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Chronic inflammatory bowel disease has recently been reported in association with glycogen storage disease type 1 B. We report two cases of children affected by this disease in whom chronic recurrent ileocolitis and severe oesophagitis developed.
Growth impairment of undefined aetiology occurs in approximately 30% of children with chronic inflammatory bowel disease. We measured urinary growth hormone concentrations in 36 children with chronic inflammatory bowel disease and 51 normal controls. The median urinary concentration of growth hormone in the stunted children with chronic inflammatory bowel disease was 15.8 ng/g creatinine (range 4.3-32.6), compared with 11.7 ng/g creatinine (range 4.1-35.9) in those with normal growth. The difference was statistically not significant (p = 0.15). Moreover, there was no significant difference between the patients and the control group. One stunted patient had a urinary growth hormone (UGH) concentration below the normal range, whereas four patients with normal height were also below the normal range. Four of these five patients (80%) were on corticosteroid treatment at the time of urinary collection, whereas only 26% of the patients with normal UGH were also on corticosteroid treatment. We conclude that growth retardation in children with chronic inflammatory bowel disease is probably not related to growth hormone deficiency but must involve other mechanisms.
Trials of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) suggest that it may be useful in patients intolerant of azathioprine. We examined the safety and efficacy of MMF in IBD patients intolerant of or unresponsive to azathioprine. Twelve patients [seven with Crohn's disease (CD); seven women; mean age 40 years, range 14-76 years] were treated with MMF 500 mg b.i.d. for a mean of 12.5 weeks. Intolerance was defined as the development of side effects that resolved on discontinuing MMF. Improvement was described as symptomatic improvement, decreased steroid use, or disease entering endoscopic remission. Four patients responded with symptomatic improvement and reduced steroids or mesalazine requirement. Three patients developed headache, nausea, or arthralgia. Three patients developed profuse bloody diarrhea, and in two cases with previously quiescent ulcerative colitis (UC), the source was shown to be ulcers in a drug-induced colitis with histologic features similar to those previously reported in four renal transplant patients on MMF. There is no clear evidence of efficacy of MMF in the treatment of IBD, and its use in this condition should be confined to a randomized controlled trial. Moreover, as patients with UC may be unduly prone to colonic injury, MMF may not be a suitable drug for its treatment.
BACKGROUND AND AIMS: Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations. METHODS: Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques. RESULTS: The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmitted v 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076. CONCLUSIONS: This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation.
It would be ideal to treat inflammatory bowel disease with topical corticosteroids that are either not absorbed through the mucosa, or have a substantial first-pass hepatic metabolism. The topical use of hydrocortisone, prednisolone-21-phosphate or betamethasone is often associated with systemic side-effects. Newer corticosteroid preparations (prednisolone metasulphobenzoate, tixocortol pivalate, fluticasone propionate, beclomethasone dipropionate and budesonide) are usually associated with minimal systemic corticosteroid activity. This article reviews the clinical activity and safety of these newer preparations.
BACKGROUND: Primary sclerosing cholangitis (PSC), which is a progressive cholestatic liver disease of unknown etiology, is strongly correlated with inflammatory bowel disease (IBD). GOALS: To determine the prevalence and describe the characteristics of PSC in patients with IBD in Turkey. STUDY: We determined the prevalence of PSC in patients with IBD admitted to our department during a 6-year period. Also, patients with PSC were investigated from an IBD aspect. Regardless of whether the patient had symptoms such as itching, jaundice, and abdominal pain, endoscopic retrograde cholangiopancreatography was performed on those with elevated alkaline phosphatase, and liver biopsy was done if endoscopic retrograde cholangiopancreatography failed to bring about the diagnosis. RESULTS: Overall prevalence of PSC was 9 of 386 (2.3%) patients with ulcerative colitis (UC) and 4 of 110 (3.6%) patients with Crohn's disease (CD). Inflammatory bowel disease was established in 13 of 18 (72.2%; UC, 50.0%; CD, 22.2%) patients who were being observed for PSC. The male-to-female ratio was 5:4 in UC and 3:1 in CD patients with PSC. The mean age at diagnosis of PSC was 43.6 years (range, 30-54 years) in patients with UC and 30.5 years (range, 26-41 years) in patients with CD. In patients with UC, the extension of colitis was total in seven patients (7/110, 6.3%) and left-sided in two patients (2/142, 1.4%). In patients with CD, the disease was located in the ileum and colon in one patient (1/47, 2.1%) and in colon alone in three patients (3/21, 14.2%). CONCLUSIONS: Prevalence of PSC-associated IBD in the Turkish community appear to be similar to the results of western origin studies.
The vast majority of patients with inflammatory bowel disease experience chronic symptoms punctuated by periodic exacerbations requiring adjustments in medical therapy or surgery. True emergencies are fortunately uncommon but have been associated with high rates of morbidity and mortality. Patients presenting with fulminant colitis, toxic megacolon, or perforation require prompt identification as well as intensive medical therapy and monitoring by physicians and surgeons experienced in the care of such patients. Recent advances in the evaluation and treatment of these complicated patients are reviewed.
Ulcerative colitis and Crohn's disease are inflammatory disorders of the gastrointestinal tract that are distributed unevenly within populations and throughout the world. Although the exact causes of inflammatory bowel disease (IBD) remain unknown, study of the epidemiology of IBD has provided insight into pathogenesis. This article examines the geographic, ethnic, and other trends of IBD; risk factors (including genetic and environmental); and the natural history of IBD.
BACKGROUND: Azathioprine therapy is discontinued in one-third of patients with inflammatory bowel disease because of toxicity or a lack of clinical response. Patients with thiopurine methyltransferase (TPMT) deficiency are intolerant to azathioprine, whilst carriers are at increased risk of side-effects. AIM: To evaluate the importance of TPMT activity in the management of azathioprine therapy in inflammatory bowel disease. METHODS: Clinical response, adverse effects and haematological parameters were determined and correlated with TPMT enzyme activity and genotype in 106 patients with inflammatory bowel disease. RESULTS: Ninety-six patients had high TPMT activity, and 10 had intermediate activity. Nineteen patients (18%) were intolerant to azathioprine. Fifteen (16%) of those with high TPMT activity were intolerant, compared with five (50%) with intermediate activity [odds ratio (OR), 5.4; 95% confidence interval (CI), 1.5-19.8]. Complete remission was achieved in 63% of cases, and complete or partial remission in 79%. Interestingly, very high TPMT activity (> 14 units/mL red blood cells) was significantly associated with non-response, irrespective of the time on azathioprine (OR, 0.21; 95% CI, 0.07-0.68). TPMT gene mutations correlated with TPMT activity. CONCLUSIONS: Inflammatory bowel disease patients with intermediate TPMT activity have an increased risk of azathioprine toxicity. Conversely, very high TPMT activity predicts treatment failure. TPMT genotype predicted TPMT phenotype in this study.
OBJECTIVE: To study the morbidity and mortality of inflammatory bowel disease in Australia and whether it decreases life expectancy. DESIGN: A retrospective review of patient case notes from two Sydney teaching hospitals and the consulting rooms of the 17 gastroenterologists appointed to these hospitals, examining all presentations with a diagnosis of inflammatory bowel disease from January 1977 to September 1992. RESULTS: 997 cases were identified: 533 with ulcerative colitis, 417 with Crohn's disease, and 47 with indeterminate colitis. In patients diagnosed from 1977 onwards (n = 730), no difference in survival was demonstrated for inflammatory bowel disease overall, or any subgroup, or in males or females, as compared with an age- and sex-matched control population. Gastrointestinal malignancies occurred in 19 cases (18 colorectal carcinoma and one cholangiocarcinoma). The most commonly encountered problems were the use of immunosuppressants and the need for surgery. Inflammatory bowel disease, particularly Crohn's disease, entails appreciable morbidity. CONCLUSION: Since 1977, despite a significant requirement for medical and surgical treatment in patients with inflammatory bowel disease, there has been no adverse effect on survival in a specialist-referred cohort as compared with the general population.
Thirty-three patients suspected of suffering from inflammatory bowel disease were studied. Autologous leucocytes were labelled with indium 111 oxine and re-injected simultaneously with 0.3-0.5 mg of technetium 99m granulocyte-specific monoclonal antibody BW 250/183. Two scans were obtained, the early scan 3-4 h postinjection (p.i.) and the late scan 18-24 h p.i. Using the endoscopy study as standard, the diagnostic accuracy of both agents was determined. Sensitivity, specificity and accuracy of 111In scans was 88.8%, 100.0% and 93.7% at 4 h and 94.7%, 100.0% and 96.9% at 24 h, respectively. Concerning the results using antibodies, the values were 61.1%, 100.0% and 78.1% at 4 h and 78.9%, 92.8% and 84.8% at 24 h, respectively. Segmental analysis showed concordance in 89.3% and 93.3% of the cases at 4 and 24 h, respectively. Though less sensitive and less accurate than scanning employing indium 111 leucocytes, BW 250/183 granulocyte-specific scintigraphy can be used for inflammatory bowel disease diagnosis and localization.
INTRODUCTION: A hypercoagulable state has been recognized in patients with inflammatory bowel disease. OBJECTIVE: The aim of this study was to determine the frequency of single and combined thrombophilic abnormalities in patients from northern Portugal with Crohn's disease or ulcerative colitis, without a history of thrombosis. METHODS A cross-sectional study involving 116 patients (42 with ulcerative colitis, 74 with Crohn's disease), and 141 randomly chosen asymptomatic blood donors was carried out. Prothrombotic variables and genetic abnormalities were assessed. RESULTS: The prevalence of single prothrombotic abnormalities (only one alteration) in inflammatory bowel disease patients was higher than in the reference population (26% and 18%, respectively; P < 0.02). The allelic frequency of genetic polymorphisms was higher in Crohn's disease and ulcerative colitis for MTHFR C677T, ACE Del and PAI-1 4G (P < 0.001) than in the reference population. The prevalence of combined thrombophilic abnormalities (at least two alterations) in both Crohn's disease and ulcerative colitis was also higher (22% and 21%, respectively) than in the reference population (9%; P < 0.01). These differences were not related to age or gender; however, in Crohn's disease the frequency of two or more abnormalities was related to disease activity (odds ratio 3.0 [1.3-6.7]). CONCLUSION: Higher prevalences of single and combined thrombophilic defects were found in inflammatory bowel disease patients, factors that could be involved in the disease pathogenesis.
Thirty-seven patients with nonspecific inflammatory bowel disease were examined with an ultrasonic colonoscope and the inflammation classified as mucosal or transmural. Mucosal inflammation was characterized by preservation of the five-layer structure of the wall with thickening of the submucosa. Transmural inflammation was endosonographically defined as sectional interruption or loss of the five-layer structure. In 14 of the 37 patients a colectomy was performed. Examination of 3 of the 14 resected specimens revealed inflammation confined to the mucosa. This was consistent in all three cases with the preoperative endosonographic evaluation. Eleven of the 14 resected specimens showed sectional transmural inflammation. Ultrasonographically all of the 11 patients fulfilled the criteria for transmural inflammation, whereas endoscopic and microscopic signs were consistent with transmural inflammation in 9 of the 11. Endosonography of the colon enables definition of mucosal inflammation thus providing criteria for selection of patient for ileoanal pouch construction.
The controversy in the treatment of inflammatory bowel disease is how to decide surgical vs. medical management in each case. Of 309 patients with ulcerative colitis in our department, 63 (20%) patients had received surgical treatment. The mean age was 33.5 +/- 13.7 years old and the mean duration from onset to operation was 6.72 +/- 5.51 years. The indications for surgical treatment were 47 (75%) resistant cases against medical treatment, 9 (14%) severe cases and 7 (11%) cancer or dysplasia cases. In surgical cases compared with medical ones, the ratio of total duration (months)/number of admission showed below 10, and the total amount of used steroid was over 300 mg per month. These ratios were considered to be the useful markers for surgical indication. Operative procedures were 15 total proctocolectomy+ileostomy, 29 total colectomy+ileorectal anastomosis, 13 total proctocolectomy+ileoanal anastomosis and 6 others. Restorative proctocolectomy using double stapling method with two stage operation was chosen in 8 patients because of easier and safer operative procedure and a few complications. We conclude that early surgical treatment for the patients resistant against medical management is considered to improve the patients' quality of life.
Extraintestinal manifestations have been described with inflammatory bowel disease (IBD). Cardiac involvement in IBD is rare and may present as pericardial effusion, myopericarditis and conduction defects. Here we present a case of IBD with asymptomatic pericardial tamponade. A 37-year-old African-American man with ulcerative colitis with history of previous colectomy with ileorectal anastomosis was hospitalized for resection of the stricture of ileorectal anastomosis. The patient was afebrile with stable vitals and modest jugular venous distension, but no pulsus paradoxus. Cardiopulmonary examination was normal. A CT scan done to evaluate rise in liver function tests following removal of stricture showed a large 3.1 cm pericardial effusion. A transthoracic 2-D echocardiogram showed a moderate-sized posterior pericardial effusion limiting left ventricular filling. Central venous pressure was 18 mm Hg and the patient underwent drainage of 300 ml of old bloody pericardial effusion. Pericardial biopsy showed organizing fibrinohemorrhagic chronically inflamed pericardium without granuloma or neoplastic process. Serologies for EBV, Coxsackie virus and hepatitides were negative. Drug-related pericarditis seems less likely as the patient was not on sulfasalazine, and ANA, dsDNA and rheumatoid factor titers were negative. The patient was diagnosed to have pericardial tamponade associated with IBD.
BACKGROUND: Thiopurines have proven efficacy in inflammatory bowel disease. However, concerns regarding toxicity have limited the use of these agents as first line of medical therapy. METHODS: Review of the literature regarding metabolism, efficacy and side effects. RESULTS: In clinical trials, up to 15% of patients discontinued 6-mercaptopurine or its pro-drug azathioprine prematurely due to adverse events. These events may be divided into dose-independent idiosyncratic reactions and dose-related, pharmacologically explainable toxicity. Dose-independent reactions include skin rash, fever, diarrhoea and pancreatitis. Most frequently observed dose-dependent adverse events are nausea, malaise and myelotoxicity. Furthermore, dose-dependent and dose-independent hepatotoxicity may occur. Recent insights obtained by therapeutic drug monitoring in patients on azathioprine or 6-mercaptopurine have led to strategies to reduce toxicity. One strategy is to detect poor metabolisers of thiopurines by establishing the activity of the key enzyme thiopurine methyltransferase. However, the clinical relevance of this strategy is still a point of debate. Another strategy is to administer 6-thioguanine, which is an agent close to the effective 6-thioguanine nucleotides. CONCLUSION: Therapeutic drug monitoring of thiopurines resulted in strategies to reduce toxicity. The value of these strategies has yet to be proven in prospective randomized trials.
The redox homeostasis of patients with inflammatory bowel disease is not balanced because of malnutrition and malabsorption. The seriousness of this illness often hinders the intake and use of bioactive agents. We have just a small amount of knowledge about how patients can get access to these important materials. The authors' aim was to edit a questionnaire, which can estimate, with large precision, the amount of fruit and vegetable consumption among a random-chosen group of IBD patients. We also thought that the measuring of tea, fruit-juice and wine consumption is also important in order to see whether the intake of these can help the intake of natural polyphenol, vitamin and trace elements. For this study 50 IBD patients (25 male, 25 female, 35-67 years) and 50 healthy people (35 male, 15 female, 25-47 years) were asked. During the completion of the questionnaire in 8 cases (5 male, 3 female) the provided data could not be accepted, because of inaccuracy. During this study, it became obvious that the intake of polyphenols was not enough if we focus on the average daily consumption of fruits and vegetables. Red wine cannot be considered efficient for replacing polyphenols, because more than the half of patients doesn't drink it at all, or drink it once or twice a month. From the aspect of drinking tea or eating fruits, the situation is much better. The participants' (92 people) consumption of vegetables and fruits is reduced to a small variety, which is not beneficial. Mostly used plants often caused different disorders, and that is why a controlled recommendation of polyphenol, vitamin, trace element and fiber would be favorable.
BACKGROUND: The prevalence and clinical significance of cytomegalovirus infection is reportedly high in patients with refractory inflammatory bowel disease but is unknown in unselected patients with active disease. METHODS: In patients admitted for active inflammatory bowel disease, we prospectively studied the presence and significance of cytomegalovirus infection using anti-cytomegalovirus antibodies, cytomegalovirus viraemia and antigenaemia and cytomegalovirus inclusions and cytomegalovirus immunochemistry staining in ileocolonic biopsies. RESULTS: A total of 64 patients were included (ulcerative colitis, n = 23; Crohn's disease, n = 41), 18 of whom had been on high-dose oral steroids and 11 on immunosuppressants. Anti-cytomegalovirus IgG and IgM were positive in 42 (66%) and 3 (5%) patients respectively. Blood or urine cytomegalovirus replication markers were found in 4 (6%) patients, all of whom had ulcerative colitis. Three patients had cytomegalovirus viraemia and received anti-viral treatment with ganciclovir. Only one of these patients had cytomegalovirus antigenaemia and also associated biopsy-proven cytomegalovirus colitis, probably as a primary cytomegalovirus infection. This patient is the only one who benefitted from anti-viral therapy. CONCLUSIONS: Cytomegalovirus infection is infrequent in in-patients with active inflammatory bowel disease. Systematic search of cytomegalovirus replication markers should not be performed. Isolated viraemia without associated antigenaemia or direct demonstration of cytomegalovirus in ileocolonic biopsies does not warrant anti-viral therapy.