Coeliac disease and hereditary haemochromatosis: association and implications

Coeliac disease and hereditary haemochromatosis are genetic disorders paradoxically associated with altered intestinal absorption of iron. Hereditary haemochromatosis is the most common autosomal recessive disease in the Caucasian population and is characterised by an iron overload state. Coeliac disease, or gluten sensitive enteropathy, on the other hand is frequently associated with iron deficiency anaemia. We report the cases of two patients who developed both coeliac disease and hereditary haemochromatosis. We review the literature of this rare association and examine how the clinical presentation is modified by their co-existence and the potential genetic linkage of these two disorders.     

First-degree Relatives Are Frequently Affected in Coeliac Disease and Dermatitis Herpetiformis

Background: Coeliac disease and dermatitis herpetiformis are phenotypically distinct gluten-sensitive diseases. Coeliac disease is known to cluster in families, whereas there is little evidence for dermatitis herpetiformis and for the occurrence of both diseases in the same families. Methods: The study group comprised 380 patients with coeliac disease and 281 patients with dermatitis herpetiformis, with a total of 3158 first-degree relatives, followed up for a mean of 14 years. The patients were questioned about affected first-degree relatives. The prevalence and incidence of biopsy-proven coeliac disease and dermatitis herpetiformis in relatives were determined. Results: Seventy-three (19.2%) patients with coeliac disease and 51 (18.1%) with dermatitis herpetiformis had affected first-degree relatives. The prevalence among relatives was similar for both diseases; 4.7% and 3.9% of the relatives had coeliac disease and 0.8% and 1.5% had dermatitis herpetiformis, respectively. The disease prevalence was 7% among siblings, 4.5% among parents and 3.5% among children. The annual incidence was 3/1000 relatives, which is 15 times higher than among the general population. Coeliac disease and dermatitis herpetiformis were mixed in several multiple-case families. Conclusions: The present long-term follow-up study of coeliac disease and dermatitis herpetiformis shows that every fifth patient can have affected first-degree relatives, and that the prevalence among relatives is 5.5%. Dermatitis herpetiformis segregates also in the families of patients with coeliac disease, and vice versa, indicating the same genetic background.     

First-degree relatives are frequently affected in coeliac disease and dermatitis herpetiformis

BACKGROUND: Coeliac disease and dermatitis herpetiformis are phenotypically distinct gluten-sensitive diseases. Coeliac disease is known to cluster in families, whereas there is little evidence for dermatitis herpetiformis and for the occurrence of both diseases in the same families. METHODS: The study group comprised 380 patients with coeliac disease and 281 patients with dermatitis herpetiformis, with a total of 3158 first-degree relatives, followed up for a mean of 14 years. The patients were questioned about affected first-degree relatives. The prevalence and incidence of biopsy-proven coeliac disease and dermatitis herpetiformis in relatives were determined. RESULTS: Seventy-three (19.2%) patients with coeliac disease and 51 (18.1%) with dermatitis herpetiformis had affected first-degree relatives. The prevalence among relatives was similar for both diseases; 4.7% and 3.9% of the relatives had coeliac disease and 0.8% and 1.5% had dermatitis herpetiformis, respectively. The disease prevalence was 7% among siblings, 4.5% among parents and 3.5% among children. The annual incidence was 3/1,000 relatives, which is 15 times higher than among the general population. Coeliac disease and dermatitis herpetiformis were mixed in several multiple-case families. CONCLUSIONS: The present long-term follow-up study of coeliac disease and dermatitis herpetiformis shows that every fifth patient can have affected first-degree relatives, and that the prevalence among relatives is 5.5%. Dermatitis herpetiformis segregates also in the families of patients with coeliac disease, and vice versa, indicating the same genetic background.     

Does coeliac disease affect colorectal practice?

Introduction Screening studies of healthy volunteers have determined that coeliac disease affects 1% of the adult European population. Despite this, the majority of cases are unrecognised. Coeliac disease often presents in adults with non-specific gastrointestinal symptoms. This may suggest that unrecognised cases are being seen in colorectal clinics with vague gastrointestinal symptoms, iron deficiency anaemia or irritable bowel syndrome. In addition, cases of coeliac disease may also be presenting as an emergency admission with non-specific abdominal pain. Objective This review provides an update of the published data on case finding for coeliac disease, with the aim of improving the recognition of this disease in clinical practice. The authors of this review have no conflict of interests in presenting this paper. None of the authors have any interest or financial benefits from promoting the application of the commercial tests mentioned in this article. Dr. DS Sanders is an associate medical advisor for Coeliac UK (National Medical Charity). This is an honorary post with no financial benefits.     

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.     

Coeliac Disease: Frequent Occurrence After Clinical Onset of Insulin-dependent Diabetes Mellitus

Coeliac disease was searched for in a series of 776 children with newly diagnosed IDDM. During the follow-up of 2 to 3 years from diagnosis, reticulin and gliadin antibodies were measured, and a jejunal biopsy was performed in those cases with high levels of antibodies; 19 children were identified with coeliac disease, giving the prevalence of 2.4 %. In only one case had coeliac disease been diagnosed before IDDM. Nine patients with proven coeliac disease were negative for antibodies when IDDM was diagnosed, but became positive within 24 months. All patients found to have coeliac disease were positive for IgA reticulin antibodies, but only 12 of 18 (67 %) showed a high level of IgA gliadin antibodies. Of the 18 patients genotyped for HLA DR locus, 14 (78 %) were positive for DR3 and 10 (56 %) were positive for DR4. DQB1*0201 allele was present in 17 of 18 patients (94 %). Coeliac disease in children with IDDM tends to develop soon after diabetes is diagnosed. Routine screening for coeliac disease is recommended repeatedly during the first years after the diagnosis of IDDM.     

Refractory coeliac disease: remission with infliximab and immunomodulators

Coeliac disease is a T-cell-mediated enteropathy induced by gluten. A minority of patients who fail to respond to a gluten-free diet may require intervention with immunomodulating drugs. We report a case of refractory coeliac disease where remission was induced by the anti-tumour necrosis factor-alpha antibody infliximab and was maintained with prednisolone and azathioprine.     

Small bowel adenocarcinoma as first presentation of coeliac disease

Coeliac disease is a chronic inflammatory disease of the gut with increased risk of gastrointestinal malignancy. Although enteropathy T-cell lymphoma is the most common neoplasm in coeliacs, an increased frequency of small bowel carcinoma has been described. A case is described of jejunal carcinoma as first presentation of coeliac disease, in which gastrointestinal and extraintestinal symptoms of disease developed only after surgical resection and disappeared after gluten withdrawal.     

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.     

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.     

Liver involvement in coeliac disease]

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.     

Coeliac disease and diabetes

Coeliac disease is associated with type 1 diabetes mellitus more than ten times more frequently than it is present in nondiabetic population. It often exists with minimal signs or without them. It may cause different complications if it would remain without treatment. Active screening of coeliac disease and similarly of autoimmune thyreopathy is therefore an integral part of examination in type 1 diabetic patients.     

Osteitis fibrosa cystica, coeliac disease and Turner syndrome. A case report.

Today, osteitis fibrosa cystica is seldom present in primary hyperparathyroidism while it is mainly observed in uraemic osteodystrophy. We describe the case of a 54-year-old woman who was found to have huge bone cysts due to osteitis fibrosa cystica in the long bones. A parathyroid adenoma was identified and removed. Coeliac disease and Turner syndrome were diagnosed. Metabolic bone disease due to secondary hyperparathyroidism is common in coeliac disease; however, osteitis fibrosa cystica has not yet been described.     

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet

BACKGROUND: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. Aim: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. PATIENTS AND METHODS: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher's exact test. RESULTS: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8-25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5-11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13-42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2-86.2%) non-coeliac subjects with oesophagitis. CONCLUSION: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.     

OLIGOARTHRITIS-A PRESENTING FEATURE OF OCCULT COELIAC DISEASE

Seven cases of arthritis related to coeliac disease have beendescribed in the English literature, all with features of malabsorption.We describe a patient with an acute inflammatory oligoarthritisand little evidence of intestinal malabsorption who was subsequentlyfound to have asymptomatic coeliac disease on intestinal biopsy.His arthritis responded to gluten free diet and is now in remission.A greater awareness of the association between coeliac diseaseand arthritis is needed, especially because both these conditionsare potentially curable. KEY WORDS: Coeliac disease, Malabsorption, Inflammatory oligoarthritis     

Coeliac disease--has the time come for routine mass screening? In 2002--2010--2020?

It might be clinically relevant to have a very low threshold when screening for coeliac disease. The question is how low? In countries familiar with coeliac disease, the classic pattern of severe malabsorption and cachexia, as described in textbooks, has become rare. Coeliac disease is not born in the minds of doctors diagnosing dyspepsia and/or irritable bowel syndrome, or associated auto-immune diseases, such as thyroid, diabetes mellitus type I, Sj?gren's disease etc. The consequence is a delay in diagnosis, with secondary problems as long term autoimmune stimulation, osteoporosis and secondary malignancies. Enteropathy associated T-cell lymphomas are well known, but considering coeliac disease in T-cell lymphomas outside the gastrointestinal tract is not yet common sense. Large-scale screening studies on coeliac disease have been published and suggest a prevalence of coeliac disease in USA, Europe, Middle-East and Australia of about 1:200. Coeliac disease can be classified due to all these studies as an important health problem. However nation-wide screening programmes have not started yet, which are common for phenylketonuria and other metabolic defects. Probably they will be initiated as pilot-studies in national programmes within 10 years at the age of 2, and due to the bimodal distribution in CD with a later peak in the fourth decade, at 40 years. Additional data about cohorts of certain age groups are mandatory (f.i. 40 and/or 60 years), while initial discussions begin with national health authorities.     

Diagnostic methods beyond conventional histology in coeliac disease diagnosis

BackgroundCoeliac disease diagnostic criteria currently require the detection of small bowel mucosal villous atrophy and crypt hyperplasia.AimsTo compare conventional histological examination to the determination of small bowel mucosal intraepithelial lymphocytes (IELs) and to serum and intestinal coeliac autoantibodies in untreated coeliac disease with villous atrophy and in mild enteropathy coeliac disease.Patients and methodsStudy comprised consecutive adult patients with coeliac disease suspicion; villous height–crypt depth ratio (Vh/CrD), the densities of CD3+, γδ+ and villous tip IELs and serum and intestinal transglutaminase 2 (TG2)-targeted autoantibodies were studied. Coeliac disease was diagnosed in 223 and excluded in 608 patients. Further, 66 patients were considered to suffer from mild enteropathy coeliac disease. Control group consisted of 138 patients.ResultsVh/CrD determination detected 77% of untreated coeliac disease patients. Serum coeliac autoantibodies had 84% sensitivity for untreated coeliac disease with villous atrophy and 70% sensitivity for mild enteropathy coeliac disease; the specificity was 100%. Intestinal TG2-targeted autoantibodies had sensitivities of 100% and 93%, and 100% specificity, respectively. γδ+ and villous tip IELs proved more reliable than CD3+ IELs.ConclusionsConventional histological examination as the golden standard in coeliac disease diagnosis is questionable. Serum and especially intestinal TG2-targeted autoantibodies seem promising in future coeliac disease diagnostics.     

High prevalence of undiagnosed coeliac disease in adults: a Swedish population-based study

OBJECTIVE: To determine the prevalence of coeliac disease in a population-based sample of Swedish adults. DESIGN: Population-based cross-sectional study. SETTING: Northern Sweden. SUBJECTS: A total of 1894 adults (76%) out of 2500 invited, randomly selected from the population register after stratification for age and sex. MAIN OUTCOME MEASURES: Prevalence of biopsy verified coeliac disease, symptoms of undiagnosed cases, and results of antiendomysium and antigliadin serum antibody tests. RESULTS: Coeliac disease was confirmed by intestinal biopsy showing enteropathy in 10 individuals (seven women and three men), corresponding to a prevalence of 5.3 per 1000 (95% CI = 2.5-9.7). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms compatible with coeliac disease. All individuals with antiendomysium antibody positivity who were subjected to a small intestinal biopsy had enteropathy. Furthermore, all of them also had elevated levels of antigliadin antibodies type IgA and/or IgG. CONCLUSIONS: Coeliac disease is common, albeit mostly undiagnosed, in Swedish adults. It is likely that the situation is no better in other countries. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case-finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.     

Rheumatic complaints as a presenting symptom in patients with coeliac disease.

Twenty-three cases of coeliac disease were found after a small bowel biopsy had been carried out on seventy patients with various rheumatic complaints. The prevalence of coeliac disease in patients with rheumatic disorders was estimated to be 1 in 243. The majority (19) of these cases were found by screening patient sera with a reticulin antibody test. Sj?gren's syndrome was the most frequent rheumatic diagnosis, with a total of six cases. Coeliac disease may occur concomitantly with various rheumatic complaints, and serological screening is advisable.     

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.