Perla Vicari

Brain Magnetic Resonance Imaging Abnormalities in Adult Patients With Sickle Cell Disease Correlation With Transcranial Doppler Findings

Background and Purpose— Brain imaging abnormalities were reported in up to 44% of children with sickle cell disease (SCD). The prevalence of neuroimaging abnormalities in adult patients with SCD and their relationship to transcranial Doppler is still unclear. Our objectives were to study the frequency of MRI and MR angiography abnormalities in adults with SCD and to define what transcranial Doppler velocities are associated with intracranial stenoses detected by MR angiography. Methods— We examined all adult patients (>16 years) with SCD followed in the hematology outpatient clinic at our university hospital with MRI, MR angiography, and transcranial Doppler. Results— We evaluated 50 patients. The overall prevalence of MRI abnormalities was 60%. Abnormal MRI findings were more frequent when vessel tortuosity or stenoses were present on MR angiography (P<0.01). Patients with intracranial stenoses had significantly higher time-averaged maximum mean velocities (P=0.01). A time-averaged maximum mean velocity of 123.5 cm/s allowed the diagnosis of middle cerebral artery or internal carotid artery intracranial stenosis with sensitivity of 100% and specificity of 73% with an area under the receiver operator characteristic curve of 0.91 (CI, 0.79 to 1.00). Conclusions— The frequency of brain imaging abnormalities detected by MRI/MR angiography in adults with SCD was higher than that described for children. Transcranial Doppler velocities in adult patients with intracranial stenoses were lower than those described for the pediatric population with SCD.

Priapism is Associated with Sleep Hypoxemia in Sickle Cell Disease

PURPOSE We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease. MATERIALS AND METHODS This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations. RESULTS The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index. CONCLUSIONS Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.

Myonecrosis in sickle cell anemia: case report and review of the literature.

Vascular occlusion is responsible for most of the severe complications of sickle cell anemia (SCA). The involvement of muscle and fascia is uncommon in SCA, but myonecrosis may occur in SCA crisis. The data accumulated in the literature is limited to only a few reports describing mainly adult patients presenting with severe muscular pain. We report a rare case of sickle myonecrosis and secondary involvement of an associated joint after a severe painful crisis in the left thigh.

Can thalidomide be effective to treat plasma cell leptomeningeal infiltration

To the Editor: Dear Sir, In May 2000, a previously healthy, 52-yr-old woman was diagnosed with Salmon-Durie stage IIIA, IgG j multiple myeloma (MM). She was initially treated with six cycles of intravenous (i.v.) vincristine 0.4 mg days 1–4; i.v. doxorubicin 9 mg/m days + 198 1–4; P. O dexamethasone days 1–4, 9–12, 17–20 (VAD) every 4 weeks), the last interrupted because of Staphylococcus aureus endocarditis. At this time, during the infection treatment, she developed radicular symptoms associated with a paravertebral mass identified on computed tomography scan. The biopsy ruled out an abscess and showed a plasmacytoma. The patient underwent lumbar spinal irradiation (4000 cGy) followed by six cycles of i.v. cyclophosphamide 750 mg/m day 1: i.v. doxorubicin 50 mg/m day 1; vincristine 1, 4 mg/m day 1; P. O prednisone 60 mg/m days 1–5 (CHOP), achieving complete clinical response. In December 2000, few days before the harvest of peripheral stem-cell for autologous transplantation, she was confused and hemiparetic on physical examination. A cranial magnetic resonance imaging showed a left parietal mass. Cerebrospinal fluid (CSF) showed 250 cells/ mm, with 100% of plasma cells (Fig. 1). This finding was confirmed by flow cytometry analysis of CSF (CD45–, CD38+, j+). There were no other signs of systemic activity of the disease (no serum or urinary M protein, <5% plasma cells in the bone marrow). She was treated on oral dexamethasone (40 mg on days 1–4, 9–12, 17–20 with interval doses of 16 mg/d) and three doses of weekly intrathecal chemotherapy (methotrexate 12 mg and dexamethasone 2 mg). Despite a brief period of symptomatic relief, there was no CSF cleansing (CSF on 11/30/2001: 640 cells/mm, 100% plasma cell; CSF on 02/14/2002: 80 cells/ mm, 100% plasma cells) and the neurologic symptoms ended up progressing (see Table 1). The patient was then treated with thalidomide (Thal) 800 mg/d for 30 d with simultaneous cranial radiation, achieving total dose of 1000 cGy. Radiotherapy was interrupted because the patient’s focal deficits worsened and her mental status deteriorated, resulting in progression to death 3 months after detection of the central nervous system involvement. In this study, we describe a very unusual complication in MM with 53 cases previously related in the literature. Meningeal myelomatosis, defined as meningeal involvement by plasma cells in the CSF, although might be a presenting feature, has usually been described in the setting of pre-existing MM (1). It tends to occur in stage III disease and is associated with plasma cell leukemia in 20% of patients. Few patients were reported to relapse with meningeal compromising and limited disease outside the central nervous system (CNS) (2). We questioned the role of the paraspinal plasmacytoma as the seeding source of plasma cells into CSF (3). As the meningeal myelomatosis represents a dismal event, with 1– 2 months median survival despite aggressive local treatment, associated or not with systemic therapy (1), we tried to treat this patient with Thal and radiotherapy following intrathecal chemotherapy and high dose glucocorticoid. We were expecting a better outcome than that previously reported, assuming the usefulness of Thal in relapsed/ refractory MM patients (4), the high angiogenesis Fig. 1. Cytospin of CSF sample showing 100% of dysplasic plasmocytes, confirming the diagnosis of leptomenigeal infiltration in our patient, ·1000. Eur J Haematol 2003: 70: 198–199 Printed in UK. All rights reserved Copyright Blackwell Munksgaard 2003

Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient

Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

Absence of Association between TNF-α Polymorphism and Cerebral Large-Vessel Abnormalities in Adults with Sickle Cell Anemia

Stroke is a serious complication of sickle cell anemia (SCA) affecting children and adults. Recent reports suggested that tumor necrosis factor-α (TNF-α) (–308) polymorphism is an important risk factor for stroke in children with SCA. The role of TNF-α polymorphism in the frequency of brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) abnormalities in adults with SCA is still uncertain. Our objective was to evaluate the frequency of TNF-α polymorphism in adults with SCA and to correlate it to brain MRI and MRA findings. TNF-α (–308) polymorphism was determined in 49 adults with SCA. All subjects were evaluated with brain MRI/MRA to establish the presence of intracranial abnormalities. Thirty-three (67.3%) had abnormal brain MRA scans, 8 (16.3%) had intracranial stenosis and 29 (59.2%) showed arterial tortuosity. Forty-one (83.7%) had the GG genotype and 8 had the GA genotype. There was no correlation between homozygosity for G allele and MRA or MRI abnormalities. Although TNF-α (–308) polymorphism is a potential predictor of the genetic risk for stroke in children, we found no association between the polymorphism and large vessel abnormalities in adults with SCA.

Exercise‐Induced Abnormal Increase of Systolic Pulmonary Artery Pressure in Adult Patients With Sickle Cell Anemia: An Exercise Stress Echocardiography Study

Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle cell anemia (SCA). Exercise echocardiography (EE) can detect latent PH. We sought to investigate the occurrence of exercise‐induced abnormal response of systolic pulmonary artery pressure (SPAP) in adult patients with SCA and normal SPAP at rest, and to identify the independent predictors of this abnormal response.

Duffy-negative is associated with hemolytic phenotype of sickle cell anemia.

Universidade Federal de Sao Paulo, Disciplina Hematol & Hemoterapia, BR-04023900 Sao Paulo, Brazil

Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia.

Sickle cell anemia (SCA), a disorder characterized by both acute and chronic inflammation, exhibits substantial phenotypic variability. Interleukin-1 beta (IL-1β) and IL-6 are important in acute and chronic diseases, and their single nucleotide polymorphisms (SNPs) have been considered as predictors of prognosis in several inflammatory conditions. This study aims at exploring possible association of IL-1β and IL-6 SNPs as potential genetic modifiers and or predictors of SCA clinical and laboratory phenotypes. This cross-sectional study involved 107 SCA patients and 110 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1β (-511C>T and +3954C>T) and IL-6 (-597G>A and -174G>C) genes. Associations between these SNPs and the clinical and laboratory profiles of patients with SCA were then determined. Allelic and genotypic frequencies of IL-1β and IL-6 SNPs between patients with SCA and controls were similar and followed HWE. IL-1β +3954C>T SNP was associated with increased risk of osteonecrosis, elevated pulmonary arterial pressure and lower absolute reticulocyte count, while IL-6 -597G>A was associated with higher likelihood of retinopathy and leg ulcer. These data indicate that IL-1β and IL-6 gene SNPs are associated with SCA complications among Brazilian patients and may act as genetic predictors of SCA clinical heterogeneity.

Priapismo na doença falciforme

Priapism is a common complication of sickle cell disease. It is defined as a painful and persistent penil erection not accompanied by sexual desire or stimulation, usually lasting for more than 4 hours. The typical forms of priapism in sickle cell disease are low-flow and recurrent priapism (stuttering). The first-line treatment for this complication is not totally clear. Several treatments have been proposed such as adrenergic agents, gonadotropin-releasing hormone analogues, diethylstilbestrol, hydroxyurea. If conservative treatments fail, surgical intervention is required with cavernous shunts. This study reviewed the incidence, pathogenesis and management of sickle cell priapism.