Search Results (45)

Conventionally, drug-induced liver injury (DILI) exists in two types: idiosyncratic and intrinsic. Both types are classified as non-immune disorders, thereby ignoring that some iDILI cases may have an immune or autoimmune background that requires a different therapeutic approach because steroids may be helpful. The purpose of this analysis was to analyze and classify the subtypes of iDILI which, indeed, show autoimmune or immune features among four cohorts, namely idiosyncratic DILI type 1: idiosyncratic drug-induced autoimmune hepatitis (DIAIH), to be differentiated from the classic drug-unrelated idiosyncratic autoimmune hepatitis (AIH); idiosyncratic DILI type 2: human leucocyte antigen-based idiosyncratic drug-induced autoimmune hepatitis; idiosyncratic DILI type 3: anti-cytochrome P450-based idiosyncratic drug-induced autoimmune hepatitis; and idiosyncratic DILI type 4: immune-based idiosyncratic drug-induced liver injury associated with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In conclusion, the traditional non-immune and non-autoimmune iDILI, as well as the four immune or autoimmune iDILI subtypes, are now well classified and clinically characterized by the broadly applied Roussel Uclaf Causality Assessment Method (RUCAM), facilitating additional immunology and therapy studies for the four subtypes, all of which could benefit from steroid treatment. Full article

Stevens–Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) is a severe mucocutaneous reaction often induced by medications. The co-occurrence of SJS/TEN and COVID-19 presents a unique challenge due to overlapping inflammatory pathways. This case study examined the cytokine profile of a patient with both TEN (triggered by lamotrigine) and COVID-19. The clinical history of the patient, including lamotrigine exposure and COVID-19 diagnosis, was documented. A 13-cytokine profile assessment was performed in peripheral blood mononuclear cells from the patient and their parents by using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). A 6-year-old male patient developed lamotrigine-induced TEN with concomitant COVID-19 affecting 90% of the body surface area. Compared with their parents, who were positive for COVID-19, IL-6, IL-4, and IL-12 were modulated (downregulated) by TEN. The cytokine profile showed elevated levels of IL-1α, IL-1β, IL-5, IL-8, NF-κβ, and interferons (IFN; α, β, and γ), indicating a robust antiviral response. The immune profile suggested a hyperactivated immune state that contributed to the severity of the patient’s clinical manifestations, leading to death 18 days after hospitalization. Understanding the immune response is important for developing future targeted therapeutic strategies and improving patient outcomes. Further research is needed to explore the interaction between drug-induced SJS/TEN and infections. Full article

Background/Objectives: Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare but severe skin conditions, often triggered by medications, that can be life-threatening. These conditions frequently affect the eyes, causing ocular surface disease, which can result in visual impairment or blindness. Although the exact mechanisms behind SJS/TEN remain unclear, key inflammatory mediators such as IL-1β, IL-6, and RIPK3 are believed to play critical roles in inflammation, necroptosis, and regulatory processes. Investigating these factors offers new insights into the disease’s underlying mechanisms and potential targets for treatment. This study aims to determine the roles of IL-1β, IL-6, and RIPK3 in the pathogenesis of SJS/TEN. Methods: The study examined the expression levels of IL-1β, IL-6, and RIPK3 in skin biopsies from patients with biopsy-confirmed SJS/TEN, using lichen planus as a positive control and normal skin as a baseline control. Immunohistochemistry was employed for this analysis. Additionally, the impact of SJS/TEN patient plasma on mitochondrial function was assessed in platelets and human corneal epithelial (H-CET) cells. Using a fluorescent plate reader, mitochondrial activity and superoxide ion levels were measured, comparing plasma from SJS/TEN patients to normal human plasma. Results: Skin biopsies from SJS/TEN patients showed a significantly higher expression of IL-1β, IL-6, and RIPK3 compared to both lichen planus and normal controls. Furthermore, plasma from SJS/TEN patients significantly reduced platelet viability and increased mitochondrial and total cellular superoxide ions, as demonstrated by elevated levels of MitoSOX Red and CellROX Red. Conclusions: These findings suggest that IL-1β, IL-6, and RIPK3 may contribute to the pathogenesis of SJS/TEN and highlight their potential as targets for therapeutic intervention. Full article

Background and Objectives: Toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS) are rare yet life-threatening dermatologic conditions characterized by severe skin and mucous membrane involvement. Accurate prognostic systems are crucial for clinical management to assess disease severity and predict outcomes. The primary objective of this study was to assess the epidemiological characteristics and clinical outcomes of patients with Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap over a 17-year period at a specialized burn center. The secondary objectives were to evaluate the performance of existing prognostic scoring systems (SCORTEN, Re-SCORTEN, and ABCD-10) in predicting mortality and to propose a novel classification tree model to improve mortality prediction. Materials and Methods: A 17-year retrospective study at a burn center included 68 patients with SJS, SJS/TEN overlap, or TEN. Demographic, clinical, laboratory data, and prognostic scores (SCORTEN, Re-SCORTEN, ABCD-10) were collected and analyzed for associations with mortality. A classification tree was created to detect unknown determinants of SJS/TEN mortality. Results: The drug most frequently associated with the occurrence of SJS/TEN was metamizole. The mortality rate was 51%. Affected body surface area, platelet count, and serum blood urea nitrogen differed significantly between survivors and non-survivors. Regarding the scoring systems, only the Re-SCORTEN showed reliable differentiation for these groups. A classification tree model achieved an accuracy of 89% in predicting the mortality risk. In the ROC curve analysis, the AUC values were 0.88 for the classification tree, 0.66 for Re-SCORTEN, 0.61 for SCORTEN, and 0.56 for ABCD-10. Conclusions: This study explores mortality predictors in SJS/TEN via a classification tree model, highlighting potential factors for further investigation. While cautioning against immediate clinical application due to data constraints, the findings underscore the need for larger studies to validate and refine prediction models in this context. Full article

Background: Fixed drug eruption (FDE) is a type of drug-induced skin inflammation characterized by the recurrence of lesions in the same region following repeated exposure to the causative drug. FDE typically presents as localized spots or plaques without systemic symptoms; however, it can manifest in other forms, such as blisters and papules. In FDE, effector memory CD8-positive T cells that remain dormant in the basal layer after a previous inflammation are reactivated upon re-exposure to the causative drug, leading to the development of erythema at the same sites. Case Presentation: Herein, we report the case of a 23-year-old man who developed ibuprofen-induced multiple FDE. The diagnosis was confirmed by detecting a rash immediately following ibuprofen administration, and histopathological findings were consistent with FDE. Ibuprofen is widely available as an over-the-counter medication, and patients may not always report its use—making the diagnosis of ibuprofen-induced FDE particularly challenging. Approximately 24 h following drug-induced CD8-positive T cell activation, regulatory T cells normally infiltrate the epidermis to suppress inflammation and promote resolution. However, in multiple FDE, CD8-positive T cell activity may outweigh that of regulatory T cells, causing uncontrolled inflammation and leading to the spread of poorly-demarcated lesions that can progress to severe drug reactions such as Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). We reviewed 13 cases of ibuprofen-induced multiple FDE. Conclusions: Over-the-counter medications can cause multiple FDEs, and the repeated administration of the causative drug can result in severe reactions such as SJS/TEN. The early diagnosis and strict discontinuation of the causative drugs are therefore crucial. Full article

Lyell’s syndrome or Toxic Epidermal Necrolysis (TEN) is a rare and life-threatening dermatological disease. Most commonly, this syndrome is drug-induced, and is a result of an immune-allergic reaction to medications. Anti-cancer drugs were not the most frequent groups of therapeutic agents related to Lyell’s syndrome, but the emergence of new therapeutic classes, particularly targeted therapy and immunotherapy, is changing current data. We present two cases of Lyell’s syndrome induced by anticancer drugs. (1) TEN in a man treated for metastatic urothelial carcinoma with Enfortumab Vedotin. (2) TEN in a man with metastatic melanoma treated with Nivolumab and Ipilimumab. Despite quick medical treatment and transfer to a severe burn unit, both patients died of TEN. Full article

Background and Objectives: The amniotic membrane is widely used in the treatment of chronic wounds, in toxic epidermal necrolysis (TEN), and in the treatment of burns. In our clinical practice, we use amniotic dressings on shallow skin wounds caused by burns. Counteracting infections is an important aspect of working with burn wounds. Therefore, the main goals of this work are to demonstrate the usefulness of amniotic membrane soaked in antiseptics for the prevention of wound infections and to compare the antibacterial efficacy of selected variants of allogeneic and xenogeneic amniotic membrane grafts soaked in specific antiseptic agents. Materials and Methods: The studied material consisted of human and pig placenta. The human and animal amnions were divided in two parts. The first part consisted of amniotic discs placed on rigid mesh discs and preparing the fresh amnion. The second part of the amnion was frozen at a temperature of −80 °C for 24 h. Then, it was radio-sterilized with a dose of 35 kGy. The amniotic discs were placed on rigid mesh to prepare the radiation-sterilized amnion. The amniotic discs were placed in a 12-well plate and immersed in 3 mL of the appropriate antiseptic solutions: Prontosan, Braunol, Borasol, Microdacyn, Octenilin, Sutrisept, and NaCl as a control. The amniotic discs were incubated in antiseptics for 3 h. The microbiological tests were conducted by placing the antiseptic-infused amniotic discs on microbiological media inoculated with hospital strains. Results: The largest average zone of growth inhibition was observed in dressings soaked with Sutrisept, Braunol, and Prontosan. The greatest inhibition of bacterial growth was achieved for radiation-sterilized porcine amnion impregnated with Braunol and Sutrisept, as well as for radiation-sterilized human amnion impregnated with Braunol. Conclusions: Human and porcine amniotic membrane is effective in carrying antiseptics. Radiation-sterilized amnion seems to inhibit the growth of microorganisms better than fresh amnion. Full article

(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level. Full article

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of severe cutaneous adverse reactions to drugs (SCARs) with several international recommendations for global medical management, ranging from pharmacological systemic therapy to skin wound care. There is no defined best management of the skin wounds in SJS/TEN. The care of wounds is essential to initiate re-epithelialization. Our objective is to improve the cicatrization process, avoiding scarring due to deepening of the wounds, as well as prevent infections, achieve pain control, and avoid loss of serum proteins, fluids, and electrolytes. In this retrospective case series, we highlight the value of systemic therapy and the use of silver nitrate for wound management in four patients with TEN. Full article

Stevens–Johnson syndrome (SJS) and the more severe variant, toxic epidermal necrolysis (TEN), are a spectrum of mucocutaneous reactions with potentially devastating ocular consequences. Ocular complications occur in about 70% of patients with Stevens–Johnson syndrome, and 35% continue with chronic disease. We report an unusual presentation of isolated ocular Stevens–Johnson syndrome in a patient with recently diagnosed ulcerative colitis being treated with Infliximab. The case had an insidious and atypical onset and represented a diagnostic dilemma. The diagnosis was more difficult, due to the fact that the inciting agent had long been stopped. Severe bacterial conjunctivitis such as that caused by Chlamydia Trachomatis, Corynebacterium diphtheria, and Neisseria Gonorrhea can cause forniceal shortening and symblepharon; this diagnosis was ruled out with microbiological swabs. A conjunctival biopsy was the key to diagnosis. Treatment involved high-dose IV steroids and dual immunosuppression with Infliximab and mycophenolate mofetil. We sought to employ interventions with the greatest impacts on our patient’s condition. Our experience contributes to the growing evidence supporting intensive ophthalmic management of SJS to prevent long-term vision loss. Full article

Tenoxicam, a selective cyclooxygenase (COX)-2 inhibitor, has potent analgesic and anti-inflammatory effects and is frequently used for out-of-hospital pain control. Even though other non-steroidal anti-inflammatory drugs were incriminated in Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) appearance, the literature is scarce regarding this agent. We report a case of tenoxicam-induced toxic epidermal necrolysis, detailing the multidisciplinary approach in a patient presenting skin detachment of 90% of the total body surface area, with concomitant ocular, oral, nasal, and vaginal mucosae involvement. A skin biopsy confirmed the diagnosis. The immediate cessation of the incriminated drug and rapid initiation of systemic steroids, along with topical therapies, and isolation into a specific environmental condition to limit skin infection were the cornerstones of therapeutic management. The patient was discharged with skin hyperpigmentation area and mild anxiety as long-term sequels. This report emphasized that severe or complicated cases should be transferred to a specialized burn center to reduce mortality risk and long-term morbidity. Full article

Toxic epidermal necrolysis (TEN) is a rare life-threatening mucocutaneous reaction characterized by epidermal detachment. Treatment success relies on early diagnosis, rapid withdrawal of the causative drug and supportive care. However, clinical evidence for therapeutic management and specific treatment is insufficient and controversial. We describe the successful management of a TEN case secondary to sulfadoxine managed in our intensive care unit. The patient presented a generalized exanthema with mucocutaneous detachment affecting 45% of the body surface area, positive Nikolsky sign, perianal enanthema and conjunctival hyperemia. Treatment with intravenous immunoglobulins and corticosteroids was prescribed, as well as calcium folinate to prevent myelotoxicity of the causative drug. In this case, hemodialysis was dismissed due to the low efficiency of this technique in removing the triggering drug. Our case report confirms the efficacy of corticosteroids, IGIV, topical treatment on mucocutaneous lesions and supportive care for the management of TEN secondary to sulfadoxine. Full article

The incidence of severe cutaneous drug eruptions during the COVID-19 period in Sweden has not been studied previously. Our aim was to compare the incidence of these skin reactions in a Swedish health region during the COVID-19 pandemic period with that of the year after: we conducted a retrospective, observational cohort study using data from a national registry of patients diagnosed with cutaneous drug eruptions during the pandemic in Sweden. We included the number of patients diagnosed with severe cutaneous drug eruptions at the Department of Dermatology in the Jonkoping health region during the COVID-19 pandemic (1 April 2020 to 31 March 2021) and the reference period (1 April 2021 to 31 March 2022). We examined the monthly occurrences of cutaneous drug eruptions in three dermatology clinics within the Jonkoping health region. The frequency of these eruptions was determined for two distinct time periods: during the pandemic and post-pandemic. The study included 102 patients with cutaneous drug eruptions: 29 patients were diagnosed during the COVID-19 pandemic period and 73 were diagnosed during the reference period. The difference in the number of cutaneous drug eruptions cases (p-value = 0.0001, 95% CI 1.4995–3.5500, OR 2.3072) during the pandemic period compared to the post-pandemic period was significant. To our knowledge, the impact of the pandemic on cutaneous drug eruptions has not been investigated in EU countries. The increasing and differentiation of the number of diagnosed cutaneous drug eruptions cases after the pandemic could be explained by the removal of COVID-19 restrictions and the more frequent health-seeking behavior during the post-pandemic period. Full article

Toxic epidermal necrolysis (TEN) is a rare, acute mucocutaneous life-threatening disease. Although research has focused on the pathophysiological and therapeutic aspects of the disease, there is a paucity of data in the literature regarding pain management and sedation in the intensive care unit (ICU). Most therapies have been extrapolated from other situations and/or the general ICU population. These patients present unique challenges during the progression of the disease and could end up requiring invasive mechanical ventilation due to inadequate pain management, which is potentially avoidable through a comprehensive treatment approach. In this review, we will present clinical and pathophysiological aspects of TEN, analyze pain pathways and relevant pharmacology, and propose therapeutic alternatives based on a rational and multimodal approach. Full article

In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens–Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient’s survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions. Full article