Incidence Of Toxic Epidermal Necrolysis Research Articles

Stevens-Johnson Syndrome

Stevens-Johnson Syndrome (SJS) is an antibody-mediated disease characterized by prodromal symptoms followed by severe mucocutaneous manifestations. The more severe form of SJS is Toxic Epidermal Necrolysis (TEN), which causes an inflammatory response resulting in keratinocyte necrosis and perivascular lymphocyte infiltration. The incidence of SJS is said to be 1 - 6 per one million people per year, while the incidence of TEN is only 0.4 - 1.2 per one million people per year. So far, similar studies on SJS/TEN cases in Indonesia are minimal as this disease is one of the rare cases. SJS/TEN is an emergency with high mortality and disability. Moderate to severe cases have a mortality rate of 5-15%. In this case, the patient was a 62-year-old male. Based on history and physical examination, the patient was diagnosed with Stevens-Johnson Syndrome (SJS). In the dermatologic status of the manus region dextra and sinistra, sagging bulla was found, and in the anterior thorax region, erosive lesions due to ruptured bulla were found. In the medialis femoris region dextra, multiple erythematous, annular macular lesions were found. There were erosions and crusts on the labial and genital regions.

COVID-19 INFECTION AND STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS: ONE MORE THING TO WORRY ABOUT?

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) are fatal cutaneous side effects occasionally seen in the ICU. Although HIV is a known risk factor for SJS/TEN, we yet do not know the relation of COVID-19 infection to these severe cutaneous adverse reactions (SCAR) [1]. Here we present a case of a young man with COVID-19 and HIV infection who developed SCAR. CASE PRESENTATION: 40-year-old male with past medical history of substance abuse, HCV, HIV infection (not on ART) presented with odynophagia, voice change and drooling. COVID-19 testing in ED was positive. Head and neck CT scan revealed retropharyngeal abscess. He was intubated emergently due to inability to manage secretions and increased work of breathing. Abscess was managed conservatively with Ampicillin/Sulbactam and methylprednisone. On antibiotic day #3, he developed purple rashes with dark brown vesicles on his face, neck and anterior chest (Image 1). The following day, this evolved into an extensive bullous eruption with de-epithelization and epithelial loss, with lesions including face, eye lids, eyes, neck, upper trunk, bilateral upper extremities, back, genitalia and bilateral lower extremities (Image 2,3). Dermatology was consulted with concern for SJS/TEN and Ampicillin/Sulbactam was discontinued. His skin biopsy demonstrated full thickness epidermal necrosis. He was managed with pain medication, IV fluids, wound care and intravenous immunoglobulin.Meanwhile, his CD4 count was 65 with viral load of 174,000 which he was started on Atovaquone for PJP prophylaxis. COVID-19 markers were elevated on admission (CRP 2.49, Ferritin 546, D-dimer 0.69 LDH 299), and remained elevated throughout his hospital stay. Chest X-ray showed bibasilar hypoventilatory change with bilateral pleural effusions. Prophylactic low molecular weight heparin and methylprednisone were initiated.Patient was transferred to other facility burn ICU for further management. Despite full care, his skin lesions worsened, and patient passed away on hospital day 15. DISCUSSION: It has been reported that concomitant HIV and viral infections can precipitate SCAR [2]. However, we know little about COVID-19 infection and its relation to SCAR. There are few documented cases of COVID-19 associated SCAR but like other viral infections, SARS-COV-2 may be another risk factor for SCAR [3]. CONCLUSIONS: This case may lead clinicians to include SCAR as a differential when evaluating newly developed cutaneous lesions in COVID-19 patients. It is also essential to monitor the skin when COVID-19 patients are being treated with possible culprits. REFERENCE #1: Incidence of Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome in an HIV Cohort. AM J Clin Dermatol. 2012 Feb 1;13(1):49-54. REFERENCE #2: Nonimmediate Allergic Reactions Induced by Drugs: Pathogenesis and Diagnostic Tests. J Investig Allergol Clin Immununol. 2009;19(2):80-90. REFERENCE #3: A case report of toxic epidermal necrolysis (TEN) in a patient with COVID-19 treated with hydroxychloroquine: are these two partners in crime? Clin Mol Allergy. 2020 Oct 6;18:19. DISCLOSURES: No relevant relationships by Gregory Bassmann, source=Web Response No relevant relationships by Vignesh Harish, source=Web Response No relevant relationships by Kyunghoon Rhee, source=Web Response No relevant relationships by Zainab Shafi, source=Web Response

Toxic Epidermal Necrolysis vs Lupus Flare?

SESSION TITLE: Critical Care 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS) are severe mucocutaneous reactions characterized by extensive necrosis and detachment of epidermis. Systemic lupus erythematosus (SLE) patients are at increased risk of SJS/TEN. Here we discuss a patient with SLE who developed TEN. CASE PRESENTATION: A 45 year old female with discoid and systemic lupus erythematosus presented to dermatology with bullous skin lesions 2 days after starting gabapentin, naproxen, and duloxetine. Despite stopping her new medications, she developed a facial rash which spread to her trunk and extremities, affecting 30% body surface area. She had denuded oral mucosa and conjunctival hyperemia with no photosensitivity or eosinophilia. Complements were normal. Wedge biopsy showed acute on chronic vacuolar interface dermatitis with epidermal ulceration and partial to full-thickness epidermal necrosis, suggestive of chronic discoid lupus with superimposed bullous eruption. The patient was admitted to the ICU and treated with intravenous immunoglobulin for three days. Home medications were held. Supportive care included intravenous hydration, reverse isolation in heated environment, specialized wound care, oral and eye care. Methicillin resistant staphylococcus aureus bacteremia was treated. The patient clinically improved and was in reepithelialization phase at time of discharge. DISCUSSION: The incidence of TEN is 0.4-1.2% per million. In patients with SJS/TEN, the prevalence of SLE is estimated to be 1.2% (compared to 0.02-0.05% in the general population). It is unclear if the predisposition for TEN in SLE patients is because of the underlying inflammatory state or because of medications SLE patients often require, such as NSAIDs. Differentiating SLE from TEN is complicated by clinical and histologic similarities. Pathology often demonstrates subepidermal vacuoles, necrotic keratinocytes, and confluent epidermal necrosis, which is found in SLE and TEN. Bullous eruptions and erosive mucosal involvement are typical features in TEN, but can also be found in SLE. This patient developed skin and mucosal lesions after starting new medications and had improvement without steroids, which makes active SLE less likely. Normal complement and serology also supports the clinical diagnosis of TEN over active SLE. CONCLUSIONS: Mortality in patients with SJS and TEN exceeds 10 and 30% respectively. Because the management of active SLE lesions and TEN differ greatly, early recognition of TEN can be life saving. High index of suspicion, early biopsy, and serology can be helpful in differentiating such cases. Reference #1: M. Ziemer, et al, “Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature,” Brit J Dermatol 2012; 166 (3), 575-600. Reference #2: Ranario JS, et al. Bullous lesions in a patient with systemic lupus erythematosus. J Clin Aesthet Dermatol 2014; 7:44-49 DISCLOSURE: The following authors have nothing to disclose: Gauri Behari, Sukhdeep Malhi, Bradley Tymchuk, Ronnie Self II, Suman Lata, Ibrahim El-Abbassi No Product/Research Disclosure Information

Early Recognition and Prevention of Toxic Epidermal Necrolysis: A Cautionary Report of Two Cases and Literature Review

Toxic epidermal necrolysis (TEN) is a rare and devastating side effect of medication use characterized by epidermal apoptosis associated with massive epidermal dissociation over more than 30% of the total body surface area; fever; bullae; and generalized rash. This reaction often initially presents in the form of oral facial rashes and erosions. It is regularly misdiagnosed as less extensive forms of pemphigoid conditions, erythema multiforme, and Stevens-Johnson syndrome. The early signs are initially seen by primary care physicians and dental care providers, especially oral and maxillofacial surgeons. Incidence of TEN is low, and presentation of the disease is rapid and distinguishable. The first-line treatment staple for TEN is immediate cessation of the offending drug; however, this is complicated by the prevalence with which TEN-causing drugs are prescribed. Among others, onset of TEN is associated with nonsteroidal anti-inflammatory drugs; sulfonamides; cephalosporins; aromatic anticonvulsants; and allopurinol, making early identification difficult. Furthermore, duration of TEN is associated with medication clearance, which can complicate treatment when TEN is caused by drugs with long half-lives.

Incidence of Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome in an HIV Cohort

The incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been reported to be between 0.95 and 1 per 1000 individuals with AIDS. Accessibility to a cohort of individuals with HIV with known drug exposure (including drug, dose, and time of exposure) and collection of adverse-event information may provide an opportunity to determine an incidence rate of SJS and TEN. The primary objective of this analysis was to determine the incidence of confirmed SJS and TEN in a cohort of Canadian HIV patients who were receiving HIV and HIV-related medications. This was a retrospective analysis of an HIV cohort. The Ontario HIV Treatment Network (OHTN) cohort population was eligible for this analysis. A search of the OHTN database was conducted to determine whether cases with a diagnosis of SJS or TEN were included. Search terms included 'TEN,' 'SJS,' 'epidermal necrolysis,' and 'erythema multiforme.' All SJS and TEN cases recorded in the OHTN database between January 1995 and August 2008 were obtained. Diagnostic criteria for SJS and TEN were established and two reviewers examined the medical records to confirm the SJS or TEN diagnosis. Drug exposure and utilization were documented. Incidence rates for the entire cohort were calculated. Seventeen cases over seven OHTN study sites were identified from an approximate cohort sample size of 3700. There were 15 men (88%). The mean ± SD age was 51.6 ± 11.3 years and time since HIV diagnosis was 16.1 ± 4.4 years. Only one patient reported experiencing a previous SJS or TEN episode. Of the 17 cases, clinical experts diagnosed five cases as true SJS and/or TEN, two cases were labeled as indeterminant, and the remaining cases were considered not SJS or TEN. Among the confirmed cases, drugs taken included nevirapine, trimethoprim/sulfamethoxazole (cotrimoxazole), stavudine (d4T), and clarithromycin. The incidence of SJS and/or TEN was 5-7 per 3710 or approximately 1-2 per 1000 individuals in this cohort with HIV. Careful diagnosis of this adverse event is required for an accurate measure of incidence and to avoid false inflation of the incidence.

Stevens-Johnson Syndrome Associated with Codeine in a Child

Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are part of a spectrum of mucocutaneous disorders with similar clinical features. The incidence of TEN and StevensJohnson syndrome has been estimated at 0.4 to 1.2 and 1 to 6 cases per million person-years, respectively.[1-3] Factors such as race, age, gender and socioeconomic status do not appear to affect the epidemiology of the two disorders. The pathophysiology of these skin syndromes remains unknown. Stevens-Johnson syndrome is considered to be a milder form of TEN. StevensJohnson syndrome typically presents as small blisters on dusky pruritic macules on the face and upper trunk, occurring 1 to 3 weeks after drug exposure. The rash progresses rapidly to include the epithelium of the gastrointestinal and respiratory tracts and eyes, and it usually reaches its maximum within hours to days.[4] Detachment of less than 10% of the epidermis is considered StevensJohnson syndrome, while involvement of greater than 30% of the body surface is diagnosed as TEN. Fever is usually higher in TEN than in StevensJohnson syndrome. Mortality depends upon the extent of skin necrosis and damage to other systems and is usually below 5% for Stevens-Johnson syndrome and as high as 30% in cases of TEN.[1,5] Patients may be severely dehydrated with electrolyte abnormalities, and anaemia, lymphopenia and pre-renal azotemia are common. Bacterial colonisation of the skin and decreased immune response increases the likelihood of sepsis, the major cause of death.[4] Thirty-five percent of patients with TEN and fewer with Stevens-Johnson syndrome experience ocular sequelae including formation of synechiae between the eyelids and the conjunctiva, corneal erosions and scarring, and punctate keratitis.[6] Neutropenia, visceral involvement and high blood urea nitrogen levels are associated with a poorer prognosis. While both are primarily associated with drug use, infections, including mycoplasma pneumonia and viruses, are also implicated in the Stevens-Johnson syndrome. The drugs most often causing Stevens-Johnson syndrome and TEN include sulfonamides, aminopenicillins, phenytoin and nonsteroidal anti-inflammatory drugs (NSAIDs). Despite its wide clinical use for cough suppression and pain control, codeine has not been implicated as a cause of Stevens-Johnson syndrome. We report a paediatric case of Stevens-Johnson syndrome associated with codeine phosphate.

The Seasonal Variation in Incidence of Toxic Epidermal Necrolysis

The Seasonal Variation in Incidence of Toxic Epidermal Necrolysis

Sindrome de Lyell num doente com SIDA.

Toxic epidermal necrolysis (TEN), or Lyell's syndrome, is a rare cutaneous reaction, most often drug related with drugs such as sulfonamides, non-steroidal anti-inflammatory drugs, anti-convulsants and allopurinol. It is characterised by extensive mucocutaneous detachment and usually associated with severe constitutional symptoms. The mortality rate is about 20-66%. The incidence of TEN is increasing among HIV-infected patients, mostly those in an advanced stage of the disease. Although the pathophysiology of TEN is still unclear, data have been reported that support different aetiologies: an immune mechanism, an abnormal pattern of drug biotransformation and a modulating genetic susceptibility. The diagnosis of Lyell's syndrome is mainly clinical because the confirmation of the drug involved is more difficult since there are no safe and reliable skin or in vitro tests that are generally available. THe authors report a case of TEN in a patient with AIDS whose clinical characteristics and evolution are a particular example of this pathology and of the related problems of diagnosis and therapeutics. The fact that this patient presented a prior adverse drug reaction (ADR) besides Lyell's syndrome and a later cutaneous hyperreactivity, raised a complex problem: the risk of reintroducing drugs previously withdrawn due to their possible association with ADRs and the absolute need to treat active disorders. In view of the increased risk of severe cutaneous ADRs, namely TEN, in patients with AIDS, the authors point out the need to set up new guidelines concerning both an early and accurate diagnosis and treatment of these situations and the management of subsequent therapeutics.

Toxic Epidermal Necrolysis in Singapore, 1989 Through 1993: Incidence and Antecedent Drug Exposure

Before 1990, the incidence of toxic epidermal necrolysis (TEN) was largely undetermined. Since then, there have been published figures on the incidence of TEN in the United States, 1 France, 2 Germany, 3 and Italy, 4 but no figures have been published for a country in Asia. These figures have estimated the incidence to be 0.5 per million per year in the United States among persons using standard outpatient regimens. In the general population in Europe, the incidence is estimated to be 0.9 to 1.3 persons per million per year; 90% to 95% of such cases are believed to be caused by drug therapy. The present study is an estimate of the incidence of drug-induced TEN in Singapore from 1989 through 1993. Methods. The total number of citizens and permanent residents in the 5-year period from 1989 through 1993 form the population base. All known cases of TEN from eight

Toxic epidermal necrolysis: An expanding field of knowledge

Toxic epidermal necrolysis (TEN) is the most dramatic, the most severe, and oneofthe mostoften studied cutaneous drug reactions. Since the first Workshop onTEN heldinCreteil,France,in 1985,1 knowledge of this disease has expanded. Progress has been achieved in nosology, epidemiology, drug causes, pathogenesis, and treatment. TEN ischaracterizedby extensive detachment of the epidermis undergoing full-thickness necrosis.r Because of many resemblances to Stevens-Johnson syndrome (SJS), TEN isoften considered the most severe form of an erythema multiforme (EM) spectrum.2-4 It was recently proposed that EM major is actually distinct from SJS on the basis of clinical criteria.' Our current concept is to separate an EM spectrum (EM minor combined with EM major), from an SJS/TEN spectrum. The first, characterizedby typical target lesions, are postinfectious disorders,often recurrent but with lowmorbidity. The second, characterized by widespread blisters and purpuric macules, are usually severe drug-induced reactions with high morbidity and poor prognosis. In thisconceptSJS andTEN mightbeonlytypes of the samedrug-induced process that varyin severity. Because the extent of necrolysis is one of the principal prognostic factors, we proposed a threegrade classification: SJS, mucosalerosions and epidermal detachment below 10%; overlap SJS-TEN, epidermaldetachmentbetween 10% and30%; TEN, epidermaldetachment more than 30%.5 The incidence ofTEN is 1 to 1.3/million/yearin France, Italy, Germany, and the United States.v? Bone marrow transplant recipients, patients with systemic lupuserythematosus, andabove allpatients with AIDS are at higher risk.3 The incidence of TEN in HIV-positive patientshasbeenestimated at l/1000/year, or 1000 times greater than in the

Toxic epidermal necrolysis (Lyell syndrome) in 77 elderly patients.

Toxic epidermal necrolysis is a rare, severe drug-induced disorder characterized by extensive epidermal loss. This study used the data of a national survey looking for all cases which occurred during a five-year period. The incidence of toxic epidermal necrolysis (cases/million/year) was 2.7 times higher among elderly than among younger adults. In the elderly population no female preponderance was found but clinical patterns were similar. The fatality of toxic epidermal necrolysis was twice as high in the elderly patients (51%) as in the younger (25%). The drugs incriminated in most cases of toxic epidermal necrolysis were the same in both groups (NSAIDs, antibacterials and anticonvulsants).

Drug-induced toxic epidermal necrolysis (Lyell syndrome) in patients infected with the human immunodeficiency virus

Although patients infected with the human immunodeficiency virus (HIV) are predisposed to cutaneous adverse drug reactions, only a few cases of toxic epidermal necrolysis (TEN) have been reported in this setting. Our purpose was to examine the features of TEN in HIV-infected patients. We performed a retrospective analysis of all HIV-infected patients in a series of 80 consecutive cases of TEN during a 6-year period. Fourteen patients were HIV infected. They had typical TEN, with epidermal detachment involving 20.6% +/- 8.0% of the skin surface. Suspected drugs were sulfadiazine, trimethoprim-sulfamethoxazole, sulfadoxine, clindamycin, phenobarbital, and chlormezanone. Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a dramatically increased risk of TEN. During our study period 15 cases of AIDS-associated TEN occurred in the greater Paris area, whereas 0.04 case would have been expected if the incidence of TEN were the same in these patients as in the general population. HIV-infected patients, especially those with AIDS, may develop TEN that shares many similarities with the disease in immunocompetent patients.

Incidence of Toxic Epidermal Necrolysis in Italy

To the Editor.— In the January 1990 issue of theArchives, two articles were of great interest to us, both concerning the incidence of toxic epidermal necrolysis. 1,2 The study by Roujeau and colleagues was a nationwide surveillance in France covering the period 1981 through 1985. The incidence was estimated from two different sets of data (direct inquiry to dermatologists and mortality data) as 1.2 and 1.3 cases per million per year, respectively. The other study utilized the data system at Group Health Cooperative of Puget Sound, Seattle, Wash, covering about 260 000 people, and considered all hospitilization for toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome in that area from 1972 through 1984. The incidence of toxic epidermal necrolysis was estimated at about 0.5 per million per year. In January 1989, we started a case-control surveillance of Stevens-Johnson syndrome and toxic epidermal necrolysis covering 33 dermatological services (hospital and

The Incidence of Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis

We carried out a study to estimate the incidence of erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) requiring hospitalization and to determine which drug therapies were associated with these reactions. We reviewed the clinical records of all patients who were hospitalized with these discharge diagnoses at Group Health Cooperative (GHC) of Puget Sound, Seattle, Wash, from 1972 through 1986. During this 14-year period, an average of about 260,000 persons, with demographic characteristics similar to those of the general population, received their care from GHC, and there were about 25,000 admissions to hospitals per year at the GHC hospitals. Based on International Classification of Diseases-Adapted coding, a total of 61 suspect cases of EM, SJS, or TEN were identified from the computerized hospital discharge file. Based on record review and the application of a uniform set of diagnostic criteria, a total of 37 patients (61%) were classified as having EM, SJS, or TEN. Of these, 16 cases (43%) were attributed to drugs administered to these patients prior to hospitalization. The overall incidence of hospitalization for EM, SJS, or TEN due to all causes was 4.2 per 10(6) person-years. The incidence of TEN alone due to all causes was 0.5 per 10(6) person-years. The incidence of EM, SJS, or TEN associated with drug use were 7.0, 1.8, and 9.0 per 10(6) person-years, respectively, for persons younger than 20 years of age, 20 to 64 years of age, and 65 years of age and older. Drug therapies with reaction rates in excess of 1 per 100,000 exposed individuals include phenobarbital (20 per 100,000), nitrofurantoin (7 per 100,000), sulfamethoxazole and trimethoprim, and ampicillin (both 3 per 100,000), and amoxicillin (2 per 100,000). Overall, our data suggest that cases of EM, SJS, and TEN sufficiently severe to require hospitalization are infrequent among outpatients using well-established drug therapies. A continuing challenge is the evaluation of these severe cutaneous reactions that are associated with newly marketed or less frequently prescribed drug therapies.

Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981-1985

We looked retrospectively for all cases of toxic epidermal necrolysis that occurred in France over a 5-year period to appreciate the incidence of this disorder and its drug etiology. Of the 399 cases identified, we obtained detailed information on 344 cases and validated 253 cases. From response rates (66% to 98%), we estimated the actual total number of cases to be 333, and the incidence of toxic epidermal necrolysis in France to 1.2 cases per million per year. An independent estimation derived from death certificates gave a figure of 1.3 cases per million per year. When the number of cases with a given drug present were related to the defined daily doses of that drug sold over the 5-year period, the highest ratios were for sulfadiazin (230.10(-8], isoxica (41.10(-8], oxyphenbutazone (18.10(-8], phenytoin (14.10(-8], fenbufen (13.10(-8], and cotrimoxazole (12.10(-8]. This first nationwide study confirmed the rarity of toxic epidermal necrolysis. Within the two main classes of responsible drugs (antibacterial sulfonamides and nonsteroidal anti-inflammatory agents) the risks linked to different drugs appeared quite different, even for closely chemically related products.