Specific acute colonic disorders

This article reviews a variety of specific colonic disorders that may have been an acute clinical presentation. Less common causes of colonic obstruction include volvulus, intussusception, and hernias. Nonobstructive colonic dilatation is most often due to pseudo-obstructions and toxic megacolon. Several miscellaneous disorders discussed include colonic perforation, complications of leukemia that may affect the colon, and pseudomembranous colitis. The pathogenesis and clinical aspects of these disorders are reviewed, but the radiologic features are emphasized.     

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.     

Toxic megacolon of ulcerative colitis in infancy

A 12-week-old white male infant with ulcerative colitis and toxic megacolon is described. His diarrhea and rectal bleeding responded to prednisone. He subsequently developed toxic dilatation of the transverse colon while on salicylazosulfapyridine and one week after discontinuation of prednisone. His toxic megacolon disappeared during close medical observation, readministration of prednisone, and avoidance of repeated abdominal examinations. One year later sigmoidoscopy showed only friable mucosa and the barium enema showed the presence of ulcerative colitis but with improvement from the initial study. Currently he is taking 375 mg of salicylazosulfapyridine daily. Growth and development are normal and he is asymptomatic.     

Crohn's colitis: the fate of the rectum

Previous reports suggest that up to 70% of patients undergoing surgery for Crohn's disease of the large bowel do not have gastrointestinal continuity restored and require a permanent ileostomy. In this study the experience with patients requiring surgical treatment of large bowel Crohn's disease is reviewed with particular reference to the management of the rectum. The records of 19 elective and 25 urgent colonic resections performed for large bowel Crohn's disease in 44 patients (16 males, 28 females; mean age 41 years, range 17-76) between 1983 and 1995 were reviewed. Staged proctectomy was performed in 5 of 12 patients who had colectomy for acute colitis and in one patient who had had an elective colectomy. Permanent ileostomy was required in 72% of patients with acute Crohn's colitis and 84% of patients who had elective surgery for large bowel Crohn's. Over 70% of patients having surgical treatment of Crohn's disease of the large bowel required permanent ileostomy. No cases of cancer developed in patients with retained rectal stumps.     

The surgical management of toxic dilatation of the colon: a report of 28 cases and review of the literature

Experience with 28 patients with toxic dilatation of the colon is reviewed. The operative mortality in this series was 32% (9/28). Eight of the 9 patients who died were found to have colonic perforations at operation; in contrast, the group of patients with no perforations had a mortality rate of only 6%. Colonic perforation and sepsis were the most significant factors contributing to mortality and morbidity in this series. A review of the literature showed an overall operative mortality rate of 19.5% for patients with toxic megacolon; the mortality rate was 41% for patients with perforations and 8.8% for patients without perforations. It appears that the keystone to successful management is the avoidance of colonic perforation and sepsis; protracted medical management of toxic megacolon seems to have been at least partly responsible for these complications. Sixteen of the 18 survivors following subtotal colectomy required removal of the rectum within 9 months because of continued symptoms and disease in the rectal stump.     

The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients

The records of a series of 700 patients with inflammatory bowel disease, 498 with Crohn's disease and 202 with ulcerative colitis, have been analyzed to determine the relative incidence and characteristic features of their extra-intestinal manifestations. The group with Crohn's disease included 62 with colitis, 223 with ileocolitis, and 213 with regional enteritis. A consideration of the clinical patterns and an understanding of their pathophysiology suggested a subdivision into two main groups: one "colitis related" and one related to the pathophysiology of the small nonspecific third group. Group A, colitis related, comprises joint, skin, mouth, and eye disease. The complications might be immunologically determined, were closely associated with active inflammation, and often responded to medical or surgical treatment of the underlying bowel disease. They occurred in 36% of the entire series of patients: joints were involved in 23%, skin in 15%, and mouth and eye each in 4%. Pyoderma gangrenosum was observed most often in ulcerative colitis and erythema nodosum most often in granulomatous colitis. The incidence of Group A complications was higher in disease involving the colon (42%) than in disease restricted exclusively to the small bowel (23%). There were interrelationships among the various members of Group A, with multiple manifestations occurring in a third of affected patients. Group B, related to small bowel pathophysiology, includes malabsorption, gallstones, kidney stones, and non-calculous hydronephrosis and hydroureter. Disorders in this group were generally related to the severity of the disease in the small bowel and tended to persist even in the absence of active inflammation. In contrast to Group A, this group occurred most frequently in small bowel disease, and least in colonic disease. Malabsorption was virtually confined to the patients with small bowel disease (10% incidence), while gallstones and renal stones were also both more frequent in Crohn's disease (11% and 9% respectively), the latter usually in association with small bowel resection or ileostomy. Group C, found in a small percentage of patients, consists of nonspecific complications, including osteoporosis (3%), liver disease (5%), peptic ulcer (10%), and amyloidosis (1%).     

Crohn's disease and intestinal carcinoma: presentation of 2 cases and review of the literature

We present the cases of two patients with Crohn's disease with consequent adenocarcinoma of the bowel. The first patient underwent an ileo-colic bypass 23 years before, a mucinous adenocarcinoma (Duke's stage C) was found on the anastomotic tract and on the excluded bowel, in areas within histologically recognizable Crohn's disease. In the second patient both the adenocarcinoma (Duke's stage C) of the transverse colon and the Crohn's disease (without any clinical evidence) in active phase has been found at the same time. We underline that such association seems to be not so rare as it seemed in the past. Accurate observation of patients, long time sufferers from the Crohn's disease, is advised to single out possible neoplastic complications at an early stage.     

Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease

Inflammatory bowel diseases are treated in some cases by local administration of anti-inflammatory drugs. Local delivery of drugs in the colon following oral administration may lead to improved efficacy/side-effect profiles and may improve patient compliance. This review covers a number of issues important in the design of oral delivery systems of glucocorticosteroids for local therapy of colonic inflammation. The choice of specific glucocorticosteroids is based on the drug's physicochemical and pharmacological properties. The conditions under which an orally administered glucocorticosteroid (or other drug) must be delivered to treat ulcerative colitis are also discussed. These conditions include variations in local pH, transit throughout the gastrointestinal tract, the potential role of gut microflora, and drug dissolution in both the healthy and diseased large intestine. The effective delivery of topically-active glucocorticosteroids in ulcerative colitis and Crohn's colitis patients is complex, but if successful could improve their usefulness.     

Pericarditis in chronic inflammatory bowel disease: underlying disease or side effects of therapy? Clinical problem solving

Pericarditis and myocarditis are rare extraintestinal manifestations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease). Pericarditis as a side effect induced by sulfasalazine or 5-aminosalicylic acid, drugs used in the therapy of these diseases, was first described only 7 years ago. In older case reports the relationship between the use of these drugs and pericarditis is unclear. We analyze the reported cases of 68 patients (38 men, 24 women) with ulcerative colitis (n = 45) or Crohn's disease (n = 15) who had one or more episodes of pericarditis or myopericarditis. Pericarditis was not associated with high activity of bowel disease in all cases. In most cases therapy with corticosteroids led to uneventful recovery. In drug induced pericarditis omission of the 5-ASA therapy was sufficient in a few cases. There was one fatal case (with myocarditis). The decision whether pericarditis is a symptom of the underlying disease or a side effect of the drug used for the treatment of the disease is not always easy. We present an analysis (clinical problem solving) of a pertinent observation in a patient with Crohn's disease and pericarditis, showing the dilemma of pericarditis in chronic inflammatory bowel disease and its therapy.     

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.     

Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.     

Cytomegalovirus as the cause of toxic dilatation of the colon

Toxic dilatation of the colon is sometimes a complication which occurs during exacerbations of inflammatory bowel disease. It often requires immediate surgical intervention. We describe here a male patient with known ulcerative colitis who was investigated for fever of unknown cause, diarrhoea, and general illness. Upon admission he had only modest symptoms of colitis and received no immunosuppressive treatment. The condition worsened considerably, and subsequent colonoscopy demonstrated widespread lesions compatible with viral disease, but not with ulcerative colitis. Antiviral treatment for cytomegalovirus was started immediately, but progression of the condition with toxic dilatation called for a rapid colectomy. Histological examination showed widespread lesions compatible with cytomegalovirus infection. This clinical picture is rarely seen in immunocompetent patients.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Sonography of inflammatory bowel disease: findings and value in differential diagnosis

OBJECTIVE: Inflammatory bowel diseases produce segmental or diffuse mural thickening of the intestine that can be detected and evaluated by using sonography. The purpose of this study was to evaluate the sonographic findings and determine their diagnostic value in patients with inflammatory bowel diseases. MATERIALS AND METHODS: We reviewed sonograms of 81 patients with inflammatory bowel diseases. The findings were compared with those of barium study, colonoscopy, and surgery. Forty-five patients had tuberculous enterocolitis, 13 had ulcerative colitis, eight had Crohn's disease, five had ischemic colitis, two had Beh?et's syndrome, and eight had unspecified colitis. Diagnosis was based on surgical and pathologic findings in 23; results of barium study and endoscopic biopsy in 20; and results of barium study, colonoscopic findings, and clinical findings in 38. RESULTS: Seventy-two patients (89%) had sonograms that showed segmental or diffuse mural thickening and a paucity of luminal content in the involved bowel. Involved areas were the ileocecal region in the cases of tuberculous enterocolitis and Beh?et's syndrome, the left side of the colon in ulcerative colitis, and the colon and terminal part of the ileum in Crohn's disease. In ischemic colitis, the distribution of involved bowel was nonspecific. Sonographic findings correlated well with the findings of barium enema or colonoscopy in terms of the involved segments of the bowel. Mesenteric lymphadenitis, omental thickening, and ascites were frequently observed in cases of tuberculous enterocolitis. CONCLUSION: Sonographic evidence of mural thickening of the bowel with a paucity of luminal content may be helpful in the detection of inflammatory bowel diseases. However, the findings are nonspecific, and the differential diagnosis must be related to the specific segment of the bowel involved.     

Colonic drug targeting

Specific targeting of drugs to the colon is recognized to have several therapeutic advantages. Drugs which are destroyed by the stomach acid and/or metabolized by pancreatic enzymes are slightly affected in the colon, and sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Treatment of colonic diseases such as ulcerative colitis, colorectal cancer and Crohn's disease is more effective with direct delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents require smaller doses. This article is aimed at providing insight into the design considerations and evaluation of colonic drug delivery systems. For this purpose, the anatomy and physiology of the lower gastrointestinal tract are surveyed. Furthermore, the biopharmaceutical aspects are considered in relation to drug absorption in the colon and hence various approaches to colon-specific drug delivery are discussed.     

Failure of colonoscopic surveillance in ulcerative colitis

A prospective surveillance programme for patients with longstanding (> = 8 years), extensive (> = splenic flexure) ulcerative colitis was undertaken between 1978 and 1990. It comprised annual colonoscopy with pancolonic biopsy. One hundred and sixty patients were entered into the programme and had 739 colonoscopies (4.6 colonoscopies per patient; 709 patient years follow up). Eight eight per cent of examinations reached the right colon. There was no procedure related death. One Dukes's A cancer was detected. Forty one patients (25%) defaulted. Of these 25 remain well; 13 are unaccounted for, and one died from colonic cancer. One patient had colectomy for medical reasons, and another died of carcinoma of the pancreas. Retrospectively an additional 16 eligible patients were identified who had not been recruited. Of these, 14 remain well, two are unaccounted for. None developed colonic cancer. Four patients refused colonoscopy. All remain well. Over the same period seven other cases of colonic cancer were found in association with ulcerative colitis, two in patients who had erroneously been diagnosed as having only proctitis and were therefore not entered into the programme, but were found at operation to have total colitis, one in a patient with colitis of seven years duration, and four patients who had previously attended the clinic but had been lost to follow up before 1978 and then had represented with new symptoms during the surveillance period. Thus, of the nine colitis related cancers diagnosed in this centre during the study period only one was detected by the surveillance programme. The results of this large study, a a review of published works, cast doubts on the effectiveness of colonoscopic surveillance programmes in detecting colorectal cancer in patients with ulcerative colitis.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

Segmental tuberculosis of the colon diagnosed by colonoscopy

Segmental tuberculosis of the colon is a rare clinical entity. In the absence of pulmonary or ileocecal involvement, colonic tuberculosis may be difficult to differentiate from neoplasm or Crohn's disease by symptomatic and radiological means. Colonoscopy and biopsy can, however, establish the diagnosis and prevent operative intervention, as indicated in the present report. A patient with a radiologically demonstrated strictured lesion of the sigmoid colon was found at colonoscopy to have several hemorrhagic transverse ulcers ranging in diameter between 1-4.5 cm. Multiple target colonoscopic biopsies, specifically from the ulcer beds, revealed necrotizing granulomas and acid-fast bacilli. Antituberculous chemotherapy produced remarkable symptomatic, radiographic and endoscopic improvements and averted exploratory laparotomy for the establishment of the diagnosis. This case report points out the importance of colonoscopic biopsy as a useful diagnostic modality in this disease.     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Severe chronic iron deficiency in a 17-year-old student

A 17 year old male suffered from iron deficiency of undetermined cause for 2 years. Iron substitution was able to correct it for short periods. With the exception of fatigue and recurring abdominal pain attributed to oral iron therapy no further symptoms were present. The physical status on admission was unremarkable. The laboratory detected intestinal disorders, an anemia of the chronic type without evidence for malignancy or renal failure suggested an inflammatory gastro-intestinal disorder. In spite of a twice negative noninvasive test for gluten-intolerance the clinician favored in his differential diagnosis non tropical sprue over inflammatory bowel disease (IBD, Crohn's disease, Whipple's disease). Histopathology of small bowel specimens did not indicate sprue. An ileo-colonoscopy revealed severe ulcerating ileitis and mild chronic colitis. The histologic specimen revealed a severe ileal inflammation with cosinophilia and the colon specimens epitheloid microgranuloma. These findings are highly compatible with the diagnosis of Crohn's disease. Iron deficiency anemia is common in Crohn's disease. In the current case it is due to disturbed iron uptake. Iron deficiency anemia as sole symptom of Crohn's disease is extremely rare.