Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study.

OBJECTIVE: To analyse the efficacy and tolerance of infliximab in refractory Takayasu arteritis (TA). METHODS: French multicentre retrospective study that included patients with TA. Clinical disease activity was defined as new vascular and/or constitutional signs. RESULTS: Fifteen patients with TA [median age 41 (range 17-61) years; 13 women] were included. At initiation of infliximab therapy, 14 patients were treated with CSs [prednisone; median dose 20 (range 5-35) mg/day], MTX (n = 7) or AZA (n = 4). Infliximab was used at median 5 (range 3-5) mg/kg at a median of every 6 (range 4-8) weeks. A partial or good overall response was noted in 13 (87%) of the 15 cases, 10 (77%) of the 13 cases and 8 (73%) of the 11 cases at 3, 6 and 12 months, respectively. Clinical and biological activities significantly decreased within 3 months (from 11 at baseline to 4 patients at 12 months; P < 0.05), and similarly for CS dose [from median 20 (range 5-35) mg/day at baseline to median 6 (range 2.5-30) mg/day at 12 months; P < 0.05]. Only one patient was still steroid-dependent at 12 months (vs 8 cases before infliximab). CRP regressed from a median 30 (range 4-70) mg/l to 5 (range 0-57) mg/l and 6 (0-50) mg/l at 3 and 6 months, respectively (P < 0.05). Side effects were two infusion-related reactions, one pulmonary tuberculosis, one severe bacterial infection and EBV reactivation. CONCLUSION: This study confirms the interest of infliximab in terms of clinical and biological response, as well as the steroid-sparing effect in TA.

Update on oral cyanocobalamin (vitamin B12) treatment in elderly patients.

The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Prospective randomized studies (n=3), a systematic review by the Cochrane group (n=1) and prospective studies in a well defined population (n=5) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature does not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment. This review confirms the previously reported efficacy of oral cobalamin treatment in elderly patients. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections.

Parvovirus B19 infection as a cause of cytopenia with a lupus-like presentation in the elderly: A case report.

Most cases of parvovirus B19 infection are asymptomatic and occur in childhood; half of all 15-year-old adolescents have specific anti-parvovirus B19 antibodies. Here, we report a rare case of parvovirus B19 primary infection, rare due to (1) its occurrence in a geriatric patient (an 82-year-old woman), (2) its lupus-like presentation, and (3) its potential role in precipitating congestive heart failure.

Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy.

The aim of this work was to review the literature concerning cobalamin deficiency in elderly patients. Articles were identified through searches of PubMed-MEDLINE (January 1990 to June 2006), restricted to: English and French language, human subjects, elderly patients (>65 years), clinical trial, review and guidelines. Additional unpublished data from our cohort with cobalamin deficiency at the University Hospital of Strasbourg, France, were also considered. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. The recently identified food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or from its binding proteins. This syndrome is usually the consequence of atrophic gastritis, related or not to Helicobacter pylori infection, and of the long-term ingestion of antacids and biguanides (in around 60% of the patients). Management of cobalamin deficiency has been well established with the use of cobalamin injections. However, new routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption.

Idiosyncratic drug-induced agranulocytosis: Update of an old disorder.

In this paper, we review the literature on idiosyncratic drug-induced agranulocytosis, a rare but life-threatening potential adverse event of most drugs. Articles were identified through MEDLINE searches (1966-2005). Additional references were localized through a review of textbooks on hematology and internal medicine, and information gleaned from international meetings. Additional unpublished data from our cohort with drug-induced agranulocytosis at the University Hospital of Strasbourg, France, were also considered. Searches were done using the following key words: "agranulocytosis", "drug-induced agranulocytosis", and "idiosyncratic agranulocytosis" and were restricted to: English- and French-language, human subjects, clinical trial, review, and guidelines. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. What we found is that, over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis has remained stable - 2.4-15.4 cases per million - despite the emergence of new causative drugs, mainly antibiotics, antiplatelet agents, and antithyroid drugs. To date, drug-induced agranulocytosis remains a serious adverse event due to the frequency of severe sepsis with severe deep infections (such as pneumonia), septicemia, and septic shock in about two-thirds of all patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count below 0.1x10(9)/L are poor prognostic factors. Nevertheless, with appropriate management using pre-established procedures, with intravenous broad-spectrum antibiotic therapy, and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, health care professionals should be aware of this adverse event and its management.

Immunoglobulin deficiency in patients with Streptococcus pneumoniae or Haemophilus influenzae invasive infections.

OBJECTIVES: Immunoglobulin (Ig) deficiency is a well-known risk factor for Streptococcus pneumoniae or Haemophilus influenzae infections and noteworthy invasive diseases. However, the proportion of these deficiencies in cases of invasive disease is unknown. The objective of this study was to evaluate the rate of Ig deficiency in cases of invasive disease. METHODS: A prospective study was conducted from January 2008 to October 2010 in two French hospitals. Measurement of Ig levels was carried out in patients hospitalized for invasive diseases. RESULTS: A total of 119 patients were enrolled in the study, with nine cases of H. influenzae and 110 cases of S. pneumoniae invasive disease. There were 18 cases of meningitis, 79 of invasive pneumonia, and 22 other invasive diseases. Forty-five patients (37.8%) had an Ig abnormality, 37 of whom had an Ig deficiency (20 IgG <6g/l, four isolated IgA <0.7g/l, and 13 isolated IgM <0.5g/l), while eight had an elevated monoclonal paraprotein. Nineteen of these 45 patients had a clearly defined Ig abnormality, with five primary deficiencies (three common variable immunodeficiencies and two complete IgA deficiencies) and 14 secondary deficiencies, mainly lymphoproliferative disorders. All these deficiencies were either not known or not substituted. CONCLUSIONS: Humoral deficiency is frequent in patients with S. pneumoniae or H. influenzae invasive disease and Ig dosage should be proposed systematically after such infections.

Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009-2013 French PharmacoVigilance assessment.

BACKGROUND: Romiplostim and eltrombopag, the two marketed thrombopoietin receptor agonists (TPO-RAs), have distinct binding sites and might have distinct pharmacodynamic mechanisms. The aim of this study was to compare their adverse drug reaction (ADR) patterns. METHODS: We selected in the French PharmacoVigilance Database all ADRs associated with TPO-RAs from TPO-RA marketing until the 31st of December 2013. Medical charts were reviewed. We conducted disproportionality analyses comparing romiplostim exposure in the reports of a given ADR pattern (thrombosis, neurological, cutaneous, gastrointestinal or hematological) to romiplostim exposure in all other TPO-RA-related ADR reports. Reporting Odds Ratios (RORs) were adjusted for age and gender. We also compared the number of reports of a given ADR pattern per million daily defined doses (DDDs) dispensed in France during the study period. RESULTS: We described 45 reports (53 ADRs) with romiplostim and 26 reports (37 ADRs) with eltrombopag. There were 19 venous thromboses. At least one other risk factor was present in 83.3% of the cases. Ten (55.6%) patients had been splenectomized previously. There were eight arterial thromboses. Another risk factor was noticed in all cases. There was no signal for an excess risk of thrombosis with romiplostim versus eltrombopag (ROR: 1.45, 95% CI [0.48-4.45]). There was a signal for a higher risk of gastrointestinal ADRs with eltrombopag (ROR: 30.28, 95% CI [3.23-383.86]) and of hematological ADRs with romiplostim (ROR: 14.36, 95% CI [1.73-119.08]). Dispensing data-adjusted comparisons led to similar results. CONCLUSIONS: This study suggests different ADR patterns between romiplostim and eltrombopag.

Anemia in elderly patients: new insight into an old disorder.

Anemia is an important healthcare concern among the elderly. In these patients, the anemia is often mild, with a hemoglobin level >10 g/dL. It is usually well tolerated, but might be responsible for several proteiform and/or atypical presenting complaints. In the elderly, anemia is usually of multifactorial origin, including chronic inflammation, chronic kidney disease, nutrient deficiencies and iron deficiency (approximately two-thirds of all cases). The remaining cases are unexplained (unknown etiology). In the elderly, the classic diagnosis of anemia, which is based on the mean corpuscular volume associated with a low hemoglobin level, might not be accurate. A predefined standardized diagnostic procedure should be followed. In the common case of frail elderly patients, all investigations should be carefully considered and invasive examinations undertaken where justified (risk-benefit balance). Nevertheless, most cases of anemia require further investigation and the underlying cause should be identified and treated whenever possible.

Anaemia in the elderly: an aetiologic profile of a prospective cohort of 95 hospitalised patients.

BACKGROUND AND OBJECTIVES: Anaemia is a significant problem in the elderly, and the cause of anaemia in approximately one third of the general population is unidentified. To date, only a few studies have focused on hospitalised patients. PATIENTS AND METHODS: We prospectively included anaemic patients (according to OMS criteria) aged 65 years and older who were hospitalised in the internal medicine department. The typical clinical data were collected, and a standardised set of biological tests, including cupraemia was performed. RESULTS: Of 360 total patients, 191 (53%) patients were anaemic; however, 96 patients were excluded because their data were incomplete. Of the remaining 95 patients that were included, 45 were men (47.4%) and 50 were women (52.6%); the mean patient age was 79.7 years (66-101 years). At least one cause of anaemia was diagnosed in 87 of the 95 (91.6%) patients, and anaemia was multifactorial in 44 of the 95 (46.3%) cases. The five most prominent causes of anaemia were inflammation (62.1%), iron deficiency (30.5%), folic acid deficiency (21%), chronic renal failure (17.9%) and cobalamin deficiency (11.6%). Microcytosis was present in only 27.5% of the patients who had an iron deficiency, and macrocytosis was present in only 7.4% of the patients who had a folic acid and/or cobalamin deficiency. The cause of anaemia could not be identified for 8 of the patients. The cupraemia was normal in all the patients. CONCLUSION: A predefined protocol for older hospitalised patients was ability to identify the aetiology of anaemia in 91.6% of the cases; strikingly, anaemia was frequently caused by more than one factor (43.5%). Diagnostic orientation based on the mean corpuscular volume does not appear to correlate with mean cellular volume profile. Finally, anaemia caused by an unknown aetiology is rare and copper deficiency was not documented in any case.

18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: case-series and literature review.

OBJECTIVES: To describe FDG-PET/CT in amyloid light-chain (AL) amyloidosis. METHODS: We describe a French multicenter study which included patients with AL amyloidosis who had undergone a FDG-PET/CT during follow-up. RESULTS: Ten patients with AL amyloidosis (median age 62 years [59-85]) were analyzed. AL amyloidosis was of λ-type in 7/10 cases (70%) and localized amyloidosis in 4/10 cases (40%). AL amyloidosis was primary in 7/10 (70%) cases and associated with Waldenstrom's macroglobulinemia (n = 2) and plasmocytoma (n = 1) in the remaining cases. Median delay between diagnosis and PET was 1 month [0-51]. PET was positive in seven (70%) patients and showed a median FDG SUV of 6.5 [ 4-15 ]. FDG uptakes with positive PET were localized in seven patients, namely in the nasopharynx (n = 3), bronchopulmonary (n = 2), duodenal, cutaneous, bone, joint and muscular areas (n = 1, each). FDG uptakes on PET were concordant with the known organ impairment in 6/7 cases (86%) and showed unknown nasopharyngeal and mesenteric localization in one case each. PET was negative in the patient with cardiac amyloidosis and two patients with pulmonary amyloidosis. CONCLUSION: High FDG uptake may be present in patients with AL amyloidosis, however prospective studies are needed in order to determine the place of FDG PET in AL amyloidosis.

[Food-cobalamin syndrome]. / Syndrome de non-dissociation de la vitamine B12 de ses proteines porteuses ou de maldigestion des cobalamines alimentaires.

Food-cobalamin malabsorption is a new well-characterized syndrome. In association with pernicious anemia, it is the leading etiology of cobalamin deficiency in adult, especially in elderly patient. Currently, it is an exclusion diagnosis that requires a well-codified clinical strategy for diagnosis. There are several causes of food-cobalamin malabsorption, mainly gastric disorders and drugs (metformin and anti-acid drugs). Current treatment modality includes oral cobalamin administration with lower doses than in pernicious anemia. Studies are in the way to better characterize the food-cobalamin malabsorption in a clinical practice perspective and to validate the usefulness of oral cobalamin therapy.

[Nutritional anemias in elderly patients]. / Anémies carentielles du sujet âgé.

Nutritional deficiencies cause one third of the cases of anemia in the elderly. The urgency of anemia management in elderly patients depends on tolerance and repercussions, rather than only on the hemoglobin level. Iron, vitamin B12 and folate are the most common deficiencies, and their levels should be tested. Chronic gastrointestinal bleeding is the principal cause of iron-deficiency anemia. Management is based on supplementation combined with effective etiological treatment.

[Thrombocytopenia during pregnancy: from etiologic diagnosis to therapeutic management]. / Thrombopénie et grossesse: du diagnostic étiologique à la prise en charge thérapeutique.

Thrombocytopenia complicates 10% of all pregnancies. It has many potential causes, but three are responsible for almost all cases: incidental gestational thrombocytopenia (IGT) (74%), preeclampsia and HELLP (hemolysis, elevated liver function tests, low platelet count) syndrome (21%) and immune thrombocytopenic purpura (ITP) (4%). Although there is no risk of maternal or fetal hemorrhage with IGT, a benign disorder, preeclampsia, HELLP syndrome and ITP expose mother and child to potentially life-threatening complications. Other rare causes are also associated with severe complications: thrombotic thrombocytopenic purpura, hemolytic and uremic syndrome, disseminated intravascular coagulation and von Willebrand disease type IIB. Because risks for mother and child vary so greatly according to the cause of thrombocytopenia, an accurate etiologic diagnosis is essential to ensure optimal therapeutic management.

Update of nutrient-deficiency anemia in elderly patients.

Anemia, defined as a hemoglobin level < 13 g/dL in men and < 12 g/dL in women, is an important healthcare concern among the elderly. Nutrient-deficiency anemia represents one third of all anemias in elderly patients. About two thirds of nutrient-deficiency anemia is associated with iron deficiency and most of those cases are the result of chronic blood loss from gastrointestinal lesions. The remaining cases of nutrient-deficiency anemia are usually associated with vitamin B12, most frequently related to food-cobalamin malabsorption, and/or folate deficiency and are easily treated (nutrient-deficiency replacement).