Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

Association of HLA class-II genes and anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease

BACKGROUND: Occupational respiratory allergy to green coffee beans (GCB) and to castor beans (CB) was studied in 112 workers in a modern coffee manufacturing plant of Trieste (Italy), where the process is completely automatic, the environmental conditions are good and where exposure to CB can be considered absent because since 1970, only new sacks have been used for coffee transportation. METHODS: All subjects were interviewed by a trained doctor using a questionnaire to investigate allergic symptoms and predisposing factors. Sensitization to GCB and to common allergens (pollens, molds, house dust mites) were evaluated by the skin-prick test. The serum of subjects with a positive skin-prick test to CGB or who had symptoms at work was tested for specific IgE (RAST) for GCB and CB. Lung function was evaluated by a Ponigraph spirometer. RESULTS: Sensitization to GCB was found in 25.8% of green coffee workers (31 cases), in 2.7% of roasted coffee workers (37 cases) and in 4.5% of the clerks (44 cases), p < 0.01. The evaluation of IgE specific for CB gave positive results only in 3 of 10 subjects sensitized to GCB. A total of 20% of GCB workers (6 cases) complained of work-related respiratory symptoms (asthma and/or rhinitis) compared with only one subject in the roasted coffee group and one in the control group (p < 0.01). Asthma was reported by 2/31 of the green coffee workers and by 1/44 of roasted coffee workers. CONCLUSIONS: There was a significant correlation between sensitization to GCB and work related symptoms (p < 0.01), common allergic symptoms (p < 0.05) and atopy by prick test (< 0.01). These results point to the need to evaluate atopic status in workers and identify the most susceptible subjects, with the aim of informing them of their at-risk status and monitoring their progress. This makes it possible to diagnose sooner those symptoms possibly indicative of a work-related disease, because even in presence of good environmental conditions and even when symptoms are mild, it is almost always the atopic subjects who are affected.     

Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Anti-cardiolipin (aCL) antibodies have been shown to be associated with thrombosis. Recently, the antibodies against the anti-cardiolipin cofactor beta2-glycoprotein I (a(beta2)GPI) have been found with higher specificity for thrombosis. The presence of these antibodies was assessed in 128 patients with IBD [83 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)] and 100 healthy controls (blood donors). Patients with UC and CD had a significantly higher prevalence of aCL (18.1% and 15.6%, respectively) than healthy controls (HC) (3%). Eleven IBD patients (8.6%) but no HC had a(beta2)GPI. None of the IBD patients with a history of thrombosis had aCL and only one of them (a UC patient with deep vein thrombosis of the right leg) had a high titer of IgG a(beta2)GPI. In conclusion, these data show that both aCL and a(beta2)GPI are significantly associated with IBD but further studies are needed to determine the significance of our findings.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Medical therapies for inflammatory bowel disease

Inflammatory bowel disease is a spectrum of disorders whose etiology and pathogenesis are unclear. No therapy is standard; many modalities exist for management. New drugs, improved formulations of existing drugs, combination therapy and biologic agents offer more effective relief and maintain disease remission.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Detection of anti-colon antibodies in inflammatory bowel disease using human cultured colonic cells

BACKGROUND: Investigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available. AIMS: To examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen. Subjects: Patients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied. METHODS: Comparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis. RESULTS: Sera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn's disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (p<0. 05). The immune response was not associated with one predominant antigen. CONCLUSIONS: Fixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn's disease.     

Thromboembolic complications in inflammatory bowel disease

Thromboembolic complications during the course of inflammatory bowel disease are infrequent but are mainly found in young patients and are associated with a high morbimortality. The etiopathogenesis of these complications has been widely debated and the existence of coagulation alterations and fibrinolysis have been suggested. Nonetheless, the mechanism must be complex since not only do not all the patients with these alterations present this complication but neither do all the patients with thromboembolism have recognized coagulation disorders. The most common clinical presentation is deep vein thrombosis with pulmonary embolism with arterial thrombosis being rare. Five patients with Crohn's disease and two with ulcerative colitis who presented a total of new thromboembolic episodes, six arterial (1 in primitive iliac artery, 1 in common femoral artery, 1 in humeral-axillary artery, 2 in internal carotid and 1 in superior mesenteric artery) and three of venous localization (1 in brachyocephalic-subclavian trunk, 1 axillary and 1 iliac-femoral/pulmonary thromboembolism) are reported. An updated review of the etiopathogenesis, presentation, treatment and prophylaxis of the thromboembolic complications of inflammatory bowel disease is presented.     

Gastrointestinal pH profiles in patients with inflammatory bowel disease

BACKGROUND: 5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating. AIM: To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen. METHODS: Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn's disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease). RESULTS: The median gastric pH values in the patient groups (Crohn's disease 2.4, range 1.5-4.1; ulcerative colitis 1.95, range 1.55-4.4) were significantly higher than those observed in the controls (1.55, range 0.95-2.6). In the small bowel and colonic segments, all the pH values of Crohn's disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission. CONCLUSIONS: The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.     

Growth of prepubertal children with inflammatory bowel disease

BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.     

Bone assessment in patients with ileal pouch-anal anastomosis for inflammatory bowel disease

BACKGROUND: Patients with ulcerative colitis are at risk of low bone mineral density (BMD). Proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis diminishes the risk of bone disease. The aims of this study were to assess the mechanism of low BMD and to measure bone density changes after IPAA. METHODS: Twenty patients with IPAA for ulcerative colitis, of mean(s.d.) age 38(9) (range 21-58) years, had measurements of lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry, a mean(s.d.) 28(23) (range 3-84) months after proctocolectomy. Serum levels of calcium, phosphate, parathyroid hormone, osteocalcin and 25-hydroxy vitamin D were determined. Fifteen patients were followed for 28(12) (range 8-50) months. RESULTS: At baseline, six patients had spine BMD more than two standard deviations below the normal value, and three had vertebral crush fractures. Mean vitamin D values were normal and no patient had osteomalacia. BMD increased with time elapsed since IPAA (spine: r = 0.71, P = 0.005). During follow-up, mean(s.d.) changes in bone density were +2.3(3.8) and +2.1(5.6) per cent per year at the spine and femoral neck respectively. CONCLUSION: These results suggest that in patients with IPAA for ulcerative colitis, low BMD is not associated with vitamin D malabsorption and may be reversible after surgery.     

Bone mineral density assessment in children with inflammatory bowel disease

BACKGROUND & AIMS: Children with inflammatory bowel disease (IBD) are at risk for osteoporosis because of undernutrition, delayed puberty, and prolonged corticosteroid use. The aim of this study was to compare bone mineral density (BMD) in children with IBD with that in normal children and to assess the effects of nutritional and hormonal factors and corticosteroid dosages on BMD. METHODS: One hundred sixty-two subjects (99 with IBD and 63 healthy sibling controls) were enrolled. Patients underwent anthropometric assessment, pubertal staging, bone age radiography, and BMD assessment by dual energy x-ray absorptiometry of the lumbar spine, femoral neck, and radius. Laboratory evaluations included serum calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, osteocalcin, urinary N-telopeptides, albumin, insulin-like growth factor I, and testosterone or estradiol. Cumulative corticosteroid doses were calculated. RESULTS: BMD Z scores at the lumbar spine and femoral neck were lower in patients with IBD, and lower in those with Crohn's disease compared with those with ulcerative colitis. Low BMD persisted after correction for bone age in girls with Crohn's disease (lumbar spine, P = 0.004; femoral neck, P = 0.002). Cumulative corticosteroid dose was a significant predictor of reduced BMD. BMD did not correlate with measures of calcium homeostasis, except elevated serum phosphate and urine calcium levels in girls. CONCLUSIONS: Low BMD occurs in children with IBD (more in Crohn's disease than in ulcerative colitis), especially pubertal and postpubertal girls. Cumulative corticosteroid dose is a predictor of low BMD, but other factors in Crohn's disease remain undetermined.     

Colorectal cancer in idiopathic inflammatory bowel disease

The development of colorectal cancer is the most serious long-term problem faced by patients with extensive ulcerative colitis and Crohn's colitis, with an incidence 20-fold higher and an average age of onset 20 years younger than colorectal cancer in the general population. This report summarizes the epidemiology, pathology, and recent advances in the molecular pathogenesis of colorectal cancer in inflammatory bowel disease and of its acknowledged precursor, mucosal dysplasia. It also reviews the rationale behind the use of endoscopic surveillance for dysplasia as a means of reducing cancer mortality, as well as some of the issues involved in its effective implementation.     

Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.