[HLA-B58.01 and allopurinol hypersensitivity renal vasculitis in a Chinese patient]. / HLA-B58.01 et vascularite rénale d'hypersensibilité à l'allopurinol chez un patient chinois.

INTRODUCTION: Allopurinol, widely used in the treatment of hyperuricemia and gout, has been shown to cause severe cutaneous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as systemic reactions such as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms). The HLA-B*5801 allele is known to be a risk factor for severe cutaneous manifestations of hypersensitivity to allopurinol, mostly in Asian populations. OBSERVATION: We report the observation of a 47-year-old Chinese patient, with no previous medical history, carrying the HLA-B*5801 allele, who developed an isolated allopurinol hypersensitivity necrotizing renal vasculitis without cutaneous manifestations. DISCUSSION: . The identification of this allele should be proposed before prescribing allopurinol in patients originating from certain regions of Asia, and the imputability of allopurinol should be evoked in case of necrotizing renal vasculitis, even without associated cutaneous involvement.

[Amiodarone-induced optic neuropathy: A rare side effect]. / Un effet indésirable rare de l'amiodarone : la neuropathie optique.

INTRODUCTION: The diagnosis of bilateral papilledema implies emergency medical care to look for intracranial hypertension and arteritic ischemic neuropathy. However, other causes must also be mentioned, including drugs. Too often underrated because of their usual benignity, drug side ophthalmological effects can be severe and are typically bilateral. CASE REPORT: An 80-year-old woman was hospitalized for bilateral papilledema, predominantly in the left eye, with lowered visual acuity. After ruling out intracranial hypertension, arteritic ischemic optic neuropathy, non-arteritic, and inflammatory bilateral papilledema, the diagnosis was toxic optic neuropathy. CONCLUSION: Bilateral edematous optic neuropathy is a known side effect of amiodarone, uncommon but to be known because of the large number of patients benefiting from this treatment.

Informativeness of patient initial reports of adverse drug reactions. Can it be improved by a pharmacovigilance centre?

PURPOSE: Little is known about the informativeness of initial patient reports before they are reviewed by a pharmacovigilance centre (PVC). We aim to describe the patterns of patient adverse drug reaction (ADR) reporting in France and estimate the contribution of a review by a PVC assessor on the informativeness of these reports. METHODS: A retrospective study was conducted on patient reports between July 2011 and July 2015. Informativeness of 16 key elements of information (including drug start and end date, duration of treatment, time to onset and duration of the ADR, outcome, medical history and concomitant medication) was assessed in initial reports before and after review by a pharmacovigilance assessor. RESULTS: Overall, 240 reports concerning 522 ADR and involving 278 drugs were reported over this 4-year period. Mean number of available key elements of information in initial reports was increased from 11/16 to 15/16 after review of reports by the PVC. Time to onset and duration of the ADR were respectively available in only 51 and 58% of the reports before review compared to 83 and 90% after review. Medical history and concomitant medication were missing in 75% of the initial reports compared to less than 30% of the reports after review. Contacting the reporter enabled an increase of informativeness of most elements of information for more than 90% of the reports. CONCLUSION: Patient reports often need to be completed on key elements of information that are required to assess reports. Both upstream education of patients and downstream intervention of a pharmacovigilance assessor to complete missing information could help to enhance the informativeness of such reports.

[Rituximab-induced acute thrombocytopenia in a patient with chronic lymphocytic leukemia]. / Un cas de thrombopénie aiguë au rituximab dans la leucémie lymphoïde chronique.

INTRODUCTION: Rituximab is a chimeric anti-CD20 monoclonal antibody generally well tolerated. However, a severe but rare rituximab-related immune-toxic syndrome, associating fever, chills and thrombocytopenia can occur shortly after the infusion. CASE REPORT: We report a case of severe acute rituximab-induced thrombocytopenia with favorable outcome in a patient with chronic lymphocytic leukemia and discuss the possible underlying mechanisms. CONCLUSION: Despite the potential initial severity of rituximab-induced thrombocytopenia in CLL, chemotherapy should not be discontinued; tolerance might increase as the hematologic disorder is controlled.

[Neuroleptic associated hypothermia: a new case report and study of spontaneous reports to the French pharmacovigilance network]. / L'hypothermie aux neuroleptiques, une complication méconnue : à propos d'un nouveau cas et revue de la base de la pharmacovigilance française.

INTRODUCTION: Neuroleptics are the main antipsychotic agents used in psychiatric or medicine departments. The occurrence of hyperthermia, particularly in the context of the neuroleptic malignant syndrome, is a well-known side effect of these treatments. Conversely, the occurrence of hypothermia is less known from clinicians. CASE REPORT: We reported a 72-year-old woman, who presented with hypothermia associated with treatment with neuroleptics. This patient had no other medical comorbidities. Because of persistent hypothermia, altered consciousness and bradycardia, exhaustive diagnostic work-up as well as a prolonged hospitalization were necessary. The results of a review of the national French pharmacovigilance database showed that nearly a quarter (153/614) of drug-related hypothermia are attributed to psychotropic drug, mainly neuroleptics (99/153). CONCLUSION: A better awareness of hypothermia associated to neuroleptics should facilitate early diagnosis and reporting this side effect of neuroleptics.

[Capecitabine-induced subacute cutaneous lupus: a case report]. / Lupus cutané subaigu induit par la capécitabine : un cas.

BACKGROUND: More than 100 drugs have been registered as inducing subacute cutaneous lupus erythematosus (SCLE). Recently, some types of chemotherapy have also been incriminated. If SCLE develops in a setting of neoplasia, two possibilities should be considered: it is either a paraneoplastic syndrome or it is caused by the chemotherapy, thus calling for important decisions on the benefit/risk of stopping potentially effective medication. We report a case of SCLE induced by Xeloda (capecitabine). PATIENTS AND METHODS: A 50-year-old female patient consulted with an annular erythematosquamous and pruriginous eruption, predominantly on areas of the body exposed to sunlight, occurring 4 months after the initiation of capecitabine for advanced colon cancer. She had presented systemic lupus erythematosus (SLE) for many years, which was not treated, was not progressive and had no cutaneous manifestations. The appearance of the cutaneous lesions, positivity for anti-SSA antibodies and the histological aspect led to diagnosis of SCLE. The lesions were resistant to treatment with hydroxychloroquine and systemic corticosteroids, but disappeared after discontinuation of capecitabine, suggesting chemotherapy-induced SCLE. DISCUSSION: Some types of chemotherapy such as capecitabine may reveal or induce SCLE lesions, whether or not there is a previous history of SLE. Cases of chemotherapy-induced cutaneous lupus reported to the French pharmacovigilance agency are rare, but this side effect must be recognised due to the constantly rising use of this type of anticancer agent.

Bevacizumab-induced serious side-effects: a review of the French pharmacovigilance database.

PURPOSE: Bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor, is widely used in association with standard chemotherapy in metastatic cancer. Well tolerated, bevacizumab is sometimes associated with serious adverse drug reactions (ADRs). The objective of this study is to describe the profile of ADRs related to bevacizumab and reported to the French Pharmacovigilance system. METHOD: All serious cases of ADRs associated with bevacizumab recorded in the French Pharmacovigilance database up to November 31, 2010 were identified and analyzed, focusing on patient information, drug exposure, and characteristics of the ADRs. Categorical variables were compared using the chi-square test when appropriate. RESULTS: A total of 351 serious cases involving 626 ADRs were recorded in the database during the study interval. The most frequent ADRs reported involved the gastrointestinal system (21.9%). The most frequent ADRs included gastrointestinal perforation (4.8%), thromboembolic events (4.0%), pulmonary embolism (3.2%), hypertension (2.7%), gastrointestinal hemorrhage (2.7%), and cerebral hemorrhage or vascular accident (2.6%). The median duration of bevacizumab exposure was four cycles (range 1-30) when ADRs occurred. In 18 cases of death directly caused by ADRs, 50% occurred after only one cycle. In cases of disability, 40% of ADRs were neurologic: neuropathy, paralysis, and paresis. CONCLUSION: To the best of our knowledge, this is the first analysis of bevacizumab safety profile using data collected in a national pharmacovigilance database. Our study confirms the frequency and seriousness of gastrointestinal, thromboembolic, and hemorrhage events with bevacizumab use and provides a picture of the bevacizumab safety profile in daily medical practice, despite intrinsic limitations.

[Severe hypoglycemia induced by tramadol: two new cases of an unlisted side effect]. / Hypoglycémies sévères au tramadol : deux nouvelles observations d'un effet indésirable non référencé

INTRODUCTION: Tramadol is a weak opioid analgesic used as a step two analgesic, approved in France for the treatment of moderate to severe pain in adult patients. The most common side effects are gastrointestinal and neurologic. Hypoglycaemia is an almost unknown side effect. CASE REPORTS: We report two patients who presented with severe hypoglycaemia related to oral administration of tramadol in non diabetic patients. The underlying mechanisms of hypoglycaemia induced by tramadol are unclear. The only weak opioid analgesic drug reported to cause hypoglycaemia is propoxyphene, which has been widely used in France. The recent withdrawal of dextropropoxyphene in France might increase the prescriptions of tramadol and healthcare professionals should be aware of the risk of hypoglycaemia. CONCLUSION: The risk of hypoglycaemia should be added to the summary of product characteristics of tramadol.

[Analysis of addictive behaviours among new prisoners in France using the OPPIDUM program]. / Evaluation des conduites addictives chez les personnes entrant en milieu pénitentiaire à partir du programme OPPIDUM du réseau des centres d'évaluation et d'information sur la pharmacodépendance (CEIP).

INTRODUCTION: The data on consumption of psychoactive substances among new prisoners are documented but not detailed with precision. Nevertheless, analyzing the consumption's characteristics of psychoactive products would led to a better caring of subjects at the entry in the prison. The consumption of psychoactive drugs the week before the imprisonments of subjects seen in prison were studied from the Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) program's between 2003 and 2006. These were compared to those of others subjects with an history of abuse/dependence or under an opiate maintenance therapy presented in other structures of care. METHODS: OPPIDUM is an annual cross-sectional national study, repeated each year in October since several years. It is based on the Network of the Centres for Evaluation and Information on Pharmacodependence (CEIP) which recruits, via the medical system (drug users outpatient care centers, psychiatric units, drug-addict units...), subjects presenting a drug dependency or benefiting of an opiate maintenance treatment. RESULTS: During the four years between (2003 to 2006), 13,008 subjects were included. Seven percent (n=893) of them were in prison. They are younger and present worse social-economical indicators compared to the others subjects seen in other structures of care. In comparison to other subjects, the prisoners consume more products, more illicit ones and more benzodiazepines like flunitrazepam and clonazepam before their imprisonment. The medicines are consumed with higher doses and are more often obtained illegally (35% vs 14%). These subjects are less often under an opiate maintenance therapy (51% vs 74%). Between 2003 and 2006 the consumption of cocaine, increased from 18% to 28% for the patients before their confinement and from 11% to 21% for the heroine. Nevertheless, the consumption of benzodiazepines have decreased passing from 41% to 25%; and the consumption and of opiate maintenance treatment taken out of a protocol have decreased from 11% to 4%. DISCUSSION: This study underlines the specificity of the characteristics of consumption of psychotropic drugs before the imprisonment of the subjects with history of abuse/dependence or under an opiate maintenance therapy by report to consumers presented in other structures of care. It outlines the need to optimize the care by a better knowledge of the consumption of psychoactive products.