Drug-induced lupus (DIL) is an idiosyncratic side effect of treatments in which symptoms overlap with those of systemic lupus erythematosus (SLE). The spectrum of DIL constantly evolves with that of ...the pharmacopoeia. Here, we used VigiBase, the WHO global individual case safety reports (ICSRs) database, to identify the main drugs associated with DIL.
We analysed all ICSRs classified as 'systemic lupus erythematosus' according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase. The drugs considered in the analysis were those not used to treat SLE, with a positive lower end of the 95% credibility interval for the information component (IC
) ≥0, an indicator value for disproportionate Bayesian reporting.
A total of 12 166 DIL ICSRs were identified using VigiBase. From those, 8163 ICSRs reporting on 118 suspected drugs with IC
≥0 were extracted. The median age at DIL onset was 49 years and the female to male sex ratio was 4.3. The median delay between start of suspected treatment and DIL occurrence was 172 days. DIL was reported as serious adverse event in 55.4%. Among the 118 suspected drugs, 42 had not been previously reported in association with DIL. The drugs associated with the highest number of DIL cases were infliximab, adalimumab, etanercept, procainamide and hydralazine.
This study enables the identification of 118 drugs associated with DIL. The list of suspected drugs may prove useful to physicians when confronted with potential DIL cases.
NCT03480529.
Epidermal necrolysis (EN) encompasses Stevens-Johnson syndrome (SJS, < 10% of the skin affected), Lyell syndrome (toxic epidermal necrolysis, TEN, with ≥30% of the skin affected) and an overlap ...syndrome (10 to 29% of the skin affected). These rare diseases are caused, in 85% of cases, by pharmacological treatments, with symptoms occurring 4 to 28 days after treatment initiation. Mortality is 20 to 25% during the acute phase, and almost all patients display disabling sequelae (mostly ocular impairment and psychological distress).The objective of this French national diagnosis and care protocol (protocole national de diagnostic et de soins; PNDS), based on a critical literature review and on a multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with EN. This PNDS, written by the French National Reference Center for Toxic Bullous Dermatoses was updated in 2017 ( https://www.has-sante.fr/portail/jcms/c_1012735/fr/necrolyse-epidermique-syndromes-de-stevens-johnson-et-de-lyell ). The cornerstone of the management of these patients during the acute phase is an immediate withdrawal of the responsible drug, patient management in a dermatology department, intensive care or burn units used to dealing with this disease, supportive care and close monitoring, the prevention and treatment of infections, and a multidisciplinary approach to sequelae. Based on published data, it is not currently possible to recommend any specific immunomodulatory treatment. Only the culprit drug and chemically similar molecules must be lifelong contraindicated.
Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a ...real-life large pharmacovigilance database.
A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database.
Analysis of adverse events reported as 'atrial fibrillation' (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0.
530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17-7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender.
This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.
Cystic lymphatic malformations (LMs) are rare chronic conditions which management differs according to the type (macrocystic LMs, microcystic LMs or both). Studies are lacking due to rarity of the ...pathology. We aimed to establish a French National Diagnosis and Care Protocol (PNDS: Protocole National de Diagnostic et de Soins), to provide health professionals with free open access synthesis on optimal management and care of patients with LMs ( https://www.has-sante.fr/upload/docs/application/pdf/2021-03/malformations_lymphatiques_kystiques_-_pnds.pdf ). The process included a critical review of the literature and multidisciplinary expert consensus. LMs are congenital but are not always discovered at birth. Nearly 75% of them are located in the head and neck because of the highly dense lymphatic system in this region. Physical examination (showing painless masses with normal skin color and depressible consistency, or cutaneous/mucosal lymphangiectasia) and color Doppler ultrasonography, usually allow for diagnosis. MRI (involving T2 sequences with fat saturation in at least two spatial planes) is the tool of choice for evaluating anatomical extension, characterizing lesions (microcystic and macrocystic), and before considering therapeutic management. A biopsy, coupled to a blood sample, can also be used for molecular biology analyses, to search for activating mutations of the PIK3CA gene, particularly with LM integrating in a syndromic form (CLOVES or Klippel-Trenaunay syndrome) but also in certain isolated (or common) LMs. The spontaneous evolution of LMs, in particular microcystic forms, is often toward progressive aggravation, with an increase in the number of vesicles, thickening, increased oozing and bleeding, while pure macrocystic LMs may regress due to "natural sclerosis", i.e. fibrosis secondary to an inflammatory reorganization after common infantile infections. In case of voluminous LMs or syndromic forms, functional and psychological repercussions can be major, deteriorating the patient's quality of life. LMs must be treated by physicians integrated in multidisciplinary teams, and be personalized. Management is a life-long process that involves one or several of these therapies: conservative management, physical therapy (compression), sclerotherapy, surgery, drugs such as mTOR inhibitors (sirolimus), that has shown efficacy in decreasing the volume of LMs, and, more recently, PI3K-inhibitors in syndromic forms. Psychological and social support is necessary, taking into account the patient and his family.
Background Randomized controlled trials (RCTs) are considered the gold standard for assessing efficacy and short-term harm of medicines. However, several studies have come to the conclusion that harm ...is less well reported than efficacy outcomes. Objective To describe harm reporting in publications on dermatological RCTs and assess parameters that could influence the quality of harm reporting. Methods Methodologic systematic review of dermatologic RCTs published from 2010 to 2014 in 5 dermatological journals. Results Among 110 assessed publications on RCTs, 80 (73%) adequately reported harm and 52% adequately reported its severity. Overall, 40% of the assessed manuscripts perfectly reported and discussed harm. The adequate reporting of harm was significantly associated with the type of trial (odds ratio OR 4.41, 95% confidence interval CI 1.60-12.35 for multicenter compared with monocentric trials) and having a predefined method for collecting harm data (OR 5.93, 95% CI 2.26-15.56). Reporting of harm severity was better in pharmacologic trials (OR 6.48, 95% CI 2.00-21.0) compared with nonpharmacologic trials and in trials for which a method for collecting harm (OR 5.65, 95% CI 2.00-16.4) and its severity (OR 3.60, 95% CI 1.00-12.8) was defined before the study onset. Limitations Assessment was restricted to RCTs and 5 dermatological journals. Conclusion Harm is quite well reported in dermatologic journals. Efforts should be made on reporting severity of harm.
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