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BACKGROUND: While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions. CASE PRESENTATION: A man in his forties contacted his general practitioner because of increasing functional dyspnoea. He had completed a course of dicloxacillin a few months previously for a skin abscess on his abdomen. Bloodwork revealed severe anaemia (haemoglobin 5.4 g/dL), which required transfusion. Subsequent testing excluded iron and vitamin deficiency anaemia, haemolysis and malignancy. Initial bone marrow biopsy was of suboptimal quality. However, repeat tissue sample supported a diagnosis of pure red cell aplasia. The patient improved with ciclosporin treatment, which was gradually tapered. INTERPRETATION: Pure red cell aplasia should be considered in patients with new onset isolated anaemia with severe reticulocytopenia. Diagnosis depends on obtaining representative tissue from bone marrow biopsy. It is difficult to conclude for this patient whether the aetiology of his pure red cell aplasia was idiopathic or secondary to recent dicloxacillin use.
Asunto(s)
Anemia , Neoplasias , Aplasia Pura de Células Rojas , Humanos , Masculino , Anemia/etiología , Anemia/complicaciones , Médula Ósea , Dicloxacilina , Neoplasias/complicaciones , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/etiología , AdultoRESUMEN
BACKGROUND: Systemic lupus erythematosus and anti-phospholipid syndrome may cause severe haematological complications despite few other symptoms of disease. CASE PRESENTATION: A previously healthy woman in her late twenties was admitted to hospital with chest pain and dyspnoea. CT of the thorax revealed bilateral pulmonary embolism and urine sampling showed haematuria and proteinuria. A few days after hospital admission, she developed transfusion-requiring anaemia. The investigation revealed a positive direct antiglobulin test, presence of anti-nuclear antibodies, lupus anticoagulant, anti-cardiolipin and anti-glycoprotein antibodies. INTERPRETATION: Pulmonary embolism in a young, previously healthy woman may be caused by different predisposing conditions. Systemic lupus erythematosus with accompanying anti-phospholipid syndrome was the diagnosis in this case. Severe autoimmune haemolytic disease may occur as a secondary phenomenon to systemic lupus erythematosus, and the condition must not be overlooked.
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Síndrome Antifosfolípido , Lupus Eritematoso Sistémico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Disnea/etiología , Femenino , Humanos , Inhibidor de Coagulación del Lupus , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Proteinuria/etiologíaRESUMEN
BACKGROUND: Elevated serum ferritin levels are common findings in clinical practice, usually caused by inflammation, liver disease, high alcohol consumption or malignancy, although it can occur in association with rare genetic conditions. CASE PRESENTATION: We describe a male in his sixties with persistent hyperferritinaemia without associated iron overload and subsequent development of cataract. The patient himself suggested hyperferritinaemia-cataract syndrome as a diagnosis, which was subsequently confirmed with mutation analysis of the light chain ferritin (FTL) gene. Such mutations are inherited in an autosomal dominant pattern. INTERPRETATION: Mutations in FTL are known to interfere with the balance between iron levels and ferritin production. When common causes of hyperferritinaemia are excluded, rare conditions should be considered in order to avoid unnecessary procedures and treatment. Genetic analyses are available for all clinicians and should be requested upon the right indications.
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Catarata , Trastornos del Metabolismo del Hierro , Catarata/diagnóstico , Catarata/genética , Ferritinas , Pruebas Genéticas , Humanos , Trastornos del Metabolismo del Hierro/diagnóstico , Trastornos del Metabolismo del Hierro/genética , Masculino , Mutación , LinajeRESUMEN
VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a JAK2V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the UBA1 gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the DNMT3 too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in JAK2 mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.
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T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.
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Leucemia Prolinfocítica de Células T , Leucemia Prolinfocítica , Humanos , Alemtuzumab/uso terapéutico , Leucemia Prolinfocítica/diagnóstico , Leucemia Prolinfocítica/genética , Leucemia Prolinfocítica/terapia , Leucemia Prolinfocítica de Células T/diagnóstico , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/terapiaRESUMEN
Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In this review, we have performed a review of a selection of the literature based on the authors' own experiences and assessments in accordance with international recommendations and guidelines. We address the biology, etiology, and epidemiology of hyperferritinemia. Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed.
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HFE hemochromatosis is characterized by increased iron absorption and iron overload due to variants of the iron-regulating HFE gene. Overt disease is mainly associated with homozygosity for the C282Y variant, although the H63D variant in compound heterozygosity with C282Y (C282Y/H63D) contributes to disease manifestation. In this observational study, we describe the association between biochemical findings, age, gender and HFE genotype in patients referred from general practice to a tertiary care referral center for diagnostic workup based on suspected hemochromatosis due to persistent hyperferritinemia and HFE variants. C282Y and H63D homozygosity were, respectively, the most and least prevalent genotypes and we found a considerable variation in transferrin saturation and ferritin levels independent of HFE genotype, which may indeed represent a diagnostic challenge in general practice. While our results confirm C282Y homozygosity as the major cause of iron accumulation, non-C282Y homozygotes also displayed mild to moderate hyperferritinemia with median ferritin levels at 500-700 µg/L, well above the reference cut-off. Such findings have traditionally been ignored in the clinic, and initiation of iron depletion has largely been restricted to C282Y homozygotes. Nevertheless, superfluous iron can aggravate pathogenesis in combination with other diseases and risk factors, such as inflammation, cancer and hepatopathy, and this possibility should not be neglected by clinicians.
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Ferritinas/sangre , Genotipo , Proteína de la Hemocromatosis/genética , Hemocromatosis/genética , Transferrina/metabolismo , Femenino , Hemocromatosis/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases. CASE PRESENTATION: The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae. CONCLUSIONS: We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality.