Interstitial nephritis in patients with inflammatory bowel disease treated with mesalamine

Mesalamines are slow-release formulations of 5-aminosalicylic acid (5-ASA) and are effective as primary treatment and maintenance therapy in inflammatory bowel disease. Interstitial nephritis is a recognized side effect. We report two cases of biopsy-confirmed interstitial nephritis in patients being treated with 5-ASA. Both had a trial of steroid therapy. One patient had partial recovery of renal function but the other patient was in chronic renal failure and likely was approaching the need for dialysis. Interstitial nephritis is an under-recognized complication of 5-ASA therapy. Early identification and withdrawal of this drug can lead to a partial or complete reversal of renal dysfunction.     

Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine

AIM: To assess the characteristics and clinical course of nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease treated with azathioprine, so as to estimate the frequency of this complication and search for risk factors. METHODS: Cases were identified through a systematic survey of patients followed at 11 centres. At one centre, the cumulative risk of NRH was estimated and a case-control study was undertaken to identify risk factors. RESULTS: 37 cases of NRH (30 male, 7 female) were identified between 1994 and 2005. The median dose of azathioprine was 2 mg/kg/d (range 1.5 to 3.0). The median time between the start of azathioprine and the diagnosis of NRH was 48 months (range 6 to 187). After a median follow up period of 16 months (range 1 to 138), 14 patients developed complications of portal hypertension. Using multivariate analysis, male sex and stricturing behaviour were the two risk factors associated with NRH in patients treated with azathioprine. The cumulative risk calculated from the database (one centre) was 0.5% at 5 years (95% confidence interval, 0.11 to 0.89) and 1.25% at 10 years (0.29 to 2.21). CONCLUSIONS: NRH is a rare but potentially severe complication of azathioprine in patients with inflammatory bowel disease. Clinicians should be aware of this complication, and should monitor liver function tests and platelet counts closely in their patients.     

Renal tubular proteinuria in patients with irritable bowel syndrome

OBJECTIVE: Irritable bowel syndrome (IBS) is a common condition that is poorly understood. We have previously demonstrated tubular protinuria in patients with inflammatory bowel disease. This study examined whether tubular proteinuria was a feature of IBS. METHODS: Eighty control subjects (male:female, 28:52; age range 20-65 years) and 21 patients with IBS (male:female, 9:12; age range 16-64 years) (not significant) were recruited. Patients with known renal disease, hypertension, diabetes or microbiological evidence of urinary infection were excluded. The IBS patients all fulfilled the ROME II criteria. None had preceding gastroenteritis. Urinary alpha1-microglobulin (alpha1-M) was measured in a second-voided morning urine sample and corrected for urinary concentration by measurement of creatine. Blood samples were analysed for haematochemical indices including C-reactive protein. Statistical analysis was by unpaired t test. RESULTS: None of the IBS patients were reclassified with inflammatory bowel disease over a 5-year follow up period. All had normal haematochemical parameters. Mean +/- standard deviation urinary alpha1-M concentrations were significantly higher in IBS patients than controls (IBS patients, 1.17 +/- 0.65 mg/mmol; controls, 0.75 +/- 0.36 mg/mmol; P < 0.01) and exceeded 1.5 mg/mmol (the upper reference limit) in seven patients. There was no difference in urinary alpha1-M concentrations in the diarrhoea-predominant and constipation-predominant groups (mean +/- standard deviation, 1.342 +/- 0.65 versus 0.76 +/- 0.48 mg/mmol; P = 0.062). CONCLUSIONS: Urinary alpha1-M concentration is commonly increased in IBS, suggesting the presence of renal proximal tubular injury.     

Osteoporosis in patients with inflammatory bowel disease.

Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.     

Phagocyte dysfunction and inflammatory bowel disease

Inflammatory bowel diseases are common chronic inflammatory disorders. The majority are idiopathic and can be broadly divided into Crohn's disease and ulcerative colitis. Their cause is unknown, but most hypotheses focus on a primary role for T-cell dysfunction. Conversely, there is a collection of congenital disorders of phagocyte function that result not only in immunodeficiency but also in noninfectious inflammatory bowel disease. In all cases, the latter is strikingly reminiscent of the clinical and pathological features of Crohn's disease. This coincides with recent work demonstrating that despite previous emphasis on adaptive immune dysfunction, patients with Crohn's disease actually possess an unusually weak acute innate inflammatory response. This review consolidates the literature on inflammatory bowel disease in congenital immunodeficiencies and considers the role of phagocyte dysfunction in Crohn's disease. Concepts about pathogenesis and treatment that can be carried across these disorders are also discussed.     

男性炎症性肠病患者的性功能障碍

男性性功能障碍与治疗炎症性肠病(inflammatory bowel disease,IBD)的药物、IBD伴发的抑郁情绪及治疗抑郁的药物以及直肠结肠切除术合并回肠带肛管吻合术(IPAA)等相关。在治疗炎症性肠病的药物中,氨甲喋呤及柳氮磺胺吡啶是最有可能导致勃起功能障碍的。抑郁是引起性功能障碍最重要的决定性因素,治疗抑郁的药物也可能引发男性性功能障碍。IPAA可能会引起男性性功能障碍,但是大部分患者可被西地那非纠正。本文为临床医生治疗男性IBD患者的性功能障碍提供参考。     

Pulmonary complications in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Between 1996 and 1998 we investigated the occurrence of lung disorders in 82 patients with inflammatory bowel disease (30 patients with ulcerative colitis and 52 patients with Crohn's disease) and a control group of 60 subjects. The aim of our study was to determine the occurrence of pulmonary complications in patients with inflammatory bowel disease, to investigate whether ulcerative colitis or Crohn's disease are connected with a typical lung function disorder, with the inflammatory activity of the disease or if they depend on the presence of other extraintestinal manifestations. METHODOLOGY: We investigated the occurrence of lung disorders in terms of the following parameters: clinical pulmonary symptoms, chest radiography and pulmonary function tests (body plethysmography, pneumotachography, lung transfer capacity for carbon monoxide, and blood gas analysis). RESULTS: Lung function abnormalities were significantly more frequent in patients with inflammatory bowel disease as compared to controls (p<0.001). There was no apparent correlation between these abnormalities and either bowel disease activity or drug administration (sulphasalazine, mesalazine). CONCLUSIONS: Despite the lack of radiological abnormalities, we identified a high incidence of pulmonary function abnormalities (suspicious of interstitial lung disorder) in patients with inflammatory bowel disease; 56.7% of patients with ulcerative colitis and 57.7% of patients with Crohn's disease had reduced lung transfer factor.     

Psychiatric illness in patients with inflammatory bowel disease.

One hundred and sixty two consecutive patients attending a clinic for inflammatory bowel disease (91 Crohn's, 71 ulcerative colitis) were assessed for the presence of anxiety and depression using a simple self-rating questionnaire (HAD scale) and a detailed evaluation (DSM-III). The overall prevalence of psychiatric illness (DSM-III) in ulcerative colitis and Crohn's disease was 34% and 33% respectively. There was no statistically significant association in ulcerative colitis patients between the presence of psychiatric illness and the present physical illness. Psychiatric illness was more common in the physically ill patients with Crohn's disease, compared with those who were well: 50% v 8% (p less than 0.01), using (HAD) criteria 66% v 37% (p less than 0.001). The presence of patients between the presence of psychiatric illness and the presence of physical illness. Psychiatric who were well: 50% v 8% (p less than 0.01) by DSM-III criteria, using (HAD) criteria 66% v 37% (p less than 0.001). The presence of psychiatric illness adversely affected physical recovery. Seventeen percent recovered when psychiatrically ill v 53% when psychiatrically well (p less than 0.025). The HAD scale was assessed as a screening method for psychiatric illness in this medical setting and had a sensitivity of 76% and a specificity of 79%.     

Cytokine production in patients with inflammatory bowel disease.

The production of cytokines in peripheral blood mononuclear leukocytes of patients with inflammatory bowel disease was investigated. T cell subset analysis and differential white blood cell counts were also performed. Thirty five patients with ulcerative colitis, 14 with Crohn's disease, and 15 age matched healthy volunteers were studied. No differences were observed in T cell subsets and OKT4/OKT8 ratios in patients with ulcerative colitis or Crohn's disease compared with controls. Interleukin 1 beta production was significantly increased in active ulcerative colitis and Crohn's disease, compared with values in controls, but returned to control levels in the inactive stages. In addition, in active ulcerative colitis and Crohn's disease, there were significant correlations between the interleukin 1 beta production and the ulcerative colitis activity index or Crohn's disease activity index. Interleukin 2 production was also significantly increased in the active ulcerative colitis and significantly correlated to the activity index, but there was no change in Crohn's disease patients compared with controls. Gamma interferon production in patients was the same as that in controls. This study suggests that the interleukin 1 beta and 2 values in peripheral mononuclear leukocytes of active untreated inflammatory bowel disease are indicators of the disease states of ulcerative colitis or Crohn's disease, or both.     

Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.

BACKGROUND & AIMS: The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease. METHODS: All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993. RESULTS: Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000. CONCLUSIONS: Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.     

Vaccinations in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.     

Reduced bone density in patients with inflammatory bowel disease.

BACKGROUND: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment. AIMS: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities. METHODS: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover. RESULTS: There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation. CONCLUSIONS: The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.