Serum Angiotensin-converting-enzyme in Crohn''s Disease

The serum angiotensin-converting-enzyme levels in patients with Crohn's disease have been determined. There is no significant difference in the serum levels of angiotensin-converting-enzyme in patients with active Crohn's disease, inactive Crohn's disease or Crohn's disease with demonstrated granuloma and normal controls. Patients with active Crohn's disease who are no steroid treatment do have significantly lower levels.     

Corticosteroids in Crohn's disease

Crohn's disease is a lifelong illness characterized by chronic recurrent flares. The precise etiology of Crohn's disease is unknown. However, it appears to involve an enhanced systemic immune response and intensified local intestinal mucosal inflammatory activity, mediated through various inflammatory cells and an array of proinflammatory cytokines. Corticosteroids have been the mainstay of treatment of Crohn's disease. The controlled trials of the National Cooperative Crohn's Disease Study and the European Cooperative Crohn's Disease Study established that corticosteroids were effective for the induction of remission in Crohn's disease for the duration of the studies (6-17 wk). However, corticosteroids have not been shown to have an impact on the maintenance of long term remission in patients with Crohn's disease. In addition, they are associated with a high potential for dependence and serious toxic side effects. Alternative classes of medical therapy for Crohn's disease, including modified corticosteroids and a group of new biological therapies, have proven to be efficacious in the management of active and/or quiescent Crohn's disease.     

Granuloma-positive Crohn's disease.

BACKGROUND: The epithelioid granuloma is a characteristic histological feature of Crohn's disease. In some pathological classification schemes, the criteria for a definite, probable or possible diagnosis have been listed, with the epithelioid granuloma indicating definite Crohn's disease. METHODS: In the present evaluation, 247 prospectively evaluated Crohn's disease patients (24.3%), from a consecutively accumulated population database of 1015 patients, were found to have an epithelioid granuloma. The recently devised Montreal classification for Crohn's disease was then applied to this granuloma-positive cohort of Crohn's disease patients to define age at diagnosis for men and women, disease site and disease behaviour. RESULTS: The investigation showed that patients with Crohn's disease and granulomas were most often diagnosed early in the course of their disease, particularly women. Their disease was often extensive, with ileocolonic and upper gastrointestinal tract involvement. Finally, disease behaviour was most often complex, especially with penetrating disease complications. CONCLUSION: Using homogeneous (ie, 'reagent-grade') patient cohorts defined by a recently devised classification method for Crohn's disease, the study demonstrated that an epithelioid granuloma may represent a histopathological marker for an early biological event in the etiopathogenesis of Crohn's disease, and this may have predictive significance with respect to the location and clinical behaviour of Crohn's disease.     

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohn's disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohn's disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.     

Colorectal cancer complicating Crohn's disease.

Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.     

A search for a transmissible agent in Crohn's disease.

Controversy exists as to whether a transmissible agent is responsible for Crohn's disease. Previous reports have suggested that sarcoid-like granulomas can develop in animals following inoculation of homogenates derived from bowel affected by Crohn's disease. This study involved the injection of Crohn's tissue homogenates into experimental animals under a variety of conditions which might be expected to favour the demonstration of such an agent. Homogenates have been inoculated into the ileum of rats, mice, and rabbits and also given inoculated into ileum and footpads of rats which have previously been rendered lymphoedematous by surgical interruption of the draining lymphatics. Bowel homogenates from a total of 17 patients with Crohn's disease have been injected into 91 experimental animals. No macroscopic or microscopic changes indicative of Crohn's disease were detected. Thus study does not support the suggestion that a transmissible agent is present in Crohn's disease.     

Is Crohn's disease caused by a mycobacterium? Comparisons with leprosy,tuberculosis, and Johne's disease

Although Crohn's disease is considered to be autoimmune in origin, there is increasing evidence that it may have an infectious cause. The most plausible candidate is Mycobacterium avium subspecies paratuberculosis (MAP). Intriguingly, Koch's postulates may have been fulfilled for MAP and Crohn's disease, even though they still have not been met for Mycobacterium leprae and leprosy. In animals MAP causes Johne's disease, a chronic wasting intestinal diarrhoeal disease evocative of Crohn's disease. Johne's disease occurs in wild and domesticated animals, including dairy herds. Viable MAP is found in human and cow milk, and is not reliably killed by standard pasteurisation. MAP is ubiquitous in the environment including in potable water. Since cell-wall-deficient MAP usually cannot be identified by Ziehl-Neelsen staining, identification of MAP in human beings requires culture or detection of MAP DNA or RNA. If infectious in origin, Crohn's disease should be curable with appropriate antibiotics. Many studies that argue against a causative role for MAP in Crohn's disease have used antibiotics that are inactive against MAP. However, trials that include macrolide antibiotics indicate that a cure for Crohn's disease is possible. The necessary length of therapy remains to be determined. Mycobacterial diseases have protean clinical manifestations, as does Crohn's disease. The necessity of stratifying Crohn's disease into two clinical manifestations (perforating and non-perforating) when interpreting the results of antibiotic therapy is discussed. Rational studies to evaluate appropriate therapies to cure Crohn's disease are proposed.     

Sigmoid volvulus as a complication of ileal Crohn's disease

Intestinal volvulus in patients with Crohn's disease is rare and we could find only one report of sigmoid volvulus with active Crohn's colitis. We have seen a 54-year-old woman with long-standing Crohn's disease who developed large-bowel obstruction. After eventual detorsion of the sigmoid volvulus, we found that her ileum was involved with active Crohn's disease and that her colonic mucosa was free of mucosal lesions. In this case, we suspect that the reactivation of the ileal Crohn's disease as well as other features commonly associated with Crohn's disease contributed to the development of sigmoid volvulus by causing fixation, torsion, and dilatation of distal bowel.     

Are we giving biologics too late？ The case for early late use

Corticosteroids and immunomodulators have been the mainstay therapies for Crohn＇s disease. Corticosteroids are highly effective to control symptoms in the shortterm, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn＇s disease. In the last decade, medical therapy for Crohn＇s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn＇s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn＇s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn＇s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn＇s disease remain still unanswered.     

Capsule endoscopy vs. push enteroscopy and enteroclysis in suspected small-bowel Crohn's disease

BACKGROUND: The diagnosis of small-bowel Crohn's disease sometimes is difficult and may be missed by conventional imaging studies. Capsule endoscopy might identify small-bowel disease undetected by other investigations. METHODS: Patients with or without known Crohn's disease who were suspected to have small-bowel Crohn's disease were prospectively evaluated with push enteroscopy, enteroclysis, and capsule endoscopy. Each examiner was blinded to results of other investigations. Referring doctors were required to complete questionnaires before and after the investigations. RESULTS: Twenty-two patients were known to have Crohn's disease (Group 1), and 21 were suspected to have small-bowel Crohn's disease (Group 2). In Group 1, capsule endoscopy detected more erosions than the other two investigations (p < 0.001). In Group 2, a new diagnosis of Crohn's disease was made in two patients, but there was no significant difference in yield compared with the other two investigations. Referring physicians rated the usefulness of capsule endoscopy as 4.4 on a scale of 5. Capsule endoscopy changed management for 30 patients (70%). CONCLUSIONS: Capsule endoscopy has a higher yield than push enteroscopy and enteroclysis in patients with known Crohn's disease when small-bowel mucosal disease is suspected, and this leads to a change in management in the majority of these patients.     

Metastatic Crohn''s disease of thigh and forearm

Cutaneous involvement with Crohn's disease at a site separated from the gastrointestinal tract by normal skin is termed metastatic Crohn's disease. Such a complication is extremely rare and previous reports have emphasised the flexural distribution of the ulcerated lesions. We report a patient who developed Crohn's disease involving the skin of the thigh and forearm several months after a panproctocolectomy for colorectal Crohn's disease.     

Consequences of ileal pouch-anal anastomosis for Crohn's colitis

Patients with Crohn's colitis are generally not considered candidates for the ileal pouch-anal anastomosis (IPAA). procedure. We reviewed 362 consecutive patients undergoing IPAA and analyzed the outcome of this procedure on 25 patients with a preoperative diagnosis of mucosal ulcerative colitis who were subsequently proven to have Crohn's disease. The mean follow-up was 38.1 months. Sixteen patients have a functioning pouch, seven have required pouch excision, one is diverted, and one has died. Only one of nine patients in whom there was a preoperative clinical feature suggestive of Crohn's disease has a functioning pouch, with complications uniformly occurring within months of ileostomy closure. In contrast, 15 of 16 patients without preoperative features of Crohn's disease have maintained their pouch, generally with good results. These data suggest that patients in whom there is clinical and pathologic evidence of Crohn's disease do very poorly without meaningful symptom-free intervals. However, patients without any clinical features of Crohn's disease, despite a histopathologic diagnosis of Crohn's colitis, have had a good outcome with IPAA thus far.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29 to May 4, 1990.     

Crohn's disease in two married couples.

Only two examples of married couples where both partners have developed Crohn's disease have been reported previously from the United Kingdom. We describe two further examples; one where the index patient had developed Crohn's disease before marriage, and the spouse subsequently developed Crohn's disease and a second example in which both spouses developed Crohn's disease after marriage.     

Liver abscess in Crohn's disease. Report of four cases and review of the literature

Four patients with liver abscesses and Crohn's disease are described, and reports of 14 cases in the English language literature are reviewed. The incidence of liver abscess in patients with Crohn's disease (114-297 per 100,000) appears to be higher than that of liver abscess in the general population (8-16 per 100,000). Frequently the clinical manifestations of liver abscess are mistaken for a reactivation of Crohn's disease, and diagnosis is delayed. In comparison to patients with liver abscess in the general population, patients with Crohn's disease and liver abscess are considerably younger, are more likely to have multiple rather than solitary abscesses, and usually have a predisposing intraabdominal focus of infection, rather than a biliary one. Streptococci, especially Streptococcus milleri, are the most frequent cause of liver abscess in patients with Crohn's disease. Liver scanning should be performed routinely in patients with Crohn's disease in whom a febrile illness cannot be completely explained by bowel disease, or in whom fever does not respond to drainage of intraabdominal abscesses.     

Treatment of fistulizing Crohn's disease

The appropriate treatment of patients with fistulas in the setting of Crohn's disease requires a knowledge of the specific medical and surgical literature of fistulizing Crohn's. The patient with symptomatic fistulizing Crohn's disease may respond differently to specific medical therapy than a patient with symptomatic obstructing Crohn's disease. Certain medications that are useful for the treatment of patients with obstructive Crohn's disease may not be helpful in the treatment of fistulas in patients with fistulizing Crohn's disease (e.g., corticosteroids and mesalamine); in fact, some medications are believed to be detrimental (e.g., corticosteroids). Few studies have been performed to assess the efficacy of specific medications on fistulas directly. To date, there has been only one published prospective randomized controlled trial that was designed to assess the efficacy and safety of a specific medication on fistulas in patients with Crohn's disease; it showed clinical efficacy over placebo in a statistically significant manner. The judicious use of surgery remains an integral part of the management of certain presentations of fistulizing Crohn's disease, and the appropriate integration of surgical and medical therapy is of paramount importance in the management of these patients. This review provides an overview of pertinent medical and surgical literature as it pertains to management of patients with fistulizing Crohn's disease.     

Crohn's disease associated with autoimmune neutropenia

We report a 29-year-old woman with a 20-year history of Crohn's disease and neutropenia. Because of repeated complications of Crohn's disease, she has undergone three intestinal resections and also has had recurrent skin abscesses, sinusitis, and pneumonia. Persistent neutropenia has been noted throughout the course of her disease, and antineutrophil antibodies have been detected in her serum and that of her younger brother, who also has Crohn's disease and neutropenia. We discuss autoimmune neutropenia in the context of other autoimmune manifestations of Crohn's disease and speculate as to its possible contributory role in the pathogenesis of Crohn's disease.     

Crohn's disease with life-threatening hemorrhage from terminal ileum: successful control by superselective arterial embolization

A case of life-threatening lower gastrointestinal hemorrhage from Crohn's disease is reported. Several promising studies have recently been published that describe superselective embolization for the treatment of massive lower gastrointestinal hemorrhage in patients with bleeding colonic diverticular disease and angiodysplasia, and success rates of 74%–93% have been reported. But in patients with Crohn's disease, successful superselective embolization has rarely been reported. This is a report of successful superselective embolization in a patient with Crohn's disease; this should be the initial treatment of choice in Crohn's disease in an attempt to avoid surgical resection, because repeated resections predispose patients to the development of short-bowel syndrome.     

Monozygotic triplets with Crohn's disease of the colon

Female monozygotic triplets all developed Crohn's disease within a period of 11 mo. The monozygosity was demonstrated by analysis of 24 genetic markers of different chromosomal localization. Crohn's disease was diagnosed using clinical, radiologic, and endoscopic findings. Histologic evaluation of bowel tissue was consistent with Crohn's disease. All 3 patients had colon involvement; the terminal ileum appeared normal. The patient in whom Crohn's disease was first diagnosed had the severest course. Our observations support the role of a genetic influence in the manifestation of Crohn's disease. Nevertheless, environmental factors or microorganisms, or both, have to be taken into account, perhaps as factors promoting the outbreak of Crohn's disease.     

Mycobacteria and inflammatory bowel disease. Results of culture

We have been able to isolate mycobacteria from intestinal specimens obtained by surgical resection or endoscopic biopsy from patients with Crohn's disease, ulcerative colitis, and noninflammatory bowel diseases. Nineteen slow-growing (Runyon groups I and III) and 17 rapid-growing (Runyon group IV) mycobacterial isolates were obtained. Slow-growing mycobacteria were recovered from approximately one-third of intestinal biopsy specimens from Crohn's disease, one-quarter of ulcerative colitis biopsies, and 40% of biopsies from noninflammatory bowel disease patients. Isolates were most commonly members of the Mycobacterium avium-complex. One isolate (from an ulcerative colitis patient) was biochemically similar to the Mycobacterium strain previously associated with Crohn's disease, and one from a Crohn's disease patient was Mycobacterium kansasii. The rapid-growing organisms were members of the Mycobacterium fortuitum-complex. In addition to conventional mycobacteria, spheroplasts (cell wall-defective forms) were isolated from 12 patients with Crohn's disease (most often from surgically resected colon) and 3 patients with ulcerative colitis; none were isolated from non-inflammatory bowel disease patients. We have been unable to identify a consistent relationship between the presence, or the species, of Mycobacterium and Crohn's disease. Our results do not support the proposed role of a specific mycobacterium in the pathogenesis of Crohn's disease. The cause of Crohn's disease remains unclear.     

Ileitis due to Yersinia pseudotuberculosis in Crohn's disease

We present the case of a young woman with fulminating terminal ileitis due to Yersinia pseudotuberculosis, in whom Crohn's disease was subsequently diagnosed. Serological testing was prompted by radiological, macroscopic and histological changes which were atypical of Crohn's disease. We speculate that Y. pseudotuberculosis ileitis may occasionally produce an acute exacerbation of Crohn's disease, but that its occurrence may not be diagnosed if the atypical features are not recognised. In this case, the classical features of Y. pseudotuberculosis may have been modified by pre-existing Crohn's disease. We propose that, because of defects in mucosal barrier function and immunological function, patients with Crohn's may have increased susceptibility to infection by Yersinia sp.