Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review / Diálise peritoneal com múltiplas trocas bem-sucedida em paciente com grave toxicidade hematológica por metotrexato: relato de caso e revisão de literatura

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.

Resumo Apesar de sua toxicidade, o metotrexato é um medicamento eficaz no controle de várias doenças. A mielossupressão, um de seus principais efeitos adversos, aumenta em gravidade e frequência nos pacientes com insuficiência renal. Apresentamos o caso de um homem de 68 anos de idade com doença renal terminal relacionada à vasculite associada ao ANCA em diálise peritoneal, que recebeu a medicação em dose baixa em função da atividade da doença e que teve como complicação pancitopenia grave com mucosite, tratada com medidas de suporte e diálise peritoneal com múltiplas trocas. Revisamos 20 casos publicados até o presente momento sobre pancitopenia associada a metotrexato em pacientes em diálise. Foi identificada alta morbidade e mortalidade, razão pela qual seu uso nesse tipo de paciente não é recomendado. No entanto, quando esta complicação ocorre, uma opção terapêutica pode ser o uso de diálise peritoneal com múltiplas trocas, além da terapia de suporte para toxicidade medicamentosa. Maiores estudos são necessários para demonstrar o papel da diálise peritoneal com múltiplas trocas na remoção desse medicamento.

Premières données nigériennes à propos des étiologies de la Pancytopénie : une étude sur 285 patients au service d'Onco-Hématologie de l'Hôpital National de Niamey

Introduction : La pancytopénie est définie comme étant une baisse associée des lignées érythrocytaire, granulocytaire et plaquettaire. L'origine est centrale ou périphérique. Cliniquement elle est caractérisée par une pâleur, de la fièvre et un syndrome hémorragique. C'est la première étude spécifique consacrée à ce sujet. Matériels et Méthodes: Il s'agit d'une étude portant sur 285 dossiers de patients sur 14 années. La pancytopénie était définie en présence des critères suivants : un taux d'Hb < 11 g/dl ; un taux de globules blancs (GB) < 4000/mmᶾ avec un taux de PNN < 1500 /mmᶾ ; un taux de plaquettes < 150 000/mmᶾ.Les paramètres étudiés avaient porté sur l'âge, le sexe, les signes cliniques (Pâleur, asthénie, fièvre, syndrome hémorragique), les résultats des examens paracliniques : hémogramme, myélogramme, biopsie ostéo-médullaire, goutte épaisse, sérologie VIH, hémocultures et échographie. Les critères de non inclusion étaient les cas de bicytopénie et les pancytopénie chimio-induite. Résultats : La fréquence des pancytopénies était de 20,5 cas/an; le sex-ratio: 0,8. La population était très jeune avec 70% de moins de 45 ans. Les principales manifestations cliniques étaient: la pâleur (271 cas : 95,1%), asthénie (253 cas: 88,8%), le syndrome tumoral (143 cas: 50,1%), la fièvre (133 cas: 46,7%), le syndrome hémorragique (48 cas: 17%). Les étiologies étaient dominées par les carences vitaminiques (87 cas : 30,5%), l'hypersplénisme (67 cas : 23,5%), les infections (45 cas : 15,8%), les hémopathies malignes (19 cas : 6,7%). Conclusion: Les étiologies des pancytopénies sont dominées par les carences vitaminiques et l'hypersplénisme. L'enquête étiologique doit être essentiellement axée sur ces 2 causes après avoir éliminé un syndrome infectieux et une leucémie aigüe qui sont souvent des urgences

Mycophenolate mofetil as an alternative treatment for autoimmune hepatitis

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease characterized by hepatocellular inflammation, necrosis, and fibrosis, which can progress to cirrhosis and fulminant hepatic failure. The standard treatment for AIH includes corticosteroids alone or in combination with azathioprine. Although most patients achieve remission using the standard regimen, some patients do not respond due to either drug intolerance or refractory disease; in such cases alternative immunosuppressive agents should be explored. The second-line therapies are cyclophilin inhibitors such as cyclosporine A or tacrolimus, and nowadays mycophenolate mofetil (MMF) is widely used if azathioprine-based therapies are not tolerated. Although these are recommended as an alternative to the first-line regimen, there is insufficient evidence for the efficacy of second-line therapies, with the evidence based mainly on expert opinion. Therefore, we report an AIH patient receiving the standard regimen in whom remission did not occur due to side effects to azathioprine, but was successfully treated with MMF in combination with corticosteroids as an alternative to the standard regimen.

Marrow hypoplasia: a rare complication of untreated Grave’s disease / Hipoplasia de medula óssea: uma rara complicação da doença de Graves não tratada

Atypical presentation forms of hyperthyroidism are always a challenge to the clinician. We present a female patient with the typical symptoms of thyrotoxicosis, without any thionamides treatment before, associated with pancytopenia, which recovered after euthyroidism state was achieved. Although the major cases of pancytopenia in Grave’s disease are seen as a complication of antithyroid drugs (thioamides), in this case report the alteration in blood tests was associated with untreated hyperthyroidism. In the literature review, we found 19 case reports between 1981 to 2012, but it has been related to a hypercellular bone marrow with periferic destruction. Our case, however, is about a hypocellular bone marrow without fibrosis or fat tissue replacement, which proceeded with a periferic improvement following thyroid treatment. Although rare, pancytopenia, when present, may develop as an unusual and severe manifestation in untreated subjects.

Formas atípicas de apresentação do hipertireoidismo são sempre um desafio para o clínico. Apresentamos uma paciente do sexo feminino, com sintomas típicos de tireotoxicose associado a um quadro de pancitopenia sem nenhum tratamento prévio com tionamidas. A melhora da alteração hematológica ocorreu após recuperação do eutireoidismo. Embora a maioria dos casos de pancitopenia na doença de Graves seja uma complicação das drogas antitireoidianas (tionamidas), neste caso a alteração hematológica foi associada ao quadro de hipertireoidismo não tratado. Após uma revisão na literatura, encontramos 19 relatos de caso descritos no período de 1981 a 2012, nos quais o quadro de pancitopenia estava relacionado à hipercelularidade medular com destruição periférica das células sanguíneas. Nosso caso, entretanto, trata-se de uma pancitopenia com medula óssea hipocelular, sem infiltração por tecido adiposo ou fibrose, que evoluiu com melhora dos elementos do sangue periférico após tratamento do hipertireoidismo. Embora rara, a pancitopenia, quando presente, pode se manifestar como uma severa manifestação se não tratada a condição desencadeadora.

Enfermedad renal poliquística autosómica recesiva: reporte de un caso / Autosomal recessive polycystic kidney disease: a case report

La enfermedad renal poliquística es una enfermedad genética que se caracteriza por dilataciones quísticas progresivas de los túbulos renales, presentándose de forma autosómica dominante o recesiva, con una incidencia de 1 en 1.000 y 1 en 20.000 nacidos vivos, respectivamente según series internacionales. La variedad autosómica recesiva puede ser letal en el período neonatal debido a insuficiencia respiratoria secundaria a hipoplasia pulmonar, y puede manifestarse durante la infancia con hipertensión arterial, talla baja y complicaciones secundarias a hipertensión portal. PRESENTACIÓN DEL CASO: paciente preescolar de 3 años 11 meses, con antecedente de restricción del crecimiento fetal y oligohidroamnios en período prenatal, presenta cuadro de decaimiento, palidez y dificultad alimentaria progresiva con vómitos posprandiales, destacando al examen físico un soplo cardíaco, hipertensión arterial, esplenomegalia, circulación colateral, además de talla baja. En exámenes destaca un hemograma con pancitopenia periférica, ecografía abdominal con hepatoesplenomegalia, hallazgos compatibles con enfermedad renal poliquística autosómica recesiva y fibrosis periportal, cintigrama renal con hipofunción renal bilateral, test de sangre oculta en deposiciones positivo, endoscopía digestiva alta convárices esofágicas pequeñas, radiografía de carpo con edad ósea retrasada y ecocardiografía con cardiomegalia. DISCUSIÓN: se requiere un alto índice de sospecha ante esta enfermedad poco frecuente, que cursa con hipertensión portal, siendo el recuento de plaquetas el mejor predictor de severidad. Dado que carece de tratamiento curativo y su historia natural es progresar haciala insuficiencia renal terminal, su tratamiento se enfoca en las complicaciones secundarias al daño hepático y renal...

Polycystic Kidney Disease is a genetic disorder characterized by progressive cystic dilations of the renal ducts, presenting as autosomal dominant or recessive forms with an incidence of 1 in 1.000 and 1 in 20.000 births, respectively, according to international series. The autosomal recessive variety can be lethal in the neonatal period due to respiratory failure secondary to pulmonary hypoplasia and can manifest during childhood with hypertension, short stature and complications of portal hypertension. CASE REPORT: 3 years and 11 months old preschoolar with antecedent of fetal growth restriction and oligohydramnios during prenatal period, and a historyof asthenia, pallor and progressive feeding difficulty with postprandial vomiting. Physical examination shows cardiac bruit, hypertension, splenomegaly, caput medusae and short stature. Laboratory tests with peripheral pancytopenia; abdominal ultrasonography showed hepatosplenomegaly, findings consistent with autosomal recessive polycystic kidney disease and periportalfibrosis; renal scintigraphy with bilateral kidney failure; a positive fecal occult blood test; an upper endoscopy that shows small esophageal varices; a hand radiography that shows bone age delayed and an echocardiography with cardiomegaly. DISCUSSION: This infrequent disease requires a high degree of suspicion by the clinician and presents with portal hypertension, with platelet count being the best predictor of severity. This condition has no cure and will progress to end-stage renal disease in any moment, so the aim is to minimize and treat renal and hepatic complications...

Subacute combined spinal cord degeneration and pancytopenia secondary to severe vitamin B12 deficiency / Degenarión combinada subaguda medular y pancitopenia secundaria a déficit severo de vitamina B12

CONTEXT: Decreased vitamin B12 concentration does not usually result in clinical or hematological abnormalities. Subacute combined spinal cord degeneration and pancytopenia are two serious and rarely displayed consequences that appear in severe deficits. CASE REPORT: We present the case of a patient with subacute combined spinal cord degeneration and pancytopenia secondary to severe and sustained vitamin B12 deficiency. Such cases are rare nowadays and have potentially fatal consequences. CONCLUSIONS: Vitamin B12 deficiency should be taken into consideration in the differential diagnosis in cases of blood disorders or severe neurological symptoms. Early diagnosis and treatment can avoid irreversible consequences.

CONTEXTO: El descenso de la concentración de vitamina B12 no suele derivar en alteraciones clínicas o hematológicas. La degeneración combinada subaguda medular y la pancitopenia son dos consecuencias graves y poco frecuentes que aparecen en los déficit severos. CASO CLÍNICO: Presentamos el caso de un paciente con una degeneración combinada subaguda medular y pancitopenia secundarios a un déficit severo y mantenido de vitamina B12. Un caso poco común en nuestros días y con consecuencias potencialmente fatales. CONCLUSIONES: Debemos considerar el déficit de vitamina B12 dentro del diagnóstico diferencial en caso de alteraciones hematológicas o síntomas neurológicos graves. Su diagnóstico y tratamento precoz pueden evitar secuelas irreversibles.

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.

Pediatric patients with bicytopenia/pancytopenia: Review of etiologies and clinico-hematological profile at a tertiary center.

Background: The etiology of bicytopenia/pancytopenia varies widely in children, ranging from transient marrow viral suppression to marrow infiltration by fatal malignancy. Depending on the etiology, the clinical presentation can be with fever, pallor or infection. Knowing the exact etiology is important for specific treatment and prognostication. Aims: To evaluate the etiological and clinico-hematological profile in children with bicytopenia and pancytopenia. Materials and Methods: A review of bicytopenic and pancytopenic children referred for bone marrow examination from January 2007 to December 2008 was done. Detailed history, clinical examination and hematological parameters at presentation were recorded. Results and Conclusion: During the study period, a total of 990 children were referred for bone marrow examination for different indications. Of these, 571 (57.7%) had either pancytopenia (17.7%) or bicytopenia (40%). Commonest form of bicytopenia was anemia and thrombocytopenia seen in 77.5% cases, followed by anemia and leukopenia in 17.3% and leukopenia and thrombocytopenia in 5.5% cases. Most common etiology was acute leukemia (66.9%) in bicytopenic children and aplastic anemia (33.8%) in pancytopenic children. Children with bicytopenia had a higher incidence of underlying malignancy (69.5% vs. 26.6%), splenomegaly (60.5% vs. 37.4%), lymphadenopathy (41.8% vs. 15.1%) and circulating blasts (64.6% vs. 20.1%) and a lower incidence of bleeding manifestations (12.1% vs. 26.6%) as compared to children with pancytopenia.

Megaloblastic anemia: Back in focus.

Megaloblastic anemia (MA), in most instances in developing countries, results from deficiency of vitamin B12 or folic acid. Over the last two to three decades, incidence of MA seems to be increasing. Of the two micronutrients, folic acid deficiency contributed to MA in a large majority of cases. Now deficiency of B12 is far more common. In addition to anemia, occurrence of neutropenia and/or thrombocytopenia is increasingly being reported. Among cases presenting with pancytopenia, MA stands out as an important (commonest cause in some series) cause. This article focuses on these and certain other aspects of MA. Possible causes of increasing incidence of MA are discussed. Observations on other clinical features like neurocognitive dysfunction, associated hyperhomocysteinemeia and occurrence of tremors and thrombocytosis during treatment are highlighted.

Fulminant pancytopenia due to cytomegalovirus infection in an immunocompetent adult

A case of severe and irreversible pancytopenia secondary to acute primary cytomegalovirus infection in an immunocompetent woman is described. The patient presented with thrombocytopenia, lymphopenia, anemia, and abnormal liver function tests. Treatment with corticosteroids and intravenous immunoglobulin was ineffective in reconstituting hemopoiesis. The patient developed severe sepsis and eventually expired.

Megaloblastic anemia patient admitted with pancytopenia and walking difficulty with normal vitamin B12 and MCV levels

Vitamin B12 deficiency may cause hematologic, gastrointestinal, psychiatric and neurological symptoms. Sub-acute combined degeneration of spinal cord, which develops in the deficiency of vitamin B12, may be reversible in case of early diagnosis and treatment. We describe the management of a 50-years old female who got admitted with pancytopenia and elevated LDH, with walking difficulties since last 15 days. B12 and folic acid levels were found in normal ranges. Megaloblastic changes were observed in the bone marrow examination. Abnormal hyperintence signal changes were observed in T2-weighed cervical spinal cord Magnetic Resonance Imaging in posterior row. Due to the high homocysteine level, treatment with parenteral B12 vitamin was initiated. Following the 3-months treatment, hematologic counts and neurological symptoms of the patient were found to be completely recovered at the control visit. Vitamin B12 deficiency should be considered for the patients with pancytopenia, elevated LDH levels and neurological symptoms, even if vitamin B12 and MCV levels are in normal ranges. Vitamin B12 deficiency should be confirmed with the additional assays, such as, the assessment of serum homocysteine and methylmalonic acid levels, and the treatment should be started promptly

Reactive haemophagocytic lymphohistiocytosis.

We present a series of five cases diagnosed and treated as reactive haemophagocytic lymphohistiocytosis (HLH) in three tertiary referral centers of Kolkata, within a time frame of 3 months. The initial presentations were very variable, the most prominent clinical feature being - acute renal failure in the first patient, convulsions in the second, encephalopathy the third, marked cervical lymphadenopathy in the fourth and polyserositis in the fifth. All had a history of prolonged fever preceding admission and hepatosplenomegaly on examination. Investigations revealed multi-organ involvement with pancytopenia;- haemophagocytosis was eventually diagnosed by bone marrow examination. These cases highlight the diagnostic challenge posed by infection associated haemophagocytosis and the need for maintaining a high index of suspicion to promptly diagnose and treat this potentially life threatening condition.

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

Brucellosis concomitant with acute leukemia.

We present two patients with brucellosis concomitant with acute leukemia. Co-existence of acute leukemia with brucellosis which may have similar symptoms, have not been reported earlier. The first case presented with generalized arthralgia, fever, paleness and pancytopenia. The second patient had mild leucopenia and thrombocytopenia. She presented with fever. We carried out the chemotherapy for both ALL and brucellosis simultaneously. While the first patient's fever disappeared within 3 days, the second patient's fever had continued on subfebril level for five days and then disappeared. We achieved the remission in both patients and no reactivation was observed during the follow-up period.

Macrophage activation syndrome.

Macrophage Activation Syndrome is a rare and potentially fatal disease, to be considered in patients with a SIRS like clinical presentation. Falling ESR and hyperferritinemia in the appropriate clinical setting can be the greatest clues. We report a case in which a female admitted with fever and rash, initially had systemic inflammatory response syndrome (SIRS) like clinical presentation, but eventually proved to be a rare case of fatal Macrophage Activation Syndrome.

Utilidad del estudio microscópico de medula ósea en pacientes con infección por VIH y pancitopenia / Usefulness of bone marrow microscopic examination in HIV-infected patients with pancytopenia

Introducción: El papel del examen de la medula ósea, en el diagnóstico de fiebre prolongada en pacientes con infección por VIH, ha sido bien establecido, pero aún no está bien estudiada la importancia de la información morfológica y etiológica obtenida en el subgrupo de pacientes con pancitopenia coexistente. Material y métodos: En un estudio prospectivo reclutamos 31 pacientes con infección por VIH, con pancitopenia coexistente, con o sin fiebre. Se llevó a cabo en todos los casos el exámen microscópico de la médula ósea, además de otros estudios para concretar un diagnóstico específico. Resultados: La infección por Parvovirus correspondió a cinco casos, Histoplasma capsulatum cuatro casos, Mycobacterium tuberculosis dos casos, complejo Mycobacterium avium tres casos, VIH en tres casos, Salmonella typhi dos casos, sin agente aislado y neumonía en dos casos, sin agente aislado e infección intestinal en dos casos. Hubo un solo caso de cada una de las siguientes etiologías: Citomegalovirus, trimetoprim-sulfametoxazol, Enfermedad de Hodgkin, hiperesplenismo, Acinetobacter, sin agente aislado y apendicitis por Escherichia coli, y síndrome hemofagocítico. Se logró el diagnóstico más probable mediante el análisis microscópico de la medula ósea en 12 de 31 pacientes (38.7%). Conclusión: En este subgrupo de pacientes, el análisis microscópico de la medula ósea es un procedimiento apropiado, que permite además, un diagnóstico temprano en pacientes con y sin episodios febriles.

INTRODUCTION: The role of bone marrow examination in the diagnosis of prolongedfever in HIV infected patients, has been well established, but the importance of the morphological and etiological analysis, obtained in patients with coexisting pancytopenia, has not been adequately described. MATERIALS AND METHODS: In a prospective study, we recruited 31 HIV-infected patients with coexisting pancytopenia, with or withoutfever. Bone marrow examination was performed in all cases. Other studies were done to confirm diagnosis. RESULTS: Parvovirus infection was observed in 5 patients, Histoplasma capsulatum in 4, Mycobacterium tuberculosis in 2, Mycobacterium avium complex in 3, HIV in 3, Salmonella typhi in 2, pneumonia and an unknown agent in 2 and intestinal infection and an unknown agent in 2. Only one patient was included in the following diagnostic etiologies: cytomegalovirus, trimethoprim sulfamethoxazole, Hodgkin's disease, hypersplenism, acinetobacter, appendicitis with an unknown agent, E. coli, and hemophagocytic syndrome. We obtained a probable diagnosis in 12 out of 31 patients (38.7), using bone marrow examination. CONCLUSION: In this subgroup of patients, the microscopic analysis of bone marrow is an important clinical approach that can lead to an early diagnosis of patients with and without fever.

Megaloblastic anaemia, seen in 48 cases of pancytopenia

To assess megaloblastic anaemia in patients presenting with pancytopenia. Descriptive study. Hospitalized patients referred for bone marrow examination for the work up of pancytopenia were selected. Complete blood count was done on haematology auto analyzer. Bone marrow aspiration was done for cytology. Perl's iron staining was done in patients showing low blood indices. Forty eight [48] patients underwent bone marrow aspiration for cytology for the work up of pancytopenia. Nineteen [19] patients [39%] showed megaloblastic anaemia. Macrocytosis and hypersegmented neutrophils were the most common finding on peripheral blood smear. Fregmented red cells were seen in 13 patients showing classical finding of megaloblastic anaemia. Megaloblastic anaemia was found to be the most common cause of pancytopenia. Diagnosis of megaloblastic anaemia requires only complete blood count, peripheral blood smear and bone marrow cytology, which is cost effective. Nutritional factors and recurrent infection seem to be associated strongly with megaloblastic anemia

Paroxysmal nocturnal hemoglobinuria with onset in childhood: a case report.

A twelve-year-old boy presented with recurrent episodes of anemia. Complete blood counts showed pancytopenia. Bone marrow was hypercellular with erythroid hyperplasia and depleted stores of iron. Positive Ham's test and sucrose lysis test revealed that he had paroxysmal nocturnal hemoglobinuria. There was a delay of nearly two years in the diagnosis in this patient. Paroxysmal nocturnal hemoglobinuria is rare in childhood. It must however be considered in a child who presents with unexplained anemia or bone marrow failure so that an early and accurate diagnosis is reached.