Laser Phototherapy for Stevens-Johnson Syndrome: A Case Report

Background and Objective: Stevens-Johnson syndrome (SJS) is a life-threatening dermatosis characterized by epidermal sloughing and stomatitis. We report the case of a 7-year-old boy in whom laser phototherapy (LPT) was highly effective in reversing the effects of an initial episode of SJS that had apparently developed in association with treatment with phenobarbital for a seizure disorder. The patient was first seen in the intensive care unit (ICU) of our institution with fever, cutaneous lesions on his extremities, trunk, face, and neck; mucosal involvement of his genitalia and eyes (conjunctivitis); ulcerative intraoral lesions; and swollen, crusted, and bleeding lips. He reported severe pain at the sites of his intraoral and skin lesions and was unable to eat, speak, swallow, or open his mouth. Materials and Methods: Trying to prevent and minimize secondary infections, gastric problems, pain, and other complications, the patient was given clindamycin, ranitidine, dipyrone, diphenhydramine (Benadryl) drops, and morphine. In addition, he was instructed to use bicarbonate solution and Ketoconazole (Xylogel) in the oral cavity. Because of the lack of progress of the patient, the LPT was selected. Results: At 5 days after the initial session of LPT, the patient was able to eat gelatin, and on the following day, the number and severity of his intraoral lesions and his labial crusting and swelling had diminished. By 6 days after his initial session of LPT, most of the patient's intraoral lesions had disappeared, and the few that remained were painless; the patient was able to eat solid food by himself and was removed from the ICU. Ten sessions of LPT were conducted in the hospital. The patient underwent three further and consecutive sessions at the School of Dentistry, when complete healing of his oral lesions was observed. Conclusion: The outcome in this case suggests that LPT may be a new adjuvant modality for SJS complications.

Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review

The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome.

In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for lymphocyte transformation test

BACKGROUND Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS Fifteen patients with SJS/TEN with the ALDEN score ≥ 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFNγ in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNγ. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFNγ production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.

[Drug-induced Stevens-Johnson syndrome in a patient with AIDS]

The Stevens-Johnson syndrome is a severe potentially life-threatening form of the erythema multiforme, affecting both skin and mucous membranes. We present a case of a 49-year-old male patient with AIDS who developed a Stevens-Johnson syndrome while being treated with pyrimethamine, sulfadiazine and phenytoin for cerebral toxoplasmosis. Further diagnostic evaluation of this dangerous cutaneous affection may prove difficult for several reasons. In particular, in patients with AIDS who are more susceptible for adverse drug reactions and who are simultaneously receiving a variety of drugs with a considerable potential of cutaneous side effects, therapy cannot be withhold for lack of therapeutic alternatives. Moreover, the low lymphocyte count in this case may have made reliable testing with lymphocyte transformation studies impossible. The evaluation and the differential diagnosis of the drug-induced Stevens-Johnson syndrome are discussed. Especially long- and moderately long-acting sulfonamides belong to the most important agents that can cause a drug-induced Stevens-Johnson syndrome. The pathogenesis and the risk factors for cutaneous hypersensitivity reactions in HIV-infected patients are only poorly understood. These kind of reactions, however, seem to occur more often in patients with a more advanced immunodeficiency.

Patient experiences of serious adverse drug reactions and their attitudes to medicines:a qualitative study of survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK

Background: Adverse drug reactions (ADRs) cause significant morbidity and mortality and account for around 6.5% of hospital admissions. Patient experiences of serious ADRs and their long-term impact on patients' lives, including their influence on current attitudes towards medicines, have not been previously explored. Objective: The aim of the study was to explore the experiences, beliefs, and attitudes of survivors of serious ADRs, using drug-induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) as a paradigm. Methods: A retrospective, qualitative study was undertaken using detailed semi-structured interviews. Fourteen adult survivors of SJS and TEN, admitted to two teaching hospitals in the UK, one the location of a tertiary burns centre, were interviewed. Interview transcripts were independently analysed by three different researchers and themes emerging from the text identified. Results: All 14 patients were aware that their condition was drug induced, and all but one knew the specific drug(s) implicated. Several expressed surprise at the perceived lack of awareness of the ADR amongst healthcare professionals, and described how the ADR was mistaken for another condition. Survivors believed that causes of the ADR included (i) being given too high a dose of the drug; (ii) medical staff ignoring existing allergies; and (iii) failure to monitor blood tests. Only two believed that the reaction was unavoidable. Those who believed that the condition could have been avoided had less trust in healthcare professionals. The ADR had a persisting impact on their current lives physically and psychologically. Many now avoided medicines altogether and were fearful of becoming ill enough to need them. © 2011 Adis Data Information BV. All rights reserved. Conclusions: Life-threatening ADRs continued to affect patients’ lives long after the event. Patients’ beliefs regarding the cause of the ADR differed, and may have influenced their trust in healthcare professionals and medicines. We propose that clear communication during the acute phase of a serious ADR may therefore be important.

Síndroma de Stevens-Johnson e Necrólise Tóxica Epidérmica. Um Estudo Retrospectivo de 15 Anos

A Síndroma de Stevens-Johnson (SSJ), a Síndroma de Sobreposição (SS) e a Necrólise Tóxica Epidérmica (NTE) são emergências médicas raras, mas com elevadas morbilidade e mortalidade. A literatura referente às características destas doenças em Portugal é muito escassa. Procedeu-se à análise dos registos clínicos dos 20 doentes internados na Unidade de Queimados (UQ) do Hospital de São José nos últimos 15 anos com o diagnóstico de SSJ, SS ou NTE. A maior parte das toxidermias foi do tipo NTE (65%), seguida do SS (25%) e do SSJ (10%). A idade média foi 57,1 ± 19,0 anos. A duração média do internamento foi de 12,6 ± 7,8 dias. A mortalidade foi de 50%, sendo significativamente maior que os 16,4% de mortalidade global registada na UQ no mesmo período (p < 0,01). A área de superfície corporal total envolvida foi de 43,9 ± 28,6 %. O agente causal mais frequentemente implicado foi o alopurinol (35%), seguido da exposição à luz ultravioleta e metoxipsoraleno (15%). Catorze doentes (70%) foram tratados com corticóides nos primeiros dias de internamento, enquanto seis doentes (30%) foram tratados conservadoramente. A mortalidade foi menor nos doentes tratados com corticóides (42,8% vs 66,7%), embora esta diferença não fosse estatisticamente significativa. As taxas de infecção também não diferiram significativamente nos dois grupos. O SCORTEN nas primeiras 24 horas demonstrou ser um bom preditor de mortalidade. São necessários mais estudos para tentar reduzir a mortalidade nestas doenças.

Genotipificación de HLA-B en pacientes colombianos afectados por el síndrome Stevens-Johnson y la Necrólisis Epidérmica Tóxica

Las reacciones alérgicas a medicamentos cutáneas severas (RAM) como el Síndrome Stevens Johnson (SJS) y la Necrólisis Epidérmica Tóxica (NET),caracterizadas por exantema, erosión de la piel y las membranas mucosas, flictenas, desprendimiento de la piel secundario a la muerte de queratinocitos y compromiso ocular. Son infrecuentes en la población pero con elevada morbi-mortalidad, se presentan luego de la administración de diferentes fármacos. En Asia se ha asociado el alelo HLA-B*15:02 como marcador genético para SJS. En Colombia no hay datos de la incidencia de estas RAM, ni de la relación con medicamentos específicos o potenciales y tampoco estudios de aproximación genómica de genes de susceptibilidad.

Síndrome de Stevens-Johnson e Ibuprofeno

Introdução: A síndrome de Stevens-Johnson é uma doença rara com mortalidade de 1 a 5% e morbilidade significativa. Ocorre na sequência de uma reacção de hipersensibilidade imuno-mediada com susceptibilidade individual associada a factores genéticos. Pode ser desencadeada por agentes infecciosos, mas na maior parte dos casos o factor desencadeante é a exposição a fármacos. Caso clínico: Criança de 3 anos, previamente saudável, internada por febre alta, exantema papulovesicular generalizado com predomínio no tronco, dorso e face, enantema e hiperémia conjuntival. Posteriormente verificou-se coalescência das lesões cutâneas com evolução para necrose e descamação. Tinha adicionalmente erosões da mucosa oral, estomatite, edema e eritema dos lábios, períneo e balanite. Fotofobia, hiperémia conjuntival, edema palpebral, exsudado ocular sem sinéquias e córnea sem lesões. Duas semanas antes tinha sido medicado pela primeira vez com ibuprofeno e na admissão hospitalar realizou uma nova administração. Nega ingestão de outros fármacos. PCR para vírus do grupo herpes nas lesões, exames culturais negativos e serologias para Mycoplasma pneumoniae, Borrelia burgdoferi, vírus da hepatite B, Epstein-Barr e citomegalovírus negativos. TASO e anti-DNaseB sem alterações. IFI para vírus respiratórios negativa. Posteriormente identificou-se enterovírus por PCR nas fezes de que se aguarda cultura viral. Foi interrompida a administração de ibuprofeno e realizada terapêutica de suporte com fluidoterapia endovenosa, nutrição parentérica, analgesia sistémica e tópica. Manteve febre durante 10 dias, registando-se regressão progressiva da sintomatologia com melhoria das lesões ao fim de 3 semanas. Programou-se seguimento para rastreio de complicações cutâneo-mucosas e oftalmológicas e estudo de alergias medicamentosas. Comentários: O diagnóstico da síndrome de Stevens-Johnson é clínico e, em caso de dúvida, histológico, suportado por história de exposição a fármacos ou intercorrência infecciosa. A ingestão de ibuprofeno pela primeira vez com agravamento após a reexposição ao fármaco leva-nos a suspeitar ser esta a etiologia mais provável. Contudo, a identificação de enterovírus não permite excluir este agente como interveniente na doença.

Necrólise epidérmica tóxica/síndrome de Stevens Johnson: emergência em dermatologia pediátrica

Contexto: É descrito caso clínico de farmacodermia grave e de alta letalidade, cujo reconhecimento imediato é fundamental. Relato decaso: Paciente do sexo masculino de três anos de idade, cuja mãe refere histórico de crises convulsivas, consultou-se com neurologistaparticular, que prescreveu ácido valproico. Uma semana depois, voltou a ter crise convulsiva, sendo então introduzida lamotrigina.Poucos dias depois, a criança começou apresentar tosse e coriza hialina. Procurou pronto-socorro de sua cidade e foi orientada a usarfluimucil. Iniciou, então, febre e exantema máculo-papular inicialmente na face, que depois se generalizou. Foi levantada a hipótesediagnóstica de farmacodermia secundária à associação de anticonvulsivante. Discussão: Síndrome de Stevens-Johnson e necróliseepidérmica tóxica são variantes do mesmo processo mucocutâneo agudo, raro e grave, causado principalmente por reação adversaa fármacos e caracterizado por erupção cutânea macular de padrão eritematoso, formação de bolhas de conteúdo sero-hemático edestacamento epidérmico. As afecções são diferenciadas pela porcentagem de superfície corpórea acometida, sendo menor que10% na síndrome de Stevens-Johnson, e maior que 30% na necrólise epidérmica tóxica. O prognóstico pode ser estimado através doescore Severity Illness Score for Toxic Epidermal Necrolysis (SCORTEN), que prevê mortalidade de até 90% para os casos mais graves.O tratamento consiste na interrupção imediata da droga, transferência do paciente para unidade de queimados ou unidade de terapiaintensiva, e medidas de suporte. Terapias adjuvantes, como imunoglobulinas intravenosas e corticosteroides, ainda não têm papelconsolidado na literatura. Conclusões: Relata-se afecção rara e extremamente grave cuja suspeição clínica é importante na conduçãodo tratamento.

Dry eye in childhood: Epidemiological and clinical aspects

Because dry eye disease is rare in children and its pathogenesis is less well known than in adults, its diagnosis is often overlooked. It can occur in association with a number of congenital, autoimmune, endocrine, and inflammatory disorders, or under certain environmental and nutritional conditions. In some cases, early detection allows the underlying cause of the dry eye to be successfully treated and eliminated. In other cases, the disease may represent a lifelong problem, whose proper management can prevent ulceration and scarring of the ocular surface. Because of the association of pediatric dry eye with other conditions, a multidisciplinary approach to diagnosis and treatment is usually required. The purpose of this review is to enhance physician awareness of dry eye in children, to describe the most frequently associated conditions, and to discuss the diagnostic and therapeutic options available.

Formes sévères d'hypersensibilité médicamenteuse retardée [Severe delayed drug hypersensitivity reactions].

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests.

To cite this article: Ponvert C, Perrin Y, Bados-Albiero A, Le Bourgeois M, Karila C, Delacourt C, Scheinmann P, De Blic J. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol 2011; 22: 411-418. ABSTRACT: Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p < 0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p < 0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity.