Hemophagocytic lymphohistiocytosis as a presentation of inflammatory bowel disease / Linfohistiocitosis hemofagocítica como presentación de la enfermedad inflamatoria intestinal

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is considered a medical emergency that should be recognized in patients with fever, splenomegaly, and progressive deterioration of the general condition. Laboratory findings include cytopenia, hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. For HLH diagnosis, it is essential, although not mandatory, to perform a bone marrow biopsy. Given its nature, secondary causes of HLH should be sought, mainly infections, hemato-oncological disorders, autoimmune diseases, and auto-inflammatory conditions. Case report: We present the case of a female adolescent who presented with fever and lower gastrointestinal bleeding. Upon admission, acute liver failure and pancytopenia were documented. A bone marrow aspirate was performed, which revealed hemophagocytosis; other tests confirmed HLH diagnosis. During the diagnostic approach, inflammatory bowel disease was diagnosed. The patient received first-line treatment with an adequate response. Conclusions: Inflammatory bowel disease can be considered a cause of secondary HLH, particularly in patients with suggestive symptoms, such as digestive bleeding in the absence of other secondary causes of HLH.

Resumen Introducción: La linfohistiocitosis hemofagocítica (LHH) es considerada una urgencia médica que debe reconocerse en pacientes con deterioro progresivo del estado general, fiebre, pancitopenia y esplenomegalia. Los hallazgos de laboratorio incluyen citopenia, hipertrigliceridemia, hipofibrinogenemia e hiperferritinemia. Para su diagnóstico es importante, aunque no obligatoria, la realización de aspirado de médula ósea. Dada su naturaleza, se deben buscar causas secundarias de LHH, principalmente enfermedades infecciosas, hematooncológicas, autoinmunitarias y autoinflamatorias. Caso clínico: Se presenta el caso de una adolescente que inició con fiebre y sangrado digestivo bajo. A su ingreso, se documentó falla hepática aguda y pancitopenia. Se realizó aspirado de médula ósea y se encontró hemofagocitocis; el resto de los exámenes concluyeron LHH. Durante su abordaje se diagnosticó enfermedad inflamatoria intestinal. La paciente recibió tratamiento de primera línea con adecuada respuesta. Conclusiones: La enfermedad inflamatoria intestinal puede considerarse como una causa secundaria de LHH, en particular en pacientes con clínica sugestiva, como es el sangrado digestivo, en ausencia de otras causas secundarias de LHH.

Infecção por parvovírus B19 em receptores de transplante renal: série de caso / Parvovirus B19 infection in kidney transplant recipients: a case series

Os receptores de transplante renal são mais suscetíveis a infecções, entre elas o parvovírus B19, que pode ser transmitido por via respiratória, adquirido por meio do enxerto ou por reativação de infecção latente. A anemia normocítica normocrômica, com diminuição dos reticulócitos e resistência ao tratamento com eritropoietina, é a principal forma de apresentação da infecção por parvovírus B19 em transplante renal. O diagnóstico requer alto índice de suspeição clínica e realização de testes diagnósticos selecionados. Tratamento com imunoglobulina e suspensão dos imunossupressores durante a infecção mostraram-se eficazes. Os autores relatam sua experiência com cinco casos de infecção por parvovírus B19 em receptores de transplante renal de um hospital universitário. Os aspectos clínicos, diagnósticos e terapêuticos são revistos.

Kidney transplant recipients are more susceptible to infections, including by parvovirus B19, spread through the respiratory tract, acquired through the graft or reactivation of latent infection. Normocytic normochromic anemia, with decreased reticulocytes and resistance to erythropoietin treatment, is the most common presentation of Parvovirus B19 infection in renal transplant. Diagnosis requires a higher clinical suspicion and the performance of selected diagnostic tests. Treatment with immunoglobulin and suspension of immunosuppressive therapy during the infection may be effective. The authors report five cases of PB19 infection in kidney transplant patients at a hospital. The clinical, diagnostic, and treatment features are reviewed.

Pancitopenia y aplasia medular asociada a abatacept en una paciente con Artritis Reumatoide / Pancytopenia and medular aplasia associated to abatacept in a patient with rheumatoid arthritis

El tratamiento de pacientes con artritis reumatoide (AR) debe ser temprano y agresivo para prevenir el daño articular y la discapacidad. Los fármacos no biológicos modificadoes de enfermedad, como el metotrexato, han sido utilizados par controlar la actividad de la enfermedad y para prevenir el daño de las articulaciones. Existen pacientes con AR resistentes al tratamiento con fármacos modificadores de la enfermedad y otros que no responden adecuadamente a la terapia con inhibidores de factores de necrosis tumoral. Nosotros describimos el caso de una paciente de sexo femenino de 77 años que se presentó al servicio de emergencias con fiebre, mucositis y mal estado general luego de recibir una dosis de abatacept. A su ingreso el laboratorio demostró: glóbulos blancos 500 cel/mm3, neutrófilos 150 cel/mm3, plaquetas 21000 cel/mm3, hematocrito 29%, VCM 81, LDH 314 UI/L, función renal y hepatograma normales. En el examen clínico se objetivaron ulceras y lesiones ampollares en mucosa yugal. El medulograma evidenció hipocelularidad, con disminución de las tres series. El informe anatomopatológico fue de médula ósea hipoplásica. Recibió tratamiento con factor estimulante de colonias de neutrófilos, ácido fólico y metilprednisona, con resolución del cuadro a los 3 días de instituido el tratamiento. Hasta nuestro conocimiento esta es la primera comunicación de pancitopenia asociada a abatacept es una paciente con artritis AR intolerante a metotrexato

Treatment of patient with rheumatoid arthritis (RA) should be early and aggressive to prevent joint injury and disability. Disease-modifying antirheumatic drugs (DMARDs) like methotrexate has been used as initial treatment toward the disease activity and to prevento joint damage. Some patients with RA are resistant to initial therapy with nonbiiologic DMARDs or TNF inhibitiors. We described a 77 years old women who presented to the emergency room with fever andoral lesions after been treated with abatacept. On examination patient appeared ill. She had oral ulcers. laboratory testing showed white cells count 500 cells per mm3, hematocrit 29 %, platelets count 21000 cells per mm3, LDH 314 U/l. Renal and liver functions were normal. Bone marrow showed decreased in the three cells lineages. Patient was treated with granulocyte colony-stimulating factor, folic acid, and prednisone. Patient improved her physical and laboratory features three days after admission. This case showed the rare association between pancytopenia and abatacept in a patient with RA

Pancitopenia em pacientes com anemia perniciosa. Estudo descritivo de 33 casos. / Pancytopenia in patients with pernicious anemia. Descriptive study of 33 cases.

Objetivo: Discriminar as variáveis de sexo e idade nos pacientes com anemia perniciosa; estudar seu perfil hematimétrico; verificar a prevalência de outras doenças autoimunes e anemia perniciosa; analisar a incidência da pancitopenia e sua relação com alterações laboratoriais comum na doença; e avaliar a frequência dos autoanticorpos anticélulas parietais e antifator intrínseco. Métodos: Estudo transversal descritivo, de base clínica e laboratorial, de 33 prontuários de pacientes com anemia perniciosa, diagnosticados em um ambulatório de hospital terciário de atenção à saúde, no período de junho de 2009 a junho de 2014. Para analisar a relação da presença e da ausência de pancitopenia com os níveis da enzima lactato desidrogenase e vitamina B12, foi utilizado o teste qui quadrado. O programa utilizado foi o software Epi Info, versão 7. Resultados: Na amostra, 63,6% eram mulheres, e a idade média geral foi de 47,3 anos. Doenças autoimunes estavam associadas em 30,3% dos pacientes. A pancitopenia esteve presente em 39,4% dos pacientes. Houve significância estatística na relação da pancitopenia com os níveis de enzima lactato desidrogenase (p<0,05). A prevalência do antifator intrínseco foi de 69,7% e dos autoanticorpos anticélulas parietais foi de 72,7%. Conclusão: A pancitopenia mostrou-se um achado significante na população com anemia perniciosa, assim como níveis elevado de LDH, acrescentando a anemia perniciosa como um diagnóstico diferencial de tais alterações laboratoriais.(AU)

Objective: To discriminate the gender and age variables in patients with pernicious anemia; to study erythrocyte profile; to check the prevalence of other autoimmune diseases and pernicious anemia; to analyze the incidence of pancytopenia and its relationship with common laboratory abnormalities in the disease; to evaluate the frequency of anti-gastric parietal cell antibodies, and anti-intrinsic factor antibodies. Methods: Descriptive, cross-sectional study of clinical and laboratorybased medical records of 33 patients with pernicious anemia diagnosed in an outpatient's department of a tertiary healthcare center, in the period between June 2009 and June 2014. To analyze the relationship between the presence and absence of pancytopenia with levels of lactate dehydrogenase enzyme and levels of Vitamin B12 we used the chi-squared test. The software used was Epininfo version 7. Results: The sample showed 63.6% women and 36.4% men with a mean age of 47.3 years. Autoimmune diseases were associated in 30.3% of the patients. Pancytopenia was present in 39.4% of patients. There was statistically significant relationship of pancytopenia with lactate dehydrogenase enzyme levels (p <0.05). The frequency of anti-intrinsic factor antibodies was 69.7%, and the antigastric parietal cell antibodies was 72.7%. Conclusion: Pancytopenia proved to be a significant finding among the population with pernicious anemia and high levels of LDH, which includes pernicious anemia as a differential diagnosis of such laboratory alterations.(AU)

Revesz syndrome

Revesz syndrome is a rare variant of dyskeratosis congenita and is characterized by bilateral exudative retinopathy, alterations in the anterior ocular segment, intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure, cerebral calcification, cerebellar hypoplasia and psychomotor retardation. Few patients with this syndrome have been reported, and significant clinical variations exist among patients. This report describes the first Brazilian case of Revesz syndrome and its ocular and clinical features.

A síndrome de Revesz é uma rara variante de disceratose congênita caracterizada por retinopatia exsudativa bilateral, alterações no segmento anterior ocular, retardo do crescimento intrauterino, pilificação fina e escassa, pigmentação cutânea reticular, falência da medula óssea, calcificações cerebrais, hipoplasia cerebelar e retardo neuropsicomotor. Há variações clínicas significativas entre os poucos relatos desta patologia existentes na literatura. Descrevemos o primeiro caso brasileiro de síndrome Revesz e suas características clínicas e oculares.

Etiological profile of pancytopenia in adults in Marrakesh, Morocco

This retrospective study evaluated the frequency of different causes of pancytopenia in all adult patients with pancytopenia presenting to the Department of Haematology of Mohamed VI Hospital, Marrakesh from 1 January 2008 to 31 December 2010. A total of 118 cases of pancytopenia were found [average of 39 cases per year]. The mean age of patients was 52 years [range 18-82 years] and 52.5% were male. The main clinical signs were pallor [100%], asthenia [100%] and fever [30.5%]. Mean haemoglobin was 6.5 g/dL [range 2.9-9.2 g/dL], mean white blood cell count was 2360/mm[3] [range 840-3360/mm[3]] and platelet count 66 000/mm[3] [range 3000-123 000/mm[3]]. Bone marrow aspiration was performed in 112 patients; megaloblastosis was found in 32.2% and marrow blasts in 23.7%. Anaemia due to vitamin B[12] deficiency [32.2%], acute leukaemia [23.7%] and aplastic anaemia [15.2%] were the main causes of pancytopenia. Given the incidence of acute leukemia among our cases, patients presenting with pancytopenia require urgent diagnosis and treatment

Parvovirus B19 presenting with persistent pancytopenia in a patient of T-ALL post induction chemotherapy diagnosed on bone marrow examination.

Manifestations of parvovirus B19 vary even in the normal host from asymptomatic or subclinical infection to a spectrum of illness with symptoms during viremic and immune complex mediated stage of disease. We report the morphological findings of parvovirus B19 infection (confirmed on serology) in a patient of T-acute lymphoblastic lymphoma (T-ALL) who underwent induction phase of chemotherapy (MCP 842 protocol). Persistent pancytopenia in the bone marrow aspirate with mild increase in blasts was thought to be due to failure to achieve marrow remission. However, giant pronormoblasts with prominent intranuclear inclusions confirmed on trephine biopsy led to the suspicion of parvovirus B19 infection which was later confirmed on serology. This case is presented to report the rarely seen classical morphological feature of parvovirus infection on bone marrow examination which was incidentally the first investigation to diagnose the viremic phase of the infection, indicating that a high index of suspicion needs to be kept in mind while examining bone marrows of susceptible patients.

Case report: chediak-higashi syndrome

Chediak-Higashi Syndrome is a rare inherited autosomal recessive disorder of immune system. Susceptibility to infection due to phagocyte dysfunction ranges from recurrent skin infection to over whelming fatal systemic infection. A three year old boy presented by dark skin all over the body except tiny areas of hypopigmentation. He suffered from repeated attacks of fever, cough, bloody diarrhea. On examination there was severe pallor, grey silver hair, generalized lymphadenopathy and hepatosplenomegaly. His investigations showed pancytopenia and giant lysosomal granules in the cytoplasm of neutrophils and lymphocytes. He received antibiotics for several times but in last episode he looked terminally ill and his parents refused medical advice for admission and took him to home

Prevalence of megaloblastic anaemia in a paediatric unit

Megaloblastic anaemia is common in paediatric population of developing countries. The objective of this study was to find out the prevalence of megaloblastic anaemia in Paediatric Unit of District Headquarter Teaching Hospital, Dera Ismail Khan. A retrospective analysis of forty bone marrow aspirates was performed to find out the prevalence of megaloblastic anaemia in Paediatric unit of District Headquarter Teaching Hospital Dera Ismail Khan, from January 2007 to December 2008. Both male and female indoor patients up to 12 years of age were included in the study. Blood count and peripheral smear findings revealed anaemia in 40[100%], leukopenia in 17 [42.5%] and thrombocytopenia in 36 [90%] patients. Bicytopenia was present in 18 [45%] and pancytopenia in 17 [42.5%] patients. Analysis of the bone marrow findings showed megaloblastic anaemia in 23 [57.5%], bone marrow hypoplasia /aplasia in 8[20%] and Leukaemia in 6 [15%] patients. So megaloblastic anaemia was the most prevalent finding in this study. Next was bone marrow hypoplasia /aplasia, followed by leukaemia. Megaloblastic anaemia is the most prevalent diagnosis and the major cause of bicytopenia and pancytopenia in the bone marrow aspirates performed in the Paediatric unit of District Headquarter Teaching Hospital District Dera Ismail Khan

A neonate with petechiae and pancytopenia at birth as uncommon presentation of congenital HIV infection.

The authors describe a Thai newborn boy who was presented with petechiae, hepatosplenomegaly and pancytopenia at birth caused by congenital HIV infection. His clinical presentations were appeared on the early onset after birth. The bone marrow finding has shown hypocellularity which was also rare in HIV-infected children.

Bone marrow examination in cases of pancytopenia.

This study was carried to identify the causes of pancytopenia and to find out the bone marrow morphology in cases of pancytopenia. It was a cross sectional study conducted over a period of two years in the Department of Pathology, Tribhuvan University Teaching Hospital. Bone marrow aspiration smears of patients fulfilling the criteria of pancytopenia were examined. The data obtained were analyzed using measures of central tendency. One hundred and forty eight cases underwent bone marrow aspiration and it constituted 15.74% of total cases. Mean age was 30 years (range, 1-79 years). 42 cases were children (28.37%). Male: female ratio was 1.5:1. The commonest cause was hypoplastic bone marrow seen in 43 cases (29%) followed by megaloblastic anemia in 35 cases (23.64%), and hematological malignancy in 32 cases (21.62%). Erythroid hyperplasia was seen in 29 cases (19.6%) and normal bone marrow was seen in 5 cases (3.38%). There was one case each of Niemann-Pick disease and metastatic neuroblastoma in children and chronic pure red cell aplasia and leishmaniasis in adults. Acute leukemia was the commonest hematological malignancy. In children, commonest finding was hypoplastic bone marrow (38.1%) while in adults megaloblastic anemia (30.18%) was commonest finding followed by hypoplastic anemia (25.47%). In present study bone marrow examination was able to establish diagnosis in 77% of cases. Hypoplastic marrow was the commonest diagnosis, followed by megaloblastic anemia, and hematological malignancies.

Clinico-hematological profile of Pancytopenia in Manipur, India

To determine the etiology and clinical profile of pancytopenia in Manipur, India Prospective study Department of Pathology, Regional Institute of Medical Sciences [RIMS], Imphal, Manipur, a renowned referral hospital in north-east India Fifty cases of pancytopenia were examined in the department of Pathology, RIMS hospital, Imphal, Manipur,India, during a two year period from November 1999 to October 2001. Bone marrow aspiration and examination Correlation between pancytopenia and clinico-hematological diagnosis Hypoplastic anemia was the commonest cause of pancytopenia [22%] followed by megaloblastic anemia and myelodysplastic syndrome [18% each]. The other causes include subleukemic / aleukaemic leukemia [14%], iron deficiency anemia [8%], HIV infection [6%], congenital dyserythropoietic anemia [CDA, 4%], pyrexia of unknown origin [PUO] with hepatosplenomegaly [4%], congenital hepatic fibrosis [2%] and systemic lupus erythomatosus [SLE, 2%]. Rare causes of pancytopenia including iron deficiency anemia, HIV infection and CDA have to be kept in mind as possible disorders manifesting as pancytopenia

Leucopenia as presentation of sarcoidosis

A 20-year-old male Saudi national presented initially with leucopenia and splenomegaly. The absence of other signs of disease, progressive pancytopenia and normal bone marrow examination posed a diagnostic dilemma as to the cause of hypersplenism. Subsequently, the patient had splenectomy the histopathological appearance of which was non-caseating granuloma. A high level of angiotension converting enzyme [ACE] was found in this patient. Sarcoidosis is a recognized cause of hypersplenism, and though the disease is not yet widely described in this part of the world. It is the most probable diagnosis in this patient

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.

Hemophagocytic Syndrome Associated with Kikuchi's Disease

A 13-yr-old female was admitted to our hospital with fever, seizure, and cervical lym-phadenopathy. Laboratory data showed pancytopenia, elevation of serum transaminase, lactate dehydrogenase, triglyceride, and ferritin levels. Lymph node biopsy revealed features of Kikuchi's disease and there were signs of histiocytosis and hemophagocytic phenomenon in bone marrow. She recovered after treatment with intravenous immunoglobulin and corticosteroids therapy. Hemophagocytic syndrome can be associated with Kikuchi's disease especially in childhood and seems to have a less aggressive clinical course and better prognosis.

Pancytopenia--a six year study.

All cases of pancytopenia seen over a six year period in two hematology centres were analysed. Patients receiving myelotoxic chemotherapy or those with leukemic cells in peripheral smear were excluded. There were a total of 166 cases. The four major causes were: aplastic anaemia in 49, megaloblastic anaemia in 37, aleukemic leukemia or lymphoma in 30 and hypersplenism in 19 cases. Bone marrow aspiration was often unsuccessful in obtaining an adequate sample, while biopsy was usually diagnostic. Both bone marrow aspiration and biopsy should be performed simultaneously in pancytopenic patients when the diagnosis is elusive. Megaloblastic anaemia is a major cause of pancytopenia, and may present acutely in the critically ill. It is a rapidly correctable disorder and should not be missed.

Diagnóstico e tratamento de complicaçöes agudas do transplante de células progenitoras hematopoéticas / Diagnosis and treatment of acute complications of hematopoietic stem cell transplantation

Nesta revisäo, säo discutidos os princípios do diagnóstico e tratamento das principais complicaçöes agudas, näo infecciosas, do transplante de células progenitoras hematopoéticas: pancitopenia, incompatibilidade no sistema ABO, mucosite, doença veno-oclusiva hepática, cistite hemorrágica, penumonite intersticial, cardiotoxicidade e doença do enxerto-contra-hospedeiro aguda. Oito casos clínicos, extraídos da casuística da nossa Unidade de TMO, säo descritos brevemente para ilustrar aspectos particulares das doenças discutidas no trabalho.

Pancytopenia due to hemophagocytic syndrome as the presenting manifestation of tuberculosis.

We report here an unusual hematologic manifestation of tuberculosis. A 40 year old male presented with pancytopenia due to hemophagocytic syndrome. Further investigations revealed he had tuberculosis.