[Isolated hemorrhagic pleurisy due to Panton-Valentine leukocidin-positive Staphylococcus aureus]. / Pleurésie hémorragique isolée à Staphylococcus aureus à leucocidine de Panton-Valentine.

Panton-Valentine leucocidin is a major virulence factor produced by some strains of Staphylococcus aureus (SA-PVL). The best-described invasive infection is a necrotizing haemorrhagic pneumonia. Pleural effusion is not uncommon but is always associated with a parenchymal lesion. Here, we report a case of haemorrhagic pleurisy attributable to isolated SA-PVL.

[Hemorrhagic syndrome due to a heparin-like anticoagulant in a patient with systemic lupus erythematosus]. / Syndrome hémorragique dû à un anticoagulant héparine-like chez un patient lupique.

INTRODUCTION: In systemic lupus erythematosus, hemostasis disorders are mainly thrombotic, but more rarely hemorrhagic. CASE REPORT: A 25-year-old man presented with a macrophagic activation syndrome revealing a systemic lupus erythematosus, secondarily complicated by a hemorrhagic syndrome ; biological investigations revealed an increase thrombin time and an activated partial thromboplastin time, normalized by protamin neutralization in vitro, thus confirming the presence of a heparin-like anticoagulant. The hemostasis balance normalized after the specific treatment of lupus. CONCLUSION: This rare anomaly of hemostasis balance has been described in blood cancers and solid cancers. This is the first description of a case associated with an autoimmune connective tissue disorder such as lupus. After one year of follow-up, no diagnosis of blood or solid cancer was made.

[Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?] / Prévention de la pré-éclampsie en 2018 en population générale et chez la femme lupique : à l'aube d'une médecine personnalisée ?

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring.

Pregnancy and primary Sjögren's syndrome: management and outcomes in a multicentre retrospective study of 54 pregnancies.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (≤ 37+6 WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 ± 21.57 vs. 60.46 ± 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.

Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA).

PURPOSE: Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. METHODS: Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'étude français des artérites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. RESULTS: The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. CONCLUSIONS: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.

[Pathophysiology of primary Sjögren's syndrome]. / Physiopathologie du syndrome de Gougerot-Sjögren primitif.

Primary Sgögren's syndrome (SSP) is one of the most common connective tissue disorder with an estimated prevalence between 0.6 and 1.7% of the general population. Lymphocytic infiltration of salivary gland is easily accessible favoring the diagnosis, and clinical and fundamental research. However, while many advances have been obtained in the recent decades, the pathophysiology of SSP remains unclear combining environmental factors with genetic predisposition. A central role tends to be attributed to salivary gland epithelial cells, originally designated as "innocent bystanders" and to B cells through the intervention of survey factors like BAFF. New T cells subsets are also carefully studied, particularly natural T regulatory and Th17 cells. They could indeed represent new therapeutic targets.

[Adult-onset Still's disease as a manifestation of malignancy: report of a patient with melanoma and literature review]. / Pseudomaladie de Still et néoplasie : une observation de mélanome et revue de la littérature.

INTRODUCTION: A malignancy must be carefully excluded before ruling in the diagnosis of adult onset Still's disease (AOSD). However, an occult or poorly symptomatic malignancy can easily be overlooked. CASE REPORT: We report a 50-year-old female patient who presented with features of adult onset Still's disease (AOSD), in fact heralding a malignant melanoma with fatal outcome since discovered lately, at a metastatic stage. In retrospect, the only significant atypical feature was cholestatic hepatitis, which soon disappeared upon institution of glucocorticoid treatment. The literature review identified 27 additional cases of AOSD-like disease associated with malignancy published since 1980 including solid cancer in 61% of the cases (especially breast and lung) and haematological malignancies in 39% of the cases (especially malignant lymphoma). The interval between OASD-like symptoms and malignancy averaged 8 months, and AOSD most often preceding malignancy. Although idiopathic AOSD and neoplastic AOSD-like disease are often indistinguishable initially, some features could point toward the latter: an onset of AOSD after the age of 40 years, the presence of atypical clinical, biological, or immunological features in less than one third of the cases, and a poor response to NAIDS or systemic glucocorticoids in 61% of the cases. CONCLUSION: Making the differential diagnosis of malignancy-associated AOSD in a timely fashion remains a primary goal, even in the most typical cases and those showing good initial therapeutic response.

[Pathophysiology of giant cell arteritis]. / Physiopathologie de l'artérite à cellules géantes.

Giant cell arteritis is a large-vessel vasculitis affecting all three layers of the arterial wall. Histopathology of this vasculitis consists of an inflammatory infiltrate with CD4(+) T cells, macrophages, multinucleated giant cells, forming granulomas in the media. This infiltrate is associated with a destruction of the arterial wall, a fragmentation of the internal elastic lamina and a vascular remodeling leading to intimal hyperplasia. Recent studies have clarified the role of Th17 cells in the initial phase of the disease, pro-inflammatory cytokines and vascular smooth muscle cells in vascular remodeling. This review aims to update data on giant cell arteritis pathogenesis and to propose clues of investigation for a better understanding of this condition.

European League Against Rheumatism Sjögren's Syndrome Disease Activity Index and European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index: a complete picture of primary Sjögren's syndrome patients.

OBJECTIVE: The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) and the EULAR SS Patient-Reported Index (ESSPRI) were recently developed. We aimed to determine whether patients' symptoms differed between patients with and without systemic involvement and if the disease-specific indices correlated with each other in primary SS. METHODS: Fifteen French centers included 395 primary SS patients in the Assessment of Systemic Signs and Evolution in Sjögren's Syndrome Cohort. At enrollment, physicians completed the ESSDAI, the SS Disease Activity Index (SSDAI), and the Sjögren's Systemic Clinical Activity Index (SCAI), and patients completed the ESSPRI, the Sicca Symptoms Inventory, and the Profile of Fatigue and Discomfort. All scores were compared between patients with and without systemic involvement. Correlations between scores of systemic activity and patients' symptoms were obtained. RESULTS: At enrollment, 120 (30.4%) patients had never experienced systemic complication and 155 (39.2%) patients and 120 (30.4%) patients had, respectively, only past or current systemic manifestations. Past or current systemic patients had higher levels of symptoms, except dryness. The ESSDAI did not correlate with the patient-scored ESSPRI (rho = 0.06, P = 0.30), whereas the SSDAI and the SCAI, which include subjective items, did correlate (rho = 0.28 and 0.25, respectively; P < 0.0001 for both). CONCLUSION: Alterations of common patient-reported outcomes are present in all patients with primary SS, including those with systemic complications. However, patient symptoms and systemic complications are 2 different facets of primary SS. Therefore, the use of both systemic and patients' indices, such as the ESSDAI and ESSPRI, are useful. Since these 2 facets weakly overlap, one should identify which of both components is the main target of the treatment to test, when designing clinical trials in primary SS.

[Small fibre neuropathy in primary Sjögren syndrome]. / Neuropathie des petites fibres au cours du syndrome de Sjögren primitif.

PURPOSE: About forty percent of the patients with primary Sjögren's syndrome (pSS) experience chronic neuropathic pain with normal electrodiagnostic studies. Two previous studies suggest that chronic neuropathic pain in pSS is due to small fiber neuropathy (SFN). Quantification of epidermal nerve fiber density after skin biopsy has been validated to diagnose small fiber neuropathy. METHODS: Skin biopsy was performed in 14 consecutive pSS patients (satisfying the american-european classification criteria) with chronic neuropathic pain and normal electrodiagnostic studies suggesting SFN. RESULTS: Fourteen female pSS patients exhibited chronic neuropathic pain [burning sensation (n=14), prickling (n=4), dysesthesia (n=8)] with paroxystic exacerbations (n=10) and allodynia (n=13), for a mean period of 18.4±12.4 months. Neuropathic pain involved mostly hands and feet (n=13), with a distal (n=9) and leg (n=4) predominant distribution. Neurological examination disclosed normal deep tendon responses and absence of motor weakness (n=14). Small fiber neuropathy was confirmed by skin biopsy in 13 cases. Epidermal nerve fiber density was decreased in distal [(n=12), mean 3.5±1.7 fibers/mm (N>6.9)] and proximal site of biopsy [(n=9), mean 7.04±2.63 fibers/mm (N>9.3)]. CONCLUSION: Small fiber neuropathy is commonly responsible of chronic neuropathic pain in pSS. Prevalence, physiopathology and neurological evolution of such neuropathies still remain unknown.

Primary Sjogren's syndrome in men.

OBJECTIVE: To determine whether there were any clinical and biological differences between male and female patients with primary Sjogren's syndrome (pSS) in a large bicentric series of patient. METHODS: We studied 419 consecutive patients (mean age at onset 53.6 years, mean disease outcome 73 months) with pSS according to American-European criteria, attending two different Departments of Internal Medicine in France. The 42 (9%) male patients in this cohort comprised the male group described in this study. RESULTS: Extraglandular manifestations during the course of the disease were present in 37 (89%) of our male patients with pSS. The extraglandular manifestations were similar among the two groups except that the male patients showed a lower frequency of depression or asthaenia (5% vs. 20%, p = 0.014) compared with the females. A significantly greater percentage of women reported lymphopaenia (26% vs. 8%, p = 0.02) and leucopaenia (18% vs. 3%, p = 0.015) at onset, but thrombopaenia was more common in the male patients (21% vs. 6%, p = 0.001). Lymphoma development was slightly more common in the male patients, but with no statistical significance (10% vs. 3%, p = 0.06), and occurred earlier after the SS diagnosis (log rank test p = 0.04). CONCLUSION: Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.

Evaluation of at-home phlebotomy for iron overload: feasibility and satisfaction of patients and healthcare workers.

OBJECTIVE: This study aimed to evaluate at-home phlebotomy and the satisfaction of iron-overload patients and healthcare workers with the procedure. METHODS: Forty-two patients underwent at-home phlebotomy between 2003 and 2006. The phlebotomy was performed by the patient's nurse, who was trained by the private healthcare firm that also took charge of the disposal of the blood products. Data concerning these phlebotomies were collected via telephone interviews with all 42 patients, as well as 35 nurses and 40 primary-care physicians. The Limousin Regional Health Observatory processed the data collection. RESULTS: Ninety percent (38/42) of the patients, 80% (28/35) of the nurses and 67% (27/40) of the primary-care physicians responded. For 80% of the patients, phlebotomy volume and frequency were as prescribed. Patients chose home phlebotomy for personal reasons, or because of the limited availability of French Blood Establishment facilities (68%), or in response to being offered it by their hospital physician (32%). For 81.6% of the patients, at-home phlebotomy was more satisfactory than phlebotomy in hospital or at the French Blood Establishment and, for 84%, the constraints required were fully acceptable. The nurses considered that these homecare procedures were within their area of responsibility (100%), but felt that the remuneration was insufficient (65%). Ninety-six percent of the primary-care physicians said they were correctly informed, but only 40% felt that they were truly committed to the procedure. CONCLUSION: At-home phlebotomy is feasible, less costly than institutional phlebotomy and improves patient comfort.

[Abrupt onset of papulovesicular lesions: diagnostic features and outcome]. / Eruptions varioliformes aiguës: aspects diagnostiques et évolutifs.

INTRODUCTION: Abrupt onset of papular lesions, with ulcero necrotic evolution could refers to many dermatitis. Febrile ulceronecrotic Mucha-Habermann disease is an unusual severe form of pityriasis lichenoides and varioliform acuta (PLEVA) characterized with ulceronecrotic eruption potentially associated with high fever and systemic symptoms leading to death. Lymphomatoid papulosis is a recurrent papulonodular eruption with an initial presentation close to PLEVA. While this disorder usually has a benign course, about 10% of the patients develop lymphoproliferative disorders such as CD30+ lymphoma. EXEGESIS: The authors reported an acute form of PLEVA in a young man hospitalized in internal medicine unit with fever and ulcero-necrotic papulo-vesicular lesions. Treatment with tetracycline was successful. They also report a case of lymphomatoïd pustulosis that occurred in a 34 years old woman with an extensive nodulo-pustular eruption characterized by central necrosis and ulceration. Histopathological examination revealed CD30 lymphocytic infiltration leading to diagnosis. CONCLUSION: Theses two dermatosis, uncommon and clinically similar, are both characterized with an unpredictable evolution that to be known by internist.

[Adverse drug related events in a postemergency unit: prospective cohort study with 6 months follow up]. / Iatrogénie chez le sujet âgé de plus de 75 ans dans un service de posturgences. Etude prospective de cohorte avec suivi à six mois.

PURPOSE: To analyse iatrogenic events in elderly people and determine the part of unplanned admission in postemergency units directly related to thus iatrogenic events. METHODS: The authors conducted a prospective chart review on treatments and potentials adverse drug-related events of all elderly consecutively hospitalized between January and Marsh 2003 in a postemergency department. A 6 months prospective evaluation after discharge was made for all elderly with adverse drug-related event. RESULTS: One hundred (and) eighty-six elderly (mean age 83+/-5.7 years) were prospectively included. Eighty-one per cent are ambulatory with a self-medication administration in spite of a real disability (activity of daily-living: 4.5+/-1.8). The number of medications consumed ranged from 0 to 15 and averaged 6, with to different source of prescriptions in 34% of the cases. The treatment was recently modified in 41 cases (22%). Adverse drug related events accounted in 55 cases (29%) and hospitalization was directly related to iatrogenic event in 32 cases (17%). Adverse drug related events could be avoided in half cases. There was no death directly related with adverse drug reactions. Follow up after discharge was obtained in 47 cases and pointed out elderly disability: 34 were again hospitalized, 14 admitted in nursing home facilities and 12 died. Treatment was equivalent to our prescription only in 35% of the cases; on the other hand, we found only four elderly with medication directly related to previous adverse event. DISCUSSION: Theses results pointed out once again polymedication observed in frail elderly people leading to extreme difficulty to prescription due to polypathology. Prescription renewal could be related to adverse drug related events and precipitated elderly people in disability leading to institutionalization.

[Polymyositis induced or associated with lipid-lowering drugs: five cases]. / Polymyosites induites ou associées aux traitements hypolipémiants? A propos de cinq cas.

PURPOSE: Rhabdomyolysis and myositis are rare, dose-related complications of statins and fenofibrates. The outcome is favorable as a rule with rapid regression after stopping the responsible drug. Recently, various auto-immune disease with evidence of hypersensitivity to HMG-CoA reductase inhibitors or fibrates drugs have been reported. Less than ten cases of dermatomyositis and polymyositis due to cholesterol-lowering drugs (CLD) have been previously reported. Five more cases polymyositis associated with CLD are reported. METHODS: Symptoms were compatible with diagnosis of polymyositis according to Bohan and Peter and with previous reported criteria for drug-induced myopathy in all cases. None of these patients had previous other connective tissue disorders. RESULTS: Five patients (median age 68 [54-78], female N =4) with CLD treatment (statin N =4, fenofibrates N =1) have developed iatrogenic polymyositis. All of them presented both proximal muscular weakness and increased muscle enzyme levels. One patient had iatrogenic antisynthetase syndrome characterized by mechanic's hand, Raynaud's phenomenon and anti JO1 antibodies. One other had sclerodermic hand oedema. Antinuclear antibodies were positive in 4 cases and muscle biopsy revealed polymyositis infiltrate in 4 cases. CLD treatment was discontinued with partial clinical improvement in 3 cases. Clinical remission was obtained with corticosteroid (N =5) in association with immunosuppresive agents in 3 cases. CONCLUSION: Muscular symptoms in patient with CLD treatment could be the first symptom of a polymyositis revealed or increased by this treatment and must encourage physician with antinuclear antibodies screening especially in case of proximal muscular weakness and increased muscle enzyme levels.

Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases.

BACKGROUND: Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. OBJECTIVE: To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. METHODS: Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. RESULTS: Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. CONCLUSIONS: Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.