Toxic Epidermal Necrolysis: Part II. Prognosis, Sequelae, Diagnosis, Differential Diagnosis, Prevention, and Treatment
TL;DR: Diagnostics that measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the potential to differentiate early TEN from other, less serious drug reactions, but these tests have not been validated and are not readily available.
Abstract: Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. TEN has a high mortality rate, making early diagnosis and treatment of paramount importance. New but experimental diagnostic tools that measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the potential to differentiate early TEN from other, less serious drug reactions, but these tests have not been validated and are not readily available. The mainstay of treatment for TEN involves discontinuation of the offending drug, specialized care in an intensive care unit or burn center, and supportive therapy. Pharmacogenetic studies have clearly established a link between human leukocyte antigen allotype and TEN. Human leukocyte antigen testing should be performed on patients of East Asian descent before the initiation of carbamezapine and on all patients before the initiation of abacavir. The effectiveness of systemic steroids, intravenous immunoglobulins, plasmapheresis, cyclosporine, biologics, and other agents is uncertain.
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TL;DR: The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.
Abstract: The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
1,691 citations
TL;DR: In this article, the authors present characteristics and subgroup analyses from the first 1257 patients enrolled in the study, and conclude that there are no differences in outcomes of patients with short vs long latency of DILI.
576 citations
01 Jan 2011
TL;DR: This review focuses on the development of HLA-B*5701 genetic screening as a means of preventing drug hypersensitivity reactions and the international current research situation.
Abstract: Abacavir hypersensitivity reactions(ABC HSR) is a multi-organ hypersensitivity syndrome caused by abacavir which has been prescribed for the treatment of HIV infection in the West.In 2001 a strong predictive association of carriage of HLA-B*5701 allele with abacavir hypersensitivity reactions was described.Afterwards,a large number of studies were designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir.This review focuses on the development of HLA-B*5701 genetic screening as a means of preventing drug hypersensitivity reactions and the international current research situation.
275 citations
TL;DR: Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid.
Abstract: Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the rapid development of nonfollicular, sterile pustules on an erythematous base. It is attributed to drugs in the majority of cases. Antibiotics are the most common cause of acute generalized exanthematous pustulosis; however, a wide variety of drugs has been associated with this condition. Typically, within 48 hours of ingesting the causative medication, there is acute onset of fever and pustulosis with leukocytosis. In severe cases there can be mucous membrane and systemic organ involvement. Histologic findings include intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils. Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid.
218 citations
Journal Article•
TL;DR: In this article, the authors describe the most common skin adverse drug reactions, including toxic epidermal necrolysis (TEN), drug reaction with Eosinophilia and systemic symptoms (DRESS), which can result in death.
Abstract: Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. Drug reactions are self-limited diseases and therefore, generally treatment is symptomatic. Prompt diagnosis, identification of, and early withdrawal of all suspect drugs are the most important preliminaries. The management of the patients must be undertaken in specialized intensive care units, with the same main types of therapy as for burns: warming of the environment, correction of electrolyte disturbances, administration of a high caloric enteral intake, and prevention of sepsis. Efficacy of drugs used in some case reports is difficult to evaluate: intravenous immunoglobulins, cyclosporin, cyclophosphamide, pentoxyfilline, and thalidomide have all been tried. Corticosteroid use is debated and is probably deleterious in late forms of TEN. For DRESS, corticoids are used in cases of life-threatening systemic impairment. Specific nursing care and adequate topical management reduce associated morbidity and allow a more rapid re-epithelialization of skin lesions. After healing, follow-up is needed for ophthalmologic and mucous membrane sequelae. Sunblocks are recommended. Testing for glycemia must be done. Avoidance of the responsible drug and chemically related compounds is essential for the patient and first-degree relatives.
211 citations
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TL;DR: This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture of Japan and by a Research Grant from the Princess Takamatsu Cancer Research Fund, and performed in part through Special Coordination Funds of the Science and Technology Agency of the Japanese Government.
5,054 citations
TL;DR: HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir and showed that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug.
Abstract: Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir. Methods This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701–positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir. Results The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001). Conclusions HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)
1,594 citations
TL;DR: This paper showed that there is a strong association in Han Chinese between the human leukocyte antigen HLA-B*1502 and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures.
Abstract: Stevens-Johnson syndrome and the related disease toxic epidermal necrolysis are life-threatening reactions of the skin to particular types of medication. Here we show that there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures. It should be possible to exploit this association in a highly reliable test to predict severe adverse reaction, as well as for investigation of the pathogenesis of Stevens-Johnson syndrome.
1,557 citations
TL;DR: This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents.
Abstract: • Background and Design.— To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme—like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema. Results.— The following consensus classification in five categories was proposed: bullous erythema multiforme , detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome , detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome— toxic epidermal necrolysis , detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots , detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots , detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts. Conclusion.— This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attibuted to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations. ( Arch Dermatol. 1993;129:92-96)
1,449 citations
TL;DR: In this population of HIV-1-positive individuals, withholding abacavir in those with HLA-B*5701, H LA-DR7, and Hla-DQ3 should reduce the prevalence of hypersensitivity from 9% to 2.5% without inappropriately denying abacvir to any patient.
1,366 citations