Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients.

BACKGROUND: Rescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. AIM: To present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12 months. METHODS: In this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5 mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for >12 weeks, corticosteroid treatment for >8 weeks before hospitalisation, previous IFX therapy or Crohn's disease. RESULTS: Probability of colectomy-free survival at 3 months was 0.71 (95% CI, 0.64-0.77), at 12 months 0.64 (95% CI, 0.57-0.70), at 3 years 0.59 (95% CI, 0.52-0.66) and at 5 years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12 months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14 days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12 months. There were three (1.4%) deaths during the first 3 months. CONCLUSIONS: Infliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14 days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.

Increased prevalence of anti-gliadin IgA-antibodies with aberrant duodenal histopathological findings in patients with IgA-nephropathy and related disorders.

BACKGROUND: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce. DESIGN: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients). RESULTS: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönlein's purpura had elevated IgA-antibodies to tissue transglutaminase. Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I) . One patient with chronic glomerulnephritis also had Marsh I. CONCLUSIONS: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.

Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised, double blind, placebo controlled study.

BACKGROUND AND AIMS: Oral aminosalicylates are well established in the treatment of active mild/moderate ulcerative colitis (UC) when the disease is extensive (that is, beyond the splenic flexure). The majority of clinical symptoms relate to disease activity in the distal part of the colon and therefore this study was designed to investigate if adding a mesalazine enema to oral mesalazine has additional benefit for patients with extensive mild/moderate active UC. METHODS: A randomised double blind study was performed in 127 ambulatory patients. All received 4 g/day (twice daily dosing) oral mesalazine for eight weeks. During the initial four weeks, they additionally received an enema at bedtime containing 1 g of mesalazine or placebo. Disease activity was assessed using the ulcerative colitis disease activity index, with clinical and endoscopic signs at four and eight weeks. RESULTS: Remission was obtained in 44% (95% confidence interval (CI) 31%, 58%) of the mesalazine enema group (Me) and in 34% (95% CI 21%, 49%) of the placebo enema group (Pl) at four weeks (p = 0.31) and in 64% (95% CI 50%, 76%) of the Me group versus 43% (95% CI 28%, 58%) of the Pl group at eight weeks (p = 0.03). Improvement was obtained in 89% (95% CI 78%, 96%) of the Me group versus 62% (95% CI 46%, 75%) of the Pl group at four weeks (p = 0.0008) and in 86% (95% CI 75%, 94%) of the Me group versus 68% (95% CI 53%, 81%) of the Pl group at eight weeks (p = 0.026). CONCLUSION: In patients with extensive mild/moderate active UC, the combination therapy is superior to oral therapy. It is safe, well accepted, and may be regarded as firstline treatment.

Antibody levels in adult patients with coeliac disease during gluten-free diet: a rapid initial decrease of clinical importance.

OBJECTIVE: Analysis of antibodies against tissue transglutaminase (tTG) has been shown valuable in the diagnosis of coeliac disease (CD) but how quickly serum titres decrease after introduction of a gluten-free diet (GFD) is not known in adults. CD is a well-recognized disorder amongst the general population and many persons try a GFD for fairly vague symptoms before they seek medical advice. Therefore, it is important to determine the time that the serologic tests remain predictive of the disease after the introduction of a GFD. METHODS: Sera were taken from 22 consecutively biopsy-proven adult patients with CD in connection with the diagnostic biopsy. The patients were followed for 1 year and sera were taken after 1, 3, 6 and 12 months after start of a GFD. Sera were stored at -20 degrees C and analysed for IgA antibodies against gliadin, endomysium and two different commercial tTG assays based on recombinant human tTG (tTGrh) and guinea-pig liver (tTGgp). RESULTS: Twenty patients could be followed during GFD and all antibody titres fell sharply within 1 month after introduction of a GFD and continued to decline during the survey interval. Thirty days after beginning the diet only 58, 84, 74 and 53% of all patients had positive antibody levels of tTGrh, tTGgp, EmA and AGA respectively. CONCLUSIONS: As the antibodies used to confirm the diagnosis of CD fall rapidly and continue to decline following the introduction of a GFD, it is important that health care providers carefully inquire about the possibility of self-prescribed diets before patients sought medical attention.

Intestinal tissue transglutaminase in coeliac disease of children and adults: ultrastructural localization and variation in expression.

BACKGROUND: Tissue transglutaminase is the main antigen for the anti-endomysial antibodies used for diagnosis of coeliac disease and can with some specificity in vitro deamidate gliadins generating potent epitopes. The intestinal levels and the ultrastructural localization of tissue transglutaminase in normal and affected persons were investigated to provide further information on its role in this disease. Intestinal biopsies were taken from normal and coeliac children and adults. METHODS: The level of transglutaminase was analysed by means of a quantitative enzymatic assay and its ultrastructural localization by immunogold electronmicroscopy using a monoclonal antibody against tissue transglutaminase. RESULTS: In relation to normal individuals, the enzymatic activity of tissue transglutaminase in adult coeliac patients was increased. The enzyme was found in the enterocytes and in increased amount just beneath the enterocytes, where cytosolic and nuclear labelling of distinct elongated cells was seen in addition to extracellular labelling close to collagen fibrils. In children, the enzymatic activity and the immunogold labelling could not be shown to be related to disease. In all cases the enzyme activity was EDTA-sensitive. CONCLUSIONS: The increased amount of tissue transglutaminase activity in coeliac adults was shown to be due to the appearance of the enzyme in enterocytes and increased expression in the lamina propria. No evidence was found to support the idea of a changed localization or changed amounts as primary elements in coeliac disease pathogenesis, nor for the involvement of non-calcium dependent microbial transglutaminases.

High rate of gastrointestinal symptoms in celiac patients living on a gluten-free diet: controlled study.

OBJECTIVES: The aim of this study was to determine the occurrence of GI symptoms in adults with celiac disease (CD) treated with a gluten-free diet for several years. METHODS: We studied a cohort of adults with CD (n = 51; 59% women) aged 45-64 yr and proved to be in remission after 8-12 yr of treatment. They were examined by the GI Symptom Rating Scale, which comprises five syndromes: indigestion, diarrhea, constipation, abdominal pain, and reflux. A general population sample (n = 182; 57% women) of same age served as controls. RESULTS: Subjects with CD reported significantly more GI symptoms than the general population sample, as assessed by the GI Symptom Rating Scale total score (p < 0.01). This was particularly true for women with CD who scored worse than female controls for all syndromes on the GI Symptom Rating Scale. By contrast, the men with CD reported no more symptoms than male controls. The women with CD showed generally more complaints than the men with CD did, notably within indigestion, constipation, and abdominal pain, corresponding to a 2-fold higher rate of GI symptoms (60% vs 29%; p < 0.04). CONCLUSIONS: Adult CD patients on a gluten-free diet for several years experienced significantly more GI symptoms than the general population sample. This may have some of its origin in the composition of a gluten-free diet. The symptoms were more pronounced in the women. This may raise questions of an association with their subjective health status, which has been shown to be lower than in men with CD.

Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years.

BACKGROUND: Patients with coeliac disease are advised to keep to a lifelong gluten-free diet to remain well. Uncertainty still exists as to whether this gives a nutritionally balanced diet. AIM: To assess the vitamin nutrition status of a series of coeliac patients living on a gluten-free diet for 10 years. METHODS: Thirty adults with coeliac disease (mean age, 55 years; range, 45-64 years; 60% women), in biopsy-proven remission following 8-12 years of dietary treatment, were studied. We measured the total plasma homocysteine level, a metabolic marker of folate, vitamin B-6 and vitamin B-12 deficiency, and related plasma vitamin levels. The daily vitamin intake level was assessed using a 4-day food record. Normative data were obtained from the general population of the same age. RESULTS: Coeliac patients showed a higher total plasma homocysteine level than the general population, indicative of a poor vitamin status. In accordance, the plasma levels of folate and pyridoxal 5'-phosphate (active form of vitamin B-6) were low in 37% and 20%, respectively, and accounted for 33% of the variation of the total plasma homocysteine level (P < 0.008). The mean daily intakes of folate and vitamin B-12, but not of vitamin B-6, were significantly lower in coeliac patients than in controls. CONCLUSIONS: Half of the adult coeliac patients carefully treated with a gluten-free diet for several years showed signs of a poor vitamin status. This may have clinical implications considering the linkage between vitamin deficiency, elevated total plasma homocysteine levels and cardiovascular disease. The results may suggest that, when following up adults with coeliac disease, the vitamin status should be reviewed.

Living with coeliac disease: controlled study of the burden of illness.

BACKGROUND: Coeliac patients improve vastly when started on a gluten-free diet. After 10 years. however, women show a lower level of subjective health than men do. We investigated whether this could be explained by differences in the perceived disease burden. METHODS: We studied 68 coeliac patients (34 women) (mean age 57 years, range 32-75) and matched type-2 diabetes controls treated for a mean of 10 years. They were examined by a 9-item Burden of Illness (BI) protocol comprising perceived worries, restrictions and subjective outcome. The subjective health was assessed with the Short Form 36 Health Survey (SF-36) questionnaire. RESULTS: The importance of complying with the diet was ranked similarly high by male and female coeliac patients. However, women were less satisfied with the outcome at 10 years than men were, and expressed more concern about the impact on socializing with friends and having to abstain from important things in life. None of these aspects distinguished male and female diabetic patients. Coeliac women showed a higher BI sum score than men did, and this was inversely related to their SF-36 General health, Vitality and Mental Health scores. CONCLUSIONS: Coeliac women adhering to the treatment regimen for several years perceive the disease burden to be worse than men do. In the light of similar differences in their quality of life, inquiry is warranted into the way coeliac men and women are coping with the disorder.

Quality of life of adult coeliac patients treated for 10 years.

BACKGROUND: For patients with coeliac disease, adherence to a gluten-free diet (GFD) is essential to restore the intestinal mucosa. It is less clear whether this ensures well-being of the patient. We have therefore assessed aspects of the quality of life of adult coeliac patients who had been on a GFD for 10 years. METHODS: By means of the Short Form 36 Health Survey (SF-36), the subjective health status was measured in 89 adult coeliac patients (61% women) aged 35-74 years. Patients shown to be in histologic remission (n=60) were evaluated by means of the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: The coeliac patients scored significantly lower in the SF-36 than general population, notably within the General Health and Vitality domains. The low scoring was confined to the female patients, who also reported significantly more gastrointestinal symptoms in the GSRS than the male coeliacs. The functional status and perceived health of the coeliac patients appeared unrelated to their biopsy findings. CONCLUSIONS: After 10 years on a GFD adult coeliac patients fail to attain the same degree of subjective health as the general population. This is particularly true for female patients and suggests that factors beyond normalization of the intestinal mucosa are of importance for the perceived health status of coeliacs diagnosed in adult life.

Adult coeliac disease within a defined geographic area in Sweden. A study of prevalence and associated diseases.

An epidemiologic study of coeliac disease in a geographically defined area of Sweden showed that the prevalence was 95.5/10(5) inhabitants aged 15 years or more. The highest prevalence, 178/10(5) inhabitants, was found in the age group 65-74 years. The lowest prevalence, 39/10(5) inhabitants, was found in patients aged 15-24 years. Among the associated diseases an especially high incidence of associated thyroid disease was observed: thyrotoxicosis occurred in 5.0% and hypothyroidism in 5.8% of the patients.