Sacral inflammatory pseudotumor revealed by paraneoplastic syndrome

There is still debate on whether inflammatory pseudotumor should be considered benign or malignant. This lesion has only been reported twice in bone, apart from cases complicating foreign body reaction to joint replacement arthroplasty. We report here a third case, localized at the sacrum. A 31-year-old man had inflammatory dorsalgia and polyarthralgia without synovitis but with fever, asthenia, and erythema nodosa. Biological tests and X-rays were not informative, but technetium scintigraphy revealed a high level of left sacroiliac tracer binding. Several nonsteroidal anti-inflammatory drugs and sulfasalazine treatment were given over 3 months but ineffective. Pelvic magnetic resonance imaging showed an osteolytic tumor of the sacrum. Biopsy suggested a malignant fibrosarcoma, but complete evaluation after surgical resection demonstrated an inflammatory pseudotumor. All clinical symptoms disappeared within a few days after surgery, which is suggestive of a paraneoplastic syndrome. No relapse has occurred after 4 years.     

Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers

Hepatic parenchymal changes associated with Budd-Chiari syndrome (BCS) have been tentatively explained by combined arterial and portal perfusion disturbances in addition to the complete occlusion of hepatic veins. The aim of this study was to correlate pretransplant course and vascular imaging with pathologic findings in livers explanted for BCS. Seventeen consecutive white patients who underwent transplantation for severe classic BCS were retrospectively analyzed. Pretransplant course was 1 year or less in 8 patients and more than 1 year in 9 patients. Thrombophilia was found in 16 patients (94%). Imaging showed decreased portal perfusion in 16 patients (94%) and increased arterial perfusion in 9 patients. Histology showed obstructive portal venopathy and nodular regenerative hyperplasia (NRH) aspects in all cases, large regenerative nodules resembling focal nodular hyperplasia (FNH) in 9 cases, and cirrhosis in 2 cases. Patients with increased arterial inflow had large regenerative nodules and a protracted pretransplant course. Patients with acute thrombi in portal veins had parenchymal infarcts (2 cases) and a short pretransplant course. In conclusion, patients with severe BCS have a constant impaired perfusion inflow unrelated to progression of cirrhosis but related to the outcome. An early decrease in portal perfusion is observed in the short term and is responsible for NRH or infarcts if complicated with large thrombi. An increase in arterial perfusion compensates impaired portal flow in chronic BCS. Arterial hyperemia contributes to the development of large regenerative nodules that are FNH-like. This pathologic situation offers an interesting vascular model to further understand the parenchymal response to changes in hepatic blood flow.     

Inhibition of rat liver fibrogenesis through noradrenergic antagonism

The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Two weeks of CCl4 induced an approximately 5-fold increase in the area of fibrosis as compared with controls. The addition of 6-hydroxydopamine (OHDA), a toxin that destroys noradrenergic fibers, decreased fibrosis by 60%. After 6 weeks of CCl4, the area of fibrosis increased about 30-fold in CCl4-treated animals and was decreased by 36% with OHDA. At 2 weeks, OHDA abrogated the CCl4-induced increase in mRNA level of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), an inhibitor of extracellular matrix degradation, and it greatly reduced it at 6 weeks. Finally, when rats treated with CCl4 for 2 weeks also received prazosin, an antagonist of alpha1-adrenergic receptors, fibrosis was decreased by 83%. In conclusion, destruction of noradrenergic fibers or antagonism of noradrenergic signaling through alpha1 receptors inhibited the development of liver fibrosis. Because adrenoreceptor antagonists have a very sound safety profile, they appear as attractive drugs to reduce liver fibrogenesis.     

Therapeutic vaccination against chronic viral infections

Chronic viral infections such as those caused by hepatitis B virus, human papilloma virus, herpes simplex virus, and HIV, in theory, present logical targets of active specific immunotherapy. Indeed, immunological mechanisms are involved in several aspects of their pathogenesis and natural course, such as virus persistence, destruction of infected cells and control of viral replication. Therapeutic vaccination could therefore be an adequate replacement for, or adjunct to, existing therapies. Almost all approaches to therapeutic vaccination have been evaluated in those four disease areas. Despite encouraging results in animals none of these attempts has, so far, been completely successful in the human setting. However, with a better understanding of the immunological mechanisms involved in the control of disease successful therapeutic vaccines, used alone or in combination with other therapies, are an achievable goal.     

Bone mineral density and bone metabolism in spondylarthropathies

AIMS: To study the prevalence of osteoporosis in a group of patients with spondyloarthropathy and to investigate bone turnover markers and correlation between bone mineral density and the age at the beginning of the disease. PATIENTS AND METHOD: Patients with spondyloarthropathy as defined by New York and ESSG criteria. Bone mineral density was measured at the lumbar spine and hip with Hologic QDR 1000. Serum levels of osteocalcin, deoxypyridinoline, 25 vitamin D, creatinine and parathyroid hormone were measured. RESULTS: 50 patients were included in the study: 37 men, mean age 40,2+/-13,8 years. Vertebral osteopenia was observed in 34% while femoral osteopenia occurred in 40% of patients. Serum vitamin D was low in 70% of patients without parathyroid hormone or kidney function modification. Markers of bone turn over were increased in 29% of patients. There was no correlation between these biological markers and the bone mineral density. We observed a significative correlation (P=0,02) between the age at the beginning of the disease and the bone mineral density. CONCLUSION: Osteopenia is present in patients with spondyloarthropathy without any correlation with the bone turnover biological markers. We observed a significative correlation between the age at the beginning of the disease and bone mineral density.     

Clinical-scale selective depletion of alloreactive T cells using an anti-CD25 immunotoxin

Allogeneic hematopoietic stem cell transplantation is the treatment of choice for many hematological malignancies. Its efficacy is limited by graft-versus-host disease (GVHD), the leading cause of post-transplant morbidity and mortality. GVHD is mediated by a subpopulation of T cells in the stem cell graft. Ex vivo T cell depletion of all T cells of the graft can prevent development of GVHD but can lead to a delay in immune reconstitution and an increase of potentially lethal opportunistic infections and leukemic relapses. Hypothetically, an approach that enables a selective depletion of the alloreactive donor T cells that cause GVHD while preserving third party (anti-leukemic and anti-microbial) reactivity would be optimal for recipients of HSCT. Our preliminary data demonstrated that an anti-CD25 immunotoxin, which reacts with a cell surface activation antigen, can selectively deplete alloreactive donor T cells activated by non-leukemic recipient white blood cells while preserving the beneficial third-party reactivity in vitro. In this report we describe a method for clinical-scale ex vivo selective depletion of alloreactive donor T cells using the anti-CD25 immunotoxin, RFT5-SMPT-dgRTA. Two logs of alloreactive T cells could be selectively depleted while preserving third party reactivity. This method was reproducible in 10 pre-clinical experiments with 8 HLA-mismatched healthy volunteer pairs and 2 HLA-matched sibling donor/patient pairs.     

Confidence in the diagnosis of early spondylarthropathy: a prospective follow-up of 270 early arthritis patients

OBJECTIVE: To study the confidence of office-based rheumatologists (OBR) and a college of 5 experts in their diagnosis of spondylarthropathy (SpA) for early arthritis after more than 2 years of follow-up; to determine whether at that time the degree of confidence was improved by the fulfilment of the ESSG criteria. METHODS: 270 patients with early-onset (< 1 year) arthritis were prospectively followed-up for 29+/-11 months. At the final examination, OBR and the college of 5 experts rated their confidence in the diagnosis of SpA on a 0-10 analogue scale and on a 1-4 Likert scale, respectively. RESULTS: After 29+/-11 months OBR had classified 56 patients (21%) as SpA, while a collegial diagnosis of probable (N = 32) or certain SpA (N = 14) was made for 46 patients (17%). At the final examination OBR confidence in their diagnosis (gold standard) was only 6.7+/-2.4 for all 56 cases of SpA. The cumulative fulfilment of ESSG criteria for SpA after 29+/-11 months correlated with the confidence of OBR and the experts in SpA, but improved only slightly the final confidence of OBR (7.1+/-2.3 versus 6.7+/-2.4 for all 56 SpA). Similarly, OBR confidence for the 18/56 SpA patients positive for HLA-B27 was only 7.1+/-2.0. Only 21 of these 56 patients were considered as SpA at baseline, although 37/56 (66%) had fulfilled ESSG criteria since thefirst examination. CONCLUSION: This study indicates a probable lack of consensus on the nosology of early SpA and the limited help provided by the ESSG criteria to differentiate early SpA from otherforms of arthritis at baseline.     

Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center

BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS: One hundred and sixteen patients with non-cirrhotic chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital between 1971 and 1977 were followed until December 1998 or until death. Patients with significant alcohol intake were excluded from the study. Variables obtained at the time of diagnosis, including epidemiological, clinical, laboratory, and histological data were recorded to determine risk factors associated with the development of liver cirrhosis and hepatic decompensation. RESULTS: Based on complete follow-up data, the development of liver cirrhosis and hepatic decompensation was evaluated in 94 and 114 of the 116 patients, respectively. Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate aminotransferase (AST) value higher than 70 IU/L was associated with development of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at 10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently associated to the development of hepatic decompensation was the presence of fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9). Liver-related death occurred only in seven (6%) of 114 patients. In comparison with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C diagnosed in 1999 were younger, more often asymptomatic, had lower AST and alanine aminotransferase (ALT) values and had significantly lower grade and stage histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate of progression to liver cirrhosis over a prolonged follow-up. However, this might be related to the fact that two decades ago the diagnosis was made at a significantly more advanced stage of the disease. Patients at high risk of progression can be identified by biochemical and histological variables at the time of diagnosis.