Primary cutaneous aspergillosis and idiopathic bone marrow aplasia

Abstract: We describe the case of a 9-year-old boy with idiopathic bone marrow aplasia and severe neutropenia, who developed skin ulcers under cardiac monitoring electrodes. The diagnosis of primary cutaneous aspergillosis was made after the second biopsy and culture. Imaging investigation did not reveal internal fungal infection. The child was treated, but did not improve and died 3 months after admission. The report highlights and discusses the preventable risk of aspergillus skin infection in immunocompromised patients.

Increased expression of HLA DR2 in acquired aplastic anemia and its impact on response to immunosuppressive therapy

To study the frequency of HLA DR2 status of patients with aplastic anemia and their response to immunosuppressive therapy at a tertiary care hospital. Thirty eight consecutive patients of acquired aplastic anemia were evaluated with respect to demographic features, severity of HLA DR2 status and response outcome to immunosuppressive therapy. The mean age of the patients was 24.6 years + 16.4 with a male to female ratio of 2.8:1. Positivity of HLA DR2 was markedly high in acquired aplastic anemia patients. Twenty four [65%] out of 38 patients as compared to 45 [15%] of 300 healthy controls [p<0.0001] were positive for HLA DR2. Response to immunosuppressive therapy, which included antilymphocyte globulin, cyclosporin and methylprednisolone, was available in sixteen HLA DR2 positive patients and was found satisfactory in 12/16 [75%] patients. HLA DR2 was significantly higher in patients with acquired aplastic anemia and favourable response to immunosuppressive therapy was also associated with HLA DR2 positivity

Amibas de vida libre y anemia aplástica grave en niños / Aplastic anemia and free-living amoeba in two children

Introducción. Las amibas de vida libre habitualmente viven como fagótrofas en el agua y suelo donde se alimentan de bacterias; también pueden producir infecciones del sistema nervioso central y otros tejidos en seres humanos y animales. La anemia aplástica es una entidad caracterizada por pancitopenia secundaria a disminución de la producción en médula ósea de todos los elementos formes de la sangre y ausencia de enfermedad primaria que infiltre, reemplace o anule la hematopoyesis activa. Casos clínicos. Se presentan 2 niños con historia de sangrados, pancitopenia y el diagnóstico de anemia aplástica grave por biopsia y aspirado de médula ósea, que finalmente fallecieron. Se muestran los hallazgos de amibas de vida libre en la médula. Conclusión. En estos casos no se encontró agente causal de la anemia aplástica, y se sugiere a las amibas como oportunistas del padecimiento.

Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais.

The objective of this study was to analyse human leukocyte antigen (HLA) and disease association in common blood diseases [chronic myelogenous leukemia (CML), acute nonlymphocytic leukemia (ANLL), thalassemia and severe aplastic anemia] in Thais. The subjects were patients from the Hematological Clinic, Departments of Medicine and Pediatrics, Ramathibodi Hospital who were referred for HLA typing for bone marrow transplantation (BMT) at the Histocompatibility Laboratory from March 1988 to September 1997. A total of 129 patients had complete HLA-ABC typing. The patients included 45 CML, 40 ANLL, 26 thalassemia (Thal) and 18 severe aplastic anemia (SAA). Of these, 88 patients were typed for HLA class II. The HLA class I (ABC) and II (DR, DQ) typings were performed by microlymphocytotoxicity test. It was found that HLA class I was associated with CML, ANLL and Thal, whereas, HLA class II was associated with SAA. HLA-B8 and HLA-B18 were increased in CML with R.R. values of 12.2 and 3.9, respectively, whereas, HLA-B18 was increased in ANLL with R.R. value of 4.5. In addition, HLA-DR2 and DR3 were increased in SAA with R.R. values of 3.8 and 4.8, respectively. For Thal, HLA-A2 and B46 were increased in Thal in Central Thais with R.R. values of 3.3 and 6.1, respectively, whereas, HLA-B13 was increased in Thal in Northern Thais with R.R. value of 8.5. On the other hand, HLA-B7 was absent in CML. HLA-Cw7 was decreased in CML and SAA, whereas, HLA-DR6 was decreased in ANLL and SAA. Furthermore, HLA-Cw6 was also decreased in CML, whereas, HLA-A33 and Bw4 were decreased in SAA. Although the sample size of each disease was small, the increase of HLA-DR2 was observed in SAA in Thais which was similar to other studies in different ethnic groups. These preliminary data may be useful for further study in HLA and blood disease association.

Delayed activation-induced T lymphocytes death in aplastic anemia: related with abnormal Fas system

OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS: There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal control s and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fa s antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.

Estudio inmunogenético en niños con anemia aplástica / Immunogenetic study in children with aplastic anemia

La anemia aplástica es un padecimiento en el que posiblemente haya cierta participación del sistema inmune. Con el fin de explorar esta posibilidad, en el presente trabajo, se estudiaron las frecuencias fenotípicas de los antígenos clase I y clase II del complejo principal de histocompatibilidad, en la sangre de 14 pacientes con anemia aplástica y en 100 sujetos tomados como grupo de comparación. Los pacientes mostraron tener una mayor frecuencia de los antígenos HLA-B21 (P=0.03, RM=4.04) y HLA-DR2 y HLA DR5 (P=0.002, RM=5.33). Los resultados parecen apoyar el fondo autoinmune del padecimiento y sugieren que estos antígenos puedieran servir como marcadores de la susceptibilidad para desarrollar anemia aplástica.

Inhibition of hematopoiesis by a plasma factor in a case of aplastic anemia associated with systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) may be associated with inhibition of hematopoiesis mediated by antibodies, T-cells or both. A 41-year-old woman with a five-year history of SLE treated with prednisone was admitted to Cabrini Medical Center in New York. The patient complained of fever, chills, arthralgias, general malaise, weakness and dyspnea on exertion, and showed malar rash, pallor, and a systolic ejection murmur along the left sternal border. Admission work up included a CBC with evidence of moderate pancytopenia, a normal EKG, and a normal chest X-ray. The patient's anemia was symptomatic and required a transfusion of packed red blood cells (PRBC's). Bone marrow biopsy and aspiration revealed an aplastic marrow with few hypoplastic islands of hematopoietic elements. The patient was treated with plasmapheresis, achieving immediate progress towards recovery. Bone marrow culture studies (erythroid BFU-E, and myeloid CFU-GM) were done by incubating various titers of the patient's acute phase plasma with normal bone marrow cells. This was done to determine if the patient's plasma contained any hematopoietic inhibitory activity, as has been reported in other cases. Our experiments demonstrated marked inhibition of erymathropoiesis and myelopoiesis in vitro, when various titers of the patient's plasma were included in the culture media. Control plasma produced no inhibition. These studies support the hypothesis that a circulating antibody which inhibits hematopoiesis may be produced in SLE patients with aplastic anemia, and be responsible for it

Peripheral blood lymphocyte subsets after allogeneic bone marrow transplantation: reconstitution and correlation with the occurrence of acute graft-versus-host disease.

Peripheral blood lymphocyte subsets were enumerated at regular intervals during the first year after allogeneic bone marrow transplantation (BMT) in 21 Chinese patients. Eight of these patients had acute graft-versus-host disease (GVHD) while they were assessed at the time of engraftment. Our results show in patients receiving allogeneic BMT: (1) T and NK cells were the predominant lymphocyte subsets in the early reconstitution stage while B cells were severely depleted; (2) absolute numbers of the major lymphocyte subsets normalised in 4-5 months; (3) an increased percentage of T cells that expressed the activation antigen HLA-DR and a reversed CD4:CD8 ratio were observed throughout the first 12 months after BMT; (4) patients with acute GVHD had significantly higher white cell count and NK cell percentage than those not complicated by acute GVHD.

Alteración de la distribución de subpoblaciones T en la sangre periférica de pacientes con anemia severa idiopática / Changes in distribution of T subpopulations in the peripheral blood of patients with severe idiopathic anemia

Se efectuaron estudios inmunológicos en células mononucleares de sangre periférica de 17 pacientes con diagnóstico de aplasia severa de médula ósea (AMO): a) fenotipo linfocitario; b) respuesta proliferativa a la PHA; c) valoración de la producción de interleukina 2 (IL2) y expresión del antígeno CD25 (Tac). El rango de edad fue de 4 a 25 años. De los diecisiete enfermos 15 presentaron una disminución significativa de la relación CD4/CD8 (0,72 + ou- 0,19 VN: 1,8 + ou - 0,6). La respuesta proliferativa a la PHA fue normal en el 80% y sólo 2 pacientes mostraron una respuesta disminuida. La producción de IL2 por células mononucleares estimuladas con PHA se encontró significativamente aumentada con deficiencia en la expresión del antígeno CD25. En los 2 pacientes restantes observamos una relación CD4/CD8 normal, no respuesta proliferativa a la PHA e hipoproducción de IL2. Estos datos sugieren la existencia de diferentes grupos de AMO que presentan grados de compromiso inmunológico vaiable y que podrían delinearse mediante perfiles de laboratorio. Por otra parte, la alteración en la distribución de poblaciones reguladoras, fundamentalmente a expensas de una disminución absoluta de la subpoblación CD4+ en la mayoría de nuestros pacientes, asociada a la hiperproducción de IL2 y alteración diferente de expresión del antígeno Tac sugiere la existencia de alteraciones funcionales de esta subpoblación en pacientes con AMO