Does colitis associated with primary sclerosing cholangitis represent an actual subset of ulcerative colitis?

BACKGROUND/AIMS: The clinical course and endoscopic features of colitis associated with primary sclerosing cholangitis have not been well documented. METHODOLOGY: Since 1980, a total of 485 patients with ulcerative colitis have been seen in our departments. During this period, we experienced 6 patients with primary sclerosing cholangitis, 4 of whom had ulcerative colitis concomitantly. RESULTS: Colitis preceded primary sclerosing cholangitis in 3 of the 4 patients. There were 2 males and 2 females. One patient had left-sided colitis while 3 had total colitis, 1 with a first attack and 3 with relapsing-remitting type. Two of the 4 patients had colonoscopically dominant inflammation in the proximal colon with continuous histological inflammation from the rectum to the proximal colon. Three colitic patients have been well controlled with oral sulfasalzine or mesalazine administration. Only 1 female patient had been hospitalized twice for moderately severe attacks of ulcerative colitis that required systemic prednisolone administration, however, this patient quickly responded to this treatment for each admission. CONCLUSIONS: Colitis associated with primary sclerosing cholangitis exhibited atypical colonoscopic findings and exhibited milder disease activity than ulcerative colitis without primary sclerosing cholangitis.

Crohn's disease complicated by adult-onset Still's disease.

A 31-year-old man with Crohn's disease developed arthritis, spiking fever, and skin rash indistinguishable from that of adult-onset Still's disease. He was admitted to our hospital because of a periumbilical intestinal skin fistula. Crohn's disease had been diagnosed in 1991, and had required intestinal resection twice, and schizophrenia had been diagnosed in 1993. He developed polyarthritis and spiking fever, accompanied by a macular skin rash on both forearms. Marked hepatosplenomegaly and bilateral pleural effusion were detected on computed tomography examination. These findings are indistinguishable from those of adult-onset Still's disease. Because his mental status had deteriorated following high-dose prednisolone on a previous admission, he was treated with an immunosuppressive agent on this occasion, with the treatment being successful. This is the first report of adult-onset Still's disease complicating Crohn's disease. In patients with Crohn's disease, polyarthritis and skin rash can easily be misdiagnosed as enteropathic arthritis with erythema nodosum associated with the Crohn's disease. Although adult-onset Still's disease may not be fatal, early diagnosis is important because it can, in rare cases, result in life-threatening complications.

Cross-reactivity of yeast antigens in human colon and peripheral leukocytes.

Elevation of the serum anti-Saccharomyces cerevisiae antibody (ASCA) level has been reported in patients with Crohn's disease. This study investigated the antigenic distribution of S. cerevisiae in human colon and peripheral leukocytes. ASCA was isolated from sera from patients with Crohn's disease using immuno-affinity chromatography and then biotinylated and assayed immunohistologically and immunocytologically to determine the distribution of antigens recognized by ASCA in human colon and peripheral leukocytes. Immunoblot analysis of yeast extract and human peripheral leukocytes was performed. Immunohistological study using biotinylated ASCA revealed the presence of yeast-like particles in the granulation tissue of inflamed colonic mucosa. Biotinylated ASCA also stained lymphocytes and polymorphonuclear cells infiltrating inflamed intestine. Monocytes in epithelioid granulomas of colon with Crohn's disease were also stained. Polymorphonuclear leukocytes in peripheral blood were also stained with biotinylated ASCA. The antigens reactive to ASCA among heat-extracted, non-heat-extracted yeast antigens, and human leukocyte extract differed. The findings of cross-reactivity of polymorphonuclear leukocytes with S. cerevisiae antigen and the presence of S. cerevisiae antigen in Crohn's disease granulomas suggest the possibility of involvement of S. cerevisiae in the pathogenesis of Crohn's disease.

Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease.

Although the cytokine network plays a key role in the inflammatory responses in inflammatory bowel disease, no comprehensive analysis of the intestinal cytokine network has been reported. We analyzed messenger RNA levels for various cytokines in human intestine by real-time quantitative polymerase chain reaction to clarify the cytokine profiles involved in the pathogenesis of inflammatory bowel disease. Biopsy specimens were obtained from 23 patients with ulcerative colitis (15 men, 8 women, mean age of 44.1 years), 17 patients with Crohn's disease (15 men, 2 women, mean age of 21.6 years), and 8 normal controls (6 men, 2 women, mean age of 62.7 years) who underwent colonoscopy for suspected colonic disease. Messenger RNA was isolated from two biopsy samples and reverse-transcribed to obtain cDNA. Mucosal mRNA levels for IL-1beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-gamma and TNF-alpha were simultaneously analyzed by real-time quantitative polymerase chain reaction. In patients with active ulcerative colitis, IL-1beta, IL-4, IL-5, IL-8, IL-12p40, IFN-gamma and TNF-alpha mRNA levels were significantly higher than those in controls. In patients with active Crohn's disease, IL-1beta, IL-8, and IL-12p40 mRNA levels were significantly higher than those in controls. Mucosal level of IL-12p40 mRNA was significantly higher in patients with inactive Crohn's disease than in controls. Both Th1 and Th2 cytokine mRNA levels were increased in colonic mucosa of patients with ulcerative colitis suggesting the possibility that cellular and humoral immunity play roles in the pathogenesis of this disease. In patients with Crohn's disease, Th1 cytokine mRNA levels were increased in colonic mucosa, suggesting predominance of cellular immunity in the pathogenesis of this disease.

Heterogeneity of HPLC profiles of human class II MHC-bound peptides isolated from intestine with inflammatory bowel disease.

Studies of the T-cell-receptor repertoire and oligoclonal expansion of lamina propria T cells in patients with Crohn's disease suggest restricted antigen processing in this disease. We examined HPLC elution profiles of HLA-DR-bound peptides isolated from human intestine. Surgical samples of colon and ileum were obtained from patients with ulcerative colitis, patients with Crohn's disease, and normal colon from patients undergoing colon carcinoma treatment as controls. Specimens were homogenized and HLA-DR molecules were isolated using anti-HLA-DR antibody-coupled immunoaffinity chromatography. HLA-DR-bound peptides were dissociated from the HLA-DR groove by acid treatment, isolated, and analyzed by reversed-phase HPLC. HPLC elution profiles of HLA-DR-bound peptides were similar in patients with ulcerative colitis and controls. Large peaks were found in patients with Crohn's disease, but the retention times of these peaks differed among individuals. Elution profiles of HLA-DR bound peptides suggest that specific antigen presentation might occur in patients with Crohn's disease, although the specific antigens appear to differ between patients.

Three cases of primary sclerosing cholangitis associated with ulcerative colitis; diagnostic usefulness of magnetic resonance cholangiopancreatography.

BACKGROUND/AIMS: Primary sclerosing cholangitis is often accompanied by inflammatory bowel disease in western countries. However, the incidence of primary sclerosing cholangitis in patients with ulcerative colitis appears to be much lower in Japan. METHODOLOGY: Between 1980 and 1998, a total of 402 patients with ulcerative colitis were seen in our department. The patients were evaluated by abdominal ultrasonography, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography when persisting abnormalities of biochemical findings suggested the presence of hepatobiliary diseases. RESULTS: Of the 402 patients with ulcerative colitis, 3 patients with primary sclerosing cholangitis were found. There were 2 men and 1 woman. One patient had left-sided colitis while 2 had total colitis. Magnetic resonance cholangiopancreatography was done in 2 of these 3 patients and demonstrated diagnostic features of primary sclerosing cholangitis. All 3 patients had intra- and extrahepatic involvement by primary sclerosing cholangitis. One male patient died due to progressive hepatic failure. The other male patient was treated with ursodeoxycholic acid, but serum alkaline phosphatase level remained above the normal range. The female patient maintained normal serum alkaline phosphatase levels without specific medication. CONCLUSIONS: Magnetic resonance cholangiopancreatography is the most safe and convincing tool for the diagnosis of coexistent primary sclerosing cholangitis in the patients with ulcerative colitis.