[Activated partial thromboplastin time prolongation in paediatrics. Retrospective monocentric study at the Nice University Hospital]. / Allongement isolé du temps de céphaline activé en pédiatrie. Étude rétrospective monocentrique au CHU de Nice.

UNLABELLED: The study of hemostasis often arises in paediatrics. Evidence of activated partial thromboplastin time (aPTT) prolongation sometime due to the presence of a circulating anticoagulant (antiphospholipid syndrome [APS]) may be embarrassing for the physician. AIM OF THE STUDY: To evaluate the prevalence of this situation, to identify the leading indicators and assess their impact. PATIENTS AND METHOD: All children aged 1 to 18 years old undergoing blood sample whatever was the reason, at the Nice University Hospital with existing isolated aPTT prolongation, were included. The assessment was completed by a mixing test, calculation of Rosner's index as well as the study of an APS and the measurement of factor VIII, IX, XI, XII. RESULTS: Between July 2006 and March 2008, 27 of 1845 children observed (1.5%) were selected for further study. Mean age was 6.17 years old. For 16 of the patients, aPTT prolongation was fortuitously discovered. Symptomatic subjects were older (9.8 vs. 5.2 years of age; P = 0.03). A significantly higher aPTT was indicative of an APS and predicted a positive Rosner Test outcome. A prolongated kaolin clotting time, observed among the younger subjects (3.45 vs. 8.88 years of age; P = 0.0011), was associated with a high aPTT prolongation (57.3 vs. 42.6s; P = 0.0009). CONCLUSION: In our study, the discovery of a prolongated aPTT is most often incidental and tends to occur during winter. The presence of a highly prolongated aPTT, abnormal kaolin clotting time and positive Rosner Test are strong predictors of the existence of an APS, especially in very young children. These antibodies are nonpathogenic and transitional.

Altered glycosylation of leukosialin, CD43, in HIV-1-infected cells of the CEM line.

CD43 (leukosialin, gpL115, sialophorin) is a major sialoglycoprotein widely expressed on hematopoietic cells that is defective in the congenital immunodeficiency Wiskott-Aldrich syndrome. It is thought to play an important role in cell-cell interactions and to be a costimulatory molecule for T lymphocyte activation. Using a metabolic 35SO4(2-) radiolabeling assay or biotinylation of cell surface proteins, we describe here that CD43 are sulfated molecules the glycosylation of which is altered in human immunodeficiency virus type 1 (HIV-1)-infected leukemic T cells of the CEM line. Hyposialylation of O-glycans and changed substitution on N-acetylgalactosamine residues are observed. The glycosylation defect is associated with an impairment of CD43-mediated homotypic aggregation which can be restored by resialylation. The hyposialylation of CD43 on HIV-1+ cells may explain the high prevalence of autoantibodies directed against nonsialylated CD43 that have been detected in HIV-1-infected individuals. A defect in glycosylation of important molecules such as CD43 or, as we recently described, CD45 may explain alterations of T cell functions and viability in HIV-1-infected individuals. In addition, a possible implication of hyposialylation in the HIV-1-infected cells entrapment in lymph nodes could be envisioned.

Bridging the gap between adult and paediatric outcomes in HIV-1 vertically infected children: a single-centre comparison with adult data.

UNLABELLED: Prognosis of HIV-1 infection dramatically improved during the last decade. Meanwhile, treatment-induced virological success has always been different in adult and children patients. AIM: To compare 10 years of follow up in HIV-1 vertically infected children and adult patients. METHODS: Monocentric retrospective longitudinal analysis of vertically HIV-1-infected children and adult patients followed in the Nice University Hospital between 1999 and 2008. Immunological, virological and antiretroviral treatment data were recorded. RESULTS: Forty children and 1752 adult patients were included. Between 1996 and 2008, the percentage of children receiving HAART increased from 3.2% to 91%. Mean CD4% in the paediatric group remained stable between 29 +/- 8.1% in 1998 and 30 +/- 9.4% in 2008. Mean adult CD4-cell count significantly increased from 410 in 1998 to 556 cells/mL in 2008. Logistic regression analysis showed that the children-to-adult difference for indetectability (HIV PCR-RNA below 400 copies/mL) was significant (p < 0.0001) with an odds ratio of 0.61 (CI(95th): 0.52-0.72). Year-to-patient interaction was also significant with a decreasing divergence over time (p: 0.038). CONCLUSION: Nowadays as in adult patients, the control of HIV-1 replication is achieved in nearly eight of 10 children and the percentage of patients with severe immunodeficiency dramatically decreased compared with the mid 1990s.

Severe hyperhomocysteinemia and peripheral neuropathy as side effects of nitrous oxide in two patients with sickle cell disease.

Nitrous oxide (N2O) is a widely used anesthetic agent. We report two patients with sickle cell disease (SCD) who presented with complications following the use of N2O. Patient 1, a 15-year-old girl, presented severe hyperhomocysteinemia, pancytopenia, vitamin B12 deficiency, and peripheral polyneuropathy after massive use of N2O for pain management. At the 1-year follow-up, hyperhomocysteinemia and B12 deficiency had resolved, but she had persisting mild symptoms of polyneuropathy. Patient 2, a 17-year-old boy, presented only severe hyperhomocysteinemia, only partially corrected by initial B12 supplementation. Careful monitoring of N2O use, especially in patients with SCD, is mandatory to prevent complications.

[Second pregnancies in HIV-1-infected women. A prospective monocentric study]. / Secondes grossesses chez les femmes VIH-1 séropositives. Etude prospective monocentrique.

OBJECTIVES: To evaluate the influence of successive pregnancies on the materno-foetal prognosis in a population of HIV-infected women. Clinical, biological data and treatment strategies were compared during iterative pregnancies. PATIENTS AND METHODS: We conducted a monocentric prospective study between August 1995 and January 2007 in a French university hospital (Nice). RESULTS: Twenty-six HIV-infected women had two consecutive pregnancies during our study. We noticed an increase in CD4 cell count between the two pregnancies. Viral load variations were non significant. The maternal's prophylaxis changed. Percentage of HAART increased from 26 to 54%. Modes of delivery, HIV or treatments side-effects remained the same between the successive pregnancies. DISCUSSION AND CONCLUSION: Successive pregnancies do not seem to influence the materno-foetal prognosis related to HIV infection.

[A case of acquired encephalopathy in a child. A cause that we thought had disappeared]. / Un cas d'encéphalopathie acquise de l'enfant. A propos d'une cause que l'on croyait disparue.

Subacute central nervous system infection must be considered in any infant presenting with progressive encephalopathy. We present the case of an 18-month-old child with normal neuromotor development until the age of 14 months admitted for spastic hypertonia of the legs and arms associated with axial hypotonia. The mother reported that she recently had been found to be HIV-seropositive. HIV antibodies were negative during the first trimester of pregnancy. On the child's blood sample, the HIV test was positive associated with a major decrease in CD4 cell count. Viral load (ARN-PCR) was 720 copies par millilitre. On brain MRI, hypersignals were found in the white matter. HIV related encephalopathy caused by maternal fetal transmission was diagnosed. After 2 months of antiretroviral treatment (azidothymidine, lamivudine, and boosted lopinavir), the child's neurological condition improved. HIV infection must be suspected in all infants with progressive encephalopathy. The HIV test in pregnant women must be proposed at the beginning of pregnancy and repeated during the last trimester.

[Management of autoimmune thrombocytopenic purpura: a prospective study of 147 children from the regional network RHémaP]. / Purpura thrombocytopénique auto-immun: à propos d'une cohorte prospective de 147 enfants pris en charge dans le réseau d'hématologie pédiatrique des régions PACA et Corse (RHémaP).

AIM: Assessment of the impact of guidelines from a regional pediatric network to standardize the management of childhood immune thrombocytopenic purpura (ITP). MATERIALS AND METHODS: Consensus guidelines were drawn up in centers of the pediatric network for hematological diseases, RHémaP, and a cohort of children referred for ITP in these centers was set up. A 1-year follow-up was recorded for each patient over a 43-month period. RESULTS: We report data from a cohort of 147 children. At diagnosis, we recorded severe thrombocytopenia (median=8G/l) and 141 children had hemorrhagic symptoms (96%). Only 23 children had a bone marrow aspiration (BMA) at diagnosis (16.3%), which meant a high level of implementation of the RHémaP recommendations (96%) since indications of BMA were limited to rare indications. For 135 children (91.8%), treatment fulfilled the RHémaP guidelines that were mainly based on the platelet count: 121 received intraveinous immunoglobulin (IVIG) and 14 were not treated. Among those who received IVIG, 110 were good responders (91%) at the 96-h evaluation (platelet count greater than 20G/l), nine (7.4%) were poor responders, and 1 died of intracranial hemorrhage. At 6 months, chronic ITP was observed in 40 children (32.8%). Chronic ITP was associated with a higher platelet count at diagnosis and an older age (p<10(-3) and p=10(-3), respectively). CONCLUSION: The practices recorded over a 43-month period in our cohort fulfilled the RhémaP guidelines and we conclude that we managed to standardize regional practices for children with ITP. We observed conventional epidemiological characteristics in this cohort. Older children and higher platelet count at diagnosis were significantly associated with higher frequency of chronic ITP.

[6-mercaptopurine-related hand-foot syndrome in a four-year-old child]. / Syndrome mains-pieds secondaire à la prise de 6-mercaptopurine chez un enfant de quatre ans.

BACKGROUND: Hand-foot syndrome (HFS) is a dose-dependent cutaneous side effect of cytostatic chemotherapy. It has also been described under the names of acral erythema and palmoplantar erythrodysesthesia. We report a case of HFS during treatment of acute lymphoblastic leukemia with 6-mercaptopurine (6-MP) (Purinethol) in a four-year-old child. PATIENTS AND METHODS: A four-year-old boy treated for acute lymphoblastic leukemia developed dry and painful palmar and plantar erythema with fissures. The rash began three weeks after up-titration of 6-MP. There was no past history of cutaneous disease and no other potential trigger factors. The rash ceased after 6-MP withdrawal. DISCUSSION: To our knowledge, this is the first case of HFS due to 6-MP therapy in a child. 6-MP is a major reference drug for the management of acute lymphoblastic leukemia. Numerous cytostatic drugs have been involved in such eruptions.

[Polycythemia vera and JAK-2 mutation in childhood: a case report]. / Polyglobulie de Vaquez et mutation JAK-2 chez l'enfant: à propos d'une observation.

Erythrocytosis is a rare disorder in childhood and is mainly secondary to causes such as long-term chronic cardiopulmonary diseases or haemoglobin dysfunction. In some cases, polycythaemia is found when renal, hepatic or cerebellar tumours are diagnosed. Polycythemia vera (PV) is uncommon in paediatrics and usually clinical and biological features are used to diagnose and classify PV. The V617F mutation of JAK-2 has been described recently and is found in almost 90% of adult patients with PV. This mutation allows now a reliable and early diagnosis. Therapeutic management is based on phlebotomy and cytoreductive therapy. In young adults and children, interferon alpha is theoretically superior as it is effective and there is no risk of inducing leukemia. We report here a case of PV in a 10-year-old girl with the V617F JAK-2 mutation.

Multiphenotypic acute leukemias: clinicopathologic correlations and response to therapy.

Multiphenotypic acute leukemias (MAL), defined by the coexpression on most blast cells of antigens classically attributed to different lineages, remain a rare event. We isolated a series of 26 such cases from a cohort of 1565 leukemic patients whose cells were immunophenotyped at diagnosis. Markers of B and myeloid lineage (BM) were associated in 16 cases (62%), 3 coexpressed B and T markers (BT), and T-cell and myeloid antigens (TM) were found in 7 (27%). A tumoral syndrome was observed in 69% of the patients, without significant differences between the immunophenotypic subgroups. Median event free survivals in the three immunophenotypic subgroups as defined were respectively 24 months for BM-MAL, 4 months for TM-MAL and 7 months for BT-MAL respectively. The poorer prognosis of TM-MAL was significantly different from that of BM-MAL (p < 0.001). This concurred with the poorer prognosis associated with CD7 expression or absence or CD10, both characteristic features of TM-MAL.

[HIV exposure accidents in children. Experience at the emergency admission services of the CHU of Nice]. / Accidents d'exposition au VIH chez l'enfant. Expérience du service d'admission d'urgence du CHU de Nice.

UNLABELLED: Accidental exposure to human immunodeficiency virus (HIV), either by injury with a discarded syringe or after sexual abuse, increases among the children population. PATIENTS AND METHODS: The entire period of the study was seven-year. Twenty-eight children (14 males, 14 females) underwent three visits after an accidental exposure at Day 0, Day 30th and Day 90th. During each visit, a physical examination, liver enzymes, Ag P24, PCR-RNA HIV, B, C hepatitis serologies were performed. An antiretroviral prophylaxis was proposed when a high risk of HIV transmission was recognized. Anti hepatitis B globulins were administrated when no previous immunization had been made. RESULTS: The median age was 9.3 years (range: 1.5 to 16.7 years). 93% of the children consulted within 48 hours after exposure. Five of them consulted after a sexual aggression with penetration, two after a mucosus exposition and two after deep needle injuries. The source of the contamination was known in five cases. Nine patients were given an antiretroviral treatment for four weeks (seven bitherapy, two tritherapy), with no major side effects. Eighteen and 11 children were seen at the second and third visits, respectively. No case of HIV or HCV infection was observed. CONCLUSION: No case of infection after injury with a discarded syringe was found in our study. This situation differs from what is observed in health care workers, where the higher risk factor is observed. Even if no contamination was found after sexual aggression in our population, the risk of HIV is actual. This is why we propose an antiretroviral prophylaxis against HIV in only one indication, corresponding to sexual penetration.

[Maternal-fetal transmission of HIV]. / La transmission maternofoetale du VIH.

HIV infection in children is mainly the result of a mother-to-child transmission. The contamination during pregnancy is well known but intrapartum vertical transmission may also occur through ascending infection, blood exchange between mother and child, or direct contact with vaginal or cervical secretions. In addition HIV can be transmitted via breast milk. The reported rates of vertical transmission are highly variable: 14.4% in a European study, 18.3% in a French survey, 20 to 25% in the USA, 35 to 50% in Africa. It is unclear whether such a large variation of the rate of transmission is due to methodological differences or to different distributions of risk factors in the populations. There are some known predictive factors of HIV transmission such as low CD4 cells count, positive p24 antigenaemia and elevated concentrations of virus. The role of other factors is still debated: prematurity, virus (CMV, HTLV-1, HVB, HVC), C section prior labour, rupture of membranes. The prevention of HIV infection in infants is mainly based on contra-indication of pregnancy in infected women, desinfection of the vagina at the beginning of labour, early protection of the newborn by avoiding skin lesions and immediate washing, preventive treatment by zidovudin during pregnancy.

[Antiretroviral therapy and prevention of maternal-fetal transmission of HIV-1. Current and future strategies]. / Antirétroviraux et prophylaxie de la transmission maternofoetale du VIH-1. Stratégies actuelles et futures.

Azidothymidine is effective and recommended for the prophylaxis of vertical HIV transmission. Data regarding this treatment have been collected over the last decade, leading to it being widely prescribed despite the lack of information concerning its long term toxicity. Antiretroviral drug combinations administered during pregnancy appear to ensure a better protection of both mothers and their offspring. However, data available on the adverse effects of these therapies during pregnancy are scarce and mainly obtained from in vitro or animal models. Therefore there is a need for multicentric trial including long-term follow-up of exposed patients.

[Cystic papillary tumor of the pancreas: a rare etiology of abdominal mass in children]. / Tumeur kystique et papillaire du pancréas: une cause rare de masse abdominale.

BACKGROUND: Malignant pancreatic tumors are very uncommon in childhood. CASE REPORT: A 13-year-old girl was admitted for investigation of an abdominal mass with fever. Ten months earlier, clinical examination performed for similar symptoms found an epigastric mass which resolved spontaneously. Radiological investigations showed a well-encapsulated cystic tumor in the pancreas. Excision revealed a papillary cystic tumor of the pancreas. CONCLUSION: Papillary cystic tumor of the pancreas is an unfrequent cause of abdominal mass in children. Its excellent prognosis after complete excision is quite different from that of other malignant pancreatic tumors.

[Jacobsen's syndrome, thrombopenia and humoral immunodeficiency]. / Syndrome de Jacobsen, thrombopénie et déficit immunitaire humoral.

BACKGROUND: Clinical features of Jacobsen syndrome include facial dysmorphism, congenital heart defects, digit anomalies and mild to moderate psychomotor retardation. Thrombocytopenia or pancytopenia is observed in one half of patients. PATIENTS: Two unrelated children, a 6-month- and a 12-year-old, presented with a moderate thrombocytopenia associated with the clinical features of Jacobsen syndrome. Bone marrow aspirates showed, in both patients, normal cellularity with an increased number of micromegacaryocytes. Chromosome analysis showed a partial deletion of the long arm of chromosome 11. The 12-year-old patient had a history of upper respiratory airways infections with immune humoral deficiency (decreased level of IgA and IgM) which, to our knowledge, has never been reported. CONCLUSION: Jacobsen syndrome is a cause of inherited thrombocytopenia in children. Humoral immune functions must be explored in patients with a history of repeated infections.

[Type 2N von Willebrand disease (Normandy)]. / La maladie de Willebrand de type 2N "Normandie". À propos d'une observation.

Willebrand disease is the most common constitutional abnormality of hemostasis. It reflects a qualitative or quantitative abnormality of von Willebrand factor (vWF) responsible for hemorrhagic syndrome, mainly mucosal, of variable expression. Type 2N (Normandy) is a rare form of von Willebrand disease due to a qualitative abnormality of vWF that disrupts its ability to bind to factor VIII. The disease biologically combines APTT prolongation, a lower level of factor VIII, and a normal or subnormal rate of vWF, which may suggest a mild form of hemophilia A. This confusion can lead not only to a misdiagnosis but also to inappropriate treatment.

[Galactosemia associated with Rogers syndrome in a 10-month-old infant]. / Galactosémie congénitale associée à un syndrome de Rogers chez une petite fille de 10 mois.

Galactosemia and congenital Rogers syndrome or thiamine-responsive megaloblastic anemia are 2 rare inherited metabolic diseases. The combination of the 2 diseases has never been reported in the literature. We describe the case of an infant followed for congenital galactosemia since the age of 8 days, with thiamine-responsive megaloblastic anemia diagnosed at the age of 10 months. Galactosemia's symptoms occur in the first 2 weeks of life with severe liver disease. Total eviction of the galactose allows complete regression and prevention of early symptoms but does not prevent late complications. Rogers syndrome associates megaloblastic anemia, deafness, and diabetes mellitus that begin in childhood. Supplementation with thiamine allows regression of anemia and prevents the onset of diabetes at least until adolescence.