Primary biliary cirrhosis: when and why does the disease develop?

Primary biliary cirrhosis is a chronic cholestatic liver disease with an autoimmune pathogenesis, that generally develops in adult life, often in perimenopausal age. The clinical features are heterogeneous, ranging from an asymptomatic presentation to end-stage liver disease. Primary biliary cirrhosis is unknown in children and its natural history has yet to be elucidated. Following a Canadian report of primary biliary cirrhosis in two girls (16 and 15 years old), we describe a clinical case developing at 17 years of age. A temporal association between Borrelia Burgdorferi infection and diagnosis of primary biliary cirrhosis was observed.

[Comparison of ultrasonography and sialography vs. magnetic resonance in the diagnosis of the primary Sjogren's syndrome]. / La risonanza magnetica nucleare nella diagnosi della sindrome di Sjögren primitiva. Confronto con le metodiche ecografica e scialografica.

To date there is no agreement as to which imaging technique is best for the evaluation of the oral component of primary Sjögren's Syndrome (SS). The purpose of the present study has, therefore, been to determine the reliability of Magnetic Resonance (MR) in the evaluation of salivary alterations in patients with SS. The study involved 23 patients suffering from SS according to the European criteria. All the patients underwent ultrasonography and MR of the major salivary glands, parotid sialography and biopsy of the minor salivary glands. The first control group was made up of 50 healthy subjects who underwent parotid ultrasonography. The second control group comprised 23 subjects who underwent MR of the head and neck for other non parotid pathology. The ultrasonography, MR and sialography images were evaluated by a single observer during a single session and scored from 0 to 4. In the SS patients ultrasonography was abnormal in all 23 cases (100%): 3 patients showed grade 1 alterations (13%); 5 grade 2 (21.7%); 9 grade 3 (39.1%); 6 grade 4 (26.1%). In the healthy controls, grade 0 was found in 36 subjects (72%) while the remaining 14 subjects revealed grade 1 alterations (28%). Using MR imaging only one of the SS patients showed grade 0 alterations (4.3%), 7 showed grade 1 alterations (30.4%), 9 grade 2 (39.1%), 5 grade 3 (21.7%) and only 1 grade 4 (4.3%). MR imaging sensitivity was 95.8% while specificity was 100%. For ultrasonography, considering grade 1 as non pathological, we found a sensitivity of 88.4% and specificity of 100%. The MR score for SS patients was compared to that obtained with sialography and ultrasonography. There was a good correlation between MR and sialography (r = 0.528, p = 0.010) while the correlation between MR and ultrasonography was not statistically significant. This study confirms that, of the diagnostic procedures available for evaluation of salivary gland involvement in SS, the most useful initial examination is ultrasonography. When there is some doubt or there are subtleties, MR is a valid alternative to classical sialography.

Effects of cyclosporin on joint damage in rheumatoid arthritis. The Italian Rheumatologists Study Group on Rheumatoid Arthritis.

According to the most recent literature, few antirheumatic drugs can claim disease-controlling properties over the anatomical joint damage in rheumatoid arthritis (RA). A small number of studies have favored one or another of the available agents, in particular parenteral gold salts, sulphasalazine and methotrexate, but the evidence regarding their efficacy is not convincing when analysed using methodological criteria known to be important in evaluating radiologic evidence of joint damage. The radiologic results in long-standing RA patients have shown that CsA may be of benefit in reducing disease progression. Data from the second year of a clinical trial designed to compare the disease-controlling, anti-rheumatic properties of CsA with those of conventional disease-modifying anti-rheumatic drugs (DMARDs) in early RA support the hypothesis that CsA may be useful in delaying the appearance of new joint erosion.

[The ankle and hindfoot of rheumatoid arthritis patients: study with computerized tomography]. / La caviglia e il retropiede nei pazienti con artrite reumatoide: studio mediante Tomografia Computerizzata.

To study ankle and hindfoot involvement, we used Computed Tomography (CT) in 38 rheumatoid arthritis (RA) patients (32 women, 6 men, mean age: 56.3 +/- 10.1 years, mean disease duration: 9.9 +/- 6 years) all presenting a definite clinical disease of these joints. The scans were performed on 3rd generation CT equipment (GE ProSpeed SX), with coronally oriented scans 3 mm thick. Bone erosions and joint space narrowing (present/absent) of both talocrural and posterior talocalcaneal joints were assessed and heel valgus angle was measured. Ankle changes (erosion plus joint narrowing) were observed in 15 patients (39.5%, 17 of 76 lower limbs), talocalcaneal changes in 18 (47.4%, 31 lower limbs) and valgus deformity of the hindfoot in 22 (57.9%, 40 lower limbs). Involvement of talocrural and talocalcaneal joints as well as alignment abnormalities were symmetrical in 13.3%, 77.8% and 81.8% of the cases, respectively. All the CT findings were significantly related to disease duration (p = 0.02) and hindfoot injuries to Ritchie index too (p < 0.05). No relationship with seropositivity was observed. Our study confirms that radiographic changes do not entirely mirror clinical evidence and shows that CT does not represent a routine examination for RA patients, but could be reserved to those with prolonged disease or severe heel deformity to plan surgery.

Thyroid gland disorders in primary Sjögren's syndrome.

OBJECTIVES: To evaluate the frequency of thyroid disorders in primary Sjögen's syndrome. PATIENTS AND METHODS: 121 consecutive patients meeting Vitali's criteria for primary Sjögren's syndrome and 74 with rheumatoid arthritis underwent thyroid hormone assays, tests for antimicrosomal and antithyroglobulin antibodies, tests for antinuclear antibodies and antibodies to extractable nuclear antigens. Antimicrosomal and antithyroglobulin antibodies were also assayed in 404 controls. RESULTS: frequencies were calculated separately in males and females, and data in females were subjected to statistical analysis. As compared with controls, Sjögren's syndrome patients were more likely to have antimicrosomal antibodies (9% versus 17.6%, P < 0.05) and both Sjögren's syndrome and rheumatoid arthritis patients were more likely to have antithyroglobulin antibodies (1% versus 13.4% and 10.9%, respectively, P < 0.0001). Hypothyroidism was more common among Sjögren's syndrome patients (13.4%) than rheumatoid arthritis patients (3.1%) (P < 0.05). Sjögren's syndrome patients with thyroid disorders were less likely to have antinuclear antibodies, rheumatoid factors or a Chisholm's stage 3 or 4 lip biopsy. CONCLUSIONS: our data confirm that thyroid disorders are more common in primary Sjögren's syndrome than in rheumatoid arthritis and controls. Production of autoantibodies and severe histologic lesions were less common in Sjögren's syndrome patients with than without thyroid disorders.

Juvenile onset of primary Sjögren's syndrome: report of 10 cases.

OBJECTIVE: Ten new cases with primary Sjögren's syndrome (pSS) whose disease began before age 16 are described. Special attention is paid both to the follow-up and treatment of this condition. METHODS: Cases with juvenile pSS were retrospectively identified from our series of 180 pSS patients. Ocular, salivary, and extraglandular manifestations as well as a full laboratory evaluation including HLA-DR typing were retrieved. RESULTS: A disease prevalence of 5.5% (10 cases, 8 female and 2 male) was found in our series. The mean age at onset was 11.0 years, but the disease started at the age of 4 in 2 patients. At onset, parotid swelling was found in 6 cases and extraglandular manifestations in 3. Throughout the follow-up period (mean 48.6 months from the time of diagnosis), the clinical picture was similar to that of pSS in adults, but oral involvement was generally milder. Extraglandular manifestations were always present but never severe. Pertinent laboratory abnormalities (e.g. rheumatoid factor, polyclonal hypergammaglobulinemia, leukopenia, increased ESR, ANA and anti-SSA/SSB antibodies) were found in all patients. Specifically, ANA and anti-SSA were always positive. Moreover, in our cases histocompatibility antigens HLA-DR3 and DR 52 were closely associated with the disease. Clinical outcome was difficult to predict; however, no serious complications have been observed so far. We obtained good results with low-dose steroids and/or hydroxychloroquine, especially with regard to the extraglandular manifestations and laboratory abnormalities. CONCLUSION: We confirm that juvenile pSS is not a rare condition. It closely resembles pSS in adults except for the extremely high prevalence of recurrent parotitis and immunological findings.

Pancreatic exocrine involvement in primary Sjögren's syndrome.

Exocrine pancreatic involvement of primary Sjögren's syndrome (SS) was studied. Pancreatic enzyme levels (total amylase, pancreatic isoamylase and immunoreactive trypsin) along with anti-ductuli antibodies (Ab) were studied in 77 patients with primary SS. In 10 patients with normal and 10 with abnormal enzyme levels pancreatic CT scans were also obtained. All enzyme levels were significantly increased in comparison to the control group. Immunoreactive trypsin was found to be the most frequently increased enzyme (35.3% of pSS patients). Anti-ductuli Ab were not found in any patient. Pancreatic CT scans were normal in all subjects with enzymatic increase, whereas 2 abnormal scans were demonstrated in patients without enzyme changes. Our study suggests that exocrine pancreatic involvement is frequent when measured by enzyme levels. Nevertheless, we were unable to demonstrate any morphological lesion by CT scan.

[Diagnostic value of labial salivary biopsy in Sjogren's syndrome: report of 182 cases]. / Valore diagnostico della biopsia delle ghiandole salivari minori nella sindrome di Sjögren (Studio su 182 casi).

Various sets of criteria have been suggested in order to establish a diagnosis of Sjögren's syndrome (SS) in as much as evaluation of the salivary component is highly controversial. Our study was aimed at investigating both sensitivity and specificity of labial salivary gland biopsy (LSGB), as well as at comparing this method with other diagnostic procedures commonly employed in SS. LSGB was performed in 182 patients (174 female and 8 male, mean age 51.2) with xerostomia, dry eyes, parotid swelling and/or serological abnormalities such as positive rheumatoid factors, antinuclear antibodies, leukopenia and hypergammaglobulinemia. Diagnosis of SS was made according to the criteria recently proposed by Vitali et al. (1993). Severity of histologic changes was graded according to the Chisholm and Mason scoring system. Bioptic samples were considered abnormal when at least one focus of mononuclear cells/4mm2 was observed. The following parameters were also assessed in each patient: questionnaire of symptoms, Saxon test, sialography, salivary dynamic scintiscan, Schirmer-I-test, rose Bengal score, ANA, anti-SSA/SSB antibodies and rheumatoid factors. According to the above diagnostic criteria, 108 out of 182 patients had SS, 90 primary and 18 secondary. For 74 there were not enough data for a definite diagnosis of SS. In 9 cases (4 with and 5 without SS) LSGB was excluded because no glandular tissue was found in the specimens. Among the remaining 173, Grades 3 or 4 were found in 74 patients (71.2%) with SS and only in 1 case (1.4%) without SS. LSGB showed a very high specificity (98.6%) and a rather good sensitivity (72.5%). However, biopsy was crucial for diagnosis in only 11 cases (14.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lacrimo-auricolo-dento-digital syndrome mimicking primary juvenile Sjögren's syndrome.

We describe a 24 year old female patient affected with symptoms of severe xerostomia and keratoconjunctivitis sicca since her childhood. She also had several malformations involving face and digits as well as cup shaped ears, enamel dysplasia and absence of lacrimal puncta. Hence, the diagnosis of Lacrimo-Auricolo-Dento-Digital (LADD) syndrome was made. The main differences between this rare, inherited disease and primary juvenile Sjögren's syndrome are pointed out.

An immunohistochemical study of immunological phenomena in minor salivary glands in patients with Sjögren's syndrome.

Using different monoclonal antibodies, we performed an immunofluorescent technique on labial salivary glands in order to investigate the immunological phenomena involved in Sjögren's syndrome (SS). An aberrant expression of HLA-DR molecules was detected on cytoplasm of epithelial labial salivary cells in 9 out of 19 (47%) patients, with SS. No such expression was found in 8 patients without SS or in 3 normal controls. HLA-DQ molecules were demonstrated also in two out of ten SS patients without HLA-DR. A lymphocytic infiltration was not correlated with the expression of class II molecules. T cells bearing gamma delta receptors were not detected. The intracellular adhesion molecules (ICAM-1) and lymphocyte function associated antigen-1 (LFA-1) were not found on epithelial glandular salivary cells of patients and controls. In conclusion, these data suggested that the absence of ICAM-1 and LFA-1 in salivary cells and the absence of infiltrating T cells bearing gamma delta receptors exclude their immunopathogenetic role in SS; moreover, these data demonstrated that the aberrant expression of HLA class II molecules on epithelial salivary cells of patients with SS is not a phenomenon correlated with the lymphocytic infiltration.

Gastric involvement in primary Sjögren's syndrome.

Gastric involvement was investigated in twenty Italian patients with primary Sjögren's syndrome (pSS). Gastric complaints were present in 11 cases (55%) and endoscopic abnormalities in 10 (50%) including 2 cases with active duodenal ulcer. Only two patients (10%) showed moderate chronic atrophic gastritis (AG), while most (85%) had superficial gastritis (SG). No correlations were found among endoscopy, histology and gastric symptoms. Mean serum group I pepsinogen (PG I) levels were significantly higher (p < 0.01) and PG I concentrations in the fundus of the stomach were significantly lower (p < 0.05) in pSS patients than in a matched control group of dyspeptic subjects. Serum and antral gastrin levels were elevated in 3 cases with pSS (15%) including the two with AG, although the mean levels were not different from the controls. Antibodies to gastric parietal cells (PCA) were detected in two cases (10%) including 1 with AG. The present study contradicts previous reports claiming that AG with hypopepsinogenemia is a prominent feature in Sjögren's syndrome. We suggest that, at least in Italian patients, pSS is often associated with SG and high PG I levels.

Renal artery thrombosis and hypertension in a 13 year old girl with antiphospholipid syndrome.

The case of a 13 year old girl with renal artery thrombosis and hypertension is described. A cerebrovascular accident and a probable occlusion of the superior mesenteric artery also occurred. Very high levels of 'lupus anticoagulant', anticardiolipin antibodies as well as false positive Venereal Disease Research Laboratory tests were repeatedly shown. Moreover, the patient fulfilled at least four classification criteria for systemic lupus erythematosus, but only a slight positivity for antinucleolar antibodies was present. The striking relation between antiphospholipid antibody levels and clinical events and the treatment of this complex syndrome are discussed.