Rodolfo Ferrari

Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis.

OBJECTIVES:The clinical impact of antinuclear antibodies in primary biliary cirrhosis is uncertain. We analyzed in detail the antinuclear antibodies reactivity of primary biliary cirrhosis patients and correlated the fine specificities observed with clinical, biochemical, and immunologic parameters.METHODS:A total of 96 consecutive primary biliary cirrhosis patients and 283 pathologic controls were studied. To dissect the fine antinuclear antibodies specificities we used different techniques, such as indirect immunofluorescence on cryostat tissue sections and cell culture (HEp-2 cells), counterimmunoelectrophoresis with thymus and spleen extracts, ELISA assays with recombinant Sp100 and purified gp210 and Lamin B receptor, and immunoblot with several recombinant nuclear and cytoplasmic antigens.RESULTS:Antinuclear antibodies were detected in 53% of patients, with the following hierarchy of specificities: 27% anti-Sp100, 16% ldquo;multiple nuclear dots,” 16% anti-gp210, 16% anti-centromere, 7% XR1, 6% anti-lamin B receptor, 5% anti–SS-A/Ro, 5% anti-ribonucleoprotein, 4% XR2, 2% anti–SS-B/La, 2% perinuclear antineutrophil cytoplasmic antibodies, and 1% anti–double-stranded deoxyribonucleic acid. Several patients showed multiple specificities. The “multiple nuclear dots” pattern was detected more often in antimitochondrial antibodies negative patients. In particular, primary biliary cirrhosis specific antinuclear antibodies (anti-Sp100, anti-gp210, and anti-lamin B receptor) were detected in nine of 13 antimitochondrial negative primary biliary cirrhosis cases. Anti-gp210 was more frequent in patients with more pronounced cholestasis and more impaired liver function.CONCLUSIONS:Antinuclear antibodies reactivities are present in more than half of primary biliary cirrhosis patients and target diverse autoantigens located in distinct subnuclear structures. Anti-gp210 identifies a subgroup of primary biliary cirrhosis patients with more serious liver disease. Positivity for anti-Sp100, anti-gp210, and anti-lamin B receptor, either alone or in combination, may act as a serologic marker of antimitochondrial antibodies negative primary biliary cirrhosis.

Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases

Antibodies to the bakers yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohns disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p‐ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA‐positive and negative patients were analysed and compared. ASCA are predominant in Crohns disease (70%); among liver patients, PSC and AMA‐negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0·05). In PSC the detection of either ASCA or p‐ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p‐ANCA predict the occurrence of a concomitant inflammatory bowel disease.

Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the general population

The significance of non‐organ specific antibodies (NOSAs) in HCV‐related chronic hepatitis is largely unclear. In this study we evaluated the prevalence of NOSAs in a non‐selected population of HCV‐infected subjects. One hundred and seventy anti‐HCV positive and 192 anti‐HCV negative sex and age‐matched subjects (median age 64 years, range 7–91 years, female 68%) enrolled from the general population of a small Italian town were evaluated for NOSAs by indirect immunofluorescence on rat tissue sections and HEp‐2 cells, and by counterimmunoelectrophoresis with thymus and spleen extracts as the antigen source. One hundred and sixty‐three (96%) HCV‐infected subjects had normal ALT serum levels and no evidence of liver disease. NOSAs were found in 31 out of 170 (18%) anti‐HCV positive subjects and in 20 out of 192 (10%) controls (P = NS), with similar median titre (1:40) and range (1:40 to 1:160). Neither liver/kidney microsomal antibody type 1 nor antiactin reactivity were detected. No significant association between NOSAs and HCV genotypes was observed. In the general population, HCV‐infected subjects and healthy controls have a similar prevalence of NOSAs. Without continuous liver damage HCV infection is unlikely to induce the appearance of NOSAs.

Acute icteric hepatitis induced by a short course of low-dose cyclophosphamide in a patient with lupus nephritis

To the Editor: Bone marrow suppression, vomiting, mucositis, hemorrhagic cystitis, and infertility are known toxic effects of prolonged and high-dose cyclophosphamide therapy. Cyclophosphamide-induced hepatotoxicity has been sporadically reported in patients treated for long periods and/or with high cumulative doses (1–5). We describe a patient with systemic lupus erythematosus who developed acute icteric hepatitis following a short course of low-dose cyclophosphamide. In March 2003, a 48-year-old woman with lupus nephritis (diffuse proliferative glomerulonephritis, class IV WHO) was referred to us for increasing fatigue, nausea, and vomiting. She was frankly jaundiced, with dark urine, pale stools, and nontender hepatomegaly. Total bilirubin was 11.33 mg/dl (conjugated 10.3), aspartate aminotransferase (AST) 4224 IU/L (normal, <37), alanine aminotransferase (ALT) 4222 IU/L (normal, <40), alkaline phosphatase 364 IU/L (normal, <280), gammaglutamyltranspeptidase 136 IU/L (normal, <50), and prothrombin time 61% (INR 1.32). Blood and platelet counts and renal

Rebounds after discharge from the emergency department for community-acquired pneumonia: focus on the usefulness of severity scoring systems

Background: Community-acquired pneumonia (CAP) is common cause of hospital admission and leading cause of morbidity and mortality. Severity scoring systems are used to predict risk profile, outcome and mortality, and to help decisions about management strategies. Aim of the work and Methods: To critically analyze pneumonia “rebound” cases, once discharged from the emergency department (ED) and afterwards admitted. We conducted an observational clinical study in the acute setting of a university teaching hospital, prospectively analyzing, in a 1 year period, demographic, medical, clinical and laboratory data, and the outcome. Results: 249 patients were discharged home with diagnosis of CAP; 80 cases (32.1%) resulted in the high-intermediate risk class according to CURB-65 or CRB-65. Twelve patients (4.8%) presented to the ED twice and were then admitted. At their first visit 5 were in the high-intermediate risk group; just 4 of them were in the non-low risk group at the time of their admission. The rebound cohort showed some peculiar abnormalities in laboratory parameters (coagulation and renal function) and severe chest X-rays characteristics. None died in 30 days. Conclusions: The power of CURB-65 to correctly predict mortality for CAP patients discharged home from the ED is not confirmed by our results; careful clinical judgement seems to be irreplaceable in the management process. Many patients with a high-intermediate risk according to CURB-65 can be safely treated as outpatients, according to adequate welfare conditions; we identified a subgroup of cases that should worth a special attention and, therefore, a brief observation period in the ED before the final decision to safely discharge or admit. (www.actabiomedica.it)