Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. Objective The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. Methods Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. Results Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n = 21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. Limitations All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. Conclusion Early dermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.

Distinguishing Stevens-Johnson syndrome/toxic epidermal necrolysis from clinical mimickers during inpatient dermatologic consultation—A retrospective chart review

Aim. To determine the probable causative factors, clinical features, and treatment outcomes of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap in children. Methods. A 20-year database review of all children diagnosed with SJS/TEN/SJS-TEN overlap at the King Chulalongkorn Memorial Hospital, Thailand. Results. 36 patients (M : F, 16 : 20) with the mean age of years were identified. There were 20 cases of SJS, 4 cases of SJS-TEN overlap, and 12 cases of TEN. Drugs were the leading cause for the diseases (72.3%); antiepileptics were the most common culprits (36.1%). Cutaneous morphology at presentation was morbilliform rash (83.3%), blister (38.9%), targetoid lesions (25.0%), and purpuric macules (2.8%). Oral mucosa (97.2%) and eye (83.3%) were the 2 most common mucosal involvements. Majority of the cases (77.8%) were treated with systemic corticosteroids, intravenous immunoglobulin, or both. Treatment outcomes between those who received systemic therapy and those who received only supportive care were comparable. Skin and eye were the principal sites of short-term and long-term complications. Conclusions. SJS/TEN are not common but are serious diseases which lead to significant morbidities in children. Early withdrawal of suspicious causes and meticulous supportive care are very important. This study found that the systemic therapy was not superior to supportive care because the treatment outcomes for both groups were comparable.

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Clinical Features and Treatment Outcomes among Children with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A 20-Year Study in a Tertiary Referral Hospital.

BACKGROUND Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening adverse drug reactions (ADRs) that are commonly caused by medications. Apart from their contribution to morbidity and mortality, these diseases may also present substantial consequences on health care resources. In this study, we aimed to identify the incidence, causative drugs, and economic consequences of these serious ADRs and potential drug-drug interactions (DDIs) during treatment. METHODS A retrospective study that included 150 patients diagnosed with drug-induced SJS, SJS-TEN overlap, and TEN, from 2009 to 2013 in a referral hospital in West Java Province, Indonesia, was conducted to analyze the causative drugs, cost of illness (COI) as a representation of economic consequences, and potential DDIs during treatment. RESULTS The results showed that analgesic-antipyretic drugs were the most frequently implicated drugs. The COIs for SJS, SJS-TEN overlap, and TEN patients were 119.49, 139.21, and 162.08 US dollars per day, respectively. Furthermore, potential DDIs with several therapeutic medications and corticosteroids used to treat SJS, SJS-TEN overlap, and TEN were also identified. CONCLUSION This study showed that analgesic-antipyretic was the major causative drug which contributed to SJS, SJS-TEN overlap, and TEN. Furthermore, our results also showed that SJS, SJS-TEN overlap, and TEN may cause considerable financial consequences to patients.

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Incidence, causative drugs, and economic consequences of drug-induced SJS, TEN, and SJS-TEN overlap and potential drug-drug interactions during treatment: a retrospective analysis at an Indonesian referral hospital.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Severe delayed drug hypersensitivity reactions comprise different clinical entities and can involve different immune-mediated mechanisms. Common examples are severe cutaneous adverse reactions and druginduced internal organ injuries. The incidence of such reactions is overall low but seems to be on the rise reaching numbers as high as 9 per million individuals-years in the case of SJS/TEN and DRESS. Such conditions carry an important associated morbidity, and mortality can attain 40% in SJS/TEN patients, making these hypersensitivity reactions important targets when implementing preventive measures. Several risk factors have been identified for reaction severity; some are transverse, such as older age and underlying chronic diseases. The recent advances in pharmacogenetics allowed the identification of specific populations with higher risk and permitted strategic avoidance of certain drugs being HLA-B*57:01 screening in patients initiating abacavir the best successful example. In this work, we reviewed the epidemiology of SCARs and liver/kidney/lung drug-induced immune-mediated reactions. We focus on particular aspects such as prevalence and incidence, drugs involved, mortality and risk factors.

Epidemiology and risk factors for severe delayed drug hypersensitivity reactions.

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening dermatologic conditions. Although, the incidence of SJS/TEN in Thailand is high, information on cost of care for SJS/TEN is limited. This study aims to estimate healthcare resource utilization and cost of SJS/TEN in Thailand, using hospital perspective. Methods: A retrospective study using an electronic health database from a university-affiliated hospital in Thailand was undertaken. Patients admitted with SJS/TEN from 2002 to 2007 were included. Direct medical cost was estimated by the cost-to-charge ratio. Cost was converted to 2013 value by consumer price index, and converted to $US using 31 Baht/ 1 $US. The healthcare resource utilization was also estimated. Results: A total of 157 patients were included with average age of 45.3±23.0 years. About 146 patients (93.0%) were diagnosed as SJS and the remaining (7.0%) were diagnosed as TEN. Most of the patients (83.4%) were treated with systemic corticosteroids. Overall, mortality rate was 8.3%, while the average length of stay (LOS) was 10.1±13.2 days. The average cost of managing SJS/TEN for all patients was $1,064±$2,558. The average cost for SJS patients was $1,019±$2,601 while that for TEN patients was $1,660±$1,887. Conclusions: Healthcare resource utilization and cost of care for SJS/TEN in Thailand were tremendous. The findings are important for policy makers to allocate healthcare resources and develop strategies to prevent SJS/TEN which could decrease length of stay and cost of care.

C Inprasong

Papers

Healthcare utilization and cost of Stevens-Johnson syndrome and toxic epidermal necrolysis management in Thailand