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Background and Aim: Despite widespread recommendations and use of intravenous corticosteroids (IVCS) for the treatment of acute flares of ulcerative colitis and Crohn's disease, limited evidence exists comparing outcomes of the two most common regimens, intravenous methylprednisolone (IVMP) and intravenous hydrocortisone (IVHC). IVHC has stronger mineralocorticoid effects compared with IVMP and may cause higher rates of hypokalemia. We aimed to determine differences in clinical outcomes including requirement for inpatient rescue therapy, bowel resection, and rates of hypokalemia., Methods: We conducted a multicenter cohort study of all adult patients admitted with an acute flare of inflammatory bowel disease (IBD) to the three tertiary hospitals in Auckland, New Zealand, where the protocol at each institution is either IVMP 60 mg daily or IVHC 100 mg four times daily. All patients requiring IVCS between 20 June 2016 and 30 June 2018 were included. The IVCS protocol was then changed at one hospital, where further data were collected for a further 12 months from 30 January 2019 until 30 December 2019., Results: There were 359 patients, including 129 (35.9%) patients receiving IVMP and 230 (64.1%) patients receiving IVHC. IVMP treatment was associated with a greater requirement for rescue therapy than IVHC (36.4% vs 19.6%, P = 0.001; odds ratio [OR] = 2.79; 95% confidence interval [CI], 1.64-4.75, P < 0.001), but also reduced rates of hypokalemia (55.8% vs 67.0%, P = 0.04; OR = 0.49; 95% CI, 0.30-0.81, P = 0.005). There was no difference between treatment groups for the median length of admission (5 days, interquartile range [IQR] 3-8), median duration of IVCS treatment (3 days, IQR 2-5), or bowel resection within 30 days of admission (12.4% vs 11.7%; OR = 1.04)., Conclusion: For the treatment of an acute flare of IBD, treatment with IVMP results in significantly more requirement for inpatient rescue biologic or cyclosporin. In addition, it causes statistically significant less hypokalemia than IVHC, although in practice differences are negligible., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The management of patients with ulcerative colitis who are dependent on corticosteroid for control of symptoms, or refractory to corticosteroids or standard immunosuppressive therapy, is challenging. The development of newer medical therapies has increased the options for managing patients in this situation, but access and funding remain limited. This guideline summarises the literature regarding this situation and provides guidance as to the management of refractory colitis in the New Zealand setting.

Background: Escherichia coli, listeria, and streptococcal antigens have been found in Crohn's disease tissues. Antibodies to Klebsiella pneumoniae have been found in patients with inflammatory bowel disease and ankylosing spondylitis. The presence of these bacterial antigens in Crohn's granulomas would be of aetiological interest, while their presence in ulcers alone would be more likely to indicate secondary infection., Aim: To investigate inflammatory bowel disease tissues for the presence of these bacteria., Methods: Formalin fixed, paraffin processed sections from 53 patients (19 ulcerative colitis, 23 Crohn's disease; 11 normal tissues from cancer resections) were studied by immunohistochemistry. Control tissue consisted of normal human small bowel injected submucosally with either E coli, Listeria monocytogenes, Proteus mirabilis, or Klebsiella pneumoniae serotypes K2, 3, 17, 21, 26, 36, and 50, and colonic biopsies from a child with E coli 0114 infection. Tissues were stained by Gram-Twort, and with specific antibodies for E coli (Dako B357), L monocytogenes (Difco 2302-50), and K pneumoniae (Biogenesis 5580-5208) using an immunoperoxidase technique., Results: Positive staining for E coli was observed on the luminal surface epithelium and in ulcers in 35% of Crohn's disease patients, 26% of ulcerative colitis patients, and no normal controls. Superficial staining for L monocytogenes was observed in one case of ulcerative colitis only. Staining for K pneumoniae was observed in one case of ulcerative colitis and one of Crohn's disease. No granulomas, giant cells, or germinal centres stained positively for any of the three bacterial antigens., Conclusions: These data do not support a primary role for E coli, L monocytogenes, and K pneumoniae in inflammatory bowel disease. The presence of E coli antigens in ulcers suggests secondary infection in these lesions.

Background: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3)., Aim: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease., Methods: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls., Results: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01)., Conclusion: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study.

Objective: To assess the changing distribution of disease within the large bowel in patients presenting with ulcerative proctitis or proctosigmoiditis. To evaluate the influence of clinical exacerbations, smoking, parity and family history in disease extension., Design: Retrospective single-centre study in a university hospital., Methods: Case records of patients presenting over a 40-year period were examined to evaluate the clinical course and disease distribution from initial presentation to final follow-up. For each patient whose disease extended to the more proximal colon, an age- and sex-matched control patient was identified whose disease remained confined to the original site. Patients completed a questionnaire to provide information on family history, smoking and parity. The differences in clinical exacerbations, family history, smoking and parity were then compared between the two groups., Results: Among 145 patients presenting with proctitis or proctosigmoiditis followed prospectively for a median period of 10.9 years, the disease extended in 53 patients. Using actuarial methods the disease progressed beyond the rectosigmoid area in 16% of patients at 5 years and 31% at 10 years. Among the patients whose disease progressed, progression was preceded in 68% of cases by a clinical exacerbation of the colitis. When patients whose disease progressed were compared with those whose disease remained confined to the original site, no differences were detected in the number of clinical exacerbations, smoking habit, family history or parity., Conclusions: The factors that are associated with the extension of colitis are probably different from those that predisposed an individual to develop inflammatory bowel disease initially.

The risk of developing colorectal cancer has been compared in two identically selected cohorts of patients with extensive Crohn's colitis (n = 125) and extensive ulcerative colitis (n = 486). In both groups the effects of selection bias have been reduced wherever possible. There was an 18-fold increase in the risk of developing colorectal cancer in extensive Crohn's colitis and a 19-fold increase in risk in extensive ulcerative colitis when compared with the general population, matched for age, sex, and years at risk. The absolute cumulative frequency of risk for developing colorectal cancer in extensive colitis was 8% at 22 years from onset of symptoms in the Crohn's disease group and 7% at 20 years from onset in the ulcerative colitis group. The relative risk of colorectal cancer was increased in both ulcerative colitis and Crohn's disease among those patients whose colitis started before the age of 25 years. Whether the absolute risk is greater in the younger age group or merely reflects that the expected number of carcinomas increases with age is uncertain. While there is an increased risk of developing colorectal cancer in extensive colitis the number of patients with Crohn's disease who actually develop colorectal cancer is small because many patients with extensive Crohn's colitis undergo colectomy early in the course of their disease to relieve persistent symptoms unresponsive to medical treatment.