Search Results (64)

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks. Full article

Lamotrigine is the drug of choice for the treatment of depressive episodes in bipolar disorder (BD). Despite its generally favorable tolerability profile, lamotrigine use is associated with a risk of Cutaneous Adverse Drug Reactions (cADRs), including Stevens–Johnson Syndrome (SJS) and Lyell’s syndrome, also known as toxic epidermal necrolysis (TEN). Genetic markers HLA and, in particular, HLA-B 15:02 and HLA-A 31:01 are crucial in predicting individuals’ susceptibility to developing the symptoms. The symptoms are triggered by type IV hypersensitivity developing because of CTL and NK cell activation, leading to keratinocyte apoptosis, epidermal necrosis and skin detachment. The exact pharmacotherapy that should be widely utilized in treating affected patients has not yet been established. New therapies including JAK inhibitors or cyclosporine show potential in improving outcomes by reducing mortality and enhancing the period of recovery. Key factors in preventing cADRs may include adequate patient observation, gradual titration of the patient’s dose, and reduction of risk factors through screening for HLA polymorphisms. When the initial symptoms of cADR are identified, it is imperative to make an immediate decision to discontinue treatment, as this can significantly reduce the risk of progression to SJS/TEN and systemic complications. The purpose of this review is to identify a significant correlation between lamotrigine use in BD and the occurrence of SJS by showing the risk factors, neuropharmacological mechanisms, immune response and correctness of pharmacotherapy. Full article

Background and Objectives: The primary objective of this study was to identify factors predictive of laryngeal involvement in patients with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The secondary objective was to observe the effect of laryngeal involvement upon short-term patient prognosis, including intensive care unit (ICU) stay and intubation rates. We present the largest cohort of patients examined for upper aerodigestive manifestations of SJS/TEN. Materials and Methods: We performed a retrospective observational analytic study of patients at a state-wide Australian Burns referral center between January 2013 to December 2022. Inclusion criteria were adult patients who underwent flexible nasendoscopy (FNE) with biopsy-proven SJS/TEN. Data collected from medical records included patient factors, aerodigestive symptoms, bedside examination, FNE findings, TEN-specific severity-of-illness score (SCORTEN) on admission, and patient outcomes such as intubation and ICU admission. Results: Fifty-four patients with biopsy-proven SJS/TEN underwent FNE, with 17 (31.5%) identified to have laryngeal involvement. Laryngeal involvement was not significantly associated with intubation, ICU stay, or mortality (p > 0.05). The presence of either aerodigestive symptoms or oral cavity involvement was highly sensitive (94.1%, 95% CI 73.0–99.7%) for laryngeal involvement. Conclusions: We did not find laryngeal involvement in SJS/TEN to significantly impact short-term outcomes, including intubation or mortality. FNE is the gold standard of upper aerodigestive assessment. Simple clinical evaluation of the oral cavity and a history of aerodigestive symptoms also provided a sensitive predictor of the laryngeal complications of SJS/TEN. Full article

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

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

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