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.

Pediatric Erythema Multiforme in the Emergency Department: More Than "Just a Rash".

OBJECTIVES: Erythema multiforme (EM) is characterized by symmetrical acrally distributed target lesions; however, other conditions can mimic the clinical features of EM. Although it is typically self-limiting, alternative diagnoses may be life-threatening and require immediate identification and treatment. This study aimed to investigate the clinical spectrum and accuracy of diagnosis of pediatric EM in the emergency department (ED). METHODS: A retrospective, descriptive study of all pediatric patients with an ED information system diagnosis of EM at 2 EDs in Southeast Queensland between January 2010 and July 2013. Cases were evaluated using previously established EM classification criteria. RESULTS: Seventy patients (34 males and 36 females) with a diagnosis of EM were identified. From 57 cases where a diagnosis could be established, 9 cases fulfilled the classification criteria for EM. No patients had mucosal involvement, and therefore, all 9 cases were classified as EM minor, with the majority (89%) attributed to viral infection. Of the 48 cases that did not fit the criteria, the most common condition misdiagnosed as EM was urticaria multiforme (n = 20). CONCLUSIONS: In the ED setting, EM in children is frequently misdiagnosed. Greater awareness of diagnostic factors for EM may improve diagnostic accuracy. Teledermatology and incentives to include clinical pictures in the (electronic) medical record may be useful adjuncts for patients with suspected EM and other dermatological conditions.

Paediatric Erythema Multiforme: Epidemiological, Clinical and Laboratory Characteristics.

Erythema multiforme (EM) is an immune-mediated reaction presenting as acrofacial target lesions. Most studies utilize the outdated classification, which includes EM, Stevens-Johnson syndrome and toxic epidermal necrolysis as related entities. We describe here epidemiological, aetiological, clinical, laboratory and treatment characteristics of paediatric EM. This is a retrospective single-centre study, performed between 2000 and 2013. Of 119 children given a diagnosis of EM, only 30 met clinical criteria and were included in this study. Most misdiagnosed cases were non-specific eruptions and urticaria multiforme. Mean age was 11.3 years. Fifty percent had mucosal involvement. An aetiology was observed in half of the patients. Seventy percent of patients were admitted to hospital, 46.7% were treated with systemic steroids. Sixteen percent had recurrent EM. The most common identified infectious agent associated with EM in this study was Mycoplasma pneumonia and the cases associated with this infection may represent the recent entity, mycoplasma-induced rash and mucositis. Association with herpes simplex virus was not observed. Despite being a benign, self-limiting condition, children were over-treated in terms of hospitalization and therapy.

[Childhood postinfectious erythema multiforme]. / Érythème polymorphe postinfectieux de l'enfant.

Postinfectious erythema multiforme is an uncommon skin disease in childhood that can have a strong impact, especially in infants if there is involvement of the mucous membranes. The lesion is targeted (central bullous lesions with three concentric circles). Its diagnosis is typically made clinically. Atypical forms are the highly inflammatory, mainly bullous type, with exclusive involvement of the mucous membrane, or recurrent erythema multiforme. The diagnosis of erythema multiforme is frequently suspected in children with urticaria multiforme. Kawasaki disease and toxic epidermal necrolysis may have a target-like skin aspect with mucosal involvement, and should be considered when planning treatment. The two major infectious etiologies in children are Mycoplasma pneumoniae and Herpes simplex. More recently, postvaccination erythema multiforme has been reported with the majority of vaccines used in pediatric practice. The prognosis is usually good but requires observation of the mucosal involvement because of the risk of serious complications. The treatment of erythema multiforme is essentially symptomatic, with etiology-related treatment.

Mycoplasma pneumoniae-Induced Mucocutaneous Rash: A New Syndrome Distinct from Erythema Multiforme? Report of a New Case and Review of the Literature. / Exantema mucocutáneo inducido por Mycoplasma pneumoniae: ¿un nuevo síndrome separado del eritema multiforme? Un nuevo caso y revisión de la literatura.

Respiratory tract infection due to Mycoplasma pneumoniae can provoke cutaneous and mucosal rashes, which have been classified within the spectrum of erythema multiforme or Stevens-Johnson syndrome. This classification is of therapeutic and prognostic importance and has generated intense debate in the literature. A recent systematic review of 202 cases of mucocutaneous rashes associated with M. pneumoniae infection concluded that these rashes might constitute a distinct entity, for which the term Mycoplasma-induced rash and mucositis was proposed. We describe a patient with acute M pneumoniae respiratory tract infection who presented mucosal and cutaneous lesions that were difficult to classify as erythema multiforme or Stevens-Johnson syndrome; the lesions were compatible with the proposed new disease.

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.

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.

Shape and configuration of skin lesions: targetoid lesions.

What is probably the first description of targetoid or iris lesions, as they appear in erythema multiforme (EM), can be found in Thomas Bateman's 1836 textbook "Practical Synopsis of Cutaneous Diseases According to the Arrangement of Dr. Willan." EM was initially described by Bateman and later by von Hebra as an acute self-limiting skin disease, symmetrically distributed on the extremities with typical concentric "targetoid" or "iris" lesions, and often recurrent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were added to this syndrome later. A newer classification has created two disease spectra: EM consisting of EM minor and EM major (or bullous EM), and SJS and TEN. EM minor and EM major are often recurrent, postinfectious (especially after herpes and mycoplasma) disorders with low morbidity and almost no mortality. SJS and TEN are usually severe drug-induced reactions with high morbidity and poor prognosis. The target lesions found in each form of the disease are described and defined. Although the term "target lesion" originated from the description of EM and despite its being the dominant lesion in this disease, it is not pathognomonic for EM, and these lesions can sometimes appear in other diseases. Short descriptions of these other diseases are presented.

Targetoid spongiotic reaction pattern: A case series of seven paediatric patients.

We present seven cases of a targetoid eruption, clinically mimicking erythema multiforme, occurring in paediatric patients aged 12 months to 14 years. All patients presented with a pruritic targetoid eruption on body and acral sites which spared mucosal areas. All patients demonstrated a spongiotic reaction pattern on histology without lichenoid change and demonstrated excellent responses to either oral prednisolone or topical corticosteroids. We propose the term 'targetoid spongiotic reaction pattern (TSRP)' for our subset of paediatric patients. We review the literature regarding targetoid eruptions in the paediatric population.

Oral mucosal diseases: erythema multiforme.

Erythema multiforme (EM) is a rare acute mucocutaneous condition caused by a hypersensitivity reaction with the appearance of cytotoxic T lymphocytes in the epithelium that induce apoptosis in keratinocytes, which leads to satellite cell necrosis. EM can be triggered by a range of factors, but the best documented association is with preceding infection with herpes simplex virus (HSV). Most other cases are initiated by drugs. EM has been classified into a number of variants, mainly minor and major forms, as it may involve the mouth alone, or present as a skin eruption with or without oral or other lesions of the mucous membrane. EM minor typically affects only one mucosa, and may be associated with symmetrical target skin lesions on the extremities. EM major typically involves two or more mucous membranes with more variable skin involvement. A severe variant of EM major is Stevens-Johnson syndrome, which typically extensively involves the skin. Both EM major and Stevens-Johnson syndrome can involve internal organs and produce systemic symptoms. Treatment of EM is controversial, as there is no reliable evidence. Precipitants should be avoided or treated and, in severe cases, corticosteroids may be needed. Toxic epidermal necrolysis may be similar to Stevens-Johnson syndrome, but many experts regard it as a discrete disease, and therefore it is not discussed here.

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.

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.

Mucosal disease series. Number IV. Erythema multiforme.

Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction characterised by a skin eruption, with or without oral or other mucous membrane lesions. Occasionally EM may involve the mouth alone. EM has been classified into a number of different variants based on the degree of mucosal involvement and the nature and distribution of the skin lesions. EM minor typically affects no more than one mucosa, is the most common form and may be associated with symmetrical target lesions on the extremities. EM major is more severe, typically involving two or more mucous membranes with more variable skin involvement - which is used to distinguish it from Stevens-Johnson syndrome (SJS), where there is extensive skin involvement and significant morbidity and a mortality rate of 5-15%. Both EM major and SJS can involve internal organs and typically are associated with systemic symptoms. Toxic epidermal necrolysis (TEN) may be a severe manifestation of EM, but some experts regard it as a discrete disease. EM can be triggered by a number of factors, but the best documented is preceding infection with herpes simplex virus (HSV), the lesions resulting from a cell mediated immune reaction triggered by HSV-DNA. SJS and TEN are usually initiated by drugs, and the tissue damage is mediated by soluble factors including Fas and FasL.

Bupropion-induced erythema multiforme.

The high rate of dermatologic adverse effects associated with bupropion use may extend to its sustained-release preparation, currently prescribed extensively for smoking cessation as well as for treatment of depressive conditions. We report what we believe to be the first case, in a 31-year-old woman, of erythema multiforme after administration of sustained-release bupropion (Wellbutrin SR) for treatment of depression. This report emphasizes that prescribers must aggressively follow up their patients who have rashes or urticaria, discontinuing the medication as soon as erythema multiforme is suspected and watching closely for the emergence of potentially life-threatening dermatologic conditions.

Necrólisis epidérmica tóxica y síndrome de Stevens-Johnson: clasificación y actualidad terapéutica / Toxic epidermal necrolysis and Stevens-Johnson syndrome: new issues in classification and therapy

La necrólisis epidérmica tóxica (NET) y el síndrome de Stevens-Johnson (SSJ) constituyen un espectro de la misma enfermedad, compartiendo aspectos etiológicos, patogenéticos, histológicos y terapéuticos. Casi todos (si no todos) los casos son inducidos por fármacos. NET y SSJ pueden distinguirse clínicamente del eritema multiforme, que debe considerarse una enfermedad distinta. La patogenia de la NET y del SSJ es poco conocida, pero se acepta que intervienen reacciones inmunológicas y un mecanismo final de apoptosis masiva de queratinocitos epidérmicos. El tratamiento consiste en la retirada del fármaco causal y medidas de soporte, evitando la administración de corticosteroides. Se han descrito tratamientos que pretenden detener la evolución del cuadro, entre ellos ciclofosfamida, ciclosporina, plasmaféresis, pentoxifilina e inmunoglobulinas i.v. Su eficacia está por demostrar (AU)

Diferenciación entre eritema multiforme, síndrome de Stevens-Jhonson y necrólisis epidérmica tóxica / Differentiation between eritema multiforms, syndrome of Stevens-Jhonson and toxic epidérmica necrólisis

Dentro del amplio espectro del eritema multiforme, en ocasiones es difícil diferenciar entre el síndrome de Stevens-Jhonson (SSJ) y la necrólisis epidérmica tóxica (NET), llegándose incluso a establecerse un nuevo síndrome denominado Overlap SSj-NET en una nueva clasificación. Se presenta un caso clínico con esta entidad y se complementa con una breve información sobre eritema multiforme, su clasificación y probable etiología.

Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme.

A new classification, based on the pattern and distribution of cutaneous lesions, separates erythema multiforme major from Stevens-Johnson syndrome. A retrospective re-classification of 76 cases supported the validity of that separation by demonstrating differing causes and pathology. Another prospective international case-control study found differing demographic characteristics and risk factors between erythema multiforme major on the one hand and Stevens-Johnson syndrome or toxic epidermal necrolysis on the other. Erythema multiforme major was mainly related to Herpes virus infection, while Stevens-Johnson syndrome and toxic epidermal necrolysis were associated with drug reactions.