abacavir and Stevens-Johnson-Syndrome

Controversies exist with regard to in vivo approaches to delayed immunologically mediated adverse drug reactions, such as exanthem (maculopapular eruption), drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and fixed drug eruptions. In particular, widespread differences exist between regions and practice on the availability and use of intradermal and patch testing, the standard drug concentrations used, the use of additional drugs in intradermal and patch testing to help determine cross-reactivity, the timing of testing in relation to the occurrence of the adverse drug reaction, the use of testing in specific phenotypes, and the use of oral challenge in conjunction with delayed intradermal and patch testing to ascertain drug tolerance. It was noted that there have been advances in the science of delayed T cell-mediated reactions that have shed light on immunopathogenesis and provided a mechanism of preprescription screening in the case of HLA-B*57:01 and abacavir hypersensitivity and HLA-B*15:02 and carbamazepine Stevens-Johnson syndrome/toxic epidermal necrolysis in Southeast Asian subjects. Future directions should include the collaboration of large international networks to develop and standardize in vivo diagnostic approaches, such as skin testing and patch testing, combined with ex vivo and in vitro laboratory approaches.

Topics: Animals; Asian People; Carbamazepine; Dideoxynucleosides; HLA-B Antigens; HLA-B15 Antigen; Humans; Skin Tests; Stevens-Johnson Syndrome

Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine.

Topics: Allopurinol; Anti-HIV Agents; Anticonvulsants; Biomarkers; Carbamazepine; Dideoxynucleosides; Genetic Markers; Gout Suppressants; HLA-B Antigens; Humans; Inactivation, Metabolic; Pharmacogenetics; Precision Medicine; Prognosis; Safety-Based Drug Withdrawals; Stevens-Johnson Syndrome

Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions.

Topics: Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Gene Expression Regulation; Genetic Heterogeneity; HIV Infections; HLA Antigens; Humans; Models, Immunological; Pharmacogenetics; Receptors, Antigen, T-Cell; Stevens-Johnson Syndrome; T-Lymphocytes

Immune-mediated (IM) adverse drug reactions (ADRs) are an underrecognized source of preventable morbidity, mortality, and cost. Increasingly, genetic variation in the HLA loci is associated with risk of severe reactions, highlighting the importance of T-cell immune responses in the mechanisms of both B cell-mediated and primary T cell-mediated IM-ADRs. In this review we summarize the role of host genetics, microbes, and drugs in IM-ADR development; expand on the existing models of IM-ADR pathogenesis to address multiple unexplained observations; discuss the implications of this work in clinical practice today; and describe future applications for preclinical drug toxicity screening, drug design, and development.

Topics: Allopurinol; B-Lymphocytes; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Gene Expression Regulation; Genetic Loci; HLA Antigens; Humans; Models, Immunological; Pharmacogenetics; Stevens-Johnson Syndrome; T-Lymphocytes; Virus Diseases

Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacologic target (type A ADR) or an unintended target (type B ADR). Immunologically mediated type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms syndrome, and Stevens-Johnson syndrome/toxic epidermal necrolysis, can be severe and result in a diverse set of clinical manifestations that include fever and rash, as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell-mediated ADRs are strikingly similar to those displayed by patients with autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for immunologically mediated type B ADRs. Because methods to predict type 1 diabetes by using genetic and immunologic biomarkers have been developed to a high level of accuracy (predicting 100% of subjects likely to progress), new research strategies based on these methods might also improve the ability to predict drug hypersensitivity.

Topics: Autoimmunity; Carbamazepine; Diabetes Mellitus, Type 1; Dideoxynucleosides; Drug Hypersensitivity; Gene Expression Regulation; HLA Antigens; Humans; Models, Molecular; Pharmacogenetics; Prognosis; Receptors, Antigen, T-Cell; Stevens-Johnson Syndrome; T-Lymphocytes; Virus Diseases

Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.

Topics: Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Genotype; HLA-B Antigens; Humans; Nevirapine; Pharmacogenetics; Protein Conformation; Stevens-Johnson Syndrome

Different responses, in terms both of efficacy and toxicity, are commonly observed for any drug administered to apparently homogeneous groups of patients. It is estimated that adverse drug reactions (ADRs) cause 3-6% of all hospitalizations, accounting for 5% to 9% of hospital admission costs. The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis. SCARs are associated with significant mortality and require prompt diagnosis and adequate treatment. Pharmacogenetics studies individual variants in the DNA sequence associated with drug efficacy and toxicity, allowing prescription of a drug to patients expected to benefit from it, and excluding from treatment those who are at risk of developing ADRs. Pharmacogenetics already achieved several important results in the prevention of SCARs, and pharmacogenetic testing is now recommended by regulatory agencies before administration of abacavir and carbamazepine, leading to reduced incidence of SCARs. In this review, the pharmacogenetic associations of SCARs that have been validated in independent, case-control association studies will be presented. By familiarizing with principles of pharmacogenetics, dermatologists should be able to correlate specific cutaneous ADR phenotypes to the underlying genotype, thus contributing to better drug safety and facilitating drug discovery, development and approval.

Topics: Allopurinol; Anti-HIV Agents; Anticonvulsants; Biomarkers; Carbamazepine; Dideoxynucleosides; Drug Eruptions; Drug Hypersensitivity Syndrome; Enzyme Inhibitors; Genes, MHC Class I; Genome-Wide Association Study; Genotype; HLA Antigens; Humans; Nevirapine; Pharmacogenetics; Polymorphism, Single Nucleotide; Stevens-Johnson Syndrome

T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity.

Topics: Alleles; Allopurinol; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity Syndrome; Gene Expression; Genetic Predisposition to Disease; HLA Antigens; Humans; Stevens-Johnson Syndrome; T-Lymphocytes

Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.

Topics: Alleles; Allopurinol; Amoxicillin-Potassium Clavulanate Combination; Azetidines; Benzylamines; Carbamazepine; Chemical and Drug Induced Liver Injury; Diclofenac; Dideoxynucleosides; Drug Hypersensitivity; Floxacillin; Genetic Markers; HLA Antigens; HLA-A Antigens; HLA-B Antigens; HLA-DQ alpha-Chains; Humans; Lapatinib; Pharmacogenetics; Quinazolines; Skin; Stevens-Johnson Syndrome; Ticlopidine

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

Topics: Alleles; Allopurinol; Anti-HIV Agents; Anticonvulsants; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity Syndrome; Drug-Related Side Effects and Adverse Reactions; Enzyme Inhibitors; Genome-Wide Association Study; HLA Antigens; HLA-B Antigens; HLA-B15 Antigen; Humans; Stevens-Johnson Syndrome

The human leucocyte antigen (HLA) system is well known for its association with certain diseases such as ankylosing spondylitis, celiac disease and many others. More recently, severe and even fatal drug hypersensitivity reactions linked to particular HLA alleles have been discovered. The significance of these discoveries has led the European Medicines Agency (EMA) and its member state agencies to recommend HLA gene testing before initiation of drug treatment. To date, the following drugs have been identified as causing significant drug hypersensitivity reactions in patients who have the following HLA alleles: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02/A*31:01 and finally allopurinol and HLA-B*58:01. This review will outline and discuss these three drugs and their associated HLA alleles as well as examine the pathogenesis of the drug hypersensitivity reactions.

Topics: Alleles; Allopurinol; Anti-HIV Agents; Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Gene Frequency; Genetic Testing; HLA-B Antigens; HLA-B15 Antigen; Humans; Pharmacogenetics; Stevens-Johnson Syndrome

Drug hypersensitivity reactions and severe cutaneous adverse drug reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, are examples of serious adverse drug reactions mediated through a combination of metabolic and immunological mechanisms that could traditionally not have been predicted based on the pharmacological characteristics of the drug alone. The discovery of new associations between these syndromes and specific HLA has created the promise that risk for these reactions could be predicted through pharmacogenetic screening, thereby avoiding serious morbidity and mortality associated with these types of drug reactions. Despite this, several hurdles exist in the translation of these associations into pharmacogenetic tests that could be routinely used in the clinical setting. HLA-B*5701 screening to prevent abacavir hypersensitivity syndrome is an example of a test now in widespread routine clinical use in the developed world.

Topics: Diagnostic Uses of Chemicals; Dideoxynucleosides; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Forecasting; HLA-B Antigens; Humans; Pharmaceutical Preparations; Pharmacogenetics; Stevens-Johnson Syndrome

The present article reviews the recent literature on the identification of human leukocyte antigen (HLA) alleles as major susceptible genes for drug hypersensitivity and discusses the clinical implications.. Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to drug hypersensitivity. The genetic associations can be drug specific, such as HLA-B*1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), HLA-B*5701 with abacavir hypersensitivity and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions. A genetic association can also be phenotype-specific, as B*1502 is associated solely with carbamazepine-SJS/TEN, and not with either maculopapular eruption or hypersensitivity syndrome. Furthermore, a genetic association can also be ethnicity specific; carbamazepine-SJS/TEN associated with B*1502 is seen in south-east Asians but not in whites, which may be explained by the different allele frequencies.. The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity when the HLA molecule presents an antigenic drug for T cell activation. The high sensitivity/specificity of some markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity. Application of HLA-B*1502 genotyping as a screening tool before prescribing carbamazepine could be a valuable tool in preventing carbamazepine-induced SJS/TEN in south-east Asian countries.

Topics: Allopurinol; Carbamazepine; Dideoxynucleosides; Drug Eruptions; Drug Hypersensitivity; Genetic Predisposition to Disease; HLA Antigens; HLA-B Antigens; Humans; Pharmacogenetics; Stevens-Johnson Syndrome

The primary goal of the highly active antiretroviral treatment is to improve HIV-infected patient immune function through maintaining viral suppression. However, this treatment may lead to adverse events, some of them potentially serious. This article emphasizes on the antiretroviral therapy associated adverse events and their management recommendations, especially for serious or potentially life-threatening cases. Adverse events analyzed in this article include side effects derived from mitochondrial toxicity, abacavir hypersensitivity reaction, hepatotoxicity, skin rash and Stevens-Johnson syndrome, increased bleeding episodes in hemophilic patients and nephrotoxicity. In some cases, a high suspicion is needed because the onset symptoms may be unspecific.

Topics: Antiretroviral Therapy, Highly Active; Dideoxynucleosides; Exanthema; Hemorrhage; HIV Infections; Humans; Liver Failure; Mitochondrial Myopathies; Stevens-Johnson Syndrome

CIRCUMSTANCES AND CHARACTERISTICS: The risk of toxiderma is greater in patients infected by the human immunodeficiency virus (HIV). The most common toxidermas are maculopapular exanthema and drug hypersensitivity reactions. These toxidermas are predominantly observed with non-nucleoside reverse transcriptase analogs (nevirapine, efavirenz) and abacavir. Toxiderma has also been observed with other nucleoside reverse transcriptase analogs (zalcitabine) and protease inhibitors. REGARDING SEVERITY: The toxidermas observed are usually benign (maculopapular exanthema) and do not always require suspension of the treatment. However, certain toxidermas (Stevens-Johnson syndrome, Lyell syndrome and drug hypersensitivity syndrome) may be life-threatening and therefore contraindicate the continuation of treatment and also its sudden reintroduction. PREVENTION AND PRACTICAL APPROACH: Several studies have assessed the risk factors for toxiderma induced by nevirapine and hypersensitivity reactions to abacavir. The practical approach varies depending on the drug responsible, the clinical form of the toxiderma and the possible alternatives.

Topics: Alkynes; Anti-HIV Agents; Anti-Inflammatory Agents; Benzoxazines; Cyclopropanes; Dideoxynucleosides; Drug Hypersensitivity; Exanthema; Histamine H1 Antagonists; HIV Infections; HIV Protease Inhibitors; Humans; Nevirapine; Oxazines; Reverse Transcriptase Inhibitors; Risk Factors; Steroids; Stevens-Johnson Syndrome

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are antiretroviral drugs often used in the first-line treatment regimen of HIV1 infection worldwide. We report a case of successive gynecomastia and Stevens-Johnson syndrome (SJS) respectively induced by efavirenz and nevirapine in a single patient.. A 16-year-old boy, HIV1-infected since birth, was started on antiretroviral treatment (ART) in August 2015 and was taking a regimen comprising abacavir, lamivudine and efavirenz. In April 2016, when his weight reached 35kg, abacavir was replaced with tenofovir. Bilateral breast enlargement, previously hidden by the patient, was diagnosed two years after the start of ART. History-taking, physical examination and laboratory tests ruled out known causes of gynecomastia, and efavirenz was thus considered the most likely cause. This drug was then withdrawn and replaced with nevirapine in July 2017. Thirty-three days after the patient started nevirapine treatment, a skin rash appeared. Physical examination revealed erythematous macules and flaccid bullae with estimated skin detachment of 10%. There were also conjunctival, buccal and genital lesions. A diagnosis was made of SJS induced by nevirapine. Three months after withdrawal of efavirenz, breast size decreased by 3cm on the left breast and 2cm on the right breast; two months after the SJS, cutaneous sequelae alone persisted, such as diffuse hyperchromic macules.. Recognition of gynecomastia as a side-effect of efavirenz is important to allow the condition to be treated while it is still potentially reversible. Moreover, when efavirenz is replaced, a protease inhibitor should be preferred to nevirapine.

Topics: Adolescent; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Dideoxynucleosides; Drug Substitution; Gynecomastia; HIV Infections; Humans; Lamivudine; Male; Mucositis; Nevirapine; Reverse Transcriptase Inhibitors; Stevens-Johnson Syndrome

Allergic reactions to drugs are a serious public health concern. In 2013, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop on drug allergy. International experts in the field of drug allergy with backgrounds in allergy, immunology, infectious diseases, dermatology, clinical pharmacology, and pharmacogenomics discussed the current state of drug allergy research. These experts were joined by representatives from several National Institutes of Health institutes and the US Food and Drug Administration. The participants identified important advances that make new research directions feasible and made suggestions for research priorities and for development of infrastructure to advance our knowledge of the mechanisms, diagnosis, management, and prevention of drug allergy. The workshop summary and recommendations are presented herein.

Topics: Carbamazepine; Dideoxynucleosides; Drug Hypersensitivity; Gene Expression; Haptens; HLA Antigens; Humans; Immunoglobulin E; National Institute of Allergy and Infectious Diseases (U.S.); Practice Guidelines as Topic; Receptors, Antigen, T-Cell; Stevens-Johnson Syndrome; Terminology as Topic; Translational Research, Biomedical; United States; Virus Diseases

Drug hypersensitivity reactions are an immune-mediated reaction to otherwise innocuous antigens derived from drugs. These reactions can affect many different organs, with the skin being the commonest. Skin involvement can range in severity with hypersensitivity syndrome (or DRESS) and the blistering reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), also termed serious cutaneous adverse drug reactions, being the most severe and most feared. There is increasing evidence for the role of the immune system in the pathogenesis of these reactions, with drug-specific T cells having been identified in many patients. Until recently, very little was known about the predisposition to these reactions. However, the availability of more accurate molecular typing methods, and the ability to analyse the whole genome in an unbiased fashion, has led to some remarkable findings of the role of the HLA genes as genomic biomarkers of predisposition. The 'revolution' started with abacavir where the predisposition to hypersensitivity was linked to HLA-B*57:01, which was confirmed in a clinical trial, and where its implementation has shown to reduce the incidence of hypersensitivity in a cost-effective manner. Since then, associations have also been shown for allopurinol (HLA-B*58:01)- and carbamazepine (HLA-B*1502 and HLA-A*3101)-induced serious cutaneous adverse drug reactions. The latter is interesting since the association with HLA-B*1502 is present in certain South-Eastern Asian populations, and the predisposition is phenotype specific (only for SJS/TEN). The utility of this biomarker has been shown in a prospective cohort study performed in Taiwan. By contrast, the association with HLA-A*3101 is seen in more diverse ethnic groups, and predisposes to mild as well more severe cutaneous reactions associated with carbamazepine. It is important to note that strong HLA associations have also been shown with a number of drugs that cause liver injury including flucloxacillin, lumiracoxib, lapatinib and ximelagatran, indicating that the immune system is also important in the pathogenesis of other forms of drug-induced organ toxicity. The crucial question as to whether these HLA alleles are truly causative or acting as surrogate markers of predisposition, however, is still unclear, and will require further investigations in larger patient cohorts, through the use of bioinformatic techniques, fine mapping using next generation sequencing technologies and functional stud

Topics: Allopurinol; Anti-Bacterial Agents; Anti-HIV Agents; Anticonvulsants; Antimetabolites; Biomarkers; Carbamazepine; Chemical and Drug Induced Liver Injury; Dideoxynucleosides; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Genome-Wide Association Study; HLA Antigens; HLA-A Antigens; HLA-B Antigens; Humans; Immune System; Predictive Value of Tests; Stevens-Johnson Syndrome

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two variants on a spectrum of severe systemic hypersensitivity characterized by blistering maculopapular lesions and desquamation of the skin and mucus membranes. Although several causative agents, including infections, have been reported for SJS/TEN, medications remain the most common cause. We report the case of a 42-year-old man with human immunodeficiency virus (HIV) who developed TEN 4 months after starting treatment with darunavir and abacavir. The patient presented with upper body lesions, oral mucosal ulcerations, and impending airway compromise. He was intubated and admitted to the burns unit. Score for Toxic Epidermal Necrolysis (SCORTEN) was 5, with > 90% predicted mortality. However, after intravenous immunoglobulin and supportive treatment, the patient made a remarkable recovery. Abacavir and darunavir may be associated with SJS/TEN. TEN should be considered a risk for patients with HIV and should be monitored for cutaneous eruptions for several months after changes in treatment regimen.

Topics: Adult; Antiviral Agents; Darunavir; Dideoxynucleosides; HIV Infections; HIV-1; Humans; Immunoglobulins, Intravenous; Male; Risk Factors; Stevens-Johnson Syndrome; Sulfonamides; Treatment Outcome

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Didanosine; Dideoxynucleosides; HIV Infections; HIV-Associated Lipodystrophy Syndrome; Humans; Male; Nevirapine; Reverse Transcriptase Inhibitors; Stavudine; Stevens-Johnson Syndrome

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Dideoxynucleosides; Humans; Male; Stevens-Johnson Syndrome