Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum DNA cannot be detected by PCR in Crohn's disease tissue.

BACKGROUND: The etiology of Crohn's disease remains unknown. A putative mycobacterial cause of the disease is still controversial. AIMS: To assess the mycobacterial hypothesis in Crohn's disease using a polymerase chain reaction technique. PATIENTS AND METHODS: Nested polymerase chain reaction with primers on the 16S-rRNA coding region (16S-rDNA) and with primers specific both to the insertion sequences (IS) 900, and IS 901/902 were used to amplify Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum DNA in frozen endoscopic intestinal biopsies or surgical resection specimens from patients with Crohn's disease (n = 47: 25 endoscopic biopsies and 22 surgical resection samples, +/- lymph nodes), ulcerative colitis (n = 27), and non inflammatory bowel diseases (n = 20: colonic tumors and diverticulitis). Positive as well as negative controls were used throughout the study. RESULTS: All strains of Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum tested were positive for both primer systems. Of the 94 biopsies tested, 5 (2 Crohn's disease, 1 ulcerative colitis and 2 controls) were positive with the 16S-rDNA primers but did not correspond to Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum. None of the specimens was positive with the IS primers. CONCLUSION: These results do not support the hypothesis that Mycobacterium paratuberculosis, or Mycobacterium avium subsp. silvaticum play a role in Crohn's disease.

Crohn's disease stable remission after human immunodeficiency virus infection.

We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.

[Morbid associations in Crohn's disease. Study of a series of 832 patients]. / Associations morbides au cours de la maladie de Crohn. Etude à partir d'une série de 832 patients.

OBJECTIVES: Depending its frequency, the association in the same subject of Crohn's disease and another pathology can be fortuitous or the expression of genetic or environmental interrelationships. The aim of our study was to identify among a series of patients with Crohn's disease preliminary data which would be suggestive of a significant association between Crohn's disease and other pathologies. PATIENTS AND METHODS: Personal and familial histories were collected in 832 patients with Crohn's disease who were seen consecutively in the same hospital clinic from 1974 to 1994. RESULTS: We found 4 cases (0.5%) of associated Crohn's disease-multiple sclerosis and Crohn's disease-rheumatoid purpura in the same patient. Each of the following genetic diseases was associated with Crohn's disease in one patient (0.1%): Charcot-Marie-Tooth disease, deuteroanopia, multiple exostosis, familial ichthyosis, periodic disease. CONCLUSION: We describe for the first time sporadic cases of associated Crohn's disease and another rare disease, Charcot-Marie-Tooth disease, familial ichthyosis and periodic disease. We suggest that there is a significant interrelationship between personal and familial histories of Crohn's disease and multiple sclerosis which should be verified in prospective studies.

Macronutrient intake and malabsorption in HIV infection: a comparison with other malabsorptive states.

BACKGROUND: Wasting is a major complication of HIV infection. The role of malabsorption in wasting is controversial. AIMS: To assess oral intake and malabsorption in a cohort of weight losing HIV infected patients, with or without chronic diarrhoea. METHODS: A prospective study using a predefined protocol for HIV infected patients was performed in a gastroenterology and nutrition unit in a university hospital. A retrospective comparison was made with HIV negative patients with malabsorption due either to small bowel disease or resection. Body weight and height, serum albumin, oral intake of macronutrients, faecal weight, and faecal fat were measured. RESULTS: Seventy nine weight losing HIV infected patients were studied. Among the 66 patients with more than 5% lipid malabsorption, wasting was significantly greater in patients with cryptosporidiosis (n = 22) than in patients with microsporidiosis (n = 18) who exhibited significantly more wasting than patients with no identified enteropathogen (n = 26) (body mass index 16.8 (14.0-20.7), 18.9 (16.5-21.3), 19.7 (15.9-23), respectively). When controlling for the level of lipid malabsorption, HIV infected patients had a significantly lower energy intake than HIV negative patients with chronic malabsorption. In HIV infected patients, but not in other categories of malabsorbers, body mass index correlated significantly with energy intake (r = 0.33, 95% confidence intervals 0.12 to 0.51). CONCLUSION: In weight losing HIV infected patients, reduced energy intake is superimposed on malabsorption and significantly contributes to wasting.

The role of anatomic factors in nutritional autonomy after extensive small bowel resection.

BACKGROUND: It is difficult to predict which patients with a postsurgical short bowel will require long-term parenteral nutrition. METHODS: We performed a retrospective prognostic study for the time to home parenteral nutrition or death from malnutrition (nonautonomy), on the basis of 103 patients with a residual short bowel of 17 to 150 cm. The influence of anatomic variables was summarized through the use of Cox regression model. RESULTS: Of the 103 patients included, 24 lost nutritional autonomy. Three anatomic variables were identified as having independent predictive information; remaining small bowel length (measured on small bowel x-rays; p = .0001), and jejunoileal anastomosis (p = .01) promoted autonomy, whereas end jejunostomy (p = .002) increased the risk of losing nutritional autonomy. CONCLUSIONS: On the basis of these results and on the relative weight of these variables, high-risk patients for loss of nutritional autonomy were defined as those with jejunoileal anastomosis and a remaining small bowel length < 35 cm, patients with jejunocolic anastomosis and remaining small bowel length < 60 cm, and patients with an end jejunostomy and remaining small bowel length < 115 cm. This classification was thereafter validated on a prospective series of 32 patients.

Treatment of refractory diarrhoea in AIDS with acetorphan and octreotide: a randomized crossover study.

OBJECTIVE: To compare the efficacy and tolerance of acetorphan, an orally active enkephalinase inhibitor whose antidiarrhoeal properties derive from a purely antisecretory activity, to that of octreotide, a subcutaneously administered somatostatin analogue, in the treatment of refractory diarrhoea in AIDS patients. DESIGN: An open randomized crossover trial. SETTING: The inpatient medical units of three hospitals. PATIENTS: Thirteen adult inpatients with AIDS and refractory diarrhoea that lasted for 35 +/- 8 weeks despite use of traditional antidiarrhoeal agents and was characterized by 7.0 +/- 1.2 stools/day, weighing 1033 +/- 174 g/day with a lipid output of 18.8 +/- 3.5 g/day. INTERVENTIONS: Acetorphan (100-300 mg thrice daily) and octreotide (50-150 micrograms thrice daily) were given in random order during two 1-week periods. MAIN OUTCOME MEASURES: Response was defined as a reduction by at least one-third of both daily stool number and weight. RESULTS: The mean daily stool number was reduced to 4.6 +/- 1.1 with acetorphan (P < or = 0.05) but was 5.6 +/- 1.2 with octreotide (NS). Whereas two patients responded to both treatments, two responded to acetorphan alone and one to octreotide alone. Daily lipid output in faeces was reduced non-significantly with acetorphan (11.5 +/- 2.3 g) but was nearly doubled with octreotide (33.7 +/- 12.0 g). Acetorphan was very well tolerated. CONCLUSION: Enkephalinase inhibitors may be a useful alternative to somatostatin analogues in the management of refractory diarrhoea in AIDS.

[Prognosis in pancolonic forms of hemorrhagic rectocolitis]. / Pronostic des formes pancoliques de rectocolite hémorragique.

OBJECTIVE: To assess the prognosis of pancolitis in ulcerative colitis including survival, colectomy rate, colon cancer risk, activity of disease, functional and socioprofessional impact. METHODS: Retrospective study of 130 cases of ulcerative pancolitis referred consecutively to Rothschild Hospital from 1962 to 1993. They were 58 men and 72 women. The mean age at onset of ulcerative colitis was 30 years (range: 5-77). The extension to the right colon was secondary in 68% of patients. The period of observation ranged from 0.8 year to 46 years from the onset, with a median of 10.6 years. Three patients were lost to follow up. RESULTS: Eight patients died, the survival rate being 93% at 10 years. Surgical treatment was performed in 85 patients. The cumulative colectomy rates were 61% and 77% at 10 and 20 years respectively. Colonic cancer developed in three patients, corresponding to a cumulative risk after 25 years of 6% in unoperated patients and 1.9% in the whole series. No cancer occurred after colectomy and ileorectal anastomosis. In the group of unoperated patients there was a decrease of activity of the disease during the first fifteen years. The quality of life of colectomized patients with reestablishment of intestinal continuity and of those treated conservatively did not differ significantly. CONCLUSION: In this series, long term prognosis of ulcerative pancolitis was favourable. The high colectomy rate was balanced by a very low risk of colorectal cancer.

Effects of cigarette smoking on the long-term course of Crohn's disease.

BACKGROUND & AIMS: In Crohn's disease, smoking increases the risk for surgical procedures. The influence of smoking on the overall severity of the disease remains controversial. The purpose of the study was to examine the effects of smoking on the long-term course of Crohn's disease and the relationship between smoking and therapy. METHODS: The medical charts of 400 consecutive patients whose smoking habits were specified by direct interview were reviewed. RESULTS: Frequency and extent of excisional surgery were not significantly different in smokers and nonsmokers, but smokers required more glucocorticoids and immunosuppressive drugs. The effect of smoking on the need for immunosuppressive drugs was dose-dependent and was significant in women but not in men. For female smokers, the 10-year risk of immunosuppressive therapy was 52% +/- 11% compared with 24% +/- 10% for nonsmokers (P < 0.001). The risk of surgery increased only in patients who smoked and did not take immunosuppressive drugs. The surgical rate increased significantly during smoking in 19 patients who started smoking after diagnosis and decreased significantly in 34 patients who stopped compared with matched controls. CONCLUSIONS: Patients who smoke, particularly women and heavy smokers, run a high risk of developing severe disease. Immunosuppressive therapy neutralizes the influence of smoking on surgical rates.

[Functional diarrheas are not, in most cases, minor clinical forms of lymphocytic or collagenous colitis]. / Les diarrhées fonctionnelles ne sont pas, pour la plupart, des formes cliniques mineures de colite lymphocytaire ou collagène.

AIM: The aim of the study was to test the hypothesis that some patients with functional diarrhea could actually suffer from a mild clinical pattern of collagenous or lymphocytic colitis. PATIENTS AND METHODS: Twenty consecutive patients with chronic diarrhea were included in the study if the colonic mucosa appeared normal during colonoscopy. From multiple colonic biopsies were established a conventional histological diagnosis and a quantitative histological diagnosis. This latter diagnosis was based on the semiquantitative evaluation of epithelial morphological alterations and lamina propria monocellular infiltration, and on the determination of both intraepithelial lymphocyte count and subepithelial collagen layer thickness. Multiple colonic biopsies from 12 control patients without diarrhea were analyzed according to the same protocol. RESULTS: Among the 20 patients with diarrhea, the quantitative diagnosis of collagenous colitis was made in 3 patients (thickness of the collagen band between 11 and 26 microns) and the diagnosis of lymphocytic colitis in one (21% of intraepithelial lymphocytes). The percentage of intraepithelial lymphocytes did not differ between the 16 remaining patients and the controls (12 +/- 5% and 9 +/- 4%, respectively). Similarly, the score of surface epithelial damage and the score of lamina propria infiltration in patients with diarrhea (1.2 +/- 1.0 et 1.7 +/- 1.5) were not different from the values in the control group (1.3 +/- 1.3 et 1.5 +/- 1.2). The mean fecal weight in patients with diarrhea but without colitis was 161 +/- 130 g/d. All the values of fecal weight were below 300 g/d, except in one patient with a past history of truncular vagotomy. CONCLUSIONS: These results suggest that most of the patients with functional diarrhea do not suffer from mild clinical patterns of collagenous or lymphocytic colitis.

[Effects of preoperative artificial nutrition in intestinal resections for Crohn disease]. / Effets de la nutrition artificielle préopératoire dans les résections intestinales pour maladie de Crohn.

UNLABELLED: Artificial nutrition prior to bowel resection has not been evaluated fully. The aim of the present study was to assess the effects of preoperative artificial nutrition upon postoperative complications, length of resected bowel and relapses of Crohn disease. RESULTS: Between 1990 and 1994, 108 consecutive patients underwent bowel resection for Crohn disease. Thirty nine patients had received exclusive enteral nutrition (n = 14) or parenteral nutrition (n = 25) for 19 +/- 10 days. Patients who had received artificial nutrition were more malnourished and had complicated Crohn disease (fistulae, abscesses) more often than patients operated without artificial nutrition. After 19 days of artificial nutrition, the nutritional state of patients was not significantly improved. Postoperative complication rate was higher in patients operated after artificial nutrition (33 vs. 16%; P = 0.03). Using multivariate prognosis analysis, the extent of colic resection was significantly associated with postoperative complications (P = 0.0003). Length of resected bowel and relapse rates were similar in patients with or without preoperative nutrition. CONCLUSION: Artificial nutrition prior to bowel resection for Crohn's disease is indicated in patients with the most severe form of the disease. A preoperative nutrition of 19 days does not seem to reduce postoperative complications nor the length of resected bowel.

Intestinal histoplasmosis in AIDS patients: report of three cases observed in France and review of the literature.

We report three cases of colonic histoplasmosis observed in a non-endemic area in patients with AIDS. The patients presented with fever, abdominal pain and an abdominal mass in the right lower quadrant. Diagnosis was obtained using Gomori-Crocott staining of endoscopic or surgical biopsies. One patient died without specific treatment and two patients had a complete remission when treated with intravenous amphotericin B but suffered a relapse when given oral itraconazole. Thus, physicians in areas where intestinal histoplasmosis is not endemic should be aware of the condition. Diagnosis can easily be obtained using Gomori-Crocott staining of colonoscopic biopsies; this should avoid unnecessary laparotomies and allow specific treatment to be instituted rapidly.

[The clinical activity of Crohn's disease in the Paris area is maximal in the spring]. / L'activité clinique de la maladie de Crohn en région parisienne est maximale au printemps.

The aim of this study was to look for seasonal fluctuations in the clinical course of Crohn's disease. Eighty-three patients residing in the Paris area were included in the study and they had all undergone continuous clinical monitoring throughout the first three years of the disease. During this period, the clinical activity of the disease was ranked monthly on a semi-qualitative scale ranging from 0 to 4. The dates of corticosteroid treatment and of resection surgery carried out during the first three years of the disease were also recorded. The mean clinical score varied significantly (P < 0.0001) for different months of the year, the three highest scores being recorded during the three months of Spring-time (April, May and June). The number of months of corticosteroid treatment differed significantly (P < 0.05) for the various seasons, the six highest values being reported during Spring and Summer months. The number of intestinal resections differed significantly (p < 0.05) during different seasons, the highest incidence again being reported during Spring. This study demonstrates seasonal variations in the clinical course of Crohn' disease in the Paris area, with a peak occurring in the Spring.

Classification of the sequelae of bowel resection for Crohn's disease.

A postoperative handicap index designed to predict diarrhoea and malnutrition following bowel resection in patients with Crohn's disease is proposed. The index takes into account the location and extent of resection, and its value can be calculated from operative records. Retrospective (n = 218) and prospective (n = 68) series of patients were studied. Diarrhoea and malnutrition developed in 102 patients (47 per cent) and 13 patients (6 per cent) respectively in the retrospective series, and in 40 (59 per cent) and one (1 per cent) of those in the prospective series. The handicap index correlated with faecal weight and faecal fat in 112 patients tested. Positive and negative predictive values of an index score greater than 20 for the development of diarrhoea, and over 50 for the development of malnutrition, were 0.64 and 0.90, and 0.60 and 0.99 respectively in the retrospective series; values were 0.80 and 0.71, and 0.25 and 1.00 in the prospective series. The postoperative handicap index is a useful tool for predicting the functional consequences of bowel resection for Crohn's disease.

Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection.

We report six cases of toxic megacolon in patients with human immunodeficiency virus (HIV). One case, at an early stage of HIV infection, mimicked a severe attack of Crohn's disease, with a negative search for infectious agents. Subtotal colectomy was successfully performed with an uneventful postoperative course. The five other cases concerned patients with acquired immunodeficiency syndrome at a late stage of immunodeficiency. They were related to Clostridium difficile or cytomegalovirus (CMV) intestinal infection in two and three patients, respectively. One case of CMV colitis presented macroscopically and histologically as pseudomembranous colitis. Emergency subtotal colectomy, performed in the first four patients with acquired immunodeficiency syndrome was followed by a fatal postoperative outcome. The last patient treated conservatively by colonoscopic decompression, in association with anti-CMV therapy, had a favorable short-term outcome. From the experience of our series and data from the literature, we discuss the best diagnostic and therapeutic approach to toxic megacolon in patients with HIV.

Drug induced lymphocytic colitis.

Three cases are presented of lymphocytic colitis with chronic diarrhoea concurrent with longterm use of Cyclo 3 Fort, a phlebotonic drug used in France. The histological and immunopathological features of lymphocytic colitis are described. We show that lymphocytic colitis is drug induced, particularly in one patient where the immunopathological features of mucosal immune cell activation were induced by drug rechallenge. It is concluded that lymphocytic colitis may be drug induced, secondary to a chronic activation of the mucosal immune system by one or several components of the drug.

[Treatment of Crohn disease in adults]. / Traitement de la maladie de Crohn de l'adulte.

Corticosteroids are an efficient treatment for active Crohn's disease. The treatment has to be undertaken with a daily intake equivalent to 1 mg/kg per day of prednisolone for a 3 to 7 week period. Immunosuppressive agents are indicated in case of corticodependency or in case of large intestinal resection. Artificial nutrition (enteral or parenteral) is proposed in corticoresistant forms, and is usually followed by an immunosuppressive therapy. Surgical management is reserved for complications, including resistance to all medical therapy. Surgical resection has to be limited in order to avoid a short bowel syndrome. Surgery should not be considered as the ideal therapy as it has been demonstrated that recurrence after surgery increases at distance. 5-aminosalycilates compounds are an alternative therapy in mild attacks. Mesalazine may reduce the recurrence and could be considered as a possible maintenance treatment.

[Lamprene in ano-perineal lesions of Crohn's disease. A retrospective study]. / Le Lamprène dans les localisations ano-périnéales de la maladie de Crohn. Une étude rétrospective.

UNLABELLED: The efficacy of clofazimine (Lamprene) was analysed retrospectively in twenty one patients with anoperineal lesions (APL) of Crohn's disease. Clofazimine is known for its antimycobacterial, antiinflammatory and immunomodifier properties. It is used with success in leprosy and certain dermatological disorders. A number of clinical and laboratory arguments suggest the probability of a role of mycobacteria in the etiology of Crohn's disease. METHODS: twenty one patients with ileo-colono-anal or bucco-colono-anal Crohn's disease formed the basis of this study. They had been treated in various ways for APL, without success. They had APL of varying degrees of advancement (primary lesions: seven cases; secondary lesions: ten cases; major advanced lesions: four cases). Treatment with Lamprene was given for three to 38 months (mean: 12 months), the mean cumulative dose being 40 grams (4 to 146). Other therapeutic measures were started simultaneously in twelve patients: medical in six cases, medico-surgical in four cases and surgical only in two cases. The aim of treatment in fourteen cases was to obtain the healing of ulcerated lesions and/or fistulas, in three patients to delay dilatation sessions and in four patients to avoid proctectomy in the short-term. RESULTS: ten patients showed no improvement while eleven were improved (with regression of primary lesions in ten cases). Taking combined treatment into consideration, the link between the result obtained and Lamprene was considered probable in five cases, possible in four cases and uncertain in one case. Lamprene was well tolerated in general. It was not possible to evaluate the efficacy of treatment regarding intestinal disease. CONCLUSION: the efficacy of Lamprene in ano-perineal lesions of Crohn's disease is possible and is worthy of evaluation in a controlled trial.

[The risk of extra-colonic extension in Crohn's colitis]. / Le risque d'extension extra-colique au cours de la colite de Crohn.

One hundred and two patients with Crohn's colitis present on average for 8 years, were studied retrospectively in order to determine whether or not a group of patients existed in whom the disease remained limited to the colon, and if such a group could be identified early on in the course of the disorder. At the time of the diagnosis of Crohn's disease, 34 patients had a concomitant anoperineal lesion, while 68 had disease affecting the colon only. In the latter, at the end of the follow-up period, the disease remained exclusively limited to the colon in 39 cases (57 p. cent). The actuarial rate of non-extra-colonic spread was 75, 40 and 35 p. cent at 5, 10 and 15 years respectively. Spread involved above all the anoperineal region (55 p. cent at 10 years), and less often the ileum (20 p. cent at 10 years). In patients monitored for at least 6 years, there was no significant difference between those in whom disease had spread and those in whom it remained limited to the colon, regarding the main initial clinical findings by history and examination, the same applying after the disease had been present for 3 years. These results would go against the existence of a specific entity of "Crohn's disease affecting the colon as an organ" and support the opinion that coloproctectomy with a pouch should be avoided in colitis due to Crohn's disease.

Absorption of zidovudine in patients with diarrhoea.

Many patients with AIDS have gastrointestinal complaints, including the major clinical disorder of chronic diarrhoea. The pharmacokinetics of zidovudine was studied in 9 male patients with HIV infection and diarrhoea to establish whether drug absorption was impaired in them. The peak plasma concentration and AUC after a single oral dose of 200 mg, were the same as those reported in 6 healthy male volunteers (3.1 vs 4.0 mumol.l-1 and 7.2 vs 5.2 mumol.h.l-1, respectively). Since the bioavailability of zidovudine is not particularly impaired, oral zidovudine therapy can be maintained in patients with diarrhoea.