Terminal ileitis after kidney transplantation : Crohn's disease or other? Case reports and literature review.

The finding of a terminal ileitis after kidney transplantation can cause a diagnostic challenge. Because the development of Crohn's disease under immunosuppressive therapy is unlikely, this diagnosis should only be considered after exclusion of infectious disease and drug-related intestinal toxicity. Defining the underlying cause of terminal ileitis is often hampered by a shortage of specific diagnostic tests or their lack of sensitivity. We present three patients with terminal ileitis after kidney transplantation resulting from different etiologies. Subsequently, we describe the characteristics that can help to make the differential diagnosis.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Fatal Clostridium difficile enteritis caused by the BI/NAP1/027 strain: a case series of ileal C. difficile infections.

Clostridium difficile generally causes diarrhoea and colitis. Small-bowel infections are considered to be rare. Twelve cases of ileal C. difficile infections are presented, including the first reported case proven to be caused by the hypervirulent BI/NAP1/027 strain. This case series suggests that small bowel involvement in C. difficile infections may be more frequent than previously thought.

NKT cells are critical for the initiation of an inflammatory bowel response against Toxoplasma gondii.

We demonstrated in this study the critical role of NKT cells in the lethal ileitis induced in C57BL/6 mice after infection with Toxoplasma gondii. This intestinal inflammation is caused by overproduction of IFN-gamma in the lamina propria. The implication of NKT cells was confirmed by the observation that NKT cell-deficient mice (Jalpha281(-/-)) are more resistant than C57BL/6 mice to the development of lethal ileitis. Jalpha281(-/-) mice failed to overexpress IFN-gamma in the intestine early after infection. This detrimental effect of NKT cells is blocked by treatment with alpha-galactosylceramide, which prevents death in C57BL/6, but not in Jalpha281(-/-), mice. This protective effect is characterized by a shift in cytokine production by NKT cells toward a Th2 profile and correlates with an increased number of mesenteric Foxp3 lymphocytes. Using chimeric mice in which only NKT cells are deficient in the IL-10 gene and mice treated with anti-CD25 mAb, we identified regulatory T cells as the source of the IL-10 required for manifestation of the protective effect of alpha-galactosylceramide treatment. Our results highlight the participation of NKT cells in the parasite clearance by shifting the cytokine profile toward a Th1 pattern and simultaneously to immunopathological manifestation when this Th1 immune response remains uncontrolled.

[Intestinal resection in the treatment of Crohn disease. Retrospective study of a series of 106 cases]. / Résection intestinale dans le traitement de la Maladie de Crohn. Etude rétrospective d'une série de 106 cas.

Crohn's disease needs medical and surgical management. Most patients are operated and surgical procedure the most often realised is intestinal resection. The authors report their experience of 106 intestinal resection performed between 01/01/1980 and 31/12/1992, in the "service de Chirurgie C" of the "CHU de Nancy" for patients operated for the first time for Crohn's disease. They were 54 men and 52 women with an average age of 31.7 years at operative time. The following clinical patterns were established: small intestine 36, colonic 10 and ileocolic 60 patients. The average length of evolution before surgery was 4.5 years. The main indication was intestinal obstruction in small intestine patterns (91%) and poor response to medical therapy in colonic patterns (30%). Usual surgical procedure was to remove all visibly diseased bowell with healthy margin of resection, as judged by gross examination, of 3 to 5 cm. Postoperative morbidity was low (17.9%) with 3 anastomotic leakages. Postoperative morbidity was 1.9% (2 patients). The average duration of follow-up was 4 years. Among the 106 patients operated for the first time for their Crohn's disease, 19 (18%) were operated again, at least one time, during the follow-up. The quality of life of operated patients is considered as good with only one patient very invalidated by a short small bowel syndrome. According to the data of their series and the literature, the authors conclude that in Crohn's disease, excisional surgery is able to improve patients clinical status account to a low morbidity and mortality, with a low risk of short small bowel syndrome as clinical course but it does not avoid recurrence.

[Factors of recurrence in Crohn disease]. / Facteurs de récidive dans la maladie de Crohn.

The surgical treatment of complications of Crohn's disease is often postponed, because of the threat of short gut and high recurrence rates. We reviewed retrospectively 286 cases of intestinal resection to evaluate factors influencing the recurrence of Crohn's disease after surgery. Recurrence was defined as the need for reoperation. Risk factors used as independent variables are all subject of controversy in recent literature. These factors included: smoking, blood transfusion, contamination, localisation of the disease, length of resection, microscopic margins and the duration of follow-up. A logistic regression model was calculated, using recurrence as the dependent variable. The mean follow-up is 55 months. Kaplan Meier was used to measure the recurrence rate. Duration of follow-up is the most important variable. The length of resection and the positive margins can statistically predict recurrence (p = 0.046 et p = 0.016), both having a predictive value of 72%. A resection with clear margins decreases the recurrence rate significantly (15%) (p = 0.0025).

[Crohn's disease of the small intestine: place of surgery in 1992]. / Maladie de Crohn de l'intestin grêle: place de la chirurgie en 1992.

Crohn's disease (CD) is a chronic pan-enteric inflammatory disease of unknown etiology. Although treatment of CD of small intestine is at present principally medical, in the majority of cases surgical intervention is unavoidable, essentially to treat complications such as occlusion, intra- and/or extra-abdominal abscess, certain fistulae, intraperitoneal perforation, profuse hemorrhage and neoplastic degeneration. Surgery may also be indicated during acute episodes of corticotherapy resistant CD, and as a valid alternative to only partially effective long term corticoid treatment of an active chronic disease. Experience has shown that surgery should be as conservative as possible, "stricturoplasty" being the treatment of choice for stenotic lesions. Postoperative follow-up conditions have still to be formulated because of the marked variations in manifestations of recurrence of the disease.

[Long-term prognosis of Crohn's disease].

Two hundred and three patients with Crohn's disease seen at our clinics and affiliated centers from April 1973 to August 1988 were followed for 4.4 +/- 3.2 years (mean +/- SD), in order to evaluate the prognosis of Crohn's disease in Japan. These 203 patients (142 males and 61 females) fulfilled the following criteria; 1) they have been followed at the outpatients clinic for more than six months or 2) they have been admitted to us for more than a month. Of these, 83 (40.9%) had ileitis, 60 (29.6%) ileocolitis, 25 (12.3%) colitis, 15 (7.5%) miscellaneous types and the remaining 20 (9.9%) had undergone bowel resection. Cumulative survival rate and cumulative probability of surgery were calculated by life table method. Cumulative survival rate in these patients was compared with expected survival rate of sex and age matched general population. Cumulative survival rates five and ten years after diagnosis were 98.9% and 98.9%, respectively. There were no significant differences in the survival rates between two groups. Cumulative probability of surgery five and ten years after onset of symptoms were 16.2% and 39.1%, respectively. Cumulative probability of surgery five and ten years after diagnosis were 25.9% and 46.9%, respectively. From these results, the prognosis of Japanese patients with Crohn's disease appears to superior to that in European and American literatures.

Early complications after surgery for Crohn's disease.

A group of 212 patients operated upon for Crohn's disease were studied and the early postoperative complications with related problems were assessed. The morbidity was 28.3 per cent, 60 patients had at least one complication, mainly of septic nature. The mortality was 3.3 per cent (7 patients), sepsis and deep vein thrombosis with pulmonary embolism were the most common causes of death. Postoperative complications were significantly higher (39.7%) (p less than 0.001) in patients with a pre-operative nutritional deficit and in those who had urgent surgery (44.4%) (p less than 0.001). Among patients with pre-operative sepsis, the morbidity was also higher (34.6%), but was not significant. Peri-anastomotic complications (dehiscence, abscess, fistula, bleeding) were apparently more frequent (45.4%) in patients with histological residual Crohn's disease at macroscopically free resection margins although this contrasts with previous series. A proper pre-operative diagnostic approach, adequate peri-operative protein-caloric repletion, antibiotic therapy, prevention of thromboembolism and elective surgery, are still the primary tools in reducing the morbidity and mortality after surgery for Crohn's disease.

Free perforation in Crohn's disease: I. A survey of 99 cases.

A review of more than 181 reported cases of free perforation in Crohn's disease yielded 84 cases that fulfilled rigorous criteria for classification as spontaneous free perforation with generalized peritonitis. An additional 15 cases from The Mount Sinai Hospital, derived from a population of 1010 patients with Crohn's disease, bring the total number to 99. Separately tabulated are 116 other cases either occurring in bypassed segments, developing after surgery, presenting with ruptured abscesses, or not definitively documented. Most reported perforations in the literature occurred in the distal small bowel. Among the Crohn's disease patients in our hospital, however, the incidence of colonic and small bowel perforation were 1.6 and 0.7%, respectively, with the highest frequency actually occurring in diseased segments of jejunum (2/50 = 4%). Free perforation was the presenting manifestation of the disease in 25 of the 84 reported cases. In our 15 patients, although perforation was never the presenting manifestation, it tended to occur early in the course of the disease (mean 3.5 years from onset of symptoms). Ninety-six of the 99 cases were operated on. The three patients treated without surgery all died. Mortality was most frequent following simple suture in the earliest reported case (39%), but considerably less frequent after resection and anastomosis (3.7%). All 18 patients treated by resection and diversion survived. Immediate surgery with resection and/or diversion therefore appears to be appropriate treatment for free perforation in Crohn's disease.

Crohn's disease in the elderly.

The natural history of Crohn's disease in 47 patients, 60 years of age or older at the time of diagnosis has been defined, and their clinical management and long term prognosis reviewed. Distal colonic involvement is common in this group while extensive colonic and diffuse small bowel disease is rare. Distal colonic involvement usually carries a good prognosis except for those few patients who present with perforation which accounts for most of the disease related mortality. The pattern of distal ileal disease is similar to that observed in the younger patients except for the acute nature of symptoms at first presentation, and the low recurrence rates after initial surgical resection.

Differences in pathogenesis, incidence and outcome of perforation in inflammatory bowel disease.

We have studied the patient records of 49 or 1,623 patients in whom perforation occurred during the course of inflammatory intestinal disease. Perforation occurred most commonly with toxic megacolon in UC, but without toxic megacolon in Crohn's disease of the colon. The incidence of perforation was significantly greater in UC than in Crohn's disease involving the colon. This was due primarily to the higher incidence of perforations with toxic megacolon in the former. The incidence of toxic megacolon was significantly greater in ulcerative colitis than in Crohn's disease involving the colon (CC and IC) and in UC than in ileocolitis. Although almost twice as frequent in UC than in Crohn's colitis alone, a significant difference could not be demonstrated in this series for patients with UC compared with CC. In UC, the incidence of perforation was 28 times as frequent if toxic colonic dilation occurred, compared with ten times the frequency of TCD in Crohn's disease involving the colon. There was a significantly higher incidence of perforation in patients with UC with toxic megacolon. The incidence of colonic perforation in the absence of toxic megacolon was similar in the two series (7 of 552 for UC, 1.2 per cent, versus 11 of 607 for CDC, 1.8 per cent). Mortality was no different in toxic megacolon in patients with UC compared with those with Crohn's disease or in patients with UC with free perforation compared with those with sealed perforation. Mortality was significantly greater in patients with perforation in UC than in those with Crohn's disease in the absence of toxic megacolon. All 15 patients with spontaneous free perforation in Crohn's disease treated by resection or exteriorization with diversion survived compared with four of seven deaths of free perforation in UC. We have no explanation for the remarkable difference in survival of free perforation in the absence of toxic megacolon in UC and CD, but it may be due to differing immunologic states or pathogenetic mechanisms.

Crohn's disease of the distal ileum.

A clinical and statistical analysis has been undertaken in a consecutive series of 227 patients with Crohn's disease involving the distal ileum under long-term review between 1944 and 1978. We have determined the long-term prognosis, cumulative reoperation rates after each resection, mortality rates, and their causes. Actuarial analysis has shown that the reoperation rates are similar after first, second, and third resections. There was no evidence that additional operations increase the risk of yet more resections. Reoperation rates were very little influenced by the age at diagnosis of the underlying Crohn's disease. A short interval from diagnosis of Crohn's disease to the first resection tended to increase the reoperation rate in the short term but there was no overall long-term effect. There was a two-fold increase in mortality risk when compared with the general population. Half the deaths were unrelated to the underlying Crohn's disease and, in this group, the incidence and causes were similar to those expected in the general population matched for age, sex, and years at risk. Of the disease related deaths many occurred in the early years of experience. Only four patients in the series have died of Crohn's disease in the last 10 years. One hundred and ninety-three patients are still alive after a mean interval of 16.1 years from the diagnosis of Crohn's disease. Full information is available on 185, of whom 161 are well and symptom free. Seven have minor problems, while 17 are unwell (nine with radiological evidence of recurrent disease).

Mortality in Crohn's disease.

Two hundred and nineteen Cardiff residents were identified with Crohn's disease between 1934 and 1976, during which period 40 of them died. Young patients diagnosed under the age of 20 years had a significantly raised standardized mortality rate (SMR) which was 11. The risk of death was particularly high during the first two and a half years after diagnosis and again after the disease had been present for more than about 13 years. Case fatality has not diminished during the last 40 years despite changes in treatment.