Introduction. - Immune-mediated necrotizing myopathy (IMNM) is a form of statin myopathy characterized by the presence of antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A Objectives. - The aim of this study was to investigate the relationship between the different statins and the risk of IMNM. Methods. - A two-time approach was used. First, we performed a descriptive analysis of the French national pharmacovigilance database (FNPV) for the period from 1985 to december2020. To identify relevant cases, we used Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) related to IMNM. We performed a quantitative and qualitative review of individual case safety reports (ICSRs) recorded in the french vigilance spontaneous reporting system. In a second time, we performed a comparative analysis with the World Health Organization global individual case safety reports database (Vigibase). The association between IMNM and statins exposure was assessed by calculating the reporting odds ratio (ROR) and its 95% confidence interval. Results. - After analysis, a total of 25 ICSRs were related to IMNM in the FNPV. The suspected statins were atorvastatin (n = 21), simvastatin (n = 2), pravastatin (n = 1) and rosuvastatin (n = 1). In Vigibase, 567 notifications were identified. A significant ROR value was found for atorvastatin, pitavastatin, simvastatin, pravastatin and rosuvastatin. Conclusion. - Atorvastatin presents the highest risk of IMNM. Our data suggest that the occur- rence of IMNM is a class effect. (c) 2023 Societe franc , aise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.

Sweet's syndrome is an acute febrile neutrophilic dermatosis first described in 1964 by Robert Douglas Sweet. The pathophysiological mechanism is not fully established; however, several cases of Sweet's syndrome have been reported following drug administration. To investigate the existence of pharmacovigilance signals between drugs and the occurrence of Sweet's syndrome, we performed a case/non-case study on reports of ‘acute febrile neutrophilic dermatosis’ registered in the French pharmacovigilance database. Reporting odds ratio (ROR) with its 95% confidence interval were calculated. Amongthe 994 789 reports recorded in the database, 136 were Sweet's syndrome, of which 50.7% were men and the median age was 59 years (range 15–91). A total of 224 drugs were mentioned as suspects: 21.0% were antibacterials, 19.2% were antineoplastics and 12.1% were immunosuppressants. Median time to onset from drug initiation to the development of Sweet's syndrome was 15 days (range 1–1095). The highest RORs were observed with bortezomib (74.04 [40.8–134.2]), azacitidine (72.14 [29.4–176.9]), perfilgrastim (67.05 [21.2–211.6]), azathioprine (55.46 [34.8–88.4]) and bendamustine (35.84 [11.4–112.8]). Pharmacovigilance signals have been observed between the occurrence of Sweet's syndrome and colony-stimulating factors, immunosuppressants, antineoplastics and antibiotics. Clinicians should be aware of the potential associations with these drugs and should be encouraged to report any case of drug-induced Sweet's syndrome.

Journal of the European Academy of Dermatology and VenereologyVolume 37, Issue 4 p. e456-e459 COVID-19 SPECIAL FORUM - LETTER TO THE EDITOR Epidermal necrolysis after COVID−19 vaccination: An exploratory analysis using World Health Organization VigiBase Btisseme Ahouach, Btisseme Ahouach orcid.org/0000-0003-2406-1839 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, FranceSearch for more papers by this authorEmmanuelle Diaz, Corresponding Author Emmanuelle Diaz [email protected] orcid.org/0000-0002-6829-4450 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France Correspondence Emmanuelle Diaz, Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France. Email: [email protected]Search for more papers by this authorBlandine Bertin, Blandine Bertin Pharmacovigilance Center, Hospital University Pharmacotoxicology Department, Hospices Civils de Lyon HCL, Lyon, FranceSearch for more papers by this authorBenoit Ben Said, Benoit Ben Said Dermatology Department, Edouard Herriot Hospital, Lyon, France Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, FranceSearch for more papers by this authorSandrine Combret, Sandrine Combret Pharmacovigilance Department, Dijon University Hospital, Dijon, FranceSearch for more papers by this authorAurélie Grandvuillemin, Aurélie Grandvuillemin Pharmacovigilance Department, Dijon University Hospital, Dijon, FranceSearch for more papers by this authorNadine Petitpain, Nadine Petitpain Pharmacovigilance Department, Nancy-Brabois Hospital, Vandoeuvre-lès-Nancy, FranceSearch for more papers by this authorMarie Blanche Rabier, Marie Blanche Rabier Pharmacovigilance Department, Besançon University Hospital, Besançon, FranceSearch for more papers by this authorLaure Thomas, Laure Thomas Pharmacovigilance Department, Henri-Mondor Hospital AP-HP, Créteil, FranceSearch for more papers by this authorThierry Trenque, Thierry Trenque Pharmacovigilance Department, University Hospitals of Reims, Reims, FranceSearch for more papers by this authorSaskia Ingen-Housz-Oro, Saskia Ingen-Housz-Oro orcid.org/0000-0002-5383-7096 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, France Univ Paris Est Créteil Epiderme, UPEC, Créteil, FranceSearch for more papers by this authorBénédicte Lebrun-Vignes, Bénédicte Lebrun-Vignes Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, France Univ Paris Est Créteil Epiderme, UPEC, Créteil, France Pharmacovigilance Department, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, Paris, FranceSearch for more papers by this author Btisseme Ahouach, Btisseme Ahouach orcid.org/0000-0003-2406-1839 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, FranceSearch for more papers by this authorEmmanuelle Diaz, Corresponding Author Emmanuelle Diaz [email protected] orcid.org/0000-0002-6829-4450 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France Correspondence Emmanuelle Diaz, Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France. Email: [email protected]Search for more papers by this authorBlandine Bertin, Blandine Bertin Pharmacovigilance Center, Hospital University Pharmacotoxicology Department, Hospices Civils de Lyon HCL, Lyon, FranceSearch for more papers by this authorBenoit Ben Said, Benoit Ben Said Dermatology Department, Edouard Herriot Hospital, Lyon, France Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, FranceSearch for more papers by this authorSandrine Combret, Sandrine Combret Pharmacovigilance Department, Dijon University Hospital, Dijon, FranceSearch for more papers by this authorAurélie Grandvuillemin, Aurélie Grandvuillemin Pharmacovigilance Department, Dijon University Hospital, Dijon, FranceSearch for more papers by this authorNadine Petitpain, Nadine Petitpain Pharmacovigilance Department, Nancy-Brabois Hospital, Vandoeuvre-lès-Nancy, FranceSearch for more papers by this authorMarie Blanche Rabier, Marie Blanche Rabier Pharmacovigilance Department, Besançon University Hospital, Besançon, FranceSearch for more papers by this authorLaure Thomas, Laure Thomas Pharmacovigilance Department, Henri-Mondor Hospital AP-HP, Créteil, FranceSearch for more papers by this authorThierry Trenque, Thierry Trenque Pharmacovigilance Department, University Hospitals of Reims, Reims, FranceSearch for more papers by this authorSaskia Ingen-Housz-Oro, Saskia Ingen-Housz-Oro orcid.org/0000-0002-5383-7096 Dermatology Department, Henri-Mondor Hospital AP-HP, Créteil, France Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, France Univ Paris Est Créteil Epiderme, UPEC, Créteil, FranceSearch for more papers by this authorBénédicte Lebrun-Vignes, Bénédicte Lebrun-Vignes Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL, Créteil, France Univ Paris Est Créteil Epiderme, UPEC, Créteil, France Pharmacovigilance Department, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne Université, Paris, FranceSearch for more papers by this author First published: 06 January 2023 https://doi.org/10.1111/jdv.18845 Saskia Ingen-Housz-Oro and Bénédicte Lebrun-Vignes are equally contributors. The information comes from a variety of sources, and the probability that the suspected adverse effect is drug-related is not the same in all cases. The information does not represent the opinion of the UMC or the World Health Organization. The French National Agency for the Safety of Medicines and Health Products (ANSM) is another database used by the authors as a data source. Disclaimer: The content of [Epidermal necrolysis after COVID-19 vaccination: An exploratory analysis using World Health Organization VigiBase] engages only its author and is not validated by the ANSM. 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Background: Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described.Objectives: To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema.Methods: This retrospective and descriptive study included a query of the French national pharmaco-vigilance database, together with a national call for cases among dermatologists.Results: We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema.Limitations: Retrospective study, with possible missing data or memory bias.Conclusion: Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferen-tially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required. ( J Am Acad Dermatol 2023;88:380-7.)

AIM Sweet's syndrome is an acute febrile neutrophilic dermatosis first described in 1964 by Robert Douglas Sweet. The pathophysiological mechanism is not fully established, however several cases of Sweet's syndrome have been reported following drug administration. METHODS To investigate the existence of pharmacovigilance signals between drugs and the occurrence of Sweet's syndrome, we performed a case/non-case study on reports of "acute febrile neutrophilic dermatosis" registered in the French pharmacovigilance database. Reporting Odds Ratio (ROR) with its 95% confidence interval were calculated. RESULTS Among the 994,789 reports recorded in the database, 136 were Sweet's syndrome. 50.7% of patients were men; median age was 59 years (range 15-91). 224 drugs were mentioned as suspects: 21.0% were antibacterials, 19.2% were antineoplastics, 12.1% were immunosuppressants. Median time to onset from drug initiation to the development of Sweet's syndrome was 15 days (range 1-1095). Highest ROR were observed with bortezomib (74.04 [40.8-134.2]), azacitidine (72.14 [29.4-176.9]), perfilgrastim (67.05 [21.2-211.6]), azathioprine (55.46 [34.8-88.4]) and bendamustine (35.84 [11.4-112.8]). CONCLUSION Pharmacovigilance signals have been observed between the occurrence of Sweet's syndrome and colony-stimulating factors, immunosuppressants, antineoplastics and antibiotics. Clinicians should be aware of the potential associations with these drugs and encourage reporting any case of drug-induced Sweet's syndrome.

Background:Amoxicillin crystalluria (AC), potentially responsible for acute kidney injury (AKI), is reported more and more frequently in patients treated with high doses of intravenous amoxicillin (HDIVA). The main objective of this study was to evaluate AC incidence in these patients. The secondary objectives were to identify factors associated with AC and to evaluate its impact on the risk of AKI.Methods:This multicentre, observational, cohort study was conducted between Mar 18, 2014 and Aug 16, 2019 in Dijon, Nancy, and Reims University Hospitals as well as Châlon-sur-Saône, Charleville-Mézières, and Troyes general hospitals in France. Adult patients (≥18 years) treated with HDIVA and having been tested for AC at least once during treatment were included. Clinical, biological, and therapeutic characteristics of the patients were collected. A univariable mixed logistic regression model assessed the factors associated with AC. A multivariable Cox model with AC as a time-dependent variable assessed the prognostic factors for AKI. ClinicalTrials.gov number: NCT02853292.Findings:Of the 112 included patients, 27 (24.1%, 95% CI [16.2-32.0]) developed at least one episode of AC within a mean of 5.1 days. The factors associated with its occurrence were the concomitant use of angiotensin converting enzyme (ACE) inhibitors (OR=4.6, 95% CI [2.2-9.3], p<0.0001) and the decrease of urinary pH (OR=2.1 for one pH point decrease, 95% CI [1.2-3.7], p=0.009). 20 patients (17.9%) presented with AKI, within a mean time of 10.9 days. The main factor associated with the occurrence of AKI was the occurrence of AC (aHR=7.4, 95% CI [2.5-22.2], p=0.0003).Interpretation:AC occurred in a quarter of patients treated with HDIVA and was highly prognostic of AKI.Funding:None.

PURPOSE:Pembrolizumab is a humanized monoclonal antibody that binds to the programmed cell-death protein-1 (PD-1) on immune T-cells, thus blocking PD-1 activity. Pembrolizumab is indicated for the treatment of advanced melanoma, metastatic non-small-cell lung cancer, and head and neck squamous cell carcinoma. However, it is associated with immune-related adverse events.METHODS:We investigated the association between pembrolizumab and immune-mediated necrotizing myopathy (IMNM). We analyzed reports in the World Health Organization's global individual case safety report database, Vigibase, up to January 2020 with the MedDRA lower level term "IMNM." The association between exposure to pembrolizumab and occurrence of the adverse event was estimated by disproportionality analysis. The reporting odds ratio (ROR) was calculated with 95% confidence intervals (CIs). We analyzed the criteria of diagnosis of the adverse reaction.RESULTS:Five-hundred sixty-seven notifications were identified as IMNM of which 14 with pembrolizumab. The ROR was 17.59 (95% CI: 9.4-32.9).CONCLUSION:The diagnosis of IMNM does not always take into account recent criteria for the diagnosis of this pathology. This study highlights the existence of a signal, as well as the need for collaboration between oncologists and neurologists for these neurological pathologies.

Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis is an auto-immune neurological disorder characterized by the presence in the cerebrospinal fluid (CSF) of antibodies against the GluN1 subunit of NMDA receptors in the brain. The etiology of the disease remains largely unknown. In this study, we aimed to investigate the possible existence of pharmacovigilance signals relating to a link between vaccination and the occurrence of anti-NMDAR encephalitis. We performed a case/non-case study using data from the World Health Organization pharmacovigilance database (VigiBase) up to 31 December 2021. All individual case study reports (ICSRs) linked to a vaccine and coded with the MedDRA Lower Level Term (LLT) “anti-NMDA receptor encephalitis” were analysed. We calculated the Reporting Odds Ratio (ROR) and 95% Confidence Interval (CI) for each type of vaccine. A total of 29,758,737 ICSRs were registered in VigiBase, of which 70 were coded under the selected LLT, and 29/70 (41.4%) involved a vaccine. Of these cases, 53.8% involved children aged younger than 15 years. The median time to onset of anti-NMDAR encephalitis after vaccination was 4 days (range 0–730). The highest RORs were observed for the diphtheria/polio/tetanus/pertussis vaccine [54.72 (95% CI 26.2–114.3)], yellow fever vaccine [50.02 (95% CI 15.7–159)] and human papillomavirus vaccine [32.89 (15.8–68.7)]. All cases were coded as serious; 13 patients did not recover, or were left with permanent sequelae. Nine patients recovered without sequelae or are on the path to recovery, and one patient died. In summary, pharmacovigilance signals were observed for anti-NMDAR encephalitis and vaccination. Clinicians need to be aware of this potential risk, and encourage to report any case of anti-NMDAR encephalitis occurring after vaccination.