Short- and long-term therapeutic efficacy of nutritional therapy and corticosteroids in paediatric Crohn''s disease

BACKGROUND: Comparative data on the therapeutic efficacy of different enteral nutrition formulas and corticosteroids to obtain clinical remission and to induce mucosal healing influencing long-term disease course in paediatric Crohn's disease are still scarce. AIMS: To investigate the efficacy of nutritional therapy using three different formulas versus corticosteroids to achieve clinical remission as well as to induce intestinal mucosal healing in active Crohn's disease children. Duration of remission and effect on growth recovery were also assessed. PATIENTS AND METHODS: Clinical, laboratory, endoscopic and histological data of all new diagnosed active Crohn's disease paediatric cases were retrospectively recorded and reviewed. Thirty-seven children (median age 12.1 years) received nutritional therapy (12 polymeric; 13 semi-elemental; 12 elemental diet) and 10 subjects (median age 12.4 years) received corticosteroids. RESULTS: Similar clinical remission rate were observed after 8 weeks of treatment: 86.5% children receiving nutritional therapy versus 90% treated with corticosteroids. Improvement in mucosal inflammation occurred in 26 out of 37 (64.8%) patients on nutritional therapy and in 4 out of 10 (40%) children on steroids (p < 0.05). Finally, seven subjects on nutritional therapy and none on corticosteroids achieved complete mucosal healing (p < 0.005) at the end of the treatment. Nutritional therapy was more effective than corticosteroids in improving nutritional status and linear growth recovery. Compared to corticosteroids, the duration of clinical remission was longer in the nutritional therapy groups without differences among the three different formulas. CONCLUSIONS: In children with active Crohn's disease, nutritional therapy is more effective than corticosteroids to improve intestinal inflammation and to maintain a more sustained clinical remission.     

Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process.

The high incidence of clinical remission after faecal diversion for Crohn's colitis suggests the faecal stream may play a part in the inflammatory mechanism. The effect of faecal diversion (n = 22) and restoration of intestinal continuity (n = 10) was assessed in patients with Crohn's colitis and compared with controls. Faecal diversion produced significant improvement in the disease activity index mean (SEM) (before 176 (9); after 114 (9), p < 0.01) and serum albumin concentrations (before 33 (3.0); after 38 (3.0), p < 0.05) in all patients with Crohn's colitis. The crypt cell production rate (CCPR) was maintained after faecal diversion for Crohn's colitis but fell in the control group (before = 3.6 (0.8)), at two (1.4 (0.4), p < 0.02), and six weeks (1.6 (0.4), p < 0.05). Mucosal glucosamine synthetase activity, reflecting glycoprotein synthesis, was significantly lower in patients with Crohn's colitis (analysis of variance p < 0.05) after diversion but was maintained in the control group. Restoration of intestinal continuity failed to produce reciprocal changes. The sustained cellular proliferation and fall in glycoprotein synthesis in Crohn's colitis after faecal diversion may represent the end of an exaggerated protective response and regenerative hyperplasia after exclusion of the faecal stream. This study suggests the faecal stream may participate in the inflammatory process in Crohn's colitis. The underlying mechanism is unknown.     

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.     

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.     

Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation to disease activity and response to therapy.

Crohn's disease is characterised by gradual development of intestinal fibrotic lesions containing large amounts of collagen type I, III, and V. Measurement of circulating connective tissue metabolites has emerged as a useful tool for assessment of fibroproliferative activity in various diseases. Serum concentrations of procollagen peptides, N-terminal propeptide of type III procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP), reflect the synthesis rate of the parent collagens, while the C-terminal telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP, and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn's disease. S-ICTP was significantly increased, median 6.2 micrograms/l (95% CI 5.2 to 8.7 micrograms/l) versus controls 2.6 micrograms/l (2.5 to 2.7 micrograms/l) (p < 0.0001), S-PICP reduced, 100 micrograms/l (80 to 110 micrograms/l) versus 132 micrograms/l (124 to 141 micrograms/l) (p = 0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therapy exhibited an increase in S-PICP (p = 0.0052). S-PIIINP changed significantly (p = 0.0002), however, exhibiting a biphasic pattern. S-ICTP decreased (p = 0.015) in treatment responders but remained above the upper normal limit even when clinical remission had been achieved. Non-responders showed no significant changes in any of the marker molecules of collagen synthesis or degradation. Correlations were found between S-PIIINP and S-PICP (p < 0.005) and S-ICTP (p < 0.02), and between S-ICTP and S-orosomucoid (p < 0.005) and S-C reactive protein (p < 0.02). By contrast, there was no relation between the connective tissue metabolites and Harvey Bradshaw Index. These data provide evidence that collagen I degradation is increased not only in active Crohn's disease, but also in patients entering clinical remission. The concurrent normal/low-normal values of markers of collagen formation may reflect a changed local or systemic elimination of the propeptides.     

Intestinal permeability in Crohn's disease and effects of elemental dietary therapy]

Enteral intake of non-metabolic monosacharide and disaccharide, followed by measurement of the urinary excretion ratio of the two, is a method used to investigate intestinal permeability. L/R ratio (lactulose/1-rhamnose urinary excretion ratio) is considered an indicator of permeability of the small intestine. An increased L/R ratio is caused by mucosal disorders of the small intestine. The L/R ratio in all patients (n = 92) with Crohn's disease was 0.079 +/- 0.081 (mean +/- S.D.), which was significantly higher than the value in normal controls (0.027 +/- 0.009, n = 20, p < 0.05). In 39 patients with Crohn's disease, we assessed intestinal permeability before after treatment with an elemental diet, and during remission. The L/R ratio was 0.120 +/- 0.092, before treatment and 0.065 +/- 0.097 after treatment (p < 0.05), showing increased intestinal permeability before elemental dietary treatment. During remission, the L/R ratio was 0.035 +/- 0.028; this did not differ significantly from the value obtained after treatment. We conclude that intestinal permeability is useful for investigating disease activity in patients with Crohn's disease.     

Transglutaminases in Crohn's disease.

Transglutaminases are a family of Ca-dependent enzymes involved in various biological events. Circulating transglutaminase (factor XIIIa) is decreased in blood of patients with inflammatory bowel diseases. There is evidence that factor XIIIa and tissue type transglutaminase, present in cell cytosol, bind to various proteins of the extracellular matrix. This study examined the value of serum transglutaminase assay in the treatment and follow up of Crohn's disease and then investigated the intestinal location of both forms of transglutaminases by immunohistochemistry in normal and abnormal tissues. Serum transglutaminase activity was assayed in 36 patients with active Crohn's disease (CDAI > 150). Eighteen patients were studied prospectively from relapse into remission. A significant inverse correlation (p < 0.001) was found between circulating transglutaminase and Crohn's disease activity index; a correlation was also found between serum transglutaminase and serum orosomucoid (p < 0.01) and C reactive protein (p < 0.01). Patients were prospectively studied until clinical remission showed improvement in both their CDAI score mean (SD) (230 (46) to 72 (34), p < 0.01) and transglutaminase activity mean (SD) (0.61 (0.12) to 0.93 (0.13) mU/ml, p < 0.01). The immunohistochemistry assessment showed a colocalisation of factor XIIIa and tissue transglutaminase to the extracellular matrix of damaged tissues. In conclusion, these data confirm the value of serum transglutaminase assay as marker of Crohn's disease activity, extend the utility of serum transglutaminase assay to follow up of the disease, and emphasised the role of different types of transglutaminases in extracellular matrix assembly in the damaged tissues.     

Polymeric enteral diets as primary treatment of active Crohn's disease: a prospective steroid controlled trial.

Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease.     

Randomized, double blind controlled trial of subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn's disease

BACKGROUND: Interleukin-11 has shown benefit in animal inflammatory bowel disease models. Recently, recombinant human interleukin-11 (rhIL-11) has been observed to induce remission in a subset of patients with mild to moderate Crohn's disease (CD). The present study compared the efficacy of rhIL-11 versus prednisolone in remission induction in CD. METHODS: Patients with active CD were randomly assigned to receive either subcutaneous rhIL-11 (1 mg once weekly) and prednisolone placebo tablets, or active prednisolone (60 mg/day) and rhIL-11 placebo, for 12 weeks. Prednisolone/placebo was tapered after week 1, and patients were assessed every second week. RESULTS: Fifty-one patients received medication: 13/27 (rhIL-11) and 17/24 (prednisolone) completed 12 weeks of treatment. Remission rates (intent to treat) for rhIL-11 versus prednisolone were 4% versus 46% at week 4 (p < 0.001) and 19% versus 50% at week 6 (p < 0.05). Response to treatment (deltaCDAI > 100) was seen in 19% (rhIL-11) versus 63% (prednisolone) after 4 weeks (p < 0.002) and 37% versus 63% after 6 weeks (p = 0.1). After 12 weeks of treatment, it was observed that 22% (rhIL-11) versus 21% (prednisolone) had remained in remission. Frequent side effects of rhIL-11 included fever (n = 3), rash (4), arthralgia/arthritis (3), nausea/vomiting (3), and headache (6). CONCLUSION: rhIL-11 is well tolerated but significantly inferior when compared to prednisolone in short-term remission induction in patients with active CD. In this patient cohort, both treatments appeared to be poor in maintaining remission over a period of 3 months.     

Comparison of amino acid v peptide based enteral diets in active Crohn's disease: clinical and nutritional outcome.

Elemental diets are considered an effective primary treatment for active Crohn's disease. This study examined the hypothesis that improvement occurs because of the presence of amino acids or the low fat content, or both. A randomised, controlled trial was undertaken in 40 patients with active Crohn's disease to evaluate clinical and nutritional outcomes after an amino acid based diet containing 3% fat was given by a feeding tube compared with a peptide based diet containing 33% fat. After three weeks' treatment, clinical remission occurred in 84% of patients who were given the amino acid diet and 75% of patients who received the peptide diet (p = 0.38). Plasma linoleic acid concentration was reduced after the amino acid but not the peptide diet. An increase in total body nitrogen was associated with the magnitude of nutritional depletion before treatment and at six months' follow up, only patients who showed gains in total body nitrogen after enteral nutrition had a sustained clinical remission. This study shows that peptide based high fat diets are as effective as amino acid low fat diets for achieving clinical remission in active Crohn's disease. Improved total body protein stores but not essential fatty acid depletion may be an important indicator of a sustained remission.     

Anti-inflammatory effects of enteral diet components on Crohn''s disease-affected tissues in vitro

BACKGROUND: The mechanism of action of elemental diet in Crohn's disease treatment, is unknown. Alteration of bacterial flora, low antigenicity, low fat content and improvement of nutritional status are postulated to play a role in the anti-inflammatory effect of elemental diet. AIM: To determine whether elemental diet or its modifications has a direct anti-inflammatory effect on colonic tissue biopsies in vitro. PATIENTS AND METHODS: Colonic or ileal biopsies from 39 patients with inflammatory bowel disease and control patients were incubated for 24 hours with enteral diets in which nitrogen sources were amino acids as in elemental diet, casein or whey. Tissues were incubated with elemental diet, casein or whey, at dilutions of 1:5, 1:10 or 1:20 in Waymouth's complete medium; a medium control was also included. Tissue viability was assessed by bromodeoxyuridine uptake. Interleukin-1beta, interleukin-1 receptor antagonist and interleukin-10 concentrations in supernatants were measured by immunoassay (enzyme-linked immunosorbent assay). RESULTS: Incubation of tissues from Crohn's disease with elemental diet resulted in an increase in the ratio of interleukin-1 receptor antagonist/interleukin-1beta vs control statistically significant at 1:10 (89.6+/-17 vs 45.7+/-9. 1, p<0.05). Incubation of Crohn's tissue with casein resulted in a significant increase of interleukin-1 receptor antagonist/interleukin-1beta ratio at dilutions 1:20, 1:10 and 1:5 (101.8+/-22.0, p=0.05, 142.8+/-24.6, p<0.05; 109.7+/-25.0, p=0.05). In ulcerative colitis tissue and non-inflamed non-inflammatory bowel disease control tissue, no significant increase in interleukin 1 receptor antagonist/interleukin-1beta ratio was seen after incubation with elemental diet, casein and whey. CONCLUSION: Elemental diet incubation increases anti-inflammatory:proinflammatory cytokine ratio in Crohn's disease and this anti-inflammatory effect is not specifically due to amino acid composition, as diets containing casein have similar anti-inflammatory effects.     

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease

BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.     

Oral nutritional supplementation is effective in the maintenance of remission in Crohn''s disease

Background. Enteral feeding with either elemental or polymeric diets is an established primary therapy for active Crohn's disease. However, the role of supplementing normal food with elemental diet in the long-term management of Crohn's disease has hitherto not been explored.

Patients and methods. A series of 39 consecutive patients with Crohn's disease in clinical remission were studied. Of these, 21 patients (Group 1) received oral nutritional supplementation, taken in addition to their normal diet. Their outcome (relapse rate, Crohn's disease activity index, inflammatory markers) was compared with that of 18 patients (Group 2), who were maintained on a normal unrestricted diet over an observation period of 12 months.

Results. A total of 17 patients (81%) tolerated the nutritional supplementation. On an intention-to-treat basis, 10 patients (48%) remained in remission for 12 months, compared to 4/18 (22%) patients in Group 2, p<0.0003. Their Crohn's disease activity index and CRP remained stable while their weight and body mass index improved during the period of nutrition therapy. Seven patients in Group 1 and 14 in Group 2 relapsed at a mean of 7.4±0.9 and 6.2±0.4 months, respectively. The response to nutrition supplement was independent of age, sex, disease duration or location. Four patients (1945) were intolerant to enteral feeding.

Conclusions. Nutritional supplementation is safe, well tolerated and effective in the long-term management of patients with quiescent Crohn's disease.     

Elemental diet in the management of Crohn''s disease during pregnancy.

Four patients with Crohn's disease were treated with an elemental diet during pregnancy. Two had active disease and two also had symptoms of small intestinal obstruction. All went into a clinical remission within a few days of starting treatment. Treatment periods varied from two to four weeks, and were followed by elemental diet as a supplement to normal food in two patients. At term, all delivered a healthy infant. These patients indicate that elemental diet is a safe form of treatment for Crohn's disease during pregnancy and may be considered as an alternative to conventional drug treatments which carry a theoretical risk of teratogenesis.     

Controlled trial comparing two types of enteral nutrition in treatment of active Crohn''s disease: elemental versus polymeric diet.

To determine whether an elemental diet or a polymeric defined formula diet would be more effective for treating active Crohn's disease, we conducted a prospective randomised clinical trial in 30 patients with active Crohn's disease unresponsive to steroids and/or complicated by malnutrition. They received a four to six week enteral nutrition course with either an elemental diet or a polymeric diet. Clinical remission occurred in 10 of the 15 patients on elemental diet compared with 11 of the 15 patients assigned to polymeric diet. Both groups showed similar improvements in nutritional status, biological inflammation, alpha 1 antitrypsin clearance, and colonoscopic lesions (diminished in 17 out of 24 patients). Most patients relapsed during the year after discharge. We conclude that enteral nutrition, whatever the diet, is an efficient primary therapy for active Crohn's disease but does not influence the long term outcome.     

Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.

OBJECTIVES--To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS--Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS--Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS--Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment.     

Microalbuminuria in inflammatory bowel disease.

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.     

Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica: a double blind, prospective comparison between prednisolone and deflazacort.

OBJECTIVE: To compare the long term effects of low dosage prednisolone or deflazacort treatments on bone mass in patients with polymyalgia rheumatica. METHODS: Thirty patients with polymyalgia rheumatica were allocated on a random double blind basis to receive treatment with prednisolone or deflazacort. Bone mineral content (BMC) was measured in the lumbar spine and in the distal forearm before treatment and three, six, and 12 months after treatment. RESULTS: At three months the decrease in lumbar BMC and bone mineral density (BMD) was significantly greater in the deflazacort group than in the prednisolone group (p < 0.05), but at six and 12 months there was no difference between the two groups. In all patients after one year there was a significant loss of BMC: a 6.4% loss in lumbar BMC and a 1.8% loss in distal forearm BMC. Loss in lumbar BMC after six months was correlated to the cumulative dose of corticosteroid (r = 0.4; p < 0.05) and was significantly greater in the group of patients who had persisting symptoms of polymyalgia at six weeks, three months, or both, after treatment started (p = 0.05). CONCLUSION: This low dose study failed to reveal any calcium sparing properties of deflazacort compared with prednisolone. Possible explanations for this finding are discussed.     

Treatment of active Crohn's disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial

BACKGROUND AND AIMS: Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn's disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn's disease. PATIENTS AND METHODS: Fifty children with a paediatric Crohn's disease activity index (PCDAI)>20 were randomly assigned to receive 50% (PEN) or 100% (TEN) of their energy requirement as elemental formula for six weeks. The PEN group was encouraged to eat an unrestricted diet while those receiving TEN were not allowed to eat. The primary outcome was achievement of remission (PCDAI<10). Secondary analyses of changes in erythrocyte sedimentation rate (ESR), C reactive protein, albumin, and platelets were performed to look for evidence of anti-inflammatory effects. RESULTS: Remission rate with PEN was lower than with TEN (15% v 42%; p=0.035). Although PCDAI fell in both groups (p=0.001 for both), the reduction was greater with TEN (p=0.005). Moreover, the fall in PCDAI with PEN was due to symptomatic and nutritional benefits. With both treatments there were significant improvements in relation to abdominal pain, "sense of wellbeing", and nutritional status. However, only TEN led to a reduction in diarrhoea (p=0.02), an increase in haemoglobin and albumin, and a fall in platelets and ESR. CONCLUSIONS: TEN suppresses inflammation in active Crohn's disease but PEN does not. This suggests that long term nutritional supplementation, although beneficial to some patients, is unlikely to suppress inflammation and so prevent disease relapse.     

Microalbuminuria correlates with intestinal histopathological grading in patients with inflammatory bowel disease.

It has previously been shown that microalbuminuria is a useful disease activity marker for inflammatory bowel disease (IBD). Microalbuminuria correlates strongly with the markers of clinical and laboratory disease activity such as erythrocyte sedimentation rate (ESR), and C reactive protein (CRP). The aim of this study was to discover if microalbuminuria accurately reflects the intestinal inflammation by correlating it with intestinal inflammation using a standard histopathological grading system in patients with ulcerative colitis and Crohn's colitis. Forty two patients with IBD who had undergone endoscopic examination of the entire colon for the assessment of severity and extent of the disease (Crohn's colitis (n = 21), ulcerative colitis (n = 21)) were recruited to the study. Patients with small bowel Crohn's disease were not studied. Twenty four patients had left sided colonic disease and 18 patients had extensive colonic disease. Each patient's colonic biopsy specimens were scored blindly by a histopathologist and a composite score was compiled on the basis of the severity of changes in the enterocytes and crypts and the cellularity of the lamina propria. A clinical disease activity was obtained using the simple index of Harvey and Bradshaw. Microalbuminuria was measured in all patients by an immunoturbiditimetric method. ESR and CRP were also measured, as indicators of acute phase response in the same patients. It was found that patients with active IBD had higher concentrations of microalbuminuria compared with those patients in remission (median 222 micrograms/min (range 40-686 micrograms/min) v median 96 micrograms/min (range 30-376 micrograms/min); p < 0.001)). Significantly higher concentrations of microalbuminuria were also detected in patients with extensive colonic IBD compared with those patients with left sided disease (median 297 micrograms/min (range 132-686 micrograms/min) v median 101 micrograms/min (range 30-433 micrograms/min); p < 0.001)). A strong positive correlation was seen between microalbuminuria and intestinal histopathological score in IBD patient groups with left sided colitis (r = 0.77; p < 0.001) and extensive disease (r = 0.71; p < 0.01). The standard histopathological grading system correlated with the clinical disease activity (r = 0.64; p < 0.005) and CRP (r = 0.62; p < 0.02), however, it did not correlate with ESR. In conclusion, the strong correlation of microalbuminuria with a standard intestinal histopathological grading system suggests that microalbuminuria accurately reflects the severity of colonic inflammation in patients with Crohn's colitis and ulcerative colitis.