Lydia Kossiva

Variation of serum C-reactive protein (CRP) over time in pediatric cancer patients with febrile illness and its relevance to identified pathogen

OBJECTIVE To evaluate the correlation of serum CRP with clinical and laboratory parameters proven to be related to the cause of infection in pediatric cancer patients. METHODS We studied prospectively for a 12-month period, 37 pediatric cancer patients, who presented with 70 episodes of febrile illness (38 bacterial and 13 viral infections). At fevers onset and 48 h later, infection indices, such as CRP, WBC, ANC were measured in the peripheral blood. Moreover we calculated the change rate of CRP over 48 h [CRP/t=(CRP48h-initial CRP)/t (t=2 days)]. Cultures of biological fluids, PCR and antibody detection of infectious agents were also obtained. RESULTS When comparing patients with viral vs. bacterial infections, mean CRP levels on admission (11.0 vs. 33.1mg/L, p=0.005) and at 48 h (13.4 vs. 71.9 mg/L, p=0.0007), and CRP/t (0.9 vs. 18.8 mg/L/day, p=0.030) were significantly lower in the group with viral infection. At 48 h - follow-up, patients with positive culture had higher CRP levels (57.3 vs. 43.3mg/L, p=0.048) and higher CRP/t (15.9 vs. 7.7 mg/L/day, p=0.025), compared to those without proven infection. CRP/t at 48 h was correlated with both the fever duration (r=0.27, p=0.027) and maximum temperature (Tmax) during the febrile episode (r=0.30, p=0.013). CONCLUSIONS Single CRP values on fever initiation can differentiate between viral and bacterial infections in febrile pediatric cancer patients. Moreover the change rate of CRP over time (CRP/t) is offered as a prognostic index of bacterial infection and a marker of the total duration of fever and Tmax.

Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia.

Diamond Blackfan Anemia (DBA) is a rare congenital, bone marrow failure syndrome characterized by normochromic macrocytic anemia, reticulocytopenia and absence or insufficiency of erythroid precursors in normocellular bone marrow, frequently associated with somatic malformations. Here, we present our findings from the study of 17 patients recorded in the Greek DBA registry.

Acute renal failure in a child with thrombocytopenic purpura caused by acute Epstein-Barr virus infection after treatment with anti-D immunoglobulin.

Immune thrombocytopenia (ITP) in children is usually a benign, self-limiting disorder. An acute Epstein-Barr virus (EBV) infection usually causes atypical lymphocytosis and mild decrease in platelets. Severe thrombocytopenia is an extremely rare complication. Anti-D immunoglobulin has been used for treatment of ITP in Rh(D)-positive nonsplenectomized patients. Severe hemolysis and acute renal failure are extremely rare complications that may be aggravated by the presence of an acute EBV infection. It is believed that anti-D immunoglobulin triggers an unusual virus-induced immune response causing hemolysis. We present a 4-year-old girl with ITP caused by an acute EBV infection that developed acute kidney injury following treatment with anti-D immunoglobulin. The patient recovered completely from thrombocytopenia and renal dysfunction. Intravascular hemolysis and acute kidney injury are consistent with anti-D immunoglobulin mechanism of action. Pediatric patients treated with anti-D immunoglobulin for ITP should be closely monitored for signs and symptoms of hemolysis that may be aggravated by the presence of EBV infection leading to impaired renal function.

Deep vein thrombosis and pulmonary embolism in a child with diabetic ketoacidosis and protein s deficiency: a case report.

Introduction: Diabetic ketoacidosis (DKA) is considered a hypercoagulable state, which may be exacerbated in patients with thrombophilia and lead to thrombosis. Case Report: We report on a 5.5-year-old boy, who was admitted to the pediatric department with DKA due to newly diagnosed type 1 diabetes. Low-grade fever was reported for 6 days prior to admission and continued during DKA management, with negative septic screening. After DKA management, the child developed symptoms of iliofemoral deep vein thrombosis (DVT). A family history of protein S (PS) deficiency was revealed. He was initially treated intravenously with antibiotics and unfractionated heparin, which, after 2 days, was switched to low-molecular-weight heparin and vitamin K antagonist (VKA) due to poor anticoagulant response. On the 6th day of anticoagulant treatment, the patient presented with pulmonary embolism (PE); he continued with VKA and antibiotics, with significant clinical improvement. Prolonged fever was attributed to DVT and PE. The patient was discharged on oral anticoagulants and insulin. Conclusion: We report on a child with congenital PS deficiency and DKA who developed DVT and PE despite anticoagulant treatment. It is important in children presenting with DKA to seek thoroughly for a medical history of thrombophilia and to start early thromboprophylaxis in such cases in order to prevent a possible thrombosis.

Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children: a single-center study.

Background: Differential diagnosis of childhood infections is important. Several biochemical indices steer diagnosis toward bacterial agents, although the data are often not definitive. Hepcidin is a central component of blood iron, and ferritin alterations occur during infections. We measured hepcidin changes and evaluated ferritin to iron ratio (FIR) in patients with suspected infections. Methods: We studied 69 children with infection and an equal number of matched controls during a 3-year period. A bacterial agent was demonstrated in 17 and a viral pathogen in 52 of the patients. Hematologic and biochemical tests were performed on all children including ferritin, iron and hepcidin. FIR was calculated and receiver operating characteristic curve analysis was performed to evaluate the best FIR cutoff value to discriminate between patients and controls and between patients with bacterial infections and viral infections. Results: Hepcidin, ferritin and FIR were significantly higher and iron values significantly lower in febrile patients than its controls. Patients with bacterial infection had significantly lower iron and higher FIR than those with viral infection. FIR had high accuracy discriminating patients from controls but only moderate accuracy discriminating bacterial from viral infected patients. Conclusions: If further studies with larger samples confirm these observations, FIR could be used as an inexpensive, rapid and easily performed complementary index for diagnosis of bacterial infections.

Visceral leishmaniasis: a common cause of post-infectious febrile pancytopenia in children in an endemic area: experience of a children's tertiary hospital.

Background Visceral leishmaniasis (VL, kala-azar) is caused by Leishmania spp, a parasite that is commonly encountered in Mediterranean countries. Leishmaniasis usually presents with fever, hepatosplenomegaly, lymphadenopathy, and pancytopenia. Objectives The aim of the study was to prospectively examine the characteristics of cytopenia associated with VL and compare it with other post–infectious cytopenias observed in children with febrile illnesses. Methods We studied 112 children, aged (mean) 4.0 (SD, 3.8) years (range, 0–14 years), who were admitted to the pediatric ward because of febrile cytopenia associated with infections, during a 2-year period (March 2005 to June 2007). Study participants were investigated with measurement of acute-phase reactants, bacterial cultures, and serologic tests. Results Pancytopenia was detected in 9 (8%) of 112 patients (5 boys), with a mean age of 4.5 (SD, 3.0) years.The mean value of white blood cell was 3827 (SD, 1455)/mL; absolute neutrophil count, 1229 (SD, 655)/mL; hemoglobin, 8.3 (SD, 1.1) g/dL; and platelet count, 88,200 (SD, 20,186)/mL. All patients with pancytopenia had fever (mean duration, 8.9 [SD, 8.7] days) (maximum temperature, 39.5°C [SD, 0.6°C]) and hepatosplenomegaly (9/9), whereas 2 of 9 had lymphadenopathy. In these patients, a bone marrow aspiration was performed, and VL was detected in all 9 samples. They were treated with liposomal amphotericin B and had an excellent response rate. Pancytopenia resolved within a mean period of 17.6 (SD, 17.3) days (range, 8–60 days), and there was no relapse during a 2 years’ follow-up. Conclusions In endemic countries, leishmaniasis is the main cause of febrile pancytopenia among children in whom hematologic malignancy has been ruled out.

Weight gain in children on oxcarbazepine monotherapy.

BACKGROUND Studies of the effect of oxcarbazepine (OXC) on body growth of children with epilepsy are rare and their results are controversial. To the contrary, many studies have shown significant weight gain following valproate (VPA) treatment. PURPOSE To prospectively evaluate the effect of OXC monotherapy on growth patterns of children with epilepsy and compare it with the effect of VPA monotherapy. METHOD Fifty-nine otherwise healthy children, aged 3.7-15.9 years, with primary generalized, partial or partial with secondary generalization seizure disorder, were included in the study. Twenty six children were placed on OXC and thirty three on VPA monotherapy. Body weight (BW), height and body mass index (BMI) as well as their standard deviation scores (SDS), were evaluated prior to as well as 8 months post initiation of OXC or VPA therapy. RESULTS Eight months post OXC-treatment, BW, SDS-BW, BMI and SDS-BMI increased significantly. The increase was similar to that observed in the VPA group. An additional 15.4% of children in the OXC group and 21.2% in the VPA group became overweight or obese. The effect of both OXC and VPA therapy on linear growth did not reach statistical significance. CONCLUSION Similarly to VPA, OXC monotherapy resulted in a significant weight gain in children with epilepsy. Careful monitoring for excess weight gain along with counseling on adapting a healthy lifestyle should be offered to children on OXC therapy.

The epidemiology, clinical course and outcome of febrile cytopenia in children.

Transient infectious neutropenia of mild‐to‐moderate severity is common and resolves spontaneously within weeks. This was the first prospective study of the whole spectrum of febrile cytopenia in noncancer patients followed‐up for 2 years. It aimed to assess its aetiology, duration and outcome.

Patients with eating disorders showed no signs of coeliac disease before and after nutritional intervention.

This study assessed the presence of specific antibodies for coeliac disease in outpatients suffering from eating disorders before and after nutritional intervention. We also evaluated whether those patients should undergo regular screening for coeliac disease.

Transient Effect of Anti-cd20 Therapy in a Child With 22q11.2 Deletion Syndrome and Severe Steroid Refractory Cytopenias: A Case Report

We report on the development of steroid-refractory recurrent cytopenias in a child with 22q11.2 deletion syndrome. His first hematological complication was autoimmune hemolytic anemia at 3 months of age. Thereafter, he developed severe autoimmune cytopenias of all 3 hematological lineages with poor response to steroids and intravenous immunoglobulin. At the age of 2½ years, a course of anti-CD20 therapy (Rituximab) was given with transient hematological recovery. Because of persistent symptoms, bone marrow transplantation from a matched unrelated donor was performed. Although the data in the use of anti-CD20 therapy in children with 22q11.2 deletion syndrome and autoimmune cytopenias are limited, our experience suggests its potential benefit.