Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report / 中西医结合学报

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Fulvestrant-induced toxic epidermal necrolysis

Abstract Toxic epidermal necrolysis is a condition with massive keratinocyte apoptosis, and it is associated with high mortality rates. Fulvestrant, an estrogen receptor antagonist, is indicated in the treatment of estrogen receptor-positive metastatic breast cancer in postmenopausal women. To our knowledge, this is the first described case of toxic epidermal necrolysis due to fulvestrant. A 56-year-old woman received 500 mg of intramuscular fulvestrant monthly for metastatic ductal carcinoma of the breast. Five days after the first dose, the patient presented with a maculopapular rash that evolved to blisters, and a detachment of the epidermis in over 30% of the total body surface area. Histological analysis was compatible with toxic epidermal necrolysis. Fulvestrant was discontinued, topical management and supportive care were initiated.

Síndrome de Stevens-Johnson asociado al tratamiento con metotrexato de la leucemia linfoblástica aguda: a propósito de un caso / Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report

La necrólisis epidérmica tóxica y el síndrome de StevensJohnson son enfermedades mucocutáneas raras que están asociadas a una evolución prolongada y a un desenlace potencialmente mortal. Principalmente están inducidas por fármacos y las tasas de mortalidad son muy elevadas. Aunque la piel es la más comprometida, también pueden estar afectados múltiples aparatos o sistemas como el cardiovascular, pulmonar, gastrointestinal y urinario. En este artículo, describimos el caso de un paciente con síndrome de Stevens-Johnson asociado al tratamiento con metotrexato, quien desarrolló insuficiencia cardíaca aguda y hemorragia gastrointestinal además de las manifestaciones en la piel. El paciente recibió un tratamiento satisfactorio con metilprednisolona e inmunoglobulina por vía intravenosa y continuó la quimioterapia con metotrexato.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare mucocutaneous diseases which are associated with a prolonged course and potentially lethal outcome. They are mostly drug induced and mortality rates are very high. Although mostly skin is involved, multiple organ systems such as cardiovascular, pulmonary, gastrointestinal, and urinary systems may be affected. Here, we report a case of StevensJohnson Syndrome associated with methotrexate treatment who developed acute cardiac failure and gastrointestinal hemorrhage beside skin findings. He had been treated with intravenous immunglobulin and methylprednisolone succesfully and continued chemotherapy with methotrexate treatment again.

Necrolisis epidérmica tóxica en el curso de un síndrome hemofagocítico secundario a linfoma de Hodgkin: caso clínico / Toxic epidermal necrolysis during a hemophagocytic syndrome secondary to Hodgkin lymphoma: report of one case

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.

Stevens-Johnson syndrome and toxic epidermal necrolysis: epidemiological and clinical outcomes analysis in public hospitals

Abstract: Background: Adverse drug reactions are harmful and involuntary responses to drugs that occur at doses normally used for a given condition. Among them are Stevens-Johnson syndrome and toxic epidermal necrolysis, both rare and potentially fatal conditions. Objectives: To analyze the epidemiological and clinical characteristics related to patients diagnosed with Stevens-Johnson syndrome and toxic epidermal necrolysis in public hospitals in the Federal District - Brazil. Methods: Retrospective, cross-sectional and descriptive study, in which data were collected referring to patients hospitalized in the public healthcare system of the Federal District from 1999 to 2014. Results: Between 1999 and 2014, 86 cases of hospitalized patients with diagnosis of Stevens-Johnson syndrome and toxic epidermal necrolysis in the Federal District were reported. The majority of patients were women; the most affected age group was 0 to 10 years. Patients older than 60 years (elderly) represent 6.98% of the cases. Most patients admitted to the referral hospital were discharged. However, occurrence of deaths exceeded that of discharge in elderly patients. Limitations of the study: There is fragility in the registry of hospitalization of patients, both in the hospital information system and in the medical records of the reference hospital. Conclusion: There is a need for greater production and better dissemination of information on the incidence of adverse drug reactions.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials

ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a review / Síndrome de Stevens-Johnson e necrólise epidérmica tóxica: revisão

SUMMARY Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs). Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal.

RESUMO A síndrome de Stevens-Johnson (SSJ) e a necrólise epidérmica tóxica (NET) são doenças mucocutâneas pouco frequentes, agudas e potencialmente ameaçadoras à vida. Representam uma reação de hipersensibilidade e podem ser desencadeadas por fármacos, infecções e neoplasias. Dentre os principais medicamentos descritos como causadores do quadro estão o alopurinol, alguns antibióticos do grupo das sulfonamidas, anticonvulsivantes, como carbamazepina, e alguns anti-inflamatórios não esteroidais. A necrose dos queratinócitos manifesta-se clinicamente pelo descolamento epidérmico, levando a um aspecto de pele escaldada. A erupção inicia-se no tronco, com posterior generalização, geralmente poupando as áreas palmoplantares. As máculas tornam-se violáceas e há descolamento epidérmico, dando origem a bolhas flácidas, que confluem e se rompem, deixando áreas extensas erosadas. A pele perilesional apresenta sinal de Nikolsky positivo. A SSJ e a NET representam espectros da mesma doença, diferenciando-se pelo grau de descolamento epidérmico. O tratamento da SSJ e da NET é fundamentado em três medidas: retirada da droga ofensora, especialmente as medicações conhecidamente de alto risco; medidas de suporte e intervenções ativas. O diagnóstico precoce da entidade, o reconhecimento do agente causal e a retirada imediata do fármaco são as mais importantes ações, visto que a evolução dos casos é muitas vezes rápida e fatal.

Stevens-Johnson syndrome and toxic epidermal necrolysis at the University Hospital of the West Indies, Jamaica / El síndrome de Stevens-Johnson y la necrólisis epidérmica tóxica en el Hospital Universitario de West Indies, Jamaica

OBJECTIVE: Stevens-Johnson syndrome and toxic epidermal necrolysis are uncommon acute dermatologic disorders. The purpose of this study was to examine the frequency, aetiology and outcome of cases of Stevens-Johnson syndrome and toxic epidermal necrolysis admitted to the dermatology ward at the University Hospital of the West Indies. METHODS: This was a retrospective study looking at all patients who were admitted with a diagnosis of Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome and toxic epidermal necrolysis over a nine-year period. RESULTS: The results showed almost equal numbers of males and females. The drugs most commonly implicated were phenytoin and cotrimoxazole. The most common complications were hepatic impairment and ophthalmic complications. CONCLUSION: Stevens-Johnson syndrome and toxic epidermal necrolysis contribute significantly to morbidity and mortality of patients on the dermatology ward although mortality was low compared to other studies.

OBJETIVO: El síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET) son trastornos dermatológicos agudos poco frecuentes. El propósito de este estudio fue examinar la frecuencia, la etiología y el resultado de casos de síndrome Stevens-Johnson y necrólisis epidérmica tóxica ingresados en la sala de dermatología del Hospital Universitario de West Indies. MÉTODOS: Se trata de un estudio retrospectivo con todos los pacientes que fueron ingresados con diagnóstico de síndrome de Stevens-Johnson, síndrome de solapamiento entre el síndrome de Stevens-Johnson y NET, y necrólisis epidérmica tóxica, por un período de nueve años. RESULTADOS: Los resultados mostraron casi igual número de varones y hembras. Los fármacos más comúnmente implicados fueron la fenitoína y el cotrimoxazol. Las complicaciones más frecuentes fueron deterioro hepático y complicaciones oftálmicas. CONCLUSIÓN: El síndrome Stevens-Johnson y la necrólisis epidérmica tóxica contribuyen significativamente a la morbilidad y mortalidad de los pacientes en la Sala de Dermatología, aunque la mortalidad fue baja en comparación con otros estudios.

A systematic review of the drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Indian population.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous drug reactions. No large scale epidemiological data are available for this disorder in India. Aims: To carry out a systematic review of the published evidence of the drug-induced SJS and TEN in Indian population. Methods: Publications from 1995 to 2011 describing SJS and TEN in Indian population were searched in PubMed, MEDLINE, EMBASE and UK PUBMED Central electronic databases. Data were collected for the causative drugs and other clinical characteristics of SJS and TEN from the selected studies.Results: From 225 references, 10 references were included as per selection criteria. The major causative drugs were antimicrobials (37.27%), anti-epileptics (35.73%) and non-steroidal anti-inflammatory drugs (15.93%). Carbamazepine (18.25%), phenytoin (13.37%), fluoroquinolones (8.48%) and paracetamol (6.17%) were most commonly implicated drugs. Regional differences were observed for fluoroquinolones, sulfa drugs and carbamazepine. Total 62.96% of patients showed systemic complications. Most common complications were ocular (40.29%) and septicemia (17.65%). Higher mortality was observed for TEN as compared to SJS (odd ratio-7.19; 95% confidence interval (CI) 1.62-31.92; p = 0.0023). Observed mortality is higher than expected as per SCORTEN score 3. Duration of hospital stay was significantly higher in TEN (20.6 days; 95% CI 14.4-26.8) as compared to SJS (9.7 days; 95% CI 5.8-13.6; p = 0.020). Cost of management was significantly higher in TEN (Rs. 7910; 95% CI 5672-10147; p < 0.0001) as compared to SJS (Rs 2460; 95% CI 1762-3158). No statistical data were described for steroid use in the studies included. Conclusion: Carbamazepine, phenytoin, fluoroquinolones and paracetamol were the major causative drugs. TEN is showing higher mortality, morbidity and economic burden than SJS.

Intravenous immunoglobulin in the treatment of vancomycin-induced toxic epidermal necrolysis

Toxic epidermal necrolysis [TEN], an uncommon but potentially life-threatening skin reaction, is frequently induced by drugs. The mucocutaneous reaction is characterised by bullous detachment of the epidermis and mucous membranes. We present a 9-month-old male with methylmalonic acidaemia, generalised hypotonia, and global developmental delay. He presented with a 3-day history of fever, cough, shortness of breath, and vomiting. Eruption appeared after 5 days of vancomycin treatment. The eruption involved almost 60% of the total body surface area and both eyes. He was successfully treated with intravenous immunoglobulin [IVIG], antibiotics, and appropriate wound management and made a full recovery with negligible sequelae despite the severity of his disease. Important components of successful treatment include early recognition, intensive care, prompt withdrawal of the causative agent, early administration of IVIG, appropriate fluid resuscitation, and control of infection. IVIG might be beneficial in the treatment of TEN; however, controlled studies are needed to evaluate IVIG compared to other modalities

Necrolisis epidérmica tóxica como manifestación de lupus eritematoso sistémico: reporte de un caso y revisión de la literatura / Toxic epidermal necrolysis as a manifestation of systemic lupus erythematosus: report on a case and literature review

Presents a case of a young woman with a recent diagnose of systemic lupus erythematosus (SLE), with a sligth initial skin condition that envolves into toxic epidermal necrolysis (TENS): On account of this case, areview is presented of the physiopathology, clinical presentation and treatment of this infrequent form of dermatological manifestation of (SLE).

Se presenta el caso de una joven con diagnóstico reciente de lupus eritematoso sistémico (LES), con compromiso cutáneo inicial leve que evoluciona hacia necrolisis epidérmico tóxica (NET). A propósito de ello, se revisa la fisioptología, presentación clínica y tratamiento de esta infrecuente forma de manifestación dermatológica de LES.

Toxic Epidermal Necrolysis with Ocular Involvement Following Vaccination for Hemorrhagic Fever with Renal Syndrome

We report a case of toxic epidermal necrolysis with ocular involvement following vaccination for hemorrhagic fever with renal syndrome. A healthy 20-year-old male soldier presented with confluent purpuric and erythematous dusky red macules evolving to flaccid blister and epidermal detachment on the whole body with conjunctival injection. The patient had no antecedent medical or surgical conditions except for two doses of hemorrhagic fever with renal syndrome vaccination. With supportive care, skin lesions were improved. Ophthalmic examinations revealed conjunctival injection with epithelial defects in both eyes. Ocular complications were resolved after amniotic membrane transplantation. Toxic epidermal necrolysis may be considered as a possible complication of hemorrhagic fever with renal syndrome vaccination.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Toxic epidermal necrolysis and agranulocytosis: Rare adverse effects of ciprofloxacin.

Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

Stevens Johnson syndrome, toxic epidermal necrolysis and SJS-TEN overlap: a retrospective study of causative drugs and clinical outcome.

BACKGROUND AND AIMS: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap are serious adverse cutaneous drug reactions. Drugs are often implicated in these reactions. METHODS: A retrospective analysis of inpatients' data with these dermatological diagnoses were carried out for three years, to study the causative drugs, clinical outcome, and mortality in these conditions. RESULTS: Thirty patients (15 TEN, nine SJS-TEN overlap, and six SJS) were admitted. In 21 cases, multiple drugs were implicated whereas single drugs were responsible in nine. Anticonvulsants (35.08%) were the most commonly implicated drugs followed by antibiotics (33.33%) and NSAIDS (24.56%). Twenty-five patients recovered whereas five died (four TEN, one SJS-TEN overlap). CONCLUSION: Anticonvulsants, antibiotics and NSAIDs were the most frequently implicated drugs. TEN causes higher mortality than both SJS and SJS-TEN overlap.