Recurrent necroinflammatory disease of multiple organs and colon. Systemic presentation of inflammatory bowel disease or gut involvement during systemic disorder.

A 30-year-old man with a recurrent febrile illness resembling infection is described. Because he presented with an acute abdomen, he underwent a laparotomy, which showed the paraaortic and mesenteric lymph nodes to be changed into an abscess-like granulomatous tissue made up of necrotized granulocytes. During further flare-ups, the disease affected the spleen, skin, colon, peripheral nerve, and muscle. Histology on the biopsy materials of both the skin and colon, and on the surgically removed spleen showed the same invading pathologic tissue. Exhaustive investigation disclosed no pathogen, and the flare-ups responded repeatedly to high-dose steroids. This patient's picture has recently been defined as a syndrome of chronic granulomatosis based on several published cases. As a distinctive feature, in our patient the granulomas affected also the colon. For the present, and for another previously described similar case we analyzed the factors that might permit the differential diagnosis between the above-mentioned granulomatous syndrome and Crohn's colitis.

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

Primary biliary cirrhosis: lung involvement.

Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumour necrosis factor in serum and synovial fluid of patients with active and severe rheumatoid arthritis.

Fifteen serum samples and 29 synovial fluids of patients with rheumatoid arthritis (RA) were examined for the presence of tumour necrosis factor (TNF). The assay for TNF was based on the cytotoxic activity of this cytokine for human melanoma cells in tissue culture. High concentrations of TNF were found in serum samples of patients with severe RA, who had increased erythrocyte sedimentation rate and serum alpha 2 macroglobulin, but decreased haemoglobin and serum iron concentrations. Tumour necrosis factor was also found in the synovial fluid of 16 out of 29 patients. High TNF concentrations were found in fluids with greater than 10(10) leucocytes/l. Tumour necrosis factor was not detected in the serum of normal subjects or in synovial fluid of patients with osteoarthritis. A mediator of inflammation, such as TNF, may contribute to the severity of RA.

HLA antigens and clinical manifestations in Crohn's disease.

A clinical, radiological and immunogenetical study was carried out on 51 Crohn's patients. Rheumatological disorders were found in 16 of them, with higher frequency in those with colon involvement only. A statistically significant increase in the frequencies of HLA-A9 and HLA-Cw3 was noted: Cw3 showed a particularly high frequency in males, and A9 in younger patients. The frequency of HLA-B27 was significantly increased in the patients with colon involvement. In the group of 16 patients with rheumatic diseases HLA antigen frequencies were not significantly different from the control population.