Lactose malabsorption in adult patients with Crohn's disease

In order to evaluate, in adult patients with Crohn's disease (CD), the prevalence of lactose malabsorption and intolerance, and the percentage who can tolerate a physiologic amount of milk in their diet, we tested 37 patients with CD (19 with intestinal resection, and 18 without) and 67 healthy controls (C) with the H2-breath test after they had ingested increasing loads of lactose as 10% solution (12.5 g, 25 g, and 50 g). Patients with malabsorption after the 12.5-g dose were tested further with 250 ml of milk. In the total group of patients and in the subgroup of those with resection, the prevalence of malabsorption was higher than in controls at all lactose loads; in patients who had not undergone resection, no significant difference was observed with the 12.5-g dose. Eleven of 18 patients who were malabsorbers with the 12.5-g dose had malabsorption also with 250 ml milk; however, only three of them (8% of the total group) experienced symptoms of intolerance. We conclude that, in adult patients with CD, 1) the prevalence of lactose malabsorption is increased, 2) in patients who have undergone intestinal resection, malabsorption occurs at a lower dose of the sugar than in patients who did not, and 3) since only 8% of patients experienced symptoms of intolerance after the ingestion of milk 250 ml, this amount can be empirically inserted in the daily diet of an adult with CD.     

Incidence and Clinical Significance of Lactose Malabsorption in Adult Coeliac Disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day—statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Incidence and clinical significance of lactose malabsorption in adult coeliac disease

Fifty-one adult patients with coeliac disease, verified by a proximal small-intestinal biopsy, were investigated. Before treatment with a gluten-free and low-lactose diet 52% showed a slight rise in blood glucose during the lactose tolerance test. Seventy-nine per cent of these patients had watery stools, and 88% had three or more bowel movements a day--statistically significantly different from the coeliac patients with a normal lactose tolerance test. After treatment 12% had a flat lactose tolerance curve. Half of them (6%) had specific lactase deficiency. This is approximately the incidence of lactose malabsorption in the general Danish population. The small-intestinal disaccharidases and alkaline phosphatase levels were severely depressed before treatment. After treatment the activities increased, but not to normal. We conclude that lactose malabsorption is a clinically important condition in many patients with untreated coeliac disease, giving rise to more frequent and more watery stools. In well-treated coeliac disease lactose malabsorption is not commoner than in the general population. The lactose activity in a proximal intestinal biopsy specimen was found to be an unreliable indicator of lactose malabsorption in coeliac disease.     

Hydrogen breath test quantification and clinical correlation of lactose malabsorption in adult irritable bowel syndrome and ulcerative colitis

Lactose malabsorption was studied, by hydrogen breath test, in 72 adults suffering from irritable bowel syndrome, in 20 ulcerative colitis patients, and in 69 healthy subjects. The minimum dose of lactose required to cause a positive breath test was determined, and the symptoms caused and the resulting hydrogen eliminated quantified. A high incidence of lactose malabsorption was shown at standard doses (up to 50 g) in both the healthy subjects (70%) and the patients (86% and 85%, respectively). In the irritable bowel syndrome and the ulcerative colitis groups, symptoms occurred with a smaller quantity of breath hydrogen, presumably in association with a greater individual sensitivity of the colon to distension. The threshold lactose dose was notably lower in the diseased subjects who registered as evidence a prevalence of malabsorption at a 20-g lactose load. The pathogenetic role of lactose malabsorption in the irritable bowel syndrome is emphasized, as is the importance of the personal lactose tolerance.     

The incidence of lactose malabsorption in ulcerative colitis.

120 Danish patients with ulcerative colitis, admitted consecutively to a Department of Gastroenterology, were investigated for lactose malabsorption. The prevalence was 9.2 percent, which is not significantly higher than that in a mixed Danish gastroenterological material, There was no difference in distribution according to age and sex, and the incidence was not correlated to the severity of the ulcerative colitis. The possible reasons for the wide variation in the incidence of lactose malabsorption in materials of patients with ulcerative colitis are discussed, and it is concluded that the main cause must be that the materials with the highest incidence include patients of races and ethnic groups in which lactose malabsorption is a common finding.     

Cow''s Milk Protein Sensitivity during Infancy in Patients with Inflammatory Bowel Disease

Seventy-eight patients with inflammatory bowel disease (35 with Crohn's disease and 43 with ulcerative colitis) and a control population of 36 children without organic disease were surveyed to determine the frequency of symptoms compatible with cow's milk-protein sensitivity during infancy. The incidence of a history compatible with cow's milk sensitivity was 8.5% (3/35) in patients with Crohn's disease and 2.8% (1/36) in controls. Patients with ulcerative colitis had a significantly greater prevalence of symptoms, compared with the other patient groups (20.9%, 9/43; p less than 0.03). In addition, patients with a history of cow's milk allergy, who subsequently developed ulcerative colitis, did so at an earlier age (6.68 +/- 2.05 yr vs. 10.62 +/- 0.74 yr: p less than 0.02) than those without a history of cow's milk sensitivity. Thus, there appears to be a potential relationship between early cow's milk sensitivity and the development of ulcerative colitis.     

Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease

AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or Crohn's disease (n=38).METHODS: Clinical remission was defined as a Crohn's Disease Activity Index<150 for Crohn's disease and number of non-bloody stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10 mg/day.RESULTS: Seventy-three per cent of patients with ulcerative colitis had distal or left-sided colitis and 84% of patients with Crohn's disease had pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%) patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease (NS). In patients treated at least 6 months by azathioprine, clinical remission rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS). Complete corticosteroids weaning was obtained significantly more often in ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%; P<0.05).CONCLUSION: Azathioprine seems to be at least as effective and equally tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or Crohn's disease patients.     

Environmental risk factors in Crohn's disease and ulcerative colitis (excluding tobacco and appendicectomy)

A rapid increase in the incidence of Crohn's disease and ulcerative colitis in developed countries, the occurrence of Crohn's disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn's disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.     

Seropositivity in Dutch Crohn's disease patients against primed nude mouse lymph nodes, and the difference with lymphocytotoxic antibodies.

Sera from patients with Crohn's disease have been reported to show positive immunofluorescence with lymph nodes of nude mice primed with a filtrate of intestinal tissue affected with Crohn's disease. An indirect immunofluorescence assay was used to test sera of 63 unrelated patients with Crohn's disease, 21 with ulcerative colitis and 36 control subjects against lymph nodes of athymic nude (nu/nu) mice which had been injected with Crohn's disease and ulcerative colitis intestinal tissue filtrates. Forty nine per cent of Crohn's disease patients, 10% of ulcerative colitis patients and 3% of control sera reacted against lymph nodes of mice injected injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were with intestinal tissue homogenate from Dutch Crohn's patients. With the lymph nodes of mice injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were positive, whereas all ulcerative colitis and control sera were negative. Lymph nodes from 18 of the 19 mice injected with Crohn's disease tissue filtrates reacted with Crohn's disease sera, whereas only three of these 19 mice reacted with ulcerative colitis sera. A comparative study, carried out in parallel with Crohn's disease filtrate induced hyperplastic lymph nodes from the Bilthoven colony (W2) and from the New York colony (E671) using sera from 54 Crohn's disease patients from Leiden, showed immunoreactivity with 44 and 57% of the Crohn's disease sera against the two hyperplastic lymph nodes. Thirty six of the 54 Crohn's disease sera (67%) reacted with either or both lymph nodes. Only 11% of the Crohn's disease sera which were examined for immunofluorescence and lymphocytotoxic antibodies had lymphocytotoxic antibodies, whereas 40% and 46% of the same sera showed positive immunofluorescence against E671 and W2, respectively. Absorption studies indicated that lymphocytotoxic antibodies activity and the immunofluorescence against the primed nude mouse lymph node are mediated by different serum antibodies in Crohn's disease. The reproducibility of the nude mouse immunofluorescence test system for a preferential immunoreactivity of Crohn's disease sera against Crohn's disease tissue primed murine lymph nodes has been confirmed by the present study. Further studies are necessary to find out whether crossreactive antigen(s) as recognised by some of the Crohn's disease sera in mice injected with ulcerative colitis tissue filtrate is similar to the antigen(s) detected by Crohn's disease sera in mice injected with Crohn's disease tissue filtrates.     

Lactose Malabsorption in Patients Operated Upon for Peptic Ulcer

A lactose tolerance test was performed and small intestinal mucosal disaccharidase activity was determined in 12 patients operated upon for peptic ulcer who had lactose malabsorption. Most patients were misjudged, since they were considered to suffer from post-operative complaints (vagotomy diarrhoea, afferent loop syndrome, recurrent ulcer and dumping). Three patients did not develop symptoms of milk intolerance until immediately after an operation for peptic ulcer; in 3 other patients this operation exacerbated the existing symptoms after consumption of milk. Two patients had steatorrhoea, which disappeared or diminished when lactose excluded from the diet.     

Cellular immune reactions against common antigen, small intestine, and colon antigen in patients with Crohn's disease, ulcerative colitis, and cirrhosis of the liver.

Patients with ulcerative colitis showed in 71-93%, patients with cirrhosis of the liver in 64-91%, cellular immunity against Common Antigen (CA) and human fetal intestinal antigens as measured by the leucocyte migration test (LMIT). Patients with Crohn's disease exhibited cellular immune reactions to a lesser degree - from these only patients without immunosuppressive therapy differed significantly from normal controls (p less than 0.05). Approximately 30% of patients with Crohn's disease and ulcerative colitis had elevated antibody titers against intestinal antigens and CA. A high percentage of patients in both diseases showed a reciprocal relationship between cellular and humoral immunity. It was concluded that Crohn's disease and ulcerative colitis can be separated in most cases using intestinal antigens and CA in the LMIT. The occurrence of cellular immunity against these antigens cannot be interpreted as being the only pathogenetic principle in these two diseases. It is also concluded that there appears to be only a weak immune tolerance against intestinal antigens. The high percentage of cellular immune reactions in patients with cirrhosis of the liver demonstrates that this group may have an impairment of the physiological elimination of antigens by the liver.     

Intestinal perforation during simultaneous lactose tolerance test and motility investigation

Summary A case of intestinal perforation, in a patient without lactose malabsorption but with Crohn's disease in the terminal ileum, which occurred during simultaneous lactose tolerance test and investigation of intestinal tract motility by use of a radio pill is reported. The mechanism is assumed to be the intestinal motility accentuated by the lactose administration in spite of normal absorption of lactose, so that the radio pill was ejected through the intestinal wall proximal to the affected segment.     

Disodium cromoglycate in the treatment of ulcerative colitis and Crohn''s disease

A controlled clinical study on disodium cromoglycate (DSCG) at a dose of 800 mg per day versus placebo was carried out in 141 patients with ulcerative colitis and 25 patients with Crohn's disease. Those of the ulcerative colitis patients who had been on sulphasalazine treatment continued that treatment during the trial (101 patients). Forty patients were intolerant of sulphasalazine. No patient received steroids during the last month before the study. Patients with Crohn's disease had their possible sulphasalazine treatment stopped before the trial. No beneficial effect of DSCG as compared with placebo was found, as the DSCG and the placebo group showed the same number of relapses in patients with a clinically inactive ulcerative colitis at the start of the trial and the same number of patients improving, deteriorating, and maintaining steady state in patients with clinically active ulcerative colitis at the start of the trial. There was no difference between relapse rate in DSCG and placebo groups in patients with Crohn's disease. No correlation between the eosinophil count in rectal mucosa and the outcome of the attack of ulcerative colitis could be demonstrated.     

Lactose intolerance in Jewish patients with ulcerative colitis

Seventy patients with ulcerative colitis had lactose tolerance tests. Of 51 non-Jewish patients, 12 (23.5%) had lactose intolerance, whereas of 19 Jewish patients, 16 (84.2%) had lactose intolerance. This difference is significant (P<0.001). The control group of 41 Jews without ulcerative colitis had a 71% incidence of lactose intolerance, whereas of 53 non-Jewish controls, only 20.7% had such intolerance. These results are also statistically valid (P<0.001). This suggested that segregation of the genes for ulcerative colitis as well as for lactase deficiency in Jews is a possible reason for the high incidence of lactase deficiency found in patients with ulcerative colitis.Supported by a grant from The Hartford Foundation.     

The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden

Previous population-based incidence studies of inflammatory bowel disease are limited by small numbers, short duration, or inadequate case-finding. To address these problems, we identified all persons with confirmed ulcerative colitis (n = 2509) or Crohn's disease (n = 1469) in the Uppsala Health Care Region from 1965 to 1983. Age-specific incidence rates by sex were slightly greater for males with ulcerative colitis and females with Crohn's disease. Incidence rates for ulcerative colitis and Crohn's disease were higher in urban than rural areas. The annual incidence rate of ulcerative colitis increased from less than 7 per 100,000 to more than 12 per 100,000 during the study period, while the rate for Crohn's disease remained between 5 and 7 per 100,000. The increase in the incidence of ulcerative colitis was the result of a marked increase in the number of patients with ulcerative proctitis. Analyses by 5-year birth cohorts suggest that those born from 1945 through 1954 were at higher risk for ulcerative colitis and Crohn's disease, and that this effect was accounted for by those born in the first half of the year. The seasonality in the cohort effect, combined with the urban preponderance of disease, suggests that environmental causes may be involved in ulcerative colitis and Crohn's disease.     

Epidemiological aspects of inflammatory bowel disease in the Pamplona area.

OBJECTIVES: to analyze retrospectively our hospital records on patients diagnosed during the period from 1983 to 1993 as having Crohn's disease or ulcerative colitis, and to estimate the incidence and epidemiological characteristics of these diseases in the Pamplona health administration area. METHODS: 246 patients were diagnosed has having inflammatory bowel disease (147 with ulcerative colitis, 97 with Crohn's disease, and 2 with indeterminate colitis. RESULTS: mean incidence was 2.47 +/- 0.96 per 100 000 inhabitants for Crohn's disease, and 3.75 +/- 1.5 per 100 000 inhabitants for ulcerative colitis (p < 0.05). There was a nonsignificant increase in incidence during the study period. Age, sex, alcohol intake, smoking habit and familial aggregation were analyzed. CONCLUSIONS: mean estimated incidence of Crohn's disease and ulcerative colitis in our setting during 1983-1993 was similar to that reported more recently for other parts of Spain. In our setting, ulcerative colitis was significantly more frequent that Crohn's disease, and familial aggregation was lower among patients who had the former disease. Crohn's disease was diagnosed at earlier ages, and cigarette smoking was more frequent among patients with this disease.     

Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

BACKGROUND/AIMS: Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. METHODS: Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. RESULTS: Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. CONCLUSIONS: Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.     

Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD

Current smoking increases the risk of developing Crohn's disease and worsens its course, increasing the need for steroids, immunosuppressants, and re-operations. On the contrary, smoking protects against ulcerative colitis and after disease onset improves its course, decreasing the need for colectomy. Smoking cessation improves Crohn's disease and worsens ulcerative colitis. Achieving smoking cessation in Crohn's disease is thus an important goal of therapy, whereas patients with ulcerative colitis should not be discouraged to quit, because the beneficial effect of smoking for their disease is counterbalanced by the deleterious respiratory and cardiovascular effects of tobacco. Physical activity improves quality of life without detrimental effect on disease activity, and may contribute to increase muscle mass and to prevent osteoporosis. Regarding nutrition, a Western diet may be associated with an increased risk of IBD, and a case-control study revealed an increased consumption of linoleic acid before diagnosis of ulcerative colitis. Liquid diets may improve Crohn's disease flares and decrease the need for steroids; however, there are no defined diets able to improve the disease course, and in Crohn's disease, supplementation with omega-3 fatty acids did not show a significant benefit. Obesity is becoming more prevalent in IBD and may be associated with higher disease activity. In total, adhering to four simple lifestyle factors - never smoking, physical activity, prudent diet and body mass index <25 - may have a strong impact both on the prevention of major chronic diseases and on the course of IBD.     

Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease

BACKGROUND: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. METHODS AND RESULTS: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. CONCLUSIONS: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.