Search Results (66)

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

The landscape of available therapeutic options for treatment of genitourinary (GU) cancers is expanding dramatically. Many of these treatments have distinct, sometimes severe, skin toxicities including morbilliform, bullous, pustular, lichenoid, eczematous, psoriasiform, and palmoplantar eruptions. Pruritus and skin pigmentation changes have also been noted. This review aims to synthesize dermatologic events observed with antibody drug conjugates, poly (ADP-ribose) polymerase (PARP) inhibitors, androgen receptor pathway inhibitors, tyrosine kinase inhibitors, immune checkpoint inhibitors, and the combination of these agents used for the treatment of GU cancers. It provides a guide on diagnosis and initial management of these rashes for medical oncologists. 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

Optimizing quantum circuits is critical for enhancing computational speed and mitigating errors caused by quantum noise. Effective optimization must be achieved without compromising the correctness of the computations. This survey explores recent advancements in quantum circuit optimization, encompassing both hardware-independent and hardware-dependent techniques. It reviews state-of-the-art approaches, including analytical algorithms, heuristic strategies, machine learning-based methods, and hybrid quantum-classical frameworks. The paper highlights the strengths and limitations of each method, along with the challenges they pose. Furthermore, it identifies potential research opportunities in this evolving field, offering insights into the future directions of quantum circuit optimization. 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

Hepatic encephalopathy (HE) is a neuropsychiatric condition frequently associated with cirrhosis and portosystemic shunting (PSS). It imposes a significant clinical and economic burden, with increasing attention toward identifying modifiable factors that could improve outcomes. Emerging evidence suggests that vitamin D deficiency (VDD), prevalent in patients with cirrhosis, may contribute to the development and severity of HE. This review explores the association between VDD and HE by analyzing the underlying pathophysiology, including oxidative stress, ammonia accumulation, and impaired hepatic function. Additionally, we summarize recent studies highlighting the correlation between low serum 25-hydroxy vitamin D (25-OHD) levels and worsening grades of HE. Despite strong observational data, interventional studies on vitamin D (VD) supplementation for HE remains limited. Current evidence suggests that VD’s antioxidant properties may alleviate oxidative stress in HE, with potential benefits in mitigating disease severity. Future research should focus on longitudinal studies and randomized controlled trials to evaluate the clinical impact of VD supplementation on HE outcomes and explore VD’s role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Understanding the therapeutic potential of VD could lead to improved management strategies for HE and cirrhotic patients at large. Full article

Background/Objectives: The landscape of advanced melanoma treatments has shifted dramatically in recent years. Target therapy and immunotherapy have changed the management of patients with both metastatic (stage IV according to AJCC 8th ed.) and nodal (stage IIB/C and III) disease. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, high-grade or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining a patient’s quality of life is of paramount importance. Methods: We undertook a prospective, monocentric, and descriptive study in Bologna, Italy, including patients referred to the Oncologic Dermatology Unit of IRCCS AOU of Bologna who developed biopsy-proven cutaneous adverse events (AE) under treatment with immunotherapy for cutaneous melanoma with nodal (stage IIB/C, III) and metastatic (stage IV) disease from January 2016 to April 2024. Results: In 202 identified patients, 75 (37.5%) developed skin AEs. Ipilimumab was causal for 48.1% of skin AEs, followed by nivolumab (37%) and pembrolizumab (31.4%). Recorded types of skin AEs included erythematous rash, vitiligo, alopecia, lichenoid, maculopapular, acneiform, urticarial, psoriasiform, granulomatous, eczematous, and severe cutaneous AEs, such as Erythema multiforme/Stevens-Johnson syndrome and bullous autoimmune dermatoses. Most AEs were low-grade [CTCAE 1–2] (97%) and typically occurred after 10 weeks of treatment. Conclusions: This study comprehensively describes skin AEs occurring during systemic treatment with ICIs for cutaneous melanoma at a single center. Full article

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field. Full article

Type 2 diabetes (T2DM) is a chronic metabolic disease with a steadily increasing prevalence worldwide. Diabetes affects the function of many organs, including the skin. Pharmacotherapy for T2DM is mainly based on oral hypoglycemic drugs. The therapeutic strategy is chosen taking into account the individual patient’s characteristics, among other comorbidities. Antidiabetic drugs can induce cutaneous adverse reactions (CADRs) ranging in severity from mild erythema to serious disorders such as DRESS or Stevens–Johnson syndrome. CADRs can result from hypersensitivity to the drug but can also be related to the mechanism of action of the drug or cross-reactivity with drugs of similar structure. This paper reviews CADRs induced by oral antidiabetic drugs, considering their dermatological manifestations and possible pathomechanisms. Particular attention was paid to specific dermatological conditions such as dipeptidylpeptidase 4 inhibitor-associated bullous pemphigoid or Fournier’s gangrene associated with sodium-glucose cotransporter 2 inhibitor therapy. Knowledge of the dermatological manifestations of CADRs is important in clinical practice. Recognition of a skin lesion resulting from an adverse drug reaction allows for appropriate management, which in this case is primarily related to drug discontinuation. This is particularly important in the treatment of T2DM since this disease has a high prevalence in the elderly, who are at higher risk of adverse drug reactions. 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

Background: Boston Keratoprosthesis Type I (BI-KPro I) is a synthetic cornea that can be used to restore vision in patients with corneal blindness. This retrospective study evaluated the outcomes of BI-KPro implantation in 118 patients. Material: The mean age of the patients was 56.76 ± 14.24 years. Indications for keratoprosthesis implantation were as follows: graft failure, 47 (39.83%); ocular burn, 38 (32.20%); neurotrophic keratopathy, 11 (9.32%), mucous membrane pemphigoid 9 (7.67%); autoimmune, 6 (5.08%); Stevens–Johnson syndrome, 4 (3.39%); and aniridia (2.54%). Methods: The surgeries were performed between March 2019 and June 2022 at a single clinical center in two locations. The postoperative visual acuity, complications, and need for additional surgical procedures were analyzed. Results: The Best Corrected Visual Acuity before surgery was 0.01 ± 0.006. After one year (V1), it was 0.30 ± 0.27; at two years (V2), it was 0.27 ± 0.26; and at three years (V3), it was 0.21 ± 0.23. The percentage of patients with visual acuity better than 0.1 on the Snellen chart was 37.29% after 1 year, 49.35% after 2 years, and 46.81% after 3 years of follow up. The most common complications were glaucoma (78 patients; 66.1%), corneal melting (22 patients; 18.6%), and retroprosthetic membranes (20 patients; 17.0%). Conclusions: The BI-KPro can significantly improve visual acuity. The worst long-term results were obtained in the group of patients with autoimmune diseases; therefore, careful consideration should be given to implanting BI-KPro in this group. The high incidence of de novo glaucoma or the progression of pre-existing glaucoma suggests the need for careful monitoring. Full article

Psychotropic medications, commonly prescribed for psychiatric disorders, can have underappreciated dermatological side effects. This in-depth review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes the dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics. We delve into the spectrum of dermatological conditions, from mild issues like dry skin and acne to severe complications such as Stevens–Johnson syndrome and drug-induced lupus erythematosus. In conclusion, a comprehensive understanding of the dermatological side effects of psychotropic medications is essential for healthcare providers, enabling a holistic approach to patient care. This review is a valuable resource for clinicians, researchers, and educators, facilitating better-informed decision-making in the treatment of mental health disorders while prioritizing skin health and overall well-being. 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