Clinical significance of granuloma in Crohn＇s disease

AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS: Fifty-six patients with newly diagnosed CD were included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is mote often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.     

Anorectal Crohn's disease

A group of 86 patients with anorectal Crohn's disease were followed up from ten to 40 years to determine the course of the disease and the number of patients who later required proctectomy. The overall cumulative probability of avoiding proctectomy was 91.6 percent at ten years and 82.5 percent at 20 years. Resection of all proximal Crohn's disease did not ameliorate the anorectal disease, except in patients who had all proximal disease removed and had no recurrence. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Diego, California, May 5 to 10, 1985.     

Urinary zinc excretion in Crohn's disease

In order to study the reliability of urinary zinc levels as an index of zinc metabolism and status in Crohn's disease, we evaluated plasma and urinary zinc concentrations, urinary 3-methylhistidine excretion, and Crohn's disease activity index (CDAI) in 42 patients affected by Crohn's disease. Plasma zinc correlated directly with albuminemia (P=0.01) and inversely with CDAI (P=0.001). Urinary zinc excretion correlated directly with urinary 3-methylhistidine (P=0.001) and plasma zinc levels (P=0.01), and inversely with CDAI (P=0.05). However, from multiple regression analysis, it was found that zincemia is influenced by CDAI and not by albumin, whereas zincuria is related to urinary 3-methylhistidine and plasma zinc, and not to CDAI. Our conclusion is that, in Crohn's disease, zincuria can be an index of zinc status when used together with measurements of lean body mass and turnover and factors influencing plasma ultrafiltrable zinc fraction.     

Rectovaginal fistula in Crohn's disease

Rectovaginal fistulas in the setting of Crohn's disease present a difficult management dilemma. Some patients with this problem require proctocolectomy, yet other patients with minimal symptoms never require an operation for treatment of the rectovaginal fistula. For a small percentage of patients, local surgical repair of the fistula may be warranted. Since 1980, this study has attempted local repair in seven patients with symptomatic rectovaginal fistulas from Crohn's disease. Five patients underwent staged repair of the fistula. Closure of the colostomy was eventually possible in three of these patients. Two of the three patients have had no evidence of recurrence at followup in excess of two years. The third patient required an ileostomy for intestinal disease and had no recurrence of the fistula. Two patients underwent primary repair of the rectovaginal fistula without fecal diversion; in one of these patients, the fistula recurred ten days after operation, necessitating a diverting ileostomy. The other patient remains cured 26 months after repair. The results of this review indicate that in the setting of quiescent rectal disease, an attempt to repair the fistula can be expected to have a reasonable chance of success. The presence of a rectovaginal fistula in a patient with Crohn's disease does not mandate removal of the rectum. Poster presentation at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim. California, June 12 to 17, 1988.     

Total parenteral nutrition in Crohn's disease

The effect of total parenteral nutrition on 19 patients suffering from severe active Crohn's disease was studied. Total parenteral nutrition was effective as primary therapy in 56 per cent. In the remaining patients, it was highly effective as supportive therapy, enabling them to undergo uneventful major surgery.     

Immune status in healthy relatives of patients with familial Crohn's disease

Immune-mediated mechanisms and genetic factors are believed to be involved in the pathogenesis of Crohn's disease. We studied T- and B-cell subpopulation proportions and various functionnal assays, including proliferative responses to PHA and Con A, Con A-induced suppressive activity, and natural killer cell assay toward the K562 cell line, in the peripheral blood of 22 patients with inactive familial Crohn's disease and their 35 healthy relatives including nine families. HLA-A, -B, and -DR antigens were determined in all the subjects. With the exception of minor abnormalities of suppressor cell activity present in some relatives of two families, neither significant impairments of immunological parameters in patients or their relatives nor concordant segregation of HLA haplotypes and disease were observed. These data indicate that peripheral immune abnormalities previously described in patients with Crohn's disease do not constitute primary factors involved in the disease itself and that familial incidence in Crohn's disease cannot be linked to immunological markers presently studied.     

Crohn's disease of the esophagus

Esophageal involvement in patients with Crohn's disease is uncommon. Histologic proof is rarely obtained by means of endoscopic biopsies. Moreover, the natural history of this condition and its response to therapy are largely unknown. We report a case of biopsy-proven esophageal Crohn's disease, which presented with a stricture of the distal third of the esophagus and was successfully treated by progressive endoscopic dilatation.     

Enteroduodenal fistulas in Crohn's disease

A case report of a patient suffering from an ileoduodenal fistula due to Crohn's disease is presented. Other reports are reviewed and different views on the treatment of such a fistula are discussed.     

Crohn's disease in a 92-year-old male

A case of Crohn's disease in an extremely elderly man (92-years-old) is reported. He was admitted for abdominal pain and was operated on under a diagnosis of ischemic colitis. At the mucosal surface, many linear and irregularly shaped shallow ulcers were found on the mesenteric side. Microscopically, transmural inflammatory cell infiltration, bead-like lymphoid aggregates around the propriate muscle, small epithelioid cell granulomas, fissure, and volcano-like streamers of inflammatory cells were found. Nerve fibers in Meissner's and Auerbach's plexi seemed to be increased in number, and some were hyperplastic. There was no feature of ischemic colitis or Yersinia enteritis. Serially sectioned tissue specimens did not show dysplastic mucosal change. Many cases of Crohn's disease in the elderly have been reported but an extremely elderly patient such as the present one is very rare, especially in Japan. Characteristics of elderly patients with Crohn's disease are discussed.     

Surgical management of anorectal fistulas in Crohn's disease

A retrospective review of patients with Crohn's disease treated at our institution from 1973 to 1986 revealed 35 patients operated upon for anorectal fistulas. Twenty-nine had low intermuscular fistulas (multiple in seven), and six had high intermuscular (supralevator) fistulas. Fistulotomy alone was performed in 19 patients, and eight underwent partial fistulotomy and seton insertion. Five additional patients had proximal fecal diversion before fistulotomy. Three patients with severe colonic and anorectal disease underwent proctocolectomy as the initial procedure. Of the 32 patients who had fistulotomy performed, complete healing occurred in 30. Seven patients who healed required more than one operation for fistula. One patient was left with an asymptomatic fistula, and one required proctectomy for persistent symptomatic fistula and proctitis. Success of operation correlated with absence of rectal disease and quiescent disease elsewhere in the gastrointestinal tract. Aggressive medical treatment is required to control bowel disease preoperatively. In the majority of patients, subsequent surgery is justified and healing can be anticipated. Read at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12 to 17, 1988. Read at the XIIth Biennial Congress of the International Society of University Colon and Rectal Surgeons, Glasgow, Scotland, July 10 to 14, 1988.     

Strictureplasty for active Crohn's disease

Background and aims Several studies over the last 20 years have confirmed the safety and efficacy of strictureplasty in the treatment of obstructive Crohn's disease. However, almost all of these studies use strictureplasty to treat fibrotic strictures: limited resection being preferred to treat active disease strictures. One study dating from 1986 used strictureplasty to treat purely active disease strictures, with disappointing results. No other similar studies have been published. We investigate the complication and recrudescence rates together with the intervention-free intervals in patients undergoing strictureplasty for active disease strictures.Methods A retrospective review of 14 patients who underwent strictureplasty either in isolation or in combination with limited resection for active small bowel Crohn's disease between 1996 and 2004 was undertaken.Results A total of 73 strictureplasties were carried out. There was no operative mortality; however, one patient subsequently died from metastatic small bowel adenocarcinoma arising from existing Crohn's disease. One patient subsequently developed complications directly attributed to strictureplasty and required further surgery. Three patients developed recrudescent disease and required further surgery in the form of either strictureplasty, limited resection or both. All patients undergoing strictureplasty with resection and over 70% of patients undergoing strictureplasty alone were intervention-free at 41 months. With extended follow-up, the same proportion of patients would remain intervention-free at 70 months or longer.Conclusions The use of strictureplasty in active disease strictures is well tolerated and has similar, if not better, recurrence and complication rates when compared with limited resection in patients with similar disease profiles.     

The resectional reoperation rate for Crohn's disease in a general community hospital

The severity of Crohn's disease has not been objectively estimated for patients treated at community hospitals. During an 11-year period, 105 patients underwent initial intestinal resection for Crohn's disease at a large community hospital. Follow-up data were actuarially analyzed. The overall resectional reoperation rate was 4.0 per cent per year the first seven years after initial resection and 1.9 per cent per year for the next ten years. Patients with small-bowel disease had a better prognosis than did patients with ileocolic disease. Patients who were less than 30 years of age at initial resection needed a second resection more often than did older patients. The 81 patients with initial resection after 1970 have had the lowest resectional reoperation rate yet reported: 2.8 per cent per year for ten years. The resectional reoperation rate for patients with Crohn's disease treated at this community hospital compares favorably with reoperation rates reported for patients at referral centers Read at the meeting of the American Society of Colon and Rectal Surgeons, San Francisco, California, May 2 to 6, 1982.     

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18=M, 16=C 21=C plus M, 17=P). After two weeks, improvement was reported as follows: M=67 percent, C=17 percent, C plus M=71 percent, P=35 percent. In the metronidazole group, two patients required surgery and one had trouble-some side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M=44 percent, C=62 percent, C plus M=57 percent, P=41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.     

Metastatic crohn's disease

PURPOSE: Metastatic Crohn's disease is a rare complication of Crohn's disease that has been infrequently reported in the literature. We report a case where submammary, inguinal, and perineal disease was observed in a patient many years after a proctocolectomy. The proliferative and polypoid morphology of the cutaneous lesions has not been previously described. In addition, this case describes severe cutaneous metastatic Crohn's disease in the absence of active gastrointestinal disease, which to our knowledge has not been reported in the literature. RESULTS: A 55-year-old female with a 25-year history of Crohn's disease was investigated and treated over a 12-month period for metastatic Crohn's disease involving the submammary, inguinal, and perineal areas. These proliferative lesions with erythema and ulceration were histologically consistent with metastatic Crohn's disease. Gram and Ziehl Nielsen stains revealed no pathogenic organisms. The use of topical solutions, antibiotics, immunosuppression, and surgery failed to produce any significant benefit. A review of 42 cases of metastatic Crohn's disease in the literature is reported. CONCLUSION: Cutaneous metastatic Crohn's disease has an extremely variable macroscopic appearance and may be a source of considerable morbidity. It can be present without other significant symptomatology, although it more commonly parallels gastrointestinal disease activity. There are no trials to guide current treatment, which is mainly based on anecdotal reporting.     

The long-term outcome in Crohn's disease

The long-term outcome of Crohn's disease was reviewed in 139 patients who were treated at the Cleveland Clinic for a minimum of 15 years. At the time of diagnosis, 38 (27 percent), 39 (28 percent) and 62 (43 percent) patients had small-bowel, large-bowel, and ileocolic patterns of disease, respectively. The disease progressed with time and, eventually, 104 (75 percent) patients had ileocolic disease. One hundred twenty-two patients (88 percent) underwent at least one definitive operation for the disease. Forty-four (32 percent) patients had proctocolectomies and 65 (47 percent) have ileostomies. Associated manifestations of Crohn's disease occurred in a high proportion of patients; perianal disease in 78 (56 percent), intestinal fistulas in 45 (32 percent), extraintestinal disease in 49 (35 percent). Six patients died of causes directly related to the disease. Specific complications tend to occur at definite times in the course of the disease. Crohn's disease is not a benign condition. There is a relentless progression of the disease and a high incidence of complications when patients are followed over a long period. Read at the meeting of the American Society of Colon and Rectal Surgeons, Houston, Texas, May 11 to 15, 1986.     

Results of operation for rectovaginal fistula in Crohn's disease

A retrospective review of patients with Crohn's disease treated at our institution from 1973 to 1986 revealed 12 patients operated on for rectovaginal fistula. Disease involved the large intestine in 10 patients. Primary fistula repair was performed in four patients and four others had staged repair with preliminary fecal diversion. Four patients with severe colonic and anorectal disease had proctocolectomy performed as the first procedure. Of eight patients who underwent fistula repair, complete healing occurred in six. One patient has a persistent fistula, which is minimally symptomatic, and the other required proctocolectomy after three unsuccessful repairs. Success of operation correlated with quiescent intestinal disease and absence of rectal involvement. In selected patients with symptomatic fistulas, surgical repair is indicated and healing can be anticipated. Read at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12–17, 1988.     

Clinical course of Crohn's disease in Italy

The clinical course of Crohn's disease in 131 patients was studied for a mean period of 4.2±3.2 years. The clinical activity of the disease, expressed as percentage of patients per year in an active phase, is high in the first year (70.2 percent) and progressively decreases during subsequent years (25 percent after seven years). The percentage of patients who needed steroid treatment is high during the first year (68 percent) and falls to 19 percent after seven years. An operative risk rate of 54 percent was registered, with a probability of reoperation equal to 34 percent. Clinical relapse after the first surgery occurred in 70 percent of cases. The registered mortality was 6.9 percent, with a ratio of 6 to 1 between observed and expected mortality. In conclusion, the disease, while showing a tendency to reduce its activity over the years, is burdened by a risk of surgery and mortality which progressively increases with time     

Multiple vitamin status in Crohn's disease

We measured serum, blood, or red cell concentrations of various vitamins in 24 patients with Crohn's disease who had been free from any nutritional treatment, and compared them with those in 24 healthy controls. Twelve of the patients were affected in the small bowel only, two in the large bowel only, and the remaining 10 in both the small and large bowel. The fat-soluble vitamins A and E were significantly decreased in patients with Crohn's disease compared to controls. Among the water-soluble vitamins, vitamins B₁, B₂, and B₆, and folic acid were more depleted in patients with Crohn's disease than in the controls, whereas vitamins B₁₂ and C, nicotinic acid, and biotin were not different between the two groups, and pantothenic acid was increased in patients with Crohn's disease. In addition, vitamin B₂ and nicotinic acid showed a negative correlation with the Crohn's disease activity index. These findings suggest that there is a variety of vitamin deficiencies in Crohn's disease prior to treatment and also that concentrations of some vitamins, such as vitamin B₂ and nicotinic acid, may reflect the severity of the disease.     

Cholangiocarcinoma and Crohn's disease

Summary Cholangiocarcinoma is an infrequent complication of inflammatory bowel disease. Although increasing numbers of cholangiocarcinomas are being reported in association with ulcerative colitis, the occurrence of this disease in patients with Crohn's disease is rare. To understand this complication better, we have reported the case of a patient with Crohn's disease in whom cholangiocarcinoma subsequently developed and reviewed the literature.     

Coexisting Crohn's disease and ulcerative colitis

This case report describes a patient initially presenting with Crohn's disease of the ileum who subsequently developed ulcerative proctocolitis. Reports of patients with both inflammatory bowel disease confirmed by histopathologic examination are rare.