Search

Unlabelled: Castleman disease is a distinct lymphoproliferative disorder of unknown origin. Seven new cases in children are reported here and 76 cases from the paediatric literature are reviewed. The disease has been reported in 46 females and 37 males, their age ranging from 2 months to 17 years. The disease was localized in 72 cases and multicentric in 11 cases. The hyalinovascular type was more frequently encountered (54%) than the plasma cell type (24%). Laboratory abnormalities were more often associated with the plasma cell type and were mainly represented by anaemia and hypergammaglobulinaemia. Treatment of the localized tumour consisted of surgical excision, whereas treatment of the multicentric form was medical, comprising prednisone and other immunosuppressor drugs. The disease in the paediatric population seems to have a more favourable course than in adults., Conclusion: The paediatric features of the disease suggest that Castleman disease in this population could represent an earlier form of the pathology or even suggest a benign lymphoproliferative disorder.

We retrospectively analyzed the bone marrow (BM) smears of 10 children with mitochondrial cytopathies. Light microscopic examination showed large and coalescent cytoplasmic vacuolization of some BM precursors in nine cases, including two children with normal peripheral blood counts and four with sideroblastic anemia. BM ultrastructural study showed abnormal mitochondria in the erythroid lineage in all three children studied. Ultrastructural studies in two cases revealed a population of giant mitochondria with abnormal ultrastructure coexisting with a population of normal mitochondria in proerythroblasts, basophil erythroblasts, and less commonly in more mature erythroblasts. In a third child, mitochondria were normal in size with cristae either absent or exhibiting abnormal longitudinal orientation. Heteroplasmic segregation of mitochondria during cell division could account for the finding of a double population of cells on ultrastructural examination. These features suggest that cytologic and ultrastructural BM examination could be useful for the diagnosis of mitochondrial disorders. That is, when large and coalescent cytoplasmic vacuoles of BM precursor cells are present, the clinician should search for mitochondrial cytopathy in a child with unexplained cytopenia(s).

Background: Benign intracranial hypertension is due to an increased intracranial pressure of unknown cause. The initial symptoms, complications and associations with medical conditions are discussed., Case Report: A 6-year-old girl developed symptoms of benign intracranial hypertension following reduction of oral corticosteroid therapy. Laboratory studies and head-computed tomographic scan were normal. Examination of the optic discs showed bilateral papilledema and the cerebrospinal fluid pressure was increased. The patient was given prednisone therapy 1 mg/kg daily initially, associated with acetazolamide, and removal of 25 mL of cerebrospinal fluid. All the symptoms resolved and the treatment was gradually decreased. The child developed no further visual failure., Conclusion: Benign intracranial hypertension with the risk of permanent visual loss is a complication underrecognized in children. All patients receiving large doses of the corticosteroids who complain of headache or blurring vision, particularly following a reduction of corticosteroid dosage, should have an ophtalmoscopic examination to exclude this complication.

Porphyrias, a group of inborn errors of heme synthesis, are classified as hepatic or erythropoietic according to clinical data and the main site of expression of the specific enzymatic defect. Hereditary coproporphyria (HC) is an acute hepatic porphyria with autosomal dominant inheritance caused by deficient activity of coproporphyrinogen III oxidase (COX). Typical clinical manifestations of the disease are acute attacks of neurological dysfunction; skin photosensitivity may also be present. We report a variant form of HC characterized by a unifying syndrome in which hematologic disorders predominate: harderoporphyria. Harderoporphyric patients exhibit jaundice, severe chronic hemolytic anemia of early onset associated with hepatosplenomegaly, and skin photosensitivity. Neither abdominal pain nor neuropsychiatric symptoms are observed. COX activity is markedly decreased. In a first harderoporphyric family, with three affected siblings, a homozygous K404E mutation has been previously characterized. In the present study, molecular investigations in a second family with neonatal hemolytic anemia and harderoporphyria revealed two heterozygous point mutations in the COX gene. One allele bore the missense mutation K404E previously described. The second allele bore an A-->G transition at the third position of the donor splice site in intron 6. This new COX gene mutation resulted in exon 6 skipping and the absence of functional protein production. In contrast with other COX gene defects that produce the classical hepatic porphyria presentation, our data suggest that the K404E substitution (either in the homozygous or compound heterozygous state associated with a mutation leading to the absence of functional mRNA or protein) is responsible for the specific hematologic clinical manifestations of harderoporphyria.

Sideroblastic anemia associated with vacuolization of haemopoietic precursors can be observed in some constitutional diseases associated with mitochondrial DNA deletion. In this condition, it is the haematological expression of a multi-tissue disorder. Haemopoiesis is polyclonal, without abnormality of nuclear DNA differing from the acquired idiopathic sideroblastic anemias which arise from a clonal transformed stem cell. This model of childhood polyclonal myelodysplasia can be observed in others myelodysplasias associated with constitutional polymalformative syndromes.

We report four cases of Noonan syndrome associated with chronic myelomonocytic leukemia in childhood. These children shared some hematologic features: thrombocytopenia, splenomegaly in the first months of life, occurrence of chronic myelomonocytic leukemia without abnormalities of the initial bone marrow karyotype, and, in three cases, improvement of the hematologic disease. A common pathophysiologic process in such patients is suggested.

Background: Effectiveness of subtotal splenectomy, a procedure recently advocated as an alternative treatment to total splenectomy for patients with hereditary spherocytosis (HS), has been evaluated., Methods and Patients: Eighty-eight patients (74 children) with HS were included in this series. Clinical presentations ranged from asymptomatic cases to severe transfusion-dependent forms. Stunting of growth occurred in four cases; chronic fatigue was observed in 30 cases and cholelithiasis in 21 cases. Among the red cell indices measured by laser light scattering on Technicon H2, the most reliable for diagnosis was the abnormal percentage of hyperdense red cells (98% of HS patients). Osmotic gradient ektacytometry, used to measure membrane deformability and impairment of maximal deformability due to a reduction of erythrocyte surface, always showed the characteristic curves of HS., Results: Subtotal splenectomy was performed in 24 patients leading to a remnant spleen of about 25% of normal for age volume. This decreased the hemolytic rate while adequately sustaining the phagocytic function of the spleen (assessed by percentage of "pitted erythrocytes" and technetium 99n scans of the remnant). However, the observed reduction in hemolytic rate was not as extensive as that observed after total splenectomy (six cases) and subtotal splenectomy did not entirely prevent risk of cholethiasis (three cases)., Conclusion: This subtotal splenectomy (+/-cholecystectomy) has to be particularly considered for children with transfusion-dependent forms of HS, in order to obtain the benefits of increased hemoglobin levels without the pending risk throughout life of overwhelming post-splenectomy infections.

Myelodysplastic syndromes (MDS) in children constitute a heterogeneous disorder, including 'primary' MDS and MDS associated with constitutional abnormalities. The Franco-American-British (FAB) cytological classification for adults can be applied for childhood in 50 to 100% of the cases. The transformation into acute myeloblastic leukemia often occurs, but stabilisation or spontaneous regression of the disease may also be observed. The therapeutic decision is difficult because there is no predictive factor of the course of the disease. Allogenic bone marrow transplantation is the best curative option when treatment is necessary.

Unlabelled: This report documents the occurrence of a nephrotic syndrome in five children with Hodgkin disease. In two cases the nephrotic syndrome predated the diagnosis of lymphoma by 6 months and 12 months respectively, while in the other three, the two disorders occurred simultaneously. The nephrotic syndrome resolved in four cases during effective treatment for active Hodgkin disease, while proteinuria remained unchanged in the fifth case with partial control of the lymphoma. The occurrence of a nephrotic syndrome as a manifestation of active Hodgkin disease suggests that some immunological abnormalities play a role in the pathogenesis of the association., Conclusion: The possibility of glomerular dysfunction although rare must be considered and actively looked for in all cases of Hodgkin disease. Similarly, any unusual sign or symptom noted in patients with nephrotic syndrome, particularly receiving or having received immunosuppressants, requires thorough investigation to determine the presence or absence of lymphoma.

Total splenectomy eliminates the splenic destruction of erythrocytes with impaired deformability. However, concern has increased over the lifelong risk of overwhelming postsplenectomy infections in splenectomized patients, a risk reduced but not totally suppressed by appropriate prophylaxis. Partial splenectomy, as long as 80% to 90% of the enlarged spleen is removed and less than 25% of the normal spleen volume is retained, is a logical alternative, both preserving the phagocytic and immune function of the spleen and decreasing erythrocyte destruction. A 12-year experience has shown that subtotal splenectomy is efficient in decreasing hemolysis, although to a lesser extent than total splenectomy, with sustained results over years in most patients, and indirect evidence argues for the integrity of phagocytic function. Such a surgical procedure should be considered in transfusion-dependent infants with hereditary spherocytosis and in older patients with erythrocyte membrane defects, provided further follow-up confirms the experience of the past 12 years.

Myelodysplasia in childhood can be associated with constitutional abnormalities. Two main situations can be observed: constitutional diseases such as Down's Syndrome may be the first step of a malignant stem cell transformation leading to monoclonal hematopoiesis. However, in other situations such as mitochondrial cytopathies or other polymalformative syndromes, myelodysplasia may simply be the hematological expression of a multi-tissue constitutional disease. In such cases, the bone marrow karyotype is usually found to be normal and, in affected females, clonality studies show a polyclonal pattern. Clonality assessment should be, when possible, a mandatory step before any major therapeutic decision during the course of childhood myelodysplasia.

Background: Hematological changes are uncommon in childhood sarcoidosis., Case Report: Case 1. This patient developed severe hemolytic anemia associated with splenomegaly at the age of 11 months. A second episode of hemolysis was seen at the age of 6 years; it was associated with thrombocytopenia and hypogammaglobulinemia. A partial splenectomy permitted histological diagnosis of sarcoidosis that was confirmed by elevated angiotensin-converting enzyme level, and subsequently developement of pulmonary involvement. Case 2. This boy suffered from autoimmune hemolytic anemia and thrombocytopenia associated with splenomegaly at the age of 3 years. At the age of 7 years, he had splenomegaly, enlarged cervical and lomboaortic lymph nodes and hypogammaglobulinemia. Diagnosis of sarcoidosis was made from lymph nodes and spleen biopsies after splenectomy; the patient had increased angiotensin-converting enzyme concentration, and subsequently developed specific renal involvement., Conclusion: Association of hemolytic anemia, thrombocytopenia, hypogammaglobulinemia and splenomegaly should suggest the diagnosis of sarcoidosis and could be considered as part of the disease spectrum.

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as 'primary' (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the fur girls studied exhibited a polyclonal pattern of X-inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues. This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.

Objective: Recall the main elements suggesting the diagnosis of hyperimmunoglobulinemia D based on a family case of chronic urticaria., Case Report: A boy and his mother presented the same signs of urticaria, fever and joint pain. Laboratory results showed an inflammatory syndrome in both. In the child, the first manifestations occurred during the age of one year. Hyperimmunoglobulinemia D was confirmed by persistently high serum levels., Conclusion: The diagnosis of hyperimmunoglobuliemia D can be entertained in a child in a family with chronic urticaria. Fever, joint pain, digestive disorders and enlarged lymph nodes are suggestive and the diagnosis is confirmed by a clear elevation of serum IgD.

We report two cases of childhood myelodysplasia (MDS) related to a mitochondrial (mt) cytopathy that illustrate the difficulty in recognizing such disorders in patients with solely haematological signs. Both patients have refractory anaemia with ring sideroblasts and vacuolization of haemopoietic precursors. These cytological features are similar to those observed in Pearson's disease, recently identified as a mitochondrial disease, and are strongly suggestive of a mitochondrial enzyme defect. The diagnosis of mitochondrial cytopathy was established on Southern blotting of mt DNA, showing a mt DNA deletion, or on the impairment of the respiratory chain enzyme activities. The absence of cytogenic abnormalities, and the polyclonal pattern of peripheral neutrophil and lymphocyte fractions, suggest that, in mt cytopathies, MDS cannot be considered as a truly malignant disorder.

The authors report a case of septic venous sinus thrombosis (VST) and meningitis occurring as an early complication of mastoiditis caused by Fusobacterium necrophorum. CT scan was normal, and cerebral angiography was required to diagnose the VST. The evolution was favourable with appropriate antimicrobial therapy and steroids.

Even in endemic zones, congenital malaria, first described in 1876, is rarely encountered. The incidence has greatly increased however over the last 10 years suggesting several diagnostic problems. We observed a case of infected twins born to an asymptomatic mother which would throw some light on the pathophysiology involved in congenital transmission. A 2-month old infant was hospitalized for surgical cure of an umbilical hernia. Haemolytic anaemia (6.3 g/dl) and fever (39 degrees C) were observed during the postoperative period. A wide spectrum antibiotherapy was prescribed but the temperature remained at 39 degrees C. A blood swab cultured one week after the operation revealed Plasmodium falciparum. The infant's twin sister was in apparently good health but was also found to be anaemic (6.1 mg/dl Hg) and a blood sample was positive for P. falciparum. For the mother, the search for parasites was negative. Serology tests performed at diagnosis revealed anti-P. falciparum antibodies at 1/1600, 1/3200 and 1/6400 in the infant, his twin sister and the mother. Outcome was favourable. The mother had arrived in France from Togo 14 months earlier and had not returned to an endemic zone. She had had frequent episodes of fever in Togo and had taken quinine, but no episode of fever had occurred during the pregnancy or delivery. This twin case of vertical mother-infant transmission is the equivalent to transfusional malaria since red cells pass the placental barrier near the end of pregnancy, even when no placental lesion exists. Congenital transfusional malaria must however be dissociated from congenital infective malaria resulting from early primoinfection in endemic areas.

Seven patients with glycogen storage disease type Ib suffering from severe and/or recurrent bacterial infections were treated with glycosylated recombinant G-CSF (Lenograstim). Mean follow up was 20.8 months (range 9-30 months). In all cases a median dose of 5 micrograms/kg/day resulted in rapid clinical improvement, associated in 6/7 with an increase in absolute polymorphonuclear (PMN) count. In the remaining subject, a striking amelioration of infectious status contrasted with a persistently low PMN count. Liver transplantation in one patient resolved metabolic complications but did not improve PMN count or the infectious status, while neutropenia was corrected by G-CSF. Prevention of recurrent infections was achieved in all cases with intermittent therapy. Short term treatment was well tolerated, thrombocytopenia in two patients (WHO grade 0 and grade 3) recovering after decrease of G-CSF dosage.

Myelodysplastic syndromes are clonal haemopathies known to exist in elderly people where they are classified into 5 categories: refractory anaemia, acquired idiopathic sideroblastic anaemia, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts undergoing acute transformation, and chronic myelomonocytic leukaemia. Transformation into acute leukaemia is frequent. These syndromes seem to be rarer in children, but they are often misdiagnosed. Some of their forms are particular to childhood. They include association with constitutional blood diseases predisposing to acute leukaemia, or with congenital or non-congenital malformative syndromes; there are hypoplastic forms, forms evolving towards stabilization of haematological abnormalities, and border forms with certain myeloproliferative syndromes. The diagnosis of myelodysplasia rests on morphological, functional, biochemical, isotopic data reflecting inefficient haematopoiesis, and on cytogenetic data. Studies of clonality and malignancy markers will in the near future enable us to distinguish between true preleukaemic states and polyclonal constitutional or virus-induced myelodysplasias, probably more frequent in children. The choice of treatment depends on the severity of the myelodysplastic syndrome, defined by the initial partial blastosis, the presence of cytogenetic anomaly and the certainty of clonality. In cases with poor prognosis, early bone marrow allograft is the only possible treatment.

A case of cerebral sarcoidosis of fortuitous discovery is reported in an adolescent. Neurosarcoidosis is exceedingly rare in the pediatric age groups. Clinical manifestations are widely variable and nonspecific, making diagnosis difficult in patients without extraneurologic involvement. The mainstay of management is early, prolonged corticosteroid therapy. Outcome varies with location of the lesions.

Background: As in adults, myelodysplastic syndromes in children are often preleukemic and their spontaneous remission is exceptional., Case Reports: Case 1. A girl, aged 8 years, developed pancytopenia with macrocytic anemia. The myelogram and bone marrow biopsy showed dyserythropoiesis with macroblastosis, but without sideroblasts. The chromosome configuration was normal and the negative results of other investigations led to the diagnosis of refractory anemia without any known cause. Bone marrow transplantation was considered, but a spontaneous remission intervened and has persisted for 3 years. Case 2. A girl, aged 5 years, was investigated for worsening of a macrocytic anemia that had been present for 3 years, without changes of granulocytes and platelets. The myelogram showed dyserythropoiesis with megaloblastosis and sideroblasts. No known cause could be identified. As for the preceding patient, a spontaneous remission occurred, and has persisted for 3 years. Case 3. A girl, aged 5 months, developed pancytopenia. The myelogram showed dys-megakaryocytopoiesis. All hematologic data spontaneously normalized after 1 year, and have remained so 1 year later., Conclusion: The spontaneous remission, that has occurred in our 3 patients, has been reported in one only adult. This possibility precludes considering all the myelodysplastic syndrome in children as preleukemic, and suggests that bone marrow transplantation is not urgent in these situations.

Three children with Kawasaki disease had liver biopsies because of evidence of hepatic disease. Cholangitis or bile duct injury and proliferation were found. Similar damage to the hepatic ductular system may explain the hydrops of the gallbladder sometimes seen in this disease.

The authors report two cases of splenic and hepatosplenic candidiasis occurring during a protracted neutropenia induced by chemotherapy for acute leukemia (lymphoblastic and myeloblastic respectively). Fungal infection was revealed by persistent or recurrent fever after correction of neutropenia. Diagnosis was suggested by findings at abdominal ultrasonography. It was confirmed by histological analysis which, in the first case, required open liver biopsy. In both cases, lack of improvement of splenic lesions despite treatment with Amphotericin B followed by fluconazole led to splenectomy. Both patients received postoperative anti fungal therapy with Ampho B and at one year's follow up, the patient who had the hepatosplenic candidiasis seems to have recovered.

We describe the development of transversal white bands on all the nails in a three-year-old receiving chemotherapy for leukemia. The various nail changes reported during anti-cancer chemotherapy are reviewed.

The anaemia most frequently encountered in paediatrics is iron deficiency anaemia. The deficiency may be latent or patent. It may be responsible for repeated infections and interfere with the child's psychomotor development. The disease is most often due to a low intake of dietary iron, and it can be prevented by supplementing the mothers during pregnancy and by an adequate diet. Folic acid and vitamin B12 deficiencies are much rarely encountered. Vitamin E deficiency may result in haemolysis, notably in premature infants.