Thrombotic thrombocytopenic purpura associated with everolimus use in a renal transplant patient

Thrombotic microangiopathy (TMA) in renal transplantation (RTX) generally develops during treatment with calcineurin inhibitors. We present a RTX case that developed TMA under everolimus treatment. A 40-year-old woman received a kidney allograft from her 77-year-old mother. She initially received tacrolimus, mycophenolate mofetil and steroids. She was discharged with a creatinine level of 2.2 mg/dl after treatment for a cellular rejection attack within the first two weeks after transplantation. Later on, tacrolimus was replaced with everolimus. One year later, she presented with fever and increased creatinine level (4 mg/dl), anemia and thrombocytopenia. Her peripheral blood smear revealed signs of microangiopathic hemolysis. Bone marrow examination revealed an increased number of megakaryocytes. We diagnosed the case as TMA and initiated plasma exchange, I.V. pulse steroid treatment and stopped everolimus. This approach improved laboratory and clinic abnormalities. The development of TMA after treatment with everolimus and the exclusion of other possible causes suggested TMA associated with proliferating signal inhibitors (PSIs) in our case.     

Kikuchi-Fujimoto disease: a rare but important cause of fever and lymphadenopathy in pregnant women

We report a case of Kikuchi-Fujimoto disease (KFD) in a 28-year-old pregnant woman with prolonged fever and generalized lymphadenopathy. We evaluated the patient for etiology of the fever and adenopathy, which were unresponsive to antibiotic therapy. Cervical lymph node histology showed KFD. Currently, there is scant data available regarding the course and treatment of KFD during pregnancy. We administered steroid therapy (prednisone 1 mg/kg/day) to control severe systemic and constitutional symptoms. We observed a reduction in lymph node size as well as abatement of fever and other constitutional symptoms. The patient carried the fetus to full term with no apparent adverse effect. Our experience showed that steroid therapy may be used effectively to control KFD-related symptoms after the first 16 weeks without terminating the pregnancy.     

Prognostic significance of Fas (CD95/APO-1) positivity in patients with primary nodal diffuse large B-cell lymphoma

Fas (CD95/APO-1) is a protein that is mainly related to apoptosis of lymphoid cells. The increment of Fas expression is associated with long-term survival in various malignancies. However, there are limited studies regarding the effect of Fas expression on the course and prognosis of non-Hodgkin's lymphoma. The aim of this study was to investigate the significance of immunohistochemical Fas expression on the prognosis of nodal diffuse large B-cell lymphoma. A total of 63 patients with primary nodal diffuse large B-cell lymphoma diagnosed in the Erciyes University Department of Hematology between 1990 and 2003 were included in the study. The median age of the patients was 55 years old (range 19-102 years old). The median follow-up period was 19 months (2-132 months). Histopathological sections were stained immunohistochemically and evaluated by light microscopy for Fas, bcl-2, and p53. Clinical and laboratory parameters including Fas, bcl-2, and p53 positivity, age, sex, performance status, clinical stage, presence of B symptoms, bone marrow involvement, extranodal involvement, and lactic dehydrogenase levels were evaluated to compare overall survival. Complete remission was obtained in 28 patients (44.4%) after first-line chemotherapy. Fas positivity, male gender, good performance status, clinical stage I-II, absence of B symptoms, normal lactic dehydrogenase value, and absence of bone marrow involvement were favorable prognostic factors for complete remission in statistical analysis. Multivariate analysis revealed that positive Fas expression and ECOG performance status were independent prognostic factors for overall survival. Also, Fas-positive patients had significantly prolonged progression-free survival. Immunohistochemical Fas positivity was a favorable prognostic factor for complete remission and overall and progression-free survival in primary nodal diffuse large B-cell lymphoma.     

Acute lymphoblastic leukemia associated with brucellosis in two patients with fever and pancytopenia

Brucellosis is a disease involving the lymphoproliferative system, which may lead to changes in the hematological parameters; however, pancytopenia is a rare finding. However, malignant diseases in association with brucellosis are rarely the cause of pancytopenia. Herein, two cases with fever and pancytopenia, diagnosed as simultaneous acute lymphoblastic leukemia and brucellosis are presented. Anti-leukemic therapy and brucellosis treatment were administered simultaneously, and normal blood parameters obtained. The first patient is in complete remission; the other recovered from the brucellosis, but later died due to a leukemic relapse.     

The claw paw mutation reveals a role for Lgi4 in peripheral nerve development

Peripheral nerve development results from multiple cellular interactions between axons, Schwann cells and the surrounding mesenchymal tissue. The delayed axonal sorting and hypomyelination throughout the peripheral nervous system of claw paw (clp) mutant mice suggest that the clp gene product is critical for these interactions. Here we identify the clp mutation as a 225-bp insertion in the Lgi4 gene. Lgi4 encodes a secreted and glycosylated leucine-rich repeat protein and is expressed in Schwann cells. The clp mutation affects Lgi4 mRNA splicing, resulting in a mutant protein that is retained in the cell. Additionally, siRNA-mediated downregulation of Lgi4 in wild-type neuron-Schwann cell cocultures inhibits myelination, whereas exogenous Lgi4 restores myelination in clp/clp cultures. Thus, the abnormalities observed in clp mice are attributable to the loss of Lgi4 function, and they identify Lgi4 as a new component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation.