[Diagnosis and treatment of iron overload]. / Diagnostic et traitement d'une surcharge en fer.

Etiological investigation of hyperferritinemia includes a full clinical examination, with the measurement of waist circumference, and simple biological tests including transferrin saturation. The classification between hyperferritinemia without iron overload (inflammation, excessive alcohol intake, cytolysis, L-ferritin mutation) or with iron overload is then relatively easy. Dysmetabolic iron overload syndrome is the most common iron overload disease and is defined by an unexplained serum ferritin level elevation associated with various metabolic syndrome criteria and mild hepatic iron content increase assessed by magnetic resonance imaging. Bloodlettings are often poorly tolerated without clear benefit. Type 1 genetic hemochromatosis (homozygous C282Y mutation on the HFE gene) leads to iron accumulation through an increase of dietary iron absorption due to hypohepcidinemia. More than 95% of hemochromatosis are type 1 hemochromatosis but the phenotypic expression is highly variable. Elastography is recommended to identify advanced hepatic fibrosis when serum ferritin exceeds 1000µg/L. Life expectancy is normal when bloodlettings are started early. Ferroportin gene mutation is an autosomal dominant disease with generally moderate iron overload. Chelators are used in iron overload associated with anaemia (myelodysplastic syndromes or transfusion-dependent thalassemia). Chelation is initiated when hepatic iron content exceeds 120µmol/g. Deferasirox is often used as first-line therapy, but deferiprone may be of interest despite haematological toxicity (neutropenia). Deferoxamine (parenteral route) is the treatment of choice for severe iron overload or emergency conditions.

Direct oral anticoagulants: an alternative treatment for thrombotic antiphospholipid syndrome?

Background Direct oral anticoagulants (DOACs) demonstrate a lower risk-benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29-40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.

[Natural history of portal cavernoma without liver disease. A single centre retrospective study of 32 cases]. / Évolution naturelle des cavernomes portaux non liés à une hépatopathie. Étude rétrospective monocentrique de 32 observations.

PURPOSE: Portal cavernoma follows a chronic occlusion of the portal vein. The long-term consequences of portal cavernoma are not well known. The objective of this study was to report the aetiology of the portal cavernoma and its natural course after excluding liver diseases causes. METHODOLOGY: A single centre retrospective study based on the data collected from the radiology department of the Clermont-Ferrand hospital was conducted from 2000 to 2011. All the patients for whom an imagery found a portal cavernoma have been looked for excluding the patients having a liver disease whatever the aetiology and the Budd-Chiari syndrome. RESULTS: Thirty-two cases (18 women and 14 men) were selected. The mean age at diagnosis was 54.2 years and the mean follow-up period was 5.4 years. The discovery of a portal cavernoma was incidental for 8 cases. An aetiology was found for 24 cases: it was an haematological aetiology in 15 cases (10 myeloproliferative syndromes, 2 antiphospholid syndromes, 1 thalassemia major, 1 hyperhomocysteinemia, 1 prothrombin gene mutation), a general aetiology in 2 cases (1 coeliac disease, 1 pancreatic neoplasia), and a local inflammation in 7 cases. A dysmorphic aspect of the liver was noticed on medical imaging for 11 out of the 32 cases. A liver biopsy was performed in 4 patients and was normal for all of them. Sixteen patients developed oesophageal varices, 4 patients developed ascites, 3 developed asymptomatic biliary compression by the portal cavernoma, and the patient who had been followed for the longest time (15 years) developed an encephalopathy. CONCLUSION: In addition to its underlying etiology, the prognosis of portal is mainly related to the occurrence of oesophageal varices that may develop during the follow-up of the patients.

[Anticoagulation and peripartum management]. / Influence des anticoagulants sur la prise en charge péri-partum.

OBJECTIVE: To compare peripartum management of anticoagulated patients concerning locoregional analgesia, post-partum hemorrhage and thrombotic events according to planified interruption or not of antithrombotic therapy. PATIENTS AND METHODS: We conducted a single tertiary care center retrospective study of all deliveries associated with antithrombotic therapy from January 2005 to September 2011. RESULTS: We identified 120 cases with prophylactic (71%) or curative (29%) anticoagulation. Two thrombotic events occurred. In case of curative therapy, the use of locoregional analgesia was lower (P<0.0001) and post-partum hemorrhage occurred more frequently (P=0.07) compared to prophylactic therapy. According to planified interruption or not of antithrombotic therapy, we observed a more prolonged duration of therapeutic interruption before delivery (55.6h±63.3 vs 26.4 h±11.6, P<0.0001), higher use of locoregional analgesia (83% vs 71%, P=0.02) but no difference concerning cesarean rate (35% vs 39%, P=0.8) or post-partum hemorrhage (13% vs 14%, P=0.9). CONCLUSION: In case of curative anticoagulation, plannified interruption favours the use of perimedullar analgesia after 24hour delay. In case of preventive anticoagulation, plannified interruption appears unnecessary as the 12hour delay is easier to reach.

[Antenatal management for patients with increased risk of post-partum hemorrhage (excluding abnormal placentation)]. / Prise en charge anténatale des patientes à risque d'hémorragie du post-partum (hors anomalies de l'insertion placentaire).

OBJECTIVES: To describe management and screening for high-risk patients concerning post-partum hemorrhage (PPH) and antenatal management for severe anemia, thrombopenia, bleeding disorders and anticoagulant therapy. METHODS: Bibliographic search restricted to French and English languages using Medline database and recommendations of medical societies. RESULTS: The appropriate place for delivery should be chosen after multidisciplinary concertation based on level of risk (especially past-history of severe PPH and bleeding disorder) and easy access to blood products (Professional Consensus). Prevention for severe anemia is mainly based on oral iron supplementation (grade B). Explorations are required in case of thrombopenia<100Giga/L (grade C). Patients with bleeding disorder require the assistance of a physician skilled in hemostasis for perinatal management (grade C). Preventive anticoagulant therapy has no impact on PPH risk and perimedullar analgesia is usually authorized 12hours after last injection (grade C). Curative anticoagulant therapy slightly increases PPH risk and perimedullar analgesia is authorized only after 24hours since last injection (Professional Consensus). CONCLUSION: Prenatal identification of high-risk patients concerning PPH implies multidisciplinary concertation to determine the most appropriate birthplace where technical and human resources are available.

[Screening for chronic obstructive pulmonary disease by electronic mini-spirometry in general practice]. / Dépistage de la broncho-pneumopathie chronique obstructive par minispirométrie électronique en médecine générale.

INTRODUCTION: Screening for COPD is currently considered to be insufficient. Electronic mini-spirometers allow screening for COPD in general practice. OBJECTIVES: To assess the prevalence of COPD in a population of at-risk patients in general practice (GP) and to identify the high-risk factors for the disease. METHODS: A cross-sectional study was performed in a GP setting. Patients aged between 40 and 75years with a history of smoking, occupational exposure to toxic substances or chronic respiratory symptoms were offered airflow assessments by electronic mini-spirometry. For any value of FEV1/FEV6 less than 70 %, screening for COPD was considered as positive. RESULTS: Of the 778 patients seen during routine consultations, 273 (35.1 %) fulfilled the inclusion criteria. The test was positive in 128 of the eligible patients (46.9 %). The prevalence of proven COPD (ratio<70 %) was 13.9 % (38 patients). The high-risk factors were age over 60years (P=0.03), body mass index over 28 (P=0.04), smoking history of more than 30pack-years (P<0.0001), presence of clinical signs (P<0.0001) and industrial exposure to toxic substances (P=0.03). CONCLUSIONS: Targeted screening of patients with risk factors for COPD can be performed in a GP setting. An electronic mini-spirometer is a reliable and inexpensive screening tool.

[Iron chelating therapy in adults: How and when ?]. / Les chélateurs du fer : quand et comment les utiliser chez l'adulte ?

Iron overload can lead to tissue damage derived from free radical toxicity. Phlebotomy is the treatment of choice for treating iron overload. However, iron chelating therapy can be used if phlebotomies are impossible, mainly because of anemia. In thalassemia major, iron chelating therapy has dramatically improved life expectancy; it is also used in sickle cell disease and myelodysplastic syndromes. Desferioxamine is the gold standard of iron chelation, but parenteral administration and the burden of a daily infusion pump hinder optimal compliance. Deferiprone is orally active but should be administered three times a day. It has the advantage of removing toxic iron from myocardium, but agranulocytosis (1 %) can limit its use. Deferasirox is orally active in a single daily dose, is well tolerated but its cardiac effect is limited. Iron chelating therapy can be considered if serum ferritin is above 1000µg/L and if liver iron concentration assessing by MRI exceeds 80µmol/g. MRI is a very important mean to monitor cardiac iron load. If the relaxing parameter T2* is lower than 20ms, a cardiac effective iron chelator agent or an association with deferoxamine should be used. Benefit/risk ratio should be closely evaluated, mainly in myelodysplastic syndromes.

[Nasosinusal and cervical sarcoidosis: a case series of three patients and literature review]. / Sarcoïdose nasosinusienne et cervicale traitée par infliximab : trois observations et revue de la littérature.

INTRODUCTION: Sinonasal sarcoidosis is difficult to treat. Infliximab seems to be useful in the treatment of sarcoidosis of the upper respiratory tract. CASE SERIES: We report three cases of sinonasal sarcoidosis in two women of 36 and 42-year-old and in a 64-year-old man. Resistance or dependence to corticosteroids and absence of efficacy of methotrexate therapy in one patient led to administer anti-TNFα therapy with infliximab. Outcome was favourable on sarcoid lesions but treatment was discontinued because of infectious complications and worsening of sarcoid chest involvement. CONCLUSION: This case series suggests that infliximab might be useful for the treatment of sarcoidosis with sinonasal involvement.

Systematic screening for occult cancer in elderly patients with venous thromboembolism: a prospective study.

BACKGROUND: Cancer is an established risk factor for venous thromboembolism (VTE) and the incidence of cancer increases in the elderly. The benefit of screening for occult cancers in this population is still not clear. AIM: To evaluate a systematic screening programme for cancer in elderly patients with VTE. METHODS: This was a prospective study with a 12-month follow-up period. It was conducted in a single centre in consecutive patients over the age of 70 years who had a confirmed diagnosis of VTE. Predefined non-invasive screening techniques for cancer with clinical, laboratory (including tumour markers) and radiological investigations (abdominal ultrasound, chest X-ray and a thoraco-abdominopelvic computed tomography scan) were evaluated. RESULTS: Fifty patients with a median age of 80 years (range: 70 to 94 years) were included. One patient was diagnosed with chronic lymphocytic leukaemia at inclusion and cancers were found in three other patients during the follow-up period (rectosigmoid adenocarcinoma with hepatic metastases, hepatocellular carcinoma and gastric adenocarcinoma). Only one of the four cancers could have been treated at an earlier stage. The mortality rate of the entire cohort after 12 months was 28%. Two patients died as a direct consequence of cancer. DISCUSSION: In this study of elderly patients, a non-invasive screening strategy did not detect several cancers that were subsequently overt clinically. A full history, clinical examination and routine laboratory investigations might be the optimal first-line strategy to detect cancer after the diagnosis of VTE in elderly patients, but regular clinical examinations during follow up are warranted.

[Type 2 diabetes and universal health care for low-income groups: a case-control study]. / Diabète de type 2 et précarité : une étude cas-témoins.

PURPOSE: In 2007 in France, type 2 diabetes involved 2.5 million people, and 4.5 million patients received free healthcare coverage under the universal healthcare coverage program (CMU) for low-income households. An optimal glycemic control and adequate diabetes monitoring can reduce the incidence of complications. The objective of this study was to compare the diabetes care of low-income patients (as defined by CMU coverage) with the rest of the population. METHODS: A retrospective case-control study (non-CMU and CMU) over a one-year period of glycemic control for both populations through private laboratory data (number and values of HbA1c) and of individuals monitoring through data from the regional health insurance public institute. RESULTS: Regarding glycemic control, 154 patients were included. The number of annual HbA1c tests was similar between CMU and non-CMU patients. The mean HbA1c value was higher for CMU patients (8.7% versus 8%; P<0.01). Regarding monitoring, 1254 patients were included. Over a one-year period, the number of HbA1c tests, lipid profile tests, serum creatinine measures and cardiology consultations were similar across groups. However, CMU patients benefited from less microalbuminuria testing (P<0.001), ophthalmologic monitoring visits (P<0.01), endocrinology consultations (P<0.01), and from more general physician consultations (P<0.001). CONCLUSIONS: Receiving CMU health coverage was associated with a poorer glycemic control and lesser specialized monitoring than that was observed in control patients. Across the population, follow-up recommendations are far from being implemented satisfactorily.

Rituximab-induced serum sickness in refractory immune thrombocytopenic purpura.

Serum sickness may occur in patients treated with chimeric monoclonal antibody. Rituximab, an anti-CD20 chimeric monoclonal antibody, is used with increasing frequency in chronic immune thrombocytopenic purpura (ITP). Rituximab is relatively safe; however, serum sickness is reported in 1-20% of patients, more commonly among those with autoimmune conditions. We describe a case of serum sickness in a patient with ITP and review the literature of rituximab-induced serum sickness.

[Abdominal manifestations of Henoch-Schönlein purpura in adults. A retrospective study of 23 cases]. / Atteintes digestives du purpura rhumatoïde de l'adulte. Etude d'une série rétrospective de 23 patients.

INTRODUCTION: Gastrointestinal manifestations of Henoch-Schönlein purpura (HSP) in adults may be severe. Data about treatment are controversial and the outcome is seldom described. METHODS: Twenty-three patients with gastrointestinal manifestations of HSP (ACR criteria) were retrospectively studied. We proposed to use clinical and radiological (CT scan) severity scores to assess the usefulness and the efficacy of corticosteroid therapy. RESULTS: Age at onset ranged from 16 to 80 years (median 39). Gastrointestinal manifestations included abdominal pain (96%), vomiting (52%), gastrointestinal bleeding (39%), diarrhoea (13%) and intestinal obstruction (9%). Scores of disease clinical severity were calculated in 21 patients. Fourteen, three and four had severe, intermediate and mild disease, respectively. Ten patients in the group with severe clinical involvement underwent CT scan that showed severe radiological involvement (parietal thickening of several bowel loops of the same segment or several segments with ileal involvement). Eleven patients out of 14 with clinically severe disease were given corticosteroids. Two patients out of three with intermediate and three patients out of four with mild scores also received corticosteroids. The others received supportive care. In-patients with severe clinical scores, gastrointestinal symptoms improved within 2 days when they were given corticosteroids and within 12.3 days without corticosteroids (p<0.0002). No side effect was observed with steroid therapy. CONCLUSION: These results suggest that corticosteroids may reduce abdominal symptoms of HSP in adults with clinically severe disease. They are safe when CT scan is performed.

[Genetic iron overloads and hepatic insulin-resistance iron overload syndrome: an update]. / Surcharges en fer d'origine génétique et hépatosidérose dysmétabolique.

Hepcidin inhibits intestinal absorption of iron through internalisation of ferroportin. Its discovery helps to better understand the genetic iron overloads. The insulin resistance-hepatic iron overload (IR-HIO)--also coined as the dysmetabolic iron overload syndrome--is a common cause or iron overload. This article is a review about genetic iron overloads and IR-HIO. Type 1 haemochromatosis C282Y +/+ accounts for 95% of the haemochromatosis. Hepatic fibrosis may develop if serum ferritin is higher than 1000 microg/l but can be partially reversible with phlebotomies. Juvenile haemochromatosis (type 2) and type 3 haemochromatosis (mutation of the transferrin receptor 2) are very uncommon. Several mutations of the ferroportin gene can cause usually mild iron overload of autosomal dominant inheritance. Aceruleoplasminemia is an uncommon disorder involving cerebral iron overload. The causes and consequences of the IR-HIO are unknown. Treatment of IR-HIO is focused on metabolic syndrome and phlebotomies are questionable because the overload is moderate and intestinal absorption of iron seems to be low. MRI (or other non invasive methods) is needed to truly assess iron overload because serum ferritin overestimates it in metabolic syndrome. Several points have to be elucidated: how HFE interferes with hepcidin in type 1 haemochromatosis; the causes of variability of iron overload; the benefits of populations screening; the advantage of phlebotomies in IR-HIO; the use of new oral iron chelators.

[Nodular thrombophlebitis and granulomatous systemic disease]. / Thrombophlébites nodulaires et maladies systémiques granulomateuses.

INTRODUCTION: Nodular thrombophlebitis is septal hypodermitis characterised by vasculitis with vein thrombosis. It may indicate serious underlying disorders. EXEGESIS: We present two cases of nodular superficial phlebitis, which revealed tuberculosis and sarcoidosis. CONCLUSION: Nodular thrombophlebitis are classic during evolution of Behçet disease or Buerger vasculitis. In sarcoidosis, erythema nodosum and granulomatous involvement are the most common cutaneous manifestation. Nodular thrombophlebitis has never been described. Panniculitis are classical in tuberculosis. But most cases are erythema nodosum and cases of erythema induratum of Bazin. Nodular thrombophlebitis could reveal thrombophilic abnormalities, and even more neoplasms especially when they are recurrent and migratory.

Treatment of isolated severe immune hemolytic anaemia associated with systemic lupus erythematosus: 26 cases.

The aim of this study was to evaluate the response to treatment and the long-term outcome in a cohort of patients in whom severe autoimmune hemolytic anaemia (AHA) was the leading manifestation of systemic lupus erythematosus (SLE). Twenty-six women with severe isolated AHA were included. Corticosteroids were used as the initial treatment for all patients in our study. An initial response was obtained in all but one patient (96%). The overall recurrence rate was three per 100 person-years, with an expected recurrence-free proportion of 73% with a 180 months median follow-up. Seven patients (27%) experienced a relapse of AHA. We found a higher proportion of pleuritis in relapsing patients. Only three patients experienced multiple relapses despite splenectomy and several immunosuppressants. Steroid-sparing effect of hydroxychloroquine and azathioprine could not be assessed because most of the patients received these treatments for other reasons than AHA. Intravenous immunoglobulins induced transient response in three cases. Splenectomy was efficient to definitively control AHA in one patient but two patients quickly experienced relapses while one patient did not benefit. Five patients received immunosuppressants that induced only transient responses. Rituximab was long-term efficient in one case. In conclusion, severe AHA is a serious complication of SLE that warrants appropriate management. On the basis of our experience, the ideal treatment of isolated AHA should be oral corticosteroids in first-line treatment. Our study does not support an important role for splenectomy. Patients refractory to conventional therapy should be treated either with few toxic immunosuppressive drugs, danazol or rituximab.

Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study.

OBJECTIVES: This work aims at studying the effect of daily versus twice weekly long-term Fe supplementation on Fe absorption and status in Fe-deficient women. DESIGN AND METHODS: The study design is a randomized controlled open study carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France. Twenty-four young women participated in this study and were randomized into two groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation, blood samples were obtained, and women received orally about 5 mg of 57Fe, and blood was sampled at different times over 24 h. The 57Fe absorption was evaluated by calculating the areas under the curves (AUC). Fe and oxidative stress status were also assessed. RESULTS: 57Fe absorption was similar in both groups on D10 but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe status was more improved in Group 1 than in Group 2. Oxidative stress status remained statistically unchanged. CONCLUSIONS: Our study shows that daily Fe supplementation is able to correct an Fe deficiency much more than twice weekly Fe supplementation in young women.

[Infections associated to severe thrombotic events and antiphospholipid antibodies]. / Infections associées à des évènements thrombotiques sévères avec présence d'anticorps antiphospholipides.

The authors present 2 cases of infections in which the presence of antiphospholipid antibodies (APL), anticardiolipin and anti-beta2-GP1, was associated to the occurrence of significant thrombotic events: 1) a 55-year-old male patient whose serology (indirect immunofluorescence) revealed Coxiella burnetii infection (phase 2 antigens) with IgG at 1,600 and IgM at 50 (significant titer: IgG>or=200 and IgM>or=50); 2) and a 20-year-old male patient with a CMV infection confirmed by serology (IgG: 44 U/ml, significant threshold 6, IgM: 2.1 U/ml, significant threshold 0.9).