Valentine Brousse

Osteopenia and vitamin D deficiency in children with sickle cell disease.

Objectives:  To assess the prevalence in children with sickle cell disease of low bone mineral density (BMD), a feature found in up to 82% of adults but not well known in children.

Nebulized Antibiotics in Cystic Fibrosis

Nebulization is a useful administration route in cystic fibrosis (CF) as it delivers antibiotics directly to the endobronchial site of infection and is associated with decreased toxicity because of limited systemic absorption. It is assumed that the concentration of antibiotics in bronchial secretions should be as high as 10 times the minimum inhibiting concentration to allow penetration of antibiotics into biofilms, suppress inhibitory factors and promote bactericidal effectiveness. However, effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles of a size in the respirable range.Three antibiotics are commonly used for inhalation: tobramycin, amikacin and colistin (colomycin). Placebo-controlled studies evaluating antibiotic aerosol maintenance in stable patients chronically infected with Pseudomonas aeruginosa indicate a significant improvement of lung function and a reduction of the number of hospital admissions for an acute exacerbation of CF.TOBI®1 is a recently marketed preservative- and sulfate-free formula of tobramycin, specially designed for diffusion in the bronchioles and optimal tolerance. A wide-scope study involving 520 patients compared TOBI® (300mg twice daily; n = 258) with placebo (n = 262) for three 28-day cycles with each cycle separated by a 28-day period of no treatment. Respiratory function was significantly improved as early as in the second week and remained so for the rest of the trial even during periods without aerosol treatment. There was also a parallel decrease in the relative risk of hospitalization, the number of days of hospitalization and the number of days on intravenous antipyocyanic treatment. Toxicity studies carried out so far have shown no renal or ototoxicity with nebulized tobramycin. Introduction or selection of resistant bacteria is relatively rare but remains a matter of concern.Aerosol maintenance treatment with an appropriate antibiotic in a high enough dosage can be recommended for patients with CF who are chronically infected with P. aeruginosa.

Myocardial ischaemia in children with sickle cell disease

Background: The heart may be involved in children affected with sickle cell disease (SCD) via several mechanisms. Principally, chronic anaemia increases cardiac output and may cause left ventricular enlargement and cardiac insufficiency. Aims: To investigate whether the heart also suffers from ischaemia in SCD, as has already been shown for other organs (bone, brain, etc), and to look for risk factors predisposing to this complication. Methods: Twenty two children with SCD, and chest pain or ECG or echocardiographic signs (left ventricle dilation or hypokinesis) suggesting myocardial ischaemia were subjected to thallium-201 (201Tl) single photon emission computed tomography (SPECT). Results: Eight children had a normal SPECT, 14 an abnormal one. Myocardial perfusion defects were reversible in nine, fixed in five. Patients with perfusion defects tended to be older and have more severe disease. Five had had cardiac symptoms (episodes of cardiac failure in three, ventricular fibrillation in one, angina in one). Myocardial perfusion was reassessed after six months of hydroxyurea treatment in three patients, and was found to be improved. Conclusions: Myocardial perfusion defects are present in children with SCD and may be demonstrated using SPECT. Hydroxyurea improved perfusion in three patients.

Acute splenic sequestration crisis in sickle cell disease: cohort study of 190 paediatric patients

Acute splenic sequestration crisis (ASSC) is an unpredictable life‐threatening complication of sickle cell disease (SCD) in infants. Here, our objective was to update available clinical information on ASSC. We retrospectively studied the 190 patients who were diagnosed at birth with SS or Sbeta0 in the Paris conurbation between 2000 and 2009 and who experienced ASSC. They had 437 ASSC episodes (0·06/patient‐year). Median age at the first episode was 1·4 years (0·1–7) and 67% of patients had more than one episode. Age was the only factor predicting recurrence: the risk was lower when the first episode occurred after 2 years versus before 1 year of age (hazard ratio, 0·60; 95% confidence interval, 0·41–0·88; P = 0·025). A concomitant clinical event was found in 57% of episodes. The mortality rate was 0·53%. The treatment consisted in watchful waiting without prophylactic blood transfusions or splenectomy in 103 (54%) patients and in a blood transfusion programme in 55 (29%) patients. Overall, splenectomy was performed in 71 (37%) patients, at a median age of 4·5 years (range, 1·9–9·4). In conclusion, aggressive treatment may be warranted in patients experiencing ASSC before 2 years of age. Randomized controlled trials are needed to define the best treatment modalities.

Feasibility and efficacy of chronic transfusion for stroke prevention in children with sickle cell disease

Objectives:  In children with sickle cell disease (SCD), chronic transfusion to maintain haemoglobin S (HbS) below 30% markedly decreases both the risk of a first stroke when transcranial Doppler (TCD) ultrasonography shows abnormal cerebral blood flow velocities and the risk of recurrent stroke. Maintaining HbS below 30% may be difficult, especially in countries where blood donors and recipients belong to different ethnic groups and where the availability of closely matched blood products is limited. We assessed the feasibility and efficacy of chronic transfusion with an HbS target of 30% in children with SCD living in the Paris area.

Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines.

We conducted a retrospective study on newborns with sickle‐cell disease (SCD), born 1995–2009, followed in a multicentre hospital‐based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°‐thalassaemia) with 6776 patient‐years of follow‐up were analysed (mean age 7·1 ± 3·9 years). SCD‐related deaths (n = 13) occurred only in SS‐genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non‐compliance was associated with a 10‐fold higher risk of SCD‐related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso‐occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin <70 g/l received intensification, mainly for other severity criteria. Overall, hydroxycarbamide was under‐prescribed, given to 2/3 of severe vaso‐occlusive patients and 1/3 of severely anaemic patients. Nevertheless, introduction of the on‐line guidelines was concomitant with an improvement in medical care in the 2006–2009 cohort with a trend towards increased survival at 5 years, from 98·3% to 99·2%, significantly increased TCD coverage (P = 0·004) and earlier initiation of intensification of therapy (P ≤ 0·01).

Asymptomatic atrophy of the temporal median raphe of the retina associated with cerebral vasculopathy in homozygous sickle cell disease

A 13-year-old girl with homozygous sickle cell disease was referred for vision loss in her left eye of 1 years duration. Clinical findings were consistent with a past retinal arterial occlusion. In the asymptomatic right eye, spectral domain optical coherence tomography showed a severe atrophy of the inner retinal layers of the temporal median raphe; a significant internal carotid stenosis was also present. We hypothesize that specific atrophy of the retinal temporal median raphe resulted from chronic ischemia. The inner layers of the retina are vascularized by terminal vessels and the median raphe can therefore be regarded as a junction territory; its atrophy may represent an ocular equivalent of a silent border zone cerebral infarct.

Anemia in children: prevalence, causes, diagnostic work-up, and long-term consequences

ABSTRACT Introduction: Anemia in children is a major public health problem throughout the world. It is often multifactorial, iron deficiency being the most frequent etiology. Consequences are diverse and largely under evaluated. Areas covered: This paper briefly reviews the main causes and focus on the potential consequences of acute and chronic anemia in children. Expert commentary: Anemia in children should never be trivialized. Even if iron deficiency is frequently involved, other potentially life-threatening causes are possible and should be looked for. The exact contribution of anemia to child mortality and morbidity is difficult to assess because of overlapping comorbidities. Chronic anemia may impair growth, cardiac function and cognitive development in infants but other consequences are rather poorly described and should be explored more thoroughly.

Management of iron overload in hemoglobinopathies

Hemoglobinopathies, thalassemia and sickle cell disease are among the most frequent monogenic diseases in the world. Transfusion has improved dramatically their prognosis, but provokes iron overload, which induces multiple organ damages. Iron overload is related to accumulation of iron released from hemolysis and transfused red cell, but also, in thalassemic patients, secondary to ineffective erythropoiesis, which increases intestinal iron absorption via decreased hepcidin production. Transfusion-related cardiac iron overload remains a main cause of death in thalassemia in well-resourced countries, and is responsible for severe hepatic damages in sickle cell disease. Regular monitoring by Magnetic Resonance Imaging (MRI) using myocardial T2* (ms) and Liver Iron Content (LIC) (mg of iron/g dry weight) are now standards of care in chronically transfused patients. Serum ferritin level measurements and record of the total number of transfused erythrocyte concentrates are also helpful tools. Three iron chelators are currently available, deferoxamine, which must be injected subcutaneously or intravenously, and two oral chelators, deferiprone and deferasirox. We will review the main characteristics of these drugs and their indications.