General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Toxic Epidermal Necrolysis and Steven-Johnson Syndrome: A Comprehensive Review.

Significance: Toxic epidermal necrolysis (TEN) and Steven-Johnson syndrome (SJS) are potentially fatal acute mucocutaneous vesiculobullous disorders. Evidence to date suggests that outcomes for patients with both TEN and SJS are largely dependent on stopping the causative agent, followed by supportive care and appropriate wound management in a specialized burns unit. These are life-threatening conditions characterized by widespread full-thickness cutaneous and mucosal necrosis. This article outlines the approach to holistic management of such patients, in a specialized unit, highlighting various practical aspects of wound care to prevent complications such as infection, mucosal and adhesions, and ocular scaring. Recent Advances: There is improved understanding of pain and morbidity with regard to the type and frequency of dressing changes. More modern dressings, such as nanocrystalline, are currently favored as they may be kept in situ for longer periods. The most recent evidence on systemic agents, such as corticosteroids and cyclosporine, and novel treatments, are also discussed. Critical Issues: Following cessation of the culprit trigger, management in a specialized burns unit is the most important management step. It is now understood that a multidisciplinary team is essential in the care of these patients. Following admission of such patients, dermatology, ear, nose, and throat surgery, ophthalmology, urology, colorectal surgery, and gynecology should all be consulted to prevent disease sequelae. Future Directions: Looking forward, research is aimed at achieving prospective data on the efficacy of systemic immunomodulating agents and dressing types. Tertiary centers with burns units should develop policies for such patients to ensure that the relevant teams are consulted promptly to avoid mucocutaneous complications.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

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.

Influencia de los factores neonatales y maternos en la prevalencia de vérnix caseosa / Influence of Neonatal and Maternal Factors on the Prevalence of Vernix Caseosa

Al nacimiento la vérnix caseosa puede cubrir toda la superficie corporal o acumularse sólo en la espalda y los pliegues. En los últimos años ha aumentado el interés por su composición, funciones y aplicaciones en la edad adulta. Nuestro objetivo fue conocer la prevalencia de la vérnix caseosa en los recién nacidos del Área Sanitaria de Ferrol, y ver cómo repercutían los parámetros neonatales y maternos en su desarrollo. Realizamos un estudio prospectivo de 1.000 recién nacidos vistos en los primeros tres días de vida en nuestro hospital. Encontramos vérnix caseosa en el 49,2% de los neonatos. El perfil clínico de presencia de vérnix caseosa sería: recién nacido de sexo femenino, sano, a término, con peso elevado producto de una gestante no primigesta, con ingesta de fármacos y suplementos dietéticos durante el embarazo sometida a un parto eutócico. Existe relación entre ausencia de vérnix caseosa y la presencia de descamación fisiológica y de eritema tóxico neonatal (AU)

At birth, vernix caseosa can cover the whole body surface or accumulate only on the back and in the skin folds. Interest in its composition and function and its possible applications in adults has increased in recent years. The objective of this study was to determine the prevalence of vernix caseosa in newborn infants in the health care area of Ferrol, Spain, and to assess its relationship with neonatal and maternal factors. We performed a prospective study of 1000 newborns seen within the first 3days of life in our hospital. Vernix caseosa was observed in 42.9% of cases. The clinical profile associated with the presence of vernix caseosa was the following: healthy newborn girl with a high birth weight, born at term by normal vaginal delivery to a multiparous mother who had received medication and dietary supplements during pregnancy. The absence of vernix caseosa was associated with the presence of physiological scaling of the newborn and erythema toxicum neonatorum (AU)

Analysis of body constitution of fifty-two patients with Stevens-Johnson Syndrome (SJS) using Kampo Medical Questionnaires: prediction of SJS based on body constitution using decision tree.

UNLABELLED: Reports have indicated a relationship between adverse drug reaction (ADR) and Human Leukocyte Antigen (HLA) polymorphism and a relationship between Body Constitution (BC) and HLA polymorphism. Thus, a relationship between ADR and BC is suggested. We therefore created a questionnaire (hereinafter "Questionnaire") to survey the typical BC of Stevens-Johnson Syndrome (SJS) patients to determine how they differ from healthy persons, and studied the relationship between the development of SJS and BC. The Questionnaire had 30 typical items selected from those relevant to the BC necessary for the diagnosis and therapy of Sho-syndrome in Kampo Medicine. In the comparison of the prevalence of BCs between SJS patients and control persons, the prevalence of three BCs in the SJS group was significantly higher than that in the control group: 1) Does your throat ever feel closed up? ANSWER: Yes, 2) Do you easily feel hot flashes or burning cheeks even though your hands and feet feel cold? ANSWER: Yes, and 3) Do your lips or gums look dull red? ANSWER: Yes. In the analysis using the decision tree, the concentrated group of SJS patients (eighty-fold) was extracted using two decision trees consisting of 3 index variables. Persons with BCs from any of 1) to 3) are suggested to be at high risk of developing SJS.

Uso de inmunoglobulina intravenosa en el tratamiento de necrólisis epidérmica tóxica y síndrome de Stevens-Johnson / Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome

La necrólisis epidérmica tóxica (NET) y el síndrome de Stevens-Johnson (SSJ) se describen como variantes de una misma enfermedad con diferente severidad y constituyen las reacciones cutáneas más frecuentes en niños con una considerable morbilidad. Varias comunicaciones apoyan el uso de la inmunoglobulina intravenosa (IGIV) para el tratamiento de tales entidades. Nosotros presentamos el caso de 2 pacientes, uno con NET y uno con SSJ en quienes se utilizó inmunoglobulina con resultados exitosos. Además hacemos una revisión de la evolución de 13 pacientes con NET y SSJ en los últimos 10 años en el Hospital Infantil de México en quienes se utilizó tratamiento convencional

Toxic epidermal necrolysis and Stevens-Johnson syndrome are described as variants of the same disease with distinct severity and constitute the most frequent cutaneous reactions in children, causing considerable morbidity. Several reports support the use of intravenous immunoglobulin therapy in these entities. We report the cases of two patients, one with toxic epidermal necrolysis and the other with Stevens-Johnson syndrome, in whom immunoglobulin treatment was successfully used. We also reviewed the outcomes of 13 patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in the previous 10 years in the Hospital Infantil de Mexico, in whom conventional treatment was used

Epidemiological study of severe cutaneous adverse drug reactions in a city district of China.

BACKGROUND: An epidemiological study of severe cutaneous adverse drug reactions (SCADRs) in China has not been reported. AIMS: To estimate the incidence of SCADRs in a city district of China. METHODS: A retrospective study was performed in Peking University Third Hospital, the only hospital in Haidian district, Beijing with a dermatology ward. The medical records of inpatients with SCADRs from January 1994 to December 2002 were studied. RESULTS: The prevalence rates for overall SCADRs, Stevens-Johnson syndrome (SJS), exfoliative dermatitis (ED), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) among hospitalized patients were 0.32, 0.15, 0.10, 0.04 and 0.07 per thousand, respectively. The risk of SCADRs from systemic drugs among hospitalized patients was 0.03/1000 (0.02/1000 for SJS, and 0.01/1000 for ED and DRESS). The reported incidence of SCADRs in Haidian district was not less than 1.8 per million person-years. The reported incidence of ED, SJS, TEN and DRESS in Haidian district was not less than 0.6, 0.8, 0.05 and 0.4 per million person-years, respectively. The most common underlying disorders were infection, pain-related diseases and epilepsy. Antibiotics were the most common offending drugs followed by anticonvulsants and traditional Chinese medicines (TCM). CONCLUSIONS: These results confirm the relatively low incidence of SCADRs in China. Antibiotics, anticonvulsants and TCM are the most common causative drugs.