How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Endoscopic treatment of strictures in Crohn's disease.

Patients with Crohn's disease often develop (recurring) intestinal stenosis. This is a result of continuous activation of fibrogenic cells by ongoing inflammation. Surgery is usually needed and consists of intestinal resection or strictureplasty. Medical therapy has not proven to be successful. Over the years endoscopic treatment has become more important. Uncomplicated stenosis, with a maximal length of 4 cm, can be treated by balloon dilatation. Indications, procedure and results are discussed. More recently, local corticosteroid injection in addition to balloon dilatation has been studied, but it remains to be seen whether long-term prevention of re-stenosis occurs. Other endoscopic therapies and new developments are also discussed in this chapter.

[Cutaneous nocardiosis as an opportunistic infection]. / Cutane nocardiose als opportunistische infectie.

A 46-year-old man who had been treated with azathioprine and budesonide for Crohn's disease for the past eight years developed a purulent skin condition on the right ring finger. Despite surgical drainage and treatment with amoxicillin and flucloxacillin, the condition spread itself over the hand and lower arm, partly per continuum and partly in jumps. The patient did not feel ill and there were no systemic symptoms. Ultimately, Nocardia asteroides was cultured from the wound and complete cure was achieved after 8 months' treatment with co-trimoxazole. Infections with Nocardia spp. are rare but may occur more often and run a more fulminant course in patients under treatment with immunosuppressants. Cutaneous nocardiosis generally has a characteristic lymphogenous spreading pattern, but an atypical picture with pustules, pyoderma, cellulitis or abscess formation is also possible. In non-cutaneous nocardiosis there is usually pneumonia or lung abscess, possibly with secondary haematogenous spread to the central nervous system or skin. Culturing Nocardia requires more time than usual but can be promoted by special culture media. Treatment of the infection with co-trimoxazole is the method of choice and is almost always successful in cases of cutaneous nocardiosis.

Sclerosing pancreato-cholangitis responsive to steroid therapy.

Four patients with weight loss, jaundice, a sonolucent swelling of the pancreas, and multiple bile-duct strictures are described. These cases of sclerosing pancreato-cholangitis responded to steroid therapy.

Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue.

OBJECTIVE: To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity. METHODS: Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques. RESULTS: Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation. CONCLUSION: Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.