Claire Le Jeunne

Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virus-infected patient.

Tenofovir is a nucleoside reverse transcription inhibitor used to treat human immunodeficiency virus patients with early treatment failure. Increasing numbers of cases of tubular dysfunction and Fanconi syndrome have been reported in patients treated with tenofovir, after the detection of biochemical abnormalities during routine assessments. Some patients have acute renal failure, and bone involvement is observed in rare cases. We describe a case of chronic metabolic complications with bone fractures related to tenofovir treatment. Several factors that increased the renal toxicity of tenofovir included low body mass index, concomitant use of nonsteroidal anti-inflammatory agents, and other antiretroviral drugs, including ritonavir.

Sarcoidosis Occurring After Lymphoma: Report of 14 Patients and Review of the Literature

AbstractSarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or 18fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or 18FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse.

Molecular analysis of vascular smooth muscle cells from patients with giant cell arteritis: Targeting endothelin-1 receptor to control proliferation ☆

OBJECTIVEnThe pathophysiology of giant cell arteritis (GCA) and the mechanisms underlying vascular remodeling, are poorly understood. We aimed to compare vascular smooth muscle cells (VSMCs) from patients with GCA and controls by a proteomic and gene expression profile approach and to identify the signaling pathways involved in proliferation.nnnMETHODSnVSMCs were cultured from temporal artery biopsies (TABs) from patients with biopsy-proven GCA (TAB+-GCA), biopsy-negative GCA (TAB--GCA), and diagnosis other than GCA (GCA-control). VSMCs from normal human aorta (HAoSMC) were used as controls. 2D-differential in-gel electrophoresis and Affymetrix chips were used to compare proteomes and gene expression profiles of VSMCs. Proliferation was assessed by BrdU incorporation assay. TAB+-GCA and GCA-control TABs underwent immunohistochemistry staining for endothelin-1 (ET-1) and receptors ETAR and ETBR.nnnRESULTSnWe identified 16, 30 and 2 protein spots differentially expressed between TAB+-GCA and GCA-control VSMCs, TAB+-GCA and TAB--GCA VSMCs and TAB--GCA and GCA-control VSMCs, respectively (fold change ≥1.5 and p≤0.05). Among the 153 proteins differentially expressed between TAB+-GCA and HAoSMC VSMCs, many were linked with ET-1. Genes differentially expressed between TAB+-GCA and GCA-control VSMCs were involved in proliferation. ET-1 was identified as a link between genes of interest. Proliferation was reduced for TAB+-GCA VSMCs on treatment with the endothelin antagonist macitentan and its active metabolite. Patients showing transmural expression of ET-1 in temporal artery lesions received a significantly higher glucocorticoid daily dose after 6-month follow-up.nnnCONCLUSIONnInhibiting the proliferation with macitentan, combined with glucocorticoids, might be a promising therapeutic approach for patients with GCA.

Musculoskeletal Symptoms in Patients With Cryopyrin-Associated Periodic Syndromes: A Large Database Study

To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin‐associated periodic syndromes (CAPS).

Granulomatosis with polyangiitis according to geographic origin and ethnicity: clinical-biological presentation and outcome in a French population.

Objectives. Granulomatosis with polyangiitis (GPA) mainly affects white Europeans, but rarely GPA may also affect non-Europeans. This study aimed to describe GPA clinical-biological presentation and outcome in black sub-Saharan Africans and Afro-Caribbeans and in North Africans. Methods. Among 914 GPA patients included in the French Vasculitis Study Group database, geographic origin and ethnicity were known for 760. Clinical-biological presentations and outcomes of white Europeans vs black sub-Saharans and Afro-Caribbeans and vs North Africans were analysed. Results. Among the 760 patients, 689 (91%) were white Europeans, 33 (4.3%) were North Africans and 22 (2.9%) were sub-Saharans (n = 8) or Afro-Caribbeans (French West Indies, n = 14). Black sub-Saharans and Afro-Caribbeans, compared with white Europeans, were significantly younger at GPA diagnosis (P = 0.003), had more frequent central nervous system involvement (P = 0.02), subglottic stenosis (P = 0.002) and pachymeningitis (P = 0.009), and tended to have more frequent chondritis and retroorbital tumour. Median serum creatinine levels and Birmingham Vasculitis Activity Score were significantly lower in sub-Saharans and Afro-Caribbeans (P = 0.002 and P = 0.003, respectively). In contrast, in comparison with white Europeans, North Africans had only less frequent arthralgias (P = 0.004). Time to relapse was shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans [adjusted HR = 1.96 (95% CI: 1.09, 3.51) (P = 0.02)], and did not differ for North Africans. In contrast, overall survival was not significantly different according to ethnicity. Conclusion. Our findings indicated different GPA clinical presentations in white Europeans and sub-Saharans and Afro-Caribbeans, with black patients having more frequent severe granulomatous manifestations. In addition, time to relapse was significantly shorter for black sub-Saharans and Afro-Caribbeans compared with white Europeans.

Pneumococcal and influenza vaccination rates in patients treated with corticosteroids and/or immunosuppressive therapies for systemic autoimmune diseases: A cross-sectional study.

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 23 juin 2016

Feasibility of a nontargeted active opt-in HIV, HBV, and HCV testing in an academic emergency department

HIV screening is recommended by Centers for Disease Control and Prevention (CDC) for all patients between 13 and 64 years of age in all healthcare settings [including emergency departments (EDs)] after the patient is notified that testing will be carried out, unless the patient declines (opt-out screening) [1,2]. In France, anonymous counseling and testing is provided in dedicated sites [Anonymous and Free Testing Centers, called Centres de dépistage anonymes et gratuits, (CDAG)] or by general practitioners. However, around 40% of cases identified are in people with advanced infection, and belong mostly to groups not focused on by the current testing policy [3]. As primary healthcare settings reach 14 million patients annually [4], EDs could be sites for improvement in testing policy. Despite the recommendations of the CDC, it remains unclear how best to approach the identification of undiagnosed HIV infection in the ED from the bare-minimum approach (diagnostic testing) to universal testing as an integrated part of routine health-care services in EDs, regardless of risk or clinical presentation [5,6]. Few data (no data in the European and French emergency system) are available on the feasibility, acceptability, and prevalence of virological screening in EDs; the aims of this study are to assess the spontaneous demand (active opt-in HIV, HBV, and HCV screening) and determine HIV, HBV, and HCV prevalence in an ED.

Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus

BACKGROUNDnDilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear.nnnMETHODSnWe analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies.nnnRESULTSnAmong 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM.nnnCONCLUSIONnNeonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.

Paraneoplasic dermatomyositis sine dermatitis associated with a tumor of the renal excretion system.

To the Editor: Sir, dermatomyositis and cancer association is well established. Dermatomyositis is an inflammatory, complement-mediated microangiopathicdisease thatmay reveal thepresenceof various types of cancer, mainly digestive cancers.We report the first case of dermatomyositis associatedwith a cancer of the excretory system of the kidney in an adult patient. A 77-year-old patient was admitted in our medical department for acute rhabdomyolysis. He was a retired shopkeeper with a reasonable level of fitness for his age (taking daily exercise). He suffered from asthenia, progressing over the previous 2 months, and he experienced the abrupt onset of muscle weakness with myalgia during his daily exercise. An initial evaluation by his general practitioner revealed creatine phosphokinase (CPK) levels of 35 634 IU/L (n < 170 IU/L), alanine aminotransferase (ALT) levels of 388 IU/L (n < 40 IU/L), aspartic aminotransferase (AST) levels of 850 IU/L (n < 40 IU/L), creatinaemia of 132 mmol/L, and a C-reactive protein concentration of 16 mg/L (n < 3 mg/L). He presented bilateral, symmetric muscle loss, with proximal predominance affecting all 4 limbs, and strong myalgia. Skin examination was unremarkable. Electromyogram revealed a myogenic trace for all 4 limbs, the deltoid muscle biopsy showed many pericapillary and perivenular inflammatory infiltrates in the interstitial tissue and signs of microangiopathy in the form of C5b-9 deposits on the endomysial muscle capillaries, signing dermatomyositis. Immunological tests were negative (antinuclear antibodies, soluble antinuclear antigen antibodies, and anti-Jo1 antibodies). Treatment with corticosteroids (intravenous methyl prednisone 1 g/d, 3 consecutive days relayed with prednisone: 1 mg/kg/d) allowed an initial improvement of the motor deficit and the decrease in CPK levels in 4 days. Fifteen days after the start of immunosuppressive therapy, the patient experienced problems in swallowing, with a particular difficulty with liquids, and displayed a marked worsening of muscle weakness in all 4 limbs, requiring readmission to hospital. He also displayed massive muscle wasting, with the loss of 6 kg in one week. Immunosuppressive therapy was intensified with intravenous immunoglobulin infusions (1 g/kg/d, 2 days). A search for neoplasic disease revealed a tumor of the excretory system of the left kidney on CT scan, with adenopathies of the left renal pedicle. Pathological analysis after left nephrourectomy and ganglial curettage concluded urothelial carcinoma displaying extensive malpighian differentiation and vascular and lymph node invasion. A clear clinical improvement was observed immediately after surgery despite incomplete tumoral resection. CPK levels were normal within 7 days. Dermatomyositis is a rare condition characterized by a high frequency of association with solid cancers. Early diagnosis and resection of the cancer are essential to improve the prognosis. Dermatomyositis in our patient was confirmed histologically, based on muscle biopsy and immunological marker. The patient presented no cutaneous signs of dermatomyositis. However, cutaneous lesions may be discreet and may occur later than muscular signs or, exceptionally, may not occur at all (dermatomyositis sine dermatitis). This association is unique, only one previous case has been reported, with no histological confirmation due to the death of the patient.

Les 100 médicaments essentiels. Une approche de médecine interne = 100 essential drugs. An internal medicine approach

PURPOSEnUp to 4600 drugs in about 15,000 pharmaceutical forms are available in France which may be a source of misuse with increased occurrence of side effects and costs. While the World Health Organization is encouraging each developed country to work out its own list of essential drugs. The list provided in 2008 by the French Office for the safety of health products has had so far limited impact on practice, so it became obvious to a group of internists to work out a wise list of 100 essential medicines covering 95% of the disorders observed in France.nnnMETHODSnIn June 2011, 10 internists agreed to each provide a list of 100 essential medicines, according to individual experience. In December 2011, a meeting of the participants provided a list as initial consensus and mandated five among them to make proposals for those areas neglected by too many participants or in which needless dispersion of medicines was stated. After internet-facilitated exchanges, an additional list was validated in mild-January 2012.nnnRESULTSnFifty-four drugs were included in the list of initial consensus (including nine selected by all 10 participants), and 46 in the additional list. So the final wise list included 100xa0drugs. In June 2012, 56 of these drugs were available as generics. This list was compared to those lists set out by five countries in the European Union.nnnCONCLUSIONnGenerating such a list is feasible. Undoubtedly still non-comprehensive, this list will benefit from the expertise of 14xa0general practitioners who are currently working out a similar list across France. The final list will be submitted for validation by the French associations of generalist teachers and Internists.