Evaluation of different laboratory tests and activity indices reflecting the inflammatory activity of Crohn's disease.

In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.     

An unusual endoscopic diagnosis for acute epigastric pain

Chemotactic, phagocytic, and oxidative metabolic activity of exudative leukocytes was measured in patients with Crohn's disease (n = 20) and with ulcerative colitis (n = 20). Unstimulated and casein-stimulated migration in Boyden chambers did not differ from that of healthy controls (n = 21). Patients with Crohn's disease had reduced serum-independent phagocytosis compared with healthy controls (p < 0.01) and patients with ulcerative colitis (p < 0.01). Serum-dependent phagocytosis by leukocytes from patients with Crohn's disease did not differ from that in controls but was slightly increased in patients with ulcerative colitis (p < 0.02). Unstimulated leukocytes showed increased oxidative metabolic activity in both patient groups compared with controls (p < 0.01), which was negatively correlated with the disease activity in Crohn's disease (p < 0.02). The study shows that mobilized leukocytes from patients with Crohn's disease differ from those mobilized in ulcerative colitis and supports the concept of an abnormal inflammatory reaction in Crohn's disease.     

The Effect of Dietary Yeast on the Activity of Stable Chronic Crohn's Disease

The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during I month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p < 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p < 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p < 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease.     

Accuracy and cost of diagnostic strategies for patients with suspected Crohn's disease

ObjectiveTo evaluate accuracy and cost of non-invasive diagnostic strategies including magnetic resonance imaging, intestinal ultrasonography, ileocolonoscopy and video-capsule endoscopy in suspected Crohn's disease.MethodsA decision-analytic model was used to assess the costs in low (25%), intermediate (50%) or high (75%) pre-test probability of Crohn's disease. Based on the published accuracy of diagnostic modalities and Bayes' rule, we calculated post-test probability of Crohn's disease using different strategies, starting from ileocolonoscopy, ultrasonography or magnetic resonance. Each strategy was considered successful when post-test probability was > 95% or < 5%.ResultsWith low pre-test probability, only ileocolonoscopy as the first investigation could exclude or confirm Crohn's disease while a normal ultrasonography may exclude Crohn's disease. With high pre-test probability, ileocolonoscopy or ultrasonography as the first test may confirm Crohn's disease, but at least 3 negative tests are required to exclude Crohn's disease.The cost to diagnose one patient was cheapest utilising an ultrasonography-based strategy both in low (ultrasonography €1076; ileocolonoscopy €2005; magnetic resonance €4515) and high pre-test probability of Crohn's disease (ultrasonography €321; ileocolonoscopy €712; magnetic resonance €1412).ConclusionThe accuracy and cost of these strategies depend on pre-test probability of Crohn's disease and vary according to the first test used. Ileocolonoscopy plus ultrasonography is the most accurate and less expensive initial diagnostic strategy.     

Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population

Objective. Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark. Material and methods. Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined. Results. Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene–dosage effect was observed (OR_adj.smoking 22.2; p<0.001 for carrying two CARD15 mutations versus OR_adj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (OR_adj.smoking 3.6; p<0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p<0.001), but no multiplicative effect of smoking on CARD15 genotypes was found. Conclusions. In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future.     

Role of the CARD15 gene in the pathogenesis of Crohn disease: phenotypic classification and prognostic implications

Annese V, Bassotti G, Napolitano G, Usai P, Andriulli A, Vantrappen G. Gastrointestinal motility disorders in patients with inactive Crohn's disease. Scand J Gastroenterol 1997; 32:1107–1117.

Background: Although some symptoms of Crohn's disease may be related to gastrointestinal motility disorders, studies on gastrointestinal motility in inactive Crohn's disease are lacking. Methods: Fasting and postprandial motor activity (1 h) was recorded in the gastric antrum and upper small intestine of 35 patients with inactive Crohn's disease and 18 controls, using conventional manometry. Results: Motor disorders were observed in 26 of 35 patients. The number of phase-II contractions was reduced (1.3 ±0.7/min versus 1.8±.6/min in controls; P< 0.02) (mean ± standard deviation), whereas the incidence of propagated single (2.2 ± 3.2/h versus 0.5 ± 0.6/h; P< 0.03) and clustered contractions (3.8 ± 7/h versus 1.1 ±1.4, P < 0.04) was markedly increased. Motor abnormalities were more frequent and severe in patients with Crohn's ileitis than in controls, and in patients with gastrointestinal symptoms than in asymptomatic patients. Conclusion: Most patients with inactive, uncomplicated Crohn's disease show marked gastrointestinal motor disorders, characterized either by reduced incidence of small-bowel contractions and increased incidence of single or clustered propagated contractions.     

Jejunal release of prostaglandin E2 in Crohn's disease: Relation to disease activity and first-degree relatives

Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first-degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n= 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE₂ and albumin were measured and their luminal release was calculated. Luminal release of PGE₂ was significantly higher in patients with Crohn's disease than in control subjects [69.7 ± 11.5 and 34.0±4.7 pg/cm per h (3.7±0.6 and 1.8±0.3 ng/L), respectively, P <0.01]. The PGE₂ levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE₂ in first-degree relatives [53.6±7.0 pg/cm per h (2.9±0.4 ng/L), P <0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin. The stimulated jejunal synthesis of prostaglandins observed in patients with Crohn's disease and to some extent in their relatives may constitute a response to altered genetic mucosal characteristics.     

The pharmacokinetic effect of adalimumab on thiopurine metabolism in Crohn's disease patients

Background and aimsA drug interaction between infliximab and azathioprine has previously been reported in Crohn's disease patients: the concentration of the main active thiopurine metabolites, the 6-thioguanine nucleotides (6-TGN), increased 1–3 weeks after the first infliximab infusion by 50% compared to baseline.The aim of this prospective study was to determine the effect of adalimumab on thiopurine metabolism in Crohn's disease patients, evaluated by 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) concentration measurement.MethodsCrohn's disease patients on azathioprine or mercaptopurine maintenance therapy starting with concomitant adalimumab treatment were included. 6-TGN and 6-MMPR concentrations were determined before initiation of adalimumab and after 2, 4, 6 and 12 weeks of combination therapy. The activity of three essential enzymes involving thiopurine metabolism, thiopurine S-methyltransferase (TPMT), hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and inosine-triphosphate pyrophosphatase (ITPase), was evaluated at baseline and week 4. Clinical outcome was evaluated by the Crohn's disease activity index and C-reactive protein concentrations at baseline, week 4 and week 12.ResultsTwelve Crohn's disease patients were analyzed. During the follow-up period of 12 weeks the median 6-TGN and 6-MMPR concentrations did not significantly change compared to baseline. TPMT, ITPase and HGPRT enzyme activity did not change either after 4 weeks. In two patients (17%) myelotoxicity was observed within 2–4 weeks, in whom both low therapeutic 6-TGN and 6-MMPR concentrations were found.ConclusionsIn this study in Crohn's disease patients no pharmacokinetic interaction was shown between adalimumab and the conventional thiopurines, azathioprine and mercaptopurine.     

Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease

Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease. Material and methods. Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04–7.21) and 4.94 (1.83–13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease. Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.     

Activity of Crohn's disease assessed by measurement of superior mesenteric artery flow with Doppler ultrasound

Purpose: To investigate the value of superior mesenteric artery (SMA) Doppler flow measurements as a marker for disease activity in patients with Crohn's disease.Materials and Methods: Duplex Doppler sonographic measurements of SMA bloodflow volume were obtained in 90 patients with suspected or known Crohn's disease in three separate studies. The first study was a pilot study to ascertain the value of Doppler measurements in patients with proven active or inactive disease and to check our performance. In two following studies prospectively a correlation was sought between the independent assessment of Doppler flow measurements and our standard of reference based on clinical history, physical examination, laboratory values, endoscopy, surgery and/or follow-up and prospectively a correlation was sought between Doppler studies and the results of enteroclysis.Results: In all but two patients (study II) adequate measurements of SMA flow were obtained. In the active patient groups the Doppler SMA flow was significantly increased (P<0.05) compared to the inactive patient groups and the control groups.Conclusion: These studies show that SMA Doppler flow measurements can be used as a parameter to assess disease activity in patients with Crohn's disease.     

Capsule endoscopy in clinical routine in patients with suspected disease of the small intestine: A 2-year prospective study

Objective. Capsule endoscopy is a promising method for examining the small intestine. The study was performed to evaluate the use of capsule endoscopy in clinical routine in patients with suspected disease of the small intestine. Material and methods. Consecutive patients with clinically suspected disease of the small intestine referred for capsule endoscopy between 1 January 2003 and 31 December 2004 were included in the study. All patients had previously completed a conventional diagnostic work-up with upper and lower endoscopy as well as abdominal CT scan or small-bowel enteroclysis. Results. A total of 167 patients were referred during the time period and 195 procedures were performed. Seventeen (8.7%) of the procedures were unsuccessful, with no visualization of the small bowel. In the remaining procedures the caecum was reached in 83%. The reason for referral was gastrointestinal bleeding (30%), iron-deficiency anaemia (25%), abdominal pain (15%), diarrhoea (13%) and Crohn's disease (12%). Pathology was found in 27% of the patients, with the highest diagnostic yield in patients referred for Crohn's disease (60%) and the lowest yield (4%) in patients referred for abdominal pain. There were no complications, with the exception of one patient referred for Crohn's disease who had transient abdominal pain during the procedure. Conclusions. Capsule endoscopy is a safe and well-tolerated procedure. In unselected patients with clinically suspected disease of the small intestine, the procedure gives additional information to conventional diagnostic procedures in 27% of patients. Incomplete examination of the small intestine was frequent in our group of patients.     

Normal Inflammatory Bowel Disease Mucosa Conceals Alterations in Natural Killer Cell Activity

Non -major histocompatibility complex-restricted cytotoxicity or natural killer (NK) activity could be detected in all intestinal lamina propria mononuclear cell preparations of histologically normal mucosa from 57 patients with gastrointestinal disease. Similar levels of NK activity were detected among the different disease groups. Within the inflammatory bowel disease patient group, however, Crohn's disease patients showed a threefold higher level of NK activity than detected in ulcerative colitis patients. Cytotoxicity levels in Crohn's disease patients were also higher than in the control carcinoma patients, whereas ulcerative colitis patients had considerably lower cytotoxicity levels than the carcinoma patients. Thus, unaffected normal inflammatory bowel disease mucosa conceals alterations in NK activity which might occur before the inflammation. The colon adenocarcinoma cell line Caco-2 was found to be a representative target for detecting individual differences in NK activity of lamina propria mononuclear cells compared with standard K-562 targets. The latter can be of relevance when studying mucosal immunoregulatory mechanisms in intestinal disease.     

Intestinal Permeability to Polyethylene Glycols in Monozygotic Twins with Crohn's Disease

Background: A deranged mucosal permeability, demonstrated in several studies, has been proposed to play a role in the pathogenesis of Crohn's disease. The possibility of a genetically determined alteration of paracellular transport has been indicated in some investigations. The identification of a group of monozygotic twin pairs concordant and discordant for Crohn's disease prompted this investigation.

Methods: Intestinal absorption after an oral load of different-sized polyethylene glycols (mol.wt, 458–810) was studied as 6-h urinary recovery. The study groups comprised twins with Crohn's disease (n = 19) and their healthy twin siblings (n = 9), non-twin patients with Crohn's disease (n = 14), and healthy controls (n = 30).

Results: No differences were found in the absorption of polyethylene glycols between the study groups.

Conclusion: The results give no support to the hypothesis of a genetically determined intestinal leakiness in Crohn's disease.     

Small bowel capsule endoscopy for management of Crohn's disease: A retrospective tertiary care centre experience

BackgroundThe role of small bowel capsule endoscopy in the management of established Crohn's disease is uncertain.MethodsA retrospective study of small bowel capsule endoscopy tests performed in a referral centre from 2008 to 2011; 77 tests were performed in patients with known Crohn's disease. Six patients were excluded due to capsule test retention. Patients were classified into 4 indication groups: unexplained anaemia (G1, n = 6); discrepancy between clinical symptoms and morphology (G2, n = 25), full assessment of Crohn's disease location (G3, n = 37) and evaluation of mucosal healing (G4, n = 3).ResultsTwenty-seven (38%) patients had no lesions, 32 (45%) moderate and 12 (17%) severe lesions. Endoscopic lesions were found in 4/6 (67%) G1 patients, 11/25 (44%) G2 and 28/37 (76%) G3 (p < 0.03). Three months after endoscopy was performed, 38/71 patients experienced a change in their treatment that was significantly associated with the severity of endoscopic lesions and with test indications; in 60%, 20% and 58% of patients from G1, G2 and G3, respectively (p < 0.01).ConclusionSmall bowel capsule endoscopy resulted in management changes in the majority of patients with established Crohn's disease.     

Outcome of restorative proctocolectomy when the diagnosis is suggestive of Crohn's disease.

Twenty of 81 patients treated by restorative proctocolectomy for presumed ulcerative colitis had some features of Crohn''s disease: 10 were classified as definite Crohn''s disease and 10 as indeterminate colitis. These pathological features were first apparent during synchronous colectomy and pouch construction in 10 of 11 cases. In the remainder, histological features of possible Crohn''s disease were first identified during rectal excision (n = 6), preliminary subtotal colectomy (n = 2), and after pouch excision (= 2). Complications were marginally more common in patients with features of possible Crohn''s disease: pelvic sepsis 30% (Crohn''s disease 30%, indeterminate colitis 30%) v 20%, fistulas 45% (Crohn''s disease 30%, indeterminate colitis 60%) v 16%; ileal stenosis 40% (Crohn''s disease 40%, indeterminate colitis 40%) v 21%, pouchitis 50% (Crohn''s disease 50%, indeterminate colitis 50%) v 26%, and small bowel obstruction 25% (Crohn''s disease 30%, indeterminate colitis 30%) v 13%. Pouch excision or a persistent proximal stoma has been necessary in six patients with possible Crohn''s disease (30%) (Crohn''s disease 3 cases 30%, indeterminate colitis 3 cases 30%) compared with nine (15%) of the remainder. Median hospital stay, however, was the same and stool frequency in those with a functioning pouch were comparable. These results show that there is a higher complication rate if there are features of Crohn''s disease but that the medium term functional results are acceptable if the pouch can be retained.     

The association of Haptoglobin polymorphism with Crohn's disease in Israel

ObjectivesHaptoglobin is a α²-sialoglycoprotein with hemoglobin binding capacity. Functional differences between the Hp phenotypes with the Hp 1-1 protein being a superior anti-inflammatory to the Hp 2-2 protein have been identified. The aim of our study was to investigate the possible role of Hp polymorphism in the susceptibility to Crohn's disease and its clinical course.MethodsHp phenotypes were determined for 382 Israeli CD patients and 3243 healthy controls. Phenotypic data for all Crohn's disease patients were carefully characterized. Analysis was preformed to evaluate the association between Hp polymorphism and Crohn's disease.ResultsThe frequency of Haptoglobin 1-1 was lower in Crohn's disease patients than in healthy individuals (6.28% vs. 9.28%, P = 0.057). There was no association between Haptoglobin phenotypes and disease location, behavior or extra-intestinal manifestations. No association was found between the Haptoglobin polymorphism and the frequency of the three Crohn's disease associated NOD2 mutations examined.ConclusionsWe found a borderline significant decrease of the Haptoglobin 1-1 phenotype in Israeli Crohn's disease patients compared to healthy controls. Our findings may support the importance of inflammation in Crohn's disease pathogenesis and the protective function of Haptoglobin 1-1 in the susceptibility for Crohn's disease.     

Polymorphonuclear leukocyte function in ulcerative colitis and Crohn's disease

The aim of this study was to determine whether polymorphonuclear leukocyte chemotaxis, adhesion, and electrophoretic mobility were altered in inflammatory bowel disease and whether such alterations could be related to prior ingestion of immune complexes. Polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease showed significantly impaired stimulated migration (P<0.05), increased adhesiveness (P<0.01 in ulcerative colitis,P<0.001 in Crohn's disease), and reduced electrophoretic mobility (P<0.02 in ulcerative colitis,P<0.001 in Crohn's disease) compared with healthy controls. The disease control of patients with rheumatoid arthritis demonstrated reduced stimulated migration (P<0.025) but normal adhesion. Preincubating normal cells in inflammatory bowel disease sera suggested that the altered migration and adhesion were due to circulating serum factors. Circulating immune complexes, detected by the C1q PEG binding assay, were present in 12.5% of patients with ulcerative colitis and 30% with Crohn's disease. Direct immunofluorescence of polymorphonuclear leukocytes suggested binding and/or ingestion of complexes in 57% of patients with ulcerative colitis, and 67% with Crohn's disease. There was a dorect correlation between positive immunofluorescence and impaired cell migration in ulcerative colitis (P<0.05), but no such relationship was found in the other parameters of polymorph function.     

Therapy of Crohn's disease in childhood

The aim of therapy in Crohn's disease in childhood is to induce and to maintain a remission of disease activity so that normal growth and development of the child may occur. Enteral nutrition may now be recommended as the first-line treatment for most children with Crohn's disease. However, the evidence for remission is better for children with Crohn's disease of the small intestine rather than of the large intestine. There is evidence that amino acid feeds (elemental), whole protein (polymeric) and. protein hydrolysate feeds (semi-elemental) may all be successful. Such a therapeutic approach can lead to healing of the mucosa and down-regulation of inflammation. However, in some cases surgery is required, particularly in children with growth failure and delayed puberty. Drug therapy also continues to have a role in therapy especially with severe colonic disease.     

Disappearance of Gastritis after Eradication of Helicobacter pylori: A Morphometric Study

Background: Patients with intestinal disease are at risk of developing selenium deficiency due to impaired intestinal absorption. The aim of the present study was to evaluate selenium status and to identify predictive factors of selenium depletion in patients with gastrointestinal disease. Methods: The concentration of selenium and the activity of glutathione peroxidase in plasma and erythrocytes were measured by fluorometry and by spectrophotometry. Eighty-six patients with Crohn's disease, 40 patients with ulcerative colitis, and 39 patients with various other gastrointestinal diseases were studied. Twenty-seven patients (16%) received home parenteral nutrition. Stool mass, faecal fat, and vitamin B₁₂ absorption were analysed in 100 patients. Results: The plasma selenium concentration was decreased in 85% of the patients receiving supplementary parenteral nutrition and in 20% of the patients receiving oral nutrition, among them in 26% of the patients with Crohn's disease. Almost all patients with ulcerative colitis had normal selenium levels. A statistically significant correlation was found between plasma selenium and vitamin B₁₂ absorption, stool mass, faecal fat excretion, body mass index, P-albumin, P-zinc, and the length of the remaining small bowel. Stepwise regression analyses showed that the strongest predictors of selenium deficiency were stool mass, vitamin B₁₂ absorption, and the length of the small-bowel resection. _Conclusion: Selenium deficiency is common in patients with severe gastrointestinal disorders. The deficiency is mainly related to malabsorption, and a low selenium level was almost invariably present in patients who needed parenteral supplementation due to gut failure.     

Oral cyclosporin in refractory inflammatory bowel disease

Background: The role of cyclosporin in patients with severe, refractory inflammatory bowel disease is unclear. Methods: A seven year retrospective review of patients treated with oral cyclosporin for inflammatory bowel disease refractory to conventional medical therapy was undertaken. Results: Twenty-eight patients (13 ulcerative colitis and 15 Crohn's disease) received oral cyclosporin for a mean of nine months (range 0.25–27 months). Within four weeks of starting cyclosporin, a complete clinical response occurred in 15 patients (nine with ulcerative colitis and six with Crohn's colitis), in whom conventional maintenance treatment was instituted concurrently. The clinical response was sustained during cyclosporin treatment in ten, but maintained after cyclosporin withdrawal in only five patients (18% of entire study group). Four of the five patients who relapsed after cyclosporin withdrawal had failed previously to respond to azathioprine. None of the five patients with continuing remission after cyclosporin withdrawal had received azathioprine in the past. There were three clinically significant infections and 14 cases of impaired renal function during treatment. Conclusions: Oral cyclosporin induces remission in some patients with severe ulcerative colitis or Crohn's colitis, but its benefits in cases refractory to azathioprine are overshadowed by a high frequency of relapse after drug withdrawal. (Aust NZ J Med 1998; 28: 179–183.)