Effect of an elemental diet (Vivonex) on the absorption abnormalities and histological appearances of the jejunum in untreated adult coeliac disease.

The effect of an elemental diet (Vivonex) together with a gluten-free diet on the absorption of water, sodium and chloride in the jejunum was studied in 4 patients with untreated adult coeliac disease before and after a 1-month course of therapy. The morphology of the jejunum was also studied by jejunal biopsy taken at the same time as the intestinal perfusion. The results were compared with those obtained in 4 patients with adult coeliac disease treated with a gluten-free diet alone. No marked improvement was noted in the transportation of water, sodium and chloride after either treatment with Vivonex and a gluten-free diet or after a gluten-free diet alone, and no marked histological changes were found. Clinical improvement occurred in both groups of patients, in that the diarrhoea improved in all patients and they generally felt better. There appears to be no additional advantage of using an elemental diet with a gluten-free diet in the initial management of adult coeliac disease.     

Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.     

Splanchnic haemodynamics in patients with coeliac disease: effects of a gluten-free diet

BACKGROUND: Coeliac disease is characterized by structural and functional changes in the small bowel which may also result in haemodynamic changes. AIMS: To establish whether splanchnic haemodynamics can be modified by a gluten-free diet. PATIENTS: Ten coeliac patients and 10 paired healthy subjects. METHODS: Echo-Doppler measurements were made of splanchnic vessels both fasting and after a standard meal before and after 9 months of a gluten-free diet. RESULTS: In comparison to controls, coeliac patients had higher superior mesenteric artery blood velocity and flow, with lower resistance indexes and higher portal vein velocity and flow, particularly 3 h after a meal. Postprandial hyperaemia was reduced and delayed in time. Intrasplenic resistance indexes were also significantly lower both fasting and after a meal. After 9 months of a gluten-free diet, no significant differences were observed between coeliac patients and controls, both fasting and after a meal. CONCLUSIONS: Splanchnic haemodynamics is significantly changed in coeliac patients, mainly after a meal. On treatment with a gluten-free diet, both fasting and postprandial haemodynamics became normal.     

Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance

An increased incidence of coeliac disease has recently been reported in patients with idiopathic dilated cardiomyopathy. This report deals with three patients with idiopathic dilated cardiomyopathy and coeliac disease who underwent clinical and laboratory evaluation to establish the effect of a gluten-free diet on cardiac performance. Two patients observed the gluten-free diet regimen very strictly, and, after a 28-month follow-up period, showed an improvement in echocardiographic parameters as well as in cardiological features and quality of life, as evaluated by the Minnesota Living with Heart Failure questionnaire and the Gastrointestinal Symptom Rating Scale questionnaire. The third patient did not observe the gluten-free diet and presented a worsening in the echocardiographic parameters and cardiological symptoms which required supplementary drug therapy. These preliminary data appear to suggest that the gluten-free diet may have a beneficial effect on cardiac performance in patients with idiopathic dilated cardiomyopathy.     

Treatment of life-threatening type I refractory coeliac disease with long-term infliximab.

Whereas medical approach to coeliac disease is well defined, treatment of patients who fail to respond to a gluten-free diet remains still problematic. We describe the case of a 68 years DQ-2 positive male who lost response to a strict gluten-free diet after an initial response over a 3-year period. His conditions became critical despite high dose prednisone treatment. After a careful differential diagnosis, the patient was classified as having a type I refractory coeliac disease and a single infusion of infliximab at 5mg/kg was given with excellent clinical results. However, clinical response was lost despite background therapy with azathioprine. Six months after the single infusion an induction therapy with infliximab and, thereafter, maintenance every 8 weeks was administered with excellent clinical results. Since small bowel histology recovered very slowly treatment was continued over the following 2 years with a return to near normal architecture. This case shows that anti-tumour necrosis factor treatment may be used in carefully selected patients with type I refractory coeliac disease.     

Are lower gastrointestinal investigations necessary in patients with coeliac disease?

BACKGROUND: Colonoscopy may be indicated in patients with coeliac disease who present with iron deficiency anaemia or in coeliac disease patients who have persisting diarrhoea despite being on a gluten-free diet. However, there are limited data to support this approach. METHODS: We prospectively recruited patients who were found to have coeliac disease, having been referred with newly diagnosed iron deficiency anaemia. We also recruited a second group of patients with known coeliac disease. These patients had persisting diarrhoea despite being on a gluten-free diet for 6 months. All patients had colonoscopy and were matched with controls (without coeliac disease) who had similar indications for colonoscopy. RESULTS: Ninety-eight consecutive new patients with coeliac disease and concurrent iron deficiency anaemia had colonoscopy performed. Twelve (12.2%) had pathology, three of which were carcinomas. This diagnostic yield was not significantly different from the findings in the control group 62/362 (17.1%) P=0.24. In coeliac disease patients with persisting diarrhoea (n=37), the diagnostic yield at colonoscopy was 1/37 (2.7%). This was significantly lower than our findings in the control group with chronic diarrhoea 55/390 (14%) P=0.05. CONCLUSION: Colonoscopy should be considered in patients with coeliac disease (over the age of 45 years) who present with iron deficiency anaemia. Whilst, for coeliac disease patients with persisting diarrhoea (on a gluten-free diet) in the absence of sinister symptoms, a flexible sigmoidoscopy may be the initial investigation in order to exclude microscopic colitis. However, further larger prospective studies are required to evaluate this approach.     

Is coeliac disease a potentially treatable cause of liver failure?

Hypertransaminasaemia is a common abnormality found in up to 40% of untreated coeliac patients, which resolves with the institution of a gluten-free diet. A much rarer occurrence is the association of chronic liver disease with coeliac disease. Primary biliary cirrhosis, primary sclerosing cholangitis, and chronic autoimmune hepatitis have all been recognized in coeliac patients. More recently, the occurrence of coeliac disease in patients with chronic liver disease is found to be 10 times greater than that in the general population. Of particular note are the 13 patients reported to date with liver failure and coeliac disease. Among those patients commenced on a gluten-free diet an improvement in liver function was observed. The relationship between coeliac disease, a gluten-free diet, and the course of chronic liver disease needs to be clarified.     

Psychoneurotic symptoms and alexithymia in coeliac disease

Objective. Depression, psychological problems and the impairment of quality of life are reported to occur in untreated coeliac disease. Alexithymia (“no words for feelings”) is associated with various gastrointestinal disorders. The aim of this study was to evaluate whether patients with coeliac disease suffer from psychoneurotic symptoms or alexithymia, and whether a gluten-free diet has an impact on the symptoms. Material and methods. The Crown-Crisp Experiential Index (CCEI) and its six subscales were applied to measure neurotic psychopathology, and the 20-item version of the Toronto Alexithymia Scale (TAS-20) and its 3-factor scales to measure alexithymia. The testing was carried out in 20 consecutive adult patients with biopsy-proven coeliac disease before and after one year of treatment on a gluten-free diet. The data were compared with those obtained earlier in non-coeliac Finnish subjects. Results. Somatic anxiety was higher in coeliac disease patients before the introduction of the gluten-free diet than after adhering to the diet. Otherwise, the diet had no significant impact on the CCEI scores. The patients were not suffering from alexithymia, but the TAS-20 score improved significantly during the follow-up. The scores did not differ from those published in the Finnish population. Conclusions. Psychological problems were not common in adult coeliac disease patients. Gluten-free diet had only a minor influence on the symptoms. Common knowledge about coeliac disease and the readily available gluten-free products may have had an impact on these results.     

Effect of gluten-free diet on splenic hypofunction of adult coeliac disease.

Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.     

Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density.

BACKGROUND: Patients with coeliac disease have low bone mineral density (BMD), but the underlying mechanisms are unclear. Our aim was to study circulating insulin-like growth factor I (IGF-I) and its possible relationship to BMD in adults with untreated coeliac disease and after 1 year on a gluten-free diet. METHODS: In 29 consecutive adult coeliac patients fasting IGF-I and BMD (n = 28) were examined before and 1 year after starting a gluten-free diet. Intact parathyroid hormone (PTH) was measured (n = 20) before the gluten-free diet was started. RESULTS: Untreated coeliac patients had lower IGF-I values than controls matched for age and sex, and their BMD was low. A relationship was observed between BMD and IGF-I but not independent of age and body mass index. During the 1st year on a gluten-free diet BMD increased (P < 0.001), as did the circulating IGF-I levels in 21 of the 29 patients (P = 0.078). In the subgroup of 14 patients with normal initial PTH the increase in IGF-I correlated positively with the increase in BMD (femoral trochanter, r = 0.62, P < 0.05, and lumbar spine, r = 0.70, P < 0.02). CONCLUSIONS: BMD and circulating IGF-I levels are low in adults with untreated coeliac disease. In patients with normal initial PTH level there is an association between the change in BMD and circulating IGF-I, although this parallel increase may not be causally connected.     

Infliximab in refractory coeliac disease

Coeliac disease is generally well controlled with gluten-free diet but a small proportion of patients require corticosteroids or immunomodulatory agents. Response to anti-tumour necrosis factor (anti-TNF) agents raises interesting questions about both the pathogenesis of coeliac disease and the mechanism of action of anti-TNF agents. Refractory coeliac disease poses a therapeutic challenge to clinicians and carefully selected patients may benefit from anti-TNF therapy.     

Should we screen reflux oesophagitis patients for coeliac disease?

OBJECTIVES: Oesophagitis and gastro-oesophageal reflux have been implicated recently in the manifestations of coeliac disease. The aim was to investigate this association in a primary-care setting. METHODS: First, the prevalence of coeliac disease was calculated in 1198 adults with oesophagitis, in 2541 adults with reflux symptoms and in 200 adults suffering from dysphagia; 5459 patients with a history consistent with dyspepsia and 709 patients with a suspicion of coeliac disease served as controls. Second, the prevalence of oesophagitis was estimated in 382 untreated and 232 treated coeliac patients; controls here comprised 5404 patients with dyspeptic symptoms and 2525 patients with reflux symptoms. Third, oesophagitis and oesophageal reflux symptoms were investigated before and after a gluten-free diet was followed in 67 adults with coeliac disease. The diagnosis of coeliac disease was based on small-bowel histology; histological exclusion of the disease was unambiguous in all controls. Oesophagitis was identified by endoscopic inspection. RESULTS: Altogether, 0.9% of patients with oesophagitis and 0.6% of those with oesophageal reflux symptoms had coeliac disease. The corresponding percentages were 1.0% in patients with dyspepsia and 12% with suspicion of coeliac disease. The prevalence of oesophagitis was 5.2% in untreated coeliac disease, 5.6% in treated coeliac disease, 7.0% in patients with dyspepsia, and 27% in symptomatic reflux disease. In coeliac patients, the reflux symptoms were mild but nevertheless were alleviated on a gluten-free diet. CONCLUSIONS: This study does not support the conception that patients with reflux oesophagitis should be screened vigorously for coeliac disease. The association between these two conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for reflux symptoms in coeliac disease.     

Coeliac Disease: Histopathological Findings in the Small Intestinal Mucosa Studied by a Peroral Biopsy Technique

Villous atrophy, changes in the surface epithelium, mucosal thickening, and glandular hypertrophy were a feature of all the mucosal biopsies from the small intestine obtained from eight coeliac children. No histological differences were observed between the children previously treated with intermittent gluten-free diets and the untreated children. Serial biopsy studies were carried out on one coeliac child before and after treatment with a gluten-free diet over a period of two years. On the whole they confirmed the irreversible nature of the observed histopathological changes but minor improvements could not be excluded. Mucosal abnormalities in coeliac disease are the same as in adult idiopathic steatorrhoea, where they are observed in patients with or without a response to a gluten-free diet. It is concluded that the elimination of gluten from the diet has little if any influence on the histopathological abnormalities observed in coeliac disease.     

Case-finding in coeliac disease should be intensified

Large-scale screening studies on CD have been published and suggest a prevalence of CD in USA, Europe, Middle-East and Australia of about 1:100. The costs of finding coeliacs hasn't been discussed in these studies. Coeliac disease can be classified to be an important health problem. It might be relevant to have a low threshold for biopsies when screening for coeliac disease. Screening asymptomatics may be harmful for individuals. A lifelong gluten-free diet is not easy to maintain and quality of life may deteriorate. In countries familiar with coeliac disease, the classic pattern of severe malabsorption and cachexia, as described in textbooks, has become rare. CD is not borne in minds of doctors diagnosing dyspepsia and/or irritable bowel disease, or associated auto-immune diseases. The consequence is a delay in diagnosis, with secondary problems as long term auto-immune stimulation, osteoporosis and secondary malignancies. Enteropathy associated T-cell lymphomas are well known, but considering coeliac disease in T-cell lymphomas presenting outside the GE-tract is uncommon. Nation-wide screening programmes have not started, which are common for phenylketonury and other metabolic defects. It is debatable whether coeliacs found by screening adhere to a gluten-free diet similar to symptomatic coeliacs. Whether a gluten-free diet is of benefit to this subgroup is controversial.     

Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience

BACKGROUND: Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common. AIM: To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease. Design and METHODS: Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL). RESULTS: No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease. CONCLUSION: Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2-15 years). A total of 52% of the RCD II patients developed EATL within 4-6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.     

Plasma concentrations of glucagon-like peptide-2 in adult patients with treated and untreated coeliac disease

BACKGROUND: Coeliac disease is a common chronic inflammatory enteropathy characterized by villous atrophy and crypt hyperplasia in the small intestine. The mechanism of the intestinal damage in coeliac disease remains unclear. Glucagon-like peptide (GLP)-2 is an enterotrophic peptide that causes crypt hyperplasia and intestinal cell proliferation. We postulate that GLP-2 may be involved in the mucosal changes found in coeliac disease. OBJECTIVES: To study plasma concentrations of GLP-2 in untreated patients with coeliac disease and determine the response to a gluten-free diet (GFD). METHODS: A 440 kcal gluten-free test meal was given to seven controls and 12 coeliac patients at three time intervals: (1) before commencing a GFD; (2) 3 months after a GFD; and (3) 9 months after a GFD. Serial blood sampling was performed over a 2-h period. Each sample was analysed using radioimmunoassay for GLP-2, GLP-1, N-terminal glucagon (N-glucagon) and C-terminal glucagon (C-glucagon). RESULTS: Untreated coeliac patients had significantly higher basal and peak GLP-2 and N-glucagon plasma concentrations compared with controls. After 3 months on a GFD, there was a significant decrease in basal GLP-2 plasma concentrations. There was no significant difference between GLP-1 or C-glucagon in untreated coeliac patients compared with controls. CONCLUSION: This is the first reported study of GLP-2 in coeliac disease. After a GFD there is recovery of the intestine and a reduction in the GLP-2 trophic response. Our findings support the theory that GLP-2 may be part of the mucosal healing and maintenance mechanisms in coeliac disease.     

Coeliac disease

Increased awareness of non-classical presentations and more reliable screening tests have led to higher detection rates for coeliac disease in elderly adults. Clinical presentations are influenced largely by the long-standing course of the subclinical disease before diagnosis. In the majority of elderly patients, weight loss, diarrhoea and iron deficiency anaemia are present. With a delay in diagnosis, there are increased risks of associated autoimmune diseases, of neoplasms (mostly small bowel lymphoma) and of metabolic bone diseases. Thyroid disease is the most common autoimmune disease. Lymphoma may be the initial presentation or may complicate the clinical course of well established coeliac disease. Osteopenia is very common at presentation, can be clinically severe and require specific therapy in addition to the gluten-free diet. The high risk of complications in elderly patients with coeliac disease warrants a systematic approach in their investigation and management.     

IgA-class transglutaminase antibodies in evaluating the efficacy of gluten-free diet in coeliac disease

OBJECTIVE : Serum IgA-class tissue transglutaminase antibody has proved effective in screening for coeliac disease. The response to a gluten-free diet has been assessed on the basis of small-intestinal morphology. We investigated whether the tissue transglutaminase antibody test could substitute biopsy in this respect, and whether the test is better than the endomysial antibody test in follow-up. DESIGN : Controlled cross sectional, and follow-up study. METHODS : Serum IgA-class tissue transglutaminase antibodies and endomysial antibodies were determined in 87 coeliac adults on a gluten-free diet. All underwent small bowel biopsy, and the mucosal morphology was interpreted along with Marsh's grading 0-3. In 30 patients histological and serological data could be analysed before and after adopting the diet; Marsh 3 was considered inadequate mucosal recovery during the diet. RESULTS : Of the 87 coeliac patients 27 showed Marsh 3 villous atrophy on gluten-free diet; of these 27, tissue transglutaminase antibody was within normal limits in 16 (59%) and endomysial antibody in 20 (74%). Two (7%) out of 29 with normal mucosa (Marsh 0) had positive tissue transglutaminase antibodies. Six (55%) out of 11 admitting regular dietary lapses remained tissue transglutaminase antibody negative. In the follow-up, serum IgA-class tissue transglutaminase antibody was initially positive in 28 (93%) out of 30 untreated patients; even a significant decrease in tissue transglutaminase antibody did not guarantee mucosal recovery. CONCLUSIONS : A substantial number of coeliac patients with negative tissue transglutaminase or endomysial antibodies may still have manifest mucosal villous atrophy. Small bowel biopsy is therefore still necessary to ensure that the gluten-free diet is adequate.     

Adult celiac disease and hepatopathy

A retrospective study was performed in order to evaluate the prevalence of significant hepatic disease in patients with coeliac disease and its outcome after a gluten-free diet. Out of 46 patients with coeliac disease, 28 (60.87%) presented abnormal liver function test. These tests were normal after a gluten-free diet in 20 patients; one patient presented an acute B-virus hepatitis and in the remaining 7 patients a chronic liver disease was diagnosed (2 chronic persistent hepatitis, 1 chronic active hepatitis, 1 steatosis, 2 cirrhosis and 1 primary biliary cirrhosis). In conclusion, the high prevalence of significant hepatic disease in our patients with coeliac disease (15%) suggests an association between both disorders. Gluten-free diet does not modify the course of hepatic disease.     

Is serum citrulline measurement clinically useful in coeliac disease?

Citrulline (CIT), a non-protein amino acid in circulating blood, is almost exclusively contained in the enterocytes of small bowel mucosa and may represent a reliable marker of functioning enterocyte mass. The aim of this study was to evaluate the clinical utility of measuring serum citrulline levels in a group of patients affected by coeliac disease (CD). Fifty healthy volunteers, 21 patients with untreated coeliac disease and 6 patients with refractory coeliac disease took part in the study. Serum citrulline levels and duodenal lesions were evaluated at the time of diagnosis, and after at least 24 months of gluten-free diet. Serum citrulline concentrations were determined by ion exchange chromatography. In comparison to healthy volunteers, serum citrulline concentrations were significantly lower in untreated and refractory coeliac disease patients. No significant difference was found between untreated and refractory coeliac disease patients and between patients with different patterns of clinical presentation or various degrees of duodenal lesions. After a gluten-free diet, the mean of serum citrulline concentration was increased in all but one patient. Although, as expected, serum citrulline levels turned out to be low in coeliac disease, the clinical utility of their measurement is, at least, questionable in this condition.