Şebnem Yılmaz

Etanercept for therapy‐resistant macrophage activation syndrome

Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of childhood rheumatic diseases, especially systemic onset juvenile idiopathic arthritis (SoJIA). We report a 4‐year‐old girl with probable SoJIA who presented with MAS. She did not respond to pulse methyl prednisolone and Cyclosporine A (CsA). She also failed to respond to intravenous immunoglobulin (IVIG) therapy. Etanercept was started, based on the observation of increased serum levels of tumor necrosis factor‐alpha (TNF‐α) in patients with MAS. Her condition improved following etanercept, suggesting that etanercept might have a therapeutic role in resistant MAS. Pediatr Blood Cancer 2008;50:419–421.

Parvovirus B19: A cause for aplastic crisis and hemophagocytic lymphohistiocytosis†

A 17-year-old female patient with hereditary spherocytosis (HS) presented with fatigue, nausea, headache, and fever for 2 days. On physical examination, she had high fever, pallor, icterus, and mild splenomegaly. Peripheral blood examination demonstrated a Hb level of 8.2 g/dL, WBC 1.9 10/L, platelets 74 10/L,MCV88.9 fL,MCH33.9 pg, MCHC 38.1 g/dL, and reticulocyte 0.7%. The peripheral blood smear revealed 70% neutrophils, 18% lymphocytes, 10% monocytes and 2% band neutrophils, vacuolization in neutrophils andmonocytes;many spherocytes. Bonemarrow aspirate showed hypocellularity with many hemophagocytic histiocytes, giant proerythroblasts, and absence of mature erythroblasts, suggesting a parvovirus infection (Fig. 1). On the second day of hospitalization, her Hb level decreased to 5.6 g/dL. Hepatomegaly developed and splenomegaly progressed. Serum ferritin level was 7,478 ng/mL, triglyceride 1.17 nmol/L and fibrinogen 2.31 g/L. Prothrombin and partial thromboplastin time were within normal limits, but the D-dimer level was very high (3,004 mg/L). The serum folic acid levelwas normal. Parvovirus B19 IgMand IgGwas found to be positive by indirect immunofluoroscent assay. Secondary hemophagocytic lymphohistiocytosis (HLH) and aplastic crisis due to Parvovirus B19 infection was diagnosed. She received red blood cell transfusions and intravenous immunoglobulin was given for the HLH. Shewas discharged from the hospital after a marked clinical and hematological improvement on day 6 with a Hb level of 9.9 g/dL, WBC 4.8 10/L and platelets 198 10/L. Ten days later, her 13-year-old brother, who also had HS, presented with similar clinical features and Parvovirus B19 infection. He improved with red blood cell transfusions and supportive treatment. In patients with hemolytic anemia, with shortened red cell survival time and expanded marrow erythropoiesis, Parvovirus B19 infection can lead to a transient aplastic crisis. Giant proerythroblasts and absence of mature erythroblasts are characteristic findings of parvovirus infection [1–3].

ASSESSMENT OF FEBRILE NEUTROPENIA EPISODES IN CHILDREN WITH ACUTE LEUKEMIA TREATED WITH BFM PROTOCOLS

The authors overviewed 239 febrile neutropenia (FN) episodes in 82 pediatric leukemia cases treated with BFM treatment protocols. FN was observed mostly during consolidation therapy. Mucositis was the most identified focus; gram-negative microorganisms were the most identified pathogens. Five patients developed invasive fungal infections. Fever resolved after mean 5.3 days and mean antibiotic administration time was 12.7 days. Addition of G-CSF to antimicrobial therapy shortened the duration of neutropenia, but it did not affect duration of fever resolution and antibiotic administration. The duration of neutropenia, fever resolution, and antibiotic administration was significantly longer in children with acute myeloid leukemia. The authors conclude that children with acute leukemia have severe prolonged neutropenia and are in high risk. In these patients, prediction of the risk of bacteremia based on clinical and laboratory features is important for immediate empiric broad-spectrum antimicrobial therapy and for higher survival rate.

An Economic Approach to the Management of High-Quality Processes

Modern manufacturing developments have forced researchers to investigate alternative quality control techniques for high-quality processes. The cumulative count of conforming (CCC) control chart is a powerful alternative approach for monitoring high-quality processes for which traditional control charts are inadequate. This study develops a mathematical model for the economic design of the CCC control chart and presents an application of the proposed model. On the basis of the results of the application, the economic and classical CCC control chart designs of the CCC control chart are compared. The optimal design parameters for different defective fractions are tabulated, and a sensitivity analysis of the model is presented for the CCC control chart user to determine the optimal economic design parameters and minimum hourly costs for one production run according to different defective fractions, cost, time, and process parameters. Copyright

CLINICAL FEATURES, TREATMENT RESPONSES, AND OUTCOME OF CHILDREN WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA

The authors investigated demographics, clinical and laboratory features, treatment responses, and outcomes of 93 children (median age 5 years) admitted for idiopathic thrombocytopenic purpura (ITP). The therapy responses of high-dose methylprednisolone (HDMP) (n = 77) and intravenous immunoglobulin (IVIG) (n = 10) treatments were similar. None of the patients with hemorrhage died. Fifteen patients (16.1%) had progressed into chronic ITP. Seven infants had a probable relationship with vaccination; none of these infants progressed into chronic ITP. In conclusion, the overall prognosis in childhood ITP is good. The therapy responses of HDMP and IVIG treatments are similar. Also, ITP cases who havw vaccination history have a benign course.

Autoimmune lymphoproliferative syndrome: report of two cases and review of the literature

Abstract. Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease occurring in childhood. Recently, it has been shown that heritable mutations in Fas or Fas ligand genes, which regulate lymphocyte survival by triggering apoptosis of lymphocytes, are the most frequent cause of ALPS. Patients with ALPS frequently have lymphadenopathy, splenomegaly and hepatomegaly, especially at young ages. A positive result of the Direct Coombs test, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura are the most common features of autoimmunity in patients with ALPS. Elevated numbers and percentages (>1%) of double-negative (CD4–CD8–) T cells, and characteristic pathologic findings in lymph nodes or spleen are other important diagnostic features. In this report, we present the clinical, immunologic, and pathologic features of two children who were diagnosed with ALPS. The early recognition of ALPS in children with enlarged lymph nodes, hepatosplenomegaly, and autoimmune hematologic features has important diagnostic and prognostic value in avoiding expensive and time-consuming studies and unnecessary treatments. The ratio of CD4–CD8– T cells, immunoglobulin levels and the histopathologic features of lymph nodes should be rapidly determined in these patients in order to establish an early diagnosis and treatment.

A Case with Unexplained Bleeding from Multiple Sites: Munchausen Syndrome by Proxy

Munchausen syndrome by proxy (MBP) is an extreme form of child abuse where children were unnecessarily treated or investigated for medical conditions that were falsified by their caregivers. Here the authors report a 16-year-old female with the complaints of bleeding from multiple and unusual sites, including hemoptysis, hematuria, bloody tears, and bloody nipple discharge, all of which are only witnessed by her mother. Extensive investigation revealed no organic etiologies for bleeding. The diagnosis of MBP was put by a multidisciplinary team. The diagnosis of MBP must be kept in mind in conditions where there is no underlying organic pathology in a bleeding patient.

Cerebral venous thrombosis in a patient with Evans syndrome: a rare association

In this report we describe a case of extensive cerebral venous thrombosis in a patient with Evans syndrome. A 19-year-old male patient with Evans syndrome was admitted to the hospital with the complaints of headache, convulsive seizure, and vomiting. The cerebral venous thrombosis including left lateral, left sigmoid, straight sinus, and vena jugularis interna was diagnosed by cerebral magnetic resonance angiography. When the thrombosis developed, he was in hematological remission and he was not receiving any medications except lamivudine for chronic hepatitis B infection. As a genetic prothrombotic risk factor, he had heterozygous prothrombin G20210A gene mutation. His clinical and radiologic findings improved after unfractionated heparin and subsequently with coumadin therapy. On follow-up, cerebral venous thrombosis reoccurred in different localizations, but complete recanalization could be obtained with antithrombotic therapy. We present the case since the association of cerebral venous thrombosis and Evans syndrome is very rare.

RHABDOMYOLYSIS DUE TO Escherichia coli SEPSIS IN THREE PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

Rhabdomyolysis with myoglobinuria is an uncommon complication of bacterial sepsis. The authors describe three pediatric acute lymphoblastic leukemia patients who developed rhabdomyolysis during a neutropenic sepsis episode due to Escherichia coli. All of the patients needed hemodynamic supportive treatment because of septic shock. Broad-spectrum antibiotics, alkalinization, and intravenous fluid therapy was given. One patient with renal insufficiency died, despite aggressive treatment. Muscle pain and dark urine color should alert physicians to the possibility of rhabdomyolysis in immunocompromised patients with sepsis. Early and appropriate treatment is critical in these patients to prevent renal failure and shock, and for a better outcome.

Isolated myelosarcoma development in an adolescent chronic myeloid leukemia patient with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).

Additional chromosomal abnormalities are found in 5-20% of patients during chronic phase of chronic myeloid leukemia and in 60-80% preceding or accompanying blast crisis. These abnormalities are important in disease progression and, because they may occur before hematological and clinical symptoms, can be taken as a prognostic indicator. An adolescent with chronic myeloid leukemia initially presented with extreme thrombocytosis, increased megakaryopoiesis with dysmorphic features, and focal myelofibrosis in bone marrow examinations and then developed isolated myelosarcoma 1 year after onset, with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).