Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), which include Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also known as drug-induced hypersensitivity syndrome), acute generalized exanthematous pustulosis, and generalized bullous fixed drug eruption, are life-threatening conditions. The pathogenesis of SCARs involves T cell receptors recognizing drug antigens presented by human leukocyte antigens, triggering the activation of distinct T cell subsets. These cells interact with keratinocytes and various immune cells, orchestrating cutaneous lesions and systemic manifestations. Genetic predisposition, impaired drug metabolism, viral reactivation or infections, and heterologous immunity influence SCAR development and clinical presentation. Specific genetic associations with distinct SCAR phenotypes have been identified, leading to the implementation of genetic screening before prescription in various countries to prevent SCARs. Whilst systemic corticosteroids and conventional immunomodulators have been the primary therapeutic agents, evolving strategies, including biologics and small molecules targeting tumour necrosis factor, different cytokines, or Janus kinase signalling pathways, signify a shift towards a precision management paradigm that considers individual clinical presentations.

Steven-Jonhson Syndrome in a Patient With Dengue Infection in Peru: A Case Report.

Stevens-Johnson syndrome is an infrequent condition affecting the skin and mucous membranes, it involves cutaneous detachment with high mortality without adequate treatment. We present the case of a 40-year-old male with a history of epilepsy treated with valproic acid and lamotrigine, previously diagnosed with dengue. Evaluation showed erythematous blisters on skin and mucosa with bleeding and desquamation, covering 10% of the body surface. The patient progressed favorably with the medical care received. Stevens-Johnson syndrome should be studied in association with arboviral diseases.

Cutaneous Hypersensitivity Reactions to Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has transformed the management of various malignancies. Alongside their therapeutic success, the widespread application of ICIs has unveiled a spectrum of immune-related adverse events (irAEs), most often affecting the skin. Cutaneous irAEs (cirAEs) encompass a range from common morbilliform and lichenoid rashes to more severe conditions such as bullous dermatoses and psoriasiform eruptions, each presenting distinct clinical challenges. Moreover, less common but clinically severe cutaneous reactions like toxic epidermal necrolysis have also been observed. cirAEs are frequently observed, with an incidence ranging from 37% to 70% for anti-cytotoxic T lymphocyte-associated antigen-4 antibodies and 17% to 40% for anti- programmed death-1/anti-programmed death ligand-1 antibodies. Recognizing the critical need for effective therapeutic strategies, this review carefully examines current approaches and guidelines for managing cirAEs.

Etanercept treatment for pediatric toxic epidermal necrolysis induced by deflazacort: a case report and literature review.

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disorder commonly caused by drugs. TEN is often treated with corticosteroids, intravenous immunoglobulin (IVIG), or cyclosporine; however, the efficacy of these treatments is controversial. Etanercept (a TNF-α antagonist) was proven to decrease skin-healing time in a randomized clinical trial. Herein, we report the case of a 44-month-old boy who developed TEN due to deflazacort as the probable culprit drug and was successfully treated with etanercept. The patient presented to the emergency department complaining of erythematous maculopapular rashes and vesicles all over the face and body, with vesicles on the hands, feet, and trunk. Symptoms started 4 days before presentation, with edema of the upper lip, which progressed to erythematous macules over the body. He was started on deflazacort for nephrotic syndrome 21 days before the visit. Approximately 20% of the body surface area (BSA) was covered by vesicular lesions. Under the diagnosis of Steven Johnson syndrome/TEN, deflazacort was discontinued, and intravenous dexamethasone (1.5 mg/kg/day), a 5-day course of IVIG (0.4 mg/kg/day), and cyclosporine (3 mg/kg/day) were administered. The lesions seemed to be stationary for 3 days, but on the 6th day of hospitalization, when IVIG was discontinued, the vesicular lesions progressed to approximately 60% of the BSA. Etanercept 0.8 mg/kg was administered subcutaneously. Lesions stopped progressing, and bullous lesions started epithelialization. However, on the 15th day, around 30% of the BSA was still involved; thus, a second dose of etanercept was administered. No acute or sub-acute complications were observed. In conclusion, the use of etanercept in children with TEN that is not controlled with conventional therapy is both effective and safe.

Effectiveness of early treatment with plasma exchange in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially fatal medical conditions that lack established treatment. Therapeutic plasma exchange (PE) is a potential treatment option; however, its effectiveness is unclear. We aimed to evaluate the effectiveness of PE in patients with SJS/TEN. A retrospective cohort study was conducted using data from the Japanese National Administrative Claims database from 2016 to 2021. The analysis included 256 patients diagnosed with SJS/TEN who were admitted to the intensive care unit, of whom 38 received PE and 218 did not. The outcomes of patients who did and did not receive PE within the first 24 h of admission were compared. The risk ratios and 95% confidence intervals of the PE group compared with those of the no-PE group were as follows: in-hospital mortality, 0.983 (0.870-1.155); 30-day mortality rate, 1.057 (0.954-1.217); 50-day mortality rate, 1.023 (0.916-1.186); and length of hospital stay, 1.163 (0.762-1.365). This study does not provide evidence of a benefit of PE in reducing mortality or length of hospital stay in patients with severe SJS/TEN.

Ornidazole induced Stevens-Johnson syndrome without body surface involved: A case report.

RATIONALE: Ornidazole is a synthetic nitroimidazole derivative that is commonly prescribed for antiparasitic or anti-anaerobic infections. It is generally well tolerated, with known side effects including gastrointestinal tract, anaphylaxis, and central nervous system reactions. Ornidazole-induced binocular reactive keratitis and several mucocutaneous lesions have been rarely reported. PATIENT CONCERNS: A 52-year-old woman who suffered from vaginitis and received an ornidazole vaginal plug (0.5 g). Approximately 20 minutes after the suppository was inserted into the vagina, her lips were swollen and valva and labia were burning. Her eyes were red, sore, and watery. DIAGNOSIS: She was diagnosed as Steven-Johnson syndrome by the ophthalmologist. According to the Naranjo scale, the adverse drug reaction was evaluated to be probable and severe. INTERVENTIONS: Dexamethasone was intravenous administrated as anti-inflammatory therapy for 10 days. Eye drops were locally given to relieve edema and promote healing of the epithelium. The symptoms of her eyes, lips, vulva and crissum were soon relieved. OUTCOMES: The patient was discharge from hospital with improved symptoms. LESSONS: In order to avoid severe adverse effect, the patient should not use metronidazole ether orally or vaginally. The case emphasized the importance of rapid and accurate diagnosis of Steven-Johnson syndrome induced by ornidazole vaginal plug, especially when the eye symptoms were the chief complaint without body skin involved.

Comment on: Proposal for a new diagnostic classification of photodistributed Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap (SJS/TEN), collectively referred to SJS/TEN, form a spectrum of severe life-threatening adverse drug reactions whose pathomechanism is not fully understood. The article "Photodistributed Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Proposal for a New Diagnostic Classification" by McKinley et. al., discusses a distinct distribution of epidermal necrosis in SJS/TEN, attributable to preceding exposure to ultraviolet radiation (UVR), and relative sparing of photo-protected areas. After reviewing numerous cases within the Immune-mediated Adverse drug Reactions in African HIV endemic setting Register and Biorepository (IMARI-SA) at the University of Cape Town with a similar clinical pattern as those published by McKinley et. al., we propose that the relative sparing of some areas giving an impression of photo-distribution is due to localised increase in skin pressure that reduces the blood supply in that area below a critical threshold. A dip in blood supply below this critical threshold quantitively limited T lymphocytes and cytokines that drive SJS/TEN to reach and damage the skin.

A Case Report of Cefixime, Paracetamol, and Nimesulide Induced Toxic Epidermal Necrolysis in a Woman with Dengue Infection without any Other Associated Comorbidities.

BACKGROUND: Toxic Epidermal Necrolysis (TEN) is a rare, acute, and life-threatening mucocutaneous disease that occurs after the administration of certain drugs, resulting in extensive keratinocyte cell death, skin involvement at the dermal-epidermal junction, and extensive bullous skin eruptions and sloughing. Many published case reports have observed the presence of fever with a viral infection, drug, and/or genetic association as a possible trigger for TEN but associated with other comorbidities. Physicians still struggle to predict which individuals could be predisposed to TEN. The case report that we present had a history of multiple drug intake and fever due to dengue virus infection but was not associated with any other comorbidity. CASE PRESENTATION: We present an unusual case of a 32-year-old woman of Western Indian origin who had developed dengue infection and suffered toxic epidermal necrolysis following a five-day course of a third-generation cephalosporin antibiotic, cefixime and a three-day course of 2 analgesic drugs, paracetamol (acetaminophen), and nimesulide, with the adverse event occurring on the fifth day of the dengue infection. The offending drugs were stopped, and patient survived with supportive management and hydration. CONCLUSION: The presence of comorbidities may not always be the triggering factor for TEN, though it can affect patient outcomes. Rational drug use is always recommended for patient care. Further research is required to understand the pathomechanism behind the viral-drug-gene interaction.

Fast, bedside diagnosis of toxic epidermal necrolysis using ex vivo confocal laser scanning microscopy: A retrospective study.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe life-threatening drug eruption with rapid evolution. A fast histologic differentiation between TEN and clinically similarly looking staphylococcal scalded skin syndrome is of vital importance for relevant treatment decision. The recently developed ex vivo confocal laser scanning microscopy (CLSM) offers innovative and extremely fast histological visualization of fresh tissue specimens. OBJECTIVE: To assess the diagnostic efficacy of ex vivo CLSM in comparison with standard histopathology for TEN. METHODS: We performed side-by-side comparison of TEN specimens analysed with ex vivo CLSM and haematoxylin and eosin staining. Analysis focused on typical histopathological features of TEN, including epidermal cleavage in the basal layer and confluent epidermal necrosis. We retrospectively assessed the diagnostic performance of ex vivo CLSM for TEN in clinically confirmed cases. RESULTS: We report substantial agreement between ex vivo CLSM and classical histology for the detection of subepidermal cleavage and confluent epidermal necrosis. When considering full-thickness epidermal loss, epidermal cleavage in the basal layer showed the highest diagnostic performance, reaching 87.5% sensitivity and 100% specificity. CONCLUSION: Based on our data, ex vivo CSLM appears as a rapid, resource-optimizing, and reliable approach for morphological TEN emergency screening on fresh skin samples.

Penicillamine-induced Stevens Johnson Syndrome-toxic Epidermal Necrolysis (SJS-TEN) Overlap in an HIV-infected Patient with Wilson's Disease and Hepatitis B.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are severe adverse drug reactions characterized by widespread blistering and mucositis. Wilson's disease is a rare, autosomal recessive disorder that results in excessive copper accumulation in the body, where penicillamine is an effective treatment option for copper chelation. Penicillamineinduced SJS-TEN is a rare but potentially fatal adverse effect. There is increased susceptibility to SJS/TEN in HIV infection due to immunosuppression and chronic liver disease due to impaired hepatic function. OBJECTIVE: To diagnose and manage the occurrence of the rare severe adverse cutaneous drug reactions in the backdrop of immunosuppression and chronic liver disease. CASE REPORT: We are reporting penicillamine-induced SJS-TEN overlap in a 30-year-old male with Wilson's disease, HIV and Hepatitis B who was treated with intravenous immunoglobulins. The patient later developed neurotrophic ulcer in the right cornea as a delayed sequela. CONCLUSION: Our case report emphasizes that there is an increased predisposition to SJS/TEN in immunocompromised and chronic liver disease patients. Physicians should be well aware of the potential danger of SJS/TEN in this subset of patients, even while prescribing a relatively safer drug.

Paracetamol (Acetaminophen)-associated SJS, TEN, AGEP, and DRESS Syndromes - A Narrative Review.

INTRODUCTION: Paracetamol (Acetaminophen) is a very common OTC drug that is found in more than 200 OTC products sold as pain, cough and cold remedies. Paracetamol is commonly used as an antipyretic to reduce fever and as an alternative to Non-steroidal anti-inflammatory drugs (NSAIDs) that are contraindicated in certain patients to relieve mild-moderate pain. OBJECTIVE: This review article focuses on SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes associated with the use of paracetamol or paracetamol-containing products. METHODS: To find published articles relevant to paracetamol-associated SJS, TEN, AGEP, and DRESS, we searched the online databases Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists using keywords like Stevens-Johnson Syndrome, Acetaminophen, Paracetamol, Toxic epidermal necrolysis, Acute generalized exanthematous pustulosis, Drug reaction with eosinophilia and systemic symptoms. RESULTS: The paracetamol-associated SJS, TEN, SJS/TEN overlap, AGEP, and DRESS syndromes have been identified by a number of publications. CONCLUSION: When evaluating drug-induced hypersensitivity skin reactions, healthcare professionals, including prescribers, pharmacists, and others, should be aware of this rare risk. Patients who exhibit signs and symptoms of paracetamol-associated hypersensitivity should be referred to physicians by pharmacists for further treatment. At the first sign of a skin rash or other hypersensitivity reaction while taking paracetamol, patients should be told to stop taking it and see a doctor right away.

Characteristics of mild and severe apalutamide-related cutaneous adverse events in patients with prostate cancer: A review of the literature.

Apalutamide is an antiandrogen used to treat prostate cancer. Although it sometimes induces mild cutaneous adverse events and occasionally severe ones, clinical differences between severe and mild cases remain unclear. To assess the risks in patients experiencing apalutamide-related cutaneous adverse events (ARCAEs), we aimed to characterize severe and mild ARCAEs in terms of onset time and lymphocyte transformation test (LTT) for apalutamide. We reviewed 41 ARCAE cases: 24 from our institute and 17 from the literature, comprising (i) eight severe cases including six with toxic epidermal necrolysis, one with acute generalized exanthematous pustulosis, and one with drug reaction with eosinophilia and systemic symptoms, and (ii) 33 mild cases. Patients with evere cases developed ARCAEs significantly earlier than patients with mild cases (5.2 vs 9.6 weeks). No severe cases appeared ≥8 weeks after initiation of apalutamide. LTTs showed positive results in two of seven mild cases (28.6%) and four of four severe cases (100.0%). In conclusion, we found that severe ARCAEs are characterized by earlier onset and LTT positivity. Dermatologists and urologists should pay special attention to patients who develop ARCAEs <8 weeks after initiating apalutamide and/or show positive LTT results.

Cutaneous adverse drug reactions.

Cutaneous adverse drug reactions (ADRs) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Maculopapular exanthema and urticaria are the most common types of cutaneous ADR. Serious cutaneous ADRs, which may cause permanent sequelae or have fatal outcome, may represent 2% of all cutaneous ADR and must be quickly identified to guide their management. These serious reactions include bullous manifestations (epidermal necrolysis i.e. Stevens-Johnson syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Some risk factors for developing cutaneous ADRs have been identified, including immunosuppression, autoimmunity or genetic variants. All drugs can cause cutaneous ADRs, the most commonly implicated being antibiotics (especially aminopenicillins and sulfonamides), anticonvulsants, allopurinol, antineoplastic drugs, non-steroidal anti-inflammatory drugs and iodinated contrast media. Pathophysiology is related to immediate or delayed "idiosyncratic" immunologic mechanisms, i.e., usually not related to dose, and pharmacologic/toxic mechanisms, commonly dose-dependent and/or time-dependent. If an immuno-allergic mechanism is suspected, allergological explorations (including epicutaneous patch testing and/or intradermal test) are often possible to clarify drug causality, however these have a variable sensitivity according to the drug and to the ADR type. No in vivo or in vitro test can consistently confirm the drug causality. To determine the origin of a rash, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis (especially infectious etiologies) is required, completed with a literature search. Reporting to pharmacovigilance system is therefore essential both to analyze drug causality at individual level, and to contribute to knowledge of the drug at population level, especially for serious cutaneous ADRs or in cases involving newly marketed drugs.