Association of paediatric autoimmune cytopenia and inflammatory bowel disease suggests a common genetic origin.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.

[Transfusion and its specific problems in pediatrics and neonatology]. / La transfusion et ses problématiques particulières en pédiatrie et néonatologie.

Principles of transfusion strategy have been used for neonates and children similar to adults. However, due to substantial discrepancies between physiology/pathology in children and in their adult counterparts, decisions, indications, and doses are different from those of adults, especially in neonates. Specific data and practice guidelines for blood product transfusion are reported owing to the experience of pediatrics and neonatology units and partners of the French Blood product bank.

Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

[Campylobacter infections in children]. / Infections à Campylobacter chez l'enfant.

Campylobacter infections are essentially enteric infections frequently occurring before 15 years of age. The main species responsible for these infections is Campylobacter jejuni. The infection is observed mainly during summertime, and boys are more often affected than girls. The transmission is usually food-borne (poultry or cross-contamination of raw food). Environmental contamination is also possible. In addition to the digestive symptoms, systemic infectious complications or postinfectious complications (joints, neurological) can occur. The infection is more severe in immunosuppressed patients. Conventional diagnosis by culture is now challenged by molecular and immunoenzymatic methods, which have greater sensitivity. An adapted antimicrobial treatment improves the digestive symptoms. A dual antibiotic therapy is necessary in case of systemic infection or secondary localization of the infection.

Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.

Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective. Because both methods of administration provide similar efficacies, a cost-minimization analysis was performed. First, costs were calculated through a simulation testing different hypothesis on costs drivers. Secondly, costs were estimated on the basis of field data collected by a questionnaire completed by a population of patients suffering from agammaglobulinaemia and hyper-immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented. Results of the simulation showed that direct medical costs ranged from 19 484 euro for home-based IVIG to 25 583 euro for hospital-based IVIG, with home-based SCIG in between at 24 952 euro per year. Estimations made from field data were found to be different, with significantly higher costs for IVIG. This result was explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While the theoretical model showed very little difference between SCIG and hospital-based IVIG costs, SCIG appears to be 25% less expensive with field data because of lower doses used in SCIG patients. The reality of the dose difference between both routes of administration needs to be confirmed by further and more specific studies.

[Chronic exanthema in a child with congenital rubella]. / Exanthème chronique chez un enfant atteint de rubéole congénitale.

BACKGROUND: Since congenital rubella has become extremely uncommon following the introduction of rubella vaccination, cutaneous signs are currently rarely reported. PATIENTS AND METHODS: An infant, presenting congenital rubella (seroconversion of the mother for rubella at 11 weeks' amenorrhoea), presented diffuse exanthema between the ages of seven and 24 months. In a setting of congenital rubella syndrome, the infant presented psychomotor retardation, deafness, hypoplasia of the pulmonary artery and under-nourishment. Humoral and cell-mediated immunodeficiency was also noted. DISCUSSION: The cutaneous signs of congenital rubella were first described in the 1960s and 1970s; they are rare and appear after a symptom-free period before resolving spontaneously several months later. Standard findings include chronic exanthema of the face and extremities associating reticulated erythema and pigmented macular papules. Exanthema indicates chronic and persistent viral infection, a common situation in newborn babies and infants following maternal-foetal infection. The persistence of viral infection in infants is attributed to immature cellular immunity, which would otherwise either eradicate the virus or ensure passage to the latency phase. In the present case, there was also relative humoral immunodeficiency resulting from foetal rubella infection. The symptom-free interval before the onset of rash and other clinical signs may be due to the relative transient protection afforded by the presence of maternal immunoglobulines G.

[Evans' syndrome: a retrospective study from the ship (French Society of Pediatric Hematology and Immunology) (36 cases)]. / Syndrome d'Evans: étude rétrospective de la société d'hématologie et d'immunologie pédiatrique (36 cas).

UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.

Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit--multicenter studies of the French LAME (Leucémie Aiguë Myéloblastique Enfant) Cooperative Group.

From 1989 to 1998, 341 children were included in the French multicentric LAME (Leucémie Aiguë Myéloblastique Enfant) trials. A total of 309 children were registered in the LAME 89/91 protocol. This intensive regimen included an induction phase (mitoxantrone plus cytarabine), two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase and amsacrine; 276 (90%) achieved a CR. The 5-year overall survival (OS) and event-free survival (EFS) were 60+/-4 and 48+/-4%, respectively. From 1997, timed-sequencing of the LAME SP induction chemotherapy led to an unacceptable frequency of consolidation delay; future improvements are unlikely to come from further increases in intensity. The role of allogenic bone-marrow transplantation from an HLA-identical sibling in CR1 was examined. The disease-free survival (DFS) was 52+/-4% for non-allografted patients and 57+/-7% for allografted patients (P=NS); a better OS for allografted patients was shown and could be related either to allo-BMT early in CR1 or to a second allo-BMT in CR2. For the complete responders after consolidation therapy, the 5-year OS was significantly better in patients randomized for no maintenance therapy (MT-) than in patients randomized for MT (77.6+/-8 vs 59+/-8%; P=0.05), while the 5-year DFS was not significantly different. Exposure to low-dose MT might contribute to clinical drug resistance and treatment failure in relapsing patients.

Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children.

We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.