Selective immunoglobulin a deficiency, ulcerative colitis, and gluten-sensitive enteropathy--a unique association.

A patient with selective immunoglobulin A deficiency, severe ulcerative colitis, and malabsorption had a flat jejunal mucosa demonstrated by peroral biopsy. Treatment at different times with a gluten-free diet for the jejunal lesion and corticosteroids for the ulcerative colitis, led to improvement of the malabsorption. A repeat jejunal biopsy demonstrated histological improvement of the jejunal mucosa, even though the colitis remained active. The occurrence of immunoglobulin A deficiency in a patient with ulcerative colitis and gluten-sensitive enteropathy is uncommon.     

Acute cryptogenic liver failure in an untreated coeliac patient: a case report

Coeliac disease is an autoimmune enteropathy triggered by the ingestion of gluten in susceptible individuals. The clinical presentation of coeliac disease is variable and several extra-intestinal manifestations, as well as an association with autoimmune diseases, have been described. In particular, there are many links between liver disease and coeliac disease. Here we report the case of a young Caucasian woman with acute liver failure, selected as a possible candidate for liver transplantation. Investigation of the patient led to the diagnosis of coeliac disease. A gluten-free diet led to the reversal of the severe liver failure, without the necessity for any surgical or medical treatment.     

Supposed coeliac disease during childhood and its presentation 14-38 years later

Thirty-five subjects treated with a gluten-free diet for a chronic gastrointestinal disorder (no biopsy performed) in early childhood were re-examined 14-38 (median, 28) years later. Twenty-one accepted jejunal biopsy at re-examination. None of those studied were on a gluten-free diet at the time of the study. Ten of 21 biopsy specimens were abnormal--6 with flat mucosa and very low disaccharidase levels, indicating coeliac disease, and 4 with low disaccharidase activity but morphologically normal mucosa. Three of the six subjects with flat mucosa showed a slight fat and lactose malabsorption, but their clinical condition did not suggest serious intestinal disease. Ingestion of gluten throughout most of childhood did not appear to affect growth, as evaluated by final height. Jejunal biopsy is recommended in all patients with gastrointestinal symptoms that are not otherwise explainable if their medical history shows a period of gluten-free diet for a chronic gastrointestinal disorder in childhood.     

Nutritional consequences of celiac disease and the gluten-free diet

Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals and represents a major health issue. The immune mediated response results in villous atrophy of the small intestine with subsequent malabsorption. The classic mode of presentation is that of a malabsorption syndrome resulting in deficiencies of macro and micronutrients. The gluten-free diet is the only treatment currently available for this disorder. The aim of this special report is to elucidate and explain the various nutritional deficiencies seen in newly diagnosed patients with celiac disease and while on the gluten-free diet. Though initiation of the gluten-free diet results in improvement of symptoms and most deficiencies, certain nutritional limitations are associated with the gluten-free diet.     

Successful infliximab treatment for steroid-refractory celiac disease: a case report

Celiac disease is a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. The majority of patients responds to a gluten-free diet but a small number do not. After the exclusion of gluten in the diet, ulcerative jejunititis, and an enteropathy-associated T-cell lymphoma, another treatment modalities, such as systemic steroids and immunosuppressives, may be necessary. This article reports the case of a 47-year-old white woman with immunoglobulin A deficiency. She was diagnosed with celiac disease with subtotal villous atrophy on jejunal biopsy together with positive antiendomysium and antigliadin immunoglobulin G antibodies. Despite close adherence to a gluten-free diet, her weight continued to decrease, she had diarrhea, and her distal duodenal histology showed no improvement. Some improvement in her symptoms was observed with cyclosporine and systemic steroids, but this was not sustained. Recent evidence has suggested that anti-tumor necrosis factor alpha antibodies have a role in the amelioration of an animal model of villous atrophy, and after careful consideration, she was treated with infliximab. There was a dramatic improvement in her weight, symptoms, and distal duodenal histology. The response has been maintained for 18 months while on azathioprine therapy. It is concluded that infliximab is an effective treatment that may be considered in a small number of patients with refractory celiac disease, resistant to other therapy.     

Discordance for childhood coeliac disease in monozygotic twins

Discordance for childhood coeliac disease in monozygotic twin boys is reported. The diagnosis of coeliac disease in the second-born twin was established by demonstration of a flat small intestinal mucosa on biopsy and a clinical response to a gluten-free diet. The first-born twin had a normal small intestinal mucosa. Phenotypic, genotypic, and dermatoglyphic observations as well as gross observation of the placenta and membranes provided strong evidence that these twin boys were monozygotic.     

Frontal cortical perfusion abnormalities related to gluten intake and associated autoimmune disease in adult coeliac disease: Tc-ECD brain SPECT study

OBJECTIVE: Since brain perfusion abnormalities have been described by single-photon emission computed tomography in some autoimmune diseases, the aim of the present study was to evaluate the incidence of perfusion abnormalities by brain single-photon emission computed tomography in a group of coeliac disease patients, and to investigate whether gluten intake and associated autoimmune diseases may be considered risk factors in causing cerebral impairment. METHODS: Thirty-four adult coeliac patients (16 on a gluten-free diet and 18 on a gluten-containing diet, 18 (53%) with autoimmune diseases) underwent 99mTc-ethyl cysteinate dimer brain single-photon emission computed tomography and qualitative evaluation of brain perfusion was performed together with a semiquantitative estimation using the asymmetry index. Ten subjects on our database, matched for sex, age and ethnic group, who were proved normal by histology ofjejunal mucosa (four males and six females; median age 39 years, range 27-55 years), were included as control group. RESULTS: Twenty-four out of 34 patients (71%) showed brain single-photon emission computed tomography abnormalities confirmed by abnormal regional asymmetry index (>5%; range 5.8-18.5%). Topographic comparison of the brain areas showed that the more significant abnormalities were localised in frontal regions, and were significantly different from controls only in coeliac disease patients on unrestricted diet. The prevalence of single-photon emission computed tomography abnormalities was similar in coeliac disease patients with (74%) and without (69%) associated autoimmune disease. CONCLUSIONS: Abnormalities of brain perfusion seem common in coeliac disease. This phenomenon is similar to that previously described in other autoimmune diseases, but does not appear to be related to associated autoimmunity and, at least in the frontal region, may be improved by a gluten-free diet.     

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.     

Maladie cæliaque associée à un granulome sarcoïdosique cutané

Coeliac disease associated with cutaneous sarcoidosis granuloma.Coeliac disease can be associated with numerous internal, skin and mucosa involvments: their physiopathology is often obscure. We report the case of a 14-year old female patient who suffered from a coeliac disease diagnosed in 1988 with considerable improvement with a gluten-free diet. Her two daughters also presented coeliac disease and her sister suffered from nevoid basal cell carcinoma syndrome. Four years later, she presented non pruriginous small nodules over both lower extremities. Skin biopsy revealed a non-caseating granuloma into the derm: we only could evocate sarcoidosis affecting the skin. The dermatological lesions improved during the following weeks with a gluten free diet and relapsed each time this diet was stopped. Many clinical associations with coeliac disease have been described with numerous visceral and skin-mucosa involvments. Eight cases of coeliac disease associated with sarcoidosis affecting the lung have been reported: in five cases, coeliac disease preceded sarcoidosis and in one case sarcoidosis relapsed each time gluten was reinlroduced like in our case. This two diseases seem to share immunological and genetic disturbances.     

Prevalence and clinical relevance of enteropathy associated with systemic autoimmune diseases

ObjectiveTo assess whether systemic autoimmune diseases are a risk group for coeliac disease and if there is a systemic autoimmune diseases-associated enteropathy.Methods183 patients with systemic autoimmune diseases were included. Duodenal biopsy was carried out on patients with positive coeliac genetics (HLA-DQ2-DQ8) and/or serology and/or symptoms of the coeliac disease spectrum. When enteropathy was found, causes, including gluten sensitivity, were investigated and categorized according to a sequentially applied treatment. Results were analysed with Chi-square or Fisher exact tests.ResultsThe prevalence of coeliac disease with atrophy was 0.55% (1 of 183 patients). Thirty-eight of the 109 patients (34.8%) who underwent duodenal biopsy had lymphocytic enteropathy (8 infectious, 5 due to gluten sensitive enteropathy, 5 HLA-DQ2/DQ8 who did not accept gluten-free diet and 20 of unknown aetiology). Lymphocytic enteropathy was unrelated to disease activity or immunosuppressants. HLA-DQ2 was more frequent in connective tissue disease (41.5%) compared with systemic vasculitis and autoinflammatory diseases (17.9%) (p = 0.02), whereas a lower percentage of lymphocytic enteropathy was observed in the former (20.2% vs. 41.6%). Lymphocytic enteropathy was clinically irrelevant in cases with no definite aetiology.DiscussionOne third of systemic autoimmune diseases patients had enteropathy of uncertain clinical meaning in the majority of cases, which was rarely due to gluten sensitive enteropathy.     

Sorbitol H2-breath test versus anti-endomysium antibodies to assess histological recovery after gluten-free diet in coeliac disease.

Background. Gluten-free diet plays a key role in treatment of coeliac disease, but it is difficult to evaluate its effect on improvement of villous architecture using sensitive non-invasive tests.

Aims. To compare sorbitol H₂-Breath Test with antiendomysial antibodies in the follow-up of coeliac disease to detect histological recovery.

Methods. A total of 38 consecutive patients with coeliac disease were studied. All underwent Sorbitol H₂-Breath Test, antiendomysial and oesophagogastroduodenoscopy with multiple bioptic samples before diet and then 6, 12 and 18 months after gluten-free diet. Expiratory samples were collected before patients drank the test solution (5 g sorbitol in 150 ml tap water) and thereafter every 30 min for 4 hours. An increase in H₂ concentration of ≥20 ppm, above fasting baseline was considered positive for sorbitol malabsorption. Antiendomysial antibodies were evaluated by the indirect immunofluorescent method.

Results. Antiendomysial antibodies were positive in 32/38 patients before gluten-free diet (84.21%), while they were positive in 20/34 (54.82%), 2/16 (12.5916) and 0/2 (0%) cases after 6, 12 and 18 months of gluten-free diet, respectively, no correlation being found with improvement of histological lesions (p=ns). As far as concerns sorbitol H₂-Breath Test, maximal cut-off value (in ppm) decreased progressively and parallel to histological recovery during follow-up. Indeed, it decreased from a mean 63 ppm before diet to 35, 19 and 12 ppm, after 6, 12 and 18 months of gluten-free diet, with a statistical difference being found before and after [p<0.001]. Likewise, the peak value (in minutes) appeared progressively later during follow-up, parallel to histological recovery. In fact, it appeared at a mean of 119 minutes before gluten-free diet, while it appears at a mean of 164, 195 and 219 minutes after 6, 12 and 18 months on glutenfree diet. A statistical difference before and after start of gluten-free diet was found also in this case (p<0.001). Conclusions. Sorbitol H2-Breath Test is better than antiendomysial antibodies in revealing histological recovery in the follow-up of coeliac patients after the start of gluten-free diet due to its good correlation with histological damage. Moreover, it also appears to be able to detect dietary mistakes of the patients on gluten-free diet.     

Transient paraproteinaemia in a patient with coeliac disease.

A case is reported of a 43 year old man who suffered from a grass pollen allergy and a malabsorption syndrome and in whom a paraproteinaemia was found. The grass pollen hypersensitivity was abolished by desensitization. The malabsorption syndrome was found to be due to coeliac disease--that is, a "flat" mucosa of the jejunum with an almost normal ileal mucosa--followed by clinical recovery and morphological improvement on a gluten-free diet. A short period of gluten reintroduction caused deterioration of the jejunum. The monoclonal immunoglobulin (IgG-gamma) diminished and disappeared in the course of three years. Although it has not been possible to demonstrate that this paraprotein had anti-gliadin activity, it is suggested that the constant stimulation of the gut reticuloendothelial system by gluten might bear some relation to the appearance of the paraproteinaemia.     

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.     

A case of small-intestinal mucosal atrophy

A patient is described with a severe malabsorption syndrome which failed to respond to a gluten-free diet. Although subtotal villous atrophy was present in the jejunal mucosa, histological features of subepithelial fibrosis and apparently normal enterocytes were not suggestive of coeliac disease. The findings of decreased mucosal thickness, of a normal mitotic rate in the crypt cell population, and of the decreased rate of loss of epithelial cells further suggested that the disease process producing the `flat' mucosa was not that of coeliac disease.

The condition was complicated by ileal ulceration and active tuberculosis.

     

Celiac disease in adults: clinical aspects--role of endoscopy]

Adult coeliac disease has a broad clinical spectrum and remains undetected for years. Among subclinical deficiency states, attributable to coeliac enteropathy, combined iron and folic acid malabsorption is predominant. An unexplained recurrent iron anaemia is an indication for small intestinal biopsy. Gastro-intestinal disorders are present in only 50% of the cases. Coeliac disease is frequently associated with other major histocompatibility complex (MMC)-linked diseases which are mediated by immunological mechanisms: dermatitis herpetiformis, oral ulcerations, IgA nephropathy, rheumatoid arthritis, sarcoidosis. Dermatitis herpetiformis is a useful model for examination of the spectrum of mucosal changes that typify gluten sensitivity and subliminal lesions without villous atrophy. An increased interest is devoted to the intra-epithelial T-lymphocyte population, not only in the small intestine, but at the level of the stomach and the colon. A "rectal challenge" test has been proposed for detecting gluten sensitivity in coeliac patients. Such a test could be an original method of screening, reducing so the need of small intestinal biopsy. The preliminary results are to be confirmed. Until now, jejunoscopy remains mandatory for the diagnosis and the survey of intestinal lesions related to 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.     

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.     

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.