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Epidermal necrolysis (EN) is a rare life-threatening condition, usually drug-induced and characterised by a diffuse epidermal and mucosal detachment. Calcinosis cutis is reported in various skin diseases, occurring preferentially with tissue damage, but has never been described in EN. Clinical, biological and histopathological characteristics of three patients were retrospectively obtained from medical charts. Immunohistochemistry of classical osteogenic markers was used to explore the pathogenesis of the calcifications; their chemical composition was determined by $\mu $Fourier transform infra-red ($\mu $FTIR) spectroscopy and their localization and morphology by field-emission scanning electron microscopy (FE-SEM). In a recent letter, part of the results of this investigation has been already presented. In this contribution, we have added original data to this previous letter. We have investigated a set of biopsies corresponding to patients who presented atypical healing retardation due to calcinosis cutis. Through FE-SEM observations at the nanometre scale, we describe different areas where are present voluminous calcifications at the surface, submicrometre spherical entities within the papillary dermis and then large “normal” fibres. FE-SEM observations show clearly that “large” calcifications are the result of an agglomeration of small spherical entities. Moreover, micrometre scale spherical entities are the results of an agglomeration of nanometer scale spherical entities. Finally, the last set of data seems to show that the starting point of the calcifications process is “distant” from the epidermis in part of the dermis which appears undamaged. Regarding the chemical composition of large calcifications, different $\mu $FTIR maps which underlined the presence of calcium-phosphate apatite have been gathered. Moreover, histopathology indicates that these pathological calcifications are not induced following a trans-differentiation of the skin cells into an osteochondrogenic phenotype. The association of caspofungin administration, known to induce in vitro intracellular calcium influx, and inflammation, induced by EN, known to favor dystrophic calcifications in various inflammatory skin diseases, could explain this never-before reported occurrence of calcinosis cutis.

Background 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. Objectives To directly compare the incidence, cause and prognosis of adult and paediatric EN. Methods 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. Results 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). Conclusions 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. [ABSTRACT FROM AUTHOR]

Background: Patch tests (PTs) are recommended to identify the culprit drug in non‐immediate cutaneous adverse drug reactions (NICADRs). We recently reported that, in patients with NICADRs, a unique reading of PTs at day (D)2 compared with an additional second late reading at D4 missed almost half (45.3%) of the positive PTs. Objectives: To assess the change in sensitivity of the PT reading on D4 compared with the reading on D3. Methods: We performed a retrospective (July 2020–June 2023) monocentric study of patients who had PTs with two readings for a NICADR. We compared reading on D3 and the second reading on D4 for the suspected drug (primary outcome) and for the related drugs tested simultaneously (secondary outcome). Results: During the study period, 249 patients underwent patch testing with D3 and D4 readings. Regarding the primary outcome, the first reading at D3 was positive for 13.7% of patients, and the reading at D4 for 24.9% of patients (p < 0.0001). Regarding the secondary outcome, only 9.6% of patients had all their positive PT at D3 compared with 24.9% of patients at D4 (p < 0.0001). Considering the evaluated drug classes, no statistical difference was observed. However, we highlight that D3 reading detected all positive carbamazepine PTs (n = 3) while positive clindamycin PTs (n = 4) were identified only with the help of the second reading on D4. Conclusion: This study showed that, an additional D4 reading compared with a single D3 reading enhanced the sensitivity of PTs to identify culprit drugs and related. Further studies should replicate these findings and evaluate the medico‐economic balance and safety of a single reading of PTs on D4. [ABSTRACT FROM AUTHOR]

This article discusses the diagnosis and treatment of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, a rare and severe drug hypersensitivity reaction. The incidence of DRESS is low, ranging from two to five cases per million per year, with a mortality rate of 5-10%. The diagnosis of DRESS is challenging due to its complex clinical presentation and overlap with other conditions. The article provides a diagnostic algorithm and treatment recommendations based on a comprehensive literature review and expert consensus. Corticosteroids are the mainstay of treatment, and second-line therapies may be considered for refractory cases. Prospective clinical trials are needed to further validate treatment approaches. [Extracted from the article]

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life‐threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population. Objectives: To describe the spectrum of drugs associated with SJS‐TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase). Methods: Disproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case–non‐case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC025). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years. Results: Among 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS‐TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti‐infectious drugs. The five drugs with the highest IC025 were lamotrigine (IC025 4.99), carbamazepine (IC025 4.88), phenobarbital (IC025 4.67), phenytoin (IC025 4.52) and nimesulide (IC025 4.23). Acetaminophen was significantly associated with paediatric SJS‐TEN (IC025 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses. Conclusions: This study updates the spectrum of drugs potentially associated with paediatric SJS‐TEN. [ABSTRACT FROM AUTHOR]

Background and purpose: Peripheral neuropathy is a frequent complication of brentuximab vedotin (BV), used in CD30+ lymphoma treatment. Classic BV‐induced neuropathy (BV‐CN) is a mild distal sensory axonal polyneuropathy. Severe BV‐induced inflammatory neuropathies (BV‐IN) have been described. BV‐IN contribute to lymphoma‐associated morbidity but might be immunotherapy‐responsive. Our primary objective was to evaluate the rate of BV‐IN. Our secondary objectives were to determine risk factors and warning signs. Methods: We conducted a retrospective cohort study on all patients treated with BV at our center between April 2014 and September 2021. Clinical, biological, and electrophysiological data were collected. BV‐induced neuropathy was defined as the occurrence of neuropathy up to 3 months after BV discontinuation. BV‐IN was defined with criteria adapted from European Academy of Neurology/Peripheral Nerve Society 2021 electrodiagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Other neuropathies were classified as BV‐CN. Results: Among 83 patients, 41 (49%) developed neuropathy: 35 BV‐CN and 6 BV‐IN. Thus, the rate of BV‐IN was 7.2%. Compared to patients with BV‐CN, no predisposing factor was identified. However, patients with BV‐IN more frequently presented muscle weakness (67% vs. 5.7%, p < 0.05), gait disorders (83% vs. 20%, p < 0.05), or acute or subacute onset (67% vs. 14%, p < 0.05). BV‐IN was frequently more severe (Common Terminology Criteria for Adverse Events grade ≥3; 50% vs. 0%, p < 0.05). Four patients were treated with immunotherapy. Conclusions: Brentuximab vedotin‐induced neuropathy is an overlooked complication. Based on four easily identifiable "red flags", we provide an algorithm to help non‐neurologist physicians that care for BV‐treated patients to detect BV‐IN. The aim of the algorithm is to decrease the diagnostic and management delay of this disabling neuropathy. [ABSTRACT FROM AUTHOR]

The article published in the British Journal of Dermatology explores the occurrence of candidaemia and Candida colonization in patients with epidermal necrolysis (EN), such as Stevens–Johnson syndrome and toxic epidermal necrolysis. The study, conducted in a medical intensive care unit in France from 2000 to 2023, aimed to describe the epidemiology of fungal infections in these patients. The research compared the characteristics and outcomes of patients with candidaemia, positive mycological skin cultures for Candida sp., and negative mycological skin cultures. [Extracted from the article]