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PubMed1999

Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis.

BACKGROUND: The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population. METHODS: The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test. RESULTS: In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients (67%), observed from 3 months to 65 months, have continued without corticosteroid therapy. Side effects included pancreatitis and shingles that resulted in discontinuation of 5-acetylsalicylic acid, leukopenia corrected by withholding 6-mercaptopurine, and self-resolved hepatitis. CONCLUSIONS: The data support the safety of 6-mercaptopurine and azathioprine use in the treatment of pediatric patients with ulcerative colitis; side effects were minimal and reversible. Eighteen (90%) of 20 patients tolerated the therapy well. The results also show that 12 (75%) of 16 pediatric patients with ulcerative colitis will benefit from the use of 6-mercaptopurine and azathioprine after initial discontinuation of corticosteroid therapy. Although 6-mercaptopurine and azathioprine may not prevent further relapses, medical management of these flares may be less intense and may not require long-term corticosteroid use. Prospective clinical trials in pediatric patients are necessary to delineate further the role of 6-mercaptopurine and azathioprine in pediatric ulcerative colitis.

Adolescent↗
PubMed2003

Experimental colitis in rats with portal hypertension and liver disease.

Within the colonic mucosa of rats with portal hypertension and liver cirrhosis, there is an increased generation of inflammatory mediators, such as leukotriene B4 and endothelin-1, and increased generation of nitric oxide. Nitric oxide overproduction may induce tissue injury. This study was undertaken to assess whether the colonic mucosa of rats with portal hypertension and liver disease have increased susceptibility to damage by noxious agents. In this study, acetic acid colitis was induced in rats with portal vein ligation and in control groups, and iodoacetamide colitis was induced in rats with partial portal vein ligation and cirrhosis due to bile duct ligation and in control groups. Rats with acetic acid colitis and those with iodoacetamide-induced colitis were studied 24 and 72 hours, respectively, after induction of colitis. Portal hypertension alone and portal hypertension with cirrhosis were present in the portal vein ligation and bile duct ligation models, respectively. In the rats with acetic acid, colitis lesion area, colonic mucosal myeloperoxidase activity, and prostaglandin E2 generation were not different between the portal vein ligation groups with and without colitis. Nitric oxide activity was higher only in the groups with colitis, irrespective of the presence of portal hypertension. In the group of rats with iodoacetamide colitis, colonic lesion area and colonic mucosal myeloperoxidase activity were similar in all groups with colitis. Colonic mucosal prostaglandin E2 generation was lower in the portal vein ligation and bile duct ligation rats with colitis compared with a control group. We concluded that rats with experimental portal hypertension do not have increased damage when induced by either acetic acid or iodoacetamide.

Alkylating Agents↗
PubMed2005

Prevalence and outcome of allergic colitis in healthy infants with rectal bleeding: a prospective cohort study.

OBJECTIVES: Allergic colitis is often diagnosed clinically in healthy infants with rectal bleeding and often treated with costly hypoallergenic formula. The true prevalence of allergic colitis is unknown. We tested the hypothesis that allergic colitis is overdiagnosed in healthy infants with rectal bleeding. The authors also determined whether rectal bleeding in infants without allergic colitis would resolve without diet change. METHODS: For the purposes of this study, allergic colitis was defined histologically as colonic mucosa with >or= 6 eosinophils per high power field and/or eosinophils in colonic crypts or muscularis mucosae. We surveyed all 56 Ohio NASPGHAN members to determine standard practice regarding the evaluation of rectal bleeding in infants. In addition, infants <or= 6 months old with rectal bleeding were recruited from the referral area of Cincinnati Children's Hospital Medical Center. All infants underwent flexible sigmoidoscopy with biopsies at 5, 10 and 15 cm. Formula or maternal diet was changed only for infants with histologic findings of allergic colitis as defined. Study subjects were followed for 9 weeks. RESULTS: In the survey of NASPGHAN members, 84% indicated they would empirically change the diet of an infant with rectal bleeding to treat presumed allergic colitis. In our study population, however, only 14 of 22 (64%; 95% confidence interval, 41-83) infants with rectal bleeding had allergic colitis. Five (23%) had normal biopsies and three (14%) had nonspecific colitis. Rectal bleeding in all infants with normal biopsies or nonspecific colitis resolved without diet change except for 1 infant subsequently diagnosed with infantile inflammatory bowel disease. CONCLUSION: A significant proportion of infants with rectal bleeding may not have allergic colitis and may undergo unnecessary, expensive formula or maternal diet changes that may discourage breast-feeding.

Cohort Studies↗
PubMed2006

Systematic review: microscopic colitis.

BACKGROUND: Collagenous and lymphocytic colitis are fairly common causes of chronic non-bloody diarrhoea, especially in elderly female. AIM: To present a systematic review of microscopic colitis. METHODS: A PubMed search using the MeSH terms microscopic colitis, collagenous colitis, lymphocytic colitis and chronic diarrhoea was performed. RESULTS: Annual incidence of each disorder is 4-6/100,000 inhabitants. The aetiology is unknown. Clinical characteristics are well described and there is an association with autoimmune diseases. Budesonide is the best-documented short-term treatment of collagenous colitis. In meta-analysis pooled odds ratio for clinical response after 6-8 weeks of treatment was 12.3 (95% CI: 5.5-27.5) in comparison with placebo. The evidence for bismuth subsalicylate is weaker and the effectiveness of other alternatives such as loperamide, cholestyramine, aminosalicylates, probiotics, or Boswellia serrata extract is unknown. Although unproven, in unresponsive severe disease azathioprine or methotrexate may be tried. No controlled trials have been carried out in lymphocytic colitis. The long-term prognosis of microscopic colitis is good, serious complications are rare and there is no increased mortality. CONCLUSIONS: Clinical and epidemiological aspects of microscopic colitis are well described. Budesonide is the best-documented short-term therapy in collagenous colitis, but the optimal long-term strategy needs further study. Controlled treatment data of lymphocytic colitis are awaited for.

Aged↗
PubMed2001

Appendectomy protects against the development of ulcerative colitis and reduces its recurrence: results of a multicenter case-controlled study in Japan.

OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multicenter clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 +/- 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 +/- 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appenectomy group than in the group that did not undergo appendectomies (57. 1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration of disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has a negative association with and perhaps a preventive effect on the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis.

Adult↗
PubMed1996

Diagnostic difficulty arising from rectal recovery in ulcerative colitis.

AIMS: To ascertain whether the dogma that a normal rectal biopsy precludes a diagnosis of ulcerative colitis is correct. METHODS: Rectal biopsy specimens from a prospective group of 24 asymptomatic patients, with an established diagnosis of ulcerative colitis, were examined in a blinded study alongside 10 normal rectal biopsy specimens from an age and sex matched patient cohort without ulcerative colitis. Each biopsy specimen was assessed by three pathologists and ascribed to one of four categories: normal; borderline abnormality (one or more minor nonspecific abnormalities which, when combined, did not fulfil the minimal acceptable criteria for a diagnosis of ulcerative colitis); minimal features of chronic ulcerative colitis; and unequivocal ulcerative colitis. RESULTS: Two patients with ulcerative colitis had normal biopsy specimens; nine specimens were categorised as borderline abnormality, one as showing the minimal changes of chronic ulcerative colitis, and 12 as having the typical changes of chronic ulcerative colitis. Thus, 11 (46%) of the 24 patients had a rectal biopsy specimen that was devoid of the acceptable attributes on which a diagnosis is established, despite a confident previous diagnosis. Ten of these 11 cases had disease limited to the rectum. Review of all previous histological biopsy specimens (n = 164) and clinical data, including drug treatment, failed to identify any attributes that might be prognostic markers for future rectal mucosal healing. CONCLUSIONS: A normal rectal biopsy specimen, though uncommon, may occur in longstanding colitis. Moreover, in 46% of these asymptomatic but established cases the degree of healing may preclude a diagnosis of ulcerative colitis without comprehensive clinical and radiological details. Pathologists need to be aware of this minimal end of the spectrum of disease.

Adult↗
PubMed1998

Reduction of acute and reactivated colitis in rats by an inhibitor of neutrophil activation.

Neutrophils have been implicated as major contributors to tissue injury in inflammatory bowel disease. In this study, we have assessed the effects of an inhibitor of neutrophil activation and adherence, NPC-18915 (4-¿2-[2-(2-benzofuranyl)phenyl]-(E)-ethenyl¿benzoic acid sodium salt), in models of both acute and reactivated colitis. Acute colitis was induced by intracolonic administration of a hapten. In other rats, colitis was reactivated 6 wk after a bout of acute colitis by subcutaneous administration of the hapten. NPC-18915 given during the first 4 days after induction of acute colitis significantly reduced tissue injury and the incidence of diarrhea and adhesions. When treatment of NPC-18915 was initiated after colitis was firmly established (48 h posthapten), it did not produce a significant effect. NPC-18915 was effective at significantly reducing colonic injury and granulocyte infiltration in the reactivated colitis model, and a similar effect could be observed in rats treated with antineutrophil serum. These results demonstrate that an inhibitor of neutrophil activation is effective in both acute and reactivated colitis, although in the former case, effectiveness is only seen when the drug is given before full establishment of colitis. These results also suggest that neutrophils, are a critical effector cell of hapten-induced colitis in the rat, particularly in the case of reactivated colitis.

Acute Disease↗
PubMed1990

Gastrointestinal motility in patients with ulcerative colitis.

In the first study 62 patients with ulcerative colitis and 20 healthy controls were fed a test meal of mashed potatoes and baked beans containing transit markers. Mouth-to-caecum transit was significantly slower in the patients than in controls; gastric emptying, however, was similar. Patients with active colitis had proximal colonic stasis, with rapid transit through the rectosigmoid region. In the patients with quiescent colitis the colonic distribution of markers was normal. Stool weight and frequency were significantly higher in the patients with active colitis. In the second study anorectal function was assessed in 29 patients with ulcerative colitis and in 12 healthy controls by measuring interluminal pressures at multiple sites in the anus and rectum before and during serial distention of a rectal balloon. Overall, resting and maximum squeeze sphincter pressures did not differ in patients with active or quiescent colitis and controls; however, in six patients with moderately severe colitis and incontinence, maximum squeeze pressure was significantly lower than in controls. The rectal volumes required to induce sensations of wind, a desire to defaecate, and pain were significantly lower in the patients with active colitis than patients with quiescent colitis and controls. Rectal pressures in response to rectal distention were higher in patients with active colitis. During disease remission rectal sensitivity decreased and rectal compliance increased. In the third study integrated pressure activity of the sigmoid colon, rectum, and anus was studied in patients with ulcerative colitis and healthy controls before and during provocation by rectal infusion of 1500 ml of warm saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Colitis, Ulcerative↗
PubMed2003

Changes of CD8+CD28- T regulatory cells in rat model of colitis induced by 2,4-dinitrofluorobenzene.

AIM: To determine the changes of CD8+ T subsets especially CD8+CD28- T regulatory cells in rat model of experimental colitis induced by 2,4-dinitrofluorobenzene (DNFB). METHODS: The rat model of experimental colitis was induced by enema with DNFB. Ten days later, colonic intraepithelial and splenic lymphocytes were isolated from colitis animals (n=16) and controls (n=8). The proportion of CD8+ T cells, CD8+CD28+ T cells and CD8+CD28- T regulatory cells were determined by flow cytometry. RESULTS: The model of experimental colitis was successfully established by DNFB that was demonstrated by bloody diarrhea, weight loss and colonic histopathology. The proportion of CD8+ T cells in either splenic or colonic intraepithelial lymphocytes was not significantly different between colitis animals and controls (spleen: 34.6+/-7.24% vs 33.5+/-9.41%, colon: 14.0+/-8.93% vs 18.0+/-4.06%, P>0.05). But CD8+CD28- T regulatory cells from colitis animals were significantly more than those from controls (spleen: 11.3+/-2.26% vs 5.64+/-1.01%, colon: 6.50+/-5.37% vs 1.07+/-0.65%, P<0.05). In contrast, CD8+CD28+ T cells from colitis animals were less than those from controls (spleen: 23.3+/-6.14% vs 27.8+/-9.70%, P=0.06; colon: 7.52+/-4.18% vs 16.9+/-4.07%, P<0.05). The proportion of CD8+CD28- T regulatory cells in splenic and colon intraepithelial CD8+ T cells from colitis animals was higher than that from controls (spleen: 33.3+/-5.49% vs 18.4+/-7.26%, colon: 46.0+/-14.3% vs 6.10+/-3.72%, P<0.005). CONCLUSION: Experimental colitis of rats can be induced by DNFB with simplicity and good reproducibility. The proportion of CD8+CD28- T regulatory cells in rats with experimental colitis is increased, which may be associated with the pathogenesis of colitis.

Animals↗
PubMed1999

Frequency and clinical evolution of indeterminate colitis: a retrospective multi-centre study in northern Italy. GSMII (Gruppo di Studio per le Malattie Infiammatorie Intestinali).

OBJECTIVE: To evaluate the prevalence and the clinical evolution of patients with an initial diagnosis of indeterminate colitis. DESIGN: Retrospective, observational study. SETTING: Fifteen gastrointestinal units in northern Italy. PARTICIPANTS: Patients with an initial diagnosis of indeterminate colitis seen between 1988 and 1993. INTERVENTIONS: Patients were traced through a common database and centres were requested to update their clinical follow-up. MAIN OUTCOME MEASURES: Frequency of patients with an initial diagnosis of indeterminate colitis among those with IBD; rate of patients who subsequently had a definite diagnosis of either Crohn's disease or ulcerative colitis. RESULTS: Fifty out of 1113 IBD patients (4.6%) had been diagnosed as having indeterminate colitis. During follow-up, 37 patients (72.5%) had a definite diagnosis of either Crohn's disease or ulcerative colitis. The cumulative probability of having a definite diagnosis of either ulcerative colitis or Crohn's disease was 80% 8 years after the first one (i.e. the first diagnosis). The probability of having a diagnosis of Crohn's disease was increased in patients with fever at onset, segmental endoscopic lesions or extra-intestinal complications and in current smokers. The probability of having a diagnosis of ulcerative colitis was increased in patients who had not undergone appendectomy before diagnosis. CONCLUSIONS: In our area, indeterminate colitis accounts for about 5% of initial diagnoses of IBD. In about 80% of patients, a diagnosis of either ulcerative colitis or Crohn's disease is made within 8 years. Several clinical and demographic features can help in identifying those patients more likely to have a subsequent diagnosis of Crohn's disease and those more likely to have a subsequent diagnosis of ulcerative colitis.

Adolescent↗
PubMed2001

Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect.

Oral tolerance is a recognized procedure for induction of antigen-specific peripheral immune hyporesponsiveness. Recently, it has been shown that oral tolerance can be used to prevent experimental colitis. The aim of this study was to test whether induction of oral tolerance toward proteins extracted from inflammatory and noninflammatory colons can alleviate preexisting experimental colitis. Colitis was induced in BALB/c mice by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-induced colitis or normal colons, before, or 7 days after colitis was induced. Standard clinical, macroscopic, and microscopic scores were used for colitis assessment. Serum interferon gamma (IFNgamma) and interleukin (IL)4 levels were measured by enzyme-linked immunosorbent assay. Feeding of colitis- or normal colon-extracted proteins before, or following colitis induction, ameliorated colonic inflammation as shown by decreased diarrhea, increased body weight, reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness, and edema. Histological parameters for colitis were markedly improved in tolerized animals, and there was a significant reduction in inflammatory response and mucosal ulcerations. Tolerized mice developed an increase in IL4 and a decrease in IFNgamma serum levels. The results show that induction of oral tolerance to colitis- or normal colon-extracted proteins down-regulated preexisting anticolon immune response, thereby ameliorating experimental colitis. Tolerance induction was mediated via a shift from a proinflammatory T helper (Th)1 to an anti-inflammatory Th2 immune response.

Animals↗
PubMedDate not supplied

Nodular duodenitis involving CD8+ cell infiltration in patients with ulcerative colitis.

BACKGROUND/AIMS: Limited efforts have been made to determine changes in the upper gastrointestinal tract in ulcerative colitis. The aim of this study was to analyze gastroduodenal lesions in patients with ulcerative colitis. METHODOLOGY: The endoscopical appearance of lesions in the duodenum and stomach was first examined. Biopsy specimens taken from 25 patients with ulcerative colitis, as well as 21 with Crohn's disease and 16 with nonspecific gastroduodenitis who had no Helicobacter pylori infection, were then evaluated by histology and immunohistochemistry for CD8, CD68 and HLA-DR. In ulcerative colitis patients, the HLA-phenotype was also analyzed by the standard NIH complement-dependent microlymphocyte toxicity assay. RESULTS: Endoscopically evident alteration of nodularity in the descending part of duodenum was prominent in ulcerative colitis and Crohn's disease, but not gastroduodenitis. Histological inflammatory change of the duodenal bulb in ulcerative colitis and Crohn's disease was mild as compared to gastroduodenitis cases. Endoscopic and histological change (redness and deformity of villi) in the duodenum were more prominent in ulcerative colitis patients with pancolitis than those with left-sided/proctitis. CD8+ cells infiltrating both the duodenum and stomach were increased in ulcerative colitis and Crohn's disease as compared to gastroduodenitis whereas focal perifoveolar accumulation of CD68+ cells and enhanced epithelial expression of HLA-DR were characteristic of Crohn's disease. Histopathological alteration in the duodenum was particularly prevalent in ulcerative colitis patients with HLA-DR4 and Cw1. CONCLUSIONS: Nodular, histologically mild duodenitis involving CD8+ cell infiltration, the severity of which positively correlates with the extent of colitis, is characteristic of ulcerative colitis.

Adolescent↗
PubMedDate not supplied

Role of bile acids in lymphocytic colitis.

BACKGROUND/AIMS: A high prevalence of bile acid malabsorption and a high response rate to bile acid binders are seen in collagenous colitis. Our aim was to explore if bile acids play a role in lymphocytic colitis, which is unknown. METHODOLOGY: Patients with lymphocytic colitis completed a diagnostic program, including the 75SeHCAT (75Se-labelled homocholic acid-taurine) test and registration of symptoms. Prevalence of bile acid malabsorption, response to bile acid binders, correlation between 75SeHCAT and histopathology were determined. The 75SeHCAT values were compared with 29 controls. RESULTS: Two out of 23 with lymphocytic colitis had a 75SeHCAT retention < or = 10%. The median 75SeHCAT value in lymphocytic colitis, 24% (range: 1.7-53), was lower than in the control group, 38% (range: 8-91) (P < 0.02). Forty-six per cent (6/13) responded to bile acid binders. No correlation was found between the 75SeHCAT values and degree of colonic inflammation. Two patients developed collagenous colitis. CONCLUSIONS: Bile acid malabsorption is more uncommon in lymphocytic colitis than in collagenous colitis. The 75SeHCAT values, however, suggest a role of bile acids in lymphocytic colitis. The conversion of 2 patients to collagenous colitis and disturbed absorption of bile acids also in lymphocytic colitis is consistent with the idea that the two forms represent variants of the same disease.

Adult↗
PubMed2006

Chronic colitis promotes tumor development.

Patients with chronic ulcerative colitis have a significantly increased risk of colorectal cancer development. This study was aimed at clarifying whether colitis promotes tumor development or not. A dose of 200 mg/kg body weight 1,2-dimethylhydrazine was given to male Wistar rats. Four weeks later, 5% acetic acid (colitis group) or 0.9% saline (control group) was administered intrarectally once a week for 12 weeks and the rats were sacrificed after 27 weeks of dimethylhydrazine injection. Macroscopic lesions (ML) were more frequently detected in the colitis group than in the control group without statistical significance. However, the number of ML per rat with ML was largest in the colitis group (4.50 vs. 1.33; p=0.039). Eleven of 13 tumors were sessile in the colitis group, while three of five were pedunculated in the control group (p=0.044). All ML of 3 mm or more in diameter in the control group were intramucosal well-differentiated tumors. In the colitis group, 4 of 13 tumors were poorly or moderately differentiated or mucinous carcinomas, and 11 of 13 invaded the submucosal layer or deeper (p=0.003). The number of aberrant crypt foci per rat was smaller in the colitis group than in the control group. The number of crypt orifices was larger in the colitis group than in the control group (23.6 vs. 8.8: p<0.001). Significantly higher proliferative activity of normal-appearing mucosa was noted in the colitis group in all three parts of the colon. Colitis is suggested to promote colonic tumor development.

1,2-Dimethylhydrazine↗
PubMed1992

Intravenous immunoglobulin therapy for active, extensive, and medically refractory idiopathic ulcerative or Crohn's colitis.

To determine whether intravenous immunoglobulin produces demonstrable clinical improvement in patients with refractory idiopathic inflammatory bowel disease, a pilot, open-label, nonrandomized, safety and therapeutic efficacy study was carried out at a tertiary care referral medical center. Twelve consecutive patients with refractory idiopathic colitis (nine ulcerative colitis, three Crohn's colitis) who were reluctant to receive immunosuppressive therapy or have surgical intervention were referred by physicians not participating as investigators in this study. Eleven patients were symptomatic for at least 6 months, with endoscopically moderate or severe mucosal inflammation despite medical therapy, including systemic corticosteroids in all cases, and one patient was dependent on oral prednisone to remain in clinical remission. Ten patients had extensive colitis, six of whom had pancolitis and four of whom had colitis extending to the hepatic flexure or transverse colon. Nine patients required hospitalization for treatment of colitis. Intravenous immunoglobulin was administered in one or two induction phases (2 g/kg over 2 or 5 days), followed by a maintenance phase (200-500 mg/kg every 2 wk for 12 or 24 wk). Tapering of systemic corticosteroid therapy was attempted, whereas other medications for idiopathic colitis were continued. Treatment response was assessed clinically and by colonoscopy with multiple biopsies whenever possible. Immunoglobulin therapy was well-tolerated and did not produce any biochemical abnormalities. In six patients who completed the treatment protocol, mean reductions +/- SE were achieved in subjective symptoms as quantified by a colitis activity score, 13.3 +/- 1.2 to 4.7 +/- 0.9 (p less than 0.001), and daily mg dose of prednisone, 41.7 +/- 8.0 to 1.9 +/- 1.2 (p less than 0.001). For all 12 patients, statistically significant reductions were achieved in the colitis activity score and daily prednisone dose. Of five patients who completed the treatment protocol and improved clinically, four underwent post-treatment colonoscopic and biopsy evaluations and had unequivocal reductions in the intensity of colonic mucosal inflammation. Three patients who had objective improvement with intravenous immunoglobulin experienced relapses of colitis after discontinuation of this therapy. Six patients did not complete the treatment protocol, two of whom required surgical intervention and four of whom withdrew to undergo colectomy electively. Intravenous immunoglobulin may be beneficial in subsets of patients with idiopathic colitis. The results of our pilot study justify the undertaking of a prospective, randomized controlled trial to determine the efficacy of intravenous immunoglobulin in carefully defined subsets of patients with idiopathic inflammatory bowel disease.

Adolescent↗
PubMed1989

[Ischemic and inflammatory colitis in elderly subjects over 70].

Twenty-five cases of non-infectious, macroscopic colitis, observed consecutively in patients over 70, were studied. The final diagnosis was, in 12 instances, ischemic colitis, in 10 instances cryptogenetic colitis (6 ulcerative colitis and 4 Crohn's diseases), and in 3 instances, non-classified colitis. The clinical manifestations consisted of rectal bleeding (92%), abdominal pain (76%) and diarrhea (56%). In 3 cases, the ano-perineal lesions observed in Crohn's diseases were noted and, in one case, a pyoderma gangrenosum was present. Endoscopy and/or barium enema showed a lesion of the left colon in 92% of the cases and of the sigmoid colon in 80% of the cases. The prognosis was severe, requiring surgery in 32% of the cases (5 ischemic colitis, 3 cryptogenetic colitis), and a 24% mortality (3 ischemic colitis, 3 ulcerative colitis), secondary to the condition and the extent of the colic involvement. The best factors of the etiological diagnosis of colitis were: the type of onset of the symptoms, the presence of anal or cutaneous lesions, the information provided by endoscopy and histology, which were specific in 11 out of 20 cases. In 5 cases, the diagnosis was only made by examination of the surgical specimen; in 3 cases, the diagnosis remained uncertain. These results suggest that the clinical data combined with an early, minimally traumatizing left endoscopy in elderly patients, should allow a quick, positive and etiological diagnosis of colitis, in order to initiate a suitable treatment in most cases.

Aged↗
PubMed1996

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study].

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities.

Colitis↗
PubMed2006

Who are susceptible to pseudomembranous colitis among patients with presumed antibiotic-associated diarrhea?

PURPOSE: Pseudomembranous colitis is a severe form of antibiotic-associated diarrhea. However, there have been no reports about the factors that make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. This study was designed to determine the clinical risk factors for pseudomembranous colitis among the patients with presumed antibiotic-associated diarrhea. METHODS: This was a retrospective study of 150 consecutive patients admitted to our institution between January 2000 and December 2004 with a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent sigmoidoscopy or colonoscopy because of diarrhea after administration of antibiotics. Pseudomembranous colitis was confirmed both endoscopically and histologically. Various clinical parameters were compared between the pseudomembranous colitis group and non-pseudomembranous colitis group. RESULTS: The mean age of patients was 61 years, and 60 percent (90/150) was female. Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than 15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029) were significant parameters for pseudomembranous colitis. On multivariate analysis, the important clinical risk factors were advanced age (older than aged 70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208-6.131; P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1; 95 percent confidence interval, 2.1-12.259; P < 0.0001). When both risk factors were present, the positive predictive value of pseudomembranous colitis was 0.86. CONCLUSIONS: Advanced age and long hospital stay may make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. Therefore, pseudomembranous colitis should be first suspected in cases with presumed antibiotic-associated diarrhea having such risk factors.

Aged↗