Altered bone metabolism in inflammatory bowel disease : There is a difference between Crohn's disease and ulcerative colitis

Objectives. The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases. Design and setting. This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992-95 in one research clinic in Milan. Subjects and methods. Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 \ub1 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. \ub1 12.5 years) entered the study. Thirty healthy subjects were selected as sex- and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D3; 1,25-hydroxycholecalciferol, 1,25(OH)D3) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen C-terminal telopeptide, ICTP) were evaluated. Results. Spine and femur T scores were similar in the two groups (spine: CD = -1.49 \ub1 1.46; UC = -1.67 \ub1 1.13; femur: CD = -1.80 \ub1 1.36; UC = 1.60 \ub1 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D3 concentrations were significantly lower in both CD and UC patients compared with controls (P < 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 \ub1 5.06, UC = 10.03 \ub1 6.24, C = 6.58 \ub1 2.87, P < 0.05 vs. C) and ICTP (CD = 5.74 \ub1 3.94, UC = 10.2 \ub1 8.47, C = 3.48 \ub1 0.95, P < 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r2 = 0.107. F = 5.49) and significantly related to sex (more negative in males: r2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r2 = 0.283, F = 7.3). Conclusions. These data show that IBD patients have a diffuse osteopenia, the degree of which is not different in CD and UC; however, bone turnover is significantly higher in UC. Finally, osteopenia is related to disease duration in CD, whilst it is related to the male sex and glucocorticoid treatment in UC

Non-hodgkin&apos;s lymphoma and AIDS: Frequency of gastrointestinal involvement in a large italian series

Even though the close association between AIDS and non-Hodgkin's lymphoma (NHL) is widely known, few studies have evaluated the frequency of gastrointestinal involvement in a large series of AIDS patients with heterogeneous risk factors. We therefore reviewed the demographic and clinical features of patients with AIDS and NHL seen at our institution over a period of 5 years. NHLs complicated AIDS in 70 of 786 (9% cases in our study. All but one of the tumours were of high-or intermediate-grade histologic subtype, and 80% of 56 patients with diagnosis made during lifetime had disease stages III or IV, most with extranodal localization. The gastrointestinal tract was involved in 23 cases (33% 13 of whom had an antemortem diagnosis. All these patients complained of significant symptoms, the most frequent being GI bleeding followed by recurrent abdominal pain with or without masses. Three patients had evidence of lymphomatous disease along both the upper and lower GI tract, but more often a single localization was present. Prognosis of patients with NHLs was very poor, and there was no significant difference in survival between patients with and without GI localization at the time of initial diagnosis. \ua9 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Family history of irritable bowel syndrome is the major determinant of persistent abdominal complaints in young adults with a history of pediatric recurrent abdominal pain

AIM: To assess the late outcome of teen-agers with a previous history of recurrent abdominal pain (RAP) or irritable bowel syndrome (IBS). METHODS: A group of 67 children with RAP referred to the department from January 1986 to December 1995 was followed up between 5 and 13 years after the initial diagnosis by means of a structured telephone interview. We hypothesized that those patients with persistent adult IBS-like symptoms would be significantly more likely to report a family history of IBS in comparison with adults with no persistent abdominal complaint. RESULTS: Out of the 52 trackable subjects, 15 were found to present IBS-like symptoms at follow-up (29%) whereas the majority (37 subjects) did not. Subjects with IBS-like symptoms were almost three times more likely to present at least one sibling with similar symptoms compared to subjects not complaining (40.0% vs 16.0%), respectively (P < 0.05 at Student t test). Subjects with IBS-like symptoms also reported a higher prevalence of extra-intestinal symptoms, such as back pain, fibromyalgia, headache, fatigue and sleep disturbances. CONCLUSION: The study confirms previous observations indicating that pediatric RAP can predict later development of IBS. The latter appears to be greatly influenced by intrafamilial aggregation of symptoms, possibly through the learning of a specific illness behavior

Association of NOD2/CARD15 mutations on Crohn's disease phenotype in an Italian population

AIMS: To confirm the prevalence of NOD2/CARD15 mutations in Italian inflammatory bowel disease patients and to define the role of the different mutations on Crohn's disease phenotype. PATIENTS AND METHODS: A total of 177 patients with Crohn's disease and 92 patients with ulcerative colitis and 164 control participants were investigated for the presence of Arg702Trp, Gly908Arg and Leu1007fsinsC NOD2/CARD15 mutations.Allele frequencies in Crohn's disease and ulcerative colitis patients were compared with those observed in the control population. Genotype-phenotype correlations with the major clinical features were also established and estimated risks (odds ratio with 95% confidence interval) for the mutations were calculated by logistic regression and multiple correspondent analysis. RESULTS: Gly908Arg and Leu1007fsinsC mutations were significantly more frequent in Crohn's disease patients compared with healthy controls (P<0.01 and <0.003 respectively). Indeed, using a logistic regression model adding terms for age (differently distributed between cases and controls) and sex, a significantly increased risk of having Crohn's disease compared with healthy controls was found for all NOD2 mutations: Leu1007fsinsC (odds ratio=7.35; 95% confidence interval: 1.73-31.3), Gly908Arg (odds ratio=5.70; 95% confidence interval: 1.37-23.7) and Arg702Trp (odds ratio=2.45; 95% confidence interval: 1.10-5.47).As far as the genotype-phenotype correlations are concerned, by multivariate conditional logistic regression methods, we found a significant association between Gly908Arg mutations and familial history of inflammatory bowel disease, between Leu1007fsinsC mutations and appendectomy and between Arg702Trp mutations and fibrostenotic phenotype of Crohn's disease. A nonsignificant association between Arg702Trp variants and ileal disease was also found (odds ratio=8, 95% confidence interval: 0.99-64.9). CONCLUSIONS: The results of the study confirm a significant association of CARD15 gene mutations in our Italian Crohn's disease population and the impact of different NOD2/CARD15 mutations on specific disease phenotypes

Validation of the Italian translation of the Inflammatory bowel disease questionnaire

Background: Health-related quality of life is an important measure of treatment outcome; its evaluation requires the use of internationally validated ad hoc questionnaires. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ) is the most used specific instrument. Aim: To assess the validity and reliability of the Italian translation of the IBDQ. Methods: The IBDQ underwent forward and backward translation; 13 patients were enrolled for cognitive testing of the Italian version to increase clarity. For field testing, 113 patients (65 with Crohn's disease and 48 with ulcerative colitis) completed both the IBDQ and the generic instrument 36-item Short Form Health Survey scale (SF-36). Results: Data quality was optimal with high completeness and low floor and ceiling effect. Item internal consistency was satisfied for 100% of patients, while discriminant validity showed a few items with higher correlations with other scales. Cronbach's alpha coefficient was 0.96. Test-retest correlations indicated good reliability (Pearson R 0.81). Exploratory factor analysis indicated that the original grouping of the item was suboptimal. The score proved sensitive to disease activity, gender and quality of life as measured by the SF-36. Conclusions: The Italian translation of the McMaster Inflammatory Bowel Disease Questionnaire sounds natural and is easy to understand. A field test gave results comparable to other international validations, supporting its use in cross-national surveys

Severe abdominal pain in patients with AIDS: Frequency, clinical aspects, causes, and outcome

Parente F, Cernuschi M, Antinori S, Lazzarin A, Moroni M, Fasan M, Rizzardini G, Rovati V, Morandi E, Molteni P, Bianchi Porro G. Severe abdominal pain in patients with AIDS: frequency, clinical aspects, causes, and outcome. Scand J Gastroenterol 1994;29:511-515. Background: The exact prevalence of abdominal pain in AIDS patients, as well as the entire spectrum of causative disorders, has not yet been well defined. In addition, the existing data derive almost exclusively from surgical series describing only those patients who have undergone emergency surgical procedures. Methods: We reviewed our experience with patients presenting with severe abdominal pain from a large series of non-selected consecutive AIDS patients seen at our institution over a period of 4 years. Results: Of 458 patients, 71 (15% had severe abdominal pain, and its occurrence was associated with a reduced patient survival. Specific diagnoses were made premortem in 42 patients (59% potential causes of pain were identified at postmortem examination in 23 patients (33% whereas no specific causes were found in 6 patients (8% Most of the causative disorders (65% were AIDS-related, whereas HIV-independent pathologic conditions were found in only 18% of the patients. The predominant site of pain, combined with a few key symptoms, had a high predictive diagnostic value in nearly half of the patients. The indications for emergency laparotomy were limited and substantially similar to those of the non-HIV population. Conclusions: Severe abdominal pain frequently complicates the course of AIDS, and its occurrence is associated with reduced survival. In most patients it is due to disorders closely associated with the HIV infection. Specific causes of pain may be identified in most of the cases by an appropriate diagnostic evaluation. \ua9 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis

BACKGROUND & AIMS: It is uncertain whether mucosal healing after the first course of corticosteroids therapy predicts outcome in patients with ulcerative colitis (UC). We evaluated whether early clinical and endoscopic responses to this therapy are associated with late outcomes in UC. METHODS: Patients with newly diagnosed UC who were prescribed corticosteroid therapy (n = 157) were followed up for 5 years. They were evaluated using clinical (Powel-Tuck [PT]) and endoscopic (Baron) indexes after 3 and 6 months, then every 6 months. Outcomes at month 3 (early response) were used to identify patients with complete (group A: PT, 0-1; Baron, 0), partial (group B: PT, 0-1; Baron, 1-3), or no response (group C: persistence of clinical and endoscopic activity). The association between early and late outcomes was assessed. RESULTS: After 5 years, there were significant differences between complete and partial responders in the rates of hospitalization (25% in group A vs 48.7% in group B; P = .0152; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.21-6.72), immunosuppression therapy (5% in group A vs 25.6% in group B; P = .0030; OR, 6.55; 95% CI, 1.67-25.67), colectomy (3.3% in group A vs 18.0% in group B; P = .0265; OR, 6.34; 95% CI, 1.24-32.37), and their combination (26.7% in group A vs 48.7% in group B; P = .0249; OR, 2.61; 95% CI, 1.12-6.11). After multivariate analysis, lack of mucosal healing was the only factor associated with negative outcomes at 5 years (immunosuppressors: hazard risk [HR], 10.581; 95% CI, 2.193-51.039; P = .0033; hospitalization: HR, 3.634; 95% CI, 1.556-8.485; P = .0029; colectomy: HR, 8.397; 95% CI, 1.278-55.186; P = .0268). CONCLUSIONS: No mucosal healing after corticosteroid therapy is associated with a more aggressive disease course