Epidermal Necrolysis Research Articles

Reactive Infectious Mucocutaneous Eruption with Extensive Cutaneous Involvement

Abstract Recently, there has been discussion to reclassify pediatric Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) as drug-induced epidermal necrolysis (DEN), separating it from infectious etiologies and redefining pediatric mucocutaneous eruptions as either reactive infectious mucocutaneous eruption (RIME) or DEN. In this report, we describe a previously healthy 4-year-old girl with rapidly progressive mucocutaneous blistering involving four mucosal membranes and 37.5% of total body surface area (BSA) following a prodromal rhinovirus and enterovirus infection. The symptoms occurred in the absence of an inciting medication and improved with only supportive care. This case illustrates a rare occurrence of RIME with TEN-like BSA involvement, prompting a review of the literature exploring the relationship between BSA involvement in RIME and its influence on patient outcomes. Findings support the proposed reclassification of SJS/TEN as DEN and postinfectious mucocutaneous eruptions as RIME.

Life-threatening Rash Due to Lamotrigine and a Failure to Understand Its Pharmacology: How Forensic Detective Work Uses Medical Knowledge and Clinical Pharmacology to Solve Cases.

This column is the second of a 3-part series describing cases where general medical knowledge, including psychiatric and clinical pharmacology, were instrumental in determining dereliction and direct cause in a malpractice suit. This case summarizes how lamotrigine can cause dangerous consequences if its pharmacology is not properly understood. The case also illustrates how the 4 Ds of a forensic malpractice suit were met in this case. First, there was duty on the part of the prescriber which, if followed, would have prevented or minimized the damages experienced by the patient. Dereliction in the performance of a patient-physician treatment contract was a direct cause of the development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in this patient. An immune-mediated reaction to lamotrigine or one of its metabolites has been extensively reported in the literature, with the risk of this reaction increasing at higher doses and with more rapid titration, fulfilling the elements of direct cause. Dereliction implies a deviation from the standard of care. On the basis of the clinical information from the package insert, more likely than not a deviation from the standard of care occurred in this case when lamotrigine was titrated faster than recommended by the package insert.

Pattern of Adverse Drug Reactions in Extremes of Age Group Reported to a Tertiary Care Hospital

ABSTRACT Background: The World Health Organization (WHO), defined adverse drug reactions (ADRs) as “any noxious and unintended response to a drug, which occurs at doses normally used in humans for prophylaxis, diagnosis and treatment of the disease or for the modification of physiological functions.” Pediatrics (≤12 years) and geriatrics (≥65 years) are the extreme age groups that are more vulnerable for ADRs. Aim and Objectives: To determine ADRs time-plausible relationship, clinical spectrum, causality, and severity in extreme age group patients. Materials and Methods: All the ADRs reported to ADR monitoring center among geriatrics and pediatrics patients after Institutional Ethics Committee approval were collected from January 2015 to July 2022. The collected reports were analyzed for ADR pattern, drug groups, Causality (as per WHO-Uppsala Monitoring Centre scale) and severity (Modified Hartwig scale). Results: Out of 4705 ADRs, 176 (3.74%) were reported in geriatric and 181 (3.84%) in pediatric patients. In geriatric patients, anti-neoplastic drugs followed by cardiovascular drugs were the most commonly implicated drugs, erythematous rash and dyspnea were the most common ADRs. Erythematous rash and diarrhea were the most commonly ADRs and immunological agents followed by antimicrobials were implicated drugs in pediatric patients. In geriatric patients 84.1% were mild, 14.8% moderate, and 1.1% severe reactions whereas in pediatric group 91.2% were mild, 8.3% moderate, and 0.5% severe ADRs. Two cases of toxic epidermal necrolysis and one case of Steven–Johnson syndrome were reported in geriatric and pediatric patients respectively. Causality assessment of the majority of ADRs in geriatric age group was possible (79.5%) and in pediatric age group it was probable (61.3%). Conclusion: Extreme age group populations are more vulnerable to ADRs due to comorbidities, polypharmacy and drug interactions in elderly people and immature hepatobiliary and renal systems in pediatric age. Hence, active surveillance of drugs and education of prescribers will help to minimize the risk of ADRs in this susceptible population.

Phenytoin-induced toxic epidermal necrolysis (TEN). Combined treatment with steroids and human intravenous immunoglobulin: Case report

Background. Toxic epidermal necrolysis (TEN) is a severe systemic disease that affects the skin and mucosa, with a mortality rate above 30%. Pharmaceutical drugs are the main causal agents of this reaction, with most cases being largely associated with phenytoin. There is no generally accepted treatment for TEN. The administration of systemic corticosteroids combined with human intravenous immunoglobulin (IVIG) may be a possible adjuvant therapy. Case presentation. A 72-year-old patient who received phenytoin for four weeks as a prophylactic treatment after undergoing surgery to drain a chronic subdural hematoma developed TEN-compatible symptoms, which prompted treatment with methylprednisolone (1 g/day for 3 days) combined with IVIG (0.5 gr/kg/day for 5 days), with favorable response. Conclusion. Our patient’s response to the combination of corticosteroids and IVIG was favorable. However, due to the nature of this report, the function this combination of drugs has must be further researched.

Lornoxicam induced Toxic Epidermal Necrolysis (TEN) in a 54 years old female: A case report and its systematic literature review with respect to its causes and treatment overview

Lornoxicam induced Toxic Epidermal Necrolysis (TEN) in a 54 years old female: A case report and its systematic literature review with respect to its causes and treatment overview

Line-field confocal optical coherence tomography for real-time differential diagnosis of toxic epidermal necrolysis versus staphylococcal scalded skin syndrome.

We present here the cases of a 31-year-old male and a 68-year-old female, both presented with extensive erythema, a positive Nikolsky’s sign and major pain. Line-field Confocal Optical Coherence Tomography (LC-OCT) LC-OCT is a fast imaging tool able to visualize the cleavage level and epidermal necrosis to distinguish staphylococcal scalded skin syndrome from toxic epidermal necrolysis.

Immunological Drug-Drug Interactions Affect the Efficacy and Safety of Immune Checkpoint Inhibitor Therapies.

With the rapid expansion in the development and clinical utility of immune checkpoint inhibitors (ICIs) for oncology, the continual evaluation of the safety profile of such agents is imperative. The safety profile of ICIs as monotherapy is dominated by immune-related adverse events, which can be considered as an extension of the mechanism of action of these immunomodulatory drugs. Further to this, an emerging theme is that ICI treatment can significantly impact upon the tolerability of coadministered medications. Numerous reports in literature indicate that ICIs may alter the immunological perception of coadministered drugs, resulting in undesirable reactions to a variety of concomitant medications. These reactions can be severe in manifestation, including hepatotoxicity and Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN), but may also have detrimental impact on malignancy control. To minimize the impact of such drug-drug interactions on patients, it is imperative to identify medications that may cause these reactions, understand the underlying mechanisms, consider the timing and dosing of comedication, and explore alternative medications with comparable efficacies. Improving our understanding of how concomitant medications affect the safety and efficacy of ICIs can allow for potential culprit drugs to be identified/removed/desensitized. This approach will allow the continuation of ICI therapy that may have been discontinued otherwise, thereby improving malignant control and patient and drug development outcomes.

Combined corticosteroid and etanercept therapy in toxic epidermal necrolysis

Combined corticosteroid and etanercept therapy in toxic epidermal necrolysis

Management of a Case of Toxic Epidermal Necrolysis in Intensive Care Unit

Management of a Case of Toxic Epidermal Necrolysis in Intensive Care Unit

Amnion as an Innovative Antiseptic Carrier: A Comparison of the Efficacy of Allogeneic and Xenogeneic Transplantations in the Context of Burn Therapy.

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.

Stevens Johnson Syndrome Review

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are dermatologic emergencies that are distinguished by extensive epidermal necrolysis and sloughing. The incidence rates are location-dependent. Mortality rates vary from 4.8-9% to 14.8-48%, with females being more frequently affected than males. Supportive care, infection control, wound care, and fluid and electrolyte management comprise nonpharmacologic treatment for SJS/TEN patients. The identification and cessation of the causative substance are the most critical components. The management of fluid, electrolytes, and nutrition is essential for SJS/TEN patients, as they have lower fluid requirements than burn patients. Prophylactic antibiotics do not improve outcomes; however, infection prevention necessitates appropriate wound care and antiseptic handling. The decision to pursue surgical debridement is contingent upon the location of care, and the function of this treatment option has been a subject of controversy. Anti-shear therapy, which entails the preservation of denuded epidermis and the aspiration of blister fluid, has been demonstrated to be effective in decreasing mortality rates. The disease's rarity has resulted in a scarcity of prospective studies on pharmacologic treatment for SJS/TEN. There have been reports of a variety of treatment regimens that involve corticosteroids, IVIg, cyclosporine, and TNF-alpha inhibitors. However, it is difficult to ascertain whether the disease's remission was caused by a specific treatment or the natural course of the disease. Studies have demonstrated that supportive care and cyclosporine have the potential to serve as alternative treatments for SJS/TEN. A meta-analysis of 10 studies revealed that patients who received cyclosporine had a survival advantage, while a meta-analysis of 67 studies revealed that the combination of corticosteroids and IVIg resulted in statistically significant improvements in outcomes. The severity of illness scores in patients with SJS/TEN overlap or TEN was reduced by plasmapheresis, which entails plasmapheresis and corticosteroids. In 86.8% of patients, TNF-alpha inhibitors have also demonstrated positive outcomes, despite their immunosuppressive properties. Nevertheless, the most effective pharmacological treatment for SJS/TEN must be determined by taking into account practical factors, such as cost. There is a lack of consensus regarding the most effective treatment, and additional research is required to ascertain the most effective treatment.

Stevens Johnson Syndrome and Toxic Epidermal Necrolysis Updates on Management

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are dermatologic emergencies characterized by extensive epidermal necrolysis and sloughing. The incidence rates vary depending on location, with the UK experiencing an annual incidence of 5.76 cases per million individuals from 1995 to 2013. Females are more frequently afflicted than males, with mortality rates ranging from 4.8-9% to 14.8-48%. Nonpharmacologic treatment for SJS/TEN patients includes supportive care, fluid and electrolyte management, infection control, and wound care. The most critical component is the identification and cessation of the causative substance. Management of fluid, electrolytes, and nutrition is crucial for SJS/TEN patients, as they have lower fluid requirements than burn patients. Prophylactic antibiotics do not enhance outcomes, but infection prevention requires appropriate wound care and antiseptic handling. The role of surgical debridement has been a topic of controversy, and the decision to pursue this treatment option depends on the location of care. Anti-shear therapy, which involves aspiration of blister fluid and preservation of denuded epidermis, has been shown to be effective in reducing mortality rates. Pharmacologic treatment for SJS/TEN has been the subject of few prospective studies due to the disease's rarity. Various treatment regimens involving corticosteroids, IVIg, cyclosporine, and TNF-alpha inhibitors have been reported, but it is challenging to determine whether the disease's remission was due to a specific treatment or the natural course of the disease.

Candidaemia and Candida colonization in patients with epidermal necrolysis: aretrospective case series.

Sepsis is a leading cause of death in patients with epidermal necrolysis (EN). However, fungal infections have rarely been reported. From a monocentric retrospective study conducted between 2000 and 2023 in the medical intensive care unit of the reference centre for severe drug reactions in France, we report on the epidemiology of candidaemia and Candida sp. colonization in patients with EN. Of 155 patients with EN who were admitted to the ICU, 36 had a positive Candida sp. skin culture without candidaemia, 12 developed candidaemia and 107 had a negative skin culture and no candidaemia. Skin cultures showed a good sensitivity [89%; 95% CI (52–100%)] and excellent negative predictive values [99%; 95% CI (94–100%)] for candidaemia.

Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis: Macules, Papules, and Bullae.

The objective of this discussion paper is to illuminate the importance of early identification and treatment of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). SJS/TEN may occur as quickly as 4 days, more commonly 4 to 8 weeks after starting a new medication and early identification is essential. A review of literature revealed there is a lack of diagnostic awareness related to the clinical presentation and diverse populations at risk for this devastating syndrome. A Boolean search was conducted, and six quantitative and qualitative research articles were discovered that indicate a knowledge disparity between "rash" versus SJS/TEN. Research indicates evidence-based best clinical practices for nurses and health care practitioners for assessment of risks, clinical presentation, and treatment. Prompt diagnosis and discontinuation of the suspected medication will reduce potential life-threatening sequelae.

Mucositis y exantema, ¿qué hay de nuevo? Erupción mucocutánea infecciosa reactiva

Reactive infectious mucocutaneous eruption (RIME) is a recently emerged term that describes cases of post-infectious mucositis associated with different etiological agents (viral and bacterial). It is part of the spectrum of Stevens-Johnson syndrome (SSJ) / toxic epidermal necrolysis (NET), although it presents with milder symptoms, with predominantly mucosal involvement. Treatment consists of supportive measures, and may include targeted antibiotic therapy and systemic corticosteroid therapy in cases with extensive involvement.

Management of pain in the inpatient and non-surgical outpatient dermatology settings: A narrative review.

Pain is frequently encountered in dermatology practice, which impairs the activities of daily living, adds to psychological morbidity, and therefore compromises the quality of life. It ranges from mild to severe in intensity across various dermatoses and requires prompt addressal and treatment. Diseases such as extensive pemphigus vulgaris and Stevens-Johnson syndrome are especially painful and require a multidisciplinary approach with the involvement of a pain specialist in their management. The main pathogenic types of pain include visceral nociceptive, somatic nociceptive, and neuropathic types, the latter two being most relevant in dermatological disorders. Somatic nociceptive pain is often seen in patients of Stevens-Johnson syndrome/ Toxic epidermal necrolysis, epidermolysis bullosa, pemphigus vulgaris, erythema nodosum, and hidradenitis suppurativa, while neuropathic pain is part of the disease process in dermatoses like leprosy, herpes zoster, and dysesthesia syndromes. Therapeutic approaches to pain management include the use of non-opioids (acetaminophen, non-steroidal anti-inflammatory agents), opioids, and non-pharmacological therapies, along with appropriate management of the underlying dermatosis. World Health Organisation (WHO) analgesic ladder remains the most commonly employed guideline for the management of pain, although treatment needs individualisation depending on the nature and severity of pain (acute/chronic), type of dermatosis, and patient factors. There is a paucity of literature pertaining to pain management in dermatology and this topic is often neglected due to a lack of awareness and knowledge of the topic. The present review aims to discuss the pain pathway, various painful conditions in the setting of medical dermatology practice, and their management along with relevant pharmacology of the commonly used analgesics.

Comparison of incidence, causes and prognosis of adultand paediatric epidermal necrolysis: a French population-based study.

Epidermal necrolysis (EN), comprising Stevens-Johnson syndrome and toxic EN, is a rare and severe blistering reaction, mainly induced by drugs. Differences between paediatric and adult patients regarding incidence, causes and outcomes have been discussed but are based on a limited number of patients from small case series. To directly compare the incidence, cause and prognosis of adult and paediatric EN. We used data from the French Health System Database (1 January 2013-31 December 2022). We identified adult and paediatric patients hospitalized for EN using the International Classification of Diseases, 10th Revision codes combined with validated algorithms. Outcomes were the incidence of EN; the presence of a suspected drug before EN onset (defined as a new drug dispensation from 5 to 56 days prehospitalization); and in-hospital mortality. To estimate the association between paediatric EN and the presence of a suspect drug, we computed a multivariable logistic regression with odd ratios (ORs). To estimate the association with mortality, we computed a multivariable Cox proportional hazard ratio (HR) model. A total of 1440 patients [799 (55.5%) female] with EN were included, comprising 219 children and 1221 adults. Among children, the incidence of EN was 1.5 cases [95% confidence interval (CI) 1.3-1.7] per 1 million person-years vs. 2.6 cases (95% CI 2.5-2.7) in adults. Moreover, children had less chance of being given a culprit drug before the onset of EN [n = 93/219 (42.5%) vs. n = 829/1221 (67.9%)], with an adjusted OR of 0.43 (95% CI 0.32-0.59; P < 0.001), together with a better prognosis: the mortality rate in paediatric patients was 1.4% (95% CI 0.4-3.7) vs. 19.4% (95% CI 17.3-21.7) in adults. The adjusted HR for in-hospital mortality in children was 0.12 (95% CI 0.04-0.38; P < 0.001). Paediatric EN appears to be rarer, with less chance of being caused by drugs and has a better prognosis than adult EN. These results suggest the existence of different underlying pathophysiological mechanisms and clinical particularities between adult and paediatric patients with EN.

Safety evaluation of ceftazidime/avibactam based on FAERS database.

To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.

Protein Haptenation and Its Role in Allergy.

Humans are exposed to numerous electrophilic chemicals either as medicines, in the workplace, in nature, or through use of many common cosmetic and household products. Covalent modification of human proteins by such chemicals, or protein haptenation, is a common occurrence in cells and may result in generation of antigenic species, leading to development of hypersensitivity reactions. Ranging in severity of symptoms from local cutaneous reactions and rhinitis to potentially life-threatening anaphylaxis and severe hypersensitivity reactions such as Stephen-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), all these reactions have the same Molecular Initiating Event (MIE), i.e. haptenation. However, not all individuals who are exposed to electrophilic chemicals develop symptoms of hypersensitivity. In the present review, we examine common chemistry behind the haptenation reactions leading to formation of neoantigens. We explore simple reactions involving single molecule additions to a nucleophilic side chain of proteins and complex reactions involving multiple electrophilic centers on a single molecule or involving more than one electrophilic molecule as well as the generation of reactive molecules from the interaction with cellular detoxification mechanisms. Besides generation of antigenic species and enabling activation of the immune system, we explore additional events which result directly from the presence of electrophilic chemicals in cells, including activation of key defense mechanisms and immediate consequences of those reactions, and explore their potential effects. We discuss the factors that work in concert with haptenation leading to the development of hypersensitivity reactions and those that may act to prevent it from developing. We also review the potential harnessing of the specificity of haptenation in the design of potent covalent therapeutic inhibitors.

First-Line Antituberculosis Drug Challenge Reactions in Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome in an HIV Endemic Setting

BackgroundIn high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. ObjectiveWe aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. MethodsPatients hospitalized with FLTD-associated DRESS from 2013–2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. ResultsSADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. ConclusionsSADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.