Granulomas of the appendix: is it Crohn's disease?

An epidemiologic study was performed 1) to estimate the occurrence of epithelioid granulomas in the appendix wall among patients in whom an appendectomy had been performed, 2) to identify patients with granulomas in the appendix who had symptoms and history compatible with Crohn's disease, and 3) to estimate the long-term prognosis. Within a 5-year period 6051 patients in Copenhagen County underwent appendectomy. Six patients (0.1%) had epithelioid granulomas of the appendix (0.2 per 10(5) inhabitants per year). Follow-up of the six patients for 9-11 years (median, 9.5 years) showed that all had been free of gastrointestinal symptoms since the operation. Among the 373 patients diagnosed as having Crohn's disease in Copenhagen County between 1962 and 1987, 3 patients had their disease initially confined to the appendix. Follow-up in these patients showed no recurrence within a median of 6 years (range, 4-7 years). Patients with epithelioid granulomas of the appendix have an excellent long-term prognosis, which could be explained by the fact that the condition seems to be unrelated to Crohn's disease.     

Appendiceal carcinoids in Crohn's disease.

Earlier investigations demonstrate an increased risk for colon cancer in Crohn's disease. For other intestinal neoplasms, such as carcinoids, studies are limited. In Crohn's disease, repeated endoscopic and imaging studies along with intestinal resections may facilitate clinical recognition of neoplastic diseases, including appendiceal neoplasms. To date, however, only sporadic cases of appendiceal carcinoids have been described in Crohn's disease. In the present study, in a single clinician database of 1000 Crohn's disease patients, three of the 441 patients who had undergone intestinal resection had appendiceal carcinoids, all of which were pathologically confirmed. All were observed in female patients and were not suspected before surgical treatment. In one case, even though management was not altered, the tumour had already invaded serosal fat indicating a potential for more advanced disease. In this series, a carcinoid tumour was found in a resection specimen during a later clinical case review and another was a microcarcinoid, implying that these tumours may be overlooked in Crohn's disease. The percentage detected in the entire database (0.3%) exceeds the reported rates of detection of appendiceal carcinoids after removal of the appendix for appendicitis, as well as the rate of detection of appendiceal carcinoids in autopsy studies. This percentage would be higher if only those having an intestinal resection were considered (0.68%). Additional studies are needed to further define this risk of appendiceal carcinoids in Crohn's disease.     

Isolated Crohn's disease of the appendix as a source of enterorrhagia

BACKGROUND: Crohn's disease confined to the appendix is relatively rare as a sole primary manifestation of the disease. Young people are more affected. The medical history and the physical examination are similar to the findings in acute appendicitis, but the manifestations are protracted. On physical examination there are signs of peritoneal irritation and an abdominal mass is palpable in the right iliac fossa. AIMS: To report a case of Crohn's disease confined to the appendix and presenting with enterorrhagia. The source of the bleeding was localized by colonoscopy. PATIENT: A 16-year old caucasian male without past history of gastrointestinal symptoms, presented with two episodes of enterorrhagia within a period of one year. In the second episode colonoscopy identified the appendicular ostium as the source of bleeding. RESULTS: At operation the cecum and terminal ileum were normal in thickness and texture, and an inflammatory appendix adherent to the omentum was removed. Microscopically there were non-caseating granulomas, intense infiltration of the wall with plasma cells, lymphocytes and macrophages. The patient has not suffered recurrence, and a colonoscopy realized 2 years after the operation did not show signs of Crohn's disease. CONCLUSION: This case, like others in the literature, appendectomy is curative, but a 5-year follow-up is mandatory. When a young patient presents with enterorrhagia, this diagnosis has to be considered.     

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. Accepted: 17 July 1998     

Acute suppurative appendicitis

A case is presented of acute suppurative appendicitis occurring with Crohn's disease. The association is rare (only five other cases described), but if diagnostic uncertainty exists, laparotomy should be performed early. If, at laparotomy for suspected appendicitis, Crohn's terminal ileitis is incidentally found, the appendix should be removed.     

Crohn''s Disease of the Appendix Presenting as Acute Appendicitis

A patient is reported who initially presented with findings simulating acute appendicitis and who was subsequently found to have Crohn's disease isolated to the appendix. Although the hazard of appendectomy in Crohn's disease is well known, it is interesting that none of the known patients with isolated appendiceal Crohn's disease has developed a fistula. Three of the 15 reported cases of Crohn's disease solely involving the appendix developed granulomatous changes involving other regions of the bowel as long as four years following the initial diagnosis. Because of the rarity of this condition, however, specific conclusions regarding the likehood of future recurrence cannot be drawn. We stress increased physician awareness of this entity in order to emphasize long-term follow-up for such patients.     

Crohn''s Disease of the Appendix, Manifested as Acute Appendicitis with Postoperative Fistula

Two cases are reported of Crohn's disease localized to the appendix and manifested as acute appendicitis; after appendectomy a fistula developed. In none of 18 patients with Crohn's disease reported by other authors, where the appendix was the primary site, did a fistula develop postoperatively. When the appendix is the primary site of Crohn's disease the presence of mild inflammation of adjacent organs such as the terminal ileum may be mistakenly attributed to ordinary appendicitis. If, at exploratory laparotomy performed on a tentative diagnosis of appendicitis, Crohn's disease is suspected in the adjacent intestine, it is proposed that appendectomy should be followed by at least 10 days of total parenteral nutrition to minimize the risk of a fistula developing.     

How do patients with Crohn's disease fare on home parenteral nutrition?

The United Kingdom and Ireland Register of Home Parenteral Nutrition (HPN) contains details on 237 cases treated between 1977 and 1987. One hundred courses of HPN were given to 89 patients for complications of Crohn's disease. Six registering centers provided 87 percent of the courses of treatment. The short-bowel syndrome was a factor in 60 patients, fistulas in 29 patients, and exacerbation of the disease in 41 patients. Thirty patients had more than one complication. The age distribution of patients with Crohn's disease was the same as for all HPN patients. Nine patients have died and eight have ceased HPN because of complications from the treatment. Fifty two percent of the patients had no complications. Patients with Crohn's disease on HPN had a significantly better lifestyle than the group as a whole (P<.05) and had lower sepsis and complication rates (P<.01 and 0.001, respectively). The 60 Crohn's patients with short-bowel syndrome spent a significantly longer time on HPN than Crohn's patients overall (P<.05). Only 15 of these have been able to cease treatment and resume enteral feeding, compared with 23 of the other 40 patients who were able to resume enteral nutrition after a median of three months. Analysis of the authors' group of 35 patients included in the 100 showed that the only nutritional parameters of use in monitoring the patients' well-being were weight and serum albumin. Eighty percent of the patients with Crohn's disease who were treated by HPN have either successfully resumed enteral feeding or are successfully managing their own HPN. HPN is a safe and effective treatment for patients with acute or chronic intestinal failure from Crohn's disease. Authors writing on behalf of the HPN Register of the United Kingdom and Ireland.     

Crohn''s Disease of the Appendix Presenting as Lower Intestinal Hemorrhage and Cecal Mass

A rare case of Crohn's disease confined to the appendix and presenting with bright rectal bleeding is documented.     

Rectourethroperineal Fistula in Crohn''s Disease

We report the ninth case of a rectourethral fistula in Crohn's disease. The patient had undergone numerous surgical procedures for complications of severe ileocolitis before developing a rectourethroperineal fistula. His symptoms were confined to urine leaking from the perineal opening; the most common symptom of rectourethral fistula in Crohn's disease. He underwent surgical repair by an abdominoperineal approach and has been free of recurrence for a period of 2 years. The literature suggests that the incidence of rectourethral fistulae in patients with Crohn's disease is approximately 0.3% and that this complication comprises 6.2-11.1% of all genitourinary fistulae in Crohn's disease.     

Prevalence rates and an evaluation of reported risk factors for osteonecrosis (avascular necrosis) in Crohn's disease.

Avascular necrosis (osteonecrosis) occurs in Crohn's disease, but the rate of this particular complication is not known. Over 20 years, 877 patients with Crohn's disease, 492 women (56.1%) and 385 men (43.9%), were evaluated with patient follow-up data available for a mean of 7.8 years. In this group, four men were seen with osteonecrosis. No woman was affected. All patients had typical radiological, magnetic resonance imaging or pathological changes of osteonecrosis involving the femoral heads, while two also had superimposed avascular necrosis involving the humeral heads. Patient ages ranged from 19 to 36 years at the time of diagnosis of their Crohn's disease, and all were white. In one patient, disease was confined to the colon, while three patients had disease involving the terminal ileum and colon. Disease behaviour in two patients was classified as penetrating because of concomitant ischiorectal abscesses, while one patient developed a metastatic colon carcinoma. Ankylosing spondylitis was present in two patients, but no other extraintestinal manifestations developed. Two patients received corticosteroids as well as parenteral nutrition during the course of their disease. Two patients did not receive corticosteroids or parenteral nutrition. Of 877 patients with Crohn's disease, 484 (55. 1%) received corticosteroids during the course of the disease, 196 (22.4%) received at least one course of parenteral nutrition, and 125 (14.3%) received both corticosteroids and parenteral nutrition. A total of 311 patients (35.5%) had at least one small intestinal resection. The overall rate of avascular necrosis in Crohn's disease was less than 0.5% but for men with Crohn's disease was about 1%. In this series, risk of osteonecrosis could not be attributed to corticosteroid use, parenteral nutrition or both forms of therapy administered together. Small intestinal resection with loss of small intestinal absorptive area was not a risk factor for the development of osteonecrosis. Avascular necrosis (or osteonecrosis) is a very rare extraintestinal osseous complication that may occur in Crohn's disease, independent of previously reported risk factors, including corticosteroids or parenteral nutrition with lipid emulsions.     

Genetic and serological markers to identify phenotypic subgroups in a Dutch Crohn’s disease population

BACKGROUND AND AIMS: Both genetic and microbial factors seem to play a pivotal role in the aetiopathogenesis of Crohn's disease. The CARD15 frameshift mutation might link host genetic factors and the indigenous microbial flora, since CARD15 expression is stimulated by peptidoglycan, thereby activating NF-kappaB. It is hypothesised that CARD15 mutation carriers have defective anti-microbial reactions, resulting in more penetrating lesions and antibody responses, which are now being used as highly specific markers for Crohn's disease. The serological marker anti-Saccharomyces cerevisiae antibody directed against cell wall oligomannosidic epitopes has high specificity for Crohn's disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup of Crohn's disease patients, mostly with colonic involvement. METHODS: We investigated the incidence of two CARD15 mutations (3020insC and 2722G>C), anti-S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in 108 (73F/35M) patients with Crohn's disease with a mean duration of disease since diagnosis of 16 (1-41) years in relation to their phenotype, according to the Vienna classification. RESULTS: The prevalence of CARD15 frameshift mutation was 21%. Of all patients, 62% were anti-S. cerevisiae antibody positive, and 9% had perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti-S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies was higher in the mutation carriers compared to non-carriers. Remarkably, all patients with a CARD15 mutation and positive anti-S. cerevisiae antibody had ileal disease. Carriership of the mutation was significantly associated with penetrating behaviour of the disease and weakly associated with stricturing behaviour. Furthermore, anti-S. cerevisiae antibody was associated with ileal disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic antibody positive patients showed ulcerative-like behaviour of disease (by means of colonic localisation). CONCLUSIONS: Genetic and serologic markers might be useful in defining patient subgroups. This may result in a more accurate prediction of disease behaviour, prognosis and therapeutic approach.     

Crohn＇s disease in one mixed-race population in Brazil

AIM To evaluate the classification and severity of Crohn's disease in different racial groups.METHODS Patients with Crohn's disease from the outpatient clinic of the University Hospital Prof. Edgard Santos were enrolled in the study. This hospital is a reference centre for inflammatory bowel disease. Race was determined using self-identification. The Vienna's classification was applied for all subjects. The severity of Crohn's disease was determined according to the number of surgical procedures, hospital admissions in the last year and treatment with steroids and immunosuppressors. Statistical analysis was calculated using t test for means, χ2 or F for proportions. A P value ＜ 0.05 was considered to be significant.RESULTS Sixty-five patients were enrolled. Non-white patients were more frequently diagnosed with Crohn's disease in the age less than 40 years than white patients. The behaviour of disease was similar in both groups with a high frequency of the penetrating form.There was a tendency for non-white patients to have a greater frequency of hospital admissions in the last year compared to white subjects. Non-whites also had a higher rate of colonic and upper gastrointestinal involvement, and were also more frequently on treatment with immunossupressors than white patients although this difference was not statistically significant.CONCLUSION Non-white patients with Crohn's disease had an earlier diagnosis and appeared to have had a more severe disease presentation than white patients.     

Treatment of Pyoderma Gangrenosum with Infliximab in Crohn's Disease

Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen in 1 to 5% of patients with inflammatory bowel disease. The pathogenesis of PG has yet to be determined but may be related to abnormal T cell responses and the production of TNF-alpha, a powerful proinflammatory cytokine. Infliximab, a chimeric monoclonal antibody to TNF-alpha, has been approved for the treatment of Crohn's disease. We present four patients with PG treated with Infliximab for fistulizing Crohn's in whom complete healing of PG was achieved. Four patients with active fistulizing Crohn's disease and PG were treated. All patients were females ranging in age from 48 to 60 years, with a mean age of 54 years. Three of four patients had PG lesions located on the lower extremities; one patient had peristomal disease. All patients had at least colonic involvement of their Crohn's. The patients received either a single infusion or a series of three 5 mg/kg Infliximab infusions. All four patients demonstrated rapid healing of PG within 4 weeks of the first infusion of Infliximab. PG healing followed improvement in bowel disease. Complete resolution without recurrence was noted in all patients. Rapid resolution of PG was noted in four female patients with fistulizing Crohn's disease treated with Infliximab. Healing was complete, without recurrence. The anti-TNF-alpha properties of Infliximab suggest that healing may be mediated by the drug's effect on cytokine pathways, perhaps by blunted T cell activation early in the inflammatory cascade. We suggest an independent effect of Infliximab on PG.     

Preoperative clues to Crohn's disease in suspected, acute appendicitis. Report of 12 cases and review of the literature.

Twelve patients who underwent laparotomy for suspected acute appendicitis were found to have Crohn's disease of the terminal ileum. Appendectomy was performed in all although in only four patients was the appendix grossly inflamed. Postoperative complications, either abscess or fistula, developed in four patients (33%). Careful investigation of the records revealed some preoperative diagnostic clues: a history of recurrent abdominal pain and/or diarrhea (83%), physical examination revealing normal temperature (50%), and laboratory results compatible with a chronic process such as microcytic anemia (33%) and hypoproteinemia/hypoalbuminemia/hypocholesterolemia (50%). As the differential diagnosis between Crohn's disease and appendicitis is difficult and the surgical approach to the appendix in the presence of Crohn's disease is controversial, we illuminate some practical points in the preoperative evaluation of these patients and deal with the question of whether appendectomy should be performed in these patients.     

Gallbladder bile composition in patients with Crohn＇s disease

AIM:To further elucidate the pathogenesis andmechanisms of the high risk of gallstone formation inCrohn's disease.METHODS:Gallbladder bile was obtained from patientswith Crohn's disease who were admitted for electivesurgery (17 with ileal/ileocolonic disease and 7 withCrohn's colitis).Fourteen gallstone patients servedas controls.Duodenal bile was obtained from tenhealthy subjects before and after the treatment withursodeoxycholic acid.Bile was analyzed for biliary lipids,bile acids,bilirubin,crystals,and crystal detection time(CDT).Cholesterol saturation index was calculated.RESULTS:The biliary concentration of bilirubin wasabout 50% higher in patients with Crohn's disease thanin patients with cholesterol gallstones.Ten of the patientswith Crohn's disease involving ileum and three of thosewith Crohn's colitis had cholesterol saturated bile.Fourpatients with ileal disease and one of those with colonicdisease displayed cholesterol crystals in their bile.About1/3 of the patients with Crohn's disease had a shortCDT.Treatment of healthy subjects with ursodeoxycholicacid did not increase the concentration of bilirubin induodenal bile.Several patients with Crohn's disease,with or without ileal resection/disease had gallbladderbile supersaturated with cholesterol and short CDT andcontained cholesterol crystals.The biliary concentrationof bilirubin was also increased in patients with Crohn'scolitis probably not due to bile acid malabsorption.CONCLUSION:Several factors may be of importance forthe high risk of developing gallstones of both cholesteroland pigment types in patients with Crohn's disease.     

Granulomatous disease of the appendix manifesting as a cecal mass: Report of a case

We report the case of a 29-year-old man in whom isolated involvement of the appendix with granulomatous colitis or Crohn's disease manifested as a cecal mass. Appendectomy was performed. At operation the terminal ileum did not appear to be grossly involved. Careful long-term follow-up is essential in these patients to detect recurrent disease.     

Hepatitis related to cytomegalovirus infection in two patients with Crohn''s disease treated with azathioprine

Azathioprine-related side-effects occur in about 15% of treated patients. Liver toxicity is a rare complication of this drug, but is considered, in most cases, a contraindication to the continuation of treatment. However, abnormal liver tests may occur in patients under azathioprine treatment also due to infections. The distinction between toxic and infective causes of abnormal liver tests is important in order to identify patients that can be rechallenged with the drug. Cytomegalovirus infection is common in immunosuppressed transplant recipients, while the incidence is lower in patients with inflammatory bowel disease treated with immunosuppressive drugs. To our knowledge, only 2 cases of cytomegalovirus hepatitis occurring during azathioprine treatment for Crohn's disease had been reported so far. Here, we describe two patients who experienced mild hepatitis associated with the onset of cytomegalovirus infection during azathioprine treatment. The infection was documented by the appearance of IgM anti cytomegalovirus. Both cases were self-limiting. In one of the 2 patients, azathioprine was given again after resolution of the hepatitis with good control of Crohn's disease and without other complications. We also retrospectively evaluated the incidence of liver abnormalities assessed by blood tests in 58 consecutive patients with Crohn's disease treated with azathioprine at our institution. Abnormal results were obtained in 8 out of these 58 patients, requiring discontinuation of the drug in 3 patients, two of whom were the cytomegalovirus cases described above.     

Microsatellite Instability Is Uncommon in Intestinal Mucosa of Patients with Crohn's Disease

Patients with long-standing inflammatory bowel disease have an increased risk for colorectal carcinoma. Microsatellite instability occurs in colonic neoplasms and has been reported in colonic tissues from patients with ulcerative colitis. Patients with Crohn's disease also have an increased risk for colorectal cancer, although it is lower than that associated with ulcerative colitis. This study was designed to determine whether microsatellite instability occurs in Crohn's disease, and whether it occurs with similar frequency to that observed in ulcerative colitis. In all, 177 tissue samples from 33 patients with Crohn's disease were evaluated for microsatellite alterations. Microsatellite instability occurred in five different tissue samples from one of 33 Crohn's disease patients. Four of the five tissue samples showed microsatellite instability at more than one locus. We conclude that microsatellite instability is less common in Crohn's disease than ulcerative colitis and may reflect differences in cancer risk between these two forms of inflammatory bowel disease.     

Epidemiologic aspects of Crohn's disease: a population based study in Olmsted County, Minnesota, 1943-1982.

The overall age and sex adjusted incidence of Crohn's disease among Olmsted County, Minnesota, residents was 4.0 per 100,000 person-year in the period 1943-1982. Ileitis, ileocolitis, and colitis each accounted for about one third of the 103 incidence cases. Incidence rates were greater in woman than men, were higher in the urban portions of the county, and rose over time. Overall, the natural history of Crohn's disease in the community may be milder than that reported for patients at referral centres, as over half of all patients had no complications and only a third required surgery for Crohn's disease. Only one developed adenocarcinoma of the colon (relative risk = 2.0, NS). Survival was relatively unimpaired for the cohort, but Crohn's disease may have played a role in half of the deaths. The prevalence of Crohn's disease was 90.5/100,000 population on 1 January 1980.