Search

Non-Hodgkin's lymphomas are characterized by its clinical and pathological polymorphism. In the stomach, MALT lymphomas are common and mostly associated with Helicobacter Pylori infection. We report a case of 76-year old women with a medical history of chronic stomach pain, addressed for the investigation of normochromic normocytic anemia. The clinical picture included signs of digestive hemorrhage and stomach pain. Gastrointestinal endoscopy and histology noted an unspecified ulcer-budding tumor without signs of Helibacter pylori infection. Immunohistochemistry concluded to diffuse large B cell lymphoma with CD79b +, BCL10 +/-, BCL2+, BCL6 +, MUM1+. The Ann Arbor classification was stage IE. The serology of Helicobacter pylori was negative. Pre-treatment investigation noted a comorbity with Hepatitis C infection. This study has two interests. Firstly the rarity of the localization of this lymphoma, and secondly, the etiopathological interest because of association with hepatitis C virus.

The authors report one case of systemic lupus erythematosus revealed by chronic anemia. This was a 29-year-old patient with long-term fever, chronic skin and joint lesions with isolated hypochrome microcytic haemolytic anemia on the hemogram. The diagnosis of SLE was made three years after the onset of symptomatology based on seven of the American Rheumatology Association's (ARA) criteria out of 11, including positive immunological status (antinuclear antibodies and native DNA). This observation shows the interest of evoking SLE, while looking for signs in a young woman with multiple and varied symptoms with signs of skin, kidney, osteoarticular and hematological disorders. Les auteurs rapportent un cas de lupus erythemateux dissemine revele par une anemie chronique. IL s’agissait d’une patiente de 29 ans presentant une fievre au long cours, des lesions cutanees et articulaires d’evolution chronique avec a l’hemogramme une anemie hemolytique isolee hypochrome microcytaire. Le diagnostic de LED a ete retenu trois annees apres le debut de la symptomatologie devant sept criteres sur 11 de L’American Rheumatology Association (ARA) dont le bilan immunologique positif (anticorps antinucleaires et DNA natif). Cette observation montre l’interet d’evoquer le LED, tout en recherchant les signes chez une femme jeune presentant une symptomatologie multiple et variee avec les signes d’atteintes cutanee, renale, osteo-articulaire et hematologique.

In Cote d'Ivoire, sickle cell disease affects 14% of the population. It is responsible for significant morbidity and mortality. Transfusion is a significant element in the management of major sickle cell anemia, which exposes them to post-transfusion hemochromatosis. The biological diagnosis is based on the determination of serum iron and the transferrin saturation coefficient (CST). As the determination of the CST was not available in our exercise context in Cote d'Ivoire, we determined only the ferritinemia. The interest of this work lies in the therapeutic implication linked to the identification of patients at risk of hemochromatosis because chelators are difficult to access for most patients. This was a prospective, descriptive and analytical study, on polytransfused sickle cell patients, followed at the transfusion therapy unit (UTT) of the CNTS of Abidjan, from 2010 to 2018. We included 78 sickle cell patients, all ages and genders who have received at least ten transfusions. The ferritinemia assay was carried out by ELISA. Transfusion exchange, with 59% of cases, was the most used mode of transfusion. The mean ferritinemia was 1719.19 ng / ml. Hyperferritinemia was found in 63% of patients. Most of the patients were on a long-term transfusion program with an average of 27.5 bags of red blood cell concentrates. Thirty-two patients had received at least 20 bags of red blood cell concentrates. We noted 21 patients treated, including 3 with deferoxamine and 18 treated with oral deferasirox. We have identified 33 sickle cell anemia patients at risk for hemochromatosis. The determinants of the risk of hemochromatosis were the high number of blood bags and the method of transfusion.

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent. Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed. Results: 612 SCD patients (483 SS or Sβ0, 99 SC, and 19 Sβ+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders. Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies.

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Arteres et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSβ0 , 44% of HbSC, 38% of HbSβ+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSβ0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle β-zero-thalassemia [Sβ0], 495 SC, and 161 sickle β+-thalassemia [Sβ+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sβ0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sβ0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Chronic kidney disease is one of the leading causes of mortality in patients with sickle cell disease. However, it has been almost exclusively studied in patients with the SS phenotype and in high-income countries, despite more than 80% of patients living in Africa. We looked for the determinants of glomerulopathy in a multinational cohort of patients with sickle cell disease of different phenotypes in sub-Saharan Africa.In the CADRE cohort, we prospectively included patients 3 years and older with sickle cell disease of all haemoglobin phenotypes in Cameroon, Côte d'Ivoire, Mali, and Senegal. All individuals were assessed at steady state. The main outcome of interest was albuminuria defined as a urine albumin-to-creatinine ratio of greater than 30 mg/g. We investigated the clinical and biological determinants (including haemolysis markers) of albuminuria in two main phenotype groups (SS and Sβ(0); SC and Sβ(+)) with further stratification by age and country.The study is ongoing because of follow-up. 2582 patients with sickle cell disease were included (1776 SS, 136 Sβ(0), 511 SC, and 159 Sβ(+)). 644 patients with the SS and Sβ(0) phenotypes (33·7%, 95% CI 31·6-35·8) and 110 with the SC and Sβ(+) phenotypes (16·4%, 13·6-19·2) had albuminuria. In the SS and Sβ(0) group, albuminuria was detected in 144 (27%) of 527 children younger than 10 years and its frequency increased with age (29 [48%] of 60 patients aged40 years). Multivariable analysis showed that albuminuria was associated with age (odds ratio 1·43, 95% CI 1·20-1·71; p0·0001), female sex (1·35, 1·02-1·82; p=0·045), low haemoglobin (0·79, 0·66-0·93; p=0·006), high lactate dehydrogenase concentrations (1·33, 1·14-1·58; p=0·0009), and, using Côte d'Ivoire as the reference, Mali (2·49, 1·64-3·79; p=0·042) and Cameroon (1·59, 1·01-2·51; p=0·0007) in patients with the SS and Sβ(0) phenotypes. The magnitude of the association of albuminuria with haemoglobin and lactate dehydrogenase concentrations increased with age. In the SC and Sβ(+) patients, only low haemoglobin (0·69, 0·48-0·97; p=0·029), high blood pressure (1·63, 1·17-2·27; p=0·0017), and Mali (3·75, 1·75-8·04; p0·0001) were associated with albuminuria.Hyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and Sβ(0) phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and Sβ(+) phenotypes. However, both phenotypes are associated with a high prevalence of albuminuria in childhood. Therefore, screening for albuminuria is advised in African children with sickle cell disease to detect early renal damage.Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.

Introduction Growth failure has been a well-known complication of sickle cell disease (SCD) since the 70s. More recent studies show that the proportion of underweight children with SCD has decreased significantly, thanks to modern treatments (in particular hydroxyurea and iterative transfusions), with a tendency towards overweight and even obesity. However, most studies have been carried out in high-income countries, while 80% of the affected children are born in sub-Saharan Africa, where the environment and the medical care are entirely different. We carried out a case-control study nested in a multinational African cohort to study the growth of sickle cell children and the possible factors influencing growth failure. Methods We performed a case-control transversal study nested in the CADRE cohort that includes SCD patients from five African countries: Cameroon, Gabon, Côte d'Ivoire, Mali and Senegal. All children aged 5 to 21 years-old from this cohort were included in our study. Healthy controls were recruited among the patients' siblings or the children of health workers from each center. The main parameters studied were: medical history, height, weight, blood pressure; hemoglobin phenotype (SS, Sβ0, SC or Sβ +); complete blood count; hemolysis markers (LDH and bilirubin); microalbuminuria; echocardiographic parameters. The primary endpoint was growth failure, defined as a weight, height or BMI below the 5th percentile of the WHO growth charts. We described the frequency of growth failure according to hemoglobin phenotype, age and sex. Then we assessed by multivariate logistic regression in two SCD phenotypic groups (SS or Sβ0 and SC or Sβ +) the association between growth failure and the biological characteristics or the history of SCD-related complications. Results 2296 patients (1799 SS, 114 Sβ0, 287 SC, 96 Sβ+ patients and 287 controls were enrolled in Cameroon (n=735), Ivory Coast (n=380), Gabon (n=298), Mali (n=589) and Senegal (n=581). Overall, 48% of the patients were male and their median [interquartile range] age was 12 [8-16] years-old. Growth failure was diagnosed in 51% of SS, 58% of Sβ0, 44% of SC, 38% of Sβ+patients and 32% of controls, with deeper underweight than linear growth retardation. Beyond the age of 18, the mean BMI of SCD patients was again similar to that of controls in girls, but remained lower in boys, whereas the mean height was similar to that of controls regardless of sex (Figures a to d). Growth failure was more frequent in boys than in girls and maximal between 13 and 16 years-old (Figures e and f). In univariate analysis, the prevalence of growth retardation was associated with the country (highest in Senegal, lowest in Cameroon), age, male sex, hemoglobin phenotype, levels of anemia and hemolysis (p Conclusion In sub-Saharan Africa, growth failure occurs in more than half of the SCD children and concerns weight more than height. Its prevalence is particularly high in SS or Sβ0 patients and during adolescence, due to pubertal delay. Growth failure in SCD children is associated with male sex, anemia and high hemolysis markers independently of the hemoglobin phenotype, but is not independently associated with the occurrence of acute or chronic vascular complications of sickle cell disease, apart from microalbuminuria. However, the long-term consequences of growth failure in sickle cell disease should be evaluated in a longitudinal study. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction About 80 % of sickle cell disease (SCD) patients live in sub-Saharan Africa whereas most studies on SCD are performed in Europe and America. Hyperhemolysis is thought to play a major role in the pathological process of SCD vasculopathy. Nevertheless, the paradigm of hyperhemolysis is controversial and has never been studied in the African context. We aim to analyze the association between hemolysis and clinical vascular complications among SCD African patients. Methods CADRE is a multinational cohort of SCD African patients aged 3 years and older, included prospectively and explored in a steady state. All patients from the CADRE cohort in Ivory Coast, Cameroun and Mali were included in the present study. Patients were classified in SS-Sβ0 phenotype or SC-Sβ+ phenotype. SCD vascular complications (pulmonary arterial hypertension (PAH), microalbuminuria, leg ulcers, priapism, stroke and osteonecrosis) were assessed using clinical examination, laboratory exams and echocardiography. Hemolysis was measured by a composite score, created with a principal component analysis, that included LDH, hemoglobin and bilirubin rates and clinical icterus. The association between hyperhemolysis (upper quartile of the hemolysis score) and the vascular complications was assessed using multivariate regression analysis in the whole population with further stratification by hemoglobin phenotype. Results We included 2409 patients among which 1751 SS-Sβ0 patients and 658 SC-Sβ+ patients. Compared to SC-Sβ+ patients, SS-Sβ0 patients were younger (15 years old versus 21 years old) and exhibited more leg ulcers (166 (9.5%) versus 24 (3.7%)) and microalbuminuria (573 (42.4%) versus 119 (20.0%)). The hemolysis score was higher in SS-Sβ0 patients as compared to SC-Sβ+ patients (median 1.18 versus 0.43, Figure). After adjustment for age, sex and country, hyperhemolysis was associated with microalbuminuria (OR = 1.59 [1.17-2.16]) and priapism (OR=1.58 [1.01-2.49]) (Table). In SS-Sβ0 patients, hyperhemolysis was associated with microalbuminuria (OR=1.54 [1.10-2.15]) and there was a trend to an association with PAH (OR=1.65 [0.91-2.98]) and priapism (OR=1.50 [0.95-2.39]). In SC-Sβ+ patients, only the association between hyperhemolysis and microalbuminuria remained significant. Sensibility analysis in the adult population showed that hyperhemolysis was significantly associated with all the SCD vascular complications, except for osteonecrosis. Conclusion In African SCD patients, associations between hyperhemolysis and SCD vascular complications were statistically significant but of modest magnitude, and depended on the hemoglobin phenotype. These results suggest that in the African context, hemolysis is not a major determinant of the development of SCD vasculopathy. Table. Associations between SCD complications and hemolysis score (quartiles 1 to 3 versus quartile 4) in the whole population: multivariate analysis with adjustment for age, sex, country and hemoglobin phenotype % of patients with the complication Multivariate analysis N event/N total Quartiles 1 to 3 Quartile 4 OR IC 95% P value PAH* 115/431 6.14 7.08 1.58 0.89-2.83 0.123 Urine albumin/creatinine > 30mg/g 724/1991 24.88 45.36 1.59 1.17-2.16 0.004 Leg ulcer, lifetime 190/2409 6.80 11.01 1.20 0.81-1.78 0.355 Priapism, lifetime ** 160/1095 13.27 17.90 1.58 1.01-2.49 0.046 Stroke, lifetime 25/2409 0.79 1.77 1.32 0.49-3.54 0.578 Osteonecrosis, lifetime 277/2409 11.22 12.28 1.00 0.70-1.43 1.000 PAH: Pulmonary Arterial Hypertension. * Patients from Mali and Cameroun only ** Males only Figure 1. Distribution of the hemolysis score: global population, SS-Sβ0 patients and SC-Sβ+ patients Figure 1. Distribution of the hemolysis score: global population, SS-Sβ0 patients and SC-Sβ+ patients Disclosures No relevant conflicts of interest to declare.

Introduction Sickle cell disease (SCD) is not only responsible for acute vaso-occlusive events but also for chronic vasculopathy that affects many organs including kidneys. Animal studies have suggested that SCD vasculopathy mainly results from chronic hemolysis. However hemolysis markers have not been consistently associated with clinical vascular complications. Moreover, SCD vasculopathy events have been almost exclusively studied in the USA or in Europe, although more than 80% of SCD patients are born and living in sub-Saharan Africa, a very different environment. We have settled the first multinational African SCD cohort to measure the incidence of SCD vascular complications and looked for their predictive factors in sub-Saharan Africa. We present here our first results, focusing on SCD nephropathy with glomerular involvement and urinary loss of albumin. Methods CADRE is an ongoing cohort of SCD patients in five African countries: Cameroon, Gabon, Ivory Coast, Mali, and Senegal. Included subjects are enrolled at steady state and undergo clinical exam, blood sampling for hemoglobin electrophoresis, blood count, creatinine, lactate dehydrogenase (LDH) and bilirubin levels, and urine sample for albumin and creatinine levels, as well as echocardiography. Main outcome for the present study was micro or macroalbuminuria defined as urine albumin/creatinine ratio >30 mg/g, that has been shown to be predictive of chronic renal insufficiency in SCD. We differentiated two main SCD groups: 1) SS and Sβ0 and 2) SC and Sβ+. Frequency of albuminuria at inclusion was calculated in both groups, with further stratification according to age. We looked for clinical and biological correlates to albuminuria in both groups using multivariate logistic regression. Results In June 2013, 3850 SCD patients have been recruited, among them 3032 (2290 SS, 445 SC, 202 Sβ+, 95 Sβ0) had available complete inclusion data. Median age was 15 and 20 years in SS/Sβ0 and SC/Sβ+ group, respectively, with similar female/male ratio of 1.2. Frequency of albuminuria was 36.9% [34.4-38.7] in SS/Sβ0 and 16.1% [13.2-19.9] in SC/Sβ+ patients, and increased significantly with age in SS/Sβ0 patients (Fig 1). Albuminuria remained significantly higher in SS/Sβ0 group than in SC/Sβ+ group, after adjustment for age, sex, country, blood pressure and hemoglobin level (p Conclusion SCD glomerulopathy is frequent in sub Saharan Africa affecting more a third of patients. Children ( Disclosures: No relevant conflicts of interest to declare.