Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

CONTEXT: Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. OBJECTIVE: To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. DESIGN: Prospective study from August 2010 to December 2014. SETTING: Endocrinology outpatient clinic in a single centre. PATIENTS: Consecutive patients (n = 206) with newly diagnosed GD. INTERVENTION: ATD therapy. MAIN OUTCOME MEASURES: Prevalence and factors predicting neutropenia (<2 × 109 /l) and change in neutrophil counts following ATD. RESULTS: At diagnosis, 29 (14·1%) of GD individuals had neutropenia. Non-Caucasians [odds ratio (95% CI) of 4·06 (1·14-14·45), P = 0·03] and patients with higher serum thyroid hormone levels [OR 1·07 (1·02-1·13), P = 0·002 for serum FT3] were the only independent predictors of neutropenia. All patients with neutropenia had normalized blood neutrophil levels after achieving euthyroidism with ATD therapy. In patients in whom data were available posteuthyroidism (n = 149), change in neutrophil count after achieving euthyroidism was independently related to reduction in thyroid hormone levels (P < 0·01). CONCLUSIONS: GD is associated with neutropenia in one in seven patients at diagnosis, especially in non-Caucasians and those with higher serum thyroid hormone levels. Neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy.

Cutaneous features of intravascular lymphoma.

Intravascular lymphoma (IVL) is a subset of extranodal non-Hodgkin lymphoma, with an estimated incidence of <1 case per million people. It is characterised by extensive proliferation of lymphoma cells within small to medium-sized blood vessels. Most IVLs are B-cell tumours. IVL can present primarily in any organ system, including the skin. The disease is often disseminated at diagnosis. The overall mortality rate is thought to be >80%, and >50% of patients are diagnosed at postmortem examination. There is wide variability in the clinical appearance of cutaneous lesions, which may simulate inflammatory skin disease. Therefore, awareness by dermatologists is important to enable early diagnosis when cutaneous signs are present. We report two patients with unexplained systemic disease and a skin eruption, leading to the diagnosis of IVL, and outline the range of cutaneous features reported.

Best practice in primary care pathology: review 7.

This seventh best-practice review examines four series of common primary care questions in laboratory medicine: (1) blood count abnormalities 2; (2) cardiac troponins; (3) high-density lipoprotein cholesterol; and (4) viral diseases 2. The review is presented in a question-answer format, with authorship attributed for each question series. The recommendations are a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. The recommendations are not standards, but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

High prevalence of anemia after cardiac transplantation in children.

BACKGROUND: Chronic anemia is common in adults after successful cardiac transplantation. However, the prevalence of anemia in children after cardiac transplantation is uncertain. The purpose of this study was to investigate the prevalence and causes of chronic anemia in well children after cardiac transplantation and in particular to define the role, if any, of iron deficiency, which is important and relatively common in normal children. METHODS: Twenty children (ages 7 months to 16 years) who were well 4 months to 6 years after cardiac transplantation were studied. Fourteen children (70%) were anemic and enrolled in a prospective trial of iron supplementation. RESULTS: In the majority of children, serum iron and erythropoietin levels were low, although serum ferritin and zinc protoporphyrin levels tended to be normal or high. Only one child demonstrated a definite response to iron supplementation, although the hemoglobin level remained low. CONCLUSIONS: Anemia is highly prevalent in this population, and, despite the presence of low serum iron and transferrin saturation, anemia is not usually due to iron deficiency. Although the diagnosis of iron deficiency in this group is difficult and must not be missed, inappropriate therapy should be avoided. In the majority of children, there appears to be an anemia of chronic disease which may be secondary to chronic inflammation or an effect of cyclosporine on erythropoietin production.

Distinction between aleukaemic prodrome of childhood acute lymphoblastic leukaemia and aplastic anaemia.

AIMS: To document the features of the so-called aplastic presentation of childhood acute lymphoblastic leukaemia (ALL) and to determine whether this prodrome can be distinguished from aplasia. METHODS: The peripheral blood and bone marrow appearances of all cases of childhood ALL presenting in one health region of England in 13 years and eight months were reviewed. All cases presenting with cytopenia without circulating blasts and marrow aspirates with no infiltrate of blasts were studied in detail. RESULTS: Four of 305 (1.3%) children presented in this way. All four had reticulin fibrosis and increased cellularity in all or part of the marrow biopsy specimen. All were girls. Three had common and one surface membrane immunoglobulin positive ALL. Reassessment of this prodrome, by combining the features of four previously reported series of similar cases with the present one, highlighted the female preponderance (19 of 22 cases), bone marrow fibrosis (10 of 11 evaluable cases), prominent bone marrow lymphocytes (14 of 22 cases) and temporary recovery (all 12 evaluable cases). Six of 14 evaluable cases had bone marrow biopsy specimen appearances of apparently uniform hypocellularity, but only one of these did not have fibrosis. CONCLUSIONS: If, in addition to an aspirate, a bone marrow trephine biopsy is carried out the prodrome can be distinguished from aplasia in most cases. The similarity of this prodrome to aplastic anaemia is merely superficial. Clinicians and morphologists may fail to appreciate the implications of this mode of presentation if the term "aplastic" continues to be used to describe this aleukaemic prodrome of ALL.

Hyaline-vascular variant of angiofollicular lymph node hyperplasia with systemic manifestations and response to corticosteroids.

We report two cases of angiofollicular lymph node hyperplasia of the hyaline-vascular type. The patients were atypical in having systemic complications, which are much more commonly seen in the plasma cell variant of this disorder. In each case, the diagnosis was established some years after the initial presentation. Both patients presented with unusual systemic manifestations. The exact mechanism underlying the associated features is unknown, but these cases provide some evidence that the disease is primarily a vascular proliferative or inflammatory disorder. All manifestations of the disease responded to the administration of prednisolone with rapid reduction of dosage to less than 10 mg daily. Maintenance therapy may be required to prevent relapse.

Acute lymphoblastic leukaemia of the L3 subtype in adults in the Northern health region of England 1983-99.

AIM: Acute lymphoblastic leukaemia (ALL) with an L3 morphological FAB type is regarded by some as being synonymous with B cell ALL or ALL with a Burkitt-type chromosomal translocation-t(8;14), t(2;8), t(8;22). This paper describes a series from a population based study of 24 patients with L3 ALL presenting over 17 years. METHODS: Clinical data were collected prospectively from all adult patients presenting with acute leukaemia in the Northern region since 1982. Data from all patients diagnosed with FAB type L3 ALL were analysed. RESULTS: Overall, L3 ALL accounts for 8.6% of all adult ALL and it is more common in the elderly than has hitherto been recognised. In addition to classic Burkitt-type translocations (11 of 24 cases), the t(14;18) translocation, which is characteristically found in lower grade lymphomas such as follicular lymphoma, is frequently present (five of 24 cases). CONCLUSION: The presence of L3 ALL is often associated with non-Burkitt-type translocations and the presence of a t(14;18) translocation may indicate that in some cases a clinically non-apparent lymphoproliferative disorder, such as a low grade follicular lymphoma, has transformed to a more aggressive form and, thus, presents as a de novo acute leukaemia.

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE: To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN: Three year retrospective study. SETTING: Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS: 60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES: Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS: All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION: Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.

The addition of oral idarubicin to a chlorambucil/dexamethasone combination has a significant impact on time to treatment failure but none on overall survival in patients with low grade non-Hodgkin's lymphoma: Results of the Scotland and Newcastle Lymphoma Group randomized NHL VIII trial.

Two hundred untreated patients with low grade NHL (KIEL), including 155 follicular NHL, were randomized to six courses of treatment with chlorambucil 20 mg m-2 for 3 days and dexamethasone 4 mg bd for 5 days (CD) vs the same regimen plus oral idarubicin 10 mg m-2 for 3 days (CID). Responding patients could be randomized to no further treatment or maintenance treatment for up to 36 months with alpha interferon. Complete remissions/CRu were more frequent in the CID arm (35% vs 24%) but the overall response rate was similar; 87/91 (96%) vs 86/92 (93%). Overall survival (OS) did not differ between the two arms. Time to treatment failure (TTTF) was prolonged in the CID arm, p = 0.03; median time 28 vs 19 months. TTTF for the B-cell follicular group alone was for CID (77 patients) 33 months vs 18 months for CD (78 patients). Interferon conferred no apparent benefit. The Follicular Lymphoma International Prognostic Index (FLIPI) is confirmed as a good predictor of risk groups including a group of 23% with shorter survival. The addition of the oral anthracycline, idarubicin, led to a significant improvement in TTTF with low toxicity. The use of radiotherapy in this sub-group may have contributed to this result. CID is a potential for combination with antibody therapy particularly in older patient groups.

Demonstration of lesions of cerebral toxoplasmosis by computerized tomography.

A patient who was treated for 11 years with cytotoxic drugs for Hodgkin's disease developed cerebral toxoplasmosis. Discrete lesions including an occipital abscess were visualized in the brain by computerized tomography (CT). This permitted a brain biopsy to be taken but the appearances were non-specific. At post-mortem pseudocysts of Toxoplasma gondii were found in several sites within the CNS. The recognition of these CT appearances as being due to toxoplasmosis should in future prompt serological investigation and urgent treatment of this potentially curable condition, despite negative biopsy material.

Growth of clinical haematology in South Tees Health District 1983-5.

A review of the workload of two newly appointed clinical haematologists in a health district with a population of 307,000 showed that the clinical case load increased rapidly in the first two years. The management of patients with blood disorders, which had previously been dispersed among many departments both within and outside the district, was now concentrated within a single unit with occasional referral as appropriate to regional centres. The development of a clinical haematology service in district general hospitals cannot occur without funding and facilities, including suitably located beds for haematology patients and specifically appointed junior medical staff. Highly trained and experienced nursing staff are essential for the management of patients with bone marrow failure; day care facilities and community nursing are also valuable. Changes and developments in the laboratory as a result of these additional clinical activities are also necessary.

The effects of therapeutic dialysis and renal transplantation on uraemic serum inhibitors of erythropoiesis in vitro.

The methyl cellulose culture system using human bone marrow and erythropoietin (Ep) at different concentrations was used to examine the effects of uraemic sera on erythropoiesis in vitro. Sera from undialysed patients with advanced uraemia (plasma creatinine greater than 900 mumol/l) when added to cultures at 10% with Ep at 2.0 u/ml were consistently inhibitory to the growth of erythroid burst-forming units (BFU-E). No inhibition of erythroid colony-forming units (CFU-E) was observed at this Ep concentration but inhibition was consistently demonstrated with Ep at 0.2 u/ml. Sera from undialysed patients with less severe uraemia (plasma creatinine less than 900 mumol/l) were not inhibitory to BFU-E or CFU-E at Ep 2.0 u/ml. Sera from patients with stable, functioning renal transplants were stimulatory to erythropoiesis in vitro with Ep at 2.0 u/ml. This finding is consistent with the normal or increased haematocrits often found following renal transplantation. Sera from patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) were not significantly different from normal in their effect on BFU-E growth in vitro and were slightly but significantly stimulatory to the growth of CFU-E. This suggests that these two forms of dialysis are equally effective in reducing the activity of uraemic inhibitors in serum and that inhibition of the marrow response to Ep and/or burst-promoting activity (BPA) is unlikely to be a major factor in the continued anaemia of dialysis patients.

Leukoencephalopathy after prophylactic radiation for leukaemia in ataxia telangiectasia.

Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. We report a 51/2 year old boy who had undiagnosed ataxia telangiectasia when he presented with acute lymphoblastic leukaemia. He subsequently developed a chemoradiation induced leukoencephalopathy after conventional central nervous system prophylaxis.

Management of the patient with multiple myeloma and renal failure.

Renal impairment is a common feature of multiple myeloma. Management of these patients requires an understanding of some of the basic principles of haematology and nephrology.

Interpretation of iron studies in adolescent haemochromatosis.

We report the case of a 14-year-old girl who originally presented at the age of eight with a history of bloody stools, abdominal pain and weight loss. Initial iron studies showed raised serum iron and transferrin saturation but low ferritin and were interpreted as consistent with iron deficiency under treatment. As she had not taken any supplemental iron she later underwent genetic testing for the Cys282Tyr and His63Asp mutations of the HFE gene. On the basis of these results, she was diagnosed as having hereditary haemochromatosis (HH). This case highlights that a low serum ferritin does not exclude the diagnosis of HH and that the availability of genetic testing can now enable probands and affected family members to be identified.

Immunotherapy using BCG during remission induction and as the sole form of maintenance in acute myeloid leukaemia.

Thirty-two adults with acute myeloid leukaemia (AML) were randomized to receive, from the time of diagnosis, either chemotherapy alone (C group) or chemotherapy plus Bacille Calmette-Guérin vaccine (BCG) (C+I group). After remission induction and consolidation, chemotherapy was stopped in both groups but BCG was continued in the C+I group. The overall survival of the C+I group was significantly increased (P less than 0.05). There was no significant increase in the duration of first remission in the C+I group (0.05 less than P less than 0.1) nor in the time from first relapse to death (0.05 less than P less than 0.1). There was no significant difference in the incidence of first or second remissions, and the time taken to enter remission did not differ significantly between the two groups. Comparison with the results of other trials suggests that the use of maintenance chemotherapy in addition to immunotherapy produces longer remissions. Five patients in the C group developed leukaemic central-nervous-system (CSN) involvement, in comparison with none in the C+I group. CNS relapse did not produce a significant decrease in remission length (P greater than 0.1) but reduction in survival after CNS relapse was highly significant (P = 0.001). These results suggest that administration of BCG from an early stage in the treatment of AML may protect the CNS against leukaemic infiltration and therefore serve as a simple, innocuous form of CNS prophylaxis.