermal detachment >10% of the total body surface area. The SCORTEN value did not correlate with the severity of eye involvement in the acute setting.

In the pursuit of classifying severe cutaneous adverse reactions.

We suggest adding an additional type of lesion to the existing 4 types of lesions of the erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), namely "flat typical target" and call the original typical targets "raised typical target." The EM group would consist of raised typical targets and raised atypical targets, similar to the original definition, and the SJS/TEN group would consist of flat typical targets, flat atypical targets and macules with or without blisters. In our proposed modified classification (Table 1), all the lesions that are found in the EM group are raised, whereas all lesions that characterize the SJS/TEN group are flat, even though they have blisters on them.

[Toxic epidermal necrolysis]. / Epidermolyse nécrosante suraiguë de Lyell ou toxic epidermal necrolysis.

The toxic epidermal necrolysis (TEN) is an immunologic reaction in the skin with apoptosis of kératinocytes: most cases are reactions against drugs. The main features of this reaction are a separation of the epidermis and erosions of the mucus membranes, associated with a reduction of the general condition with kidney and liver failure. This leads to problems similar to those observed in severely burned patients. The mortality high of patients with TEN can be reduced, if the responsible drug is immediately withdrawn and if the patient is treated in a specialized burns intensive care unit. The medical treatment to stop the chain reaction of apoptosis is still under discussion. Through a case report, this article will focus on the complexity of the treatment of patients with TEN and will point out the importance of a multidisciplinary approach.

Erythema multiforme and related disorders.

Erythema multiforme (EM) and related disorders comprise a group of mucocutaneous disorders characterized by variable degrees of mucosal and cutaneous blistering and ulceration that occasionally can give rise to systemic upset and possibly compromise life. The clinical classification of these disorders has often been variable, thus making definitive diagnosis sometimes difficult. Despite being often caused by, or at least associated with, infection or drug therapy, the pathogenic mechanisms of these disorders remain unclear, and as a consequence, there are no evidence-based, reliably effective therapies. The present article reviews aspects of EM and related disorders of relevance to oral medicine clinical practice and highlights the associated potential etiologic agents, pathogenic mechanisms and therapies.

Drug Rash with eosinophilia and systemic symptoms versus Stevens-Johnson Syndrome--a case that indicates a stumbling block in the current classification.

A 43-year-old man developed a skin eruption characterized by 'macules with blisters' typical to Stevens-Johnson syndrome, as well as erosions of the lips and buccal mucosa, 2 weeks after he had started treatment with lamotrigine. He had a fever (39.6 degrees C), elevated liver enzymes and atypical lymphocytes in the peripheral blood. This undoubtedly reflects a case of Stevens-Johnson syndrome induced by lamotrigine, but it can also fulfill the criteria of anticonvulsant hypersensitivity syndrome or drug rash with eosinophilia and systemic signs. A case that precisely fits the definition of two syndromes that have different characteristics, different treatments and different prognoses indicates that there is a flaw in the classification.

SCORTEN overestimates mortality in the setting of a standardized treatment protocol.

Toxic epidermal necrolysis (TEN) is a rare, severe, exfoliative disorder with a high mortality rate. SCORTEN is a recently developed scoring system that estimates severity and predicts mortality in patients with TEN based on seven independent clinical risk factors recorded within the first 24 hours of admission. An increasing SCORTEN level predicts a higher mortality rate. For more than 20 years, the treatment of TEN at our institution has involved the use of a standardized clinical pathway that includes removal of sloughed epidermis, dermal protection with porcine xenograft, early enteral nutrition, and critical care monitoring. We hypothesize that this standardized clinical approach will result in a lower mortality rate than predicted by SCORTEN. A retrospective review was performed on all patients treated for TEN using the standardized pathway from February 1987 to March 2004. SCORTEN was calculated in each patient. One hundred nine patients were treated for TEN during the study period. Overall observed mortality was 20% compared with a SCORTEN predicted mortality of 30%, resulting in a relative reduction in mortality of 33% (P = .011). In addition, observed probability of death was lower than predicted at all levels, except at SCORTEN score of 6 or greater. In conclusion, TEN remains a life-threatening disease with a high mortality rate. Our standardized treatment protocol results in significantly improved outcomes compared to those predicted by SCORTEN.

Drug rash with eosinophilia and systemic symptoms vs toxic epidermal necrolysis: the dilemma of classification.

According to contemporary vernacular, when the cutaneous manifestations of drug rash with eosinophilia and systemic signs (DRESS) syndrome are those of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the condition is defined as "DRESS syndrome with severe cutaneous reactions". In this article, we have presented arguments for and against including patients with skin lesions of the SJS/TEN syndromes who also have fever (practically all of the patients) and internal organ involvement (most of the patients) under the definition of DRESS syndrome. After weighing the arguments for and against this alteration of definition, we conclude that it makes more sense for patients with SJS/TEN to be classified as such and not be lumped together under the misleading label of DRESS syndrome.