Titres of anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease are not related to disease activity.

In the systemic vasculitides, serial measurement of titres of anti-neutrophil cytoplasmic autoantibodies (ANCA) is useful for follow-up of disease activity and prediction of relapses. ANCA have been detected in patients with inflammatory bowel disease, but their relation to disease activity in these diseases is unclear. We analysed the relation between disease activity and ANCA titres as determined by indirect immunofluorescence in paired samples obtained during active disease and at remission from individual patients with ulcerative colitis (n=60) and Crohn's disease (n=101). In addition, patients were followed prospectively, to study the fluctuations of ANCA with time in relation to disease activity. We did not detect a correlation between disease activity and ANCA titres, either in paired samples from active disease and remission, or in serial samples, either in ulcerative colitis or in Crohn's disease. In contrast to the ANCA-associated systemic vasculitides, serial measurement of ANCA titres is not useful in the monitoring of disease activity in patients with inflammatory bowel disease.     

Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn's disease

BACKGROUND: In inflammatory bowel diseases, changes in autonomic enteric regulation may also affect neural cardiovascular control. However, while cardiac autonomic modulation has been shown to be impaired in active ulcerative colitis, the occurrence of cardiovascular autonomic alterations, also in the quiescent phase of inflammatory bowel diseases, is still a matter of debate. The aim of our study was thus to explore the features of cardiovascular autonomic regulation in ulcerative colitis and Crohn's disease during their remission phase. MATERIALS AND METHODS: Autonomic cardiovascular control was evaluated by time- and frequency-domain indexes of spontaneous heart rate and blood pressure variability and by assessing the baroreflex heart rate control (sequence technique) in 26 patients with ulcerative colitis, in 26 patients with Crohn's disease and in 23 healthy controls. RESULTS: The groups were matched for age, gender and body mass index. They had similar blood pressure mean levels and variability. By contrast, mean heart rate, its overall variability (standard deviation), and baroreflex sensitivity were lower in ulcerative colitis patients than in controls. Moreover, all indexes related to cardiac vagal control were significantly lower in ulcerative colitis patients with respect not only to controls but also to Crohn's disease patients. CONCLUSIONS: Cardiac vagal control is impaired in quiescent ulcerative colitis only, and not in Crohn's disease, while in both bowel diseases vascular control appears preserved. Since cardiovagal modulation seems related to anti-inflammatory mechanisms, the reduced parasympathetic cardiac regulation in apparently quiescent ulcerative colitis suggests that such systemic derangement is accompanied by local subclinical inflammations, even in the absence of clinically active inflammatory processes.     

An investigation into the validity of the present classification of inflammatory bowel disease

To assess the validity of the present subdivision of patients with inflammatory bowel disease into those with Crohn's disease of the small bowel or of the colon and those with ulcerative colitis, 252 patients with inflammatory bowel disease have been studied by questionnaire and case note review. One hundred and seventy-two variables concerning the nature and frequency of symptoms in remission and relapse, the incidence of complications and results of investigation have been analysed by computer. As expected, there were many highly significant variables between patients with ulcerative colitis and those with Crohn's disease of the small bowel. The latter showed evidence of a more severe disease course with more complications. There were similar, although less marked, differences between patients with Crohn's disease of the colon and those with Crohn's disease of the small bowel. There were very few differences in disease course between patients with Crohn's disease of the colon and those with ulcerative colitis. The results suggest that while separate classification of patients with Crohn's disease of the small bowel is justified on clinical grounds, the present separation of patients with disease confined to the colon into groups labelled ulcerative colitis or Crohn's disease of the colon is not. Alternative methods of classification should therefore be investigated.     

Serum levels of C-reactive protein in Crohn''s disease and ulcerative colitis

Prospective measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn's disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C-reactive protein levels were raised in both groups but were significantly higher in Crohn's disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C-reactive protein concentration were 4, 0-65 mg/l in Crohn's disease v. 0, 0-15 mg/l in ulcerative colitis, P less than 0.01; in moderate disease the values were 15, 1-100 mg/l v. 3, 0-29 mg/l respectively, P less than 0.05 and in cases of severe disease, 85, 15-183 mg/l v. 12, 2-33 mg/l respectively, P less than 0.001. Erythrocyte sedimentation rate was also higher in Crohn's disease but did not closely reflect disease activity in individual patients. C-reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohn's disease. The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohn's disease.     

Human chorionic gonadotropin and alpha chain of glycoprotein hormones in patients with inflammatory bowel disease

In twenty patients with Crohn's disease and ten patients with ulcerative colitis serum levels of human chorionic gonadotropin and the common alpha-subunit of glycoprotein hormones were determined by radioimmunoassay. In contrast to published data, all serum samples except one revealed levels within the normal range of 148 controls (human chorionic gonadotropin levels up to 3.9 IU/l, alpha-subunit up to 3.8 micrograms/l). Neither the serum levels of human chorionic gonadotropin nor of the alpha-subunit differed significantly between patients with Crohn's disease (median/maximum: 0.9/4.4 IU/l; 0.7/3.6 micrograms/l) and ulcerative colitis (1.0/3.4 IU/l; 0.8/2.2 micrograms/l). Furthermore, the serum levels studied in patients with active (0.9/3.0 IU/l; 0.7/3.5 micrograms/l) and inactive (0.9/4.4 IU/l; 0.8/3.6 micrograms/l) Crohn's disease and in patients with active (1.1/3.4 IU/l; 0.9/2.2 micrograms/l) and inactive (0.9/2.9 IU/l; 0.8/1.3 micrograms/l) ulcerative colitis were not significantly different. There was no relationship of the duration of the disease or a bowel resection to the serum levels of human chorionic gonadotropin or the alpha-subunit. It is concluded that both parameters are not useful as markers in patients with Crohn's disease or ulcerative colitis. The normal serum levels found in patients with inflammatory bowel diseases indicate human chorionic gonadotropin as a highly specific marker for malignant diseases.     

Autoimmunity, inflammatory bowel disease and hyposplenism.

The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.     

Serum amyloid A protein compared with C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein as a monitor of inflammatory bowel disease

The serum concentrations of serum amyloid A protein (SAA), C-reactive protein (CRP), alpha 1-antichymotrypsin (alpha 1-ACT) and alpha 1-acid glycoprotein (alpha 1-AGP) have been measured in eighty-six patients with Crohn's disease, twenty-five patients with ulcerative colitis and twenty-two patients with the irritable bowel syndrome. In the Crohn's and ulcerative colitis group significant increases in concentration were observed in all four proteins, which parallelled disease severity as defined by other conventional laboratory parameters formulated into a simple activity index. In the irritable bowel group no significant changes were seen. Serum amyloid A and CRP concentrations were significantly lower in ulcerative colitis than in Crohn's disease when mild, but did not differ significantly when severe. Serum amyloid A correlated well with CRP (r = 0.83) and alpha 1-ACT (r = 0.80), but less well with alpha 1-AGP (r = 0.65). Serum amyloid A was the most sensitive protein (77%) but had the lowest specificity (74%). C-reactive protein was less sensitive (58%) than SAA but had greater specificity (100%). Alpha 1-ACT had a sensitivity and specificity similar to CRP and, therefore, provided little or no additional information. Alpha 1-AGP, although also 100% specific, had the lowest sensitivity (34%) and, therefore, is probably the least useful acute phase monitor of inflammatory bowel disease. The role, and associated problems, of SAA measurements are discussed.     

Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis

BACKGROUND: As platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and beta-thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis. PATIENTS AND METHODS: In a prospective study, the platelet count, platelet factor 4 and beta-thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation. RESULTS: Platelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and beta-thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non-inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and beta-thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and beta-thromboglobulin. However, even after 12 months of follow-up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and beta-thromboglobulin were significantly higher than the levels of the controls. CONCLUSION: Platelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and beta-thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre-thrombotic state of disease.     

Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0). 2. Gas-liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 +/- 4) and Crohn's disease (20 +/- 3) than in controls (13 +/- 5 micrograms/mg of protein) (means +/- SD). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations. 3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease. 4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.     

Ultrasonographic findings correspond to clinical, endoscopic, and histologic findings in inflammatory bowel disease and other enterocolitides.

OBJECTIVE: To compare results obtained by abdominal ultrasonography with clinical findings, including endoscopic and histologic findings, to evaluate the location and activity of inflammatory bowel disease, including disease controls in children. METHODS: Ninety-two ultrasonographic scans and 41 colonoscopic examinations with biopsies were performed in 78 patients (1 month to 17.8 years of age) with Crohn's disease (n = 26), ulcerative colitis (n = 21), inflammatory bowel disease of indeterminate type (n = 2), and disease controls (other intestinal disorders, including infectious and ischemic lesions; n = 29). Laboratory parameters for inflammatory bowel disease were determined, and disease activity was assessed by a combination of clinical and laboratory data. Bowel wall thickness and echo texture were recorded in a standardized way by ultrasonography and compared with endoscopic and histologic findings in a segment-by-segment comparison. RESULTS: Sensitivity and specificity of ultrasonography in detecting patients with severe macroscopic lesions depicted on endoscopy were 77% and 83%, respectively. Sensitivity and specificity of ultrasonography in detecting patients with severe histologic inflammation were 75% and 82%. There was a statistically significant correlation between maximal bowel wall thickness and disease activity score (P < .01). CONCLUSIONS: Abdominal ultrasonography may be helpful in evaluating the location, severity, and inflammatory activity of inflammatory bowel disease in children and young adults.     

Epidemiological survey of coeliac disease and inflammatory bowel disease in first-degree relatives of coeliac patients

One hundred and sixty-two of 182 patients with coeliac disease provided satisfactory details of family size and the prevalence of coeliac disease and inflammatory bowel disease among their first-degree relatives. Patients ranged in age from 11 months to 79 years with a mean age of 41 (+/- 23) years. Twenty patients had at least one first-degree relative with coeliac disease: a total of 25 of 861 relatives were affected (prevalence = 2904/100,000) compared with an expected 0.9 cases (prevalence = 100/100,000; p less than 0.001). Six relatives had inflammatory bowel disease (prevalence = 697/100,000) compared with an expected 1.3 cases (prevalence = 150/100,000; p less than 0.001). Five of these had ulcerative colitis, and one had Crohn's disease. The relative risk of ulcerative colitis is, therefore, five times greater for first-degree relatives of people with coeliac disease than for the general population (95 per cent confidence interval, 4.7-7.2). There is a clear association between coeliac disease and ulcerative colitis, which may point to factors involved in the aetiology of colitis.     

Ultrasound findings in Crohn's disease and ulcerative colitis: a prospective study

In a prospective study, 118 patients with Crohn's disease, 51 patients with ulcerative colitis, and 72 patients with no disease of the intestine proximal to the rectum were evaluated by ultrasound. In Crohn's disease, thickening of the bowel wall and inflammatory masses were detected in 72.0% of the patients. With a transducer having optimal imaging properties in the near range, these findings were detected in 87.2% of a group of 47 patients. In ulcerative colitis, bowel wall thickening was detected in 52.9% of all patients. Thickening of the bowel wall was more marked in Crohn's disease than in ulcerative colitis. Most pathologic findings in Crohn's disease were located in the right lower abdomen, whereas those in ulcerative colitis were in the left abdomen, in particular in the lower quadrant. The frequency of wall thickening was correlated to the activity of the disease in ulcerative colitis but not in Crohn's disease. Considerably increased wall thickness, when localized in the right lower quadrant and found in combination with inflammatory masses or an abscess, suggests Crohn's disease.     

Anti-tissue transglutaminase antibodies in inflammatory bowel disease: new evidence.

Anti-tissue transglutaminase, previously held to be identical to anti-endomysial antibodies in celiac sprue, has been reported in inflammatory bowel disease patients. To investigate these data further, we evaluated serum and intestinal anti-tissue transglutaminase in inflammatory bowel disease patients, with respect to the Crohn's disease activity index and the integrated disease activity index. Study population comprised: 49 patients with Crohn's disease and 29 patients with ulcerative colitis; 45 patients with celiac sprue and 85 autoimmune patients as disease controls; and 58 volunteers as healthy controls. Immunoglobulin A (IgA) anti-recombinant human tissue transglutaminase and anti-endomysial antibody detection in sera and fecal supernatants were performed. Adsorption of positive sera with recombinant human tissue transglutaminase were also performed. Marked increased anti-tissue transglutaminase concentrations were found in celiac sprue, while low-positive values were also found in Crohn's disease and ulcerative colitis. Anti-endomysial antibodies were detectable only in celiac sprue. Antigen adsorption resulted in a significant reduction of the anti-tissue transglutaminase either in celiac sprue or inflammatory bowel disease sera. A significant correlation between anti-tissue transglutaminase and Crohn's disease activity index or integrated disease activity index scores was found. Anti-tissue transglutaminase was also detectable in fecal supernatants from inflammatory bowel disease patients. Data highlight that both circulating and intestinal anti-tissue transglutaminases are detectable in inflammatory bowel disease, and that they are related to disease activity. These features underline that, in addition to anti-tissue transglutaminase, an anti-endomysial antibody test is necessary in the diagnostic work-up of celiac sprue, especially in patients with known inflammatory bowel disease.     

Platelet count, platelet function, coagulation activity and fibrinolysis in the acute phase of inflammatory bowel disease

Twenty two patients with exacerbation of inflammatory bowel disease (19 with Crohn's disease, 3 with ulcerative colitis) and thrombocytosis were tested for possible activation of the coagulation and platelet system. Fifteen patients had abnormal platelet function i.e. unphysiologically high sensitivity in vitro towards ADP 2 mumol/l aggregation induction. In 81.8% of the patients we found enhanced fibrinogen concentrations. In 22.7% of the patients thrombin-antithrombin III values exceeded the upper limit of the reference range, and in 68.2% of the patients the D-Dimer concentration exceeded the upper reference limit as a result of reactive fibrinolysis. The altered platelet count and function, and the increased levels of fibrinogen and thrombin-antithrombin III with reactive fibrinolysis activation indicate the presence of prethrombotic factors in patients with exacerbation of inflammatory bowel disease. The presence of enhanced fibrinolysis in these patients might have consequences for the therapeutic treatment.     

Serum lysozyme, serum proteins, and immunoglobulin determinations in nonspecific inflammatory bowel disease

The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5 +/- 6.8 microgram/ml) and ulcerative colitis (9.6 +/- 4.1 microgram/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0 +/- 1.5 microgram/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of nonspecific inflammatory bowel disease.     

Algorithm of diagnosis and treatment of complicated forms of nonspecific ulcerative colitis and Crohn's disease

AIM: To detect complicated forms of nonspecific ulcerative colitis and Crohn's disease, to calculate treatment algorithm. MATERIAL AND METHODS: The results of a 20-year prospective trial including 313 patients with nonspecific ulcerative colitis (n = 180) and Crohn's disease (n = 133) have been analysed. The following parameters were considered: clinical findings with calculated index of the disease activity, endoscopic, x-ray and morphological data. All the information was processed using computer programs Biostat and Exell 97 Mean and standard deviations were calculated. Chi-square and Fisher's criteria were used. RESULTS: Complicated forms of nonspecific ulcerative colitis and Crohn's disease were detected and characterized. Programs of treatment of complicated forms of intestinal inflammatory diseases and measures for maintenance of the remission are proposed.     

Clinical features, morbidity and mortality of Scottish children with inflammatory bowel disease

From the Scottish Hospitals in-patients statistics for the years 1968-1983 all children and teenagers (a total of 1257) admitted to a National Health Service hospital with Crohn's disease or ulcerative colitis were identified. Case records of samples of patients with onset of symptoms at or before age 16 years were examined to establish the features, morbidity and mortality of unselected cohorts of young patients with inflammatory bowel disease. Median delay in diagnosis was less than six months. Anatomical distribution for Crohn's disease was similar to that in adults (small bowel 30 per cent; large bowel 28 per cent; small and large bowel 38 per cent) and almost half the patients with ulcerative colitis had extensive colitis. The morbidity was substantial in both. In-patient days for Crohn's disease ranged from seven to 322, median 64 days and for ulcerative colitis one to 275, median 30 days. At diagnosis, 11 of 40 young children with Crohn's disease but none of 14 with ulcerative colitis, were below the third centile for height. Despite treatment with corticosteroids 72 per cent of patients with Crohn's disease and 30 per cent of patients with ulcerative colitis required surgical treatment. Seventeen per cent have a permanent stoma. There were only six deaths, all before 1978.     

Analysis of direct tissue isoelectric focused protein profiles of resected intestinal mucosa and endoscopic biopsies from patients with inflammatory bowel disease.

Direct tissue isoelectric focusing was used as a procedure to analyze differences in soluble tissue protein profiles of resected intestinal segments and endoscopic biopsies from patients with ulcerative colitis, Crohn's disease, and colonic cancer. Extraction of tissue proteins was accomplished by electrophoresis of mucosal cryostat sections on agarose gels across a broad pH gradient. The inflamed colonic mucosa from Crohn's disease patients showed similar isoelectric focusing protein patterns. Small bowel mucosa from a patient with both colonic diverticular disease and Crohn's disease showed protein patterns identical with that of the mucosa from a patient with only Crohn's disease. The inflamed mucosae from ulcerative colitis patients revealed identical protein patterns but were distinct from those of non-inflamed ulcerative colitis mucosa and from the inflamed mucosae from Crohn's disease patients. Non-inflamed small bowel mucosae from cancer, ulcerative colitis, and Crohn's disease patients showed distinct protein patterns which were absent in the non-inflamed large bowel mucosae. The inflamed resected ileum of a Crohn's disease patient exhibited protein patterns similar to those of the biopsy of an inflamed mid-transverse large bowel. Mucosal biopsies from inflamed sigmoid colon of a Crohn's disease patient showed different protein patterns than those in biopsies from the inflamed mid-transverse colon. Thus, distinctive isoelectric focusing protein patterns may be useful in differentiating Crohn's colitis and ulcerative colitis when granulomata are absent, and in resolving indeterminant colitis to one of these classic inflammatory bowel diseases.     

Autoimmunity, Inflammatory Bowel Disease and Hyposplenism

The presence or absence of nine autoantibodies were assessedin 44 patients with ulcerative colitis (17 with hyposplenism)and 22 patients with Crohn's disease (eight with hyposplenism).The purpose of the study was to determine whether hyposplenismin inflammatory bowel disease is associated with an increasedtendency to autoimmunity, or whether autoimmunity is linkednot to hyposplenism itself but to the underlying bowel disease.The results strongly suggest that the latter hypothesis is correct.There was a much higher frequency of autoantibodies in patientswith ulcerative colitis than in those with Crohn's disease (P0.01),suggesting that autoimmune factors are more important in thepathogenesis of ulcerative colitis than in Crohn's disease.     

Epidemiological Survey of Coeliac Disease and Inflammatory Bowel Disease in First-Degree Relatives of Coeliac Patients

One hundred and sixty-two of 182 patients with coeliac diseaseprovided satisfactory details of family size and the prevalenceof coeliac disease and inflammatory bowel disease among theirfirst-degree relatives. Patients ranged in age from 11 monthsto 79 years with a mean age of 41 (± 23) years. Twentypatients had at least one first-degree relative with coeliacdisease: a total of 25 of 861 relatives were affected (prevalence=2904/100,000)compared with an expected 0.9 cases (prevalence=100/100,000;p <0.001). Six relatives had inflammatory bowel disease (prevalence=697/100,000)compared with an expected 1.3 cases (prevalence=150/100,000;p <0.001). Five of these had ulcerative colitis, and onehad Crohn's disease. The relative risk of ulcerative colitisis, therefore, five times greater for first-degree relativesof people with coeliac disease than for the general population(95 per cent confidence interval, 4.7–7.2). There is clearassociation between coeliac disease and ulcerative colitis,which may point to factors involved in the aetiology of colitis.