Vasculopathie cérébrale de l’enfant drépanocytaire : points clés et nouveautés

Cerebral vasculopathy is a common and severe complication of sickle cell disease in children. The pathophysiology consists of progressive damage to the basal intracranial arteries and cerebral microcirculation, while chronic anemia worsens exposure to cerebral hypoxia. It results in stroke and subclinical or poorly symptomatic ischemic lesions. Many clinical, biological, and radiological risk factors have been identified. The prevention strategy through systematic transcranial Doppler screening of large-vessel vasculopathy has revolutionized the management of this disease and has greatly decreased the risk of developing stroke. MRI-MRA is a complementary diagnostic tool for anatomical analysis of parenchymal and vascular lesions, which is used for chronic disease monitoring or in the context of an acute neurological event. New exploration opportunities are offered by submandibular Doppler sonography and indirect evaluation methods of cerebral oxygenation and perfusion. If chronic blood transfusion therapy is used to prevent the occurrence and recurrence of cerebral complications of sickle cell disease, only allogeneic hematopoietic stem cell transplantation can safely and definitively stop the transfusion program. It should therefore be proposed early, before irreversible cerebral or vascular lesions occur. Hydroxycarbamide treatment has recently emerged as a potential substitute for chronic transfusions for the maintenance of transcranial Doppler velocities, but only after an initial treatment by transfusions and provided there is close follow-up. In the long run, cerebral vascular damage can cause progressive cognitive impairment and disability, even in children without radiologically identified lesions, indicating the importance of systematic and repeated neuropsychological testing.     

重金属毒物镉对儿童健康的影响

镉是环境中普遍存在的重金属毒物之一.长期低剂量暴露于镉的环境中对肾脏、肝脏、肺脏、骨骼等多种组织器官造成损害,甚至致癌致畸.其中以肾脏、骨骼及肺脏损害较重.肾损害早期可表现为肾小管重吸收功能障碍,晚期可发展为肾功能不全.近年来对儿童体内镉负荷水平及健康损害的报道逐步增多.临床中应用尿β2-微球蛋白、α1-微球蛋白和尿N-乙酰-β-D氨基葡萄糖苷酶检测镉所致的早期肾小管功能障碍.生物学标志物肾损伤分子-l在检测镉所致肾小管损伤中逐步得到应用,可能优于传统指标.     

Effect of G-6 PD deficiency on sickle cell disease in Saudi Arabia

High incidence of G6PD deficiency has been reported in areas of the eastern province of Saudi Arabia where sickle cell gene is also prevalent. This study was conducted to assess the co-incidence of this enzymopathy with Hb S and its influence upon the clinical and hematological expression of sickle cell disease. Eighty three children with SS disease, 145 patients with sickle cell trait and 100 random cord blood as samples with normal Hb AF, and an FS electrophoretic pattern respectively were examined. The frequency of interaction of G6PD deficiency with Hb S was found significantly increased but no effect of this enzyme defect was discerned on the clinical and hematological status of homozygous sickle cell disease.     

Pneumonia in young children with homozygous sickle cell disease: risk and clinical features

The incidence and clinical features of pneumonia have been examined in children with homozygous sickle cell (SS) disease and in age/sex matched control children with a normal haemoglobin (AA) genotype followed in a cohort study of sickle cell disease from birth.Survival curve analysis indicated a similar incidence of pneumonia in the two genotypes up to the ages of 8 months after which pneumonia became significantly more prevalent in SS disease, the relative risk exceeding a factor of four by 4 years of age. Children with SS disease were also more prone to multiple episodes. Comparison of clinical features in the two genotypes yielded no difference in sex or seasonal involvement, or in the results of bacteriological and radiological investigations. Children with SS disease and pneumonia had an increased frequency and increased duration of hospital admission, and mortality was confined to this group.It is concluded that children with SS disease have an increased prevalence of single and multiple attacks of pneumonia and that these events run a more serous clinical course than in control children.Abbreviations SS sickle cell disease - AA normal haemoglobin genotype     

Systemic lupus erythematosus and sickle cell disease

A case of 10-year-old girl with an unusual association of sickle cell disease (SCO) with systemic lupus erythematosus (SLE) is presented. The report discusses the clues to the diagnosis of this rare combination with review of relevant literature and highlights the diagnostic dilemma that may arise because of the similarity of symptoms.     

Splenectomy and acute splenic sequestration crises in sickle cell disease

Acute splenic sequestration crises (ASSC) is one of the complications of sickle cell disease (SCD) that can be life-threatening due to loss of blood volume. Over a 5-year period, we have treated 19 patients ranging in age from 4 to 32 years with ASSC. There were 14 males and 5 females; 17 had homozygous SCD and the other 2 had sickle thalassemia. Two patients presented with severe anemia and acute circulatory collapse; 1 of them developed residual weakness of his limbs and decreased visual acuity. Nine patients underwent splenectomy after major episodes of sequestration while the remaining 10 had recurrent minor episodes of sequestration. The clinical features and the role of splenectomy are discussed.     

Calcified pulmonary thromboembolism in a child with sickle cell disease: value of multidetector CT in patients with acute chest syndrome

The incidence of pulmonary embolism in children is not clearly known, but is believed to be low. Risk factors for pulmonary thromboembolism include central venous catheter, malignancy, surgery, infection, trauma, and congenital hypercoagulable disorders. Children with sickle cell disease are prothrombotic and are at an increased risk of thromboembolism. The incidence of this event is unknown because these children are often not thoroughly imaged. We report here a case of a calcified pulmonary thromboembolism in a child with sickle cell disease and emphasize the use of multidetector CT in detection of pulmonary thromboembolism in children with sickle cell disease.     

早期诊断急性肾损伤的生物学标志物研究现状

急性肾损伤(AKI)是一种常见的严重疾病.由于缺乏诊断AKI的早期生物学标志物,往往导致早期有效治疗的延误.目前对于诊断AKI新的生物学标志物的研究已发展到了临床研究阶段,最有希望成为早期诊断AKI的生物学标志物包括中性粒细胞明胶酶相关脂质运载蛋白、IL-18、肾损伤分子-1和L-脂肪酸结合蛋白.本文就近年来关于上述几种生物学标志物的研究作一综述,为应用早期诊断AKI的生物学标志物提供理论依据.     

IRON DEFICIENCY IN SICKLE CELL DISEASE

Abstract. Nagaraj Rao, J. and Sur, A. M. (Department of Paediatrics, Medical College and Hospital, Nagpur, India). Iron deficiency in sickle cell disease. Acta Paediatr Scand, 69:337, 1980.—Iron studies were performed on 25 children with homozygous sickle cell disease. The majority (80%) of patients had never been transfused. Surprisingly, the results showed that all had low serum iron and low transferrin saturation. Three children had no marrow iron stores while the rest had diminished amounts of iron. This may be an important finding in view of recent efforts at fortifying common salt with iron. The exact effects of iron deficiency on sickle cell disease are not known and a controlled trial is called for.     

早产儿脑损伤生物标志物的研究进展

随着围产及新生儿监护技术的不断发展,早产儿的生存率不断提高,与此同时早产儿脑损伤的发生率也在逐渐上升,常遗留不同程度的认知障碍与运动障碍。脑损伤生物标志物检测是诊断脑损伤的重要手段,根据损伤细胞的性质不同可分为神经胶质细胞损伤标志物、神经元损伤标志物及其他生物标志物等几大类,而其中较为成熟并广泛应用于临床的有S100B蛋白、髓鞘碱性蛋白、神经元特异性烯醇化酶等生物标志物。最新研究发现胶质纤维酸性蛋白、神经丝轻链蛋白、α-Ⅱ血影蛋白裂解产物、趋化因子、褪黑素及尿液代谢组学等指标可提示早产儿潜在脑损伤,检测这些生物标志物有助于早产儿脑损伤的早期诊断及早期治疗,对改善其神经发育预后至关重要。该文就早产儿脑损伤生物标志物的最新研究进展作一综述,以期为早产儿脑损伤的早期诊断及早期治疗提供有效依据。     

Microalbuminuria as a predictor of early glomerular injury in children with sickle cell disease

Objective : A cross sectional study was carried out to determine the prevalence of microalbuminuria in the pediatric patients with sickle cell disease.Methods : The study was carried out on 64 pediatric patients aged less than 14 years with documented HbSS, HbAS and HbS beta thalassemia, Microalbuminuria was estimated using single radial immuno diffusion technique. Majority of the study subjects were of HbSS type. 38.5% had symptoms for >2 years. 18.8% of the study population had significant microalbuminuria (19.2% of SS types and 18.8% of Hb AS types).Result : Microalbuminuria excretion was significantly more in patients >9 years of age as compared to young patients (p<0.05). Mean serum creatinine levels did not show any significant difference in the various study groups.Conclusion : Microalbuminuria estimation is a very important clinical marker of preclinical glomerular damage in patients with sickle cell disease. Its estimation would help in the early detection of such patients and prompt initiation of therapy.     

Clinical practice

Proteinuria detection in children is a challenge. Five percent to 15% and 0.4–1% of school children present either transient (benign) or persistent increased amount of protein in urine, respectively. Persistent proteinuria constitutes not only a sign of overt kidney disease but may also be the first indicator of silent renal damage. Proteinuria is a marker for hyperfiltration in individuals with reduced nephron mass and one of the most important independent risk factor for renal disease progression as well. It constitutes the single most important risk factor for future loss of kidney function, preceding glomerular filtration rate reduction. Further, proteinuria itself is diagnostic of cardiovascular disease with prognostic value and target organ involvement in high-risk populations such as diabetic, obese, hypertensive children, or those with known reduced renal mass or previous renal injury. Current strategies to prevent CKD progression, a concept known as renoprotection, are focused on reducing urinary protein excretion among other factors. Reversibility of organ damage in early stages is possible; therefore, pediatricians should screen children for proteinuria or microalbuminuria, mainly in high-risk groups.     

The spleen in the sickling disorders: an update

In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal “autosplenectomy” emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management.     

Multicentric Bilateral Renal Cell Carcinomas and Avascular Leiomyoma in a Child

We report a unique case of multicentric bilateral renal cell carcinomas and a simultaneous large renal vascular leiomyoma in an 11 -year-old child with sickle cell anemia. The patient presented with several episodes of massive hematuria. Abdominal sonography and computed tomography demonstrated bilateral renal neoplasms and the patient was clinically thought to have bilateral Wilms' tumor. An initial biopsy of the lower pole of right kidney revealed a renal cell carcinoma. Accordingly, bilateral renal angiography followed by right total nephrectomy and left upper pole partial nephrectomy were performed. Pathologic studies showed multicentric, bilateral renal cell carcinomas (two in the right kidney and one in the left kidney), of clear, granular, and oncocytic cell types. A simultaneous large vascular leiomyoma was also present in the right kidney. The smooth muscle nature of the leiomyoma was determined by light microscopy, immunohistology, and electron microscropy. The diagnostic difficulties in distinguishing them from other renal tumors are discussed.     

Bone infarction in children with sickle cell disease: early diagnosis and differentiation from osteomyelitis

An early differential diagnosis between bone infarction and osteomyelitis in sickle cell patients is practically impossible using routine laboratory methods. Twenty radioisotope studies in sickle cell patients during vaso-occlusive crises, were analyzed. A three stage process can be described. In the first stage a decreased uptake can be demonstrated by Tc 99 m methylene diphosphanate (MDP) bone scanning. In osteomyelitis, an increased uptake area is usually seen at this early stage, corresponding to increased uptake in Ga-67 citrate scanning. At the second stage, approximately a week later, normal uptake can be seen. Two to four weeks later an area of increased uptake is recorded that corresponds to the healing process, stage three. We recommend therefore Tc 99m MDP bone scanning in the early stages if clinical signs and symptoms suggest a vaso occlusive crisis or osteomyelitis in a sickle cell patient. This study can be followed by a Ga-67 citrate scintigraphy in doubtful cases. Later studies should be used for the assessment of the healing process. Two illustrative case reports are included.     

Ischaemic cholangiopathy and sickle cell disease

We report a case of a 6-year-old girl of Afro-Caribbean origin, known to have sickle cell disease (SCD), with recurrent history of jaundice and abdominal pain. She was extensively investigated, including endoscopic retrograde cholangiopancreatography (ERCP), which revealed diffuse cholangiopathy of both extrahepatic and intrahepatic bile ducts. A pigtail stent was placed and balloon dilatation was performed for stricture of the extrahepatic duct. Since then, she remains well and asymptomatic. We suggest that cholangiopathy is the consequence of sickling in the end arteries of the biliary arterial tree.     

Ethical aspects of neonatal screening for sickle cell disease in Western European countries

Sickle cell disease raises some important ethical questions regarding neonatal screening in Western European countries such as France, England or Belgium, which have already introduced either universal or selective screening. Such screening is aimed at benefiting children affected with major sickle cell syndrome. It also detects heterozygous babies and, in doing so, heterozygous parents. The latter information, which is ignored most of the time, risks making parents feel guilty and can raise fears of stigmatization. Whether it would change their future reproductive decisions requires further studies, for cultural and religious reasons may have a strong negative influence on the request for prenatal diagnosis. Disclosure of the child's illness may oblige the family to remain in the country they have emigrated to because it offers the best chance of treatment. As a result, links between the family and its original community are modified. Parents must more or less sever links with their family in Africa and try to trust and adapt to the public health services in Europe.

Conclusion: Neonatal screening of sickle cell disease is highly ethical in facilitating the prevention of the early death of affected children. It also detects heterozygous parents and offers at-risk couples the possibility to perform a prenatal diagnosis during the next pregnancy. Adequate counselling must consider the risk of stigmatization that carrier status represents, especially for women in many cultural beliefs, and the numerous cultural and religious reasons which limit parental uptake for prenatal diagnosis. Disclosure of their child's illness may oblige immigrant families to stay in Europe, where free and adapted healthcare is available.     

Fulminant liver failure in a 12-year-old girl with sickle cell anaemia: Favourable outcome after exchange transfusions

Acute liver failure is unusual unusual in sickle cell anaemia. We describe a child with homozygous sickle cell anaemia who developed acute liver disease of abrupt onset during an episode of limb pain. She presented with sudden onset of persistent vomiting, headache, lethargy, epistaxis, and painful liver enlargement. Laboratory investigations were indicative of cholestasis and severe liver failure with profound prolonged clotting times, hypofibrinogenaemia, elevated serum ammonia and lactic acidosis. The symptoms were promptly and completely reversed by two partial exchange transfusions. No evidence of viral infection was found. Cholelithiasis was ruled out by ultrasonography. The child recovered from what appeared to be massive hepatic sickling with no apparent sequelae.Conclusion Massive hepatic sickling should be considered in the differential diagnosis of a child with homozygous sickle cell disease who suddenly develops acute liver failure. Exchange transfusion should be promptly carried out so as to reverse ischaemic hepatic injury.     

急性肾损伤与早期诊断生物标志物

急性肾损伤（acute kidney injury,AKI）是一种临床常见的综合征。目前国内外临床上对肾损伤的评估仍然依赖于血肌酐和尿量的变化,缺乏有效的生物标志物来早期识别,导致治疗延迟,AKI病死率居高不下。寻找理想的生物标志物,实现AKI早期诊治是亟待解决的临床实际问题。儿童AKI与成人相比具有一定特殊性,已发现的AKI生物学标志物是否适用于儿童及新生儿尚需进一步验证。文章通过对颇具儿科临床应用前景的几种AKI生物标志物及其作为早期识别AKI标志物的优点和局限性进行综述,为儿童AKI的早期诊断提供方向。