Magnus Ström

Reversal of osteopenia with diet in adult coeliac disease.

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.

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.

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 find...

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease

Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn’s disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11 450 pmol/8×108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

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.

Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies? 100% positive predictive value for celiac disease in adults.

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.

Clinical trial: colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study

Aliment Pharmacol Ther 2010; 32: 984–989

Bone Mineral Density in Coeliac Disease

Patients with coeliac disease may have osteomalacia or osteoporosis, even in the absence of abdominal symptoms. Little is known about the effects of a gluten-free diet and villous restitution on the bone mineral density in adult patients with coeliac disease. Of the 288 patients with coeliac disease in our unit, 13 (5%) had persistent villous atrophy of the small bowel despite dietary recommendations over at least the previous 4 years. For each of these 13 patients, 1 or 2 controls with coeliac disease, matched for age, gender, menopausal state, and dermatitis herpetiformis, whose intestinal mucosa had normalized at least 4 years earlier, were identified (n = 17). Bone mineral density was measured in the forearm using single-photon absorptiometry and in the femoral neck and trochanter using dual-energy X-ray absorptiometry. Bone mineral density was reduced at all sites in patients with persistent villous atrophy compared with patients responsive to diet and healthy controls. Bone mineral density in patients responsive to diet did not differ from that in healthy controls. Persistent villous atrophy is associated with low bone mineral density, underlining the importance of keeping to a proper diet.

Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome.

BACKGROUND & AIMS Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences. METHODS We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest. RESULTS The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls. CONCLUSIONS Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

Three Years' Follow-up of Bone Density in Adult Coeliac Disease: Significance of Secondary Hyperparathyroidism

BACKGROUND The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. METHODS One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. RESULTS SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. CONCLUSIONS Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.Background: The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. Methods: One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. Results: SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. Conclusions: Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.