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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.

In systemic lupus erythematosus, hemostasis disorders are mainly thrombotic, but more rarely hemorrhagic.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.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.

Upper digestive symptoms may be present in up to 50% of patients with primary Sjögren syndrome (pSS). We report a retrospective cohort of gastroparesis in a population of pSS presenting unexplained dyspepsia. Delayed gastric emptying was defined by a gastric emptying time above 113min or by a retention percentage at 4h more than 10% on scintigraphy.Eleven patients with primary Sjögren syndrome and gastroparesis were included in a retrospective study. Every patients were women of age 48±18y. The average time of gastric emptying was 725,18±704,45min. 64% of patients had abdominal pain or gastric heaviness. A central or peripheral neurologic involvement was described in respectively 9 and 27% of cases. The diagnostic delay of gastroparesis was higher than 24 months.In primary Sjögren syndrome, gastroparesis should be suspected in case of unexplained dyspepsia, and a scintigraphy performed to prove the diagnosis. A neurologic involvement could explain gastroparesis, but prospective studies are needed for a better understanding of this disorder.

Resume Propos. – La recherche d'anticorps antiphospholipides (aPL) : les anticorps anticardiolipines (aCL) ou un anticoagulant circulant (ACC), est indispensable au diagnostic du syndrome des antiphospholipides (SAPL). Cependant les techniques utilisees pour leur depistage peuvent etre a l'origine de faux-positifs. Methodes. – Nous avons cherche a definir l'influence d'une hypergammaglobulinemie (HG) sur les titres d'anticorps antiphospholipides par l'etude de 232 patients presentant, a au moins deux reprises, des aPL a titre significatif. Resultats. – La population est composee de 93 SAPL dont 76 primaires, ayant presente 138 manifestations thrombotiques et de 139 patients sans SAPL, population composee de 95 maladies auto-immunes, de 28 patients sans pathologie associee et de 16 patients porteurs d'une neoplasie evolutive. En comparant les patients porteurs d'un SAPL aux patients porteurs d'aPL asymptomatiques, notre etude ne montre pas d'influence de l'HG sur la presence d'un anticoagulant circulant ou sur l'index de Rosner. En revanche, les titres d'aCL d'isotype G et M ainsi que ceux des anticorps anti-beta2-GP1 IgM sont significativement augmentes en presence d'une HG dans la population sans SAPL ( p Conclusion. – Si, en pratique clinique, le diagnostic de SAPL repose sur la presence d'anticorps anticardiolipine ou anti-beta2–GP1, il semble donc necessaire de tenir compte de la presence de facteurs interferant avec les techniques Elisa commerciales comme une HG afin d'eviter de porter un tel diagnostic par exces.

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.

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.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.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.

To analyse iatrogenic events in elderly people and determine the part of unplanned admission in postemergency units directly related to thus iatrogenic events.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.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.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.

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.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.Theses two dermatosis, uncommon and clinically similar, are both characterized with an unpredictable evolution that to be known by internist.

Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study.Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C.More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment.Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.

Antiphospholipid antibodies (aPL), anticardiolipin antibodies (aCL) or lupus anticoagulant (LA), are indispensable for the diagnosis of antiphospholipid syndrome (APS). However, antiphospholipid assays can generate false positive results.We have studied the influence of hypergammaglobulinemia (HG) on aPL antibodies titers in 232 patients twice as positive for aPL antibodies.Out of 232 patients, 93 have an APS (76 primary APS, 17 secondary APS). Thrombosis occurred 138 times in APS patients. Of 139 patients without APS, 95 have an auto-immune disease, 28 have an isolated prolonged KCT and 16 an evolutive neoplasia. LA seems to be the best marker of APS. On the other hand aCL IgG and M, anti-beta2-GP1 IgM titers are significantly higher in patients without APS but with HG.Those results suggest that biological APS diagnosis should be carefully performed in patients with HG. In this case, other additional risk factors must be considered for the etiological diagnosis of thrombosis.

To evaluate patient compliance with drug therapy in temporal arteritis and to determine the characteristics of compliant or non-compliant patients.Inpatients and outpatients from an Internal Medicine Unit were interviewed. Compliance with drug dosage and administration time was assessed with a questionnaire for the following drugs: glucocorticoids, calcium, vitamin D, diphosphonates (prevention of glucocorticoid-induced osteoporosis).Forty-nine patients were interviewed (61% female, mean age = 73.7 years). Glucocorticoids were prescribed to 96% of the patients, calcium and vitamin D to 86% and diphosphonates to 49%. Compliance with drug therapy was 87%, 60%, 68% and 51%, respectively, for all treatments. It was independent from the disease duration. Male were more compliant than female (P = 0.012).Half of the patients with temporal arteritis are non-compliant with drug therapy. The questionnaire is simple. It can be used in everyday clinical practice to study and improve patient compliance.

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.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.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.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.

The Cogan's syndrome is characterized by the association of vestibulo-auditory dysfunction, non syphilitic interstitial keratitis or another significant inflammatory eye lesion. Some authors consider this disease as a vasculitis, because it is frequently associated with systemic manifestations. Based on Cogan's diagnostic criteria, Cogan's syndrome may be part of other systemic diseases, as polyarteritis nodosa or Wegener's granulomatosis.We report the case of a patient who presented with a Cogan's syndrome and developed further sarcoidosis.If Cogan's syndrome is characterized as systemic disease because of its association with aortitis or other vasculitis, on the other hand, clinical presentation may be part of many other systemic diseases.

The association of antiphosphatidylethanolamine antibodies (aPE) as the only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed. The aPE was described as the sole antibody in many cases suggesting APS. aPE was not included in the Sapporo criteria for the classification of APS.We investigated the clinical features of 20 patients with aPE only; 17 patients had symptoms potentially related to APS (group 1) and three had other manifestations (group 2).There were 15 women and five men, mean age was 35 +/- 12 years at the beginning. In group 1 (n = 17), ten patients presented arterial thrombosis, nine venous thrombosis (five had both), and six microvascular thrombosis (livedo reticularis, lacunar pathology). The aPE positivity was persistent in 13 patients. A subgroup of four patients (three women) presented arteriosclerosis with peripheral arteriopathy which started before 45 years of age. They had another atherosclerosis risk factor associated with aPE persistence. In group 2 (n = 3), there was no thrombotic event, one demyelinating pathology, one microvascular pathology, and one arterial dysplasia. The aPE positivity was never confirmed. Finally, 13 patients presented an APS with aPE only, confirmed at least 8 weeks later.Our study points out that testing for aPE would be of interest for patients when symptoms were potentially related to APS, particularly when other antiphospholipid antibodies were negative. This description questions the enlargement of the APS biological criteria defined in Sapporo. The role of aPE in atherosclerosis is considered.

Antisynthetase syndrome (AS) is frequently revealed by interstitial lung disease and arthritis. There are mechanic's hand, Raynaud's phenomenon and anti aminoacyl t-RNA synthetase antibodies. The anti JO-1 antibody is the most frequently identified. We report five cases of antisynthetase syndrome with particular clinical features and good response to corticosteroids.There are three women and two men with a median age of 59 years at presentation (range: 44-77). Three patients progressively developed AS: the symptoms are dyspnea (three). Raynaud's phenomenon (one), purpura (one) and hyperkeratosis, scaling and fissuring on the lateral sides of the fingers (two). Patients always had skin signs: hyperkeratosis and scaling (five), purpura (one), Raynaud's phenomenon with normal capillaroscopy (two). Lung disease is present in the five cases with interstitial lesions in CT scans (five), trouble of CO diffusion (three/three) and lymphocytic alveolitis (two/two). Moderate muscular disorders are present in five cases (moderate elevated muscular enzyme: five, positive muscle histology: two). Anti-JO-1 antibodies are present in five cases. AS is associated with connective tissue diseases: rheumatoid polyarthritis in one case and Gougerot-Sjögren in three cases. No malignant tumour is associated. Patients have received oral corticosteroid treatment (five/five) with high doses of intravenous perfusions (three/five) with, initially, a good response. For only one patient, immunosuppressive treatment was necessary because of the articular relapse. The interstitial lung disease had a good response to corticosteroids therapy alone in four cases. Because of the relapse during the tapering off of corticosteroids, corticosteroids were increased in one case and immunosuppressive therapy was required in one case.The prognosis of AS depends of the interstitial lung disease. High doses of corticosteroids are required. In our study, the response to corticosteroids is good. Immunosuppressive agents must be added in severe and progressive form of interstitial lung disease in AS.

Henoch-Schoenlein purpura has been reported to be associated with parvovirus B19 infection, particularly in children and rarely in adults. We report the case of a 42-year-old patient presenting with this association.A 42-year-old patient was admitted to our medical center because of lower limb purpura. Henoch-Schoenlein purpura diagnosis was confirmed on histological findings (kidney biopsy) and concomitantly parvovirus B19 infection was proved by serological test (IgM+). Association of Henoch-Schoenlein purpura and parvovirus B19 infection has already been described. However, none of the reported studies demonstrated clearly the link between these two diseases. With regard to this observation, we wonder about the systematic use of the parvovirus B19 serological test in patients presenting first Henoch-Schoenlein purpura. Indeed, parvovirus B19-induced vasculitis is habitually controlled with intravenous immunoglobulins.A prospective study should explore the link between Henoch-Schoenlein purpura and primary parvovirus B19 infection. Moreover, we should evaluate intravenous immunoglobulins' efficacy in Henoch-Schoenlein purpura associated with active parvovirus B19 infection in order to improve the prognosis of this disease.

To better individualize drug hypersensitivity reaction, Bocquet et al. have recently called this adverse drug reaction DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).We report two cases of DRESS and highlight the main characteristics of this syndrome. Two patients presented severe febrile skin eruption following drug intake (carbamazepine or sulfazalazine), with hypereosinophilia and hepatitis. All symptoms resolved after drug withdrawal and corticosteroid therapy. DRESS syndrome is an idiosyncratic reaction characterised by febrile eruption, occurring 2 to 6 weeks after the beginning of the treatment, accompanied by systemic symptoms and biological abnormalities (hypereosinophilia, hepatitis). Some complications can occur. This syndrome can be fatal. Numerous drugs can be responsible for this reaction to medication. The physiopathology has not yet been elucidated, and the treatment is not codified, but the triggering agent must immediately be stopped. Corticotherapy is sometimes used.It is important to recognize this entity recently named DRESS syndrome because it can mimic other pathologies, is potentially serious, and because withdrawal of the incriminating drug is imperative.

To determine aged-related variations in clinical and biological presentation and outcome in Wegener's granulomatosis.In a retrospective cohort study of 35 patients with a diagnosis of Wegener's granulomatosis, 24 patients (69%) younger than 60 years of age and 11 (31%) aged 60 years or older were compared for clinical and biological characteristics.Clinical presentation was the same in the two groups; lymphopenia was more common in the elderly group (P0.05). Despite a similar treatment regime, outcome was significantly worse for the elderly group (or = 60 years), with a mortality rate of 36% versus 8% in the control group. Mortality was essentially due to delayed infectious complications, raising the problem of a less intensive immunosuppressive treatment after remission.

In case of unexplained weight loss, chest X-ray, abdominal ultrasonography and gastroscopy are usually recommended. However, gastroscopy is not usually performed in elderly patients.We evaluated 77 patients (mean age: 80 +/- 8 years) hospitalized in our geriatric unit between January 1995 and May 1997 for unexplained weight loss. All patients underwent chest X-ray, abdominal ultrasonography and gastroscopy.These investigations led to diagnosis in respectively 17, 15 and 46 patients. The etiology of weight loss was unique in 47 patients, while in 30 other patients at least two or three causes could be described. Gastroscopy appeared to be the most useful test, as it allowed description of eight cases of cancer, 29 cases of peptic ulcer, two cases of candidosis, and one case of actinomycosis in patients who did not present any clinical sign.Sixty-five patients were followed-up for a mean period of 13 +/- 21 month; 33 patients died. The condition of 23 patients improved either slightly or definitely. Simple investigations led to diagnosis in 95% of the cases. However, 42% of the patients died within 3 months. Gastroscopy appears to be the most valuable test, leading to diagnosis in more than half of the cases. With adapted treatment, the condition of 75% of the patients with gastro-intestinal lesions improved.

The incidence of tuberculosis is increasing, particularly in the elderly, and has various clinical presentations.We describe the case of a 78-year-old woman who presented tuberculous pleuropericarditis. This case is atypical, due to infection localisation, negativity of the tuberculin skin test, and mixed pleural effusion. Following antituberculosis antibiotic therapy and corticotherapy, the outcome was favorable.Due to atypical and non-specific clinical presentation, diagnosis of tuberculosis may be particularly difficult in the elderly.

In a 43-year old male suffering from idiopathic hypereosinophilic syndrome (HES) since 1984, successfully treated with alpha interferon (alpha IFN) for 32 months, a severe Raynaud's phenomenon of the four extremities occurred and eventually evolved into digital necrosis within a few weeks. The arterial echography/doppler and plethysmography patterns were suggestive of isolated small-to medium-size digital artery occlusions. An extensive search for an aetiology of digital necrosis, including complete tests of autoimmunity, remained negative. Two months later, despite alpha IFN withdrawal and intravenous infusions of ilomedin, the digital ischemia evolved to extensive necrosis that necessitated several amputations and a definitive spinal chord stimulation. Pathologic examination of arteries showed no vasculitis but diffuse arterial occlusions by thrombi.